spironolactone/hydrochlorothiazide (Rx)

Brand and Other Names:Aldactazide
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

spironolactone/hydrochlorothiazide

tablet

  • 25mg/25mg
  • 50mg/50mg

Edema, Ascites, Congestive Heart Failure

1-8 tablets/day PO (spironolactone 25 mg/hydrochlorothiazide 25 mg)

1-4 tablets/day PO (spironolactone 50 mg/hydrochlorothiazide 50 mg)

Hypertension, Hypokalemia (Diuretic Induced)

2-4 tablets/day PO (spironolactone 25 mg/hydrochlorothiazide 25 mg)

1-2 tablets/day PO (spironolactone 50 mg/hydrochlorothiazide 50 mg)

Renal Impairment

CrCL <30 mL/min: Hydrochlorothiazide efficacy decreased

Not for administration in hyperkalemia, anuria, acute renal insufficiency, or significant impairment of renal excretory function

Hepatic Impairment

Acute or severe hepatic failure: Contraindicated

Safety and efficacy not established

Avoid spironolactone doses >25 mg/day in heart failure, or patients with CrCl< 30 mL/min; heart failure and risk of hyperkalemia is higher in older adults taking doses > 25 mg/day, or taking concomitant angiotensin-converting enzyme inhibitor, angiotensin-receptor blocker, NSAID, or potassium supplement

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Interactions

Interaction Checker

and spironolactone/hydrochlorothiazide

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              • amiloride

                amiloride and spironolactone both increase serum potassium. Avoid or Use Alternate Drug.

                amiloride, spironolactone. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hyperkalemia.

              • 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.

              • carbamazepine

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

              • cyclophosphamide

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

              • cyclosporine

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

                spironolactone and cyclosporine both increase serum potassium. Avoid or Use Alternate Drug. Coadministration not recommended

              • dofetilide

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

              • drospirenone

                drospirenone and spironolactone both increase serum potassium. Avoid or Use Alternate Drug.

                drospirenone, spironolactone. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hyperkalemia.

              • eplerenone

                spironolactone, eplerenone. Mechanism: pharmacodynamic synergism. Contraindicated. Hyperkalemia.

              • 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, spironolactone. 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.

              • 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.

              • potassium acid phosphate

                spironolactone and potassium acid phosphate both increase serum potassium. Avoid or Use Alternate Drug.

              • potassium chloride

                spironolactone and potassium chloride both increase serum potassium. Avoid or Use Alternate Drug.

              • potassium citrate

                spironolactone and potassium citrate both increase serum potassium. Avoid or Use Alternate Drug.

              • potassium phosphates, IV

                spironolactone and potassium phosphates, IV both increase serum potassium. 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.

              • 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.

              • triamterene

                spironolactone and triamterene both increase serum potassium. Avoid or Use Alternate Drug.

                spironolactone, triamterene. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hyperkalemia.

              Monitor Closely (208)

              • acebutolol

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

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

              • aceclofenac

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

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

              • acemetacin

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

                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

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

              • 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 spironolactone by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

              • amifostine

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

                amifostine, 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.

              • ampicillin

                ampicillin increases effects of spironolactone by unspecified interaction mechanism. Use Caution/Monitor. Hyperkalemia.

              • 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.

              • arformoterol

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

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

              • aspirin

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

                aspirin decreases effects of spironolactone by unspecified interaction mechanism. Use Caution/Monitor. When used concomitantly, spironolactone dose may need to be titrated to higher maintenance dose and the patient should be observed closely to determine if the desired effect is obtained.

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

              • 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 spironolactone by unspecified interaction mechanism. Use Caution/Monitor. When used concomitantly, spironolactone dose may need to be titrated to higher maintenance dose and the patient should be observed closely to determine if the desired effect is obtained.

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

              • aspirin/citric acid/sodium bicarbonate

                aspirin/citric acid/sodium bicarbonate decreases effects of spironolactone by unspecified interaction mechanism. Use Caution/Monitor. When used concomitantly, spironolactone dose may need to be titrated to higher maintenance dose and the patient should be observed closely to determine if the desired effect is obtained.

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

                spironolactone and aspirin/citric acid/sodium bicarbonate both increase serum potassium. Modify Therapy/Monitor Closely.

              • atenolol

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

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

              • avanafil

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

                avanafil increases effects of spironolactone 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 and spironolactone both increase serum potassium. 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.

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

              • betaxolol

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

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

              • bisoprolol

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

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

              • bretylium

                spironolactone, 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.

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

              • buprenorphine, long-acting injection

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

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

              • calcifediol

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

              • canagliflozin

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

              • candesartan

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

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

              • captopril

                captopril, spironolactone. Either increases toxicity of the other by Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Risk of hyperkalemia. Monitor blood pressure and potassium.

                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.

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

              • carbidopa

                carbidopa increases effects of spironolactone 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 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.

              • carvedilol

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

                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

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

              • 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.

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

                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.

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

              • chlorthalidone

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

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

              • cholestyramine

                cholestyramine, spironolactone. unspecified interaction mechanism. Use Caution/Monitor. Hyperkalemic metabolic acidosis reported when coadministered.

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

              • cholic acid

                spironolactone increases toxicity of cholic acid by decreasing elimination. Modify Therapy/Monitor Closely. Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP). May exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms. If concomitant use is necessary, monitor serum transaminases and bilirubin.

              • citalopram

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

              • choline magnesium trisalicylate

                spironolactone and choline magnesium trisalicylate both increase serum potassium. Modify Therapy/Monitor Closely.

              • 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.

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

              • 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.

              • dichlorphenamide

                dichlorphenamide, spironolactone. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Both drugs can cause metabolic acidosis.

              • deflazacort

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

              • diazoxide

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

              • dichlorphenamide

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

              • diclofenac

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

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

              • dicloxacillin

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

              • diflunisal

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

              • diflunisal

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

              • digoxin

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

                spironolactone increases levels of digoxin by Other (see comment). Use Caution/Monitor. Comment: Spironolactone may cause false elevation of digoxin assay.

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

                spironolactone, digoxin. Mechanism: decreasing renal clearance. Use Caution/Monitor. False digoxin assay results may be obtained.

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

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

              • disopyramide

                spironolactone increases effects of disopyramide by pharmacodynamic synergism. Use Caution/Monitor. Additive cardiovascular depression.

              • dobutamine

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

              • dobutamine

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

              • dofetilide

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

              • dopexamine

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

                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, spironolactone. 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.

              • 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.

              • enalapril

                enalapril, spironolactone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

              • ephedrine

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

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

              • epinephrine

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

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

              • epinephrine racemic

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

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

              • esmolol

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

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

              • ethacrynic acid

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

                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.

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

              • 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.

              • fenbufen

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

              • 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

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

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

              • fentanyl

                fentanyl decreases effects of spironolactone 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 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 spironolactone 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 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 spironolactone 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 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).

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

              • finerenone

                spironolactone and finerenone both increase serum potassium. Modify Therapy/Monitor Closely. Finerenone dose adjustment based on current serum potassium concentration. Monitor serum potassium and adjust finerenone dose as described in the prescribing information as necessary.

              • flurbiprofen

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

              • flurbiprofen

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

              • formoterol

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

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

              • fosinopril

                fosinopril, spironolactone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

              • furosemide

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

              • furosemide

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

              • gentamicin

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

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

              • hydrochlorothiazide

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

              • ibuprofen

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

              • ibuprofen

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

              • ibuprofen IV

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

                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.

              • imidapril

                imidapril, spironolactone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

              • 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

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

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

              • indomethacin

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

                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.

              • irbesartan

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

              • 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.

              • isoproterenol

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

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

              • 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.

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

              • ketoprofen

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

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

              • ketorolac

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

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

              • ketorolac intranasal

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

                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.

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

              • levalbuterol

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

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

              • levodopa

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

                levodopa increases effects of spironolactone 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.

              • lisinopril

                lisinopril, spironolactone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

              • 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.

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

              • losartan

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

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

              • lurasidone

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

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

              • meclofenamate

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

                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.

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

              • meloxicam

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

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

              • metaproterenol

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

                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

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

              • metolazone

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

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

              • metoprolol

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

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

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

              • midazolam

                spironolactone will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. midazolam dose may need to be adjusted

              • mometasone inhaled

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

              • mitotane

                spironolactone decreases effects of mitotane by pharmacodynamic antagonism. Use Caution/Monitor.

              • moexipril

                moexipril, spironolactone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

              • 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.

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

              • nadolol

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

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

              • nafcillin

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

              • naproxen

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

              • 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.

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

              • nitroglycerin rectal

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

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

              • noni juice

                spironolactone and noni juice both increase serum potassium. Use Caution/Monitor.

              • norepinephrine

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

              • norepinephrine

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

              • 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. .

                oliceridine decreases effects of spironolactone 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 spironolactone both increase serum potassium. Modify Therapy/Monitor Closely.

                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.

              • ospemifene

                spironolactone, ospemifene. Either increases levels of the other by plasma protein binding competition. Modify Therapy/Monitor Closely.

              • oxaprozin

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

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

              • parecoxib

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

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

              • penbutolol

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

                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.

              • perindopril

                perindopril, spironolactone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

              • pindolol

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

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

              • pirbuterol

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

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

              • piroxicam

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

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

              • pivmecillinam

                pivmecillinam increases effects of spironolactone by unspecified interaction mechanism. Use Caution/Monitor. Hyperkalemia.

                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 citrate/citric acid

                spironolactone and potassium citrate/citric acid both increase serum potassium. Use Caution/Monitor.

              • 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.

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

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

              • pseudoephedrine

                spironolactone decreases effects of pseudoephedrine by pharmacodynamic antagonism. 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.

              • quinapril

                quinapril, spironolactone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

              • ramipril

                ramipril, spironolactone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

              • repaglinide

                spironolactone will increase the level or effect of repaglinide by Other (see comment). Use Caution/Monitor. Spironolactone inhibits CYP2C8; repaglinice dose may need to be adjusted as it is metabolized by CYP2C8

              • sacubitril/valsartan

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

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

              • salicylates (non-asa)

                spironolactone and salicylates (non-asa) both increase serum potassium. Modify Therapy/Monitor Closely.

                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.

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

              • salsalate

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

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

              • shark cartilage

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

              • sirolimus

                spironolactone will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. sirolimus dose may need to be adjusted

              • 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.

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

              • spironolactone

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

              • succinylcholine

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

              • succinylcholine

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

              • sulfasalazine

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

                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.

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

              • tacrolimus

                spironolactone will increase the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. tacrolimus dose may need to be adjusted

              • tadalafil

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

              • tadalafil

                tadalafil increases effects of spironolactone 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.

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

              • temocillin

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

                temocillin increases effects of spironolactone by unspecified interaction mechanism. Use Caution/Monitor. Hyperkalemia.

              • terbutaline

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

                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.

                ticarcillin increases effects of spironolactone by unspecified interaction mechanism. Use Caution/Monitor. Hyperkalemia.

              • timolol

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

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

              • tolfenamic acid

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

                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.

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

              • tolvaptan

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

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

              • 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

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

              • torsemide

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

              • trandolapril

                trandolapril, spironolactone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

              • 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.

              • trimethoprim

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

              • umeclidinium bromide/vilanterol inhaled

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

              • valsartan

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

                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

              • voclosporin

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

              • 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.

              • warfarin

                spironolactone decreases effects of warfarin by unknown mechanism. Use Caution/Monitor. Interaction is theorized to result from increased concentration of clotting factors as a result of diuresis.

              • xipamide

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

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

              Minor (162)

              • acarbose

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

              • aceclofenac

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

              • acemetacin

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

              • acyclovir

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

              • agrimony

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

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

              • albuterol

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

              • ammonium chloride

                spironolactone, ammonium chloride. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of systemic acidosis.

              • 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 spironolactone by pharmacodynamic synergism. Minor/Significance Unknown.

                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 spironolactone by pharmacodynamic synergism. Minor/Significance Unknown.

              • 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.

              • cadexomer iodine

                cadexomer iodine, spironolactone. Mechanism: decreasing renal clearance. Minor/Significance Unknown. Hyperkalemia.

              • calcitriol topical

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

              • calcium acetate

                spironolactone decreases levels of calcium acetate by increasing renal clearance. Minor/Significance Unknown.

                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.

                spironolactone decreases levels of calcium carbonate by increasing renal clearance. Minor/Significance Unknown.

              • calcium chloride

                spironolactone decreases levels of calcium chloride by increasing renal clearance. Minor/Significance Unknown.

                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.

                spironolactone decreases levels of calcium citrate by increasing renal clearance. Minor/Significance Unknown.

              • calcium gluconate

                spironolactone decreases levels of calcium gluconate by increasing renal clearance. Minor/Significance Unknown.

                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.

              • cornsilk

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

              • 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.

                epoprostenol increases effects of spironolactone 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.

              • forskolin

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

                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.

              • iodinated glycerol

                iodinated glycerol, spironolactone. Mechanism: decreasing renal clearance. Minor/Significance Unknown. Hyperkalemia.

              • 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.

              • iodine

                iodine, spironolactone. Mechanism: decreasing renal clearance. Minor/Significance Unknown. Hyperkalemia.

              • isoproterenol

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

              • ketoprofen

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

              • ketorolac

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

              • ketorolac intranasal

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

              • L-methylfolate

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

              • levalbuterol

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

              • lornoxicam

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

              • magnesium chloride

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

                spironolactone increases levels of magnesium chloride by decreasing renal clearance. Minor/Significance Unknown.

              • magnesium citrate

                spironolactone increases levels of magnesium citrate by decreasing renal clearance. Minor/Significance Unknown.

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

              • magnesium hydroxide

                spironolactone increases levels of magnesium hydroxide by decreasing renal clearance. Minor/Significance Unknown.

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

              • magnesium oxide

                spironolactone increases levels of magnesium oxide by decreasing renal clearance. Minor/Significance Unknown.

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

              • magnesium sulfate

                spironolactone increases levels of magnesium sulfate by decreasing renal clearance. Minor/Significance Unknown.

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

              • maitake

                maitake increases effects of spironolactone 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.

              • meloxicam

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

              • memantine

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

              • mesalamine

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

              • metaproterenol

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

              • metformin

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

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

              • methotrexate

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

              • methylprednisolone

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

              • metolazone

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

              • midodrine

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

              • miglitol

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

              • minoxidil

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

                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.

              • nitazoxanide

                nitazoxanide, spironolactone. Either increases levels of the other by Mechanism: plasma protein binding competition. 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.

              • noni juice

                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 spironolactone by pharmacodynamic synergism. Minor/Significance Unknown.

                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.

              • reishi

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

              • oxaprozin

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

              • parecoxib

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

              • penicillin G aqueous

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

              • penicillin VK

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

              • pioglitazone

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

              • piperacillin

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

              • pirbuterol

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

              • piroxicam

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

              • prednisolone

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

              • prednisone

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

              • quinine

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

              • reishi

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

              • repaglinide

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

              • 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, spironolactone. 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.

              • sulfadiazine

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

              • sulfadiazine

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

              • sulfamethoxazole

                spironolactone, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.

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

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

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

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

              • sulfasalazine

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

              • sulfisoxazole

                spironolactone increases levels of sulfisoxazole by unspecified interaction mechanism. 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 spironolactone by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.

                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.

              • treprostinil

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

              • tolbutamide

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

              • tolfenamic acid

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

              • tolmetin

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

              • treprostinil

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

              • triamcinolone acetonide injectable suspension

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

              • triamterene

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

              • trilostane

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

              • trimethoprim

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

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

                spironolactone, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.

              • valganciclovir

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

              • verapamil

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

              • verteporfin

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

              • vildagliptin

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

              • willow bark

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

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              Adverse Effects

              Frequency Not Defined

              Spironolactone

              • Drowsiness
              • Lethargy
              • Headache
              • Stevens-Johnson Syndrome
              • Rash
              • Urticaria
              • Gynecomastia
              • Impotence
              • Menstrual disorders
              • Abdominal cramping
              • Diarrhea
              • Gastritis
              • Nausea/vomiting
              • Drug rash with eosinophilia and systemic symptoms (DRESS)
              • Toxic epidermal necrolysis

              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

              Black Box Warnings

              Spironolactone has been shown to be a tumorigen in chronic toxicity studies in rats; use only for specified indications

              Fixed-dose combination

              • Fixed-dose combination drugs are not indicated for initial therapy of edema or hypertension; edema or hypertension requires therapy titrated to the individual patient
              • If the fixed combination represents the dosage so determined, its use may be more convenient in patient management
              • Treatment of hypertension and edema is not static, but must be reevaluated as conditions in each patient warrant

              Contraindications

              Hypersensitivity to spironolactone, hydrochlorothiazide, or sulfonamides

              Acute renal failure

              Acute/severe hepatic failure

              Anuria

              Hyperkalemia

              Addison’s disease or other conditions associated with hyperkalemia

              Coadministration with eplerenone

              Cautions

              Somnolence and dizziness reported

              Caution with hepatic impairment

              Spironolactone

              • May cause hyperkalemia; risk may be increased in patients with renal insufficiency, diabetes mellitus, or if coadministered with other drugs/diet that raise serum potassium levels
              • Gynecomastia reported

              Hydrochlorothiazide

              • May cause hypokalemia and hyponatremia; risk of hypokalemia may be increased in patients with cirrhosis, brisk diuresis, or if coadministered with other drugs that lower serum potassium
              • May cause hypomagnesemia, which can then result in hypokalemia which appears difficult to treat despite potassium repletion
              • May alter glucose tolerance and increase risk for hyperglycemia
              • May increase serum levels of calcium and uric acid by decreasing urinary excretion; may also increase cholesterol and triglycerides
              • Thiazides diuretics may add to or potentiate the action of other antihypertensive drugs
              • Sensitivity reactions to thiazides may occur in patients with or without a history of allergy or bronchial asthma
              • Sulfonamide derivatives, including thiazides, have been reported to exacerbate or activate systemic lupus erythematosus
              • Instruct patients to protect skin from sun and undergo regular skin cancer screening
              • Angle-closure glaucoma
                • Hydrochlorothiazide can cause acute angle-closure glaucoma and elevated intraocular pressure with or without noticeable acute myopic shift and/or choroidal effusions
                • May occur within hours of initiating therapy; discontinue therapy immediately in patients with acute decreases in visual acuity or ocular pain
                • Additional medical or surgical treatments may be needed if intraocular pressure remains uncontrolled
                • Untreated angle-closure glaucoma may result in permanent visual field loss
                • Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy
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              Pregnancy & Lactation

              Pregnancy Category: C

              Lactation: discontinue drug or do not nurse

              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

              Spironolactone: Aldosterone antagonist with diuretic and antihypertensive effects; competitive binding of receptors at aldosterone-dependent Na-K exchange site in distal tubules results in increased excretion of Na+, Cl-, and H2O and retention of K+ and H+

              Hydrochlorothiazide: Thiazide diuretic; inhibits sodium reabsorption in distal renal tubules, resulting in increased excretion of water and of sodium, potassium, and hydrogen ions

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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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              • Compare formulary status to other drugs in the same class.
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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.