VERAPAMIL HCL
Clinical safety rating: safe
CYP3A4 inhibitors can increase levels and inducers can decrease levels Can cause bradycardia and heart failure.
Verapamil is a phenylalkylamine calcium channel blocker that inhibits voltage-dependent L-type calcium channels in cardiac and vascular smooth muscle, reducing calcium influx, leading to negative inotropic, chronotropic, and dromotropic effects, and vasodilation.
| Metabolism | Hepatic via CYP3A4, CYP1A2, and CYP2C8; extensive first-pass metabolism; metabolites include norverapamil (active). |
| Excretion | Renal (70% as metabolites, 3-4% unchanged); fecal (16% as metabolites); biliary (minor). |
| Half-life | Terminal half-life: 4.5-12 hours (mean 4.8 hours in healthy adults); prolonged in hepatic cirrhosis (up to 30 hours). |
| Protein binding | ~90% bound primarily to albumin; also binds to alpha-1-acid glycoprotein. |
| Volume of Distribution | 3.0-5.5 L/kg; extensive tissue distribution, crosses blood-brain barrier. |
| Bioavailability | Oral immediate-release: 20-35% (due to extensive first-pass metabolism); IV: 100%. |
| Onset of Action | IV: 1-5 minutes; Oral: 30 minutes to 2 hours (immediate-release). |
| Duration of Action | IV: 10-20 minutes; Oral immediate-release: 4-6 hours; sustained-release: 24 hours. |
For hypertension: initial 80 mg orally three times daily; maintenance 240-480 mg/day in divided doses. For angina: 80-120 mg orally three times daily. For supraventricular arrhythmias: IV 5-10 mg over 2 minutes; may repeat 10 mg after 30 minutes. For prophylaxis: oral 240-480 mg/day in divided doses.
| Dosage form | Injectable |
| Renal impairment | No specific dose adjustment for mild to moderate renal impairment (CrCl >10 mL/min). In severe renal impairment (CrCl <10 mL/min), reduce dose by 50-75% and monitor heart rate. |
| Liver impairment | In hepatic impairment: reduce dose by 50% in Child-Pugh class A; use 25% of normal dose for class B and C, with careful monitoring. |
| Pediatric use | For supraventricular tachycardia: IV 0.1-0.3 mg/kg/dose over 2 minutes (max 5 mg in first dose, 10 mg total). For hypertension: oral extended-release, initial 3-4 mg/kg/day in divided doses; adjust as needed up to 8 mg/kg/day (max 360 mg/day). |
| Geriatric use | Start at lowest adult dose due to increased bioavailability and reduced clearance; initial oral dose 40 mg two to three times daily. Titrate slowly. For IV, give the lower end of dose (2.5-5 mg). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CYP3A4 inhibitors can increase levels and inducers can decrease levels Can cause bradycardia and heart failure.
| FDA category | Animal |
| Breastfeeding | Verapamil is excreted into breast milk with a milk-to-plasma ratio of approximately 0.6. Low levels in milk; unlikely to harm infant. Monitor infant for bradycardia, hypotension, and constipation. Consider alternatives in preterm infants or those with cardiovascular compromise. |
| Teratogenic Risk | Verapamil crosses the placenta. First trimester: Limited data, no significant increase in congenital anomalies, but risk cannot be excluded. Second and third trimesters: Associated with maternal hypotension and fetal hypoxia; may cause intrauterine growth restriction, fetal bradycardia, and neonatal hypoglycemia. Use only if clearly needed. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | angina |
| Serious Effects |
["Severe left ventricular dysfunction (ejection fraction <30%) or cardiogenic shock","Sick sinus syndrome or second- or third-degree AV block (except with functioning pacemaker)","Atrial fibrillation/flutter with accessory bypass tract (e.g., Wolff-Parkinson-White syndrome)","Hypersensitivity to verapamil"]
| Precautions | ["May cause heart failure or worsen pre-existing heart failure due to negative inotropic effects","Hypotension","Bradycardia and AV block (avoid in sick sinus syndrome or advanced AV block without pacemaker)","Hepatic impairment reduces clearance, requiring dose adjustment","Avoid in patients with ventricular tachycardia (e.g., wide-complex tachycardia) unless supraventricular origin confirmed","May increase digoxin levels via P-glycoprotein inhibition"] |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate regularly during pregnancy. Fetal monitoring for growth and heart rate, especially in third trimester. Neonatal monitoring for bradycardia, hypotension, and hypoglycemia after delivery. |
| Fertility Effects | No known significant effects on fertility in humans. In animal studies, no impairment of fertility observed. |