Oscient Pharmaceuticals has announced the launching of Factive(R) (gemifloxacin) which was approved by the FDA in 2003, stating that their product is safe and well tolerated, claiming a low adverse drug reaction rate consisting mainly of diarrhea (3.6%), rash (2.8%) and nausea (2.7%). Factive(R) is a member of a class of extremely potent chemotherapeutic agents commonly referred to as fluoroquinolones (quinolones).

In sharp contrast to the statements made by Oscient Pharmaceuticals, regarding the safety profile of Factive(R), the FDA has recently added the following warnings to gemifloxacin as well as all drugs within this class of chemotherapeutic agents, (fluoroquinolones) concerning:

- Irreversible Peripheral neuropathy
- Tendon Effects such as spontaneous tendon rupture both during and after therapy
- Caffeine accumulation resulting in CNS stimulation
- Pseudomembranous colitis (life-threatening diarrhea)
- QTc interval prolongation (ventricular arrhythmias including torsades de pointes)
- Commitment use of Non-steroidal anti-inflammatory agents (provoking convulsions)

“QT Effects: 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…Pharmacokinetic studies between gemifloxacin and drugs that prolong the QTc interval such as erythromycin, antipsychotics, and tricyclic antidepressants have not been performed…”

“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.” (Note: This is a much abbreviated form of the warnings added to the other fluoroquinolones and the statements to the effect that such a condition may be irreversible are missing from the warnings found within the package inserts for Factive(R))

“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. 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.”

“CNS Effects: In clinical studies with gemifloxacin, central nervous system (CNS) effects have been reported infrequently. As with other fluoroquinolones, gemifloxacin should be used with caution in patients with CNS diseases such as epilepsy or patients predisposed to convulsions. Although not seen in gemifloxacin clinical trials, convulsions, increased intracranial pressure, and toxic psychosis have been reported in patients receiving other fluoroquinolones. CNS stimulation which may lead to tremors, restlessness, anxiety, lightheadedness, confusion, hallucinations, paranoia, depression, insomnia, and rarely suicidal thoughts or acts may also be caused by other fluoroquinolones…”

“Antibiotic Associated Colitis: Pseudomembranous colitis has been reported with nearly all antibacterial agents, including gemifloxacin, 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 any antibacterial agent. 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 the primary cause of antibiotic-associated colitis."

Other adverse drug reactions associated with Factive(R) included: abdominal pain, anorexia, arthralgia, constipation, dermatitis, dizziness, dry mouth, dyspepsia, fatigue, flatulence, fungal infection, gastritis, genital moniliasis, hyperglycemia, insomnia, leukopenia, moniliasis, pruritus, somnolence, taste perversion, thrombocythemia, urticaria, vaginitis, and vomiting.

Other adverse events reported from clinical trials included: abnormal urine, anemia, asthenia, back pain, bilirubinemia, dyspnea, eczema, eosinophilia, flushing, gastroenteritis, granulocytopenia, hot flashes, increased GGT, leg cramps, myalgia, nervousness, non-specified gastrointestinal disorder, pain, pharyngitis, pneumonia, thrombocyotopenia, tremor, vertigo, and vision abnormality.

Peripheral neuropathy may result in a life long disability. Spontaneous tendon rupture, first reported in 1982 (Bailey et al), as well as Peripheral Neuropathy (reported in 1988) continues to be unrecognized as being associated with fluoroquinolone therapy by the treating physician who fails to recognize, treat and report such events. Such crippling and at time fatal reactions are far more serious then the reports of nausea, diarrhea, and rash being referred to by Oscient Pharmaceuticals within their safety profile.

Fluoroquinolones should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. In the absence of a proven or strongly suspected bacterial infection or a prophylactic indication, the use of drugs within this class is unlikely to provide benefit to the patient and increases the risk of the development of serious and irreversible adverse drug reactions as outlined above. Contrary to what physicians are being told, Fluoroquinolones are NOT to be considered a first line agent but a drug of last resort when all else fails. These warnings issued by the FDA regarding irreversible disease states such as Peripheral Neuropathy as well as potentially fatal reactions such as Rhabdomyolysis, Pseudomembranous Colitis, Steven Johnson Syndrome, and Torsades de Pointes should prevent a physicians from utilizing such a drug when safer alternatives are available. This, however, does not occur. The statements made by Oscient Pharmaceuticals, concerning the safety issues surrounding this drug, fails to convey such a warning and continues to promote the patently false assumption that fluoroquinolones are a "safe and effective antibiotic", much to both the patient and the treating physician's demise.

On December 15, 2001 the FDA sent a non-approval letter to Oscient Pharmaceuticals regarding their initial application for Factive(R) (gemifloxacin). No reasons were ever disclosed regarding why this application was rejected. Two years after rejecting this application the FDA approved this drug. Though never confirmed, as no reason for this rejection was ever made public, it was strongly suspected that this rejection was due to the severe rashes associated with gemifloxacin. Which in some cases covered greater than 60% of the body area involved. Within the package insert it is stated:

“…7% of the rashes were reported as severe, and severity appeared to correlate with the extent of the rash. In 68% of the subjects reporting a severe rash and approximately 25% of all those reporting rash, >60% of the body surface area was involved…”

Dr. Steven Galson, acting director of the FDA's Center for Drug Evaluation said Friday, November 19, 2004, "we categorically reject accusations the agency has done a poor job of protecting the public against dangerous drugs.” Yet the FDA continues to approve new drugs within this class of chemotherapeutic agents, witnessed by the recent approval received by Oscient Pharmaceuticals for Factive(R). The FDA also provides “rubber stamp” approval of new indications for older drugs currently utilized in clinical practice today. Based upon these recent warnings one would hardly consider fluoroquinolones to be anything but a “dangerous drug”, one that the FDA allows to be marketed as a “safe and effective antibiotic with minimum side effects”. It appears that the statements being made by Dr. Galson are based upon political expediency, not fact. One also has to wonder why Factive(R) does not include the same detailed warnings one finds within the package inserts for the other drugs within this class, even though such adverse reactions are stated as being a “class effect”.

The Fluoroquinolone Toxicity Research Foundation has been providing documentation regarding these severe adverse reactions to Dr. Galson for years only to find that the FDA ignores such reports when approving these drugs. Dr. Jay S. Cohen released a study in 2001, which detailed the horrendous damage suffered for years on end by the patients afflicted with this disease state, peripheral neuropathy. The FDA was fully aware of Dr. Cohen’s study two years prior to approving Factive(R). Dr. Cohen’s study was conducted upon various members of one of the leading quinolone adverse drug reaction forums found on the Internet. Such adverse reactions had been reported on that forum since 1999 and continue unabated to date. (Cohen J.S., Peripheral Neuropathy with Fluoroquinolone Antibiotics. Annals of Pharmacotherapy, Dec. 001;35(12):1540-47.)