Dosing and uses of Factive (gemifloxacin)
Adult dosage forms and strengths
tablets
- 320mg
Acute Exacerbations of Chronic Bronchitis
320 mg PO qDay x5 days
Limitations-of-use: Reserve fluoroquinolones for patients who do not have other available treatment options for acute bacterial exacerbation of chronic bronchitis
Pneumonia (community-acquired)
(Multidrug resistant S. pneumoniae; K. pneumoniae; M. catarrhalis): 320 mg PO qDay x7 days
(S. pneumoniae; M. pneumoniae; H. influenzae; C. pneumoniae): 320 mg PO qDay x 5days
Dosage modifications
Renal impairment
- CrCl <40 mL/min: Decrease dose by 50%
Other Indications & Uses
Mild-to-moderate community-acquired pneumonia caused by Streptococcus pneumoniae (including multi-drug resistant), H. influenzae, H. parainfluenzae, K. pneumoniae, Chlamydia pneumoniae, Moraxella catarrhalis, Mycoplasma pneumoniae
Possibly effective against S. aureus (MSSA), S. pyogenes, Acinetobacter lwoffi, Klebsiella oxytoca, Legionella pneumophila, Proteus vulgaris
Pediatric dosage forms and strengths
Safety and efficacy not established
Factive (gemifloxacin) adverse (side) effects
1-10%
Diarrhea (5%)
Headache (4%)
Nausea (4%)
Rash (4%)
Transaminases increased (1-4%)
Abdominal pain (2%)
Dizziness (2%)
Vomiting (2%)
Neutropenia (1%)
Platelets increased (1%)
Thrombocythemia (1%)
GGT increased (1%)
<1%
Peripheral neuropathy
Photosensitivity
Tendon rupture
Postmarketing Reports
Blood and lymphatic disorders: Agranulocytosis, pancytopenia
Cardiovascular disorders: Ventricular tachyarrhythmias (including in very rare cases cardiac arrest and torsade de pointes)
Ear and labyrinth disorders: Hearing impairment, including deafness (reversible in most cases)
Eye disorders: Vision loss (especially in the course of CNS reactions, transient in majority of cases)
Hepatobiliary disorders: Hepatitis, hepatic failure, jaundice, acute hepatic necrosis
Immune system disorders: Anaphylactic reactions including shock, angioedema (including laryngeal edema)
Musculoskeletal/connective tissue disorders: Tendon rupture, arthralgia, myalgia
Nervous system disorders: Exacerbation of myasthenia gravis symptoms, altered coordination, abnormal gait, muscle weakness, peripheral neuropathy, poly neuropathy
Central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion)
Psychiatric disorders: Psychotic reaction (very rarely culminating in self-injurious behavior, such as suicidal ideation/thoughts or suicide attempts)
Renal and urinary disorders: Renal dysfunction, interstitial nephritis
Respiratory disorders: Allergic pneumonitis
Skin and tissue disorders: Photosensitivity/phototoxicity reaction, Stevens-Johnson syndrome, Toxic epidermal necrolysis
Warnings
Black box warnings
Fluoroquinolones have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together including: tendinitis and tendon rupture, peripheral neuropathy, and CNS effects
Discontinue the drug immediately and avoid use of systemic fluoroquinolones in patients who experience any of these serious adverse reactions
May exacerbate muscle weakness in patients with myasthenia gravis; avoid fluoroquinolones with known history of myasthenia gravis
Serious adverse effects and limitations-of-use
- Both oral and injectable fluroquinolones are associated with disabling side effects involving tendons, muscles, joints, nerves and the central nervous system
- These side effects can occur hours to weeks after exposure to fluoroquinolones and may potentially be permanent
- Discontinue the drug immediately and avoid use of systemic fluoroquinolones in patients who experience any of these serious adverse reactions
- Because the risk of these serious side effects generally outweighs the benefits for patients with acute bacterial sinusitis, acute exacerbation of chronic bronchitis, and uncomplicated UTIs, that fluoroquinolones should be reserved for use in patients with these conditions who have no alternative treatment options
- For some serious bacterial infections, including anthrax, plague, and bacterial pneumonia among others, the benefits of fluoroquinolones outweigh the risks and it is appropriate for them to remain available as a therapeutic option
Contraindications
All drugs or conditions that prolong QT intervaL
Documented hypersensitivity to gemifloxacin or other fluoroquinolones
Cautions
May prolong QT intervaL
May cause maculopapular rash
Although not reported in gemifloxacin clinical trials, convulsions, increased intracranial pressure (including pseudotumor cerebri), and toxic psychosis reported with other fluoroquinolones
Peripheral neuropathy: Sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias, and weakness reported; peripheral neuropathy may occur rapidly after initiating and may potentially become permanent
In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy
Not drug of first choice in pediatrics due to increased incidence of adverse events compared to controls, including arthropathy; no data exist for dose for pediatric patients with renal impairment (ie, CrCl <50 mL/min)
Fluoroquinolones are associated with increased risk of tendinitis and tendon rupture in all ages, this risk is further increased in older patients usually over 60 yr, in patients taking corticosteroid drugs, and in patients with kidney, heart, or lung transplants
Acute onset of retinal detachment increased 4.5-fold with oral fluoroquinolones in a single case-controlled study - JAMA 2012;307(13):1414-1419; another study disputes these findings (relative risk, 1.29) - JAMA 2013;310(20):2184-2190
Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion); these reactions can occur within hours to weeks after starting therapy, including in patients of any age or without pre-existing risk factors; discontinue therapy immediately at first signs or symptoms of any serious adverse reaction; in addition, avoid use of fluoroquinolones, in patients who have experienced any serious adverse reactions associated with fluoroquinolones
Risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in patients over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants; other factors that may independently increase risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis
Pregnancy and lactation
Pregnancy category: C
Lactation: excretion in milk unknown; do not use unless benefit to mother outweighs risk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Factive (gemifloxacin)
Mechanism of action
Acts by inhibiting both DNA gyrase and topoisomerase IV, which are essential for bacterial growth. Because of this dual mechanism, MIC values remain in the susceptible range for some double mutants (eg, S pneumoniae)
Absorption
Bioavailability: 71%
Peak Plasma Time: 0.5-2 hr
Peak Plasma Concentration: 1.61 mcg/mL
AUC: 9.93 mcg•hr/mL
Distribution
Protein bound: 60-70%
Metabolism
Hepatic (limited)
Elimination
Half-Life: 5-9 hr
Dialyzable: yes (20-30%)
Excretion: feces (60%); urine (40%)
