Clorpres

Browse PDR's full list of drug information

Clorpres

Classes

Centrally Acting Alpha Agonist with Diuretics

Administration
Oral Administration

Clonidine may be taken without regard to food ; chlorthalidone is generally recommended to be administered with food.
If therapy is to be discontinued, slowly taper dose over 2—4 days to avoid withdrawal symptoms.

Adverse Reactions
Severe

bradycardia / Rapid / 0.5-0.5
angioedema / Rapid / 0.5-0.5
AV block / Early / Incidence not known
heart failure / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
vasculitis / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
aplastic anemia / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known

Moderate

constipation / Delayed / 10.0-10.0
orthostatic hypotension / Delayed / 3.0-3.0
impotence (erectile dysfunction) / Delayed / 3.0-3.0
depression / Delayed / 1.0-1.0
urinary retention / Early / 0-1.0
elevated hepatic enzymes / Delayed / 1.0-1.0
withdrawal / Early / 0-1.0
sinus tachycardia / Rapid / 0.5-0.5
palpitations / Early / 0.5-0.5
xanthopsia / Delayed / Incidence not known
hallucinations / Early / Incidence not known
delirium / Early / Incidence not known
parotitis / Delayed / Incidence not known
peripheral vasoconstriction / Rapid / Incidence not known
hypotension / Rapid / Incidence not known
metabolic alkalosis / Delayed / Incidence not known
hypokalemia / Delayed / Incidence not known
hypochloremia / Delayed / Incidence not known
hyponatremia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
blurred vision / Early / Incidence not known
jaundice / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
diabetes mellitus / Delayed / Incidence not known
glycosuria / Early / Incidence not known
hyperuricemia / Delayed / Incidence not known
gout / Delayed / Incidence not known
hypertension / Early / Incidence not known

Mild

xerostomia / Early / 0-40.0
drowsiness / Early / 10.0-33.0
dizziness / Early / 16.0-16.0
weakness / Early / 10.0-10.0
nausea / Early / 5.0-5.0
vomiting / Early / 5.0-5.0
fatigue / Early / 4.0-4.0
libido decrease / Delayed / 3.0-3.0
malaise / Early / 1.0-1.0
weight gain / Delayed / 1.0-1.0
anorexia / Delayed / 1.0-1.0
rash / Early / 1.0-1.0
nocturia / Early / 1.0-1.0
pruritus / Rapid / 0.7-0.7
myalgia / Early / 0.6-0.6
arthralgia / Delayed / 0.6-0.6
insomnia / Early / 0.5-0.5
urticaria / Rapid / 0.5-0.5
muscle cramps / Delayed / 0.3-0.3
alopecia / Delayed / 0.2-0.2
gynecomastia / Delayed / 0.1-0.1
increased urinary frequency / Early / 1.0
paresthesias / Delayed / Incidence not known
headache / Early / Incidence not known
anxiety / Delayed / Incidence not known
vertigo / Early / Incidence not known
restlessness / Early / Incidence not known
diarrhea / Early / Incidence not known
photosensitivity / Delayed / Incidence not known
pallor / Early / Incidence not known
purpura / Delayed / Incidence not known
nasal dryness / Early / Incidence not known
fever / Early / Incidence not known

Common Brand Names

Clorpres

Dea Class

Rx

Description

Combination thiazide diuretic (chlorthalidone) and centrally acting alpha2 adrenergic agonist (clonidine).
Used for hypertension, but not for initial therapy; used if fixed dose represents effective dosages for the patient after titration.
The fixed combination may be more convenient than taking each drug individually.

Dosage And Indications
For the treatment of hypertension.
NOTE: Clonidine; chlorthalidone fixed combination therapy is not indicated for initial antihypertensive therapy. The initial dose must be titrated to the individual patient. If the fixed combination represents the individual dosages required for the patient, its use may be more convenient in patient management.
Oral dosage Adults

Initially, a minimum of 1 tablet (0.1 mg clonidine with 15 mg chlorthalidone) PO once daily or twice daily. May titrate dosage of clonidine by 0.1 mg/day as needed up to a maximum of 1 tablet (0.3 mg clonidine with 15 mg chlorthalidone) PO twice daily for a maximum of 0.6 mg/day clonidine with 30 mg/day chlorthalidone. Geriatric patients benefit from lower initial dosing.

Dosing Considerations
Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available. Clonidine dosage reductions may be considered in severe hepatic impairment due to substantial metabolism of clonidine. Chlorthalidone is primarily renally eliminated; however, diuretics should be titrated slowly in patients with substantial hepatic disease since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

Renal Impairment

CrCl >= 30 mL/min: Specific guidelines for dosage adjustments in renal impairment are not available. Carefully titrate clonidine dosage, and monitor patient for bradycardia, sedation or hypotension. Chlorthalidone may precipitate azotemia in some patients with renal disease, so monitor accordingly.
CrCl < 30 mL/min: In general, thiazide diuretics are not effective. Chlorthalidone is contraindicated in patients with anuria.

Drug Interactions

Acarbose: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Codeine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and codeine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Acetaminophen; Dextromethorphan; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Acetaminophen; Dichloralphenazone; Isometheptene: (Major) Isometheptene has sympathomimetic properties. Patients taking antihypertensive agents may need to have their therapy modified. Careful blood pressure monitoring is recommended. (Major) Sympathomimetics can antagonize the antihypertensive effects of adrenergic agonists when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Acetaminophen; Guaifenesin; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Hydrocodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and hydrocodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Acetaminophen; Ibuprofen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Acetaminophen; Oxycodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and oxycodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Acetaminophen; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Acetazolamide: (Moderate) Acetazolamide promotes electrolyte excretion including hydrogen ions, sodium, and potassium. It can enhance the sodium depleting effects of other diuretics when used concurrently. Pre-existing hypokalemia and hyperuricemia can also be potentiated by carbonic anhydrase inhibitors. Monitor serum potassium to determine the need for potassium supplementation and alteration in drug therapy. (Moderate) The concomitant administration of diuretics with other antihypertensive agents can result in additive hypotensive effects. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
Aclidinium; Formoterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Acrivastine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Albuterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Albuterol; Budesonide: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Aldesleukin, IL-2: (Moderate) Antihypertensive agents may potentiate the hypotension seen with aldesleukin, IL-2. (Moderate) Thiazide diuretics may potentiate the hypotension seen with aldesleukin, IL 2.
Alemtuzumab: (Moderate) Alemtuzumab may cause hypotension. Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischemic heart disease and in patients on antihypertensive agents. (Moderate) Alemtuzumab may cause hypotension. Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischemic heart disease and in patients on antihypertensive agents.
Alendronate; Cholecalciferol: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Alfentanil: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with alfentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Allopurinol: (Moderate) Monitor renal function and for signs and symptoms of hypersensitivity and skin rash during concomitant use of allopurinol and thiazide diuretics; reduce the allopurinol dose in persons with renal impairment and concomitant thiazide diuretic use. Concomitant use may increase the risk of severe skin rash and renal impairment may further increase the risk. Discontinue allopurinol at the first appearance of skin rash or other signs which may indicate a hypersensitivity when using these drugs concomitantly.
Alogliptin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Alogliptin; Metformin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Alogliptin; Pioglitazone: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Alpha-glucosidase Inhibitors: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Alprazolam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as thiazide diuretics, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil. (Minor) The concomitant use of systemic alprostadil injection and central-acting antihypertensive agents may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
Amifostine: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses. (Major) Patients receiving central-acting adrenergic agents should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Aminolevulinic Acid: (Moderate) Thiazide diuretics may cause photosensitivity and may increase the photosensitization effects of photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.
Amiodarone: (Moderate) Monitor for potential bradycardia or atrioventricular block during coadministration with amiodarone. Clonidine can produce bradycardia and should be used cautiously in patients who are receiving other drugs that lower the heart rate.
Amitriptyline: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Amlodipine; Benazepril: (Major) Discontinue the thiazide diuretic prior to starting benazepril, if possible, or start benazepril at the lower dose of 5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure.
Amlodipine; Celecoxib: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Amoxapine: (Major) Concurrent use of clonidine with amoxapine should be avoided when possible, due to multiple possible interactions. Clonidine's antihypertensive effect can be reduced by cyclic antidepressants; occasionally, the hypertension will occur within the first few days of combined therapy. If coadministration of amoxapine with clonidine cannot be avoided, the patient should be closely monitored for increased blood pressure and clonidine dosages adjusted as needed. In addition, concurrent administration of a cyclic antidepressant and clonidine may result in additive CNS depression or other side effects; clonidine produces mental depression as a side effect in roughly 1% of patients. In rats, the coadministration of a cyclic antidepressant (amitriptyline) with clonidine resulted in corneal lesions, but the human implications of these animal study findings are unknown.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Amphetamine: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving clonidine and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents.
Amphetamine; Dextroamphetamine Salts: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving clonidine and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents.
Amphetamine; Dextroamphetamine: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving clonidine and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents.
Amphotericin B lipid complex (ABLC): (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Amphotericin B liposomal (LAmB): (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Amphotericin B: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Anticholinergics: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Apomorphine: (Moderate) Use of central-acting adrenergic agents and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination. (Moderate) Use of thiazide diuretics and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Apraclonidine: (Minor) Alpha blockers as a class may reduce heart rate and blood pressure. While no specific drug interactions have been identified with systemic agents and apraclonidine during clinical trials, it is theoretically possible that additive blood pressure reductions could occur when apraclonidine is combined with the use of antihypertensive agents. Patients using cardiovascular drugs concomitantly with apraclonidine should have their pulse and blood pressure monitored periodically.
Arformoterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Aripiprazole: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. (Minor) Due to aripiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents.
Arsenic Trioxide: (Moderate) Concomitant use of thiazide diuretics and arsenic trioxide should be done cautiously. Electrolyte abnormalities, such as hypokalemia and hypomagnesemia, may increase the risk for QT prolongation and torsade de pointes.
Articaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant clonidine and epinephrine use. Clonidine may potentiate the pressor effects of epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Asenapine: (Moderate) Secondary to alpha-blockade, asenapine can produce vasodilation that may result in additive effects during concurrent use of antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of asenapine and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and codeine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Aspirin, ASA; Omeprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Aspirin, ASA; Oxycodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and oxycodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Atracurium: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Atropine: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with clonidine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Baclofen: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
Barbiturates: (Moderate) Barbiturates may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
Belladonna; Opium: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with opium. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Benazepril: (Major) Discontinue the thiazide diuretic prior to starting benazepril, if possible, or start benazepril at the lower dose of 5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure.
Benazepril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the thiazide diuretic prior to starting benazepril, if possible, or start benazepril at the lower dose of 5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure.
Benzhydrocodone; Acetaminophen: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with benzhydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Benzodiazepines: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Thiazide diuretics may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde. (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Benzphetamine: (Major) Benzphetamine can increase both systolic and diastolic blood pressure and may counteract the activity of clonidine. This represents a pharmacodynamic, and not a pharmacokinetic, interaction. Close monitoring of blood pressure, especially in patients who are taking antihypertensive agents, may be needed. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
Benztropine: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Beta-agonists: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Beta-blockers: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Bortezomib: (Moderate) Patients on antihypertensive agents receiving bortezomib treatment may require close monitoring of their blood pressure and dosage adjustment of their medication. During clinical trials of bortezomib, hypotension was reported in roughly 12 percent of patients. (Moderate) Patients on antihypertensive agents receiving bortezomib treatment may require close monitoring of their blood pressure and dosage adjustment of their medication. During clinical trials of bortezomib, hypotension was reported in roughly 12 percent of patients.
Brexpiprazole: (Moderate) Due to brexpiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents.
Brompheniramine; Dextromethorphan; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Brompheniramine; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Brompheniramine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Budesonide; Formoterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Budesonide; Glycopyrrolate; Formoterol: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Bupivacaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant clonidine and epinephrine use. Clonidine may potentiate the pressor effects of epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Bupivacaine; Meloxicam: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Buprenorphine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and buprenorphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Buprenorphine; Naloxone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and buprenorphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and codeine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and codeine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Cabergoline: (Moderate) Cabergoline should be used cautiously with antihypertensive agents, including clonidine. Cabergoline has been associated with hypotension. Initial doses of cabergoline higher than 1 mg may produce orthostatic hypotension. It may be advisable to monitor blood pressure. (Moderate) Cabergoline should be used cautiously with antihypertensive agents, including thiazide diuretics. Cabergoline has been associated with hypotension. Initial doses of cabergoline higher than 1 mg may produce orthostatic hypotension. It may be advisable to monitor blood pressure.
Calcium Phosphate, Supersaturated: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as diuretics, may increase the risk of acute phosphate nephropathy in patients taking sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous.
Calcium: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Calcium; Vitamin D: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Canagliflozin: (Major) Assess and correct volume status before initiating canagliflozin in persons receiving concomitant thiazide diuretics. Monitor for signs and symptoms of volume depletion and loss of glycemic control after initiating therapy due to increased risk for volume depletion or hypotension and loss of blood glucose control. Persons receiving thiazide diuretics may be at increased risk for volume depletion or hypotension with concomitant canagliflozin therapy. Thiazide diuretics tend to produce hyperglycemia and may lead to loss of glycemic control. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Canagliflozin; Metformin: (Major) Assess and correct volume status before initiating canagliflozin in persons receiving concomitant thiazide diuretics. Monitor for signs and symptoms of volume depletion and loss of glycemic control after initiating therapy due to increased risk for volume depletion or hypotension and loss of blood glucose control. Persons receiving thiazide diuretics may be at increased risk for volume depletion or hypotension with concomitant canagliflozin therapy. Thiazide diuretics tend to produce hyperglycemia and may lead to loss of glycemic control. (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and central-acting adrenergic agents. CNS depressants can potentiate the effects of cannabidiol.
Captopril: (Major) Discontinue the thiazide diuretic prior to starting captopril, if possible, or start captopril at the lower dose of 6.25 or 12.5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure.
Captopril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the thiazide diuretic prior to starting captopril, if possible, or start captopril at the lower dose of 6.25 or 12.5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure.
Carbamazepine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Carbidopa; Levodopa: (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs. (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Carbidopa; Levodopa; Entacapone: (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs. (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Carbonic anhydrase inhibitors: (Moderate) The concomitant administration of diuretics with other antihypertensive agents can result in additive hypotensive effects. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
Cardiac glycosides: (Moderate) Clonidine can produce bradycardia and should be used cautiously in patients who are receiving other drugs that lower the heart rate such as cardiac glycosides. (Moderate) Monitor serum magnesium and potassium during concomitant cardiac glycoside and thiazide diuretic use. Potassium-depleting diuretics are a major contributing factor to digoxin toxicity.
Cariprazine: (Moderate) Orthostatic vital signs should be monitored in patients who are at risk for hypotension, such as those receiving cariprazine in combination with antihypertensive agents. Atypical antipsychotics may cause orthostatic hypotension and syncope, most commonly during treatment initiation and dosage increases. Patients should be informed about measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider a cariprazine dose reduction if hypotension occurs.
Celecoxib: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Celecoxib; Tramadol: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and tramadol; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and clonidine. Concurrent use may result in additive CNS depression.
Ceritinib: (Major) Avoid concomitant use of ceritinib with clonidine if possible due to the risk of additive bradycardia. Both ceritinib and clonidine can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Cetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and clonidine due to the risk for additive CNS depression.
Cetirizine; Pseudoephedrine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and clonidine due to the risk for additive CNS depression. (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Chlordiazepoxide: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Chlordiazepoxide; Amitriptyline: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines. (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Chlordiazepoxide; Clidinium: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines. (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Chloroprocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
Chlorpheniramine; Codeine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and codeine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Chlorpheniramine; Hydrocodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and hydrocodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Chlorpheniramine; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Chlorpheniramine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Chlorpromazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Chlorpropamide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a po

tential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Cholestyramine: (Moderate) Cholestyramine, an ion exchange resin, binds hydrochlorothiazide and reduces its absorption from the gastrointestinal tract by up to 85% when co-administered as single doses. Although the manufacturer for Questran recommends that other medicines be taken at least 1 hour before or 4-6 hours after cholestyramine, it has been recommended that thiazides be administered at least 4 hours before or after cholestyramine to minimize the reduction in absorption. By administering hydrochlorothiazide at least 4 hours before cholestyramine, the decrease in absorption of hydrochlorothiazide is approximately 30-35%.
Cidofovir: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Cisapride: (Major) Cisapride should be used with great caution in patients receiving thiazide diuretics. Drugs that are associated with depletion of electrolytes may cause cisapride-induced cardiac arrhythmias. Serum electrolytes and creatinine should be assessed prior to administration of cisapride and whenever conditions develop that may affect electrolyte imbalance or renal function.
Cisatracurium: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Citalopram: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and citalopram use; consider discontinuing citalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Clindamycin; Tretinoin: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Clomipramine: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Clonazepam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Clorazepate: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Clozapine: (Moderate) Caution is advisable during concurrent use of clozapine and thiazide diuretics as concurrent use may increase the risk and severity of hypotension. In addition, electrolyte imbalance caused by thiazide diuretics may increase the risk of QT prolongation by clozapine. (Moderate) Clozapine used concomitantly with the antihypertensive agents can increase the risk and severity of hypotension by potentiating the effect of the antihypertensive drug.
Cocaine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Codeine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and codeine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Codeine; Guaifenesin: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and codeine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and codeine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Codeine; Phenylephrine; Promethazine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression. (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and codeine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Codeine; Promethazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression. (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and codeine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Co-Enzyme Q10, Ubiquinone: (Moderate) Monitor blood pressure during concomitant co-enzyme Q10 (ubiquinone) and central-acting adrenergic agents use. Concomitant use may result in additive hypotension. (Moderate) Monitor blood pressure during concomitant co-enzyme Q10 (ubiquinone) and thiazide diuretic use. Concomitant use may result in additive hypotension.
Colestipol: (Moderate) Although to a lesser extent than cholestyramine, colestipol also has been shown to inhibit the GI absorption and therapeutic response of thiazide diuretics. Single doses of colestipol resins reduce the absorption of HCTZ by up to 43%. Administering thiazide diuretics at least 2 hours before colestipol has been suggested to minimize the interaction.
COMT inhibitors: (Major) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including clonidine, due to the possibility of additive sedation and hypotension. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Corticosteroids: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Corticotropin, ACTH: (Minor) Monitor potassium concentrations during concomitant corticotropin and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticotropin and thiazide diuretics cause increased renal potassium loss.
Cosyntropin: (Moderate) Use cosyntropin cautiously in patients receiving diuretics. Cosyntropin may accentuate the electrolyte loss associated with diuretic therapy.
Crizotinib: (Major) Avoid coadministration of crizotinib with agents known to cause bradycardia, such as clonidine, to the extent possible due to the risk of additive bradycardia. If concomitant use is unavoidable, monitor heart rate and blood pressure regularly. An interruption of crizotinib therapy or dose adjustment may be necessary if bradycardia occurs.
Cyclobenzaprine: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of clonidine and cyclobenzaprine; a clonidine dose adjustment may be necessary. Concomitant use may result in decreased clonidine efficacy and/or additive CNS depression. The hypotensive effect of clonidine may be reduced by tricyclic antidepressants, and cyclobenzaprine is structurally related to the tricyclic antidepressants.
Cyclophosphamide: (Moderate) Closely monitor complete blood counts if coadministration of cyclophosphamide with thiazide diuretics is necessary as there is an increased risk of hematologic toxicity and immunosuppression.
Cyclosporine: (Minor) Clonidine can inhibit cyclosporine-induced glomerular vasoconstriction and has been shown to offset cyclosporine-induced nephrotoxicity. Clonidine may adversely affect cyclosporine pharmacokinetics; limited data suggest that cyclosporine concentrations increase - dramatically, in some cases - when clonidine is added. Until more data are available, clinicians should use clonidine cautiously in patients stabilized on cyclosporine.
Dapagliflozin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Dapagliflozin; Metformin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Dapagliflozin; Saxagliptin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Desipramine: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Desloratadine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Desmopressin: (Moderate) Monitor serum sodium more frequently during concomitant desmopressin and thiazide diuretic use due to increased risk of water intoxication with hyponatremia.
Desvenlafaxine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Deutetrabenazine: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as clonidine, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Dexlansoprazole: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
Dextroamphetamine: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving clonidine and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Dextromethorphan; Guaifenesin; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Dextromethorphan; Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension. (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Diazepam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Diazoxide: (Moderate) Additive hypotensive effects can occur with the concomitant administration of diazoxide with other antihypertensive agents. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving other antihypertensive agents. Diazoxide can enhance the hyperglycemic, hyperuricemic and antihypertensive effects of thiazide diuretics. (Moderate) Enhanced hyperglycemia is possible during concurrent use of diazoxide and thiazide diuretics. Additive hypotensive effects can also occur with the concomitant administration of diazoxide with thiazide diuretics.
Dichlorphenamide: (Moderate) Use dichlorphenamide and diuretics together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including loop diuretics and thiazide diuretics. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Diclofenac: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Diclofenac; Misoprostol: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Dicyclomine: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Diethylpropion: (Major) Diethylpropion has vasopressor effects and may limit the benefit of thiazide diuretics. Although leading drug interaction texts differ in the potential for an interaction between diethylpropion and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications. (Major) Sympathomimetics, such as diethylpropion, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Diflunisal: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Digoxin: (Moderate) Clonidine can produce bradycardia and should be used cautiously in patients who are receiving other drugs that lower the heart rate such as cardiac glycosides. (Moderate) Monitor serum magnesium and potassium during concomitant cardiac glycoside and thiazide diuretic use. Potassium-depleting diuretics are a major contributing factor to digoxin toxicity.
Diltiazem: (Moderate) Avoid concomitant use of diltiazem and extended-release clonidine tablets. Monitor heart rate during concomitant use of diltiazem and other clonidine formulations. Concomitant use may potentiate bradycardia and risk of AV block. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported during the use of diltiazem and clonidine.
Dipeptidyl Peptidase-4 Inhibitors: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Diphenhydramine; Ibuprofen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Diphenhydramine; Naproxen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Diphenhydramine; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Diphenoxylate; Atropine: (Moderate) Concurrent administration of diphenoxylate/difenoxin with clonidine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Dobutamine: (Major) Sympathomimetics, such as dobutamine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control. (Moderate) Sympathomimetics can antagonize the effects of antihypertensives such as metolazone when administered concomitantly.
Dofetilide: (Contraindicated) Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for dofetilide-induced torsade de pointes. Additionally, in patients treated with either hydrochlorothiazide 50 mg or hydrochlorothiazide/triamterene 50 mg/100 mg daily in combination with dofetilide 500 mcg twice daily for 5 days, dofetilide AUC and Cmax concentrations increased by 27% and 21%, respectively, for the hydrochlorothiazide alone group and by 30% and 16%, respectively, for the hydrochlorothiazide/triamterene group. Furthermore, a 197% and 190% QTc increase over time was seen in the hydrochlorothiazide and hydrochlorothiazide/triamterene groups, respectively. Based on these findings, the manufacturer of dofetilide contraindicates the concomitant use of hydrochlorothiazide (alone or in combination with other drugs such as triamterene); these findings can be explained both by an increase in the plasma concentration of dofetilide and a reduction in the serum potassium concentration. In a population pharmacokinetic analysis of plasma dofetilide concentrations, the mean dofetilide clearance of dofetilide was 16% lower in patients on thiazide diuretics. It is prudent to avoid the use of any thiazide diuretic in combination with dofetilide.
Dolasetron: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Dopamine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives such as metolazone when administered concomitantly. (Moderate) Sympathomimetics, such as dopamine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Doxepin: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Droperidol: (Moderate) Caution is advised when using droperidol in combination with thiazide diuretics which may lead to electrolyte abnormalities, especially hypokalemia or hypomagnesemia, as such abnormalities may increase the risk for QT prolongation or cardiac arrhythmias.
Dulaglutide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Duloxetine: (Moderate) Monitor blood pressure during concomitant duloxetine and central-acting adrenergic agent use. Concomitant use increases the risk for hypotension, including orthostatic hypotension and syncope. Consider reducing the duloxetine dose or discontinuing duloxetine if symptomatic orthostatic hypotension, falls, or syncope occur during treatment. (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Empagliflozin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Empagliflozin; Linagliptin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Empagliflozin; Linagliptin; Metformin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Empagliflozin; Metformin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Enalapril, Enalaprilat: (Major) Discontinue the thiazide diuretic prior to starting enalapril, if possible, or start enalapril at the lower dose of 2.5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure.
Enalapril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the thiazide diuretic prior to starting enalapril, if possible, or start enalapril at the lower dose of 2.5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure.
Ephedrine: (Major) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by thiazide diuretics. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) Carefully monitor blood pressure in patients who have received both ephedrine and clonidine; clonidine augments the pressor effect of ephedrine.
Ephedrine; Guaifenesin: (Major) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by thiazide diuretics. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) Carefully monitor blood pressure in patients who have received both ephedrine and clonidine; clonidine augments the pressor effect of ephedrine.
Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant clonidine and epinephrine use. Clonidine may potentiate the pressor effects of epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Epoprostenol: (Moderate) The concomitant administration of epoprostenol with other antihypertensive agents can result in additive hypotensive effects. This can be therapeutically advantageous, but dosages must be adjusted accordingly.
Ertugliflozin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Ertugliflozin; Metformin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Ertugliflozin; Sitagliptin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Escitalopram: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Esketamine: (Major) Closely monitor patients receiving esketamine and clonidine for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
Esomeprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant esomeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Estazolam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Estradiol: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormone therapy should be monitored for antihypertensive effectiveness.
Ethanol: (Major) Advise patients to avoid alcohol use while taking clonidine. Clonidine may potentiate the CNS-depressive effects of alcohol. (Major) Advise patients to avoid alcohol while taking thiazide diuretics. Ingesting alcohol can increase the risk for orthostatic hypotension when taking a thiazide diuretic.
Etodolac: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Etomidate: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Exenatide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and clonidine. Concurrent use may result in additive CNS depression.
Fenoprofen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Fentanyl: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and fentanyl; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Fexofenadine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) Monitor blood pressure during concomitant fish oil and central-acting adrenergic agent use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Flavoxate: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Fluocinolone; Hydroquinone; Tretinoin: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Fluoxetine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and fluoxetine use; consider discontinuing fluoxetine if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Fluphenazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Flurazepam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Flurbiprofen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Fluticasone; Salmeterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Fluticasone; Umeclidinium; Vilanterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Fluticasone; Vilanterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Fluvoxamine: (Moderate) Patients receiving a diuretic during treatment with fluvoxamine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/L have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of fluvoxamine should be considered in patients who develop symptomatic hyponatremia.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Formoterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Formoterol; Mometasone: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Fosinopril: (Major) Discontinue the thiazide diuretic prior to starting fosinopril, if possible, or start fosinopril at a lower dose to minimize hypotension. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure.
Fosinopril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the thiazide diuretic prior to starting fosinopril, if possible, or start fosinopril at a lower dose to minimize hypotension. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and clonidine. Concomitant use of gabapentin with clonidine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
General anesthetics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Glimepiride: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Glipizide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Glipizide; Metformin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Glyburide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Glyburide; Metformin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Glycopyrrolate: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Glycopyrrolate; Formoterol: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Granisetron: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Guaifenesin; Hydrocodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and hydrocodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Guaifenesin; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Halobetasol; Tazarotene: (Moderate) The manufacturer states that tazarotene should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Haloperidol: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. (Moderate) Disturbances of orthostatic regulation (e.g., orthostatic hypotension, dizziness, fatigue) and additive sedation may occur in patients receiving concomitant clonidine and antipsychotics. Also, based on observations in patients in a state of alcoholic delirium, high intravenous doses of clonidine may increase the arrhythmogenic potential (QT prolongation, ventricular fibrillation) of high intravenous doses of haloperidol. A causal relationship and relevance for clonidine oral tablets have not been established.
Homatropine; Hydrocodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and hydrocodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Hydrochlorothiazide, HCTZ; Moexipril: (Major) Discontinue the thiazide diuretic prior to starting moexipril, if possible, or start moexipril at the lower dose of 3.75 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure.
Hydrocodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and hydrocodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Hydrocodone; Ibuprofen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and hydrocodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Hydrocodone; Pseudoephedrine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and hydrocodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Hydromorphone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydromorphone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Hyoscyamine: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Thiazide diuretics may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde. (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Ibuprofen lysine: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Ibuprofen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Ibuprofen; Famotidine: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Ibuprofen; Oxycodone: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and oxycodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Ibuprofen; Pseudoephedrine: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Icosapent ethyl: (Moderate) Thiazide diuretics may exacerbate hypertriglyceridemia and should be discontinued or changed to alternate therapy, if possible, prior to initiation of icosapent ethyl.
Iloperidone: (Moderate) Secondary to alpha-blockade, iloperidone can produce vasodilation that may result in additive effects during concurrent use with antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of iloperidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Iloprost: (Moderate) Further reductions in blood pressure may occur when inhaled iloprost is administered to patients receiving other antihypertensive agents.
Imipramine: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Incretin Mimetics: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Indacaterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Indacaterol; Glycopyrrolate: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Indomethacin: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Inotersen: (Moderate) Use caution with concomitant use of inotersen and diuretics due to the risk of glomerulonephritis and nephrotoxicity.
Insulin Degludec; Liraglutide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Insulin Glargine; Lixisenatide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Insulins: (Moderate) 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. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Intravenous Lipid Emulsions: (Moderate) Monitor blood pressure during concomitant fish oil and central-acting adrenergic agent use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Ipratropium; Albuterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Isocarboxazid: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
Isoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Isoproterenol: (Major) Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control. (Moderate) The pharmacologic effects of isoproterenol may cause an increase in blood pressure. If isoproterenol is used concomitantly with antihypertensives, the blood pressure should be monitored as the administration of isoproterenol can compromise the effectiveness of antihypertensive agents.
Isosorbide Dinitrate, ISDN: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Isosorbide Mononitrate: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Ketamine: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Ketoprofen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Ketorolac: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Lansoprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant lansoprazole and thiazide diuretic use due to risk for hypomagnesemia.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Monitor magnesium concentration before and periodically during concomitant lansoprazole and thiazide diuretic use due to risk for hypomagnesemia.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and clonidine. Concurrent use may result in additive CNS depression. Additionally, monitor heart rate if lasmiditan is coadministered with clonidine as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and clonidine. Dosage adjustments of lemborexant and clonidine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Lesinurad; Allopurinol: (Moderate) Monitor renal function and for signs and symptoms of hypersensitivity and skin rash during concomitant use of allopurinol and thiazide diuretics; reduce the allopurinol dose in persons with renal impairment and concomitant thiazide diuretic use. Concomitant use may increase the risk of severe skin rash and renal impairment may further increase the risk. Discontinue allopurinol at the first appearance of skin rash or other signs which may indicate a hypersensitivity when using these drugs concomitantly.
Levalbuterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Levocetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and clonidine due to the risk for additive CNS depression.
Levodopa: (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs. (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Levomilnacipran: (Moderate) Because levomilnacipran inhibits norepinephrine reuptake, coadministration with clonidine may inhibit clonidine's antihypertensive effect. (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Levorphanol: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with levorphanol. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Lidocaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant clonidine and epinephrine use. Clonidine may potentiate the pressor effects of epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Linagliptin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Linagliptin; Metformin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Liraglutide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Lisdexamfetamine: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving clonidine and lisdexamfetamine. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents.
Lisinopril: (Major) Discontinue the thiazide diuretic prior to starting lisinopril, if possible, or start lisinopril at the lower dose of 5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure.
Lisinopril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the thiazide diuretic prior to starting lisinopril, if possible, or start lisinopril at the lower dose of 5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure.
Lithium: (Moderate) Monitor lithium concentrations during concomitant use with thiazide diuretics; consider lower lithium starting doses and titrating slowly while frequently monitoring lithium concentrations and for signs of lithium toxicity. Thiazide diuretics reduce the renal clearance of lithium and increase the risk for lithium toxicity.
Lixisenatide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Lofexidine: (Major) Lofexidine is a central alpha-2 adrenergic agonist, and its effects can be additive to other medications in the same class. Monitor for excessive hypotension, bradycardia, and sedation during coadministration. Patients being given lofexidine in an outpatient setting should be capable of and instructed on self-monitoring for hypotension, orthostasis, bradycardia, and associated symptoms. If clinically significant or symptomatic hypotension and/or bradycardia occur, the next dose of lofexidine should be reduced in amount, delayed, or skipped.
Loop diuretics: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Loratadine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Lorazepam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Lumateperone: (Moderate) Monitor for excessive sedation, somnolence, and orthostatic hypotension during coadministration of lumateperone and clonidine. Concurrent use may result in additive CNS depression or orthostasis.
Lurasidone: (Moderate) Due to the antagonism of lurasidone at alpha-1 adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents. If concurrent use of lurasidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Macimorelin: (Major) Avoid use of macimorelin with drugs that may transiently elevate growth hormone concentrations, such as clonidine. Healthcare providers are advised to discontinue clonidine therapy and observe a sufficient washout period before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test.
Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as diuretics.
Mannitol: (Major) Avoid use of other diuretics with mannitol, if possible. Concomitant administration may potentiate the renal toxicity of mannitol.
Maprotiline: (Major) Concurrent use of clonidine with maprotiline should be avoided when possible, due to multiple possible interactions. Clonidine's antihypertensive effect can be reduced by cyclic antidepressants, such as maprotiline. If coadministration of maprotiline with clonidine cannot be avoided, the patient should be closely monitored for increased blood pressure and clonidine dosages adjusted as needed.
Meclofenamate Sodium: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Mefenamic Acid: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Meglitinides: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Meloxicam: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Meperidine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with meperidine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Metaproterenol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Metformin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Metformin; Repaglinide: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Metformin; Rosiglitazone: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Metformin; Saxagliptin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Metformin; Sitagliptin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Methadone: (Moderate) Diuretics can cause electrolyte disturbances such as hypomagnesemia and hypokalemia, which may prolong the QT interval. As methadone may also prolong the QT interval, cautious coadministration with diuretics is needed. In addition, opiate agonists may potentiate orthostatic hypotension when used concurrently with diuretics.
Methamphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like clonidine, when clonidine is used for blood pressure control. Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
Methazolamide: (Moderate) The concomitant administration of diuretics with other antihypertensive agents can result in additive hypotensive effects. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly. (Moderate) Thiazide diuretics may increase the risk of hypokalemia if used concurrently with methazolamide. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy. There may also be an additive diuretic or hyperuricemic effect.
Methenamine: (Moderate) Thiazide diuretics may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde.
Methenamine; Sodium Acid Phosphate: (Moderate) Thiazide diuretics may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Thiazide diuretics may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde. (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Methenamine; Sodium Salicylate: (Moderate) Thiazide diuretics may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde.
Methotrexate: (Moderate) Monitor for increased methotrexate-related adverse reactions during concomitant thiazide diuretic use. Thiazide diuretics may decrease renal excretion of cytotoxic agents and enhance their myelosuppressive effects.
Methoxsalen: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
Methscopolamine: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Methylphenidate Derivatives: (Moderate) Monitor blood pressure during concomitant clonidine and methylphenidate use; a clonidine dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Metoclopramide: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
Midazolam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Midodrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control. (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly.
Miglitol: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does no t appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Milnacipran: (Moderate) Because milnacipran inhibits norepinephrine reuptake, coadministration with clonidine may inhibit clonidine's antihypertensive effect. (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response. (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Mirtazapine: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and mirtazapine. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression. Mirtazapine and clonidine have pharmacologic actions that potentially oppose one another. Mirtazapine inhibits central alpha-2 autoreceptors (located presynaptically on noradrenergic neurons) and stimulating norepinephrine and stimulates the serotonergic system through antagonism at alpha-2 heteroreceptors. Clonidine exerts its antihypertensive effect by stimulating the central alpha-2 autoreceptors, thereby causing a reduction in the synthesis and release of norepinephrine. (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and mirtazapine use; consider discontinuing mirtazapine if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Mivacurium: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Moexipril: (Major) Discontinue the thiazide diuretic prior to starting moexipril, if possible, or start moexipril at the lower dose of 3.75 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure.
Monoamine oxidase inhibitors: (Moderate) Monitor blood pressure closely if clonidine is coadministered with monoamine oxidase inhibitors (MAOIs). Additive hypotensive effects may be seen when MAOIs are combined with antihypertensives.
Morphine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Morphine; Naltrexone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Nabilone: (Major) Monitor for excessive sedation and somnolence during coadministration of nabilone and clonidine. Concurrent use may result in additive CNS depression.
Nabumetone: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Naproxen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Naproxen; Esomeprazole: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (Moderate) Monitor magnesium concentration before and periodically during concomitant esomeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Naproxen; Pseudoephedrine: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Nateglinide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Nefazodone: (Minor) Although relatively infrequent, nefazodone may cause orthostatic hypotension in some patients; this effect may be additive with antihypertensive agents. Blood pressure monitoring and dosage adjustments of either drug may be necessary.
Neostigmine; Glycopyrrolate: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents. (Moderate) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. Clonidine has been shown to inhibit niacin-induced flushing. The interaction is harmless unless niacin augments the hypotensive actions of clonidine.
Niacin; Simvastatin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. Clonidine has been shown to inhibit niacin-induced flushing. The interaction is harmless unless niacin augments the hypotensive actions of clonidine.
Nitrates: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Nitroglycerin: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Nitroprusside: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure. (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
Non-Ionic Contrast Media: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure.
Nonsteroidal antiinflammatory drugs: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Norepinephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control. (Moderate) Thiazide diuretics can cause decreased arterial responsiveness to norepinephrine, but the effect is not sufficient to preclude their coadministration.
Nortriptyline: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Octreotide: (Moderate) Patients receiving diuretics or other agents to control fluid and electrolyte balance may require dosage adjustments while receiving octreotide due to additive effects.
Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Fluoxetine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and fluoxetine use; consider discontinuing fluoxetine if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia. (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Samidorphan: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Oliceridine: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Olodaterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Omeprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Omeprazole; Sodium Bicarbonate: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Opiate Agonists: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Oxaprozin: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Oxazepam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Oxybutynin: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Oxycodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and oxycodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Oxymetazoline: (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by clonidine. If these drugs are used together, closely monitor for changes in blood pressure. (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by diuretics. If these drugs are used together, closely monitor for changes in blood pressure.
Oxymorphone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with oxymorphone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Paliperidone: (Moderate) Paliperidone may cause orthostatic hypotension, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving paliperidone and central-acting adrenergic agents who are susceptible to hypotension. (Moderate) Paliperidone may cause orthostatic hypotension, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving paliperidone and thiazide diuretics who are susceptible to hypotension.
Pancuronium: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Pantoprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant pantoprazole and thiazide diuretic use due to risk for hypomagnesemia.
Paroxetine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and paroxetine use; consider discontinuing paroxetine if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Pasireotide: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Pentamidine: (Moderate) Drugs that are associated with hypokalemia and/or hypomagnesemia such as thiazide diuretics should be used with caution in patients also receiving pentamidine. Since pentamidine may cause QT prolongation independently of electrolyte imbalances, the risk for cardiac arrhythmias is potentiated by the concomitant use of agents associated with electrolyte loss. Closely monitor serum electrolytes during pentamidine therapy.
Pentazocine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with pentazocine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Pentazocine; Naloxone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with pentazocine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Pentoxifylline: (Moderate) Pentoxifylline has been used concurrently with antihypertensive drugs (beta blockers, diuretics) without observed problems. Small decreases in blood pressure have been observed in some patients treated with pentoxifylline; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensives. If indicated, dosage of the antihypertensive agents should be reduced.
Perindopril: (Major) Discontinue the thiazide diuretic prior to starting perindopril, if possible, or start perindopril at a lower dose to minimize hypotension. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure.
Perindopril; Amlodipine: (Major) Discontinue the thiazide diuretic prior to starting perindopril, if possible, or start perindopril at a lower dose to minimize hypotension. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure.
Perphenazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Perphenazine; Amitriptyline: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression. (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Phendimetrazine: (Major) Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control. (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly.
Phenelzine: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenelzine use due to risk for additive hypotension.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Phenothiazines: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Phentermine: (Moderate) Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control. (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly.
Phentermine; Topiramate: (Moderate) Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control. (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly.
Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Photosensitizing agents (topical): (Moderate) Thiazide diuretics may cause photosensitivity and may increase the photosensitization effects of photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.
Pimozide: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment. (Moderate) Disturbances of orthostatic regulation (e.g., orthostatic hypotension, dizziness, fatigue) and additive sedation may be induced or exacerbated in patients receiving concomitant clonidine and antipsychotics. Caution patients to avoid hazardous tasks, such as driving or operating machinery, until the effects of concurrent use are known. Also, based on observations in patients in a state of alcoholic delirium, it has been suggested that high intravenous doses of clonidine may increase the arrhythmogenic potential (QT prolongation, ventricular fibrillation) of high intravenous doses of haloperidol. A causal relationship and relevance for clonidine oral tablets have not been established.
Pioglitazone: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Pioglitazone; Glimepiride: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Pioglitazone; Metformin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Piroxicam: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Polycarbophil: (Moderate) Coadministration may lead to hypercalcemia because thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Each 625 mg of calcium polycarbophil contains a substantial amount of calcium (approximately 125 mg). Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium polycarbophil is used concomitantly, monitoring of serum calcium may be prudent.
Polyethylene Glycol; Electrolytes: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as diuretics.
Polyethylene Glycol; Electrolytes; Ascorbic Acid: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as diuretics.
Ponesimod: (Major) Avoid concomitant use of ponesimod and medications that may decrease heart rate such as clonidine due to the risk for severe bradycardia and heart block. Consider consultation from a cardiologist if concomitant use is necessary.
Porfimer: (Major) Avoid coadministration of porfimer with thiazide diuretics due to the risk of increased photosensitivity. Porfimer is a light-activated drug used in photodynamic therapy; all patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like thiazide diuretics may increase the risk of a photosensitivity reaction.
Pramlintide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Prazosin: (Moderate) Prazosin is well-known to produce a 'first-dose' phenomenon. Some patients develop significant hypotension shortly after administration of the first dose. The first dose response (acute postural hypotension) of prazosin may be exaggerated in patients who are receiving beta-adrenergic blockers, diuretics, or other antihypertensive agents. Concomitant administration of prazosin with other antihypertensive agents is not prohibited, however. This can be therapeutically advantageous, but lower dosages of each agent should be used. (Moderate) Prazosin is well-known to produce a 'first-dose' phenomenon. Some patients develop significant hypotension shortly after administration of the first dose. The first dose response (acute postural hypotension) of prazosin may be exaggerated in patients who are receiving beta-adrenergic blockers, diuretics, or other antihypertensive agents. Concomitant administration of prazosin with other antihypertensive agents is not prohibited, however. This can be therapeutically advantageous, but lower dosages of each agent should be used.
Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and clonidine. Concomitant use of pregabalin with clonidine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Prilocaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant clonidine and epinephrine use. Clonidine may potentiate the pressor effects of epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Probenecid: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Probenecid; Colchicine: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Procainamide: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects. (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
Prochlorperazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Promethazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Promethazine; Dextromethorphan: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Promethazine; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Propantheline: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Propofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Protriptyline: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Pseudoephedrine; Triprolidine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Quazepam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Quetiapine: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of clonidine and quetiapine. Coadministration may induce or exacerbate orthostatic regulation disturbances, such as orthostatic hypotension, dizziness, or fatigue, as well as produce additive CNS depression.
Quinapril: (Major) Discontinue the thiazide diuretic prior to starting quinapril, if possible, or start quinapril at the lower dose of 5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure.
Quinapril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the thiazide diuretic prior to starting quinapril, if possible, or start quinapril at the lower dose of 5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure.
Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension. (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Rabeprazole: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
Ramipril: (Major) Discontinue the thiazide diuretic prior to starting ramipril, if possible, or start ramipril at a lower dose to minimize hypotension. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure.
Rasagiline: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Orthostatic hypotension has been reported during administration of rasagiline; caution is advised during concurrent use with antihypertensive agents. Patients receiving rasagiline in combination with an antihypertensive should be instructed to rise slowly from a sitting position, and to report syncope, and changes in heart rate or blood pressure to their health care provider. Rasagiline is a selective MAO-B inhibitor at manufacturer recommended doses; therefore, serious hypertensive reactions with agents affecting catecholamine release (e.g., guanabenz, reserpine, guanethidine) are unlikely.
Remifentanil: (Moderate) Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
Remimazolam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Repaglinide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Risperidone: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly. (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Rocuronium: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Rosiglitazone: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Salicylates: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Salmeterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Saxagliptin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Scopolamine: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Semaglutide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Serotonin norepinephrine reuptake inhibitors: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Sertraline: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and sertraline use; consider discontinuing sertraline if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Sevoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
SGLT2 Inhibitors: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Silodosin: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
Sitagliptin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as diuretics, may increase the risk of acute phosphate nephropathy in patients taking sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Moderate) Use caution when prescribing sodium picosulfate; magnesium oxide; anhydrous citric acid in patients taking concomitant medications that may affect renal function such as diuretics. In addition, use caution in patients receiving drugs where hypokalemia is a particular risk.
Solifenacin: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms. Risk versus benefit should be addressed in patients receiving diuretics and solifenacin.
Sotagliflozin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and clonidine. CNS depressants can potentiate the effects of stiripentol.
Streptozocin: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Succinylcholine: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Sufentanil: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Sulfacetamide: (Moderate) Sulfonamides may cause photosensitization and may increase the photosensitizing effects of thiazide diuretics.
Sulfacetamide; Sulfur: (Moderate) Sulfonamides may cause photosensitization and may increase the photosensitizing effects of thiazide diuretics.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
Sulfonylureas: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Sulindac: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Sumatriptan; Naproxen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Tapentadol: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with tapentadol. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Tazarotene: (Moderate) The manufacturer states that tazarotene should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Tegaserod: (Minor) Coadminisitration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
Temazepam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Terbutaline: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Tetrabenazine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly. (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
Tetracaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of tetracaine and antihypertensive agents. (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of tetracaine and antihypertensive agents.
Thiazolidinediones: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as t remor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Thioridazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Tiotropium; Olodaterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Tirzepatide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Tizanidine: (Major) The use of tizanidine with other alpha 2-adrenergic agonists (such as central-acting adrenergic agonist antihypertensive agents) should be avoided because hypotensive effects may be cumulative. Tizanidine is an alpha 2-adrenergic agonist that can produce hypotension. Syncope has been reported in the postmarketing setting. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and tizanidine use due to risk for additive hypotension.
Tolazamide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Tolbutamide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Tolmetin: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Tolterodine: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Tolvaptan: (Moderate) Monitor serum sodium closely if tolvaptan and thiazide diuretics are used together. Coadministration increases the risk of too rapid correction of serum sodium.
Toremifene: (Moderate) Monitor serum calcium levels in patients receiving concomitant treatment with toremifene and thiazide diuretics. Thiazide diuretics decrease renal calcium excretion and may increase the risk of hypercalcemia in patients receiving toremifene.
Tramadol: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and tramadol; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Tramadol; Acetaminophen: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and tramadol; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Trandolapril: (Major) Discontinue the thiazide diuretic prior to starting trandolapril, if possible, or start trandolapril at the lower dose of 0.5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure.
Trandolapril; Verapamil: (Major) Discontinue the thiazide diuretic prior to starting trandolapril, if possible, or start trandolapril at the lower dose of 0.5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure. (Moderate) Avoid concomitant use of verapamil and extended-release clonidine tablets. Monitor heart rate during concomitant use of verapamil and other clonidine formulations. Concomitant use may potentiate bradycardia and risk of AV block. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported during the use of verapamil and clonidine.
Tranylcypromine: (Contraindicated) The use of hypotensive agents and tranylcypromine is contraindicated by the manufacturer of tranylcypromine because the effects of hypotensive agents may be markedly potentiated.
Trazodone: (Moderate) Monitor for unusual drowsiness or excess sedation during coadministration of clonidine and trazodone due to risk for additive CNS depression. (Minor) Due to additive hypotensive effects, patients receiving antihypertensive agents concurrently with trazodone may have excessive hypotension. Decreased dosage of the antihypertensive agent may be required when given with trazodone.
Treprostinil: (Moderate) Thiazide diuretics can enhance the hypotensive effects of antihypertensive agents or diuretics if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly.
Tretinoin, ATRA: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Tretinoin; Benzoyl Peroxide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Triazolam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Tricyclic antidepressants: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Trifluoperazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Trihexyphenidyl: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Trimipramine: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Trospium: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Umeclidinium; Vilanterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Valdecoxib: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Vecuronium: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Venlafaxine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Verapamil: (Moderate) Avoid concomitant use of verapamil and extended-release clonidine tablets. Monitor heart rate during concomitant use of verapamil and other clonidine formulations. Concomitant use may potentiate bradycardia and risk of AV block. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported during the use of verapamil and clonidine.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with thiazide diuretics is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like thiazide diuretics may increase the risk of a photosensitivity reaction.
Vilazodone: (Moderate) Patients receiving vilazodone with medications known to cause hyponatremia, such as diuretics, may be at increased risk of developing hyponatremia. Hyponatremia has occurred in association with the use of antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. Hyponatremia may manifest as headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness which may result in falls. Severe manifestations include hallucinations, syncope, seizure, coma, respiratory arrest, and death. Symptomatic hyponatremia may require discontinuation of vilazodone, as well as implementation of the appropriate medical interventions.
Vitamin D analogs: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Vitamin D: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Vitamin D: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Vorinostat: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Vortioxetine: (Moderate) Patients receiving a diuretic during treatment with vortioxetine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Clinically significant hyponatremia has been reported during therapy with vortioxetine. One case involving serum sodium levels lower than 110 mmol/l has occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of vortioxetine should be considered in patients who develop symptomatic hyponatremia.
Warfarin: (Moderate) Chlorthalidone has been associated with a decreased anticoagulation response to warfarin. Monitor coagulation parameters and adjust warfarin dosage as needed.
Ziconotide: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Ziprasidone: (Moderate) Monitor potassium and magnesium levels when thiazide diuretics are used during ziprasidone therapy. The risk of QT prolongation from ziprasidone is increased in the presence of hypokalemia or hypomagnesemia. (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.

How Supplied

Clorpres Oral Tab: 0.1-15mg, 0.2-15mg, 0.3-15mg

Maximum Dosage
Adults

0.6 mg/day PO clonidine; 30 mg/day PO chlorthalidone when used in this combination.

Geriatric

0.6 mg/day PO clonidine; 30 mg/day PO chlorthalidone when used in this combination.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Use not established.

Neonates

Use not established.

Mechanism Of Action

Chlorthalidone; clonidine combines 2 antihypertensive agents with different mechanisms to lower blood pressure.
Chlorthalidone: Chlorthalidone is a thiazide diuretic that increases the excretion of sodium, chloride, and water by inhibiting sodium ion transport across the renal tubular epithelium. Its primary site of action is the distal convoluted tubule of the nephron. The diuretic effects of chlorthalidone lead to a decreased cardiac output, plasma volume, extracellular fluid volume, total exchangeable sodium, glomerular filtration rate, and renal plasma flow. The mechanism of its antihypertensive effect appears to be sodium and water depletion; however, the exact mechanism of action of chlorthalidone and similar drugs is not fully clear. The onset of hypotensive action of chlorthalidone is about 2 hours, with peak effects occurring in 2 to 6 hours and the duration of action lasting 48 to 72 hours. Other effects of chlorthalidone, which also occur with the thiazide diuretics, are dose-related reductions in serum potassium levels, elevations in serum uric acid and blood glucose, and it can lead to decreased sodium and chloride levels. It should be noted that chlorthalidone may decrease serum-protein bound iodine (PBI) levels without signs of thyroid disturbance.
Clonidine: Clonidine is an agonist at presynaptic alpha-2-receptors in the brainstem. Stimulation of these receptors results in the inhibition of sympathetic outflow from the central nervous system. Suppression of efferent sympathetic pathways decreases vascular tone in the heart, kidneys, and peripheral vasculature; lowers peripheral resistance; and reduces blood pressure. Blood pressure begins to decrease within 30 to 60 minutes of clonidine administration, with maximal hypotensive effects occurring in 2 to 4 hours. Renal blood flow and glomerular filtration rate remain essentially unchanged. Orthostatic symptoms are mild and infrequent since normal postural reflexes remain intact. In the supine position, decreased sympathetic tone reduces cardiac output (15% to 20%) with essentially no change in the total peripheral resistance. In the erect position (45-degree tilt), there is a smaller reduction in cardiac output and a decrease of peripheral resistance. Cardiac output tends to return to control values during chronic therapy with clonidine; peripheral resistance remains decreased. Most patients who take clonidine therapy experience slowing of the pulse rate but the drug does not alter normal hemodynamic response to exercise. Some studies have shown that renin and aldosterone output are reduced in patients taking clonidine. In addition, excretion of catecholamines is reduced; the exact mechanism of these actions is not clear. It is possible that tolerance may develop in some patients, and in such patients further evaluation of treatment may be needed.

Pharmacokinetics

Chlorthalidone; clonidine is administered orally.
 
Chlorthalidone: The drug is 75% bound to plasma proteins and is also highly bound to red blood cells; studies have found 7 to 10 times greater concentrations of chlorthalidone in erythrocytes than in plasma. Chlorthalidone crosses the placenta and is distributed into human breast milk. The majority of the drug is excreted unchanged in the urine; non-renal routes of elimination have yet to be determined. The mean half-life of chlorthalidone is approximately 40 to 60 hours.
Clonidine: Fifty percent (50%) of the absorbed clonidine dose is metabolized in the liver. About 40% to 60% of the absorbed dose is recovered in the urine as unchanged drug in 24 hours post-dose. The plasma half-life of the drug is approximately 12 to 16 hours. The half-life increases up to 41 hours in patients with severe impairment of renal function.

Oral Route

Chlorthalidone: The bioavailability of chlorthalidone after oral administration is about 65%.
Clonidine: Clonidine is rapidly and completely absorbed following oral administration; bioavailability approaches 100%. Peak concentrations of clonidine are reached approximately 3 to 5 hours after oral administration. After oral administration, approximately 40% to 60% of the absorbed dose is recovered in the urine as unchanged drug in 24 hours. About 50% of the absorbed dose is metabolized in the liver.

Pregnancy And Lactation
Pregnancy

Clonidine is classified as a FDA pregnancy risk category C drug and chlorthalidone is classified as a pregnancy category B drug. Therefore the combination is FDA pregnancy risk category C. Adequate and well-controlled studies have not been performed in humans. One study found that clonidine crosses the placenta easily, and its concentrations were equal in maternal serum and umbilical cord serum and amniotic fluid concentrations were up to four times that found in serum. Chlorthalidone is structurally related to the thiazide diuretics; thiazides cross the placental barrier and appear in cord blood. The benefits of chlorthalidone must be weighed against possible hazards to the fetus, such as fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in the adult. The manufacturer of chlorthalidone; clonidine states that the drug should only be used during pregnancy only if clearly needed.

Because of the potential for serious adverse reactions in nursing infants from chlorthalidone, a decision should be made whether to discontinue nursing or to discontinue chlorthalidone; clonidine, taking into account the importance of the drug to the mother. Alternative drugs (e.g., hydrochlorothiazide and other antihypertensive agents) may be preferred during lactation. Clonidine is excreted in breast milk at concentrations that may exceed maternal plasma and should be administered cautiously to breast-feeding women. In addition, clonidine may affect prolactin and oxytocin concentrations, which may theoretically impact establishment of lactation in select individuals. Chlorthalidone is structurally related to the thiazide diuretics which are excreted in human milk ; low doses may be acceptable during lactation but intense diuresis may impact milk production. Alternative drugs (e.g., hydrochlorothiazide and other antihypertensive agents) may be preferred during lactation. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.