The Fluoroquinolone Toxicity Research Foundation

 
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Cipro Label Changes Research   See downloads for: Adobe Files



NDA 19-537/S-053, S-054
NDA 20-780/S-017, S-018
Bayer Corporation Pharmaceutical Division
Attention: Andrew S. Verderame
Director, Regulatory Affairs
400 Morgan Lane
West Haven, CT 06516-4175
Dear Mr. Verderame:
Please refer to your supplemental new drug applications, which were submitted under section
505(b) of the Federal Food, Drug, and Cosmetic Act for the following:
NDA # Drug Product Supplement
Number
Letter Date Receipt Date
S-053 April 7, 2004 April 9, 2004 19-537 Cipro  (ciprofloxacin
hydrochloride) Tablets, 100
mg, 250 mg, 500 mg, 750mg S-054 April 7, 2004 April 9, 2004
S-017 April 7, 2004 April 9, 2004 20-780 Cipro  (ciprofloxacin) Oral
Suspension, 5% and 10%
S-018 April 7, 2004 April 9, 2004
NDA 19-537/S-053 (tablets) and NDA 20-780/S-017 (oral solution) were submitted as Changes
Being Effected (CBE) and provide for additional safety information in the label. Revisions are
included in the PRECAUTIONS, Drug Interactions subsection of the package insert.
NDA 19-537/SLR-054 (tablets) and NDA 20-780/SLR-018 (oral solution) were submitted as
CBE and provide for the addition of quinolone class labeling in the WARNINGS section,
PRECAUTIONS, Information for Patients subsection and ADVERSE REACTIONS, Post-Marketing
Adverse Events subsection as was requested in the supplement request letter on
November 26, 2003 and the facsimile from the Division dated March 10, 2004.
These supplements provide for the following changes to the Cipro  Tablet and Oral Suspension
label. Deleted text is noted by strikethrough and added text is noted by double underline:
1. The following revisions were made under the WARNINGS section:
NDA 19-537/ S-053, S-054
NDA 20-780/S-017, S-018
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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, including ciprofloxacin.
Ciprofloxacin should be discontinued if the patient experiences symptoms of neuropathy
including pain, burning, tingling, numbness, and/or weakness, or is found to have deficits in
light touch, pain, temperature, position sense, vibratory sensation, and/or motor strength in
order to prevent the development of an irreversible condition.
Tendon Rupture: Effects: Ruptures of the shoulder, hand, and Achilles and other tendon
ruptures tendon or other tendons that required surgical repair or resulted in prolonged disability have
been reported in patients receiving quinolones, including ciprofloxacin. Post-marketing surveillance
reports indicate that the this risk may be increased in patients receiving concomitant corticosteroids,
especially in the elderly. Ciprofloxacin 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, including ciprofloxacin.
2. The following bullet was added to the PRECAUTIONS, Information for Patients
subsection:•
that peripheral neuropathies have been associated with ciprofloxacin use. If symptoms of
peripheral neuropathy including pain, burning, tingling, numbness and/or weakness
develop, they should discontinue treatment and contact their physicians.
3. The following revisions were made under the PRECAUTIONS, Drug Interactions
subsection:
Non-steroidal anti-inflammatory Animal studies have shown that the drugs (but not acetyl salicylic
acid) in combination of very high doses of quinolones have been shown to provoke convulsions in pre-clinical
studies.
4. The following revisions were made under the ADVERSE REACTIONS, Post-Marketing
Adverse Events subsection:
Post-Marketing Adverse Events: The following adverse events have been reported from worldwide
marketing experience with quinolones, including ciprofloxacin. Because these events are reported
voluntarily from a population of uncertain size, it is not always possible to reliably estimate their
frequency or establish a causal relationship to drug exposure. Decisions to include these events in
labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2)
frequency of the reporting, or (3) strength of causal connection to the drug.
Agitation, agranulocytosis, albuminuria, anaphylactic reactions, anosmia, candiduria,
cholesterol elevation (serum), confusion, constipation, delirium, dyspepsia, dysphagia,
erythema multiforme, exfoliative dermatitis, fixed eruption, flatulence, glucose elevation
(blood), hemolytic anemia, hepatic failure, hepatic necrosis, hyperesthesia, hypertonia,
hypesthesia, hypotension (postural), jaundice, marrow depression (life threatening),
methemoglobinemia, monoliasis moniliasis (oral, gastrointestinal, vaginal), myalgia,
NDA 19-537/ S-053, S-054
NDA 20-780/S-017, S-018
Page 3
myasthenia, myasthenia gravis (possible exacerbation), myoclonus, nystagmus, pancreatitis,
pancytopenia (life threatening or fatal outcome), peripheral neuropathy, phenytoin alteration
(serum), potassium elevation (serum), prothrombin time prolongation or decrease,
pseudomembranous colitis (The onset of pseudomembranous colitis symptoms may occur
during or after antimicrobial treatment.), psychosis (toxic), renal calculi, serum sickness like
reaction, Stevens-Johnson syndrome, taste loss, tendonitis, tendon rupture, torsades de pointes,
toxic epidermal necrolysis, triglyceride elevation (serum), twitching, vaginal candidiasis, and
vasculitis. (See PRECAUTIONS.)
We completed our review of these applications and they are 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 April 7, 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. 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 supplements NDA 19-537/S-053,
S-054 and NDA 20-780/S-017, S-018." Approval of these submissions by FDA is not required
before the labeling is used.
If you issue a letter communicating important information about these drug products (i.e., a
“Dear Health Care Professional” letter), we request that you submit a copy of the letter to each
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 the requirements for an approved NDA set forth
under 21 CFR 314.80 and 314.81.
NDA 19-537/ S-053, S-054
NDA 20-780/S-017, S-018
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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