Antilipemic Agent
PREGNANCY RECOMMENDATION: Contraindicated
BREASTFEEDING RECOMMENDATION: Contraindicated
PREGNANCY SUMMARY
No reports describing the use of pitavastatin in human pregnancy have been located. The absence of human pregnancy experience prevents an assessment of the embryo and/or fetal risk. Because the interruption of cholesterol-lowering therapy during pregnancy should have no apparent effect on the long-term treatment of hyperlipidemia, pitavastatin should not be used during pregnancy. Moreover, cholesterol and other products of cholesterol biosynthesis are essential components for fetal development (1). Women taking this agent before conception should stop the therapy before becoming pregnant and certainly on recognition of pregnancy. Accidental use of the drug during gestation, though, apparently has no proven consequences for the fetus.
FETAL RISK SUMMARY
Pitavastatin, a synthetic 3-hydroxy-3-methyl-coenzyme A (HMG-CoA) reductase inhibitor (a statin) that is lipophilic, is indicated as an adjunctive therapy to diet to reduce elevated total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and triglycerides and to increase high-density lipoprotein cholesterol. It has the same mechanism of action as other agents available in this class, atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin (cerivastatin was withdrawn from the market in 2001). Pitavastatin is metabolized to inactive metabolites. Plasma protein binding is high (>99%), mainly to albumin and α-1-acid glycoprotein, and the mean plasma elimination half-life is about 12 hours (1).
Reproduction studies have been conducted in rats and rabbits. In rats during organogenesis, doses resulting in systemic exposures up to 22 times the human systemic exposure at 4 mg/day based on AUC (HSE), the lowest dose tested, caused no adverse effects. When the drug was given from organogenesis through weaning, maternal toxicity (mortality at about ≥3 times the HSE and impaired lactation at about ≥1 times the HSE) contributed to the decreased survival of neonates. In rabbits, maternal toxicity (reduced body weight and abortions) were observed at 4 times the HSE (1).
Carcinogenicity studies in mice were negative, but high doses (295 times the HSE) caused thyroid follicular cell tumors in rats. Pitavastatin was not mutagenic in several assays but high doses that also caused cytotoxicity were clastogenic. High doses caused no adverse effects on male and female rat fertility (1).
It is not known if pitavastatin crosses the human placenta. The molecular weight (about 813 for the free acid) and elimination half-life suggest that it will cross, but the high plasma protein binding might limit the exposure. The drug does cross the rat placenta (1).
BREASTFEEDING SUMMARY
No reports describing the use of pitavastatin during human lactation have been located. The molecular weight (about 813 for the free acid) and elimination half-life (about 12 hours) suggest that it will be excreted into breast milk, but the high plasma protein binding might limit the amount. At least two similar agents (fluvastatin and pravastatin) appear in human milk. Because of the potential for adverse effects in the nursing infant, the drug should not be used during lactation.
Reference
1.Product information. Livalo. Kowa Pharmaceuticals America, 2009.