[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]]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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
----------------------------------------------------------------------------------------------------------------
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