Benazepril: uses, appearance and warnings

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. Benazepril Hydrochloride Tablets are an angiotensin-converting enzyme (ACE) inhibitor 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. ( 1 )

Tablets: 5 mg, 10 mg, 20 mg, and 40 mg • Each 5 mg tablet is light yellow, capsule-shaped, film-coated, debossed with “ANI” on one side and “524” on the other. • Each 10 mg tablet is dark yellow, capsule-shaped, film-coated, debossed with “ANI” on one side and “525” on the other. • Each 20 mg tablet is light pink, capsule-shaped, film-coated, debossed with “ANI” on one side and “526” on the other. • Each 40 mg tablet is dark pink capsule-shaped, film-coated, debossed with “ANI” on one side and “527” on the other. • Tablets: 5 mg, 10 mg, 20 mg, 40 mg

Benazepril Hydrochloride Tablets USP, 5 mg are light yellow, capsule-shaped, film-coated tablets, debossed with “ANI” on one side and “524” on the other. The are available in: Bottles of 100 tablets NDC 62559-524-01 Bottles of 500 tablets NDC 62559-524-05 Benazepril Hydrochloride Tablets USP, 10 mg are dark yellow, capsule-shaped, film-coated tablets, debossed with “ANI” on one side and “525” on the other. The are available in: Bottles of 100 tablets NDC 62559-525-01 Bottles of 500 tablets NDC 62559-525-05 Benazepril Hydrochloride Tablets USP, 20 mg are light pink, capsule-shaped, film-coated tablets, debossed with “ANI” on one side and “526” on the other. The are available in: Bottles of 100 tablets NDC 62559-526-01 Bottles of 500 tablets NDC 62559-526-05 Benazepril Hydrochloride Tablets USP, 40 mg are dark pink, capsule-shaped, film-coated tablets, debossed with “ANI” on one side and “527” on the other. The are available in: Bottles of 100 tablets NDC 62559-527-01 Bottles of 500 tablets NDC 62559-527-05 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from moisture. Dispense in a tight, light-resistant container as defined in the USP.

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 [see Warnings and Precautions (5.2) ] . Do not coadminister aliskiren with angiotensin receptor blockers, ACE inhibitors, including; Benazepril Hydrochloride Tablets in patients with diabetes [see Drug Interactions (7.4) ] . • Angioedema or history of hereditary or idiopathic angioedema ( 4 ) • Hypersensitivity ( 4 ) • Coadministration with aliskiren in patients with diabetes ( 4 )

• Angioedema: Discontinue benazepril hydrochloride and treat appropriately. ( 5.2 ) • Monitor renal function periodically. ( 5.3 ) • Monitor blood pressure after initiation. ( 5.4 ) • Hyperkalemia: Monitor serum potassium periodically. ( 5.5 ) • Hepatic toxicity: Monitor for jaundice or signs of liver failure. ( 5.6 ) 5.1. Fetal Toxicity Benazepril hydrochloride 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 Hydrochloride Tablets as soon as possible [see Use in Specific Populations (8.1) ] . 5.2. Angioedema and Anaphylactoid Reactions Angioedema 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 hydrochloride. Patients with involvement of the tongue, glottis or larynx are likely to experience airway obstruction, especially those with a history of airway surgery. Benazepril hydrochloride 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 [see Contraindications (4) ] . ACE inhibitors have been associated with a higher rate of angioedema in Black than in non-Black patients. 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 [see Drug Interactions (7.7) ] . Intestinal 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 Anaphylactoid Reactions During Desensitization Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. Anaphylactoid Reactions During Dialysis 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. 5.3. Impaired Renal Function Monitor renal function periodically in patients treated with benazepril hydrochloride. Changes in renal function, including acute renal failure, can be caused by drugs that inhibit the renin-angiotensin system. Patients whose renal function may depend on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, post-myocardial infarction, or volume depletion) may be at particular risk of developing acute renal failure on benazepril hydrochloride. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on benazepril hydrochloride. 5.4. Hypotension Benazepril hydrochloride can cause symptomatic hypotension, sometimes complicated by oliguria, progressive azotemia, acute renal failure, or death. Patients at risk of excessive hypotension include those with the following conditions or characteristics: heart failure with systolic blood pressure below 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. In such patients, follow closely for the first 2 weeks of treatment and whenever the dose of benazepril or diuretic is increased. Avoid use of benazepril hydrochloride in patients who are hemodynamically unstable after acute MI. Surgery/Anesthesia In patients undergoing major surgery or during anesthesia with agents that produce hypotension, benazepril hydrochloride may block angiotensin II formation secondary to compensatory renin release. If hypotension occurs, correct by volume expansion. 5.5. Hyperkalemia Serum potassium should be monitored periodically in patients receiving benazepril hydrochloride. Drugs that inhibit the renin-angiotensin system can cause hyperkalemia. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements and/or potassium-containing salt substitutes [see Drug Interactions (7.1) ] . 5.6. Hepatic Failure ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. …

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Benazepril hydrochloride has been evaluated for safety in over 6000 patients with hypertension; over 700 of these patients were treated for at least one year. The overall incidence of reported adverse events was similar in benazepril hydrochloride and placebo patients. The reported side effects were generally mild and transient, and there was no relation between side effects and age, duration of therapy, or total dosage within the range of 2 to 80 mg. Discontinuation of therapy because of a side effect was required in approximately 5% of U.S. …

• Diuretics: Excessive drop in blood pressure ( 7.1 ) • Antidiabetics: Increased risk of hypoglycemia ( 7.2 ) • NSAIDS: Increased risk of renal impairment and loss of antihypertensive efficacy ( 7.3 ) • Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension and hyperkalemia ( 7.4 ) • Lithium: Symptoms of lithium toxicity ( 7.6 ) • Neprilysin Inhibitor: Increased risk of angioedema ( 7.7 ) • Gold: Nitritoid reactions ( 7.8 ) 7.1. Diuretics Hypotension Patients on diuretics, especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with benazepril hydrochloride. …