Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.

BENAZEPRIL HCL

Chemistry - Benazepril HCl, an angiotensin converting enzyme inhibitor, occurs as white to off-white crystalline powder. It is soluble in water and ethanol. Benazepril does not contain a sulfhydryl group in its structure.

Storage, Stability, Compatibility

Benazepril (and combination products) tablets should be stored at temperatures less than 86°F (30°C) and protected from moisture. They should be dispensed in tight containers.

Pharmacology - BENAZEPRIL HCL

Benazepril is a prodrug, and has little pharmacologic activity of its own. Afterbeing hydrolyzed in the liver to benazeprilat, the drug inhibits the conversion of angiotensin I toangiotensin II by inhibiting angiotensin-converting enzyme (ACE). Angiotensin II acts both as avasoconstrictor and stimulates production of aldosterone in the adrenal cortex. By blocking angiotensin II formation, ACE inhibitors generally reduce blood pressure in hypertensive patients and vascular resistance in patients with congestive heart failure.
Like enalapril and lisinopril, but not captopril, benazepril does not contain a sulfhydryl group.
ACE inhibitors containing sulfhydryl groups (e.g., captopril) may have a greater tendency towardscausing immune-mediated reactions.
Uses, Indications - Benazepril may be useful as a vasodilator in the treatment of heart failure andas a an antihypertensive agent. It may also be of benefit in treating the effects associated withvalvular heart disease and left to right shunts. ACE inhibitors may also be of benefit in the adjunctive treatment of chronic renal failure and for protein losing nephropathies.

Pharmacokinetics - BENAZEPRIL HCL

In healthy dogs, benazepril after oral dosing is rapidly absorbed and converted into the active metabolite benazeprilat with peak levels of benazeprilat occurring approximately 75 minutes after dosing. The elimination half-life of benazeprilat is approximately 3.5 hoursin healthy dogs.
In humans, approximately 37% of an oral dose is absorbed after oral dosing and food apparentlydoes not affect the extent of absorption. About 95% of the parent drug and active metabolite arebound to serum proteins. Benazepril and benazeprilat are primarily eliminated via the kidneys andmild to moderate renal dysfunction apparently does not significantly alter elimination as biliaryclearance may compensate somewhat for reductions in renal clearances. Hepatic dysfunction or agedoes not appreciably alter benazeprilat levels.
Contraindications/Precautions /Reproductive Safety - Benazepril is contraindicated in patientswho have demonstrated hypersensitivity to the ACE inhibitors.
ACE inhibitors should be used with caution in patients with hyponatremia or sodium depletion, coronary or cerebrovascular insufficiency, preexisting hematologic abnormalities or a collagenvascular disease (e.g., SLE). Patients with severe CHF should be monitored very closely uponinitiation of therapy.
Benazepril apparently crosses the placenta. High doses of ACE inhibitors in rodents have causeddecreased fetal weights and increases in fetal and maternal death rates; no teratogenic effects havebeen reported to date, but use during pregnancy should occur only when the potential benefits oftherapy outweigh the risks to the offspring.
Minimal amounts of benazepril and benazeprilat enter maternal milk and do not apparently conveymuch risk to nursing offspring.

Adverse Effects, Warnings

Benazepril's adverse effect profile in dogs is not well described, butother ACE inhibitors effects in dogs usually center around GI distress (anorexia, vomiting, diarrhea). Potentially, hypotension, renal dysfunction and hyperkalemia could occur. Because itlacks a sulfhydryl group (unlike captopril), there is less likelihood that immune-mediated reactionswill occur, but rashes, neutropenia and agranulocytosis have been reported in humans.
Overdosage - In overdose situations, the primary concern is hypotension; supportive treatment withvolume expansion with normal saline is recommended to correct blood pressure. Because of thedrug's long duration of action, prolonged monitoring and treatment may be required. Recentmassive overdoses should be managed using gut emptying protocols as appropriate.

Drug Interactions

Concomitant diuretics or other vasodilators may cause hypotension if usedwith benazepril; titrate dosages carefully. Some clinicians recommend reducing furosemide doses(by 25 - 50%) when adding enalapril to therapy in CHF.
Hyperkalemia may develop if given with potassium or potassium sparing diuretics (e.g., spironolactone).
Non-steroidal anti-inflammatory agents (NSAIDs) may reduce the clinical efficacy of ACEinhibitors when they are being used as an antihypertensive agent. Indomethacin appears to be mostlikely to evoke this problem.Laboratory Considerations - When using iodohippurate sodium I123/I134 or Technetium
Tc99 pententate renal imaging in patients with renal artery stenosis, ACE inhibitors may cause areversible decrease in localization and excretion of these agents in the affected kidney which maylead to confusion in test interpretation.
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