T-3811
  Garenoxacin
  Schering-Plough Europe
  Toyama Chemical

  No Package Insert Available
  Still undergoing regulatory approval
  Safety Profile: Lack of efficacy and unacceptable ADR profile
  DO NOT USE

http://www.emea.europa.eu/humandocs/PDFs/EPAR/garenoxacinmesylate/H-747-WAR.pdf

http://www.emea.europa.eu/humandocs/PDFs/EPAR/garenoxacinmesylate/34117407en.pdf

T-3811 (Garenoxacin) is a new type of oral and injectable quinolone antibacterial agent. It is called a des-fluoroquinolone, because it lacks a fluorine atom at the 6th position of the conventional quinolone structure. It shows potent antibacterial activity against various drug-resistant bacteria including MRSA (Methicillin-resistant Staphylococcus aureus) and PRSP (Penicillin-resistant Streptococcus pneumoniae), all of which are regarded as a serious problem in the field of infectious diseases. T-3811 has the same CNS related toxicity, phototoxicity and articular toxicity compared to existing drugs. In September 1998, Toyama Chemical granted Bristol-Myers Squibb (BMS), a major U.S. pharmaceutical company, the rights to develop and market the T-3811 worldwide (except Japan). In 2003, Toyama Chemical reacquired all rights from BMS. In June 2004, Toyama Chemical successfully concluded a licensing agreement for T-3811 with Schering-Plough, a major US pharmaceutical company. In Japan, Toyama Chemical has received a marketing approval for an oral formulations in July 2007. However such approval was NOT forthcoming in Europe

In view of the potentially fatal consequences of anaphylactic reactions to the fluoroquinolone class and other quinolones doctors should take care when prescribing these drugs.

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.
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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.
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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.