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). |
| Molecular Weight | 491.07 |
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 | Limited human data; animal studies show some adverse effects. Use only if clearly needed. |
| 2nd trimester | May cause fetal bradycardia and hypoxia; use caution. Monitor fetal heart rate. |
| 3rd trimester | Can cause uterine relaxation, maternal hypotension, and fetal distress. Avoid near term. |
Clinical note
CYP3A4 inhibitors can increase levels and inducers can decrease levels Can cause bradycardia and heart failure.
| Placental transfer | Crosses placenta; fetal plasma levels approximately 50% of maternal levels. |
| Breastfeeding | Verapamil is excreted into breast milk in small amounts (estimated infant dose ~1% maternal). Monitor infant for bradycardia, hypotension, and constipation. Generally considered compatible with breastfeeding. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | angina |
| Serious Effects |
Severe left ventricular dysfunctionCardiogenic shockSick sinus syndrome (without pacemaker)Second- or third-degree AV block (without pacemaker)Atrial flutter/fibrillation with accessory bypass tract (e.g., WPW syndrome)Concomitant use with ivabradine
| 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 |
| Food/Dietary |
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| Lactation Rating |
| L2 (Safer) |
| 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. |
| 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. |
| Grapefruit and grapefruit juice increase verapamil plasma concentrations by inhibiting CYP3A4 metabolism; avoid concurrent use. High-sodium foods can counteract the antihypertensive effect; maintain low-sodium diet. Alcohol may potentiate hypotensive effects; limit or avoid alcohol consumption. St. John's wort may reduce verapamil efficacy; avoid concurrent use. |
| Clinical Pearls | Avoid IV verapamil in patients with pre-existing severe left ventricular dysfunction or heart failure. Use with caution in patients with hypertrophic cardiomyopathy due to risk of pulmonary edema. Contraindicated in patients with second- or third-degree AV block unless a functioning pacemaker is present. May cause gingival hyperplasia with chronic use; ensure good oral hygiene. Diltiazem is a preferred alternative in patients with concurrent atrial fibrillation and systolic heart failure. IV verapamil can cause precipitous hypotension; have calcium gluconate available for reversal. Verapamil increases serum levels of cyclosporine, tacrolimus, and sirolimus; monitor levels closely. In elderly patients, start with lowest effective dose due to age-related decline in hepatic metabolism. Sustained-release formulations should not be crushed or chewed. Verapamil may cause constipation, especially in the elderly; consider stool softeners. May increase bleeding risk in patients on anticoagulants due to altered platelet function. |
| Patient Advice | Avoid taking verapamil with grapefruit or grapefruit juice; it can increase blood levels of the medication. · Do not abruptly stop taking this medication; sudden discontinuation may cause chest pain or heart attack. · If you miss a dose, take it as soon as you remember unless it is almost time for your next dose. Do not double the dose. · Inform your healthcare provider if you experience swelling of the ankles or feet, shortness of breath, or irregular heartbeat. · This medication may cause constipation; increase fluid and fiber intake to prevent this. · If you are using extended-release tablets, swallow them whole; do not crush, chew, or break them. · Avoid drinking alcohol while taking verapamil; it may worsen side effects like dizziness or drowsiness. · Tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding before starting this medication. · Keep all appointments for blood pressure and heart monitoring while on this medication. |