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Benazepril Hydrochloride

Class: Angiotensin-Converting Enzyme Inhibitors
- ACE Inhibitors
VA Class: CV400
Chemical Name: [S*-(R*,R*)]-3-[[1[(ethoxycarbonyl)-3-phenylpropyl]amino]-2,3,4,5-tetrahydro-2-oxo-1-H-1benzazepine-1-acetic acid monohydrochloride
CAS Number: 86541-74-4
Brands: Lotensin

Medically reviewed by Drugs.com. Last updated on Nov 5, 2018.

Warning

  • Can cause fetal and neonatal morbidity and mortality if used during pregnancy.1 11 12 48 49 51 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • If pregnancy is detected, discontinue as soon as possible.1 11 12 51

Introduction

Benazepril is a nonsulfhydryl ACE inhibitor.1 2 3 4

Uses for Benazepril Hydrochloride

Hypertension

Benazepril is used for management of hypertension (alone or in combination with other classes of antihypertensive agents);1 4 1200 may be used in fixed combination with amlodipine or hydrochlorothiazide when such combined therapy is indicated.11 12

ACE inhibitors are recommended as one of several preferred agents for the initial management of hypertension according to current evidence-based hypertension guidelines; other preferred options include angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics.501 502 503 504 1200 While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.501 502 504 1200 1213

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).501 502 503 504 515 1200 1201

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.1200 (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults1200

Category

SBP (mm Hg)

DBP (mm Hg)

Normal

<120

and

<80

Elevated

120–129

and

<80

Hypertension, Stage 1

130–139

or

80–89

Hypertension, Stage 2

≥140

or

≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP.1200 However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.501 503 504 505 506 507 508 515 523 526 530 1200 1201 1207 1209 1222 1223 1229

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.1200 In addition, an SBP goal of <130 mm Hg generally is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg.1200 These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.1200 1202 1210

Other hypertension guidelines generally have based target BP goals on age and comorbidities.501 504 536 Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk and have used higher BP thresholds and target BPs in elderly patients501 504 536 compared with those recommended by the 2017 ACC/AHA hypertension guideline.1200

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the current ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.1222 1223 1224 1229

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient’s BP treatment goal.1200 1220

For decisions regarding when to initiate drug therapy (BP threshold), the current ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.1200 1207 ASCVD risk assessment is recommended by ACC/AHA for all adults with hypertension.1200

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).1200

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP of ≥130 mm Hg or an average DBP ≥80 mm Hg.1200

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg.1200 Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.502 1200

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP.1200 Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.1200

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to ACE inhibitors.25 26 46 47 501 504 1200 However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar BP lowering in black patients as in other racial groups.1200

Manufacturer states addition of benazepril to amlodipine usually does not provide additional antihypertensive effects in blacks but appears to reduce development of amlodipine-associated edema regardless of race.12

ACE inhibitors may be preferred in hypertensive patients with heart failure, ischemic heart disease, diabetes mellitus, CKD, or cerebrovascular disease or post-MI.501 502 504 523 524 525 526 527 534 535 536 543 1200 1214 1215

Heart Failure

ACE inhibitors are used for management of heart failure, usually in conjunction with other agents such as cardiac glycosides, diuretics, and β-adrenergic blocking agents (β-blockers).31 32 33 34 35 524 700

Some evidence indicates that therapy with an ACE inhibitor may be less effective than angiotensin receptor-neprilysin inhibitor (ARNI) therapy (e.g., sacubitril/valsartan) in reducing cardiovascular death and heart failure-related hospitalization.700 702

ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend that patients with chronic symptomatic heart failure with reduced left ventricular ejection fraction (LVEF) (NYHA class II or III) who are able to tolerate an ACE inhibitor or angiotensin II receptor antagonist be switched to therapy containing an ARNI to further reduce morbidity and mortality.700

Diabetic Nephropathy

A recommended agent in the management of patients with diabetes mellitus and persistent albuminuria who have modestly elevated (30–300 mg/24 hours) or higher (>300 mg/24 hours) levels of urinary albumin excretion; slows rate of progression of renal disease in such patients.40 41 42 43 44 50 535 536 1232

Benazepril Hydrochloride Dosage and Administration

General

BP Monitoring and Treatment Goals

  • Monitor BP regularly (i.e., monthly) during therapy and adjust dosage of the antihypertensive drug until BP controlled.1200

  • If unacceptable adverse effects occur, discontinue drug and initiate another antihypertensive agent from a different pharmacologic class.1216

  • If adequate BP response not achieved with a single antihypertensive agent, either increase dosage of single drug or add a second drug with demonstrated benefit and preferably a complementary mechanism of action (e.g., calcium-channel blocker, thiazide diuretic).1200 1216 Many patients will require at least 2 drugs from different pharmacologic classes to achieve BP goal; if goal BP still not achieved, add a third drug.1200 1216 1220

Administration

Oral Administration

Administer benazepril orally once or twice daily without regard to meals.1

Administer benazepril as an extemporaneously prepared oral suspension in pediatric patients unable to swallow tablets or in those for whom the calculated daily dosage does not correspond to the available tablet strengths.1

Reconstitution

Preparation of extemporaneous suspension containing benazepril hydrochloride 2 mg/mL: Add 75 mL of suspending vehicle (Ora-Plus) to a polyethylene terephthalate (PET) bottle containing fifteen 20-mg tablets of benazepril hydrochloride; shake the contents for ≥2 minutes.1 Allow concentrated suspension to stand for a minimum of 60 minutes following reconstitution, then shake for a minimum of 1 additional minute.1 Dilute the concentrated suspension with 75 mL of syrup (Ora-Sweet); shake the container to disperse the ingredients.1 Shake suspension before dispensing each dose.1

Dosage

Benazepril is available as benazepril hydrochloride; dosage expressed in terms of the salt.1 11 12

Pediatric Patients

Hypertension
Oral

Children ≥6 years of age: Initially, 0.2 mg/kg (up to 10 mg) once daily.1 1150 Adjust dosage until the desired BP goal is achieved (up to maximum dosage of 0.6 mg/kg or 40 mg daily).1 1150 Some experts state that dosage should be increased every 2–4 weeks until BP controlled, maximum dosage reached, or adverse effects occur.1150

Adults

Hypertension
Benazepril Therapy
Oral

Initially, 10 mg once daily in patients not receiving a diuretic.1 4

In patients currently receiving diuretic therapy, 5 mg initially.1

Usual dosage: Manufacturer states 20–40 mg daily, given in 1 dose or 2 divided doses.1 Some experts state 10–40 mg daily, given in 1 dose or 2 divided doses.1200

Divided-dose regimen has been more effective in controlling trough (pre-dose) BP than the same dose given once daily.1

If BP not controlled with benazepril alone, a second antihypertensive agent (e.g., diuretic1 ) may be added.1 1200

Benazepril/Hydrochlorothiazide Fixed-combination Therapy
Oral

Manufacturer states fixed-combination preparation should not be used for initial antihypertensive therapy.11

If BP is not adequately controlled by monotherapy with benazepril or hydrochlorothiazide, can switch to the fixed-combination preparation containing benazepril hydrochloride 10 mg and hydrochlorothiazide 12.5 mg initially.11 Adjust dosage of either or both drugs according to patient’s response.11

If BP is controlled with benazepril and hydrochlorothiazide (administered separately), can switch to the fixed-combination preparation containing the corresponding individual doses for convenience.11

Benazepril/Amlodipine Fixed-combination Therapy
Oral

Manufacturer states fixed-combination preparation should not be used for initial antihypertensive therapy.12

With the fixed combination in dosages of benazepril hydrochloride 10–40 mg daily and amlodipine 2.5–10 mg daily, BP response increased with increasing amlodipine dosage in all patient groups and increased with increasing benazepril hydrochloride dosage in nonblack patient groups.12

If BP is not adequately controlled by monotherapy with benazepril or amlodipine, can switch to benazepril/amlodipine fixed combination.12

If BP is adequately controlled by monotherapy with amlodipine, but edema has developed, can switch to benazepril/amlodipine fixed combination to achieve adequate BP control without edema.12 May be prudent to reduce amlodipine dosage, especially in nonblack patients, when benazepril is initiated to avoid excessive antihypertensive response.12

If BP is controlled with benazepril and amlodipine (administered separately), can switch to the fixed-combination preparation containing the corresponding individual doses for convenience.12

Adjust dosage of benazepril/amlodipine fixed combination according to patient’s response.12

Prescribing Limits

Pediatric Patients

Hypertension
Oral

Maximum 0.6 mg/kg or 40 mg of benazepril hydrochloride daily.1 1150

Adults

Hypertension
Benazepril Therapy
Oral

Maximum 80 mg of benazepril hydrochloride daily.1

Benazepril/Hydrochlorothiazide Fixed-combination Therapy
Oral

Maximum 20 mg of benazepril hydrochloride and 25 mg of hydrochlorothiazide daily.11

Benazepril/Amlodipine Fixed-combination Therapy
Oral

Maximum 40 mg of benazepril hydrochloride and 10 mg of amlodipine daily.12

Special Populations

The following information addresses dosage of benazepril hydrochloride in special populations. Dosages of drugs administered in fixed combination with benazepril hydrochloride also may require adjustment in certain patient populations; the need for such dosage adjustments must be considered in the context of cautions, precautions, and contraindications specific to that population and drug.11 12

Hepatic Impairment

Preparations containing benazepril hydrochloride in fixed combination with 5 or 10 mg of amlodipine exceed the initial recommended dosage of amlodipine (2.5 mg daily) in patients with hepatic impairment.12

Renal Impairment

Systemic exposure to benazeprilat may be increased.1 (See Absorption: Special Populations, under Pharmacokinetics.)

Initially, benazepril hydrochloride 5 mg once daily in adults with Clcr <30 mL/minute or Scr >3 mg/dL; titrate until BP is controlled or to maximum of 40 mg daily.1 Use of benazepril not recommended in pediatric patients with Clcr <30 mL/minute per 1.73 m2.1

Safety and efficacy of benazepril in fixed combination with hydrochlorothiazide not established in patients with Clcr ≤30 mL/minute.11

Preparations containing benazepril in fixed combination with amlodipine are not recommended in patients with Clcr ≤30 mL/minute or Scr >3 mg/dL.12

Geriatric Patients

Select dosage of benazepril hydrochloride carefully.1 11 12 (See Geriatric Use under Cautions.)

Preparations containing benazepril in fixed combination with 5 or 10 mg of amlodipine exceed the initial recommended dosage (2.5 mg daily) of amlodipine in geriatric patients.12

Cautions for Benazepril Hydrochloride

Contraindications

  • Known hypersensitivity (e.g., history of angioedema) to benazepril, another ACE inhibitor, or any ingredient in the formulation.1 11 12

  • History of angioedema with or without prior ACE inhibitor therapy.1 11 12

  • Concomitant aliskiren therapy in patients with diabetes mellitus.1 11 12

  • Concomitant therapy with a neprilysin inhibitor (e.g., sacubitril).1 Do not administer within 36 hours of switching to or from sacubitril/valsartan.1

  • When benazepril is used in fixed combination with hydrochlorothiazide or amlodipine, consider contraindications associated with the concomitant agent.11 12

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

Possible reduction in fetal renal function and increase in fetal and neonatal morbidity and mortality when benazepril is used during pregnancy.1 11 12 14 15 16 17 18 19 20 48 49 51 (See Boxed Warning.) Such potential risks occur throughout pregnancy,49 especially during the second and third trimesters.1 49 ACE inhibitors (e.g., benazepril) also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.48 49 Potential neonatal effects include skull hypoplasia, anuria, hypotension, renal failure, and death.1 11 12 Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations.1 11 12

Discontinue ACE inhibitors (e.g., benazepril) as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.1 11 12 49 Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.8 19

Sensitivity Reactions

Anaphylactoid reactions and/or angioedema possible with ACE inhibitors; if associated with laryngeal edema, may be fatal.1 11 12

Head and neck angioedema reported in patients receiving an ACE inhibitor and at a higher rate in black patients compared with patients of other races.1 11 Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor.1

Concomitant use of an ACE inhibitor and a mammalian target of rapamycin (mTOR) inhibitor or a neprilysin inhibitor (e.g., sacubitril) may increase the risk of angioedema; monitor patients for signs of angioedema during such concomitant therapy.1 11

Institute immediate medical intervention (e.g., epinephrine) for involvement of tongue, glottis, or larynx; monitor until complete and sustained resolution of angioedema manifestations has occurred.1 11 12

Intestinal angioedema possible with ACE inhibitors; consider in differential diagnosis of patients who develop abdominal pain.1 11 12

Anaphylactoid reactions reported in patients receiving ACE inhibitors while undergoing LDL apheresis with dextran sulfate absorption or following initiation of hemodialysis that utilized high-flux membrane.1 11 12 In such patients, immediately stop dialysis and initiate aggressive treatment.1 Antihistamine treatment has been ineffective in alleviating symptoms in these situations.1 Consider using a different type of dialysis membrane or a different class of antihypertensive drug.1

Life-threatening anaphylactoid reactions reported in at least 2 patients receiving ACE inhibitors while undergoing desensitization treatment with hymenoptera venom.1 11 12

Benazepril contraindicated in patients with a history of angioedema with or without prior ACE inhibitor therapy.1 11 12

Other Warnings and Precautions

Renal Effects

Deterioration of renal function, including acute renal failure, may occur in patients receiving ACE inhibitor therapy.1 11 12

Patients whose renal function depends on the activity of the renin-angiotensin system, particularly those with unilateral or bilateral renal artery stenosis, CKD, severe congestive heart failure, MI, or volume depletion, may be at particular risk of developing acute renal failure while receiving benazepril.1 11 12

Increases in BUN and Scr have occurred in patients with unilateral or bilateral renal artery stenosis; such increases generally reversible following discontinuance of benazepril and/or diuretic therapy.11

Closely monitor renal function following initiation of benazepril therapy.1 11 12 Consider withholding or discontinuing therapy in patients who develop clinically important decreases in renal function.1 11 12

Cardiovascular Effects

Possible symptomatic hypotension with ACE inhibitors, particularly in patients with heart failure and systolic BP <100 mm Hg; patients with ischemic heart disease, cerebrovascular disease, or hyponatremia; those receiving high-dose diuretic therapy or renal dialysis; or patients with volume and/or salt depletion of any etiology.1 11 12 Symptomatic hypotension also reported in patients with severe aortic stenosis.12 Correct volume and/or salt depletion before initiating benazepril.1 11 12

Risk of excessive hypotension in patients with heart failure (with or without renal impairment); may be associated with oliguria and/or progressive azotemia and, rarely, acute renal failure and/or death.1 11 12

Initiate benazepril therapy under close medical supervision in patients with heart failure; monitor closely for first 2 weeks following initiation of benazepril or diuretic therapy or any increase in benazepril or diuretic dosage.1 11 12 Avoid benazepril therapy in patients with hemodynamic instability following MI.1

Hypotension may occur in patients undergoing major surgery or during anesthesia with agents that produce hypotension; recommended treatment is fluid volume expansion.1 11 12

Generally may reinstate benazepril therapy cautiously after BP is stabilized (e.g., with volume expansion).11 12

Effects on Potassium

Hyperkalemia reported with benazepril, especially in patients with renal impairment or diabetes mellitus and those receiving other drugs that can increase serum potassium concentration (e.g., potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes).1 11 12 (See Specific Drugs under Interactions.)

Monitor serum potassium concentration periodically in these patients.1 11 12

Hepatic Effects

ACE inhibitor-associated clinical syndrome usually manifested initially by cholestatic jaundice reported; may progress to fulminant hepatic necrosis (occasionally fatal).1 11 12

If jaundice or marked elevation of liver enzymes occurs, discontinue drug and monitor patient.1 11 12

Hematologic Effects

Neutropenia and agranulocytosis reported with another ACE inhibitor (captopril);11 data insufficient to determine similar risk with benazepril.11

Consider monitoring leukocytes in patients with collagen vascular disease, especially if renal impairment exists.11

Respiratory Effects

ACE inhibitors associated with persistent, nonproductive cough; resolves after drug discontinuance.1 11 12

Consider ACE inhibitor-induced cough in the differential diagnosis of patients who develop cough during benazepril therapy.11 12

Use of Fixed Combinations

When benazepril is used in fixed combination with hydrochlorothiazide, amlodipine, or other drugs, consider cautions, precautions, contraindications, and interactions associated with these other drugs.11 12

Specific Populations

Pregnancy

Benazepril: Category D.1 11 12

Benazepril can cause fetal and neonatal morbidity and mortality when administered to a pregnant woman.1 11 12 (See Fetal/Neonatal Morbidity and Mortality under Cautions and see Boxed Warning.)

Lactation

Benazepril and benazeprilat are distributed into milk in minimal amounts.1 Discontinue nursing or the drug.1 11

Pediatric Use

If oliguria or hypotension occurs in neonates with a history of in utero exposure to benazepril, support BP and renal function; may require exchange transfusions or dialysis.1 11 12 (See Fetal/Neonatal Morbidity and Mortality under Cautions.) Benazepril crosses the placenta and can theoretically be removed from the neonatal circulation by these means; occasional reports of benefit from these maneuvers with another ACE inhibitor.1 11 12 However, experience is limited.1 11 12

Safety and efficacy of benazepril not established in children <6 years of age1 or in those with Clcr <30 mL/minute per 1.73 m2.1

Safety and efficacy of benazepril in fixed combination with amlodipine or hydrochlorothiazide not established in children.11 12

Geriatric Use

Safety and efficacy profiles of benazepril alone or in fixed combination with hydrochlorothiazide or amlodipine are similar to those in younger adults.1 11 12 However, cannot rule out increased sensitivity.1 11 12 Possible decreased elimination of benazepril due to age-related changes in renal function; cautious dosing recommended.1 11 12

Renal Impairment

Deterioration of renal function may occur in susceptible patients; use caution in patients with renal impairment.1 (See Renal Effects under Cautions.)

Use of benazepril in fixed combination with amlodipine not recommended in patients with severe renal impairment; safety and efficacy of benazepril in fixed combination with hydrochlorothiazide not established in such patients.11 12 (See Renal Impairment under Dosage and Administration.)

Black Patients

BP reduction with ACE inhibitors may be smaller in black patients compared with patients of other races.1 504 1200 (See Hypertension under Uses.)

Higher incidence of angioedema reported with ACE inhibitors in black patients compared with other races.1 26 1200

Common Adverse Effects

Benazepril: Headache, dizziness, fatigue, somnolence, postural dizziness.1

Benazepril/hydrochlorothiazide fixed combination: Dizziness, fatigue, postural dizziness, headache, cough, hypertonia, vertigo, nausea, impotence, somnolence.11

Benazepril/amlodipine fixed combination: Cough, headache, dizziness, edema.12

Interactions for Benazepril Hydrochloride

The following information addresses potential interactions with benazepril. When benazepril is used in fixed combination with hydrochlorothiazide or amlodipine, consider interactions associated with the concomitant agent.11 12

Specific Drugs

Drug

Interaction

Comments

Anticoagulants, oral

Interaction unlikely1

Antidiabetic agents (insulin, oral agents)

Possible hypoglycemia1 11

Advise diabetic patients about the possibility of hypoglycemia; monitor appropriately1 11

Antihypertensive agents (e.g., curare derivatives, guanethidine, methyldopa, β-blocking agents, vasodilators, calcium-channel blocking agents, ACE inhibitors, angiotensin II receptor antagonists, direct renin inhibitors [DRIs])

Increased antihypertensive effect1 11 12

Dual blockade of the renin-angiotensin system with angiotensin II receptor antagonists, ACE inhibitors, or aliskiren: Increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared with monotherapy;1 11 12 no additional benefit in most patients1 11 12

In general, avoid concomitant use of 2 renin-angiotensin system antagonists1 11 12

If used with other agents that affect renin-angiotensin system, closely monitor BP, renal function, and electrolytes1 11 12

Diuretics

Increased hypotensive effect1

If possible, discontinue diuretic before initiating benazepril1 (see Dosage under Dosage and Administration)

Diuretics, potassium-sparing (amiloride, spironolactone, triamterene)

Enhanced hyperkalemic effect1 11 12

Use with caution; monitor serum potassium concentrations frequently1 11 12

Gold

Nitritoid reactions (e.g., facial flushing, nausea, vomiting, hypotension) reported rarely in patients receiving sodium aurothiomalate and ACE inhibitor1 11 12

Lithium

Increased serum lithium concentrations; possible toxicity1 11 12

Lithium toxicity usually reversible following discontinuance of lithium or benazepril1

Use with caution; monitor serum lithium concentrations frequently1 11 12

mTOR inhibitors (e.g., everolimus, sirolimus, temsirolimus)

May increase risk of angioedema1 11 12

Neprilysin inhibitors (e.g., sacubitril)

May increase risk of angioedema

NSAIAs (including COX-2 inhibitors)

May result in deterioration of renal function, including possible renal failure; effects usually reversible1 11 12

Monitor renal function periodically1 11 12

Potassium supplements or potassium-containing salt substitutes

Enhanced hyperkalemic effect1 11 12

Monitor serum potassium concentrations periodically1 11 12

Benazepril Hydrochloride Pharmacokinetics

Absorption

Bioavailability

About 37% of oral benazepril dose is absorbed.1 Peak plasma concentrations of benazepril and benazeprilat achieved within 0.5–1 and 1–2 hours, respectively.1

Onset

Following a single oral benazepril dose, antihypertensive effects are observed within 1 hour, with peak BP reduction at 2–4 hours.1

During chronic benazepril therapy, maximum antihypertensive effect with any dose is achieved after 1–2 weeks.1

Duration

Pressor effect (60–90% inhibition of exogenous angiotensin I) of a single benazepril dose (10 mg) persists for up to 4 hours.1 Inhibition of plasma ACE activity (≥80–90%) for ≥24 hours with single and multiple doses of ≥10 mg.1

Food

Food does not affect absorption of benazepril.1

Peak plasma concentrations of benazeprilat are attained within 2–4 hours following oral administration of benazepril with food.1

Special Populations

In patients with cirrhosis, benazeprilat concentrations essentially unchanged.1

In patients with severe renal impairment, increased peak serum benazeprilat concentrations and increased time to steady-state benazeprilat concentrations.1

Distribution

Extent

In animal studies, benazepril and its metabolites crossed the blood-brain barrier only slightly.1 11

Benazepril crosses the placenta and is distributed into breast milk.1

Plasma Protein Binding

Benazepril: 96.7%.1

Benazeprilat: 95.3%.1

Elimination

Metabolism

Benazepril is metabolized in the liver, principally to an active metabolite, benazeprilat.1

Elimination Route

Benazepril is eliminated principally in urine (as metabolites) and to lesser extent via biliary excretion.1

Half-life

Benazeprilat: 10–11 hours.1

Special Populations

In patients with renal failure, biliary clearance of benazeprilat may compensate to some extent for reduced renal clearance.1

Stability

Storage

Oral

Extemporaneous Suspension

Benazepril hydrochloride 2 mg/mL in Ora-Sweet and Ora-Plus (see Reconstitution under Dosage and Administration): Up to 30 days at 2–8°C.1

Tablets

Benazepril: Tight container at ≤30°C.1

Benazepril/hydrochlorothiazide fixed combination: Tight, light-resistant container at ≤30ºC.11

Capsules

Benazepril/amlodipine fixed combination: Tight container at 25ºC (may be exposed to 15–30ºC).12

Actions

  • Benazepril is a prodrug; not pharmacologically active until hydrolyzed in the liver to benazeprilat.1 2 3 4

  • Benazepril suppresses the renin-angiotensin-aldosterone system.1

Advice to Patients

  • When benazepril is used in fixed combination with hydrochlorothiazide, amlodipine, or other drugs, importance of advising patients about important precautionary information regarding the concomitant agent.11 12

  • Risk of angioedema (including laryngeal edema), anaphylactoid reactions, or other sensitivity reactions.1 11 12 Importance of discontinuing drug and reporting sensitivity reactions (e.g., edema of face, eyes, lips, tongue, or extremities; hoarseness; swallowing or breathing with difficulty) immediately to clinician.1 11 12

  • Risk of symptomatic hypotension (e.g., lightheadedness, syncope), especially during initial therapy or with volume depletion secondary to excessive perspiration, vomiting, or diarrhea; importance of reporting such symptoms to clinician.1 11 12 Importance of discontinuing drug and contacting clinician promptly if syncope occurs.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

    Risk of hyperkalemia.1 Importance of avoiding the use of potassium supplements or salt substitutes containing potassium without consultation with a clinician.1

    Importance of monitoring closely for hypoglycemia in patients receiving oral antidiabetic agents or insulin, especially during first month of combined use with benazepril.1 11 12

  • Risks of use during pregnancy.1 11 12 48 49 (See Boxed Warning.)

    Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; importance of discussing other options for hypertension treatment if pregnancy occurs..1 49

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Benazepril Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

5 mg*

Benazepril Hydrochloride Tablets

Lotensin

Validus

10 mg*

Benazepril Hydrochloride Tablets

Lotensin

Validus

20 mg*

Benazepril Hydrochloride Tablets

Lotensin

Validus

40 mg*

Benazepril Hydrochloride Tablets

Lotensin

Validus

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Benazepril Hydrochloride Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

10 mg with Amlodipine Besylate 2.5 mg (of amlodipine)*

Amlodipine Besylate and Benazepril Hydrochloride Capsules (combination)

Lotrel

Novartis

10 mg with Amlodipine Besylate 5 mg (of amlodipine)*

Amlodipine Besylate and Benazepril Hydrochloride Capsules (combination)

Lotrel

Novartis

20 mg with Amlodipine Besylate 5 mg (of amlodipine)*

Amlodipine Besylate and Benazepril Hydrochloride Capsules (combination)

Lotrel

Novartis

20 mg with Amlodipine Besylate 10 mg (of amlodipine)*

Amlodipine Besylate and Benazepril Hydrochloride Capsules (combination)

Lotrel

Novartis

40 mg with Amlodipine Besylate 5 mg (of amlodipine)*

Amlodipine Besylate and Benazepril Hydrochloride Capsules

Lotrel

Novartis

40 mg with Amlodipine Besylate 10 mg (of amlodipine)*

Amlodipine Besylate and Benazepril Hydrochloride Capsules

Lotrel

Novartis

Tablets, film-coated

5 mg with Hydrochlorothiazide 6.25 mg*

Benazepril with Hydrochlorothiazide Tablets

Lotensin HCT (scored)

Validus

10 mg with Hydrochlorothiazide 12.5 mg*

Benazepril with Hydrochlorothiazide Tablets

Lotensin HCT (scored)

Validus

20 mg with Hydrochlorothiazide 12.5 mg*

Benazepril with Hydrochlorothiazide Tablets

Lotensin HCT (scored)

Validus

20 mg with Hydrochlorothiazide 25 mg*

Benazepril with Hydrochlorothiazide Tablets

Lotensin HCT (scored)

Validus

AHFS DI Essentials™. © Copyright 2019, Selected Revisions November 5, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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1218. Messerli FH, Bangalore S, Bavishi C et al. Angiotensin-converting enzyme inhibitors in hypertension: to use or not to use?. J Am Coll Cardiol. 2018; 71:1474-1482. http://www.ncbi.nlm.nih.gov/pubmed/29598869?dopt=AbstractPlus

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1229. Ioannidis JPA. Diagnosis and treatment of hypertension in the 2017 ACC/AHA guidelines and in the real world. JAMA. 2018; 319(2):115-6. http://www.ncbi.nlm.nih.gov/pubmed/29242891?dopt=AbstractPlus

1232. American Diabetes Association. 10. Microvascular complications and foot care: standards of medical care in diabetes 2018. Diabetes Care. 2018; 41:S86-S104. http://www.ncbi.nlm.nih.gov/pubmed/29222381%20?dopt=AbstractPlus

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