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Initial U.S. Approval: 2008
Cleviprex is a sterile, milky-white emulsion containing 0.5 mg/mL of clevidipine suitable for intravenous administration. Clevidipine is a dihydropyridine calcium channel blocker. Chemically, the active substance, clevidipine, is butyroxymethyl methyl 4-(2´,3´-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate. It is a racemic mixture with a molecular weight of 456.3 g/mol. Each enantiomer has equipotent antihypertensive activity.
Clevidipine is practically insoluble in water and is formulated in an oil-in-water emulsion. In addition to the active ingredient, clevidipine, Cleviprex contains soybean oil (200 mg/mL), glycerin (22.5 mg/mL), purified egg yolk phospholipids (12 mg/mL), oleic acid (0.3 mg/mL), disodium edetate (0.05 mg/mL), and sodium hydroxide to adjust pH. Cleviprex has a pH of 6.0 – 8.0 and is a ready-to-use emulsion.
Mechanism of Action
Clevidipine is a dihydropyridine L-type calcium channel blocker. L-type calcium channels mediate the influx of calcium during depolarization in arterial smooth muscle. Experiments in anesthetized rats and dogs show that clevidipine reduces mean arterial blood pressure by decreasing systemic vascular resistance. clevidipine does not reduce cardiac filling pressure (pre-load), confirming lack of effects on the venous capacitance vessels.
INDICATIONS AND USAGE
Cleviprex is a dihydropyridine calcium channel blocker indicated for the reduction of blood pressure when oral therapy is not feasible or not desirable.
At clinically relevant concentrations, clevidipine and its metabolites do not inhibit or induce any CYP450 enzymes. The potential of clevidipine to interact with other drugs is low
USE IN SPECIFIC POPULATIONS
Pediatric use: Safety and effectiveness of Cleviprex in children under 18 years of age have not been established.
Cleviprex is contraindicated in patients with:
-Allergy to soy or eggs
-Defective lipid metabolism
-Severe aortic stenosis
WARNINGS AND PRECAUTIONS
Most common adverse reactions (>2%) are headache, nausea, and vomiting.
To report SUSPECTED ADVERSE REACTIONS, contact The Medicines Company at 1-888-977-MDCO (6326) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DOSAGE AND ADMINISTRATION
For intravenous use: Cleviprex is intended for intravenous use. Titrate Cleviprex to achieve the desired blood pressure reduction. Individualize dosage depending on the blood pressure response of the patient and the goal blood pressure.
Monitoring: Monitor blood pressure and heart rate during infusion, and until vital signs stabilize.
Initial dose: Initiate intravenous infusion of Cleviprex at 1-2 mg/hour.
Dose titration: Double the dose at short (90 second) intervals initially. As the blood pressure approaches goal, increase the dose by less than doubling and lengthen the time between dose adjustments to every 5-10 minutes. An approximately 1-2 mg/hour increase will generally produce an additional 2-4 mmHg decrease in systolic pressure.
Maintenance dose: Most patients will achieve the desired therapeutic response at approximately 4-6 mg/hour. Severe hypertension is likely to require higher doses.
Maximum dose: Most patients have received maximum doses of 16 mg/hour or less. There is limited experience with short-term dosing as high as 32 mg/hour. Because of lipid load restrictions, no more than 1000 mL or an average of 21 mg/hour of Cleviprex infusion is recommended per 24-hour period. There is little experience beyond 72 hours at any dose.
Transition to an oral antihypertensive agent: Discontinue Cleviprex or titrate downward while appropriate oral therapy is established. When an oral antihypertensive agent is being instituted, consider the lag time of onset of the oral agent’s effect. Continue blood pressure monitoring until desired effect is achieved.
Special populations: Special populations were not specifically studied. In clinical trials, 78 patients with abnormal hepatic function (one or more of the following: elevated serum bilirubin, AST/SGOT, ALT/SGPT) and 121 patients with moderate to severe renal impairment were treated with Cleviprex. An initial Cleviprex infusion rate of 1-2 mg/hour is appropriate in these patients.
Table 1 is a guideline for dosing conversion from mg/hour to mL/hour.
Instructions for Administration
Maintain aseptic technique while handling Cleviprex. Cleviprex is a single-use parenteral product. Do not use if contamination is suspected. Once the stopper is punctured, use within 12 hours and discard any unused portion.
Cleviprex is supplied in sterile, pre-mixed, ready-to-use 50 mL or 100 mL vials. Invert vial gently several times before use to ensure uniformity of the emulsion prior to administration. Inspect parenteral drug products for particulate matter and discoloration prior to administration whenever solution and container permit. Administer Cleviprex using an infusion device allowing calibrated infusion rates. Commercially available standard plastic cannulae may be used to administer the infusion. Administer Cleviprex by a central line or a peripheral line.
Cleviprex should not be administered in the same line as other medications.
Cleviprex should not be diluted, but it can be administered with the following
DOSAGE FORMS AND STRENGTHS
Cleviprex is a sterile, milky white injectable emulsion for intravenous use, available in the following two configurations:
50 mL single-use vial with 0.5 mg/mL clevidipine
100 mL single-use vial with 0.5 mg/mL clevidipine
Package Insert data:
Fresenius Kabi Austria GmbH, Graz, Austria
The Medicines Company
Parsippany, New Jersey 07054
For information call: 888-977-MDCO (6326)
US Patent 5,856,346
US Patent 5,739,152
TMC PN 1220 (April 28, 2011)
Package Label - Principal Display Panel - 25mg/50mL Container