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. |
| Molecular Weight | 454.52 |
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 | Limited human data; animal studies show embryotoxicity at high doses. Use only if benefit outweighs risk. |
| 2nd trimester | May cause fetal bradycardia, hypotension, and growth restriction. Avoid if possible; use lowest effective dose with monitoring. |
| 3rd trimester | Risk of uterine atony and maternal hypotension; may interfere with labor. Avoid near term unless essential. |
Clinical note
CYP3A4 inhibitors can increase levels and inducers can decrease levels Can cause bradycardia and heart failure.
| FDA category | Animal |
| Placental transfer | Verapamil crosses the placenta; fetal concentrations are 20–94% of maternal serum levels. Higher transfer noted at term. |
| Breastfeeding |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | angina |
| Serious Effects |
Severe left ventricular dysfunction (LVEF <30%)Cardiogenic shockSecond- or third-degree AV block (unless pacemaker)Sick sinus syndrome (unless pacemaker)Atrial flutter/fibrillation with accessory bypass tract (e.g., WPW syndrome)Hypotension (systolic BP <90 mmHg)Concurrent use of IV beta-blockersKnown 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 |
| Food/Dietary |
Loading safety data…
| Verapamil is excreted into breast milk in low concentrations (estimated infant dose ~1% of maternal weight-adjusted dose). No adverse effects reported in infants, but monitor for bradycardia and hypotension, especially in neonates. Consider alternative if infant has cardiac or hepatic impairment. |
| Lactation Rating | L2 (Probably Compatible) |
| 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. |
| 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. |
| Avoid grapefruit and grapefruit juice. High-fat meals may increase absorption of extended-release formulations; maintain consistent food intake. Limit alcohol as it may exacerbate hypotension and dizziness. |
| Clinical Pearls | Verapamil is a potent vasodilator and negative inotrope; use with caution in heart failure or LV dysfunction. Avoid in patients with pre-existing conduction abnormalities (e.g., 2nd/3rd degree AV block, sick sinus syndrome) as it delays AV conduction. May increase digoxin levels by 50-70%; monitor digoxin troughs. Do not administer IV verapamil with IV beta-blockers due to risk of severe bradycardia and asystole. For SVT, IV verapamil is second-line after adenosine. In atrial fibrillation, verapamil controls ventricular rate but may not convert to sinus rhythm. Verapamil inhibits CYP3A4; significant drug interactions with statins, cyclosporine, and macrolides. Sustained-release formulations are not interchangeable with immediate-release. |
| Patient Advice | Take exactly as prescribed; do not crush or chew extended-release tablets. · Avoid grapefruit and grapefruit juice as they may increase verapamil levels and risk of side effects. · Report symptoms of heart failure (shortness of breath, swelling of ankles/feet) or very slow/pounding heartbeats. · If you miss a dose, skip it; do not double the next dose. · May cause dizziness or fatigue; avoid driving until you know how it affects you. · Do not stop suddenly without medical advice; abrupt withdrawal may worsen angina or cause rebound hypertension. · Limit alcohol intake as it can increase side effects like dizziness and slow heart rate. |