Pregnancy Category C There are no adequate and well-controlled studies of Cleviprex use in pregnant women. In animal studies, clevidipine butyrate caused increases in maternal and fetal mortality and length of gestation. Cleviprex should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

There was decreased fetal survival when pregnant rats and rabbits were treated with clevidipine butyrate during organogenesis at doses 0.7 times (on a body surface area basis) the maximum recommended human dose (MRHD) in rats and 2 times the MRHD in rabbits.

In pregnant rats dosed with clevidipine butyrate during late gestation and lactation, there were dose-related increases in maternal mortality, length of gestation and prolonged parturition at doses greater than or equal to 1/6 of the MRHD based on body surface area. When offspring of these dams were mated, they had a conception rate lower than that of controls. Clevidipine butyrate has been shown to cross the placenta in rats [see Nonclinical Toxicology (13.3)] .

Cleviprex in the labor and delivery setting has not been established as safe and effective. Other calcium channel blockers suppress uterine contractions in humans. Pregnant rats treated with clevidipine butyrate during late gestation had an increased rate of prolonged parturition.

It is not known whether clevidipine butyrate is excreted in human milk. Because many drugs are excreted in human milk, consider possible infant exposure when Cleviprex is administered to a nursing woman.

The safety and effectiveness of Cleviprex in children under 18 years of age have not been established.

Of the 1406 subjects (1307 with hypertension) treated with Cleviprex in clinical studies, 620 were ≥65 years of age and 232 were ≥75 years of age. No overall differences in safety or effectiveness were observed between these and younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, for an elderly patient doses should be titrated cautiously, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

There has been no experience of overdosage in human clinical trials. In clinical trials, doses of Cleviprex up to 106 mg/hour or 1153 mg maximum total dose were administered. The expected major effects of overdose would be hypotension and reflex tachycardia.

Discontinuation of Cleviprex leads to a reduction in antihypertensive effects within 5 to 15 minutes [see Clinical Pharmacology (12.2)] . In case of suspected overdosage, Cleviprex should be discontinued immediately and the patient’s blood pressure should be supported.

Cleviprex is a sterile, milky-white emulsion containing 0.5 mg/mL of clevidipine butyrate suitable for intravenous administration. Clevidipine butyrate is a dihydropyridine calcium channel blocker. Chemically, the active substance, clevidipine butyrate, 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. The structure and formula are:

Clevidipine butyrate is practically insoluble in water and is formulated in an oil-in-water emulsio