Levofloxacin is indicated in pediatric patients (6 months of age and older) only for the prevention of inhalational anthrax (post-exposure) and for plague [see Indications and Usage (1.7, 1.8)]. An increased incidence of musculoskeletal disorders (arthralgia, arthritis, tendinopathy, and gait abnormality) compared to controls has been observed in pediatric patients receiving levofloxacin [see Use in S pecific Populations (8.4)].
In immature rats and dogs, the oral and intravenous administration of levofloxacin resulted in increased osteochondrosis. Histopathological examination of the weight-bearing joints of immature dogs dosed with levofloxacin revealed persistent lesions of the cartilage. Other fluoroquinolones also produce similar erosions in the weight-bearing joints and other signs of arthropathy in immature animals of various species [see Animal Toxicology and/or Pharmacology (13.2)].
Fluoroquinolones, including levofloxacin, 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 levofloxacin, discontinue levofloxacin and initiate appropriate therapy immediately [see Adverse Reactions (6.2), D rug Interactions (7.3) and P atient Counseling Information (17)].
Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions (e.g., burning, erythema, exudation, vesicles, blistering, edema) involving areas exposed to light (typically the face, “V” area of the neck, extensor surfaces of the forearms, dorsa of the hands), can be associated with the use of fluoroquinolones after sun or UV light exposure. Therefore, excessive exposure to these sources of light should be avoided. Drug therapy should be discontinued if photosensitivity/phototoxicity occurs [see A dverse Reactions (6.3) and Patient Counseling Information (17)].
Prescribing levofloxacin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria [see Patient Counseling Information (17)].
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 [see Warnings and Precautions (5.1)]
- Tendinitis and Tendon Rupture [see Warnings and Precautions (5.2)]
- Peripheral Neuropathy [see Warnings and Precautions (5.3)]
- Central Nervous System Effects [see Warnings and Precautions (5.4)]
- Exacerbation of Myasthenia Gravis [see Warnings and Precautions (5.5)]
- Other Serious and Sometimes Fatal Reactions [see Warnings and Precautions (5.6)]
- Hypersensitivity Reactions [see Warnings and Precautions (5.7)]
- Hepatotoxicity [see Warnings and Precautions (5.8)]
- Risk of Aortic Aneurysm and Dissection [see Warnings and Precautions (5.9)]
- Clostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.10)]
- Prolongation of the QT Interval [see Warnings and Precautions (5.11)]
- Musculoskeletal Disorders in Pediatric Patients [see Warnings and Precautions (5.12)]
- Blood Glucose Disturbances [see Warnings and Precautions (5.13)]
- Photosensitivity/Phototoxicity [see Warnings and Precautions (5.14)]
- Development of Drug Resistant Bacteria [see Warnings and Precautions (5.15)]
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 [see Dosage and Administration (2.5)] .
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 7537 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 [see Indications and Usage (1)]. 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.
|* N = 7274† N = 3758 (women)|
|System/Organ Class||Adverse Reaction||% (N = 7537)|
|Infections and Infestations||moniliasis||1|
|Psychiatric Disorders||insomnia* [see Warnings and Precautions (5.4)]||4|
|Nervous System Disorders||headachedizziness [see Warnings and Precautions (5.4)]||63|
|Respiratory, Thoracic and Mediastinal Disorders||dyspnea [see Warnings and Precautions (5.7)]||1|
|Gastrointestinal Disorders||nauseadiarrheaconstipationabdominal painvomitingdyspepsia||753222|
|Skin and Subcutaneous Tissue Disorders||rash [see Warnings and Precautions (5.7)] pruritus||21|
|Reproductive System and Breast Disorders||vaginitis||1†|
|General Disorders and Administration Site Conditions||edemainjection site reactionchest pain||111|
|* N = 7274 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.|
|System/Organ Class||Adverse Reaction|
|Infections and Infestations||genital moniliasis|
|Blood and Lymphatic System Disorders||anemiathrombocytopeniagranulocytopenia[see Warnings and Precautions (5.6)]|
|Immune System Disorders||allergic reaction [see Warnings and Precautions (5.6, 5.7)]|
|Metabolism and Nutrition Disorders||hyperglycemia hypoglycemia[see Warnings and Precautions (5.12)] hyperkalemia|
|Psychiatric Disorders||anxietyagitationconfusiondepressionhallucinationnightmare* [see Warnings and Precautions (5.4)] sleep disorder* anorexiaabnormal dreaming*|
|Nervous System Disorders||tremorconvulsions[see Warnings and Precautions (5.4)] paresthesia [see Warnings and Precautions (5.3)] vertigohypertoniahyperkinesiasabnormal gaitsomnolence* syncope|
|Respiratory, Thoracic and Mediastinal Disorders||epistaxis|
|Cardiac Disorders||cardiac arrestpalpitationventricular tachycardiaventricular arrhythmia|
|Gastrointestinal Disorders||gastritisstomatitispancreatitisesophagitisgastroenteritisglossitispseudomembranous/C. difficile colitis [see Warnings and Precautions (5.9)]|
|Hepatobiliary Disorders||abnormal hepatic functionincreased hepatic enzymesincreased alkaline phosphatase|
|Skin and Subcutaneous Tissue Disorders||urticaria [see Warnings and Precautions (5.7)]|
|Musculoskeletal and Connective Tissue Disorders||arthralgiatendinitis[see Warnings and Precautions (5.2)] myalgiaskeletal pain|
|Renal and Urinary Disorders||abnormal renal functionacute renal failure [see Warnings and Precautions (5.6)]|
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