bisoprolol/hydrochlorothiazide (Rx)

Brand and Other Names:Ziac
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

bisoprolol/hydrochlorothiazide

tablet

  • 2.5mg/6.25mg
  • 5mg/6.25mg
  • 10mg/6.25mg

Hypertension

Initial: 2.5 mg/6.25 mg tablet PO qDay

Increase based on clinical response q2 week

To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy

Maximum: 20 mg bisoprolol /12.5 mg hydrochlorothiazide PO qDay

Renal Impairment

Use caution in dosing/titrating patients with renal dysfunction

Cumulative effects of thiazides may develop with impaired renal function; dose adjustment may be necessary; azotemia may be precipitated

Hepatic Impairment

Dose adjustment necessary in severe impairment; specific dosing recomendations not studied

Administration

Combination may be substituted for the titrated individual components

Withdraw gradually over about 2 weeks

Dosage adjustment for geriatric patients usually not necessary

Dosage Forms & Strengths

bisoprolol/hydrochlorothiazide

tablet

  • 2.5mg/6.25mg
  • 5mg/6.25mg
  • 10mg/6.25mg

Hypertension (Off-label)

Initial: 2.5 mg/6.25 mg tablet PO qDay

Increase based on clinical response q2 week

To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy

Maximum: 10 mg bisoprolol /6.25 mg hydrochlorothiazide PO qDay

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Interactions

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              • acebutolol

                acebutolol and bisoprolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

              • 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.

              • atenolol

                atenolol and bisoprolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

              • betaxolol

                betaxolol and bisoprolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

              • carbamazepine

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

              • carvedilol

                bisoprolol and carvedilol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

              • celiprolol

                bisoprolol and celiprolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

              • clonidine

                clonidine, bisoprolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

              • 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.

              • digoxin

                digoxin, bisoprolol. Either decreases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

              • diltiazem

                diltiazem, bisoprolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

              • dofetilide

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

              • esmolol

                bisoprolol and esmolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

              • fexinidazole

                fexinidazole, bisoprolol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to induce bradycardia. .

              • isocarboxazid

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

              • labetalol

                bisoprolol and labetalol both increase anti-hypertensive channel blocking. 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, bisoprolol. 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.

              • mavacamten

                bisoprolol, mavacamten. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Expect additive negative inotropic effects of mavacamten and other drugs that reduce cardiac contractility.

              • 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.

              • metoprolol

                bisoprolol and metoprolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

              • nadolol

                bisoprolol and nadolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

              • nebivolol

                bisoprolol and nebivolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

              • penbutolol

                bisoprolol and penbutolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

              • pindolol

                bisoprolol and pindolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

              • propranolol

                bisoprolol and propranolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

              • rivastigmine

                bisoprolol increases toxicity of rivastigmine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Additive bradycardia effect may result in syncope.

              • sotalol

                bisoprolol and sotalol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

              • squill

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

              • timolol

                bisoprolol and timolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

              • 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.

              • verapamil

                verapamil, bisoprolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

              Monitor Closely (248)

              • acebutolol

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

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

              • aceclofenac

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

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

                aceclofenac decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              • acemetacin

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

                acemetacin decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

              • albiglutide

                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

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

                bisoprolol decreases effects of albuterol by pharmacodynamic antagonism. Use Caution/Monitor.

              • albuterol

                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 bisoprolol by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

              • alfuzosin

                alfuzosin and bisoprolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

              • 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.

              • aluminum hydroxide

                aluminum hydroxide decreases levels of bisoprolol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

              • amifostine

                amifostine, bisoprolol. 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

                bisoprolol 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, bisoprolol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of cardiotoxicity with bradycardia.

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

              • amlodipine

                bisoprolol, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

              • amoxicillin

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

              • amobarbital

                amobarbital decreases levels of bisoprolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of amobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

              • arformoterol

                bisoprolol decreases effects of arformoterol by pharmacodynamic antagonism. Use Caution/Monitor.

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

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

              • asenapine

                asenapine and bisoprolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

              • aspirin

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

              • aspirin

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

                aspirin decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              • aspirin rectal

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

                aspirin rectal decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

              • aspirin/citric acid/sodium bicarbonate

                aspirin/citric acid/sodium bicarbonate decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

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

              • atazanavir

                atazanavir increases effects of bisoprolol by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypotension, bradycardia, AV block, and prolonged PR interval. Consider lowering beta blocker dose.

              • atenolol

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

              • atenolol

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

              • avanafil

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

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

              • beclomethasone, inhaled

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

              • bendroflumethiazide

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

              • 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.

              • betaxolol

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

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

              • bismuth subsalicylate

                bismuth subsalicylate, bisoprolol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Blockage of renal prostaglandin synthesis; may cause severe hypertension.

              • bisoprolol

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

              • bretylium

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

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

              • bumetanide

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

                bumetanide and hydrochlorothiazide both decrease serum potassium. 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.

              • butabarbital

                butabarbital decreases levels of bisoprolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butabarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

              • butalbital

                butalbital decreases levels of bisoprolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

              • 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.

              • calcium acetate

                calcium acetate decreases effects of bisoprolol by unspecified interaction mechanism. Use Caution/Monitor.

              • calcium carbonate

                calcium carbonate decreases effects of bisoprolol by unspecified interaction mechanism. Use Caution/Monitor.

                calcium carbonate decreases levels of bisoprolol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

              • calcium chloride

                calcium chloride decreases effects of bisoprolol by unspecified interaction mechanism. Use Caution/Monitor.

              • calcium citrate

                calcium citrate decreases effects of bisoprolol by unspecified interaction mechanism. Use Caution/Monitor.

              • calcium gluconate

                calcium gluconate decreases effects of bisoprolol by unspecified interaction mechanism. Use Caution/Monitor.

              • candesartan

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

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

                candesartan and bisoprolol both increase serum potassium. 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

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

              • carbenoxolone

                hydrochlorothiazide and carbenoxolone both decrease serum potassium. 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 bisoprolol 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

                bisoprolol 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

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

                celecoxib decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              • celecoxib

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

              • celiprolol

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

                bisoprolol 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.

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

              • chlorthalidone

                bisoprolol 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

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

                choline magnesium trisalicylate decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              • citalopram

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

              • clevidipine

                bisoprolol, clevidipine. Either decreases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

              • clonidine

                bisoprolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.

              • 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

                bisoprolol 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.

              • dasiglucagon

                bisoprolol decreases effects of dasiglucagon by unknown mechanism. Use Caution/Monitor. Dasiglucagon may stimulate catecholamine release; whereas beta blockers may inhibit catecholamines released in response to dasiglucagon. Coadministration may also transiently increase pulse and BP.

              • deflazacort

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

              • desflurane

                desflurane, bisoprolol. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

              • diazoxide

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

              • dichlorphenamide

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

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

              • diclofenac

                diclofenac decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

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

              • dicloxacillin

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

              • diflunisal

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

                diflunisal decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              • diflunisal

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

              • digoxin

                bisoprolol increases effects of digoxin by pharmacodynamic synergism. Use Caution/Monitor. Enhanced bradycardia.

                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.

                bisoprolol 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.

              • diltiazem

                bisoprolol and diltiazem both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

              • dobutamine

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

              • dobutamine

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

                bisoprolol decreases effects of dobutamine by pharmacodynamic antagonism. 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

                bisoprolol decreases effects of dopexamine by pharmacodynamic antagonism. Use Caution/Monitor.

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

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

              • doxazosin

                doxazosin and bisoprolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

              • drospirenone

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

              • drospirenone

                bisoprolol 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.

              • ephedrine

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

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

                bisoprolol decreases effects of ephedrine by pharmacodynamic antagonism. Use Caution/Monitor.

              • epinephrine

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

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

                bisoprolol decreases effects of epinephrine by pharmacodynamic antagonism. Use Caution/Monitor.

              • epinephrine racemic

                bisoprolol decreases effects of epinephrine racemic by pharmacodynamic antagonism. Use Caution/Monitor.

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

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

              • eprosartan

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

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

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

              • esmolol

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

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

              • ethacrynic acid

                bisoprolol 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.

              • ether

                bisoprolol, ether. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both beta blockers and ether depress the myocardium; consider lowering beta blocker dose if ether used for anesthesia.

              • etodolac

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

              • etodolac

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

                etodolac decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              • etomidate

                etomidate, bisoprolol. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

              • exenatide injectable solution

                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

                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.

              • felodipine

                bisoprolol and felodipine both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

              • fenbufen

                bisoprolol 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.

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

                fenoprofen decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              • 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).

              • fingolimod

                bisoprolol increases effects of fingolimod by pharmacodynamic synergism. Use Caution/Monitor. Both medications decrease heart rate. Monitor patients on concomitant therapy, particularly in the first 6 hours after fingolimod is initiated or after a treatment interruption of at least two weeks, for bradycardia and atrioventricular block. To identify underlying risk factors of bradycardia and AV block, obtain a new or recent ECG in patients using beta-blockers prior to starting fingolimod.

              • 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).

              • flurbiprofen

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

                flurbiprofen decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

              • formoterol

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

                bisoprolol decreases effects of formoterol by pharmacodynamic antagonism. Use Caution/Monitor.

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

              • furosemide

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

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

              • gentamicin

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

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

              • glucagon

                glucagon decreases toxicity of bisoprolol by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Coadministration of glucagon with beta-blockers may have transiently increased pulse and blood pressure.

              • ibuprofen

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

              • glucagon intranasal

                glucagon intranasal decreases toxicity of bisoprolol by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Coadministration of glucagon with beta-blockers may have transiently increased pulse and blood pressure.

              • hydralazine

                hydralazine increases effects of bisoprolol by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

              • hydrochlorothiazide

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

              • ibuprofen

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

                ibuprofen decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              • ibuprofen IV

                ibuprofen IV decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

                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

                indacaterol, inhaled, bisoprolol. Other (see comment). Use Caution/Monitor. Comment: Beta-blockers and indacaterol may interfere with the effect of each other when administered concurrently. Beta-blockers may produce severe bronchospasm in COPD patients. Therefore, patients with COPD should not normally be treated with beta-blockers. However, under certain circumstances, e.g. as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta-blockers in patients with COPD. In this setting, cardioselective beta-blockers could be considered, although they should be administered with caution.

                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

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

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

              • indomethacin

                indomethacin decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

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

              • insulin degludec

                bisoprolol, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

                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 degludec/insulin aspart

                bisoprolol, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

                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 inhaled

                bisoprolol, insulin inhaled. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

                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.

              • iodixanol

                bisoprolol increases toxicity of iodixanol by unspecified interaction mechanism. Use Caution/Monitor. Use of beta-blockers lowers the threshold for and increases the severity of contrast reactions, and reduces the responsiveness of treatment of hypersensitivity reactions with epinephrine. .

              • irbesartan

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

              • irbesartan

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

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

              • isoproterenol

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

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

                bisoprolol decreases effects of isoproterenol by pharmacodynamic antagonism. Use Caution/Monitor.

              • isradipine

                bisoprolol, isradipine. Either decreases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

              • 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.

              • ivabradine

                ivabradine, bisoprolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.

              • ketamine

                ketamine, bisoprolol. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

              • ketoprofen

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

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

                ketoprofen decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              • ketorolac

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

                ketorolac decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

                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 bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

                bisoprolol 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. .

              • labetalol

                bisoprolol 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.

              • lasmiditan

                bisoprolol increases effects of lasmiditan by pharmacodynamic synergism. Use Caution/Monitor. Lasmiditan has been associated with a lowering of heart rate (HR). In a drug interaction study, addition of a single 200-mg dose of lasmiditan to propranolol decreased HR by an additional 5 bpm compared to propranolol alone, for a mean maximum of 19 bpm.

              • levalbuterol

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

              • levalbuterol

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

                bisoprolol decreases effects of levalbuterol by pharmacodynamic antagonism. 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 bisoprolol 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.

              • lornoxicam

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

                lornoxicam decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              • 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.

              • lornoxicam

                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.

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

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

              • lurasidone

                lurasidone increases effects of bisoprolol 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.

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

              • meclofenamate

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

                meclofenamate decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

              • mefenamic acid

                mefenamic acid decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

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

              • mefloquine

                mefloquine increases levels of bisoprolol by decreasing metabolism. Use Caution/Monitor. Risk of arrhythmia.

              • meloxicam

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

              • meloxicam

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

                meloxicam decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              • metaproterenol

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

                bisoprolol decreases effects of metaproterenol by pharmacodynamic antagonism. Use Caution/Monitor.

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

              • methoxsalen

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

              • methyclothiazide

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

              • methylphenidate transdermal

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

              • metolazone

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

                bisoprolol increases and metolazone decreases serum potassium. Effect of interaction is not clear, use caution. 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.

                bisoprolol 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.

              • mometasone inhaled

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

              • moxisylyte

                moxisylyte and bisoprolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

              • mycophenolate

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

              • nabumetone

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

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

                nabumetone decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              • nadolol

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

                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

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

                naproxen decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              • 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.

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

              • nicardipine

                bisoprolol, nicardipine. Either decreases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

              • nitroglycerin rectal

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

              • nifedipine

                bisoprolol, nifedipine. Either decreases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

              • nimodipine

                bisoprolol, nimodipine. Either decreases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

              • nisoldipine

                bisoprolol, nisoldipine. Either decreases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

              • nitroglycerin rectal

                nitroglycerin rectal, bisoprolol. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Beta-blockers blunt the reflex tachycardia produced by nitroglycerin without preventing its hypotensive effects. If beta-blockers are used with nitroglycerin in patients with angina pectoris, additional hypotensive effects may occur.

              • norepinephrine

                bisoprolol decreases effects of norepinephrine by pharmacodynamic antagonism. Use Caution/Monitor.

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

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

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

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

              • 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

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

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

                oxaprozin decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              • oxymetazoline topical

                oxymetazoline topical increases and bisoprolol decreases sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • parecoxib

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

              • parecoxib

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

                parecoxib decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              • penbutolol

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

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

              • penicillin G aqueous

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

              • pentobarbital

                pentobarbital decreases levels of bisoprolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of pentobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

              • phenobarbital

                phenobarbital decreases levels of bisoprolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

              • phenoxybenzamine

                phenoxybenzamine and bisoprolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

              • phentolamine

                phentolamine and bisoprolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

              • pindolol

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

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

              • pirbuterol

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

                bisoprolol decreases effects of pirbuterol by pharmacodynamic antagonism. Use Caution/Monitor.

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

              • piroxicam

                piroxicam decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

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

              • pivmecillinam

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

              • ponesimod

                ponesimod and bisoprolol both increase pharmacodynamic synergism. Use Caution/Monitor. Beta-blockers may have additive effects on lowering HR. Consider resting HR before initiating ponesimod in patients on stable dose of beta-blocker. Refer to the ponesimod prescribing information for more dosing information.

              • 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.

                bisoprolol and potassium acid phosphate both increase serum potassium. Modify Therapy/Monitor Closely.

              • potassium chloride

                bisoprolol and potassium chloride both increase serum potassium. Modify Therapy/Monitor Closely.

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

              • potassium citrate

                bisoprolol 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.

              • prazosin

                prazosin and bisoprolol both increase anti-hypertensive channel blocking. 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.

              • primidone

                primidone decreases levels of bisoprolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of primidone. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

              • procainamide

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

              • propofol

                propofol, bisoprolol. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

              • propranolol

                bisoprolol 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

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

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

              • 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) decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

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

              • salmeterol

                bisoprolol decreases effects of salmeterol by pharmacodynamic antagonism. Use Caution/Monitor.

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

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

              • salsalate

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

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

                salsalate decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              • saquinavir

                saquinavir, bisoprolol. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Use alternatives if available. Increased risk of PR prolongation and cardiac arrhythmias.

              • shark cartilage

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

              • secobarbital

                secobarbital decreases levels of bisoprolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of secobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

              • sevoflurane

                sevoflurane, bisoprolol. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

              • sildenafil

                bisoprolol increases effects of sildenafil by additive vasodilation. Use Caution/Monitor. Sildenafil has systemic vasodilatory properties and may further lower blood pressure in patients taking antihypertensive medications. Monitor blood pressure response to sildenafil in patients receiving concurrent blood pressure lowering therapy.

              • silodosin

                silodosin and bisoprolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

              • siponimod

                siponimod, bisoprolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Caution when siponimod is initiated in patients receiving beta-blocker treatment because of additive effects on lowering heart rate. Temporary interruption of beta-blocker may be needed before initiating siponimod. Beta-blocker treatment can be initiated in patients receiving stable doses of siponimod.

              • sodium bicarbonate

                sodium bicarbonate decreases levels of bisoprolol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

              • sodium citrate/citric acid

                sodium citrate/citric acid decreases levels of bisoprolol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

              • 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/potassium sulfate/magnesium sulfate

                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

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

                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.

                bisoprolol 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.

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

              • sulfasalazine

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

                sulfasalazine decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

              • sulindac

                bisoprolol 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.

                sulindac decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              • tadalafil

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

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

              • telmisartan

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

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

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

              • temocillin

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

              • terazosin

                terazosin and bisoprolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

              • terbutaline

                bisoprolol decreases effects of terbutaline by pharmacodynamic antagonism. Use Caution/Monitor.

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

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

              • theophylline

                bisoprolol, theophylline. Other (see comment). Use Caution/Monitor. Comment: Beta blockers (esp. non selective) antagonize theophylline effects, while at the same time increasing theophylline levels and toxicity (mechanism: decreased theophylline metabolism). Smoking increases risk of interaction.

              • ticarcillin

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

              • timolol

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

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

              • tolfenamic acid

                tolfenamic acid decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

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

              • tolmetin

                tolmetin decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

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

              • tolvaptan

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

                bisoprolol 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

                bisoprolol 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.

              • triamterene

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

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

              • trientine

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

              • valsartan

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

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

              • 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.

              • verapamil

                bisoprolol and verapamil both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

              • 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.

              • xipamide

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

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

              Minor (164)

              • 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.

              • adenosine

                bisoprolol, adenosine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Bradycardia.

              • agrimony

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

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

              • albuterol

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

              • brimonidine

                brimonidine increases effects of bisoprolol 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.

              • cevimeline

                cevimeline increases effects of bisoprolol by unspecified interaction mechanism. 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.

              • cocaine

                bisoprolol increases effects of cocaine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of angina.

              • colestipol

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

              • cornsilk

                cornsilk increases effects of bisoprolol by pharmacodynamic synergism. 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.

              • dihydroergotamine

                dihydroergotamine, bisoprolol. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive vasospasm.

              • dihydroergotamine intranasal

                dihydroergotamine intranasal, bisoprolol. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive vasospasm.

              • dipyridamole

                dipyridamole, bisoprolol. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of bradycardia.

              • dobutamine

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

              • dopexamine

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

              • 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.

              • escitalopram

                escitalopram increases levels of bisoprolol by decreasing metabolism. Minor/Significance Unknown.

              • 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.

              • fenoldopam

                fenoldopam increases effects of bisoprolol by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.

              • 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 bisoprolol by pharmacodynamic synergism. Minor/Significance Unknown.

                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.

              • guanfacine

                bisoprolol, guanfacine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.

              • 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.

              • imaging agents (gadolinium)

                bisoprolol, imaging agents (gadolinium). Mechanism: unknown. Minor/Significance Unknown. Increased risk of anaphylaxis from contrast media.

              • 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.

              • levobetaxolol

                levobetaxolol increases effects of bisoprolol by pharmacodynamic synergism. Minor/Significance Unknown.

              • 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.

              • maitake

                maitake increases effects of bisoprolol by pharmacodynamic synergism. 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.

              • melatonin

                melatonin decreases toxicity of bisoprolol by pharmacodynamic antagonism. Minor/Significance Unknown. Melatonin may correct beta blocker induced sleep disturbances.

              • 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.

              • metipranolol ophthalmic

                metipranolol ophthalmic increases effects of bisoprolol by pharmacodynamic synergism. Minor/Significance Unknown.

              • 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.

              • neostigmine

                bisoprolol, neostigmine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive bradycardia.

              • noni juice

                bisoprolol 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 bisoprolol 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.

              • physostigmine

                bisoprolol, physostigmine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive bradycardia.

              • pilocarpine

                pilocarpine increases effects of bisoprolol by pharmacodynamic synergism. 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 bisoprolol by pharmacodynamic synergism. Minor/Significance Unknown.

                reishi increases effects of hydrochlorothiazide 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.

              • rifampin

                rifampin decreases levels of bisoprolol by increasing 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.

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

                shepherd's purse, hydrochlorothiazide. 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.

              • tizanidine

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

              • 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 bisoprolol by pharmacodynamic synergism. Minor/Significance Unknown.

                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.

              • yohimbe

                bisoprolol decreases toxicity of yohimbe by pharmacodynamic antagonism. Minor/Significance Unknown.

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              Adverse Effects

              No adverse effects specific to the combination have been observed; adverse effects limited to those previously reported with bisoprolol fumarate and hydrochlorothiazide

              1-10%

              Bisoprolol fumarate

              • Arthralgia (2-3%)
              • Chest pain (1-2%)
              • Diarrhea (3%)
              • Dyspnea (1-2%)
              • Fatigue (6-8%)
              • Hypoaesthesia (1-2%)
              • Insomnia (2-3%)
              • Nausea/vomiting (2%)
              • Rhinitis (3-4%)
              • Sinusitis (2%)
              • Upper respiratory infection (5%)
              • Weakness (≤2%)

              <1%

              Acne

              Angioedema

              Abdominal pain

              Alopecia

              Bronchospasm

              Cutaneous

              Dermatitis

              Depression

              Edema

              Flushing

              Gout

              Impotence

              Psoriasis

              Tinnitus

              Tremor

              Xerostomia

              Vertigo

              Somnolence

              Rash

              Pharyngitis

              Hyperkalemia

              Hyperglycemia

              Hyperphosphatemia

              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
              • Hypomagnesemia
              • Dizziness
              • Headache
              • Hyperuricemia

              Postmarketing Reports

              Hydrochlorothiazide

              • Non-melanoma skin cancer
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              Warnings

              Contraindications

              Anuria

              Cardiogenic shock

              Heart block 2°/3°

              Hypersensitivity to either component or sulfonamide derivatives

              Overt cardiac failure

              Marked sinus bradycardia

              Cautions

              Although the probability of developing hypokalemia is reduced with therapy because of very low dose of HCTZ employed, periodic determination of serum electrolytes should be performed, and patients should be observed for signs of fluid or electrolyte disturbances, eg, hyponatremia, hypochloremic alkalosis, hypokalemia, and hypomagnesemia

              Thiazides have been shown to increase urinary excretion of magnesium; this may result in hypomagnesemia; warning signs or symptoms of fluid and electrolyte imbalance include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting

              Hypokalemia may develop, especially with brisk diuresis when severe cirrhosis is present, during concomitant use of corticosteroids or adrenocorticotropic hormone (ACTH) or after prolonged therapy; interference with adequate oral electrolyte intake will also contribute to hypokalemia; hypokalemia and hypomagnesemia can provoke ventricular arrhythmias or sensitize or exaggerate the response of the heart to the toxic effects of digitalis; hypokalemia may be avoided or treated by potassium supplementation or increased intake of potassium-rich foods

              Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction rather than salt administration, except in rare instances when hyponatremia is life-threatening; in actual salt depletion, appropriate replacement is therapy of choice

              Calcium excretion is decreased by thiazides, and pathologic changes in parathyroid glands, with hypercalcemia and hypophosphatemia, have been observed in a few patients on prolonged thiazide therapy

              Hyperuricemia or acute gout may be precipitated in certain patients receiving thiazide diuretics; bisoprolol fumarate, alone or in combination with HCTZ, has been associated with increases in uric acid; however, in U.S. clinical trials, the incidence of treatment-related increases in uric acid was higher during therapy with HCTZ 25 mg (25%) than with B/H 6.25 mg (10%); because of the very low dose of HCTZ employed, hyperuricemia may be less likely with this drug combination

              In general, beta-blocking agents should be avoided in patients with overt congestive failure; however, in some patients with compensated cardiac failure, it may be necessary to utilize these agents; in such situations, they must be used cautiously

              Continued depression of the myocardium with beta-blockers can, in some patients, precipitate cardiac failure; at the first signs or symptoms of heart failure, discontinuation of therapy should be considered; in some cases, therapy can be continued while heart failure is treated with other drugs

              Exacerbations of angina pectoris and, in some instances, myocardial infarction or ventricular arrhythmia, are observed in patients with coronary artery disease following abrupt cessation of therapy with beta-blockers; such patients should be cautioned against interruption or discontinuation of therapy without physician’s advice; even in patients without overt coronary artery disease, it may be advisable to taper therapy with over approximately 1 week with patient under careful observation; if withdrawal symptoms occur, beta-blocking agent therapy should be reinstituted,at least temporarily

              Beta-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease; exercise caution in such individuals

              Patients with bronchospastic pulmonary disease should, in general, not receive beta-blockers; because of relative beta1 selectivity of bisoprolol fumarate, the drug may be used with caution in patients with bronchospastic disease who do not respond to, or who cannot tolerate other antihypertensive treatment; Since beta1- selectivity is not absolute, the lowest possible dose of ZIAC should be used. Abeta2 agonist (bronchodilator) should be made available

              Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery; however, impaired ability of the heart to respond to reflex adrenergic stimuli may augment risks of general anesthesia and surgical procedures

              Beta-blockers may mask some manifestations of hypoglycemia, particularly tachycardia; nonselective beta-blockers may potentiate insulin-induced hypoglycemia and delay recovery of serum glucose levels; because of its beta1-selectivity, this is less likely with bisoprolol fumarate; however, patients subject to spontaneous hypoglycemia, or diabetic patients receiving insulin or oral hypoglycemic agents, should be cautioned about these possibilities; also, latent diabetes mellitus may become manifest and diabetic patients given thiazides may require adjustment of insulin dose; because of the very low dose of HCTZ employed, this may be less likely with this drug combination

              Beta-adrenergic blockade may mask clinical signs of hyperthyroidism, such as tachycardia; abrupt withdrawal of beta-blockade may be followed by exacerbation of symptoms of hyperthyroidism or may precipitate thyroid storm

              Cumulative effects of thiazides may develop in patients with impaired renal function; in such patients, thiazides may precipitate azotemia; in subjects with creatinine clearance < 40 mL/min, the plasma half-life of bisoprolol fumarate is increased up to threefold, as compared to healthy subjects; if progressive renal impairment becomes apparent, therapy should be discontinued

              This drug combination should be used with caution in patients with impaired hepatic function or progressive liver disease; thiazides may alter fluid and electrolyte balance, which may precipitate hepatic coma; also, elimination of bisoprolol fumarate is significantly slower in patients with cirrhosis than in healthy subjects

              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
              • Symptoms may include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation
              • Untreated, the acute angle-closure glaucoma may result in permanent visual field loss
              • The primary treatment is to discontinue hydrochlorothiazide 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
              • Instruct patients taking hydrochlorothiazide to immediately consult their healthcare provider if visual field defects, decreased visual acuity, or ocular pain occur
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              Pregnancy & Lactation

              Pregnancy

              There are no adequate and well-controlled studies on pregnant women; therapy should be used during pregnancy only if potential benefit justifies risk to fetus

              Animal data

              • In rats, bisoprolol fumarate/hydrochlorothiazide (B/H) combination was not teratogenic at doses up to 51.4 mg/kg/day of bisoprolol fumarate in combination with 128.6 mg/kg/day of hydrochlorothiazide; bisoprolol fumarate and hydrochlorothiazide doses used in rat study are, as multiples of MRHD in combination, 129 and 514 times greater, respectively, on a bodyweight basis, and 26 and 106 times greater, respectively, on basis of body surface area
              • The drug combination was maternotoxic (decreased body weight and food consumption) at B5.7/H14.3 (mg/kg/day) and higher, and fetotoxic (increased late resorptions) at B17.1/H42.9 (mg/kg/day) and higher; maternotoxicity was present at 14/57 times MRHD of B/H, respectively, on a bodyweight basis, and 3/12 times MRHD of B/H doses, respectively, on basis of body surface area
              • Fetotoxicity was present at 43/172 times the MRHD of B/H, respectively, on body weight basis, and 9/35 times MRHD of B/H doses, respectively, on basis of body surface area; in rabbits, the B/H combination was not teratogenic at doses of B10/H25 (mg/kg/day); bisoprolol fumarate and hydrochlorothiazide used in rabbit study were not teratogenic at 25/100 times B/H MRHD, respectively, on a bodyweight basis, and 10/40 times B/H MRHD, respectively, on basis of body surface area
              • The drug combination was maternotoxic (decreased body weight) at B1/H2.5 (mg/kg/day) and higher, and fetotoxic (increased resorptions) at B10/H25 (mg/kg/day); the multiples of the MRHD for the B/H combination that were maternotoxic are, respectively, 2.5/10 (on the basis of body weight) and 1/4 (on the basis of body surface area), and for fetotoxicity were, respectively 25/100 (on basis of body weight) and 10/40 (on basis of body surface area)
              • Thiazides cross the placental barrier and appear in the cord blood; the use of thiazides in pregnant women requires that anticipated benefit be weighed against possible hazards to the fetus; these hazards include fetal or neonatal jaundice, pancreatitis, thrombocytopenia, and possibly other adverse reactions that have occurred in the adult
              • See also individual agents

              Impairment of fertility

              • Reproduction studies in rats did not show impairment of fertility with bisoprolol fumarate/hydrochlorothiazide combination doses containing up to 30 mg/kg/day of bisoprolol fumarate in combination with 75 mg/kg/day of hydrochlorothiazide
              • On a bodyweight basis, these doses are 75 and 300 times, respectively, MRHD of bisoprolol fumarate and hydrochlorothiazide; on body surface area basis, these study doses are 15 and 62 times, respectively, MRHD

              Lactation

              Bisoprolol fumarate alone or in combination with HCTZ has not been studied in nursing mothers; thiazides are excreted in human breast milk; small amounts of bisoprolol fumarate(<2% of the dose) have been detected in milk of lactating rats; because of potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue drug, taking into account importance of drug to mother

              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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              Pharmacology

              Mechanism of Action

              Bisoprolol fumarate/hydrochlorothiazide is a fixed-combination tablet that combines a Beta adrenergic receptor blocker, bisoprolol fumarate, and a thiazide diuretic, hydrochlorothiazide

              Bisoprolol fumarate, a cardioselective inhibitor of beta(1)-adrenoceptor, has no significant intrinsic sympathomimetic activity or membrane stabilizing activity in its therapeutic dosage; exhibits beta(2)-adrenoceptors inhibition and negative chronotropic effect

              Hydrochlorothiazide is a thiazide diuretic that inhibits Na reabsorption in distal renal tubules resulting in increased excretion of Na+ and water, also K+ and H+ ions

              Pharmacokinetics

              Bisoprolol

              • Half-Life: 9-12 hr (normal renal function); 27-36 hr (CrCl <40mL/min); 8-22 hr (hepatic cirrhosis)
              • Bioavailability: 80%
              • Peak plasma time: 2-4 hr
              • Onset: 1-2 hr
              • Protein bound: 30%
              • Excretion: Urine (50%); feces (<2%)
              • Metabolism: Liver, not metabolized by P450 CYP2D6; about 20% first-pass metabolism

              Hydrochlorothiazide

              • Half-Life: 6-15 hr
              • Bioavailability: 70%
              • Onset: 2 hr (diuresis); 4-6 hr (peak effect)
              • Duration: 6-12 hr (diuresis); 1 wk (HTN)
              • Vd: 3.6-7.8 L/kg
              • Peak Plasma:1.5-2.5 hr
              • Protein Bound: 68%
              • Metabolism: Minimally metabolized
              • Clearance: 335 mL/min
              • Excretion: Urine 50-70%
              • Dialyzable: No
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              Patient Handout

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              Formulary

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              Tier Description
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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.