Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
LOTREL vs ALDORIL 25
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.
Combination of methyldopa, a centrally acting alpha-2 adrenergic agonist that reduces sympathetic outflow, and hydrochlorothiazide, a thiazide diuretic that inhibits sodium reabsorption in the distal convoluted tubule, reducing plasma volume.
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.
Oral: 1 tablet (hydrochlorothiazide 25 mg/methyldopa 250 mg) twice daily; increase as needed to max 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.
7-16 hours (terminal). In renal impairment, half-life may exceed 24 hours, requiring dose adjustment.
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 primarily via hepatic conjugation and renal excretion; 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: ~85% unchanged. Biliary/fecal: ~15% as metabolites.
Amlodipine: ~93% (plasma proteins). Benazepril: ~96.7%; benazeprilat: ~95.3% (primarily albumin).
Methyldopa: less than 10% bound to plasma proteins. Hydrochlorothiazide: ~70% bound to plasma proteins (primarily albumin).
Amlodipine: 21 L/kg (large Vd indicates extensive tissue distribution). Benazeprilat: 0.11-0.13 L/kg (limited extravascular distribution).
Methyldopa: 0.3-0.6 L/kg (distributes widely, including CNS). Hydrochlorothiazide: 0.8-1.5 L/kg (distributes into extracellular fluid).
Amlodipine: 64-90% (oral). Benazepril: >30% (oral; rapidly converted to active benazeprilat).
Methyldopa: oral bioavailability ~25% (first-pass metabolism). Hydrochlorothiazide: oral bioavailability ~60-80%.
GFR ≥30 m L/min: No adjustment. GFR <30 m L/min: Not recommended. Hemodialysis: Avoid.
GFR 30-50 m L/min: use with caution, reduce dose. GFR <30 m L/min: not recommended.
Child-Pugh A: No dose adjustment. Child-Pugh B: Reduce dose or avoid. Child-Pugh C: Contraindicated.
Child-Pugh A: no adjustment; Child-Pugh B or C: contraindicated due to methyldopa hepatotoxicity risk.
Not established in pediatric patients (safety and efficacy not evaluated).
Not established; avoid use in children.
Initiate with amlodipine 2.5 mg/benazepril 10 mg daily; titrate slowly due to increased risk of hypotension and renal impairment.
Start at lowest dose (1 tablet daily); monitor for orthostatic hypotension, sedation, and electrolyte imbalance.
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
May cause sedation, depression, positive direct Coombs test, hemolytic anemia, hepatotoxicity, fluid/electrolyte imbalance, and sensitivity reactions; monitor liver function, CBC, and electrolytes.
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)
Hypersensitivity to methyldopa, hydrochlorothiazide, or sulfonamides; active hepatic disease; anuria; history of methyldopa-induced liver disorders.
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 to optimize antihypertensive effect. Limit alcohol intake. Do not consume large amounts of potassium-rich foods (e.g., bananas, oranges, spinach) unless advised by a healthcare provider, as hydrochlorothiazide can alter potassium levels.
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: Limited human data, but animal studies show no teratogenicity at therapeutic doses. Second and third trimesters: Associated with fetal hypotension, oligohydramnios, and renal dysfunction due to methyldopa component. Hydrochlorothiazide may cause fetal electrolyte imbalances.
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 is excreted in breast milk with M/P ratio of approximately 0.2-0.5; hydrochlorothiazide M/P ratio ~0.5-0.6. Considered compatible with breastfeeding by AAP, but monitor infant for hypotension and electrolyte disturbances.
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.
No standard dose adjustment required, but increased plasma volume in pregnancy may necessitate higher doses of methyldopa. Monitor clinical response and adjust accordingly.
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 25 is a fixed-dose combination of methyldopa (250 mg) and hydrochlorothiazide (25 mg). Monitor for hypotension, especially during initial therapy or with volume depletion. Methyldopa may cause a positive direct Coombs test and hemolytic anemia; discontinue if anemia develops. Hydrochlorothiazide can cause electrolyte imbalances, hyperglycemia, and hyperuricemia. Avoid use in patients with pheochromocytoma or active liver disease.
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.
Take this medication exactly as prescribed, usually once or twice daily.,Rise slowly from sitting or lying to prevent dizziness from low blood pressure.,Avoid alcohol, which can increase dizziness and drowsiness.,Report any signs of infection, unusual tiredness, or yellowing of skin/eyes.,Use sun protection as hydrochlorothiazide may increase sun sensitivity.,Do not use potassium supplements or salt substitutes without consulting your doctor.
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 25, 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 25 is a Antihypertensive Combination that works by Combination of methyldopa, a centrally acting alpha-2 adrenergic agonist that reduces sympathetic outflow, and hydrochlorothiazide, a thiazide diuretic that inhibits sodium reabsorption in the distal convoluted tubule, reducing plasma volume.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between LOTREL and ALDORIL 25 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 25 is: Oral: 1 tablet (hydrochlorothiazide 25 mg/methyldopa 250 mg) twice daily; increase as needed to max 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 25 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 25 is classified as Category C. First trimester: Limited human data, but animal studies show no teratogenicity at therapeutic doses. Second and third trimesters: Associated with fetal hypotension, oligohydramnios. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.