AMOXAPINE

Fetal Risk Summary

No published reports linking the use of amoxapine with congenital defects have been located. Reproductive studies in mice, rats, and rabbits have found no teratogenicity, but embryotoxicity was observed in rats and rabbits given oral doses approximating the human dose (1). Intrauterine death, stillbirths, decreased weight, and decreased neonatal survival (days 0–4) were seen with oral doses at 3–10 times the human dose.

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 19 newborns had been exposed to amoxapine during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of three (15.8%) major birth defects were observed (one expected). Data on the specific types of defects were not available, but no cases of cardiovascular defects, oral clefts, spina bifida, polydactyly, limb reduction defects, or hypospadias were observed. Although the total incidence of anomalies is high, the number of exposures is too small to draw a conclusion.

Breast Feeding Summary

Amoxapine and its metabolite are excreted into breast milk. A 29-year-old woman suffering from depression was treated with approximately 250 mg/day of amoxapine (2). She developed galactorrhea and oligomenorrhea. Milk samples were collected after 10 and 11 months of therapy and analyzed for amoxapine and the active metabolite, 8-hydroxyamoxapine. The levels of the parent compound at the sample collection times were both less than 20 ng/mL, but the metabolite was present in both samples, 45 minutes after the last dose at 10 months and 11.5 hours after the last dose at 11 months. Levels of the active metabolite at these times were 113 ng/mL and 168 ng/mL, respectively. A venous blood specimen obtained simultaneously with the first milk sample had concentrations of amoxapine and 8-hydroxyamoxapine of 97 ng/mL and 375 ng/mL, respectively. The American Academy of Pediatrics classifies amoxapine as a drug whose effect on the nursing infant is unknown but may be of concern (3).

References

1. Product information. Asendin. Lederle Laboratories, 1997.
2. Gelenberg AJ. Amoxapine, a new antidepressant, appears in human milk. J Nerv Ment Dis 1979;167:635–6.
3. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.