LOTREL
Clinical safety rating
cautionComprehensive clinical and safety monograph for LOTREL (LOTREL).
Lotrel is a combination of amlodipine (a calcium channel blocker) and benazepril (an ACE inhibitor). Amlodipine inhibits calcium ion influx across cardiac and vascular smooth muscle cells, causing vasodilation and reduced blood pressure. Benazepril inhibits angiotensin-converting enzyme, reducing angiotensin II formation, leading to vasodilation and decreased aldosterone secretion.
| Metabolism | Amlodipine is extensively metabolized in the liver via CYP3A4 to inactive metabolites. Benazepril is hydrolyzed in the liver to its active metabolite, benazeprilat, primarily by hepatic esterases; further metabolism is minimal. |
| Excretion | Amlodipine: 60% renal, 20-25% fecal. Benazeprilat: 85% renal (as benazeprilat and conjugated metabolites), 15% biliary/fecal. |
| Half-life | Amlodipine: 30-50 hours (terminal); steady state in 7-10 days. Benazeprilat: 10-11 hours (terminal); effective half-life 22-24 hours with once-daily dosing. |
| Protein binding | Amlodipine: ~93% (plasma proteins). Benazepril: ~96.7%; benazeprilat: ~95.3% (primarily albumin). |
| Volume of Distribution | Amlodipine: 21 L/kg (large Vd indicates extensive tissue distribution). Benazeprilat: 0.11-0.13 L/kg (limited extravascular distribution). |
| Bioavailability | Amlodipine: 64-90% (oral). Benazepril: >30% (oral; rapidly converted to active benazeprilat). |
| Onset of Action | Amlodipine: 2-4 hours (oral). Benazepril: 1-2 hours (oral; antihypertensive effect). |
| Duration of Action | Amlodipine: 24 hours. Benazepril: 24 hours (antihypertensive effect). |
| Molecular Weight | Amlodipine besylate: 567.1 Da; Benazepril hydrochloride: 424.9 Da (combination) |
Oral: 1 capsule (amlodipine 2.5 mg/benazepril 10 mg) once daily, titrate to maximum 10 mg/40 mg once daily.
| Dosage form | CAPSULE |
| Renal impairment | GFR ≥30 mL/min: No adjustment. GFR <30 mL/min: Not recommended. Hemodialysis: Avoid. |
| Liver impairment | Child-Pugh A: No dose adjustment. Child-Pugh B: Reduce dose or avoid. Child-Pugh C: Contraindicated. |
| Pediatric use | Not established in pediatric patients (safety and efficacy not evaluated). |
| Geriatric use | Initiate with amlodipine 2.5 mg/benazepril 10 mg daily; titrate slowly due to increased risk of hypotension and renal impairment. |
| 1st trimester | Use in first trimester is associated with potential teratogenicity due to ACE inhibitor component. Avoid unless no alternative. |
| 2nd trimester | Contraindicated in second trimester. ACE inhibitors cause fetal renal dysfunction, oligohydramnios, and skull ossification defects. |
| 3rd trimester | Contraindicated in third trimester. Risk of fetal hypotension, anuria, renal failure, and death. |
Clinical note
Comprehensive clinical and safety monograph for LOTREL (LOTREL).
| Placental transfer | Both components cross the placenta. ACE inhibitors (benazepril) are known to cross and cause fetal renin-angiotensin system interference. |
| Breastfeeding | Both amlodipine and benazepril are excreted in breast milk in low amounts. Use with caution in nursing mothers, especially in preterm or infants with renal impairment. Monitor infant for hypotension and renal effects. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Animal studies suggest possible teratogenicity; human data limited. Second and third trimesters: Exposure to angiotensin II receptor antagonists (valsartan) and calcium channel blockers (amlodipine) is associated with oligohydramnios, fetal renal dysfunction, skull hypoplasia, and hypotension. Risk is highest during second and third trimesters. Contraindicated in pregnancy. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, serum electrolytes. In pregnancy, fetal monitoring includes ultrasound for oligohydramnios, fetal growth, and renal function. Consider serial fetal ultrasound. |
| Fertility Effects | No specific human studies. Calcium channel blockers may impair sperm motility. Angiotensin II receptor antagonists have not shown adverse effects on fertility in animal studies. Clinical significance unknown. |
■ 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.
| Serious Effects |
History of angioedema related to previous ACE inhibitor therapyBilateral renal artery stenosisPregnancy (second and third trimesters)Concomitant use with aliskiren in patients with diabetes
| Precautions | Angioedema: Risk of head, neck, or intestinal angioedema, Hypotension: Symptomatic hypotension may occur, especially in volume- or salt-depleted patients, Hepatic impairment: Use with caution; may increase amlodipine exposure, Renal impairment: Monitor renal function; may increase serum creatinine, Hyperkalemia: Risk increases with renal impairment, diabetes, or concomitant potassium-sparing diuretics, Cough: Dry cough is common with ACE inhibitors, Cholestatic jaundice and hepatic failure: Rare but reported with ACE inhibitors |
| Food/Dietary | Avoid high-potassium foods (e.g., bananas, oranges, spinach, potatoes) in large amounts. No specific food restrictions beyond maintaining a balanced low-sodium diet. Grapefruit juice may increase amlodipine levels; limit or avoid consumption. |
| Clinical Pearls | LOTREL is a fixed-dose combination of amlodipine (dihydropyridine calcium channel blocker) and benazepril (ACE inhibitor). Monitor serum potassium and renal function, especially in patients with renal impairment or on potassium-sparing diuretics. Avoid use in pregnancy; discontinue immediately if pregnancy is detected. May cause angioedema; higher risk in Black patients. Use with caution in patients with aortic stenosis or hypertrophic cardiomyopathy. Amlodipine may cause peripheral edema, which is dose-dependent and not relieved by diuretics. |
| Patient Advice | Take exactly as prescribed, usually once daily. Do not stop without consulting your doctor. · Avoid potassium supplements or salt substitutes containing potassium unless directed by your doctor. · Report any swelling of face, lips, tongue, or difficulty breathing immediately (signs of angioedema). · If you become pregnant, stop the medication and contact your doctor right away. · May cause dizziness or lightheadedness; avoid driving until you know how the drug affects you. · Avoid alcohol, which can lower blood pressure further. |
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