Benazepril Hydrochloride

Name: Benazepril Hydrochloride

Uses for Benazepril Hydrochloride

Hypertension

Benazepril is used for management of hypertension (alone or in combination with other classes of antihypertensive agents);1 4 500 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; other options include angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics.501 502 503 504 While there may be individual differences with respect to specific outcomes, these antihypertensive drug classes all produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.500 501 502 504 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).500 501 502 503 504 515

ACE inhibitors may be preferred in hypertensive patients with heart failure, ischemic heart disease, diabetes mellitus, chronic kidney disease, or cerebrovascular disease or post-MI.500 501 502 504 520 523 524 525 526 527 534 535 536 543

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to ACE inhibitors.25 26 46 47 500 501 504 However, diminished response to an ACE inhibitor is largely eliminated when administered concomitantly with a calcium-channel blocker or thiazide diuretic.500 504

The optimum BP threshold for initiating antihypertensive drug therapy is controversial.501 504 505 506 507 508 515 523 530 Further study needed to determine optimum BP thresholds/goals; individualize treatment decisions.501 503 507 515 526 530

JNC 7 recommends initiation of drug therapy in all patients with uncomplicated hypertension and BP ≥140/90 mm Hg;500 JNC 8 panel recommends SBP threshold of 150 mm Hg for patients ≥60 years of age.501 Although many experts agree that SBP goal of <150 mm Hg may be appropriate for patients ≥80 years of age,502 504 505 530 application of this goal to those ≥60 years of age is controversial, especially for those at higher cardiovascular risk.501 502 505 506 508 511 515

In the past, initial antihypertensive drug therapy was recommended for patients with diabetes mellitus or chronic kidney disease who had BP ≥130/80 mm Hg;500 503 current hypertension management guidelines generally recommend a BP threshold of 140/90 mm Hg for these individuals (same as for the general population of patients without these conditions), although a goal of <130/80 mm Hg may still be considered.501 502 503 504 520 530 535 536 541

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

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 50 520 535 536

Benazepril Hydrochloride Dosage and Administration

General

BP Monitoring and Treatment Goals

  • Carefully monitor BP during initial titration or subsequent upward adjustment in dosage.500 501

  • When available, use evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) to determine target dosages; target dosages usually can be achieved within 2–4 weeks but may take up to several months.501

  • If adequate BP response not achieved with a single antihypertensive agent, add a second drug with demonstrated benefit; if goal BP still not achieved with optimal dosages of 2 antihypertensive agents, add a third drug.501 May maximize dosage of the first drug before adding a second drug, or add a second drug before maximizing dosage of the initial drug.501

  • Consider initiating antihypertensive therapy with a combination of drugs if patient's BP exceeds goal BP by >20/10 mm Hg.500 501 503 504

  • Goal is to achieve and maintain optimal control of BP; individualize specific target BP based on consideration of multiple factors, including patient age and comorbidities, and currently available evidence from clinical studies.500 501 (See Hypertension under Uses.)

Administration

Oral Administration

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

Administer benazepril as 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 45 Adjust dosage until the desired BP goal is achieved (up to maximum dosage of 0.6 mg/kg or 40 mg daily).1 45

Adults

Hypertension Benazepril Therapy Oral

Initially, 10 mg once daily in patients not receiving a diuretic.1 4 13

In patients currently receiving diuretic therapy, discontinue diuretic, if possible, 2–3 days before initiating benazepril.1 May cautiously resume diuretic therapy if BP not controlled adequately with benazepril alone.1 If diuretic cannot be discontinued, increase sodium intake and give lower initial benazepril hydrochloride dose (5 mg) under close medical supervision.1 13

Adjust dosage at approximately monthly intervals (more aggressively in high-risk patients) to achieve BP control.13

Usual dosage: 20–40 mg daily, given in 1 dose or 2 divided doses.1 13

If effectiveness diminishes toward end of dosing interval in patients treated once daily, consider increasing dosage or administering benazepril in 2 divided doses.1 13

If intolerable adverse effects occur, consider dosage reduction; if adverse effects worsen or fail to resolve, may need to discontinue and switch to another antihypertensive drug class.501

Benazepril/Hydrochlorothiazide Fixed-combination Therapy Oral

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

In studies using benazepril/hydrochlorothiazide fixed combination in dosages of benazepril hydrochloride 5–20 mg daily and hydrochlorothiazide 6.25–25 mg daily, BP response increased with increasing dosages of the drugs.11

If BP is not adequately controlled by monotherapy with benazepril, can switch to the fixed-combination preparation containing benazepril hydrochloride 10 mg and hydrochlorothiazide 12.5 mg or, alternatively, benazepril hydrochloride 20 mg and hydrochlorothiazide 12.5 mg.11 Adjust dosage of either or both drugs according to patient’s response.11

If BP is controlled by monotherapy with hydrochlorothiazide 25 mg daily but potassium loss is problematic, can switch to fixed-combination preparation containing benazepril hydrochloride 5 mg and hydrochlorothiazide 6.25 mg.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

In studies using benazepril/amlodipine 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 dosage in nonblack patient groups.12

If BP is not adequately controlled by monotherapy with benazepril (or another ACE inhibitor) or amlodipine (or another dihydropyridine-derivative calcium-channel blocker), 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 similar or better 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; consider that steady-state plasma concentrations of benazepril and amlodipine are reached after 2 and 7 days, respectively.12

In small or frail individuals, preparations containing benazepril in fixed combination with 5 or 10 mg of amlodipine exceed the initial recommended dosage (2.5 mg daily) of amlodipine.12

Prescribing Limits

Pediatric Patients

Hypertension Oral

Maximum 0.6 mg/kg or 40 mg of benazepril hydrochloride daily.1 45

Adults

Hypertension Oral

Maximum 80 mg of benazepril hydrochloride daily.1

Special Populations

The following information addresses dosage of benazepril in special populations. Dosages of drugs administered in fixed combination with benazepril 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 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

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 45

Preparations containing benazepril in fixed combination with hydrochlorothiazide are not recommended in patients with Clcr ≤30 mL/minute or Scr >3 mg/dL.11 Loop diuretics are preferred to thiazides in these patients.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 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

Volume- and/or Salt-depleted Patients

Correct volume and/or salt depletion prior to initiation of benazepril therapy or initiate therapy under close medical supervision using lower initial dosage.1

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 or amlodipine, importance of advising patients of important precautionary information about the concomitant agent.11 12

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

  • Importance of reporting signs of infection (e.g., sore throat, fever).1

  • Risk of hypotension.1 Importance of informing clinicians promptly if lightheadedness or fainting occurs.1

  • Importance of adequate fluid intake; risk of volume depletion with excessive perspiration, dehydration, vomiting, or diarrhea.1

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

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (including salt substitutes containing potassium), as well as any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • 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

Novartis

10 mg*

Benazepril Hydrochloride Tablets

Lotensin

Novartis

20 mg*

Benazepril Hydrochloride Tablets

Lotensin

Novartis

40 mg*

Benazepril Hydrochloride Tablets

Lotensin

Novartis

* 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)

Novartis

10 mg with Hydrochlorothiazide 12.5 mg*

Benazepril with Hydrochlorothiazide Tablets

Lotensin HCT (scored)

Novartis

20 mg with Hydrochlorothiazide 12.5 mg*

Benazepril with Hydrochlorothiazide Tablets

Lotensin HCT (scored)

Novartis

20 mg with Hydrochlorothiazide 25 mg*

Benazepril with Hydrochlorothiazide Tablets

Lotensin HCT (scored)

Novartis

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