Captopril and hydrochlorothiazide

Drug Interactions: Captopril : 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 restrictions 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 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 : 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. Gold : Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including captopril and hydrochlorothiazide tablets.

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 non-steroidal 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 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 (see PRECAUTIONS: Drug Interactions: Hydrochlorothiazide: Lithium ).

Hydrochlorothiazide : When administered concurrently the following drugs may interact with thiazide diuretics: Alcohol, Barbiturates, or Narcotics : potentiation of orthostatic hypotension may occur. Amphotericin B, Corticosteroids, or Corticotropin (ACTH) : may intensify electrolyte imbalance, particularly hypokalemia. Monitor potassium levels; use potassium replacements if necessary. Anticoagulants (Oral) : dosage adjustments of anticoagulant medication may be necessary since hydrochlorothiazide may decrease their effects. Antigout Medications : dosage adjustments of antigout medication may be necessary since hydrochlorothiazide may raise the level of blood uric acid.

Other Antihypertensive Medications (e.g., Ganglionic or Peripheral Adrenergic Blocking Agents) : dosage adjustments may be necessary since hydrochlorothiazide may potentiate their effects. Antidiabetic Drugs (Oral Agents and Insulin): since thiazides may elevate blood glucose levels, dosage adjustments of antidiabetic agents may be necessary. Calcium Salts : Increased serum calcium levels due to decreased excretion may occur. If calcium must be prescribed, monitor serum calcium levels and adjust calcium dosage accordingly. Cardiac Glycosides : enhanced possibility of digitalis toxicity associated with hypokalemia. Monitor potassium levels (see PRECAUTIONS: Drug Interactions: Captopril ).

Cholestyramine and Colestipol Resins : Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85 and 43 percent, respectively. Diazoxide : enhanced hyperglycemic, hyperuricemic, and antihypertensive effects. Be cognizant of possible interaction; monitor blood glucose and serum uric acid levels. Lithium : diuretic agents reduce the renal clearance of lithium and increase the risk of lithium toxicity.

These drugs should be coadministered with caution and frequent monitoring of serum lithium levels is recommended (see PRECAUTIONS: Drug Interactions: Captopril: Lithium ). MAO Inhibitors : dosage adjustments of one or both agents may be necessary since hypotensive effects are enhanced. Nondepolarizing Muscle Relaxants, Preanesthetics and Anesthetics Used in Surgery (e.g., Tubocurarine Chloride and Gallamine Triethiodide) : effects of these agents may be potentiated; dosage adjustments may be required. Monitor and correct any fluid and electrolyte imbalances prior to surgery if feasible.

Non-steroidal Anti-inflammatory Agents : in some patients, the administration of a non-steroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effect of loop, potassium-sparing or thiazide diuretics. Therefore, when hydrochlorothiazide and non-steroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained. Methenamine : possible decreased effectiveness due to alkalinization of the urine. Pressor Amines (e.g., Norepinephrine) : decreased arterial responsiveness, but not sufficient to preclude effectiveness of the pressor agent for therapeutic use.

Use caution in patients taking both medications who undergo surgery. Administer preanesthetic and anesthetic agents in reduced dosage, and if possible, discontinue hydrochlorothiazide therapy one week prior to surgery. Probenecid or Sulfinpyrazone : increased dosage of these agents may be necessary since hydrochlorothiazide may have hyperuricemic effects.

Pregnancy Female patients of childbearing age should be told about the consequences of second- and third-trimester exposure to ACE inhibitors, and they should also be told that these consequences do not appear to have resulted from intrauterine ACE-inhibitor exposure that has been limited to the first trimester. These patients should be asked to report pregnancies to their physicians as soon as possible.

Nursing Mothers Both captopril and hydrochlorothiazide are excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from both drugs, a decision should be made whether to discontinue nursing or to discontinue therapy taking into account the importance of captopril and hydrochlorothiazide to the mother. (See PRECAUTIONS: Pediatric Use. )