Prochlorperazine

 Risk Factor: C
 Class: GASTROINTESTINAL AGENTS / Antiemetics

Contents of this page:

Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

Prochlorperazine is a piperazine phenothiazine. In one rat study, prochlorperazine produced significant postnatal weight decrease, increased fetal mortality, and minor behavioral changes, but no structural defects (1). In a second rat study, an increased incidence of cleft palate, a few anencephalic fetuses, and one double monster was observed (2).

The drug readily crosses the placenta (3). Prochlorperazine has been used to treat nausea and vomiting of pregnancy. Most studies have found the drug to be safe for this indication (see also Chlorpromazine) (4,5 and 6).

The Collaborative Perinatal Project (CPP) monitored 50,282 mother-child pairs, 877 of which had 1st trimester exposure to prochlorperazine (6). For use anytime during pregnancy, 2,023 exposures were recorded. No evidence was found in either group to suggest a relationship to malformations or an effect on perinatal mortality rate, birth weight, or intelligence quotient scores at 4 years of age.

In a separate study using data from the CPP, offspring of psychotic or neurotic mothers who had consumed prochlorperazine for 12 months during gestation (N=30) were significantly taller than nonexposed controls (N=71) at 4 months and at 1 year of age (7). Those who had been exposed for longer than 2 months (N=8) were also taller than controls at both ages, but not significantly so. Offspring (N=21) of normal women, who had taken the drug for more than 2 months during pregnancy, were significantly taller than nonexposed controls (N=68) at 1 year of age but no difference was measured at 7 years of age. Moreover, the mean weight of exposed children of normal mothers was significantly greater than controls at 1 year of age, but not at 7 years of age. The mechanisms behind these effects were not clear, but may have been related to the dopamine receptor-blocking action of the drug.

Five infants exposed to prochlorperazine, and, in some cases, to multiple other drugs, during the 1st trimester are described below: Cleft palate, micrognathia, congenital heart defects, skeletal defects (8) Thanatophoric dwarfism (short limb anomaly) (9) Hypoplasia of radium and ulnar bones with a vestigial wrist and hand (10) Below-the-elbow amputation in one arm and small atrophic hand attached to the stump (11) Below-the-knee amputation in one limb, with rudimentary foot attached to stump (one twin) (11) The relationship between prochlorperazine and the above defects is unknown. The case of dwarfism was probably caused by genetic factors. No evidence of amniotic bands were observed in the two cases involving amputations, both of whom were exposed during the mothers' treatment for hyperemesis gravidarum (11).

A 1963 report described phocomelia of the upper limbs in a male infant exposed to two phenothiazines during gestation (12). The mother had not taken prochlorperazine until approximately the 13th week of gestation, so no association between the drug and the defect is possible. However, the other agent, trifluoperazine, was taken early in pregnancy (see also Trifluoperazine). In another study, no increase in defects or pattern of malformations were observed in 76 infants (2 sets of twins) exposed in utero to the antiemetic (13).

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 704 newborns had been exposed to prochlorperazine during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of 24 (3.4%) major birth defects were observed (29 expected). Specific data were available for six defect categories, including (observed/expected) 6/7 cardiovascular defects, 1/1 oral clefts, 0/0 spina bifida, 1/2 polydactyly, 1/1 limb-reduction defects, and 0/2 hypospadias. These data do not support an association between the drug and congenital defects.

In summary, although there are isolated reports of congenital defects in children exposed to prochlorperazine in utero, the majority of the evidence indicates that this drug and the general class of phenothiazines are safe for both mother and fetus if used occasionally in low doses. Other reviewers have also concluded that the phenothiazines are not teratogenic (14,15).

Breast Feeding Summary

No reports describing the excretion of prochlorperazine into breast milk have been located, but the drug has been found in the milk of lactating dogs (16). Because other phenothiazines appear in human milk (e.g., chlorpromazine), excretion of prochlorperazine should be expected. Sedation is a possible effect in the nursing infant. Although prochlorperazine was listed as compatible with breast feeding in the American Academy of Pediatrics' 1983 statement (17), the agent was not included in the 1989 or 1994 revisions.

References

1. Vorhees CV, Brunner RL, Butcher RE. Psychotropic drugs as behavioral teratogens. Science 1979;205:12205. As cited in Shepard TH. Catalog of Teratogenic Agents. 6th ed. Baltimore, MD: Johns Hopkins University Press, 1989:5256.
2. Roux C. Action teratogene de la prochlorpemazine. Arch Fr Pediatr 1959;16:96871. As cited in Shepard TH. Catalog of Teratogenic Agents. 6th ed. Baltimore, MD: Johns Hopkins University Press, 1989:5256.
3. Moya F, Thorndike V. Passage of drugs across the placenta. Am J Obstet Gynecol 1962;84:177898.
4. Reider RO, Rosenthal D. Wender P, Blumenthal H. The offspring of schizophrenics. Fetal and neonatal deaths. Arch Gen Psychiatry 1975;32:20011.
5. Milkovich L, Van den Berg BJ. An evaluation of the teratogenicity of certain antinauseant drugs. Am J Obstet Gynecol 1976;125:2448.
6. 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.
7. Platt JE, Friedhoff AJ, Broman SH, Bond RN, Laska E, Lin SP. Effects of prenatal exposure to neuroleptic drugs on children's growth. Neuropsychopharmacology 1988;1:20512.
8. Ho CK, Kaufman RL, McAlister WH. Congenital malformations. Cleft palate, congenital heart disease, absent tibiae, and polydactyly. Am J Dis Child 1975;129:7146.
9. Farag RA, Ananth J. Thanatophoric dwarfism associated with prochlorperazine administration. NY State J Med 1978;78:27982.
10. Freeman R. Limb deformities: possible association with drugs. Med J Aust 1972;1:6067.
11. Rafla N. Limb deformities associated with prochlorperazine. Am J Obstet Gynecol 1987;156:1557.
12. Hall G. A case of phocomelia of the upper limbs. Med J Aust 1983;1:44950.
13. Mellin GW. Report of prochlorperazine during pregnancy from the fetal life study bank (abstract). Teratology 1975;11:28A.
14. Ayd FJ Jr. Children born of mothers treated with chlorpromazine during pregnancy. Clin Med 1964;71:175863.
15. Ananth J. Congenital malformations with psychopharmacologic agents. Compr Psychiatry 1975;16:43745.
16. Knowles JA. Excretion of drugs in milka review. J Pediatr 1965;66:106882.
17. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human breast milk. Pediatrics 1983;72:37583.
    
    

Questions and Answers

why is it ok for the doctors to prescribe me prochlorperazine in hospital but they say no during pregnancy?

i was in hospital a few weeks ago with a severe vomiting virus and i was 27 weeks pregnant, when in there they prescribed and gave me, prochlorperazine (Buccastem dissovable tablets), but when i got home, i checked out on the net that its not good to take during pregnancy, so where do i stand?

We have to balance the good of medication (stopping the vomiting, allowing you to eat, supply nutrition for the growing baby) against the bad (temporary extrapyramidal side effects, jaundice in the newborn). These effects occur when the "Compazine" was taken recently before delivery. These are the discussions that you should have with your doctor. Give her or him a call.
Old Ob Doc