Narcotic Agonist–Antagonist Analgesic
PREGNANCY RECOMMENDATION: Human Data Suggest Risk in 3rd Trimester
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
No congenital defects have been reported in humans or in experimental animals following the use of nalbuphine in pregnancy (1). 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). The use of the drug in labor may produce fetal distress and neonatal respiratory depression comparable with that produced by meperidine (1–6).
FETAL RISK SUMMARY
Nalbuphine is indicated for the relief of moderate-to-severe pain. It also is used as a supplement to balanced anesthesia, for preoperative and postoperative analgesia, and for obstetrical analgesia during labor and delivery. The plasma half-life is 5 hours (2).
Reproduction studies in rats and rabbits at doses up to 6 and 4 times, respectively, the maximum recommended human dose (MRHD) revealed no evidence of impaired fertility or fetal harm (2). Administration to rats at doses 4 times the MRHD during at least the last third of gestation and during lactation reduced both neonatal body weight and survival (2).
Nalbuphine crosses the placenta to the fetus (6–8). 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 hours. In another study, the fetal:maternal ratio was 0.74 at delivery and the estimated neonatal plasma half-life was 4.1 hours (8).
A sinusoidal fetal heart rate pattern was observed after a 10-mg IV dose administered to a woman in labor at 42 weeks’ gestation (9). 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 female infant with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively, who did well following delivery. The authors attributed the persistent sinusoidal pattern to the prolonged plasma half-life in adults (9).
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 (10). 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 (10).
In a 1991 study, IV nalbuphine (N = 70; 10 mg) and meperidine (N = 67; 50 mg) were compared for analgesia during the active phase of labor at term (11). Neither regimen had an advantage over the other, but, in the nalbuphine group, there were significantly more newborns with a 1-minute Apgar score <7 (10.6% vs. 1.7%, p <0.05). Of note, the time interval between the dose of the two drugs and delivery was not provided although it was >1 hour (11).
BREASTFEEDING SUMMARY
No reports describing the use of nalbuphine during breastfeeding have been located. The manufacturer states that small amounts (<1% of the mother’s dose) are excreted into breast milk and these amounts are clinically insignificant (2).
In a 2007 report, 18 non-breastfeeding women immediately after delivery were given IV nalbuphine (0.2 mg/kg every 4 hours) and ketoprofen (100 mg every 12 hours) for postpartum pain (12). The mean and maximum nalbuphine milk concentrations were 42 and 61 ng/mL, respectively. Assuming a milk volume of 150 mL/kg/day, the estimated mean and maximum infant doses were 7.0 and 9.0 mcg/kg/day, respectively. The relative infant dose as a percentage of the weight-adjusted maternal dose was 0.59% (12). (See Ketoprofen for additional data.)
Because nalbuphine has poor oral absorption, it is unlikely to adversely affect a nursing infant.
References
1.Miller RR. Evaluation of nalbuphine hydrochloride. Am J Hosp Pharm 1980;37:942–9.
2.Product information. Nalbuphine hydrochloride. Hospira, 2007.
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.Nicolle E, Devillier P, Delanoy B, Durand C, Bessard G. Therapeutic monitoring of nalbuphine: transplacental transfer and estimated pharmacokinetics in the neonate. Eur J Clin Pharmacol 1996;49:485–9.
9.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.
10.Podlas J, Breland BD. Patient-controlled analgesia with nalbuphine during labor. Obstet Gynecol 1987;70:202–4.
11.Dan U, Rabinovici Y, Barkai G, Modan M, Etchin A, Mashiach S. Intravenous pethidine and nalbuphine during labor: a prospective double-blind comparative study. Gynecol Obstet Invest 1991;32:39–43.
12.Jacqz-Aigrain E, Serreau R, Boissinot C, Popon M, Sobel A, Michel J, Sibony O. Excretion of ketoprofen and nalbuphine in human milk during treatment of maternal pain after delivery. Ther Drug Monit 2007;29:815–8.