BP-lowering calcium channel blocker

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Product: Cleviprex

Company: The Medicines Company

Pharmacologic class: Calcium channel blocker (dihydropyridine)

Active ingredient: Clevidipine butyrate emulsion 0.5 mg/mL; solution for IV infusion; contains lipids 0.2 g/mL (soybean oil, egg phospholipids).

Indication: To reduce BP when oral therapy is not feasible or desirable.

Pharmacology: Clevidipine is a calcium channel blocker formulated in an oil-in-water emulsion for IV infusion. Other drugs in this class include amlodipine, felodipine, nifedipine, and nisoldipine. In vivo studies indicate that this drug reduces mean arterial BP by reducing vascular resistance. It does not affect cardiac filling pressure (pre-load).

Upon infusion, it is rapidly distributed and metabolized, with a terminal half-life of about 15 minutes, and it begins to lower the BP within two to four minutes. An increase in heart rate may occur in response to the vasodilation. Clevidipine does not offer any protection against the effects of sudden beta-blocker withdrawal and is not recommended in this setting.

This drug is rapidly metabolized by esterases in the blood and in extravascular tissues, making it unlikely to interact significantly with other drugs. It was shown not to affect the CYP enzyme system.

Clinical trials: Clevidipine was evaluated in 15 studies in hypertensive patients who had perioperative hypertension, severe hypertension, or essential hypertension. Two double-blind, randomized, placebo-controlled studies were conducted with patients undergoing coronary artery bypass grafting. One study included pre-op patients with mean BP of 178/77 mm Hg, and the other included post-op patients with a mean BP of 150/71. In both studies, BP was lowered within two to four minutes of starting the clevidipine butyrate infusion.
A randomized, placebo-controlled study was conducted in 61 patients with mild-to-moderate essential hypertension (mean baseline BP 151/86). Subjects were randomized to placebo or Cleviprex at several infusion rates ranging from two to 16 mg/hour. Systolic BP effect was related to the concentration of clevidipine butyrate given; it plateaued at higher measured concentrations, with the maximal effect about 25% of baseline BP.
In an open-label study in 126 patients with severe hypertension, BP was reduced within five minues and reached a plateau between 15 and 20 minutes after starting a 2-mg/hour infusion.

Adults: >18 years: Individualize; titrate. Give by IV infusion. Initially 1-2 mg/hour; double dose at 90-second intervals until BP approaches goal, then titrate slower (adjust at 5- to 10-minute intervals). Dose increases of 1-2 mg/hour result in systolic BP lowering of about 2-4 mm Hg. Maintenance: 4-6 mg/hour; usual maximum 16-32 mg/hour. Do not exceed 1,000 mL (21 mg/hour for 24 hours) due to lipid load. Switch to oral therapy when indicated. 

Children: <18 years: not recommended. 

Contraindications: Egg or soy allergy. Defective lipid metabolism (e.g., pathologic hyperlipemia, lipoid nephrosis, acute pancreatitis with hyperlipidemia). Severe artery stenosis.

Precautions: Monitor BP and pulse during infusion and until stabilized. Heart failure (monitor). Pheochromocytoma. Monitor for rebound hypertension for at least eight hours after stopping infusion (if not given other antihypertensives after prolonged infusion). Labor & delivery. Pregnancy (Cat. C). Nursing mothers.

Adverse reactions: Headache, nausea, vomiting; hypotension, reflex tachycardia (slow infusion if occurs, do not use beta blocker); rare: MI, cardiac arrest, syncope, dyspnea.

Note: Report adverse events to The Medicines Company at 888.977.6326 and to FDA at 800.FDA.1088.

How supplied: Single-use vials—50 mL, 100 mL.

For more information, call 888.977.6326 or visit www.Cleviprex.com.

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