BENAZEPRIL HYDROCHLORIDE
Clinical safety rating: avoid
NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Risk of angioedema can occur at any time discontinue immediately.
Benazepril is a prodrug that is hydrolyzed to benazeprilat, a competitive inhibitor of angiotensin-converting enzyme (ACE). This prevents conversion of angiotensin I to angiotensin II, resulting in decreased vasoconstriction, reduced aldosterone secretion, and lower blood pressure.
| Metabolism | Benazepril is primarily metabolized by hepatic esterases to its active metabolite, benazeprilat. Minor metabolism via glucuronidation. Benazeprilat is eliminated renally. |
| Excretion | Primarily renal (80-90% of absorbed dose excreted in urine, with approximately 20-30% as benazeprilat and the rest as inactive metabolites); biliary/fecal elimination accounts for the remainder (10-20%). |
| Half-life | Benazeprilat terminal elimination half-life is approximately 10-11 hours in patients with normal renal function; clinically, steady-state is reached in 2-3 days. Half-life is prolonged in renal impairment (up to 22 hours in moderate to severe impairment), necessitating dose adjustment. |
| Protein binding | Benazeprilat is approximately 95% bound to plasma proteins, primarily serum albumin. |
| Volume of Distribution | Volume of distribution for benazeprilat is approximately 0.7 L/kg, indicating distribution into extracellular fluid and tissues. |
| Bioavailability | Oral bioavailability of benazepril is approximately 37% due to extensive first-pass hepatic metabolism; conversion to active metabolite benazeprilat is rapid and extensive. |
| Onset of Action | Oral: peak plasma concentration of benazeprilat occurs 1-2 hours after dosing, with reduction in blood pressure typically observed within 1 hour; maximum effect occurs within 2-4 hours. |
| Duration of Action | Duration of antihypertensive effect is approximately 24 hours with once-daily dosing, allowing for once-daily administration; however, some patients may experience a slight attenuation of effect at trough. |
| Molecular Weight | 424.92 Da |
Initial: 10 mg orally once daily. Titrate to 20-40 mg daily (as single dose or two divided doses). Maximum: 80 mg/day. Route: Oral.
| Dosage form | TABLET |
| Renal impairment | GFR ≥30 mL/min: No adjustment. GFR 15–29 mL/min: Initial 5 mg daily. GFR <15 mL/min (dialysis): Not recommended due to limited data; use with caution, initial 5 mg daily. |
| Liver impairment | Child-Pugh Class A or B: No data for specific adjustment; use with caution due to potential decreased clearance. Child-Pugh Class C: Avoid use unless benefits outweigh risks; no established dose. |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). No approved dosing. |
| Geriatric use | Initial dose: 5–10 mg once daily. Titrate slowly due to increased sensitivity, renal impairment risk, and potential for hypotension. Monitor renal function and electrolytes. |
| 1st trimester | First trimester: Increased risk of congenital malformations, particularly cardiovascular and central nervous system defects. Avoid use if possible. |
| 2nd trimester | Second trimester: Risk of oligohydramnios, fetal renal dysfunction, and skull ossification defects. Contraindicated. |
| 3rd trimester | Third trimester: High risk of neonatal hypotension, renal failure, and oligohydramnios. Contraindicated. |
Clinical note
NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Risk of angioedema can occur at any time discontinue immediately.
| FDA category | Contraindicated |
| Placental transfer | Crosses placenta; detectable in fetal plasma at approximately 20% of maternal plasma concentrations. |
| Breastfeeding |
■ FDA Black Box Warning
Fetal Toxicity: Drugs acting directly on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible when pregnancy is detected.
| Common Effects | heart failure |
| Serious Effects |
Hypersensitivity to benazepril or any ACE inhibitorHistory of angioedema related to prior ACE inhibitor therapyConcomitant use with aliskiren in patients with diabetes mellitus
| Precautions | Angioedema, Hyperkalemia, Renal impairment, Hypotension, Hepatic impairment, Cough, Neutropenia/Agranulocytosis |
| Food/Dietary | Avoid high-potassium foods (e.g., bananas, oranges, potatoes, spinach, tomatoes) and potassium-enriched salt substitutes, as benazepril can increase potassium levels. No significant food interactions; can be taken with or without food. |
Loading safety data…
| Minimal excretion into breast milk; however, potential for adverse effects in neonates (e.g., hypotension). Use with caution, especially in preterm infants. |
| Lactation Rating | L3 |
| Teratogenic Risk | First trimester: No convincing evidence of increased risk of major congenital malformations; however, data are limited. Second and third trimesters: Fetal hypotension, oligohydramnios, neonatal renal dysfunction, skull hypoplasia, and anuria. Exposure after 20 weeks gestation is associated with oligohydramnios and neonatal anuria. Risk of fetal/neonatal death. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, serum potassium, and urine protein. Serial fetal ultrasound to assess amniotic fluid volume and fetal growth. Fetal echocardiography if exposure in second or third trimester. |
| Fertility Effects | No human data on fertility effects. In animal studies, no adverse effects on fertility were observed at clinically relevant doses. ACE inhibitors may theoretically impair reproductive function via hemodynamic effects, but no specific data. |
| Clinical Pearls | Benazepril is a prodrug that is hepatically metabolized to its active metabolite, benazeprilat. Its clearance is reduced in hepatic impairment, but dose adjustment is not typically required. In renal impairment (CrCl <30 mL/min), initial dose reduction to 5 mg daily is recommended. Benazepril is unique among ACE inhibitors in that its biliary excretion is significant (~50%), which can be advantageous in patients with chronic kidney disease. Cough is a common side effect; consider switching to an ARB if intolerable. Monitor potassium and creatinine 1-2 weeks after initiation. Use with caution in patients on potassium-sparing diuretics or NSAIDs. |
| Patient Advice | Take benazepril exactly as prescribed, usually once daily with or without food. · Do not use salt substitutes containing potassium without consulting your doctor. · Report persistent dry cough, dizziness, or signs of angioedema (swelling of face, lips, tongue) immediately. · Avoid becoming dehydrated; drink adequate fluids unless fluid restricted. · Take your blood pressure regularly and keep a log to share with your healthcare provider. · Do not stop taking this medication abruptly without consulting your doctor. |