VERAPAMIL HYDROCHLORIDE
Clinical safety rating: safe
Animal studies have demonstrated safety
L-type calcium channel blocker; inhibits calcium ion influx across cardiac and smooth muscle cells, leading to decreased myocardial contractility, slowed AV conduction, and vasodilation.
| Metabolism | Hepatic via CYP3A4, CYP1A2, CYP2C8, CYP2C9, CYP2C19; first-pass metabolism; metabolites norverapamil (active, 20% potency) and various inactive metabolites. |
| Excretion | Approximately 70% renal (3-4% unchanged, remainder as metabolites) and 16% fecal via biliary excretion. |
| Half-life | Terminal elimination half-life 4.5-12 hours (mean 6 hours); prolonged to 9-12 hours in hepatic cirrhosis or elderly patients due to reduced clearance. |
| Protein binding | 90% bound to plasma proteins (primarily albumin and α1-acid glycoprotein). |
| Volume of Distribution | 4.5-5.0 L/kg (mean 4.5 L/kg), indicating extensive extravascular tissue distribution. |
| Bioavailability | Oral immediate-release: 20-35% due to extensive first-pass hepatic metabolism; IV: 100%. |
| Onset of Action | IV: 1-5 minutes; Oral immediate-release: 30 minutes to 2 hours; Oral extended-release: 1-2 hours. |
| Duration of Action | IV: 10-30 minutes; Oral immediate-release: 6-8 hours; Oral extended-release: 24 hours (with once-daily dosing). |
Oral: 80-120 mg three times daily; extended-release: 180-480 mg once daily. Intravenous: 5-10 mg over 2 minutes, repeat after 15-30 minutes if needed.
| Dosage form | INJECTABLE |
| Renal impairment | GFR 10-50 mL/min: use cautiously, start at lower doses (e.g., oral 40 mg three times daily). GFR <10 mL/min: avoid or reduce dose by 50%. |
| Liver impairment | Child-Pugh A: reduce dose by 20-30%. Child-Pugh B: reduce by 50%. Child-Pugh C: contraindicated or use with extreme caution. |
| Pediatric use | Oral: 4-8 mg/kg/day divided every 6-8 hours. IV: 0.1-0.3 mg/kg/dose over 2 minutes, max 5 mg. |
| Geriatric use | Start at lowest dose (e.g., oral 40 mg three times daily); titrate slowly due to reduced clearance and increased risk of hypotension and bradycardia. |
| 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.
| Breastfeeding | Verapamil is excreted into breast milk in low concentrations (M/P ratio ~0.6). Estimated infant dose <1% of maternal weight-adjusted dose. Considered compatible with breastfeeding; monitor infant for bradycardia and hypotension. |
| Teratogenic Risk | Verapamil crosses the placenta. First trimester: Limited human data; animal studies show embryotoxicity at high doses. Second/third trimesters: No consistent teratogenicity; potential for fetal bradycardia, hypotension, and growth restriction with chronic use. Avoid in pregnancy unless benefit outweighs risk. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | angina |
| Serious Effects |
["Severe left ventricular dysfunction (ejection fraction <30%)","Cardiogenic shock","Second- or third-degree AV block (except with functioning pacemaker)","Sick sinus syndrome (except with functioning pacemaker)","Atrial flutter/fibrillation with accessory bypass tract (e.g., WPW syndrome)","Hypersensitivity to verapamil","Concurrent use of IV beta-blockers (risk of asystole)"]
| Precautions | ["Heart failure: may worsen heart failure due to negative inotropic effects","Hypotension: risk especially with intravenous administration","AV block/bradycardia: avoid in sick sinus syndrome or high-grade AV block without pacemaker","Hepatic impairment: reduce dose; prolonged half-life","Conduction abnormalities: may precipitate ventricular arrhythmias in atrial flutter/fibrillation with WPW syndrome","Drug interactions: CYP3A4 inhibitors/inducers; grapefruit juice; beta-blockers; digoxin; statins; other antihypertensives"] |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and ECG for arrhythmias. Monitor fetal heart rate and growth (ultrasound) in chronic use. Assess for signs of maternal hypotension or bradycardia. |
| Fertility Effects | No established negative impact on human fertility. Animal studies show no impairment. May theoretically affect sperm motility via calcium channel blockade; clinical significance unknown. |