an active comparator: nitroglycerin (NTG, n=278), sodium nitroprusside (SNP, n=283), or nicardipine (NIC, n=193). The pooled mean maximum dose in these studies was 10 mg/hour and the mean duration of treatment was 8 hours.
There were many adverse events associated with the operative procedure in the clinical studies of Cleviprex and relatively few plausibly related to the drugs used to lower blood pressure. Thus, the ability to differentiate the adverse event profile between treatments is limited. The adverse events observed within one hour of the end of the infusion were similar in patients who received Cleviprex and in those who received comparator agents. There was no adverse reaction that was more than 2% more common on Cleviprex than on the average of all comparators.
Serious Adverse Events and Discontinuation桺erioperative Hypertension Studies
The incidence of adverse events leading to study drug discontinuation in patients with perioperative hypertension receiving Cleviprex was 5.9% versus 3.2% for all active comparators. For patients receiving Cleviprex and all active comparators the incidence of serious adverse events within one hour of drug infusion discontinuation was similar.
Severe Hypertension
The adverse events for patients with severe hypertension are based on an uncontrolled study in patients with severe hypertension (VELOCITY, n=126).
The common adverse reactions for Cleviprex in severe hypertension included headache (6.3%), nausea (4.8%), and vomiting (3.2%). The incidence of adverse events leading to study drug discontinuation for Cleviprex in severe hypertension was 4.8%
Less Common Adverse Reactions in Patients with Severe or Essential Hypertension
Adverse reactions that were reported in <1% of patients with severe or essential hypertension included:
Cardiac: myocardial infarction, cardiac arrest
Nervous system: syncope
Respiratory: dyspnea
7 DRUG INTERACTIONS
No clinical drug interaction studies were conducted. Clevidipine butyrate and its major dihydropyridine metabolite do not have the potential for blocking or inducing any CYP enzyme.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
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)].
8.2 Labor and Delivery
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 rat
