iologic Effects: In healthy volunteers, clevidipine butyrate or its major carboxylic acid metabolite, at therapeutic and supratherapeutic concentrations (approximately 2.8 times steady-state), did not prolong cardiac repolarization.
12.3 Pharmacokinetics
Clevidipine butyrate is rapidly distributed and metabolized resulting in a very short half-life. The arterial blood concentration of clevidipine butyrate declines in a multiphasic pattern following termination of the infusion. The initial phase half-life is approximately 1 minute, and accounts for 85-90% of clevidipine butyrate elimination. The terminal half-life is approximately 15 minutes.
Distribution: Clevidipine butyrate is >99.5% bound to proteins in plasma at 37癈.
The steady-state volume of distribution was determined to be 0.17 L/kg in arterial blood.
Metabolism and Elimination: Clevidipine butyrate is rapidly metabolized by hydrolysis of the ester linkage, primarily by esterases in the blood and extravascular tissues, making its elimination unlikely to be affected by hepatic or renal dysfunction. The primary metabolites are the carboxylic acid metabolite and formaldehyde formed by hydrolysis of the ester group. The carboxylic acid metabolite is inactive as an antihypertensive. This metabolite is further metabolized by glucuronidation or oxidation to the corresponding pyridine derivative. The clearance of the primary dihydropyridine metabolite is 0.03 L/h/kg and the terminal half-life is approximately 9 hours. In vitro studies show that clevidipine butyrate and its metabolite at the concentrations achieved in clinical practice will not inhibit or induce any CYP enzyme.
In a clinical study with radiolabeled clevidipine butyrate, 83% of the drug was excreted in urine and feces. The major fraction, 63-74% is excreted in the urine, 7-22% in the feces. More than 90% of the recovered radioactivity is excreted within the first 72 hours of collection.
16 HOW SUPPLIED/STORAGE AND HANDLING
Cleviprex (clevidipine butyrate) injectable emulsion is supplied as a sterile, milky white liquid emulsion product in single-use 50 mL or 100 mL glass vials at a concentration of 0.5 mg/mL of clevidipine butyrate.
NDC 65293-002-50: 50 mL vial
NDC 65293-002-00: 100 mL vial
Storage
Leave vials in cartons until use. Clevidipine butyrate is photosensitive and storage in cartons protects against photodegradation. Protection from light during administration is not required.
Store vials refrigerated at 2-8癈 (36-46癋). Do not freeze. Vials in cartons may be transferred to 25癈 (77癋, USP controlled room temperature) for a period not to exceed 2 months. Upon transfer to room temperature, mark vials in cartons 揟his product was removed from the refrigerator on _/_/_ date. It must be used or discarded 2 months after this date or the labeled expiration date (whichever date comes first).� Do not return to refrigerated storage after beginning room temperature storage.
17 PATIENT COUNSELING INFORMATIO
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Advise patients with underlying hypertension that they require continued follow up for their medical condition, and, if applicable, encourage patients to continue taking their oral antihypertensive medication(s) as directed.
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Advise patients to contact a healthcare professional immediately for any of the following signs of a new hypertensive emergency: neurological symptoms, visual changes, or evidence of congestive heart failur
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