The Fluoroquinolone Toxicity Research Foundation

 
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 Gemifloxacin   See downloads for: Adobe Files


All brand names are trademarks of their respected manufacturers.  The information being provided below is to be considered a quick reference guide.  For complete information please view the complete package insert at www.rxlist.com or by entering the drug name at Drugs@FDA
 

PDF version of the package insert can be found at the FDA website following this link. Remember Adobe Reader is required to view this.

http://www.fda.gov/cder/foi/label/2004
 

The CD containing a copy of the FDA Briefing Package (Gemifloxacin) Anti-Infective Drugs Advisory Committee (March 4, 2003) New Drug Application (NDA) 21-158 Factive (gemifloxacin mesylate) www.fda.gov/ohrms/dockets/ac/03/briefing/3931B1_02_FDA-Factive.pdf
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.
 

Gemifloxacin (Click here for safety issues)
 

Listed by Public Citizen as DO NOT USE
 Do Not Use Do Not Use
Generic drug name: gemifloxacin (gem i FLOX a sin) 
Brand name(s): FACTIVE (Oscient Pharmaceuticals)
FAMILY: Fluoroquinolones

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.
 

QUINOLONES MAY HAVE THE POTENTIAL TO PROLONG THE QTc INTERVAL OF THE ELECTROCARDIOGRAM IN SOME PATIENTS. DUE TO THE LACK OF CLINICAL EXPERIENCE, GATIFLOXACIN 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.

 

‘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

Trovafloxacin, gemifloxacin, and moxifloxacin also exhibit activity against various anaerobes (bacteroides, peptostreptococcus, etc.). Therefore, they have value in treatment of polymicrobial infections.
Some other quinolones are on the market, but for otolaryngologists they offer no advantages over the ones named above. Others are also in development.

DISADVANTAGES:

Neurological symptoms such as headache, dizziness, restlessness, stimulation, and insomnia are the most commonly experienced side effects. These are aggravated by concomitant use of nicotine, caffeine, and nonsteroidal anti-inflammatory drugs. Quinolones are used with caution in patients with suspected CNS disorders or other factors that lower the seizure threshold. Theophylline elimination time is prolonged by ciprofloxacin, so dosage adjustments of theophylline are required. Trovafloxacin use has been associated with (rare) liver damage, which prompted the withdrawal of the oral preparations from the U.S. market. However, the IV preparation is still available for treatment of infections so serious that the benefits outweigh the risks.

Quinolones are listed among the drugs that prolong the electro cardiographic Q-T interval. Others include terfenadine, astemizole, erythromycins, clarithromycin, ketoconazole, fluconazole, etc. While the more troublesome of the quinolones in this regard have been withdrawn from the market, it would still be prudent to avoid combination-use if these agents with the others listed, or with antiarrhythmic agents or in patients with bradycardia or acute myocardial ischemia. Tendon toxicity has been reported from quinolones.
Source: http://antimicrobial.entlink.net/aaolive/aao882/me.get
?web.websections.show&AAO882_699

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

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.
 

Tendinitis and tendon ruptures may occur during treatment with quinolones, particularly in elderly patients or when corticosteroids are being co-administered. FACTIVE should be discontinued if tendinitis is suspected or at the first sign of pain or inflammation and the affected limb should be rested.

In clinical studies with gemifloxacin a mean increase in QTc interval was observed (approx 5 msec).

Patients with existing or family history of glucose-6-phosphate dehydrogenase deficiency may develop haemolytic reactions  during therapy.

Adequate hydration should be maintained to prevent the formation of highly concentrated urine.

Photosensitisation has been reported with the use of quinolones.

FACTIVE should not be used in pregnant or lactating women except in those cases where the potential benefit to the mother outweighs the potential risk to the foetus.  Animal studies have shown adverse effects on embryo-foetal development and gemifloxacin-related material is excreted in the milk of lactating rats.

Pseudomembranous colitis has been reported with the use of broad spectrum antibiotics.

The following adverse reactions have been associated with gemifloxacin:

Body as a Whole: fungal overgrowth

Central Nervous System/Psychiatric: headache dizziness, insomnia

Gastrointestinal:abdominal pain, diarrhea, nausea, vomiting

Laboratory Abnormalities: asymptomatic transient elevations in liver enzymes.

Skin: maculopapular erythematous skin rash. A diffuse maculopapular or erythematous skin rash was reported in some patients taking FACTIVE in clinical trials. The rash mainly occurred after one week, was generally mild to moderate and appeared to be a type IV hypersensitivity reaction. It is recommended that treatment with FACTIVE should be discontinued if a patient experiences rash, unless the opinion of the physician dictates otherwise. urticaria, pruritus

In addition, isolated cases of the following adverse effects were observed: elevated bilirubin, tendinitis, thrombocytopenia, and photosensitivity reaction.

In common with other quinolones, reversible foetal growth retardation occurred in mice, rats and rabbits. At a maternally toxic dose in pregnant rats, there was foetal malformation; this effect was not seen in other species studied.

Phototoxicity has been reported for some other quinolones. Gemifloxacin had a lower photosensitisation potential compared with some other quinolones in preclinical studies.

As with some other quinolones reversible crystal nephropathy was observed in rats. This was considered to be due to the poor solubility of gemifloxacin at the pH of rat urine.

source: http://www.medsafe.govt.nz/Profs/Datasheet/f/Factivetab.htm