Rebuttal:

FDA Grants Approval for New Oral Solution of LEVAQUIN (R) in spite of being associated with irreversible Peripheral Neuropathy

Ortho-McNeil Pharmaceutical, Inc., in a recent press release, proudly announced the recent FDA approval of new, once-a-day formulation of Levaquinâ (levofloxacin).  Within this same press release the following statement is made: "LEVAQUIN has demonstrated safety and a low incidence of gastrointestinal and central nervous system adverse events: nausea (1.2%), diarrhea (1.0%), insomnia (0.4%), dizziness (0.3%)." (Source: Ortho-McNeil Pharmaceutical, Inc. Press Release, October 28, 2004, RARITAN, N.J., PRNewswire)

"LEVAQUIN has demonstrated safety and a low incidence of …central nervous system adverse events"

Within the package insert it is stated:
"…Convulsions and toxic psychoses have been reported in patients receiving quinolones, including levofloxacin. Quinolones may also cause increased intracranial pressure and central nervous system stimulation which may lead to tremors, restlessness, anxiety, lightheadedness, confusion, hallucinations, paranoia, depression, nightmares, insomnia, and, rarely, suicidal thoughts or acts. These reactions may occur following the first dose…" (emphasis added)
(Source: Package Insert for Levaquin: OMP DIVISION ORTHO-McNEIL PHARMACEUTICAL, INC. Raritan, New Jersey, USA 08869 U.S. Patent No. 5,053,407. Revised July 2004)

"LEVAQUIN has demonstrated safety and a low incidence of gastrointestinal…adverse events…"

Within the package insert it is stated:
"Pseudomembranous colitis has been reported with nearly all antibacterial agents, including levofloxacin, 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 one primary cause of "antibiotic-associated colitis."…"
(Source: Package Insert for Levaquin: OMP DIVISION ORTHO-McNEIL PHARMACEUTICAL, INC. Raritan, New Jersey, USA 08869 U.S. Patent No. 5,053,407. Revised July 2004)

No mention was made within this press release regarding irreversible damage to the peripheral nervous system as stated within the package insert:

"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." (emphasis added)
And the patient should be advised:
"…that peripheral neuropathies have been associated with levofloxacin use. If symptoms of peripheral neuropathy including pain, burning, tingling, adverse events numbness, and/or weakness develop, they should discontinue treatment and contact their physicians…"
(Source: Package Insert for Levaquin: OMP DIVISION ORTHO-McNEIL PHARMACEUTICAL, INC. Raritan, New Jersey, USA 08869 U.S. Patent No. 5,053,407. Revised July 2004)

No mention was made within this press release regarding spontaneous tendon rupture, which may occur both during and after therapy that resulted in prolonged disability as stated within the package insert:

"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 levofloxacin. Post-marketing surveillance reports indicate that this risk may be increased in patients receiving concomitant corticosteroids, especially 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 tendonitis or tendon rupture has been confidently excluded. Tendon rupture can occur during or after therapy with quinolones, including levofloxacin."
(Source: Package Insert for Levaquin: OMP DIVISION ORTHO-McNEIL PHARMACEUTICAL, INC. Raritan, New Jersey, USA 08869 U.S. Patent No. 5,053,407. Revised July 2004)

No mention was made within this press release regarding Torsades de pointes being a potentially life threatening cardiovascular disorder as stated within the package insert:

"Torsades de pointes: Some quinolones, including levofloxacin, 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 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."(emphasis added)
(Source: Package Insert for Levaquin: OMP DIVISION ORTHO-McNEIL PHARMACEUTICAL, INC. Raritan, New Jersey, USA 08869 U.S. Patent No. 5,053,407. Revised July 2004)

No mention was made within this press release regarding 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.
(emphasis added)
(Source: Package Insert for Levaquin: OMP DIVISION ORTHO-McNEIL PHARMACEUTICAL, INC. Raritan, New Jersey, USA 08869 U.S. Patent No. 5,053,407. Revised July 2004)

Perhaps these deliberate deletions would help explain why, when a patient presents with these adverse drug reactions he or she is told by the treating physician "…It cannot be the drug, this is a safe and effective antibiotic with a minimum of side effects…".. The various manufacturers have done a great disservice both to the patient and the physician by their failure to provide adequate warnings regarding the above mentioned adverse drug reactions VIA the issuing of a "Dear Doctor" letter when they were first made aware of such serious adverse reactions associated with fluoroquinolone therapy. Ortho-McNeil Pharmaceutical, Inc., fails to provide adequate warnings regarding irreversible disease states such as Peripheral Neuropathy as well as potentially fatal reactions such as Rhabdomyolysis, Pseudomembranous Colitis, Steven Johnson Syndrome, Torsades de Pointes within their press release but instead appears to be using the statement "LEVAQUIN has demonstrated safety and a low incidence of gastrointestinal and central nervous system adverse events: nausea (1.2%), diarrhea (1.0%), insomnia (0.4%), dizziness(0.3%)…" in an effort to minimize the serious, crippling, irreversible, and at times fatal adverse drug reactions associated with their product.

The patient remains at considerable risk for the duration as the direct result of such malfeasance. 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. 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.  Fluoroquinolones are NOT to be considered a first line agent but a drug of last resort when all else fails.  The press release of Ortho-McNeil Pharmaceutical, Inc., 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.  Apparently the FDA finds this to be totally acceptable behavior.  Those whose lives have been destroyed, having failed to receive such warnings, do not.