Captopril

Drug Interactions 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). Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including captopril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving captopril and NSAID therapy. The antihypertensive effect of ACE inhibitors, including captopril, may be attenuated by NSAIDs. 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. The possibility of hypotensive effects with captopril can be minimized by either discontinuing the diuretic or increasing the salt intake approximately one week prior to initiation of treatment with captopril tablets or initiating therapy with small doses (6.25 or 12.5 mg). Alternatively, provide medical supervision for at least one hour after the initial dose. If hypotension occurs, the patient should be placed in a supine position and, if necessary, receive an intravenous infusion of normal saline. This transient hypotensive response is not a contraindication to further doses which can be given without difficulty once the blood pressure has increased after volume expansion. Agents Having Vasodilator Activity Data on the effect of concomitant use of other vasodilators in patients receiving captopril tablets for heart failure are not available; therefore, nitroglycerin or other nitrates (as used for management of angina) or other drugs having vasodilator activity should, if possible, be discontinued before starting captopril tablets. If resumed during captopril tablets therapy, such agents should be administered cautiously, and perhaps at lower dosage. Agents Causing Renin Release Captopril’s effect will be augmented by antihypertensive agents that cause renin release. For example, diuretics (e.g., thiazides) may activate the renin-angiotensin-aldosterone system. Agents Affecting Sympathetic Activity The sympathetic nervous system may be especially important in supporting blood pressure in patients receiving captopril alone or with diuretics. Therefore, agents affecting sympathetic activity (e.g., ganglionic blocking agents or adrenergic neuron blocking agents) should be used with caution. Beta-adrenergic blocking drugs add some further antihypertensive effect to captopril, but the overall response is less than additive. Agents Increasing Serum Potassium Since captopril decreases aldosterone production, elevation of serum potassium may occur. Potassium-sparing diuretics such as spironolactone, triamterene, or amiloride, or potassium supplements should be given only for documented hypokalemia, and then with caution, since they may lead to a significant increase of serum potassium. Salt substitutes containing potassium should also be used with caution. Lithium Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving concomitant lithium and ACE inhibitor therapy. These drugs should be coadministered with caution and frequent monitoring of serum lithium levels is recommended. If a diuretic is also used, it may increase the risk of lithium toxicity. Cardiac Glycosides In a study of young healthy male subjects no evidence of a direct pharmacokinetic captopril-digoxin interaction could be found. Loop Diuretics Furosemide administered concurrently with captopril does not alter the pharmacokinetics of captopril in renally impaired hypertensive patients. Allopurinol In a study of healthy male volunteers no significant pharmacokinetic interaction occurred when captopril and allopurinol were administered concomitantly for 6 days.

Indicated for "treatment of hypertension," alone or with other agents; "treatment of congestive heart failure usually in combination with diuretics and digitalis"; to "improve survival following myocardial infarction" in clinically stable patients with left ventricular dysfunction; and "treatment of diabetic nephropathy (proteinuria greater than 500 mg/day)" in type I insulin-dependent diabetics with retinopathy.

DOSAGE AND ADMINISTRATION Captopril tablets, USP 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. The initial dose of captopril tablets, USP is 25 mg twice daily or three times a day. If satisfactory reduction of blood pressure has not been achieved after one week or two weeks, the dose may be increased to 50 mg twice daily or three times a day. Concomitant sodium restriction may be beneficial when captopril is used alone. The dose of captopril tablets, USP in hypertension usually does not exceed 50 mg three times a day. Therefore, if the blood pressure has not been satisfactorily controlled after one week to two weeks at this dose, (and the patient is not already receiving a diuretic), a modest dose of a thiazide-type diuretic (e.g., hydrochlorothiazide, 25 mg daily), should be added. The diuretic dose may be increased at one-week to two-week intervals until its highest usual antihypertensive dose is reached. If captopril is being started in a patient already receiving a diuretic, captopril therapy should be initiated under close medical supervision (see WARNINGS and PRECAUTIONS: Drug Interactions regarding hypotension), with dosage and titration of captopril as noted above. If further blood pressure reduction is required, the dose of captopril tablets, USP may be increased to 100 mg twice daily or three times a day and then, if necessary, to 150 mg twice daily or three times a day (while continuing the diuretic). The usual dose range is 25 mg to 150 mg twice daily or three times a day. A maximum daily dose of 450 mg captopril tablets, USP should not be exceeded. For patients with severe hypertension (e.g., accelerated or malignant hypertension), when temporary discontinuation of current antihypertensive therapy is not practical or desirable, or when prompt titration to more normotensive blood pressure levels is indicated, diuretic should be continued but other current antihypertensive medication stopped and captopril tablets, USP dosage promptly initiated at 25 mg twice daily or three times a day, under close medical supervision. When necessitated by the patient’s clinical condition, the daily dose of captopril tablets, USP may be increased every 24 hours or less under continuous medical supervision until a satisfactory blood pressure response is obtained or the maximum dose of captopril is reached. In this regimen, addition of a more potent diuretic, e.g., furosemide, may also be indicated. Beta-blockers may also be used in conjunction with captopril therapy (see PRECAUTIONS: Drug Interactions ), but the effects of the two drugs are less than additive. 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 mg or 12.5 mg three times a day may minimize the magnitude or duration of the hypotensive effect (see WARNINGS: Hypotension ); for these patients, titration to the usual daily dosage can then occur within the next several days. For most patients the usual initial daily dosage is 25 mg three times a day. After a dose of 50 mg three times a day 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 mg or 100 mg three times a day. A maximum daily dose of 450 mg of captopril tablets should not be exceeded. Captopril should generally be used in conjunction with a diuretic and digitalis. Captopril therapy must be initiated under very close medical supervision. Left Ventricular Dysfunction After Myocardial Infarction: The recommended dose for long-term use in patients following a myocardial infarction is a target maintenance dose of 50 mg three times a day. Therapy may be initiated as early as three days following a myocardial infarction. After a single dose of 6.25 mg, captopril therapy should be initiated at 12.5 mg three times a day. Captopril tablets, USP should then be increased to 25 mg three times a day during the next several days and to a target dose of 50 mg three times a day over the next several weeks as tolerated (see CLINICAL PHARMACOLOGY ). Captopril may be used in patients treated with other post-myocardial infarction therapies, e.g., thrombolytics, aspirin, beta blockers. Diabetic Nephropathy: The recommended dose of captopril tablets, USP for long term use to treat diabetic nephropathy is 25 mg three times a day. Other antihypertensives such as diuretics, beta blockers, centrally acting agents or vasodilators may be used in conjunction with captopril if additional therapy is required to further lower blood pressure. Dosage Adjustment in Renal 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-week 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. (See WARNINGS: Anaphylactoid reactions during membrane exposure and PRECAUTIONS: Hemodialysis . )

Common reactions include rash (in "4 to 7 of 100 patients"), taste disturbance ("2 to 4 of 100 patients developed diminution or loss of taste"), cough ("0.5 to 2%"), and hypotension. Serious reactions include neutropenia (about half of neutropenic patients developed infections), angioedema ("approximately one in 1,000 patients"), anaphylactoid reactions during hemodialysis, and rare hepatic failure beginning as cholestatic jaundice and progressing to fulminant hepatic necrosis.