Baclofen in Pregnancy and Breastfeeding
Fetal Risk Summary
Only two reports have been located that describe the use of the muscle relaxant, baclofen, in human pregnancy. Because of its specialized indication to control spasticity secondary to multiple sclerosis and other spinal cord diseases and injuries, its use in pregnancy is anticipated to be limited.
When baclofen doses 713 times the recommended human dose were administered to pregnant rats and rabbits, increased incidences of omphaloceles and incomplete sternebral ossification were observed in rat fetuses, and an increased incidence of unossified phalangeal nuclei of the fetal limbs was noted in rabbits (1). Shepard reviewed three studies involving rats, mice, and rabbits in which the drug was administered during organogenesis and all reported negative teratogenic findings (2). In contrast, a 1995 study in pregnant rats using 30 or 60 mg/kg on day 10 of gestation observed vertebral arch widening at the lower dose, similar to that produced by valproic acid in rats (3). The author concluded that baclofen could produce spina bifida or other neural tube defects in rats. Interestingly, the 60-mg/kg dose did not produce this effect, causing speculation that the dose caused a greater severity of neural tube defects, and thus a greater number of unrecorded early fetal deaths (3).
Two reports, involving three pregnancies, have been located that describe the use of baclofen in pregnant humans (4,5). A 29-year-old woman with quadriplegia due to an incomplete cervical C6-7 spinal cord lesion following discitis after discography was treated with a continuous intrathecal infusion of baclofen (1000 g/24 hours) for 15 months to control her intractable spasticity (4). Conception occurred after ovulation stimulation with clomiphene. The baclofen dose was gradually increased to 1200 g/24 hours to maintain control of her spasticity as the pregnancy progressed. Because of severe symptoms of autonomic dysfunction and loss of spasticity control (even at 1400 g/24 hours), a cesarean section was conducted under epidural bupivacaine anesthesia in the 35th week of gestation. A 2040-g healthy female infant was delivered with Apgar scores of 9 and 10 (timing not specified).
A second case report, similar to the one above, was published in 2000 (5). A 38-year-old woman became pregnant after approximately 3.5 years of continuous intrathecal baclofen infusion to control severe spasticity resulting from a complete fifth cervical vertebra (C5)-level medular injury. Good control of her spasticity was obtained with intrathecal baclofen (140 mg/day) throughout her pregnancy. A healthy, 2155-g, male infant was delivered by cesarean section at 36 weeks' gestation with Apgar scores of 9 and 10 at one and five minutes, respectively. The birth weight, length (47 cm), and head circumference (33 cm) were appropriate for gestational age (5). No major or minor malformations were noted on physical and ultrasonographic examinations and the child was developing normally at 24 months of age. Three months after delivery of her first infant, the woman became pregnant a second time and again received continuous intrathecal baclofen (140 mg/day) throughout the gestation. A repeat cesarean section was performed at 34 weeks' gestation with delivery of another healthy, 2240-g, male infant with Apgar scores of 8 and 10 at one and five minutes, respectively. The weight, length (46 cm), and head circumference (32 cm) were appropriate for gestational age. No abnormalities were noted in the infant and he was developing normally at 12 months of age (5).
Breast Feeding Summary
In an animal study, the g-aminobutyric acid agonist, baclofen, was a potent inhibitor of suckling-induced prolactin release from the anterior pituitary (6). The drug had no effect on milk ejection. Because prolactin release is required to maintain lactation, the potential for decreased milk production with chronic use may exist. However, no human studies on this topic have been located.
Small amounts of baclofen are excreted into human milk. A 20-year-old woman with spastic paraplegia, who was 14 days postpartum, was given a single 20-mg (94 mol) dose of baclofen (7). No mention was made as to whether her infant was nursing. Serum samples were drawn at 1, 3, 6, and 20 hours after the dose, and milk samples were obtained at 2, 4, 8, 14, 20, and 26 hours. The highest serum concentration measured, 1.419 mol/L, occurred at 3 hours whereas the highest milk level, 0.608 mol/L, was obtained at 4 hours. The total amount of drug recovered from the milk during the 26-hour sampling period was 22 g (0.10 (mol), or about 0.1% of the mother's dose. The authors speculated that this amount would not lead to toxic levels in a nursing infant (7). The American Academy of Pediatrics considers baclofen to be compatible with breast feeding (8).
- Product information. Lioresal. Geigy Pharmaceuticals, 1993.
- Shepard TH. Catalog of Teratogenic Agents. 6th ed. Baltimore, MD:Johns Hopkins University Press, 1989:66.
- Briner W. Muscimol- and baclofen-induced spina bifida in the rat. Med Sci Res 1995;24:639 40.
- Delhaas EM, Verhagen J. Pregnancy in a quadriplegic patient treated with continuous intrathecal baclofen infusion to manage her severe spasticity. Case report. Paraplegia 1992;30:5278.
- Munoz FC, Marco DG, Perez AV, Camacho MM. Pregnancy outcome in a woman exposed to continuous intrathecal baclofen infusion. Ann Pharmacother 2000;34:956.
- Lux VA, Somoza GM, Libertun C. Beta-(-4 chlorophenyl) GABA baclofen) inhibits prolactin and thyrotropin release by acting on the rat brain. Proc Soc Exp Biol Med 1986;183:35862.
- Eriksson G, Swahn C-G. Concentrations of baclofen in serum and breast milk from a lactating woman. Scand J Clin Lab Invest 1981;41:1857.
Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.