verapamil (Isoptin SR, Calan SR, Covera HS, Isoptin, Isoptin IV, Calan, Verap, Verapamil SR, Verelan, Verelan PM)

Dosing and uses of Calan SR, Isoptin SR (verapamil)

• Adult
• Pediatric
• Geriatric

 

Adult dosage forms and strengths

injectable solution

• 2.5mg/mL

tablet

• 40mg
• 80mg
• 120mg

tablet/capsule, extended release

• 100mg
• 120mg
• 180mg
• 200mg
• 240mg
• 300mg
• 360mg

 

Angina

Immediate release

• 80 mg PO q8hr initially; usual range: 80-120 mg PO q8hr; not to exceed 480 mg/day

Extended release

• Covera-HS: 180 mg/day PO at bedtime initially; maintenance: 180-540 mg/day PO at bedtime

 

Hypertension

Immediate release

• 80 mg PO q8hr initially; maintenance: 80-320 mg PO q12hr

Extended release

• Calan, Isoptin SR: 180 mg/day PO given in morning (120 mg/day initially if patient elderly or of small stature); for desired response, may be increased to 240 mg/day, then to 360 mg/day (either 180 mg q12hr or 240 mg in morning and 120 mg in evening)
• Verelan: 180 mg/day PO (120 mg/day initially if patient elderly or of small stature); for desired response, may be increased to 240 mg/day PO, then by 120 mg/day at weekly intervals; not to exceed 480 mg/day
• Verelan PM: 200 mg/day PO at bedtime (100 mg/day if patient elderly or of small stature); may be increased by 100 mg/day at weekly intervals as needed; not to exceed 400 mg/day
• Covera-HS: 180 mg/day PO at bedtime (120 mg/day initially if patient elderly or of small stature); for desired response, may be increased to 240 mg/day, then by 120 mg/day at weekly intervals; not to exceed 480 mg/day

 

Supraventricular Arrhythmia & Atrial Fibrillation/Flutter

2.5-5 mg IV over 2 minutes; 5-10 mg dose may be repeated after 15-30 minutes

Alternatively, 0.075-0.15 mg/kg (not to exceed 10 mg) IV over 2 minutes; dose may be repeated once 30 minutes after first dose

 

Chronic Atrial Fibrillation & Paroxysmal Supraventricular Tachycardia

Treatment of chronic atrial fibrillation (rate control); prevention of paroxysmal supraventricular tachycardia

Immediate release: 240-480 mg/day PO divided q6-8hr

 

Tardive Dyskinesia

40 mg PO q8hr; may be titrated to 120 mg q8hr

 

Migraine (Off-label)

Prophylaxis

160-320 mg PO q6-8hr

 

Dosing Modifications

Renal impairment: Use with caution; monitor ECG; for Verelan PM, manufacturer recommends 100 mg at bedtime initially; if CrCl <10 mL/min, reduce dose by 25-50%

Hepatic impairment: In cirrhosis, reduce dose by 20-50% of normal for oral and IV administration

 

Pediatric dosage forms and strengths

injectable solution

• 2.5mg/mL

tablet

• 40mg
• 80mg
• 120mg

tablet/capsule, extended release

• 100mg
• 120mg
• 180mg
• 200mg
• 240mg
• 300mg
• 360mg

 

Supraventricular Tachycardia

1-15 years old: 0.1-0.3 mg/kg (not to exceed 5 mg) IV over 2 minutes; second dose (not to exceed 10 mg) may be given after 30 minutes

Alternatively (not well established), 4-8 mg/kg/day PO divided q8hr

 

Geriatric dosage forms and strengths

In general, lower initial doses are warranted; doses should be adjusted on basis of clinical response

 

Angina

Immediate release: 80 mg PO q8hr initially; usual range: 80-120 mg PO q8hr; not to exceed 480 mg/day

Extended release (Covera-HS): 180 mg PO at bedtime initially; maintenance: 180-540 mg PO at bedtime

 

Hypertension

Immediate release: 40 mg PO q8hr initially; maintenance: 80-320 mg PO q12hr

Extended release (Calan SR, Isoptin SR, Verelan): 120 mg/day PO given in morning

Extended release (Covera-HS): 180 mg/day PO at bedtime

Extended release (Verelan PM): 100 mg/day PO at bedtime

 

Calan SR, Isoptin SR (verapamil) adverse (side) effects

>10%

Headache

Gingival hyperplasia

 

1-10%

Constipation (9%)

Dizziness (4%)

Hypotension (4%)

Dyspepsia (3%)

Nausea (3%)

Edema (2%)

Rash (2%)

Increased liver enzymes (1%)

Sleep disturbance (1%)

Dyspnea

 

Postmarketing Reports

Abnormal ECg

Hypertension

Elevated liver function test results

Asthenia

 

Warnings

Contraindications

Hypersensitivity to verapamil or other calcium channel blockers

Cardiogenic shock

Congestive heart failure

Symptomatic hypotension

Sick sinus syndrome (unless permanent pacemaker in place)

2°/3° AV block (unless permanent pacemaker in place)

 

Cautions

Aortic stenosis

Atrial fibrillation/flutter with accessory bypass tract

1° AV block

Hypertrophic cardiomyopathy (eg, idiopathic hypertrophic subaortic stenosis)

Hypotension (initially or after dose increases)

Exacerbation of angina (during initiation of treatment, after dose increase, or after withdrawal of beta blocker)

Neuromuscular transmission defects; may exacerbate myasthenia gravis

Hepatic or renal impairment

Persistent progressive dermatologic reactions

Generic products may not be bioequivalent

Do not prescribe Covera-HS or Verelan PM for shift workers

Concurrent beta-blocker therapy

Concurrent ivabradine therapy

Slows AV conduction; use cautiously with beta blockers

Hypotension and bradyarrhythmias observed with concurrent use of other CYP3A4 substrates (eg, cyclosporine, telithromycin) because of competitive metabolism

Coadministration with CYP3A4 inhibitors (eg, erythromycin, itraconazole) may decrease metabolism and thus increase toxicity

Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with concurrent use of clonidine with verapamil; monitor heart rate if coadministered

Verapamil is no longer part of Pediatric Advanced Life Support tachyarrhythmia algorithm

Potential toxic dose in patients <6 years old: 15 mg/kg

 

Pregnancy and lactation

Pregnancy category: C

Lactation: Distributed in milk; nursing infant doses range from <0.01% to 0.1% of mother’s dose; manufacturer suggests refraining from nursing (though American Academy of Pediatrics committee states that drug is compatible with nursing)

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Calan SR, Isoptin SR (verapamil)

Mechanism of action

Nondihydropyridine calcium-channel blocker: Inhibits transmembrane influx of extracellular calcium ions across membranes of myocardial cells and vascular smooth muscle cells without changing serum calcium concentrations, resulting in inhibition of cardiac and vascular smooth muscle contraction and thereby dilating main coronary and systemic arteries

Blocks slow inward calcium current responsible for sinus and AV nodal depolarization

 

Absorption

Bioavailability: 20-35%

Onset: Immediate release, 1-2 hr; IV, 1-5 min

Duration: IV, 10-20 min; PO, 6-8 hr

Peak plasma time: Immediate release, 1-2 hr; extended release, 11 hr (Covera-HS, Verelan PM), 5.21 hr (Calan SR, Isoptin SR), or 7-9 hr (Verelan)

 

Distribution

Protein bound: 94%

Vd: 3.8 L/kg

 

Metabolism

Metabolized by hepatic P450 enzyme CYP3A4

Metabolites: Norverapamil (active)

 

Elimination

Half-life: Infants, 4.4-6.9 hr; single dose, 3-7 hr; multiple doses, 4.5 hr; severe hepatic impairment, 14-16 hr

Dialyzable: HD: No

Clearance: 0.5-1 L/hr/kg

Excretion: Urine (70%), feces (9-16%)

 

Administration

IV Incompatibilities

Additive: Albumin (human), aminophylline, amphotericin B, floxacillin, hydralazine, trimethoprim/sulfamethoxazole

Y-site: Albumin (human), amphotericin B cholesteryl sulfate, ampicillin, nafcillin, oxacillin, penicillin G, propofol, sodium bicarbonate

 

IV Compatibilities

Solution: Most common solvents

Additive: Amikacin, amiodarone, ampicillin, ascorbic acid, atropine, bretylium, calcium chloride, calcium gluconate, cefamandole, cefazolin, cefotaxime, cefoxitin, chloramphenicol, cimetidine, clindamycin, dexamethasone, diazepam, digoxin, dobutamine (incompatible at 80 mg in D5W, NS), dopamine, epinephrine, erythromycin, furosemide(?), gentamicin, heparin, hydrocortisone, hydromorphone, insulin, isoproterenol, lidocaine, magnesium sulfate, mannitol, meperidine, metaraminol, methyldopa, methylprednisolone sodium succinate, metoclopramide, morphine, multivitamins, nafcillin(?), naloxone, nitroglycerin, norepinephrine, oxacillin(?), oxytocin, pancuronium, penicillin G, pentobarbital, phenobarbital, phentolamine, phenytoin, piperacillin, potassium chloride, potassium phosphates, procainamide, propranolol, protamine, quinidine, sodium bicarbonate, sodium nitroprusside, theophylline, ticarcillin, tobramycin, tolazoline, vancomycin, vasopressin, vitamins B and C

Syringe: Heparin, inamrinone, milrinone

Y-site: Argatroban, bivalirudin, ciprofloxacin, clarithromycin, dexmedetomidine, dobutamine, dopamine, famotidine, fenoldopam, gatifloxacin, Hextend, hydralazine, inamrinone, linezolid, meperidine, milrinone, penicillin G, piperacillin, ticarcillin

 

IV Administration

Direct IV over at least 2 minutes (3 minutes in older patients)

IV infusion has been performed

 

Storage

Store at room temperature; protect from light