Nifedipine

Nifedipine is a dihydropyridine calcium channel blocker with a greater vasodilating effect than amlodipine. It is used for hypertension, angina, Raynaud phenomenon, and severe hypertension in pregnancy. Formulation determines safety: immediate release capsules lower blood pressure abruptly and are not for routine hypertension outside obstetric use.

Classification. Dihydropyridine L type calcium channel blocker.

Mechanism. Blocks L type calcium channels in vascular smooth muscle, causing arteriolar dilation, reduced afterload and coronary vasodilation. Reflex tachycardia can follow the fast acting forms.

Pharmacodynamics. Immediate release: onset 20 to 30 minutes, duration 4 to 6 hours. Extended release: onset 2 to 4 hours, duration 24 hours.

Pharmacokinetics. Oral absorption nearly complete; bioavailability 45 to 70%. Half life 2 to 5 hours (immediate release). Hepatic metabolism by CYP3A4; metabolites excreted in urine. Crosses the placenta.

Hypertension, adult (extended release).

• Start 30 mg once daily; 20 mg in older adults.

• Increase after 1 to 2 weeks as needed.

• Usual maintenance 30 to 60 mg once daily; maximum 90 mg daily (up to 120 mg in some markets).

• Retard tablets: 10 to 20 mg twice daily; maximum 40 mg twice daily.

Chronic stable and vasospastic angina, adult. Extended release 30 to 60 mg once daily; maximum 90 mg daily.

Hypertension in pregnancy, maintenance. Extended release 10 to 20 mg twice daily, titrated to a maximum 80 mg daily in two divided doses.

Acute severe hypertension in pregnancy and postpartum. Immediate release 10 mg swallowed whole (not bitten and not sublingual); repeat after 20 to 30 minutes if pressure remains over 160/110 mmHg; then 10 to 20 mg every 4 to 6 hours as needed; usual maximum 180 mg in 24 hours. Aim for a pressure under 150/100 mmHg without overshooting.

Raynaud phenomenon, adult. Extended release 30 to 60 mg once daily, started in autumn.

Children, hypertension. Extended release 0.25 to 0.5 mg/kg daily, maximum 3 mg/kg or 120 mg daily; specialist. Immediate release capsules are not advised for hypertensive urgency in children.

Contraindications. Cardiogenic shock; advanced aortic stenosis; unstable angina; acute myocardial infarction within the first weeks; severe hypotension; porphyria; hypersensitivity. Immediate release capsules are not advised for non pregnant hypertensive urgency (risk of stroke or ischaemia from abrupt falls).

Warnings. Reflex tachycardia, flushing, headache, peripheral oedema, gingival hyperplasia. Worsening angina on starting in severe coronary disease. With magnesium sulphate, additive hypotension and rarely neuromuscular weakness; monitor. Extended release tablets must be swallowed whole.

Adverse effects. Headache, flushing, ankle oedema, dizziness, palpitations, fatigue, constipation, gingival overgrowth, nausea.

Interactions. Rifampicin, phenytoin and carbamazepine: markedly reduce levels. Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, clarithromycin) and grapefruit juice raise levels. Beta blockers: additive hypotension and rarely heart failure. Magnesium sulphate: hypotension. Digoxin: raised digoxin levels. Tacrolimus: raised levels.

Special groups.

• Pregnancy: first line choice for hypertension; avoid sublingual use.

• Breastfeeding: small amounts in milk; compatible.

• Older adults: start at 20 mg extended release.

• Kidney impairment: no adjustment.

• Liver impairment: reduce dose and monitor.

Formulations. Immediate release capsules 5 and 10 mg; extended release tablets 20, 30, 60, 90 mg; retard tablets 10 and 20 mg.

Administration. Oral with food or water; swallow whole. Avoid grapefruit juice. Do not pierce or bite capsules for rapid effect.

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

Monitoring. Blood pressure every 10 to 15 minutes during acute treatment in pregnancy; foetal heart rate; headache and reflex tachycardia; oedema; gum health.

Stopping. No taper is needed.

Common prescribing errors. Using immediate release capsules for chronic or non pregnant hypertensive urgency; sublingual dosing; interchanging brands of extended release without checking the release profile; combining with magnesium sulphate without monitoring.