No

Angiotensin-Converting Enzyme (ACE) Inhibitors

Treatment of hypertension, either alone or in combination with other antihypertensive agents; treatment of left ventricular dysfunction after myocardial infarction

C/D (2nd and 3rd trimesters)

It is not known whether benazepril is excreted in human milk

Breast-feeding/lactation: Crosses into breast milk. American Academy of Pediatrics considers compatible with breast-feeding.

Hypersensitivity to benazepril or any component; angioedema or serious hypersensitivity related to previous treatment with an ACE inhibitor; bilateral renal artery stenosis; primary hyperaldosteronism; patients with idiopathic or hereditary angioedema; pregnancy (2nd and 3rd trimesters)

Anaphylactic reactions can occur. Angioedema can occur at any time during treatment (especially following first dose). Careful blood pressure monitoring with first dose (hypotension can occur especially in volume depleted patients). Dosage adjustment needed in renal impairment. Use with caution in hypovolemia; collagen vascular diseases; valvular stenosis (particularly aortic stenosis); hyperkalemia; or before, during, or immediately after anesthesia. Avoid rapid dosage escalation which may lead to renal insufficiency. Hypersensitivity reactions may be seen during hemodialysis with high-flux dialysis membranes (eg, AN69). Deterioration in renal function can occur with initiation. Use with caution in unilateral renal artery stenosis and pre-existing renal insufficiency.

1% to 10%:

Cardiovascular: Postural dizziness (1.5%)

Central nervous system: Headache (6.2%), dizziness (3.6%), fatigue (2.4%), somnolence (1.6%)

Endocrine & metabolic: Hyperkalemia (1%), increased uric acid

Gastrointestinal: Nausea (1.3%)

Renal: Increased serum creatinine (2%), worsening of renal function may occur in patients with bilateral renal artery stenosis or hypovolemia

Respiratory: Cough (1.2% to 10%)

<1% (Limited to important or life-threatening symptoms): Hypotension, postural hypotension (0.3%), syncope, angina, palpitation, peripheral edema, angioedema, laryngeal edema, shock, Stevens-Johnson syndrome, pemphigus, hypersensitivity, dermatitis, rash, pruritus, photosensitivity, flushing, pancreatitis, constipation, gastritis, vomiting, melena, thrombocytopenia, hemolytic anemia, anxiety, decreased libido, hypertonia, insomnia, nervousness, paresthesia, asthma, bronchitis, dyspnea, sinusitis, urinary tract infection, arthritis, impotence, alopecia, arthralgia, myalgia, asthenia, sweating, gynecomastia

Eosinophilic pneumonitis, neutropenia, anaphylaxis, renal insufficiency and renal failure have been reported with other ACE inhibitors. In addition, a syndrome including fever, myalgia, arthralgia, interstitial nephritis, vasculitis, rash, eosinophilia, and elevated ESR has been reported to be associated with ACE inhibitors.

Mild hypotension has been the only toxic effect seen with acute overdose. Bradycardia may also occur; hyperkalemia occurs even with therapeutic doses, especially in patients with renal insufficiency and those taking NSAIDs.

Following initiation of essential overdose management, toxic symptom treatment and supportive treatment should be initiated. Hypotension usually responds to I.V. fluids or Trendelenburg positioning.

Alpha₁ blockers: Hypotensive effect increased.

Aspirin and NSAIDs may decrease ACE inhibitor efficacy.

Diuretics: Hypovolemia due to diuretics may precipitate acute hypotensive events or acute renal failure.

Insulin: Risk of hypoglycemia may be increased.

Lithium: Risk of lithium toxicity may be increased; monitor lithium levels.

Potassium-sparing diuretics or potassium supplements (amiloride, potassium, spironolactone, triamterene): Increased risk of hyperkalemia.

Trimethoprim (high dose) may increase the risk of hyperkalemia.

Competitive inhibition of angiotensin I being converted to angiotensin II, a potent vasoconstrictor, through the angiotensin I-converting enzyme (ACE) activity, with resultant lower levels of angiotensin II which causes an increase in plasma renin activity and a reduction in aldosterone secretion

Reduction in plasma angiotensin-converting enzyme activity: Oral:

Peak effect: 1-2 hours after administration of 2-20 mg dose

Duration of action: >90% inhibition for 24 hours has been observed after 5-20 mg dose

Reduction in blood pressure:

Peak effect after single oral dose: 2-6 hours

Maximum response With continuous therapy: 2 weeks

Absorption: Rapid (37% of each oral dose); food does not alter significantly; metabolite (benazeprilat) itself unsuitable for oral administration due to poor absorption

Distribution: V_d: ~8.7 L

Metabolism: Rapid and extensive in the liver to its active metabolite, benazeprilat, via enzymatic hydrolysis; undergoes significant first-pass metabolism and is completely eliminated from plasma in 4 hours

Half-life:

Parent drug: 0.6 hour

Metabolite elimination: 22 hours (from 24 hours after dosing onward)

Metabolite: 1.5-2 hours after fasting or 2-4 hours after a meal

Time to peak: 1-1.5 hours (unchanged parent drug)

Elimination: Nonrenal clearance (ie, biliary, metabolic) appears to contribute to the elimination of benazeprilat (11% to 12%), particularly in patients with severe renal impairment; hepatic clearance is the main elimination route of unchanged benazepril

Dialysis: ~6% of metabolite was removed by 4 hours of dialysis following 10 mg of benazepril administered 2 hours prior to procedure; parent compound was not found in the dialysate

Adults: Oral: Initial: 10 mg/day in patients not receiving a diuretic; 20-40 mg/day as a single dose or 2 divided doses; base dosage adjustments on peak (2-6 hours after dosing) and trough responses.

Hemodialysis: Moderately dialyzable (20% to 50%); administer dose postdialysis or administer 25% to 35% supplemental dose.

Peritoneal dialysis: Supplemental dose is not necessary.

ACE inhibitors decrease morbidity and mortality in patients with asymptomatic and symptomatic left ventricular dysfunction. In this situation, they decrease hospitalizations for, and retard progression to, congestive heart failure. ACE inhibitors are also indicated in patients postmyocardial infarction in whom left ventricular ejection fraction is <40%. When used in patients with heart failure, the target dose or maximum tolerated dose, should be achieved, if possible. Lower daily doses of ACE inhibitors have not demonstrated the same cardioprotective effects. ACE inhibitors have renal protective effects in patients with proteinuria and possibly cardioprotective effects in high-risk patients.

May cause drowsiness

May decrease lithium clearance resulting in an increase in serum lithium levels and potential lithium toxicity; monitor serum lithium levels

No information available to require special precautions

No effects or complications reported

Take exactly as directed; do not discontinue without consulting prescriber. Take first dose at bedtime. Take all doses on an empty stomach (30 minutes before or 2 hours after meals). This drug does not eliminate need for diet or exercise regimen as recommended by prescriber. May cause dizziness, fainting, lightheadedness (use caution when driving or engaging in tasks that require alertness until response to drug is known); postural hypotension (use caution when rising from lying or sitting position or climbing stairs); nausea, vomiting, abdominal pain, dry mouth, or transient loss of appetite (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help) - report if these persist. Report mouth sores; fever or chills; swelling of extremities, face, mouth, or tongue; difficulty in breathing or unusual cough; or other persistent adverse reactions. Pregnancy precautions: Do not get pregnant while taking this medication; use appropriate barrier contraceptive measures.

Watch for hypotensive effect within 1-3 hours of first dose or new higher dose; discontinue therapy immediately if angioedema of the face, extremities, lips, tongue, or glottis occurs

Tablet, as hydrochloride: 5 mg, 10 mg, 20 mg, 40 mg

Herings RM, deBoer A, Stricker BH, et al, "Hypoglycaemia Associated With Use of Inhibitors of Angiotensin Converting Enzyme," Lancet, 1995, 345(8959):1195-8.

Konstam MA, Drakup K, Baker DW, et al, "Heart Failure: Evaluation and Care of Patients With Left Ventricular Systolic Dysfunction," Clinical Practice Guideline No 11, Rockville, MD: Agency for Health Care Policy and Research, Public Health Service, U.S. Department of Health and Human Services, 1994.

McAreavey D and Robertson JIS, "Angiotensin Converting Enzyme Inhibitors and Moderate Hypertension," Drugs, 1990, 40(3):326-45.

Waeber G, Fasanella d'Amore TF, Nussberger J, et al, "Effect on Blood Pressure and the Renin-Angiotensin System of Repeated Doses of the Converting Enzyme Inhibitor CGS 14824 A," Eur J Clin Pharmacol, 1987, 31(6):643-6.

Williams JF, Bristow MR, Fowler MB, et al, "Guidelines for the Evaluation and Management of Heart Failure: Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Evaluation and Management of Heart Failure)," J Am Coll Cardiol, 1995, 26:1376-8.

Woo OF, "Captopril and Related Drugs," Poisoning and Drug Overdose, 2nd ed, Olson KR, ed, East Norwalk, CT: Appleton and Lange, 1994, 117-8.