Benazepril Hydrochloride

Trade Names:Lotensin- Tablets 5 mg- Tablets 10 mg- Tablets 20 mg- Tablets 40 mg

Pharmacology

Competitively inhibits angiotensin-converting enzyme (ACE), resulting in decreased conversion of angiotensin I to angiotensin II, a potent vasoconstrictor that stimulates aldosterone secretion. Results in decreased vasopressor activity and decreased aldosterone secretion.

Pharmacokinetics

Absorption

T _max is 0.5 to 1 h (benazepril), 1 to 2 h (benazeprilat) in fasting state, and 2 to 4 h (benazeprilat) in nonfasting state. Up to 37% absorbed.

Distribution

Protein binding is about 96.7% (benazepril) and about 95.3% (benazeprilat).

Metabolism

Converted to benazeprilat (active) by cleavage of ester group (primarily in liver). Also metabolized to glucuronide conjugates.

Elimination

Benazepril (trace amounts), benazeprilat (about 20%), benazepril glucuronide (4%), benazeprilat glucuronide (8%).

About 11% to 12% (benazeprilat).

Onset

Within 1 h.

Peak

2 to 4 h.

Duration

24 h.

Special Populations

In those with Ccr up to 30 mL/min, peak benzaprilat levels and initial t _½ increase and time to steady state may be delayed.

Indications and Usage

Treatment of hypertension.

Contraindications

Hypersensitivity to ACE inhibitors.

Dosage and Administration

PO 10 mg/day for patients not receiving a diuretic. In patients taking diuretics that cannot be discontinued, give initial dose of 5 mg. Administer without regard to meals or with food if GI upset occurs.

PO 20 to 40 mg/day as single dose or in 2 divided doses; doses up to 80 mg have been used.

PO 0.2 mg/kg/day.

PO 0.2 to 0.6 mg/kg as single dose; doses above 0.6 mg/kg (or more than 40 mg) have not been studied.

Initial dose is 5 mg/day for patients with Ccr less than 30 mL/min. Dosage may be titrated upward until BP is controlled or to a total max dose of 40 mg/day.

General Advice

For patient who cannot swallow tablets or whose calculated dose (mg/kg) does not correspond to available tablet size, use extemporaneous suspension as follows: to prepare 150 mL of 2 mg/mL suspension, add 75 mL Ora-Plus oral suspending vehicle to amber polyethylene terephthalate (PET) bottle containing 15 benazepril 20 mg tablets and shake for at least 2 min. Let stand for 1 h minimum then shake for minimum of 1 additional min, add 75 mL of Ora-Sweet oral syrup and shake to disperse ingredients.

Shake suspension before measuring dose. Measure and administer prescribed dose using dosing syringe, dosing spoon, or dosing cup.

Storage/Stability

Store tablets at or below 86°F. Protect from moisture. Store suspension in refrigerator (36° to 46°F). Discard any unused suspension after 30 days.

Drug Interactions

May decrease bioavailability of benazepril; separate administration by 1 to 2 h.

May cause symptomatic hypotension after initial dose of benazepril.

May increase lithium levels and symptoms of lithium toxicity.

May increase serum potassium levels.

May reduce effects of benazepril, especially in low-renin or volume-dependent hypertensive patients.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Angina pectoris, ECG changes, palpitations, peripheral edema, postural hypotension, symptomatic hypotension, syncope (postmarketing).

CNS

Headache (6%); dizziness (4%); fatigue, postural dizziness, somnolence (2%); anxiety, asthenia, decreased libido, hypertonia, insomnia, nervousness, paresthesia (postmarketing).

Dermatologic

Alopecia, apparent hypersensitivity (dermatitis, pruritus, rash), flushing, pemphigus, photosensitivity, Stevens-Johnson syndrome, sweating (postmarketing).

GI

Nausea (1%); constipation, gastritis, melena, pancreatitis, vomiting (postmarketing).

Genitourinary

Impotence, increased BUN, increased serum creatinine, UTI (postmarketing).

Hematologic-Lymphatic

Eosinophilia, hemolytic anemia, leukopenia, thrombocytopenia (postmarketing).

Lab Tests

Increased serum creatinine (2%); hyperkalemia, increased uric acid, increased blood glucose, increased serum bilirubin, increased liver enzymes (postmarketing).

Musculoskeletal

Arthralgia, arthritis, myalgia (postmarketing).

Renal

Protein uria (postmarketing).

Respiratory

Chronic dry cough (1%); asthma, bronchitis, eosinophilic pneumonitis, sinusitis (postmarketing).

Miscellaneous

Anaphylactoid reactions; angioedema; fetal and neonatal morbidity and death, hyponatremia, infection (postmarketing).

Precautions

Pregnancy

Category D (second and third trimester); Category C (first trimester). When pregnancy is detected, discontinue ACE inhibitors as soon as possible.

Lactation

Excreted in breast milk; avoid use in breast-feeding mothers if possible.

Children

Not recommended in children younger than 6 yr of age or if glomerular filtration rate is less than 30 mL/min.

Elderly

Consider lower starting dose and slower dose titration.

Renal Function

Reduce dose. Monitor renal function during first few weeks of therapy, when dose is increased, or during concurrent treatment with diuretic. Benazepril dose reduction or discontinuation of diuretic may be required if increases in Ccr and BUN occur.

Hazardous Tasks

May cause drowsiness, dizziness, or lightheadedness. Use with caution while driving or performing other tasks requiring mental alertness until tolerance is determined.

Photosensitivity

May occur.

Angioedema

May occur. Use with extreme caution in patients with hereditary angioedema. Angioedema of the tongue, glottis, or larynx may cause airway obstruction; consider use of subcutaneous epinephrine. Consider intestinal angioedema in differential diagnosis of patients on ACE inhibitor presenting with abdominal pain.

Concurrent diuretic use

If possible, discontinue diuretic therapy for 2 to 3 days prior to beginning benazepril therapy.

Cough

Persistent nonproductive cough, always resolving after discontinuation of therapy, has been reported with ACE inhibitors.

Fetal/Neonatal morbidity and mortality

May occur. Discontinue benazepril as soon as possible if patient becomes pregnant.

Hepatic failure

ACE inhibitors rarely have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and sometimes death.

Hyperkalemia

Has been reported. Risk factors include renal function impairment, diabetes mellitus, and concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salt substitutes.

Hypotension/First-dose effect

Significant decreases in BP may occur after first dose, especially in severely salt- or volume-depleted patients (eg, those undergoing dialysis or vigorous diuretic therapy) or those with heart failure. Risk is minimized by discontinuing use of diuretics, increasing salt intake about 1 wk before initiating benazepril, or decreasing benazepril dose.

Neutropenia/Agranulocytosis

Has occurred with other ACE inhibitors, most often in patients with renal function impairment and a collagen-vascular disease (eg, systemic lupus erythematosus).

Overdosage

Symptoms

Hypotension.

Patient Information

• Advise patient to take daily or twice daily as prescribed, without regard to meals but to take with food if stomach upset occurs.
• Advise patient to try to take each dose at about the same time each day.
• Inform patient that drug controls but not does cure hypertension and to continue taking drug as prescribed even when BP is not elevated.
• Caution patient not to change the dose or stop taking unless advised by health care provider.
• Instruct patient to continue taking other BP medications as prescribed by health care provider.
• Instruct patient in BP and pulse measurement skills.
• Advise patient to monitor and record BP and pulse at home and to inform health care provider if abnormal measurements are noted. Advise patient to take record of BP and pulse to each follow-up visit.
• Caution patient to avoid sudden position changes to prevent orthostatic hypotension.
• Instruct patient to lie or sit down if they experience dizziness or lightheadedness when standing.
• Emphasize importance of the following other modalities on BP control: weight control, regular exercise, smoking cessation, moderate intake of alcohol and salt.
• Caution patient that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to excessive fall in BP, resulting in lightheadedness or fainting.
• Advise patient that medication may cause dizziness or lightheadedness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
• Caution patient to avoid unnecessary exposure to UV light (sunlight, tanning booths) and to use sunscreen and wear protective clothing when exposed to UV light to avoid photosensitivity reaction.
• Instruct patient to stop taking drug and immediately report any of the following symptoms to health care provider: sore throat; fever; swelling of the hands or feet; irregular heartbeat; chest pains; fainting; swelling of the face, lips, eyelids, or tongue; difficulty breathing; persistent abdominal pain.
• Instruct patient to inform health care provider if they develop a persistent cough while taking this medication.

Copyright © 2009 Wolters Kluwer Health.