MAPROTILINE

Fetal Risk Summary

No published reports linking the use of maprotiline with congenital defects have been located. Animal studies have failed to demonstrate teratogenicity, carcinogenicity, mutagenicity, or impairment of fertility (1,2).

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 13 newborns had been exposed to maprotiline during the 1st trimester (F. Rosa, personal communication, FDA, 1993). Two (15.4%) major birth defects were observed (0.6 expected), one of which was an oral cleft (none expected). No anomalies were observed in five other defect categories (cardiovascular defects, spina bifida, polydactyly, limb reduction defects, and hypospadias) for which specific data were available. Although the number of exposures is small, the oral cleft is suggestive of an association, but other factors, such as concurrent drug use and chance, may be involved.

Breast Feeding Summary

Maprotiline is excreted into breast milk (3). Milk:plasma ratios of 1.5 and 1.3 have been reported following a 100-mg single dose and 150 mg in divided doses for 120 hours. Multiple dosing resulted in milk concentrations of unchanged maprotiline of 0.2 µg/mL. Although this amount is low, the significance to the nursing infant is not known.

References

1. Product information. Ludiomil. CIBA, 1993.
2. Esaki K, Tanioka Y, Tsukada M, Izumiyama K. Teratogenicity of maprotiline tested by oral administration to mice and rats. (Japanese) CIEA Preclinical Report 1976;2:69–77. As cited in Shepard TH. Catalog of Teratogenic Agents. 6th ed. Baltimore, MD: Johns Hopkins University Press, 1989:384.
3. Reiss W. The relevance of blood level determinations during the evaluation of maprotiline in man. In Murphy JE, ed. Research and Clinical Investigation in Depression. Northampton, England: Cambridge Medical Publications, 1980;19–38.