Benazepril

1. INDICATIONS AND USAGE Lotensin ® is 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.

Benazepril and benazeprilat inhibit angiotensin-converting enzyme (ACE) in human subjects and animals. Benazeprilat has much greater ACE inhibitory activity than does benazepril. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decreased aldosterone secretion. The latter decrease may result in a small increase of serum potassium. Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity.

2. DOSAGE AND ADMINISTRATION Adult Patients: Initiate with 10 mg once daily (or 5 mg if patients is on diuretic). Titrate to 40 mg daily based on blood pressure response. Pediatric patients age 6 years and above with glomerular filtration rate (GFR) >30 mL/min/1.73 m 2: Initiate with 0.2 mg/kg once daily. Maximum dose is 0.6 mg/kg once daily. Renal Impairment: Initiate with 5 mg once daily in patients with GFR <30 mL/min/1.73 m 2 (serum creatinine >3 mg/dL)

4. CONTRAINDICATIONS Lotensin is 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 Lotensin is contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer Lotensin within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor. Do not coadminister aliskiren with angiotensin receptor blockers, ACE inhibitors, including Lotensin in patients with diabetes. Angioedema or history of hereditary or idiopathic angioedema. Hypersensitivity. Coadministration with aliskiren in patients with diabetes

Boxed warning (fetal toxicity): When pregnancy is detected, discontinueLotensin as soon as possible. Drugs thatactdirectlyon the renin-angiotensin system can causeinjury and death to the developing fetus. WARNING-FETAL TOXICITY See full prescribinginformation forcomplete boxed warning. When pregnancyis detected, discontinue Lotensin as soon as possible. 5. WARNINGS AND PRECAUTIONS Angioedema: Discontinue Lotensin and treat appropriately. Monitor renal function periodically. Monitor blood pressure after initiation. Hyperkalemia: Monitor serum potassium periodically. Hepatic toxicity: Monitor for jaundice or signs of liver failure.

6. ADVERSE REACTIONS 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. Lotensin 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 Lotensin 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. patients treated with Lotensin and in 3% of patients treated with placebo.

7. DRUG INTERACTIONS Diuretics: Excessive drop in blood pressure. Antidiabetics: Increased risk of hypoglycemia. NSAIDS: Increased risk of renal impairment and loss of antihypertensive efficacy. Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension and hyperkalemia. Lithium: Symptoms of lithium toxicity. Neprilysin Inhibitor: Increased risk of angioedema. Gold: Nitritoid reactions

Do not store above 86°F (30ºC). Protect from moisture.