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Benazepril Hydrochloride

Pronunciation

Pronunciation: ben-AZ-e-pril HYE-droe-KLOR-ide
Class: ACE inhibitor

Trade Names

Benazepril Hydrochloride
- Tablets 5 mg
- Tablets 10 mg
- Tablets 20 mg
- Tablets 40 mg

Pharmacology

Competitively inhibits ACE, resulting in decreased conversion of angiotensin I to angiotensin II, a potent vasoconstrictor that stimulates aldosterone secretion. This results in decreased vasopressor activity and decreased aldosterone secretion.

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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 approximately 96.7% (benazepril) and approximately 95.3% (benazeprilat).

Metabolism

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

Elimination

The half-life following multiple dosing is 10 to 11 h (benazeprilat).

Urine

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

Nonrenal (eg, biliary)

Approximately 11% to 12% (benazeprilat).

Onset

Within 1 h.

Peak

2 to 4 h.

Duration

24 h.

Special Populations

Renal Function Impairment

In those with CrCl 30 mL/min or less, peak benzaprilat levels and initial half-life increase and time to steady state may be delayed.

Hepatic Function Impairment

The pharmacokinetics of benazeprilat are unaltered.

Elderly

The pharmacokinetics of benazepril and benazeprilat do not appear to be influenced by age.

Children

The Cl of benazeprilat for children 6 to 12 y of age was more than twice that of adults, and the elimination half-life of benazeprilat was around 5 h, one-third that observed in adults.

Indications and Usage

Treatment of hypertension.

Unlabeled Uses

Heart failure; nephropathy; prevention of recurrent stroke.

Contraindications

Hypersensitivity to ACE inhibitors; history of angioedema with or without previous ACE inhibitor treatment.

Dosage and Administration

Adults Initial dose

PO 10 mg/day for patients not receiving a diuretic. In patients taking diuretics that cannot be discontinued, give initial dose of 5 mg.

Maintenance

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

Children (6 y of age and older) Initial dose

PO 0.2 mg/kg/day.

Maintenance

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.

Renal function impairment

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

Administer without regard to meals or with food if GI upset occurs.

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

Aldosterone blockers (eg, eplerenone)

The risk of serious hyperkalemia may be increased, resulting in cardiac arrhythmias or arrest. Periodic monitoring of serum potassium level is recommended until the effect of the aldosterone blocker is established. Dose reduction of the aldosterone blocker may be necessary to decrease potassium levels.

Aliskiren

The risk of hyperkalemia may be increased. Use with caution. Closely monitor potassium concentrations.

Angiotensin II receptor antagonists (eg, telmisartan)

Coadministration of angiotensin II receptor antagonists and benazepril may be associated with an increased risk of renal dysfunction. Use with caution. Monitor renal function.

Capsaicin

Capsaicin may cause or exacerbate coughing associated with benazepril. If severe coughing develops, consider discontinuing one or both drugs.

Clozapine

An additive or synergistic hypotensive effect with postural syncope may occur when benazepril is used with clozapine. In addition, clozapine concentrations may be increased. Use with caution. Monitor BP and adjust the benazepril dose as needed.

Diuretics

Excessive reduction in BP may occur. Hypotensive effects can be minimized by discontinuing the diuretic or increasing the salt intake prior to initiation of benazepril treatment. If this is not possible, reduce the benazepril starting dose.

Everolimus

The risk of angioedema may be increased. If an interaction is suspected, discontinue one or both agents.

Gold salts (eg, sodium aurothiomalate)

The risk of nitritoid reactions (eg, facial flushing, hypotension, nausea, vomiting) may be increased. Carefully monitor patients for signs and symptoms of nitritoid reactions. If an interaction occurs, one of the agents may need to be discontinued.

Insulin

Rarely, the risk of hypoglycemia may be increased in diabetic patients. Monitor blood glucose and observe the patient for symptoms of hypoglycemia. Adjust the insulin dose as needed.

Iron salts (parenteral)

The risk of adverse reactions to parenteral iron (eg, arthralgia, fever) may be increased. If these agents must be used concurrently, monitor the patient closely. If an interaction is suspected, discontinue one of the agents.

Lithium

May increase lithium levels and symptoms of lithium toxicity. Use with caution. Monitor lithium levels frequently. Adjust the lithium dose as needed. Consider administering an alternative antihypertensive agent.

Loop diuretics (eg, bumetanide, furosemide)

The effects of loop diuretics may be decreased. Monitor the fluid status of the patient when benazepril is started or stopped. Adjust the loop diuretic dose as needed.

NSAIDs (eg, indomethacin)

The hypotensive effects of benazepril may be reduced. Monitor BP. If an interaction is suspected, discontinue the NSAID or use an alternative antihypertensive agent.

Pergolide

An additive or synergistic effect, resulting in profound hypotension, may occur. Use with caution. Consider starting with a low dose of pergolide. Closely monitor BP. If BP falls, dosage reduction may be needed.

Phenothiazines (eg, chlorpromazine)

An additive or synergistic hypotensive effect with postural syncope may occur when benazepril is used with phenothiazines. Use with caution. Monitor BP and adjust the benazepril dose as needed.

Potassium supplements, potassium-sparing diuretics (eg, amiloride, spironolactone, triamterene)

May increase serum potassium levels. If these agents are coadministered, use with caution. Frequently monitor serum potassium and adjust the dose of either drug as needed.

Salicylates (eg, aspirin)

May reduce effects of benazepril, especially in low-renin or volume-dependent hypertensive patients. Consider increasing the dosage of benazepril or stopping the salicylate if BP control or renal function deteriorates. A decrease in the salicylate dose may avoid the interaction.

Sulfonylureas (eg, glyburide)

The risk of hypoglycemia may be increased. Monitor blood glucose and observe the patient for symptoms of hypoglycemia. Adjust the sulfonylurea dose as needed.

Thiazide diuretics (eg, hydrochlorothiazide)

Benazepril can attenuate potassium loss caused by thiazide diuretics. Monitor serum potassium and adjust treatment as needed. In addition, the risk of renal failure may be increased. Monitor renal function, especially in elderly patients and patients with impaired renal function. If an interaction is suspected, stop one or both agents.

Tizanidine

The pharmacologic effects of benazepril may be increased, possibly resulting in severe hypotension. Use with caution and closely monitor BP. If hypotension occurs, supportive treatment may be necessary.

Trimethoprim

The risk of serious hyperkalemia may be increased, resulting in cardiac arrhythmias or arrest. Periodic monitoring of serum potassium level is recommended. If an interaction occurs, discontinuation of one or both drugs may be necessary.

Adverse Reactions

CNS

Headache (6%); dizziness (4%); fatigue, postural dizziness, somnolence (2%).

Dermatologic

Apparent hypersensitivity (dermatitis, pruritus, rash), Stevens-Johnson syndrome.

GI

Nausea (1%); small bowel angioedema (postmarketing).

Hematologic-Lymphatic

Agranulocytosis, neutropenia (postmarketing).

Lab Tests

Increased serum creatinine (2%); decrease in Hgb, ECG changes, eosinophilia, hyperkalemia, hyponatremia, increased blood glucose, increased BUN and serum creatinine, increased liver enzymes, increased serum bilirubin, increased uric acid, leukopenia, proteinuria.

Respiratory

Cough (1%).

Miscellaneous

Angioedema; fetal and neonatal morbidity and death; anaphylactoid reactions (postmarketing).

Precautions

Warnings

Pregnancy

When used in pregnancy, ACE inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, discontinue therapy as soon as possible.


Monitor

Ensure serum electrolytes are monitored periodically. Monitor renal function during first few weeks of therapy, when dose is increased, or during concurrent treatment with a diuretic. Monitor and record BP and pulse. Monitor WBC in patients with collagen-vascular disease.


Pregnancy

Category D (second and third trimesters); 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 y 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.

Hazardous Tasks

May cause drowsiness, dizziness, or light-headedness. 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 therapy 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 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 impairment and collagen-vascular disease (eg, systemic lupus erythematosus).

Renal effects

Changes in renal function may occur, especially in patients with severe CHF, renal artery stenosis, or preexisting renal impairment, or those who are taking a diuretic. Dose reduction or discontinuation of diuretic may be required if increases in CrCl and BUN occur.

Surgery/Anesthesia

Risk of hypotension may be increased. If hypotension occurs, correct with volume expansion.

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 light-headedness 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 light-headedness or fainting.
  • Advise patient that medication may cause dizziness or light-headedness 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.
  • Advise patient not to use potassium supplements or salt substitutes containing potassium without talking with their health care provider.
  • Advise women of childbearing age not to become pregnant while on this medication and to report pregnancies to their health care provider as soon as possible.

Copyright © 2009 Wolters Kluwer Health.

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