LOTENSIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LOTENSIN (LOTENSIN).
Benazepril is an angiotensin-converting enzyme (ACE) inhibitor that blocks the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to decreased vasopressor activity, aldosterone secretion, and increased plasma renin activity.
| Metabolism | Hepatic via glucuronidation and ester hydrolysis; primarily metabolized to benazeprilat, its active metabolite. CYP enzymes are minimally involved. |
| Excretion | Renal: ~60% unchanged in urine; Biliary/fecal: ~20% as metabolites; Total renal elimination: ~80-85% (parent drug + metabolites). |
| Half-life | Terminal elimination half-life: 12-13 hours for benazeprilat; 0.6 hours for benazepril. Clinical context: Half-life supports once-daily dosing, extending to 22-27 hours in severe renal impairment (CrCl <30 mL/min) requiring dose adjustment. |
| Protein binding | Benazeprilat: 90-93% primarily to serum albumin; Benazepril: ~96.7% bound. |
| Volume of Distribution | Benazeprilat: 0.15-0.2 L/kg; Benazepril: 0.7 L/kg. Clinical meaning: Low Vd for active metabolite indicates limited tissue distribution, predominantly in extracellular fluid. |
| Bioavailability | Oral: Benazepril ~37% (parent drug); Rapidly converted to active metabolite benazeprilat (bioavailability as ACE inhibitor ~13-18% due to extensive first-pass metabolism). |
| Onset of Action | Oral: 1 hour (therapeutic effect onset for blood pressure reduction); Maximum effect: 2-4 hours after dose. |
| Duration of Action | Duration: 24 hours (allows once-daily dosing). Clinical notes: Antihypertensive effect maintained over full dosing interval, with trough-to-peak ratio >0.5. |
| Molecular Weight | 424.5 |
10-40 mg orally once daily; initial dose 10 mg once daily; maximum 80 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-60 mL/min: initial dose 5 mg once daily; GFR <30 mL/min: initial dose 2.5 mg once daily; titrate cautiously. |
| Liver impairment | Child-Pugh Class A: 5 mg once daily; Class B-C: not recommended (insufficient data). |
| Pediatric use | Weight ≥50 kg: same as adult; <50 kg: 0.07 mg/kg (max 5 mg) once daily initially; maximum 0.6 mg/kg/day (up to 40 mg/day). |
| Geriatric use | Initial dose 2.5-5 mg once daily; adjust based on renal function. |
| 1st trimester | Contraindicated: associated with fetal renal and skull ossification defects, oligohydramnios, and neonatal renal failure. Potential for teratogenicity based on ACE inhibitor class effects. |
| 2nd trimester | Contraindicated: increased risk of fetal renal dysfunction, oligohydramnios, and neonatal adverse outcomes. ACE inhibitors cause fetal and neonatal morbidity and death. |
| 3rd trimester | Contraindicated: high risk of fetal renal dysfunction, oligohydramnios, skull ossification defects, and neonatal hypotension, hyperkalemia, and renal failure. |
Clinical note
Comprehensive clinical and safety monograph for LOTENSIN (LOTENSIN).
| Placental transfer | Crosses placenta; detectable in fetal plasma and amniotic fluid. Evidence based on animal studies and human case reports. |
| Breastfeeding | Benzazepril (benazeprilat) is excreted in breast milk in low amounts. However, potential for adverse effects in nursing infants (e.g., hypotension, renal impairment) exists. Use only if clearly needed and monitor infant for adverse effects. |
■ FDA Black Box Warning
Fetal toxicity: Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.
| Serious Effects |
History of angioedema related to previous ACE inhibitor therapyHypersensitivity to benazepril or any component of the formulationConcurrent use with aliskiren in patients with diabetes mellitusPregnancy (all trimesters)
| Precautions | Anaphylactoid reactions including angioedema (higher risk in black patients), Hypotension in volume-depleted patients, Renal impairment: monitor renal function, Hyperkalemia, Cough (common, non-productive), Use in pregnancy: associated with oligohydramnios and fetal harm |
| Food/Dietary | Avoid high-potassium foods (bananas, oranges, tomatoes, spinach, potatoes) in excess. Avoid salt substitutes containing potassium chloride. Grapefruit juice may alter drug metabolism; limited data with benazepril, but caution advised. Maintain stable intake of potassium-rich foods. |
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| Lactation Rating | L3 - Moderate Safety (limited data, potential adverse effects) |
| Teratogenic Risk | First trimester: no increased risk of major congenital malformations; second and third trimesters: fetotoxicity (oligohydramnios, fetal renal dysfunction, skull ossification defects, hypotension, anuria, renal failure, death). |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, serum potassium; fetal ultrasound for oligohydramnios and renal function; neonatal monitoring for hypotension, hyperkalemia, and oliguria. |
| Fertility Effects | No known direct effects on human fertility; animal studies show no impairment. |
| Clinical Pearls | LOTENSIN (benazepril) is an ACE inhibitor. Monitor serum creatinine and potassium within 2 weeks of initiation and periodically thereafter. Reduce dose in renal impairment (CrCl <30 mL/min). Avoid in pregnancy (black box warning). May cause angioedema, especially in African American patients. Consider alternative if cough develops. |
| Patient Advice | Report any swelling of face, lips, or throat immediately. · Avoid salt substitutes containing potassium without consulting your doctor. · Dizziness may occur; rise slowly from sitting or lying position. · Do not take if pregnant or planning pregnancy; use effective contraception. · Contact your doctor if you experience persistent cough, fainting, or signs of infection. |