Hematologic Agent (Antiplatelet)
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
Human pregnancy experience with anagrelide is limited. Except for one spontaneous abortion (SAB), all other outcomes were normal babies. Moreover, the animal data suggest low risk. The manufacturer recommends that women should not become pregnant while taking anagrelide, but the benefits of therapy must be weighed against the unknown risks on a case-by-case basis.
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 730 times the maximum recommended human dose based on BSA (MRHD) or in pregnant rabbits administered doses up to 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 275 for the free base) is low enough that passage to the embryo and/or fetus should be expected.
The first 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 1–4 mg/day. Therapy was stopped when the pregnancies were diagnosed (timing not specified), and all the women delivered normal, healthy babies.
A 2001 report described 43 pregnancies in 20 women with essential thrombocythemia (ET) (2). Only one pregnancy involved exposure to anagrelide and that one ended in a 1st trimester SAB.
A 2004 case report described the outcome of a pregnancy in which anagrelide was used throughout (3). A 25-year-old woman had been diagnosed with essential thrombocythemia (ET) several years before conception and, because she did not tolerate interferon-α, she was maintained on anagrelide 4 mg/day. She was a heterozygous carrier of the factor V Leiden mutation. When pregnancy was recognized, her dose was reduced to 1 mg/day and low molecular weight heparin was started. Because preeclampsia developed at 32 weeks’, an elective cesarean section was performed to deliver a 1400-g baby (no other data given). The infant had normal blood count parameters (3).
A 2005 report described two women with ET who became pregnant while receiving anagrelide (4). A 32-year-old woman was maintained on 1–4 mg/day, the dose adjusted to maintain a normal platelet count. She conceived against medical advice and eventually gave birth to a healthy 2.87-kg baby girl with no congenital defects and a normal full blood count. The second patient was a 28-year-old woman who was maintained on anagrelide 1.5–2.0 mg/day. Her pregnancy was discovered at 12 weeks’ gestation. The drug was discontinued and she was maintained on low-molecular-weight heparin until she gave birth to a healthy full-term, 2.1-kg male baby with no congenital defects and a normal blood count (4).
A 32-year-old woman positive for the JAK2V617F mutation ET became pregnant while receiving anagrelide (5). The drug was discontinued in the third week and she was treated with aspirin for the remainder of pregnancy. At 39 4/7 weeks, a normal, healthy 2.8-kg baby girl was born with Apgar scores of 9 and 10. The infant’s blood count was normal (5).
BREASTFEEDING SUMMARY
No reports describing the use of anagrelide during lactation have been located. The molecular weight of the compound (about 275 for the free base) is low enough that excretion into milk should be expected. The effect of this exposure on a nursing infant is unknown.
References
1.Product information. Agrylin. Roberts Pharmaceutical, 2000.
2.Wright CA, Tefferi A. A single institutional experience with 43 pregnancies in essential thrombocythemia. Eur J Hematol 2001;66:152–9.
3.Doubek M, Brychtova Y, Doubek R, Janku P, Mayer J. Anagrelide therapy in pregnancy: report of a case of essential thrombocythemia. Ann Hematol 2004;83:726–7.
4.Alkindi S, Dennison D, Pathare A. Successful outcome with anagrelide in pregnancy. Ann Hematol 2005;84:758–9.
5.Sobas MA, Perez Encinas MM, Rabunal Martinez MJ, Quinteiro Garcia C, Bello Lopez JL. Anagrelide treatment in early pregnancy in a patient with JAK2V617F-positive essential thrombocythemia: case report and literature review. Acta Haematol 2009;122:221–2.