Clevidipine

Clevidipine is an ultra short acting intravenous dihydropyridine calcium channel blocker supplied as a lipid emulsion. Blood and tissue esterases break it down within about 1 minute, so titration is rapid and recovery is quick. It is used for perioperative and emergency blood pressure control and is not available in most East African settings.

Classification. Dihydropyridine L type calcium channel blocker; arterial selective; ultra short acting.

Mechanism. Blocks L type calcium channels in arterial smooth muscle, reducing systemic vascular resistance without lowering preload or contractility.

Pharmacodynamics. Onset within 2 to 4 minutes; blood pressure returns to baseline within 5 to 15 minutes of stopping. Little reflex tachycardia compared with older agents.

Pharmacokinetics. Rapid hydrolysis by blood and tissue esterases (half life about 1 minute for the initial phase, 15 minutes terminal). Metabolites are excreted in urine and faeces. Not dependent on kidney or liver function.

Acute severe hypertension and perioperative hypertension, adult.

• Start 1 to 2 mg/hour IV.

• Double the rate every 90 seconds at first; as pressure approaches the target, increase by smaller steps every 5 to 10 minutes.

• Usual maintenance 4 to 6 mg/hour; most patients respond at 4 to 8 mg/hour.

• Maximum 21 mg/hour; total lipid load is limited to 1000 mL (about 21 mg/hour) in 24 hours.

• Changeover to oral therapy: start the oral agent and wean clevidipine over 1 to 2 hours.

• Duration: short term; experience beyond 72 hours is limited.

Children. Not established.

Contraindications. Allergy to soy, egg or egg products; defective lipid metabolism (pathological hyperlipidaemia, lipoid nephrosis, acute pancreatitis with hyperlipidaemia); severe aortic stenosis.

Warnings. Hypotension and reflex tachycardia. Lipid load: monitor triglycerides in prolonged infusions and in patients on other lipid products. Rebound hypertension after stopping. Use caution in heart failure. Do not use the same line for other drugs.

Adverse effects. Headache, nausea, vomiting, atrial fibrillation, acute renal failure, hypotension, reflex tachycardia, injection site reaction.

Interactions. Other antihypertensives add effect. Fat emulsions and lipid products: add to the lipid load. Because esterases clear it, there are no CYP3A4 interactions of note.

Special groups.

• Pregnancy: limited data; avoid unless benefit is clear.

• Breastfeeding: no data.

• Older adults: titrate in smaller steps.

• Kidney and liver impairment: no adjustment.

Formulations. Emulsion 0.5 mg/mL in 50 mL and 100 mL vials.

Administration. Infuse undiluted from a vial by pump through a dedicated peripheral or central line. Do not dilute and do not infuse through the same line as other drugs. Shake the vial gently before use. Discard an open vial after 4 hours. Use aseptic technique because the emulsion supports growth of micro-organisms.

Baseline. Blood pressure, heart rate, ECG, triglycerides if prolonged use or lipid sensitivity is likely.

Monitoring. Continuous blood pressure and heart rate; triglycerides if the infusion continues over 24 hours; line integrity.

Stopping. Stop or wean once the target pressure is held on oral therapy.

Common prescribing errors. Using it in patients with egg or soy allergy; mixing it with other drugs in the line; dilution; using up to the maximum rate for long periods without checking triglycerides.