[Federal Register Volume 64, Number 3 (Wednesday, January 6, 1999)]
[Notices]
[Pages 884-886]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-156]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
[Docket No. 77N-0240; DESI 12836]


Dipyridamole; Drugs for Human Use; Drug Efficacy Study 
Implementation; Withdrawal of Approval of Abbreviated New Drug 
Applications

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is withdrawing 
conditional approval of abbreviated new drug applications (ANDA's) and 
pertinent parts of ANDA's for certain dipyridamole drug products. FDA 
is also declaring three unapproved dipyridamole drug products unlawful. 
FDA is withdrawing approval because there is a lack of substantial 
evidence that these drugs are effective for long-term therapy of 
chronic angina pectoris.

EFFECTIVE DATE: February 5, 1999.

ADDRESSES: Requests for opinion of the applicability of this notice to 
a specific product should be identified with Docket No. 77N-0240 and 
reference number DESI 12836 and directed to the Division of 
Prescription Drug Compliance and Surveillance (HFD-330), Center for 
Drug Evaluation and Research, Food and Drug Administration, 7500 
Standish Pl., Rockville, MD 20855.

FOR FURTHER INFORMATION CONTACT: Mary E. Catchings, Center for Drug 
Evaluation and Research (HFD-7), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-594-2041.

[[Page 885]]

SUPPLEMENTARY INFORMATION: In a notice published in the Federal 
Register of January 15, 1987 (52 FR 1663), FDA revoked the temporary 
exemption for the drug products described in this document that 
permitted these products to remain on the market beyond the time limits 
scheduled for implementation of the Drug Efficacy Study. The notice 
also offered an opportunity to request a hearing on a proposal to 
withdraw approval of the conditionally approved new drug applications 
for these products insofar as they provide for the indication, long-
term therapy of chronic angina pectoris. The proposal was based on the 
conclusion that the data submitted in support of this indication did 
not constitute substantial evidence of effectiveness as required by 
section 505(e) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 
355(e)) and 21 CFR 314.126. In a notice published in the Federal 
Register of February 23, 1987 (52 FR 5501), FDA amended the January 15, 
1987, notice by adding 16 conditionally approved applications.
    In response to the notices, applicants of the products described in 
this document requested a hearing. In 1995 and 1996, FDA requested the 
applicants to inform the agency in writing whether they were still 
interested in pursuing the hearing request and advised the applicants 
that the agency would consider a lack of response in 30 days to 
constitute withdrawal of the hearing request. Some of the applicants 
requested withdrawal of the hearing request, withdrawal of approval of 
the ANDA's, or both. The remaining applicants failed to respond to the 
agency's request, thereby consenting to withdrawal of the hearing 
request. Accordingly, FDA is now withdrawing the conditional approvals 
of the ANDA's and pertinent parts of other ANDA's that lack substantial 
evidence of effectiveness for the long-term therapy of chronic angina 
pectoris (chronic angina pectoris indication).
    The following 13 ANDA's have also been approved for the indication 
``as an adjunct to coumarin anticoagulants in the prevention of 
postoperative thromboembolic complications of cardiac valve 
replacements'' (cardiac valve indication). This notice withdraws 
approval of only those parts of the applications that provide for the 
chronic angina pectoris indication.
    1. ANDA 86-944; Dipyridamole Tablets containing 25 milligrams (mg) 
of the drug per tablet; Geneva Pharmaceuticals (formerly Cord 
Laboratories, Inc.), 2555 West Midway Blvd., Broomfield, CO 80020.
    2. ANDA 87-160; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Chelsea Laboratories, Inc., P.O. Box 15686, 8606 Roading 
Rd., Cincinnati, OH 45215.
    3. ANDA 87-184; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Barr Laboratories, Inc., 2 Quaker Rd., P.O. Box 2900, 
Pomona, NY 10970.
    4. ANDA 87-561; Dipyridamole Tablets containing 75 mg of the drug 
per tablet; Geneva Pharmaceuticals.
    5. ANDA 87-562; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Geneva Pharmaceuticals.
    6. ANDA 87-716; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Barr Laboratories, Inc.
    7. ANDA 87-717; Dipyridamole Tablets containing 75 mg of the drug 
per tablet; Barr Laboratories, Inc.
    8. ANDA 88-999; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Lederle Laboratories, 401 North Middleton Rd., Pearl River, 
NY 10965.
    9. ANDA 89-000; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Lederle Laboratories.
    10. ANDA 89-001; Dipyridamole Tablets containing 75 mg of the drug 
per tablet; Lederle Laboratories.
    11. ANDA 89-425; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Purepac Pharmaceutical Co., 200 Elmora Ave., Elizabeth, NJ 
07207.
    12. ANDA 89-426; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Purepac Pharmaceutical Co.
    13. ANDA 89-427; Dipyridamole Tablets containing 75 mg of the drug 
per tablet; Purepac Pharmaceutical Co.
    The following 26 ANDA's have not been approved for the cardiac 
valve indication, and the products lack substantial evidence of 
effectiveness for the angina indication. Therefore, this document 
withdraws approval of the entire application for the products.
    1. ANDA 86-908; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Eon Labs Manufacturing, Inc. (formerly held by Lemmon Co.), 
227-15 North Conduit Ave., Laurelton, NY 11413.
    2. ANDA 87-039; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Chelsea Laboratories, Inc.
    3. ANDA 87-492; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Barr Laboratories, Inc.
    4. ANDA 87-583; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Mylan Pharmaceuticals, Inc., P.O. Box 4293, Morgantown, WV 
26505.
    5. ANDA 87-676; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Mylan Pharmaceuticals, Inc.
    6. ANDA 87-754; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Superpharm Corp., 1769 Fifth Ave., Bayshore, NY 11706.
    7. ANDA 87-755; Dipyridamole Tablets containing 75 mg of the drug 
per tablet; Superpharm Corp.
    8. ANDA 87-873; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Rosemont Pharmaceutical Corp. (formerly Pharmaceutical 
Basics, Inc.), 301 South Cherokee St., Denver, CO 80223.
    9. ANDA 87-882; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Mylan Pharmaceuticals, Inc.
    10. ANDA 87-883; Dipyridamole Tablets containing 75 mg of the drug 
per tablet; Mylan Pharmaceuticals, Inc.
    11. ANDA 88-018; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Barr Laboratories, Inc.
    12. ANDA 88-019; Dipyridamole Tablets containing 75 mg of the drug 
per tablet; Barr Laboratories, Inc.
    13. ANDA 88-300; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Unit Dose Laboratories, P.O. Box 10319, Rockford, IL 61131.
    14. ANDA 88-301; Dipyridamole Tablets containing 75 mg of the drug 
per tablet; Unit Dose Laboratories.
    15. ANDA 88-413; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Superpharm.
    16. ANDA 88-442; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Duramed Pharmaceuticals, Inc., 5040 Lester Rd., Cincinnati, 
OH 45213.
    17. ANDA 88-443; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Duramed Pharmaceuticals, Inc.
    18. ANDA 88-444; Dipyridamole Tablets containing 75 mg of the drug 
per tablet; Duramed Pharmaceuticals, Inc.
    19. ANDA 88-822; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Rosemont Pharmaceutical Corp.
    20. ANDA 88-683; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Sidmak Laboratories, Inc., P.O. Box 371, East Hanover, NJ 
07936.
    21. ANDA 88-684; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Sidmak Laboratories, Inc.
    22. ANDA 88-685; Dipyridamole Tablets containing 75 mg of the drug 
per tablet; Sidmak Laboratories, Inc.
    23. ANDA 88-945; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Danbury Pharmacal.
    24. ANDA 89-378; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Mutual Pharmaceutical Co., Inc., 1100 Orthodox St., 
Philadelphia, PA 19124.
    25. ANDA 89-379; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Mutual Pharmaceutical Co., Inc.
    26. ANDA 89-380; Dipyridamole Tablets containing 75 mg of the drug 
per tablet; Mutual Pharmaceutical Co., Inc.

[[Page 886]]

    Warner Lambert Co. requested a hearing for the three unapproved 
drug products described as follows, but later withdrew the 
applications.
    1. ANDA 89-551; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Warner Lambert Co., 201 Tabor Rd., Morris Plains, NJ 07950.
    2. ANDA 89-552; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Warner Lambert Co.
    3. ANDA 89-553; Dipyridamole Tablets containing 75 mg of the drug 
per tablet; Warner Lambert Co.
    Approval of the following four conditionally approved ANDA's is 
being withdrawn because the applicants failed to request a hearing for 
the products. Failure to file an appearance and request a hearing 
constitutes a waiver of the opportunity for a hearing.
    1. ANDA 86-884; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Chelsea Laboratories, Inc.
    2. ANDA 87-719; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Geneva Pharmaceuticals.
    3. ANDA 87-830; Dipyridamole Tablets containing 75 mg of the drug 
per tablet; Boehringer-Ingelheim Pharmaceuticals, Inc., 90 East Ridge, 
Ridgefield, CT 06877.
    4. ANDA 87-831; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Boehringer-Ingelheim Pharmaceuticals, Inc.
    The effectiveness conclusions stated in the January 15, 1987, 
notice also applied to the 24 drug products described as follows. 
Although FDA withdrew approval of the products based on the written 
requests of the applicants who no longer market them, this notice 
constitutes FDA's final conclusions on the effectiveness of the 
products for the chronic angina pectoris indication.
    1. ANDA 87-008; Dipyridamole Tablets containing 25 mg of the tablet 
per drug; Zenith Laboratories Inc., 140 Legrand Ave., Northvale, NJ 
07647 (see 62 FR 64385, December 5, 1997).
    2. ANDA 87-094; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Par Pharmaceutical, Inc., One Ram Ridge Rd., Spring Valley, 
NY 10977 (see 57 FR 7934, March 5, 1992).
    3. ANDA 87-161; Dipyridamole Tablets containing 75 mg of the drug 
per tablet; Chelsea Laboratories, Inc. (see 59 FR 29298, June 6, l994).
    4. ANDA 87-316; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Zenith Laboratories, Inc. (see 62 FR 64385, December 5, 
1997).
    5. ANDA 87-320; Dipyridamole Tablets containing 75 mg of the drug 
per tablet; Zenith Laboratories, Inc. (see 62 FR 64385, December 5, 
1997).
    6. ANDA 87-360; Dipyridamole Tablets containing 75 mg of the drug 
per tablet; Par Pharmaceutical, Inc. (see 57 FR 7934, March 5, 1992).
    7. ANDA 87-419; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Danbury Pharmacal, 131 West St., Danbury, CT 06810 (see 63 
FR 64266, November 19, 1998).
    8. ANDA 87-432, Dipyridamole Tablets containing 75 mg of the drug 
per tablet; Danbury Pharmacal (see 63 FR 64266, November 19, 1998).
    9. ANDA 87-650; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Par Pharmaceutical, Inc. (see 57 FR 7934, March 5, 1992).
    10. ANDA 87-802; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Halsey Drug Co., Inc., 1827 Pacific St., Brooklyn, NY (see 
61 FR 5562, February 13, 1996).
    11. ANDA 87-803; Dipyridamole Tablets containing 75 mg of the drug 
per tablet; Halsey Drug Co. Inc. (see 61 FR 5562, February 13, 1996).
    12. ANDA 87-843; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Lederle Laboratories (see 55 FR 49427, November 28, 1990).
    13. ANDA 88-033; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Purepac Pharmaceutical Co. (see 56 FR 9956, March 8, 1991).
    14. ANDA 88-315; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Unit Dose Laboratories (see 56 FR 9956, March 8, 1991).
    15. ANDA 88-362; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Lederle Laboratories (see 55 FR 49427, November 28, 1990).
    16. ANDA 88-363; Dipyridamole Tablets containing 75 mg of the drug 
per tablet; Lederle Laboratories (see 55 FR 49427, November 28, 1990).
    17. ANDA 88-416; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Barr Laboratories, Inc. (see 61 FR 40649, August 5, 1996).
    18. ANDA 88-417; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Barr Laboratories, Inc. (see 61 FR 40649, August 5, 1996).
    19. ANDA 88-418; Dipyridamole Tablets containing 75 mg of the drug 
per tablet; Barr Laboratories, Inc. (see 61 FR 40649, August 5, 1996).
    20. ANDA 88-466; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Halsey Drug Co. (see 61 FR 5562, February 13, 1996).
    21. ANDA 88-800; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Danbury Pharmacal (see 63 FR 64266, November 19, 1998).
    22. ANDA 89-348; Dipyridamole Tablets containing 25 mg of the drug 
per tablet; Rosemont Pharmaceutical Corp. (see 57 FR 30741, July 10, 
1992).
    23. ANDA 89-349; Dipyridamole Tablets containing 50 mg of the drug 
per tablet; Rosemont Pharmaceutical Corp. (see 52 FR 30741, July 10, 
1992).
    24. ANDA 89-350; Dipyridamole Tablets containing 75 mg of the drug 
per tablet; Rosemont Pharmaceutical Corp. (see 52 FR 30741, July 10, 
1992).
    Any drug product that is identical, related, or similar to the drug 
products named above and is not the subject of an approved new drug 
application is covered by the applications listed above and is subject 
to this notice (21 CFR 310.6). Any person who wishes to determine 
whether a specific product is covered by this notice should write to 
the Division of Prescription Drug Compliance and Surveillance (address 
above).
    The Director of the Center for Drug Evaluation and Research, under 
the Federal Food, Drug, and Cosmetic Act (sec. 505 (21 U.S.C. 355)) and 
under authority delegated to her (21 CFR 5.82), finds that, on the 
basis of new information on the drugs and the evidence available when 
the applications were approved, there is a lack of substantial evidence 
that the products named above will have the effects they purport or are 
represented to have under the conditions of use prescribed, 
recommended, or suggested in their labeling for the indication of long-
term therapy of chronic angina pectoris.
    Therefore, based on the foregoing finding, approval of the 
applications listed above and all their amendments and supplements 
insofar as they pertain to the indication, long-term therapy of chronic 
angina pectoris, is withdrawn effective February 5, 1999. Shipment in 
interstate commerce of these products or of any identical, related, or 
similar product that is not the subject of a fully approved new drug 
application will then be unlawful.

    Dated: December 14, 1998.
Janet Woodcock,
Director, Center for Drug Evaluation and Research.
[FR Doc. 99-156 Filed 1-5-99; 8:45 am]
BILLING CODE 4160-01-F