The FDA has added warnings regarding Peripheral Neuropathy, which results in irreversible damage to the nerves to the following fluoroquinolones:

Avelox

Cipro

Factive

Floxin

Levaquin

Tequin

Maxaquin

Nalidixic Acid

Noroxin

Click on the drug name to view the warning letters sent by the FDA.  A reliable source has indicated that the FDA plans on adding the following warning to ALL the drugs within this class;

New Peripheral Neuropathy Warnings added to Quinolones:

"PERIPHERAL NEUROPATHY: Rare cases of sensory or sensor motor axonal polyneuropathy affecting small and or large axons resulting in paresthesias, hypoaesthesias, dysesthesias, and weakness have been reported in patients taking quinolones including (DRUG NAME INSERTED). ( DRUG NAME INSERTED) 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."
 

Click here to read the Fluoroquinolone Toxicity Research Foundation Director's commentary regarding these new label changes.

The following has been "cut and pasted" in part from the FDA website after a diligent search regarding the label changes. It is quite possible that since this search was done that additional letters regarding these changes had been sent and this information may no longer be accurate or up to date.  The following information is for discussion purposes only and is not to be considered a complete and accurate representation of the FDA's recent actions.  Viewers are encouraged to log unto this FDA site:

U.S. Food and Drug Administration Center for Drug Evaluation and Research

 to view the entire FDA labels and letters regarding the recent label changes in order to obtain the most up to date and accurate information.

Label changes mandated by the FDA for all the quinolones and fluoroquinolones September 2004
 

Changes for Avelox (Moxifloxacin):

NDA 021334 Approval Date 4/27/2001 Bayer Pharm
NDA 021085 Approval Date 12/10/99 Bayer Pharm
NDA 021277 Approval Date 12/10/99 Bayer Pharm
AVELOX MOXIFLOXACIN Tablet and IV
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.

Tendon Effects: Ruptures of the shoulder, hand, 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 with quinolones, including moxifloxacin. Post-marketing
surveillance reports indicate that the this risk may be increased in patients receiving concomitant
corticosteroids, especially in the elderly. Moxifloxacin 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 moxifloxacin.


NDA 021598 Approval Date 4/15/2003 Licensed from Bayer AG to Alcon, Inc.
VIGAMOX MOXIFLOXACIN HYDROCHLORIDE (SOLUTION/DROPS; OPHTHALMIC
EYE DROPS)
NO WARNINGS regarding tendon or peripheral neuropathy found within the package insert dated 2003
 

Label Changes for Cipro (Ciprofloxacin)

NDA 019992 Approved 12/31/90 Alcon, Inc. c/o Alcon Research, Ltd.
CILOXAN CIPROFLOXACIN (Ointment and OPHTHALMIC EYE DROPS)
NO WARNINGS regarding tendon or peripheral neuropathy found within the package insert dated January 2003

NDA 020369 Approved 3/30/98 S.A. ALCON-COUVREUR N.V. Puurs, Belgium
CILOXAN CIPROFLOXACIN (Ointment and OPHTHALMIC EYE DROPS)
NO WARNINGS regarding tendon or peripheral neuropathy found within the package insert dated January 2003

NDA 019537 Approved 10/22/1987 Bayer
CIPROFLOXACIN EQ Base
NDA 020780 Approved 9/26/1997 Bayer
CIPROFLOXACIN FOR SUSPENSION; ORAL

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.


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, 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.)

NDA 019847 Approved 12/26/1990 Bayer Pharm
CIPROFLOXACIN IV 1% Solution
NDA 019857 Approved 12/26/1990 Bayer Pharm
CIPROFLOXACIN DEXTROSE 5% IN PLASTIC CONTAINER

Changes for NDA 19-847/S-031 (IV 1%) and NDA 19-857/S-036 (IV 0.2%)
1. The following text was added to the last two paragraphs of the WARNINGS section:
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 was added to the fifth bullet in 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.



NDA 019858 Approved 12/26/1990 Bayer Pharm
CIPRO IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER CIPROFLOXACIN Discontinued

NDA 021473 Approved 12/13/2002 Bayer Pharm
CIPRO XR CIPROFLOXACIN; CIPROFLOXACIN HYDROCHLORIDE
Changes for NDA 21-473/S-007
1. The following revisions were made in the PRECAUTIONS section:
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.

Achilles and other tendon ruptures
Tendon Effects: Ruptures of the shoulder, hand, Achilles 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 this risk may be increased in patients receiving with ciprofloxacin and other quinolones. concomitant corticosteroids, especially 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.

1. The following was added as a bullet in the PRECAUTIONS section, 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.
2. Torsade de pointes was added to the ADVERSE REACTIONS subsection.

NDA 021554 Approved 08/28/2003 Bayer Pharm
CIPRO XR CIPROFLOXACIN; CIPROFLOXACIN HYDROCHLORIDE
No warnings regarding Peripheral Neuropathy found within the package insert dated 8/2003
Only the MINIMAL WARNINGS regarding tendon issues was found:
“Achilles and other tendon ruptures that required surgical repair or resulted in prolonged disability have been reported with ciprofloxacin and other quinolones. Ciprofloxacin should be discontinued if the patient experiences pain, inflammation, or rupture of a tendon.”

NDA 020805 Approved 2/10/1998 Alcon
CIPRO HC CIPROFLOXACIN HYDROCHLORIDE; HYDROCORTISONE
NO WARNINGS regarding tendon or peripheral neuropathy found within the package insert.

NDA021537 Approved 7/18/2003 Alcon Research, Ltd.
CIPRODEX CIPROFLOXACIN; DEXAMETHASONE (SUSPENSION/DROPS; OTIC
OINTMENT)
NO LABEL INFORMATION AVAILABLE
 

Cipro Generic Equivalents:

Drug Name and
FDA Application
Number Dosage Form/Route Strength Marketing Status Company
CIPROFLOXACIN
(ANDA # 076484) Injectable; Injection 10MG/ML None (Tentative Approval) AM PHARM PARTNERS
CIPROFLOXACIN
(ANDA # 074124) TABLET; ORAL Multiple Strengths Prescription BARR
CIPROFLOXACIN
(ANDA # 076754) SOLUTION/DROPS; OPHTHALMIC EQ 0.3% BASE Prescription BAUSCH AND LOMB
CIPROFLOXACIN
(ANDA # 076992) INJECTABLE; INJECTION 10MG/ML None (Tentative Approval) BEDFORD LABS
CIPROFLOXACIN
(ANDA # 076126) TABLET; ORAL Multiple Strengths Prescription CARLSBAD
CIPROFLOXACIN
(ANDA # 076794) TABLET; ORAL 100MG None (Tentative Approval) COBALT
CIPROFLOXACIN
(ANDA # 076794) TABLET; ORAL Multiple Strengths Prescription COBALT
CIPROFLOXACIN
(ANDA # 075593) TABLET; ORAL Multiple Strengths Prescription DR REDDYS LABS LTD
CIPROFLOXACIN
(ANDA # 076593) Tablet; Oral 100MG None (Tentative Approval) EON
CIPROFLOXACIN
(ANDA # 076593) TABLET; ORAL Multiple Strengths Prescription EON
CIPROFLOXACIN
(ANDA # 075817) Tablet; Oral 100MG None (Tentative Approval) GENPHARM
CIPROFLOXACIN
(ANDA # 075817) TABLET; ORAL Multiple Strengths Prescription GENPHARM
CIPROFLOXACIN
(ANDA # 076558) TABLET; ORAL 250MG Prescription HIKMA
CIPROFLOXACIN
(ANDA # 076558) TABLET; ORAL Multiple Strengths Prescription HIKMA
CIPROFLOXACIN
(ANDA # 076089) TABLET; ORAL 100MG None (Tentative Approval) IVAX PHARMS
CIPROFLOXACIN
(ANDA # 076089) TABLET; ORAL Multiple Strengths Prescription IVAX PHARMS
CIPROFLOXACIN
(ANDA # 076138) TABLET; ORAL Multiple Strengths Prescription MARTEC
CIPROFLOXACIN
(ANDA # 075685) TABLET; ORAL Multiple Strengths Prescription MYLAN
CIPROFLOXACIN
(ANDA # 075928) SOLUTION/DROPS; OPHTHALMIC EQ 0.3% BASE Prescription NOVEX
CIPROFLOXACIN
(ANDA # 074876) Tablet; Oral 250MG None (Tentative Approval) NOVOPHARM LIMITED
CIPROFLOXACIN
(ANDA # 075747) TABLET; ORAL Multiple Strengths Prescription RANBAXY
CIPROFLOXACIN
(ANDA # 075939) TABLET; ORAL 100MG None (Tentative Approval) SANDOZ
CIPROFLOXACIN
(ANDA # 075939) TABLET; ORAL Multiple Strengths Prescription SANDOZ
CIPROFLOXACIN
(ANDA # 076912) TABLET; ORAL Multiple Strengths Prescription TARO
CIPROFLOXACIN
(ANDA # 076912) TABLET; ORAL 100MG None (Tentative Approval) TARO
CIPROFLOXACIN
(ANDA # 076136) TABLET; ORAL Multiple Strengths Prescription TEVA
CIPROFLOXACIN
(ANDA # 076639) TABLET; ORAL Multiple Strengths Prescription UNIQUE PHARM LABS
 

Label Changes for Clinafloxacin: NO INFORMATION FOUND ON THE FDA WEBSITE
 

Label Changes for Enofloxacin: NO INFORMATION FOUND ON THE FDA WEBSITE
 

Label Changes for Enrofloxacin NO INFORMATION FOUND ON THE FDA WEBSITE
 

Label Changes for Fleroxacin NO INFORMATION FOUND ON THE FDA WEBSITE
 

Label Changes for Factive (Gemifloxacin)

NDA 021158 Approved 4/4/2003 Oscient
FACTIVE GEMIFLOXACIN MESYLATE
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.
• 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;

 

Label Changes for Floxin (Ofloxacin)

FLOXIN OFLOXACIN
3. WARNINGS
• A Peripheral neuropathy subsection was added to read:
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 ofloxacin. Ofloxacin
should be discontinued if the patient experiences symptoms of neuropathy including pain,
burning, tingling, numbness, and/or weakness or other alterations of sensation including light
touch, pain, temperature, position sense, and vibratory sensation in order to prevent the
development of an irreversible condition.
NDA 19-735/S-052, S-053
Page 2
• The Tendon effects subsection was revised to read:
Tendon effects: Ruptures of the shoulder, hand, and Achilles tendon or other tendons that
required surgical repair or resulted in prolonged disability have been reported in patients
receiving quinolones, including ofloxacin. Post-marketing surveillance reports indicate that the
risk may be increased in patients receiving corticosteroids, with ofloxacin and other quinolones
especially the elderly. (see PRECAUTIONS). Ofloxacin 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 tendionitis or tendon rupture has been confidently excluded.
Tendon rupture can occur at any time during or after therapy with quinolones, including
ofloxacin.
4. PRECAUTIONS
• A Torsades de pointes subsection was added to read:
Torsades de pointes: Some quinolones, including ofloxacin, have been associated with
prolongation of the QT interval on the electrocardiogram and infrequent cases of arrhythmia.
Rare cases of torsades de pointes have been spontaneously reported during post-marketing
surveillance in patients receiving quinolones, including ofloxacin. Ofloxacin should be avoided
in patients with known prolongation of the QT interval, patients with uncorrected hypokalemia,
and patients receiving class IA (quinidine, procainamide), or class III (amiodarone, sotalol)
antiarrhythmic agents.
• The following bullet concerning peripheral neuropathy was added under Information for
Patients:•
that peripheral neuropathies have been associated with ofloxacin use. If symptoms of
peripheral neuropathy including pain, burning, tingling, numbness, and/or weakness develop,
they should discontinue treatment and contact their physicians;
• The following paragraph was added to the Geriatric Use subsection:
Elderly patients may be more sensitive to drug-associated effects on the QT interval. Therefore,
precaution should be taken when using ofloxacin with concomitant drugs that can result in
prolongation of the QT interval (e.g. class IA or class III antiarrhythmics) or in patients with
risk factors for Torsade de pointes (e.g. known QT prolongation, uncorrected hypokalemia).
(See PRECAUTIONS: GENERAL: Torsades de pointes)

FLOXIN IN DEXTROSE 5% OFLOXACIN DISCONTINUED

FLOXIN IN DEXTROSE 5% IN PLASTIC CONTAINER OFLOXACIN DISCONTINUED

FLOXIN OTIC OFLOXACIN NO WARNINGS FOUND

OCUFLOX OFLOXACIN NO WARNINGS FOUND

OFLOXACIN OFLOXACIN NO INFORMATION AVAILABLE ON THE FDA WEBSITE
GENERIC LABELS UNAVAILABLE ON THE FDA WEBSITE
 

Label Changes for Levaquin (Levofloxacin)

IQUIX LEVOFLOXACIN NO WARNINGS FOUND
 

Additional warnings added 10/2004

In immature rats and dogs, the oral and intravenous administration of levofloxacin resulted in increased osteochondrosis. Histopathological examination of the weightbearing joints of immature dogs dosed with levofloxacin revealed persistent lesions of the cartilage. Other fluoroquinolones also produce similar erosions in the weight bearing joints and other signs of arthropathy in immature animals of various species. The relevance of these findings to the clinical use of levofloxacin is unknown.

LEVAQUIN LEVOFLOXACIN
LEVAQUIN IN DEXTROSE 5% IN PLASTIC CONTAINER LEVOFLOXACIN
INJECTABLE; INJECTION:EQ 250MG /50ML(5MG/ML) ;EQ 500MG /100ML(5MG/ML) ;EQ 750MG /150ML(5MG/ML)
NDA 20-634/S-034 and NDA 20-635/S-034 were submitted as prior approval supplemental
applications and provide for revisions to the PRECAUTIONS: Geriatric Use section of the package insert regarding QTc prolongation/torsades de pointes, and the Post-Marketing Adverse Reactions section of the package insert providing for the addition of rhabdomyolysis.
These supplemental new drug applications provide for the following revisions to the package insert:
1. The following paragraph was added as the sixth paragraph of the WARNINGS section:
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 levofloxacin. Levofloxacin should be
discontinued if the patient experiences symptoms of neuropathy including pain, burning, tingling,
numbness, and/or weakness or other alterations of sensation including light touch, pain,
temperature, position sense, and vibratory sensation in order to prevent the development of an
irreversible condition.
NDA 20-634/S-033, S-034
NDA 20-635/S-033, S-034
Page 2
2. The tenth paragraph of the WARNINGS section was revised as follows:
Tendon Effects: Ruptures of the shoulder, hand, or Achilles tendon, or other tendons that required
surgical repair or resulted in prolonged disability have been reported in patients receiving
quinolones, including levofloxacin. Post-marketing surveillance reports indicate that this risk may
be increased in patients receiving concomitant corticosteroids, especially in the elderly.
Levofloxacin 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 tendinitistendonitis or
tendon rupture has been confidently excluded. Tendon rupture can occur during or after therapy
with quinolones, including levofloxacin.
3. The last paragraph of the PRECAUTIONS section, General subsection was revised as follows:
Torsades de pointes: Some quinolones, including levofloxacin, have been associated with
prolongation of the QT interval on the electrocardiogram and infrequent cases of arrhythmia.
During post-marketing surveillance, rareRare cases of torsades de pointes have been reported in
patients taking levofloxacin. These reports generally involved patients withspontaneously reported
during post-marketing surveillance in patients receiving quinolones, concurrent medical conditions or concomitant medications that may have been contributory. The risk of arrhythmias may be reduced by avoiding concurrent use with other drugs that prolong the QT interval including class Ia or class III antiarrhythmic agents; in addition, use of levofloxacin in the presence of risk factors for torsades de pointes such as hypokalemia, significant bradycardia, and cardiomyopathy should be avoided. including levofloxacin. Levofloxacin should be avoided in patients with known prolongation of the QT interval, patients with uncorrected hypokalemia, and patients receiving class IA (quinidine, procainamide), or class III (amiodarone, sotalol) antiarrhythmic agents.
As with any potent antimicrobial drug, periodic assessment of organ system functions, including
renal, hepatic, and hematopoietic, is advisable during therapy. (See WARNINGS and ADVERSE
REACTIONS.)
4. The following was added as the second bullet in the PRECAUTIONS section, Information for Patients subsection:
• that peripheral neuropathies have been associated with levofloxacin use. If symptoms of
peripheral neuropathy including pain, burning, tingling, numbness, and/or weakness develop,
they should discontinue treatment and contact their physicians;
NDA 20-634/S-033, S-034
NDA 20-635/S-033, S-034
Page 3
5. The following paragraph was added to the PRECAUTIONS section, Geriatric Use subsection:
In phase 3 clinical trials, 1,190 levofloxacin-treated patients (25%) were ¡Ý65 years of age. Of
these, 675 patients (14%) were between the ages of 65 and 74 and 515 patients (11%) were 75
years or older. No overall differences in safety or effectiveness were observed between these
subjects and younger subjects, and other reported clinical experience has not identified differences
in responses between the elderly and younger patients, but greater sensitivity of some older
individuals cannot be ruled out.
Elderly patients may be more susceptible to drug-associated effects on the QT interval. Therefore,
precaution should be taken when using levofloxacin with concomitant drugs that can result in
prolongation of the QT interval (e.g. class IA or class III antiarrhythmics) or in patients with risk
factors for Torsades de pointes (e.g. known QT prolongation, uncorrected hypokalemia). See
PRECAUTIONS: GENERAL: Torsades de Pointes.
The pharmacokinetic properties of levofloxacin in younger adults and elderly adults do not differ
significantly when creatinine clearance is taken into consideration. However since the drug is
known to be substantially excreted by the kidney, the risk of toxic reactions to this drug may be
greater in patients with impaired renal function. Because elderly patients are more likely to have
decreased renal function, care should be taken in dose selection, and it may be useful to monitor
renal function.
6. The following revisions were made in the Post-Marketing Adverse Reactions section:
Additional adverse events reported from worldwide post-marketing experience with levofloxacin
include: allergic pneumonitis, anaphylactic shock, anaphylactoid reaction, dysphonia, abnormal
EEG, encephalopathy, eosinophilia, erythema multiforme, hemolytic anemia, multi-system organ
failure, increased International Normalized Ratio (INR)/prothrombin time, peripheral neuropathy,
rhabdomyolysis, Stevens-Johnson Syndrome, tendon rupture, torsades de pointes, vasodilation.
 

QUIXIN LEVOFLOXACIN NO WARNINGS FOUND

 

Label Changes for Maxaquin (Lomefloxacin)

MAXAQUIN LOMEFLOXACIN HYDROCHLORIDE NO WARNINGS found within the FDA website package insert updated September 2003. Nor is there any mention of Peripheral Neuropathy within this particular package insert.

 

Label Changes for Nalidixic Acid (oral and iv) Discontinued
Label Changes for Neggram
2. The following sentence was added under the drug name:
To reduce the development of drug-resistant bacteria and maintain the effectiveness of NegGram
(nalidixic acid, USP) and other antibacterial drugs, NegGram should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
3. The following was added as the second paragraph of the INDICATIONS AND USAGE section:
To reduce the development of drug-resistant bacteria and maintain effectiveness of NegGram and
other antibacterial drugs, NegGram should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility
information are available, they should be considered when selecting or modifying antibacterial
therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute
to the empiric selection of therapy.
4. The CONTRAINDICATIONS section was revised as follows:
NegGram is contraindicated in patients with known hypersensitivity to nalidixic acid or to related
compounds, infants less than three months of age, and in patients with porphyria or a history of
convulsive disorders. NegGram is contraindicated in patients undergoing concomitant therapy with melphalan or other related cancer chemotherapeutic alkylating agents because of serious
gastrointestinal toxicity such as hemorrhagic ulcerative colitis or intestinal necrosis.
5. The following two paragraphs were added at the end of the WARNINGS section:
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 nalidixic acid. Nalidixic acid 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 Effects: Ruptures of the shoulder, hand, Achilles tendon or other tendons that required
surgical repair or resulted in prolonged disability have been reported in patients receiving
quinolones, including nalidixic acid. Post-marketing surveillance reports indicate that this risk may be increased in patients receiving concomitant corticosteroids, especially in the elderly. Nalidixic acid 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 nalidixic acid.
6. The following information was added at the end of the PRECAUTIONS section, General
subsection:
Cross-resistance between nalidixic acid and other quinolone derivatives such as oxolinic
acid and cinoxacin has been observed.
Caution should be observed in patients with glucose-6-phosphate dehydrogenase deficiency.
(See ADVERSE REACTIONS).
Prescribing NegGram in the absence of a proven or strongly suspected bacterial infection or
a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the
development of drug-resistant bacteria.
7. The following information was added at the end of the PRECAUTIONS section, Information for Patients subsection:
Patients should be advised NegGram may be taken with or without meals. Patients should be
advised to drink fluids liberally and not take antacids.
Patients should be advised that quinolones may be associated with hypersensitivity reactions,
even following a single dose, and to discontinue the drug at the first sign of a skin rash or other
allergic reactions.
Quinolones may cause dizziness and light-headedness, therefore, patients should know how
they react to NegGram before they operate an automobile or machinery or engage in activities
requiring mental alertness or coordination.
Patients should be advised that quinolones may increase the effects of theophylline and
caffeine. There is a possibility of caffeine accumulation when products containing caffeine are
consumed while taking quinolones. Patients should be advised to avoid excessive sunlight or
artificial ultraviolet light while receiving nalidixic acid and to discontinue therapy if phototoxicity
occurs.
Patients should be advised that convulsions have been reported in patients taking quinolones,
including nalidixic acid, and to notify their physician before taking this drug if there is a history of
this condition. Patients should be advised that mineral supplements, vitamins with iron or minerals, calcium-, aluminum-, magnesium-based antacids, sucralfate or Videx® , (didanosine),
chewable/buffered tablets of the pediatric powder for oral solution should not be taken within the
two-hour period before or within the two-hour period after taking nalidixic acid (see Drug
Interactions).
Patients should be advised:
−that nalidixic acid may cause changes in the electrocardiogram (QTc interval
prolongation)
−that nalidixic acid should be avoided in patients receiving class IA (e.g. quinidine,
Procainamide) or class III (e.g. amiodarone, sotalol) antiarrhythmic agents
−that nalidixic acid should be used with caution in subjects receiving drugs that
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 hypokalemia, bradycardia or recent myocardial
ischemia
−that peripheral neuropathies have been associated with nalidixic acid use. If
symptoms of peripheral neuropathy including pain, burning, tingling, numbness,
and/or weakness develop, they should discontinue treatment and contact their
physicians.
Patients should be counseled that antibacterial drugs including NegGram should only be
used to treat bacterial infections. They do not treat viral infections (e.g., the common cold).
When NegGram is prescribed to treat a bacterial infection, patients should be told that although
it is common to feel better early in the course of therapy, the medication should be taken exactly
as directed. Skipping doses or not completing the full course of therapy may (1) decrease the
effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will
develop resistance and will not be treatable by NegGram or other antibacterial drugs in the
future.
8. The PRECAUTIONS section, Drug Interactions subsection was revised as follows:
Elevated plasma levels of theophylline have been reported with concomitant quinolone use.
There have been reports of theophylline-related side effects in patients on concomitant therapy with quinolones and theophylline. Therefore, monitoring of theophylline plasma levels should be
considered and dosage of theophylline adjusted, as required.
Quinolones have been shown to interfere with the metabolism of caffeine. This may lead to
reduced clearance of caffeine and the prolongation of its plasma half-life.
Quinolones, including nalidixic acid, may enhance the effects of the oral anticoagulant
warfarin or its derivatives. When these products are administered concomitantly, prothrombin time
or other suitable coagulation test should be closely monitored.
Nitrofurantoin interferes with the therapeutic Since active proliferation of organisms is a
necessary condition for its antibacterial activity, the action of nalidixic acid may be inhibited by the presence of other antibacterial substances, especially bacteriostatic agents such as tetracycline,
chloramphenicol, or nitrofurantoin, which is antagonistic to nalidixic acid in vitro.
Probenecid inhibits the tubular secretion of nalidixic acid and may reduce its efficacy in the
treatment of urinary tract infections while increasing the risk of systemic side effects.
Serious gastrointestinal toxicity has been associated with the concomitant use of nalidixic
acid and the anti-cancer drug melphalan. (see CONTRAINDICATIONS)
Antacids containing magnesium, aluminum, or calcium; sucralfate or divalent or trivalent
cations such as iron; multivitamins containing zinc; and Videx®, (Didanosine), chewable/buffered
tablets or the pediatric powder for oral solution may substantially interfere with the absorption of
quinolones, resulting in systemic levels considerably lower than desired. These agents should not be taken within the two-hour period before or within the two-hour period after nalidixic acid
administration.
Elevated serum levels of cyclosporine have been reported with the concomitant use of some
quinolones and cyclosporine. Therefore, cyclosporine serum levels should be monitored and
appropriate cyclosporine dosage adjustments made when these drugs are used concomitantly.
9. The PRECAUTIONS section, Nursing Mothers subsection was revised as follows:
It is not known whether NegGram is excreted in human milk. Because other drugs are
excreted in human milk and because Since nalidixic acid is excreted in breast milk, it is
contraindicated during lactation.1 Because of the potential for serious adverse reactions in nursing
infants from NegGram, a decision should be made whether to discontinue nursing or to discontinue the drug taking into account the importance of the drug to the mother.
10. The PRECAUTIONS section, Usage in Patients Under 18 Years of Age subsection had the
following sentence added:
Toxicological studies have shown that nalidixic acid and related drugs can produce erosions of the
cartilage in weight-bearing joints and other signs of arthropathy in immature animals of most
species tested. No such joint lesions have been reported in humans to date. Nevertheless, until the
significance of this finding is clarified, this drug should only be used in patients under 18 years of
age when the potential benefit justifies the potential risk. If arthralgia occurs, treatment with
nalidixic acid should be stopped. (See WARNINGS and ANIMAL PHARMACOLOGY.)
11. Anaphylactic shock was added to the ADVERSE REACTIONS section, Allergic subsection and Peripheral neuropathy was added to the ADVERSE REACTIONS section, Other subsection:
Allergic: rash, pruritus, urticaria, angioedema, eosinophilia, arthralgia with joint stiffness
and swelling, and anaphylactoid reaction, including anaphylactic shock. Erythema Multiforme and
Stevens-Johnson syndrome have been reported with nalidixic acid and other drugs in this class.
Rash was the most frequently reported adverse reaction. Photosensitivity reactions consisting of
erythema and bullae on exposed skin surfaces usually resolve completely in 2 weeks to 2 months
after NegGram is discontinued; however, bullae may continue to appear with successive exposures
to sunlight or with mild skin trauma for up to 3 months after discontinuation of drug. (See
PRECAUTIONS.)
Other: rarely, cholestasis, paresthesia, metabolic acidosis, thrombocytopenia, leukopenia,
or hemolytic anemia, sometimes associated with glucose 6-phosphate dehydrogenase deficiency and peripheral neuropathy.
12. The OVERDOSAGE section, Treatment subsection had the following deletion:
Treatment: Reactions are short-lived (two to three hours) because the drug is rapidly
excreted. If overdosage is noted early, gastric lavage is indicated. If absorption has occurred,
increased fluid administration is advisable and supportive measures such as oxygen and means of
artificial respiration should be available. Although anticonvulsant therapy has not been used in the
few instances of overdosage reported, it may be indicated in a severe case.
 

Label Changes for Noroxin (Norfloxacin)

NDA 019384 Approved 10/31/1986 Merck
Noroxin
Pseudomembranous colitis: Pseudomembranous colitis has been reported with nearly all
antibacterial agents, including norfloxacin, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with
diarrhea subsequent to the administration of antibacterial agents.
Treatment with antibacterial agents alters the normal flora of the colon and may permit
overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one
primary cause of “antibiotic-associated colitis”.
After the diagnosis of pseudomembranous colitis has been established, therapeutic measures
should be initiated. Mild cases of pseudomembranous colitis usually respond to drug
discontinuation alone. In moderate to severe cases, consideration should be given to management
with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug
clinically effective against C. difficile colitis.
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 norfloxacin. Norfloxacin 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 effects: Ruptures of the shoulder, hand,and Achilles tendons or other tendons that
required surgical repair or resulted in prolonged disability have been reported with in patients
receiving quinolones, including norfloxacin. Post-marketing surveillance reports indicate that this
risk may be increased in patients receiving concomitant corticosteroids, especially in the elderly.
Norfloxacin 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 at any time during or after therapy with quinolones, including norfloxacin.
Syphilis treatment: Norfloxacin has not been shown to be effective in the treatment of syphilis.
Antimicrobial agents used in high doses for short periods of time to treat gonorrhea may mask or
delay the symptoms of incubating syphilis. All patients with gonorrhea should have a serologic test for syphilis at the time of diagnosis. Patients treated with norfloxacin should have a follow-up
serologic test for syphilis after three months.
2. The following text was added as the first five bullets in the PRECAUTIONS, Information for
Patients subsection:
−that norfloxacin may cause changes in the electrocardiogram (QTc interval prolongation).
−that norfloxacin should be avoided in patients receiving class IA (e.g., quinidine,
procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents.
— that norfloxacin should be used with caution in subjects receiving drugs that 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 hypokalemia, bradycardia or recent myocardial ischemia.
−that peripheral neuropathies have been associated with norfloxacin 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 text was added in the PRECAUTIONS, Drug Interactions subsection:
The concomitant administration of quinolones including norfloxacin with glyburide (a sulfonylurea agent) has, on rare occasions, resulted in severe hypoglycemia. Therefore, monitoring of blood glucose is recommended when these agents are co-administered.
4. The following text was revised in the PRECAUTIONS, Geriatric Use subsection:
Of the 340 subjects in one large clinical study of NOROXIN for treatment of urinary tract
infections, 103 patients were 65 and older, 77 of whom were 70 and older; no overall differences in safety and effectiveness were evident between these subjects and younger subjects. In clinical
practice, no difference in the type of reported adverse experiences have been observed between the
elderly and younger patients; however,patients except for a possible increased risk of tendon rupture in elderly patients receiving concomitant corticosteroids (see WARNINGS). In addition, increased risk for other adverse experiences in some older individuals cannot be ruled out (see ADVERSE REACTIONS).
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to
this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see DOSAGE AND ADMINISTRATION).
A pharmacokinetic study of NOROXIN in elderly volunteers (65 to 75 years of age with normal
renal function for their age) was carried out (see CLINICAL PHARMACOLOGY).
5. The following text was added under the ADVERSE REACTIONS, Post Marketing subsection:
Cardiovascular On rare occasions, prolonged QTc interval and ventricular arrhythmia including torsades de pointes.
Musculoskeletal Tendonitis, tendon rupture; exacerbation of myasthenia gravis (see PRECAUTIONS) ; elevated creatine kinase (CK).

1. The following revisions were made under the PRECAUTIONS, Drug Interactions subsection:
Quinolones, including norfloxacin, may enhance the effects of the oral anticoagulant oral
anticoagulants, including warfarin or its derivatives or similar agents. When these products are
administered concomitantly, prothrombin time or other suitable coagulation tests should be closely
monitored.
2. The following revisions were made under the ADVERSE REACTIONS, Post Marketing,
subsection:
Hematologic
Neutropenia; leukopenia; agranulocytosis; hemolytic anemia, sometimes associated with glucose-6-phosphate dehydrogenase deficiency; thrombocytopenia.
Special Senses
Transient hearing loss (rare),Hearing loss, tinnitus, diplopia, dysgeusia.
Other adverse events reported with quinolones include: agranulocytosis, albuminuria, candiduria,
crystalluria, cylindruria, dysphagia, elevation of blood glucose, elevation of serum cholesterol,
elevation of serum potassium, elevation of serum triglycerides, hematuria, hepatic necrosis,
symptomatic hypoglycemia, nystagmus, postural hypotension, prolongation of prothrombin time,
and vaginal candidiasis.
The following sentence was added at the beginning of the label under the Product Name:
To reduce the development of drug-resistant bacteria and maintain the effectiveness of
NOROXIN and other antibacterial drugs, NOROXIN should be used only to treat or prevent
infections that are proven or strongly suspected to be caused by bacteria.
2. The following was added as the last paragraph in the INDICATIONS AND USAGE section:
To reduce the development of drug-resistant bacteria and maintain the effectiveness of
NOROXIN and other antibacterial drugs, NOROXIN should be used only to treat or prevent
infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture
and susceptibility information are available, they should be considered in selecting or modifying
antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns
may contribute to the empiric selection of therapy.
3. The following was added as the last paragraph in the PRECAUTIONS, General subsection:
Prescribing NOROXIN in the absence of a proven or strongly suspected bacterial infection or a
prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the
development of drug-resistant bacteria.
4. The following was added as the last paragraph in the PRECAUTIONS, Information for Patients
subsection:
Patients should be counseled that antibacterial drugs including NOROXIN should only be used to
treat bacterial infections. They do not treat viral infections (e.g., the common cold). When
NOROXIN is prescribed to treat a bacterial infection, patients should be told that although it is
common to feel better early in the course of therapy, the medication should be taken exactly as
directed. Skipping doses or not completing the full course of therapy may (1) decrease the
effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop
resistance and will not be treatable by NOROXIN or other antibacterial drugs in the future.

NDA 019757 Approved 6/7/91 Merck Discontinued
CHIBROXIN NORFLOXACIN (EYE DROPS)

Generic Equivalent:
NORFLOXACIN (ANDA # 074690) Tablet; Oral 400MG None (Tentative Approval) NOVOPHARM LIMITED
 

Label Changes for Pefloxacin NO INFORMATION FOUND ON THE FDA WEBSITE
 

Label Changes for RAXAR (GREPAFLOXACIN) REMOVED FROM CLINICAL USE
 

Label Changes for Sitafloxacin NO INFORMATION FOUND ON THE FDA WEBSITE
 

Label Changes for Temafloxacin NO INFORMATION FOUND ON THE FDA WEBSITE
 

Label Changes for TEQUIN (GATIFLOXACIN )
NDA 21-061/S-023 (Tablets) and NDA 21-062/S-026 (Injection) were submitted as “Special Supplements- Changes Being Effected” (CBEs) and provide for the addition of quinolone class labeling as was requested in the Division’s supplement request letter on November 26, 2003 and the facsimiles from the Division dated March 10, and July 26, 2004. The WARNINGS: QTc Interval Prolongation, WARNINGS: Tendon Effects, WARNINGS: Peripheral Neuropathy and PRECAUTIONS: Information for Patients sections were revised. NDA 21-061/S-024 (Tablets) and NDA 21-062/ S-027 (Injection) were submitted as “Special Supplements- Changes Being Effected” (CBEs) and provide for labeling changes to the Patient Information About: and What are the possible side effects of TEQUIN? sections of the patient package insert.
NDA 21-061/S-023, S-024
NDA 21-062/S-026, S-027
Page 2
These supplements provide for the following changes to the Tequin ® (gatifloxacin) Tablets, 200
mg and 400 mg and Tequin ® (gatifloxacin) Injection, 200 mg and 400 mg label.

1. The following revisions were made under the WARNINGS section:
Deletion of the following text:
Prolongation of the QTc Interval
GATIFLOXACIN HAS THE POTENTIAL TO PROLONG THE QTc INTERVAL OF
THE ELECTROCARDIOGRAM IN SOME PATIENTS. DUE TO THE LACK OF
CLINICAL EXPERIENCE IN PATIENTS WITH KNOWN PROLONGATION OF
THE QTc INTERVAL, PATIENTS WITH UNCORRECTED HYPOKALEMIA, AND
PATIENTS RECEIVING CLASS IA (EG, QUINIDINE, PROCAINAMIDE) OR
CLASS III (EG, AMIODARONE, SOTALOL) ANTIARRHYTHMIC AGENTS,
GATIFLOXACIN SHOULD BE AVOIDED IN THESE PATIENT POPULATIONS.

The following text added:
QTc Interval Prolongation
Gatifloxacin has the potential to prolong the QTc interval of the electrocardiogram in some
patients. QTc prolongation may lead to an increased risk for ventricular arrhythmias
including torsades de pointes. Rare cases of torsades de pointes have been spontaneously
reported during postmarketing surveillance in patients receiving quinolones, including
gatifloxacin. Nearly all of these rare cases were associated with one or more of the following
factors: age over 60, female gender, underlying cardiac disease, and/or use of multiple
medications. No cardiovascular morbidity or mortality attributable to QTc prolongation has
occurred in over 44,000 patients treated with gatifloxacin in clinical trials; these include 118
patients concurrently receiving drugs known to prolong the QTc interval and 139 patients
known to have uncorrected hypokalemia (ECG monitoring was not performed). Gatifloxacin
should be avoided in patients with known prolongation of the QTc interval, patients with
uncorrected hypokalemia, and patients receiving class IA (quinidine, procainamide), or class
III (amiodarone, sotalol) antiarrhythmic agents. (See CLINICAL PHARMACOLOGY:
Electrocardiogram.)

Pharmacokinetic and pharmacodynamic studies between gatifloxacin and drugs that
prolong the QTc interval such as cisapride, erythromycin, antipsychotics, and tricyclic
antidepressants have not been performed. Gatifloxacin should be used with caution when
given concurrently with these drugs, as well as in patients with ongoing proarrhythmic
conditions, such as clinically significant bradycardia or acute myocardial ischemia.
The magnitude of QTc prolongation increases with increasing concentrations of the
drug;

The following text deleted:
QTc prolongation may lead to an increased risk for ventricular arrhythmias including torsades de pointes

The following text deleted:
No cardiovascular morbidity or mortality attributable to QTc prolongation has occurred in
over 44,000 patients treated with gatifloxacin in clinical trials; these include 118 patients
concurrently receiving drugs known to prolong the QTc interval and 139 patients known to
have uncorrected hypokalemia (ECG monitoring was not performed). During postmarketing
surveillance, rare cases of torsades de pointes have been reported in patients taking
gatifloxacin. These cases have occurred primarily in elderly patients with underlying
medical problems for which they were receiving concomitant medications known to prolong
the QTc interval; the contribution, if any, of gatifloxacin to the development of torsades de
pointes in these patients is unknown.

The following text added:
Tendon Effects
Ruptures of the shoulder, hand, and Achilles tendon or other tendons that required surgical
repair or resulted in prolonged disability have been reported in patients receiving quinolones,
including gatifloxacin. Postmarketing surveillance reports indicate that this risk may be
increased in patients receiving concomitant corticosteroids, especially the elderly.
Gatifloxacin 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 gatifloxacin.

The following text deleted:
Ruptures of the shoulder, hand, and Achilles tendons that required surgical repair or resulted
in prolonged disability have been reported in patients receiving quinolones. TEQUIN 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 during or after therapy
with quinolones.

The following text 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.

2. The following revisions were made under the PRECAUTIONS section, Information for
Patients subsection:
• that TEQUIN may cause changes in the electrocardiogram (QTc interval
prolongation);
• that TEQUIN should be avoided in patients receiving class IA (eg, quinidine,
procainamide) or class III (eg, amiodarone, sotalol) antiarrhythmic agents;
• that TEQUIN should be used with caution in subjects 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 asrecent hypokalemia,significant bradycardia, or recent
myocardial ischemia;
• to discontinue treatment and contact their physician if symptoms of peripheral
neuropathy including pain, burning, tingling, numbness and/or weakness develop;
3. The following typographical error was made in the patient package insert and will be
corrected in the final printed labeling:

Patient Information About:
TEQGUIN
(gatifloxacin)
200 mg and 400 mg Tablets
4. The following revisions were made in the patient package insert, under the
What are the possible side effects of TEQUIN? section, second paragraph:
In a few people, TEQUIN, like some other antibiotics, may produce a small effect on the
heart that is seen on an electrocardiogram test. Although this did not cause any
problems in patients who took TEQUIN in premarketing clinical trials, in theory, it could result in extremely rare cases of abnormal heartbeat, which may be
dangerous. Contact your healthcare professional if you develop heart palpitations (fast
beating) or have fainting spells.

ZYMAR GATIFLOXACIN (ophthalmic solution) NO WARNINGS FOUND

 

Label Changes for TROVAN (TROVAFLOXACIN) DISCONTINUED
TROVAN PRESERVATIVE FREE ALATROFLOXACIN MESYLATE DISCONTINUED
TROVAN/ZITHROMAX COMPLIANCE PAK AZITHROMYCIN DIHYDRATE; TROVAFLOXACIN MESYLATE DISCONTINUED

 

Label Changes for ZAGAM (SPARFLOXACIN ) DISCONTINUED

End