Benazepril Hydrochloride and Hydrochlorothiazide (Page 4 of 6)

Surgery/Anesthesia

In patients undergoing surgery or during anesthesia with agents that produce hypotension, benazepril will block the angiotensin II formation that could otherwise occur secondary to compensatory renin release. Hypotension that occurs as a result of this mechanism can be corrected by volume expansion.

Information for Patients

Angioedema

Angioedema, including laryngeal edema, can occur at any time with treatment with ACE inhibitors. A patient receiving benazepril hydrochloride and hydrochlorothiazide should be told to report immediately any signs or symptoms suggesting angioedema (swelling of face, eyes, lips, or tongue, or difficulty in breathing) and to take no more drugs until after consulting with the prescribing physician.

Pregnancy

Female patients of childbearing age should be told about the consequences of exposure to benazepril hydrochloride and hydrochlorothiazide during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physicians as soon as possible.

Symptomatic Hypotension

A patient receiving benazepril hydrochloride and hydrochlorothiazide should be cautioned that lightheadedness can occur, especially during the first days of therapy, and that it should be reported to the prescribing physician. The patient should be told that if syncope occurs, benazepril hydrochloride and hydrochlorothiazide should be discontinued until the physician has been consulted.

All patients should be cautioned that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure, with the same consequences of lightheadedness and possible syncope.

Hyperkalemia

A patient receiving benazepril hydrochloride and hydrochlorothiazide should be told not to use potassium supplements or salt substitutes containing potassium without consulting the prescribing physician.

Neutropenia

Patients should be told to promptly report any indication of infection (e.g., sore throat, fever), which could be a sign of neutropenia.

Non-melanoma Skin Cancer

Instruct patients taking hydrochlorothiazide to protect skin from the sun and undergo regular skin cancer screening.

Laboratory Tests

The hydrochlorothiazide component of benazepril hydrochloride and hydrochlorothiazide may decrease serum PBI levels without signs of thyroid disturbance.

Therapy with benazepril hydrochloride and hydrochlorothiazide should be interrupted for a few days before carrying out tests of parathyroid function.

Drug Interactions

Neprilysin Inhibitors

Patients taking concomitant neprilysin inhibitors, e.g., sacubitril may be at increased risk for angioedema.

Interactions Common for Both Benazepril and Hydrochlorothiazide

Potassium Supplements and Potassium-Sparing Diuretics

Concomitant use with benazepril hydrochloride and hydrochlorothiazide may effect potassium levels. Monitor potassium periodically.

mTOR (mammalian target of rapamycin) inhibitors

Patients receiving coadministration of ACE inhibitor and mTOR inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema (see WARNINGS).

Lithium

Renal clearance of lithium is reduced by thiazides and increase the risk of lithium toxicity. Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving ACE inhibitors during therapy with lithium. Monitor lithium levels when used concomitantly with benazepril hydrochloride and hydrochlorothiazide.

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 hypertension, 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 benazepril hydrochloride and hydrochlorothiazide and other agents that affect the RAS.

Do not coadminister aliskiren with benazepril hydrochloride and hydrochlorothiazide in patients with diabetes. Avoid use of aliskiren with benazepril hydrochloride and hydrochlorothiazide in patients with renal impairment (GFR ˂60 mL/min).

NSAIDs and Cox-2 Selective Agents

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 benazepril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving benazepril and NSAID therapy.

The antihypertensive effect of benazepril and hydrochlorothiazide may be attenuated by NSAIDs.

Benazepril

Benazepril has been used concomitantly with beta-adrenergic-blocking agents, calcium-blocking agents, cimetidine, diuretics, digoxin, hydralazine, and naproxen without evidence of clinically important adverse interactions. Other ACE inhibitors have had less than additive effects with beta-adrenergic blockers, presumably because drugs of both classes lower blood pressure by inhibiting parts of the renin-angiotensin system.

Interaction studies with warfarin and acenocoumarol have failed to identify any clinically important effects of benazepril on the serum concentrations or clinical effects of these anticoagulants.

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.

Hydrochlorothiazide

Ion exchange resins

Stagger the dosage of hydrochlorothiazide and ion exchange resins such that hydrochlorothiazide is administered at least 4 hours before or 4 to 6 hours after the administration of 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%, respectively.

Digitalis Glycosides

Thiazide-induced hypokalemia or hypomagnesemia may predispose the patients to digoxin toxicity.

Skeletal Muscle Relaxants

Possible increased responsiveness to muscle relaxants such as curare derivatives.

Antidiabetic Agents

Dosage adjustment of antidiabetic drug may be required.

Antineoplastic Agents (e.g., cyclophosphamide, methotrexate)

Concomitant use of thiazide diuretics may reduce renal excretion of cytotoxic agents and enhance their myelosuppressive effects.

Drugs that Alter Gastrointestinal Motility

The bioavailability of thiazide-type diuretics may be increased by anticholinergic agents (e.g., atropine, biperiden), apparently due to a decrease in gastrointestinal motility and the stomach emptying rate. Conversely, pro-kinetic drugs may decrease the bioavailability of thiazide diuretics.

Cyclosporin

Concomitant treatment with diuretics may increase the risk of hyperuricaemia and gout-type complications.

Alcohol, Barbiturates or Narcotics

Concomitant administration of thiazide diuretics with alcohol, barbiturates, or narcotics may potentiate orthostatic hypotension.

Pressor Amines

Hydrochlorothiazide may reduce the response to pressor amines such as noradrenaline but the clinical significance of this effect is not sufficient to preclude their use.