CALAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CALAN (CALAN).
Verapamil inhibits calcium ion influx through voltage-gated L-type calcium channels in cardiac and vascular smooth muscle, leading to decreased myocardial contractility, slowed AV conduction, and vasodilation.
| Metabolism | Extensively metabolized in the liver via CYP3A4, CYP1A2, and CYP2C8 isoenzymes; undergoes N-dealkylation and O-demethylation; first-pass metabolism results in low bioavailability (20-35%). |
| Excretion | Approximately 70% renal (3-4% unchanged, remainder as metabolites) and 25% biliary/fecal. |
| Half-life | Terminal elimination half-life is 3-7 hours for immediate-release; can be prolonged to 12-16 hours with sustained-release due to slow absorption; increased in hepatic impairment. |
| Protein binding | Approximately 90% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Vd 4-5 L/kg; indicates extensive tissue distribution beyond plasma volume. |
| Bioavailability | Oral bioavailability is 20-35% due to extensive first-pass hepatic metabolism; IV bioavailability is 100%. |
| Onset of Action | Oral immediate-release: 30 minutes; IV: 2-5 minutes. |
| Duration of Action | Oral immediate-release: 6-8 hours; sustained-release: 24 hours; IV: 10-20 minutes for antiarrhythmic effect. |
Initial: 80-120 mg orally 3 times daily; maintenance: 240-480 mg/day in 3-4 divided doses. IV: 5-10 mg over 2 minutes, may repeat after 15-30 minutes.
| Dosage form | TABLET |
| Renal impairment | CrCl <30 mL/min: reduce dose by 50% and monitor carefully. |
| Liver impairment | Child-Pugh A: 50% of normal dose; Child-Pugh B: 25% of normal dose; Child-Pugh C: contraindicated or use with extreme caution. |
| Pediatric use | Oral: 4-8 mg/kg/day in 3 divided doses; IV: 0.1-0.3 mg/kg over 2 minutes, max 5 mg. |
| Geriatric use | Start at lowest dose (e.g., 40 mg 3 times daily) and titrate slowly; monitor for hypotension and bradycardia. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CALAN (CALAN).
| Breastfeeding | Verapamil (CALAN) is excreted into breast milk; M/P ratio approximately 0.6. The relative infant dose is low (estimated <5% of maternal weight-adjusted dose). No adverse effects reported in breastfed infants. Caution in preterm infants or those with renal impairment. |
| Teratogenic Risk | First trimester: No increased risk of major malformations observed in human studies; animal studies show fetal toxicity at high doses. Second and third trimesters: May cause fetal bradycardia, hypotension, and impaired placental perfusion; avoid use for pregnancy-induced hypertension due to risk of fetal hypoxia. |
■ FDA Black Box Warning
Contains verapamil hydrochloride. Risk of serious adverse effects including hypotension, bradycardia, AV block, and cardiac arrest. Must not be administered to patients with severe left ventricular dysfunction, cardiogenic shock, or sick sinus syndrome (unless paced).
| Serious Effects |
Severe left ventricular dysfunction, cardiogenic shock, sick sinus syndrome (without pacemaker), second- or third-degree AV block (without pacemaker), atrial flutter/fibrillation with accessory bypass tract (e.g., WPW syndrome), concurrent use of IV beta-blockers.
| Precautions | May cause hypotension, bradycardia, AV block, and exacerbation of heart failure. Avoid in patients with pre-existing conduction abnormalities. Use caution with beta-blockers, digoxin, and CYP3A4 inhibitors. Abrupt withdrawal may exacerbate angina. May increase lithium and carbamazepine levels. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they inhibit CYP3A4 metabolism, increasing verapamil levels and risk of toxicity. Limit alcohol intake as it may enhance hypotensive effects. High-fat meals may delay absorption but not extent; take consistently with regard to meals. |
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| Fetal Monitoring | Maternal: Blood pressure, heart rate, ECG for arrhythmias. Fetal: Heart rate monitoring for bradycardia; ultrasound for growth restriction if used long-term in pregnancy. |
| Fertility Effects | No evidence of adverse effects on fertility in humans; animal studies show no impairment. |
| Clinical Pearls | Calan (verapamil) is a class IV antiarrhythmic and calcium channel blocker. Use caution in patients with hepatic impairment due to reduced clearance; dose adjustment may be needed. Avoid in patients with pre-existing bradycardia, second- or third-degree AV block, or sick sinus syndrome unless a pacemaker is present. May increase digoxin levels; monitor digoxin concentrations. Use with caution in patients with hypertrophic cardiomyopathy. For IV administration, have calcium gluconate available to reverse hypotension or bradycardia. Not recommended for use in acute myocardial infarction or cardiogenic shock. |
| Patient Advice | Take exactly as prescribed; do not skip doses or stop abruptly without consulting your doctor. · Avoid grapefruit juice as it can increase verapamil levels and risk of side effects. · If you miss a dose, take it as soon as you remember unless it is almost time for the next dose; do not double the dose. · Avoid alcohol as it may worsen side effects like dizziness or low blood pressure. · Report symptoms of bradycardia (slow heart rate), palpitations, shortness of breath, or swelling of ankles/feet. · This medication may cause dizziness; avoid driving or operating machinery until you know how it affects you. · Do not consume grapefruit or its juice during treatment. · Keep a regular medication schedule and do not change brands without doctor approval. |