VERELAN PM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VERELAN PM (VERELAN PM).
Verapamil is a calcium channel blocker that inhibits the influx of calcium ions across the cardiac and vascular smooth muscle cells, thereby reducing myocardial contractility, sinoatrial and atrioventricular node conduction, and vascular tone.
| Metabolism | Hepatic metabolism primarily via CYP3A4, CYP1A2, and CYP2C8; forms several metabolites including norverapamil (active). |
| Excretion | Primarily hepatic metabolism (>95%), with 3-4% excreted unchanged in urine; biliary/fecal excretion accounts for <1% of unchanged drug. |
| Half-life | Terminal elimination half-life 7.2 ± 1.5 hours after oral administration, prolonged in hepatic impairment (up to 14-16 hours) and elderly; steady-state achieved after 3-4 days. |
| Protein binding | 90% bound to plasma proteins (primarily albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | 3-4 L/kg (mean 3.4 L/kg), indicating extensive tissue distribution; higher Vd with cirrhosis. |
| Bioavailability | Oral (extended-release): 40-50% due to first-pass hepatic metabolism; food slightly increases AUC (10-15%) but not clinically significant. |
| Onset of Action | Oral (extended-release): 1-2 hours for detectable serum concentrations, 2-4 hours for measurable reduction in blood pressure or angina symptoms. |
| Duration of Action | 24 hours with once-daily dosing; antihypertensive effect maintained over 24-hour dosing interval, but variability exists; food may prolong duration slightly. |
| Molecular Weight | 454.6 |
Verelan PM (verapamil hydrochloride) is an extended-release oral capsule administered once daily at bedtime. Typical adult dose for hypertension is 200 mg to 400 mg once daily at bedtime. Initial dose is 200 mg, titrated upward as needed. Maximum recommended dose is 400 mg daily.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | No specific dose adjustment is recommended for renal impairment. However, verapamil is not significantly removed by hemodialysis. Use with caution in patients with impaired renal function as they may be more sensitive to antihypertensive effects. |
| Liver impairment | In patients with impaired hepatic function (Child-Pugh score A or B), dose should be reduced by 50% to 70% of normal dose as verapamil is extensively metabolized by the liver. For Child-Pugh class C, use is contraindicated or avoid if possible; if necessary, use lowest possible dose with careful monitoring. |
| Pediatric use | Pediatric use is not recommended as safety and efficacy in children have not been established. No official weight-based dosing guidelines exist for Verelan PM in pediatric patients. Alternative formulations (e.g., immediate-release verapamil) are used off-label with dosing based on weight (e.g., 4-8 mg/kg/day in divided doses) but not for Verelan PM specifically. |
| Geriatric use |
| 1st trimester | Verapamil crosses the placenta. Animal studies have shown adverse effects on fetus at high doses; no adequate human studies. Use only if benefit outweighs risk. |
| 2nd trimester | Verapamil exposure during second trimester may cause fetal bradycardia and hypotension; monitor fetal heart rate. Use only if clearly needed. |
| 3rd trimester | Verapamil may cause uterine relaxation and premature labor; may also cause fetal bradycardia, hypotension, and hypoglycemia. Avoid near term unless essential. |
Clinical note
Comprehensive clinical and safety monograph for VERELAN PM (VERELAN PM).
| Placental transfer | Verapamil crosses the placenta with a cord-to-maternal plasma ratio of approximately 0.2-0.4. |
| Breastfeeding | Verapamil is excreted into breast milk in small amounts (relative infant dose <2% of maternal weight-adjusted dose). No adverse effects reported in breastfed infants. However, monitor for signs of hypotension or bradycardia. |
■ FDA Black Box Warning
None.
| Serious Effects |
Severe left ventricular dysfunction (ejection fraction <30%)Hypotension (systolic <90 mmHg)Cardiogenic shockSick sinus syndrome or second/third-degree AV block (unless pacemaker placed)Atrial flutter/fibrillation with accessory bypass tract (e.g., WPW syndrome)Concomitant use of IV beta-blockers (risk of myocardial depression)
| Precautions | Heart failure: May worsen heart failure due to negative inotropic effects., Hypotension: May cause excessive hypotension, especially with IV use., Bradycardia and AV block: Risk of bradycardia and AV block, especially in patients with sick sinus syndrome or pre-existing conduction defects., Hepatic impairment: Use with caution; doses may need reduction., Neuromuscular transmission: May potentiate neuromuscular blocking agents. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they increase verapamil plasma concentration. High-fat meals may delay absorption but do not require specific avoidance. Alcohol may enhance hypotensive effect. Maintain consistent sodium intake. |
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| In elderly patients, start with the lowest available dose (200 mg once daily at bedtime). Titrate slowly due to increased sensitivity to antihypertensive effects and higher risk of bradycardia, constipation, and hypotension. Maximum dose may be lower than in younger adults. Monitor renal and hepatic function as age-related decline may require dose adjustment. |
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | Verapamil (VERELAN PM) is classified as FDA Pregnancy Category C. First trimester: Limited human data; animal studies have shown embryotoxicity and teratogenicity (skeletal abnormalities) at high doses. Second and third trimesters: Can cause maternal hypotension, which may reduce uteroplacental blood flow; potential for fetal hypoxia and growth restriction. Risk of neonatal bradycardia and hypoglycemia if used near term. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate regularly. Fetal heart rate monitoring during labor if used for preterm labor. Assess fetal growth via ultrasound if long-term use. Neonatal monitoring for bradycardia, hypotension, and hypoglycemia after delivery. |
| Fertility Effects | In animal studies, verapamil did not impair fertility. In humans, no significant effects on female fertility reported. Limited data on male fertility; theoretical risk of reversible sperm motility impairment due to calcium channel blockade. |
| Clinical Pearls | VERELAN PM (verapamil hydrochloride extended-release) is a calcium channel blocker indicated for hypertension. Administer once daily at bedtime to minimize peak concentration-related adverse effects. Avoid in patients with pre-existing severe left ventricular dysfunction, hypotension, or sick sinus syndrome without a pacemaker. Coadministration with beta-blockers may increase risk of heart block. Monitor renal and hepatic function; dose adjustment needed in hepatic impairment. Grapefruit juice increases verapamil exposure; avoid concurrent use. |
| Patient Advice | Take this medication at bedtime each day, as directed by your doctor. · Swallow the capsule whole; do not crush, chew, or open it. · Avoid drinking grapefruit juice while taking this medicine. · Do not stop taking this medication abruptly; consult your doctor if you experience any side effects. · This medicine may cause dizziness or fatigue; avoid driving or operating machinery until you know how it affects you. · Inform your healthcare provider about all other medications you are taking, especially beta-blockers, digoxin, or statins. |