spironolactone/hydrochlorothiazide (Rx)

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

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.

• abiraterone

  Serious - Use Alternative (1)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.

• acarbose

  Minor (1)hydrochlorothiazide decreases effects of acarbose by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• acebutolol

  Monitor Closely (2)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

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of aceclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• acemetacin

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of acemetacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• acyclovir

  Minor (1)hydrochlorothiazide will increase the level or effect of acyclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• agrimony

  Minor (2)agrimony increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  agrimony increases effects of spironolactone by pharmacodynamic synergism. Minor/Significance Unknown.

• albiglutide

  Monitor Closely (1)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

  Monitor Closely (2)spironolactone increases and albuterol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
  
  albuterol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (1)albuterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• aldesleukin

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (1)amiloride increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.Serious - Use Alternative (2)amiloride, spironolactone. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hyperkalemia.
  
  amiloride and spironolactone both increase serum potassium. Avoid or Use Alternate Drug.

• aminohippurate sodium

  Minor (1)hydrochlorothiazide will increase the level or effect of aminohippurate sodium by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• aminolevulinic acid oral

  Serious - Use Alternative (1)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

  Serious - Use Alternative (1)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.

• amiodarone

  Monitor Closely (1)amiodarone will increase the level or effect of hydrochlorothiazide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• ammonium chloride

  Minor (1)spironolactone, ammonium chloride. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of systemic acidosis.

• amoxicillin

  Monitor Closely (1)amoxicillin, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• ampicillin

  Monitor Closely (1)ampicillin increases effects of spironolactone by unspecified interaction mechanism. Use Caution/Monitor. Hyperkalemia.Minor (1)hydrochlorothiazide increases levels of ampicillin by decreasing renal clearance. Minor/Significance Unknown.

• arformoterol

  Monitor Closely (2)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.Minor (1)arformoterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• aspirin

  Monitor Closely (3)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.Minor (1)hydrochlorothiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• aspirin rectal

  Monitor Closely (3)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.Minor (1)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

  Monitor Closely (3)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.Minor (1)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.

• atenolol

  Monitor Closely (2)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

  Monitor Closely (2)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.

• balsalazide

  Minor (1)hydrochlorothiazide will increase the level or effect of balsalazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• beclomethasone, inhaled

  Monitor Closely (1)beclomethasone, inhaled increases toxicity of hydrochlorothiazide by increasing elimination. Use Caution/Monitor. May increase the hypokalemic effects of thiazide diuretics.

• benazepril

  Monitor Closely (2)benazepril and spironolactone both increase serum potassium. Use Caution/Monitor.
  
  benazepril increases toxicity of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypotensive effects; increased risk of nephrotoxicity.

• bendroflumethiazide

  Monitor Closely (2)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.Minor (1)bendroflumethiazide will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• betaxolol

  Monitor Closely (2)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.

• birch

  Minor (2)birch increases effects of spironolactone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  birch increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

• bisoprolol

  Monitor Closely (2)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.

• bitter melon

  Minor (1)bitter melon, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• bretylium

  Monitor Closely (2)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.

• brimonidine

  Minor (2)brimonidine increases effects of spironolactone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  brimonidine increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

• budesonide

  Minor (1)budesonide, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• bumetanide

  Monitor Closely (2)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

  Monitor Closely (2)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.

• cadexomer iodine

  Minor (1)cadexomer iodine, spironolactone. Mechanism: decreasing renal clearance. Minor/Significance Unknown. Hyperkalemia.

• calcifediol

  Monitor Closely (1)hydrochlorothiazide increases toxicity of calcifediol by Other (see comment). Use Caution/Monitor. Comment: Thiazide diuretics may increase serum calcium by decreasing urinary calcium excretion.

• calcitriol topical

  Minor (1)calcitriol topical, hydrochlorothiazide. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential additive hypercalcemia.

• calcium acetate

  Minor (2)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

  Minor (2)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

  Minor (2)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

  Minor (2)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

  Minor (2)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.

• canagliflozin

  Monitor Closely (1)spironolactone and canagliflozin both increase serum potassium. Use Caution/Monitor.

• candesartan

  Monitor Closely (2)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

  Monitor Closely (2)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.

• carbamazepine

  Serious - Use Alternative (1)carbamazepine, hydrochlorothiazide. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of systemic hyponatremia.

• carbenoxolone

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide, carbenoxolone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypokalemic effects.

• carbidopa

  Monitor Closely (2)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

  Monitor Closely (2)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.

• cefadroxil

  Minor (1)cefadroxil will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefamandole

  Minor (1)cefamandole will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefpirome

  Minor (1)cefpirome will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefprozil

  Monitor Closely (1)hydrochlorothiazide will increase the level or effect of cefprozil by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.Minor (1)cefprozil will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ceftibuten

  Minor (1)ceftibuten will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• celecoxib

  Monitor Closely (2)spironolactone and celecoxib both increase serum potassium. Modify Therapy/Monitor Closely.
  
  celecoxib increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)hydrochlorothiazide will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• celiprolol

  Monitor Closely (3)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.

• cephalexin

  Minor (1)cephalexin will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chlorothiazide

  Monitor Closely (2)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.Minor (1)chlorothiazide will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chlorpropamide

  Minor (2)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

  Monitor Closely (2)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.Minor (1)chlorthalidone will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cholestyramine

  Monitor Closely (2)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

  Monitor Closely (1)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.

• choline magnesium trisalicylate

  Monitor Closely (1)spironolactone and choline magnesium trisalicylate both increase serum potassium. Modify Therapy/Monitor Closely.

• citalopram

  Monitor Closely (1)hydrochlorothiazide, citalopram. pharmacodynamic synergism. Use Caution/Monitor. Possible additive hyponatremia.

• colestipol

  Minor (1)colestipol decreases levels of hydrochlorothiazide by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• cornsilk

  Monitor Closely (1)cornsilk increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypokalemia (theoretical interaction).Minor (1)cornsilk increases effects of spironolactone by pharmacodynamic synergism. Minor/Significance Unknown.

• corticotropin

  Monitor Closely (1)corticotropin increases toxicity of hydrochlorothiazide by increasing renal clearance. Use Caution/Monitor. May enhance hypokalemic effect of thiazide diuretics.

• cortisone

  Minor (1)cortisone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• cosyntropin

  Minor (1)cosyntropin, hydrochlorothiazide. pharmacodynamic synergism. Minor/Significance Unknown. Possible enhanced electrolyte loss.

• cyclopenthiazide

  Monitor Closely (2)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.Minor (1)cyclopenthiazide will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cyclophosphamide

  Serious - Use Alternative (1)hydrochlorothiazide increases toxicity of cyclophosphamide by decreasing renal clearance. Avoid or Use Alternate Drug. Increased myelosuppressive effects.

• cyclosporine

  Monitor Closely (1)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.Serious - Use Alternative (2)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

• dalteparin

  Monitor Closely (1)spironolactone, dalteparin. Either increases toxicity of the other by serum potassium. Use Caution/Monitor. Both drugs may increase serum potassium levels.

• deflazacort

  Monitor Closely (1)hydrochlorothiazide and deflazacort both decrease serum potassium. Use Caution/Monitor.Minor (1)deflazacort, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• dexamethasone

  Minor (1)dexamethasone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• diazoxide

  Monitor Closely (1)hydrochlorothiazide increases toxicity of diazoxide by unspecified interaction mechanism. Use Caution/Monitor. May enhance hyperglycemic effects of diazoxide.Minor (1)diazoxide, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hyperglycemia.

• dichlorphenamide

  Monitor Closely (2)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

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of diclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• dicloxacillin

  Monitor Closely (1)dicloxacillin, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• diflunisal

  Monitor Closely (2)spironolactone and diflunisal both increase serum potassium. Modify Therapy/Monitor Closely.
  
  diflunisal increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)hydrochlorothiazide will increase the level or effect of diflunisal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• digoxin

  Monitor Closely (6)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

  Monitor Closely (1)spironolactone increases effects of disopyramide by pharmacodynamic synergism. Use Caution/Monitor. Additive cardiovascular depression.

• dobutamine

  Monitor Closely (2)dobutamine and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.
  
  spironolactone increases and dobutamine decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.Minor (1)dobutamine, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• dofetilide

  Monitor Closely (1)dofetilide will increase the level or effect of hydrochlorothiazide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.Serious - Use Alternative (1)hydrochlorothiazide increases levels of dofetilide by decreasing renal clearance. Contraindicated. Risk of prolonged QTc interval.

• dopexamine

  Monitor Closely (2)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.Minor (1)dopexamine, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• drospirenone

  Monitor Closely (1)drospirenone increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.Serious - Use Alternative (2)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.

• empagliflozin

  Monitor Closely (2)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.
  
  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.

• enalapril

  Monitor Closely (1)enalapril, spironolactone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

• enoxaparin

  Monitor Closely (1)spironolactone, enoxaparin. Either increases toxicity of the other by serum potassium. Use Caution/Monitor. Both drugs may increase serum potassium levels.

• ephedrine

  Monitor Closely (2)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.Minor (1)ephedrine, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• epinephrine

  Monitor Closely (2)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.Minor (1)epinephrine, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• epinephrine racemic

  Monitor Closely (2)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.Minor (1)epinephrine racemic, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• eplerenone

  Serious - Use Alternative (1)spironolactone, eplerenone. Mechanism: pharmacodynamic synergism. Contraindicated. Hyperkalemia.

• epoprostenol

  Minor (2)epoprostenol increases effects of spironolactone by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.
  
  epoprostenol increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.

• eprosartan

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of etodolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• exenatide injectable solution

  Monitor Closely (1)hydrochlorothiazide decreases effects of exenatide injectable solution by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

• exenatide injectable suspension

  Monitor Closely (1)hydrochlorothiazide decreases effects of exenatide injectable suspension by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

• fenbufen

  Monitor Closely (1)spironolactone and fenbufen both increase serum potassium. Modify Therapy/Monitor Closely.Minor (1)hydrochlorothiazide will increase the level or effect of fenbufen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fenoprofen

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of fenoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fentanyl

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (1)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.

• fludrocortisone

  Minor (1)fludrocortisone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• flurbiprofen

  Monitor Closely (2)spironolactone and flurbiprofen both increase serum potassium. Modify Therapy/Monitor Closely.
  
  flurbiprofen increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)hydrochlorothiazide will increase the level or effect of flurbiprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fo-ti

  Minor (1)fo-ti increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia (theoretical).

• folic acid

  Minor (1)hydrochlorothiazide decreases levels of folic acid by increasing renal clearance. Minor/Significance Unknown.

• formoterol

  Monitor Closely (2)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.Minor (1)formoterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• forskolin

  Minor (2)forskolin increases effects of spironolactone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  forskolin increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

• fosinopril

  Monitor Closely (1)fosinopril, spironolactone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

• furosemide

  Monitor Closely (2)spironolactone increases and furosemide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
  
  furosemide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

• ganciclovir

  Minor (1)hydrochlorothiazide will increase the level or effect of ganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• gentamicin

  Monitor Closely (2)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.

• glimepiride

  Minor (1)hydrochlorothiazide decreases effects of glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• glipizide

  Minor (1)hydrochlorothiazide decreases effects of glipizide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• glyburide

  Minor (1)hydrochlorothiazide decreases effects of glyburide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• goldenrod

  Minor (2)goldenrod increases effects of spironolactone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  goldenrod increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

• heparin

  Monitor Closely (1)spironolactone, heparin. Either increases toxicity of the other by serum potassium. Use Caution/Monitor. Both drugs may increase serum potassium levels.

• hydrochlorothiazide

  Monitor Closely (1)spironolactone increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• hydrocortisone

  Minor (1)hydrocortisone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• ibuprofen

  Monitor Closely (2)ibuprofen increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  spironolactone and ibuprofen both increase serum potassium. Modify Therapy/Monitor Closely.Minor (1)hydrochlorothiazide will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ibuprofen IV

  Monitor Closely (3)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

  Monitor Closely (1)imidapril, spironolactone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

• indacaterol, inhaled

  Monitor Closely (2)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

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of indapamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• indomethacin

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of indomethacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• insulin aspart

  Minor (1)hydrochlorothiazide decreases effects of insulin aspart by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• insulin degludec

  Monitor Closely (1)hydrochlorothiazide decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

• insulin degludec/insulin aspart

  Monitor Closely (1)hydrochlorothiazide decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

• insulin detemir

  Minor (1)hydrochlorothiazide decreases effects of insulin detemir by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• insulin glargine

  Minor (1)hydrochlorothiazide decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• insulin glulisine

  Minor (1)hydrochlorothiazide decreases effects of insulin glulisine by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• insulin inhaled

  Monitor Closely (1)hydrochlorothiazide decreases effects of insulin inhaled by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

• insulin lispro

  Minor (1)hydrochlorothiazide decreases effects of insulin lispro by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• insulin NPH

  Minor (1)hydrochlorothiazide decreases effects of insulin NPH by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• insulin regular human

  Minor (1)hydrochlorothiazide decreases effects of insulin regular human by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• iodinated glycerol

  Minor (1)iodinated glycerol, spironolactone. Mechanism: decreasing renal clearance. Minor/Significance Unknown. Hyperkalemia.

• iodine

  Minor (1)iodine, spironolactone. Mechanism: decreasing renal clearance. Minor/Significance Unknown. Hyperkalemia.

• irbesartan

  Monitor Closely (2)irbesartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  irbesartan and spironolactone both increase serum potassium. Modify Therapy/Monitor Closely.

• isocarboxazid

  Serious - Use Alternative (1)isocarboxazid, hydrochlorothiazide. Other (see comment). Contraindicated. Comment: Additive hypotensive effects may be seen when MAOI's are combined with antihypertensives.

• isoproterenol

  Monitor Closely (2)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.Minor (1)isoproterenol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• juniper

  Monitor Closely (2)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

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of ketoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketorolac

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of ketorolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketorolac intranasal

  Monitor Closely (2)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. .Minor (1)hydrochlorothiazide will increase the level or effect of ketorolac intranasal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• L-methylfolate

  Minor (1)hydrochlorothiazide decreases levels of L-methylfolate by increasing renal clearance. Minor/Significance Unknown.

• labetalol

  Monitor Closely (2)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

  Monitor Closely (2)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.Minor (1)levalbuterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• levodopa

  Monitor Closely (2)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

  Monitor Closely (1)hydrochlorothiazide increases toxicity of lily of the valley by Other (see comment). Use Caution/Monitor. Comment: Increased risk of cardiac toxicity due to K+ depletion.

• liraglutide

  Monitor Closely (1)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.

• lisinopril

  Monitor Closely (1)lisinopril, spironolactone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

• lithium

  Monitor Closely (1)hydrochlorothiazide increases toxicity of lithium by decreasing elimination. Use Caution/Monitor.

• lofexidine

  Serious - Use Alternative (2)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.

• loperamide

  Monitor Closely (1)spironolactone will increase the level or effect of loperamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• lornoxicam

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of lornoxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• losartan

  Monitor Closely (2)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

  Monitor Closely (2)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.

• magnesium chloride

  Minor (2)spironolactone increases levels of magnesium chloride by decreasing renal clearance. Minor/Significance Unknown.
  
  hydrochlorothiazide decreases levels of magnesium chloride by increasing renal clearance. Minor/Significance Unknown.

• magnesium citrate

  Minor (2)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

  Minor (2)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

  Minor (2)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

  Minor (2)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

  Monitor Closely (1)maitake increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypokalemia (theoretical interaction).Minor (1)maitake increases effects of spironolactone by pharmacodynamic synergism. Minor/Significance Unknown.

• maraviroc

  Monitor Closely (1)maraviroc, spironolactone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.

• meclofenamate

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of meclofenamate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mefenamic acid

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of mefenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• meloxicam

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of meloxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• memantine

  Minor (1)hydrochlorothiazide will increase the level or effect of memantine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mesalamine

  Minor (1)hydrochlorothiazide will increase the level or effect of mesalamine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• metaproterenol

  Monitor Closely (2)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.Minor (1)metaproterenol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• metformin

  Minor (2)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

  Minor (1)hydrochlorothiazide increases toxicity of methotrexate by decreasing elimination. Minor/Significance Unknown. Increased myelosuppression.

• methoxsalen

  Monitor Closely (1)methoxsalen, hydrochlorothiazide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive photosensitizing effects.

• methyclothiazide

  Monitor Closely (1)spironolactone increases and methyclothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely. .

• methyl aminolevulinate

  Serious - Use Alternative (1)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.

• methylphenidate transdermal

  Monitor Closely (2)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.

• methylprednisolone

  Minor (1)methylprednisolone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• metolazone

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of metolazone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• metoprolol

  Monitor Closely (3)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

  Monitor Closely (1)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

• midodrine

  Minor (1)hydrochlorothiazide will increase the level or effect of midodrine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• miglitol

  Minor (1)hydrochlorothiazide decreases effects of miglitol by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• minoxidil

  Minor (2)spironolactone increases effects of minoxidil by pharmacodynamic synergism. Minor/Significance Unknown.
  
  hydrochlorothiazide increases effects of minoxidil by pharmacodynamic synergism. Minor/Significance Unknown.

• mitotane

  Monitor Closely (1)spironolactone decreases effects of mitotane by pharmacodynamic antagonism. Use Caution/Monitor.

• moexipril

  Monitor Closely (1)moexipril, spironolactone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

• mometasone inhaled

  Monitor Closely (1)mometasone inhaled increases toxicity of hydrochlorothiazide by Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may increase hypokalemic effect of loop diuretics.

• mycophenolate

  Monitor Closely (1)hydrochlorothiazide will increase the level or effect of mycophenolate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

• nabumetone

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of nabumetone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• nadolol

  Monitor Closely (2)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

  Monitor Closely (1)nafcillin, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• naproxen

  Monitor Closely (2)spironolactone and naproxen both increase serum potassium. Modify Therapy/Monitor Closely.
  
  naproxen increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)hydrochlorothiazide will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• nateglinide

  Minor (1)hydrochlorothiazide decreases effects of nateglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• nebivolol

  Monitor Closely (2)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.

• nitazoxanide

  Minor (1)nitazoxanide, spironolactone. Either increases levels of the other by Mechanism: plasma protein binding competition. Minor/Significance Unknown.

• nitroglycerin rectal

  Monitor Closely (2)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

  Monitor Closely (1)spironolactone and noni juice both increase serum potassium. Use Caution/Monitor.Minor (1)noni juice increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

• norepinephrine

  Monitor Closely (2)spironolactone increases and norepinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
  
  norepinephrine and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (2)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.
  
  norepinephrine, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• octacosanol

  Minor (2)octacosanol increases effects of spironolactone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  octacosanol increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

• ofloxacin

  Minor (1)hydrochlorothiazide will increase the level or effect of ofloxacin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• oliceridine

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (1)hydrochlorothiazide and olodaterol inhaled both decrease serum potassium. Use Caution/Monitor.

• ospemifene

  Monitor Closely (1)spironolactone, ospemifene. Either increases levels of the other by plasma protein binding competition. Modify Therapy/Monitor Closely.

• oxaprozin

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of oxaprozin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• parecoxib

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of parecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• patiromer

  Minor (1)patiromer, spironolactone. cation binding in GI tract. Minor/Significance Unknown. No observed clinically important interaction. No separation of dosing required.

• penbutolol

  Monitor Closely (2)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

  Monitor Closely (1)penicillin G aqueous, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.Minor (1)hydrochlorothiazide increases levels of penicillin G aqueous by decreasing renal clearance. Minor/Significance Unknown.

• penicillin VK

  Minor (1)hydrochlorothiazide increases levels of penicillin VK by decreasing renal clearance. Minor/Significance Unknown.

• perindopril

  Monitor Closely (1)perindopril, spironolactone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

• pindolol

  Monitor Closely (2)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.

• pioglitazone

  Minor (1)hydrochlorothiazide decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• piperacillin

  Minor (1)hydrochlorothiazide increases levels of piperacillin by decreasing renal clearance. Minor/Significance Unknown.

• pirbuterol

  Monitor Closely (2)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.Minor (1)pirbuterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• piroxicam

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of piroxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• pivmecillinam

  Monitor Closely (2)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

  Monitor Closely (1)hydrochlorothiazide, porfimer. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced photosensitivity.

• potassium acid phosphate

  Monitor Closely (1)potassium acid phosphate increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)spironolactone and potassium acid phosphate both increase serum potassium. Avoid or Use Alternate Drug.

• potassium chloride

  Monitor Closely (1)potassium chloride increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)spironolactone and potassium chloride both increase serum potassium. Avoid or Use Alternate Drug.

• potassium citrate

  Monitor Closely (1)potassium citrate increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)spironolactone and potassium citrate both increase serum potassium. Avoid or Use Alternate Drug.

• potassium citrate/citric acid

  Monitor Closely (1)spironolactone and potassium citrate/citric acid both increase serum potassium. Use Caution/Monitor.

• potassium phosphates, IV

  Serious - Use Alternative (1)spironolactone and potassium phosphates, IV both increase serum potassium. Avoid or Use Alternate Drug.

• prednisolone

  Minor (1)prednisolone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• prednisone

  Minor (1)prednisone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• probenecid

  Monitor Closely (1)hydrochlorothiazide will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

• procainamide

  Monitor Closely (1)hydrochlorothiazide will increase the level or effect of procainamide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• propranolol

  Monitor Closely (2)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

  Monitor Closely (1)spironolactone decreases effects of pseudoephedrine by pharmacodynamic antagonism. Use Caution/Monitor.

• quinapril

  Monitor Closely (1)quinapril, spironolactone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

• quinidine

  Monitor Closely (1)quinidine will increase the level or effect of hydrochlorothiazide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• quinine

  Minor (1)hydrochlorothiazide will increase the level or effect of quinine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ramipril

  Monitor Closely (1)ramipril, spironolactone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

• reishi

  Minor (2)reishi increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  reishi increases effects of spironolactone by pharmacodynamic synergism. Minor/Significance Unknown.

• repaglinide

  Monitor Closely (1)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 CYP2C8Minor (1)hydrochlorothiazide decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• rose hips

  Minor (1)rose hips will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• rosiglitazone

  Minor (1)hydrochlorothiazide decreases effects of rosiglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• sacubitril/valsartan

  Monitor Closely (2)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)

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of salicylates (non-asa) by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• salmeterol

  Monitor Closely (2)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.Minor (1)salmeterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• salsalate

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of salsalate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• saxagliptin

  Minor (1)hydrochlorothiazide decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• shark cartilage

  Monitor Closely (1)hydrochlorothiazide, shark cartilage. Other (see comment). Use Caution/Monitor. Comment: May lead to hypercalcemia (theoretical).

• shepherd's purse

  Minor (2)shepherd's purse, spironolactone. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.
  
  shepherd's purse, hydrochlorothiazide. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.

• sirolimus

  Monitor Closely (1)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

• sitagliptin

  Minor (1)hydrochlorothiazide decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• sodium sulfate/?magnesium sulfate/potassium chloride

  Monitor Closely (1)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

  Monitor Closely (1)hydrochlorothiazide and sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol both decrease serum potassium. Modify Therapy/Monitor Closely.

• sodium sulfate/potassium sulfate/magnesium sulfate

  Monitor Closely (1)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

  Monitor Closely (2)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

  Monitor Closely (1)sparsentan and spironolactone both increase serum potassium. Use Caution/Monitor. Monitor serum potassium frequently.

• spironolactone

  Monitor Closely (1)spironolactone increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• squill

  Serious - Use Alternative (1)hydrochlorothiazide increases toxicity of squill by Other (see comment). Avoid or Use Alternate Drug. Comment: Potassium depletion may enhance toxicity of squill.

• succinylcholine

  Monitor Closely (2)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.

• sulfadiazine

  Minor (2)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

  Minor (5)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

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of sulfasalazine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sulfisoxazole

  Minor (2)hydrochlorothiazide increases levels of sulfisoxazole by unspecified interaction mechanism. Minor/Significance Unknown.
  
  spironolactone increases levels of sulfisoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• sulindac

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of sulindac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• tacrolimus

  Monitor Closely (1)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

  Monitor Closely (2)tadalafil increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.
  
  tadalafil increases effects of spironolactone by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

• telmisartan

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (2)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.Minor (2)hydrochlorothiazide, terbutaline. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypokalemic effects.
  
  terbutaline, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• ticarcillin

  Monitor Closely (2)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

  Monitor Closely (2)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.

• tizanidine

  Minor (2)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

  Minor (1)hydrochlorothiazide decreases effects of tolazamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• tolbutamide

  Minor (1)hydrochlorothiazide decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• tolfenamic acid

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of tolfenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• tolmetin

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of tolmetin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• tolvaptan

  Monitor Closely (2)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

  Monitor Closely (1)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

  Monitor Closely (2)spironolactone increases and torsemide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
  
  torsemide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

• trandolapril

  Monitor Closely (1)trandolapril, spironolactone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

• treprostinil

  Minor (2)treprostinil increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  treprostinil increases effects of spironolactone by pharmacodynamic synergism. Minor/Significance Unknown.

• tretinoin

  Serious - Use Alternative (1)hydrochlorothiazide, tretinoin. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

• tretinoin topical

  Serious - Use Alternative (1)hydrochlorothiazide, tretinoin topical. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

• triamcinolone acetonide injectable suspension

  Minor (1)triamcinolone acetonide injectable suspension, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• triamterene

  Monitor Closely (1)triamterene increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.Serious - Use Alternative (2)spironolactone, triamterene. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hyperkalemia.
  
  spironolactone and triamterene both increase serum potassium. Avoid or Use Alternate Drug.Minor (1)hydrochlorothiazide will increase the level or effect of triamterene by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• trientine

  Monitor Closely (1)hydrochlorothiazide decreases levels of trientine by increasing renal clearance. Use Caution/Monitor.

• trilostane

  Minor (1)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

  Monitor Closely (1)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.Minor (3)hydrochlorothiazide will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  spironolactone, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.
  
  hydrochlorothiazide, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.

• umeclidinium bromide/vilanterol inhaled

  Monitor Closely (1)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

• valganciclovir

  Minor (1)hydrochlorothiazide will increase the level or effect of valganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• valsartan

  Monitor Closely (2)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.

• verapamil

  Minor (1)hydrochlorothiazide will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• verteporfin

  Minor (1)hydrochlorothiazide, verteporfin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased phototoxicity.

• vilanterol/fluticasone furoate inhaled

  Monitor Closely (1)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

• vildagliptin

  Minor (1)hydrochlorothiazide decreases effects of vildagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• vitamin D

  Monitor Closely (1)hydrochlorothiazide increases effects of vitamin D by Other (see comment). Use Caution/Monitor. Comment: Combination may increase hypercalcemic effect of vitamin D analogs. Use with caution.

• voclosporin

  Monitor Closely (1)voclosporin and spironolactone both increase serum potassium. Use Caution/Monitor.

• willow bark

  Minor (1)hydrochlorothiazide will increase the level or effect of willow bark by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• xipamide

  Monitor Closely (2)xipamide increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor.
  
  xipamide increases effects of spironolactone by pharmacodynamic synergism. Use Caution/Monitor.