Captopril

Hypertension Captopril tablets are indicated for the treatment of hypertension. In using captopril tablets, consideration should be given to the risk of neutropenia/agranulocytosis. 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. Captopril tablets are 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.

The mechanism of action of captopril tablets have 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. However, there is no consistent correlation between renin levels and response to the drug. Renin, an enzyme synthesized by the kidneys, is released into the circulation where it acts on a plasma globulin substrate to produce angiotensin I, a relatively inactive decapeptide. Angiotensin I is then converted by angiotensin converting enzyme (ACE) to angiotensin II, a potent endogenous vasoconstrictor substance. Angiotensin II also stimulates aldosterone secretion from the adrenal cortex, thereby contributing to sodium and fluid retention.

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 captopril tablets. The initial dose of captopril tablets 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 captopril tablets are used alone. The dose of captopril tablets in hypertension usually does not exceed 50 mg t.i.d.

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). Do not co-administer aliskiren with captopril tablets in patients with diabetes. Captopril tablets are contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer captopril tablets within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor.

Boxed warning (fetal toxicity): When pregnancy is detected, discontinue captopril tablets as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. See WARNINGS: Fetal Toxicity Anaphylactoid and Possibly Related Reactions Presumably because angiotensin-converting enzyme inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors (including captopril tablets) may be subject to a variety of adverse reactions, some of them serious. Head and Neck Angioedema Angioedema involving the extremities, face, lips, mucous membranes, tongue, glottis or larynx has been seen in patients treated with ACE inhibitors, including captopril. If angioedema involves the tongue, glottis or larynx, airway obstruction may occur and be fatal.

Reported incidences are based on clinical trials involving approximately 7000 patients. Renal About one of 100 patients developed proteinuria. Each of the following has been reported in approximately 1 to 2 of 1000 patients and are of uncertain relationship to drug use: renal insufficiency, renal failure, nephrotic syndrome, polyuria, oliguria, and urinary frequency. Hematologic Neutropenia/agranulocytosis has occurred. Cases of anemia, thrombocytopenia, and pancytopenia have been reported. Dermatologic Rash, often with pruritus, and sometimes with fever, arthralgia, and eosinophilia, occurred in about 4 to 7 (depending on renal status and dose) of 100 patients, usually during the first four weeks of therapy. It is usually maculopapular, and rarely urticarial.

Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on captopril tablets and other agents that block the RAS. Do not coadminister aliskiren with captopril tablets in patients with diabetes. Avoid use of aliskiren with captopril tablets in patients with renal impairment (GFR < 60 ml/min).

Store at 20° to 25°C (68° to 77°F). Protect from moisture.