The incidence of drug-related adverse reactions in patients during Phase 3 clinical trials conducted in North America was 6.3%. Among patients receiving levofloxacin therapy, 3.9% discontinued levofloxacin therapy due to adverse experiences. The overall incidence, type and distribution of adverse events were 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 1.3%, diarrhea 1%, vaginitis 0.7%, insomnia 0.5%, abdominal pain 0.4%, flatulence 0.4%, pruritus 0.4%, dizziness 0.3%, dyspepsia 0.3%, rash 0.3%, genital moniliasis 0.2%, taste perversion 0.2%, vomiting 0.2%, constipation 0.1%, fungal infection 0.1%, genital pruritis 0.1%, headache 0.1%, moniliasis 0.1%, nervousness 0.1%, erythematous rash 0.1%, urticaria 0.1%.
In clinical trials, the following events occurred in >3%, regardless of drug relationship: Nausea 7.2%, headache 6.4%, diarrhea 5.6%, insomnia 4.6%, injection site reaction 3.5% and constipation 3.2%.
In clinical trials, the following events occurred in 1-3% of patients, regardless of drug relationship: Dizziness 2.7%, abdominal pain 2.5%, dyspepsia 2.4%, vomiting 2.3%, vaginitis 1.8%, injection site pain 1.7%, flatulence 1.5%, pain 1.4%, pruritus 1.3%, sinusitis 1.3%, chest pain 1.2%, fatigue 1.2%, rash 1.2%, back pain 1.1%, injection site inflammation 1.1%, rhinitis 1% and taste perversion 1%.
In clinical trials, the following events, of potential medical importance, occurred at a rate of <1%, regardless of drug relationship: Autonomic Nervous System Disorders:
Body as a Whole-General Disorders:
Asthenia, edema, fever, malaise, rigors, substernal chest pain and syncope.
General Cardiovascular Disorders:
Cardiac failure, circulatory failure, hypertension and hypotension.
Central and Peripheral Nervous System Disorders:
Abnormal coordination, coma, convulsions (seizures), hyperkinesia, hypertonia, hypoesthesia, involuntary muscle contractions, paresthesia, paralysis, speech disorder, stupor, tremor and vertigo.
Gastrointestinal System Disorders:
Dry mouth, dysphagia, gastroenteritis, G.I. hemorrhage, pancreatitis, pseudomembranous colitis and tongue edema.
Hearing and Vestibular Disorders:
Ear disorder (not otherwise specified) and tinnitus.
Heart Rate and Rhythm Disorders:
Arrhythmia, atrial fibrillation, bradycardia, cardiac arrest, heart block, palpitation, supraventricular tachycardia, tachycardia and ventricular fibrillation.
Liver and Biliary System Disorders:
Abnormal hepatic function, cholelithiasis, hepatic coma and jaundice.
Metabolic and Nutritional Disorders:
Aggravated diabetes mellitus, dehydration, hyperglycemia, hyperkalemia, hypoglycemia, hypokalemia, increased LDH and decreased weight.
Musculoskeletal System Disorders:
Arthralgia, arthritis, arthrosis, muscle weakness, myalgia, osteomyelitis, rhabdomyolysis, synovitis and tendinitis.
Myo-, Endo-, Pericardial and Valve Disorders:
Angina pectoris, coronary thrombosis and myocardial infarction.
Other Special Senses Disorders:
Platelet, Bleeding and Clotting Disorders:
Abnormal platelets, embolism (blood clot), epistaxis, purpura and thrombocytopenia.
Abnormal dreaming, aggressive reaction, agitation, anorexia, anxiety, confusion, delirium, depression, emotional lability, hallucination, impaired concentration, impotence, manic reaction, mental deficiency, nervousness, paranoia, sleep disorder, somnolence and withdrawal syndrome.
Red Blood Cell Disorders:
Resistance Mechanism Disorders:
Fungal infection and genital moniliasis.
Respiratory System Disorders:
ARDS, asthma, coughing, dyspnea, haemoptysis, hypoxia, pleural effusion and respiratory insufficiency.
Skin and Appendages Disorders:
Erythema nodosum, genital pruritus, increased sweating, skin disorder, skin exfoliation, skin ulceration and urticaria.
Urinary System Disorders:
Abnormal renal function, acute renal failure, face edema and haematuria.
Vascular (Extracardiac) Disorders:
Cerebrovascular disorder and phlebitis.
Abnormal vision, conjunctivitis and diplopia.
White Cell and RES Disorders:
Granulocytopenia, leukocytosis, leukopenia, lymphadenopathy, abnormal WBC (not otherwise specified).
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 laboratory abnormalities appeared in 2.2% of patients receiving levofloxacin. It is not known whether these abnormalities were caused by the drug or the underlying condition being treated.
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, multisystem organ failure, increased International Normalized Ratio (INR)/prothrombin time, Stevens-Johnson syndrome, tendon rupture, torsade de pointes and vasodilation, Exacerbation of myasthenia gravis.