[Federal Register Volume 73, Number 175 (Tuesday, September 9, 2008)]
[Notices]
[Pages 52357-52358]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-20938]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket Nos. FDA-2006-P-0081 (formerly Docket No. 2006P-0178) and FDA-
2005-P-0369 (formerly Docket No. 2005P-0023)]
Determination That TEQUIN (Gatifloxacin) Was Withdrawn From Sale
for Reasons of Safety or Effectiveness
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) has determined that
TEQUIN (gatifloxacin) Tablets, Injection, and Oral Suspension, were
withdrawn from sale for reasons of safety or effectiveness. This
determination means that FDA will not accept or approve abbreviated new
drug applications (ANDAs) for gatifloxacin oral tablets, injection, or
oral suspension that refer to any previously approved dosage forms and
strengths of TEQUIN (gatifloxacin).
FOR FURTHER INFORMATION CONTACT: Elena Cohen, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, rm. 6228, Silver Spring, MD 20993-0002, 301-
796-3602.
SUPPLEMENTARY INFORMATION: In 1984, Congress enacted the Drug Price
Competition and Patent Term Restoration Act of 1984 (Public Law 98-417)
(the 1984 amendments), which authorized the approval of duplicate
versions of drug products under an ANDA procedure. ANDA applicants
must, with certain exceptions, show that the drug for which they are
seeking approval contains the same active ingredient in the same
strength and dosage form as the ``listed drug,'' which is a version of
the drug that was previously approved under a new drug application
(NDA). ANDA applicants do not have to repeat the extensive clinical
testing otherwise necessary to gain approval of an NDA. The only
clinical data required in an ANDA are data to show that the drug that
is the subject of the ANDA is bioequivalent to the listed drug.
The 1984 amendments include what is now section 505(j)(7) of the
Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 355(j)(7)),
which requires FDA to publish a list of all approved drugs. FDA
publishes this list as part of the ``Approved Drug Products With
Therapeutic Equivalence Evaluations,'' which is generally known as the
``Orange Book.'' Drugs are removed from the list if the agency
withdraws or suspends approval of the drug's NDA or ANDA for reasons of
safety or effectiveness, or if FDA determines that the listed drug was
withdrawn from sale for reasons of safety or effectiveness (section
505(j)(7)(C) of the act; Sec. 314.162 (21 CFR 314.162)).
FDA will not approve an ANDA if the listed drug has been withdrawn
from sale for safety or effectiveness reasons (section 505(j)(4)(I) of
the act). Under Sec. 314.161(a)(1) (21 CFR 314.161(a)(1)), the agency
must determine whether a listed drug was withdrawn from sale for
reasons of safety or effectiveness before an ANDA that refers to that
listed drug may be approved. A drug that has been withdrawn from the
market for safety or effectiveness reasons is not a listed drug (21 CFR
314.3(b)). FDA may not approve an ANDA that does not refer to a listed
drug. FDA currently has pending one or more ANDAs that refer to TEQUIN
(gatifloxacin).
Bristol-Myers Squibb Co. (BMS) is the holder of three NDAs\1\ for
TEQUIN tablets, injection, and oral suspension as listed in the
following table:
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\1\ On December 17, 1999, FDA approved NDAs 21-061 and 21-062
for community-acquired pneumonia, acute bacterial exacerbation of
chronic bronchitis, acute bacterial sinusitis, uncomplicated urinary
tract infections, complicated urinary tract infections,
pyelonephritis, and uncomplicated gonorrhea. The December 17, 1999,
approval letter also stated that indications for uncomplicated skin
and skin structure infections were approvable pending the submission
of certain postmarketing data. For administrative purposes, the
agency assigned administrative NDAs 21-404 (TEQUIN Tablets) and 21-
405 (TEQUIN Injections) for the treatment of uncomplicated skin and
skin structure infections. BMS provided a complete response, and
upon approval on October 17, 2002, NDAs 21-404 and 21-405 were
retired by FDA. The approvals and all other submissions for the
treatment of uncomplicated skin and skin structure infections were
incorporated in the original NDAs, 21-061 and 21-062. NDAs 21-404
and 21-405 are not listed in the Orange Book, but can be found
through a search at Drugs@FDA.
Table 1.--Approved TEQUIN Products
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Active Dosage Form/
NDA No. Ingredients Strength Route
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21-061 Gatifloxacin 200 milligrams (mg) Tablet; oral
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21-061 Gatifloxacin 400 mg Tablet; oral
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21-062 Gatifloxacin Equivalent to 10 mg/ Injectable;
milliliter (mL) (200 injection
mg)
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21-062 Gatifloxacin 400 mg/40 mL (10 mg/ Injectable;
mL) injection
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21-062 Gatifloxacin in 200 mg/100 mL (2 mg/ Injectable;
dextrose 5% in mL) injection
plastic
container
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21-062 Gatifloxacin in 400 mg/200mL (2 mg/ Injectable;
dextrose 5% in mL) injection
plastic
container
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21-678 Gatifloxacin 200 mg/5 mL Suspension; oral
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TEQUIN is an antibacterial drug indicated for the treatment of
infections due to susceptible strains of designated microorganisms in
the following conditions: Acute bacterial exacerbation of chronic
bronchitis; acute sinusitis;
[[Page 52358]]
community-acquired pneumonia; uncomplicated skin and skin structure
infections; uncomplicated and complicated urinary tract infections;
pyelonephritis; uncomplicated urethral and cervical gonorrhea; and
acute, uncomplicated rectal infections in women.
In January 2003, FDA received revised product labeling relating to
several approved supplements for TEQUIN (gatifloxacin). This revised
labeling deleted references to TEQUIN injection, 10 milligrams/
milliliter (mg/mL) (200 mg), indicating that this product was no longer
being marketed; therefore, the product was moved from the prescription
drug product list to the ``Discontinued Drug Product List'' section of
the Orange Book. In response to a citizen petition from Apotex Corp.
(Docket No. FDA-2005-P-0369),\2\ FDA stated, in the Federal Register of
February 3, 2006 (71 FR 5858), that TEQUIN injection, 10 mg/mL (200
mg), was not withdrawn for reasons of safety and effectiveness.
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\2\ This citizen petition was originally assigned docket number
2005P-0023/CP1. The number was changed to FDA-2005-P-0369 as a
result of FDA's transition to its new docketing system
(Regulations.gov) in January 2008.
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On May 1, 2006, Public Citizen Research Group submitted a citizen
petition (Docket No. FDA-2006-P-0081),\3\ under 21 CFR 10.30,
requesting that FDA immediately ban TEQUIN because of the increased
risk of dysglycemia (hypoglycemia, low blood sugar, and hyperglycemia,
high blood sugar) in humans. Public Citizen states that it reached its
conclusion based on: (1) The relatively high numbers and rates of
gatifloxacin-associated dysglycemia adverse event reports calculated
from data collected by FDA's Adverse Event Reporting System (AERS) and
Health Canada's Adverse Drug Reaction Monitoring Program; (2) a study
by Park-Wyllie et al., published in March 2006 in the New England
Journal of Medicine, that showed that patients (diabetic and
nondiabetic) receiving gatifloxacin had approximately 17 times the odds
of having a hyperglycemic episode and 4 times the odds of having a
hypoglycemic episode compared to those taking macrolide antibiotics;
and (3) the relatively high numbers and rates of gatifloxacin-
associated dysglycemic events in the manufacturer's safety studies in
uninfected patients and other studies in infected patients, including
clinical trials, cohort studies, case-control studies, postmarketing
surveillance studies, and case reports.
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\3\ This citizen petition was originally assigned docket number
2006P-0178. The number was changed to FDA-2006-P-0081 as a result of
FDA's transition to its new docketing system (Regulations.gov) in
January 2008.
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In June 2006, BMS announced that it would no longer market TEQUIN.
In light of pending ANDAs and the citizen petition, FDA examined
whether all TEQUIN products, including TEQUIN (gatifloxacin) injection,
10 mg/mL (200 mg), were withdrawn from the market for reasons of safety
or effectiveness. After considering the citizen petition and reviewing
agency records concerning the drug product, analyses of AERS reports,
and relevant literature, FDA has determined under Sec. 314.161 that
TEQUIN was withdrawn from sale for reasons of safety or effectiveness.
Accordingly, the agency will remove all TEQUIN products from the Orange
Book (Sec. 314.162). FDA will not accept or approve ANDAs that refer
to these drug products.
Therefore, the agency has determined, under Sec. 314.161, that all
dosage forms and strengths of TEQUIN (gatifloxacin) listed in the table
of this document were withdrawn from sale for reasons of safety. TEQUIN
(gatifloxacin) will be removed from the list of drug products published
in the Orange Book. FDA will not accept or approve ANDAs that refer to
any dosage form or strength of TEQUIN (gatifloxacin).
Dated: September 2, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-20938 Filed 9-8-08; 8:45 am]
BILLING CODE 4160-01-S