Benazepril

Benazepril is an Antihypertensive agent belonging to Angiotensin-converting enzyme (ACE ) inhibitors.

Benazepril is used in the treatment of Hypertension.

The absolute bioavailability of Benazepril is Rapid (37%); food does not alter significantly; metabolite (benazeprilat) itself is unsuitable for oral administration due to poor absorption The volume of distribution was approx 8.7 L/kg. The Plasma protein binding was >97% of Benazepril and metabolite (benazeprilat-95%). The hepatic metabolism was mainly through benazeprilat, via enzymatic hydrolysis; with extensive first-pass effect. It gets excreted Via Urine (trace amounts as benazepril; 20% as benazeprilat; 12% as other metabolites).

The common side effects are hives, severe stomach pain, difficulty breathing, swelling in your face or throat, or severe skin reaction (fever, sore throat, burning in your eyes, skin pain, red or purple skin rash that spreads and causes blistering and peeling).

Benazepril is available in the form of a dosage form such as tablets.

Benazepril is available in the USA, Canada, Spain, France India.

Benazeprilat, the active metabolite of Benazepril, competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. Inhibition of ACE results in decreased plasma angiotensin II. As angiotensin II is a vasoconstrictor and a negative-feedback mediator for renin activity, lower concentrations result in a decrease in blood pressure and stimulation of baroreceptor reflex mechanisms, which leads to decreased vasopressor activity and to decreased aldosterone secretion.

Benazepril is available in the form of a dosage form such as tablets.

Benazepril comes as a tablet to take by mouth. It is usually taken once or twice a day with or without food.

Benazepril is used alone or in combination with other medications to treat high blood pressure. Benazepril is in a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It works by decreasing certain chemicals that tighten the blood vessels, so blood flows more smoothly.

Benazepril is used to treat high blood pressure (hypertension). Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. Benazepril is an ACE inhibitor and works by relaxing blood vessels so that blood can flow more easily.

It is indicated for the treatment of hypertension, and to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.

The dosage and the duration of treatment should be as per the clinical judgment of the treating physician.

Benazepril is available in various dosage strengths: 5 mg, 10 mg, 20 mg, 40 mg

Benazepril is available in the form of a dosage form such as tablets..

Dose Adjustment in Kidney Patients:

• CrCl ≥30 mL/minute/1.73m2: No dosage adjustment necessary.
• CrCl <30 mL/minute/1.73m2
• Initial: 5 mg once daily; maximum dose: 40 mg/day
• Hemodialysis: 25% to 50% of the usual dose; supplemental dose is unnecessary.
• Peritoneal dialysis: 25% to 50% of usual dose; supplemental dose is not necessary

Dose Adjustment in Pediatric Patients.

Hypertension:

Children ≥6 years and Adolescents:

Oral: Initial: 0.2 mg/kg/dose once daily as monotherapy;

Maximum initial dose: 10 mg/day; maintenance: 0.1-0.6 mg/kg/dose once daily; maximum daily dose: 40 mg/day

Benazepril is used in the treatment of Hypertension.

Hypertension:- It has been observed that the low-salt Dietary Approach to Stop Hypertension (DASH) diet lowers blood pressure. Sometimes after a few weeks, its effects on blood pressure become noticeable.

Benazepril may be contraindicated in the following

● Hypersensitivity to benazepril, other ACE inhibitors, or any component of the formulation; history of angioedema (with or without prior ACE inhibitor therapy); concomitant use with aliskiren in patients with diabetes mellitus; coadministration with or within 36 hours of switching to or from a neprilysin inhibitor (eg, sacubitril).

The treating physician must closely monitor the patient and keep pharmacovigilance as follows.

Concerns related to adverse effects:

Hypersensitivity reactions: Anaphylactic/anaphylactoid reactions can occur with ACE inhibitors. Severe anaphylactoid reactions may be seen during hemodialysis (eg, CVVHD) with high-flux dialysis membranes (eg, AN69), and rarely, during low-density lipoprotein apheresis with dextran sulfate cellulose. Rare cases of anaphylactoid reactions have been reported in patients undergoing sensitization treatment with Hymenoptera (bee, wasp) venom while receiving ACE inhibitors.

Hypotension/syncope: Symptomatic hypotension with or without syncope can occur with ACE inhibitors (usually with the first several doses); effects are most often observed in volume-depleted patients; correct volume depletion prior to initiation; close monitoring of the patient is required especially with initial dosing and dosing increases; blood pressure must be lowered at a rate appropriate for the patient’s clinical condition. Although dose reduction may be necessary, hypotension is not a reason for discontinuation of future ACE inhibitor use, especially in patients with heart failure where a reduction in systolic blood pressure is a desirable observation.

Disease-related concerns:

• Aortic stenosis: Use with caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia.

• Ascites: Generally, avoid use in patients with ascites due to cirrhosis or refractory ascites; if use cannot be avoided in patients with ascites due to cirrhosis, monitor blood pressure and renal function carefully to avoid rapid development of renal failure.

• Cardiovascular disease: Initiation of therapy in patients with ischemic heart disease or cerebrovascular disease warrants close observation due to the potential consequences of falling blood pressure (eg, MI, stroke). Fluid replacement, if needed, may restore blood pressure; therapy may then be resumed. Discontinue therapy in patients whose hypotension recurs.

• Collagen vascular disease: Use with caution in patients with collagen vascular disease especially with concomitant renal impairment; they may be at increased risk for hematologic toxicity.

• Diabetes: Use with caution in patients with diabetes receiving insulin or oral antidiabetic agents; may be at increased risk for episodes of hypoglycemia.

• Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction: Use with caution in patients with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition.

• Renal impairment: Use with caution in preexisting renal insufficiency; dosage adjustment may be needed. Avoid rapid dosage escalation which may lead to further renal impairment.

Special populations:

• Race/Ethnicity: In Black patients, the BP-lowering effects of ACE inhibitors may be less pronounced. The exact mechanism is not known; differences in the renin-angiotensin-aldosterone system, low renin levels, and salt sensitivity more commonly found in Black patients may contribute.

• Surgical patients: In patients on chronic ACE inhibitor therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia; use caution before, during, or immediately after major surgery. Cardiopulmonary bypass, intraoperative blood loss, or vasodilating anesthesia increases endogenous renin release. The use of ACE inhibitors perioperatively will blunt angiotensin II formation and may result in hypotension. However, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent. Based on current research and clinical guidelines in patients undergoing non-cardiac surgery, continuing ACE inhibitors is reasonable in the perioperative period. If ACE inhibitors are held before surgery, it is reasonable to restart postoperatively as soon as clinically feasible.

Other warnings/precautions:

• Appropriate use: Before taking this medicine You should not use Lotrel (a combination of Amlodipine + Benazepril) if you are allergic to amlodipine or benazepril, or if: you have had angioedema ( hives or severe swelling of deep skin tissues sometimes caused by allergic reaction).

Avoid taking alcohol with benazepril as it may result in side effects like headache, dizziness, and faintness.

Because of the low levels of benazepril and benazeprilat in breastmilk, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants. The relative infant dose (RID) of benazepril and benazeprilat are <0.1% of the weight-adjusted maternal dose when calculated using the highest average breast milk concentration located and compared to a weight-adjusted maternal dose of 20 mg/day. In general, breastfeeding is considered acceptable when the RID of medication is <10% (Anderson 2016; Ito 2000).

Pregnancy Category X

Benazepril crosses the placenta. Exposure to an angiotensin-converting enzyme (ACE) inhibitor during the first trimester of pregnancy may be associated with an increased risk of fetal malformations; however, outcomes observed may also be influenced by maternal disease. [US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected. Drugs that act on the renin-angiotensin system are associated with oligohydramnios. Oligohydramnios, due to decreased fetal renal function, may lead to fetal lung hypoplasia and skeletal malformations. Their use in pregnancy is also associated with anuria, hypotension, renal failure, skull hypoplasia, and death in the fetus/neonate. Infants exposed to an ACE inhibitor in utero should be monitored for hyperkalemia, hypotension, and oliguria. Oligohydramnios may not appear until after an irreversible fetal injury has occurred. Exchange transfusions or dialysis may be required to reverse hypotension or improve renal function. Chronic maternal hypertension is also associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to the duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, preeclampsia, delivery complications, stroke, and myocardial infarction.

When treatment of hypertension in pregnancy is indicated, ACE inhibitors should generally be avoided due to their adverse fetal events; use in pregnant women should only be considered for cases of hypertension refractory to other medications. ACE inhibitors are not recommended for the treatment of heart failure in pregnancy.

Salt Substitutes: Those who are taking benazepril should avoid sodium, calcium, and magnesium-rich foods. The salts may reduce the blood-pressure-lowering effect of benazepril.

The adverse reactions related to the molecule Benazepril can be categorized as

● Common Adverse effects: cough, headache, dizziness, drowsiness

● Less Common adverse effects: Swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, hoarseness, difficulty in breathing or swallowing, light headedness, fainting, rash, yellowing of the skin or eyes, fever, sore throat, chills, and other signs of infection.

The clinically relevant drug interactions of Benazepril are briefly summarized here.

Symptoms: Hypotension which may be associated with electrolyte disturbances and renal failure.

Management: Supportive treatment. If ingestion is recent, consider the administration of activated charcoal; gastric decontamination (e.g. vomiting, gastric lavage) may be considered in the early period after ingestion. Monitor blood pressure and clinical symptoms. Ensure adequate hydration. Infuse 0.9% NaCl to treat marked hypotension and consider vasopressors (e.g. catecholamines) if necessary. Consider dialysis in patients with severe renal impairment.

Pharmacodynamics:

Benazepril, a prodrug of benazeprilat, is an ACE inhibitor. It competitively inhibits the conversion of angiotensin I to angiotensin II (a potent vasoconstrictor) through the angiotensin I-converting enzyme (ACE) activity, thereby reducing the levels of angiotensin II which leads to an increase in plasma renin activity and decreased aldosterone secretion.

Pharmacokinetics:

• Absorption: Rapidly absorbed. Time to peak plasma concentrations: Benazepril: 0.5-1 hour; benazeprilat: 1-2 hours (fasting state); 2-4 hours (nonfasting state).
• Distribution: Crosses the placenta (benazepril); enters breast milk in small amounts (benazepril and benazeprilat). Volume of distribution: Approx 8.7 L. Plasma protein binding: Approx 97% (benazepril); approx 95% (benazeprilat).
• Metabolism: Rapidly and extensively metabolized in the liver to benazeprilat (active metabolite) via enzymatic hydrolysis; both benazepril and benazeprilat undergo glucuronidation. Undergoes extensive first-pass metabolism.
• Excretion: Mainly via urine (approx 37%; 20% as benazeprilat, 12% as other metabolites, trace amounts of benazepril); feces (approx 11-12% as benazeprilat). Elimination half-life: Benazeprilat: 10-11 hours (effective); 22 hours (terminal).

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