Levofloxacin (Page 7 of 17)

6.3 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, reliably estimating their frequency or establishing a causal relationship to drug exposure is not always possible.

Table 6: Postmarketing Reports of Adverse Drug Reactions

System/Organ Class	Adverse Reaction
Blood and Lymphatic System Disorders	pancytopenia aplastic anemia leukopenia hemolytic anemia [see WARNINGS AND PRECAUTIONS (5.4)] eosinophilia
Immune System Disorders	hypersensitivity reactions, sometimes fatal including: anaphylactic/anaphylactoid reactions anaphylactic shock angioneurotic edema serum sickness [see WARNINGS AND PRECAUTIONS (5.3, 5.4)]
Psychiatric Disorders	psychosis paranoia isolated reports of suicide attempt and suicidal ideation [see WARNINGS AND PRECAUTIONS (5.6)]
Nervous System Disorders	exacerbation of myasthenia gravis [see WARNINGS AND PRECAUTIONS (5.2)] anosmia ageusia parosmia dysgeusia peripheral neuropathy (may be irreversible) [see WARNINGS AND PRECAUTIONS (5.8)] isolated reports of encephalopathy abnormal electroencephalogram (EEG) dysphonia pseudotumor cerebri [see WARNINGS AND PRECAUTIONS (5.6)]
Eye Disorders	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 [see WARNINGS AND PRECAUTIONS (5.9)] tachycardia
Vascular Disorders	vasodilatation
Respiratory, Thoracic and Mediastinal Disorders	isolated reports of allergic pneumonitis [see WARNINGS AND PRECAUTIONS (5.4)]
Hepatobiliary Disorders	hepatic failure (including fatal cases) hepatitis jaundice [see WARNINGS AND PRECAUTIONS (5.4),(5.5)]
Skin and Subcutaneous Tissue Disorders	bullous eruptions to include: Stevens-Johnson Syndrome toxic epidermal necrolysis erythema multiforme [see WARNINGS AND PRECAUTIONS (5.4)] photosensitivity/phototoxicity reaction [see WARNINGS AND PRECAUTIONS (5.12)] leukocytoclastic vasculitis
Musculoskeletal and Connective Tissue Disorders	tendon rupture [see WARNINGS AND PRECAUTIONS (5.1)] muscle injury, including rupture rhabdomyolysis
Renal and Urinary Disorders	interstitial nephritis [see WARNINGS AND PRECAUTIONS (5.4)]
General Disorders and Administration Site Conditions	multi-organ failure pyrexia
Investigations	prothrombin time prolonged international normalized ratio prolonged muscle enzymes increased

7 DRUG INTERACTIONS

7.1 Chelation Agents: Antacids, Sucralfate, Metal Cations, Multivitamins

While the chelation by divalent cations is less marked than with other fluoroquinolones, concurrent administration of levofloxacin tablets with antacids containing magnesium, or aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc may interfere with the gastrointestinal absorption of levofloxacin, resulting in systemic levels considerably lower than desired. Tablets with antacids containing magnesium, aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc or didanosine may substantially interfere with the gastrointestinal absorption of levofloxacin, resulting in systemic levels considerably lower than desired. These agents should be taken at least two hours before or two hours after oral levofloxacin administration.

7.2 Warfarin

No significant effect of levofloxacin on the peak plasma concentrations, AUC, and other disposition parameters for R- and S- warfarin was detected in a clinical study involving healthy volunteers. Similarly, no apparent effect of warfarin on levofloxacin absorption and disposition was observed. However, there have been reports during the postmarketing experience in patients that levofloxacin enhances the effects of warfarin. Elevations of the prothrombin time in the setting of concurrent warfarin and levofloxacin use have been associated with episodes of bleeding. Prothrombin time, International Normalized Ratio (INR), or other suitable anticoagulation tests should be closely monitored if levofloxacin is administered concomitantly with warfarin. Patients should also be monitored for evidence of bleeding [see ADVERSE REACTIONS (6.3); PATIENT COUNSELING INFORMATION (17.4)].

7.3 Antidiabetic Agents

Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with fluoroquinolones and an antidiabetic agent. Therefore, careful monitoring of blood glucose is recommended when these agents are co-administered [see WARNINGS AND PRECAUTIONS (5.11); ADVERSE REACTIONS (6.2), PATIENT COUNSELING INFORMATION (17.4)].