Dosing & Uses
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
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (0)
Serious - Use Alternative (21)
- abiraterone
spironolactone increases toxicity of abiraterone by pharmacodynamic synergism. Contraindicated. Spironolactone binds to androgen receptor and may increase prostate-specific antigen (PSA) levels in abiraterone-treated prostate cancer patients.
- 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 (211)
- 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.
- dalteparin
spironolactone, dalteparin. Either increases toxicity of the other by serum potassium. Use Caution/Monitor. Both drugs may increase serum potassium levels.
- 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.
dichlorphenamide, spironolactone. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Both drugs can cause metabolic acidosis. - 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.
- enoxaparin
spironolactone, enoxaparin. Either increases toxicity of the other by serum potassium. Use Caution/Monitor. Both drugs may increase serum potassium levels.
- 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. - heparin
spironolactone, heparin. Either increases toxicity of the other by serum potassium. Use Caution/Monitor. Both drugs may increase serum potassium levels.
- ibuprofen
ibuprofen increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- hydrochlorothiazide
spironolactone increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- 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.
- loperamide
spironolactone will increase the level or effect of loperamide by P-glycoprotein (MDR1) efflux transporter. 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. .
- methylphenidate transdermal
methylphenidate transdermal decreases effects of hydrochlorothiazide by anti-hypertensive channel blocking. Use Caution/Monitor.
methylphenidate transdermal decreases effects of spironolactone by anti-hypertensive channel blocking. Use Caution/Monitor. - 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 chloride/magnesium sulfate/polyethylene glycol
hydrochlorothiazide and sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol both decrease serum potassium. Modify Therapy/Monitor Closely.
- 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.
- 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. - sparsentan
sparsentan and spironolactone both increase serum potassium. Use Caution/Monitor. Monitor serum potassium frequently.
- 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 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.
- 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.
- patiromer
patiromer, spironolactone. cation binding in GI tract. Minor/Significance Unknown. No observed clinically important interaction. No separation of dosing required.
- oxaprozin
hydrochlorothiazide will increase the level or effect of oxaprozin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
- parecoxib
hydrochlorothiazide will increase the level or effect of parecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
- penicillin G aqueous
hydrochlorothiazide increases levels of penicillin G aqueous by decreasing renal clearance. Minor/Significance Unknown.
- penicillin VK
hydrochlorothiazide increases levels of penicillin VK by decreasing renal clearance. Minor/Significance Unknown.
- pioglitazone
hydrochlorothiazide decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- piperacillin
hydrochlorothiazide increases levels of piperacillin by decreasing renal clearance. Minor/Significance Unknown.
- pirbuterol
pirbuterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.
- piroxicam
hydrochlorothiazide will increase the level or effect of piroxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
- prednisolone
prednisolone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.
- prednisone
prednisone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.
- quinine
hydrochlorothiazide will increase the level or effect of quinine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
- reishi
reishi increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.
reishi increases effects of spironolactone 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.
- shepherd's purse
shepherd's purse, spironolactone. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.
- 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, 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
hydrochlorothiazide increases levels of sulfadiazine by unspecified interaction mechanism. Minor/Significance Unknown.
spironolactone 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.
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
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
Significant impairment of renal excretory function
Hypercalcemia
Acute/severe hepatic failure
Anuria
Hyperkalemia
Addison’s disease or other conditions associated with hyperkalemia
Cautions
Somnolence and dizziness reported to occur in some patients;caution advised when driving or operating machinery until response to initial treatment determined
Use with caution in patients with impaired hepatic function;minor alterations of fluid and electrolyte balance may precipitate hepatic coma
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 may develop in association with use of spironolactone; physicians should be alert to its possible onset; the development ofgynecomastia appears to be related to both dosage level and duration of therapy and is normally reversible when the drug is discontinued; in rare instances, some breast enlargement may persist when therapy is discontinued
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
- Potassium supplementation, either in the form of medication or a diet rich in potassium, should not ordinarily be given in association with therapy; excessive potassium intake may cause hyperkalemia in patients receiving therapy
- Therapy should not be administered concurrently with other potassium-sparing diuretics; spironolactone, when used with ACE inhibitors or indomethacin, even in presence of a diuretic, has been associated with severe hyperkalemia; extreme caution should be exercised when therapy is given concomitantly with these drugs
- 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; monitor calcium levels in patients with hypercalcemia receiving therapy
- 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
- Thiazides should be used with caution in severe renal disease; in patients with renal disease, thiazides may precipitate azotemia; cumulative effects of the drug may develop in patients with impaired renal function
-
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
Drug interaction overview
- Lithium generally should not be given with diuretics
- Drugs that may lead to severe hyperkalemia may include other potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, aldosterone blockers, non-steroidal anti-inflammatory drugs (eg, indomethacin, heparin, and low molecular weight heparin, other drugs known to cause hyperkalemia, potassium supplements, diet rich in potassium, salt substitutes containing potassium
Pregnancy & Lactation
Pregnancy
Hydrochlorothiazide: Studies in which hydrochlorothiazide was orally administered to pregnant mice and rats during their respective periods of major organogenesis at doses up to 3000 and 1000 mg hydrochlorothiazide/kg, respectively, provided no evidence of harm to fetus; there are, however, no adequate and well-controlled studies in pregnant women
Spironolactone: There are no adequate and well-controlled studies in pregnant women; spironolactone has known endocrine effects in animals including progestational and antiandrogenic effects; antiandrogenic effects can result in apparent estrogenic side effects in humans, such as gynecomastia; therefore, use in pregnant women requires that the anticipated benefit be weighed against possible hazards to fetus
Teratology studies with spironolactone have been carried out in mice and rabbits at doses of up to 20 mg/kg/day; on body surface area basis, this dose in the mouse is substantially below maximum recommended human dose and, in rabbit, approximates the maximum recommended human dose; no teratogenic or other embryo-toxic effects were observed in mice, but the 20 mg/kg dose caused an increased rate of resorption and a lower number of live fetuses in rabbits
Because of its antiandrogenic activity and the requirement of testosterone for male morphogenesis, spironolactone may have potential for adversely affecting sex differentiation of the male during embryogenesis
Spironolactone or its metabolites may, and hydrochlorothiazide does, cross placental barrier and appear in cord blood; use of this drug combination in pregnant women requires that the anticipated benefit be weighed against possible hazards to fetus; the hazards include fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adult
Lactation
Canrenone, a major (and active) metabolite of spironolactone, appears in human breast milk; because spironolactone has been found to be tumorigenic in rats, a decision should be made whether to discontinue the drug, taking into account importance of the drug to the mother; if use of the drug is deemed essential, an alternative method of infant feeding should be instituted
Thiazides are excreted in human milk in small amounts; thiazides when given at high doses can cause intense diuresis which can in turn inhibit milk production; the use of this drug combination during breastfeeding is not recommended; if this drug combination is used during breastfeeding, doses should be kept as low as possible
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.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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