AMLODIPINE MALEATE; BENAZEPRIL HYDROCHLORIDE
Clinical safety rating: avoid
NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Risk of angioedema can occur at any time discontinue immediately.
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 and reduced aldosterone secretion.
| Metabolism | Amlodipine is extensively metabolized in the liver via CYP3A4. Benazepril is hydrolyzed in the liver to its active metabolite benazeprilat, with minimal further metabolism. |
| Excretion | Renal: Amlodipine 10% unchanged, benazeprilat (active metabolite) 50-60% in urine; biliary/fecal: amlodipine 20-25% as metabolites, benazeprilat 10-20% in feces. |
| Half-life | Amlodipine: 30-50 h (terminal), allowing once-daily dosing; benazeprilat: 10-11 h (terminal), effective for 24 h. |
| Protein binding | Amlodipine: 93-98% bound to plasma proteins; benazeprilat: ~90% bound to albumin. |
| Volume of Distribution | Amlodipine: 21 L/kg (large, extensive tissue distribution); benazeprilat: 0.7 L/kg. |
| Bioavailability | Amlodipine: 64-90%; benazepril: >37% (benazeprilat, active moiety) after rapid metabolism. |
| Onset of Action | Oral: Amlodipine 30-50 min, benazepril 1-2 h for antihypertensive effect. |
| Duration of Action | Amlodipine: 24 h (once-daily), sustained with missed doses; benazepril: 24 h (once-daily) but may require dose adjustment in renal impairment. |
| Molecular Weight | Amlodipine maleate: 408.9 Da (as free base); benazepril hydrochloride: 424.9 Da (as free base). For the combination product, reference individual components. |
Initial: 2.5-5 mg amlodipine / 10-20 mg benazepril orally once daily, titrated to 10/40 mg once daily based on response.
| Dosage form | CAPSULE |
| Renal impairment | If GFR 15-29 mL/min: maximum 5/20 mg daily. If GFR <15 mL/min or dialysis: not recommended. |
| Liver impairment | Child-Pugh A or B: initial amlodipine 2.5 mg once daily; Child-Pugh C: avoid use. |
| Pediatric use | Safety and efficacy not established in patients <18 years. |
| Geriatric use | Initiate at 2.5/10 mg once daily; titrate slowly due to increased sensitivity and decreased renal function. |
| 1st trimester | Amlodipine maleate: No well-controlled studies in pregnant women; use only if benefit outweighs risk. Human data limited; animal studies show no teratogenicity but embryotoxicity at high doses. |
| 2nd trimester | Benazepril hydrochloride: Contraindicated in second and third trimesters due to risk of oligohydramnios and fetal renal dysfunction. Discontinue as soon as pregnancy detected. |
| 3rd trimester | Benazepril hydrochloride: Same as second trimester. May cause fetal hypotension, hyperkalemia, and skull hypoplasia. |
Clinical note
NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Risk of angioedema can occur at any time discontinue immediately.
| FDA category | Contraindicated |
| Placental transfer | Amlodipine crosses placenta; benazepril and benazeprilat cross placenta in animals and humans, with evidence of fetal exposure. |
■ 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.
| Common Effects | heart failure |
| Serious Effects |
History of angioedema related to previous ACE inhibitor therapyHereditary or idiopathic angioedemaPregnancy (especially second and third trimesters)Concomitant use with aliskiren in patients with diabetes mellitus
| Precautions | Fetal toxicity, Angioedema, Hypotension, Hepatic impairment, Renal impairment, Hyperkalemia, Symptomatic hypotension in volume- or salt-depleted patients |
| Food/Dietary | Avoid high-potassium foods (e.g., bananas, oranges, potatoes, spinach) in large amounts if taking with benazepril, as ACE inhibitors can increase potassium levels. Grapefruit and grapefruit juice should be avoided as they may increase amlodipine levels. No other significant food interactions. |
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| Breastfeeding | Amlodipine is excreted in breast milk in low amounts; no adverse effects reported in infants. Benazepril and its active metabolite are excreted in breast milk in very low concentrations; unlikely to affect nursing infant. However, caution is advised due to potential renal effects in premature infants. |
| Lactation Rating | L3: Moderately Safe |
| Teratogenic Risk | First trimester: ACE inhibitors (benazepril) associated with increased risk of congenital malformations (cardiovascular, CNS). Second/third trimesters: ACE inhibitors cause fetal renal hypoperfusion, oligohydramnios, pulmonary hypoplasia, and neonatal anuria. Amlodipine: limited human data; animal studies show delayed parturition, fetal death at high doses. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function (serum creatinine, BUN), electrolytes. Monitor fetal ultrasound for oligohydramnios, fetal growth. Neonatal monitoring for hypotension, hyperkalemia, renal function. |
| Fertility Effects | Amlodipine: no known effect on fertility in humans. Benazepril: no evidence of impaired fertility. Based on animal studies, no significant reproductive toxicity. |
| Clinical Pearls | Combination of amlodipine (calcium channel blocker) and benazepril (ACE inhibitor) provides synergistic antihypertensive effect. Monitor renal function and serum potassium, especially in patients with renal impairment or those taking potassium-sparing diuretics. Amlodipine may cause peripheral edema; benazepril may cause cough. Avoid use in pregnancy due to risk of fetal harm. |
| Patient Advice | Take this medication exactly as prescribed, usually once daily with or without food. · Avoid potassium supplements and salt substitutes containing potassium unless directed by your doctor. · Notify your doctor if you become pregnant or plan to become pregnant; this medication can harm the unborn baby. · Common side effects include swelling of the ankles or feet, cough, dizziness, or headache; report persistent cough or severe swelling. · Rise slowly from sitting or lying positions to minimize dizziness. · Do not stop taking this medication abruptly without consulting your doctor. |