Parasympatholytic
PREGNANCY RECOMMENDATION: Limited Human Data—Probably Compatible
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
One surveillance study found a possible association between benztropine and cardiovascular defects, but confirmation is required. Exposure near term has been associated with paralytic ileus in the newborn.
FETAL RISK SUMMARY
Benztropine is an anticholinergic agent structurally related to atropine (see also Atropine). It also has antihistaminic activity. In a large prospective study, 2323 patients were exposed to this class of drugs during the 1st trimester, 4 of whom took benztropine (1). A possible association was found in the total group with minor, but not major, malformations.
In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 84 newborns had been exposed to benztropine during the 1st trimester (F. Rosa, personal communication, FDA, 1993). Four (4.8%) major birth defects were observed (three expected), three of which were cardiovascular defects (one expected). No anomalies were observed in five other categories of defects (oral clefts, spina bifida, polydactyly, limb reduction defects, and hypospadias) for which specific data were available. Based on a small number of exposures, a possible association is suggested with cardiovascular defects.
Paralytic ileus has been observed in two newborns exposed to chlorpromazine and benztropine at term (2). In one of these infants, other anticholinergic drugs may have contributed to the effect (see Doxepin). The small left colon syndrome was characterized by decreased intestinal motility, abdominal distention, vomiting, and failure to pass meconium. The condition cleared rapidly in both infants after a Gastrografin enema.
A 2008 case report described a 25-year-old pregnant woman who was under treatment for bipolar disorder with lithium carbonate (500 mg twice daily), haloperidol (5 mg twice daily), and benzotropine (2 mg twice daily) (3). Her pregnancy was normal until the last 2 weeks when she began to lose weight and developed hypertension. At 39 weeks, a cesarean section delivered a 2.500-kg male infant with Apgar scores of 9 and 10 at 1 and 5 minutes, respectively. Both the infant and placental weights were below the mean for the population. In addition, the maternal plasma concentrations of phosphatidylcholine and free choline were also below the population means in the 3rd trimester. Because these nutrients are important in pregnancy, the authors speculated that one of her drugs, most likely lithium, was the cause of the low birth and placenta weights (3).
BREASTFEEDING SUMMARY
No reports describing the use of benztropine during human lactation have been located. In general, however, agents in this class are probably compatible with breastfeeding. (See Atropine.)
References
1.Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977:346–53.
2.Falterman CG, Richardson CJ. Small left colon syndrome associated with maternal ingestion of psychotropic drugs. J Pediatr 1980;97:308–10.
3.Gossell-Williams M, Fletcher H, Zeisel SH. Unexpected depletion in plasma choline and phosphatidylcholine concentrations in a pregnant woman with bipolar affective disorder being treated with lithium, haloperidol and benzotropine: a case report. J Med Case Rep 2008;2:55. doi:10.1186/ 1752-1947-2-55.