Risk Factor: C
Class: Central nervous system drugs/ Tranquilizers
Fetal Risk Summary
Perphenazine is a piperazine phenothiazine in the same group as prochlorperazine (see Prochlorperazine). The phenothiazines readily cross the placenta to the fetus (1).
The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 63 of which had 1st trimester exposure to perphenazine (2). For use anytime during pregnancy, 166 exposures were recorded. No evidence was found in either group to suggest a relationship to malformations, nor an effect on perinatal mortality rates, birth weight, or intelligence quotient scores at 4 years of age.
In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 140 newborns had been exposed to perphenazine during the 1st trimester (F. Rosa, personal communication, FDA, 1993). Five (3.6%) major birth defects were observed (six expected), four of which were cardiovascular defects (one expected). No anomalies were observed in five other defect categories (oral clefts, spina bifida, polydactyly, limb reduction defects, and hypospadias) for which specific data were available. The number of cardiovascular defects is suggestive of a possible association, but other factors, including the mother’s disease, concurrent drug use, and chance, may be involved.
A case of maternal suicide attempt with a combination of amitriptyline (725 mg) and perphenazine (58 mg) at 8 days’ gestation was described in a 1980 abstract (3). An infant was eventually delivered with multiple congenital defects. The abnormalities included microcephaly, cotton-like hair with pronounced shedding, cleft palate, micrognathia, ambiguous genitalia, foot deformities, and undetectable dermal ridges (3).
Perphenazine has been used as an antiemetic during normal labor without producing any observable effect on the newborn (4).
Although occasional published reports have attempted to link various phenothiazine compounds with congenital defects, the bulk of the evidence suggests that the therapeutic use of these drugs are safe for the mother and fetus (see also Chlorpromazine). A possible association between perphenazine, amitriptyline, or both and congenital defects is suggested by a single case, but without confirming evidence no conclusions can be reached.
Breast Feeding Summary
Perphenazine is excreted into human milk (5). A 50-kg, lactating 22-year-old woman was taking perphenazine 12 mg twice daily (480 g/kg) for postpartum psychosis. She had a 1-month-old child. During a 24-hour interval, she produced 510 mL of milk that contained 3.2 ng/mL (7.8 nmol/L) of perphenazine. Because of toxicity, her dose was decreased to 8 mg twice daily, with a proportionate decrease in the concentration in milk to 2.1 ng/mL. The mean milk:plasma ratio from samples drawn at various times during the day was approximately 1. Calculated on the infant’s weight of 3.5 kg, the authors estimated that the infant would consume about 0.1% of the mother’s dose, based on a g/kg/day basis. Because they did not consider this exposure to be clinically significant, breast feeding was started. For the next 3.5 months while the mother was on perphenazine, the infant’s growth and development were normal. Although no adverse effects were observed in this single case, the American Academy of Pediatrics considers the effects of the drug on the nursing infant to be unknown, but they may be of concern (6).
- Moya F, Thorndike V. Passage of drugs across the placenta. Am J Obstet Gynecol 1962;84:177898.
- Slone D, Siskind V, Heinonen OP, Monson RR, Kaufman DW, Shapiro S. Antenatal exposure to the phenothiazines in relation to congenital malformations, perinatal mortality rate, birth weight, and intelligence quotient score. Am J Obstet Gynecol 1977;128:4868.
- Wertelecki W, Purvis-Smith SG, Blackburn WR. Amitriptyline/perphenazine maternal overdose and birth defects (abstract). Teratology 1980;21:74A.
- McGarry JM. A double-blind comparison of the anti-emetic effect during labour of metoclopramide and perphenazine. Br J Anaesth 1971;43:6135.
- Olesen OV, Bartels U, Poulsen JH. Perphenazine in breast milk and serum. Am J Psychiatry 1990;147:13789.
- Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.