Phase 3 clinical trials Levaquin

ADVERSE REACTIONS

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 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 1.3%, diarrhea 1.0%, 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%, rash erythematous 0.1%, urticaria 0.1%.

In clinical trials, the following events occurred in >3% of patients, regardless of drug relationship:
nausea 7.2%, headache 6.4%, diarrhea 5.6%, insomnia 4.6%, injection site reaction 3.5%, constipation 3.2%.

In clinical trials, the following events occurred in 1 to 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 1.0%, taste perversion 1.0%.

In clinical trials, the following events, of potential medical importance, occurred at a rate of less than 1.0% regardless of drug
relationship:

Autonomic Nervous System Disorders: postural hypotension

Body as a Whole - General Disorders: asthenia, edema, fever, malaise, rigors, substernal chest pain, syncope

Cardiovascular Disorders, General: cardiac failure, circulatory failure, hypertension, hypotension

Central and Peripheral Nervous System Disorders: abnormal coordination, coma, convulsions (seizures), hyperkinesia, hyperto-nia, hypoaesthesia, involuntary muscle contractions, paresthesia, paralysis, speech disorder, stupor, tremor, vertigo

Gastro-Intestinal System Disorders: dry mouth, dysphagia, gastroenteritis, G.I. hemorrhage, pancreatitis, pseudomembranous colitis, tongue edema

Hearing and Vestibular Disorders: ear disorder (not otherwise specified), tinnitus

Heart Rate and Rhythm Disorders: arrhythmia, atrial fibrillation, bradycardia, cardiac arrest, heart block, palpita-tion, supraventricular tachycardia, tachycardia, ventricular fibrillation

Liver and Biliary System Disorders: abnormal hepatic function, cholelithiasis, hepatic coma, jaundice

Metabolic and Nutritional Disorders: aggravated diabetes mellitus, dehydration, hyperglycemia, hyperkalemia, hypoglycemia, hypokalemia, increased LDH, weight decrease

Musculo-Skeletal System Disorders: arthralgia, arthritis, arthrosis, muscle weakness, myalgia, osteomyelitis, rhab-domyolysis, synovitis, tendinitis

Myo, Endo, Pericardial and Valve Disorders: angina pectoris, coronary thrombosis, myocardial infarction

Neoplasms: carcinoma

Other Special Senses Disorders: parosmia

Platelet, Bleeding and Clotting Disorders: abnormal platelets, embolism (blood clot), epistaxis, purpura, thrombocytopenia

Psychiatric Disorders: abnormal dreaming, aggressive reaction, agitation, anorexia, anxiety, confu-sion, delirium, depression, emotional lability, hallucination, impaired concen-tration, impotence, manic reaction, mental deficiency, nervousness, paranoia, sleep disorder, somnolence, withdrawal syndrome
 
Red Blood Cell Disorders: anemia

Reproductive Disorders: ejaculation failure

Resistance Mechanism Disorders: fungal infection, genital moniliasis

Respiratory System Disorders: ARDS, asthma, coughing, dyspnea, haemoptysis, hypoxia, pleural effusion, respiratory insufficiency

Skin and Appendages Disorders: erythema nodosum, genital pruritus, increased sweating, skin disorder, skin exfoliation, skin ulceration, urticaria

Urinary System Disorders: abnormal renal function, acute renal failure, face edema, haematuria

Vascular (Extracardiac) Disorders: cerebrovascular disorder, phlebitis

Vision Disorders: abnormal vision, conjunctivitis, diplopia
White Cell and RES Disorders: granulocytopenia, leukocytosis, leukopenia, lymphadenopathy, WBC abnor-mal (not otherwise specified)
 

In clinical trials using multiple-dose therapy, ophthalmologic abnormalities, including cataracts and multiple punctate lentic-ular 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.
 
Blood Chemistry: decreased glucose

Hematology: decreased lymphocytes

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.