[Federal Register Volume 63, Number 242 (Thursday, December 17, 1998)]
[Notices]
[Pages 69631-69632]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-33455]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
[Docket No. 78N-0280; DESI Nos. 740, 1543, and 7661]


Estrogens for Postpartum Breast Engorgement; Withdrawal of 
Approval of the Labeled Indication for Postpartum Breast Engorgement in 
Estrogen-Containing Drug Products; Final Order

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is withdrawing approval 
of estrogen-containing drugs insofar as they are indicated for use in 
postpartum breast engorgement. The basis for the action is that 
estrogens are not shown to be safe for that use.

EFFECTIVE DATE: December 17, 1998.
FOR FURTHER INFORMATION CONTACT: David T. Read, Center for Drug 
Evaluation and Research (HFD-7), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-594-2041.

SUPPLEMENTARY INFORMATION: For many years, estrogen-containing drug 
products were used to suppress postpartum breast engorgement. By the 
1970's, however, the use of estrogens was shown to be associated with 
an increased risk of puerperal thromboembolism. Moreover, estrogen 
dosages for the suppression of postpartum breast engorgement were 
higher than for other labeled indications. The risk of thromboembolism 
was first evaluated by the FDA Obstetrics and Gynecology Advisory 
Committee, now called the Advisory Committee for Reproductive Health 
Drugs (the Committee), on July 15 and 16, 1976. At that time, the 
Committee recommended that estrogen drug products indicated for the 
suppression of postpartum breast engorgement contain an insert stating 
that the risk of thromboembolism should be considered in conjunction 
with the risk-free alternative of the use of breast binding and mild 
analgesics. On January 31, 1978, after additional risk evaluation, the 
Committee recommended that estrogen-containing drug products' 
indication for the suppression of postpartum breast engorgement be 
withdrawn.
    In a notice of opportunity for hearing (NOOH) published in the 
Federal Register of October 24, 1978 (43 FR 49564), the agency proposed 
to

[[Page 69632]]

withdraw approval of all new drug applications (NDA's) for estrogen-
containing drug products labeled for use in postpartum breast 
engorgement approved either before or after the Drug Amendments of 1962 
(Pub. L. 87-781). The NOOH also applied to any identical, similar, or 
related drug product whether or not it was the subject of an NDA. The 
NOOH listed the following NDA's:
    1. NDA 0-740; Di-Ovocylin Injection containing estradiol 
dipropionate; Ciba Pharmaceutical Co., Division Ciba Giegy Corp., 556 
Morris Ave., Summit, NJ 07901.
    2. NDA 4-039; Stilbestrol Ect. containing diethylstilbestrol; Eli 
Lilly & Co., Box 618, Indianapolis, IN 46206.
    3. NDA 4-041; Stilbestrol Tablets and Injection containing 
diethylstilbestrol; Eli Lilly & Co.
    4. NDA 4-056; Stilbestrol Tablets, Injection, and Suppositories 
containing diethylstilbestrol; E. R. Squibb & Sons, Inc., Box 4000, 
Princeton, NJ 08540.
    5. NDA 4-073; Stilbestrol Perles, Injection and Suppositories 
containing diethylstilbestrol; The Upjohn Co., 7171 Portage Rd., 
Kalamazoo, MI 49002.
    6. NDA 4-782; Premarin Tablets containing conjugated estrogens; 
Ayerst Laboratories, Division of American Home Products Corp., 685 
Third Ave., New York, NY 10017.
    7. NDA 4-823; Estrone Injection containing estrone; Abbott 
Laboratories, 14th and Sheridan Rd., North Chicago, IL 60064.
    8. NDA 5-159; Diethylstilbestrol Dipropionate Tablets containing 
diethylstilbestrol dipropionate; Blueline Laboratories, Inc., 302 South 
Broadway, St. Louis, MO 63102.
    9. NDA 5-233; Diethylstilbestrol Tablets containing 
diethylstilbestrol; High Chemical Co., 1760 North Howard St., 
Philadelphia, PA 19122.
    10. NDA 5-292; Estinyl Tablets containing ethinyl estradiol; 
Schering Corp., Galloping Hill Rd., Kenilworth, NJ 07033.
    11. NDA 7-661; AE Tablets and Tylosterone Tablets containing 
diethylstilbestrol and methyltestosterone; Eli Lilly & Co.
    12. NDA 8-099; Tylosterone Injection containing diethylstilbestrol 
and methyltestosterone; Eli Lilly & Co.
    13. NDA 8-102; Tace Tablets and Capsules containing 
chlorotrianisene; Merrell-National Laboratories, Division of 
Richardson-Merrell Inc., 110 East Amity Rd., Cincinnati, OH 45215.
    14. NDA 8-579; Vallestril Tablets containing methallenestril; 
Searle Laboratories, Division of G. D. Searle & Co., Box 5100, Chicago, 
IL 60680.
    15. NDA 9-402; Delestrogen Injection, Delestrogen 4X Injection, and 
Delestrogen 2X Injection containing estradiol valerate; E. R. Squibb & 
Sons, Inc.
    16. NDA 9-545; Deladumone Injection containing testosterone 
enanthate and estradiol valerate; E. R. Squibb & Sons, Inc.
    17. NDA 10-597; Tace-Androgen Capsules containing chlorotrianisene 
and methyltestosterone; Merrell-National Laboratories.
    18. NDA 11-444; Tace Capsules containing chlorotrianisene and Tace 
with Ergonovine Capsules containing chlorotrianisene and ergonovine 
maleate; Merrell-National Laboratories.
    19. NDA 16-235; Tace 72-Milligram Capsule containing 
chlorotrianisene; Merrell-National Laboratories.
    20. NDA 16-768; Estrovis Tablets containing quinestrol; Warner 
Chilcott Laboratories, Division Warner Lambert Co., 201 Tabor Rd., Box 
W, Morris Plains, NJ 07950.
    In response to the NOOH, Merrell-National Laboratories, Parke-
Davis, E. R. Squibb & Sons, Inc., Byk-Gulden, Inc., and the American 
College of Obstetricians and Gynecologists (the College) requested 
hearings, but the firms voluntarily agreed to remove the indication 
from their labeling. Since then, the College and the firms, or their 
respective successors in interest, have withdrawn their hearing 
requests. (The approvals of NDA 7-661, NDA 8-099, and NDA 9-545 were 
withdrawn in a Federal Register notice of October 29, 1998 (63 FR 
58053); the approval of NDA 10-597 was withdrawn in a Federal Register 
notice of June 25, 1993 (58 FR 34466); the approval of NDA 16-768 was 
withdrawn in a Federal Register notice of March 27, 1996 (61 FR 
13506).)
    Therefore, for reasons stated in the NOOH of October 24, 1978, as 
well as the reasons discussed above, the Director of the Center for 
Drug Evaluation and Research hereby withdraws approval of any estrogen-
containing drug product insofar as it is labeled for the suppression of 
postpartum breast engorgement. (In the Federal Register of January 17, 
1995 (60 FR 3404), FDA withdrew approval of bromocriptine mesylate for 
the indication of the prevention of physiological lactation, i.e., 
postpartum breast engorgement; today's action means, therefore, that no 
product is currently approved for this indication.) This notice is 
issued under authority delegated to the Commissioner of Food and Drugs 
(21 CFR 5.10(a)(1)) and redelegated to the Director of the Center for 
Drug Evaluation and Research (21 CFR 5.82).

    Dated: November 30, 1998.
Janet Woodcock,
Director, Center for Drug Evaluation and Research.
[FR Doc. 98-33455 Filed 12-16-98; 8:45 am]
BILLING CODE 4160-01-F