Factive Side Effects, and Drug Interactions - Gemifloxacin mesylate

Factive Side Effects, and Drug Interactions - Gemifloxacin mesylate

SIDE EFFECTS

In clinical studies, 6775 patients received daily oral doses of 320 mg gemifloxacin. In addition, 1797 healthy volunteers and 81 patients with renal or hepatic impairment received single or repeat doses of gemifloxacin in clinical pharmacology studies. The majority of adverse reactions experienced by patients in clinical trials were considered to be of mild to moderate severity.

Gemifloxacin was discontinued because of an adverse event (possibly or probably related) in 2.2% of patients, primarily due to rash (0.9%), nausea (0.3%), diarrhea (0.3%), urticaria (0.3%) and vomiting (0.2%). Comparator antibiotics were discontinued because of an adverse event at an overall comparable rate of 2.1%, primarily due to diarrhea (0.5%), nausea (0.3%), vomiting (0.3%) and rash (0.3%).

Drug-related adverse events, classified as possibly or probably related with a frequency of =1% for patients receiving 320 mg of gemifloxacin versus comparator drug (beta-lactam antibiotics, macrolides or other fluoroquinolones) are as follows: diarrhea 3.6% vs. 4.6%; rash 2.8% vs. 0.6%; nausea 2.7% vs. 3.2%; headache 1.2% vs. 1.5%; abdominal pain 0.9% vs. 1.1%; vomiting 0.9% vs. 1.1%; dizziness 0.8% vs. 1.5%; and taste perversion 0.3% vs. 1.9%.

Gemifloxacin appears to have a low potential for photosensitivity. In clinical trials, treatment-related photosensitivity occurred in only 0.039% (3/7659) of patients.

Additional drug-related adverse events (possibly or probably related) in >0.1% to 1% of patients who received 320 mg of gemifloxacin were: abdominal pain, anorexia, arthralgia, constipation, dermatitis, dizziness, dry mouth, dyspepsia, fatigue, flatulence, fungal infection, gastritis, genital moniliasis, hyperglycemia, insomnia, leukopenia, moniliasis, pruritus, somnolence, taste perversion, thrombocythemia, urticaria, vaginitis, and vomiting.

Other adverse events reported from clinical trials which have potential clinical significance and which were considered to have a suspected relationship to the drug, that occurred in =0.1% of patients were: abnormal urine, anemia, asthenia, back pain, bilirubinemia, dyspnea, eczema, eosinophilia, flushing, gastroenteritis, granulocytopenia, hot flashes, increased GGT, leg cramps, myalgia, nervousness, non-specified gastrointestinal disorder, pain, pharyngitis, pneumonia, thrombocyotopenia, tremor, vertigo, and vision abnormality.

In clinical trials of acute bacterial exacerbation of chronic bronchitis (ABECB) and community acquired pneumonia (CAP), the incidences of rash were as follows (Table 3):

Gemifloxacin appears to have a low potential for photosensitivity. In clinical trials, treatment-related photosensitivity occurred in only 0.039% (3/7659) of patients.

Additional drug-related adverse events (possibly or probably related) in >0.1% to 1% of patients who received 320 mg of gemifloxacin were: abdominal pain, anorexia, arthralgia, constipation, dermatitis, dizziness, dry mouth, dyspepsia, fatigue, flatulence, fungal infection, gastritis, genital moniliasis, hyperglycemia, insomnia, leukopenia, moniliasis, pruritus, somnolence, taste perversion, thrombocythemia, urticaria, vaginitis, and vomiting.

Other adverse events reported from clinical trials which have potential clinical significance and which were considered to have a suspected relationship to the drug, that occurred in £0.1% of patients were: abnormal urine, anemia, asthenia, back pain, bilirubinemia, dyspnea, eczema, eosinophilia, flushing, gastroenteritis, granulocytopenia, hot flashes, increase GGT, leg cramps, myalgia, nervousness, non-specified gastrointestinal disorder, pain, pharyngitis, pneumonia, thrombocyotopenia, tremor, vertigo, and vision abnormality.

In clinical trials of acute bacterial exacerbation of chronic bronchitis (ABECB) and community acquired pneumonia (CAP), the incidences of rash were as follows (Table 4):

(see PRECAUTIONS)

Laboratory Changes: The percentages of patients who received multiple doses of gemifloxacin and had a laboratory abnormality are listed below. It is not known whether these abnormalities were related to gemifloxacin or an underlying condition.

Clinical Chemistry: increased ALT (1.5%), increased AST (1.1%), increased creatine phosphokinase (0.6%), increased potassium (0.5%), decreased sodium (0.3%), increased gammaglutamyl transferase (0.5%), increased alkaline phosphatase (0.3%), increased total bilirubin (0.3%), increased blood urea nitrogen (0.3%), decreased calcium (0.2%), decreased albumin (0.3%), increased serum creatinine (0.2%), decreased total protein (0.1%) and increased calcium (<0.1%).

CPK elevations were noted infrequently: 0.8% in gemifloxacin patients vs. 0.4% in the comparator patients.

Hematology: increased platelets (0.9%), decreased neutrophils (0.5%), increased neutrophils (0.5%), decreased hematocrit (0.3%), decreased hemoglobin (0.2 %), decreased platelets (0.2%), decreased red blood cells (0.1%), increased hematocrit (0.1%), increased hemoglobin (0.1%), and increased red blood cells (0.1%).

In clinical studies, approximately 7% of the gemifloxacin treated patients had elevated ALT values immediately prior to entry into the study. Of these patients, approximately 10% showed a further elevation of their ALT at the on-therapy visit and 5% showed a further elevation at the end of therapy visit. None of these patients demonstrated evidence of hepatocellular jaundice. For the pooled comparators, approximately 6% of patients had elevated ALT values immediately prior to entry into the study. Of these patients, approximately 7% showed a further elevation of their ALT at the on-therapy visit and 4% showed a further elevation at the end of therapy visit.

In a clinical trial where 638 patients received either a single 640 mg dose of gemifloxacin or 250 mg bid of ciprofloxacin for 3 days, there was an increased incidence of ALT elevations in the gemifloxacin arm (3.9%) vs. the comparator arm (1.0%). In this study, two patients experienced ALT elevations of 8 to10 times the upper limit of normal. These elevations were asymptomatic and reversible.

Administration of repeat doses of FACTIVE had no effect on the repeat dose pharmacokinetics of theophylline, digoxin or an ethinylestradiol/levonorgestrol oral contraceptive product in healthy subjects. (See CLINICAL PHARMACOLOGY: Drug-Drug Interactions.)

Concomitant administration of FACTIVE and calcium carbonate, cimetidine, omeprazole, or an estrogen/progesterone oral contraceptive produced minor changes in the pharmacokinetics of gemifloxacin, which were considered to be without clinical significance. (See CLINICAL PHARMACOLOGY.)

Concomitant administration of FACTIVE with probenecid resulted in a 45% increase in systemic exposure to gemifloxacin. (See CLINICAL PHARMACOLOGY.)

FACTIVE had no significant effect on the anticoagulant effect of warfarin in healthy subjects on stable warfarin therapy. However, because some quinolones have been reported to enhance the anticoagulant effects of warfarin or its derivatives in patients, the prothrombin time or other suitable coagulation test should be closely monitored if a quinolone antimicrobial is administered concomitantly with warfarin or its derivatives.

Quinolones form chelates with alkaline earth and transition metals. The absorption of oral gemifloxacin is significantly reduced by the concomitant administration of an antacid containing aluminum and magnesium. Magnesium- and/or aluminum-containing antacids, products containing ferrous sulfate (iron), multivitamin preparations containing zinc or other metal cations, or Videx (didanosine) chewable/buffered tablets or the pediatric powder for oral solution should not be taken within 3 hours before or 2 hours after FACTIVE. Sucralfate should not be taken within 2 hours of FACTIVE. (See CLINICAL PHARMACOLOGY.)