Nicardipine

Nicardipine is a dihydropyridine calcium channel blocker with a short half life when given by infusion, which allows titration in acute severe hypertension. It has strong cerebral and coronary vasodilating effects. Oral forms exist for hypertension and angina but are less used.

Classification. Dihydropyridine L type calcium channel blocker; vascular selective.

Mechanism. Blocks L type calcium channels in vascular smooth muscle, causing arteriolar dilation and reducing systemic resistance. Little direct effect on the atrioventricular node.

Pharmacodynamics. IV onset within 5 to 15 minutes; effect lasts 4 to 6 hours after a prolonged infusion is stopped. Reflex tachycardia is modest. Cardiac output rises or is maintained.

Pharmacokinetics. Extensive hepatic metabolism by CYP3A4 and CYP2C. IV half life about 40 minutes initially and 8 hours terminally. Metabolites excreted in urine and faeces.

Acute severe hypertension, adult (including hypertensive emergency).

• Start 5 mg/hour IV infusion.

• Increase by 2.5 mg/hour every 15 minutes (every 5 minutes for rapid control) until the target is reached.

• Maximum 15 mg/hour.

• When the target is reached, reduce to 3 mg/hour or the lowest rate that holds pressure.

• Aim to lower mean arterial pressure by no more than 25% in the first hour, then toward 160/100 mmHg over 2 to 6 hours. In intracerebral haemorrhage or acute stroke the target is set by the neurology or neurosurgical team.

• Switch to oral therapy as the infusion is weaned.

Hypertension in pregnancy (severe, specialist). Same infusion range; labetalol and nifedipine are first line, and nicardipine is an alternative where available.

Hypertension, adult (oral). Immediate release 20 mg three times daily; usual range 20 to 40 mg three times daily; modified release 30 to 60 mg twice daily. Maximum 120 mg daily in most labels.

Children. IV infusion 0.5 to 3 micrograms/kg/minute in specialist care.

Contraindications. Advanced aortic stenosis; hypersensitivity; unstable angina or acute myocardial infarction (oral forms); cardiogenic shock; severe hypotension.

Warnings. Hypotension, reflex tachycardia and myocardial ischaemia (rapid titration). Avoid in acute heart failure. Phlebitis at peripheral sites; rotate the site every 12 hours. Caution in kidney and liver impairment. Rarely worsens angina on initiation.

Adverse effects. Headache, flushing, hypotension, tachycardia, nausea and vomiting, oedema, dizziness, phlebitis.

Interactions. Ciclosporin, tacrolimus: raised levels. Strong CYP3A4 inhibitors (itraconazole, ritonavir) raise nicardipine. Beta blockers: additive hypotension and bradycardia. Cimetidine raises levels. Digoxin: raised levels with oral use.

Special groups.

• Pregnancy: limited data; used in severe hypertension when other agents fail.

• Breastfeeding: appears in milk in small amounts; avoid or monitor the infant.

• Older adults: start low; hypotension risk.

• Kidney impairment: titrate cautiously; clearance is largely hepatic.

• Liver impairment: reduce the dose; clearance falls.

Formulations. Premixed bags 20 mg in 200 mL (0.1 mg/mL) and 40 mg in 200 mL (0.2 mg/mL); concentrate 2.5 mg/mL must be diluted; oral capsules 20 and 30 mg; modified release 30 and 45 mg.

Preparation. Dilute concentrate to 0.1 mg/mL in 0.9% sodium chloride or 5% glucose. Infuse through a large peripheral vein or a central line. Incompatible with sodium bicarbonate and lactated Ringer solution.

Baseline. Blood pressure (both arms), heart rate, ECG, creatinine, ischaemia symptoms.

Monitoring. Continuous or every 5 minute blood pressure during titration; heart rate; infusion site; neurological status in stroke; urine output.

Stopping. Wean the infusion once oral therapy takes effect.

Common prescribing errors. Lowering pressure too fast in stroke or aortic dissection; using it in aortic stenosis; confusing mg/hour with micrograms/kg/minute; leaving the same peripheral site for more than 12 hours.