Levofloxacinside effects

The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling: Disabling and Potentially Irreversible Serious Adverse Reactions Tendinitis and Tendon Rupture Peripheral Neuropathy Central Nervous System Effects Exacerbation of Myasthenia Gravis Other Serious and Sometimes Fatal Reactions Hypersensitivity Reactions Hepatotoxicity Risk of Aortic Aneurysm and Dissection Clostridium difficile -Associated Diarrhea Prolongation of the QT Interval Musculoskeletal Disorders in Pediatric Patients Blood Glucose Disturbances Photosensitivity/Phototoxicity Development of Drug Resistant Bacteria Crystalluria and cylindruria have been reported with quinolones, including levofloxacin. Therefore, adequate hydration of patients receiving levofloxacin should be maintained to prevent the formation of a highly concentrated urine. The most common reactions (≥ 3%) were nausea, headache, diarrhea, insomnia, constipation and dizziness. To report SUSPECTED ADVERSE REACTIONS, contact Viona Pharmaceuticals Inc. at 1-888-304-5011 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to levofloxacin in 7,537 patients in 29 pooled Phase 3 clinical trials. The population studied had a mean age of 50 years (approximately 74% of the population was < 65 years of age), 50% were male, 71% were Caucasian, 19% were Black. Patients were treated with levofloxacin for a wide variety of infectious diseases. Patients received levofloxacin doses of 750 mg once daily, 250 mg once daily, or 500 mg once or twice daily. Treatment duration was usually 3 to 14 days, and the mean number of days on therapy was 10 days. The overall incidence, type and distribution of adverse reactions was similar in patients receiving levofloxacin doses of 750 mg once daily, 250 mg once daily, and 500 mg once or twice daily. Discontinuation of levofloxacin due to adverse drug reactions occurred in 4.3% of patients overall, 3.8% of patients treated with the 250 mg and 500 mg doses and 5.4% of patients treated with the 750 mg dose. The most common adverse drug reactions leading to discontinuation with the 250 and 500 mg doses were gastrointestinal (1.4%), primarily nausea (0.6%); vomiting (0.4%); dizziness (0.3%); and headache (0.2%). The most common adverse drug reactions leading to discontinuation with the 750 mg dose were gastrointestinal (1.2%), primarily nausea (0.6%), vomiting (0.5%); dizziness (0.3%); and headache (0.3%). Adverse reactions occurring in ≥ 1% of levofloxacin-treated patients and less common adverse reactions, occurring in 0.1 to < 1% of levofloxacin-treated patients, are shown in Table 4 and Table 5, respectively. The most common adverse drug reactions (≥ 3%) are nausea, headache, diarrhea, insomnia, constipation, and dizziness. Table4 Common ( ≥ 1%) Adverse Reactions Reported in Clinical Trials with Levofloxacin # * N = 7,274 † N=3,758 (women) # pool of studies included IV and oral administration System/Organ Class Adverse Reaction % (N=7,537) Infections and Infestations moniliasis 1 Psychiatric Disorders Insomnia * 4 Nervous System Disorders headache dizziness 6 3 Respiratory, Thoracic and Mediastinal Disorders dyspnea 1 Gastrointestinal Disorders nausea diarrhea constipation abdominal pain vomiting dyspepsia 7 5 3 2 2 2 Skin and Subcutaneous Tissue Disorders rash pruritus 2 1 Reproductive System and Breast Disorders vaginitis 1 † General Disorders and Administration Site Conditions edema injection site reaction chest pain 1 1 1 Table 5 Less Common (0.1 to 1%) Adverse Reactions Reported in Clinical Trials with Levofloxacin (N=7,537) * N = 7,274 System/Organ Class Adverse Reaction Infections and Infestations genital moniliasis Blood and Lymphatic System Disorders anemia thrombocytopenia granulocytopenia Immune System Disorders allergic reaction Metabolism and Nutrition Disorders hyperglycemia hypoglycemia hyperkalemia Psychiatric Disorders anxiety agitation confusion depression hallucination nightmare * sleep disorder * anorexia abnormal dreaming * Nervous System Disorders tremor convulsions paresthesia vertigo hypertonia hyperkinesias abnormal gait somnolence * syncope Respiratory, Thoracic and Mediastinal Disorders epistaxis Cardiac Disorders cardiac arrest palpitation ventricular tachycardia ventricular arrhythmia Vascular Disorders phlebitis Gastrointestinal Disorders gastritis stomatitis pancreatitis esophagitis gastroenteritis glossitis pseudomembranous/ C. difficile colitis Hepatobiliary Disorders abnormal hepatic function increased hepatic enzymes increased alkaline phosphatase Skin and Subcutaneous Tissue Disorders urticaria Musculoskeletal and Connective Tissue Disorders arthralgia tendinitis myalgia skeletal pain Renal and Urinary Disorders abnormal renal function acute renal failure In clinical trials using multiple-dose therapy, ophthalmologic abnormalities, including cataracts and multiple punctate lenticular opacities, have been noted in patients undergoing treatment with quinolones, including levofloxacin. The relationship of the drugs to these events is not presently established.

6.2 Postmarketing

Experience Table 6 lists adverse reactions that have been identified during post-approval use of levofloxacin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Table 6 Postmarketing Reports of Adverse Drug Reactions System/Organ Class Adverse Reaction Blood and Lymphatic System Disorders pancytopenia aplastic anemia leukopenia hemolytic anemia eosinophilia Immune System Disorders hypersensitivity reactions, sometimes fatal including: anaphylactic/anaphylactoid reactions anaphylactic shock angioneurotic edema serum sickness Psychiatric Disorders psychosis paranoia isolated reports of suicidal ideation, suicide attempt and completed suicide Nervous System Disorders exacerbation of myasthenia gravis anosmia ageusia parosmia dysgeusia peripheral neuropathy (may be irreversible) isolated reports of encephalopathy abnormal electroencephalogram (EEG) dysphonia pseudotumor cerebri Eye Disorders uveitis vision disturbance, including diplopia visual acuity reduced vision blurred scotoma Ear and Labyrinth Disorders hypoacusis tinnitus Cardiac Disorders isolated reports of torsade de pointes electrocardiogram QT prolonged tachycardia Acute myocardial ischemia with or without myocardial infarction occurring as part of an allergic reaction Vascular Disorders vasodilatation Respiratory, Thoracic and Mediastinal Disorders isolated reports of allergic pneumonitis Hepatobiliary Disorders hepatic failure (including fatal cases) hepatitis jaundice Skin and Subcutaneous Tissue Disorders bullous eruptions to include: Stevens-Johnson Syndrome toxic epidermal necrolysis Acute Generalized Exanthematous Pustulosis (AGEP) fixed drug eruptions erythema multiforme photosensitivity/phototoxicity reaction leukocytoclastic vasculitis Musculoskeletal and Connective Tissue Disorders tendon rupture muscle injury, including rupture rhabdomyolysis Renal and Urinary Disorders interstitial nephritis General Disorders and Administration Site Conditions multi-organ failure pyrexia Investigations prothrombin time prolonged international normalized ratio prolonged muscle enzymes increased