Risk Factor: CM
Class: Anti-infectives/ Leprostatics
Fetal Risk Summary
Clofazimine, a bright red dye with antibacterial properties against Mycobacterium leprae, is used for the treatment of lepromatous leprosy. Animal studies involving mice and rats with doses up to 50 mg/kg/day, and rabbits, 15 mg/kg/day, found no evidence of teratogenicity (1). Fetotoxicity in mice at doses 1225 times the human dose, however, included retardation of fetal skull ossification, increased incidence of abortions and stillbirths, and decreased neonatal survival (2).
A number of studies have reported the use of clofazimine throughout human pregnancies (3,4,5,6,7,8 and 9). In 13 pregnancies, three exposed newborns died shortly after birth, but none of the outcomes could be attributed to clofazimine. The causes of death were unspecified (died 3 hours after birth), prematurity and antemortem hemorrhage, and gastroenteritis (5,7). The mother of the newborn who died at 3 hours was steroid dependent, but she had stopped her prednisolone 4 weeks before delivery (5). No congenital anomalies were observed in any of the 13 infants, although some of the infants were pigmented at birth. In at least 3 infants (data not provided in 10 infants), the pigmentation gradually resolved over a 1-year period (8).
A 1982 case report described the effects of clofazimine exposure during pregnancy on two newborns (10). The first case involved a woman with erythema nodosum leprosum who was treated throughout gestation with clofazimine, 300 mg/day, and prednisone. Rifampin was also used early in pregnancy. Oligohydramnios developed just prior to delivery after a gestation of uncertain dates. Thick, foul-smelling, meconium-stained fluid was present, and the placenta showed signs of acute severe amnionitis. A 2575-g male infant was delivered vaginally who appeared normal except for his skin, which was not excessively pigmented. Bilateral hydrocele and iron deficiency anemia were diagnosed at 14 days of age with fever of unknown origin occurring then and again at 5 months of age. The infant was doing well at 12 months of age. In the second case, a woman was treated throughout pregnancy with clofazimine, 300 mg/day, for tuberculoid leprosy. A normal, healthy 3070-g female infant was delivered vaginally at an unspecified gestational age, and she is growing and developing normally at 3 years of age. Skin pigmentation was not mentioned.
A 1984 Reference examined the results of 79 pregnancies from 76 women with lepromatous leprosy, of whom 4 (5 pregnancies) were treated with clofazimine (300 mg/week) (11). No information was given on the outcome of these pregnancies, although the authors stated that clofazimine was the best drug available, if given after the 1st trimester, to prevent transient relapses and to prevent or treat erythema nodosum leprosy (11).
Breast Feeding Summary
Clofazimine is excreted into breast milk, and pigmentation of the nursing infant may result. In one case, a mother was ingesting clofazimine, between 100300 mg/day (exact dose not specified), 6 days/week, for a 6-month period (3). Her nursing infant became ruddy and then slightly hypermelanotic. The baby’s skin returned to a normal color 5 months after the mother’s medication was stopped.
- Stenger EG, Aeppli L, Peheim E, Thomann PE. Zur toxikologie des leprostaticums 3-(p-chloranilino)-10-(p-chlorophenyl)-2-10-dihydro 2(isopropyl-amino)phenazin (G-30320). Arzneimittelforschung 1970;20:7949. As cited in Shepard TH. Catalog of Teratogenic Agents. 6th ed. Baltimore, MD:Johns Hopkins University Press, 1989:157.
- Product information. Lamprene. Ciba-Geigy Corp, 1992.
- Browne SG, Hogerzeil LM. B 663 in the treatment of leprosy. Preliminary report of a pilot trial. Lepr Rev 1962;33:610.
- Imkamp FMJH. A treatment of corticosteroid-dependent lepromatous patients in persistent erythema nodosum leprosum. A clinical evaluation of G.30320 (B663). Lepr Rev 1968;39:11925.
- Plock H, Leiker DL. A long term trial with clofazimine in reactive lepromatous leprosy. Lepr Rev 1976;47:2534.
- De las Aguas JT. Treatment of leprosy with Lampren (B.663 Geigy). Int J Lepr Other Mycobact Dis 1971;39:493503.
- Schulz EJ. Forty-four months’ experience in the treatment of leprosy with clofazimine (Lamprene (Geigy)). Lepr Rev 1972;42:17887.
- Karat AB. Long-term follow-up of clofazimine (Lamprene) in the management of reactive phases of leprosy. Lepr Rev 1975;46(Suppl):1059.
- Waters MFR. Symposium on B.663 (Lamprene, Geigy) in the treatment of leprosy and leprosy reactions. Int J Lepr 1968;36:5601.
- Farb H, West DP, Pedvis-Leftick A. Clofazimine in pregnancy complicated by leprosy. Obstet Gynecol 1982;59:1223.
- Duncan ME, Pearson JMH. The association of pregnancy and leprosy. III. Erythema nodosum leprosum in pregnancy and lactation. Lepr Rev 1984;55:12942.