amlodipine-benazepril 5-20 mg generic lotrel

Uses

Benazepril hydrochloride is used alone or in combination with other classes of antihypertensive agents (e.g., thiazide diuretics) in the management of hypertension.

Hypertension

Benazepril is used alone or in combination with other classes of antihypertensive agents in the management of hypertension. ACE inhibitors are considered one of several preferred antihypertensive drugs for the initial management of hypertension; other options include angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics. 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. ACE inhibitors may be particularly useful in the management of hypertension in patients with certain coexisting conditions such as heart failure, ischemic heart disease, diabetes mellitus, chronic kidney disease, or cerebrovascular disease or following myocardial infarction. and in

In general, black hypertensive patients tend to respond better to monotherapy with thiazide diuretics or calcium-channel blockers than to monotherapy with ACE inhibitors. Although ACE inhibitors have lowered blood pressure in all races studied, monotherapy with these agents has produced a smaller reduction in blood pressure in black hypertensive patients, a population associated with low renin hypertension; however, this population difference in response does not appear to occur during combined therapy with an ACE inhibitor and a thiazide diuretic or calcium-channel blocker. In addition, ACE inhibitors appear to produce a higher incidence of angioedema in black patients than in other races. (See Race under Hypertension: Other Special Considerations for Antihypertensive Therapy, in and in .)

For additional information on the role of ACE inhibitors in the management of hypertension, and in .

Heart Failure

ACE inhibitors have been used in the management of heart failure, usually in conjunction with other agents such as cardiac glycosides, diuretics, and β-adrenergic blocking agents (β-blockers).

Current guidelines for the management of heart failure in adults generally recommend a combination of drug therapies to reduce morbidity and mortality, including neurohormonal antagonists (e.g., ACE inhibitors, angiotensin II receptor antagonists, angiotensin receptor-neprilysin inhibitors [ARNIs], β-blockers, aldosterone receptor antagonists) that inhibit the detrimental compensatory mechanisms in heart failure. Additional agents (e.g., cardiac glycosides, diuretics, sinoatrial modulators [i.e., ivabradine]) added to a heart failure treatment regimen in selected patients have been associated with symptomatic improvement and/or reduction in heart failure-related hospitalizations. Experts recommend that all asymptomatic patients with reduced left ventricular ejection fraction (LVEF) (American College of Cardiology Foundation [ACCF]/American Heart Association [AHA] stage B heart failure) receive therapy with an ACE inhibitor and β-blocker to prevent symptomatic heart failure and to reduce morbidity and mortality. If ACE inhibitors are not tolerated, then an angiotensin II receptor antagonist is recommended as alternative therapy. In patients with prior or current symptoms of chronic heart failure with reduced LVEF (ACCF/AHA stage C heart failure), ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend inhibition of the renin-angiotensin-aldosterone (RAA) system with an ACE inhibitor, angiotensin II receptor antagonist, or ARNI in conjunction with a β-blocker, and an aldosterone antagonist in selected patients, to reduce morbidity and mortality. While ACE inhibitors have been the preferred drugs for inhibition of the RAA system because of their established benefits in patients with heart failure and reduced ejection fraction, some evidence indicates that therapy with sacubitril/valsartan, an ARNI, may be more effective than ACE inhibitor therapy (enalapril) in reducing cardiovascular death and heart failure-related hospitalization in such patients. ACCF, AHA, and HFSA recommend that patients with chronic symptomatic heart failure and reduced LVEF (New York Heart Association [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. However, in patients in whom an ARNI is not appropriate, continued use of an ACE inhibitor for all classes of heart failure with reduced ejection fraction remains strongly advised. In patients in whom an ARNI or ACE inhibitor is not appropriate, an angiotensin II receptor antagonist may be used. For additional information on the use of ACE inhibitors in the management of heart failure, see Uses: Heart Failure, in and in .

Diabetic Nephropathy

Both ACE inhibitors and angiotensin II receptor antagonists have been shown to slow the rate of progression of renal disease in patients with diabetes mellitus and persistent albuminuria, and use of a drug from either class is recommended in such patients with modestly elevated (30-300 mg/24 hours) or higher (exceeding 300 mg/24 hours) levels of urinary albumin excretion. The usual precautions of ACE inhibitor or angiotensin II receptor antagonist therapy in patients with substantial renal impairment should be observed. For additional information on the use of ACE inhibitors in the treatment of diabetic nephropathy, see

Dosage and Administration

Administration

Benazepril hydrochloride is administered orally.

For adult or pediatric patients unable to swallow tablets or those children for whom the daily dose does not correspond exactly to the strength of commercially available tablets, benazepril hydrochloride may be administered orally as an extemporaneously prepared suspension.

An extemporaneous suspension containing benazepril hydrochloride 2 mg/mL can be prepared in the following manner. First, 75 mL of suspending vehicle (Ora-Plus) is added to an amber polyethylene terephthalate (PET) bottle containing fifteen 20-mg tablets of benazepril hydrochloride, and the contents are shaken for at least 2 minutes. The concentrated suspension should be allowed to stand for at least 60 minutes following reconstitution, and then should be shaken for an additional minute. The concentrated suspension of benazepril hydrochloride should be diluted with 75 mL of syrup (Ora-Sweet), and the container then shaken to disperse the ingredients. The suspension should be shaken before dispensing each dose. The extemporaneous suspension is stable for 30 days when stored at 2-8°C.

Dosage

Dosage of benazepril hydrochloride must be adjusted according to patient tolerance and response. Because of the risk of inducing hypotension, initiation of benazepril therapy requires consideration of recent and current antihypertensive therapy, the extent of blood pressure elevation, sodium intake, fluid status, and other clinical circumstances. If blood pressure is not controlled adequately with the ACE inhibitor alone, a low dosage of a diuretic may be added.

Hypertension

Benazepril Therapy

For the management of hypertension in adults not receiving a diuretic, the usual initial dosage of benazepril hydrochloride is 10 mg once daily. In patients currently receiving a diuretic, an initial benazepril hydrochloride dosage of 5 mg daily is recommended. If the blood pressure response diminishes toward the end of the dosing interval during once-daily administration, increasing the dosage or giving the drug in divided doses daily should be considered; the divided-dose regimen has been more effective in controlling trough (pre-dose) blood pressure than the same dose given once daily.

The usual maintenance dosage in adults is 20-40 mg daily, given as a single dose or in 2 divided doses daily. Higher dosages (i.e., 80 mg daily) reportedly have resulted in increased response; however, there is limited experience with such dosages. The safety and efficacy of dosages exceeding 80 mg daily have not been established. If blood pressure is not controlled with benazepril alone, a second antihypertensive agent (e.g., diuretic) may be added.

For the management of hypertension in children 6 years of age or older, the usual initial dosage of benazepril hydrochloride is 0.2 mg/kg (up to 10 mg) once daily. Dosage may be adjusted until the desired blood pressure goal is achieved. The safety and efficacy of dosages exceeding 0.6 mg/kg or in excess of 40 mg daily have not been established in pediatric patients.

The panel members appointed to the Eighth Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8 expert panel) state that evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) should be used when available to determine target dosages of antihypertensive agents. Target dosages of antihypertensive agents generally can be achieved within 2-4 weeks, but it may take up to several months.

Antihypertensive therapy should be titrated until goal blood pressure is achieved. If an adequate blood pressure response is not achieved with benazepril monotherapy, another antihypertensive agent with demonstrated benefit may be added; if goal blood pressure is still not achieved with the use of 2 antihypertensive agents at optimal dosages, a third drug may be added. In patients who experience intolerable adverse effects with benazepril, dosage reduction should be considered; if adverse effects worsen or fail to resolve, it may be necessary to discontinue the ACE inhibitor and initiate another class of antihypertensive agent.

Benazepril/Hydrochlorothiazide Fixed-combination Therapy

The manufacturers state that therapy with the commercially available preparations containing benazepril hydrochloride in fixed combination with hydrochlorothiazide should only be initiated in adults after an adequate response is not achieved with benazepril or hydrochlorothiazide monotherapy. Alternatively, the fixed combination containing benazepril with hydrochlorothiazide may be used in patients who had been receiving the drugs separately and in whom dosage of the individual drugs has been adjusted. Patients whose blood pressure is not adequately controlled with benazepril or hydrochlorothiazide monotherapy may receive the fixed combination containing 10 mg of benazepril hydrochloride and 12.5 mg of hydrochlorothiazide initially. The maximum recommended dosage of the fixed combination preparation is 20 mg of benazepril hydrochloride and 25 mg of hydrochlorothiazide once daily.

Benazepril/Amlodipine Fixed-combination Therapy

The manufacturer states that therapy with the commercially available preparations containing benazepril hydrochloride in fixed combination with amlodipine should only be initiated in adults in whom an adequate response has not been achieved with benazepril or amlodipine monotherapy. Alternatively, such fixed combinations may be used if amlodipine dosages necessary for adequate response have been associated with development of edema. The fixed combination containing benazepril hydrochloride with amlodipine also may be used in patients who have been receiving the drugs separately, provided that the optimum dosage corresponds to the ratio in the commercial fixed-combination preparation. Dosage of the fixed combination containing benazepril hydrochloride and amlodipine should be adjusted according to the patient's response. The manufacturer states that when the fixed combinations containing 10-40 mg of benazepril hydrochloride and 2.5-10 mg of amlodipine have been used, the antihypertensive effects of these combinations have increased with increasing dosages of amlodipine regardless of race; in addition, antihypertensive effects increased with increasing dosages of benazepril in nonblack patients. The addition of benazepril to amlodipine therapy usually does not provide additional antihypertensive effects in black patients. The maximum recommended dosage of the fixed combination of benazepril hydrochloride and amlodipine is 40 mg of benazepril hydrochloride and 10 mg of amlodipine daily.

Blood Pressure Monitoring and Treatment Goals

Careful monitoring of blood pressure during initial titration or subsequent upward adjustment in dosage of benazepril is recommended.

The goal of hypertension management and prevention is to achieve and maintain optimal control of blood pressure; specific target levels of blood pressure should be individualized based on consideration of multiple factors, including patient age and comorbidities, and the currently available evidence from clinical studies.

Special Populations

If benazepril is used in patients with impaired renal function, dosage must be modified in response to the degree of renal impairment, and, as with other ACE inhibitors, the theoretical risk of neutropenia must be considered. In adults with creatinine clearances less than 30 mL/minute per 1.73 m or serum creatinine concentrations exceeding 3 mg/dL, the recommended initial dosage of benazepril hydrochloride is 5 mg once daily. If an adequate response is not achieved, dosage may be increased gradually until blood pressure is controlled or a maximum benazepril hydrochloride dosage of 40 mg daily is reached. There are insufficient data to date to make recommendations regarding dosage of benazepril hydrochloride in children with creatinine clearances less than 30 mL/minute per 1.73 m, and the manufacturer recommends that benazepril therapy not be used in such patients. Safety and efficacy of the fixed combination containing benazepril and hydrochlorothiazide have not been established in patients with severe renal impairment. Use of the commercially available preparation containing benazepril in combination with amlodipine is not recommended for patients with severe renal impairment.

Because of the greater frequency of decreased renal function in geriatric patients, the manufacturer states that dosage selection should be made with care and that it may be useful to monitor renal function in such patients receiving benazepril.

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

Cautions

Contraindications

Benazepril is contraindicated in patients with known hypersensitivity to benazepril, other angiotensin-converting enzyme (ACE) inhibitors, or any ingredient in the formulation; those with a history of angioedema with or without prior ACE inhibitor therapy; and in patients with diabetes mellitus who are receiving aliskiren therapy. Benazepril also is contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril) and should not be administered within 36 hours of switching to or from sacubitril/valsartan.

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

Drugs that act directly on the renin-angiotensin system (e.g., ACE inhibitors, angiotensin II receptor antagonists) reduce fetal renal function and can cause fetal and neonatal morbidity and mortality when used during pregnancy. Such potential risks of these drugs occur throughout pregnancy, especially during the second and third trimesters. ACE inhibitors also have been reported to increase the risk of major congenital malformations when administered during the first trimester of pregnancy. Potential neonatal effects include skull hypoplasia, anuria, hypotension, renal failure, and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. ACE inhibitors (e.g., benazepril) should be discontinued as soon as possible when pregnancy is detected, unless continued use is considered lifesaving. Nearly all women can be transferred successfully to alternative therapy for the remainder of pregnancy. For additional information on the risk of ACE inhibitors during pregnancy, and in .

Sensitivity Reactions

Sensitivity reactions, including anaphylactoid reactions and angioedema (including laryngeal angioedema and tongue edema), are potentially fatal. Head and neck angioedema have occurred in patients receiving an ACE inhibitor and have been reported at a higher rate in black patients compared with patients of other races. Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor. In addition, concomitant use of an ACE inhibitor and a mammalian target of rapamycin (mTOR) inhibitor (e.g., everolimus, sirolimus, temsirolimus) or a neprilysin inhibitor (e.g., sacubitril) may increase the risk of angioedema; patients should be monitored for signs of angioedema during such concomitant therapy. Head and neck angioedema involving the tongue, glottis, or larynx may cause airway obstruction, especially in those with a history of airway surgery. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, ACE inhibitors (e.g., benazepril) should be discontinued promptly and appropriate therapy (e.g., epinephrine) and monitoring initiated until complete and sustained resolution of manifestations of angioedema has occurred.

Intestinal angioedema (occasionally without a prior history of facial angioedema or elevated serum levels of complement 1 [C1] esterase inhibitor) also has been reported in patients receiving ACE inhibitors. Intestinal angioedema, which frequently presents as abdominal pain (with or without nausea or vomiting), usually is diagnosed by abdominal CT scan, ultrasound, or surgery; symptoms usually have resolved after discontinuance of the ACE inhibitor. Intestinal angioedema should be considered in the differential diagnosis of patients who develop abdominal pain during therapy with an ACE inhibitor.

Life-threatening anaphylactoid reactions have been reported in at least 2 patients receiving ACE inhibitors while undergoing desensitization treatment with hymenoptera venom. When ACE inhibitors were temporarily discontinued before desensitization with the venom, anaphylactoid reactions did not recur; however, such reactions recurred after inadvertent rechallenge. Anaphylactoid reactions also have been reported following initiation of hemodialysis that used a high-flux membrane in patients receiving an ACE inhibitor. In addition, anaphylactoid reactions have been reported in patients undergoing low-density lipoprotein (LDL) apheresis with dextran sulfate absorption. In such patients, dialysis must be stopped immediately, and aggressive treatment for anaphylactoid reactions must be initiated. Antihistamine treatment has been ineffective in the alleviation of symptoms in these situations. In these patients, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive drug.

Other Warnings and Precautions

Renal Effects

Deterioration of renal function, including acute renal failure, may occur in patients receiving ACE inhibitor therapy. Patients whose renal function depends on the activity of the renin-angiotensin system, particularly those with unilateral or bilateral renal artery stenosis, chronic kidney disease, severe congestive heart failure, myocardial infarction (MI), or volume depletion, may be at particular risk of developing acute renal failure while receiving benazepril. Increases in BUN and serum creatinine concentrations have occurred in patients with unilateral or bilateral renal artery stenosis; such increases generally are reversible following discontinuance of benazepril and/or diuretic therapy. Renal function should be monitored periodically in patients receiving benazepril. Withholding or discontinuance of therapy should be considered in patients who develop clinically important decreases in renal function while receiving benazepril.

Cardiovascular Effects

Symptomatic hypotension may occur; patients at particular risk include those with heart failure with systolic blood pressure less than 100 mm Hg, ischemic heart disease, cerebrovascular disease, hyponatremia, high-dose diuretic therapy, renal dialysis, or severe volume and/or salt depletion of any etiology. Symptomatic hypotension also may occur in patients with severe aortic stenosis. Volume and/or salt depletion should be corrected before starting benazepril therapy.

Excessive hypotension may occur in patients with heart failure (with or without associated renal impairment), which may be associated with oliguria and/or progressive azotemia and, rarely, acute renal failure and/or death. In patients with heart failure, benazepril therapy should be started under close medical supervision and patients should be followed closely for at least 2 weeks after initiation of benazepril or diuretic therapy or dosage adjustment of either drug. (See Dosage and Administration: Dosage.) Benazepril therapy should be avoided in patients who have hemodynamic instability following MI.

If hypotension occurs, the patient should be placed in the supine position, and if necessary, an IV infusion of 0.9% sodium chloride injection to expand fluid volume may be administered. Benazepril therapy usually may be continued following restoration of blood pressure and volume.

Hypotension may occur in patients undergoing major surgery or during anesthesia with agents that produce hypotension due to ACE inhibitor blockade of angiotensin II formation secondary to compensatory renin release. Hypotension in such patients may be corrected by volume expansion.

Effects on Potassium

Hyperkalemia can develop in patients receiving drugs that inhibit the renin-angiotensin system, especially in those 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). Serum potassium concentrations should be monitored periodically in patients receiving benazepril.

Hepatic Effects

An ACE inhibitor-associated clinical syndrome manifested initially by cholestatic jaundice has occurred; the syndrome may progress to fulminant hepatic necrosis and is potentially fatal. Patients receiving an ACE inhibitor, including benazepril, who develop jaundice or marked elevations of hepatic enzymes should discontinue the drug and receive appropriate monitoring and medical follow-up.

Hematologic Effects

Neutropenia/agranulocytosis, particularly in patients with renal impairment (especially those with concomitant collagen vascular disease), have been reported with another ACE inhibitor (captopril). Data are insufficient to rule out a similar incidence of agranulocytosis with benazepril in patients without prior reactions to other ACE inhibitors. Monitoring of leukocyte counts in patients with collagen vascular disease, especially if renal impairment exists, should be considered.

Respiratory Effects

Persistent, nonproductive cough has been reported with all ACE inhibitors; this effect resolves after drug discontinuance. ACE inhibitor-induced cough should be considered in the differential diagnosis of patients who develop cough during benazepril therapy.

Use of Fixed Combinations

When hydrochlorothiazide, amlodipine, or other drugs are used in fixed combination with benazepril, the usual cautions, precautions, and contraindications associated with these other drugs must be considered in addition to those associated with benazepril.

Specific Populations

Pregnancy

Category D. Benazepril can cause fetal and neonatal morbidity and mortality when administered to a pregnant woman. Benazepril should be discontinued as soon as possible when pregnancy is detected.(See Fetal/Neonatal Morbidity and Mortality under Warnings/Precautions: Warnings, in Cautions.)

Lactation

Benazepril and benazeprilat are distributed into human milk in minimal amounts. Because of the unknown effects of benazepril or benazeprilat in nursing infants, a decision should be made whether to discontinue nursing or benazepril, taking into account the importance of the drug(s) to the woman.

Pediatric Use

If oliguria or hypotension occurs in neonates with a history of in utero exposure to benazepril, blood pressure and renal function should be supported; exchange transfusions or dialysis may be required.(See Fetal/Neonatal Morbidity and Mortality under Warnings/Precautions: Warnings, in Cautions.) Benazepril, which crosses the placenta, can theoretically be removed from the neonatal circulation by these means. There are occasional reports of benefit from these maneuvers with another ACE inhibitor; however, experience is limited.

Safety and efficacy of benazepril have not been established in children younger than 6 years of age and in pediatric patients with creatinine clearances of less than 30 mL/minute. Safety and efficacy of benazepril in fixed combination with amlodipine or hydrochlorothiazide have not been established in children. The long-term effects of benazepril on growth and development in children have not been studied. Although the safety profile of benazepril in pediatric patients is similar to that in adults, because of the potential for adverse effects on kidney development, ACE inhibitors should not be administered to pediatric patients younger than 1 year of age.

Geriatric Use

No substantial differences in safety and efficacy have been observed in geriatric patients relative to younger adults, but increased sensitivity cannot be ruled out.

Because geriatric patients are more likely to have decreased renal function, dosage should be selected cautiously; it may be useful to monitor renal function in such patients.

Renal Impairment

Renal function may decrease with ACE inhibitor therapy in susceptible patients. Benazepril should be used with caution in those with renal impairment.

Benazepril in fixed combination with amlodipine is not recommended in patients with severe renal impairment; the recommended daily dosage of benazepril hydrochloride in such patients is 5 mg, which is not available in this combination preparation. (See Dosage and Administration: Special Populations and also Renal Effects under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

Black Patients

ACE inhibitors are not as effective and are associated with a higher incidence of angioedema in black patients compared with patients of other races.(See Uses: Hypertension.)

Common Adverse Effects

Adverse effects reported in at least 2% of patients receiving benazepril and at an incidence more than 1% greater than that with placebo include headache, dizziness, somnolence, and postural dizziness. Adverse effects reported in greater than 1% of patients receiving benazepril in fixed combination with hydrochlorothiazide and possibly or probably study drug-related include dizziness, fatigue, postural dizziness, headache, cough, hypertonia, vertigo, nausea, impotence, and somnolence. Adverse effects reported in greater than 1% of patients receiving benazepril in fixed combination with amlodipine and possibly or probably drug-related include cough, headache, dizziness, and edema.

Drug Interactions

Antidiabetic Agents

Concomitant administration of benazepril and insulin or oral antidiabetic agents may increase the risk of hypoglycemia. Patients receiving these drugs concomitantly should be informed of the possibility of hypoglycemia and monitored appropriately; dosage of the antidiabetic drug may need to be altered.

Antihypertensive Agents and Drugs that Block the Renin-Angiotensin System

Benazepril potentiates the antihypertensive effect of other antihypertensive agents and drugs that block the renin-angiotensin system (e.g., curare derivatives, guanethidine, methyldopa, β-adrenergic blocking agents, vasodilators, calcium-channel blocking agents, ACE inhibitors, angiotensin II receptor antagonists, direct renin inhibitors [DRIs]).

Dual blockade of the renin-angiotensin system with angiotensin II receptor antagonists, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared with monotherapy. Most patients receiving the combination of 2 renin-angiotensin system blocking agents do not obtain additional benefit compared with monotherapy. Concomitant use of 2 renin-angiotensin system blocking agents generally should be avoided. Blood pressure, renal function, and electrolytes should be closely monitored in patients receiving benazepril with other agents that affect the renin-angiotensin system.

Diuretics

Potential pharmacokinetic and pharmacologic interaction (hypotensive effect).

Drugs Increasing Serum Potassium Concentration

Potential pharmacologic interaction (additive hyperkalemic effect). Includes potassium-sparing diuretics, potassium supplements, and other drugs that can cause hyperkalemia.(See Effects on Potassium under Warnings/Precautions: Cautions: Other Warnings and Precautions, in Cautions.)

Gold

Nitritoid reactions (e.g., facial flushing, nausea, vomiting, hypotension) have been reported rarely in patients receiving concomitant therapy with injectable gold (sodium aurothiomalate) and an ACE inhibitor.

Lithium

Potential pharmacokinetic interaction (increased lithium concentrations and clinical toxicity). Lithium toxicity usually is reversible following discontinuance of lithium or benazepril. Serum lithium concentrations should be monitored during such concomitant use.

Mammalian Target of Rapamycin Inhibitors

Concomitant use of an ACE inhibitor and a mammalian target of rapamycin (mTOR) inhibitor (e.g., everolimus, sirolimus, temsirolimus) may increase the risk of angioedema.(See Sensitivity Reactions under Cautions: Warnings/Precautions.)

Neprilysin Inhibitors

Concomitant use of benazepril and a neprilysin inhibitor (e.g., sacubitril) may increase the risk for angioedema.(See Sensitivity Reactions under Cautions: Warnings/Precautions.)

Nonsteroidal Anti-inflammatory Agents

In geriatric patients, patients who are volume depleted (including those who are receiving diuretic therapy), or in patients with compromised renal function, concomitant use of nonsteroidal anti-inflammatory agents (NSAIAs), including cyclooxygenase-2 (COX-2) inhibitors, with ACE inhibitors may result in the deterioration of renal function, including possible renal failure. These effects are usually reversible. Renal function should be monitored periodically in patients receiving concomitant benazepril and NSAIA therapy.