CALAN SR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CALAN SR (CALAN SR).
Verapamil inhibits calcium ion influx across cardiac and vascular smooth muscle cells, blocking L-type calcium channels, leading to negative inotropic, chronotropic, and dromotropic effects, and vasodilation.
| Metabolism | Primarily hepatic via CYP3A4; first-pass metabolism; major metabolite norverapamil retains 20% activity. |
| Excretion | Approximately 70% of the dose is excreted as metabolites in the urine; 3-4% as unchanged drug; 25% eliminated in feces via biliary excretion. |
| Half-life | Terminal elimination half-life is 6-12 hours (average ~8 hours) after single oral dose; may increase to 12-16 hours with chronic dosing due to saturable hepatic metabolism; clinical context: requires dosing adjustments in hepatic impairment. |
| Protein binding | Approximately 90% bound to plasma proteins (mainly albumin). |
| Volume of Distribution | 3.5 L/kg; indicates extensive tissue binding and distribution beyond plasma volume. |
| Bioavailability | Oral (sustained-release): 40-60% due to first-pass metabolism; immediate-release: 70-80% when fasting but reduced to ~50% with food. |
| Onset of Action | Oral (sustained-release): 30-60 minutes for reduction in blood pressure; peak effect at 6-8 hours. |
| Duration of Action | Oral (sustained-release): 24 hours with once-daily dosing for hypertension; 12-24 hours for angina; clinical notes: sustained-release formulation intended for once-daily use; immediate-release has duration of 6-8 hours. |
Oral: 180–240 mg once daily; maximum 480 mg/day.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | CrCl <30 mL/min: reduce dose by 50–75% of normal; initiate at lower end of dosing range. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B or C: reduce dose by 50% and monitor. |
| Pediatric use | Not FDA-approved for children; limited data: 4–8 mg/kg/day divided twice daily (immediate-release form only). |
| Geriatric use | Initiate at 120 mg once daily; titrate slowly due to increased bioavailability and prolonged half-life. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CALAN SR (CALAN SR).
| Breastfeeding | Verapamil is excreted into breast milk with a milk-to-plasma ratio (M/P) of approximately 0.23 to 0.94 (mean~0.6). Infant dose is low (<5% maternal weight-adjusted dose). No adverse effects reported in breastfed infants. Consider monitoring infant for bradycardia, hypotension, and constipation. |
| Teratogenic Risk | Verapamil (CALAN SR) is classified as FDA Pregnancy Category C. First trimester: Animal studies have shown embryotoxicity and fetotoxicity, but no well-controlled human studies exist. Risk cannot be ruled out. Second/third trimesters: May cause fetal bradycardia, hypotension, and impaired placental perfusion. Avoid use in pregnancy unless benefit outweighs risk. |
■ FDA Black Box Warning
None
| Serious Effects |
["Severe left ventricular dysfunction (ejection fraction <30%)","Cardiogenic shock","Sick sinus syndrome or 2nd/3rd degree AV block (except with functioning pacemaker)","Atrial fibrillation/flutter with accessory bypass tract (e.g., WPW)","Hypersensitivity to verapamil"]
| Precautions | ["Heart failure: may exacerbate due to negative inotropic effects","Hypotension","Bradycardia/AV block: avoid in sick sinus syndrome or high-grade AV block without pacemaker","Hepatic impairment: reduce dose","Concomitant beta-blockers: increased risk of bradycardia and heart failure","Digoxin toxicity: verapamil increases digoxin levels"] |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they can increase verapamil levels. Limit alcohol consumption as it may enhance hypotensive effects. High-fat meals may delay absorption but not significantly affect overall bioavailability. |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate regularly. Fetal monitoring: heart rate and growth via ultrasound if used in second/third trimester. Assess for signs of fetal distress and placental insufficiency. |
| Fertility Effects | In men, verapamil may decrease sperm motility and impair fertility (reversible upon discontinuation). In women, no direct evidence of impaired fertility; however, calcium channel blockers may affect tubal function and implantation. Clinical significance uncertain. |
| Clinical Pearls | CALAN SR (verapamil sustained-release) is a non-dihydropyridine calcium channel blocker used for hypertension and angina. Avoid use in patients with pre-existing severe left ventricular dysfunction, hypotension, or sick sinus syndrome without a pacemaker. Caution with concomitant beta-blockers due to risk of bradycardia or heart block. Verapamil is a potent CYP3A4 inhibitor; monitor for increased levels of statins, cyclosporine, and other CYP3A4 substrates. |
| Patient Advice | Take exactly as prescribed; do not crush or chew the extended-release tablet. · Can be taken with or without food, but avoid grapefruit and grapefruit juice. · Do not suddenly stop taking this medication; abrupt withdrawal may worsen chest pain. · Report symptoms of heart failure such as shortness of breath, swelling of ankles/feet. · May cause dizziness or fatigue; avoid driving until you know how it affects you. · Constipation is common; maintain adequate fluid and fiber intake. |