Fenofibrate (Briggs Drugs in Pregnancy and Lactation)
Three reports describing the use of fenofibrate in human pregnancy has been located. Although the near absence of human pregnancy experience prevents an assessment of the risk, the combined animal data are reason for concern if this drug is used for prolonged periods in pregnancy. As with other antilipemic agents, there is apparently no benefit in otherwise healthy women from the use of fenofibrate during gestation. However, fenofibrate may be of benefit to treat or prevent hyperlipidemia-associated pancreatitis. If used during pregnancy, the woman should be informed of the limited human data.
Fenofibrate is a prodrug that is rapidly hydrolyzed by esterases after oral administration to the active metabolite, fenofibric acid. The active metabolite is further metabolized to inactive metabolites. Fenofibric acid is indicated as adjunctive therapy to diet for the treatment of primary hypercholesterolemia or mixed dyslipidemia, and for hypertriglyceridemia. Fenofibric acid is extensively bound to serum protein (about 99%) and has an elimination half-life of 20 hours Ref.
Reproduction studies have been conducted in pregnant rats and rabbits Ref. The drug was embryocidal and teratogenic in pregnant rats given 7–10 times the maximum recommended human dose based on BSA (MRHD). At 9 times the MRHD given before and throughout gestation to rats, reproductive toxicity included delayed parturition in 100% of the dams, a 60% increase in postimplantation loss with a decrease in litter size, reduced birth weight, an increase in spina bifida, and decreased pup survival (40% at birth, 4% during neonatal period, and 0% to weaning). Similar findings were observed at 7 times the MRHD given from day 15 of gestation through weaning. When pregnant rats were dosed at 10 times the MRHD during organogenesis, an increased incidence of congenital malformations was observed, including domed head/hunched shoulders/rounded body/abnormal chest, kyphosis, stunted fetuses, elongated sternal ribs, malformed sternebrae, extra foramen in palatine, misshapen vertebrae, and supernumerary ribs Ref. Embryocidal effects were also observed in rabbits. Doses 9 and 18 times the MRHD caused abortions in 10% and 25% of the dams, respectively. At 18 times the MRHD, 7% of the fetuses died Ref.
Fenofibrate had no mutagenic potential in four different tests, but the drug was carcinogenic in rats, significantly increasing the incidence of liver carcinoma, pancreatic carcinoma and adenomas, and benign testicular interstitial cell tumors in a dose-related manner Ref. Some of these tumors (pancreatic acinar adenomas and testicular interstitial cell tumors) were also seen in a second strain of rats at lower doses Ref.
It is not known if fenofibrate or fenofibric acid cross the human placenta. Fenofibrate is rapidly metabolized and is not detected in the plasma Ref. The molecular weight of the metabolite, fenofibric acid (about 319), and the prolonged elimination half-life suggest that the drug will cross, but the high serum protein binding should limit the amount available for transfer to the embryo or fetus.
A 2011 case report described the use of fenofibrate in the 3rd trimester Ref. A 30-year-old G4P1SAB2 woman with adequately treated hypothyroidism presented at 32 weeks’ gestation with hypertriglyceridemia-associated pancreatitis. Diet alone did not control her dyslipidemia and she was started on an unspecified dose of fenofibrate. Recurrence of pancreatitis was prevented and at 35 weeks’ gestation she gave birth spontaneously to a healthy, 2452-g male infant with normal Apgar scores Ref.
A 30-year-old woman with high triglyceride levels was started on fenofibrate 267 mg/day Ref. One year later, an unplanned pregnancy was diagnosed at 8 weeks’ gestation and the drug was stopped. At 36 weeks’, a cesarean section gave birth to a healthy 3200-g (75th percentile) male infant with normal Apgar scores. No congenital anomalies were found and the infant was healthy at 1 year of age Ref.
A 2015 case report described a pregnancy outcome after early pregnancy exposure to fenofibrate Ref. A 40-year-old woman was taking fenofibrate because of acute pancreatitis due to hyperlipidemia 5 months prior. She also was being treated with carbimazole for Graves’ disease. She discontinued fenofibrate when she found out she was pregnant (unspecified gestational age). She developed acute pancreatitis at 15 weeks’ gestation and at 18 weeks’ gestation an intrauterine fetal demise was confirmed Ref.
No reports describing the use of fenofibrate in human lactation have been located. The relative low molecular weight of the active metabolite (about 319) suggests that it is excreted into breast milk. Although the effect of this exposure on a nursing infant is unknown, women taking fenofibrate should probably not breastfeed because of potential toxicity in a nursing infant.
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