VERELAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VERELAN (VERELAN).
Verapamil inhibits calcium ion influx across cardiac and smooth muscle cells, blocking L-type calcium channels, leading to vasodilation and negative chronotropic, dromotropic, and inotropic effects.
| Metabolism | Hepatic via CYP3A4, CYP1A2, CYP2C8; extensive first-pass metabolism. |
| Excretion | Renal excretion accounts for approximately 70% of elimination, with 3-4% as unchanged drug. Fecal elimination accounts for about 25%, predominantly via biliary secretion. |
| Half-life | Terminal elimination half-life is 2.8 to 7.4 hours in healthy adults, prolonged in hepatic impairment or elderly (up to 12 hours). |
| Protein binding | Approximately 83-93% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 2.7-4.3 L/kg, indicating extensive tissue binding. |
| Bioavailability | Oral bioavailability is 10-20% due to extensive first-pass metabolism; sustained-release formulations have comparable bioavailability but altered absorption profile. |
| Onset of Action | Oral: 30-60 minutes for immediate-release; extended-release: 2-4 hours for peak effect. |
| Duration of Action | Oral: 8-12 hours for immediate-release; extended-release: 24 hours. |
| Molecular Weight | 454.59 |
Hypertension: 120-240 mg ER orally once daily; maximum 480 mg/day. Angina: 80-120 mg IR orally three times daily; ER 180-360 mg once daily.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | GFR 30-50 mL/min: reduce dose by 25-50%; GFR <30 mL/min: use 50% of normal dose and monitor closely. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: reduce dose by 75% or avoid use. |
| Pediatric use | Not FDA-approved; limited data: 4-8 mg/kg/day IR divided every 6-8 hours; maximum 360 mg/day. Titrate cautiously. |
| Geriatric use | Start at low end of dosing range (e.g., 120 mg ER daily); titrate slowly due to increased bioavailability and reduced clearance. |
| 1st trimester | Verapamil crosses the placenta. Animal studies have shown embryotoxicity and fetotoxicity. No well-controlled human studies; use only if benefit outweighs risk. |
| 2nd trimester | May cause fetal bradycardia, growth restriction, and neonatal hypoglycemia. Use with caution and monitor fetal heart rate and growth. |
| 3rd trimester | Avoid near term due to risk of uterine relaxation and maternal hypotension, which may compromise placental perfusion. Neonatal side effects possible. |
Clinical note
Comprehensive clinical and safety monograph for VERELAN (VERELAN).
| Placental transfer | Verapamil crosses the placenta. Cord blood levels are approximately 20-40% of maternal plasma levels. |
| Breastfeeding | Verapamil is excreted into breast milk in low concentrations (milk/plasma ratio ~0.6). Estimated infant dose is <1% of maternal weight-adjusted dose. Generally considered compatible; however, monitor infant for bradycardia, hypotension, and drowsiness. |
â– FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
Severe hypotension (systolic BP <90 mmHg)Cardiogenic shockSecond- or third-degree AV block (unless pacemaker present)Sick sinus syndrome (unless pacemaker present)Atrial flutter/fibrillation with accessory bypass tract (e.g., WPW syndrome)Severe left ventricular dysfunction (ejection fraction <30%)Concurrent use of IV beta-blockers (risk of AV block and hypotension)Hypersensitivity to verapamil or any component
| Precautions | Heart failure: May worsen heart failure due to negative inotropic effect., Hypotension: Can cause symptomatic hypotension., Bradycardia/AV block: May cause sinus bradycardia or AV block, especially with digitalis or beta blockers., Hepatic impairment: Requires dose adjustment., Drug interactions: Increased risk of toxicity with CYP3A4 inhibitors, beta blockers, digitalis, statins, etc. |
| Food/Dietary | Avoid grapefruit and grapefruit juice; they inhibit CYP3A4 metabolism, increasing verapamil concentrations. Take with food to minimize irritation. High-fat meals may delay absorption but do not affect extent. Alcohol may potentiate hypotension. |
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| Lactation Rating | L2 (Possibly Compatible) |
| Teratogenic Risk | Verelan (verapamil) is classified as FDA Pregnancy Category C. Animal studies have shown embryotoxicity and teratogenicity at doses higher than human therapeutic doses. There are no adequate and well-controlled studies in pregnant women. First trimester: Potential risk of fetal cardiovascular and skeletal abnormalities; use only if benefit outweighs risk. Second and third trimesters: May cause maternal hypotension, fetal bradycardia, and reduced uterine blood flow; avoid in preterm labor as it may delay cervical dilation and prolong labor. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and ECG for signs of bradycardia, hypotension, or arrhythmias. Fetal heart rate monitoring is recommended due to risk of fetal bradycardia. Assess fetal growth and amniotic fluid volume periodically, especially during third trimester. Monitor for signs of uterine atony postpartum. |
| Fertility Effects | Verapamil has been associated with reversible elevations in prolactin levels, which may cause gynecomastia or galactorrhea. In animal studies, it impaired fertility with reduced conception rates. In humans, no significant adverse effects on fertility have been reported, but caution is warranted in patients attempting conception. |
| Clinical Pearls | VERELAN (verapamil hydrochloride extended-release) is a calcium channel blocker used for hypertension and angina. Avoid use in patients with severe left ventricular dysfunction, hypotension, or sick sinus syndrome without a pacemaker. May cause constipation, which can be managed with increased fluid intake and dietary fiber. Monitor PR interval on ECG as verapamil can prolong AV conduction. Use caution with beta-blockers, digoxin, and other negative inotropes due to additive effects. Grapefruit juice increases verapamil levels; avoid concurrent use. |
| Patient Advice | Take exactly as prescribed; do not crush or chew extended-release capsules. · Take with food to reduce gastrointestinal upset. · Avoid grapefruit and grapefruit juice while taking this medication. · Do not stop abruptly; sudden discontinuation may worsen angina or cause rebound hypertension. · Report symptoms of heart failure (swelling, shortness of breath) or bradycardia (slow heart rate, dizziness). · May cause constipation; increase fiber and water intake. · Avoid alcohol as it may enhance hypotensive effects. · Use caution when driving if dizziness or fatigue occurs. |