NALOXONE

Fetal Risk Summary

Naloxone is a narcotic antagonist that is used to reverse the effects of narcotic overdose. The drug has no intrinsic respiratory depressive actions or other narcotic effects of its own (1). Naloxone has been shown to cross the placenta, appearing in fetal blood 2 minutes after a maternal dose and gradually increasing over 10–30 minutes (2).

Reproduction studies in mice and rats at doses up to 50 times the usual human dose revealed no evidence of impaired fertility or fetal harm (3).

In three reports, naloxone was given to mothers in labor after the administration of meperidine (4,5 and 6). One study found that 18–40 µg/kg (maternal weight) given IV provided the best results in comparison with controls who did not receive meperidine or naloxone (5). In measurements of newborn neurobehavior, groups treated in labor with either meperidine or meperidine plus naloxone (0.4 mg) were compared with a nontreated control group (6). The control group scored better in the first 24 hours than either of the treated groups and, after 2 hours, no difference was found between meperidine or meperidine plus naloxone–treated patients. Women in active labor received 1.0 mg of morphine intrathecally followed in 1 hour by a 0.4-mg IV bolus of naloxone plus 0.6 mg/hour or placebo as constant infusion for 23 hours (7). A reduction in some morphine-induced maternal side effects was seen with naloxone, but no significant differences with placebo were found for fetal heart rate or variability, Apgar scores, umbilical venous and arterial gases, neonatal respirations, or neurobehavioral examination scores. Cord:maternal serum ratio for naloxone was 0.50. Naloxone has also been safely given to newborns within a few minutes of delivery (8,9,10,11,12 and 13).

Naloxone has been used at term to treat fetal heart rate baselines with low beat-to-beat variability not caused by maternally administered narcotics (14). This use was based on the assumption that the heart rate patterns were caused by elevated fetal endorphins. In one case, however, naloxone may have enhanced fetal asphyxia, leading to fatal respiratory failure in the newborn (14). Based on the above data, naloxone should not be given to the mother just before delivery to reverse the effects of narcotics in the fetus or newborn unless narcotic toxicity is evident. Information on its fetal effects during pregnancy, other than labor, is not available.

In a study of the effects of naloxone on fetal behavior, 54 pregnant women with gestational ages between 37 and 39 weeks were evenly divided into two groups (15). One group received 0.4 mg of naloxone and the other received an equal volume of saline placebo. In the group receiving naloxone, significant increases were observed in the number, duration, and amplitude of fetal heart rate accelerations. Significant increases were also observed in the number of fetal body movements and the percentage of time spent breathing. Moreover, significantly more fetuses exposed to naloxone were actively awake than those not exposed. The investigators attributed their findings to reversal of the effects of fetal endorphins.

Breast Feeding Summary

No data are available.

References

1. Jaffe JH, Martin WR. Opioid analgesics and antagonists. In Gilman AG, Goodman LS, Gilman A, eds. The Pharmacological Basis of Therapeutics. 6th ed. New York, NY: MacMillan, 1980:522–5.
2. Finster M, Gibbs C, Dawes GS, et al. Placental transfer of meperidine (Demerol) and naloxone (Narcan). Presented at the Annual Meeting of the American Society of Anesthesiologists, Boston, October 4, 1972. In Clark RB, Beard AG, Greifenstein FE, Barclay DL. Naloxine in the parturient and her infant. South Med J 1976;69:570–5.
3. Product information. Narcan. Endo Pharmaceuticals, 2000.
4. Clark RB. Transplacental reversal of meperidine depression in the fetus by naloxone. J Arkansas Med Soc 1971;68:128–30.
5. Clark RB, Beard AG, Greifenstein FE, Barclay DL. Naloxone in the parturient and her infant. South Med J 1976;69:570–5.
6. Hodgkinson R, Bhatt M, Grewal G, Marx GF. Neonatal neurobehavior in the first 48 hours of life: effect of the administration of meperidine with and without naloxone in the mother. Pediatrics 1978;62:294–8.
7. Brookshire GL, Shnider SM, Abboud TK, Kotelko DM, Nouiehed R, Thigpen JW, Khoo SS, Raya JA, Foutz SE, Brizgys RV. Effects of naloxone on the mother and neonate after intrathecal morphine for labor analgesia. Anesthesiology 1983;59:A417.
8. Evans JM, Hogg MIJ, Rosen M. Reversal of narcotic depression in the neonate by naloxone. Br Med J 1976;2:1098–1100.
9. Wiener PC, Hogg MIJ, Rosen M. Effects of naloxone on pethidine-induced neonatal depression. II. Intramuscular naloxone. Br Med J 1977;2:229–31.
10. Wiener PC, Hogg MIJ, Rosen M. Effects of naloxone on pethidine-induced neonatal depression. I. Intravenous naloxone. Br Med J 1977;2:228–9.
11. Gerhardt T, Bancalari E, Cohen H, Rocha LF. Use of naloxone to reverse narcotic respiratory depression in the newborn infant. J Pediatr 1977;90:1009–12.
12. Bonta BW, Gagliardi JV, Williams V, Warshaw JB. Naloxone reversal of mild neurobehavioral depression in normal newborn infants after routine obstetric analgesia. J Pediatr 1979;94:102–5.
13. Welles B, Belfrage P, de Chateau P. Effects of naloxone on newborn infant behavior after maternal analgesia with pethidine during labor. Acta Obstet Gynecol Scand 1984;63:617–9.
14. Goodlin RC. Naloxone and its possible relationship to fetal endorphin levels and fetal distress. Am J Obstet Gynecol 1981;139:16–9.
15. Arduini D, Rizzo G, Dell'Acqua S, Mancuso S, Romanini C. Effect of naloxone on fetal behavior near term. Am J Obstet Gynecol 1987;156:474–8.