ANAGRELIDE

Fetal Risk Summary

Anagrelide, an antiplatelet agent, is indicated for the reduction of elevated platelet counts and resulting risk of thrombosis in patients with thrombocythemia.

An animal teratology study observed no congenital abnormalities in pregnant rats given oral doses up to 900 mg/kg/day (730 times the maximum recommended human dose [MRHD]) based on body surface area or in pregnant rabbits administered doses up to 20 mg/kg/day (32 times the MRHD) (1). In a fertility and reproductive performance study of female rats, however, doses 49 times the MRHD or higher disrupted implantation and produced an adverse effect on embryo/fetal survival (1). The same dosage in a perinatal and postnatal study with pregnant rats caused a delay in parturition, deaths of undelivered dams and their fetuses, and increased mortality in pups that were born (1).

No reports describing the placental transfer of anagrelide in animals or humans have been located. The molecular weight of the drug (about 311 for the hydrochloride monohydrate salt) is low enough, however, that passage to the fetus should be expected.

The only reported human pregnancy exposure to anagrelide appears to be that described by the manufacturer in its product information (1). Five women became pregnant while receiving the drug at doses of 1 to 4 mg/day. Therapy was stopped when the pregnancies were diagnosed (timing not specified), and all the women delivered normal, healthy babies.

In summary, human pregnancy experience with anagrelide is limited to the above five cases, all apparently in early pregnancy. Although the outcomes were normal in each case, animal data appear to indicate a potential for embryo/fetal harm. The toxic dose in animals, however, was much higher than the dose used in humans, based on body surface area. The manufacturer recommends that women should not become pregnant while taking anagrelide, but the benefits of therapy must be weighed against the risks on a case-by-case basis. If therapy is started or continued during pregnancy, the woman should be fully informed of the potential risks to her embryo/fetus.

Breast Feeding Summary

No reports describing the use of anagrelide during lactation have been located. The molecular weight of the compound (about 311 for the hydrochloride monohydrate salt) is low enough, however, that passage into milk should be expected. The potential effects of this exposure on a nursing infant are unknown. Because the reduction in platelets is dose-related, thrombocytopenia, as well as other adverse effects, are potential complications.

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