Narcotic Agonist-Antagonist Analgesic
PREGNANCY RECOMMENDATION: Human Data Suggest Risk in 3rd Trimester
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
Although the human pregnancy experience is very limited, and there is no data during the 1st trimester, agents in this class appear to be low risk. Use during labor, however, may cause a sinusoidal fetal heart rate pattern and transient neonatal depression.
FETAL RISK SUMMARY
No reports linking the use of butorphanol with congenital defects have been located. Because it has both narcotic agonist and antagonist properties, prolonged use during gestation may result in fetal addiction with subsequent withdrawal in the newborn (see also Pentazocine). The drug is commercially available as injection and nasal spray formulations.
No teratogenic effects were observed in reproduction studies in rats and rabbits administered butorphanol during organogenesis (1). An increased frequency of stillbirth was observed in rats given 1 mg/kg (5.9 mg/m2) SC and in rabbits dosed orally with 30 mg/kg (360 mg/m2) and 60 mg/kg (720 mg/m2).
At term, butorphanol rapidly crosses the placenta, producing cord serum levels averaging 84% of maternal concentrations (2,3). Depressant effects on the newborn from in utero exposure during labor are similar to those seen with meperidine (2–4).
The use of 1 mg of butorphanol combined with 25 mg of promethazine administered IV to a woman in active labor was associated with a sinusoidal fetal heart rate pattern (5). Onset of the pattern occurred 6 minutes after drug injection and persisted for approximately 58 minutes. The newborn infant showed no effects from the abnormal heart pattern. A subsequent study to determine the incidence of sinusoidal fetal heart rate pattern after butorphanol administration was published in 1986 (6). Fifty-one women in labor who received butorphanol, 1 mg IV, were compared with a control group of 55 women who did not receive narcotic analgesia. A sinusoidal fetal heart rate pattern was observed in 75% (38 of 51) of the treated women vs. 13% (7 of 55) of controls ( p <0.001). The mean time of onset of the abnormal tracing was 12.74 minutes after butorphanol with a duration of 31.26 minutes. This duration was significantly longer than that observed in the nontreated controls (13.86 minutes; p <0.02). Because no short-term maternal or neonatal adverse effects were observed, the investigators concluded that, in the absence of other signs, the abnormal heart rate pattern was not indicative of fetal hypoxia (6).
A study comparing the effects of maternal analgesics on neonatal neurobehavior was conducted in 135 patients during their 1st day of life (7). Maternal analgesia consisted of 1 mg of butorphanol (N = 68) or 40 mg of meperidine (N = 67). No difference between the drugs was observed.
BREASTFEEDING SUMMARY
Butorphanol passes into breast milk in concentrations paralleling levels in maternal serum (3). Milk:plasma ratios after IM (12 mg) or oral (8 mg) doses were 0.7 and 1.9, respectively. Using 2 mg IM or 8 mg orally 4 times per day would result in 4 mcg excreted in the full daily milk output (1000 mL). Although it has not been studied, this amount is probably insignificant. The American Academy of Pediatrics classifies butorphanol as compatible with breastfeeding (8).
References
1.Product information. Stadol NS. Bristol-Myers Squibb, 2000.
2.Maduska AL, Hajghassemali M. A double-blind comparison of butorphanol and meperidine in labour: maternal pain relief and effect on the newborn. Can Anaesth Soc J 1978;25:398–404.
3.Pittman KA, Smyth RD, Losada M, Zighelboim I, Maduska AL, Sunshine A. Human perinatal distribution of butorphanol. Am J Obstet Gynecol 1980;138:797–800.
4.Quilligan EJ, Keegan KA, Donahue MJ. Double-blind comparison of intravenously injected butorphanol and meperidine in parturients. Int J Gynaecol Obstet 1980;18:363–7.
5.Angel JL, Knuppel RA, Lake M. Sinusoidal fetal heart rate pattern associated with intravenous butorphanol administration: a case report. Am J Obstet Gynecol 1984;149:465–7.
6.Hatjis CG, Meis PJ. Sinusoidal fetal heart rate pattern associated with butorphanol administration. Obstet Gynecol 1986;67:377–80.
7.Hodgkinson R, Huff RW, Hayashi RH, Husain FJ. Double-blind comparison of maternal analgesia and neonatal neurobehaviour following intravenous butorphanol and meperidine. J Int Med Res 1979;7:224–30.
8.Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776–89.