Indications And Usage

Hypertension: Captopril tablets, USP are indicated for the treatment of hypertension.

In using captopril, consideration should be given to the risk of neutropenia/agranulocytosis.

Captopril may be used as initial therapy for patients with normal renal function, in whom the risk is relatively low. In patients with impaired renal function, particularly those with collagen vascular disease, captopril should be reserved for hypertensives who have either developed unacceptable side effects on other drugs, or have failed to respond satisfactorily to drug combinations.

Captopril is effective alone and in combination with other antihypertensive agents, especially thiazide-type diuretics. The blood pressure lowering effects of captopril and thiazides are approximately additive.

Heart Failure: Captopril tablets are indicated in the treatment of congestive heart failure usually in combination with diuretics and digitalis. The beneficial effect of captopril in heart failure does not require the presence of digitalis, however, most controlled clinical trial experience with captopril has been in patients receiving digitalis, as well as diuretic treatment.

Left Ventricular Dysfunction After Myocardial Infarction: Captopril tablets are indicated to improve survival following myocardial infarction in clinically stable patients with left ventricular dysfunction manifested as an ejection fraction ≤40% and to reduce the incidence of overt heart failure and subsequent hospitalizations for congestive heart failure in these patients.

Diabetic Nephropathy: Captopril tablets are indicated for the treatment of diabetic nephropathy (proteinuria >500 mg/day) in patients with type I insulin-dependent diabetes mellitus and retinopathy. Captopril tablets decreases the rate of progression of renal insufficiency and development of serious adverse clinical outcomes (death or need for renal transplantation or dialysis).

In considering use of captopril tablets, it should be noted that in controlled trials ACE inhibitors have an effect on blood pressure that is less in black patients than in non-blacks. In addition, ACE inhibitors (for which adequate data are available) cause a higher rate of angioedema in black than in non-black patients.

Administration

Take this medication by mouth on an empty stomach (at least 1 hour before meals) as directed by your doctor, usually two to three times a day.

The dosage is based on your medical condition and response to treatment.

Use this medication regularly in order to get the most benefit from it. To help you remember, take it at the same times each day. It is important to continue taking this medication even if you feel well. Most people with high blood pressure do not feel sick.

Contraindications

Captopril tablets are contraindicated in patients who are hypersensitive to this product or any other angiotensin-converting enzyme inhibitor (e.g., a patient who has experienced angioedema during therapy with any other ACE inhibitor).

Precautions

Impaired Renal Function:

Hypertension - Some patients with renal disease, particularly those with severe renal artery stenosis, have developed increases in BUN and serum creatinine after reduction of blood pressure with captopril. Captopril dosage reduction and/or discontinuation of diuretic may be required. For some of these patients, it may not be possible to normalize blood pressure and maintain adequate renal perfusion.

Heart Failure - About 20 percent of patients develop stable elevations of BUN and serum creatinine greater than 20 percent above normal or baseline upon long-term treatment with captopril. Less than 5 percent of patients, generally those with severe preexisting renal disease, required discontinuation of treatment due to progressively increasing creatinine; subsequent improvement probably depends upon the severity of the underlying renal disease.

Hyperkalemia: Elevations in serum potassium have been observed in some patients treated with ACE inhibitors, including captopril. When treated with ACE inhibitors, patients at risk for the development of hyperkalemia include those with: renal insufficiency; diabetes mellitus; and those using concomitant potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes; or other drugs associated with increases in serum potassium in a trial of type I diabetic patients with proteinuria.

Cough: Presumably due to the inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been reported with all ACE inhibitors, always resolving after discontinuation of therapy. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough.

Valvular Stenosis: There is concern, on theoretical grounds, that patients with aortic stenosis might be at particular risk of decreased coronary perfusion when treated with vasodilators because they do not develop as much afterload reduction as others.

Surgery/Anesthesia: In patients undergoing major surgery or during anesthesia with agents that produce hypotension, captopril will block angiotensin II formation secondary to compensatory renin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.

Hemodialysis: Recent clinical observations have shown an association of hypersensitivity-like (anaphylactoid) reactions during hemodialysis with high-flux dialysis membranes (e.g., AN69) in patients receiving ACE inhibitors. In these patients, consideration should be given to using a different type of dialysis membrane or a different class of medication.

Information for Patients

Patients should be advised to immediately report to their physician any signs or symptoms suggesting angioedema (e.g., swelling of face, eyes, lips, tongue, larynx and extremities; difficulty in swallowing or breathing; hoarseness) and to discontinue therapy.

Patients should be told to report promptly any indication of infection (e.g., sore throat, fever), which may be a sign of neutropenia, or of progressive edema which might be related to proteinuria and nephrotic syndrome.

All patients should be cautioned that excessive perspiration and dehydration may lead to an excessive fall in blood pressure because of reduction in fluid volume. Other causes of volume depletion such as vomiting or diarrhea may also lead to a fall in blood pressure; patients should be advised to consult with the physician.

Patients should be advised not to use potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes without consulting their physician

Patients should be warned against interruption or discontinuation of medication unless instructed by the physician.

Heart failure patients on captopril therapy should be cautioned against rapid increases in physical activity.

Patients should be informed that captopril tablets should be taken one hour before meals .

Adverse Reactions

Anaphylactoid reactions.

Cardiovascular: Cardiac arrest, cerebrovascular accident/insufficiency, rhythm disturbances, orthostatic hypotension, syncope.

Dermatologic: Bullous pemphigus, erythema multiforme (including Stevens-Johnson syndrome), exfoliative dermatitis.

Gastrointestinal: Pancreatitis, glossitis, dyspepsia.

Hematologic: Anemia, including aplastic and hemolytic.

Hepatobiliary: Jaundice, hepatitis, including rare cases of necrosis, cholestasis.

Metabolic: Symptomatic hyponatremia.

Musculoskeletal: Myalgia, myasthenia.

Nervous/Psychiatric: Ataxia, confusion, depression, nervousness, somnolence.

Respiratory: Bronchospasm, eosinophilic pneumonitis, rhinitis.

Special Senses: Blurred vision.

Urogenital: Impotence.

As with other ACE inhibitors, a syndrome has been reported which may include: fever, myalgia, arthralgia, interstitial nephritis, vasculitis, rash or other dermatologic manifestations, eosinophilia and an elevated ESR.

Serum Electrolytes:

Hyperkalemia: small increases in serum potassium, especially in patients with renal impairment .

Hyponatremia: Particularly in patients receiving a low sodium diet or concomitant diuretics.

BUN/Serum Creatinine: Transient elevations of BUN or serum creatinine especially in volume or salt depleted patients or those with renovascular hypertension may occur. Rapid reduction of longstanding or markedly elevated blood pressure can result in decreases in the glomerular filtration rate and, in turn, lead to increases in BUN or serum creatinine.

Hematologic: A positive ANA has been reported.

Liver Function Tests: Elevations of liver transaminases, alkaline phosphatase, and serum bilirubin have occurred.

Pregnancy and lactation

pregnancy category: D

Excreted into human milk: Yes

Renal and liver Impairment

Because captopril is excreted primarily by the kidneys, excretion rates are reduced in patients with impaired renal function. These patients will take longer to reach steady-state captopril levels and will reach higher steady-state levels for a given daily dose than patients with normal renal function. Therefore, these patients may respond to smaller or less frequent doses.

Accordingly, for patients with significant renal impairment, initial daily dosage of captopril should be reduced, and smaller increments utilized for titration, which should be quite slow (one- to two-week intervals). After the desired therapeutic effect has been achieved, the dose should be slowly back-titrated to determine the minimal effective dose. When concomitant diuretic therapy is required, a loop diuretic (e.g., furosemide), rather than a thiazide diuretic, is preferred in patients with severe renal impairment.

Hepatic Failure

Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.

Laboratory Tests