NORVASC
Clinical safety rating
cautionComprehensive clinical and safety monograph for NORVASC (NORVASC).
Amlodipine is a dihydropyridine calcium channel blocker that inhibits the influx of extracellular calcium ions across myocardial and vascular smooth muscle cell membranes, causing vasodilation and reduction in peripheral vascular resistance and blood pressure.
| Metabolism | Extensively metabolized in the liver via CYP3A4 isoenzyme; metabolites are inactive. |
| Excretion | Renal: 60% as metabolites; Fecal: 20-25% as parent drug and metabolites; Biliary: ~10%. |
| Half-life | 30-50 hours (terminal); allows once-daily dosing; steady-state achieved after 7-8 days. |
| Protein binding | ~93% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | 21 L/kg (high, indicating extensive tissue binding). |
| Bioavailability | 64-90% (oral); mean ~80%. |
| Onset of Action | Oral: 2-4 hours to measurable effect; peak effect at 6-12 hours. |
| Duration of Action | 24 hours (antihypertensive effect); supports once-daily dosing due to long half-life. |
| Molecular Weight | 408.88 Da |
5–10 mg orally once daily; initial dose 5 mg, titrate based on response; maximum 10 mg/day.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for any degree of renal impairment. |
| Liver impairment | For Child-Pugh Class A or B: start at 2.5 mg once daily, titrate cautiously; Child-Pugh Class C: no data, consider 2.5 mg once daily. |
| Pediatric use | For hypertension: 2.5–5 mg orally once daily for children 6–17 years; for children <6 years: 0.05–0.2 mg/kg once daily, not to exceed 5 mg/day. |
| Geriatric use | Start at 2.5 mg orally once daily due to increased systemic exposure and reduced clearance; titrate slowly based on tolerance and response. |
| 1st trimester | Avoid use in first trimester. Amlodipine is associated with potential teratogenic effects in animal studies; human data are limited. Use only if potential benefit justifies risk. |
| 2nd trimester | Use with caution in second trimester. There is a risk of fetal hypotension and impaired placental perfusion. Consider alternative antihypertensives. |
| 3rd trimester | Avoid in third trimester. May cause fetal hypotension, neonatal hypotension, and uterine atony. Can interfere with labor. |
Clinical note
Comprehensive clinical and safety monograph for NORVASC (NORVASC).
| Placental transfer | Amlodipine crosses the placenta based on animal studies and detection in cord blood. Degree of transfer is moderate; fetal plasma levels are approximately 50-60% of maternal levels at steady state. |
| Breastfeeding | Amlodipine is excreted into human breast milk at low levels (relative infant dose <5% of maternal weight-adjusted dose). No adverse effects reported in breastfed infants. However, due to limited data, use with caution, especially in preterm or low-birth-weight infants. |
| Lactation Rating | L2: Safer (limited data, no known risk) |
| Teratogenic Risk | No teratogenic effects in animal studies. FDA Pregnancy Category C. First trimester: insufficient human data; risk cannot be excluded. Second and third trimesters: may cause fetal hypoxia due to maternal hypotension; avoid use in preeclampsia. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate; fetal heart rate monitoring during third trimester if used for hypertension. |
| Fertility Effects | In animal studies, no adverse effects on fertility. Human data lacking. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to amlodipine or any dihydropyridine derivativeSevere hypotension (systolic blood pressure <90 mmHg)Cardiogenic shockUnstable angina (except Prinzmetal's angina under close monitoring)Acute myocardial infarction (within first 4 weeks)Aortic stenosis (critical obstructive)
| Precautions | Risk of hypotension especially in patients with severe aortic stenosis, Worsening angina and myocardial infarction upon abrupt withdrawal or dose increase, Increased frequency, duration, or severity of angina on initiation or dose increase, Peripheral edema, Use in heart failure patients with reduced ejection fraction may increase risk of pulmonary edema and worsening heart failure, Hepatic impairment may require dose adjustment |
| Food/Dietary | Grapefruit and grapefruit juice should be avoided as they inhibit CYP3A4 metabolism, increasing amlodipine levels and risk of adverse effects. No other significant food interactions. |
| Clinical Pearls | Norvasc (amlodipine) is a dihydropyridine calcium channel blocker with a long half-life (~30-50 hours), allowing once-daily dosing. Onset of action is gradual, reducing reflex tachycardia. It is effective for hypertension and chronic stable angina, but not for acute angina. Common side effects include peripheral edema, dizziness, and flushing. Avoid abrupt discontinuation to prevent rebound hypertension. Caution in patients with severe aortic stenosis or heart failure with reduced ejection fraction (NYHA III/IV). |
| Patient Advice | Take Norvasc exactly as prescribed, usually once daily with or without food. · Do not stop taking this medication without consulting your doctor, as abrupt discontinuation can worsen blood pressure or chest pain. · Swallow the tablet whole; do not crush or chew. · Manage edema by elevating legs and avoiding prolonged standing; report severe swelling to your doctor. · Avoid grapefruit and grapefruit juice as they can increase blood levels of amlodipine and risk of side effects. · Limit alcohol intake, as it can lower blood pressure further. · Monitor blood pressure regularly and keep a log to share with your healthcare provider. |
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