Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in females exposed to THALOMID during pregnancy as well as female partners of male patients who are exposed to THALOMID. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure to THALOMID to the FDA via the MedWatch program at 1-800-FDA-1088 and to the REMS Call Center at 1-888-423-5436.

Risk Summary

Based on the mechanism of action [see Clinical Pharmacology (12.1)], human and animal data (see Data), THALOMID can cause embryo-fetal harm when administered to a pregnant female and is contraindicated during pregnancy [see Boxed Warning, Contraindications (4.1), and Warnings and Precautions (5.1)].

THALOMID is a human teratogen, inducing a high frequency of severe and life-threatening birth defects such as amelia (absence of limbs), phocomelia (short limbs), hypoplasticity of the bones, absence of bones, external ear abnormalities (including anotia, micropinna, small or absent external auditory canals), facial palsy, eye abnormalities (anophthalmos, microphthalmos), and congenital heart defects. Alimentary tract, urinary tract, and genital malformations have also been documented and mortality at or shortly after birth has been reported in about 40% of infants. Even a single dose taken by a pregnant woman can cause birth defects. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to a fetus.

If pregnancy does occur during treatment, immediately discontinue the drug. Under these conditions, refer the patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. Report any suspected fetal exposure to THALOMID to the FDA via the MedWatch program at 1-800-FDA-1088 and also the REMS Call Center at 1-888-423-5436.

Thalidomide crossed the placenta after administration to pregnant hamsters (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk in the U.S. general population of major birth defects is 2%-4% and of miscarriage is 15%-20% of clinically recognized pregnancies.

Data

Animal Data

A pre- and postnatal reproductive toxicity study was conducted in pregnant female rabbits. Compound-related increased abortion incidences and elevated fetotoxicity were observed at the lowest oral dose level of 30 mg/kg/day (approximately 1.5-fold the maximum human dose based upon BSA) and all higher dose levels. Neonatal mortality was elevated at oral dose levels to the lactating female rabbits ≥150 mg/kg/day (approximately 7.5-fold the maximum human dose based upon BSA). No delay in postnatal development, including learning and memory functions, were noted at the oral dose level to the lactating female rabbits of 150 mg/kg/day (average thalidomide concentrations in milk ranged from 22 to 36 mcg per mL).

In a study conducted in pregnant rabbits, thalidomide levels in fetal plasma were approximately 11% to 73% of the maternal Cmax. In a study conducted with 14C-thalidomide (150 mg/kg orally) in pregnant hamsters, radioactivity was detected in the embryo, and the relative concentrations of radioactivity in the embryo and maternal plasma were about the same at 4, 12 and 24 hours after dosing. Based on the radioactivity data, thalidomide crossed the placental barrier, and the fetal levels of drug-related material were approximately similar to those of maternal levels.