Levaquin Side Effects, and Drug Interactions - Levofloxacin

Levaquin Side Effects, and Drug Interactions - Levofloxacin

SIDE EFFECTS

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 maculo-papular 0. 1%, tremor 0. 1%, condi-tion 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:

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%)

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, peripheral neuropathy, rhabdomyolysis, Stevens-Johnson Syndrome, tendon rupture, torsades de pointes, vasodilation.

LEVAQUIN Tablets: While the chelation by divalent cations is less marked than with other quinolones, concurrent administration of LEVAQUIN 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 multivitamins preparations with zinc or Videx^® (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 levofloxacin administration.

LEVAQUIN Injection: There are no data concerning an interaction of intravenous quinolones with oral antacids, sucralfate, multivitamins, Videx^® (didanosine), or metal cations. However, no quinolone should be co-administered with any solution containing multivalent cations, e. g. , mag-nesium, through the same intravenous line. (See DOSAGE AND ADMINISTRATION. ) Theophylline: No significant effect of levofloxacin on the plasma concentrations, AUC, and other disposition parameters for theophylline was detected in a clinical study involving 14 healthy volunteers. Similarly, no apparent effect of theophylline on levofloxacin absorption and disposition was observed. However, concomitant administration of other quinolones with theophylline has resulted in prolonged elimination half-life, elevated serum theophylline levels, and a subsequent increase in the risk of theophylline-related adverse reactions in the patient population. Therefore, theophylline levels should be closely monitored and appropriate dosage adjustments made when levofloxacin is co-administered. Adverse reactions, including seizures, may occur with or without an elevation in serum theophylline levels. (See WARNINGS and PRECAUTIONS: General. )

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. There have been reports during the post-marketing 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.

Cyclosporine: No significant effect of levofloxacin on the peak plasma concentrations, AUC, and other disposition parameters for cyclosporine was detected in a clinical study involving healthy volunteers. However, elevated serum levels of cyclosporine have been reported in the patient population when co-administered with some other quinolones. Levofloxacin C_max and ke were slightly lower while T_max and t½ were slightly longer in the presence of cyclosporine than those observed in other studies without concomitant medication. The differences, however, are not considered to be clinically significant. Therefore, no dosage adjustment is required for levofloxacin or cyclosporine when administered concomitantly.

Digoxin: No significant effect of levofloxacin on the peak plasma concentrations, AUC, and other disposition parameters for digoxin was detected in a clinical study involving healthy volunteers. Levofloxacin absorption and disposition kinetics were similar in the presence or absence of digoxin. Therefore, no dosage adjustment for levofloxacin or digoxin is required when administered concomitantly.

Probenecid and Cimetidine: No significant effect of probenecid or cimetidine on the rate and extent of levofloxacin absorption was observed in a clinical study involving healthy volunteers. The AUC and t½ of levofloxacin were 27-38% and 30% higher, respectively, while CL/F and CL_R were 21-35% lower during concomitant treatment with probenecid or cimetidine compared to levofloxacin alone. Although these differences were statistically significant, the changes were not high enough to warrant dosage adjustment for levofloxacin when probenecid or cimetidine is co-administered.

Non-steroidal anti-inflammatory drugs: The concomitant administration of a non-steroidal anti-inflammatory drug with a quinolone, including levofloxacin, may increase the risk of CNS stimulation and convulsive seizures. (See WARNINGS and PRECAUTIONS: General. ) Antidiabetic agents: Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Therefore, careful monitoring of blood glucose is recommended when these agents are co-administered.