MECLIZINE

Fetal Risk Summary

Meclizine is a piperazine antihistamine that is frequently used as an antiemetic (see also Buclizine and Cyclizine). The drug is teratogenic in animals, causing cleft palates in rats at 25–50 times the human dose, but apparently not in humans (1). Since late 1962, the question of meclizine's effect on the fetus has been argued in numerous citations, the bulk of which are case reports and letters (2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24, 25,26,27 and 28). Three studies involving large numbers of patients have concluded that meclizine is not a human teratogen (29,30 and 31).

The Collaborative Perinatal Project (CPP) monitored 50,282 mother-child pairs, 1,014 of which had exposure to meclizine in the 1st trimester (29, p. 328). For use anytime during pregnancy, 1,463 exposures were recorded (29, p. 437). In neither group was evidence found to suggest a relationship to large categories of major or minor malformations. Several possible associations with individual malformations were found, but their statistical significance is unknown (29, pp. 328, 437, 475). Independent confirmation is required to determine the actual risk.

Respiratory defects (7 cases) Eye and ear defects (7 cases) Inguinal hernia (18 cases) Hypoplasia cordis (3 cases) Hypoplastic left heart syndrome (3 cases) The CPP study indicated a possible relationship to ocular malformations, but the authors warned that the results must be interpreted with extreme caution (32). The FDA's Over-the-counter Laxative Panel, acting on the data from the CPP study, concluded that meclizine was not teratogenic (33). A second large prospective study covering 613 1st trimester exposures supported these negative findings (30). No harmful effects were found in the exposed offspring as compared with the total sample. Finally, in a 1971 report, significantly fewer infants with malformations were exposed to antiemetics in the 1st trimester as compared with controls (31). Meclizine was the third most commonly used antiemetic.

An association between exposure during the last 2 weeks of pregnancy to antihistamines in general and retrolental fibroplasia in premature infants has been reported. See Brompheniramine for details.

Breast Feeding Summary

No reports describing the use of meclizine during human lactation have been located. The molecular weight (about 464), however, is low enough that passage into milk should be anticipated. The potential effects of this exposure on a nursing infant are unknown. Some agents in this class (e.g., see Brompheniramine and Diphenhydramine) have been classified by their manufacturer's as contraindicated during nursing because of the increased sensitivity of newborn or premature infants to antihistamines.

References

1. Product information. Antivert. Pfizer, 2000.
2. Watson GI. Meclozine (“Ancoloxin”) and foetal abnormalities. Br Med J 1962;2:1446.
3. Smithells RW. “Ancoloxin” and foetal abnormalities. Br Med J 1962;2:1539.
4. Diggorg PLC, Tomkinson JS. Meclozine and foetal abnormalities. Lancet 1962;2:1222.
5. Carter MP, Wilson FW. “Ancoloxin” and foetal abnormalities. Br Med J 1962;2:1609.
6. Macleod M. “Ancoloxin” and foetal abnormalities. Br Med J 1962;2:1609.
7. Lask S. “Ancoloxin” and foetal abnormalities. Br Med J 1962;2:1609.
8. Leck IM. “Ancoloxin” and foetal abnormalities. Br Med J 1962;2:1610.
9. McBride WG. Drugs and foetal abnormalities. Br Med J 1962;2:1681.
10. Fagg CG. “Ancoloxin” and foetal abnormalities. Br Med J 1962;2:1681.
11. Barwell TE. “Ancoloxin” and foetal abnormalities. Br Med J 1962;2:1681–2.
12. Woodall J. “Ancoloxin” and foetal abnormalities. Br Med J 1962;2:1682.
13. McBride WG. Drugs and congenital abnormalities. Lancet 1962;2:1332.
14. Lenz W. Drugs and congenital abnormalities. Lancet 1962;2:1332–3.
15. David A, Goodspeed AH. “Ancoloxin” and foetal abnormalities. Br Med J 1963;1:121.
16. Gallagher C. “Ancoloxin” and foetal abnormalities. Br Med J 1963;1:121–2.
17. Watson GI. “Ancoloxin” and foetal abnormalities. Br Med J 1963;1:122.
18. Mellin GW, Katzenstein M. Meclozine and foetal abnormalities. Lancet 1963;1:222–3.
19. Salzmann KD. “Ancoloxin” and foetal abnormalities. Br Med J 1963;1:471.
20. Burry AF. Meclozine and foetal abnormalities. Br Med J 1963;1:1476.
21. Smithells RW, Chinn ER. Meclozine and foetal abnormalities. Br Med J 1963;1:1678.
22. O'Leary JL, O'Leary JA. Nonthalidomide ectromelia. Report of a case. Obstet Gynecol 1964;23:17–20.
23. Smithells RW, Chinn ER. Meclozine and foetal malformations: a prospective study. Br Med J 1964;1:217–8.
24. Pettersson F. Meclozine and congenital malformations. Lancet 1964;1:675.
25. Yerushalmy J, Milkovich L. Evaluation of the teratogenic effect of meclizine in man. Am J Obstet Gynecol 1965;93:553–62.
26. Sadusk JF Jr, Palmisano PA. Teratogenic effect of meclizine, cyclizine, and chlorcyclizine. JAMA 1965;194:987–9.
27. Lenz W. Malformations caused by drugs in pregnancy. Am J Dis Child 1966;112:99–106.
28. Lenz W. How can the teratogenic action of a factor be established in man? South Med J 1971;64(Suppl 1):41–7.
29. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977.
30. Milkovich L, Van den Berg BJ. An evaluation of the teratogenicity of certain antinauseant drugs. Am J Obstet Gynecol 1976;125:244–8.
31. Nelson MM, Forfar JO. Associations between drugs administered during pregnancy and congenital abnormalities of the fetus. Br Med J 1971;1:523–7.
32. Shapiro S, Kaufman DW, Rosenberg L, Slone D, Monson RR, Siskind V, Heinonen OP. Meclizine in pregnancy in relation to congenital malformations. Br Med J 1978;1:483.
33. Anonymous. Pink Sheets. Meclizine, cyclizine not teratogenic. FDC Rep 1974;2.