CAPTOPRIL
DESCRIPTION
CAPOTEN (captopril tablets) is a specific competitive inhibitor of angiotensin I-converting enzyme (ACE), the enzyme responsible for the conversion of angiotensin I to angiotensin II.
CAPOTEN is available in potencies of 12.5 mg, 25 mg, 50 mg, and 100 mg as scored tablets for oral administration. Inactive ingredients: microcrystalline cellulose, corn starch, lactose, and stearic acid.
CLINICAL PHARMACOLOGY
Mechanism of Action
The mechanism of action of CAPOTEN has not yet been fully elucidated. Its beneficial effects in hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin-aldosterone system. CAPOTEN prevents the conversion of angiotensin I to angiotensin II by inhibition of ACE, a peptidyldipeptide carboxyhydrolase.
Pharmacokinetics
After oral administration of therapeutic doses of CAPOTEN, rapid absorption occurs with peak blood levels at about one hour. The presence of food in the gastrointestinal tract reduces absorption by about 30 to 40 per cent; captopril therefore should be given one hour before meals.
Pharmacodynamics
Administration of CAPOTEN results in a reduction of peripheral arterial resistance in hypertensive patients with either no change, or an increase in cardiac output. There is an increase in renal blood flow following administration of CAPOTEN and glomerular filtration rate is usually unchanged.
INDICATIONS
Hypertension: CAPOTEN is indicated for the treatment of hypertension.
CAPOTEN (captopril tablets) 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.
CAPOTEN 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: CAPOTEN is 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: CAPOTEN is 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: CAPOTEN is indicated for the treatment of diabetic nephropathy (proteinuria 500 mg/day) in patients with type I insulin-dependent diabetes mellitus and retinopathy. CAPOTEN decreases the rate of progression of renal insufficiency and development of serious adverse clinical outcomes (death or need for renal transplantation or dialysis).
DOSAGE AND ADMINISTRATION
CAPOTEN (captopril tablets) should be taken one hour before meals. Dosage must be individualized.
Hypertension: Initiation of therapy requires consideration of recent antihypertensive drug treatment, the extent of blood pressure elevation, salt restriction, and other clinical circumstances. If possible, discontinue the patient’s previous antihypertensive drug regimen for one week before starting CAPOTEN.
The initial dose of CAPOTEN is 25 mg b.i.d. or t.i.d. If satisfactory reduction of blood pressure has not been achieved after one or two weeks, the dose may be increased to 50 mg b.i.d. or t.i.d. Concomitant sodium restriction may be beneficial when CAPOTEN is used alone.
The dose of CAPOTEN in hypertension usually does not exceed 50 mg t.i.d. If further blood pressure reduction is required, the dose of CAPOTEN may be increased to 100 mg b.i.d. or t.i.d. and then, if necessary, to 150 mg b.i.d. or t.i.d. (while continuing the diuretic). The usual dose range is 25 to 150 mg b.i.d. or t.i.d. A maximum daily dose of 450 mg CAPOTEN should not be exceeded.
Heart Failure: Initiation of therapy requires consideration of recent diuretic therapy and the possibility of severe salt/volume depletion. In patients with either normal or low blood pressure, who have been vigorously treated with diuretics and who may be hyponatremic and/or hypovolemic, a starting dose of 6.25 or 12.5 mg t.i.d. may minimize the magnitude or duration of the hypotensive effect.
For most patients the usual initial daily dosage is 25 mg t.i.d. After a dose of 50 mg t.i.d. is reached, further increases in dosage should be delayed, where possible, for at least two weeks to determine if a satisfactory response occurs. Most patients studied have had a satisfactory clinical improvement at 50 or 100 mg t.i.d. A maximum daily dose of 450 mg of CAPOTEN should not be exceeded.
HOW SUPPLIED
12.5 mg tablets in bottles of 100 and 1000, 25 mg tablets in bottles of 100 and 1000, 50 mg tablets in bottles of 100 and 1000, and 100 mg tablets in bottles of 100. Unimatic ® unit-dose packs containing 100 tablets are also available for each potency: 12.5 mg, 25 mg, 50 mg.
Storage
Do not store above 86° F. Keep bottles tightly closed (protect from moisture).
CONTRAINDICATIONS
CAPOTEN is 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
General
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.
Heart Failure: About 20 per cent of patients develop stable elevations of BUN and serum creatinine greater than 20 per cent above normal or baseline upon long-term treatment with captopril.
Hyperkalemia: Elevations in serum potassium have been observed in some patients treated with ACE inhibitors, including captopril.
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.
Pregnancy Categories C (first trimester) and D (second and third trimesters)
ADVERSE REACTIONS
General: Asthenia, gynecomastia.
Cardiovascular: Cardiac arrest, cerebrovascular accident/insufficiency, rhythm disturbances, orthostatic hypotension, syncope.
Dermatologic: Bullous pemphigus, erythema multiforme (including StevensJohnson 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.
DRUG INTERACTIONS
Hypotension— Patients on Diuretic Therapy: Patients on diuretics and especially those in whom diuretic therapy was recently instituted, as well as those on severe dietary salt restriction or dialysis, may occasionally experience a precipitous reduction of blood pressure usually within the first hour after receiving the initial dose of captopril.
OVERDOSAGE
Correction of hypotension would be of primary concern. Volume expansion with an intravenous infusion of normal saline is the treatment of choice for restoration of blood pressure.
PATIENT INFORMATION
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.
