CELIPROLOL

Fetal Risk Summary

Celiprolol is a third-generation, cardioselective b-adrenergic blocking agent used in the treatment of hypertension and angina. The drug is available in some foreign countries and is approved for the treatment of pregnancy-induced hypertension (1), but clinical studies in pregnant women have not been located. It is expected to be approved for use in the United States in the near future.

Reproductive studies in rats before conception, during organogenesis, and in the perinatal period up to a maximum dose of 320 mg/kg revealed no evidence of teratogenicity or adverse effects in the offspring (2,3 and 4). Similarly, no teratogenic effects were observed in a reproductive study with rats and rabbits (5).

A study using an in vitro perfusion system of human placental tissue demonstrated that celiprolol crossed to the fetal side of the preparation (6). Although the diffusion rate of the hydrophilic celiprolol was three to four times less than those of the lipid-soluble b-blockers labetalol, propranolol, and timolol, this degree of difference has not been observed in in vivo measurements (see Labetalol and Propranolol). A study published in 1993 measured the placental passage of celiprolol in four pregnant women with hypertension who were administered an oral 200-mg dose once daily (1). Fetal plasma concentrations were 25%–50% of maternal concentrations. No mention was made if any effects on the newborn were observed.

Some b-blockers may cause intrauterine growth retardation and reduced placental weight (e.g., see Atenolol and Propranolol). Treatment beginning early in the 2nd trimester results in the greatest weight reductions. This toxicity has not been consistently demonstrated in other agents within this class, but the relatively few pharmacologic differences among the drugs suggest that the reduction in fetal and placental weights probably occurs with all at some point. The lack of toxicity documentation may reflect the number and type of patients studied, the duration of therapy, or the dosage used, rather than a true difference among b-blockers. Although growth retardation is a serious concern, the benefits of maternal therapy with b-blockers may, in some cases, outweigh the risks to the fetus and must be judged on a case-by-case basis.

[*Risk Factor D if used in 2nd or 3rd trimesters.]

Breast Feeding Summary

Studies describing the measurement of celiprolol in milk have not been located. Because other b-blockers are excreted into milk, the appearance of celiprolol in milk should be expected. As a consequence, nursing infants of mothers consuming this agent should be closely monitored for bradycardia and other signs and symptoms of b-blockade.

References

1. Kofahl B, Henke D, Hettenbach A, Mutschler E. Studies on placental transfer of celiprolol. Eur J Clin Pharmacol 1993;44:381–2.
2. Nimomiya H, Akitsuki S, Kondo J, Nishikawa K, Yamashita Y, Watanabe M, Nagawawa H, Sumi N, Nomura A. Reproduction study of celiprolol: (1) fertility study in rats. Oyo Yakuri 1989;37:201–13. As cited in Shepard TH. Catalog of Teratogenic Agents. 7th ed. Baltimore, MD:Johns Hopkins University Press, 1992:77.
3. Nimomiya H, Akitsuki S, Kondo J, Nishikawa K, Yamashita Y, Watanabe M, Nagasawa H, Sumi N, Nomura A. Reproduction study of celiprolol: (2) teratogenicity study in rats. Oyo Yakuri 1989;37:215–29. As cited in Shepard TH. Catalog of Teratogenic Agents. 7th ed. Baltimore, MD:Johns Hopkins University Press, 1992:77.
4. Ninomiya H, Akitsui S, Kondo J, Nishikawa K, Watanabe M, Nagasawa H, Sumi N, Nomura A. Reproduction study of celiprolol: (3) peri- and postnatal study in rats. Oyo Yakuri 1989;37:231–42. As cited in Shepard TH. Catalog of Teratogenic Agents. 7th ed. Baltimore, MD:Johns Hopkins University Press, 1992:77.
5. Wendtlandt W, Pittner H. Toxicological evaluation of celiprolol, a cardioselective beta-adrenergic blocking agent. Arzneimittelforschung 1983;33:41–9. As cited in Schardein JL. Chemically Induced Birth Defects. 2nd ed. New York, NY:Marcel Dekker, 1993:89.
6. Schneider H, Proegler M. Placental transfer of b-adrenergic antagonists studied in an in vitro perfusion system of human placental tissue. Am J Obstet Gynecol 1988;159:42–7.