Spironolactone

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).

Fluid and electrolyte imbalance (eg, hypomagnesemia, hyponatremia, hypocalcemia, hypochloremic alkalosis, hyperglycemia, hyperkalemia, acidosis, elevated BUN) may occur; close medical supervision and dose evaluation are required. Patients with heart failure, renal disease, or cirrhosis may be particularly susceptible. Monitor and correct electrolyte disturbances; adjust dose to avoid dehydration.

Asymptomatic hyperuricemia may occur and gout may be precipitated (rare).

Related to dose and duration of therapy; typically is reversible following discontinuation of therapy but may persist (rare).

Hyperkalemia may occur; risk of hyperkalemia is increased with renal impairment, excessive potassium intake, and patients taking certain drugs (eg, ACE inhibitors, angiotensin-II blockers, NSAIDs). Monitor closely for hyperkalemia; increases in serum potassium are dose related and rates of hyperkalemia also increase with declining renal function. The concurrent use of larger doses of ACE inhibitors (eg, ≥ lisinopril 10 mg daily in adults) also increases the risk of hyperkalemia (ACCF/AHA [Yancy 2013]). Dose reduction or interruption of therapy may be necessary with development of hyperkalemia. Use is contraindicated in patients with hyperkalemia; use caution in conditions known to cause hyperkalemia.

Shown to be a tumorigen in chronic toxicity animal studies. Avoid unnecessary use. Disease-related concerns:

Discontinue use prior to adrenal vein catheterization.

When evaluating a heart failure patient for spironolactone treatment, eGFR should be >30 mL/minute/1.73 m2 or creatinine should be ≤2.5 mg/dL (men) or ≤2 mg/dL (women) with no recent worsening and potassium 5 mEq/L or serum creatinine >4 mg/dL. The ACCF/AHA recommends considering discontinuation upon the development of serum potassium >5.5 mEq/L or worsening renal function with careful evaluation of the entire medical regimen. Avoid routine triple therapy with the combined use of an ACE inhibitor, ARB, and spironolactone. Instruct patients with heart failure to discontinue use during an episode of diarrhea or dehydration or when loop diuretic therapy is interrupted (ACCF/AHA [Yancy 2013]).

Use with caution in patients with hepatic impairment; minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

Risk of hyperkalemia is increased with declining renal function and with the concurrent use of larger doses of ACE inhibitors (eg, ≥ lisinopril 10 mg daily in adults) (ACCF/AHA [Yancy 2013]). Use with caution in patients with mild renal impairment; tablets are contraindicated with anuria, acute renal insufficiency, or significant impairment of renal excretory function. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Avoid use of tablets >25 mg/day in elderly patients with heart failure or with reduced renal function (eg, CrCl 2 [Yancy 2013]). Other warnings/precautions:

Suspension is NOT therapeutically equivalent to tablets. In patients requiring >100 mg/dose, use tablets (>100 mg/dose of suspension may result in spironolactone concentration higher than expected).