Factive
  Gemifloxacin
  Oscient Pharmaceuticals and Pfizer, S.A. de C.V.
  NDA  021158
  Latest Package Insert
  Factive 2003, 2004, 2006
  Safety Profile

  DO NOT USE 

Severe and disfiguring rashes associated with Factive.  This has been reported since 2000.

BLACK BOX WARNINGS TO BE ADDED (Read More)
 FDA is notifying the makers of fluoroquinolone antimicrobial
 drugs for systemic use of the need to add a boxed warning to
 the prescribing information about the increased risk of developing
 tendinitis and tendon rupture in patients taking fluoroquinolones
 and to develop a Medication Guide for patients.

Listed as a DO NOT USE drug
Numerous other, safer antibiotics are approved to treat the same infections as this drug

There are numerous FATAL adverse reactions associated with this drug. (Read More)

A CD containing a copy of the FDA Briefing Package (Gemifloxacin) Anti-Infective Drugs Advisory
Committee (March 4, 2003) and the New Drug Application (NDA) 21-158 Factive (gemifloxacin mesylate)
in which the adverse reactions to gemifloxacin were discussed is available at no charge upon request. 
Send the address to which the CD is to be sent to: fqresearch@aol.com and indicate that you wish
to receive a copy of this CD.

www.fda.gov/ohrms/dockets/ac/03/briefing/3931B1_02_FDA-Factive.pdf
We find serious disfiguring rashes with Factive and within the above transcript (2003)  the FDA’s advisers
actually laughed at the seriousness of this reaction:

The FDA approved the drug in 2003 to treat pneumonia and acute bronchitis. It's manufacturer,
Oscient Pharmaceuticals Corp., is seeking expanded approval to treat acute bacterial sinusitis
as well. In 2002, the FDA had declined to approve that use. Real-world use of Factive has shown
what clinical trials previously revealed: the risk of disfiguring rashes associated with the antibiotic
appears to be greater when compared with that seen in other, similar antibiotics, according to the
FDA documents. Yet this was something the FDA was fully aware of four years ago and had made
fun of it. This is the general attitude of those reviewing the new drug applications for the fluoroquinolones. 

Gemifloxacin (Factive) approval denied by the FDA due to severe side-effects such as  
severe rashes and toxicity. (circa 12/2000)


Excerpts from the March 2003 Factive meeting
 

Six YEARS later the FDA now believes that Gemifloxacin (Factive) should be studied
further because of serious skin reactions associated with its use.


When compared with other antibiotics used to treat minor infections, the incident of
serious rashes has Food and Drug Administration officials concerned about the safety
of the drug, Factive or gemifloxacin.


FDA concerned about new use of Gemifloxacin (Factive)9/2006.


The FDA March 2003 meeting regarding Gemifloxacin (Factive) and severe rashes.


In spite of the FDA's concerns Oscient Pharmaceuticals and Pfizer, S.A. de C.V. announced
the Launch of Factive(R) (Gemifloxacin Mesylate) Tablets in Mexico on 10-05-2006

‘Factive’ Glaxo SmithKline  Quinolone antibacterial agents 2001  Received a non-approvable letter
from the FDA for the treatment of respiratory tract infections.  UK licence application filed June 2001.
Seeking approval for urinary and respiratory tract infections in the EU. 
Gemifloxacin turned down by FDA [circa 2001]  The United States Food and Drug Administration has
declined to approve gemifloxacin mesylate (Factive), a quinolone antibiotic that was under review for
the treatment of respiratory tract infections. The manufacturer of the product is Glaxo Smithkline. http://www.pharmj.com/Editorial/20010120/clinical/clinical.html

On 15 April 2002, in 'GlaxoSmithKline pays $420m for two drugs', The Financial Times reported that
GlaxoSmithKline was to pay nearly 300 million pounds 'to bolster its pipeline with two new drugs'.
The article said this was because the company had experienced a number of setbacks 'in its labs
in recent years' and was seeking 'new products to fill the gap'.
Referring to how the company had abandoned 'a once-promising antibiotic that has disappointed in
clinical trials', the article commented that the company was 'handing back' Factive (to treat respiratory
infections) as this, while originally considered to have potential, produced side-effects during the
clinical trials. It also mentioned that the company had abandoned research on GI262570 (for treating
diabetes) and Tranilast (for treating blocked arteries).  GSK's decision to abandon Factive was also
reported by The Independent of 16 April 2002 in the article 'Glaxo to abandon chest infection drug
' which said the company was to abandon development 'after side effects threatened to scupper its
chances of being allowed on the market'.
Source: http://vivisection-absurd.org.uk/recent3.html

SmithKline Beecham have been dealt an embarrassing blow by US authorities who have blocked its
new antibiotic treatment FACTIVE (tested on animals) from sale in America. Analysts believe the
company expected to generate sales from the drug of £350m by 2005, and it could be another year
before the drug is ready to come to market, if it is ever approved. Factive treats an unusually wide
variety of ailments, they say. However, its potency is associated with potentially toxic side-effects
and serious rashes. Factive also belongs to a class of antibiotics which are clastogenic, which can
transform human cells, possibly making them cancerous. The drug was developed for the treatment
of respitory tract infections
source: http://canterbury.gn.apc.org/carnage/EXECUT3.HTML

The US Food and Drug Administration has declared gemifloxacin (Factive), the latest fluoroquinolone,
‘non-approvable’ in a letter to manufacturer SmithKline Beecham (now GlaxoSmithKline). The details
behind the decision have not been released by the company or the FDA; market analysts had predicted
high sales on the basis of efficacy and safety data.
Source: http://www.escriber.com/FuturePrescriber/News.asp?Action=View&Archive=True&ID=56

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, July 2001; 48:67-74:
Glaxo SmithKline 's (NYSE: GSK) gemifloxacin formulation, Factive, a new quinolone antibiotic, is
an effective and well-tolerated treatment for community-acquired pneumonia (CAP). Factive elicited
clinical responses similar to the most potent marketed quinolone, Pfizer's (NYSE: PFE) Trovan, in
patients treated according to protocol. Factive-treated patients fared better than did Trovan-treated
patients in the intent-to-treat analysis. Glaxo submitted Factive's NDA in December 1999, and one
year later the FDA issued a non-approval letter. Glaxo is working with the FDA to determine what
is necessary to gain approval. Published investigations regarding the agent's treatment effect and
adverse effect profile suggest approvability.
http://www.btechnews.com/news/2001BTNs/813mm.htm

Other adverse reactions associated with the fluoroquinolones

Peripheral Neuropathy
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.

QUINOLONES MAY HAVE THE POTENTIAL TO PROLONG THE QTc INTERVAL OF THE ELECTROCARDIOGRAM IN SOME PATIENTS. DUE TO THE LACK OF CLINICAL EXPERIENCE, QUINOLONES SHOULD BE AVOIDED IN PATIENTS WITH KNOWN PROLONGATION OF THE QTc INTERVAL, PATIENTS WITH UNCORRECTED HYPOKALEMIA, AND PATIENTS RECEIVING CLASS IA (E.G. QUINIDINE, PROCAINAMIDE) OR CLASS III (E.G. AMIODARONE, SOTALOL) ANTIARRHYTHMIC AGENTS.

Ruptures of the shoulder, hand, and Achilles tendons that required surgical repair or resulted in prolonged disability have been reported in patients receiving quinolones. Tendon rupture can occur during or after therapy with quinolones.

Quinolones may cause central nervous system (CNS) events including nervousness, agitation, insomnia, anxiety, nightmares, or paranoia.

As with other quinolones, disturbances of blood glucose, including symptomatic hyper- and hypoglycemia, have been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic (e. g., glyburide) or with insulin. In these patients, the monitoring of blood glucose is recommended.

In 2004 new warning labels added to all of the Fluoroquinolones regarding Peripheral Neuropathy (irreversible nerve damage), Tendon Damage, Heart Problems (prolonged QT Interval / Torsades de pointes), Pseudomembranous colitis, Rhabdomyolysis (muscle wasting), Steven Johnson Syndrome, as well as concurrent usage of NSAIDs contributing to the severity of these reactions.
.
Although such events have been reported since the mid sixties, the FDA waited almost forty years to add such warnings to the package inserts.  These new warnings again fail to adequately warn either the patient or the physician.

"Drug companies write the package inserts of all drugs, carefully including the information they choose and
omitting information they want to avoid. Drug companies underwrite a large percentage of continuing
education courses for doctors. In doing so, they make sure that the speakers represent the company view.
Drug companies design studies that are meant to produce favorable results and then publish the studies in
medical journals. Studies with unfavorable results are not published. Drug reps typically bring stacks of
studies, all favorable, which impress doctors, who no longer have the time or motivation to search  the
medical literature themselves. Drug reps do not include independent studies with less favorable
conclusions. Many doctors never see these." 

Source:   THE MEDICAL PROFESSION AND THE CULTURE OF CORRUPTION

PERIPHERAL NEUROPATHY (as noted above)
Achilles and other tendon ruptures that required surgical repair or resulted in prolonged disability.
Convulsions, increased intracranial pressure, and toxic psychosis.
Central nervous system (CNS) events including: dizziness, confusion, tremors, hallucinations, depression, and, ly, suicidal thoughts or acts. These reactions may occur following the first dose.
Severe hypersensitivity reactions characterized by rash, fever, eosinophilia, jaundice, and hepatic necrosis with fatal outcome
Pseudomembranous colitis and may range in severity from mild to life-threatening.
Lameness in immature dogs with permanent lesions of the cartilage.
Central nervous system (CNS) events, including nervousness, agitation, insomnia, anxiety, nightmares or paranoia.
Crystalluria
Moderate to severe photoxicity

Additional adverse events reported:

Body as a Whole: Change in serum phenytoin.

Cardiovascular: Palpitation, atrial flutter, ventricular ectopy, syncope, hypertension, angina pectoris, myocardial infarction, cardiopulmonary arrest, cerebral thromobosis. Cardiovascular collapse, cardiopulmonary arrest, myocardial infarction, arrhythmia, tachycardia, palpitation, cerebral thrombosis, syncope, cardiac murmur, hypertension, hypotension, angina pectoris. Postural hypotension, vasculitis.

Central Nervous System: Dizziness, lightheadedness, insomnia, nightmares, hallucinations, manic reaction, irritability, tremor, ataxia, convulsive seizures, lethargy, drowsiness, weakness, malaise, anorexia, phobia, depersonalization, depression, paresthesia. Convulsive seizures, paranoia, toxic psychosis, depression, dysphasia, phobia, depersonalization, manic reaction, unresponsiveness, ataxia, confusion, hallucinations, dizziness, lightheadedness, paresthesia, anxiety, tremor, insomnia, nightmares, weakness, drowsiness, irritability, malaise, lethargy Agitation, confusion, delirium, dysphasia, myoclonus, nystagmus, toxic psychosis.
.
Gastrointestinal: Painful oral mucosa, oral candidiasis, dysphagia, intestinal perforation, gastrointestinal bleeding. Cholestatic jaundice has been reported. Ileus, jaundice, gastrointestinal bleeding, C. difficle associated diarrhea, pseudomembranous colitis, pancreatitis, hepatic necrosis, intestinal perforation, dyspepsia, epigastric or abdominal pain, vomiting, constipation, oral ulceration, oral candidiasis, mouth dryness, anorexia, dysphagia, flatulence Constipation, dyspepsia, flatulence, hepatic necrosis, jaundice, pancreatitis, pseudomembranous colitis. (The onset of pseudomembranous colitis symptoms may occur during or after antimicrobial treatment.)

Hemic/Lymphatic: Agranulocytosis, hemolytic anemia, methemaglobinemia, prolongation of prothrombin time

Metabolic/Nutritional: Elevation of serum triglycerides, cholesterol, blood glucose, serum potassium.

Musculoskeletal: Arthralgia or back pain, joint stiffness, achiness, neck or chest pain, flare up of gout. Arthralgia, jaw, arm or back pain, joint stiffness, neck and chest pain, achiness, flare up of gout Myalgia, possible exacerbation of myasthenia gravis, tendinitis/tendon rupture.

Renal/Urogenital: Interstitial nephritis, nephritis, renal failure, polyuria, urinary retention, urethral bleeding, vaginitis, acidosis. Renal failure, intarstitial nephritis, hemorrhagic cystitis, renal calcuti, frequent urination, acidosis, urethral bleeding, polyuria, urinary retention, gynecomastia, candiduria, vaginitis. Crystalluria, cylindruria, hematuria, and albuminutia have also been reported.
Albuminuria, candiduria, renal calculi, vaginal candidiasis.

Respiratory: Dyspnea, epistaxis, laryngeal or pulmonary edema, hiccough, hemophysis, bronchospasm, pulmonary embolism. Respiratory arrest, pulmonary embolism, dyspnea, pulmonary edema, respiratory distress, pleural effusion, hemoptysis, epistaxis, hiccough

Skin/Hypersensitivity: Pruritus, urticaria, photosensitivity, flushing, fever, chills, angioedema, edema of the face, neck, lips, conjunctivae or hands, cutaneous candidiasis, hyperpigmentation, erytherna nodosum. Allergic reactions ranging from urticaria to anaphylactic reactions have been reported. Anaphylactic reactions, erythema multiforme/Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, vasculitis, angioedema, edema of the lips, face, neck, conjunctivae, hands or lower extremities, purpura, fever, chills, flushing, pruritus, urtigaria, cutaneous candidiasis, vesicles, increased perspiration, hyperpigmentation, erythema nodosum, photosensitivity. Allergic reactions ranging from urticaria to anaphylactic reactions have been reported. Anaphylactic reactions, erythema multiforme/Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis.

Special Senses: Blurred vision, disturbed vision (change in color perception, overbrightness of lights), decreased visual acuity, diplopia, eye pain, tinnitus, hearing loss, bad taste. Decreased visual acuity, blurred vision, disturbed vision (flashing lights, change in color perception, overbrightness of lights, diplopia), eye pain, anosmia, hearing loss, tinnitus, nystagmus, a bad taste. Also reported were agranulocytosis, prolongation of prothrombin time, and possible exacerbation of myasthenia gravis. anosmia, taste loss.
 

Adverse Laboratory Changes

Oral

Changes in Laboratory Parameters Listed as Adverse Events:

Other changes occurring ly during administration of fluoroquinolone were: elevation of serum amylase, decrease of blood glucose, pancytopenia, leukocytosis, elevated sedimentation rate, change in serum phenytoin, decreased prothrombin time, hemolytic anemia, and bleeding diathesis.
 

ANIMAL PHARMACOLOGY
Oral and I.V.