Gemifloxacin Mesylate

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.

Gemifloxacin is an antibiotic in a group of drugs called fluoroquinolones (flor-o-KWIN-o-lones). Gemifloxacin fights bacteria in the body.

Gemifloxacin is used to treat different types of bacterial infections.

Gemifloxacin may also be used for purposes not listed in this medication guide.

You should not use this medication if you have a history of myasthenia gravis, or if you are allergic to gemifloxacin or similar antibiotics such as ciprofloxacin (Cipro), levofloxacin (Levaquin), moxifloxacin (Avelox), ofloxacin (Floxin), norfloxacin (Noroxin), and others.

Before taking gemifloxacin, tell your doctor if you have a heart rhythm disorder, kidney disease, joint problems, muscle weakness or trouble breathing, a history of seizures, a history of head injury of brain tumor, a condition called pseudotumor cerebri, low levels of potassium or magnesium in your blood, a nerve disorder or history of circulation problems, a personal or family history of Long QT syndrome, or if you have ever had an allergic reaction to an antibiotic.

Avoid taking antacids, vitamin or mineral supplements, sucralfate (Carafate), or didanosine (Videx) powder or chewable tablets within 6 hours before or 2 hours after you take gemifloxacin.

Gemifloxacin may cause swelling or tearing of a tendon (the fiber that connects bones to muscles in the body), especially in the Achilles' tendon of the heel. These effects may be more likely to occur if you are over 60, if you take steroid medication, or if you have had a kidney, heart, or lung transplant. Stop taking gemifloxacin and call your doctor at once if you have sudden pain, swelling, tenderness, stiffness, or movement problems in any of your joints. Rest the joint until you receive medical care or instructions.

Do not share this medication with another person (especially a child), even if they have the same symptoms you do.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

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 mostcommonly reported adverse events with a frequency of ?2% forpatients 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 probablyrelated) 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 ?0.1% of patients were: abnormal urine, abnormal vision, anemia, arthralgia, asthenia, back pain, bilirubinemia, dyspnea, eczema, eosinophilia, facial edema, flushing, gastroenteritis, granulocytopenia, hot flashes, increased GGT, increased non-protein nitrogen, leg cramps, moniliasis, myalgia, nervousness, non-specified gastrointestinal disorder, pain, pharyngitis, photosensitivity/phototoxicity reactions, pneumonia, thrombocytopenia, tremor, vertigo. (See PRECAUTIONS.)

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):

Table 3. Incidence of Rash by Clinical Indication in Patients Treated with FACTIVE

* insufficient number of patients in this category for a meaningful analysis (See PRECAUTIONS).

Laboratory Changes

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

Clinical Chemistry: increased ALT (1.7%), increased AST (1.3%), increased creatine phosphokinase (0.7%), increased alkaline phosphatase (0.4%), increased total bilirubin (0.4%), increased potassium (0.3%), decreased sodium (0.2%), increased blood urea nitrogen (0.3%), decreased albumin (0.3%), increased serum creatinine (0.2%), decreased calcium (0.1%), decreased total protein (0.1%), decreased potassium (0.1%), increased sodium (0.1%), increased lactate dehydrogenase (<0.1%) and increased calcium (<0.1%).

CPK elevations were noted infrequently: 0.7% in FACTIVE patients vs. 0.7% in the comparator patients.

Hematology: increased platelets (1.0%), 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 FACTIVE treated patients had elevated ALT values immediately prior to entry into the study. Of these patients, approximately 15% showed a  further elevation of their ALT at the on-therapy visit and 9% 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 to 10 times the upper limit of normal.  These elevations were asymptomatic and reversible.

Post-Marketing Adverse Reactions

The majority of the post-marketing adverse events reported were cutaneous and most of these were rash. Some of these cutaneous adverse events were  considered serious.  The majority of the rashes occurred in women and in patients under 40 years of age.

The following are additional adverse reactions reported during the post-marketing use of FACTIVE. Since these reactions are reported voluntarily from a population of uncertain size, it is impossible  to reliably estimate their frequency or establish a causal relationship to FACTIVE exposure:

• peripheral neuropathy that may be irreversible;
• anaphylactic reaction, erythema multiforme, skin exfoliation, facial swelling;
• exacerbation of myasthenia gravis;
• hemorrhage, increased international normalized ratio (INR), retinal hemorrhage;
• peripheral edema;
• renal failure;
• prolonged QT, supraventricular tachycardia, syncope, transient ischemic attack;
• photosensitivity/phototoxicity reaction (See PRECAUTIONS.);
• antibiotic-associated colitis;  
• tendon rupture.

Read the entire FDA prescribing information for Factive (Gemifloxacin Mesylate)

Antibacterial; naphthyridine derivative; fluoroquinolone.1 4 12 23

Does not inhibit and is not metabolized by CYP isoenzymes.1 Pharmacokinetic interactions with drugs metabolized by CYP isoenzymes unlikely.1

Drugs that Prolong QT Interval

Potential pharmacologic interaction (additive effect on QT interval prolongation).1 Avoid use in patients receiving class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents.1 Use with caution in patients receiving other drugs that prolong QT interval (e.g., cisapride [available in US only under limited-access protocol], erythromycin, antipsychotic agents, tricyclic antidepressants).1 (See Prolongation of QT Interval under Cautions.)

Specific Drugs

• Usually bactericidal.1

• Like other fluoroquinolones, gemifloxacin inhibits bacterial DNA gyrase and topoisomerase IV.1 4 12 Unlike some fluoroquinolones, gemifloxacin targets both enzymes in susceptible S. pneumoniae.1 12

• Spectrum of activity includes gram-positive aerobic bacteria, some gram-negative aerobic bacteria, and some other organisms (e.g., Chlamydia, Mycoplasma).1 4 12 22

• More active in vitro than some other fluoroquinolones against S. pneumoniae,4 12 13 22 23 but less active than ciprofloxacin in vitro against many Enterobacteriaceae and Pseudomonas aeruginosa.4 12

• Gram-positive aerobes: Active in vitro and in clinical infections against S. pneumoniae (including penicillin-resistant and multidrug-resistant strains).1 Also active in vitro against Staphylococcus aureus (oxacillin-susceptible [methicillin-susceptible] strains only) and S. pyogenes (group A β-hemolytic streptococci).1

• Gram-negative aerobes: Active in vitro and in clinical infections against H. influenzae,1 H. parainfluenzae,1 K. pneumoniae,1 and M. catarrhalis.1 Also active in vitro against some strains of Acinetobacter, K. oxytoca, Legionella pneumophila, and Proteus vulgaris.1

• Other organisms: Active in vitro and in clinical infections against C. pneumoniae 1 and M. pneumoniae.1 Has some activity against Mycobacterium tuberculosis in vitro, but is considerably less active against mycobacteria than some other fluoroquinolones (e.g., ciprofloxacin, ofloxacin, levofloxacin).27

• Some cross-resistance occurs between gemifloxacin and other fluoroquinolones.1