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  • CLASSES

    Thiazolidinediones/Glitazone and Other Oral Antidiabetic Combinations

    DEA CLASS

    Rx

    DESCRIPTION

    Combination of glimepiride, a sulfonylurea, and rosiglitazone, a thiazolidinedione.
    Used for treatment of type 2 diabetes mellitus; combination may increase risk of hypoglycemia vs monotherapy.

    COMMON BRAND NAMES

    Avandaryl

    DOSAGE & INDICATIONS

    For the treatment of type 2 diabetes mellitus uncontrolled by diet and exercise alone.
    NOTE: Patients treated with glimepiride; rosiglitazone should be monitored for cardiovascular adverse events. The use of combination glimepiride; rosiglitazone with insulin has not been studied and is not recommended by the manufacturer.
    NOTE: When adding rosiglitazone to glimepiride in patients with or without symptomatic heart disease and diabetes, monitor closely for signs of weight gain, peripheral edema, or congestive heart failure. In general, rosiglitazone should be initiated at the lowest dose and increased gradually after at least 3 months of therapy. The risk of these symptoms is increased when higher doses of rosiglitazone are used in combination with a sulfonylurea or insulin in patients at risk of congestive heart failure. Rosiglitazone should not be added to glimepiride therapy in patients with New York Heart Association Class III or IV heart failure. Discontinue the drug if any deterioration in cardiac status occurs during therapy.
    For when treatment with a sulfonylurea or rosiglitazone alone does not result in adequate glycemic control.
    Oral dosage
    Adults

    The recommended starting dose is 1 tablet of Avandaryl 4 mg/1 mg (rosiglitazone 4 mg/glimepiride 1 mg) PO once daily with the first meal of the day. For patients previously treated with a thiazolidinedione or a sulfonylurea and switched to Avandaryl, a starting dose of 1 tablet of Avandaryl 4 mg/2 mg (rosiglitazone 4 mg/glimepiride 2 mg) PO once daily may be considered. For patients previously treated with a thiazolidinedione, upward dose titration is recommended if adequate glycemic control is not achieved (based on fasting plasma glucose concentrations) after 1—2 weeks. The glimepiride component may be increased by <= 2 mg increments every 1—2 weeks, up to the maximum recommended total daily dose of 4 mg. For patients previously treated with a sulfonylurea, it may take up to 2 weeks to see a reduction in blood glucose, and up 2—3 months to see the full effect of the rosiglitazone component; therefore, dose titration of the rosiglitazone component up to a maximum daily dose of 8 mg is recommended if adequate glycemic control is not achieved after 8—12 weeks. If additional glycemic control is needed, the glimepiride component may be increased, up to a maximum daily dose of 4 mg. No transition period is necessary when transferring patients from a sulfonylurea-containing antidiabetic agent to Avandaryl. However, patients should be observed for hypoglycemia for the first 1—2 weeks when being transferred from a longer-acting sulfonylurea (i.e., chlorpropamide). If hypoglycemia develops, consider a dosage reduction in the glimepiride component.

    Geriatric or debilitated Adult patients, or those with adrenal insufficiency

    The recommended initial dose is Avandaryl 4 mg/1 mg (rosiglitazone 4 mg/glimepiride 1 mg) PO once daily with the morning meal. Monitor patients closely and carefully titrate doses. See adult dosage for titration.

    For patients already receiving a combination of glimepiride and rosiglitazone who desire to switch to the combination tablet.
    Oral dosage
    Adults

    Substitute the combination product, using the same dose of glimepiride and rosiglitazone already being taken. The maximum recommended dose of Avandaryl is 8 mg/day PO of rosiglitazone and 4 mg/day PO of glimepiride.

    Geriatric or debilitated Adult patients, or those with adrenal insufficiency

    See adult dosage. Monitor patients closely and titrate dose carefully.

    MAXIMUM DOSAGE

    Adults

    4 mg/day PO glimepiride with 8 mg/day PO rosiglitazone.

    Elderly

    4 mg/day PO glimepiride with 8 mg/day PO rosiglitazone.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Dosage adjustments based on cardiovascular status when adding rosiglitazone to sulfonylurea therapy:
    For adults without symptomatic heart disease but one or more risk factors for congestive heart failure or an ejection fraction < 40%: Initially, rosiglitazone 4 mg PO once daily.
    For adults with symptomatic heart disease, congestive heart failure New York Heart Association Class I or II: Recommended starting dose is 2 mg PO once daily of rosiglitazone. Therefore, use of the combined glimepiride; rosiglitazone tablet is not recommended. After titrating the rosiglitazone dosage to 4 mg/day, the combination product can be utilized. Dose titration of rosiglitazone should be slow, allowing more time than normal to achieve a target HgbA1c.
    For adults with symptomatic heart disease, congestive heart failure New York Heart Association Class III or IV: Glimepiride; rosiglitazone use is not recommended.

    Hepatic Impairment

    Avoid initiating rosiglitazone in patients with hepatic impairment where the ALT is greater than 2.5 times the upper limit of normal.

    Renal Impairment

    In any patient with renal impairment, initiate therapy conservatively. An initial dose of rosiglitazone 4 mg/glimepiride 1 mg PO once daily is suggested. Titrate the dose carefully and individualize based on fasting blood glucose concentrations.

    ADMINISTRATION

    For storage information, see specific product information within the How Supplied section.
     
    A Medication Guide must be dispensed with each prescription and refill.

    Oral Administration
    Oral Solid Formulations

    Administer glimepiride; rosiglitazone combination tablets once daily with the first meal of the day.
    Monitoring of fasting plasma glucose is necessary to determine the therapeutic response to glimepiride; rosiglitazone.

    STORAGE

    Avandaryl:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    NOTE: This monograph discusses the use of glimepiride; rosiglitazone for the management of type 2 diabetes. Clinicians may wish to consult the individual drug monographs for more information.
     
    There are conflicting studies regarding the possible cardiovascular risks associated with the use of oral sulfonylurea antidiabetic agents. The largest of the trials, the United Kingdom Prospective Diabetes Study (UKPDS), has demonstrated that intensive therapy with sulfonylureas does not increase the risk of heart attack (MI) or diabetes-related death when compared to conventional therapy. In this trial, lowering blood glucose with sulfonylurea therapy did not significantly effect cardiovascular complications. A 16% reduction (not statistically significant) in the risk of combined fatal or nonfatal MI and sudden death has been reported. In a follow-up study to the UKPDS, researchers found that after 10-years of resuming typical care, patients originally randomized to intensive therapy with sulfonylureas or insulin had a 15% relative reduction (RR 0.85, 95% CI 0.74—0.97; p=0.01) in the risk of MI and a 13% relative decrease (RR 0.87, 95% CI 0.76—0.96; p=0.007) in the risk of death from any cause as compared to patients originally randomized to conventional therapy; it should be noted that these reductions in cardiovascular risks persisted even though HbA1c concentrations were similar in the 2 groups after 1 year of follow-up. In contrast, the University Group Diabetes Program (UGDP) has previously reported that the administration of oral sulfonylureas increases cardiovascular mortality compared with dietary management alone, or dietary management and insulin therapy. The UGDP study has been widely criticized for study limitations including a small sample size (i.e., 200 patients per treatment group). Despite the controversy regarding these findings, the results of the UGDP study serve as a basis for the manufacturers' warning of possible risk of cardiovascular mortality associated with the use of oral sulfonylureas.

    Acute heart failure, cardiac disease, edema, heart failure, myocardial infarction, peripheral edema, pulmonary edema

    Glimepiride; rosiglitazone should be used with caution in patients with cardiac disease. Rosiglitazone is contraindicated for use in patients with NYHA Class III or IV heart failure, and it is not recommended for use in patients with symptomatic or acute heart failure or other acute cardiac events; rosiglitazone therapy should be discontinued if deterioration in cardiac status occurs. Thiazolidinediones, including rosiglitazone, when used alone or in combination with other antidiabetic agents, can cause or exacerbate congestive heart failure. The incidence of heart failure associated with rosiglitazone use is higher in those patients receiving concomitant insulin therapy, receiving higher doses of rosiglitazone, and who have risk factors for congestive heart failure. In addition, older patients and those with a longer duration of diabetes experienced a higher incidence of cardiovascular events during clinical trials. Dose-related fluid retention, edema and weight-gain has also been reported in patients treated with rosiglitazone therapy. Concomitant use of insulin with glimepiride; rosiglitazone is not recommended. Patients should be carefully observed for signs and symptoms of heart failure including excessive, rapid weight gain, dyspnea, and/or edema (peripheral edema, pulmonary edema) after drug initiation and changes in dose. If these signs and symptoms develop, the heart failure should be managed according to current standards of care. Discontinuation or dose reduction of glimepiride; rosiglitazone must be considered. Patients treated with rosiglitazone and insulin experienced an increased incidence of edema, cardiac failure, and other cardiac adverse events (including myocardial ischemia) in clinical trials; several patients did not have prior evidence of cardiovascular disease. Patients with congestive heart failure (CHF) NYHA Class I and II treated with rosiglitazone have an increased risk of cardiovascular events. A 52-week, double-blind, placebo-controlled, echocardiographic trial was conducted in 224 patients with type 2 diabetes mellitus and NYHA Class I or II CHF (ejection fraction 45% or less) on background antidiabetic and CHF therapy. An independent committee conducted a blinded evaluation of fluid-related events (including congestive heart failure) and cardiovascular hospitalizations according to predefined criteria. Other cardiovascular adverse events were also reported by investigators. Although no treatment difference in change from baseline ejection fraction was observed, more cardiovascular adverse events were observed with rosiglitazone treatment compared with placebo during the 52-week trial. In a long-term, cardiovascular outcome trial (RECORD) in patients with type 2 diabetes, the incidence of heart failure was higher in patients treated with rosiglitazone 2.7% compared with active control 1.3% (HR 2.10, 95% CI: 1.35, 3.27). Data from long-term, prospective, randomized, controlled clinical trials of rosiglitazone versus metformin or sulfonylureas, particularly a cardiovascular outcome trial (RECORD), observed no difference in overall mortality or in major adverse cardiovascular events (MACE) and its components. A meta-analysis of mostly short-term trials suggested an increased risk for myocardial infarction (MI) with rosiglitazone compared with placebo. RECORD, a prospectively designed cardiovascular outcome trial (mean follow-up 5.5 years; n = 4,447), compared the addition of rosiglitazone to metformin or a sulfonylurea (n = 2,220) with a control group of metformin plus sulfonylurea (n = 2,227) in patients with type 2 diabetes. Non-inferiority was demonstrated for the primary endpoint, cardiovascular hospitalization or cardiovascular death, for rosiglitazone compared with control (HR 0.99, 95% CI: 0.85, 1.16) demonstrating no overall increased risk in cardiovascular morbidity or mortality. The hazard ratios for total mortality and MACE were consistent with the primary endpoint and the 95% CI similarly excluded a 20% increase in risk for rosiglitazone. The hazard ratios for the components of MACE were 0.72 (95% CI: 0.49, 1.06) for stroke, 1.14 (95% CI: 0.80, 1.63) for myocardial infarction (MI), and 0.84 (95% CI: 0.59, 1.18) for cardiovascular death. The results of RECORD are consistent with the findings of 2 earlier long-term, prospective, randomized, controlled clinical trials (each trial greater than 3 years in duration; n = 9,620 patients).In patients with impaired glucose tolerance (DREAM trial), although the incidence of cardiovascular events was higher among subjects who were randomized to rosiglitazone in combination with ramipril than among subjects randomized to ramipril alone, no statistically significant differences were observed for MACE and its components between rosiglitazone and placebo. In type 2 diabetes patients who were initiating oral agent monotherapy (ADOPT trial), no statistically significant differences were observed for MACE and its components between rosiglitazone and metformin or a sulfonylurea. In a meta-analysis of 52 double-blind, randomized, controlled clinical trials designed to assess glucose-lowering efficacy in type 2 diabetes (mean duration 6 months), a statistically significant increased risk of myocardial infarction with rosiglitazone versus pooled comparators was observed [incidence 0.4% versus 0.3%; OR 1.8, (95% CI: 1.03, 3.25)]. A statistically non-significant increased risk of MACE was observed with rosiglitazone versus pooled comparators (OR 1.44, 95% CI: 0.95, 2.20). In the placebo-controlled trials, a statistically significant increased risk of myocardial infarction [0.4% versus 0.2%, OR 2.23 (95% CI: 1.14, 4.64)] and statistically non-significant increased risk of MACE [0.7% versus 0.5%, OR 1.53 (95% CI: 0.94, 2.54)] with rosiglitazone were observed. In the active-controlled trials, there was no increased risk of myocardial infarction or MACE. Close monitoring is prudent in the rosiglitazone treated patient, especially among patients with a greater risk for cardiovascular events.

    Diabetic ketoacidosis, type 1 diabetes mellitus

    Glimepiride; rosiglitazone should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis (DKA), with or without coma. DKA should be treated with insulin.

    Sulfonylurea hypersensitivity

    Glimepiride; rosiglitazone is contraindicated in patients with a known rosiglitazone or glimepiride hypersensitivity; do not use in patients with a sulfonylurea hypersensitivity or other sulfonamide derivatives hypersensitivity. Patients who have developed an allergic reaction to sulfonamide derivatives may develop an allergic reaction to glimepiride. Allergic reactions such as angioedema, arthralgia, myalgia and vasculitis have been reported with the sulfonylureas. Hypersensitivity reactions, including cutaneous eruptions with or without pruritis as well as more serious reactions (e.g., anaphylaxis, angioedema, Stevens-Johnson syndrome, dyspnea) have been reported with glimepiride and glimepiride; rosiglitazone. If a hypersensitivity reaction is suspected, promptly discontinue glimepiride; rosiglitazone, assess for other potential causes for the reaction, and institute alternative treatment for diabetes.

    Sulfonamide hypersensitivity

    Do not use glimepiride; rosiglitazone in patients with a sulfonamide hypersensitivity. Patients who have developed an allergic reaction to sulfonamide derivatives may develop an allergic reaction to glimepiride; rosiglitazone. Hypersensitivity reactions, including cutaneous eruptions with or without pruritis as well as more serious reactions (e.g., anaphylaxis, angioedema, Stevens-Johnson syndrome, dyspnea) have been reported. Although they contain a sulfonamide side chain, sulfonylureas and other nonantibiotic sulfonamides do not contain the N4 aromatic amine or the N1-substituent that are present in sulfonamide antibiotics and thought to be responsible for hypersensitivity-type adverse reactions; the risk of cross-sensitivity in patients taking a nonantibiotic sulfonamide that have a history of sulfonamide hypersensitivity is low and has been confirmed by recent, observational studies. However, several cases in the literature report of cross-sensitivity reactions to sulfonylureas in patients with a history of sulfonamide hypersensitivity. A 57 year-old man with a self-reported sulfonamide allergy (unknown offending agent) and stable on hydrochlorothiazide and glyburide experienced possible erythema multiforme, an acute inflammatory skin reaction, and throat swelling within 30 days after initiating celecoxib, which contains a sulfonamide side chain. Although the skin reaction resolved with celecoxib discontinuation, a similar reaction occurred when glyburide and hydrochlorothiazide therapies were re-introduced. In another case report, a 71 year-old man with multiple, documented drug allergies including Stevens-Johnson syndrome to trimethoprim-sulfamethoxazole experienced a rash after receiving furosemide and after receiving glyburide, both of which contain a sulfonamide side chain. It should be noted that this patient also had a history of several non-sulfonamide allergies; he subsequently received torsemide, which also contains a sulfonamide side chain, without problems. If a hypersensitivity reaction is suspected, promptly discontinue glimepiride; rosiglitazone, assess for other potential causes for the reaction, and institute alternative treatment for diabetes.

    Adrenal insufficiency, hypercortisolism, hyperglycemia, hyperthyroidism, hypoglycemia, hypothyroidism, pituitary insufficiency

    Severe hypoglycemia is possible with glimepiride; rosiglitazone because of the glimepiride component. Proper patient selection and education are necessary to avoid hypoglycemic episodes. Older patients, or patients with renal or hepatic dysfunction may be more susceptible to the hypoglycemic effects of glimepiride. Other conditions associated with hypoglycemia include debilitated physical condition, drug interactions, malnutrition, uncontrolled adrenal insufficiency, pituitary insufficiency, or hypothyroidism. In patients with these conditions, conservative dosing of glimepiride; rosiglitazone is recommended. In addition, because hypoglycemia may be difficult to recognize in older patients and those taking certain drugs (i.e., beta-blockers or other sympatholytic agents), careful blood glucose concentration monitoring is recommended. Hyperglycemia may also affect the efficacy of antidiabetic agents; hyperglycemia-related conditions include drug interactions, female hormonal changes, high fever, severe psychological stress, and uncontrolled hypercortisolism or hyperthyroidism. Patients with any of these conditions should undergo careful monitoring of plasma glucose concentrations.

    Hepatic disease, jaundice

    Glimepiride; rosiglitazone should be used cautiously in patients with hepatic disease. Liver function tests (LFTs) should be measured prior to the initiation of therapy with glimepiride; rosiglitazone in all patients and periodically thereafter. Do not initiate glimepiride; rosiglitazone in patients with increased baseline liver enzyme levels (i.e., ALT more than 2.5 times the upper limit of normal). Patients with mildly elevated liver enzymes with ALT levels 2.5 times the upper limit of normal (ULN) or less at baseline or during therapy should be evaluated to determine the cause of the liver enzyme elevation. Initiation or continue therapy with caution in patients with mild LFT elevations; use close clinical follow-up, including more frequent LFT monitoring, to determine if the liver enzyme elevations resolve or worsen. If at any time ALT levels increase to more than 3 times the ULN in a patient taking glimepiride; rosiglitazone, LFTs should be rechecked as soon as possible. If ALT levels remain more than 3 times the ULN, discontinue glimepiride; rosiglitazoneglimepiride; rosiglitazone. If any patient develops symptoms suggesting hepatic dysfunction, which may include unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, and/or dark urine, liver enzymes should be checked. The decision whether to continue the patient on therapy with glimepiride; rosiglitazone should be guided by clinical judgment pending laboratory evaluations. If jaundice is observed, drug therapy should be discontinued. With sulfonylureas, including glimepiride, there may be an elevation of liver function tests (LFTs) in rare cases. In isolated instances, impairment of liver function (e.g., with cholestasis and jaundice), as well as hepatitis, which may also lead to hepatic failure, have been reported. Rosiglitazone has also been associated with increased LFTs and rarely hyperbilirubinemia; post-marketing reports of hepatitis and hepatic failure, with and without fatal outcome, have been reported. In pre-approval clinical trials for rosiglitazone in 4,598 patients (3,600 patient-years of exposure) and in a long-term 4- to 6-year trial in 1,456 patients (4,954 patient-years exposure), there was no evidence of drug-induced hepatotoxicity.

    Renal failure, renal impairment

    Glimepiride is substantially eliminated by the kidney. In clinical pharmacokinetic studies, the relative total clearance of glimepiride increased and the elimination of the two major metabolites was reduced, and the exposure (AUC) increased, in patients with renal impairment. Patients with a creatinine clearance (CrCl) of less than 20 mL/min had a 2.3-fold higher mean AUC for the first metabolite (M1) and an 8.6-fold higher mean AUC for the second metabolite (M2) compared to the corresponding mean AUCs in patients with CrCl greater than 50 mL/min. Reduced glimepiride elimination is a risk factor for hypoglycemia. To minimize the risk of hypoglycemia, the initial dosing, dose increments and maintenance dosage of glimepiride; rosiglitazone should be conservative in patients with renal dysfunction or renal failure. During initiation of glimepiride; rosiglitazone therapy and any subsequent dose adjustments, patients with renal impairment should be observed carefully for hypoglycemia.

    Anemia, G6PD deficiency, hemolytic anemia

    Sulfonylurea agents, including glimepiride, can cause hemolytic anemia in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency. Use glimepiride; rosiglitazone with caution in patients with G6PD deficiency and consider the use of a non-sulfonylurea oral antidiabetic agent. There are also postmarketing reports of hemolytic anemia in patients receiving glimepiride who did not have known G6PD deficiency. Decreases in hemoglobin and hematocrit occurred in a dose-related fashion in adult patients treated with rosiglitazone. The observed changes may be related to the increased plasma volume observed with treatment with rosiglitazone. However, the reduction in hemoglobin may be significant in patients with pre-existing anemia. Consider regular measurement of hematologic parameters in patients taking glimepiride; rosiglitazone.

    Bone fractures, osteoporosis

    Use rosiglitazone-containing medications with caution in patients at risk for osteopenia or osteoporosis. Long-term trials (ADOPT and RECORD) show an increased incidence of bone fractures in patients, particularly female patients, taking rosiglitazone. This increased incidence was noted after the first year of treatment and persisted during the course of the trial. The majority of the fractures in the women who received rosiglitazone occurred in the upper arm, hand, and foot. These sites of fracture are different from those usually associated with postmenopausal osteoporosis (e.g., hip or spine). Other trials suggest that this risk may also apply to men, although the risk of fracture among women appears higher than that among men. The risk of fracture should be considered in the care of patients treated with glimepiride; rosiglitazone, and attention given to assessing and maintaining bone health according to current standards of care.

    Geriatric

    Use glimepiride; rosiglitazone with caution in the geriatric patient due to increased susceptibility to the hypoglycemic effects of the drug combination and the potential for heart failure with rosiglitazone. The starting dose of the drug combination should be conservative due to the potential for renal insufficiency in the elderly and their increased sensitivity to hypoglycemic reactions, especially if they are debilitated or malnourished. In addition, hypoglycemia may be difficult to recognize in the elderly. A starting dose of 1 mg glimepiride (e.g., rosiglitazone 4 mg with glimepiride 1 mg), followed by appropriate dose titration and careful monitoring of blood glucose is recommended in these patients. Three observational studies in elderly diabetic patients (age 65 years and older) found that rosiglitazone statistically significantly increased the risk of hospitalized heart failure and all-cause mortality compared to use of pioglitazone. One other observational study in patients with a mean age of 54 years, which also included an analysis in a subpopulation of patients more than 65 years of age, found no statistically significant increase in emergency department visits or hospitalization for heart failure, or all-cause mortality, between patients treated with rosiglitazone compared to pioglitazone and reported similar results for the subpopulation of patients more than 65 years of age. One additional small, prospective, observational study found no statistically significant differences for cardiovascular mortality and all-cause mortality in patients treated with rosiglitazone compared to pioglitazone. Some uncertainty remains over the risk of heart failure due to the thiazolidinedione (TZD) agents. Geriatric patients should be carefully observed for signs and symptoms of heart failure including excessive, rapid weight gain, dyspnea, and/or edema (peripheral edema, pulmonary edema) after drug initiation and changes in dose. If these signs and symptoms develop, the heart failure should be managed according to current standards of care, and rosiglitazone should be discontinued. Accordingly, rosiglitazone is contraindicated for use in geriatric patients with NYHA Class III or IV heart failure, and it is not recommended for use in patients with symptomatic or acute heart failure; glimepiride; rosiglitazone therapy should be discontinued if deterioration in cardiac status occurs. According to the Beers Criteria, rosiglitazone is considered a potentially inappropriate medication (PIM) for use in geriatric patients with heart failure and should be avoided in this patient population due to the potential for fluid retention and exacerbation of the condition. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, the use of antidiabetic medications should include monitoring (e.g., periodic blood glucose) for effectiveness based on desired goals for that individual and to identify complications of treatment such as hypoglycemia or impaired renal function. LTCF residents receiving rosiglitazone should be monitored for visual deterioration due to new onset and/or worsening of macular edema in diabetic patients. In addition, rosiglitazone has been associated with edema and weight gain and use should be avoided in those with NYHA Stage III or Stage IV heart failure. Sulfonylureas, such as glimepiride, can cause SIADH and result in hyponatremia.

    Menstrual irregularity, polycystic ovary syndrome

    Premenopausal anovulatory females with insulin resistance, such as those with polycystic ovary syndrome (PCOS) may resume ovulation as a result of glimepiride; rosiglitazone therapy, due to the rosiglitazone component. These patients may be at risk of becoming pregnant if adequate contraception is not used. Adequate contraception should be recommended for premenopausal women during glimepiride; rosiglitazone therapy. Hormonal imbalance has been seen in preclinical studies of rosiglitazone, however, the clinical significance of this finding is not known. If unexpected menstrual irregularity occurs, the benefits of continued therapy with glimepiride; rosiglitazone should be reviewed.

    Obstetric delivery, pregnancy

    Rosiglitazone; glimepiride is classified as FDA pregnancy risk category C. Rosiglitazone is not recommended for use during pregnancy. Rosiglitazone has been reported to cross the human placenta and be detectable in fetal tissue; the clinical significance of these findings is unknown. Animal data suggest no teratogenic effects for rosiglitazone. Glimepiride and other sulfonylureas have been associated with an increased risk of intrauterine fetal death in animal studies. Prolonged (4 to 10 days) hypoglycemia has been reported in neonates born to mothers who were receiving a sulfonylurea at the time of obstetric delivery, mostly in patients taking sulfonylureas with prolonged half-lives. Therefore, the manufacturer recommends that a patient planning a pregnancy should be manged with insulin therapy instead of glimepiride; rosiglitazone during the course of her pregnancy. The American College of Obstetrician and Gynecologists recommends insulin as the therapy of choice to maintain blood glucose as close to normal as possible during pregnancy in patients with type 1 or 2 diabetes mellitus, and, if diet therapy alone is not successful, for those patients with gestational diabetes.

    Breast-feeding

    It is not known whether or not glimepiride is excreted in human milk, but other sulfonylureas are. Rosiglitazone has been found in the milk of lactating rats. It is unknown if rosiglitazone or its metabolites are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for adverse events in the infant, glimepiride; rosiglitazone should not be administered to lactating women who are breast-feeding. If therapy other than diet and exercise is needed, insulin is recommended. Other oral hypoglycemics may be considered as possible alternatives during breast-feeding. Because acarbose has limited systemic absorption, which results in minimal maternal plasma concentrations, clinically significant exposure via breast milk is not expected. Also, while the manufacturers of metformin recommend against breast-feeding while taking the drug, data have shown that metformin is excreted into breast milk in small amounts and adverse effects on infant plasma glucose have not been reported in human studies. The American Academy of Pediatrics (AAP) has previously regarded tolbutamide as compatible with breast-feeding. Although other sulfonylureas have not been evaluated by the AAP, glyburide may be a suitable alternative since it was not detected in the breast milk of lactating women who received single and multiple doses of glyburide. If any oral hypoglycemics are used during breast feeding, the nursing infant should be monitored for signs of hypoglycemia, such as increased fussiness or somnolence.

    Children

    The safe and effective use of the combination of glimepiride; rosiglitazone has not been established in children or adolescents under the age of 18 years. Data are insufficient to recommend the use of rosiglitazone in children and adolescents. In a 24-week, double-blind clinical trial, children and adolescents 10 to 17 years of age with type 2 diabetes mellitus were randomized to 2 mg PO twice daily of rosiglitazone (n = 99) or 500 mg PO twice daily of metformin (n = 101). After at least 8 weeks of therapy, 49% of rosiglitazone-treated and 55% of metformin-treated patients had their dose doubled due to a fasting plasma glucose of 126 mg/dL or more. For the overall intent-to-treat population at week 24, the mean decrease from baseline in hemoglobin A1c (HbA1c or A1C) was 0.14% for rosiglitazone-treated patients versus 0.49% for metformin-treated patients. The power in the study was not sufficient to determine if the changes in A1C between the 2 groups were significantly different. In general, patients naive to diabetic treatment experienced a greater reduction in A1C when compared to those who had been previously treated with diabetic treatment; for patients treated with rosiglitazone, a change in A1C of -0.5% for naive patients versus +0.1% for previously treated patients occurred, and in patients treated with metformin, these numbers were -0.7% for naive patients versus -0.4% for previously treated patients. In addition, patients treated with rosiglitazone gained more weight than patients treated with metformin (2.8 kg for patients treated with rosiglitazone versus 0.2 kg for patients treated with metformin). There was an insufficient number of patients in this study to establish statistically whether these observed mean treatment effects were similar or different. Treatment effects differed for patients naive to therapy with antidiabetic drugs and for patients previously treated with antidiabetic therapy.

    ADVERSE REACTIONS

    Severe

    bone fractures / Delayed / 9.3-9.3
    myocardial infarction / Delayed / 2.9-2.9
    heart failure / Delayed / 2.7-2.7
    pleural effusion / Delayed / Incidence not known
    pulmonary edema / Early / Incidence not known
    hepatic failure / Delayed / Incidence not known
    macular edema / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    pancytopenia / Delayed / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    vasculitis / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    porphyria / Delayed / Incidence not known
    SIADH / Delayed / Incidence not known

    Moderate

    hypoglycemia / Early / 3.6-5.5
    edema / Delayed / 4.8-4.8
    peripheral edema / Delayed / 4.8-4.8
    hypertension / Early / 4.4-4.4
    anemia / Delayed / 1.9-1.9
    erythema / Early / 0-1.0
    hyperbilirubinemia / Delayed / 0.3-0.3
    elevated hepatic enzymes / Delayed / 0.2-0.2
    dyspnea / Early / Incidence not known
    cholestasis / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known
    blurred vision / Early / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    hypercholesterolemia / Delayed / Incidence not known
    hyponatremia / Delayed / Incidence not known
    osteopenia / Delayed / Incidence not known

    Mild

    abdominal pain / Early / 1.0-10.0
    infection / Delayed / 9.9-9.9
    diarrhea / Early / 2.3-8.9
    nausea / Early / 1.1-7.7
    weight gain / Delayed / 6.9-6.9
    headache / Early / 1.5-5.9
    arthralgia / Delayed / 5.0-5.0
    back pain / Delayed / 4.0-4.0
    vomiting / Early / 0-4.0
    fatigue / Early / 3.6-3.6
    sinusitis / Delayed / 3.2-3.2
    pharyngitis / Delayed / 3.0-3.0
    dizziness / Early / 1.7-1.7
    asthenia / Delayed / 1.6-1.6
    maculopapular rash / Early / 0-1.0
    pruritus / Rapid / 0-1.0
    urticaria / Rapid / 0-1.0
    menstrual irregularity / Delayed / 0-0.4
    alopecia / Delayed / Incidence not known
    rash (unspecified) / Early / Incidence not known
    photosensitivity / Delayed / Incidence not known
    flushing / Rapid / Incidence not known

    DRUG INTERACTIONS

    Abiraterone: Use abiraterone, a strong CYP2C8 inhibitor, and rosiglitazone, a CYP2C8 substrate, together cautiously, as levels of rosiglitazone may be increased. Monitor closely for signs of rosiglitazone toxicity such as weight gain, edema, hypoglycemia, and anemia. If a stong CYP2C8 inhibitor, such as abiraterone, is started or stopped during rosiglitazone therapy, changes in diabetes treatment may be warranted based on clinical response.
    Acebutolol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Acetaminophen; Aspirin, ASA; Caffeine: If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Acetaminophen; Dextromethorphan; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Acetaminophen; Dichloralphenazone; Isometheptene: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood glucose concentrations. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Acetaminophen; Guaifenesin; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Acetaminophen; Propoxyphene: Propoxyphene may enhance the hypoglycemic action of antidiabetic agents. Patients should be closely monitored for changes in glycemic control while receiving propoxyphene in combination with antidiabetic agents.
    Acetaminophen; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Acetazolamide: Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
    Acetohexamide: A maximum dose of 8 mg/day of rosiglitazone is recommended when used in combination with sulfonylureas; the incidence of adverse effects including hypoglycemia is increased with larger doses. In one clinical study, rosiglitazone 4 or 8 mg/day was added to failed glimepiride plus metformin therapy. The incidence of hypoglycemia (blood glucose concentrations <= 50 mg/dl) was 18.6% in the 4 mg/day group compared with 28% in the 8 mg/day group. In addition, 4 or 8 mg/day of rosiglitazone has been added to failed glyburide plus metformin therapy. The incidence of hypoglycemia was higher in the rosiglitazone (average dose 7.4 mg/day)+glyburide+metformin group (22%) when compared to the glyburide+metformin group (3%). Patients should be instructed to monitor blood glucose concentrations more frequently. Dosage adjustments may be indicated.
    Acitretin: Retinoids have been reported to cause changes in blood sugar control in diabetics. In a study of 7 healthy male volunteers, acitretin treatment potentiated the blood glucose lowering effect of glibenclamide (a sulfonylurea similar to chlorpropamide) in 3 of the 7 subjects. Repeating the study with 6 healthy male volunteers in the absence of glibenclamide did not detect an effect of acitretin on glucose tolerance. Careful supervision of diabetic patients under treatment with acitretin is recommended, especially those taking concomitant sulfonylureas. There appears to be no pharmacokinetic interaction between acitretin and glyburide.
    Acrivastine; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Aliskiren; Valsartan: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Amiodarone: Amiodarone inhibits cytochrome P450 2C9. Caution is recommended when administering amiodarone with other CYP2C9 substrates including sulfonylureas.
    Amlodipine; Benazepril: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Amlodipine; Olmesartan: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Amlodipine; Telmisartan: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Amlodipine; Valsartan: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Amoxicillin; Clarithromycin; Lansoprazole: Clarithromycin may enhance the hypoglycemic effects of antidiabetic agents. With certain agents, such as pioglitazone and rosiglitazone, inhibition of the CYP3A4 enzyme by clarithromycin may be involved. Clarithromycin may enhance the hypoglycemic effects of glimepiride. Glimepiride is highly protein bound and may be displaced from protein binding sites by other high protein bound drugs, such as clarithromycin, leading to an increase in unbound glimepiride concentration and the potential for hypoglycemia. Patients receiving clarithromycin concomitantly with glimepiride should be monitored for changes in glycemic control.
    Amoxicillin; Clarithromycin; Omeprazole: Clarithromycin may enhance the hypoglycemic effects of antidiabetic agents. With certain agents, such as pioglitazone and rosiglitazone, inhibition of the CYP3A4 enzyme by clarithromycin may be involved. Clarithromycin may enhance the hypoglycemic effects of glimepiride. Glimepiride is highly protein bound and may be displaced from protein binding sites by other high protein bound drugs, such as clarithromycin, leading to an increase in unbound glimepiride concentration and the potential for hypoglycemia. Patients receiving clarithromycin concomitantly with glimepiride should be monitored for changes in glycemic control.
    Amphetamine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia.
    Amphetamine; Dextroamphetamine Salts: Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently.
    Amphetamine; Dextroamphetamine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia.
    Amprenavir: New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. In addition, coadministration of atazanavir with rosiglitazone may result in elevated rosiglitazone plasma concentrations. Rosiglitazone is a substrate for CYP2C8; atazanavir is a weak inhibitor of CYP2C8.
    Amyl Nitrite: The concomitant use of nitrates with rosiglitazone is not recommended. An increased risk of myocardial ischemia was observed in a subset of patients receiving nitrates with rosiglitazone. Most patients that were using nitrates had preexisting coronary artery disease. In patients with coronary artery disease that were not on nitrates, rosiglitazone therapy did not increase the risk of myocardial ischemia.
    Androgens: Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia. However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary. Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Angiotensin II receptor antagonists: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Angiotensin-converting enzyme inhibitors: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Aprepitant, Fosaprepitant: Use caution if glimepiride and aprepitant, fosaprepitant are used concurrently and monitor for a possible decrease in the efficacy of glimepiride. After administration, fosaprepitant is rapidly converted to aprepitant. Glimepiride is a CYP2C9 substrate and aprepitant is a CYP2C9 inducer. Administration of a CYP2C9 substrate, tolbutamide, on days 1, 4, 8, and 15 with a 3-day regimen of oral aprepitant (125 mg/80 mg/80 mg) decreased the tolbutamide AUC by 23% on day 4, 28% on day 8, and 15% on day 15. The AUC of tolbutamide was decreased by 8% on day 2, 16% on day 4, 15% on day 8, and 10% on day 15 when given prior to oral administration of aprepitant 40 mg on day 1, and on days 2, 4, 8, and 15. The effects of aprepitant on tolbutamide were not considered significant. When a 3-day regimen of aprepitant (125 mg/80 mg/80 mg) given to healthy patients on stabilized chronic warfarin therapy (another CYP2C9 substrate), a 34% decrease in S-warfarin trough concentrations was noted, accompanied by a 14% decrease in the INR at five days after completion of aprepitant. Use caution if rosiglitazone and aprepitant are used concurrently and monitor for a possible decrease in the efficacy of rosiglitazone. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. Rosiglitazone is an in vitro CYP2C9 substrate and aprepitant is a CYP2C9 inducer. Administration of a CYP2C9 substrate, tolbutamide, on days 1, 4, 8, and 15 with a 3-day regimen of oral aprepitant (125 mg/80 mg/80 mg) decreased the tolbutamide AUC by 23% on day 4, 28% on day 8, and 15% on day 15. The AUC of tolbutamide was decreased by 8% on day 2, 16% on day 4, 15% on day 8, and 10% on day 15 when given prior to oral administration of aprepitant 40 mg on day 1, and on days 2, 4, 8, and 15. The effects of aprepitant on tolbutamide were not considered significant. When a 3-day regimen of aprepitant (125 mg/80 mg/80 mg) given to healthy patients on stabilized chronic warfarin therapy (another CYP2C9 substrate), a 34% decrease in S-warfarin trough concentrations was noted, accompanied by a 14% decrease in the INR at five days after completion of aprepitant.
    Aripiprazole: Aripiprazole has been associated with causing hyperglycemia, even diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when aripiprazole is instituted. Patients taking sulfonylureas should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Articaine; Epinephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood glucose concentrations. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Asenapine: Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when asenapine is instituted. Atypical antipsychotics have been associated with hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma in some instances. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Patients taking sulfonylureas should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Aspirin, ASA: If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
    Aspirin, ASA; Butalbital; Caffeine: If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
    Aspirin, ASA; Caffeine; Dihydrocodeine: If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
    Aspirin, ASA; Carisoprodol: If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
    Aspirin, ASA; Carisoprodol; Codeine: If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
    Aspirin, ASA; Dipyridamole: If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
    Aspirin, ASA; Omeprazole: If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
    Aspirin, ASA; Oxycodone: If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
    Aspirin, ASA; Pravastatin: If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
    Atazanavir: New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. In addition, coadministration of atazanavir with rosiglitazone may result in elevated rosiglitazone plasma concentrations. Rosiglitazone is a substrate for CYP2C8; atazanavir is a weak inhibitor of CYP2C8.
    Atazanavir; Cobicistat: New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. In addition, coadministration of atazanavir with rosiglitazone may result in elevated rosiglitazone plasma concentrations. Rosiglitazone is a substrate for CYP2C8; atazanavir is a weak inhibitor of CYP2C8.
    Atenolol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Atenolol; Chlorthalidone: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    atypical antipsychotic: Patients taking sulfonylureas should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Avanafil: Avanafil is a weak inhibitor of CYP2C8 isoenzymes. A single avanafil (200 mg) dose increased AUC by 2% and decreased Cmax by 14% of a single rosiglitazone (8 mg) dose, a CYP2C8 substrate.
    Azelaic Acid; Copper; Folic Acid; Nicotinamide; Pyridoxine; Zinc: Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. Niacin interferes with glucose metabolism and can result in hyperglycemia; monitor patients on antidiabetic agents for loss of blood glucose control if niacin therapy is added. Niacin interferes with glucose metabolism and can result in hyperglycemia; monitor patients on antidiabetic agents for loss of blood glucose control if niacin therapy is added.
    Azelastine; Fluticasone: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Azilsartan: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Azilsartan; Chlorthalidone: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Baclofen: Because baclofen can increase blood glucose, doses of antidiabetic agents may need adjustment in patients receiving these drugs concomitantly.
    Barbiturates: Barbiturates may induce the CYP2C9 metabolism of glimepiride. Blood glucose concentrations should be monitored and possible dose adjustments of glimepiride may need to be made.
    Beclomethasone: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Benazepril: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Benazepril; Hydrochlorothiazide, HCTZ: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Bendroflumethiazide; Nadolol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Benzphetamine: Benzphetamine may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that benzphetamine can be used concurrently. Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia.
    Beta-blockers: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Betamethasone: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Betaxolol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Bexarotene: Systemic bexarotene may enhance the action of agents that enhance insulin secretion (e.g., sulfonylureas) resulting in hypoglycemia. Patients should be closely monitored while receiving bexarotene capsules in combination with any of these agents; monitor for hypoglycemia and the need for diabetic therapy adjustments. Hypoglycemia has not been associated with bexarotene monotherapy. Systemic bexarotene may enhance the action of thiazolidinediones resulting in hypoglycemia. Patients should be closely monitored while receiving bexarotene capsules in combination with these agents; monitor for hypoglycemia and the need for diabetic therapy adjustments.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents including tetracyclines. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin. Glimepiride is metabolized by CYP2C9. It is possible for serum concentrations of glimepiride to rise when coadministered with drugs that inhibit CYP2C9 like metronidazole. Monitor serum glucose concentrations if glimepiride is coadministered with metronidazole. Dosage adjustments may be necessary.
    Bismuth Subsalicylate: If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents including tetracyclines. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin. Glimepiride is metabolized by CYP2C9. It is possible for serum concentrations of glimepiride to rise when coadministered with drugs that inhibit CYP2C9 like metronidazole. Monitor serum glucose concentrations if glimepiride is coadministered with metronidazole. Dosage adjustments may be necessary. If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
    Bisoprolol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Bisoprolol; Hydrochlorothiazide, HCTZ: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Bortezomib: During clinical trials of bortezomib, hypoglycemia and hyperglycemia were reported in diabetic patients receiving antidiabetic agents. Patients on antidiabetic agents receiving bortezomib treatment may require close monitoring of their blood glucose levels and dosage adjustment of their medication. During clinical trials of bortezomib, hypoglycemia and hyperglycemia were reported in diabetic patients receiving antidiabetic agents. Patients on oral antidiabetic agents receiving bortezomib treatment may require close monitoring of their blood glucose levels and dosage adjustment of their medication.
    Bosentan: Bosentan is expected to reduce plasma concentrations of other oral antidiabetic agents that are predominantly metabolized by CYP2C9 enzymes (e.g., rosiglitazone); blood glucose monitoring is prudent following addition of bosentan therapy to such antidiabetic drugs. In addition to the theoretical cytochrome P-450 interactions, the risk of elevated hepatic enzymes is also a consideration with the use of rosiglitazone; it may be prudent to utilize alternative antidiabetic agents during bosentan therapy. Bosentan is an inducer of CYP2C9 and is expected to reduce plasma concentrations of oral antidiabetic agents that are predominantly metabolized by CYP2C9 enzymes, such as glimepiride. Blood glucose monitoring is prudent following addition of bosentan therapy to such antidiabetic drugs.
    Brexpiprazole: Patients taking sulfonylureas should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Brimonidine; Timolol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Brompheniramine; Carbetapentane; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Brompheniramine; Hydrocodone; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Brompheniramine; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Budesonide: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Budesonide; Formoterol: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Bumetanide: Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Candesartan: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Candesartan; Hydrochlorothiazide, HCTZ: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Capecitabine: Use caution if coadministration of capecitabine with glimepiride is necessary, and monitor for an increase in glimepiride-related adverse reactions such as hypoglycemia. Glimepiride is a CYP2C9 substrate; capecitabine and/or its metabolites are thought to be inhibitors of CYP2C9. In a drug interaction study, the mean AUC of another CYP2C9 substrate, S-warfarin (single dose), significantly increased after coadministration with capecitabine; the maximum observed INR value also increased by 91%. Use caution if coadministration of capecitabine with rosiglitazone is necessary, and monitor for an increase in rosiglitazone-related adverse reactions including hypoglycemia. Rosiglitazone is primarily a CYP2C8 substrate in vitro, with a lesser contribution from CYP2C9; capecitabine and/or its metabolites are thought to be inhibitors of CYP2C9. In a drug interaction study, the mean AUC of another CYP2C9 substrate, S-warfarin (single dose), significantly increased after coadministration with capecitabine; the maximum observed INR value also increased by 91%.
    Captopril: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Captopril; Hydrochlorothiazide, HCTZ: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Carbamazepine: Carbamazepine may induce the CYP2C9 metabolism of glimepiride. Blood glucose concentrations should be monitored and possible dose adjustments of glimepiride may need to be made.
    Carbetapentane; Chlorpheniramine; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Carbetapentane; Diphenhydramine; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Carbetapentane; Guaifenesin; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Carbetapentane; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Carbetapentane; Phenylephrine; Pyrilamine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Carbetapentane; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Carbinoxamine; Hydrocodone; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Carbinoxamine; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Carbinoxamine; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Carbonic anhydrase inhibitors: Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
    Cariprazine: Patients taking rosiglitazone should be closely monitored for worsening glycemic control when cariprazine is instituted. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Patients taking sulfonylureas should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Carteolol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Carvedilol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Cetirizine; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Chlophedianol; Guaifenesin; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Chloramphenicol: Clinical hypoglycemia may be observed when chloramphenicol is used in combination with sulfonylureas. If chloramphenicol is administered or discontinued in patients receiving oral sulfonylureas, patients should be monitored for hypoglycemia or loss of blood glucose control. Chloramphenicol may inhibit the hepatic metabolism of sulfonylureas. In addition, the hypoglycemic action of glyburide and glipizide may be potentiated by other drugs that are highly protein bound, such as chloramphenicol.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Chlorpheniramine; Hydrocodone; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Chlorpheniramine; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Chlorpheniramine; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Chlorpropamide: A maximum dose of 8 mg/day of rosiglitazone is recommended when used in combination with sulfonylureas; the incidence of adverse effects including hypoglycemia is increased with larger doses. In one clinical study, rosiglitazone 4 or 8 mg/day was added to failed glimepiride plus metformin therapy. The incidence of hypoglycemia (blood glucose concentrations <= 50 mg/dl) was 18.6% in the 4 mg/day group compared with 28% in the 8 mg/day group. In addition, 4 or 8 mg/day of rosiglitazone has been added to failed glyburide plus metformin therapy. The incidence of hypoglycemia was higher in the rosiglitazone (average dose 7.4 mg/day)+glyburide+metformin group (22%) when compared to the glyburide+metformin group (3%). Patients should be instructed to monitor blood glucose concentrations more frequently. Dosage adjustments may be indicated.
    Chlorthalidone; Clonidine: Clonidine may potentiate or weaken the hypoglycemic effects of antidiabetic agents and may mask the signs and symptoms of hypoglycemia. Patients receiving clonidine concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Choline Salicylate; Magnesium Salicylate: If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
    Chromium: Chromium dietary supplements may lower blood glucose. As part of the glucose tolerance factor molecule, chromium appears to facilitate the binding of insulin to insulin receptors in tissues and to aid in glucose metabolism. Because blood glucose may be lowered by the use of chromium, patients who are on antidiabetic agents may need dose adjustments. Close monitoring of blood glucose is recommended.
    Ciclesonide: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Cimetidine: Cimetidine has been shown to affect the pharmacokinetics of some oral sulfonylureas. Patients receiving sulfonylureas should be observed for evidence of altered glycemic response when cimetidine is instituted or discontinued. The mechanism of this interaction may involve either increasing the absorption or decreasing the clearance of the sulfonylurea. Asymptomatic hypoglycemia has been observed as a result of this interaction. It is unclear at this time if famotidine or nizatidine interact with oral sulfonylureas.
    Ciprofloxacin: Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including the thiazolidinediones (e.g., rosiglitazone, pioglitazone), are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Rare cases of severe hypoglycemia have been reported with concomitant use of quinolones and glyburide. Therefore, careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents are coadministered. Monitor blood glucose when quinolones and antidiabetic agents are coadministered.
    Cisapride: Because cisapride can enhance gastric emptying in diabetic patients, blood glucose can be affected, which, in turn, may affect the clinical response to the sulfonylurea oral antidiabetic agents. Monitor blood glucose and adjust if cliniically indicated.
    Clarithromycin: Clarithromycin may enhance the hypoglycemic effects of antidiabetic agents. With certain agents, such as pioglitazone and rosiglitazone, inhibition of the CYP3A4 enzyme by clarithromycin may be involved. Clarithromycin may enhance the hypoglycemic effects of glimepiride. Glimepiride is highly protein bound and may be displaced from protein binding sites by other high protein bound drugs, such as clarithromycin, leading to an increase in unbound glimepiride concentration and the potential for hypoglycemia. Patients receiving clarithromycin concomitantly with glimepiride should be monitored for changes in glycemic control.
    Clindamycin; Tretinoin: A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Clonidine: Clonidine may potentiate or weaken the hypoglycemic effects of antidiabetic agents and may mask the signs and symptoms of hypoglycemia. Patients receiving clonidine concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Clopidogrel: Coadministration of clopidogrel and rosiglitazone may result in increased serum concentrations of rosiglitazone and therefore increased risk for hypoglycemia. The dose of rosiglitazone may require adjustment during concurrent use based on clinical response. Rosiglitazone is metabolized by CYP2C8 and clopidogrel is a strong CYP2C8 inhibitor. Glimepiride is metabolized by CYP2C9. It is possible for serum concentrations of glimepiride to rise when coadministered with drugs that inhibit CYP2C9 like clopidogrel. Monitor serum glucose concentrations if glimepiride is coadministered with clopidogrel. Dosage adjustments may be necessary.
    Clozapine: Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when clozapine is instituted. Atypical antipsychotics have been associated with causing metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Patients taking sulfonylureas should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: Plasma concentrations of glimepiride may be decreased when administered concurrently with elvitegravir. Patients may experience a decreased hypoglycemic effect when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while glimepiride is a CYP2C9 substrate. Plasma concentrations of rosiglitazone may be decreased when administered concurrently with elvitegravir. Patients may experience a decreased hypoglycemic effect when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while rosiglitazone is a CYP2C9 substrate.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: Plasma concentrations of glimepiride may be decreased when administered concurrently with elvitegravir. Patients may experience a decreased hypoglycemic effect when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while glimepiride is a CYP2C9 substrate. Plasma concentrations of rosiglitazone may be decreased when administered concurrently with elvitegravir. Patients may experience a decreased hypoglycemic effect when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while rosiglitazone is a CYP2C9 substrate.
    Codeine; Phenylephrine; Promethazine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents including phenothiazines. Patients should take care and use proper techniques to limit sunlight and UV exposure. The phenothiazines such as promethazine may increase blood sugar. Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when a phenothiazine is instituted.
    Codeine; Promethazine: Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents including phenothiazines. Patients should take care and use proper techniques to limit sunlight and UV exposure. The phenothiazines such as promethazine may increase blood sugar. Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when a phenothiazine is instituted.
    Colesevelam: Colesevelam has been found to have an effect on the bioavailability of glyburide, glipizide, and glimepiride. Administer these drugs at least 4 hours before colesevelam. Drug response should also be monitored. Additionally, in patients with type 2 diabetes mellitus receiving sulfonylureas, colesevelam increased serum triglyceride concentrations by 18% compared to placebo (P<0.001). In patients taking metformin, serum triglyceride concentrations only increased by 5%. Similarly, in patients taking colesevelam for hyperlipidemia, serum triglyceride concentrations increased by 5%. Monitor patients for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are > 500 mg/dl or if hypertriglyceridemia-induced pancreatitis occurs.
    Conjugated Estrogens: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Conjugated Estrogens; Bazedoxifene: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Conjugated Estrogens; Medroxyprogesterone: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Corticosteroids: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Corticotropin, ACTH: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Cortisone: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Cyclosporine: Cyclosporine has been reported to cause hyperglycemia; this effect appears to be dose-related and caused by direct beta-cell toxicity. Therefore, a pharmacodynamic interaction is possible with all antidiabetic agents and cyclosporine. Patients should be monitored for worsening glycemic control if therapy with cyclosporine is initiated in patients receiving antidiabetic agents. Sulfonylureas may increase concentrations of cyclosporine. Retrospective data from 6 adults with post-renal transplant diabetes mellitus and normal hepatic and renal function before and after glyburide initiation were examined. The mean plasma cyclosporine concentration from 5 months of data before glyburide use was 212.3 +/- 66.4 ng/ml. In contrast, the mean plasma cyclosporine concentration from 5 months of data during glyburide use was 334.8 +/- 65.8 ng/ml. Until more data are available, when glyburide is added to cyclosporine therapy, monitor cyclosporine concentrations and adjust cyclosporine dosage as necessary. Also, monitor patients for increased cyclosporine toxicity (renal dysfunction, neurotoxicity). In addition, cyclosporine has been reported to cause hyperglycemia. Cyclosporine may have direct beta-cell toxicity, the effects of which may be dose-related. Patients should be monitored for worsening of glycemic control if cyclosporine is initiated in patients receiving antidiabetic agents.
    Danazol: Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia. However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary. Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Darunavir: New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. In addition, coadministration of atazanavir with rosiglitazone may result in elevated rosiglitazone plasma concentrations. Rosiglitazone is a substrate for CYP2C8; atazanavir is a weak inhibitor of CYP2C8.
    Darunavir; Cobicistat: New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. In addition, coadministration of atazanavir with rosiglitazone may result in elevated rosiglitazone plasma concentrations. Rosiglitazone is a substrate for CYP2C8; atazanavir is a weak inhibitor of CYP2C8.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. In addition, coadministration of atazanavir with rosiglitazone may result in elevated rosiglitazone plasma concentrations. Rosiglitazone is a substrate for CYP2C8; atazanavir is a weak inhibitor of CYP2C8.
    Deflazacort: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Demeclocycline: Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents including tetracyclines. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.
    Desloratadine; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Dexamethasone: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Dexmethylphenidate: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia.
    Dextroamphetamine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia.
    Dextromethorphan; Diphenhydramine; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Dextromethorphan; Guaifenesin; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Dextromethorphan; Promethazine: Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents including phenothiazines. Patients should take care and use proper techniques to limit sunlight and UV exposure. The phenothiazines such as promethazine may increase blood sugar. Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when a phenothiazine is instituted.
    Diazoxide: Diazoxide inhibits the release of insulin from pancreatic islet cells. Because diazoxide increases blood glucose, a pharmacodynamic interaction exists between this drug and all other antidiabetic agents. The hyperglycemic action of parenteral diazoxide can be diminished in patients receiving oral antidiabetic agents, and the dosage of the antidiabetic agent may require adjustment.
    Dienogest; Estradiol valerate: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Diethylpropion: Diethylpropion exhibits intrinsic hypoglycemic activity and can lower postprandial blood glucose concentrations. Diethylpropion should be used cautiously in diabetic patients who are stabilized on antidiabetic agents. Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia.
    Diethylstilbestrol, DES: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Diphenhydramine; Hydrocodone; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Diphenhydramine; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Disopyramide: Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Disulfiram: Glimepiride is metabolized by CYP2C9. It is possible for serum concentrations of glimepiride to rise when coadministered with drugs that inhibit CYP2C9 like disulfiram. Monitor serum glucose concentrations if glimepiride is coadministered with disulfiram. Dosage adjustments may be necessary.
    Dobutamine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood glucose concentrations. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Dopamine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood glucose concentrations. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Dorzolamide; Timolol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Doxycycline: Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents including tetracyclines. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.
    Drospirenone; Estradiol: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Drospirenone; Ethinyl Estradiol: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Drospirenone; Ethinyl Estradiol; Levomefolate: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Efavirenz: Glimepiride is metabolized by CYP2C9. It is possible for serum concentrations of glimepiride to rise when coadministered with drugs that inhibit CYP2C9 like efavirenz. Monitor serum glucose concentrations if glimepiride is coadministered with efavirenz. Dosage adjustments may be necessary.
    Efavirenz; Emtricitabine; Tenofovir: Glimepiride is metabolized by CYP2C9. It is possible for serum concentrations of glimepiride to rise when coadministered with drugs that inhibit CYP2C9 like efavirenz. Monitor serum glucose concentrations if glimepiride is coadministered with efavirenz. Dosage adjustments may be necessary.
    Elvitegravir: Plasma concentrations of glimepiride may be decreased when administered concurrently with elvitegravir. Patients may experience a decreased hypoglycemic effect when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while glimepiride is a CYP2C9 substrate. Plasma concentrations of rosiglitazone may be decreased when administered concurrently with elvitegravir. Patients may experience a decreased hypoglycemic effect when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while rosiglitazone is a CYP2C9 substrate.
    Enalapril, Enalaprilat: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Enalapril; Felodipine: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Enalapril; Hydrochlorothiazide, HCTZ: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Ephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood glucose concentrations. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Epinephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood glucose concentrations. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Eprosartan: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Eprosartan; Hydrochlorothiazide, HCTZ: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Erythromycin; Sulfisoxazole: Sulfonamides may induce hypoglycemia by increasing the secretion of insulin from the pancreas. Therefore, a pharmacodynamic interaction leading to an increased risk of hypoglycemia may occur in patients taking antidiabetic agents and sulfonamides.
    Esmolol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Esterified Estrogens: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Esterified Estrogens; Methyltestosterone: Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia. However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary. Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary. Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Estradiol Cypionate; Medroxyprogesterone: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Estradiol: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Estradiol; Levonorgestrel: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Estradiol; Norethindrone: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Estradiol; Norgestimate: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Estramustine: Estramustine may decrease glucose tolerance leading to hyperglycemia. Patients receiving antidiabetic agents should monitor their blood glucose levels frequently due to this potential pharmacodynamic interaction.
    Estrogens: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Estropipate: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Ethanol: A single administration of a moderate amount of alcohol did not increase the risk of acute hypoglycemia in type 2 diabetes mellitus patients treated with thiazolidinediones in clinical studies. However, in general, excessive amounts of alcoholic beverages can increase the risk of low blood sugar in patients with diabetes, The calories in these beverages also need consideration, as increased blood sugar may occur due to the caloric intake. Alcohol (ethanol) may cause variable effects on glycemic control when used in patients receiving antidiabetic therapy. Alcohol ingestion can decrease endogenous glucose production potentiating the risk of hypoglycemia. Alternatively, alcohol can worsen glycemic control as it provides a source of additional calories. Blood glucose concentrations should be closely monitored and dosage adjustments of antidiabetic agents may be necessary if alcohol is consumed. Patients should be encouraged to limit or moderate their intake of alcoholic beverages. Because of its effects on endogenous glucose production, patients should be encouraged to avoid alcohol ingestion during the fasting state. Many non-prescription drug products may be formulated with ethanol; instruct patients to scrutinize product labels prior to consumption. Finally, clinicians should keep in mind that ethanol ingestion by patients receiving chlorpropamide has been associated with a disulfiram-like reaction and a similar reaction may be possible in patients receiving glipizide.
    Ethinyl Estradiol: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Ethinyl Estradiol; Desogestrel: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Ethinyl Estradiol; Ethynodiol Diacetate: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Ethinyl Estradiol; Etonogestrel: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Ethinyl Estradiol; Levonorgestrel: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Ethinyl Estradiol; Norelgestromin: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Ethinyl Estradiol; Norethindrone Acetate: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Ethinyl Estradiol; Norethindrone: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Ethinyl Estradiol; Norgestimate: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Ethinyl Estradiol; Norgestrel: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Ethotoin: Phenytoin and other hydantoins have the potential to increase blood glucose and thus interact with antidiabetic agents pharmacodynamically. In addition, coadministration may result in decreased serum concentrations of chlorpropamide. Monitor blood glucose for changes in glycemic control. Dosage adjustments may be necessary in some patients. Phenytoin and other hydantoins have the potential to increase blood glucose and thus interact with antidiabetic agents pharmacodynamically. Monitor blood glucose for changes in glycemic control. Dosage adjustments may be necessary in some patients.
    Etonogestrel: Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Exenatide: The risk of hypoglycemia is increased when exenatide is used in combination with insulins or insulin secretagogues such as the sulfonylureas and glinides (e.g., nateglinide, repaglinide, or metformin; repaglinide). Although specific dose recommendations are not available, a lower dose of the insulin or secretagogue may be required to reduce the risk of hypoglycemia in this setting. Adequate blood glucose monitoring should be continued and followed.
    Fenofibrate: Fibric acid derivatives may enhance the hypoglycemic effects antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. In addition, fenofibrate may displace glyburide from protein binding sites which may lead to enhanced hypoglycemic action.
    Fexofenadine; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Fibric acid derivatives: Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Additionally, gemfibrozil has been reported to increase the plasma concentrations of rosiglitazone; the mechanism is probably inhibition of CYP2C8-mediated metabolism of rosiglitazone by gemfibrozil. A randomized crossover trial in healthy volunteers studied the effects of gemfibrozil 600 mg or placebo twice daily for 4 days, with a single 4 mg dose of rosiglitazone administered on day 3. Gemfibrozil increased rosiglitazone mean AUC by 2.3-fold and prolonged the elimination half-life from 3.6 to 7.6 hours. The rosiglitazone Cmax was increased 1.2-fold and the concentration measured 24 hours after dosing was increased 9.8-fold. There are no published reports of the potential clinical effects of this interaction. Concomitant administration of the two drugs may enhance rosiglitazone efficacy, but may also increase the risk of adverse effects. If antidiabetic agents are coadministered with gemfibrozil, it would be prudent to carefully monitor glycemic control and for signs and symptoms of adverse effects; dosage adjustment of antidiabetic agents may be necessary.
    Fluconazole: Fluconazole is an inhibitor of CYP3A4 and CYP2C9. Because rosiglitazone is a substrate of CYP2C9, concomitant use with fluconazole may increase plasma concentrations of rosiglitazone. Patients should be monitored for changes in glycemic control if rosiglitazone is coadministered with fluconazole. Fluconazole should be used cautiously with glimepiride. The combination of fluconazole and glimepiride has resulted in a > 100% increase in glimepiride AUC in healthy volunteers; blood glucose response may be altered in diabetic patients. Inhibition of CYP2C9 by fluconazole is the suspected mechanism of this interaction.
    Fludrocortisone: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Flunisolide: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Fluocinolone; Hydroquinone; Tretinoin: A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Fluorouracil, 5-FU: Glimepiride is metabolized by CYP2C9. It is possible for serum concentrations of glimepiride to rise when coadministered with drugs that inhibit CYP2C9 like fluorouracil, 5-FU. Monitor serum glucose concentrations if glimepiride is coadministered with fluorouracil, 5-FU. Dosage adjustments may be necessary.
    Fluoxetine: Fluoxetine may enhance the hypoglycemic effects of antidiabetic agents. Serum glucose should be monitored closely when fluoxetine is added to any regimen containing antidiabetic agents. Fluoxetine may enhance the hypoglycemic effects of antidiabetic agents. Serum glucose should be monitored closely when fluoxetine is added to any regimen containing antidiabetic agents.
    Fluoxetine; Olanzapine: Fluoxetine may enhance the hypoglycemic effects of antidiabetic agents. Serum glucose should be monitored closely when fluoxetine is added to any regimen containing antidiabetic agents. Fluoxetine may enhance the hypoglycemic effects of antidiabetic agents. Serum glucose should be monitored closely when fluoxetine is added to any regimen containing antidiabetic agents. Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when olanzapine is instituted. Atypical antipsychotics have been associated with causing metabolic changes, including hyperglycemia, even diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Patients taking sulfonylureas should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Fluoxymesterone: Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia. However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary. Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Fluticasone: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Fluticasone; Salmeterol: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Fluticasone; Vilanterol: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Fluvastatin: Glimepiride is metabolized by CYP2C9. It is possible for serum concentrations of glimepiride to rise when coadministered with drugs that inhibit CYP2C9 like fluvastatin. Monitor serum glucose concentrations if glimepiride is coadministered with fluvastatin. Dosage adjustments may be necessary.
    Fluvoxamine: Fluvoxamine should be used cautiously with glimepiride. The combination of fluvoxamine and glimepiride has resulted in a 43% increase in glimepiride peak plasma concentrations and an increase in glimepiride half-life in healthy volunteers; blood glucose response may be altered in diabetic patients. The mechanism of this interaction is unclear. Blood glucose concentrations should be monitored during coadministration of fluvoxamine.
    Formoterol; Mometasone: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Fosamprenavir: New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. In addition, coadministration of atazanavir with rosiglitazone may result in elevated rosiglitazone plasma concentrations. Rosiglitazone is a substrate for CYP2C8; atazanavir is a weak inhibitor of CYP2C8.
    Fosinopril: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Fosinopril; Hydrochlorothiazide, HCTZ: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Fosphenytoin: Phenytoin and other hydantoins have the potential to increase blood glucose and thus interact with antidiabetic agents pharmacodynamically. In addition, coadministration may result in decreased serum concentrations of chlorpropamide. Monitor blood glucose for changes in glycemic control. Dosage adjustments may be necessary in some patients. Phenytoin and other hydantoins have the potential to increase blood glucose and thus interact with antidiabetic agents pharmacodynamically. Monitor blood glucose for changes in glycemic control. Dosage adjustments may be necessary in some patients.
    Furosemide: Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between furosemide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely. Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Garlic, Allium sativum: Limited animal data suggest that selected constituents in Garlic, Allium sativum might have some antidiabetic activity, resulting in increased serum insulin concentrations and increased glycogen storage in the liver. Patients with diabetes frequently purchase alternative remedies that have been purported to improve glycemic control, but there is no scientific or controlled evidence in humans of this action. Limited clinical evidence suggests that garlic does not affect blood glucose in those without diabetes. Until more data are available, individuals receiving antidiabetic agents should use caution in consuming dietary supplements containing garlic, and follow their normally recommended strategies for blood glucose monitoring. Selected constituents in Garlic, Allium sativum might have some antidiabetic activity, resulting in increased serum insulin concentrations and increased glycogen storage in the liver. Until more data are available, individuals receiving antidiabetic agents should use caution in consuming dietary supplements containing garlic, and follow their normally recommended strategies for blood glucose monitoring.
    Gemfibrozil: Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. In addition, glyburide is a substrate of the OATP1B1 transporter. Gemfibrozil inhibits OATP1B1. Coadministration may result in an increase in glyburide exposure. A dose reduction of glyburide may be required if used concomitantly with gemfibrozil.
    Gemifloxacin: Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Monitor blood glucose when quinolones and antidiabetic agents are coadministered. Hyperglycemia and hypoglycemia have been reported in patients treated concomitantly with quinolones and antidiabetic agents. Rare cases of severe hypoglycemia have been reported with concomitant use of quinolones and glyburide. Therefore, careful monitoring of blood glucose is recommended when gemifloxacin and antidiabetic agents are coadministered.
    Glimepiride: A maximum dose of 8 mg/day of rosiglitazone is recommended when used in combination with sulfonylureas; the incidence of adverse effects including hypoglycemia is increased with larger doses. In one clinical study, rosiglitazone 4 or 8 mg/day was added to failed glimepiride plus metformin therapy. The incidence of hypoglycemia (blood glucose concentrations <= 50 mg/dl) was 18.6% in the 4 mg/day group compared with 28% in the 8 mg/day group. In addition, 4 or 8 mg/day of rosiglitazone has been added to failed glyburide plus metformin therapy. The incidence of hypoglycemia was higher in the rosiglitazone (average dose 7.4 mg/day)+glyburide+metformin group (22%) when compared to the glyburide+metformin group (3%). Patients should be instructed to monitor blood glucose concentrations more frequently. Dosage adjustments may be indicated.
    Glimepiride; Pioglitazone: A maximum dose of 8 mg/day of rosiglitazone is recommended when used in combination with sulfonylureas; the incidence of adverse effects including hypoglycemia is increased with larger doses. In one clinical study, rosiglitazone 4 or 8 mg/day was added to failed glimepiride plus metformin therapy. The incidence of hypoglycemia (blood glucose concentrations <= 50 mg/dl) was 18.6% in the 4 mg/day group compared with 28% in the 8 mg/day group. In addition, 4 or 8 mg/day of rosiglitazone has been added to failed glyburide plus metformin therapy. The incidence of hypoglycemia was higher in the rosiglitazone (average dose 7.4 mg/day)+glyburide+metformin group (22%) when compared to the glyburide+metformin group (3%). Patients should be instructed to monitor blood glucose concentrations more frequently. Dosage adjustments may be indicated.
    Glipizide: A maximum dose of 8 mg/day of rosiglitazone is recommended when used in combination with sulfonylureas; the incidence of adverse effects including hypoglycemia is increased with larger doses. In one clinical study, rosiglitazone 4 or 8 mg/day was added to failed glimepiride plus metformin therapy. The incidence of hypoglycemia (blood glucose concentrations <= 50 mg/dl) was 18.6% in the 4 mg/day group compared with 28% in the 8 mg/day group. In addition, 4 or 8 mg/day of rosiglitazone has been added to failed glyburide plus metformin therapy. The incidence of hypoglycemia was higher in the rosiglitazone (average dose 7.4 mg/day)+glyburide+metformin group (22%) when compared to the glyburide+metformin group (3%). Patients should be instructed to monitor blood glucose concentrations more frequently. Dosage adjustments may be indicated.
    Glipizide; Metformin: A maximum dose of 8 mg/day of rosiglitazone is recommended when used in combination with sulfonylureas; the incidence of adverse effects including hypoglycemia is increased with larger doses. In one clinical study, rosiglitazone 4 or 8 mg/day was added to failed glimepiride plus metformin therapy. The incidence of hypoglycemia (blood glucose concentrations <= 50 mg/dl) was 18.6% in the 4 mg/day group compared with 28% in the 8 mg/day group. In addition, 4 or 8 mg/day of rosiglitazone has been added to failed glyburide plus metformin therapy. The incidence of hypoglycemia was higher in the rosiglitazone (average dose 7.4 mg/day)+glyburide+metformin group (22%) when compared to the glyburide+metformin group (3%). Patients should be instructed to monitor blood glucose concentrations more frequently. Dosage adjustments may be indicated.
    Glucagon: Glucagon increases blood glucose concentrations thereby decreasing the hypoglycemic effect of antidiabetic agents. Monitor for signs indicating loss of diabetic control when therapy with glucagon is instituted. Glucagon increases blood glucose concentrations thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when therapy with glucagon is instituted.
    Glyburide: A maximum dose of 8 mg/day of rosiglitazone is recommended when used in combination with sulfonylureas; the incidence of adverse effects including hypoglycemia is increased with larger doses. In one clinical study, rosiglitazone 4 or 8 mg/day was added to failed glimepiride plus metformin therapy. The incidence of hypoglycemia (blood glucose concentrations <= 50 mg/dl) was 18.6% in the 4 mg/day group compared with 28% in the 8 mg/day group. In addition, 4 or 8 mg/day of rosiglitazone has been added to failed glyburide plus metformin therapy. The incidence of hypoglycemia was higher in the rosiglitazone (average dose 7.4 mg/day)+glyburide+metformin group (22%) when compared to the glyburide+metformin group (3%). Patients should be instructed to monitor blood glucose concentrations more frequently. Dosage adjustments may be indicated.
    Glyburide; Metformin: A maximum dose of 8 mg/day of rosiglitazone is recommended when used in combination with sulfonylureas; the incidence of adverse effects including hypoglycemia is increased with larger doses. In one clinical study, rosiglitazone 4 or 8 mg/day was added to failed glimepiride plus metformin therapy. The incidence of hypoglycemia (blood glucose concentrations <= 50 mg/dl) was 18.6% in the 4 mg/day group compared with 28% in the 8 mg/day group. In addition, 4 or 8 mg/day of rosiglitazone has been added to failed glyburide plus metformin therapy. The incidence of hypoglycemia was higher in the rosiglitazone (average dose 7.4 mg/day)+glyburide+metformin group (22%) when compared to the glyburide+metformin group (3%). Patients should be instructed to monitor blood glucose concentrations more frequently. Dosage adjustments may be indicated.
    Green Tea: Green tea catechins have been shown to decrease serum glucose concentrations in vitro. Patients with diabetes mellitus taking antidiabetic agents should be monitored closely for hypoglycemia if consuming green tea products. Green tea catechins have been shown to decrease serum glucose concentrations in vitro. Patients with diabetes mellitus taking antidiabetic agents should be monitored closely for hypoglycemia if consuming green tea products.
    Griseofulvin: Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents including griseofulvin. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.
    Guaifenesin; Hydrocodone; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Guaifenesin; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Guaifenesin; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Hydantoins: Phenytoin and other hydantoins have the potential to increase blood glucose and thus interact with antidiabetic agents pharmacodynamically. In addition, coadministration may result in decreased serum concentrations of chlorpropamide. Monitor blood glucose for changes in glycemic control. Dosage adjustments may be necessary in some patients. Phenytoin and other hydantoins have the potential to increase blood glucose and thus interact with antidiabetic agents pharmacodynamically. Monitor blood glucose for changes in glycemic control. Dosage adjustments may be necessary in some patients.
    Hydralazine; Isosorbide Dinitrate, ISDN: The concomitant use of nitrates with rosiglitazone is not recommended. An increased risk of myocardial ischemia was observed in a subset of patients receiving nitrates with rosiglitazone. Most patients that were using nitrates had preexisting coronary artery disease. In patients with coronary artery disease that were not on nitrates, rosiglitazone therapy did not increase the risk of myocardial ischemia.
    Hydrochlorothiazide, HCTZ; Irbesartan: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Hydrochlorothiazide, HCTZ; Lisinopril: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Hydrochlorothiazide, HCTZ; Losartan: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Hydrochlorothiazide, HCTZ; Metoprolol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Hydrochlorothiazide, HCTZ; Moexipril: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Hydrochlorothiazide, HCTZ; Olmesartan: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Hydrochlorothiazide, HCTZ; Propranolol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Hydrochlorothiazide, HCTZ; Quinapril: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Hydrochlorothiazide, HCTZ; Telmisartan: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Hydrochlorothiazide, HCTZ; Triamterene: Triamterene can interfere with the hypoglycemic effects of antidiabetic agents. This can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Hydrochlorothiazide, HCTZ; Valsartan: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Hydrocodone; Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Hydrocodone; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Hydrocortisone: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Hydroxychloroquine: Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including sulfonylureas, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with hydroxychloroquine and an antidiabetic agent. Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the thiazolidinediones, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with hydroxychloroquine and an antidiabetic agent.
    Hydroxyprogesterone: Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Ibuprofen; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Iloperidone: Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when iloperidone is instituted. Atypical antipsychotics have been associated with metabolic changes including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma in some instances. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Patients taking sulfonylureas should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Imatinib, STI-571: Glimepiride is metabolized by CYP2C9. It is possible for serum concentrations of glimepiride to rise when coadministered with drugs that inhibit CYP2C9 like imatinib. Monitor serum glucose concentrations if glimepiride is coadministered with imatinib. Dosage adjustments may be necessary.
    Indapamide: A potential pharmacodynamic interaction exists between indapamide and antidiabetic agents, like sulfonylureas. Indapamide can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. A potential pharmacodynamic interaction exists between indapamide and antidiabetic agents, such as thiazolidinediones. Indapamide can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia.
    Indinavir: New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. In addition, coadministration of atazanavir with rosiglitazone may result in elevated rosiglitazone plasma concentrations. Rosiglitazone is a substrate for CYP2C8; atazanavir is a weak inhibitor of CYP2C8.
    Insulin Glargine; Lixisenatide: The risk of hypoglycemia is increased when lixisenatide is used in combination with insulin secretagogues such as the sulfonylureas. Although specific dose recommendations are not available, a lower dose of the sulfonylurea may be required to reduce the risk of hypoglycemia in this setting. Adequate blood glucose monitoring should be continued and followed.
    Insulins: Use of insulins with rosiglitazone is not recommended by the manufacturer due to a potential increased risk for edema or heart failure. If heart failure develops in a patient receiving insulin and a thiazoladinedione, manage the patient according to standards of care, and discontinue or consider reducing the dose of the thiazoladinedione. Since the incidence of hypoglycemia may also be higher with combined therapy, patients should also be instructed to monitor blood glucose concentrations more frequently. In five 26-week trials involving patients with type 2 diabetes, rosiglitazone added to insulin therapy (n=867) was compared with insulin therapy alone (n=663). These trials included patients with chronic diabetes and a high prevalence of coexisting medical conditions, including peripheral neuropathy, retinopathy, ischemic heart disease, vascular disease, and congestive heart failure. In these clinical studies, an increased incidence of heart failure and other cardiovascular adverse events was seen in patients receiving combination rosiglitazone and insulin therapy compared to insulin monotherapy; the incidence of new onset or exacerbated heart failure was 0.9% in patients treated with insulin alone vs. 2% in patients treated with insulin plus rosiglitazone. Some of the patients who developed cardiac failure on combination therapy during the double blind part of the studies had no known prior evidence of congestive heart failure, or pre-existing cardiac condition. Additionally, the results of a meta-analysis that included the same 5 randomized, controlled trials mentioned previously indicate that the rate of myocardial ischemia may be increased in patients taking rosiglitazone in combination with insulin; the incidence of myocardia ischemia was 1.4% in patients receiving insulin monotherapy vs. 2.8% in patients receiving rosiglitazone and insulin combination therapy (OR 2.1 95% CI 0.9-5.1). The cardiovascular events were noted at doses of both 4 mg/day and 8 mg/day of rosiglitazone. In a sixth 26-week study, patients with baseline congestive heart failure were excluded; in this study, compared to insulin monotherapy (n=158), the addition of rosiglitazone to insulin therapy (n=161) did not increase the risk of congestive heart failure. One each of myocardial ischemia and sudden death were reported in patients taking combination therapy compared to zero patients taking insulin monotherapy. When rosiglitazone was added to insulin therapy, the incidence of hypoglycemia was higher with 8 mg/day of rosiglitazone (67%) compared to 4 mg/day (53%).
    Irbesartan: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Isocarboxazid: Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents.Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost.
    Isoniazid, INH: Although a rare side effect, isoniazid, INH may increase blood sugar. Patients receiving antidiabetic agents should closely monitor their blood glucose concentrations if isoniazid is coadministered. Isoniazid, INH may increase blood sugar. Patients receiving antidiabetic drugs should be closely monitored for loss of diabetic control when this drug is initiated.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: Although a rare side effect, isoniazid, INH may increase blood sugar. Patients receiving antidiabetic agents should closely monitor their blood glucose concentrations if isoniazid is coadministered. Isoniazid, INH may increase blood sugar. Patients receiving antidiabetic drugs should be closely monitored for loss of diabetic control when this drug is initiated. The coadministration of rifampin and rosiglitazone may decrease the concentration of rosiglitazone. This interaction is most likely due to rifampin's inhibition of the CYP2C8 and, to a lesser extent, CYP2C9 isozymes. Use caution if rifampin and rosiglitazone are to be coadministered, as decreased rosiglitazone efficacy may be seen. Blood glucose concentrations should be monitored and possible dose adjustments of rosiglitazone may need to be made.
    Isoniazid, INH; Rifampin: Although a rare side effect, isoniazid, INH may increase blood sugar. Patients receiving antidiabetic agents should closely monitor their blood glucose concentrations if isoniazid is coadministered. Isoniazid, INH may increase blood sugar. Patients receiving antidiabetic drugs should be closely monitored for loss of diabetic control when this drug is initiated. The coadministration of rifampin and rosiglitazone may decrease the concentration of rosiglitazone. This interaction is most likely due to rifampin's inhibition of the CYP2C8 and, to a lesser extent, CYP2C9 isozymes. Use caution if rifampin and rosiglitazone are to be coadministered, as decreased rosiglitazone efficacy may be seen. Blood glucose concentrations should be monitored and possible dose adjustments of rosiglitazone may need to be made.
    Isoproterenol: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood glucose concentrations. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Isosorbide Dinitrate, ISDN: The concomitant use of nitrates with rosiglitazone is not recommended. An increased risk of myocardial ischemia was observed in a subset of patients receiving nitrates with rosiglitazone. Most patients that were using nitrates had preexisting coronary artery disease. In patients with coronary artery disease that were not on nitrates, rosiglitazone therapy did not increase the risk of myocardial ischemia.
    Isosorbide Mononitrate: The concomitant use of nitrates with rosiglitazone is not recommended. An increased risk of myocardial ischemia was observed in a subset of patients receiving nitrates with rosiglitazone. Most patients that were using nitrates had preexisting coronary artery disease. In patients with coronary artery disease that were not on nitrates, rosiglitazone therapy did not increase the risk of myocardial ischemia.
    Itraconazole: Itraconazole should be used cautiously with oral antidiabetic agents like sulfonylureas. The combination of itraconazole and oral antidiabetic agents has resulted in severe hypoglycemia. Blood glucose concentrations should be monitored and possible dose adjustments of hypoglycemics may need to be made.
    Ivacaftor: Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as glimepiride. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined.
    Ketoconazole: Hypoglycemia, sometimes severe, has been reported when ketoconazole is coadministered with oral hypoglycemic agents. The most likely mechanism for this interaction is inhibition of the CYP450 metabolism of oral hypoglycemics by ketoconazole. Blood glucose concentrations should be monitored during concomitant treatment; patients should be aware of the symptoms of hypoglycemia. In some cases, dosage adjustment of the sulfonylurea may be necessary. There is no evidence that an interaction occurs between oral hypoglycemics and topical or vaginal azole antifungal preparations. If ketoconazole and rosiglitazone are to be coadministered, patients should be closely monitored. A pharmacokinetic study found that the administration of rosiglitazone to subjects who had been receiving ketoconazole resulted in increased rosiglitazone AUC, peak plasma concentrations, and half-life, and decreased rosiglitazone clearance. The clinical significance (i.e., altered blood glucose concentrations) of this interaction is unknown.
    Labetalol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Lanreotide: Lanreotide may cause increases or decreases in glucose concentrations. Patients receiving antidiabetic therapy should be closely monitored for changes in glycemic control; adjustments in the dosage of antidiabetic agents may be necessary.
    Leflunomide: Glimepiride is metabolized by CYP2C9. It is possible for serum concentrations of glimepiride to rise when coadministered with drugs that inhibit CYP2C9 like leflunomide. Monitor serum glucose concentrations if leflunomide is coadministered with any of these drugs. Dosage adjustments may be necessary.
    Leuprolide; Norethindrone: Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Levobetaxolol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Levobunolol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Levocarnitine: Chromium dietary supplements may lower blood glucose. As part of the glucose tolerance factor molecule, chromium appears to facilitate the binding of insulin to insulin receptors in tissues and to aid in glucose metabolism. Because blood glucose may be lowered by the use of chromium, patients who are on antidiabetic agents may need dose adjustments. Close monitoring of blood glucose is recommended.
    Levofloxacin: Careful monitoring of blood glucose is recommended when levofloxacin and antidiabetic agents, including the sulfonylureas, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Careful monitoring of blood glucose is recommended when levofloxacin and antidiabetic agents, including the thiazolidinediones, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent.
    Levonorgestrel: Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Linezolid: Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Lisdexamfetamine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood glucose concentrations. Monitor for loss of diabetic control when therapy with sympathomimetic agents is instituted. Also, adrenergic medications may increase glucose uptake by muscle cells and may potentiate the actions of some antidiabetic agents. Monitor blood glucose to avoid hypoglycemia or hyperglycemia.
    Lisinopril: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Lithium: Lithium may cause variable effects on glycemic control when used in patients receiving antidiabetic agents. Monitor blood glucose concentrations closely if lithium is coadministered with antidiabetic agents. Dosage adjustments of antidiabetic agents may be necessary. Lithium may cause variable effects on glycemic control when used in patients receiving antidiabetic agents. Monitor blood glucose concentrations closely if lithium is coadministered with antidiabetic agents. Dosage adjustments of antidiabetic agents may be necessary.
    Lixisenatide: The risk of hypoglycemia is increased when lixisenatide is used in combination with insulin secretagogues such as the sulfonylureas. Although specific dose recommendations are not available, a lower dose of the sulfonylurea may be required to reduce the risk of hypoglycemia in this setting. Adequate blood glucose monitoring should be continued and followed.
    Lomefloxacin: Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Rare cases of severe hypoglycemia have been reported with concomitant use of quinolones and glyburide. Therefore, careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents are coadministered. Monitor blood glucose when quinolones and antidiabetic agents are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Therefore, careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents are co-administered.
    Lopinavir; Ritonavir: New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. In addition, coadministration of atazanavir with rosiglitazone may result in elevated rosiglitazone plasma concentrations. Rosiglitazone is a substrate for CYP2C8; atazanavir is a weak inhibitor of CYP2C8.
    Loratadine; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Lorcaserin: In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Losartan: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Lovastatin; Niacin: Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Lumacaftor; Ivacaftor: Although the clinical significance of this interaction is unknown, concurrent use of rosiglitazone and lumacaftor; ivacaftor may alter the therapeutic effects of rosiglitazone; caution and close monitoring of blood glucose are advised if these drugs are administered together. Rosiglitazone is a substrate of CYP2C8 and CYP2C9. In vitro data suggest that lumacaftor; ivacaftor may induce and/or inhibit CYP2C8 and CYP2C9. The net effect on these substrates is not clear, but their exposure may be affected leading to decreased efficacy or increased or prolonged therapeutic effects and adverse events. Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as glimepiride. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined.
    Lumacaftor; Ivacaftor: Although the clinical significance of this interaction is unknown, concurrent use of rosiglitazone and lumacaftor; ivacaftor may alter the therapeutic effects of rosiglitazone; caution and close monitoring of blood glucose are advised if these drugs are administered together. Rosiglitazone is a substrate of CYP2C8 and CYP2C9. In vitro data suggest that lumacaftor; ivacaftor may induce and/or inhibit CYP2C8 and CYP2C9. The net effect on these substrates is not clear, but their exposure may be affected leading to decreased efficacy or increased or prolonged therapeutic effects and adverse events. Lumacaftor; ivacaftor may reduce the efficacy of glimepiride by decreasing its systemic exposure. If used together, monitor blood glucose concentrations closely; a glimepiride dosage adjustment may be required to obtain the desired therapeutic effect. Glimepiride is a CYP2C9 substrate; in vitro studies suggest lumacaftor; ivacaftor has the potential to induce and inhibit CYP2C9.
    Lurasidone: Patients taking rosiglitazone should be closely monitored for worsening glycemic control when treatment with lurasidone is instituted. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Patients taking sulfonylureas should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Magnesium Salicylate: If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
    Mecasermin rinfabate: Use caution in combining mecasermin, recombinant, rh-IGF-1 and mecasermin rinfabate (rh-IGF-1/rh-IGFBP-3) with antidiabetic agents. The hypoglycemic effect induced by IGF-1 activity may be exacerbated. Although the rh-IGF-1/rh-IGFBP-3 complex has less propensity to rapidly lower blood glucose compared to unbound mecasermin, hypoglycemia is possible with either agent. The amino acid sequence of mecasermin (rh-IGF-1) is approximately 50 percent homologous to insulin and cross binding with either receptor is possible. Treatment with mecasermin (rh-IGF-1) has been shown to improve insulin sensitivity and to improve glycemic control in patients with either Type 1 or Type 2 diabetes mellitus when used alone or in conjunction with insulins. Patients should be advised to eat within 20 minutes of mecasermin administration. Monitor glucose when initializing or adjusting mecasermin therapies, when adjusting concomitant antidiabetic therapy, and in the event of hypoglycemic symptoms. Use caution in combining mecasermin, recombinant, rh-IGF-1 and mecasermin rinfabate with antidiabetic agents. The hypoglycemic effect induced by IGF-1 activity may be exacerbated. Patients should be advised to eat within 20 minutes of mecasermin administration. Glucose monitoring is important when initializing or adjusting mecasermin therapies, when adjusting concomitant antidiabetic therapy, and in the event of hypoglycemic symptoms.
    Mecasermin, Recombinant, rh-IGF-1: Use caution in combining mecasermin, recombinant, rh-IGF-1 and mecasermin rinfabate (rh-IGF-1/rh-IGFBP-3) with antidiabetic agents. The hypoglycemic effect induced by IGF-1 activity may be exacerbated. Although the rh-IGF-1/rh-IGFBP-3 complex has less propensity to rapidly lower blood glucose compared to unbound mecasermin, hypoglycemia is possible with either agent. The amino acid sequence of mecasermin (rh-IGF-1) is approximately 50 percent homologous to insulin and cross binding with either receptor is possible. Treatment with mecasermin (rh-IGF-1) has been shown to improve insulin sensitivity and to improve glycemic control in patients with either Type 1 or Type 2 diabetes mellitus when used alone or in conjunction with insulins. Patients should be advised to eat within 20 minutes of mecasermin administration. Monitor glucose when initializing or adjusting mecasermin therapies, when adjusting concomitant antidiabetic therapy, and in the event of hypoglycemic symptoms. Use caution in combining mecasermin, recombinant, rh-IGF-1 and mecasermin rinfabate with antidiabetic agents. The hypoglycemic effect induced by IGF-1 activity may be exacerbated. Patients should be advised to eat within 20 minutes of mecasermin administration. Glucose monitoring is important when initializing or adjusting mecasermin therapies, when adjusting concomitant antidiabetic therapy, and in the event of hypoglycemic symptoms.
    Medroxyprogesterone: Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Megestrol: Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Meperidine; Promethazine: Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents including phenothiazines. Patients should take care and use proper techniques to limit sunlight and UV exposure. The phenothiazines such as promethazine may increase blood sugar. Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when a phenothiazine is instituted.
    Mepivacaine; Levonordefrin: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia.
    Mequinol; Tretinoin: A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Mestranol; Norethindrone: Estrogens can impair glucose tolerance and may decrease the hypoglycemic effects of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Methamphetamine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood glucose concentrations. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Methazolamide: Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
    Methotrexate: Methotrexate is partially bound to plasma proteins, and drugs that can displace methotrexate from these proteins, such as oral sulfonylureas could cause methotrexate-induced toxicity. Due to the potential toxicity of methotrexate, interactions with sulfonylureas can be very serious even if methotrexate is administered in low doses such as in the treatment of rheumatic diseases.
    Methoxsalen: Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents.
    Methylphenidate: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia.
    Methylprednisolone: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Methyltestosterone: Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia. However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary. Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Metoclopramide: Because metoclopramide can enhance gastric emptying in patients with diabetes, blood glucose can be affected, which, in turn, may affect the clinical response to antidiabetic agents. The dosing of antidiabetic agents may require adjustment in patients who receive metoclopramide concomitantly. Because metoclopramide can enhance gastric emptying in patients with diabetes, blood glucose can be affected, which, in turn, may affect the clinical response to antidiabetic agents. The dosing of antidiabetic agents may require adjustment in patients who receive metoclopramide concomitantly.
    Metoprolol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Metreleptin: Use caution when administering metreleptin to patients treated with concomitant insulins or insulin secretagogue therapy (i.e., sulfonylureas, nateglinide, repaglinide). In clinical evaluation of metreleptin, hypoglycemia occurred in 13% of patients with generalized lipodystrophy. Most reported cases occurred with concomitant insulin use, with or without oral antihyperglycemic agents. Closely monitor blood glucose in patients on concomitant insulin or insulin secretagogue therapy. Dosage adjustments to their antihyperglycemic medications may be necessary.
    Metronidazole: Glimepiride is metabolized by CYP2C9. It is possible for serum concentrations of glimepiride to rise when coadministered with drugs that inhibit CYP2C9 like metronidazole. Monitor serum glucose concentrations if glimepiride is coadministered with metronidazole. Dosage adjustments may be necessary.
    Metyrapone: In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Miconazole: Hypoglycemia, sometimes severe, has been reported when systemic azole antifungals are coadministered with sulfonylureas. No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP2C9 and CYP3A4. Although the systemic absorption of miconazole following buccal administration is minimal and plasma concentrations are substantially lower than when miconazole is given intravenously, the potential for interaction with drugs metabolized through CYP2C9 and CYP3A4 such as the sulfonylureas cannot be ruled out. Interactions with vaginal use have not been reported. Topically-applied miconazole is not expected to alter plasma concentrations of sulfonylureas.
    Miconazole; Petrolatum; Zinc Oxide: Hypoglycemia, sometimes severe, has been reported when systemic azole antifungals are coadministered with sulfonylureas. No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP2C9 and CYP3A4. Although the systemic absorption of miconazole following buccal administration is minimal and plasma concentrations are substantially lower than when miconazole is given intravenously, the potential for interaction with drugs metabolized through CYP2C9 and CYP3A4 such as the sulfonylureas cannot be ruled out. Interactions with vaginal use have not been reported. Topically-applied miconazole is not expected to alter plasma concentrations of sulfonylureas.
    Midodrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood glucose concentrations. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Minocycline: Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents including tetracyclines. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.
    Moexipril: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Mometasone: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Monoamine oxidase inhibitors: Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents.Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost.
    Montelukast: Montelukast potently inhibits CYP2C8 and is expected to decrease the metabolism of rosiglitazone, a CYP2C8 substrate.
    Moxifloxacin: Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Monitor blood glucose when quinolones and antidiabetic agents are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Rare cases of severe hypoglycemia have been reported with concomitant use of quinolones and glyburide. Therefore, careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents are coadministered. Monitor blood glucose when quinolones and antidiabetic agents are coadministered.
    Nadolol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Nandrolone Decanoate: Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia. However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary. Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Naproxen; Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Nebivolol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Nebivolol; Valsartan: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Nelfinavir: New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. In addition, coadministration of atazanavir with rosiglitazone may result in elevated rosiglitazone plasma concentrations. Rosiglitazone is a substrate for CYP2C8; atazanavir is a weak inhibitor of CYP2C8.
    Niacin, Niacinamide: Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Niacin; Simvastatin: Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Nicotine: Nicotine may increase plasma glucose. Blood glucose concentrations should be monitored more closely whenever a change in either nicotine intake or smoking status occurs; dosage adjustments in antidiabetic agents may be needed. Nicotine may increase plasma glucose. The cessation of nicotine therapy may result in a decrease in blood glucose. Blood glucose concentrations should be monitored more closely whenever a change in nicotine intake occurs; dosage adjustments in antidiabetic agents may be needed.
    Nitazoxanide: The active metabolite of nitazoxanide, tizoxanide, is highly bound to plasma proteins. Caution should be exercised when administering nitazoxanide concurrently with other highly plasma protein-bound drugs with narrow therapeutic indices because competition for binding sites may occur.
    Nitrates: The concomitant use of nitrates with rosiglitazone is not recommended. An increased risk of myocardial ischemia was observed in a subset of patients receiving nitrates with rosiglitazone. Most patients that were using nitrates had preexisting coronary artery disease. In patients with coronary artery disease that were not on nitrates, rosiglitazone therapy did not increase the risk of myocardial ischemia.
    Nitroglycerin: The concomitant use of nitrates with rosiglitazone is not recommended. An increased risk of myocardial ischemia was observed in a subset of patients receiving nitrates with rosiglitazone. Most patients that were using nitrates had preexisting coronary artery disease. In patients with coronary artery disease that were not on nitrates, rosiglitazone therapy did not increase the risk of myocardial ischemia.
    Nonsteroidal antiinflammatory drugs: NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations.
    Norepinephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood glucose concentrations. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Norethindrone: Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Norfloxacin: Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Monitor blood glucose when quinolones and antidiabetic agents are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Rare cases of severe hypoglycemia have been reported with concomitant use of quinolones and glyburide. Therefore, careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents are coadministered. Monitor blood glucose when quinolones and antidiabetic agents are coadministered.
    Norgestrel: Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Octreotide: Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added. Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Ofloxacin: Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Rare cases of severe hypoglycemia have been reported with concomitant use of quinolones and glyburide. Therefore, careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents are coadministered. Monitor blood glucose when quinolones and antidiabetic agents are coadministered. Hyperglycemia and hypoglycemia have been reported in patients treated concomitantly with quinolones and antidiabetic agents. Therefore, careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents are coadministered.
    Olanzapine: Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when olanzapine is instituted. Atypical antipsychotics have been associated with causing metabolic changes, including hyperglycemia, even diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Patients taking sulfonylureas should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Olmesartan: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Ombitasvir; Paritaprevir; Ritonavir: New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. In addition, coadministration of atazanavir with rosiglitazone may result in elevated rosiglitazone plasma concentrations. Rosiglitazone is a substrate for CYP2C8; atazanavir is a weak inhibitor of CYP2C8.
    Oritavancin: Glimepiride is metabolized by CYP2C9; oritavancin is a weak CYP2C9 inhibitor. Coadministration may result in elevated glimepiride plasma concentrations. If these drugs are administered concurrently, blood glucose should be monitored closely. Rosiglitazone is metabolized by CYP2C9; oritavancin is a weak CYP2C9 inhibitor. Coadministration may result in elevated rosiglitazone plasma concentrations. If these drugs are administered concurrently, blood glucose should be monitored closely.
    Orlistat: Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents. Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents.
    Oxandrolone: Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia. However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary. Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Oxymetholone: Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia. However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary. Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Paliperidone: Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when paliperidone is instituted. Paliperidone has been associated with metabolic changes including hyperglycemia, even diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma in some instances. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Patients taking sulfonylureas should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Pasireotide: Pasireotide may cause hyperglycemia. Closely monitor patients receiving antidiabetic therapy for changes in glycemic control; adjustments in the dosage of antidiabetic agents may be necessary during pasireotide receipt and after its discontinuation.
    Pazopanib: Pazopanib is a weak inhibitor of CYP2C8. Coadministration of pazopanib and rosiglitazone, a CYP2C8 substrate, may cause an increase in systemic concentrations of rosiglitazone. Use caution when administering these drugs concomitantly.
    Pegvisomant: Patients who have both acromegaly and diabetes mellitus and are being treated with antidiabetic agents may require dose reductions of these medications after the initiation of pegvisomant. Growth hormone decreases insulin sensitivity by opposing the effects of insulin on carbohydrate metabolism; therefore, pegvisomant, which antagonizes growth hormone, is expected to have the opposite effect. Although none of the acromegalic patients with diabetes mellitus who were treated with pegvisomant during the clinical studies developed clinically relevant hypoglycemia, such patients should monitor their blood glucose regularly, with doses of anti-diabetic medications reduced as necessary. Patients who have both acromegaly and diabetes mellitus and are being treated with oral antidiabetic agents may require dose reductions of these medications after the initiation of pegvisomant. Growth hormone decreases insulin sensitivity by opposing the effects of insulin on carbohydrate metabolism; therefore, pegvisomant, which antagonizes growth hormone, is expected to have the opposite effect. Although none of the acromegalic patients with diabetes mellitus who were treated with pegvisomant during the clinical studies developed clinically relevant hypoglycemia, such patients should monitor their blood glucose regularly, with doses of anti-diabetic medications reduced as necessary.
    Pemoline: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia.
    Penbutolol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Pentamidine: Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Pentoxifylline: Pentoxiphylline has been used concurrently with antidiabetic agents without observed problems, but it may enhance the hypoglycemic action of antidiabetic agents. Patients should be monitored for changes in glycemic control while receiving pentoxifylline in combination with antidiabetic agents.
    Perindopril: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Perindopril; Amlodipine: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Phendimetrazine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Phenelzine: Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents.Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost.
    Phenothiazines: The phenothiazines, especially chlorpromazine, may increase blood sugar. Patients should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. Patients should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. In addition, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas. The phenothiazines may increase blood sugar. Patients who are receiving antidiabetic agents should be closely monitored for worsening glycemic control when a phenothiazine is instituted.
    Phentermine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Use caution in combining with phentermine with antidiabetic agents, as requirements for antidiabetic agents may be altered. Phentermine exhibits sympathomimetic activity. Sympathomimetics may increase blood sugar via stimulation of beta2-receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Additionally, diabetic patients may have decreased requirements of insulins, sulfonylureas, or other antidiabetic agents in association with the use of phentermine and the concomitant dietary regimen and weight loss. As long as blood glucose is carefully monitored to avoid hypoglycemia or hyperglycemia, it appears that phentermine can be used concurrently.
    Phentermine; Topiramate: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Use caution in combining with phentermine with antidiabetic agents, as requirements for antidiabetic agents may be altered. Phentermine exhibits sympathomimetic activity. Sympathomimetics may increase blood sugar via stimulation of beta2-receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Additionally, diabetic patients may have decreased requirements of insulins, sulfonylureas, or other antidiabetic agents in association with the use of phentermine and the concomitant dietary regimen and weight loss. As long as blood glucose is carefully monitored to avoid hypoglycemia or hyperglycemia, it appears that phentermine can be used concurrently.
    Phenylephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Phenylephrine; Promethazine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood sugar. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents including phenothiazines. Patients should take care and use proper techniques to limit sunlight and UV exposure. The phenothiazines such as promethazine may increase blood sugar. Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when a phenothiazine is instituted.
    Phenytoin: Phenytoin and other hydantoins have the potential to increase blood glucose and thus interact with antidiabetic agents pharmacodynamically. In addition, coadministration may result in decreased serum concentrations of chlorpropamide. Monitor blood glucose for changes in glycemic control. Dosage adjustments may be necessary in some patients. Phenytoin and other hydantoins have the potential to increase blood glucose and thus interact with antidiabetic agents pharmacodynamically. Monitor blood glucose for changes in glycemic control. Dosage adjustments may be necessary in some patients.
    Photosensitizing agents: Use photosensitizing agents and sulfonylureas together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Pimavanserin: Patients taking sulfonylureas should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Pindolol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Porfimer: Use photosensitizing agents and sulfonylureas together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia. However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary. Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Prednisolone: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Prednisone: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Pregabalin: Higher rates of peripheral edema and weight gain may occur in patients who concomitantly use thiazolidinediones with pregabalin. As the thiazolidinediones and pregabalin can both cause weight gain and/or fluid retention, possibly exacerbating or leading to heart failure, care should be taken when co-administering these agents.
    Prilocaine; Epinephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Sympathomimetics may increase blood glucose concentrations. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Probenecid: Probenecid is highly protein bound, and the hypoglycemic effect of sulfonylureas made be potentiated if these drugs are coadministered.
    Progesterone: Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Progestins: Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
    Promethazine: Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents including phenothiazines. Patients should take care and use proper techniques to limit sunlight and UV exposure. The phenothiazines such as promethazine may increase blood sugar. Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when a phenothiazine is instituted.
    Propoxyphene: Propoxyphene may enhance the hypoglycemic action of antidiabetic agents. Patients should be closely monitored for changes in glycemic control while receiving propoxyphene in combination with antidiabetic agents.
    Propranolol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Protease inhibitors: New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. In addition, coadministration of atazanavir with rosiglitazone may result in elevated rosiglitazone plasma concentrations. Rosiglitazone is a substrate for CYP2C8; atazanavir is a weak inhibitor of CYP2C8.
    Pseudoephedrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Pseudoephedrine may increase blood sugar via stimulation of beta2 receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with pseudoephedrine is instituted.
    Pyrimethamine; Sulfadoxine: Sulfonamides may induce hypoglycemia by increasing the secretion of insulin from the pancreas. Therefore, a pharmacodynamic interaction leading to an increased risk of hypoglycemia may occur in patients taking antidiabetic agents and sulfonamides.
    Quetiapine: Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when quetiapine is instituted. Atypical antipsychotics have been associated with causing hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Patients taking sulfonylureas should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Quinapril: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Racepinephrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia.
    Ramipril: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Ranitidine: Ranitidine has been shown to affect the pharmacokinetics of some oral sulfonylureas. Patients receiving sulfonylureas should be observed for evidence of altered glycemic response when ranitidine is instituted or discontinued. The mechanism of this interaction may involve either increasing the absorption or decreasing the clearance of the sulfonylurea. Asymptomatic hypoglycemia has been observed as a result of this interaction. It is unclear at this time if famotidine or nizatidine interact with oral sulfonylureas.
    Rasagiline: Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor rasagiline, are added to any regimen containing antidiabetic agents.
    Reserpine: Reserpine may mask the signs and symptoms of hypoglycemia. Patients receiving reserpine concomitantly with antidiabetic agents should be monitored for changes in glycemic control. Reserpine may mask the signs and symptoms of hypoglycemia. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Rifampin: The coadministration of rifampin and rosiglitazone may decrease the concentration of rosiglitazone. This interaction is most likely due to rifampin's inhibition of the CYP2C8 and, to a lesser extent, CYP2C9 isozymes. Use caution if rifampin and rosiglitazone are to be coadministered, as decreased rosiglitazone efficacy may be seen. Blood glucose concentrations should be monitored and possible dose adjustments of rosiglitazone may need to be made.
    Rifamycins: Rifamycins induce hepatic isoenzymes CYP3A4 and CYP2C8/9. Drugs metabolized by CYP3A4 and CYP2C8/9, including sulfonylureas, may require dosage adjustments when administered concurrently with rifamycins.
    Risperidone: Patients taking sulfonylureas should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Risperidone has been associated with causing hyperglycemia, even diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when risperidone is instituted.
    Ritodrine: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia. Intravenous administration of ritodrine has been shown to elevate plasma insulin and glucose concentrations. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with ritodrine is instituted.
    Ritonavir: New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. In addition, coadministration of atazanavir with rosiglitazone may result in elevated rosiglitazone plasma concentrations. Rosiglitazone is a substrate for CYP2C8; atazanavir is a weak inhibitor of CYP2C8.
    Sacubitril; Valsartan: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Salicylates: Salicylates can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar. In large doses, salicylates can cause hyperglycemia and glycosuria.
    Salsalate: If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
    Saquinavir: New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. In addition, coadministration of atazanavir with rosiglitazone may result in elevated rosiglitazone plasma concentrations. Rosiglitazone is a substrate for CYP2C8; atazanavir is a weak inhibitor of CYP2C8.
    Selegiline: Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents.Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost.
    Somatropin, rh-GH: Administration of somatropin may result in increases in blood glucose concentrations, thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when therapy with somatropin, rh-GH is instituted. Somatropin increases blood glucose concentrations thereby decreasing the hypoglycemic effect of antidiabetic agents. Monitor for signs indicating loss of diabetic control when therapy with somatropin is instituted.
    Sotalol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Sparfloxacin: Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Rare cases of severe hypoglycemia have been reported with concomitant use of quinolones and glyburide. Therefore, careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents are coadministered. Monitor blood glucose when quinolones and antidiabetic agents are coadministered. Hyperglycemia and hypoglycemia have been reported in patients treated concomitantly with quinolones and antidiabetic agents. Therefore, careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents are coadministered.
    Sulfacetamide: Sulfonamides may cause photosensitization and may increase the photosensitizing effects of sulfonylureas. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Sulfacetamide; Sulfur: Sulfonamides may cause photosensitization and may increase the photosensitizing effects of sulfonylureas. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Sulfadiazine: Sulfonamides may induce hypoglycemia by increasing the secretion of insulin from the pancreas. Therefore, a pharmacodynamic interaction leading to an increased risk of hypoglycemia may occur in patients taking antidiabetic agents and sulfonamides.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: It is possible that an increase in the exposure of rosiglitazone may occur when coadministered with drugs that inhibit CYP2C8 such as trimethoprim. Patients should be monitored for changes in glycemic control if any CYP2C8 inhibitors are coadministered with rosiglitazone. Sulfonamides may induce hypoglycemia by increasing the secretion of insulin from the pancreas. Therefore, a pharmacodynamic interaction leading to an increased risk of hypoglycemia may occur in patients taking antidiabetic agents and sulfonamides.
    Sulfasalazine: Sulfonamides may induce hypoglycemia by increasing the secretion of insulin from the pancreas. Therefore, a pharmacodynamic interaction leading to an increased risk of hypoglycemia may occur in patients taking antidiabetic agents and sulfonamides.
    Sulfinpyrazone: Rosiglitazone is metabolized by CYP2C9. It is possible for serum concentrations of rosiglitazone to rise when coadministered with drugs that inhibit CYP2C9, including sulfinpyrazone. Monitor serum glucose concentrations if rosiglitazone and sulfinpyrazone are coadministered. Dosage adjustments may be necessary. Sulfinpyrazone is an inhibitor of CYP2C9. Sulfinpyrazone may inhibit the hepatic metabolism of sulfonylureas, CYP2C9 substrates. Patients should be monitored for an increased hypoglycemic effect.
    Sulfisoxazole: Sulfonamides may induce hypoglycemia by increasing the secretion of insulin from the pancreas. Therefore, a pharmacodynamic interaction leading to an increased risk of hypoglycemia may occur in patients taking antidiabetic agents and sulfonamides.
    Sulfonamides: Sulfonamides may induce hypoglycemia by increasing the secretion of insulin from the pancreas. Therefore, a pharmacodynamic interaction leading to an increased risk of hypoglycemia may occur in patients taking antidiabetic agents and sulfonamides. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. Also, taking these drugs together may increase risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas
    Sulfonylureas: A maximum dose of 8 mg/day of rosiglitazone is recommended when used in combination with sulfonylureas; the incidence of adverse effects including hypoglycemia is increased with larger doses. In one clinical study, rosiglitazone 4 or 8 mg/day was added to failed glimepiride plus metformin therapy. The incidence of hypoglycemia (blood glucose concentrations <= 50 mg/dl) was 18.6% in the 4 mg/day group compared with 28% in the 8 mg/day group. In addition, 4 or 8 mg/day of rosiglitazone has been added to failed glyburide plus metformin therapy. The incidence of hypoglycemia was higher in the rosiglitazone (average dose 7.4 mg/day)+glyburide+metformin group (22%) when compared to the glyburide+metformin group (3%). Patients should be instructed to monitor blood glucose concentrations more frequently. Dosage adjustments may be indicated.
    Sympathomimetics: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia.
    Tacrolimus: Patients should be monitored for worsening of glycemic control if therapy with tacrolimus is initiated in patients receiving antidiabetic agents. Tacrolimus has been reported to cause hyperglycemia and has been implicated in causing insulin-dependent diabetes mellitus in patients after renal transplantation. Tacrolimus may have direct beta-cell toxicity. Patients should be monitored for worsening of glycemic control if therapy with tacrolimus is initiated in patients receiving antidiabetic agents.
    Tegaserod: Tegaserod can enhance gastric emptying in diabetic patients, and blood glucose can be affected, which may affect the clinical response to antidiabetic drugs. Dosing of the antidiabetic agent may require adjustment in patients who receive GI prokinetic agents concomitantly. Tegaserod can enhance gastric emptying in diabetic patients, blood glucose can be affected, which, in turn, may affect the clinical response to antidiabetic agents. The dosing of antidiabetic agents may require adjustment in patients who receive GI prokinetic agents concomitantly.
    Telmisartan: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Teriflunomide: Increased monitoring is recommended if teriflunomide is administered concurrently with CYP2C8 substrates, such as rosiglitazone. In vivo studies demonstrated that teriflunomide is an inhibitor of CYP2C8. Coadministration may lead to increased exposure to CYP2C8 substrates; however, the clinical impact of this has not yet been determined. Monitor for increased adverse effects.
    Testolactone: Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia. However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary. Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Testosterone: Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia. However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary. Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Tetracycline: Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents including tetracyclines. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.
    Tetracyclines: Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents including tetracyclines. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.
    Thiazide diuretics: Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
    Thyroid hormones: Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed. Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
    Timolol: Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. Also, beta-blockers can blunt the tachycardic response and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Beta-blockers can prolong hypoglycemia or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Pharmacokinetic interactions are also possible between individual drugs. Glyburide is a substrate of drug transporter P-glycoprotein (P-gp). Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of glyburide. Patients should be monitored for changes in glycemic control.
    Tipranavir: New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. In addition, coadministration of atazanavir with rosiglitazone may result in elevated rosiglitazone plasma concentrations. Rosiglitazone is a substrate for CYP2C8; atazanavir is a weak inhibitor of CYP2C8.
    Tobacco: Tobacco smoking is known to aggravate insulin resistance. The cessation of nicotine therapy or tobacco smoking may result in a decrease in blood glucose. Blood glucose concentrations should be monitored more closely whenever a change in either nicotine intake or smoking status occurs; dosage adjustments in antidiabetic agents may be needed. Tobacco smoking is known to aggravate insulin resistance. The cessation of tobacco smoking may result in a decrease in blood glucose. Blood glucose concentrations should be monitored more closely whenever a change in either smoking status occurs; dosage adjustments in antidiabetic agents may be needed.
    Tolazamide: A maximum dose of 8 mg/day of rosiglitazone is recommended when used in combination with sulfonylureas; the incidence of adverse effects including hypoglycemia is increased with larger doses. In one clinical study, rosiglitazone 4 or 8 mg/day was added to failed glimepiride plus metformin therapy. The incidence of hypoglycemia (blood glucose concentrations <= 50 mg/dl) was 18.6% in the 4 mg/day group compared with 28% in the 8 mg/day group. In addition, 4 or 8 mg/day of rosiglitazone has been added to failed glyburide plus metformin therapy. The incidence of hypoglycemia was higher in the rosiglitazone (average dose 7.4 mg/day)+glyburide+metformin group (22%) when compared to the glyburide+metformin group (3%). Patients should be instructed to monitor blood glucose concentrations more frequently. Dosage adjustments may be indicated.
    Tolbutamide: A maximum dose of 8 mg/day of rosiglitazone is recommended when used in combination with sulfonylureas; the incidence of adverse effects including hypoglycemia is increased with larger doses. In one clinical study, rosiglitazone 4 or 8 mg/day was added to failed glimepiride plus metformin therapy. The incidence of hypoglycemia (blood glucose concentrations <= 50 mg/dl) was 18.6% in the 4 mg/day group compared with 28% in the 8 mg/day group. In addition, 4 or 8 mg/day of rosiglitazone has been added to failed glyburide plus metformin therapy. The incidence of hypoglycemia was higher in the rosiglitazone (average dose 7.4 mg/day)+glyburide+metformin group (22%) when compared to the glyburide+metformin group (3%). Patients should be instructed to monitor blood glucose concentrations more frequently. Dosage adjustments may be indicated.
    Torsemide: Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Because of this, a potential pharmacodynamic interaction exists between torsemide and all antidiabetic agents. Monitor blood glucose. Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Patients on antidiabetic medications should monitor their blood glucose regularly if torsemide is prescribed.
    Trandolapril: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Trandolapril; Verapamil: ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Tranylcypromine: Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents.Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost.
    Tretinoin, ATRA: A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Triamcinolone: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Triamterene: Triamterene can interfere with the hypoglycemic effects of antidiabetic agents. This can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Trimethoprim: It is possible that an increase in the exposure of rosiglitazone may occur when coadministered with drugs that inhibit CYP2C8 such as trimethoprim. Patients should be monitored for changes in glycemic control if any CYP2C8 inhibitors are coadministered with rosiglitazone.
    Trovafloxacin, Alatrofloxacin: Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Rare cases of severe hypoglycemia have been reported with concomitant use of quinolones and glyburide. Therefore, careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents are coadministered. Monitor blood glucose when quinolones and antidiabetic agents are coadministered.
    Valproic Acid, Divalproex Sodium: Glimepiride is metabolized by CYP2C9. It is possible for serum concentrations of glimepiride to rise when coadministered with drugs that inhibit CYP2C9 like valproic acid. Monitor serum glucose concentrations if glimepiride is coadministered with valproic acid. Dosage adjustments may be necessary.
    Valsartan: Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control.
    Vemurafenib: Concomitant use of vemurafenib and glimepiride may result in increased glimepiride concentrations. Vemurafenib is a CYP2C9 inhibitor and glimepiride is a CYP2C9 substrate. Monitor serum glucose concentrations if glimepiride is coadministered with CYP2C9 inhibitors. Dosage adjustments may be necessary. Rosiglitazone is metabolized by CYP2C9 (minor pathway) and it is possible for serum concentrations of rosiglitazone to rise when coadministered with drugs that inhibit CYP2C9, including vemurafenib. Monitor serum glucose concentrations if rosiglitazone and vemurafenib are coadministered. Dosage adjustments may be necessary.
    Verteporfin: Use photosensitizing agents and sulfonylureas together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Vilazodone: In vitro studies suggest that vilazodone may increase the plasma concentrations of CYP2C8 substrates. Because rosiglitazone is a CYP2C8 substrate, caution is advisable during co-administration of vilazodone.
    Voriconazole: Because rosiglitazone is metabolized by CYP2C9, exaggerated therapeutic effect or hypoglycemia is possible if rosiglitazone is coadministered with voriconazole. Voriconazole should be used cautiously with sulfonylureas. The combination of voriconazole and oral antidiabetic agents may result in severe hypoglycemia. Voriconazole may inhibit the metabolism of sulfonylureas. Blood glucose concentrations should be monitored and possible dose adjustments of hypoglycemics may need to be made.
    Warfarin: The interaction between oral anticoagulants and oral sulfonylureas is complex; both enhancement or reduction of hypoprothrombinemic response to oral anticoagulants has been reported in various literature accounts along with a potential for altered hypoglycemic response to the sulfonylurea. One proposed mechanism may be related to displacement of the drugs from plasma protein binding sites. Dicumarol has been reported to inhibit the metabolism of chlorpropamide and tolbutamide, however, warfarin did not exhibit a similar effect on tolbutamide kinetics. Glyburide has been reported to augment the hypoprothrombinemic response to warfarin, although other reports have showed no interaction. Warfarin appears less likely to interact with sulfonylureas than dicumarol. In clinical trials, glimepiride therapy resulted in a slight, but statistically significant decrease in pharmacodynamic response to warfarin. The reductions in effect are unlikely to be clinically important in most cases. Nevertheless, it would be wise for clinicians to use warfarin and sulfonylureas together cautiously until the combined effects of the drugs are known. Monitor the INR as indicated and be alert for altered blood sugar control when either of these drugs is added or discontinued.
    Zafirlukast: Glimepiride is metabolized by CYP2C9. It is possible for serum concentrations of glimepiride to rise when coadministered with drugs that inhibit CYP2C9 like zafirlukast. Monitor serum glucose concentrations if glimepiride is coadministered with zafirlukast. Dosage adjustments may be necessary. In vitro data indicate that zafirlukast inhibits the CYP2C9 and CYP3A4 isoenzymes at concentrations close to the clinically achieved total plasma concentrations. Until more clinical data are available, zafirlukast should be used cautiously in patients stabilized on drugs metabolized by CYP2C9, such as rosiglitazone, especially those drugs with narrow therapeutic ranges.
    Ziprasidone: Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when ziprasidone is instituted. Atypical antipsychotics have been associated with metabolic changes including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. In addition, ziprasidone is a CYP3A4 substrate and pioglitazone and troglitazone (off-market) are CYP3A4 inducers. Theoretically, there might be a decrease in ziprasidone concentrations. A dosage adjustment ofziprasidone may be necessary if these thiazolidinediones are used concomitantly. Patients taking sulfonylureas should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.

    PREGNANCY AND LACTATION

    Pregnancy

    Rosiglitazone; glimepiride is classified as FDA pregnancy risk category C. Rosiglitazone is not recommended for use during pregnancy. Rosiglitazone has been reported to cross the human placenta and be detectable in fetal tissue; the clinical significance of these findings is unknown. Animal data suggest no teratogenic effects for rosiglitazone. Glimepiride and other sulfonylureas have been associated with an increased risk of intrauterine fetal death in animal studies. Prolonged (4 to 10 days) hypoglycemia has been reported in neonates born to mothers who were receiving a sulfonylurea at the time of obstetric delivery, mostly in patients taking sulfonylureas with prolonged half-lives. Therefore, the manufacturer recommends that a patient planning a pregnancy should be manged with insulin therapy instead of glimepiride; rosiglitazone during the course of her pregnancy. The American College of Obstetrician and Gynecologists recommends insulin as the therapy of choice to maintain blood glucose as close to normal as possible during pregnancy in patients with type 1 or 2 diabetes mellitus, and, if diet therapy alone is not successful, for those patients with gestational diabetes.

    MECHANISM OF ACTION

    Glimepiride; rosiglitazone combines two antidiabetic agents with different mechanisms to improve glycemic control in patients with type 2 diabetes mellitus. Glimepiride acts primarily by increasing insulin secretion. Rosiglitazone is an insulin sensitizer that acts by enhancing peripheral glucose utilization. Neither drug is effective in patients with insulin deficiency (i.e., type 1 diabetes).
    •Glimepiride: Glimepiride lowers blood glucose by stimulating pancreatic islet cells, resulting in an increase in insulin secretion. Sulfonylureas are believed to bind to ATP-sensitive potassium-channel receptors on the pancreatic cell surface, thereby reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin. The drug is not effective in the absence of functioning beta-cells, as occurs in diabetes mellitus type 1, or when the number of viable beta-cells is low, as occurs in severe cases of diabetes mellitus type 2. Prolonged administration of glimepiride produces extrapancreatic effects that contribute to its hypoglycemic activity such as a reduction in basal hepatic glucose production and an enhanced peripheral sensitivity to insulin. Enhanced insulin sensitivity is most likely due to either an increase in insulin receptors or to changes in the events that follow insulin-receptor binding. The relative importance of these actions to the overall therapeutic effect varies from patient to patient. Glimepiride may enhance peripheral tissue insulin sensitivity to a greater degree in fatty tissue than in skeletal muscle.
    •Rosiglitazone: Rosiglitazone is an oral thiazolidinedione; its primary action is enhancement of insulin sensitivity in adipose tissue, skeletal muscle and the liver. Rosiglitazone is a highly selective and potent agonist for the peroxisome proliferator activated receptor (PPAR-gamma), which regulates the transcription of a number of insulin responsive genes. PPAR receptors can be found in key target tissues for insulin action such as adipose tissue, skeletal muscle, and the liver. Clinically, rosiglitazone decreases plasma glucose concentrations, insulin concentrations, and glycosylated hemoglobin. Additional favorable metabolic effects include decreased hepatic glucose output and reduced free fatty acid serum concentrations. Unlike glimepiride, rosiglitazone enhances tissue sensitivity to insulin rather than stimulates insulin secretion.

    PHARMACOKINETICS

    Glimepiride; rosiglitazone is administered orally.
     
    Glimepiride: Glimepiride is greater than 99.5% protein-bound. Glimepiride is completely metabolized following oral administration and has a half-life of about 5 hours initially that increases to roughly 9 hours after multiple dosing. Two metabolites are formed, the cyclohexyl hydroxy methyl derivative (M1) and the carboxyl derivative (M2). Cytochrome P450 CYP2C9 has been shown to be involved in the biotransformation of glimepiride to M1. M1 is metabolized to M2 via an unknown pathway. M2 is an inactive metabolite. In an animal model, M1 has about 1/3 the pharmacological activity of glimepiride; the clinical significance of M1 on the glucose-lowering effect of glimepiride in patients is not clear. Glimepiride is excreted in the urine (60%) and feces (40%), predominantly in the form of M1 and M2.
    Rosiglitazone: Protein binding is approximately 99.8%, primarily to albumin. Metabolism is extensive with no unchanged drug detected in urine. The major routes of metabolism include N-demethylation and hydroxylation, followed by conjugation with sulfate and glucuronic acid. In vitro data show that rosiglitazone is predominantly metabolized by cytochrome P450 CYP2C8, with CYP2C9 serving as a minor pathway. Metabolites are active, but have significantly less activity than the parent compound and are not expected to contribute to the insulin-sensitizing activity of rosiglitazone. Radiolabeled studies suggest that approximately 64% and 23% of an administered dose is eliminated in the urine and in the feces, respectively. The elimination half-life of the parent drug is about 3 to 4 hours and is independent of the dose.

    Oral Route

    The area under the curve (AUC) of both glimepiride 4 mg and rosiglitazone 4 mg administered simultaneously as separate tablets is equivalent to glimepiride 4 mg; rosiglitazone 4 mg (Avandaryl 4 mg/4 mg). The Cmax of rosiglitazone 4 mg administered as a separate tablet is also equivalent to the combination tablet; however, the Cmax of glimepiride is 13% lower when administered as the combination tablet.
     
    Glimepiride: Glimepiride is completely absorbed following oral administration. Significant absorption occurs within 1 hour, and peak serum concentrations occur in 2—3 hours. Administration of glimepiride with food slightly increases the Cmax by 55% and the AUC by 19%.
    Rosiglitazone: Absorption of rosiglitazone occurs rapidly with an absolute bioavailability of 99%. Peak plasma concentrations are achieved in about 1 hour after dosing. Administration with food does not affect overall exposure to rosiglitazone; however, the Cmax of rosiglitazone decreases by 32% when administered with food.