[Federal Register Volume 79, Number 34 (Thursday, February 20, 2014)]
[Notices]
[Pages 9744-9745]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-03596]



[[Page 9744]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2001-N-0274 (formerly 01N-0196)]


Phenylpropanolamine; Withdrawal of Approval of 13 New Drug 
Applications and 7 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 approval 
of 13 new drug applications (NDAs) and 7 abbreviated new drug 
applications (ANDAs) for products containing phenylpropanolamine. The 
basis for the withdrawals is that the products are no longer considered 
safe due to the association of phenylpropanolamine use with increased 
risk of hemorrhagic stroke. The holders of these NDAs and ANDAs have 
waived their opportunity for a hearing.

DATES: Effective February 20, 2014.

FOR FURTHER INFORMATION CONTACT: Emily Helms Williams, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6280, Silver Spring, MD 20993-0002, 301-
796-3381.

SUPPLEMENTARY INFORMATION: On November 3, 2000, the Director of FDA's 
Center for Drug Evaluation and Research (the Director) sent a letter to 
holders of NDAs and ANDAs for drug products containing 
phenylpropanolamine requesting that they voluntarily discontinue 
marketing any such products due to developments indicating an 
association between phenylpropanolamine use and increased risk of 
hemorrhagic stroke. Subsequently, in a notice published in the Federal 
Register on August 14, 2001 (66 FR 42665), the Director offered an 
opportunity for a hearing on a proposal to issue an order, under 
section 505(e) of the Federal Food, Drug, and Cosmetic Act (the FD&C 
Act) (21 U.S.C. 355(e)) and 21 CFR 314.150(a)(2), withdrawing approval 
of 13 NDAs and 8 ANDAs for products containing phenylpropanolamine. 
(Although the August 14, 2001, notice stated that FDA proposed to 
withdraw approval of 16 NDAs and 8 ANDAs, the notice listed only 13 
NDAs and 8 ANDAs.) The following products, all of which have been 
discontinued, were listed in the notice:

           Table 1--NDAs and ANDAs for Which FDA Has Proposed To Withdraw Approval of the Applications
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         Application No.                          Drug                                 Applicant
----------------------------------------------------------------------------------------------------------------
NDA 11-694.......................  Dimetane-DC Syrup................  A.H. Robins Co., P.O. Box 8299,
                                                                       Philadelphia, PA 19101.
NDA 12-152.......................  Ornade Extended-Release Tablet...  SmithKline-Beecham, 1250 South
                                                                       Collegeville Rd., P.O. Box 5089,
                                                                       Collegeville, PA 19426.
NDA 12-436.......................  Dimetapp Extended-Release Tablet.  Whitehall-Robins, 5 Giralda Farms,
                                                                       Madison, NJ 07940.
NDA 13-087.......................  Dimetapp Elixir..................  Do.
NDA 18-050.......................  Corsym Extended-Release            Medeva Americas, Inc., 755 Jefferson Rd.,
                                    Suspension.                        P.O. Box 1710, Rochester, NY 14603.
NDA 18-099.......................  Contac Extended-Release Capsule..  SmithKline Beecham Consumer Health, L.P.,
                                                                       1500 Littleton Rd., Parsippany, NJ 07054.
NDA 18-298.......................  Tavist-D Extended-Release Tablet.  Novartis Consumer Health, Inc., 560 Morris
                                                                       Ave., Summit, NJ 07901.
NDA 18-556.......................  Demazin Extended-Release Tablet..  Schering-Plough HealthCare Products, Three
                                                                       Oak Way, P.O. Box 603, Berkeley Heights,
                                                                       NJ 07922.
NDA 18-809.......................  Phenylpropanolamine Hydrochloride  Schwarz Pharma, 6140 West Executive Dr.,
                                    (HCl) Chlorpheniramine Maleate     Mequon, WI 53092.
                                    Extended-Release Capsule.
NDA 19-410.......................  Hycomine Syrup...................  Endo Pharmaceuticals, Inc., 500 Endo
                                                                       Blvd., Garden City, NY 11530.
NDA 19-411.......................  Hycomine Pediatric Syrup.........  Do.
NDA 19-613.......................  Contac Extended-Release Tablet...  Novartis Consumer Health, Inc.
NDA 20-640.......................  Tavist-D Extended-Release Tablet.  Do.
ANDA 71-099......................  Bromatapp Extended-Release Tablet  Teva Pharmaceuticals, USA, 1090 Horsham
                                                                       Rd., P.O. Box 1090, North Wales, PA
                                                                       19454.
ANDA 88-359......................  Drize Extended-Release Capsule...  B. F. Ascher & Co., Inc., 15501 West 109th
                                                                       St., Lenexa, KS 66219.
ANDA 88-681......................  Chlorpheniramine Maleate and       Chelsea Laboratories, 896 Orlando Ave.,
                                    Phenylpropanolamine HCl Extended-  West Hempstead, NY 11552.
                                    Release Capsule.
ANDA 88-687......................  Biphetap Elixir..................  Morton Grove Pharmaceuticals, Inc., 6451
                                                                       Main St., Morton Grove, IL 60053.
ANDA 88-688......................  Bromanate Elixir.................  Alpharma, U.S. Pharmaceuticals Division,
                                                                       333 Cassell Dr., suite 3500, Baltimore,
                                                                       MD 21224.
ANDA 88-723......................  Bromanate DC Syrup...............  Do.
ANDA 88-904......................  Myphetane DC Syrup...............  Morton Grove Pharmaceuticals, Inc.
ANDA 88-940......................  Chlorpheniramine Maleate and       Geneva Pharmaceuticals, Inc., 2555 West
                                    Phenylpropanolamine HCl Extended-  Midway Blvd., P.O. Box 446, Broomfield,
                                    Release Capsule.                   CO 80038.
----------------------------------------------------------------------------------------------------------------

    FDA issued the notice after an epidemiologic case-control study 
conducted by investigators at Yale University School of Medicine (Yale 
Hemorrhagic Stroke Project) demonstrated an association between 
phenylpropanolamine (an ingredient used in prescription and over-the-
counter (OTC) drug products as a nasal decongestant to relieve stuffy 
nose or nasal congestion and in OTC weight control drug products to 
control appetite) and increased risk of hemorrhagic stroke. The notice 
included FDA's belief that the data from the Yale Hemorrhagic Stroke 
Project, taken together with spontaneous reports of hemorrhagic stroke 
and reports in the published medical literature, provided evidence that 
nasal decongestant and weight control drug products containing 
phenylpropanolamine are no longer safe. The Director proposed to 
withdraw approval of the NDA and ANDA products containing 
phenylpropanolamine based on her conclusion that they were no longer

[[Page 9745]]

shown to be safe for use under the conditions that formed the basis 
upon which the applications were approved.
    In the August 14, 2001, notice, FDA provided the NDA and ANDA 
holders an opportunity to request a hearing to show why approval of the 
NDAs or ANDAs should not be withdrawn. One company, KV Pharmaceutical, 
requested a hearing by letter dated September 13, 2001, but that 
request was subsequently withdrawn by letter dated October 15, 2001. No 
other party requested a hearing on this matter following publication of 
the notice in the Federal Register. As stated above, all products 
listed in the notice were subsequently discontinued.
    Subsequent to the August 14, 2001, notice, one of the ANDAs listed 
in that notice was withdrawn. In a notice published in the Federal 
Register of February 20, 2002 (67 FR 7702), FDA withdrew approval of 
ANDA 71-099 for BROMATAPP Extended-Release Tablets after the 
application holder informed FDA that the product was no longer being 
marketed and requested withdrawal.
    In a letter to FDA dated February 25, 2013, Pfizer requested on 
behalf of its subsidiaries, Wyeth Pharmaceuticals, Inc. and A.H. 
Robins, that FDA withdraw approval of NDA 11-694 for DIMETANE-DC under 
Sec.  314.150(d), noting that the product has been discontinued and is 
no longer marketed. In that letter, Pfizer and its named subsidiaries 
waived any opportunity for a hearing provided under the August 14, 
2001, notice. In a response letter of March 28, 2013, the Agency 
acknowledged A.H. Robins' agreement to permit FDA to withdraw approval 
of DIMETANE-DC under Sec.  314.150(d) and to waive its opportunity for 
a hearing.
    For the reasons discussed in the August 14, 2001 notice, the 
Director, under section 505(e)(2) of the FD&C Act and under authority 
delegated to her by the Commissioner, finds that new evidence of 
clinical experience, not contained in the applications listed in table 
1 and not available at the time the applications were approved, shows 
that phenylpropanolamine is not shown to be safe for use under the 
conditions of use that formed the basis upon which the applications 
were approved (21 U.S.C. 355(e)(2)). Therefore, approval of the NDAs 
listed in table 1 is hereby withdrawn. Furthermore, the Director finds 
that the ANDAs listed in table 1 refer to the drugs that are the 
subject of the NDAs listed above. Therefore, as required under section 
505(j)(6) of the FD&C Act, approval of the ANDAs listed in table 1 is 
also withdrawn.
    Under 21 CFR 314.161 and 314.162(a)(1), FDA will remove the 
products containing phenylpropanolamine named in table 1 from the list 
of drug products with effective approvals published in FDA's ``Approved 
Drug Products With Therapeutic Equivalence Evaluations.'' FDA will not 
approve or accept ANDAs that refer to these drug products.

    Dated: February 14, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-03596 Filed 2-19-14; 8:45 am]
BILLING CODE 4160-01-P