PREGNANCY RECOMMENDATION: Compatible
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
The limited animal and human data suggest that droperidol does not represent a significant risk to the fetus for major anomalies. The drug is a potent antiemetic that is effective for the treatment of severe nausea and vomiting of pregnancy.
FETAL RISK SUMMARY
Droperidol is a butyrophenone derivative structurally related to haloperidol (see also Haloperidol). The agent is not teratogenic in animals, but has produced a slight increase in the mortality of newborn rats (1). After IM administration, the increased pup mortality was attributed to CNS depression of the dams resulting in their failure to remove the placentae from the offspring (1).
The relatively low molecular weight of droperidol (about 379) suggests that the drug crosses the placenta to the fetus. In humans, the placental transfer of droperidol is slow (2).
Droperidol promotes analgesia for patients undergoing cesarean section without affecting the respiration of the newborn (2,3). The drug was also administered during labor as a sedative in a study comparing 48 women treated with droperidol with 52 women receiving promethazine (4). These investigators noted eight other reports in which the drug was used in a similar manner. No serious maternal or fetal adverse effects were observed.
Droperidol has been used for the treatment of severe nausea and vomiting occurring during pregnancy (5,6). A 1996 report described the use of droperidol and other drugs (diphenhydramine, metoclopramide, and hydroxyzine) in 80 women with hyperemesis gravidarum (6). The mean gestational age at the start of treatment was 10.9 weeks and the mean total dose received for the approximately 2 days of therapy was 49.6 mg. Twelve (15%) of the women required a second hospitalization and were again treated with the same therapy. Three of the mothers (all treated in the 2nd trimester) delivered offspring with congenital defects: Poland’s syndrome, fetal alcohol syndrome, and hydrocephalus and hypoplasia of the right cerebral hemisphere. Only the latter anomaly is a potential drug effect, but the most likely cause was thought to be the result of an in utero fetal vascular accident or infection (6).
A 2001 study, using a treatment method similar to the above study, described the use of droperidol and diphenhydramine in 28 women hospitalized for hyperemesis gravidarum (7). Pregnancy outcomes in the study group were compared with a historical control of 54 women who had received conventional antiemetic therapy. Oral metoclopramide and hydroxyzine were used after discharge from the hospital. Therapy was started in the study and control groups at mean gestational ages of 9.9 and 11.1 weeks’, respectively. The study group appeared to have more severe disease than controls, as suggested by a greater mean loss from the prepregnancy weight, 2.07 vs. 0.81 kg (ns), and a slightly lower serum potassium level, 3.4 vs. 3.5 mmol/L (ns). Compared with controls, the droperidol group had a shorter duration of hospitalization (3.53 vs. 2.82 days, p = 0.023), fewer readmissions (38.9% vs. 14.3%, p = 0.025), and lower average daily nausea and vomiting scores (both p <0.001). There were no statistical differences (p>0.05) in outcomes (study vs. controls) in terms of spontaneous abortions (N = 0 vs. N = 2 [4.3%]), elective abortions (N = 3 [12.0%] vs. N = 3 [6.5%]), Apgar scores at 1, 5, and 10 minutes, age at birth (37.3 vs. 37.9 weeks’), and birth weight (3114 vs. 3347 g) (7). In controls, there was one (2.4%) major malformation of unknown cause, an acardiac fetus in a set of triplets, and one newborn with a genetic defect (Turner’s syndrome). There was also one unexplained major birth defect (4.4%) in the droperidol group (bilateral hydronephrosis), and two genetic defects (translocation of chromosomes 3 and 7; tyrosinemia) (7).
In a nonrandomized, prospective study, two doses (0.5 and 1.0 mg/hr) of droperidol plus diphenhydramine for hyperemesis gravidarum were compared with historical controls (8). The number of patients in each group was 34, 67, and 54, respectively. Data were available for major anomalies in 26, 53, and 21 infants, respectively. Major anomalies, excluding those that were obviously not drug-induced (i.e., genetic, chromosomal, or amniotic bands), observed in the study were one (clubfoot—possible genetic defect), one (bilateral hydronephrosis), and none, respectively (8).
No reports describing the use of droperidol during lactation have been located. The molecular weight (about 379) is low enough that excretion into human milk should be expected. Because the drug is only available as an injectable formulation, the opportunity for exposure of a nursing infant appears to be limited. The effect of exposure on a nursing infant is unknown.
1.Product information. Inapsine. Akorn, 1997.
2.Zhdanov GG, Ponomarev GM. The concentration of droperidol in the venous blood of the parturients and in the blood of the umbilical cord of neonates. Anesteziol Reanimatol 1980;4:14–6.
3.Smith AM, McNeil WT. Awareness during anesthesia. Br Med J 1969;1:572–3.
4.Pettit GP, Smith GA, McIlroy WL. Droperidol in obstetrics: a double-blind study. Milit Med 1976;141:316–7.
5.Martynshin MYA, Arkhengel’skii AE. Experience in treating early toxicoses of pregnancy with metoclopramide. Akush Ginekol 1981;57:44–5.
6.Nageotte MP, Briggs GG, Towers CV, Asrat T. Droperidol and diphenhydramine in the management of hyperemesis gravidarum. Am J Obstet Gynecol 1996;174:1801–6.
7.Turcotte V, Ferreira E, Duperron L. Utilité du dropéridol et de la diphenhydramine dans l’hyperemesis gravidarum. J Soc Obstet Gynaecol Can 2001;23:133–9.
8.Ferreira E, Bussieres J-F, Turcotte V, Duperron L, Ouellet G. Case-control study comparing droperidol plus diphenhydramine with conventional treatment in hyperemesis gravidarum. J Pharm Technol 2003;19:349–54.