Pharmacology Update
Clevidipine Butyrate Injectable Emulsion for Intravenous Use
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationship to this field of study.
A short-acting dihydropyridine calcium channel blocker with a rapid onset of action has been approved for intravenous use to reduce blood pressure. Clevidipine is manufactured by Hospira, Inc., and marketed as Cleviprex™ by The Medicines Company.
Indications
Clevidipine is indicated for the reduction of blood pressure when oral therapy is not feasible or not desired.1
Dosage
The drug is initiated at a dose of 1-2 mg/hr and titrated to blood pressure goal. Titration should be done by doubling the dose at 90-second intervals initially, and when blood pressure approaches goal, the increase should be less than double and the dosing interval should be lengthened to every 5-10 minutes. Most patients will achieve desired blood pressure at 4-6 mg/hr, with the majority controlled with a dose of 16 mg/hr or less.
Clevidipine is supplied as single-use vials (0.5 mg/mL) of 50 mg or 100 mL.
Potential Advantages
Clevidipine has a rapid onset of action and short duration, and is specific for arterial vasodilation. It has a linear dose response and does not require weight-based dosing.
Potential Disadvantages
Adverse events include headache, nausea, atrial fibrillation, and vomiting. The drug may cause systemic hypotension and reflex tachycardia, and may produce negative inotropic effects.1 It is contraindicated in patients with allergy to soy or egg (the emulsion contains soy bean oil and egg yolk) as well as in patients with significant lipid disorders and severe aortic stenosis.1
Comments
Clevidipine is a dihydropyridine calcium channel blocker that exerts its action on arterial smooth muscle. It has a rapid onset of action and short duration terminated by plasma esterases. Its direct action on arterial vasculature results in reduced afterload without affecting cardiac filling pressure or causing reflex tachycardia.2 Clinical effectiveness has been reported in pre- and post-operative cardiac surgery patients, patients with severe hypertension, and patients with essential hypertension.1,3-5
In pre- (n = 152) and post- (n = 110) cardiac surgery, clevidipine reduced SBP by 15% or greater compared to placebo in more than 90% of patients with a median time of 5-8 minutes.3,4 Preoperative patients had baseline SBP of 160 mmHg or greater and post-operative patients had SBP of 140 mmHg or greater. Clevidipine produced similar reductions in systolic blood pressure compared to nitroglycerin, sodium nitroprusside, and nicardipine.1
In a single-arm study in patients with severe hypertension and baseline SBP of 180 mmHg or DBP of 115 mmHg or greater (n = 131), about 90% of patients achieved prespecified target ranges within 30 minutes with a median time of 10.9 minutes.4
Common adverse events in the perioperative studies compared to placebo included acute renal failure (9% vs 2%), atrial fibrillation (21% vs 12%), and nausea (21% vs 12%).1 The discontinuation rate was 5.9% vs 3.2% for placebo. For the single-arm study in patients with severe hypertension, adverse events included headache (6.3%), nausea (4.8%), and vomiting (3.2%), with a discontinuation rate of 4.8%.
Clinical Implications
Titratable intravenous antihypertensives are typically used to treat hypertensive emergencies. These are characterized by severe elevation of BP (>180/120 mmHg) complicated by evidence of impending or progressive target-organ dysfunction.2,6 These may occur in the surgery setting, particularly early postoperatively.5 These are generally managed in an intensive care setting using agents such as labetolol, esmolol, nicardipine, and fenoldopam. The choice of agents depends on the clinical presentation.6 Clevidipine is a new agent with favorable characteristics for use in this setting. Its role will be better defined with more clinical experience.
References
1. Cleviprex Product Information. Parsipanny, NJ: The Medicines Company; August 2008.
2. Varon J. Treatment of acute severe hypertension: Current and newer agents. Drugs 2008;68:283-297.
3. Singla N, et al. Treatment of acute postoperative hypertension in cardiac surgery patients: An efficacy study of clevidipine assessing its postoperative antihypertensive effect in cardiac surgery-2 (ESCAPE-2), a randomized, double-blind, placebo-controlled trial. Anesth Analg 2008;107:59-67.
4. Pollack CV, et al. Clevidipine, an intravenous dihydropyridine calcium channel blocker, is safe and effective for the treatment of patients with acute severe hypertension. Ann Emerg Med 2008 Jun 4; Epub ahead of print.
5. Levy JH, et al. Clevidipine effectively and rapidly controls blood pressure preoperatively in cardiac surgery patients: The results of the randomized, placebo-controlled efficacy study of clevidipine assessing its preoperative antihypertensive effect in cardiac surgery-1. Anesth Analg 2007;105;918-925.
6. Marik PE, Varon J. Hypertensive crises: Challenges and management. Chest 2007;131:1949-1962. Erratum in: Chest 2007;132:1721.
A short-acting dihydropyridine calcium channel blocker with a rapid onset of action has been approved for intravenous use to reduce blood pressure.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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