Thrombolytic
PREGNANCY RECOMMENDATION: Compatible—Maternal Benefit >> Embryo–Fetal Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
One report described the use of reteplase in human pregnancy. Bleeding appears to be the potential risk but was not observed in this case. Pregnancy may increase this risk (1). However, if indicated, the maternal benefit appears to outweigh the potential risk to the embryo–fetus.
FETAL RISK SUMMARY
The enzyme reteplase is a nonglycosylated deletion mutein of tissue plasminogen activator (tPA; see also Alteplase and Tenecteplase) produced by recombinant technology in Escherichia coli. It contains 355 of the 527 amino acids of natural human tPA. Reteplase is indicated for use in the management of acute myocardial infarction for the improvement of ventricular function, the reduction in the incidence of congestive heart failure, and the reduction of mortality. The effective half-life of reteplase is 13–16 minutes, based on the measurement of thrombolytic activity (1).
Reproduction studies have been conducted in rats and rabbits. In rats, doses up to 15 times the human dose (HD) revealed no evidence of impaired fertility or teratogenicity. In rabbits, a dose 3 times the HD administered in mid-gestation resulted in genital bleeding and abortions (1).
It is not known if reteplase crosses the human placenta. The molecular weight (39,571) and very short effective half-life suggest that clinically significant amounts of the protein will not cross to the embryo–fetus.
A 2002 report described the use of reteplase for acute massive pulmonary embolism in a pregnant woman at 30 weeks’ gestation (2). The patient was given a 10 mg IV bolus followed by 90 mg IV over 2 hours with marked improvement in her condition. Heparin was given for remainder of the pregnancy. At 36 weeks’ she gave birth to a healthy male infant (no other details were provided) (2).
BREASTFEEDING SUMMARY
No reports describing the use of reteplase during human lactation have been located. However, the indication for reteplase suggests that such reports will not be forthcoming. In addition, the molecular weight (39,571) and very short effective half-life (13–16 minutes) suggest that the protein will not be excreted in clinically significant amounts into breast milk. Therefore, breastfeeding should be initiated or resumed based on the mother’s condition and not the drug therapy.
References
1.Product information. Retavase. Centocor, 2004.
2.Yap LB, Alp NJ, Forfar JC. Thrombolysis for acute massive pulmonary embolism during pregnancy. Int J Cardiol 2002;82:193–4.