NALBUPHINE

Fetal Risk Summary

No congenital defects have been reported in humans or in experimental animals following the use of nalbuphine in pregnancy (1). Reproduction studies in rats and rabbits at doses up to 14 and 31 times, respectively, the maximum recommended human dose (MRHD) revealed no evidence of impaired fertility or fetal harm (2). Administration to rats at doses 8–17 times the MRHD during at least the last third of gestation and during lactation reduced both neonatal body weight and survival (2).

Nalbuphine has both narcotic agonist and antagonist effects. Prolonged use during pregnancy could theoretically result in fetal addiction with subsequent withdrawal in the newborn (see also Pentazocine). Use of the drug in labor may produce fetal distress and neonatal respiratory depression comparable to that produced by meperidine (1,2,3,4,5 and 6).

Nalbuphine crosses the placenta to the fetus (6,7). The cord:maternal serum ratio in five women in active labor given 20 mg as an IV bolus ranged from 0.37 to 6.03 (7). A sixth patient given 15 mg had a ratio of 1.24. Umbilical cord concentrations of nalbuphine obtained 3–10 hours after a dose varied from “not detectable” to 46 ng/mL. The terminal half-life of the drug in the mothers was 2.4 ± 0.4 hours.

A sinusoidal fetal heart rate pattern was observed after a 10-mg IV dose administered to a woman in labor at 42 weeks' gestation (8). The sinusoidal pattern persisted for at least 2.25 hours, and periodic late decelerations became evident. A cesarean section was performed to deliver a healthy baby girl with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively. The infant did well following delivery. The authors attributed the persistent sinusoidal pattern to the prolonged plasma half-life in adults (8).

A 1987 Reference compared the use of nalbuphine administered during labor via either a patient-controlled analgesia (PCA) IV pump or by direct IV-push doses (9). No differences were observed between the groups in terms of fetal distress, as evidenced by late decelerations or abnormal scalp blood pH, or in Apgar scores, but specific details on the newborns were not given. However, the fetuses of women receiving nalbuphine by the PCA system had a higher incidence of variable heart rate decelerations.

[*Risk Factor D if used for prolonged periods or in high doses at term.]

Breast Feeding Summary

No reports describing the use of nalbuphine during lactation have been located. Because of the rapid transfer across the placenta, excretion into breast milk should also be expected. The manufacturer states that small amounts (less than 1% of the mother's dose) are excreted into breast milk, but that these amounts are clinically insignificant (2).

References

1. Miller RR. Evaluation of nalbuphine hydrochloride. Am J Hosp Pharm 1980;37:942–9.
2. Product information. Nubain. Endo Pharmaceuticals, 2000.
3. Guillonneau M, Jacqz-Aigrain E, De Grepy A, Zeggout H. Perinatal adverse effects of nalbuphine given during parturition. Lancet 1990;335:1588.
4. Sgro C, Escousse A, Tennenbaum D, Gouyon JB. Perinatal adverse effects of nalbuphine given during labour. Lancet 1990;336:1070.
5. Wilson CM, McClean E, Moore J, Dundee JW. A double-blind comparison of intramuscular pethidine and nalbuphine in labour. Anaesthesia 1986;41:1207–13.
6. Frank M, McAteer EJ, Cattermole R, Loughnan B, Stafford LB, Hitchcock AM. Nalbuphine for obstetric analgesia. Anaesthesia 1987;42:697–703.
7. Wilson SJ, Errick JK, Balkon J. Pharmacokinetics of nalbuphine during parturition. Am J Obstet Gynecol 1986;155:340–4.
8. Feinstein SJ, Lodeiro JG, Vintzileos AM, Campbell WA, Montgomery JT, Nochimson DJ. Sinusoidal fetal heart rate pattern after administration of nalbuphine hydrochloride: a case report. Am J Obstet Gynecol 1986;154:159–60.
9. Podlas J, Breland BD. Patient-controlled analgesia with nalbuphine during labor. Obstet Gynecol 1987;70:202–4.