Amlodipine

Amlodipine is a long acting dihydropyridine calcium channel blocker. It is a first line antihypertensive, especially for patients of African ancestry, and an antianginal. Its half life of 30 to 50 hours allows once daily dosing and forgives missed doses. Dose related ankle oedema is the main adverse effect.

Classification. Dihydropyridine L type calcium channel blocker; long acting vasodilator.

Mechanism. Blocks L type calcium channels in vascular smooth muscle, causing arteriolar dilation and reduced afterload. Little effect on the heart rate or contractility at therapeutic doses.

Pharmacodynamics. Blood pressure falls gradually over 6 to 12 hours; full effect after 1 to 2 weeks. Reduces myocardial oxygen demand and relieves coronary spasm.

Pharmacokinetics. Oral bioavailability 60 to 65%, unaffected by food; peak 6 to 12 hours; half life 30 to 50 hours; steady state at 7 to 8 days. Hepatic metabolism by CYP3A4; metabolites excreted in urine.

Hypertension, adult.

• Start 5 mg once daily; 2.5 mg in older adults, frail patients, small adults and hepatic impairment.

• Increase after 1 to 2 weeks to 10 mg once daily if needed.

• Maximum 10 mg daily.

• Combine with a renin angiotensin agent or a thiazide like diuretic if one drug is insufficient.

Chronic stable angina and vasospastic angina, adult. 5 to 10 mg once daily; maximum 10 mg.

Hypertension, children 6 to 17 years. 2.5 to 5 mg once daily; maximum 5 mg daily; specialist.

Contraindications. Severe hypotension; cardiogenic shock; unstable angina; significant aortic stenosis; hypersensitivity to dihydropyridines. Not for use in the first weeks after myocardial infarction.

Warnings. Dose related peripheral oedema (not due to fluid overload), flushing, headache. Worsening angina or myocardial infarction can occur on starting in severe obstructive coronary disease. Gingival hyperplasia with long use. Hypotension when combined with other vasodilators.

Adverse effects. Ankle oedema, flushing, headache, palpitations, dizziness, fatigue, abdominal pain, gingival overgrowth, rash.

Interactions. Simvastatin: limit simvastatin to 20 mg daily. Strong CYP3A4 inhibitors (itraconazole, ritonavir, clarithromycin) raise levels. Rifampicin and phenytoin lower levels. Ciclosporin and tacrolimus: raised immunosuppressant levels. Dantrolene IV: hyperkalaemia. Beta blockers: additive hypotension.

Special groups.

• Pregnancy: limited data; acceptable when other first line agents are unsuitable.

• Breastfeeding: small amounts in milk; acceptable.

• Older adults: start at 2.5 mg.

• Kidney impairment: no adjustment; not dialysable.

• Liver impairment: start at 2.5 mg and titrate slowly; half life lengthens.

Overdose. Profound vasodilation and delayed shock. Give calcium gluconate 10% 30 to 60 mL IV, fluids, noradrenaline, and high dose insulin with glucose; consider lipid emulsion; observe for at least 24 hours.

Formulations. Tablets 2.5, 5, 10 mg.

Administration. Oral once daily at the same time, with or without food.

Baseline. Blood pressure, heart rate, oedema, liver function if disease suspected.

Monitoring. Blood pressure at 2 to 4 weeks; oedema; gums; heart rate; adverse effects after dose increases.

Stopping. No taper is needed; the effect persists for several days.

Common prescribing errors. Treating amlodipine oedema with a diuretic; exceeding 20 mg simvastatin; starting 10 mg in older adults.