NORVASC
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NORVASC (NORVASC).
| Breastfeeding | Amlodipine is excreted in human milk. M/P ratio not determined. Limited data suggest low transfer. Consider risk of hypotension in infant. |
| 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 |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to amlodipine or any component of the formulation"]
| 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"] |
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| 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. |