The Fluoroquinolone Toxicity Research Foundation

 
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Factive Label Changes Research   See downloads for: Adobe Files



DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service
Food and Drug Administration
Rockville, MD 20857
NDA 21-158/S-003
Parexel International
Attention: Gail Glifort
Senior Regulatory Associate
2520 Meridian Parkway, Suite 200
Durham, NC 27713
Dear Ms. Glifort:
Please refer to your supplemental new drug application dated March 26, 2004, received March 30,
2004, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for FACTIVE ®
(gemifloxacin mesylate) Tablets, 320mg.
This “Changes Being Effected” (CBE) supplemental new drug application provides for the addition of
quinolone class labeling in WARNINGS and PRECAUTIONS, Information for Patients as was
requested in the supplement request letter dated November 26, 2003 and the facsimiles from the
Division dated March 10, 2004 and July 28, 2004.
We acknowledge receipt of your submissions dated August 17, 2004 and August 31, 2004.
This CBE supplemental new drug application provides for the following revisions to the package
insert:
1. WARNINGS
• The following paragraph was revised, unbolded and changed from capital letters to
lower case letters in the QT Effects subsection:
QT Effects: GEMIFLOXACIN Fluoroquinolones may prolong the QT interval in
some patients. Gemifloxacin should be avoided in patients with a history of
prolongation of the QTc interval, patients with uncorrected electrolyte disorders
(hypokalemia or hypomagnesemia), and patients receiving Class IA (e.g., quinidine,
procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic agents.
• The following subsection was added:
Peripheral Neuropathy: Rare cases of sensory or sensorimotor axonal polyneuropathy
affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias
and weakness have been reported in patients receiving quinolones.
NDA 21-158/S-003
Page 2
• The Tendon Effects subsection was revised to read:
Tendon and Cartilage Effects: Fluoroquinolones as a class have been shown to cause
arthropathy and osteochondrosis in immature rats and dogs. The relevance of these
findings to humans is unknown. Tendonitis and rupture of the shoulder, hand, and
Achilles tendons that required surgical repair or resulted in prolonged disability have
been reported in patients receiving fluoroquinolones. Gemifloxacin should be
discontinued if the patient experiences pain, inflammation, or rupture of a tendon.
Patients should rest and refrain from exercise until the diagnosis of tendonitis or tendon
rupture has been confidently excluded. Tendon rupture can occur either during or after
treatment. Elderly patients, athletes, and patients taking corticosteroids are more prone
to tendonitis.
Tendon Effects: Ruptures of the shoulder, hand, Achilles tendons or other tendons that
required surgical repair or resulted in prolonged disability have been reported in patients
receiving quinolones. Post-marketing surveillance reports indicate that this risk may be
increased in patients receiving concomitant corticosteroids, especially the elderly.
Gemifloxacin should be discontinued if the patient experiences pain, inflammation, or
rupture of a tendon. Patients should rest and refrain from exercise until the diagnosis of
tendonitis or tendon rupture has been excluded. Tendon rupture can occur during or
after therapy with quinolones.
2. PRECAUTIONS
• The Information for Patients subsection was revised to read:
Patients should be counseled:
• that FACTIVE may produce cause changes in the electrocardiogram (QTc
interval prolongation);
• that FACTIVE should be used with caution in patients receiving drugs that may
affect the QTc interval such as cisapride, erythromycin, antipsychotics, and
tricyclic antidepressants;
• to inform their physicians of any personal or family history of QTc prolongation
or proarrhythmic conditions such as recent hypokalemia, significant
bradycardia, or recent myocardial ischemia;
We completed our review of this application, as amended, and it is approved effective on the date of
this letter.
The final printed labeling (FPL) must be identical to the enclosed draft labeling (text for the package
insert submitted August 31, 2004).
The electronic labeling rule published December 11, 2003 (68 FR 69009) requires submission of
labeling content in electronic format effective June 8, 2004. For additional information, consult the
following guidances for industry regarding electronic submissions: Providing Regulatory Submissions
in Electronic Format - NDAs (January 1999) and Providing Regulatory Submissions in Electronic
Format – Content of Labeling (February 2004). The guidances specify that labeling is to be submitted
in pdf format. To assist in our review, we request that labeling also be submitted in MS Word format.
NDA 21-158/S-003
Page 3
If formatted copies of all labeling pieces (i.e., package insert, patient package insert, container labels,
and carton labels) are submitted electronically, labeling does not need to be submitted in paper.
For administrative purposes, these submissions should be designated "FPL for approved supplement
NDA 21-158/S-003." Approval of this submission by FDA is not required before the labeling is used.
If you issue a letter communicating important information about this drug product (i.e., a “Dear Health
Care Professional” letter), we request that you submit a copy of the letter to this NDA and a copy to
the following address:
MEDWATCH, HFD-410
FDA
5600 Fishers Lane
Rockville, MD 20857
We remind you that you must comply with reporting requirements for an approved NDA (21 CFR
314.80 and 314.81).
If you have any questions, call Robin Anderson, R.N., M.B.A., Labeling Reviewer at (301) 827-2127.
Sincerely,
{See appended electronic signature page}
Renata Albrecht, M.D.
Director
Division of Special Pathogen and Immunologic
Drug Products
Office of Drug Evaluation IV
Center for Drug Evaluation and Research