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  • CLASSES

    Long-acting Human Insulins and Analogs

    DEA CLASS

    Rx

    DESCRIPTION

    Hormone secreted by pancreatic beta-cells of the islets of Langerhans and essential for the metabolism and homeostasis of carbohydrate, fat, and protein.
    Insulin glargine is a once-daily basal insulin analog without pronounced peaks.

    COMMON BRAND NAMES

    BASAGLAR, Lantus, Lantus SoloStar, Toujeo SoloStar

    HOW SUPPLIED

    BASAGLAR/Lantus/Lantus SoloStar/Toujeo SoloStar Subcutaneous Inj Sol: 1mL, 100U, 300U

    DOSAGE & INDICATIONS

    For the treatment of type 1 diabetes mellitus and type 2 diabetes mellitus.
    For the treatment of type 1 diabetes mellitus.
    Subcutaneous dosage (100 units/mL, i.e., Lantus, Basaglar)
    Adults

    Initially, administer one-third of the total daily insulin requirements/dose subcutaneously once daily. Titrate dosage to achieve blood glucose control and A1C goals in conjunction with a short-acting insulin. Give the dose at the same time every day, at any time. Administration in the morning may avoid nocturnal hypoglycemia. When transferring from once daily NPH insulin, the dose is usually not changed. However, when transferring from twice-daily NPH insulin to insulin glargine, the total daily dose of NPH insulin (or other twice daily basal insulin) should be reduced by 20% and administered as single dose once daily. When transferring from once-daily Toujeo to once-daily Lantus or Basaglar, the recommended initial Lantus or Basaglar dose is 80% of the Toujeo dose that is being discontinued. Thereafter, the dosage of insulin glargine should be adjusted to response.

    Children and Adolescents 6 years and older

    Insulin requirements are highly variable and must be individualized based on patient-specific factors and type of insulin regimen. During partial remission phase, total combined daily insulin requirement is often less than 0.5 units/kg/day. Prepubertal children (outside the partial remission phase) usually require 0.7 to 1 unit/kg/day. During puberty, insulin requirements are much greater, often between 1 and 2 units/kg/day. Insulin glargine is a long-acting insulin and must be used in combination with a short-acting insulin. Typically, 4 to 5 subcutaneous insulin injections are given per day; 1 to 2 as a long-acting insulin plus 3 to 4 pre-meal rapid-acting insulin doses. The proportion supplied as the basal insulin usually ranges from 40 to 60% of the total daily dose. The FDA-approved product labeling recommends initially administering one-third of the total daily insulin requirements/dose subcutaneously once daily. Titrate dosage to achieve blood glucose control and A1C goals in conjunction with a rapid- or short-acting insulin. Give the dose at the same time every day, at any time. Administration in the morning may avoid nocturnal hypoglycemia. When transferring from once daily NPH insulin, the dose is usually not changed. However, when transferring from twice-daily NPH, the total daily dose of NPH insulin (or other twice daily basal insulin) should be reduced by 20% and administered as single dose once daily.

    Subcutaneous dosage (300 units/mL, i.e., Toujeo)
    Adults

    Initially, administer one-third to one-half of the total daily insulin requirements/dose subcutaneously once daily; the total daily dosage ranges from 1—80 units. Titrate dosage every 3—4 days to achieve blood glucose control and A1C goals in conjunction with a short-acting insulin. The maximum glucose lowering effect may take 5 days to fully achieve and the initial dose may be insufficient to cover metabolic needs in the first 24 hours. To minimize risks associated with insufficient coverage, monitor glucose daily and adjust coadministered glucose lowering therapies as necessary. Give the dose at the same time every day, at any time. Administration in the morning may avoid nocturnal hypoglycemia. Expect that patients previously controlled on Lantus or Basaglar will require a higher daily dose of Toujeo to maintain the same level of glycemic control. When transferring from once daily NPH insulin, the dose is usually not changed. However, when transferring from twice-daily NPH insulin to insulin glargine, the total daily dose of NPH insulin (or other twice daily basal insulin) should be reduced by 20% and administered as single dose once daily. Thereafter, the dosage of insulin glargine should be adjusted to response.

    For the treatment of type 2 diabetes mellitus inadequately managed by diet, exercise, and oral hypoglycemics.
    NOTE: A consensus algorithm issued by the ADA and the European Association for the Study of Diabetes lists basal or intermediate-acting insulin as a second line or third line agent in patients with type 2 diabetes not controlled on oral drugs; metformin is the initial recommended therapy in all type 2 diabetics without contraindications. Once insulin is added, therapy can be intensified (e.g., addition of prandial insulin) to achieve optimal glycemic control. In patients that are receiving a sulfonylurea, the sulfonylurea should be discontinued when insulin therapy is initiated.
    Subcutaneous dosage (100 units/mL, i.e., Lantus, Basaglar)
    Adults

    In patients naive to insulin and treated with oral hypoglycemics, 10 units (or 0.2 units/kg) subcutaneously once daily. Titrate dosage to achieve blood glucose control and A1C goals in conjunction with a short-acting insulin. Give the dose at the same time every day, at any time. Administration in the morning may avoid nocturnal hypoglycemia. When transferring from once daily NPH insulin, the dose is usually not changed. However, when transferring from twice-daily NPH insulin to insulin glargine, the total daily dose of NPH insulin (or other twice daily basal insulin) should be reduced by 20% and administered as single dose once daily. When transferring from once-daily Toujeo to once-daily Lantus or Basaglar, the recommended initial Lantus or Basaglar dose is 80% of the Toujeo dose that is being discontinued. Thereafter, the dosage of insulin glargine should be adjusted to response.

    Children and Adolescents

    Dosage varies depending on previous regimen, concurrent medications, lifestyle, etc; initial total daily insulin doses have been reported to be in the range of 0.3 to 0.5 units/kg/day. Insulin glargine may be used alone, in combination with oral medications (e.g., metformin), or with short-acting insulins for the treatment of type 2 diabetes mellitus if treatment goals are not met with oral medications alone. Regimens may range from once daily therapy to intensive management using basal-bolus regimens. Specific dosage recommendations are not available; dosage should be individualized according to age, weight, activity level, and dietary habits. Titrate dosage according blood glucose and A1C goals.

    Subcutaneous dosage (300 units/mL, i.e., Toujeo)
    Adults

    In patients naive to insulin, 0.2 units/kg/dose subcutaneously once daily; the total daily dosage ranges from 1—80 units. Titrate dosage every 3—4 days to achieve blood glucose control and A1C goals. Give the dose at the same time every day, at any time. Administration in the morning may avoid nocturnal hypoglycemia.

    For the treatment of transient neonatal diabetes mellitus†.
    Subcutaneous dosage
    Neonates

    A dose of 0.27 units/kg/day subcutaneously divided every 12 hours and administered into the abdomen or buttocks was used to control transient neonatal diabetes in a 28-week gestational age, 680 g twin. The neonate received the drug for 6 days with excellent response, with most blood glucose measurements in the euglycemic range. As a small volume of the commercially available insulin glargine 100 units/mL was necessary for the low birth weight neonate, a 1:100 dilution in 0.9% NaCl Injection was prepared to enable accurate dosing; dilution is not recommended in the FDA-approved product labeling.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Specific maximum dosage information is not available. Individualize dosage based on careful monitoring of blood glucose and other clinical parameters in all patient populations.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Dosage should be modified depending on clinical response and degree of hepatic impairment, but no quantitative recommendations are available. Some studies have noted increased circulating levels of insulin in patients with hepatic failure. Individualize dosage based on blood glucose and other clinical parameters.

    Renal Impairment

    The pharmacokinetics of insulin are generally unchanged with renal impairment; however, pharmacodynamic differences occur in insulin sensitivity as renal function declines, resulting in increased responses to a given dosage. Individualize dosage based on blood glucose and other clinical parameters.

    ADMINISTRATION

    Insulin glargine is available in two concentrations as a prefilled Solostar pen: 100 units/mL and 300 units/mL. It is essential that clinicians and patients ensure that the correct concentration of insulin glargine is used. Inadvertent use of the 300 units/mL concentration in place of the 100 units/mL concentration could result in severe overdose and hypoglycemia.

    Injectable Administration

    Insulin glargine is administered by subcutaneous injection only. Do not administer intravenously or intramuscularly.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use injections which are unusually viscous, cloudy, discolored, or contain particulate matter or clumps. Insulin glargine is clear and colorless.
    Insulin pens should never be shared among patients. Even if the disposable needle is changed, sharing may result in transmission of hepatitis viruses, HIV, or other blood-borne pathogens. Do not share pens among multiple patients in an inpatient setting; use multidose vials instead, if available, or, reserve the use of any pen for 1 patient only.

    Subcutaneous Administration

    Intermittent Subcutaneous Injection
    Administer at the same time every day.
    ONLY use insulin syringes marked in insulin units. For injection of Lantus via syringe from a vial, an amount of air equal to the dose of insulin required should be injected into the vial before drug withdrawal to avoid creating a vacuum, then withdraw dose.
    Insulin Glargine Pen:
    All pens require a priming procedure prior to first use. 
    For the Lantus SoloStar Pen 100 units/mL, always attach a new needle before each use, following the instructions provided with the pen.
    The Basaglar KwikPen 100 units/mL does not come with needles; the device is recommended for use with Becton, Dickinson & Company's insulin pen needles (sold separately). Always attach a new needle before each use, following the instructions provided with the pen.
    The Toujeo Solostar Pen 300 units/mL does not come with needles; the device is recommended for use with needles from BD (such as BD Ultra-Fine), Ypsomed (such as Clickfine), or Owen Mumford (such as Unifine Pentips) Always attach a new needle before each use, following the instructions provided with the pen.
    Lantus SoloStar Pen Priming: Always perform the safety test before any injection from the SoloStar pen to ensure proper pen function and removal of air bubbles.
    Select a dose of 2 units by turning the dosage selector.
    Remove the outer needle cap and keep it to remove the used needle after injection. Take off the inner needle cap and discard it.
    Hold the pen with the needle pointing up.
    Tap the insulin reservoir to loosen air bubbles, and press the injection button. Check to see if insulin comes out of the tip.
    If no insulin is discharged, check for air bubbles and repeat the test 2 more times to remove them. If still no insulin is discharged, change the needle and try again. If no insulin is discharged after a needle change, the pen may be damaged, and a new pen should be used.
    For injection of the dose via a SoloStar pen, check that the dose shows "0" after the safety test. Select the required dose.
    Basaglar KwikPen Priming: Always prime the pen before each injection from the KwikPen to ensure proper pen function and removal of air bubbles.
    Select a dose of 2 units by turning the dosage knob.
    Hold the pen with the needle pointing up.
    Tap the insulin reservoir to loosen air bubbles.
    Push the dose knob in until it stops, and "0" is seen in the dose window. Hold the dose knob in and count to 5 slowly. You should see insulin at the tip of the needle. If insulin is not seen, repeat the priming steps, but not more than 4 times. If insulin still does not appear, change the needle and repeat the priming steps.
    For injection of the dose, check that the dose shows "0" after the priming is complete. Then, select the required dose.Turn the dose knob to select the number of units to be injected. The dose indicator should line up with the dose.
    Toujeo Solostar Pens Priming: Always perform the safety test before any injection from the pen to ensure proper pen function.
    Select a dose of 3 units by turning the dose selector until the dose pointer is at the mark between the 2 and 4.
    Press the injection button all the way in. You should see insulin at the tip of the needle. If insulin is not seen, repeat the test, but not more than 3 times. If insulin still does not appear, change the needle and repeat the test. Do not use the pen if there is still no insulin coming out of the needle tip. Use a new pen. Never use a syringe to remove insulin from the pen. 
    You may see air bubbles in the insulin; this is normal and will not harm you.
    For injection of the dose, check that the dose shows "0" after the test is complete. Before selecting a dose, ensure that the needle is attached in order to not damage the pen. Turn the dose selector until the dose pointer lines up with the prescribed dose.
    Double-check dosage in the pen or syringe prior to administration.
    If a pen is used, a dose of more than 80 units will require multiple injections. Use a new needle for each injection.
     
    Administration
    Subcutaneous injections are usually made into the anterior and lateral aspects of the thigh, the upper arms, buttocks, or the abdomen.
    Lightly pinch a fold of skin; insert the needle; release the skin; inject at a 90 degree angle. Children or thin individuals can use a short needle and a 45 degree angle to avoid intramuscular injection. Aspiration is not necessary.
    For administration using a syringe, inject over 2 to 4 seconds. The needle should be remain in the skin for 5 seconds after injection to ensure complete delivery of the insulin dose.
    For administration using the SoloStar pen, keep the injection button pressed all the way in and slowly count to 10 before withdrawing the needle from the skin to ensure that the full dose is delivered.
    For administration using the Basaglar KwikPen, push the dose knob all the way in. Continue to hold the dose knob in and slowly count to 5 before removing the needle.
    For administration using the Toujeo Solostar Pen, keep the injection button held in and when you see "0" in the dose window, slowly count to 5 before withdrawing the needle from the skin to ensure that the full dose is delivered.
    Rotate administration sites with each injection to prevent lipodystrophy. However, staying within the same area (e.g., abdomen) is generally recommended to decrease the variability in insulin absorption from dose to dose.
    Per the manufacturer, insulin glargine should not be diluted or mixed with any other insulin or solution as the pharmacodynamic profile of insulin glargine and/or the other insulin may be altered in an unpredictable manner. Insulin glargine mixed with regular insulin immediately prior to injection in dogs caused a delay in onset of action and time to maximum effect of regular insulin. However, 2 small studies have demonstrated that mixing insulin glargine with either insulin lispro or insulin aspart does not affect glycemic control or rates of hypoglycemia in children with type 1 diabetes mellitus; one study was 10 days in duration, and the other was 6 months in duration. The insulins were mixed immediately before injection, and, in 1 study, the rapid acting insulin analog was drawn into the syringe first. Cloudiness upon mixing was noted in both studies, but neither pain upon injection nor clogging of the needle was reported.
     
    Storage of opened products:
    Do not use insulin glargine if it has been frozen. Protect from direct heat and light.
    Storage of vials: Insulin glargine vials may be stored in the refrigerator or at room temperature once opened. Once opened, vials must be used within 28 days or be discarded, even if they still contain insulin. The U.S. Pharmacopeia Dispensing Information (USP DI) recommends that an opened insulin vial may be kept at room temperature for up to one month (usually defined as 28 to 30 days). Insulin that has been kept at room temperature for longer than one month should be thrown away. The American Diabetes Association (ADA) also states that an opened insulin vial can be kept at room temperature for approximately one month. Extremes of temperature should be avoided because these can lead to significant changes in insulin action. If human insulin vials are stored under refrigeration while in use and are used beyond 30 days, the stability of these vials may be affected by a number of factors; such factors include the number of injections per day, volume of insulin remaining in the vial, exposure to light, agitation, and technique used for dose preparation. The impact of such factors is difficult to measure, and the health care professional should advise patients on an individual basis concerning long-term storage of opened insulin vials when refrigerated. The length of time an insulin can be stored while unopened is based on the expiration date.
    Storage of Lantus SoloStar pens: Store at room temperature only once opened; do not refrigerate after opening. Once removed from refrigeration, Lantus SoloStar pens should be discarded within 28 days, even if they have not been opened and even if they still contain insulin.
    Storage of Toujeo SoloStar pens: Store at room temperature only once opened; do not refrigerate after opening. Once removed from refrigeration, Toujeo SoloStar pens should be discarded within 42 days.
    Storage of Basaglar KwikPen: Store at room temperature (up to 86 degrees F [30 degrees C]) only once opened; do not refrigerate after opening. Once removed from refrigeration, the Basaglar KwikPen should be discarded within 28 days, even if it has not been opened and even if it still contains insulin.
     
    Preparation and Administration Instructions for Patients
    To prepare a dose from a vial:
    Clean the rubber stopper of the vial with an alcohol wipe. Pull back the plunger of a disposable syringe to fill the syringe with an amount of air equal to your dose of insulin (if your dose is 30 units, pull the plunger to the 30 unit mark). Insert the needle into the rubber stopper of the vial, and inject the air into the vial (this will make the insulin easier to remove). Turn the vial and syringe upside down. Making sure the tip of the needle is in the insulin, pull back on the plunger to fill the syringe with the prescribed number of units of insulin. Before removing the needle from the vial, check your syringe for air bubbles. If bubbles are present, hold the syringe straight up and flick the syringe firmly with your finger until the bubbles float to the top. Push them out with the plunger and withdraw the correct dose of insulin. Lift the vial off the syringe.
     
    To inject a dose:
    Select an injection site on the stomach, arm, buttocks, or thigh, and clean with an alcohol wipe. Pinch the skin up with your fingers about three inches apart, and insert the needle at an angle of 45 to 90 degrees. Release the skin and press the plunger all the way down to deliver the insulin. Keep the needle in the skin for at least 2 to 4 seconds so that all of the insulin is injected. Remove the needle from the skin and press gently on the injection site for a moment (but do not rub or massage). Rotate your injection site such that each site is not used more than once every 1 to 2 months. Do not use injection sites that are thickened, red, or bumpy. Never inject insulin into a vein.

    STORAGE

    BASAGLAR:
    - Avoid exposure to heat
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Do not use if product has been frozen
    - Opened container can be stored for up to 28 days at temperatures below 86 degrees F
    - Protect from light
    - Refrigerate (between 36 and 46 degrees F)
    Lantus:
    - Avoid direct heat and sunlight
    - Do not store device in refrigerator
    - Opened container can be stored for up to 28 days at temperatures below 86 degrees F
    - Protect from freezing
    - Protect from light
    - Store unopened containers in refrigerator (36 to 46 degrees F)
    Lantus SoloStar:
    - Avoid direct heat and sunlight
    - Discard if product has been frozen
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Opened container can be stored for up to 28 days at temperatures below 86 degrees F
    - Protect from freezing
    - Protect from light
    - Store unopened containers in refrigerator (36 to 46 degrees F)
    Toujeo SoloStar:
    - Discard if product has been frozen
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Protect from extreme heat
    - Protect from light
    - Store opened (in use) product at room temperature (below 86 degrees F), discard unused product after 42 days
    - Store unopened containers in refrigerator (36 to 46 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Diarrhea, fever, infection, surgery, thyroid disease, trauma, vomiting

    Changes in insulin products should be made by experienced medical personnel. Changes in insulin species source (i.e., animal versus human, etc.), purity, or brand can necessitate dosage adjustments. The physiologic response resulting from the mixing of different insulins for subcutaneous administration together may differ from the response occurring when the insulins are administered separately. Treatment must be individualized. Diabetic patients must follow a regular, prescribed diet and exercise schedule to avoid either hypo- or hyperglycemia. The timing of meals and exercise with insulin doses is extremely important, and should remain consistent, unless prescribed otherwise. Fever, thyroid disease, infection, recent trauma or surgery, diarrhea secondary to malabsorption, vomiting, and certain medications can also affect insulin requirements, requiring dosage adjustments. Diabetic patients should be given a 'sick-day' plan to take appropriate action with blood glucose monitoring and insulin glargine therapy when acute illness is present.

    Hepatic disease, renal failure, renal impairment

    Hepatic disease, renal impairment, or renal failure may affect insulin glargine dosage requirements. Some pharmacokinetic studies have shown increased circulating levels of insulin in patients with hepatic or renal failure. Insulin dosage adjustments may be needed in some patients.

    Coma, continuous subcutaneous insulin infusion (CSII) administration, diabetic ketoacidosis, hyperosmolar hyperglycemic state (HHS), intravenous administration

    Insulin glargine is not appropriate for intravenous administration (IV); the prolonged activity of insulin glargine is dependent on injection into subcutaneous tissue. IV administration of the usual subcutaneous dosage could result in severely low blood glucose concentrations. Long-acting insulin preparations should not be used for diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), diabetic coma, or other emergencies requiring rapid onset of insulin action. Several types, routes, and frequencies of administration of insulin have been studied in patients with DKA and HHS; however, the American Diabetes Association recommends that regular insulin (versus the rapid-acting analogs) by continuous intravenous infusion be used to treat these conditions unless they are considered mild. Regular insulin is also preferred for those patients with poor tissue perfusion, shock, or cardiovascular collapse, or in patients requiring insulin for the treatment of hyperkalemia. Insulin glargine should not be used for continuous subcutaneous insulin infusion (CSII) administration; only quick-acting insulins (e.g., regular insulin, insulin lispro, insulin glulisine, and insulin aspart) should be used by this route of administration.

    Geriatric, hypoglycemia

    Hypoglycemia is the most common adverse effect of insulin therapy; hypoglycemia is the major barrier to achieving optimal glycemic control long term. Insulin glargine is contraindicated during episodes of hypoglycemia. Patients at risk for hypoglycemia are those who have brittle diabetes, have received an overdose of insulin, have a delayed or decreased food intake, or undergo an excessive amount of exercise relative to their usual insulin dose. Patients at risk for severe, iatrogenic hypoglycemia include those with insulin deficiency (i.e., type 1 diabetes mellitus and advanced type 2 diabetes mellitus), those with a history of severe hypoglycemia or hypoglycemia unawareness, and those undergoing intensive insulin therapy. Patient and family education regarding hypoglycemia management is crucial; the patient and patient's family should be instructed on how to recognize and manage the symptoms of hypoglycemia. Early warning signs of hypoglycemia may be less obvious in patients with hypoglycemia unawareness which can be due to a long history of diabetes (where deficiencies in the release or response to counterregulatory hormones exist), with autonomic neuropathy, or taking beta-blockers. Patients should be aware of the need to have a readily available source of glucose (dextrose, d-glucose) or other carbohydrate to treat hypoglycemic episodes. In patients who are currently taking an alpha-glucosidase inhibitor (i.e., acarbose or miglitol) along with their insulin, oral glucose (dextrose) should be used to treat hypoglycemia; sucrose (table sugar) is unsuitable. In severe hypoglycemia, intravenous dextrose or glucagon injections may be needed. Insulin injections should not be used by the family to treat those patients who are unconscious. Geriatric patients are especially at risk for hypoglycemic episodes when using insulin. The specific reasons identified include intensive insulin therapy, use of an excessive insulin dose, improper timing of insulin administration with regards to meals, injection of the wrong type of insulin, renal failure, severe liver disease, alcohol ingestion, defective counterregulatory hormone release, missing meals/fasting, and gastroparesis. In controlled clinical studies comparing insulin glargine to NPH insulin, 15% of patients with type 1 and type 2 diabetes mellitus were 65 years of age or older; the only difference in safety and efficacy in the subpopulation was an expected higher incidence of cardiovascular events in both the insulin glargine and NPH insulin groups. Because hypoglycemic events may be difficult to recognize in some elderly patients, the initial dosing and dosing increments of any insulin product should be conservative. Severe or frequent hypoglycemia in any patient is an indication for the modification of treatment regimens, including setting higher glycemic goals.

    Hypokalemia

    In addition to hypoglycemia, hypokalemia may also occur as insulin facilitates the intracellular uptake of potassium. Patients taking insulin glargine who are at risk for hypokalemia (e.g., patients who are using potassium-lowering drugs or taking potassium concentration sensitive drugs) should be monitored closely for these effects.

    Cresol hypersensitivity

    Insulin glargine is contraindicated for use in patients hypersensitive to the insulin or the excipients in the formulations. Minor, local sensitivity characterized by redness, swelling, or itching at the site of injection does not usually contraindicate therapy. Insulin glargine contains m-cresol and should be avoided in patients with m-cresol hypersensitivity; localized reactions and general myalgias have been reported with the use of cresol as an injectable excipient. Less common, but potentially more serious, is generalized allergy to insulin, which may cause rash, pruritus, shortness of breath, wheezing, hypotension, tachycardia, and diaphoresis. Severe cases, including anaphylactoid reactions, may be life threatening.

    Pregnancy

    Insulin glargine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no adequate, well-controlled clinical studies of the use of insulin glargine in pregnant women. The American College of Obstetrician and Gynecologists (ACOG) recommends human 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. In general, insulin requirements decline during the first trimester, increase during the second and third trimesters, and then decline significantly after delivery. Post-partum, maternal insulin requirements may need adjustment. Use caution when administering long-acting insulin products near term as insulin requirements may change rapidly and dietary carbohydrate intake may be unpredictable. Careful monitoring of the patient on insulin is required throughout pregnancy. Optimizing glycemic control before conception and during pregnancy appears to improve fetal outcome; this should include the avoidance of episodes of hypoglycemia as the toxic effects of maternal hypoglycemia on the fetus have been well-documented. During the perinatal period, careful monitoring of neonates born to mothers with diabetes is recommended. Rat and rabbit studies of insulin glargine (at 7 to 50 times and 2 to 10 times, respectively, the initial recommended dose in humans) indicate that there are no significant differences in fetal outcome when compared to regular insulin. Fetal abnormalities in animal studies of insulin have not been reported when insulin is used at doses similar to those that would be used in humans; however, high doses of insulin inducing maternal hypoglycemia have been associated with fetal toxicity such as pre- and post-implantation losses and visceral/skeletal abnormalities. In animal studies with insulin aspart and regular human insulin, doses approximately 32 times and 10 times the human subcutaneous dose of 1 unit/kg/day have resulted in such abnormalities.

    Breast-feeding

    The extent of excretion of insulin glargine into breast milk is unknown; however, many drugs, including human insulin, are excreted into human milk. Use caution when administering insulin glargine to a nursing woman; use of insulin glargine is compatible with breast-feeding, but women with diabetes who are lactating may require adjustments of their insulin doses. Breast-feeding may decrease insulin requirements, despite the need for increased caloric intake. Careful observation of increased maternal caloric needs and maternal blood glucose levels are needed. Insulin is degraded in the gastrointestinal tract; therefore, any insulin secreted into breast milk would not be absorbed by a breast-feeding infant. The American Diabetes Association encourages breast-feeding in women with pre-existing diabetes mellitus or gestational diabetes; accordingly, women on insulin therapy should be encouraged to breast-feed if no other contraindications exist.

    Tobacco smoking

    Monitor blood glucose concentrations for needed insulin glargine dosage adjustments in insulin-dependent diabetic patients whenever a change in either nicotine intake or tobacco smoking status occurs. Nicotine activates neuroendocrine pathways (e.g., increases in circulating cortisol and catecholamine levels) and may increase plasma glucose. Tobacco smoking is known to aggravate insulin resistance. The cessation of nicotine therapy or tobacco smoking may result in a decrease in blood glucose or an increase the subcutaneous absorption of insulin, respectively.

    ADVERSE REACTIONS

    Severe

    insulin shock / Delayed / 0-1.0
    anaphylactoid reactions / Rapid / 0-1.0
    anaphylactic shock / Rapid / Incidence not known
    bronchospasm / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    retinopathy / Delayed / Incidence not known

    Moderate

    peripheral edema / Delayed / 20.0-20.0
    hypertension / Early / 19.6-19.6
    cataracts / Delayed / 18.1-18.1
    depression / Delayed / 10.5-10.5
    hypoglycemia / Early / 10.0
    hyperinsulinemia / Early / Incidence not known
    Somogyi effect / Delayed / Incidence not known
    hypokalemia / Delayed / Incidence not known
    lipodystrophy / Delayed / Incidence not known
    wheezing / Rapid / Incidence not known
    erythema / Early / Incidence not known
    hypotension / Rapid / Incidence not known
    antibody formation / Delayed / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known

    Mild

    infection / Delayed / 5.0-29.0
    influenza / Delayed / 18.7-18.7
    sinusitis / Delayed / 18.5-18.5
    arthralgia / Delayed / 14.2-14.2
    pharyngitis / Delayed / 7.1-12.8
    back pain / Delayed / 12.8-12.8
    cough / Delayed / 12.1-12.1
    diarrhea / Early / 10.7-10.7
    headache / Early / 5.5-10.3
    rhinitis / Early / 5.0-5.2
    injection site reaction / Rapid / 2.7-2.7
    rash (unspecified) / Early / 0-1.0
    weight gain / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    insulin resistance / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acebutolol: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    Acetaminophen; Aspirin, ASA; Caffeine: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Acetaminophen; Dextromethorphan; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Acetaminophen; Dichloralphenazone; Isometheptene: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Acetaminophen; Guaifenesin; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    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: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    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.
    Acrivastine; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Aliskiren; Hydrochlorothiazide, HCTZ: Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Aliskiren; Valsartan: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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.
    Alogliptin; Pioglitazone: The risk of heart failure and/or edema is increased when thiazolidinediones (including pioglitazone) are combined with insulins; monitor combined therapy closely for signs or symptoms of congestive heart failure. Pioglitazone should be discontinued if any deterioration in cardiac status occurs. 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.
    Amiloride; Hydrochlorothiazide, HCTZ: Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Aminosalicylate sodium, Aminosalicylic acid: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Amlodipine; Benazepril: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Amlodipine; Olmesartan: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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.
    Amlodipine; Telmisartan: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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.
    Amlodipine; Valsartan: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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.
    Amoxicillin; Clarithromycin; Lansoprazole: Clarithromycin may enhance the hypoglycemic effects of antidiabetic agents.
    Amoxicillin; Clarithromycin; Omeprazole: Clarithromycin may enhance the hypoglycemic effects of antidiabetic agents.
    Amphetamine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Amphetamine; Dextroamphetamine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Amprenavir: Monitor patients receiving insulin closely for changes in diabetic control, specifically hyperglycemia, when anti-retroviral protease inhibitors are instituted. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another 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.
    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.
    Angiotensin II receptor antagonists: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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.
    Angiotensin-converting enzyme inhibitors: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease.
    Aripiprazole: Patients taking insulin 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: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Asenapine: Patients taking insulin 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: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Aspirin, ASA; Butalbital; Caffeine: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Aspirin, ASA; Caffeine; Dihydrocodeine: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Aspirin, ASA; Carisoprodol: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Aspirin, ASA; Carisoprodol; Codeine: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Aspirin, ASA; Dipyridamole: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Aspirin, ASA; Omeprazole: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Aspirin, ASA; Oxycodone: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Aspirin, ASA; Pravastatin: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Atazanavir: Monitor patients receiving insulin closely for changes in diabetic control, specifically hyperglycemia, when anti-retroviral protease inhibitors are instituted. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another 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.
    Atazanavir; Cobicistat: Monitor patients receiving insulin closely for changes in diabetic control, specifically hyperglycemia, when anti-retroviral protease inhibitors are instituted. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another 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.
    Atenolol: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    Atenolol; Chlorthalidone: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    atypical antipsychotic: Patients taking insulin 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.
    Azelaic Acid; Copper; Folic Acid; Nicotinamide; Pyridoxine; Zinc: Monitor patients receiving insulin closely for changes in diabetic control when niacin, niacinamide is instituted or discontinued. Dosage adjustments may be necessary. Niacin interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750 to 2000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. 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: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Azilsartan: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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.
    Azilsartan; Chlorthalidone: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Baclofen: Because baclofen can increase blood glucose, doses of antidiabetic agents may need adjustment in patients receiving these drugs concomitantly.
    Beclomethasone: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Benazepril: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease.
    Benazepril; Hydrochlorothiazide, HCTZ: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Bendroflumethiazide; Nadolol: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Benzphetamine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Beta-blockers: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    Betamethasone: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Betaxolol: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    Bexarotene: Systemic bexarotene may enhance the action of insulins resulting in hypoglycemia. Patients should be closely monitored while receiving bexarotene capsules in combination with insulin; monitor for hypoglycemia and the need for diabetic therapy adjustments.
    Bismuth Subsalicylate: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Bisoprolol: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    Bisoprolol; Hydrochlorothiazide, HCTZ: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    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 medications.
    Brexpiprazole: Patients taking insulin 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: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    Brompheniramine; Carbetapentane; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Brompheniramine; Hydrocodone; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Brompheniramine; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Budesonide: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Budesonide; Formoterol: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Bumetanide: Monitor patients receiving insulin closely for worsening glycemic control when bumetanide, furosemide, and torsemide are instituted. Bumetanide, furosemide, and torsemide 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 these drugs and all antidiabetic agents.
    Candesartan: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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.
    Candesartan; Hydrochlorothiazide, HCTZ: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Captopril: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease.
    Captopril; Hydrochlorothiazide, HCTZ: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Carbetapentane; Chlorpheniramine; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Carbetapentane; Diphenhydramine; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Carbetapentane; Guaifenesin; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Carbetapentane; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Carbetapentane; Phenylephrine; Pyrilamine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Carbetapentane; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Carbinoxamine; Hydrocodone; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Carbinoxamine; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Carbinoxamine; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    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 insulin 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: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    Carvedilol: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    Cetirizine; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Chlophedianol; Guaifenesin; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Chlorothiazide: Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Chlorpheniramine; Hydrocodone; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Chlorpheniramine; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Chlorpheniramine; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Chlorpromazine: Monitor patients receiving insulin closely for worsening glycemic control when phenothiazines are instituted. The phenothiazines, especially chlorpromazine, may increase blood glucose concentrations.
    Chlorthalidone: Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Chlorthalidone; Clonidine: Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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. Monitor patients receiving insulin closely for changes in glycemic control when clonidine is instituted. Clonidine may potentiate or weaken the hypoglycemic effects of antidiabetic agents, and may also mask the signs and symptoms of hypoglycemia.
    Choline Salicylate; Magnesium Salicylate: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Chromium: Chromium appears to facilitate the binding of insulin to insulin receptors in tissues and to aide 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.
    Ciprofloxacin: Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including insulins, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent.
    Cisapride: Because cisapride 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 cisapride concomitantly.
    Clarithromycin: Clarithromycin may enhance the hypoglycemic effects of antidiabetic agents.
    Clonidine: Monitor patients receiving insulin closely for changes in glycemic control when clonidine is instituted. Clonidine may potentiate or weaken the hypoglycemic effects of antidiabetic agents, and may also mask the signs and symptoms of hypoglycemia.
    Clozapine: Patients taking insulin 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.
    Codeine; Phenylephrine; Promethazine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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. It is unclear if phenothiazines directly interact with antidiabetic agents, phenothiazines have been reported to increase blood glucose concentrations. Promethazine should be used cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    Codeine; Promethazine: It is unclear if phenothiazines directly interact with antidiabetic agents, phenothiazines have been reported to increase blood glucose concentrations. Promethazine should be used cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    Colesevelam: In patients with type 2 diabetes mellitus receiving insulins, colesevelam increased serum triglyceride concentrations by 22% compared to placebo. Monitor patients for increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are > 500 mg/dl or if hypertriglyceridemia-induced pancreatitis occurs.
    Conjugated Estrogens: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect.
    Conjugated Estrogens; Bazedoxifene: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect.
    Conjugated Estrogens; Medroxyprogesterone: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Corticosteroids: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Corticotropin, ACTH: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Cortisone: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Cyclosporine: Cyclosporine may cause hyperglycemia. Patients should be monitored for worsening of glycemic control if therapy with cyclosporine is initiated in patients receiving insulin.
    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.
    Darunavir: Monitor patients receiving insulin closely for changes in diabetic control, specifically hyperglycemia, when anti-retroviral protease inhibitors are instituted. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another 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.
    Darunavir; Cobicistat: Monitor patients receiving insulin closely for changes in diabetic control, specifically hyperglycemia, when anti-retroviral protease inhibitors are instituted. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another 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.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: Monitor patients receiving insulin closely for changes in diabetic control, specifically hyperglycemia, when anti-retroviral protease inhibitors are instituted. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another 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.
    Desiccated Thyroid: Monitor patients receiving insulin closely for changes in diabetic control whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced.
    Desloratadine; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Dexamethasone: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Dexmethylphenidate: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Dextroamphetamine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Dextromethorphan; Diphenhydramine; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Dextromethorphan; Guaifenesin; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Dextromethorphan; Promethazine: It is unclear if phenothiazines directly interact with antidiabetic agents, phenothiazines have been reported to increase blood glucose concentrations. Promethazine should be used cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    Diazoxide: The hyperglycemic action of diazoxide can be diminished in patients receiving insulin, and, conversely, the dosage of insulin may need to be adjusted when diazoxide is added to the regimen.
    Dienogest; Estradiol valerate: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Diethylpropion: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Diethylstilbestrol, DES: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Diphenhydramine; Hydrocodone; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Diphenhydramine; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Disopyramide: Monitor patients receiving disopyramide concomitantly with insulin for changes in glycemic control. Disopyramide may enhance the hypoglycemic effects of insulin.
    Dobutamine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Dopamine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Dorzolamide; Timolol: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    Drospirenone; Estradiol: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Drospirenone; Ethinyl Estradiol: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Drospirenone; Ethinyl Estradiol; Levomefolate: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Edetate Calcium Disodium, Calcium EDTA: Use caution in administration of calcium EDTA to patients with diabetes mellitus who are receiving insulin therapy. Calcium EDTA chelates the zinc in selected exogenous insulins, thereby increasing the amount of insulin available to the body and decreasing the duration of the insulin dose. Alterations in blood glucose control may result. Diabetic patients receiving calcium EDTA may require adjustments in their insulin dosage.
    Edetate Disodium, Disodium EDTA: Use caution in administration of calcium EDTA to patients with diabetes mellitus who are receiving insulin therapy. Calcium EDTA chelates the zinc in selected exogenous insulins, thereby increasing the amount of insulin available to the body and decreasing the duration of the insulin dose. Alterations in blood glucose control may result. Diabetic patients receiving calcium EDTA may require adjustments in their insulin dosage.
    Enalapril, Enalaprilat: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease.
    Enalapril; Felodipine: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease.
    Enalapril; Hydrochlorothiazide, HCTZ: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Ephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Epinephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Eprosartan: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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.
    Eprosartan; Hydrochlorothiazide, HCTZ: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Erythromycin; Sulfisoxazole: Monitor patients receiving sulfonamides concomitantly with insulin for changes in glycemic control. Sulfonamides may enhance the hypoglycemic action of insulin. 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.
    Esmolol: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    Esterified Estrogens: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect.
    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. Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect.
    Estradiol Cypionate; Medroxyprogesterone: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Estradiol: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect.
    Estradiol; Levonorgestrel: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Estradiol; Norethindrone: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Estradiol; Norgestimate: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy 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: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect.
    Estropipate: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect.
    Ethanol: Monitor patients receiving insulin closely for changes in diabetic control if alcohol (ethanol) is consumed; dosage adjustments of insulin may be necessary. Alcohol may cause variable effects on glycemic control when used in patients receiving insulin or other 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. Encourage patients 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; have patients scrutinize product labels prior to consumption.
    Ethinyl Estradiol: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect.
    Ethinyl Estradiol; Desogestrel: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Ethinyl Estradiol; Ethynodiol Diacetate: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Ethinyl Estradiol; Etonogestrel: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Ethinyl Estradiol; Levonorgestrel: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Ethinyl Estradiol; Norelgestromin: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Ethinyl Estradiol; Norethindrone Acetate: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Ethinyl Estradiol; Norethindrone: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Ethinyl Estradiol; Norgestimate: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Ethinyl Estradiol; Norgestrel: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Ethotoin: Ethotoin 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 decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Exenatide: In a 30-week safety and efficacy trial, when exenatide was initiated in combination with insulin glargine, the dose of insulin glargine was decreased by 20% in patients with an HbA1c <= 8% to minimize the risk of hypoglycemia. The manufacturer of exenatide provides an insulin glargine dose titration algorithm to aide clinicians when using exenatide with insulin glargine. Patients should also self-monitor blood glucose levels. It should be noted that extended-release exenatide has not been studied with insulin and concomitant administration cannot be recommended.
    Fenofibrate: Monitor patients receiving fibric acid derivatives concomitantly with insulin for changes in glycemic control. Fibric acid derivatives may enhance the hypoglycemic effects of insulin or other antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion.
    Fenofibric Acid: Monitor patients receiving fibric acid derivatives concomitantly with insulin for changes in glycemic control. Fibric acid derivatives may enhance the hypoglycemic effects of insulin or other antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion.
    Fexofenadine; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Fibric acid derivatives: Monitor patients receiving fibric acid derivatives concomitantly with insulin for changes in glycemic control. Fibric acid derivatives may enhance the hypoglycemic effects of insulin or other antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion.
    Fludrocortisone: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Flunisolide: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Fluoxetine: Monitor patients receiving fluoxetine concomitantly with insulin for changes in glycemic control. Fluoxetine may enhance the hypoglycemic effects of insulin and other antidiabetic agents.
    Fluoxetine; Olanzapine: Monitor patients receiving fluoxetine concomitantly with insulin for changes in glycemic control. Fluoxetine may enhance the hypoglycemic effects of insulin and other antidiabetic agents. Patients taking insulin 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.
    Fluphenazine: Monitor patients receiving insulin closely for worsening glycemic control when phenothiazines are instituted. The phenothiazines, especially chlorpromazine, may increase blood glucose concentrations.
    Fluticasone: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Fluticasone; Salmeterol: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Fluticasone; Vilanterol: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Formoterol; Mometasone: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Fosamprenavir: Monitor patients receiving insulin closely for changes in diabetic control, specifically hyperglycemia, when anti-retroviral protease inhibitors are instituted. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another 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.
    Fosinopril: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease.
    Fosinopril; Hydrochlorothiazide, HCTZ: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Fosphenytoin: Fosphenytoin 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: Monitor patients receiving insulin closely for worsening glycemic control when bumetanide, furosemide, and torsemide are instituted. Bumetanide, furosemide, and torsemide 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 these drugs and all antidiabetic agents.
    Garlic, Allium sativum: 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: Monitor patients receiving fibric acid derivatives concomitantly with insulin for changes in glycemic control. Fibric acid derivatives may enhance the hypoglycemic effects of insulin or other antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion.
    Gemifloxacin: 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; Pioglitazone: The risk of heart failure and/or edema is increased when thiazolidinediones (including pioglitazone) are combined with insulins; monitor combined therapy closely for signs or symptoms of congestive heart failure. Pioglitazone should be discontinued if any deterioration in cardiac status occurs. 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.
    Glimepiride; Rosiglitazone: 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%).
    Glucagon: Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When glucagon is administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin degludec. Glucagon is often used to treat hypoglycemia in patients with diabetes mellitus.
    Green Tea: Green tea catechins have been shown to decrease serum glucose concentrations. Patients with diabetes mellitus taking antidiabetic agents should be monitored closely for hypoglycemia if consuming green tea products.
    Guaifenesin; Hydrocodone; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Guaifenesin; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Guaifenesin; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Hydralazine; Hydrochlorothiazide, HCTZ: Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Hydrochlorothiazide, HCTZ: Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Hydrochlorothiazide, HCTZ; Irbesartan: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Hydrochlorothiazide, HCTZ; Lisinopril: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Hydrochlorothiazide, HCTZ; Losartan: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Hydrochlorothiazide, HCTZ; Methyldopa: Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Hydrochlorothiazide, HCTZ; Metoprolol: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Hydrochlorothiazide, HCTZ; Moexipril: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Hydrochlorothiazide, HCTZ; Olmesartan: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Hydrochlorothiazide, HCTZ; Propranolol: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Hydrochlorothiazide, HCTZ; Quinapril: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Hydrochlorothiazide, HCTZ; Spironolactone: Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Hydrochlorothiazide, HCTZ; Telmisartan: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Hydrochlorothiazide, HCTZ; Triamterene: Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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. Triamterene can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. Patients receiving insulin should be closely monitored for signs indicating loss of diabetic control when therapy with triamterene is instituted. In addition, patients receiving insulin should be closely monitored for signs of hypoglycemia when therapy with any of these other agents is discontinued.
    Hydrochlorothiazide, HCTZ; Valsartan: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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. Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Hydrocodone; Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Hydrocodone; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Hydrocortisone: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Hydroxyprogesterone: Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Ibuprofen; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Iloperidone: Patients taking insulin 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.
    Indapamide: A potential pharmacodynamic interaction exists between indapamide and antidiabetic agents, like insulins. Indapamide can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia.
    Indinavir: Monitor patients receiving insulin closely for changes in diabetic control, specifically hyperglycemia, when anti-retroviral protease inhibitors are instituted. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another 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.
    Irbesartan: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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.
    Isocarboxazid: Monitor patients receiving monoamine oxidase inhibitors (MAOIs) concomitantly with insulin for changes in glycemic control. Animal data indicate that MAOIs may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas.
    Isoniazid, INH: Monitor patients receiving insulin closely for changes in diabetic control when isoniazid, INH is instituted or discontinued. Although rare, isoniazid, INH may increase blood sugar. Insulin requirements may be increased when patients are administered isoniazid, INH concomitantly.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: Monitor patients receiving insulin closely for changes in diabetic control when isoniazid, INH is instituted or discontinued. Although rare, isoniazid, INH may increase blood sugar. Insulin requirements may be increased when patients are administered isoniazid, INH concomitantly.
    Isoniazid, INH; Rifampin: Monitor patients receiving insulin closely for changes in diabetic control when isoniazid, INH is instituted or discontinued. Although rare, isoniazid, INH may increase blood sugar. Insulin requirements may be increased when patients are administered isoniazid, INH concomitantly.
    Isoproterenol: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Labetalol: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    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.
    Leuprolide; Norethindrone: Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Levobetaxolol: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    Levobunolol: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    Levocarnitine: Chromium appears to facilitate the binding of insulin to insulin receptors in tissues and to aide 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: Hyperglycemia and hypoglycemia have been reported in patients treated concomitantly with quinolones and antidiabetic agents. Close monitoring of blood glucose is recommended when these agents are coadministered.
    Levonorgestrel: Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Levothyroxine: Monitor patients receiving insulin closely for changes in diabetic control whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced.
    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.
    Liothyronine: Monitor patients receiving insulin closely for changes in diabetic control whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced.
    Liotrix: Monitor patients receiving insulin closely for changes in diabetic control whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced.
    Lisdexamfetamine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Lisinopril: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease.
    Lithium: Monitor patients receiving insulin closely for changes in glycemic control when lithium is instituted; dosage adjustments of insulin may be necessary. Lithium may cause variable effects on glycemic control when used in patients receiving insulin or other antidiabetic therapy.
    Lomefloxacin: 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: Monitor patients receiving insulin closely for changes in diabetic control, specifically hyperglycemia, when anti-retroviral protease inhibitors are instituted. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another 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.
    Loratadine; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    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: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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.
    Lovastatin; Niacin: Monitor patients receiving insulin closely for changes in diabetic control when niacin, niacinamide is instituted or discontinued. Dosage adjustments may be necessary. Niacin interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750 to 2000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy.
    Lurasidone: Patients taking insulin 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: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Mecasermin rinfabate: Use caution in combining mecasermin with antidiabetic agents. The hypoglycemic effect induced by mecasermin may be exacerbated.
    Mecasermin, Recombinant, rh-IGF-1: Use caution in combining mecasermin with antidiabetic agents. The hypoglycemic effect induced by mecasermin may be exacerbated.
    Medroxyprogesterone: Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Megestrol: Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Meperidine; Promethazine: It is unclear if phenothiazines directly interact with antidiabetic agents, phenothiazines have been reported to increase blood glucose concentrations. Promethazine should be used cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    Mepivacaine; Levonordefrin: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Mesoridazine: Monitor patients receiving insulin closely for worsening glycemic control when phenothiazines are instituted. The phenothiazines, especially chlorpromazine, may increase blood glucose concentrations.
    Mestranol; Norethindrone: Monitor patients receiving insulin closely for changes in diabetic control when estrogens, progestins, or oral contraceptives are instituted or discontinued. Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Metformin; Pioglitazone: The risk of heart failure and/or edema is increased when thiazolidinediones (including pioglitazone) are combined with insulins; monitor combined therapy closely for signs or symptoms of congestive heart failure. Pioglitazone should be discontinued if any deterioration in cardiac status occurs. 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.
    Metformin; Rosiglitazone: 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%).
    Methamphetamine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    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.
    Methohexital: The risk of developing hypothermia is increased when methohexital is used with hypothermia-producing agents such as ethanol, insulins, phenothiazines, or other general anesthetics.
    Methyclothiazide: Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Methylphenidate: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Methylprednisolone: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    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.
    Metoclopramide: Because metoclopramide can enhance gastric emptying in diabetic patients, blood glucose levels can be affected by changes in the intestinal transit of food, which, in turn, may affect the dosing of antidiabetic agents, including insulin.
    Metolazone: Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Metoprolol: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    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.
    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.
    Midodrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Moexipril: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease.
    Mometasone: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Monoamine oxidase inhibitors: Monitor patients receiving monoamine oxidase inhibitors (MAOIs) concomitantly with insulin for changes in glycemic control. Animal data indicate that MAOIs may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas.
    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.
    Nadolol: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    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.
    Naproxen; Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Nebivolol: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    Nebivolol; Valsartan: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus. Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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.
    Nelfinavir: Monitor patients receiving insulin closely for changes in diabetic control, specifically hyperglycemia, when anti-retroviral protease inhibitors are instituted. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another 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.
    Niacin, Niacinamide: Monitor patients receiving insulin closely for changes in diabetic control when niacin, niacinamide is instituted or discontinued. Dosage adjustments may be necessary. Niacin interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750 to 2000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy.
    Niacin; Simvastatin: Monitor patients receiving insulin closely for changes in diabetic control when niacin, niacinamide is instituted or discontinued. Dosage adjustments may be necessary. Niacin interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750 to 2000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy.
    Nicotine: Nicotine may increase plasma glucose. Monitor blood sugar for needed insulin dosage adjustments in insulin-dependent diabetic patients whenever a change in either nicotine intake or smoking status occurs. In addition, the use of inhaled insulin is not recommended in patients who smoke. Smoking tobacco can alter the effect of inhaled insulin in several ways. First, nicotine activates neuroendocrine pathways (e.g., increases in circulating cortisol and catecholamine levels) and may increase plasma glucose. Second, tobacco smoking is known to aggravate insulin resistance. Finally, compared with non-smokers, insulin exposure after inhalation may be greater in patients who smoke. If inhaled insulin is used in this population, patients should be instructed to monitor blood glucose concentrations closely. If a change in smoking status or nicotine intake occur, patients should continue to monitor their blood glucose concentrations closely and clinicians should adjust the dose of insulin when indicated.
    Norepinephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Norethindrone: Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy 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.
    Norgestrel: Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Octreotide: Monitor patients receiving octreotide concomitantly with insulin for changes in glycemic control and adjust doses of these medications accordingly. 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.
    Ofloxacin: 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 insulin 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: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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.
    Ombitasvir; Paritaprevir; Ritonavir: Monitor patients receiving insulin closely for changes in diabetic control, specifically hyperglycemia, when anti-retroviral protease inhibitors are instituted. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another 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.
    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.
    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.
    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.
    Paliperidone: Patients taking insulin 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.
    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. Diabetic patients should monitor their blood glucose regularly with doses of anti-diabetic medications reduced as necessary.
    Pemoline: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Penbutolol: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    Pentamidine: Monitor patients receiving insulin closely for changes in glycemic control during the use of pentamidine; dosage adjustments of insulin may be necessary. Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed hyperglycemia with prolonged pentamidine therapy.
    Pentoxifylline: Monitor patients receiving pentoxifylline concomitantly with insulin for changes in glycemic control. Pentoxifylline may enhance the hypoglycemic action of insulin.
    Perindopril: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease.
    Perindopril; Amlodipine: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease.
    Perphenazine: Monitor patients receiving insulin closely for worsening glycemic control when phenothiazines are instituted. The phenothiazines, especially chlorpromazine, may increase blood glucose concentrations.
    Perphenazine; Amitriptyline: Monitor patients receiving insulin closely for worsening glycemic control when phenothiazines are instituted. The phenothiazines, especially chlorpromazine, may increase blood glucose concentrations.
    Phendimetrazine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Phenelzine: Monitor patients receiving monoamine oxidase inhibitors (MAOIs) concomitantly with insulin for changes in glycemic control. Animal data indicate that MAOIs may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas.
    Phenothiazines: Monitor patients receiving insulin closely for worsening glycemic control when phenothiazines are instituted. The phenothiazines, especially chlorpromazine, may increase blood glucose concentrations.
    Phentermine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Phentermine; Topiramate: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Phenylephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Phenylephrine; Promethazine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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. It is unclear if phenothiazines directly interact with antidiabetic agents, phenothiazines have been reported to increase blood glucose concentrations. Promethazine should be used cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    Phenytoin: 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.
    Pimavanserin: Patients taking insulin 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: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    Pioglitazone: The risk of heart failure and/or edema is increased when thiazolidinediones (including pioglitazone) are combined with insulins; monitor combined therapy closely for signs or symptoms of congestive heart failure. Pioglitazone should be discontinued if any deterioration in cardiac status occurs. 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.
    Pramlintide: Pramlintide is indicated to be used in combination with insulins; however, pramlintide increases the risk of insulin-induced hypoglycemia. Because of this increased risk, a dose reduction in mealtime insulin is warranted during the titration period with pramlintide. Per the manufacturer, insulin and pramlintide should not be combined in the same syringe or administered in the same injection site as the pharmacokinetic parameters of pramlintide are altered by regular, isophane (NPH), and premixed 70/30 insulin formulations; however, in a randomized, open-label crossover study in type 1 diabetes patients, the pharmacokinetics, pharmacodynamics, and safety of 30 mcg of pramlintide were not changed significantly when mixed with various short-acting insulins, long-acting insulins, or both immediately before injection. Because not all insulin types, doses of insulin, and doses of pramlintide were studied, mixing pramlintide with insulin prior to injection should be avoided. Furthermore, most insulins are formulated at a pH of approximately 7 and are not compatible with pramlintide which is formulated at a pH of 4.
    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.
    Prednisolone: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Prednisone: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Prilocaine; Epinephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Prochlorperazine: Monitor patients receiving insulin closely for worsening glycemic control when phenothiazines are instituted. The phenothiazines, especially chlorpromazine, may increase blood glucose concentrations.
    Progesterone: Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Progestins: Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
    Promethazine: It is unclear if phenothiazines directly interact with antidiabetic agents, phenothiazines have been reported to increase blood glucose concentrations. Promethazine should be used cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    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: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    Protease inhibitors: Monitor patients receiving insulin closely for changes in diabetic control, specifically hyperglycemia, when anti-retroviral protease inhibitors are instituted. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another 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.
    Pseudoephedrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Pyrimethamine; Sulfadoxine: Monitor patients receiving sulfonamides concomitantly with insulin for changes in glycemic control. Sulfonamides may enhance the hypoglycemic action of insulin. 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.
    Quetiapine: Patients taking insulin 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: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease.
    Racepinephrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Ramipril: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease.
    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: Monitor patients receiving insulin closely for changes in glycemic control during the use of reserpine. Reserpine may mask the signs and symptoms of hypoglycemia.
    Risperidone: Patients taking insulin 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.
    Ritodrine: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Ritonavir: Monitor patients receiving insulin closely for changes in diabetic control, specifically hyperglycemia, when anti-retroviral protease inhibitors are instituted. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another 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.
    Rosiglitazone: 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%).
    Sacubitril; Valsartan: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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.
    Salicylates: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Salsalate: Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
    Saquinavir: Monitor patients receiving insulin closely for changes in diabetic control, specifically hyperglycemia, when anti-retroviral protease inhibitors are instituted. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another 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.
    Selegiline, Transdermal: Monitor patients receiving monoamine oxidase inhibitors (MAOIs) concomitantly with insulin for changes in glycemic control. Animal data indicate that MAOIs may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas.
    Selegiline: Monitor patients receiving monoamine oxidase inhibitors (MAOIs) concomitantly with insulin for changes in glycemic control. Animal data indicate that MAOIs may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas.
    Sodium Polystyrene Sulfonate: Sodium polystyrene sulfonate should be used cautiously with other agents that can induce hypokalemia such as loop diuretics, insulins, or intravenous sodium bicarbonate. Because of differences in onset of action, sodium polystyrene sulfonate is often used with these agents. With appropriate monitoring, hypokalemia can be avoided.
    Somatropin, rh-GH: Monitor patients receiving insulin closely for worsening glycemic control when somatropin, rh-GH is instituted and for signs of hypoglycemia when somatropin, rh-GH is discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., somatropin, rh-GH) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Sotalol: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    Sparfloxacin: 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.
    Sulfadiazine: Monitor patients receiving sulfonamides concomitantly with insulin for changes in glycemic control. Sulfonamides may enhance the hypoglycemic action of insulin. 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.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: Monitor patients receiving sulfonamides concomitantly with insulin for changes in glycemic control. Sulfonamides may enhance the hypoglycemic action of insulin. 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.
    Sulfasalazine: Monitor patients receiving sulfonamides concomitantly with insulin for changes in glycemic control. Sulfonamides may enhance the hypoglycemic action of insulin. 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.
    Sulfinpyrazone: A case report describes an episode of brief hypoglycemia in a diabetic patient receiving both insulins and sulfinpyrazone. The patient responded spontaneously, and an association with sulfinpyrazone was not clearly established. In another report, no changes in insulin requirements were required when sulfinpyrazone therapy was added.
    Sulfisoxazole: Monitor patients receiving sulfonamides concomitantly with insulin for changes in glycemic control. Sulfonamides may enhance the hypoglycemic action of insulin. 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.
    Sulfonamides: Monitor patients receiving sulfonamides concomitantly with insulin for changes in glycemic control. Sulfonamides may enhance the hypoglycemic action of insulin. 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.
    Sympathomimetics: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. 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.
    Tacrolimus: Tacrolimus has been reported to cause hyperglycemia. Patients should be monitored for worsening of glycemic control if therapy with tacrolimus is initiated in patients receiving antidiabetic agents.
    Tegaserod: Because tegaserod can enhance gastric emptying in patients with diabetes, blood glucose can be affected, which, in turn, may affect the clinical response to antidiabetic agents.
    Telmisartan: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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.
    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.
    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.
    Thiazide diuretics: Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. 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.
    Thiethylperazine: Monitor patients receiving insulin closely for worsening glycemic control when phenothiazines are instituted. The phenothiazines, especially chlorpromazine, may increase blood glucose concentrations.
    Thioridazine: Monitor patients receiving insulin closely for worsening glycemic control when phenothiazines are instituted. The phenothiazines, especially chlorpromazine, may increase blood glucose concentrations.
    Thyroid hormones: Monitor patients receiving insulin closely for changes in diabetic control whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced.
    Timolol: Although no pharmacokinetic interaction has been observed between beta-blockers and antidiabetic agents, patients receiving beta-blockers and insulin concomitantly should be closely monitored for an inappropriate response. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, beta-blockers may cause a pharmacodynamic interaction with antidiabetic agents. Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Furthermore, a prospective trial in non-diabetic patients with hypertension indicated that treatment with beta-blockers increased the risk of the development of diabetes by 28% at six years. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia, specifically the tachycardic response, and exaggerate the hypertensive response to hypoglycemia. Selective beta-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    Tipranavir: Monitor patients receiving insulin closely for changes in diabetic control, specifically hyperglycemia, when anti-retroviral protease inhibitors are instituted. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another 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.
    Torsemide: Monitor patients receiving insulin closely for worsening glycemic control when bumetanide, furosemide, and torsemide are instituted. Bumetanide, furosemide, and torsemide 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 these drugs and all antidiabetic agents.
    Trandolapril: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease.
    Trandolapril; Verapamil: Monitor patients receiving angiotensin-converting enzyme inhibitors (ACE inhibitors) concomitantly with insulin for changes in glycemic control. ACE inhibitors may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, ACE inhibitors have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease.
    Tranylcypromine: Monitor patients receiving monoamine oxidase inhibitors (MAOIs) concomitantly with insulin for changes in glycemic control. Animal data indicate that MAOIs may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas.
    Triamcinolone: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Triamterene: Triamterene can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. Patients receiving insulin should be closely monitored for signs indicating loss of diabetic control when therapy with triamterene is instituted. In addition, patients receiving insulin should be closely monitored for signs of hypoglycemia when therapy with any of these other agents is discontinued.
    Trifluoperazine: Monitor patients receiving insulin closely for worsening glycemic control when phenothiazines are instituted. The phenothiazines, especially chlorpromazine, may increase blood glucose concentrations.
    Valsartan: Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin 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.
    Ziprasidone: Patients taking insulin 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

    Insulin glargine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no adequate, well-controlled clinical studies of the use of insulin glargine in pregnant women. The American College of Obstetrician and Gynecologists (ACOG) recommends human 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. In general, insulin requirements decline during the first trimester, increase during the second and third trimesters, and then decline significantly after delivery. Post-partum, maternal insulin requirements may need adjustment. Use caution when administering long-acting insulin products near term as insulin requirements may change rapidly and dietary carbohydrate intake may be unpredictable. Careful monitoring of the patient on insulin is required throughout pregnancy. Optimizing glycemic control before conception and during pregnancy appears to improve fetal outcome; this should include the avoidance of episodes of hypoglycemia as the toxic effects of maternal hypoglycemia on the fetus have been well-documented. During the perinatal period, careful monitoring of neonates born to mothers with diabetes is recommended. Rat and rabbit studies of insulin glargine (at 7 to 50 times and 2 to 10 times, respectively, the initial recommended dose in humans) indicate that there are no significant differences in fetal outcome when compared to regular insulin. Fetal abnormalities in animal studies of insulin have not been reported when insulin is used at doses similar to those that would be used in humans; however, high doses of insulin inducing maternal hypoglycemia have been associated with fetal toxicity such as pre- and post-implantation losses and visceral/skeletal abnormalities. In animal studies with insulin aspart and regular human insulin, doses approximately 32 times and 10 times the human subcutaneous dose of 1 unit/kg/day have resulted in such abnormalities.

    The extent of excretion of insulin glargine into breast milk is unknown; however, many drugs, including human insulin, are excreted into human milk. Use caution when administering insulin glargine to a nursing woman; use of insulin glargine is compatible with breast-feeding, but women with diabetes who are lactating may require adjustments of their insulin doses. Breast-feeding may decrease insulin requirements, despite the need for increased caloric intake. Careful observation of increased maternal caloric needs and maternal blood glucose levels are needed. Insulin is degraded in the gastrointestinal tract; therefore, any insulin secreted into breast milk would not be absorbed by a breast-feeding infant. The American Diabetes Association encourages breast-feeding in women with pre-existing diabetes mellitus or gestational diabetes; accordingly, women on insulin therapy should be encouraged to breast-feed if no other contraindications exist.

    MECHANISM OF ACTION

    Endogenous insulin regulates carbohydrate, fat, and protein metabolism by several mechanisms; in general, insulin promotes the storage and inhibits the breakdown of glucose, fat, and amino acids. Insulin lowers glucose concentrations by facilitating the uptake of glucose in muscle and adipose tissue and by inhibiting hepatic glucose production (glycogenolysis and gluconeogenesis). Insulin also regulates fat metabolism by enhancing the storage of fat (lipogenesis) and inhibiting the mobilization of fat for energy in adipose tissues (lipolysis and free fatty acid oxidation). Finally, insulin is involved in the regulation of protein metabolism by increasing protein synthesis and inhibiting proteolysis in muscle tissue.
     
    Diabetes mellitus type 1 is caused by insulin deficiency while diabetes mellitus type 2 is caused by a combination of insulin deficiency and resistance. Biosynthetic insulin is used as replacement therapy in patients with diabetes mellitus to temporarily restore their ability to use fats, carbohydrates, and proteins, and to convert glycogen to fat. Insulin administration also enables these patients to replete their liver glycogen stores. Commercially available insulin is prepared using recombinant DNA technology (E. coli bacteria) or enzymatic modification of beef or pork insulin to create a product identical in structure and function to endogenous human insulin.

    PHARMACOKINETICS

    Insulin glargine is administered via the subcutaneous route only. Endogenous insulin distributes widely throughout the body. A small portion is inactivated by peripheral tissues, but the majority is metabolized by the liver and kidneys. After subcutaneous injection of insulin glargine in diabetic patients, insulin glargine is metabolized at the carboxyl terminus of the Beta chain with formation of two active metabolites M1 (21A-Gly-insulin) and M2 (21A-Gly-des-30B-Thr-insulin). The in vitro activity of M1 and M2 were similar to that of insulin. Insulin is filtered and reabsorbed by the kidneys; the plasma half-life of human endogenous insulin is approximately 5—6 minutes.

    Subcutaneous Route

    Insulin glargine 100 units/mL (Lantus)
    The onset of glucose lowering activity is 1.5 hours; insulin glargine has a constant concentration/time profile over 24 hours with no pronounced peak effect. The median duration of action of insulin glargine is 24 hours. Insulin glargine should be administered once daily, at the same time everyday. After subcutaneous injection of 0.3 units/kg in patients with type 1 diabetes, the duration of action after abdominal, deltoid, or thigh subcutaneous administration was similar.
     
    Insulin glargine 100 units/mL (Basaglar)
    The median time to maximum serum insulin concentration was 12 hours after injection; serum insulin concentrations declined to baseline by approximately 24 hours.
     
    Insulin glargine 300 units/mL (Toujeo)
    On average, the onset of glucose lowering activity after single doses of 0.4, 0.6, 0.9 units/kg developed over 6 hours and mean serum insulin concentrations declined to the lower limit of quantitation by 16, 28, and > 36 hours, respectively. Steady state insulin concentrations are reached by at least day 5 of once daily subcutaneous administration of 0.4—0.6 units/kg. At steady state, the 24 hour glucose lowering effect of Toujeo was approximately 27% lower and had a different distribution profile than an equivalent dose of Lantus. The glucose lowering effect increased with each daily administration of Toujeo.