Gemifloxacin Mesylate (2 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- FACTIVE
- GEMIFLOXACIN MESYLATE
Boxed Warning
Fluoroquinolones, including FACTIVE ® , have been associated with with disabling and potentially irreversible serious adverse reactions that have occurred together (See WARNINGS) including: Tendinitis and tendon rupture Peripheral neuropathy Central nervous system effects Discontinue FACTIVE immediately and avoid the use of fluoroquinolones, including FACTIVE, in patients who experience any of these serious adverse reactions (See WARNINGS ). Fluoroquinolones, including FACTIVE, may exacerbate muscle weakness in persons with myasthenia gravis. Avoid FACTIVE in patients with known history of myasthenia gravis (See WARNINGS ). Because fluoroquinolones, including FACTIVE, have been associated with serious adverse reactions (See WARNINGS), reserve FACTIVE for use in patients who have no alternative treatment options for acute bacterial exacerbation of chronic bronchitis (See INDICATIONS AND USAGE).
Indications and Usage
FACTIVE is indicated for the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions listed below. (See DOSAGE AND ADMINISTRATION and CLINICAL STUDIES. ) Acute bacterial exacerbation of chronic bronchitis (ABECB) caused by Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, or Moraxella catarrhalis. Because fluoroquinolones, including FACTIVE, have been associated with serious adverse reactions (see WARNINGS ) and for some patients ABECB is self-limiting, reserve FACTIVE for treatment of ABECB in patients who have no alternative treatment options. Community-acquired pneumonia (of mild to moderate severity) caused by Streptococcus pneumoniae (including multi-drug resistant strains [MDRSP])*, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae, or Klebsiella pneumoniae. *MDRSP: multi-drug resistant Streptococcus pneumoniae, includes isolates previously known as PRSP (penicillin-resistant Streptococcus pneumoniae), and are strains resistant to two or more of the following antibiotics: penicillin (MIC ≥2 μg/mL), 2nd generation cephalosporins (e.g., cefuroxime), macrolides, tetracyclines and trimethoprim/sulfamethoxazole. To reduce the development of drug-resistant bacteria and maintain the effectiveness of FACTIVE and other antibacterial drugs, FACTIVE should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Dosage and Administration
FACTIVE can be taken with or without food and should be swallowed whole with a liberal amount of liquid. The recommended dose of FACTIVE is 320 mg daily, according to the following table (Table 4). Table 4. Recommended Dosage Regimen of FACTIVE The clinical decision regarding the use of a 5 or 7 day regimen should be guided by results of the initial sputum culture. INDICATION DOSE / DURATION Acute bacterial exacerbation of chronic bronchitis One 320 mg tablet daily for 5 days Community-acquired pneumonia (of mild to moderate severity) due to known or suspected S. pneumoniae, H. influenzae, M. pneumoniae, or C. pneumoniae infection One 320 mg tablet daily for 5 days due to known or suspected MDRSP*, K. pneumoniae, or M. catarrhalis infection One 320 mg tablet daily for 7 days *MDRSP: multi-drug resistant Streptococcus pneumoniae, includes isolates previously known as PRSP (penicillin-resistant Streptococcus pneumoniae), and are strains resistant to two or more of the following antibiotics: penicillin (MIC 2 µg/mL), 2nd generation cephalosporins (e.g., cefuroxime), macrolides, tetracyclines and trimethoprim/sulfamethoxazole. The recommended dose and duration of FACTIVE should not be exceeded (see Table 2). Use in Renally Impaired Patients: Dose adjustment in patients with creatinine clearance >40 mL/min is not required. Modification of the dosage is recommended for patients with creatinine clearance 40 mL/min. Table 5 provides dosage guidelines for use in patients with renal impairment. Table 5. Recommended Doses for Patients with Renal Impairment Creatinine Clearance (mL/min) Dose >40 See Usual Dosage 40 160 mg every 24 hours Patients requiring routine hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) should receive 160 mg every 24 hours. When only the serum creatinine concentration is known, the following formula may be used to estimate creatinine clearance. Creatinine Clearance Formula Women: 0.85 x the value calculated for men Use in Hepatically Imp
Contraindications
FACTIVE is contraindicated in patients with a history of hypersensitivity to gemifloxacin, fluoroquinolone antibiotic agents, or any of the product components.
Adverse Reactions
In clinical studies, 8119 patients received daily oral doses of 320 mg FACTIVE. 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. FACTIVE was discontinued because of an adverse event (determined by the investigator to be possibly or probably related to drug) in 2.0% of patients, primarily due to rash (0.8%), nausea (0.3%), diarrhea (0.3%), urticaria (0.2%) 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 (0.4%), vomiting (0.3%), rash (0.3%), abdominal pain (0.2%) and vertigo (0.2%). The most commonly reported adverse events with a frequency of ≥2% for patients receiving 320 mg FACTIVE versus comparator drug (beta-lactam antibiotics, macrolides or other fluoroquinolones) are as follows: diarrhea 5.0% vs. 6.2%; rash 3.5% vs. 1.1%; nausea 3.7% vs. 4.5%; headache 4.2% vs. 5.2%; abdominal pain 2.2% vs. 2.2%; vomiting 1.6% vs. 2.0%; and dizziness 1.7% vs. 2.6%. Adverse Events with a Frequency of Less than 1% Additional drug-related adverse events (possibly or probably related) in the 8119 patients, with a frequency of >0.1% to ≤1% included: abdominal pain, anorexia, constipation, dermatitis, dizziness, dry mouth, dyspepsia, fatigue, flatulence, fungal infection, gastritis, genital moniliasis, genital pruritus, hyperglycemia, increased alkaline phosphatase, increased ALT, increased AST, increased creatine phosphokinase, insomnia, leukopenia, 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
Drug Interactions
Antacids/Di- and Trivalent Cations: The systemic availability of gemifloxacin is significantly reduced when an aluminum- and magnesium- containing antacid is concomitantly administered (AUC decreased 85%; Cmax decreased 87%). Administration of an aluminum- and magnesium- containing antacid or ferrous sulfate (325 mg) at 3 hours before or at 2 hours after gemifloxacin did not significantly alter the systemic availability of gemifloxacin. Therefore, aluminum- and/or magnesium- containing antacids, 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 taking FACTIVE tablets. Calcium carbonate (1000 mg) given either 2 hr before or 2 hr after gemifloxacin administration showed no notable reduction in gemifloxacin systemic availability. Calcium carbonate administered simultaneously with gemifloxacin resulted in a small, not clinically significant, decrease in gemifloxacin exposure [AUC (0-inf) decreased 21% and Cmax decreased]. Sucralfate: When sucralfate (2 g) was administered 3 hours prior to gemifloxacin, the oral bioavailability of gemifloxacin was significantly reduced (53% decrease in AUC; 69% decrease in Cmax). When sucralfate (2 g) was administered 2 hours after gemifloxacin, the oral bioavailability of gemifloxacin was not significantly affected; therefore FACTIVE should be taken at least 2 hours before sucralfate. (See PRECAUTIONS .) In Vitro Metabolism: Results of in vitro inhibition studies indicate that hepatic cytochrome P450 (CYP450) enzymes do not play an important role in gemifloxacin metabolism. Therefore gemifloxacin should not cause significant in vivo pharmacokinetic interactions with other drugs that are metabolized by CYP450 enzymes. Theophylline: Gemifloxacin 320 mg at steady-state did not affect the repeat dose pharmacokinetics of theophylline (300 to 400 mg BID to
Overdosage
Any signs or symptoms of overdosage should be treated symptomatically. No specific antidote is known. In the event of acute oral overdosage, the stomach should be emptied by inducing vomiting or by gastric lavage; the patient should be carefully observed and treated symptomatically with appropriate hydration maintained. Hemodialysis removes approximately 20 to 30% of an oral dose of gemifloxacin from plasma. Mortality occurred at oral gemifloxacin doses of 1600 mg/kg in rats and 320 mg/kg in mice. The minimum lethal intravenous doses in these species were 160 and 80 mg/kg, respectively. Toxic signs after administration of a single high oral dose (400 mg/kg) of gemifloxacin to rodents included ataxia, lethargy, piloerection, tremor, and clonic convulsions.