Spironolactone and hydrochlorothiazide: uses, appearance and warnings

Spironolactone, an ingredient of spironolactone and hydrochlorothiazide tablets, has been shown to be a tumorigen in chronic toxicity studies in rats (see Precautions section). Spironolactone and hydrochlorothiazide tablets should be used only in those conditions described below. Unnecessary use of this drug should be avoided. Spironolactone and hydrochlorothiazide tablets are indicated for: Edematous conditions for patients with: Congestive heart failure: • For the management of edema and sodium retention when the patient is only partially responsive to, or is intolerant of, other therapeutic measures; • The treatment of diuretic-induced hypokalemia in patients with congestive heart failure when other measures are considered inappropriate; • The treatment of patients with congestive heart failure taking digitalis when other therapies are considered inadequate or inappropriate. Cirrhosis of the liver accompanied by edema and/or ascites: • Aldosterone levels may be exceptionally high in this condition. Spironolactone and hydrochlorothiazide tablets are indicated for maintenance therapy together with bed rest and the restriction of fluid and sodium. The nephrotic syndrome: • For nephrotic patients when treatment of the underlying disease, restriction of fluid and sodium intake, and the use of other diuretics do not provide an adequate response. Essential hypertension: • For patients with essential hypertension in whom other measures are considered inadequate or inappropriate; • In hypertensive patients for the treatment of a diuretic-induced hypokalemia when other measures are considered inappropriate; • Spironolactone and hydrochlorothiazide tablets are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including the classes to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with spironolactone and hydrochlorothiazide tablets. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. …

Spironolactone and Hydrochlorothiazide Tablets, USP are available containing 25 mg of spironolactone, USP and 25 mg of hydrochlorothiazide, USP. The 25 mg/25 mg tablets are ivory, round, unscored tablets debossed with M over 41 on one side of the tablet and blank on the other side. They are available as follows: NDC 0378-0403-01 bottles of 100 tablets NDC 0378-0403-05 bottles of 500 tablets Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from light. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. Distributed by: Mylan Pharmaceuticals Inc., a Viatris Company Morgantown, WV 26505 U.S.A. Revised: 3/2026 ALP:SPHZ:R5

Spironolactone and hydrochlorothiazide tablets are contraindicated in patients with anuria, acute renal insufficiency, significant impairment of renal excretory function, hypercalcemia, hyperkalemia, Addison’s disease, and in patients who are allergic to thiazide diuretics or to other sulfonamide-derived drugs. Spironolactone and hydrochlorothiazide may also be contraindicated in acute or severe hepatic failure.

Potassium supplementation, either in the form of medication or as a diet rich in potassium, should not ordinarily be given in association with spironolactone and hydrochlorothiazide therapy. Excessive potassium intake may cause hyperkalemia in patients receiving spironolactone and hydrochlorothiazide (see Precautions: General ). Concomitant administration of spironolactone and hydrochlorothiazide with the following drugs or potassium sources may lead to severe hyperkalemia: • other potassium-sparing diuretics • ACE inhibitors • angiotensin II receptor antagonists • aldosterone blockers • non-steroidal anti-inflammatory drugs (NSAIDs), e.g., indomethacin • heparin and low molecular weight heparin • other drugs or conditions known to cause hyperkalemia • potassium supplements • diet rich in potassium • salt substitutes containing potassium Spironolactone and hydrochlorothiazide should not be administered concurrently with other potassium-sparing diuretics. Spironolactone, when used with ACE inhibitors or indomethacin, even in the presence of a diuretic, has been associated with severe hyperkalemia. Extreme caution should be exercised when spironolactone and hydrochlorothiazide tablets are given concomitantly with these drugs (see Precautions: Drug interactions ). Spironolactone and hydrochlorothiazide should be used with caution in patients with impaired hepatic function because minor alterations of fluid and electrolyte balance may precipitate hepatic coma. Lithium generally should not be given with diuretics (see Precautions: Drug interactions ). Thiazides should be used with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function. Thiazides may add to or potentiate the action of other antihypertensive drugs. Sensitivity reactions to thiazides may occur in patients with or without a history of allergy or bronchial asthma. Sulfonamide derivatives, including thiazides, have been reported to exacerbate or activate systemic lupus erythematosus. Acute Angle-Closure Glaucoma with or without Acute Myopia and Choroidal Effusions Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute angle-closure glaucoma and elevated intraocular pressure with or without a noticeable acute myopic shift and/or choroidal effusions. Symptoms may include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated, the angle-closure glaucoma may result in permanent visual field loss. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.

The following adverse reactions have been reported and, within each category (body system), are listed in order of decreasing severity. Hydrochlorothiazide Body as a whole: Weakness. Cardiovascular: Hypotension including orthostatic hypotension (may be aggravated by alcohol, barbiturates, narcotics, or antihypertensive drugs). Digestive: Pancreatitis, jaundice (intrahepatic cholestatic jaundice), diarrhea, vomiting, sialoadenitis, cramping, constipation, gastric irritation, nausea, anorexia. Eye Disorders: Acute myopia and acute angle-closure glaucoma (see Warnings ). Hematologic: Aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia. Hypersensitivity: Anaphylactic reactions, necrotizing angitis (vasculitis and cutaneous vasculitis), respiratory distress including pneumonitis and pulmonary edema, photosensitivity, fever, urticaria, rash, purpura. …

ACE inhibitors, Angiotensin II receptor antagonists, aldosterone blockers, potassium supplements, heparin, low molecular weight heparin, and other drugs known to cause hyperkalemia Concomitant administration may lead to severe hyperkalemia. Alcohol, barbiturates, or narcotics Potentiation of orthostatic hypotension may occur. Antidiabetic drugs (e.g., oral agents, insulin) Dosage adjustment of the antidiabetic drug may be required (see Precautions ). Corticosteroids, ACTH Intensified electrolyte depletion, particularly hypokalemia, may occur. Pressor amines (e.g., norepinephrine) Both spironolactone and hydrochlorothiazide reduce the vascular responsiveness to norepinephrine. Therefore, caution should be exercised in the management of patients subjected to regional or general anesthesia while they are being treated with spironolactone and hydrochlorothiazide. …