Captopril

Hypotension ó 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 (captopril tablets, USP) 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 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. If resumed during captopril therapy, such agents should be administered cautiously, and perhaps at lower dosage.

Agents Causing Renin Release

Captoprilís 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.

Inhibitors Of Endogenous Prostaglandin Synthesis

It has been reported that indomethacin may reduce the antihypertensive effect of captopril, especially in cases of low renin hypertension. Other nonsteroidal anti-inflammatory agents (e.g., aspirin) may also have this effect.

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 coad-ministered 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 cap-topril 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 allop-urinol were administered concomitantly for 6 days.

Drug/Laboratory Test Interaction

Captopril may cause a false-positive urine test for acetone.