SPIRONOLACTONE Drug Interactions: What You Need to Know

INTERACTIONS

• Agents increasing serum potassium: Concomitant administration can lead to hyperkalemia ( 5.1 , 7.1 )
• Lithium: Increased risk of lithium toxicity ( 7.2 )
• NSAIDs: May reduce the diuretic, natriuretic and antihypertensive effect of spironolactone oral suspension ( 7.3 )
• Digoxin: Spironolactone oral suspension can interfere with radioimmunologic assays of digoxin exposure ( 7.4 )
• Cholestyramine: Hyperkalemic metabolic acidosis has been reported with concomitant use ( 7.5 )
• Acetylsalicylic Acid (ASA): ASA may reduce the efficacy of spironolactone ( 7.6 )

7.1 Drugs and Supplements Increasing Serum Potassium Concomitant administration of spironolactone oral suspension with potassium supplementation or drugs that can increase potassium may lead to severe hyperkalemia. In general, discontinue potassium supplementation in heart failure patients who start spironolactone oral suspension <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.1 ) and Clinical Pharmacology ( 12.3 )]</span> . Check serum potassium levels when ACE inhibitor or ARB therapy is altered in patients receiving spironolactone oral suspension. Examples of drugs that can increase potassium include:

• ACE inhibitors
• angiotensin receptor blockers
• aldosterone blockers
• non-steroidal anti-inflammatory drugs (NSAIDs)
• heparin and low molecular weight heparin
• trimethoprim

7.2 Lithium Like other diuretics, spironolactone oral suspension reduces the renal clearance of lithium, thus increasing the risk of lithium toxicity. Monitor lithium levels periodically when spironolactone oral suspension is coadministered <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> .

7.3 Nonsteroidal Anti-inflammatory Drugs (NSAIDs) In some patients, the administration of an NSAID can reduce the diuretic, natriuretic, and antihypertensive effect of loop, potassium-sparing, and thiazide diuretics. Therefore, when spironolactone oral suspension and NSAIDs are used concomitantly, monitor closely to determine if the desired effect of the diuretic is obtained <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> .

7.4 Digoxin Spironolactone and its metabolites increase the apparent exposure to digoxin. In patients taking concomitant digoxin, measure serum digoxin concentrations before initiating spironolactone using an assay that does not interact with spironolactone. Reduce digoxin concentrations by decreasing the dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> .

7.5 Cholestyramine Hyperkalemic metabolic acidosis has been reported in patients given spironolactone concurrently with cholestyramine.

7.6 Acetylsalicylic Acid Acetylsalicylic acid may reduce the efficacy of spironolactone. Therefore, when spironolactone oral suspension and acetylsalicylic acid are used concomitantly, spironolactone oral suspension may need to be titrated to higher maintenance dose and the patient should be observed closely to determine if the desired effect is obtained <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> .

7.7 CYP2C8 and CYP3A Substrates Spironolactone is an irreversible inhibitor for CYP2C8 and CYP3A4/5 in vitro <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> . Therefore, spironolactone may increase the exposure of other coadministered drugs that are metabolized by CYP2C8 and CYP3A4/5. Dosage adjustments of the drugs metabolized by CYP2C8 (e.g., repaglinide) and CYP3A4/5 (e.g., midazolam, sirolimus and tacrolimus) may be necessary if they are given concurrently with spironolactone.

Spironolactone oral suspension is contraindicated for patients with the following conditions:

• Hyperkalemia
• Addison’s disease
• Concomitant use of eplerenone Spironolactone oral suspension is contraindicated in patients with ( 4 ):
• Hyperkalemia
• Addison’s disease
• Concomitant use of eplerenone

AND PRECAUTIONS

• Hyperkalemia: Monitor serum potassium within one week of initiation and regularly thereafter ( Error! Hyperlink reference not valid. ).
• Hypotension and Worsening Renal Function: Monitor volume status and renal function periodically ( Error! Hyperlink reference not valid. ).
• Electrolyte and Metabolic Abnormalities: Monitor serum electrolytes, uric acid and blood glucose periodically ( Error! Hyperlink reference not valid. ).
• Gynecomastia: Spironolactone can cause gynecomastia ( Error! Hyperlink reference not valid. ).

5.1 Hyperkalemia Spironolactone can cause hyperkalemia. This risk is increased by impaired renal function or concomitant potassium supplementation, potassium-containing salt substitutes or drugs that increase potassium, such as angiotensin converting enzyme inhibitors and angiotensin receptor blockers <span class="opacity-50 text-xs">[see Drug Interactions (7.1) ]</span> . Monitor serum potassium within 1 week of initiation or titration of spironolactone and regularly thereafter. More frequent monitoring may be needed when spironolactone is given with other drugs that cause hyperkalemia or in patients with impaired renal function. If hyperkalemia occurs, decrease the dose or discontinue spironolactone and treat hyperkalemia.

5.2 Hypotension and Worsening Renal Function Excessive diuresis may cause symptomatic dehydration, hypotension and worsening renal function, particularly in salt-depleted patients or those taking angiotensin converting enzyme inhibitors and angiotensin II receptor blockers. Worsening of renal function can also occur with concomitant use of nephrotoxic drugs (e.g., aminoglycosides, cisplatin, and NSAIDs). Monitor volume status and renal function periodically.

5.3 Electrolyte and Metabolic Abnormalities In addition to causing hyperkalemia, spironolactone can cause hyponatremia, hypomagnesemia, hypocalcemia, hypochloremic alkalosis, and hyperglycemia. Asymptomatic hyperuricemia can occur and rarely gout is precipitated. Monitor serum electrolytes, uric acid and blood glucose periodically.

5.4 Gynecomastia Spironolactone can cause gynecomastia.

In Randomized Spironolactone Evaluation

Study, patients with heart failure treated with a mean dose of 26 mg of spironolactone once daily, about 9% of the male subjects developed gynecomastia. The risk of gynecomastia increases in a dose-dependent manner with an onset that varies widely from 1-2 months to over a year. Gynecomastia is usually reversible.