Felodipine

Felodipine is a vascular selective dihydropyridine calcium channel blocker given as extended release tablets. It lowers blood pressure and relieves angina. It is neutral on mortality in heart failure, which makes it a suitable add on in patients with heart failure and hypertension.

Classification. Dihydropyridine L type calcium channel blocker.

Mechanism. Blocks L type calcium channels in vascular smooth muscle, causing arteriolar dilation. High vascular selectivity gives little direct negative inotropy.

Pharmacodynamics. Blood pressure falls within 2 to 5 hours of an extended release dose; effect lasts 24 hours. Mild reflex increase in heart rate.

Pharmacokinetics. Oral absorption nearly complete but extensive first pass metabolism gives bioavailability about 15%. Half life 11 to 16 hours. Metabolised by CYP3A4; excreted in urine as inactive metabolites. Grapefruit juice increases levels.

Hypertension, adult.

• Start 5 mg once daily in the morning (2.5 mg in older adults and hepatic impairment).

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

• Usual maintenance 5 to 10 mg; maximum 10 mg daily.

Stable angina, adult. 5 mg once daily, increased to 10 mg once daily; maximum 10 mg.

Children. Not established.

Contraindications. Pregnancy; cardiogenic shock; unstable angina; acute myocardial infarction; significant aortic stenosis; uncompensated heart failure; hypersensitivity.

Warnings. Dose related ankle oedema, flushing, headache and gingival hyperplasia. Worsening angina on starting in severe coronary disease. Hypotension with other vasodilators. Maintain dental hygiene.

Adverse effects. Peripheral oedema, flushing, headache, dizziness, palpitations, fatigue, gingival overgrowth, rash.

Interactions. Strong CYP3A4 inhibitors (itraconazole, ketoconazole, ritonavir, erythromycin, clarithromycin) and grapefruit juice raise levels. Carbamazepine, phenytoin, phenobarbital and rifampicin lower levels markedly. Tacrolimus: raised tacrolimus. Beta blockers: additive hypotension.

Special groups.

• Pregnancy: avoid; foetal toxicity in animals.

• Breastfeeding: appears in milk; avoid or use only if benefit is clear.

• Older adults: start at 2.5 mg.

• Kidney impairment: no adjustment.

• Liver impairment: start at 2.5 mg; higher exposure.

Formulations. Extended release tablets 2.5, 5, 10 mg.

Administration. Swallow whole with water in the morning, on an empty stomach or with a light meal; avoid high fat meals and grapefruit juice. Do not crush, chew or split.

Baseline. Blood pressure, heart rate, oedema, liver function.

Monitoring. Blood pressure after 2 to 4 weeks and after dose changes; ankle oedema; gums; heart rate.

Stopping. No taper is needed.

Common prescribing errors. Crushing the extended release tablet; use in pregnancy; adding itraconazole or ritonavir without reducing the dose; taking with grapefruit juice.