Verapamil

Verapamil is a non dihydropyridine calcium channel blocker with strong effects on the sinoatrial and atrioventricular nodes and on myocardial contractility. It is used for supraventricular tachycardia, rate control in atrial fibrillation, angina, hypertension and cluster headache prophylaxis. It must not be combined with a beta blocker in the same patient without care, and never with IV beta blockers.

Classification. Phenylalkylamine class IV antiarrhythmic and non dihydropyridine calcium channel blocker.

Mechanism. Blocks L type calcium channels in cardiac nodal tissue, myocardium and vascular smooth muscle. Slows atrioventricular conduction, reduces contractility and dilates arteries.

Pharmacodynamics. IV onset within 1 to 2 minutes, peak 3 to 5 minutes, duration 10 to 20 minutes for conduction effect. Oral onset 1 to 2 hours. Lowers heart rate and blood pressure.

Pharmacokinetics. Oral absorption over 90% but extensive first pass metabolism leaves bioavailability 20 to 35%. Half life 3 to 7 hours after a single dose and 5 to 12 hours at steady state. Metabolised by CYP3A4; inhibits CYP3A4 and P-glycoprotein.

Supraventricular tachycardia (after vagal manoeuvres and adenosine), adult. 5 to 10 mg (about 0.075 to 0.15 mg/kg) IV over at least 2 minutes (3 minutes in older adults) with continuous ECG and blood pressure; if no response in 30 minutes, give a further 10 mg. Maximum cumulative IV dose about 20 mg.

Atrial fibrillation or flutter rate control, adult. IV 5 to 10 mg over at least 2 minutes (3 minutes in older adults) with continuous ECG and blood pressure; oral 40 to 120 mg three times daily or modified release 120 to 240 mg once daily (maximum 480 mg daily).

Angina, adult. Immediate release 80 to 120 mg three times daily; modified release 240 to 480 mg daily in one or two doses.

Hypertension, adult. Immediate release 80 mg three times daily, up to 120 mg three times daily; modified release 120 to 240 mg once daily, increased to a maximum of 480 mg daily.

Cluster headache prophylaxis, adult (specialist). 240 mg daily in divided doses, increasing to 480 mg daily with ECG monitoring.

Children. IV 0.1 to 0.3 mg/kg (maximum 5 mg) over 2 minutes in children over 1 year; avoid IV use in infants under 1 year (cardiac arrest). Oral dosing is specialist.

Contraindications. Hypotension (systolic under 90 mmHg); cardiogenic shock; second or third degree atrioventricular block; sick sinus syndrome; heart failure with reduced ejection fraction or severe left ventricular dysfunction; atrial fibrillation with an accessory atrioventricular connection (Wolff-Parkinson-White); wide complex tachycardia of uncertain or ventricular origin; recent IV beta blocker; acute myocardial infarction with heart failure.

Warnings. Severe bradycardia, heart block, asystole and hypotension, especially with beta blockers, in older adults and in hypertrophic cardiomyopathy with outflow obstruction. Constipation (common). Gingival hyperplasia. Hepatotoxicity, rarely. Do not give IV verapamil to a patient taking a beta blocker, or IV beta blocker to a patient on verapamil.

Adverse effects. Constipation, dizziness, headache, bradycardia, hypotension, oedema, flushing, nausea, gingival overgrowth.

Interactions.

• Beta blockers: bradycardia, heart block, heart failure.

• Digoxin: levels rise 50 to 75%; halve the digoxin dose and monitor levels.

• Simvastatin: limit to 10 mg daily; atorvastatin: lower doses.

• Clarithromycin, erythromycin, ritonavir, ketoconazole, itraconazole: raise verapamil.

• Rifampicin, phenytoin, carbamazepine: lower levels.

• Dabigatran: raised exposure; reduce the dose or avoid; apixaban and rivaroxaban: caution.

• Colchicine, ciclosporin, tacrolimus, midazolam: raised levels.

• Dantrolene IV: hyperkalaemia and cardiovascular collapse.

Special groups.

• Pregnancy: used for supraventricular tachycardia and hypertension when needed; monitor the foetus.

• Breastfeeding: small amounts in milk; compatible.

• Older adults: start at the lower dose; slower IV injection.

• Kidney impairment: no adjustment; caution in severe disease.

• Liver impairment: reduce to about one third of the usual dose in cirrhosis; monitor.

Overdose. Bradycardia, heart block, hypotension, hyperglycaemia. Give calcium gluconate 10% 30 to 60 mL IV (or calcium chloride 10% 10 to 20 mL via central line), atropine, high dose insulin with glucose, vasopressors; consider lipid emulsion; admit for monitored observation, since modified release preparations act for 24 hours or more.

Formulations. Tablets 40, 80, 120 mg; modified release tablets 120, 180, 240 mg; injection 2.5 mg/mL.

Administration. IV: give slowly over 2 to 3 minutes; may be diluted. Oral: take with food; modified release tablets must be swallowed whole.

Baseline. 12 lead ECG (PR interval, delta wave), blood pressure, heart rate, liver function, drug history (beta blockers, digoxin).

Monitoring. Continuous ECG and blood pressure during IV dosing, and for at least 30 minutes after; PR interval and pulse during oral therapy; bowel habit; digoxin level where used.

Stopping. Taper where practical; abrupt cessation may unmask angina or arrhythmia.

Common prescribing errors. Giving IV verapamil after an IV beta blocker; using it in wide complex tachycardia or Wolff-Parkinson-White; not halving digoxin; exceeding simvastatin 10 mg; using it in infants.