Benazepril Hydrochloride Prescribing Information
Benazepril can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue benazepril as soon as possible
Benazepril hydrochloride tablets are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs.
Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).
Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.
Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mm Hg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.
Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in Black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.
It may be used alone or in combination with thiazide diuretics.
- Adult Patients: Initiate with 10 mg once daily (or 5 mg if patients is on diuretic). Titrate to 40 mg daily based on blood pressure response. ()
2.1 Recommended DosageADULTSThe recommended initial dose for patients not receiving a diuretic is 10 mg once a day. The usual maintenance dosage range is 20 to 40 mg per day administered as a single dose or in two equally divided doses. A dose of 80 mg gives an increased response, but experience with this dose is limited. The divided regimen was more effective in controlling trough (pre-dosing) blood pressure than the same dose given as a once-daily regimen.
Use with diuretics in adultsThe recommended starting dose of benazepril hydrochloride tablets in a patient on a diuretic is 5 mg once daily. If blood pressure is not controlled with benazepril hydrochloride tablets alone, a low dose of diuretic may be added.
PEDIATRIC PATIENTS 6 YEARS OF AGE AND OLDERThe recommended starting dose for pediatric patients is 0.2 mg/kg once per day. Titrate as needed to 0.6 mg/kg once per day. Doses above 0.6 mg/kg (or in excess of 40 mg daily) have not been studied in pediatric patients.
Benazepril hydrochloride tablets are not recommended in pediatric patients less than 6 years of age or in pediatric patients with GFR less than 30 mL/min/1.73m2
[see Use in Specific Populations (8.3)]. - Pediatric patients age 6 years and above with glomerular filtration rate (GFR) > 30 mL/min/1.73 m2: Initiate with 0.2 mg/kg once daily. Maximum dose is 0.6 mg/kg once daily.
- Renal Impairment: Initiate with 5 mg once daily in patients with GFR < 30 mL/min/1.73 m2 (serum creatinine > 3 mg/dL) ()
2.2 Dose Adjustment for Renal ImpairmentFor adults with a GFR < 30 mL/min/1.73 m2(serum creatinine > 3 mg/dL), the recommended initial dose is 5 mg benazepril hydrochloride tablet once daily. Dosage may be titrated upward until blood pressure is controlled or to a maximum total daily dose of 40 mg. Benazepril hydrochloride tablets can also worsen renal function
[see Warnings and Precautions (5.3)].
Tablets: 10 mg, 20 mg, and 40 mg
- Each 10 mg tablet is dark yellow, circular, biconvex, beveled edge film-coated tablet debossed with ‘E’ on one side and ‘15’ on the other side.
- Each 20 mg tablet is pink, circular, biconvex, beveled edge film-coated tablet debossed with ‘E’ on one side and ‘16’ on the other side.
- Each 40 mg tablet is dark pink, circular, biconvex, beveled edge film-coated tablet debossed with ‘E’ on one side and ‘17’ on the other side.
- Pediatrics: Safety and effectiveness have not been established in patients < 6 years of age or with GFR < 30 mL/min/1.73m2 ()
8.3 Pediatric UseThe antihypertensive effects of benazepril have been evaluated in a double-blind study in pediatric patients 7 to 16 years of age
[see Clinical Pharmacology (12.3)]. The pharmacokinetics of benazepril have been evaluated in pediatric patients 6 to 16 years of age[see Clinical Pharmacology (12.3)]. Infants below the age of 1 year should not be given benazepril because of the risk of effects on kidney development.Safety and effectiveness of benazepril have not been established in pediatric patients less than 6 years of age or in children with glomerular filtration rate < 30 mL/min/1.73m²
[see Dosage and Administration (2.1)and Clinical Pharmacology 12.3)]. - Race: Less antihypertensive effect in Blacks as monotherapy ()
8.5 RaceACE inhibitors, including benazepril, as monotherapy, have an effect on blood pressure that is less in Black patients than in non-Blacks.
Benazepril hydrochloride tablets are contraindicated in patients:
- who are hypersensitive to benazepril or to any other ACE inhibitor
- with a history of angioedema with or without previous ACE inhibitor treatment
Benazepril hydrochloride tablets are contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer benazepril hydrochloride tablets within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor
Head and Neck Angioedema
Angioedema of the face, extremities, lips, tongue, glottis, and/or larynx including some fatal reactions, have occurred in patients treated with benazepril. Patients with involvement of the tongue, glottis or larynx are likely to experience airway obstruction, especially those with a history of airway surgery. Benazepril should be promptly discontinued and appropriate therapy and monitoring should be provided until complete and sustained resolution of signs and symptoms of angioedema has occurred.
Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor
Patients receiving coadministration of ACE inhibitor and mTOR (mammalian target of rapamycin) inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy or a neprilysin inhibitor may be at increased risk for angioedema
Intestinal angioedema has occurred in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. In some cases, the angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor.
Anaphylactoid Reactions During Desensitization
Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions.
Sudden and potentially life threatening anaphylactoid reactions have occurred in some patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. In such patients, dialysis must be stopped immediately, and aggressive therapy for anaphylactoid reactions must be initiated. Symptoms have not been relieved by antihistamines in these situations. In these patients, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.
Do not coadminister aliskiren with angiotensin receptor blockers, ACE inhibitors; including benazepril hydrochloride tablets in patients with diabetes
Dual Blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, 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 and other agents that affect the RAS.
Do not coadminister aliskiren with benazepril in patients with diabetes. Avoid use of aliskiren with benazepril in patients with renal impairment (GFR < 60 mL/min).