methyldopa/hydrochlorothiazide (Rx)

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Dosing & Uses

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Dosage Forms & Strengths

methyldopa/hydrochlorothiazide

tablet

  • 250mg/15mg
  • 250mg/25mg

Hypertension

Not for initial therapy

Usual starting dose: 250 mg methyldopa/15-25 mg hydrochlorothiazide PO q12hr; alternatively 500 mgmethyldopa/30-50 mg hydrochlorothiazide PO qDay

Avoid hydrochlorothiazide doses >50 mg qDay

Dosage strength determined by individual titration

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; if CrCl < 30 mL/min avoid use; azotemia may be precipitated

Administration

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

Since both components have a relatively short duration of action, withdrawal is followed by return of hypertension usually within 48 hours, not complicated by overshoot of blood pressure

<18 years: Safety/efficacy not established

Dose reduction may be necessary depending on patient's renal function

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Interactions

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              • 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.

              • aripiprazole

                aripiprazole decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

              • benperidol

                benperidol decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

              • carbamazepine

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

              • chlorpromazine

                chlorpromazine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

              • clozapine

                clozapine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

              • cyclophosphamide

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

              • cyclosporine

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

              • dofetilide

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

              • droperidol

                droperidol decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

              • fluphenazine

                fluphenazine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

              • haloperidol

                haloperidol decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

              • iloperidone

                iloperidone decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

              • iobenguane I 131

                methyldopa will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.

              • isocarboxazid

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

              • 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, methyldopa. 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.

              • loxapine

                loxapine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

              • 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.

              • loxapine inhaled

                loxapine inhaled decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

              • metoclopramide

                metoclopramide decreases levels of methyldopa by inhibition of GI absorption. Applies only to oral form of both agents. Contraindicated.

                metoclopramide decreases levels of methyldopa by pharmacodynamic antagonism. Contraindicated.

              • metoclopramide intranasal

                methyldopa, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

              • olanzapine

                olanzapine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

              • paliperidone

                paliperidone decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

              • perphenazine

                perphenazine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

              • pexidartinib

                methyldopa and pexidartinib both increase inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.

              • pimozide

                pimozide decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

              • pretomanid

                methyldopa, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.

              • prochlorperazine

                prochlorperazine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

              • promethazine

                promethazine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

              • quetiapine

                quetiapine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

              • risperidone

                risperidone decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

              • squill

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

              • thioridazine

                thioridazine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

              • thiothixene

                thiothixene decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

              • tranylcypromine

                tranylcypromine, methyldopa. Other (see comment). Avoid or Use Alternate Drug. Comment: Tranylcypromine inhibits the hypotensive effects of methyldopa. At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with methyldopa.

              • 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.

              • trifluoperazine

                trifluoperazine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

              Monitor Closely (202)

              • acebutolol

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

              • aceclofenac

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

              • acemetacin

                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

                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.

              • 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.

              • amiloride

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

              • amiodarone

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

              • amoxicillin

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

              • apomorphine

                apomorphine and methyldopa both increase dopaminergic effects. Use Caution/Monitor.

              • arformoterol

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

              • aspirin

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

              • aspirin rectal

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

              • aspirin/citric acid/sodium bicarbonate

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

              • atenolol

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

              • avanafil

                avanafil increases effects of hydrochlorothiazide 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.

              • 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.

              • benzphetamine

                methyldopa increases effects of benzphetamine by unknown mechanism. Use Caution/Monitor.

              • betaxolol

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

              • bisoprolol

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

              • bretylium

                methyldopa, 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

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

              • cabergoline

                cabergoline and methyldopa both increase dopaminergic effects. Use Caution/Monitor.

              • buprenorphine, long-acting injection

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

              • calcifediol

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

              • candesartan

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

              • captopril

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

              • carbenoxolone

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

              • 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.

              • carbonyl iron

                carbonyl iron decreases levels of methyldopa by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              • carvedilol

                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

                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.

                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.

              • chlorthalidone

                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.

              • citalopram

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

              • clonidine

                clonidine, methyldopa. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.

              • 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

                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.

              • deflazacort

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

              • dexfenfluramine

                methyldopa increases effects of dexfenfluramine by unknown mechanism. Use Caution/Monitor.

              • dexmethylphenidate

                methyldopa increases effects of dexmethylphenidate by unknown mechanism. Use Caution/Monitor.

              • dextroamphetamine

                methyldopa increases effects of dextroamphetamine by unknown mechanism. Use Caution/Monitor.

              • diazoxide

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

              • dichlorphenamide

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

              • diclofenac

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

              • dicloxacillin

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

              • diethylpropion

                methyldopa increases effects of diethylpropion by unknown mechanism. Use Caution/Monitor.

              • diflunisal

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

              • digoxin

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

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

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

              • dobutamine

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

                methyldopa increases effects of dobutamine by unknown mechanism. 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.

              • dopamine

                dopamine and methyldopa both increase dopaminergic effects. Use Caution/Monitor.

                methyldopa increases effects of dopamine by unknown mechanism. Use Caution/Monitor.

              • dopexamine

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

              • drospirenone

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

              • 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.

              • entacapone

                entacapone will increase the level or effect of methyldopa by decreasing metabolism. Use Caution/Monitor. Entacapone is a COMT inhibitor. Caution if coadministered with drugs metabolized by COMT. If coadministered, monitor for changes in heart rate, heart rhythm, and blood pressure.

              • ephedrine

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

                methyldopa increases effects of ephedrine by unknown mechanism. Use Caution/Monitor.

              • epinephrine

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

                methyldopa increases effects of epinephrine by unknown mechanism. Use Caution/Monitor.

              • epinephrine racemic

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

              • fenfluramine

                methyldopa increases effects of fenfluramine by unknown mechanism. Use Caution/Monitor.

              • eprosartan

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

              • esmolol

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

              • ethacrynic acid

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

              • etodolac

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

              • 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.

              • fenoprofen

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

              • fentanyl

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

              • fentanyl intranasal

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

              • fentanyl transdermal

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

              • fentanyl transmucosal

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

              • ferric maltol

                ferric maltol decreases levels of methyldopa by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              • ferrous fumarate

                ferrous fumarate decreases levels of methyldopa by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              • ferrous gluconate

                ferrous gluconate decreases levels of methyldopa by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              • ferrous sulfate

                ferrous sulfate decreases levels of methyldopa by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              • flurbiprofen

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

              • formoterol

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

              • furosemide

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

              • gentamicin

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

              • ibuprofen

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

              • ibuprofen IV

                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.

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

              • indacaterol, inhaled

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

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

              • indapamide

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

              • indomethacin

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

              • insulin degludec

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

              • insulin degludec/insulin aspart

                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

                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.

              • irbesartan

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

              • iron dextran complex

                iron dextran complex decreases levels of methyldopa by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              • iron sucrose

                iron sucrose decreases levels of methyldopa by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              • isoproterenol

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

                methyldopa increases effects of isoproterenol by unknown mechanism. Use Caution/Monitor.

              • 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.

              • levodopa

                methyldopa, levodopa. pharmacodynamic synergism. Use Caution/Monitor. Risk of additive hypotensive effects, and risk of toxic CNS effects such as psychosis.

              • ketoprofen

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

              • ketorolac

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

              • ketorolac intranasal

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

              • labetalol

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

              • levalbuterol

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

              • levodopa

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

              • lily of the valley

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

              • liraglutide

                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.

              • lisdexamfetamine

                methyldopa increases effects of lisdexamfetamine by unknown mechanism. Use Caution/Monitor.

              • lisuride

                lisuride and methyldopa both increase dopaminergic effects. Use Caution/Monitor.

              • 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.

              • lurasidone

                lurasidone increases effects of methyldopa 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).

              • methamphetamine

                methyldopa increases effects of methamphetamine by unknown mechanism. Use Caution/Monitor.

              • meclofenamate

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

              • mefenamic acid

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

              • meloxicam

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

              • metaproterenol

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

              • methoxsalen

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

              • methylenedioxymethamphetamine

                methyldopa increases effects of methylenedioxymethamphetamine by unknown mechanism. Use Caution/Monitor.

              • methylphenidate

                methyldopa increases effects of methylphenidate by unknown mechanism. Use Caution/Monitor.

              • metolazone

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

              • metoprolol

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

                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.

              • midazolam intranasal

                midazolam intranasal, methyldopa. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

              • midodrine

                methyldopa increases effects of midodrine by unknown mechanism. Use Caution/Monitor.

              • mipomersen

                mipomersen, methyldopa. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

              • mometasone inhaled

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

              • mycophenolate

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

              • nabumetone

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

              • nadolol

                nadolol, methyldopa. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Non selective beta blocker administration during withdrawal from methyldopa may result in rebound hypertension.

                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.

              • norepinephrine

                methyldopa increases effects of norepinephrine by unknown mechanism. Use Caution/Monitor.

              • 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.

              • 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. .

              • norepinephrine

                norepinephrine and hydrochlorothiazide both decrease serum potassium. 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 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.

              • opicapone

                opicapone will increase the level or effect of methyldopa by decreasing metabolism. Use Caution/Monitor. Opicapone is a COMT inhibitor. Caution if coadministered with drugs metabolized by COMT. If coadministered, monitor for changes in heart rate, heart rhythm, and blood pressure.

              • oxaprozin

                oxaprozin increases and hydrochlorothiazide decreases serum potassium. 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.

              • penbutolol

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

              • penicillin G aqueous

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

              • phendimetrazine

                methyldopa increases effects of phendimetrazine by unknown mechanism. Use Caution/Monitor.

              • phentermine

                methyldopa increases effects of phentermine by unknown mechanism. Use Caution/Monitor.

              • phenylephrine

                methyldopa increases effects of phenylephrine by unknown mechanism. Use Caution/Monitor.

              • phenylephrine PO

                methyldopa increases effects of phenylephrine PO by unknown mechanism. Use Caution/Monitor.

              • pindolol

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

                pindolol, methyldopa. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Non selective beta blocker administration during withdrawal from methyldopa may result in rebound hypertension.

              • pirbuterol

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

              • polysaccharide iron

                polysaccharide iron decreases levels of methyldopa by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              • piroxicam

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

              • pivmecillinam

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

              • porfimer

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

              • potassium acid phosphate

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

              • potassium chloride

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

              • potassium citrate

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

              • pramipexole

                methyldopa and pramipexole both increase dopaminergic effects. Use Caution/Monitor.

              • probenecid

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

              • procainamide

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

              • propranolol

                propranolol, methyldopa. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Non selective beta blocker administration during withdrawal from methyldopa may result in rebound hypertension.

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

              • propylhexedrine

                methyldopa increases effects of propylhexedrine by unknown mechanism. 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.

              • pseudoephedrine

                methyldopa increases effects of pseudoephedrine by unknown mechanism. Use Caution/Monitor.

              • ropinirole

                methyldopa and ropinirole both increase dopaminergic effects. Use Caution/Monitor.

              • rose hips

                rose hips decreases levels of methyldopa by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              • sacubitril/valsartan

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

              • salicylates (non-asa)

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

              • salmeterol

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

              • salsalate

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

              • shark cartilage

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

              • sodium sulfate/?magnesium sulfate/potassium chloride

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

              • sodium sulfate/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

                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.

              • succinylcholine

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

              • sulfasalazine

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

              • sulindac

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

              • tadalafil

                tadalafil increases effects of hydrochlorothiazide 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.

              • temocillin

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

              • terbutaline

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

              • ticarcillin

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

              • timolol

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

                timolol, methyldopa. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Non selective beta blocker administration during withdrawal from methyldopa may result in rebound hypertension.

              • tolcapone

                tolcapone will increase the level or effect of methyldopa by decreasing metabolism. Use Caution/Monitor. Tolcapone is a COMT inhibitor. Caution if coadministered with drugs metabolized by COMT. If coadministered, monitor for changes in heart rate, heart rhythm, and blood pressure.

              • tolfenamic acid

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

              • tolmetin

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

              • tolvaptan

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

                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.

              • trientine

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

              • umeclidinium bromide/vilanterol inhaled

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

              • valsartan

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

              • vilanterol/fluticasone furoate inhaled

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

              • vitamin D

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

              • xipamide

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

              • xylometazoline

                methyldopa increases effects of xylometazoline by unknown mechanism. Use Caution/Monitor.

              Minor (83)

              • acarbose

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

              • aceclofenac

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

              • acemetacin

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

              • acyclovir

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

              • agrimony

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

              • albuterol

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

              • aminohippurate sodium

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

              • ampicillin

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

              • arformoterol

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

              • aspirin

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

              • aspirin rectal

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

              • aspirin/citric acid/sodium bicarbonate

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

              • balsalazide

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

              • bendroflumethiazide

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

              • birch

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

              • bitter melon

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

              • brimonidine

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

              • budesonide

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

              • calcitriol topical

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

              • calcium acetate

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

              • calcium carbonate

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

              • calcium chloride

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

              • calcium citrate

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

              • calcium gluconate

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

              • carbenoxolone

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

              • cefadroxil

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

              • cefamandole

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

              • cefpirome

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

              • cefprozil

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

              • ceftibuten

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

              • celecoxib

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

              • cephalexin

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

              • chlorothiazide

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

              • chlorpropamide

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

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

              • chlorthalidone

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

              • colestipol

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

              • cortisone

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

              • cosyntropin

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

              • cyclopenthiazide

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

              • deflazacort

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

              • dexamethasone

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

              • diazoxide

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

              • diclofenac

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

              • diflunisal

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

              • dobutamine

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

              • dopexamine

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

              • ephedrine

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

              • epinephrine

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

              • epinephrine racemic

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

              • epoprostenol

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

              • etodolac

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

              • fenbufen

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

              • fenoprofen

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

              • fludrocortisone

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

              • flurbiprofen

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

              • fo-ti

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

              • folic acid

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

              • formoterol

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

              • forskolin

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

              • ganciclovir

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

              • glimepiride

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

              • glipizide

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

              • glyburide

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

              • goldenrod

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

              • hydrocortisone

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

              • ibuprofen

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

              • indapamide

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

              • indomethacin

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

              • insulin aspart

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

              • insulin detemir

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

              • insulin glargine

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

              • insulin glulisine

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

              • insulin lispro

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

              • insulin NPH

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

              • insulin regular human

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

              • isoproterenol

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

              • ketoprofen

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

              • ketorolac

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

              • ketorolac intranasal

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

              • L-methylfolate

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

              • levalbuterol

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

              • lithium

                methyldopa increases toxicity of lithium by unknown mechanism. 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.

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              Adverse Effects

              Frequency Not Defined

              Methyldopa

              • Angina
              • Arthralgia
              • Bradycardia
              • Orthostatic hypotension
              • Depression
              • Dizziness
              • Lethargy
              • Sedation
              • Rash, liver toxicity
              • Gynecomastia
              • Impotence
              • Dry mouth
              • Nausea/vomiting
              • Hemolytic anemia
              • Thrombocytopenia, lupus-like syndrome

              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
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              Warnings

              Black Box Warning

              Not indicated for initial therapy of hypertension; before initiating therapy requires therapy titrated to the individual patient; if fixed combination represents determined dosage for each individual agent; use may be more convenient in patient management; treatment of hypertension must be reevaluated as conditions in each patient warrant

              Contraindications

              Anuria

              Renal decompensation

              Hypersensitivity to either component or sulfonamides

              Mitral valve rheumatic heart disease

              Active liver disease, such as acute hepatitis and active cirrhosis

              Liver disorders previously associated with methyldopa therapy

              Concomitant therapy with monoamine oxidase (MAO) inhibitors

              Cautions

              This fixed-combination drug is not indicated for initial therapy of hypertension; requires therapy titrated to the individual patient before fixed-combination drug therapy initiated

              DM, fluid or electrolyte imbalance, hyperuricemia or gout, liver disease, renal disease, SLE, hypotension

              May aggravate digitalis toxicity

              Sensitivity reactions may occur with or w/o history of allergy or asthma

              Risk of male sexual dysfunction

              CHF, dialysis pts (increased risk of hypertension following procedure), edema, hemolytic anemia, severe bilateral CVD

              Avoid abrupt withdrawal

              Risk of decreased libido and impotence in men

              May impair ability to perform hazardous tasks

              Tolerance develops on prolonged therapy, especially if no concurrent diuretic (methyldopa causes Na and water retention)

              Acute transient myopia and acute angle-closure glaucoma has been reported, particularly with history of sulfonamide or penicillin allergy (hydrochlorothiazide is a sulfonamide)

              Interferes with some lab tests

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              Pregnancy & Lactation

              Pregnancy Category: C

              Lactation: both components appear in breast milk, use caution

              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

              Hydrochlorothiazide; methyldopa combines 2 antihypertensive agents with different mechanisms to lower blood pressure; effects of hydrochlorothiazide and methyldopa on blood pressure are additive

              Thiazide diuretics lower blood pressure by increasing the excretion of sodium, whereas methyldopa may lower blood pressure by stimulating central inhibitory alpha-adrenergic receptors, false neurotransmission, and/or reduction of plasma renin activity.

              Pharmacokinetics

              Methyldopa

              • Onset: 4-6 hr (PO, IV) hypotensive effect
              • Vd: 0.23 L/kg
              • Protein binding: 10-15%
              • Bioavailability: 42%
              • Half-life: 1.5-2 hr; prolonged in end stage renal disease
              • Peak plasma time: 2-4 hr
              • Excretion: Urine (70%)
              • Metabolism: Intestinal and hepatic
              • Duration: 12-24 hr (single dose); 24-48 hr (multiple dose)

              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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              Images

              No images available for this drug.
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              Patient Handout

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

              FormularyPatient Discounts

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              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
              ST Step Therapy
              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
              OR Other Restrictions
              Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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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.