irbesartan/hydrochlorothiazide (Rx)

Brand and Other Names:Avalide
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Dosing & Uses

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Dosage Forms & Strengths

irbesartan/hydrochlorothiazide

(tablet)

  • 150mg/12.5mg
  • 300mg/12.5mg

Hypertension

150 mg/12.5 mg PO qDay initially; if needed, after 1-2 weeks may titrate up to 300 mg/25 mg PO qDay

Hepatic impairment

  • No dosage adjustment necessary in patients with hepatic impairment

Renal impairment

  • Usual regimens of therapy may be followed as long as the patient’s creatinine clearance is >30 mL/min; in patients with more severe renal impairment, loop diuretics are preferred to thiazides, so this drug combination is not recommended

Dosing considerations

Not recommended as initial therapy in patients with intravascular volume depletion

Maximum antihypertensive effects are attained within 2-4 weeks after change in dose

In patients not controlled on monotherapy with irbesartan or hydrochlorothiazide, recommended doses of this drug combination, in order of increasing mean effect, are (irbesartan and hydrochlorothiazide) 150/12.5 mg, 300/12.5 mg, and 300/25 mg; the largest incremental effect will likely be in the transition from monotherapy to 150/12.5 mg

Safety and efficacy not established

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Interactions

Interaction Checker

and irbesartan/hydrochlorothiazide

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            Contraindicated (1)

            • aliskiren

              irbesartan decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ARBs in patients with diabetes; avoid coadministration with ARBs if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ARBS with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            Serious - Use Alternative (28)

            • aminolevulinic acid oral

              aminolevulinic acid oral, hydrochlorothiazide. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid administering other phototoxic drugs with aminolevulinic acid oral for 24 hr during perioperative period.

            • aminolevulinic acid topical

              hydrochlorothiazide increases toxicity of aminolevulinic acid topical by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration of photosensitizing drugs may enhance the phototoxic reaction to photodynamic therapy with aminolevulinic acid.

            • baricitinib

              irbesartan will increase the level or effect of baricitinib by decreasing elimination. Avoid or Use Alternate Drug. Coadministration of baricitinib with strong organic anion transporter 3 (OAT3) inhibitors is not recommended.

            • benazepril

              irbesartan, benazepril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • captopril

              irbesartan, captopril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • carbamazepine

              carbamazepine, hydrochlorothiazide. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of systemic hyponatremia.

            • cyclophosphamide

              hydrochlorothiazide increases toxicity of cyclophosphamide by decreasing renal clearance. Avoid or Use Alternate Drug. Increased myelosuppressive effects.

            • cyclosporine

              cyclosporine, hydrochlorothiazide. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of systemic hyponatremia.

            • dofetilide

              hydrochlorothiazide increases levels of dofetilide by decreasing renal clearance. Contraindicated. Risk of prolonged QTc interval.

            • enalapril

              irbesartan, enalapril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • erdafitinib

              irbesartan will increase the level or effect of erdafitinib by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. If coadministration of a strong CYP2C9 inhibitors is unavoidable, closely monitor adverse reactions and modify dose of erdafitinib accordingly. If strong CYP2C9 inhibitor is discontinued, consider increasing erdafitinib dose in the absence of any drug-related toxicities.

            • fosinopril

              irbesartan, fosinopril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • isocarboxazid

              isocarboxazid, hydrochlorothiazide. Other (see comment). Contraindicated. Comment: Additive hypotensive effects may be seen when MAOI's are combined with antihypertensives.

            • lisinopril

              irbesartan, lisinopril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • lithium

              irbesartan increases toxicity of lithium by decreasing renal clearance. Avoid or Use Alternate Drug.

            • lofexidine

              lofexidine, hydrochlorothiazide. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.

              lofexidine, irbesartan. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.

            • lonafarnib

              irbesartan will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

            • methyl aminolevulinate

              hydrochlorothiazide, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

            • moexipril

              irbesartan, moexipril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • perindopril

              irbesartan, perindopril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • quinapril

              irbesartan, quinapril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • ramipril

              irbesartan, ramipril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • siponimod

              irbesartan will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • squill

              hydrochlorothiazide increases toxicity of squill by Other (see comment). Avoid or Use Alternate Drug. Comment: Potassium depletion may enhance toxicity of squill.

            • trandolapril

              irbesartan, trandolapril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • tretinoin

              hydrochlorothiazide, tretinoin. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

            • tretinoin topical

              hydrochlorothiazide, tretinoin topical. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

            • tucatinib

              irbesartan will increase the level or effect of tucatinib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of tucatinib (a CYP2C8 substrate) with a strong or moderate CYP2C8 inhibitors increases tucatinib plasma concentrations and risk of toxicities.

            Monitor Closely (233)

            • acebutolol

              irbesartan and acebutolol both increase serum potassium. Use Caution/Monitor.

              acebutolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              acebutolol, irbesartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • aceclofenac

              aceclofenac increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              irbesartan and aceclofenac both increase serum potassium. Use Caution/Monitor.

            • acemetacin

              irbesartan and acemetacin both increase serum potassium. Use Caution/Monitor.

              acemetacin increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • albiglutide

              irbesartan increases effects of albiglutide by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

              hydrochlorothiazide decreases effects of albiglutide by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

            • albuterol

              irbesartan increases and albuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              albuterol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • aldesleukin

              aldesleukin increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

              aldesleukin increases effects of irbesartan by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • aliskiren

              irbesartan decreases levels of aliskiren by unspecified interaction mechanism. Use Caution/Monitor.

            • amifostine

              amifostine, hydrochlorothiazide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.

            • amifostine

              amifostine, irbesartan. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.

            • amiloride

              irbesartan and amiloride both increase serum potassium. Modify Therapy/Monitor Closely.

              amiloride increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • amiodarone

              amiodarone will increase the level or effect of hydrochlorothiazide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • aspirin

              irbesartan and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              irbesartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • amoxicillin

              amoxicillin, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • arformoterol

              arformoterol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • aspirin

              aspirin increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • aspirin rectal

              aspirin rectal increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

              irbesartan and aspirin rectal both increase serum potassium. Use Caution/Monitor.

            • aspirin/citric acid/sodium bicarbonate

              irbesartan, aspirin/citric acid/sodium bicarbonate. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              irbesartan and aspirin/citric acid/sodium bicarbonate both increase serum potassium. Use Caution/Monitor.

              aspirin/citric acid/sodium bicarbonate decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              aspirin/citric acid/sodium bicarbonate increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • atenolol

              atenolol, irbesartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

              irbesartan and atenolol both increase serum potassium. Use Caution/Monitor.

              atenolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • atogepant

              irbesartan will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • avanafil

              avanafil increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • avanafil

              avanafil increases effects of irbesartan by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • axitinib

              irbesartan increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • beclomethasone, inhaled

              beclomethasone, inhaled increases toxicity of hydrochlorothiazide by increasing elimination. Use Caution/Monitor. May increase the hypokalemic effects of thiazide diuretics.

            • benazepril

              benazepril increases toxicity of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypotensive effects; increased risk of nephrotoxicity.

            • bendroflumethiazide

              bendroflumethiazide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

              irbesartan increases and bendroflumethiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • betaxolol

              irbesartan and betaxolol both increase serum potassium. Use Caution/Monitor.

              betaxolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              betaxolol, irbesartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • bisoprolol

              bisoprolol, irbesartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

              bisoprolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              irbesartan and bisoprolol both increase serum potassium. Use Caution/Monitor.

            • bretylium

              hydrochlorothiazide, bretylium. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Each drug may cause hypotension.

              irbesartan, bretylium. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Each drug may cause hypotension.

            • brimonidine

              brimonidine increases effects of irbesartan by pharmacodynamic synergism. Use Caution/Monitor.

            • bumetanide

              bumetanide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • bumetanide

              irbesartan increases and bumetanide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • buprenorphine, long-acting injection

              buprenorphine, long-acting injection decreases effects of hydrochlorothiazide by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Opioids can reduce diuretic efficacy by inducing antidiuretic hormone release.

            • calcifediol

              hydrochlorothiazide increases toxicity of calcifediol by Other (see comment). Use Caution/Monitor. Comment: Thiazide diuretics may increase serum calcium by decreasing urinary calcium excretion.

            • canagliflozin

              irbesartan and canagliflozin both increase serum potassium. Use Caution/Monitor.

            • candesartan

              candesartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • captopril

              captopril, hydrochlorothiazide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Increased risk of nephrotoxicity. Monitor blood pressure and renal function.

            • carbenoxolone

              hydrochlorothiazide and carbenoxolone both decrease serum potassium. Use Caution/Monitor.

              irbesartan increases and carbenoxolone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • carbidopa

              carbidopa increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.

              carbidopa increases effects of irbesartan by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.

            • carvedilol

              carvedilol, irbesartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

              irbesartan and carvedilol both increase serum potassium. Use Caution/Monitor.

              carvedilol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • cefprozil

              hydrochlorothiazide will increase the level or effect of cefprozil by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • celecoxib

              irbesartan and celecoxib both increase serum potassium. Use Caution/Monitor.

              celecoxib decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              irbesartan, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • celecoxib

              celecoxib increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • celiprolol

              celiprolol, irbesartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

              celiprolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              irbesartan and celiprolol both increase serum potassium. Use Caution/Monitor.

              hydrochlorothiazide decreases levels of celiprolol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

            • chlorothiazide

              chlorothiazide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

              irbesartan increases and chlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • chlorthalidone

              irbesartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              chlorthalidone and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • cholestyramine

              cholestyramine decreases levels of hydrochlorothiazide by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

            • choline magnesium trisalicylate

              irbesartan and choline magnesium trisalicylate both increase serum potassium. Use Caution/Monitor.

              choline magnesium trisalicylate decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              irbesartan, choline magnesium trisalicylate. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • citalopram

              hydrochlorothiazide, citalopram. pharmacodynamic synergism. Use Caution/Monitor. Possible additive hyponatremia.

            • cornsilk

              cornsilk increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypokalemia (theoretical interaction).

            • corticotropin

              corticotropin increases toxicity of hydrochlorothiazide by increasing renal clearance. Use Caution/Monitor. May enhance hypokalemic effect of thiazide diuretics.

            • cyclopenthiazide

              irbesartan increases and cyclopenthiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              cyclopenthiazide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • cyclosporine

              cyclosporine increases toxicity of hydrochlorothiazide by unspecified interaction mechanism. Use Caution/Monitor. Coadministration of hydrochlorothiazide with cyclosporine may increase the risk of hypermagnesemia, hyperuricemia, and possible nephrotoxicity.

            • dalteparin

              dalteparin increases toxicity of irbesartan by Other (see comment). Use Caution/Monitor. Comment: Low molecular weight heparins may suppress adrenal aldosterone secretion, which can potentially cause hyperkalemia.

            • deflazacort

              hydrochlorothiazide and deflazacort both decrease serum potassium. Use Caution/Monitor.

            • diazoxide

              hydrochlorothiazide increases toxicity of diazoxide by unspecified interaction mechanism. Use Caution/Monitor. May enhance hyperglycemic effects of diazoxide.

            • dichlorphenamide

              dichlorphenamide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • diclofenac

              diclofenac increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              irbesartan, diclofenac. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              irbesartan and diclofenac both increase serum potassium. Use Caution/Monitor.

              diclofenac decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • dicloxacillin

              dicloxacillin, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • diflunisal

              irbesartan and diflunisal both increase serum potassium. Use Caution/Monitor.

              diflunisal decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              irbesartan, diflunisal. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • diflunisal

              diflunisal increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • digoxin

              hydrochlorothiazide increases effects of digoxin by pharmacodynamic synergism. Use Caution/Monitor. Hypokalemia increases digoxin effects.

              digoxin increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              irbesartan and digoxin both increase serum potassium. Use Caution/Monitor.

              digoxin will increase the level or effect of hydrochlorothiazide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • dobutamine

              dobutamine and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • dopexamine

              irbesartan increases and dopexamine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dofetilide

              dofetilide will increase the level or effect of hydrochlorothiazide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • dopexamine

              dopexamine and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • drospirenone

              drospirenone increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              irbesartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

            • empagliflozin

              empagliflozin, hydrochlorothiazide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of empagliflozin with diuretics results in increased urine volume and frequency of voids, which might enhance the potential for volume depletion.

            • enoxaparin

              enoxaparin increases toxicity of irbesartan by Other (see comment). Use Caution/Monitor. Comment: Low molecular weight heparins may suppress adrenal aldosterone secretion, which can potentially cause hyperkalemia.

            • ephedrine

              ephedrine and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • epinephrine

              epinephrine and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • epinephrine racemic

              epinephrine racemic and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • eplerenone

              irbesartan, eplerenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

            • eprosartan

              eprosartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • esmolol

              irbesartan and esmolol both increase serum potassium. Use Caution/Monitor.

              esmolol, irbesartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

              esmolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ethacrynic acid

              irbesartan increases and ethacrynic acid decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              ethacrynic acid and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • etodolac

              etodolac increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              irbesartan, etodolac. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              etodolac decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              irbesartan and etodolac both increase serum potassium. Use Caution/Monitor.

            • exenatide injectable solution

              irbesartan increases effects of exenatide injectable solution by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

              hydrochlorothiazide decreases effects of exenatide injectable solution by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

            • exenatide injectable suspension

              irbesartan increases effects of exenatide injectable suspension by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

              hydrochlorothiazide decreases effects of exenatide injectable suspension by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

            • fenbufen

              irbesartan and fenbufen both increase serum potassium. Use Caution/Monitor.

            • fenoprofen

              fenoprofen increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • fenoprofen

              irbesartan and fenoprofen both increase serum potassium. Use Caution/Monitor.

              fenoprofen decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              irbesartan, fenoprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • fentanyl

              fentanyl decreases effects of hydrochlorothiazide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

            • fentanyl intranasal

              fentanyl intranasal decreases effects of hydrochlorothiazide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

            • fentanyl transdermal

              fentanyl transdermal decreases effects of hydrochlorothiazide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

            • fentanyl transmucosal

              fentanyl transmucosal decreases effects of hydrochlorothiazide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

            • finerenone

              irbesartan will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.

            • flibanserin

              irbesartan will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

            • flurbiprofen

              irbesartan, flurbiprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              flurbiprofen increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              flurbiprofen decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              irbesartan and flurbiprofen both increase serum potassium. Use Caution/Monitor.

            • formoterol

              formoterol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • furosemide

              irbesartan increases and furosemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • furosemide

              furosemide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • gentamicin

              hydrochlorothiazide and gentamicin both decrease serum potassium. Use Caution/Monitor.

              irbesartan increases and gentamicin decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • heparin

              heparin increases toxicity of irbesartan by Other (see comment). Use Caution/Monitor. Comment: Low molecular weight heparins may suppress adrenal aldosterone secretion, which can potentially cause hyperkalemia.

            • ibuprofen

              ibuprofen increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • hydrochlorothiazide

              irbesartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ibuprofen

              irbesartan and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of irbesartan by pharmacodynamic antagonism. Use Caution/Monitor. Antihypertensive effect of angiotensin receptor blockers may be attenuated by NSAIDs; monitor renal function and blood pressure periodically.

              irbesartan, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • ibuprofen IV

              irbesartan, ibuprofen IV. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              irbesartan and ibuprofen IV both increase serum potassium. Use Caution/Monitor.

              ibuprofen IV decreases effects of irbesartan by pharmacodynamic antagonism. Use Caution/Monitor. Antihypertensive effect of angiotensin receptor blockers may be attenuated by NSAIDs; monitor renal function and blood pressure periodically.

              hydrochlorothiazide will increase the level or effect of ibuprofen IV by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

              ibuprofen IV increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. NSAIDs may decrease the therapeutic effects of thiazide-like diuretics; may also enhance nephrotoxic effects.

            • indacaterol, inhaled

              hydrochlorothiazide, indacaterol, inhaled. serum potassium. Use Caution/Monitor. Combination may increase risk of hypokalemia.

              indacaterol, inhaled, hydrochlorothiazide. Other (see comment). Use Caution/Monitor. Comment: Caution is advised in the coadministration of indacaterol neohaler with non-potassium-sparing diuretics.

            • indapamide

              irbesartan increases and indapamide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • indapamide

              hydrochlorothiazide and indapamide both decrease serum potassium. Use Caution/Monitor.

            • indomethacin

              irbesartan, indomethacin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              indomethacin decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              indomethacin increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              irbesartan and indomethacin both increase serum potassium. Use Caution/Monitor.

            • insulin aspart

              irbesartan increases effects of insulin aspart by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin degludec

              hydrochlorothiazide decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

            • insulin aspart protamine/insulin aspart

              irbesartan increases effects of insulin aspart protamine/insulin aspart by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin degludec

              irbesartan, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              irbesartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin degludec/insulin aspart

              irbesartan, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              hydrochlorothiazide decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

            • insulin detemir

              irbesartan increases effects of insulin detemir by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin inhaled

              hydrochlorothiazide decreases effects of insulin inhaled by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

            • insulin glargine

              irbesartan increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin glulisine

              irbesartan increases effects of insulin glulisine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin inhaled

              irbesartan, insulin inhaled. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              irbesartan increases effects of insulin inhaled by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin isophane human/insulin regular human

              irbesartan increases effects of insulin isophane human/insulin regular human by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin lispro

              irbesartan increases effects of insulin lispro by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin lispro protamine/insulin lispro

              irbesartan increases effects of insulin lispro protamine/insulin lispro by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin NPH

              irbesartan increases effects of insulin NPH by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin regular human

              irbesartan increases effects of insulin regular human by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • irbesartan

              irbesartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • isavuconazonium sulfate

              irbesartan will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isoproterenol

              isoproterenol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • ivacaftor

              irbesartan increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • juniper

              juniper, hydrochlorothiazide. Other (see comment). Use Caution/Monitor. Comment: Juniper may potentiate or interfere with diuretic therapy. Juniper has diuretic effects, but may cause kidney damage at large doses.

            • ketoprofen

              ketoprofen increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              ketoprofen decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              irbesartan and ketoprofen both increase serum potassium. Use Caution/Monitor.

              irbesartan, ketoprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • ketorolac

              irbesartan and ketorolac both increase serum potassium. Use Caution/Monitor.

              ketorolac decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              irbesartan, ketorolac. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              ketorolac increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ketorolac intranasal

              ketorolac intranasal decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              irbesartan and ketorolac intranasal both increase serum potassium. Use Caution/Monitor.

              ketorolac intranasal increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

              irbesartan, ketorolac intranasal. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • labetalol

              irbesartan and labetalol both increase serum potassium. Use Caution/Monitor.

              labetalol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              labetalol, irbesartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • lemborexant

              irbesartan will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.

            • levalbuterol

              levalbuterol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • levodopa

              levodopa increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

              levodopa increases effects of irbesartan by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

            • lily of the valley

              hydrochlorothiazide increases toxicity of lily of the valley by Other (see comment). Use Caution/Monitor. Comment: Increased risk of cardiac toxicity due to K+ depletion.

            • liraglutide

              irbesartan increases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

            • liraglutide

              hydrochlorothiazide decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

            • lithium

              hydrochlorothiazide increases toxicity of lithium by decreasing elimination. Use Caution/Monitor.

            • lomitapide

              irbesartan increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

            • lornoxicam

              irbesartan and lornoxicam both increase serum potassium. Use Caution/Monitor.

              lornoxicam increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • losartan

              losartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • maitake

              maitake increases effects of irbesartan by pharmacodynamic synergism. Use Caution/Monitor.

            • lurasidone

              lurasidone increases effects of hydrochlorothiazide by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of hypotension with concurrent use. Monitor blood pressure and adjust dose of antihypertensive agent as needed.

            • maitake

              maitake increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypokalemia (theoretical interaction).

            • maraviroc

              maraviroc, irbesartan. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.

            • meclofenamate

              irbesartan, meclofenamate. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              irbesartan and meclofenamate both increase serum potassium. Use Caution/Monitor.

              meclofenamate increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              meclofenamate decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • mefenamic acid

              mefenamic acid decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              mefenamic acid increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              irbesartan and mefenamic acid both increase serum potassium. Use Caution/Monitor.

              irbesartan, mefenamic acid. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • meloxicam

              meloxicam decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              irbesartan, meloxicam. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              irbesartan and meloxicam both increase serum potassium. Use Caution/Monitor.

              meloxicam increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • metaproterenol

              metaproterenol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • methyclothiazide

              irbesartan increases and methyclothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

            • methoxsalen

              methoxsalen, hydrochlorothiazide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive photosensitizing effects.

            • methylphenidate

              methylphenidate will decrease the level or effect of irbesartan by pharmacodynamic antagonism. Use Caution/Monitor. Methylphenidate may diminish antihypertensive effects. Monitor BP.

            • methylphenidate transdermal

              methylphenidate transdermal decreases effects of hydrochlorothiazide by anti-hypertensive channel blocking. Use Caution/Monitor.

              methylphenidate transdermal decreases effects of irbesartan by anti-hypertensive channel blocking. Use Caution/Monitor.

            • metolazone

              irbesartan increases and metolazone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              hydrochlorothiazide and metolazone both decrease serum potassium. Use Caution/Monitor.

            • metoprolol

              hydrochlorothiazide, metoprolol. Either increases toxicity of the other by Other (see comment). Modify Therapy/Monitor Closely. Comment: May cause idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma, which can lead to permanent vision loss.

              irbesartan and metoprolol both increase serum potassium. Use Caution/Monitor.

              metoprolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              metoprolol, irbesartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • midazolam intranasal

              irbesartan will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.

            • mometasone inhaled

              mometasone inhaled increases toxicity of hydrochlorothiazide by Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may increase hypokalemic effect of loop diuretics.

            • mycophenolate

              hydrochlorothiazide will increase the level or effect of mycophenolate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • nabumetone

              nabumetone decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              nabumetone increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              irbesartan, nabumetone. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              irbesartan and nabumetone both increase serum potassium. Use Caution/Monitor.

            • nadolol

              irbesartan and nadolol both increase serum potassium. Use Caution/Monitor.

              nadolol, irbesartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

              nadolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • nafcillin

              nafcillin, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • naproxen

              irbesartan and naproxen both increase serum potassium. Use Caution/Monitor.

              naproxen decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              irbesartan, naproxen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • naproxen

              naproxen increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • nebivolol

              nebivolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              irbesartan and nebivolol both increase serum potassium. Use Caution/Monitor.

              nebivolol, irbesartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • nitroglycerin rectal

              nitroglycerin rectal, irbesartan. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Observe for possible additive hypotensive effects during concomitant use. .

              nitroglycerin rectal, hydrochlorothiazide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Observe for possible additive hypotensive effects during concomitant use. .

            • norepinephrine

              norepinephrine and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • oxaprozin

              irbesartan and oxaprozin both increase serum potassium. Use Caution/Monitor.

              oxaprozin decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              irbesartan, oxaprozin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • oliceridine

              oliceridine decreases effects of hydrochlorothiazide by Other (see comment). Use Caution/Monitor. Comment: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Monitor for signs of diminished diuresis and/or effects on blood pressure and increase dosage of the diuretic as needed. .

            • olmesartan

              olmesartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • olodaterol inhaled

              hydrochlorothiazide and olodaterol inhaled both decrease serum potassium. Use Caution/Monitor.

            • oxaprozin

              oxaprozin increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • paclitaxel

              irbesartan will increase the level or effect of paclitaxel by Other (see comment). Use Caution/Monitor. Paclitaxel levels/toxicity may increase when coadministered with CYP2C8 inhibitors

            • paclitaxel protein bound

              irbesartan will increase the level or effect of paclitaxel protein bound by Other (see comment). Use Caution/Monitor. Paclitaxel levels/toxicity may increase when coadministered with CYP2C8 inhibitors

            • parecoxib

              parecoxib increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              irbesartan and parecoxib both increase serum potassium. Use Caution/Monitor.

            • penbutolol

              penbutolol, irbesartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

              irbesartan and penbutolol both increase serum potassium. Use Caution/Monitor.

              penbutolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • penicillin G aqueous

              penicillin G aqueous, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • pindolol

              irbesartan and pindolol both increase serum potassium. Use Caution/Monitor.

              pindolol, irbesartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • pindolol

              pindolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pirbuterol

              pirbuterol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • piroxicam

              piroxicam increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              irbesartan, piroxicam. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              irbesartan and piroxicam both increase serum potassium. Use Caution/Monitor.

              piroxicam decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • pivmecillinam

              pivmecillinam, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • potassium acid phosphate

              irbesartan and potassium acid phosphate both increase serum potassium. Use Caution/Monitor.

            • porfimer

              hydrochlorothiazide, porfimer. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced photosensitivity.

            • potassium acid phosphate

              potassium acid phosphate increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • potassium chloride

              irbesartan and potassium chloride both increase serum potassium. Use Caution/Monitor.

              potassium chloride increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • potassium citrate

              irbesartan and potassium citrate both increase serum potassium. Use Caution/Monitor.

              potassium citrate increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • potassium citrate/citric acid

              irbesartan and potassium citrate/citric acid both increase serum potassium. Modify Therapy/Monitor Closely.

            • probenecid

              hydrochlorothiazide will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • potassium iodide

              potassium iodide and irbesartan both increase serum potassium. Use Caution/Monitor. Potassium salts may increase the hyperkalemic effects of ARBs; the effect may be the result of aldosterone suppression in patients receiving ARBs.

            • procainamide

              hydrochlorothiazide will increase the level or effect of procainamide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • propranolol

              propranolol, irbesartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

              irbesartan and propranolol both increase serum potassium. Use Caution/Monitor.

              propranolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • quinidine

              quinidine will increase the level or effect of hydrochlorothiazide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • sacubitril/valsartan

              irbesartan and sacubitril/valsartan both increase serum potassium. Use Caution/Monitor.

            • sacubitril/valsartan

              sacubitril/valsartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • salicylates (non-asa)

              salicylates (non-asa) increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              irbesartan and salicylates (non-asa) both increase serum potassium. Use Caution/Monitor.

            • salmeterol

              salmeterol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • salsalate

              irbesartan and salsalate both increase serum potassium. Use Caution/Monitor.

              salsalate decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              irbesartan, salsalate. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • salsalate

              salsalate increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • selexipag

              irbesartan will increase the level or effect of selexipag by decreasing metabolism. Modify Therapy/Monitor Closely. Reduce selexipag dose to once daily if coadministered with moderate CYP2C8 inhibitors.

            • shark cartilage

              hydrochlorothiazide, shark cartilage. Other (see comment). Use Caution/Monitor. Comment: May lead to hypercalcemia (theoretical).

            • sodium sulfate/?magnesium sulfate/potassium chloride

              sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of hydrochlorothiazide by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

              sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of irbesartan by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

            • sodium sulfate/potassium sulfate/magnesium sulfate

              sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of irbesartan by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

              sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of hydrochlorothiazide by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

            • sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol

              hydrochlorothiazide and sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol both decrease serum potassium. Modify Therapy/Monitor Closely.

            • sotalol

              irbesartan and sotalol both increase serum potassium. Use Caution/Monitor.

              sotalol, irbesartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • sotalol

              sotalol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • spironolactone

              spironolactone increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              irbesartan and spironolactone both increase serum potassium. Modify Therapy/Monitor Closely.

            • succinylcholine

              succinylcholine increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • sulfasalazine

              irbesartan and sulfasalazine both increase serum potassium. Use Caution/Monitor.

              sulfasalazine decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              irbesartan, sulfasalazine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • sulfasalazine

              sulfasalazine increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • sulindac

              irbesartan and sulindac both increase serum potassium. Use Caution/Monitor.

              sulindac increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              irbesartan, sulindac. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              sulindac decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • synthetic human angiotensin II

              irbesartan decreases effects of synthetic human angiotensin II by pharmacodynamic antagonism. Use Caution/Monitor.

            • tadalafil

              tadalafil increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • tadalafil

              tadalafil increases effects of irbesartan by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • tazemetostat

              irbesartan will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • telmisartan

              telmisartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              irbesartan and telmisartan both increase serum potassium. Use Caution/Monitor.

            • temocillin

              temocillin, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • terbutaline

              irbesartan increases and terbutaline decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • terbutaline

              terbutaline and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • ticarcillin

              ticarcillin, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • timolol

              timolol, irbesartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

              timolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              irbesartan and timolol both increase serum potassium. Use Caution/Monitor.

            • tinidazole

              irbesartan will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tolfenamic acid

              tolfenamic acid increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • tizanidine

              tizanidine increases effects of irbesartan by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • tolfenamic acid

              irbesartan and tolfenamic acid both increase serum potassium. Use Caution/Monitor.

            • tolmetin

              tolmetin increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              tolmetin decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              irbesartan and tolmetin both increase serum potassium. Use Caution/Monitor.

              irbesartan, tolmetin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • tolvaptan

              tolvaptan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              irbesartan and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • toremifene

              hydrochlorothiazide, toremifene. Other (see comment). Use Caution/Monitor. Comment: Thiazide diuretics decrease renal calcium excretion and may increase risk of hypercalcemia in patients taking toremifene.

            • torsemide

              irbesartan increases and torsemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • torsemide

              torsemide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • treprostinil

              treprostinil increases effects of irbesartan by pharmacodynamic synergism. Use Caution/Monitor.

            • triamterene

              triamterene increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              irbesartan and triamterene both increase serum potassium. Modify Therapy/Monitor Closely.

            • trientine

              hydrochlorothiazide decreases levels of trientine by increasing renal clearance. Use Caution/Monitor.

            • trimethoprim

              trimethoprim and irbesartan both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

            • umeclidinium bromide/vilanterol inhaled

              umeclidinium bromide/vilanterol inhaled and hydrochlorothiazide both decrease serum potassium. Modify Therapy/Monitor Closely. Electrocardiographic changes and/or hypokalemia associated with non?potassium-sparing diuretics may worsen with concomitant beta-agonists, particularly if recommended dose is exceeded

            • valsartan

              valsartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • vilanterol/fluticasone furoate inhaled

              vilanterol/fluticasone furoate inhaled and hydrochlorothiazide both decrease serum potassium. Modify Therapy/Monitor Closely. Beta-agonists may acutely worsen ECG changes and/or hypokalemia resulting from non-potassium-sparing diuretics

            • vitamin D

              hydrochlorothiazide increases effects of vitamin D by Other (see comment). Use Caution/Monitor. Comment: Combination may increase hypercalcemic effect of vitamin D analogs. Use with caution.

            • voclosporin

              voclosporin and irbesartan both increase serum potassium. Use Caution/Monitor.

              voclosporin, irbesartan. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

            • xipamide

              xipamide increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor.

              xipamide increases effects of irbesartan by pharmacodynamic synergism. Use Caution/Monitor.

            Minor (155)

            • acarbose

              hydrochlorothiazide decreases effects of acarbose by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • aceclofenac

              hydrochlorothiazide will increase the level or effect of aceclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • acemetacin

              hydrochlorothiazide will increase the level or effect of acemetacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • acyclovir

              hydrochlorothiazide will increase the level or effect of acyclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • agrimony

              agrimony increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

              agrimony increases effects of irbesartan by pharmacodynamic synergism. Minor/Significance Unknown.

            • albuterol

              albuterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • cornsilk

              cornsilk increases effects of irbesartan by pharmacodynamic synergism. Minor/Significance Unknown.

            • aminohippurate sodium

              hydrochlorothiazide will increase the level or effect of aminohippurate sodium by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ampicillin

              hydrochlorothiazide increases levels of ampicillin by decreasing renal clearance. Minor/Significance Unknown.

            • arformoterol

              arformoterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • aspirin

              hydrochlorothiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • aspirin rectal

              hydrochlorothiazide will increase the level or effect of aspirin rectal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • aspirin/citric acid/sodium bicarbonate

              hydrochlorothiazide will increase the level or effect of aspirin/citric acid/sodium bicarbonate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • balsalazide

              hydrochlorothiazide will increase the level or effect of balsalazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • bendroflumethiazide

              bendroflumethiazide will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • birch

              birch increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

            • bitter melon

              bitter melon, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • brimonidine

              brimonidine increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

            • budesonide

              budesonide, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • calcitriol topical

              calcitriol topical, hydrochlorothiazide. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential additive hypercalcemia.

            • calcium acetate

              hydrochlorothiazide increases levels of calcium acetate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

            • calcium carbonate

              hydrochlorothiazide increases levels of calcium carbonate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

            • calcium chloride

              hydrochlorothiazide increases levels of calcium chloride by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

            • calcium citrate

              hydrochlorothiazide increases levels of calcium citrate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

            • calcium gluconate

              hydrochlorothiazide increases levels of calcium gluconate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

            • carbenoxolone

              hydrochlorothiazide, carbenoxolone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypokalemic effects.

            • cefadroxil

              cefadroxil will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cefamandole

              cefamandole will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cefpirome

              cefpirome will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cefprozil

              cefprozil will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ceftibuten

              ceftibuten will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • celecoxib

              hydrochlorothiazide will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cephalexin

              cephalexin will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • chlorothiazide

              chlorothiazide will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • chlorpropamide

              hydrochlorothiazide will increase the level or effect of chlorpropamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              hydrochlorothiazide decreases effects of chlorpropamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • chlorthalidone

              chlorthalidone will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • colestipol

              colestipol decreases levels of hydrochlorothiazide by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • cortisone

              cortisone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • cosyntropin

              cosyntropin, hydrochlorothiazide. pharmacodynamic synergism. Minor/Significance Unknown. Possible enhanced electrolyte loss.

            • cyclopenthiazide

              cyclopenthiazide will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • deflazacort

              deflazacort, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • dexamethasone

              dexamethasone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • diazoxide

              diazoxide, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hyperglycemia.

            • diclofenac

              hydrochlorothiazide will increase the level or effect of diclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • diflunisal

              hydrochlorothiazide will increase the level or effect of diflunisal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • dobutamine

              dobutamine, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • dopexamine

              dopexamine, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • entecavir

              irbesartan, entecavir. Either increases effects of the other by decreasing renal clearance. Minor/Significance Unknown. Coadministration with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either entecavir or the coadministered drug.

            • ephedrine

              ephedrine, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • epinephrine

              epinephrine, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • epinephrine racemic

              epinephrine racemic, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • epoprostenol

              epoprostenol increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.

            • etodolac

              hydrochlorothiazide will increase the level or effect of etodolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • fenbufen

              hydrochlorothiazide will increase the level or effect of fenbufen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • fenoprofen

              hydrochlorothiazide will increase the level or effect of fenoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • fludrocortisone

              fludrocortisone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • flurbiprofen

              hydrochlorothiazide will increase the level or effect of flurbiprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • fo-ti

              fo-ti increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia (theoretical).

            • folic acid

              hydrochlorothiazide decreases levels of folic acid by increasing renal clearance. Minor/Significance Unknown.

            • formoterol

              formoterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • forskolin

              forskolin increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

            • ganciclovir

              hydrochlorothiazide will increase the level or effect of ganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • glimepiride

              hydrochlorothiazide decreases effects of glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • glipizide

              hydrochlorothiazide decreases effects of glipizide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • glyburide

              hydrochlorothiazide decreases effects of glyburide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • goldenrod

              goldenrod increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

            • hydrocortisone

              hydrocortisone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • ibuprofen

              hydrochlorothiazide will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • indapamide

              hydrochlorothiazide will increase the level or effect of indapamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • indomethacin

              hydrochlorothiazide will increase the level or effect of indomethacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • insulin aspart

              hydrochlorothiazide decreases effects of insulin aspart by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • insulin detemir

              hydrochlorothiazide decreases effects of insulin detemir by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • insulin glargine

              hydrochlorothiazide decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • insulin glulisine

              hydrochlorothiazide decreases effects of insulin glulisine by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • insulin lispro

              hydrochlorothiazide decreases effects of insulin lispro by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • insulin NPH

              hydrochlorothiazide decreases effects of insulin NPH by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • insulin regular human

              hydrochlorothiazide decreases effects of insulin regular human by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • isoproterenol

              isoproterenol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • ketoprofen

              hydrochlorothiazide will increase the level or effect of ketoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ketorolac

              hydrochlorothiazide will increase the level or effect of ketorolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ketorolac intranasal

              hydrochlorothiazide will increase the level or effect of ketorolac intranasal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • L-methylfolate

              hydrochlorothiazide decreases levels of L-methylfolate by increasing renal clearance. Minor/Significance Unknown.

            • levalbuterol

              levalbuterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • lornoxicam

              hydrochlorothiazide will increase the level or effect of lornoxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • magnesium chloride

              hydrochlorothiazide decreases levels of magnesium chloride by increasing renal clearance. Minor/Significance Unknown.

            • magnesium citrate

              hydrochlorothiazide decreases levels of magnesium citrate by increasing renal clearance. Minor/Significance Unknown.

            • magnesium hydroxide

              hydrochlorothiazide decreases levels of magnesium hydroxide by increasing renal clearance. Minor/Significance Unknown.

            • magnesium oxide

              hydrochlorothiazide decreases levels of magnesium oxide by increasing renal clearance. Minor/Significance Unknown.

            • magnesium sulfate

              hydrochlorothiazide decreases levels of magnesium sulfate by increasing renal clearance. Minor/Significance Unknown.

            • meclofenamate

              hydrochlorothiazide will increase the level or effect of meclofenamate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • mefenamic acid

              hydrochlorothiazide will increase the level or effect of mefenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • meloxicam

              hydrochlorothiazide will increase the level or effect of meloxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • memantine

              hydrochlorothiazide will increase the level or effect of memantine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • mesalamine

              hydrochlorothiazide will increase the level or effect of mesalamine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • metaproterenol

              metaproterenol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • metformin

              hydrochlorothiazide will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              hydrochlorothiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • methotrexate

              hydrochlorothiazide increases toxicity of methotrexate by decreasing elimination. Minor/Significance Unknown. Increased myelosuppression.

            • methylprednisolone

              methylprednisolone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • metolazone

              hydrochlorothiazide will increase the level or effect of metolazone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • midodrine

              hydrochlorothiazide will increase the level or effect of midodrine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • miglitol

              hydrochlorothiazide decreases effects of miglitol by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • minoxidil

              hydrochlorothiazide increases effects of minoxidil by pharmacodynamic synergism. Minor/Significance Unknown.

            • nabumetone

              hydrochlorothiazide will increase the level or effect of nabumetone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • naproxen

              hydrochlorothiazide will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • nateglinide

              hydrochlorothiazide decreases effects of nateglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • nirmatrelvir/ritonavir

              nirmatrelvir/ritonavir will decrease the level or effect of irbesartan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. Irbesartan metabolized by glucuronidation and oxidation (mainly CYP2C9). Ritonavir is a weak CYP2C9 inducer and could potentially decrease irbesartan exposure. No dosage modification needed since induction reaches maximal effect after several days and the short duration of nirmatrelvir/ritonavir treatment.

            • noni juice

              irbesartan and noni juice both increase serum potassium. Minor/Significance Unknown.

              noni juice increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

            • norepinephrine

              norepinephrine, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

              hydrochlorothiazide decreases effects of norepinephrine by pharmacodynamic antagonism. Minor/Significance Unknown. May decrease responsiveness to norepinephrine but not enough to preclude effectiveness of the pressor agent therapeutic use.

            • octacosanol

              octacosanol increases effects of irbesartan by pharmacodynamic synergism. Minor/Significance Unknown.

            • octacosanol

              octacosanol increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

            • ofloxacin

              hydrochlorothiazide will increase the level or effect of ofloxacin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • oxaprozin

              hydrochlorothiazide will increase the level or effect of oxaprozin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • parecoxib

              hydrochlorothiazide will increase the level or effect of parecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • penicillin G aqueous

              hydrochlorothiazide increases levels of penicillin G aqueous by decreasing renal clearance. Minor/Significance Unknown.

            • penicillin VK

              hydrochlorothiazide increases levels of penicillin VK by decreasing renal clearance. Minor/Significance Unknown.

            • pioglitazone

              hydrochlorothiazide decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • piperacillin

              hydrochlorothiazide increases levels of piperacillin by decreasing renal clearance. Minor/Significance Unknown.

            • pirbuterol

              pirbuterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • piroxicam

              hydrochlorothiazide will increase the level or effect of piroxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • prednisolone

              prednisolone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • prednisone

              prednisone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • quinine

              hydrochlorothiazide will increase the level or effect of quinine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • reishi

              reishi increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

              reishi increases effects of irbesartan by pharmacodynamic synergism. Minor/Significance Unknown.

            • repaglinide

              hydrochlorothiazide decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • ruxolitinib

              irbesartan will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • rose hips

              rose hips will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • rosiglitazone

              hydrochlorothiazide decreases effects of rosiglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • ruxolitinib topical

              irbesartan will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • salicylates (non-asa)

              hydrochlorothiazide will increase the level or effect of salicylates (non-asa) by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • salmeterol

              salmeterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • salsalate

              hydrochlorothiazide will increase the level or effect of salsalate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • saxagliptin

              hydrochlorothiazide decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • shepherd's purse

              shepherd's purse, hydrochlorothiazide. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.

              shepherd's purse, irbesartan. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.

            • sitagliptin

              hydrochlorothiazide decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • sulfadiazine

              hydrochlorothiazide increases levels of sulfadiazine by unspecified interaction mechanism. Minor/Significance Unknown.

            • sulfamethoxazole

              sulfamethoxazole will increase the level or effect of hydrochlorothiazide by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              hydrochlorothiazide increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

              hydrochlorothiazide, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.

            • sulfasalazine

              hydrochlorothiazide will increase the level or effect of sulfasalazine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • sulfisoxazole

              hydrochlorothiazide increases levels of sulfisoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

            • sulindac

              hydrochlorothiazide will increase the level or effect of sulindac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • terbutaline

              terbutaline, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

              hydrochlorothiazide, terbutaline. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypokalemic effects.

            • tizanidine

              tizanidine increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.

            • tolazamide

              hydrochlorothiazide decreases effects of tolazamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • tolbutamide

              hydrochlorothiazide decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • tolfenamic acid

              hydrochlorothiazide will increase the level or effect of tolfenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • tolmetin

              hydrochlorothiazide will increase the level or effect of tolmetin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • treprostinil

              treprostinil increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

            • triamcinolone acetonide injectable suspension

              triamcinolone acetonide injectable suspension, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • triamterene

              hydrochlorothiazide will increase the level or effect of triamterene by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • trilostane

              trilostane, hydrochlorothiazide. Other (see comment). Minor/Significance Unknown. Comment: Trilostane reduces K+ loss while maintaining the natriuretic effect. Mechanism: inhibition of mineralocorticoid steroid synthesis.

            • trimethoprim

              hydrochlorothiazide will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              hydrochlorothiazide, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.

            • valganciclovir

              hydrochlorothiazide will increase the level or effect of valganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • verapamil

              hydrochlorothiazide will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • verteporfin

              hydrochlorothiazide, verteporfin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased phototoxicity.

            • vildagliptin

              hydrochlorothiazide decreases effects of vildagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • willow bark

              hydrochlorothiazide will increase the level or effect of willow bark by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

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            Adverse Effects

            Adverse reactions with combination products and individual agents

            >10%

            Irbesartan

            • Hyperkalemia (19%)

            1-10%

            Chest pain (2%)

            Tachycardia (1%)

            Abnormal urination (2%)

            Musculoskeletal pain (6%)

            Flu-like syndrome (3%)

            Edema (3%)

            Tachycardia (1%)

            Chest pain (2%)

            Creatinine increased (1%)

            Increased BUN (2%)

            Irbesartan

            • Dizziness (10%)
            • URI (9%)
            • Orthostatic hypotension (5%)
            • Fatigue (4%)
            • Diarrhea (3%)
            • Dyspepsia (2%)

            Frequency Not Defined

            Hydrochlorothiazide

            • Anorexia Epigastric distress
            • Hypotension
            • Orthostatic hypotension
            • Photosensitivity
            • Anaphylaxis
            • Anemia
            • Confusion
            • Erythema multiforme
            • Stevens-Johnson syndrome
            • Exfoliative dermatitis including toxic epidermal necrolysis
            • Dizziness
            • Hypokalemia and/or hypomagnesemia
            • Hyperuricemia
            • Headache

            Postmarketing Reports

            Urticaria

            Angioedema

            Hepatitis

            Jaundice (with irbesartan)

            Heart failure

            Sexual dysfunction

            Thrombocytopenia

            Impaired renal function, including renal failure (with irbesartan)

            Increased CPK levels (with ARBs)

            Tinnitus

            Hydrochlorothiazide

            • Non-melanoma skin cancer
            • Acute angle-closure glaucoma, acute myopia, choroidal effusion
            • Hypoglycemia in diabetic patients
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            Warnings

            Black Box Warnings

            Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system causing oligohydramnios, which may result in fetal injury and/or death

            Contraindications

            Hypersensitivity to irbesartan, hydrochlorothiazide, or sulfonamides

            Pregnancy (2nd and 3rd trimesters): Significant risk of fetal/neonatal morbidity and mortality

            Anuria

            Do not coadminister with aliskiren in patients with diabetes mellitus

            Cautions

            If CrCl <30 mL/min, use loop diuretic instead of hydrochlorothiazide

            Hyperkalemia, particularly when coadministered with potassium-sparing diuretics, potassium supplements, or salt substitutes; concurrent therapy with hydrochlorothiazide may reduce the frequency of this effect; monitor serum potassium levels periodically

            Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease since minor alterations of fluid and electrolyte balance may precipitate hepatic coma

            Dual blockade of the renin-angiotensin system with ARBs, ACE inhibitors, or aliskiren associated with increased risk for renal function changes (including acute renal failure) compared to monotherapy

            Instruct patients to protect skin from sun and undergo regular skin cancer screening

            Caution in aortic mitral stenosis, hypercholesterolemia, hypercalcemia, parathyroid disease, or anuria

            Hypotension in volume or salt depleted patients

            • Excessive reduction of blood pressure was rarely seen in patients with uncomplicated hypertension treated with irbesartan alone (<0.1%) or with irbesartan and hydrochlorothiazide (approximately 1%)
            • Initiation of antihypertensive therapy may cause symptomatic hypotension in patients with intravascular volume or sodium depletion, eg, in patients treated vigorously with diuretics or in patients on dialysis; such volume depletion should be corrected prior to administration of antihypertensive therapy
            • If hypotension occurs, the patient should be placed in supine position and, if necessary, given an intravenous infusion of normal saline; a transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized

            Impaired renal function

            • As result of inhibiting renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals
            • In patients whose renal function may depend on activity of renin-angiotensin-aldosterone system (eg, patients with severe congestive heart failure), treatment with ACE inhibitors has been associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death
            • In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or BUN have been reported; there has been no known use of irbesartan in patients with unilateral or bilateral renal artery stenosis, but a similar effect should be anticipated
            • Thiazides should be used with caution in severe renal disease; in patients with renal disease, thiazides may precipitate azotemia; cumulative effects of the drug may develop in patients with impaired renal function

            Acute angle-closure glaucoma

            • Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction resulting in acute angle-closure glaucoma and elevated intraocular pressure with or without a noticeable acute myopic shift and/or choroidal effusions
            • Cases of acute angle-closure glaucoma reported; symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation; untreated acute angle-closure glaucoma may result in permanent vision loss
            • Primary treatment is to discontinue drug intake as rapidly as possible; prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled; risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy

            Electrolyte and metabolic imbalances

            • Coadministration of this drug combination with potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, or other drugs that raise serum potassium levels may result in hyperkalemia, sometimes severe; monitor serum potassium in such patients
            • Hydrochlorothiazide can cause hypokalemia and hyponatremia; hypomagnesemia can result in hypokalemia which appears difficult to treat despite potassium repletion; drugs that inhibit the renin-angiotensin system can cause hyperkalemia; monitor serum electrolytes periodically
            • Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy
            • Hydrochlorothiazide may alter glucose tolerance and raise serum levels of cholesterol and triglycerides
            • The antihypertensive effects of the drug may be enhanced in the post-sympathectomy patient; thiazides may decrease urinary calcium excretion; thiazides may cause intermittent and slight elevation of serum calcium in absence of known disorders of calcium metabolism
            • Marked hypercalcemia may be evidence of hidden hyperparathyroidism; thiazides should be discontinued before carrying out tests for parathyroid function
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            Pregnancy & Lactation

            Pregnancy

            Therapy can cause fetal harm when administered to a pregnant woman; use of drugs that act on the renin-angiotensin system during second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death; most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in first trimester have not distinguished drugs affecting reninangiotensin system from other antihypertensive agents; when pregnancy is detected, discontinue therapy as soon as possible

            Hypertension in pregnancy increases maternal risk for preeclampsia, gestational diabetes, premature delivery, and delivery complications (eg, need for cesarean section and postpartum hemorrhage); hypertension increases fetal risk for intrauterine growth restriction and intrauterine death; pregnant women with hypertension should be carefully monitored and managed accordingly

            Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death; perform serial ultrasound examinations to assess intra-amniotic environment; fetal testing may be appropriate,

            Based on week of pregnancy; patients and physicians should be aware, however, that oligohydramnios may not appear until after fetus has sustained irreversible injury; closely observe infants with histories of in utero exposure to drug for hypotension, oliguria, and hyperkalemia and other symptoms of renal impairment; in neonates with a history of in utero exposure to drug, if oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion; exchange transfusion or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal function

            Thiazides cross the placenta, and use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults

            Lactation

            There are no available data on the presence of irbesartan in human milk, effects on milk production, or breastfed infant; irbesartan or some metabolite of irbesartan is secreted in the milk of lactating rats

            Thiazides appear in human milk; because of potential for adverse effects on nursing infant, the drug is not recommended in breastfeeding women

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Administration

            Administration

            Drug combination may be administered with or without food

            Therapy may be administered with other antihypertensive agents

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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.