Cleviprex IV therapy approved by FDA

October 13, 2008

CleviprexTM is the first new IV antihypertensive treatment to be approved by the FDA in 10 years.

Key Points

The Medicines Company recently received approval from the U.S. Food and Drug Administration (FDA) for Cleviprex (clevidipine butyrate) injectable emulsion for the reduction of blood pressure when oral therapy is not feasible or not desirable. Cleviprex is the first IV antihypertensive treatment approved in 10 years.

Cleviprex is a dihydropyridine calcium channel blocker. "It is a potent arterial vasodilator with very little or no effect on the myocardial contractility and venous capacitance," said Joel C. Marrs, PharmD, BCPS, Clinical Assistant Professor of Pharmacotherapy at Oregon State University/Oregon Health & Science University.

The first-cycle U.S. approval was based on six Phase III trials involving 1,406 medical and surgical patients treated with Cleviprex in the perioperative setting. The efficacy and safety of Cleviprex were evaluated in two double-blind, randomized, parallel, placebo-controlled, multicenter studies (ESCAPE-1 and ESCAPE-2). In the studies, Cleviprex lowered blood pressure in 2-4 minutes. "Clevidipine has the advantage of a short half-life and quick onset of action that allows blood-pressure reduction to occur quickly in severe hypertension. Its short half-life allows physicians to titrate quickly as well as gives them the opportunity to stop the drip when blood pressure falls too quickly," Marrs said. In most patients, full recovery of blood pressure is achieved 5-15 minutes after the infusion is stopped.

Cleviprex was also evaluated for safety and efficacy in the treatment of acute, severe hypertension. VELOCITY, a pivotal Phase 3 prospective, multicenter, open-label, single-arm study of 126 patients in the emergency room or intensive care unit who had acute, severe hypertension (defined as SBP greater than 180 mm Hg and/or diastolic blood pressure greater than 115 mm Hg). Cleviprex was administered using non-weight-based dosing, and infusions were adjusted to rapidly bring blood pressure to a physician-specified target range monitored by blood-pressure cuff. The primary efficacy endpoint was the percentage of patients whose SBP was successfully reduced to target range within 30 minutes of initiating therapy.

Within 30 minutes of starting clevidipine, 88.9 percent of treated patients were brought within the target range. Median time for reaching target range was 10.9 minutes. Blood pressure was maintained within the target blood-pressure range for at least 18 hours beyond the initial 30-minute period with simple dose titrations; during this time less than 2 percent of patients had blood pressure below their target range.

The most commonly reported adverse events connected with Cleviprex were headache, nausea and vomiting. Hypotension and reflex tachycardia are potential consequences of rapid upward titration. If either occurs, the manufacturer recommends decreasing the dose of Cleviprex. Beta-blockers are not recommended for the treatment of Cleviprex-induced tachycardia.

Cleviprex should be initiated at 1-2 mg/hr. The dose may be doubled at short (90-second) intervals initially. As the blood pressure reaches goal, the manufacturer recommends lengthening the times between dose adjustments to every 5-10 minutes and decreasing the amount of the dose increase. Because of lipid load restrictions, patients should not receive more than 1000-mL or an average of 21 mg/hr of Cleviprex infusion per 24-hour period. For patients who receive prolonged Cleviprex infusions and are not transitioned to other antihypertensive medications, the manufacturer recommends monitoring for possible rebound hypertension for at least 8 hours after the infusion is stopped.

Cleviprex is contraindicated in patients with an allergy to soybeans, soy products, egg, or egg products as well as in patients with defective lipid metabolism and severe aortic stenosis.

Cleviprex should not be administered in the same line as other medications and it should not be diluted. The manufacturer recommends discarding the vial if the product is not used within 4 hours after the vial is punctured. Cleviprex is supplied as a premixed milky white sterile emulsion in single-use 50-mL or 100-mL glass vials at a concentration of 0.5 mg/mL of clevidipine butyrate. Cleviprex should be refrigerated, but sealed vials in cartons may be transferred to room temperature for a period not to exceed two months.