Vazculep - Use Phenylephrine Hydrochloride

None

Pregnancy Category C

Risk Summary

There are no adequate or well-controlled studies with phenylephrine hydrochloride injection in pregnant women, nor have animal reproduction studies been conducted. Published studies in normotensive pregnant rabbits report early onset labor, increased fetal lethality, and adverse placental effects with subcutaneous phenylephrine administration during gestation at doses approximately 1.9 times the total daily human dose. Published studies in normotensive pregnant sheep report decreased uterine blood flow and decreased PaO₂ in the fetus with intravenous phenylephrine administration during late gestation at doses less than and similar to the human dose. It is not known whether VAZCULEP can cause fetal harm when administered to a pregnant woman. VAZCULEP should be given to a pregnant woman only if the potential benefit justifies the potential risk to the fetus.

Clinical Considerations

Labor and Delivery

The most common maternal adverse reactions reported in published studies of phenylephrine use during neuraxial anesthesia during Cesarean delivery include nausea and vomiting, bradycardia, reactive hypertension, and transient arrhythmias. Phenylephrine, when administered during labor or delivery, does not appear to alter either neonatal Apgar scores or umbilical artery blood-gas status.

Data

Animal Data

Studies in the published literature evaluating subcutaneously administered phenylephrine (0.33 mg/kg, TID) in normotensive pregnant rabbits reported fetal deaths, adverse histopathology findings in the placenta (necrosis, calcification and thickened vascular walls with narrowed lumen) and possible teratogenic effects (one incidence of clubbed feet, partial development of the intestine) when treatment was initiated during the first trimester or later; and premature labor when treatment was initiated at the second trimester or later. The doses administered were 1.9 times the total daily human dose of 10 mg/day based on a body surface area comparison. Published studies in pregnant normotensive sheep demonstrate that intravenous phenylephrine (4 mcg/kg/min for 30 minutes, equivalent to 3.6 to 4.1 mcg/kg/min human equivalent dose based on body surface area) administered during the third trimester of pregnancy decreased uterine blood flow by 42%. This dose is 1.1 to 1.2 times the human bolus dose of 200 mcg/60 kg person based on body surface area. Mean fetal blood pressure and heart rate fluctuated above and below controls by about 7% during the infusion. Fetal PaO₂ was significantly decreased by approximately 26% of control during the infusion. Likewise, PaCO₂ was increased and pH was decreased. The clinical significance of these findings is not clear; however, the results suggest the potential for cardiovascular effects on the fetus when phenylephrine is used during pregnancy.

It is not known whether phenylephrine is present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VAZCULEP and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. Exercise caution when VAZCULEP is administered to a nursing woman.

Safety and effectiveness in pediatric patients have not been established.

Clinical studies of phenylephrine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, 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.

In patients with liver cirrhosis [Child Pugh Class B and Class C], dose-response data indicate decreased responsiveness to phenylephrine. Start dosing in the recommended dose range but consider that you may need to give more phenylephrine in this population.

In patients with end stage renal disease (ESRD), dose-response data indicate increased responsiveness to phenylephrine. Consider starting at the lower end of the recommended dose range, and adjusting dose based on the target blood pressure goal.