Diltiazem

Diltiazem is a benzothiazepine non dihydropyridine calcium channel blocker with effects on the atrioventricular node and vascular smooth muscle, intermediate between verapamil and amlodipine. It is used for angina, hypertension, rate control in atrial fibrillation and supraventricular tachycardia. It carries similar bradycardia risks to verapamil.

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

Mechanism. Blocks L type calcium channels in nodal tissue, myocardium and arterioles, slowing atrioventricular conduction, reducing contractility modestly and lowering vascular resistance.

Pharmacodynamics. IV onset within 3 minutes with peak 2 to 7 minutes; oral immediate release onset 30 to 60 minutes. Heart rate and blood pressure fall.

Pharmacokinetics. Oral bioavailability about 40% because of first pass metabolism. Half life 3 to 5 hours (immediate release). Metabolised by CYP3A4 to an active metabolite; inhibits CYP3A4.

Atrial fibrillation or flutter rate control, adult. IV 0.25 mg/kg (usually 15 to 20 mg) over 2 minutes; if inadequate after 15 minutes, 0.35 mg/kg over 2 minutes; then infusion 5 to 15 mg/hour for up to 24 hours. Convert to oral therapy once controlled.

Supraventricular tachycardia (after adenosine), adult. IV 0.25 mg/kg over 2 minutes, with the same second dose rule.

Angina, adult. Immediate release 60 mg three times daily, increased to 120 mg three times daily; or modified release 180 to 360 mg once or twice daily. Maximum 360 mg daily in most labels (up to 480 mg in some markets).

Hypertension, adult. Modified release 120 to 240 mg once daily, up to a maximum of 360 mg daily (480 mg in some markets).

Anal fissure, topical (specialist). Diltiazem 2% cream applied to the anal margin two or three times daily for 6 to 8 weeks.

Children. Not established; specialist use only.

Contraindications. Sick sinus syndrome; second or third degree atrioventricular block; severe bradycardia (under 50/min); left ventricular failure with pulmonary congestion; heart failure with reduced ejection fraction; hypotension (systolic under 90 mmHg); acute myocardial infarction with pulmonary congestion; atrial fibrillation with an accessory atrioventricular connection; concurrent IV beta blocker.

Warnings. Bradycardia, heart block and hypotension; peripheral oedema; hepatic enzyme rise; skin reactions including rare severe forms; gingival hyperplasia.

Adverse effects. Oedema, headache, dizziness, bradycardia, flushing, nausea, constipation (less than verapamil), rash, gingival overgrowth.

Interactions.

• Beta blockers: bradycardia and heart block.

• Digoxin: levels rise modestly; monitor.

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

• Strong CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin) raise diltiazem.

• Rifampicin: markedly lowers levels.

• Ciclosporin, tacrolimus, carbamazepine, midazolam: raised levels.

Special groups.

• Pregnancy: avoid unless essential; teratogenic in animals.

• Breastfeeding: excreted in milk; avoid or use with infant monitoring.

• Older adults: start at the lowest dose; bradycardia risk.

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

• Liver impairment: reduce the dose and monitor.

Overdose. Bradycardia, heart block, hypotension: calcium, atropine, high dose insulin with glucose, vasopressors; observe modified release forms for at least 24 hours.

Formulations. Tablets 60 mg; modified release 90, 120, 180, 240, 300, 360 mg; injection 5 mg/mL; cream 2%.

Administration. IV bolus over 2 minutes with continuous ECG and blood pressure; infuse diluted in 5% glucose or 0.9% sodium chloride. Swallow modified release forms whole; consistency with meals is advised.

Baseline. 12 lead ECG, heart rate, blood pressure, ejection fraction where available, liver function.

Monitoring. Heart rate and PR interval; blood pressure; oedema; liver enzymes if symptoms.

Stopping. Taper over 1 to 2 weeks if used for angina.

Common prescribing errors. Giving IV diltiazem to a patient on a beta blocker; using it in reduced ejection fraction; not capping simvastatin at 10 mg; using it for wide complex tachycardia.