METAPROTERENOL

Fetal Risk Summary

Metaproterenol, a selective b2-adrenergic agonist, is used as a bronchodilator for bronchial asthma and for reversible bronchospasm occurring in bronchitis and emphysema.

Reproduction studies in mice, rats, and rabbits have been conducted (1). No embryotoxic or fetotoxic effects, or teratogenicity was observed in rats at 40 mg/kg (approximately 25 times the maximum recommended human oral dose [MRHOD]), but embryo toxicity was observed in mice at 31 times the MRHOD. In rabbits, oral doses 620 times the human inhalation dose and 62 times the MRHOD caused both embryotoxic and teratogenic (skeletal anomalies, hydrocephalus, and skull bone separation) effects.

No published reports linking the use of metaproterenol with congenital defects have been located. In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 361 newborns had been exposed to metaproterenol during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of 17 (4.7%) major birth defects were observed (15 expected). Specific data were available for six defect categories, including (observed/expected) 3/4 cardiovascular defects, 1/1 oral clefts, 0/0 spina bifida, 1/1 limb reduction defects, 0/1 hypospadias, and 3/1 polydactyly. Only with the latter defect is there a suggestion of a possible association, but other factors, including the mother's disease, concurrent drug use, and chance, may be involved.

Metaproterenol, has been used to prevent premature labor (2,3 and 4). Its use for this purpose has been largely assumed by ritodrine, albuterol, or terbutaline. Like all b-mimetics, metaproterenol causes maternal and, to a lesser degree, fetal tachycardia. Maternal hypotension and hyperglycemia and neonatal hypoglycemia should be expected (see also Ritodrine, Albuterol, and Terbutaline). Long-term evaluation of infants exposed in utero to b-mimetics has been reported, but not specifically for metaproterenol (5). No harmful effects in the infants were observed.

In summary, selective b2-agonists, including metaproterenol, are commonly used during gestation for the treatment of asthma (6). Fetal tachycardia may occur, but because there is no evidence of fetal injury, there is no contraindication to their use in pregnancy (6).

Breast Feeding Summary

No reports describing the use of metaproterenol during lactation have been located. However, agents in this class, including metaproterenol, are commonly used in the treatment of asthma and there is no contraindication to their use during breast feeding (6). Neonatal tachycardia, hypoglycemia, or tremor are potential adverse effects (6).

References

1. Product information. Alupent. Boehringer Ingelheim, 2000.
2. Baillie P, Meehan FP, Tyack AJ. Treatment of premature labour with orciprenaline. Br Med J 1970;4:154–5.
3. Tyack AJ, Baillie P, Meehan FP. In-vivo response of the human uterus to orciprenaline in early labour. Br Med J 1971;2:741–3.
4. Zilianti M, Aller J. Action of orciprenaline on uterine contractility during labor, maternal cardiovascular system, fetal heart rate, and acid-base balance. Am J Obstet Gynecol 1971;109:1073–9.
5. Freysz H, Willard D, Lehr A, Messer J, Boog G. A long term evaluation of infants who received a b-mimetic drug while in utero. J Perinat Med 1977;5:94–9.
6. Report of the Working Group on Asthma and Pregnancy. Management of Asthma During Pregnancy. U.S. Department of Health and Human Services, NIH Publication No. 93-3279, September 1993:19.