FDA label ceb7e4db-8aa2-eade-e053-2995a90a04ec

WARNING: SERIOUS ADVERSE REACTIONS INCLUDING TENDINITIS, TENDON RUPTURE, PERIPHERAL NEUROPATHY, CENTRAL NERVOUS SYSTEM EFFECTS AND EXACERBATION OF MYASTHENIA GRAVIS Fluoroquinolones, including ofloxacin, have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together, including: Tendinitis and tendon rupture Peripheral neuropathy Central nervous system effects (see WARNINGS ) Discontinue ofloxacin immediately and avoid the use of fluoroquinolones, including ofloxacin, in patients who experience any of these serious adverse reactions (see WARNINGS ). Fluoroquinolones, including ofloxacin, may exacerbate muscle weakness in persons with myasthenia gravis. Avoid ofloxacin in patients with known history of myasthenia gravis (see WARNINGS ). Because fluoroquinolones, including ofloxacin, have been associated with serious adverse reactions (see WARNINGS ), reserve ofloxacin for use in patients who have no alternative treatment options for the following indications: Acute exacerbation of chronic bronchitis Uncomplicated cystitis (see INDICATIONS AND USAGE )

WARNINGS Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and Tendon Rupture, Peripheral Neuropathy, and Central Nervous System Effects: Fluoroquinolones, including ofloxacin, have been associated with disabling and potentially irreversible serious adverse reactions from different body systems that can occur together in the same patient. Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion). These reactions can occur within hours to weeks after starting ofloxacin. Patients of any age or without pre-existing risk factors have experienced these adverse reactions (see WARNINGS ) Discontinue ofloxacin immediately at the first signs or symptoms of any serious adverse reaction. In addition, avoid the use of fluoroquinolones, including ofloxacin, in patients who have experienced any of these serious adverse reactions associated with fluoroquinolones. Tendinitis and Tendon Rupture: Fluoroquinolones, including ofloxacin, have been associated with an increased risk of tendinitis and tendon rupture in all ages. This adverse reaction most frequently involves the Achilles tendon, and rupture of the Achilles tendon and has been reported with the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendons. Tendinitis or tendon rupture can occur within hours or days of starting ofloxacin, or as long as several months after completion of fluoroquinolone therapy. Tendinitis and tendon rupture can occur bilaterally. The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in patients over 60 years of age, in those taking corticosteroid drugs, and in patients with kidney, heart or lung transplants. Other factors that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. Tendinitis and tendon rupture have been reported in patients taking fluoroquinolones who do not have the above risk factors. Discontinue ofloxacin immediately if the patient experiences pain, swelling, inflammation or rupture of a tendon. Avoid fluoroquinolones, including ofloxacin, in patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture (see ADVERSE REACTIONS ). Patients should be advised to rest at the first sign of tendinitis or tendon rupture, and to contact their healthcare provider regarding changing to a non-quinolone antimicrobial drug. Peripheral Neuropathy: Fluoroquinolones, including ofloxacin, have been associated with an increased risk of 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 fluoroquinolones, including ofloxacin. Symptoms may occur soon after initiation of norfloxacin and may be irreversible in some patients (see WARNINGS ). Discontinue ofloxacin immediately if the patient experiences symptoms of peripheral neuropathy including pain, burning, tingling, numbness, and/or weakness, or other alterations in sensations including light touch, pain, temperature, position sense and vibratory sensation, and/or motor strength in order to minimize the development of an irreversible condition. Avoid fluoroquinolones, including ofloxacin, in patients who have previously experienced peripheral neuropathy (see ADVERSE REACTIONS ). Central Nervous System Effects: Psychiatric Adverse Reactions: Fluoroquinolones, including ofloxacin, have been associated with an increased risk of psychiatric adverse reactions, including toxic psychoses or hallucinations; agitation; delirium, confusion, disorientation, or disturbances in attention; nervousness or restlessness, memory impairment. If these reactions occur in patients receiving ofloxacin, the drug should be discontinued and appropriate measures instituted. Central Nervous System Adverse Reactions: Fluoroquinolones have been associated with an increased risk of seizures (convulsions), increased intracranial pressure (pseudotumor cerebri), lightheadedness, or tremors. The effects of ofloxacin on brain function or on the electrical activity of the brain have not been tested. Therefore, until more information becomes available, ofloxacin, like all other quinolones, should be used with caution in patients with known or suspected CNS disorders, such as severe cerebral arteriosclerosis, epilepsy, and other factors which predispose to seizures (see ADVERSE REACTIONS ). Exacerbation of Myasthenia Gravis: Fluoroquinolones, including ofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in persons with myasthenia gravis. Postmarketing serious adverse events, including deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in persons with myasthenia gravis. Avoid ofloxacin in patients with known history of myasthenia gravis (see PRECAUTIONS, Information for Patients , and ADVERSE REACTIONS, Postmarketing Adverse Events ). THE SAFETY AND EFFICACY OF OFLOXACIN IN PEDIATRIC PATIENTS AND ADOLESCENTS (UNDER THE AGE OF 18 YEARS), PREGNANT WOMEN, AND LACTATING WOMEN HAVE NOT BEEN ESTABLISHED (see PRECAUTIONS, Pediatric Use , Pregnancy , and Nursing Mothers Subsections). In the immature rat, the oral administration of ofloxacin at 5 to 16 times the recommended maximum human dose based on mg/kg or 1 to 3 times based on mg/m 2 increased the incidence and severity of osteochondrosis. The lesions did not regress after 13 weeks of drug withdrawal. Other quinolones also produce similar erosions in the weight-bearing joints and other signs of arthropathy in immature animals of various species (see ANIMAL PHARMACOLOGY ). Hypersensitivity Reactions: Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions have been reported in patients receiving therapy with quinolones, including ofloxacin. These reactions often occur following the first dose. Some reactions have been accompanied by cardiovascular collapse, hypotension/shock, seizure, loss of consciousness, tingling, angioedema (including tongue, laryngeal, throat, or facial edema/swelling), airway obstruction (including bronchospasm, shortness of breath, and acute respiratory distress), dyspnea, urticaria, itching, and other serious skin reactions. This drug should be discontinued immediately at the first appearance of a skin rash or any other sign of hypersensitivity. Serious acute hypersensitivity reactions may require treatment with epinephrine and other resuscitative measures, including oxygen, intravenous fluids, antihistamines, corticosteroids, pressor amines, and airway management, as clinically indicated (see PRECAUTIONS and ADVERSE REACTIONS ). Other serious and sometimes fatal events, some due to hypersensitivity, and some due to uncertain etiology, have been reported rarely in patients receiving therapy with quinolones, including ofloxacin. These events may be severe and generally occur following the administration of multiple doses. Clinical manifestations may include one or more of the following: fever, rash, or severe dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome); vasculitis; arthralgia; myalgia; serum sickness; allergic pneumonitis; interstitial nephritis; acute renal insufficiency or failure; hepatitis; jaundice; acute hepatic necrosis or failure; anemia, including hemolytic and aplastic; thrombocytopenia, including thrombotic thrombocytopenic purpura; leukopenia; agranulocytosis; pancytopenia; and/or other hematologic abnormalities. The drug should be discontinued immediately at the first appearance of skin rash, jaundice, or any other sign of hypersensitivity and supportive measures instituted (see PRECAUTIONS, Information for Patients and ADVERSE REACTIONS ). Risk of Aortic Aneurysm and Dissection Epidemiologic studies report an increased rate of aortic aneurysm and dissection within two months following use of fluoroquinolones, particularly in elderly patients. The cause for the increased risk has not been identified. In patients with a known aortic aneurysm or patients who are at greater risk for aortic aneurysms, reserve OFLOXACIN for use only when there are no alternative antibacterial treatments available. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including ofloxacin tablets, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated (see ADVERSE REACTIONS ). Ofloxacin has not been shown to be effective in the treatment of syphilis. Fluoroquinolones have been associated with disturbances of blood glucose, including symptomatic hyperglycemia and hypoglycemia, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (e.g., glyburide) or with insulin. In these patients, careful monitoring of blood glucose is recommended. Severe cases of hypoglycemia resulting in coma or death have been reported. If a hypoglycemic reaction occurs in a patient being treated with ofloxacin, discontinue ofloxacin and initiate appropriate therapy immediately. Antimicrobial agents used in high doses for short periods of time to treat gonorrhea may mask or delay the symptoms of incubating syphilis. All patients with gonorrhea should have a serologic test for syphilis at the time of diagnosis. Patients treated with ofloxacin for gonorrhea should have a follow-up serologic test for syphilis after three months and, if positive, treatment with an appropriate antimicrobial should be instituted.

ADVERSE REACTIONS The following is a compilation of the data for ofloxacin based on clinical experience with both the oral and intravenous formulations. The incidence of drug-related adverse reactions in patients during Phase 2 and 3 clinical trials was 11%. Among patients receiving multiple-dose therapy, 4% discontinued ofloxacin due to adverse experiences. In clinical trials, the following events were considered likely to be drug-related in patients receiving multiple doses of ofloxacin: nausea 3%, insomnia 3%, headache 1%, dizziness 1%, diarrhea 1%, vomiting 1%, rash 1%, pruritus 1%, external genital pruritus in women 1%, vaginitis 1%, dysgeusia 1%. In clinical trials, the most frequently reported adverse events, regardless of relationship to drug, were: nausea 10%, headache 9%, insomnia 7%, external genital pruritus in women 6%, dizziness 5%, vaginitis 5%, diarrhea 4%, vomiting 4%. In clinical trials, the following events, regardless of relationship to drug, occurred in 1 to 3% of patients: abdominal pain and cramps, chest pain, decreased appetite, dry mouth, dysgeusia, fatigue, flatulence, gastrointestinal distress, nervousness, pharyngitis, pruritus, fever, rash, sleep disorders, somnolence, trunk pain, vaginal discharge, visual disturbances, and constipation. Additional events, occurring in clinical trials at a rate of less than 1%, regardless of relationship to drug, were: Body as a Whole: asthenia, chills, malaise, extremity pain, pain, epistaxis Cardiovascular System: cardiac arrest, edema, hypertension, hypotension, palpitations, vasodilation Gastrointestinal System: dyspepsia Genital/Reproductive System: burning, irritation, pain and rash of the female genitalia; dysmenorrhea; menorrhagia; metrorrhagia Musculoskeletal System: arthralgia, myalgia Nervous System: seizures, anxiety, cognitive change, depression, dream abnormality, euphoria, hallucinations, paresthesia, syncope, vertigo, tremor, confusion Nutritional/Metabolic: thirst, weight loss Respiratory System: respiratory arrest, cough, rhinorrhea Skin/Hypersensitivity: angioedema, diaphoresis, urticaria, vasculitis Special Senses: decreased hearing acuity, tinnitus, photophobia Urinary System: dysuria, urinary frequency, urinary retention The following laboratory abnormalities appeared in ≥ 1.0% of patients receiving multiple doses of ofloxacin. It is not known whether these abnormalities were caused by the drug or the underlying conditions being treated. Hematopoietic: anemia, leukopenia, leukocytosis, neutropenia, neutrophilia, increased band forms, lymphocytopenia, eosinophilia, lymphocytosis, thrombocytopenia, thrombocytosis, elevated ESR Hepatic: elevated: alkaline phosphatase, AST (SGOT), ALT (SGPT) Serum Chemistry: hyperglycemia, hypoglycemia, elevated creatinine, elevated BUN Urinary: glucosuria, proteinuria, alkalinuria, hyposthenuria, hematuria, pyuria Postmarketing Adverse Events Additional adverse events, regardless of relationship to drug, reported from worldwide marketing experience with quinolones, including ofloxacin: Clinical Cardiovascular System: cerebral thrombosis, pulmonary edema, tachycardia, hypotension/shock, syncope, torsades de pointes Endocrine/Metabolic: hyper- or hypoglycemia, especially in diabetic patients on insulin or oral hypoglycemic agents (see PRECAUTIONS, General and Drug Interactions ). Gastrointestinal System: hepatic dysfunction including: hepatic necrosis, jaundice (cholestatic or hepatocellular), hepatitis; intestinal perforation; hepatic failure (including fatal cases); pseudomembranous colitis (the onset of pseudomembranous colitis symptoms may occur during or after antimicrobial treatment), GI hemorrhage; hiccough, painful oral mucosa, pyrosis (see WARNINGS ). Genital/Reproductive System: vaginal candidiasis Hematopoietic: anemia, including hemolytic and aplastic; hemorrhage, pancytopenia, agranulocytosis, leukopenia, reversible bone marrow depression, thrombocytopenia, thrombotic thrombocytopenic purpura, petechiae, ecchymosis/bruising (see WARNINGS ) . Musculoskeletal: tendinitis/ rupture; weakness; rhabdomyolysis (see WARNINGS ). Nervous System: nightmares; suicidal thoughts or acts, disorientation, psychotic reactions, paranoia; phobia, agitation, restlessness, aggressiveness/hostility, manic reaction, emotional lability; peripheral neuropathy that may be irreversible, ataxia, incoordination; exacerbation of myasthenia gravis and extrapyramidal disorders; dysphasia, lightheadedness (see WARNINGS and PRECAUTIONS ). Respiratory System: dyspnea, bronchospasm, allergic pneumonitis, stridor (see WARNINGS ). Skin/Hypersensitivity: anaphylactic (-toid) reactions/shock; purpura, serum sickness, erythema multiforme/Stevens-Johnson syndrome, erythema nodosum, exfoliative dermatitis, hyperpigmentation, toxic epidermal necrolysis, conjunctivitis, photosensitivity/phototoxicity reaction, vesiculobullous eruption (see WARNINGS and PRECAUTIONS ). Special Senses: diplopia, nystagmus, blurred vision, disturbances of: taste, smell, hearing and equilibrium, usually reversible following discontinuation Urinary System: anuria, polyuria, renal calculi, renal failure, interstitial nephritis, hematuria (see WARNINGS and PRECAUTIONS ). Laboratory Hematopoietic: prolongation of prothrombin time Serum Chemistry: acidosis, elevation of: serum triglycerides, serum cholesterol, serum potassium, liver function tests including: GGTP, LDH, bilirubin Urinary: albuminuria, candiduria In clinical trials using multiple-dose therapy, ophthalmologic abnormalities, including cataracts and multiple punctate lenticular opacities, have been noted in patients undergoing treatment with other quinolones. The relationship of the drugs to these events is not presently established. CRYSTALLURIA and CYLINDRURIA HAVE BEEN REPORTED with other quinolones.

<table width="80%"><col width="20%" align="left" valign="top"/><col width="80%" align="left" valign="top"/><tbody><tr><td align="left" valign="top">Body as a Whole:</td><td align="left" valign="top">asthenia, chills, malaise, extremity pain, pain, epistaxis</td></tr><tr><td align="left" valign="top">Cardiovascular System:</td><td align="left" valign="top">cardiac arrest, edema, hypertension, hypotension, palpitations, vasodilation</td></tr><tr><td align="left" valign="top">Gastrointestinal System:</td><td align="left" valign="top">dyspepsia</td></tr><tr><td align="left" valign="top">Genital/Reproductive System:</td><td align="left" valign="top">burning, irritation, pain and rash of the female genitalia; dysmenorrhea; menorrhagia; metrorrhagia</td></tr><tr><td align="left" valign="top">Musculoskeletal System:</td><td align="left" valign="top">arthralgia, myalgia</td></tr><tr><td align="left" valign="top">Nervous System:</td><td align="left" valign="top">seizures, anxiety, cognitive change, depression, dream abnormality, euphoria, hallucinations, paresthesia, syncope, vertigo, tremor, confusion</td></tr><tr><td align="left" valign="top">Nutritional/Metabolic:</td><td align="left" valign="top">thirst, weight loss</td></tr><tr><td align="left" valign="top">Respiratory System:</td><td align="left" valign="top">respiratory arrest, cough, rhinorrhea</td></tr><tr><td align="left" valign="top">Skin/Hypersensitivity:</td><td align="left" valign="top">angioedema, diaphoresis, urticaria, vasculitis</td></tr><tr><td align="left" valign="top">Special Senses:</td><td align="left" valign="top">decreased hearing acuity, tinnitus, photophobia</td></tr><tr><td align="left" valign="top">Urinary System:</td><td align="left" valign="top">dysuria, urinary frequency, urinary retention</td></tr></tbody></table>

<table width="80%"><col width="20%" align="left" valign="top"/><col width="80%" align="left" valign="top"/><tbody><tr><td align="left" valign="top">Hematopoietic:</td><td align="left" valign="top">anemia, leukopenia, leukocytosis, neutropenia, neutrophilia, increased band forms, lymphocytopenia, eosinophilia, lymphocytosis, thrombocytopenia, thrombocytosis, elevated ESR</td></tr><tr><td align="left" valign="top">Hepatic:</td><td align="left" valign="top">elevated: alkaline phosphatase, AST (SGOT), ALT (SGPT)</td></tr><tr><td align="left" valign="top">Serum Chemistry:</td><td align="left" valign="top">hyperglycemia, hypoglycemia, elevated creatinine, elevated BUN</td></tr><tr><td align="left" valign="top">Urinary:</td><td align="left" valign="top">glucosuria, proteinuria, alkalinuria, hyposthenuria, hematuria, pyuria</td></tr></tbody></table>

<table width="80%"><col width="20%" align="left" valign="top"/><col width="80%" align="left" valign="top"/><tbody><tr><td align="left" valign="top">Cardiovascular System:</td><td align="left" valign="top">cerebral thrombosis, pulmonary edema, tachycardia, hypotension/shock, syncope, torsades de pointes</td></tr><tr><td align="left" valign="top">Endocrine/Metabolic:</td><td align="left" valign="top">hyper- or hypoglycemia, especially in diabetic patients on insulin or oral hypoglycemic agents (see <content styleCode="bold"><linkHtml href="#b16c32c4-d306-4403-bcaa-d0dda2b661b5">PRECAUTIONS, General</linkHtml></content> and <content styleCode="bold"><linkHtml href="#b44320d0-3606-44fc-a036-33cf8a18219a">Drug Interactions</linkHtml></content>). </td></tr><tr><td align="left" valign="top">Gastrointestinal System:</td><td align="left" valign="top">hepatic dysfunction including: hepatic necrosis, jaundice (cholestatic or hepatocellular), hepatitis; intestinal perforation; hepatic failure (including fatal cases); pseudomembranous colitis (the onset of pseudomembranous colitis symptoms may occur during or after antimicrobial treatment), GI hemorrhage; hiccough, painful oral mucosa, pyrosis (see <content styleCode="bold"><linkHtml href="#b6fbee55-cac4-4da2-8a92-cb40fe6c933d">WARNINGS</linkHtml></content>). </td></tr><tr><td align="left" valign="top">Genital/Reproductive System:</td><td align="left" valign="top">vaginal candidiasis</td></tr><tr><td align="left" valign="top">Hematopoietic:</td><td align="left" valign="top">anemia, including hemolytic and aplastic; hemorrhage, pancytopenia, agranulocytosis, leukopenia, reversible bone marrow depression, thrombocytopenia, thrombotic thrombocytopenic purpura, petechiae, ecchymosis/bruising (see <content styleCode="bold"><linkHtml href="#b6fbee55-cac4-4da2-8a92-cb40fe6c933d">WARNINGS</linkHtml></content><content styleCode="bold">)</content>. </td></tr><tr><td align="left" valign="top">Musculoskeletal:</td><td align="left" valign="top">tendinitis/ rupture; weakness; rhabdomyolysis (see <content styleCode="bold"><linkHtml href="#b6fbee55-cac4-4da2-8a92-cb40fe6c933d">WARNINGS</linkHtml></content>). </td></tr><tr><td align="left" valign="top">Nervous System:</td><td align="left" valign="top">nightmares; suicidal thoughts or acts, disorientation, psychotic reactions, paranoia; phobia, agitation, restlessness, aggressiveness/hostility, manic reaction, emotional lability; peripheral neuropathy that may be irreversible, ataxia, incoordination; exacerbation of myasthenia gravis and extrapyramidal disorders; dysphasia, lightheadedness (see <content styleCode="bold"><linkHtml href="#b6fbee55-cac4-4da2-8a92-cb40fe6c933d">WARNINGS</linkHtml></content> and <content styleCode="bold"><linkHtml href="#b2354818-06b5-48c0-9e3d-39a7fa90c73e">PRECAUTIONS</linkHtml></content>). </td></tr><tr><td align="left" valign="top">Respiratory System:</td><td align="left" valign="top">dyspnea, bronchospasm, allergic pneumonitis, stridor (see <content styleCode="bold"><linkHtml href="#b6fbee55-cac4-4da2-8a92-cb40fe6c933d">WARNINGS</linkHtml></content>). </td></tr><tr><td align="left" valign="top">Skin/Hypersensitivity:</td><td align="left" valign="top">anaphylactic (-toid) reactions/shock; purpura, serum sickness, erythema multiforme/Stevens-Johnson syndrome, erythema nodosum, exfoliative dermatitis, hyperpigmentation, toxic epidermal necrolysis, conjunctivitis, photosensitivity/phototoxicity reaction, vesiculobullous eruption (see <content styleCode="bold"><linkHtml href="#b6fbee55-cac4-4da2-8a92-cb40fe6c933d">WARNINGS</linkHtml></content> and <content styleCode="bold"><linkHtml href="#b2354818-06b5-48c0-9e3d-39a7fa90c73e">PRECAUTIONS</linkHtml></content>). </td></tr><tr><td align="left" valign="top">Special Senses:</td><td align="left" valign="top">diplopia, nystagmus, blurred vision, disturbances of: taste, smell, hearing and equilibrium, usually reversible following discontinuation</td></tr><tr><td align="left" valign="top">Urinary System:</td><td align="left" valign="top">anuria, polyuria, renal calculi, renal failure, interstitial nephritis, hematuria (see <content styleCode="bold"><linkHtml href="#b6fbee55-cac4-4da2-8a92-cb40fe6c933d">WARNINGS</linkHtml></content> and <content styleCode="bold"><linkHtml href="#b2354818-06b5-48c0-9e3d-39a7fa90c73e">PRECAUTIONS</linkHtml></content>). </td></tr></tbody></table>