Table 45. Peri natal death rates* and peri natal deaths and severe congenital anomaly (SCA) rates combined according to gravida’s nausea and vomiting (N/V) status and the drugs prescribed for N/V within the first 84 days of pregnancy. *Fetal deaths at 20 weeks and neonatal deaths. 46. Summary of all submitted studies relevant to pregnancy. Table continued across two pages. Reference Details and relevant findings. Comments Collins, 1964 Review. Based on animal data, not recommended in early - pregnancy. No evidence of fetal damage - quoting Mellin et al.,1963 McBride, 1963 Reported an incidence of congenital abnormalities of 0.1% in 6,000 deliveries of women who had taken cyclizine, Part of from a total of 21,562 deliveries over 5years 1957-1962 nonclinical congenital heart disease, 5 submission cleft palate and/or hare-lip, 5 anencephaly, 1 myeloencephalocele, 2 hydrocephalus, 1 bilateral cataract, 1 McBride, 1969 Reported an incidence of cleft palate of 0.4% in 1,125 deliveries of women who had taken cyclizine in the first 3 Not in months from a total of 25,333 deliveries over 6 years nonclinical 1956-61 submission Incidence among mothers with nausea and vomiting who did not take cyclizine was 3.64% of 1,100 deliveries ( no significant difference) Incidence mothers who did not take cyclizine was 0.08% of 24,208 deliveries. (significantly different from those with N/V suggesting N/V was the cause) Mellin et al., 1963. Of 266 babies with malformations, no mothers had Letter cyclizine. Part of nonclinical submission Milkovich L and Human incidence. While the results contain no signal for Precautions van den Berg, 1976 cyclizine the study contained only 111 patients who had Not in taken cyclizine, and the standard error for the Severe nonclinical congenital anomaly rate at 5 years was comparatively submission high. Sadusk et al., 1965 Is in list of references for the sponsor’s Clinical Summary, - but paper is only in nonclinical dossier. The report of the Part of findings of a Food and Drug Administration (FDA) nonclinical committee that on the basis of lack of evidence submission
Table 45. Peri natal death rates* and peri natal deaths and severe congenital anomaly (SCA) rates combined according to gravida’s nausea and vomiting (N/V) status and the drugs prescribed for N/V within the first 84 days of pregnancy. *Fetal deaths at 20 weeks and neonatal deaths. 46. Summary of all submitted studies relevant to pregnancy. Table continued across two pages. Reference Details and relevant findings. Comments Collins, 1964 Review. Based on animal data, not recommended in early pregnancy. No evidence of fetal damage - quoting Mellin et al.,1963 - McBride, 1963 Reported an incidence of congenital abnormalities of 0.1% in 6,000 deliveries of women who had taken cyclizine, from a total of 21,562 deliveries over 5years 1957-1962 congenital heart disease, 5 cleft palate and/or hare-lip, 5 anencephaly, 1 myeloencephalocele, 2 hydrocephalus, 1 bilateral cataract, 1 Part of nonclinical submission McBride, 1969 Reported an incidence of cleft palate of 0.4% in 1,125 deliveries of women who had taken cyclizine in the first 3 months from a total of 25,333 deliveries over 6 years 1956-61 Incidence among mothers with nausea and vomiting who did not take cyclizine was 3.64% of 1,100 deliveries ( no significant difference) Incidence mothers who did not take cyclizine was 0.08% of 24,208 deliveries. (significantly different from those with N/V suggesting N/V was the cause) Not in nonclinical submission Mellin et al., 1963. Of 266 babies with malformations, no mothers had cyclizine. Letter Part of nonclinical submission Milkovich L and van den Berg, 1976 Human incidence. While the results contain no signal for cyclizine the study contained only 111 patients who had taken cyclizine, and the standard error for the Severe congenital anomaly rate at 5 years was comparatively high. Precautions Not in nonclinical submission Sadusk et al., 1965 Is in list of references for the sponsor’s Clinical Summary, but paper is only in nonclinical dossier. The report of the findings of a Food and Drug Administration (FDA) committee that on the basis of lack of evidence - Part of nonclinical submission
auspar-cyclizine-lactate-130115.docx