Benazepril Hydrochloride
FDA Drug Information • Also known as: Benazepril Hydrochloride, Lotensin
- Brand Names
- Benazepril Hydrochloride, Lotensin
- Dosage Form
- POWDER
- Product Type
- BULK INGREDIENT
⚠ Boxed Warning (Black Box)
WARNING: FETAL TOXICITY When pregnancy is detected, discontinue benazepril hydrochloride tablets as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus [see Warnings and Precautions ( 5.1 )]. WARNING-FETAL TOXICITY See full prescribing information for complete boxed warning. When pregnancy is detected, discontinue benazepril hydrochloride tablets as soon as possible. ( 5.1 ) Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. ( 5.1 )
Description
11 DESCRIPTION Benazepril hydrochloride, USP is a white to off-white crystalline powder, soluble (> 100 mg/mL) in water, in ethanol, and in methanol. Its chemical name is benazepril 3-[[1-(ethoxy-carbonyl)-3-phenyl-(1S)-propyl]amino]-2,3,4,5-tetrahydro-2-oxo-1 H -1-(3S)-benzazepine-1-acetic acid monohydrochloride; its structural formula is Its empirical formula is C 24 H 28 N 2 O 5
What Is Benazepril Hydrochloride Used For?
1 INDICATIONS AND USAGE 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 is 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 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Adult Patients: Initiate with 10 mg once daily (or 5 mg if patient is on diuretic). Titrate to 40 mg daily based on blood pressure response. ( 2.1 ) 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) ( 2 .2) 2.1 Recommended Dosage ADULTS The recommended initial dose for patients not receiving a diuretic is 10 mg once a day. The usual maintenance dosage range is 20 to 40 mg per day administered as a single dose or in two equally divided doses. A dose of 80 mg gives an increased response, but experience with this dose is limited. The divided regimen was more effective in controlling trough (pre-dosing) blood pressure than the same dose given as a once-daily regimen. Use with diuretics in adults The recommended starting dose of benazepril hydrochloride tablets in a patient on a diuretic is 5 mg once daily. If blood pressure is not controlled with benazepril hydrochloride alone, a low dose of diuretic may be added. PEDIATRIC PATIENTS 6 YEARS OF AGE AND OLDER The recommended starting dose for pediatric patients is 0.2 mg/kg once per day. Titrate as needed to 0.6 mg/kg once per day. Doses above 0.6 mg/kg (or in excess of 40 mg daily) have not been studied in pediatric patients. Benazepril hydrochloride tablets are not recommended in pediatric patients less than 6 years of age or in pediatric patients with GFR less than 30 mL/min/1.73 m 2 [see Use in Specific Populations ( 8.3 )]. 2.2 Dose Adjustment for Renal Impairment For adults with a GFR < 30 mL/min/1.73 m 2 (serum creatinine > 3 mg/dL), the recommended initial dose is 5 mg benazepril hydrochloride tablets once daily. Dosage may be titrated upward until blood pressure is controlled or to a maximum total daily dose of 40 mg. Benazepril hydrochloride tablets can also worsen renal function [see Warnings and Precautions ( 5.3 )]. 2.3 Preparation of Suspension (for 150 mL of a 2 mg/mL Suspension) Add 75 mL of Ora-Plus ® * oral suspending vehicle to an amber polyethylene terephthalate (PET) bottle containing fifteen benazepril hydrochloride 20 mg tablets, and shake for at least two minutes. Allow the suspension to stand for a minimum of 1 hour. After the standing time, shake the suspension for a minimum of one additional minute. Add 75 mL of Ora-Sweet ® * oral syrup vehicle to the bottle and shake the suspension to disperse the ingredients. The suspension should be refrigerated at 2° to 8°C (36° to 46°F) and can be stored for up to 30 days in the PET bottle with a child-resistant screw-cap closure. Shake the suspension before each use. *Ora-Plus ® and Ora-Sweet ® are registered trademarks of Paddock Laboratories, Inc. Ora Plus ® contains carrageenan, citric acid, methylparaben, microcrystalline cellulose, carboxymethylcellulose sodium,...
Side Effects (Adverse Reactions)
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. 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. patients treated with benazepril hydrochloride and in 3% of patients treated with placebo. The most common reasons for discontinuation were headache (0.6%) and cough (0.5%). Adverse reactions seen in at least 1% greater frequency in patients treated with benazepril hydrochloride than placebo were headache (6% vs. 4%), dizziness (4% vs. 2%), somnolence (2% vs. 0%) and postural dizziness (2% vs. 0%). Adverse reactions reported in controlled clinical trials (less than 1% more on benazepril than on placebo), and rarer events seen in post-marketing experience, include the following (in some, a causal relationship to drug use is uncertain): Dermatologic: Stevens-Johnson syndrome, pemphigus, apparent hypersensitivity reactions (manifested by dermatitis, pruritus, or rash), photosensitivity, and flushing. Gastrointestinal: Nausea, pancreatitis, constipation, gastritis, vomiting, and melena. Hematologic: Thrombocytopenia and hemolytic anemia. Neurologic/Psychiatric: Anxiety, decreased libido, hypertonia, insomnia, nervousness, and paresthesia. Other: Fatigue, asthma, bronchitis, dyspnea, sinusitis, urinary tract infection, frequent urination, infection, arthritis, impotence, alopecia, arthralgia, myalgia, asthenia, sweating. Laboratory Abnormalities : Elevations of uric acid, blood glucose, serum bilirubin, and liver enzymes [see Warnings and Precautions S ( 5 )] have been reported, as have incidents of hyponatremia, electrocardiographic changes, eosinophilia, and proteinuria. The most common adverse reactions leading to discontinuation were headache (0.6%) and cough (0.5%) ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Solco Healthcare US, LLC at 1-866-257-2597 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Drug Interactions
7 DRUG INTERACTIONS Diuretics: Excessive drop in blood pressure ( 7.1 ) Antidiabetics: Increased risk of hypoglycaemia ( 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. The possibility of hypotensive effects with benazepril hydrochloride can be minimized by either discontinuing or decreasing the dose of diuretic prior to initiation of treatment with benazepril hydrochloride [see Dosage and Administration ( 2.1 )]. Hyperkalemia Potassium-sparing diuretics (spironolactone, amiloride, triamterene, and others) can increase the risk of hyperkalemia. Therefore, if concomitant use of such agents is indicated, monitor the patient’s serum potassium frequently. Benazepril hydrochloride attenuates potassium loss caused by thiazide-type diuretics. 7.2 Antidiabetics Concomitant administration of benazepril hydrochloride and antidiabetic medicines (insulins, oral hypoglycemic agents) may increase the risk of hypoglycemia. 7.3 Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including benazepril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving benazepril and NSAID therapy. The antihypertensive effect of ACE inhibitors, including benazepril, may be attenuated by NSAIDs. 7.4 Dual Blockade of the Renin-Angiotensin System (RAS) Dual Blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on benazepril hydrochloride and other agents that affect the RAS. Do not coadminister aliskiren with benazepril hydrochloride in patients with diabetes. Avoid use of aliskiren with benazepril hydrochloride in patients with renal impairment (GFR < 60 mL/min). 7.5 Mammalian Target of Rapamycin (mTOR) Inhibitors Patients...
Contraindications
4 CONTRAINDICATIONS 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 ) Co-administration with aliskiren in patients with diabetes ( 4 )
Overdosage
10 OVERDOSAGE Single oral doses of 3 g/kg benazepril were associated with significant lethality in mice. Rats, however, tolerated single oral doses of up to 6 g/kg. Reduced activity was seen at 1 g/kg in mice and at 5 g/kg in rats. Human overdoses of benazepril have not been reported, but the most common manifestation of human benazepril overdosage is likely to be hypotension, for which the usual treatment would be intravenous infusion of normal saline solution. Hypotension can be associated with electrolyte disturbances and renal failure. Benazepril is only slightly dialyzable, but consider dialysis to support patients with severely impaired renal function [see Warnings and Precautions ( 5.3 )]. If ingestion is recent, consider activated charcoal. Consider gastric decontamination (e.g., vomiting, gastric lavage) in the early period after ingestion. Monitor for blood pressure and clinical symptoms. Supportive management should be employed to ensure adequate hydration and to maintain systemic blood pressure. In the case of marked hypotension, infuse physiological saline solution; as needed, consider vasopressors (e.g., catecholamines i.v.).
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Benazepril hydrochloride tablets, USP, 5 mg, are round, white, film-coated tablets, debossed “S” on one side and “341” on the other side, packaged as follows: NDC 51407-462-01 bottle of 100 tablets (with desiccant) NDC 51407-462-05 bottle of 500 tablets (with desiccant) Benazepril hydrochloride tablets, USP, 10 mg, are round, red, film-coated tablets, debossed “S” on one side and “342” on the other side, packaged as follows: NDC 51407-463-01 bottle of 100 tablets (with desiccant) NDC 51407-463-05 bottle of 500 tablets (with desiccant) Benazepril hydrochloride tablets, USP, 20 mg, are round, grey, film-coated tablets, debossed “S” on one side and “343” on the other side, packaged as follows: NDC 51407-464-01 bottle of 100 tablets (with desiccant) NDC 51407-464-05 bottle of 500 tablets (with desiccant) Benazepril hydrochloride tablets, USP, 40 mg, are round, blue, film-coated tablets, debossed “S” on one side and “344” on the other side, packaged as follows: NDC 51407-465-01 bottle of 100 tablets (with desiccant) NDC 51407-465-05 bottle of 500 tablets (with desiccant) Store at 20-25°C (68-77°F) [See USP Controlled Room Temperature]. Protect from moisture. Dispense in tight container (USP).
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.