ADVERSE REACTIONS
The incidence of drug-related adverse reactions in patients during Phase 3 clinical trials conducted in North America was 6.2%. Among patients receiving levofloxacin therapy, 4.3% discontinued levofloxacin therapy due to adverse experiences. The overall incidence, type and distribution of adverse events was similar in patients receiving levofloxacin doses of 750 mg once daily compared to patients receiving doses from 250 mg once daily to 500 mg twice daily.
In clinical trials, the following events were considered likely to be drug-related in patients receiving levofloxacin:
nausea 1.2%, diarrhea 1.0%, vaginitis 0.6%, insomnia 0.4%, abdominal pain 0.4%, flatulence 0.3%, pruritus 0.3%, dizziness 0.3%, rash 0.3%, dyspepsia 0.2%, genital moniliasis 0.2%, moniliasis 0.2%, taste perversion 0.2%, vomiting 0.2%, injection site pain 0.2%, injection site reaction 0.2%, injection site inflammation 0.1%, constipation 0.1%, fungal infection 0.1%, genital pruritis 0.1%, headache 0.1%, nervousness 0.1%, rash erythematous 0.1%, urticaria 0.1% anorexia 0.1%, somnolence 0.1%, agitation 0.1%, rash maculopapular 0.1%, tremor 0.1%, condition aggravated 0.1%, allergic reaction 0.1%.
In clinical trials, the following events occurred in >3% of patients, regardless of drug relationship:
nausea 7.1%, headache 6.2%, diarrhea 5.5%, insomnia 5.1%, constipation 3.5%.
In clinical trials, the following events occurred in 1 to 3% of patients, regardless of drug relationship:
abdominal pain 2.7%,dizziness 2.5%, vomiting 2.5%, dyspepsia 2.3%, vaginitis 1.7%, rash 1.6%, chest pain 1.4%, pruritus 1.3%, sinusitis 1.3%, dyspnea 1.4%, fatigue 1.4%, flatulence 1.2%, pain 1.6%, back pain 1.2%, rhinitis 1.2%, anxiety 1.2%, pharyngitis 1.2%.
In clinical trials, the following events, of potential medical importance, occurred at a rate of 0.1% to 0.9%, regardless of drug relationship:
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Body as a Whole - General Disorders:
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Ascites, allergic reaction, asthenia, drug level increase, edema, enlarged abdomen, fever, headache, hot flashes, influenza-like symptoms, leg pain, malaise, rigors, substernal chest pain, syncope, multiple organ failure, changed temperature sensation, withdrawal syndrome
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Cardiovascular Disorders, General:
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Cardiac failure, hypertension, hypertension aggravated hypotension, postural hypotension
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Central and Peripheral Nervous System Disorders:
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Convulsions (seizures), dysphonia, hyperesthesia, hyperkinesia, hypertonia, hypoesthesia, involuntary muscle contractions, migraine, paresthesia, paralysis, speech disorder, stupor, tremor, vertigo, encephalopathy, abnormal gait, leg cramps, intracranial hypertension, ataxia
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Gastro-Intestinal System Disorders:
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Dry mouth, dysphagia, esophagitis, gastritis, gastroenteritis, gastroesophageal reflux, G.I. hemorrhage, glossitis, hemorrhoids, intestinal obstruction, pancreatitis, tongue edema, melena, stomatitis
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Hearing and Vestibular Disorders:
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Earache, tinnitus
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Heart Rate and Rhythm Disorders:
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Arrhythmia, arrhythmia ventricular, atrial fibrillation, bradycardia, cardiac arrest, ventricular fibrillation, heart block, palpitation, supraventricular tachycardia, ventricular tachycardia, tachycardia
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Liver and Biliary System Disorders:
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Abnormal hepatic function, cholecystitis, cholelithiasis, elevated bilirubin, hepatic enzymes increased, hepatic failure, jaundice
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Metabolic and Nutritional Disorders:
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Hypomagnesemia, thirst, dehydration, electrolyte abnormality, fluid overload, gout, hyperglycemia, hyperkalemia, hypernatremia, hypoglycemia, hypokalemia, hyponatremia, hypophosphatemia, nonprotein nitrogen increase, weight decrease
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Musculo-Skeletal System Disorders:
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Arthralgia, arthritis, arthrosis, myalgia, osteomyelitis, skeletal pain, synovitis, tendonitis, tendon disorder
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Myo, Endo, Pericardial and Valve Disorders:
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Angina pectoris, endocarditis, myocardial infarction
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Neoplasms:
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Carcinoma, thrombocythemia
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Other Special Senses Disorders:
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Parosmia, taste perversion
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Platelet, Bleeding and Clotting Disorders:
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Hematoma, epistaxis, prothrombin decreased, pulmonary embolism, purpura, thrombocytopenia
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Psychiatric Disorders:
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Abnormal dreaming, agitation, anorexia, confusion, depression, hallucination, impotence, nervousness, paroniria, sleep disorder, somnolence
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Red Blood Cell Disorders:
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Anemia
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Reproductive Disorders:
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Dysmenorrhea, leukorrhea
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Resistance Mechanism Disorders:
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Abscess, bacterial infection, fungal infection, herpes simplex, moniliasis, otitis media, sepsis, viral infection
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Respiratory System Disorders:
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Airways obstruction, aspiration, asthma, bronchitis, bronchospasm, chronic obstructive airway disease, coughing, hemoptysis, epistaxis, hypoxia, laryngitis, pharyngitis, pleural effusion, pleurisy, pneumonitis, pneumonia, pneumothorax, pulmonary collapse, pulmonary edema, respiratory depression, respiratory insufficiency, upper respiratory tract infection
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Skin and Appendages Disorders:
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Alopecia, bullous eruption, dry skin, eczema, genital pruritus, increased sweating, rash, skin exfoliation, skin ulceration, urticaria
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Urinary System Disorders:
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Abnormal renal function, acute renal failure, dysuria, hematuria, oliguria, urinary incontinence, urinary retention, urinary tract infection
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Vascular (Extracardiac) Disorders:
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Flushing, gangrene, phlebitis, purpura, thrombophlebitis (deep)
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Vision Disorders:
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Abnormal vision, eye pain, conjunctivitis
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White Cell and RES Disorders:
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Agranulocytosis, granulocytopenia, leukocytosis, lymphadenopathy
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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.
The following markedly abnormal laboratory values appeared in >2% of patients receiving levofloxacin. It is not known whether these abnormalities were caused by the drug or the underlying condition being treated.
Blood Chemistry: decreased glucose (2.2%)
Hematology: decreased lymphocytes (2.2%)
POST-MARKETING ADVERSE REACTIONS
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, Stevens-Johnson Syndrome, tendon rupture, torsades de pointes, vasodilation.
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