Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
LOTREL vs ALDORIL 15
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
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.
Methyldopa is a centrally acting alpha-2 adrenergic agonist that reduces sympathetic outflow from the brainstem, decreasing peripheral vascular resistance and blood pressure. Hydrochlorothiazide is a thiazide diuretic that inhibits sodium and chloride reabsorption in the distal convoluted tubule, reducing plasma volume and cardiac output.
Treatment of hypertension,Off-label: chronic kidney disease, heart failure, diabetic nephropathy (as part of combination therapy)
Hypertension
Oral: 1 capsule (amlodipine 2.5 mg/benazepril 10 mg) once daily, titrate to maximum 10 mg/40 mg once daily.
1 tablet (hydrochlorothiazide 15 mg, methyldopa 250 mg) orally twice daily; increase as needed up to 2 tablets twice daily.
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.
Terminal half-life: 12–17 hours; clinical context: steady-state achieved within 2–3 days; effect persists 12–24 hours
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.
Methyldopa is metabolized in the liver via conjugation and O-methylation; active metabolites include methyldopamine and methylnorepinephrine. Hydrochlorothiazide is not significantly metabolized and is excreted unchanged in urine.
Amlodipine: 60% renal, 20-25% fecal. Benazeprilat: 85% renal (as benazeprilat and conjugated metabolites), 15% biliary/fecal.
Renal: ~70% unchanged; biliary/fecal: ~30% as metabolites
Amlodipine: ~93% (plasma proteins). Benazepril: ~96.7%; benazeprilat: ~95.3% (primarily albumin).
~90%, primarily to albumin
Amlodipine: 21 L/kg (large Vd indicates extensive tissue distribution). Benazeprilat: 0.11-0.13 L/kg (limited extravascular distribution).
2–4 L/kg; clinical meaning: extensive tissue distribution, concentrating in vascular smooth muscle
Amlodipine: 64-90% (oral). Benazepril: >30% (oral; rapidly converted to active benazeprilat).
Oral: 50–60% (extensive first-pass metabolism)
GFR ≥30 m L/min: No adjustment. GFR <30 m L/min: Not recommended. Hemodialysis: Avoid.
GFR 30-50 m L/min: maximum 1 tablet twice daily. GFR <30 m L/min: avoid use.
Child-Pugh A: No dose adjustment. Child-Pugh B: Reduce dose or avoid. Child-Pugh C: Contraindicated.
Child-Pugh A: caution, reduce dose. Child-Pugh B: avoid. Child-Pugh C: contraindicated.
Not established in pediatric patients (safety and efficacy not evaluated).
Not recommended for pediatric use; safety in children under 12 years not established.
Initiate with amlodipine 2.5 mg/benazepril 10 mg daily; titrate slowly due to increased risk of hypotension and renal impairment.
Start with 1 tablet once daily; monitor for hypotension and electrolyte imbalance. Reduce initial dose by 50%.
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.
None
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
Sedation, usually transient; may impair ability to drive or operate heavy machinery.,Positive Coombs test with hemolytic anemia (rare); monitor hematocrit and Coombs test.,Hepatotoxicity (hepatic necrosis) with fever, jaundice; discontinue if liver abnormalities occur.,Fluid and electrolyte imbalance (hypokalemia, hyponatremia, hypercalcemia) due to thiazide.,May precipitate gout in hyperuricemic patients.,May exacerbate systemic lupus erythematosus.
Hypersensitivity to amlodipine, benazepril, or any component of the formulation,History of angioedema related to previous ACE inhibitor therapy,Hereditary or idiopathic angioedema,Concomitant use with aliskiren in patients with diabetes mellitus,Pregnancy (second and third trimesters)
Active hepatic disease (e.g., acute hepatitis, cirrhosis),Prior methyldopa therapy associated with liver disorders,Hypersensitivity to methyldopa or hydrochlorothiazide,Anuria,Sulfonamide allergy (cross-sensitivity with thiazides)
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.
Avoid high-sodium foods as they can reduce antihypertensive efficacy. Thiazides may cause hypokalemia; increase dietary potassium (bananas, orange juice) unless contraindicated. Alcohol may enhance orthostatic hypotension.
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.
First trimester: No increased risk of major malformations based on limited human data; animal studies show no teratogenicity at clinically relevant doses. Second/third trimesters: Fetal and neonatal adverse effects including oligohydramnios, fetal renal dysfunction, skull ossification delay, and hypotension in the neonate. Avoid use after 20 weeks gestation unless no alternative.
No data on excretion in human milk. Amlodipine is excreted in animal milk; valsartan is excreted in animal milk. M/P ratio not determined. Potential for adverse effects in nursing infant includes hypotension, renal impairment. Caution advised; avoid use during breastfeeding.
Methyldopa and hydrochlorothiazide are excreted into human milk. M/P ratio for methyldopa is approximately 0.5-1.0; for hydrochlorothiazide, M/P ratio ~2.0. Methyldopa is considered compatible with breastfeeding. Hydrochlorothiazide may suppress lactation and cause neonatal electrolyte disturbances. Use with caution; monitor infant for signs of diuresis or electrolyte imbalance.
Pharmacokinetic changes in pregnancy may alter drug levels but specific dose adjustments not established. Due to fetal risks, use is contraindicated in pregnancy; alternative therapy should be initiated.
Pharmacokinetic changes in pregnancy may include increased volume of distribution and enhanced renal clearance. No specific dose adjustment routine is recommended; dosing should be guided by clinical response. Methyldopa starting dose 250 mg twice daily, titrated to effect. Hydrochlorothiazide dose not typically adjusted, but caution due to potential volume depletion.
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.
Aldoril 15 (methyldopa 250mg + hydrochlorothiazide 15mg) is rarely used due to superior alternatives. Monitor for hepatotoxicity, hemolytic anemia, and lupus-like syndrome. Titrate slowly to avoid sedation. Contraindicated in active liver disease, pheochromocytoma, and anuria.
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.
May cause drowsiness; avoid driving until tolerance develops.,Report unexplained fever, jaundice, or dark urine immediately.,Take at bedtime to minimize sedation.,Avoid sudden discontinuation; follow prescribed tapering schedule.,Use sun protection; thiazides increase photosensitivity.
No interactions on record
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about LOTREL vs ALDORIL 15, answered by our medical review team.
LOTREL is a Antihypertensive combination that works by 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.. ALDORIL 15 is a Antihypertensive Combination that works by Methyldopa is a centrally acting alpha-2 adrenergic agonist that reduces sympathetic outflow from the brainstem, decreasing peripheral vascular resistance and blood pressure. Hydrochlorothiazide is a thiazide diuretic that inhibits sodium and chloride reabsorption in the distal convoluted tubule, reducing plasma volume and cardiac output.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between LOTREL and ALDORIL 15 depend on the specific clinical indication. These are agents from distinct pharmacological classes and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of LOTREL is: Oral: 1 capsule (amlodipine 2.5 mg/benazepril 10 mg) once daily, titrate to maximum 10 mg/40 mg once daily.. The standard adult dose of ALDORIL 15 is: 1 tablet (hydrochlorothiazide 15 mg, methyldopa 250 mg) orally twice daily; increase as needed up to 2 tablets twice daily.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between LOTREL and ALDORIL 15 in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. LOTREL is classified as Category C. First trimester: Animal studies suggest possible teratogenicity; human data limited. Second and third trimesters: Exposure to angiotensin II receptor antagonists (valsartan) and ca. ALDORIL 15 is classified as Category C. First trimester: No increased risk of major malformations based on limited human data; animal studies show no teratogenicity at clinically relevant doses. Second/third trimesters: . Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.