AMLODIPINE BESYLATE; BENAZEPRIL HYDROCHLORIDE
Clinical safety rating: avoid
Contraindicated (not allowed)
Amlodipine is a dihydropyridine calcium channel blocker that inhibits the influx of calcium ions into vascular smooth muscle and cardiac muscle, leading to vasodilation and reduced peripheral vascular resistance. Benazepril is an angiotensin-converting enzyme (ACE) inhibitor that prevents the conversion of angiotensin I to angiotensin II, resulting in vasodilation, decreased aldosterone secretion, and reduced blood pressure.
| Metabolism | Amlodipine is extensively metabolized in the liver by CYP3A4 to inactive metabolites. Benazepril is hydrolyzed in the liver to its active metabolite, benazeprilat; further metabolism is minimal. |
| Excretion | Amlodipine: ~90% metabolized to inactive metabolites, ~10% excreted unchanged in urine; metabolites excreted renally (~60%) and fecally (~20-25%). Benazepril: hydrolyzed to benazeprilat, which undergoes renal excretion (~33% as unchanged drug and metabolites) and biliary/fecal excretion (~33%), with the remainder via other routes. |
| Half-life | Amlodipine: terminal elimination half-life 30-50 hours (mean ~35 h), allowing once-daily dosing. Benazeprilat: effective half-life 10-11 hours; terminal half-life ~22 hours, with prolonged effects in renal impairment. |
| Protein binding | Amlodipine: ~93% bound to plasma proteins (mainly albumin). Benazeprilat: ~90% bound to albumin and other proteins. |
| Volume of Distribution | Amlodipine: Vd ~21 L/kg (large due to high lipophilicity), indicating extensive tissue distribution. Benazeprilat: Vd ~0.7 L/kg, representing distribution primarily in extracellular fluid. |
| Bioavailability | Amlodipine: oral bioavailability 64-90% (mean ~80%). Benazepril: oral bioavailability ~37% (as prodrug, extensively converted to benazeprilat with high first-pass metabolism). |
| Onset of Action | Oral: amlodipine onset of antihypertensive effect within 2-4 hours; benazepril onset within 1 hour. Maximum effect for both at 4-8 hours. |
| Duration of Action | Amlodipine: >24 hours due to long half-life; once-daily dosing maintains smooth BP control. Benazeprilat: duration of ACE inhibition ~24 hours, supporting once-daily administration. |
| Molecular Weight | 875.51 |
Oral, 1 capsule (amlodipine 2.5-10 mg / benazepril 10-40 mg) once daily. Start with amlodipine 2.5 mg / benazepril 10 mg, titrate based on response.
| Dosage form | CAPSULE |
| Renal impairment | GFR ≥30 mL/min: No adjustment. GFR 15-29 mL/min: Use with caution; starting dose of benazepril 5 mg (use combination with lower benazepril component if available). GFR <15 mL/min: Not recommended (benazepril contraindicated). |
| Liver impairment | Child-Pugh Class A or B: No dose adjustment for benazepril; amlodipine half-life increases, use lower starting dose (e.g., amlodipine 2.5 mg). Child-Pugh Class C: Avoid combination (contraindicated due to extensive hepatic metabolism). |
| Pediatric use | Not approved for pediatric use (safety and efficacy not established). |
| Geriatric use | Initiate with lowest available dose (amlodipine 2.5 mg / benazepril 10 mg) once daily; titrate slowly due to increased sensitivity and risk of hypotension and renal impairment. |
| 1st trimester | Use only if potential benefit justifies risk; animal studies show embryocidal effects with benazepril at human doses. Amlodipine not associated with teratogenicity. |
| 2nd trimester | Use not recommended; fetal renal dysfunction, oligohydramnios, and skull ossification defects reported with ACE inhibitors (benazepril). Risk of fetal hypotension. |
| 3rd trimester | Contraindicated; risks of fetal renal impairment, oligohydramnios, and neonatal anuria/hypotension. NSAIDs-like effect on fetal kidney. |
Clinical note
NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Risk of angioedema can occur at any time discontinue immediately.
| Placental transfer | Both components cross placenta; benazeprilat (active metabolite) crosses readily, amlodipine crosses to a lesser extent. Evidence of fetal toxicity with ACE inhibitors. |
| Breastfeeding | Amlodipine excreted in breast milk; limited data, but considered compatible. Benazepril levels in milk are low; unlikely to cause adverse effects in term infants. Monitor infant for hypotension. |
■ FDA Black Box Warning
Fetal toxicity: Drugs acting directly on the renin-angiotensin system (RAS) can cause injury and death to the developing fetus. Discontinue as soon as pregnancy is detected.
| Common Effects | heart failure |
| Serious Effects |
History of angioedema related to previous ACE inhibitor therapyPregnancyHypersensitivity to amlodipine, benazepril, or any componentConcomitant use with aliskiren in patients with diabetes mellitus
| Precautions | Fetal toxicity: Avoid use in pregnancy; discontinue if pregnancy occurs., Angioedema: Increased risk in patients with history of angioedema, including with ACE inhibitors., Hypotension: Symptomatic hypotension may occur, especially in volume-depleted patients., Hepatic impairment: Amlodipine clearance may be reduced; use with caution., Renal impairment: Monitor renal function; risk of renal impairment in patients with bilateral renal artery stenosis., Hyperkalemia: Risk factors include renal impairment, diabetes, and concomitant potassium-sparing diuretics., Cough: Common adverse effect of ACE inhibitors. |
Loading safety data…
| Lactation Rating | L3 - Moderately Safe |
| Teratogenic Risk | Pregnancy Category D: First trimester: No increased risk of major birth defects from benazepril; amlodipine not associated with teratogenicity. Second and third trimesters: ACE inhibitors (benazepril) cause oligohydramnios, fetal renal dysfunction, skull ossification defects, hypotension, and anuria; amlodipine may cause fetal hypoxia due to calcium channel blockade. |
| Fetal Monitoring | Monitor maternal blood pressure and renal function (creatinine, BUN). Fetal: ultrasonography for oligohydramnios, fetal growth, and renal function; monitor for neonatal hypotension, hyperkalemia, and renal dysfunction after delivery. |
| Fertility Effects | Benazepril: No known effect on fertility. Amlodipine: No known effect on fertility. Theoretical: ACE inhibitors may be associated with erectile dysfunction but not fertility reduction. |
| Food/Dietary | Avoid grapefruit and grapefruit juice due to potential increase in amlodipine plasma concentrations. Avoid salt substitutes high in potassium unless approved by physician. Limit alcohol as it may exacerbate hypotension. No specific interactions with other foods. |
| Clinical Pearls | Avoid use in pregnancy due to fetal renin-angiotensin system toxicity; discontinue as soon as pregnancy is detected. Monitor serum potassium and renal function periodically, especially in elderly or those with renal impairment. The combination may cause symptomatic hypotension more frequently in volume-depleted patients (e.g., diuretic users). Onset of action for blood pressure reduction is 2-4 hours, with peak effect at 6-12 hours. Angioedema risk is higher in Black patients. Use with caution in patients with severe aortic stenosis (amlodipine component). |
| Patient Advice | Take exactly as prescribed; do not stop without consulting your doctor. · Avoid pregnancy; use effective contraception and inform doctor immediately if pregnant. · May cause dizziness, lightheadedness; avoid driving or operating machinery until effects known. · Avoid potassium supplements or salt substitutes containing potassium without medical advice. · Report swelling of face, lips, or throat (angioedema) or difficulty breathing immediately. · Avoid grapefruit juice while taking this medication (increases amlodipine levels). · Limit alcohol intake as it may increase hypotensive effects. · May cause cough, headache, or ankle swelling; inform doctor if bothersome. |