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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(je mi FLOKS a sin)
Generic Available (U.S.)
No
Index Terms
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/UCM152723.pdf, must be dispensed with this medication.
REMS Components
Factive®: Released from REMS requirement 8/4/2011
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of acute exacerbation of chronic bronchitis; treatment of community-acquired pneumonia (CAP), including pneumonia caused by multidrug-resistant strains of S. pneumoniae (MDRSP)
Use: Unlabeled
Acute sinusitis
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events have been observed in some animal studies; therefore, the manufacturer classifies gemifloxacin as pregnancy category C. Quinolone exposure during human pregnancy has been reported with other agents (see Ciprofloxacin [Systemic], Ofloxacin [Systemic], and Norfloxacin [Systemic] monographs). To date, no specific teratogenic effect or increased pregnancy risk has been identified; however, because of concerns of cartilage damage in immature animals exposed to quinolones and the limited gemifloxacin specific data, gemifloxacin should only be used during pregnancy if a safer option is not available.
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
It is not known if gemifloxacin is excreted in breast milk. Breast-feeding is not recommended by the manufacturer. Nondose-related effects could include modification of bowel flora.
Contraindications
Hypersensitivity to gemifloxacin, other fluoroquinolones, or any component of the formulation
Warnings/Precautions
Boxed warnings:
• Myasthenia gravis: See “Disease-related concerns” below.
• Tendon inflammation/rupture: See “Concerns related to adverse effects” below.
Concerns related to adverse effects:
• Altered cardiac conduction: Fluoroquinolones may prolong QTc interval; avoid use in patients with a history of QTc prolongation, uncorrected hypokalemia, hypomagnesemia, or concurrent administration of other medications known to prolong the QT interval (including Class Ia and Class III antiarrhythmics, cisapride, erythromycin, antipsychotics, and tricyclic antidepressants).
• CNS effects: Tremor, restlessness, confusion, and very rarely hallucinations, increased intracranial pressure (including pseudotumor cerebri) or seizures may occur; use with caution in patients with known or suspected CNS disorder. Discontinue in patients who experience significant CNS adverse effects (eg, dizziness, hallucinations, suicidal ideations or actions).
• Glucose regulation: Fluoroquinolones have been associated with the development of serious, and sometimes fatal, hypoglycemia. These events have occurred most often in elderly patients with diabetes, but have also been reported in patients without a prior history of diabetes. Prompt identification and treatment of hypoglycemia is essential. Individual quinolones may differ in their potential to cause this effect. It was most evident with gatifloxacin (no longer marketed as s systemic formulation). Hyperglycemia has also been associated with the use of fluoroquinolones. Patients should be monitored closely for signs/symptoms of disordered glucose regulation.
• Hypersensitivity reactions: Severe hypersensitivity reactions, including anaphylaxis, have occurred with quinolone therapy. The spectrum of these reactions can vary widely; reactions may present as typical allergic symptoms (eg, itching, urticaria, rash, edema) after a single dose, or may manifest as severe idiosyncratic dermatologic (eg, Stevens-Johnson, toxic epidermal necrolysis), vascular (eg, vasculitis), pulmonary (eg, pneumonitis), renal (eg, nephritis), hepatic (eg, hepatic failure or necrosis), and/or hematologic (eg, anemia, cytopenias) events, usually after multiple doses. May cause maculopapular rash, usually 8-10 days after treatment initiation; risk factors may include age <40 years, female gender (including postmenopausal women on HRT), and treatment duration >7 days. Prompt discontinuation of drug should occur if skin rash or other symptoms arise.
• Peripheral neuropathy: The use of quinolones has been linked to peripheral neuropathy (rare); discontinue if symptoms of sensory or sensorimotor neuropathy occur.
• Phototoxicity: Avoid excessive sunlight and take precautions to limit exposure (eg, loose fitting clothing, sunscreen); may cause moderate-to-severe phototoxicity reactions. Discontinue use if photosensitivity occurs.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
• Tendon inflammation/rupture: [U.S. Boxed Warning]: There have been reports of tendon inflammation and/or rupture with quinolone antibiotics; risk may be increased with concurrent corticosteroids, organ transplant recipients, and in patients >60 years of age. Rupture of the Achilles tendon sometimes requiring surgical repair has been reported most frequently; but other tendon sites (eg, rotator cuff, biceps) have also been reported. Strenuous physical activity may be an independent risk factor for tendonitis. Discontinue at first sign of tendon inflammation or pain. May occur even after discontinuation of therapy.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with significant bradycardia or acute myocardial ischemia.
• Myasthenia gravis: [U.S. Boxed Warning]: May exacerbate muscle weakness related to myasthenia gravis. Cases of severe exacerbations, including the need for ventilatory support and deaths have been reported; avoid use in patients with myasthenia gravis.
• Renal impairment: Use with caution in renal impairment; dosage adjustment required for Clcr ≤40 mL/minute. May increase risk of tendon rupture.
• Rheumatoid arthritis: Use with caution in patients with rheumatoid arthritis; may increase risk of tendon rupture.
• Seizures: Use with caution in individuals at risk of seizures (CNS disorders or concurrent therapy with medications which may lower seizure threshold). Potential for seizures, although very rare, may be increased with concomitant NSAID therapy.
Special populations:
• Elderly: Adverse effects (eg, tendon rupture, QT changes) may be increased in the elderly.
• G6PD deficiency: Hemolytic reactions may (rarely) occur with quinolone use in patients with latent or actual G6PD deficiency.
Adverse Reactions
1% to 10%:
Central nervous system: Headache (4%), dizziness (2%)
Dermatologic: Rash (4%)
Gastrointestinal: Diarrhea (5%), nausea (4%), abdominal pain (2%), vomiting (2%)
Hematologic: Neutropenia/neutrophilia (1%), platelets increased (1%), thrombocythemia (1%),
Hepatic: Transaminases increased (1% to 4%), GGT increased (1%)
Neuromuscular & skeletal: CPK increased (1%)
<1%, postmarketing and/or case reports: Acute renal failure, alkaline phosphatase increased, anaphylactic reaction, anemia, anorexia, arthralgia, back pain, bilirubin increased, BUN increased, constipation, cramps (leg), dermatitis, dyspepsia, dyspnea, eczema, eosinophilia, erythema multiforme, facial edema, fatigue, flatulence, flushing, fungal infection, gastritis, gastroenteritis, genital moniliasis, granulocytopenia, hematocrit decreased/increased, hemoglobin decreased/increased, hemorrhage, hot flashes, hyperglycemia, hyper-/hypocalcemia, hyper-/hypokalemia, hyper-/hyponatremia, hypoalbuminemia, INR increased, insomnia, intracranial pressure increased, leukopenia, moniliasis, myalgia, myasthenia gravis exacerbation, nervousness, pain, pharyngitis, photosensitivity, pneumonia, pruritus, pseudomembranous colitis, pseudotumor cerebri, QTc prolongation, retinal hemorrhage, serum creatinine increased, skin exfoliation, somnolence, supraventricular tachycardia, syncope, taste perversion, tendonitis, tendon rupture, thrombocytopenia, TIA, tremor, urticaria, vaginitis, vertigo, vision abnormal, weakness, xerostomia
Important adverse effects reported with other agents in this drug class include (not reported for gemifloxacin): Allergic reactions, CNS stimulation, hepatic necrosis/failure, hepatitis, hypersensitivity, jaundice, pancytopenia, peripheral neuropathy, pneumonitis (eosinophilic), seizure, sensorimotor-axonal neuropathy (paresthesia, hypoesthesias, dysesthesias, weakness), serum sickness, severe dermatologic reactions (toxic epidermal necrolysis, Stevens-Johnson syndrome), thrombotic thrombocytopenia purpura, torsade de pointes, vasculitis
Metabolism/Transport Effects
None known.
Drug Interactions
Antacids: May decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of quinolones. Exceptions: Sodium Bicarbonate. Risk D: Consider therapy modification
BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Calcium Salts: May decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of both agents. Exceptions: Calcium Chloride. Risk D: Consider therapy modification
Corticosteroids (Systemic): Quinolone Antibiotics may enhance the adverse/toxic effect of Corticosteroids (Systemic). Risk of tendon-related side effects, including tendonitis and rupture, may be enhanced. Risk C: Monitor therapy
Didanosine: May decrease the serum concentration of Quinolone Antibiotics. Management: Administer oral quinolones at least 2 hours before or 6 hours after didanosine. Monitor for decreased therapeutic effects of quinolones, particularly if doses cannot be separated as recommended. This does not apply to unbuffered enteric coated didanosine. Risk D: Consider therapy modification
Insulin: May enhance the hyperglycemic effect of Quinolone Antibiotics. Insulin may enhance the hypoglycemic effect of Quinolone Antibiotics. Risk C: Monitor therapy
Iron Salts: May decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of both agents. Exceptions: Ferric Gluconate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Risk D: Consider therapy modification
Magnesium Salts: May decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of both agents. Risk D: Consider therapy modification
Mycophenolate: Quinolone Antibiotics may decrease the serum concentration of Mycophenolate. Specifically, quinolones may decrease concentrations of the active metabolite of mycophenolate. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolone Antibiotics. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolone Antibiotics. Risk C: Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Probenecid: May decrease the excretion of Gemifloxacin. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Quinolone Antibiotics. Risk C: Monitor therapy
Quinapril: May decrease the serum concentration of Quinolone Antibiotics. Management: Separate doses of quinapril and oral quinolones by at least 2 hours in order to reduce the risk of interaction. Monitor for reduced efficacy of the quinolone if these products are used concomitantly. Risk D: Consider therapy modification
Sevelamer: May decrease the absorption of Quinolone Antibiotics. Risk D: Consider therapy modification
Sucralfate: May decrease the serum concentration of Quinolone Antibiotics. Management: Administer oral quinolones at least 2 hours before or 6 hours after the sucralfate dose. Greater separation of doses may further lessen the risk for a significant interaction. Risk D: Consider therapy modification
Sulfonylureas: Quinolone Antibiotics may enhance the hypoglycemic effect of Sulfonylureas. This appears to be particularly concerning early in the course of combination therapy. Quinolone Antibiotics may diminish the hypoglycemic effect of Sulfonylureas. With longer-term combination, there is a greater risk of hyperglycemia. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification
Varenicline: Quinolone Antibiotics may increase the serum concentration of Varenicline. Management: Monitor for increased varenicline adverse effects with concomitant use of levofloxacin or other quinolone antibiotics, particulary in patients with severe renal impairment. International product labeling recommendations vary. Consult appropriate labeling. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Quinolone Antibiotics may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Zinc Salts: May decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of both agents. Exceptions: Zinc Chloride. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: Avoid dong quai, St John's wort (may also cause photosensitization).
Storage
Store at 25°C (77°F). Protect from light.
Mechanism of Action
Gemifloxacin is a DNA gyrase inhibitor and also inhibits topoisomerase IV. DNA gyrase (topoisomerase IV) is an essential bacterial enzyme that maintains the superhelical structure of DNA. DNA gyrase is required for DNA replication and transcription, DNA repair, recombination, and transposition; bactericidal
Pharmacodynamics/Kinetics
Absorption: Well absorbed from the GI tract
Distribution: Vdss: 4.2 L/kg
Protein binding: ~60% to 70%
Metabolism: Hepatic (minor); forms metabolites (CYP isoenzymes are not involved)
Bioavailability: ~71%
Half-life elimination: 7 hours (range 4-12 hours)
Time to peak, plasma: 0.5-2 hours
Excretion: Feces (61%); urine (36%)
Dosage
Usual dosage range:
Adults: Oral: 320 mg once daily
Indication-specific dosing:
Adults: Oral:
Acute exacerbations of chronic bronchitis: 320 mg once daily for 5 days
Community-acquired pneumonia (mild-to-moderate): 320 mg once daily for 5 or 7 days (decision to use 5- or 7-day regimen should be guided by initial sputum culture; 7 days are recommended for MDRSP, Klebsiella, or M. catarrhalis infection)
Sinusitis (unlabeled use): 320 mg once daily for 10 days
Elderly: Refer to adult dosing.
Dosage adjustment in renal impairment:
Clcr >40 mL/minute: No adjustment required
Clcr ≤40 mL/minute (or patients on hemodialysis/CAPD): 160 mg once daily (administer dose following hemodialysis)
Dosage adjustment in hepatic impairment: No adjustment required
Administration: Oral
May be administered with or without food, milk, or calcium supplements. Gemifloxacin should be taken 3 hours before or 2 hours after supplements (including multivitamins) containing iron, zinc, or magnesium.
Monitoring Parameters
WBC, signs/symptoms of infection, renal function
Dietary Considerations
May take tablets with or without food, milk, or calcium supplements. Gemifloxacin should be taken 3 hours before or 2 hours after supplements (including multivitamins) containing iron, zinc, or magnesium.
Patient Education
Should be taken at least 3 hours before or 2 hours after antacids or other products containing aluminum, iron, magnesium, or zinc (including multivitamins). Maintain adequate hydration, unless instructed to restrict fluid intake. May cause headache, dizziness, nausea, vomiting, abdominal discomfort, or diarrhea. Discontinue use immediately and report to prescriber if signs of tendon inflammation or pain occur or if you experience signs of allergic reaction (eg, itching, rash, respiratory difficulty, facial edema, difficulty swallowing). Report CNS changes (eg, hallucinations, suicide ideation, seizures) or signs of opportunistic infection (unusual fever or chills, vaginal itching or foul-smelling vaginal discharge, easy bruising or bleeding).
Geriatric Considerations
The risk of torsade de pointes and tendon inflammation and/or rupture associated with the concomitant use of corticosteroids and quinolones is increased in the elderly population. See Warnings/Precautions regarding tendon rupture in patients >60 years of age.
Cardiovascular Considerations
Gemifloxacin causes a dose-dependent QT prolongation. Coadministration of gemifloxacin with other drugs that also prolong the QT interval or induce bradycardia (eg, beta-blockers, amiodarone) should be avoided. Careful consideration should be given in the use of gemifloxacin in patients with cardiovascular disease, particularly in those with conduction abnormalities.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Infectious Diseases Comment
Guidelines for the treatment of CAP state gemifloxacin should not be used a first-line therapy for penicillin-sensitive S. pneumoniae.
Mental Health: Effects on Mental Status
May cause dizziness, hallucinations, and suicidal ideation
Mental Health: Effects on Psychiatric Treatment
Contraindicated with ziprasidone. May lower seizure threshold; use caution with clozapine. Gemifloxacin may prolong QT interval; avoid use with antipsychotics and TCAs.
Nursing: Physical Assessment/Monitoring
Assess allergy history before initiating therapy. Use caution in presence of bradycardia, CNS disorders, renal dysfunction, or colitis. Teach patient proper use (timing of meals, supplements, or other medications). Monitor for allergic reaction, tendon pain, and opportunistic infection.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral:
Factive®: 320 mg [scored]
Pricing: U.S. (www.drugstore.com)
Tablets (Factive)
320 mg (5): $219.99
References
American Academy of Pediatrics Committee on Drugs, "Transfer of Drugs and Other Chemicals Into Human Milk," Pediatrics, 2001, 108(3):776-89.
Calvo A, Gimenez MJ, Alou L, et al, “Ex Vivo Serum Activity (Killing Rates) After Gemifloxacin 320 mg Versus Trovafloxacin 200 mg Single Doses Against Ciprofloxacin-Susceptible and -Resistant Streptococcus pneumoniae," Int J Antimicrob Agents, 2002, 20(2):144-6.
Friedrich LV and Dougherty R, “Fatal Hypoglycemia Associated With Levofloxacin,” Pharmacotherapy, 2004, 24(12):1807-12.
Frothingham R, “Glucose Homeostasis Abnormalities Associated With Use of Gatifloxacin,” Clin Infect Dis, 2005, 41(9):1269-76.
Gavin JR 3rd, Kubin R, Choudhri S, et al, “Moxifloxacin and Glucose Homeostasis: A Pooled-Analysis of the Evidence From Clinical and Postmarketing Studies,” Drug Saf, 2004, 27(9):671-86.
Graumlich JF, Habis S, Avelino RR, et al, “Hypoglycemia in Inpatients After Gatifloxacin or Levofloxacin Therapy: Nested Case-Control Study,” Pharmacotherapy, 2005, 25(10):1296-302.
Khaliq Y and Zhanel GG, “Fluoroquinolone-Associated Tendinopathy: A Critical Review of the Literature,” Clin Infect Dis, 2003, 36(11):1404-10.
Kutlin A, Roblin PM, and Hammerschlag MR, “Effect of Gemifloxacin on Viability of Chlamydia pneumoniae (Chlamydophila pneumoniae) in an In Vitro Continuous Infection Model,” J Antimicrob Chemother, 2002, 49(5):763-7.
Lawrence KR, Adra M, and Keir C, “Hypoglycemia-Induced Anoxic Brain Injury Possibly Associated With Levofloxacin,” J Infect, 2006, 52(6):e177-80.
Lode H, File TM Jr, Mandell L, et al, “Oral Gemifloxacin Versus Sequential Therapy With Intravenous Ceftriaxone/Oral Cefuroxime With or Without a Macrolide in the Treatment of Patients Hospitalized With Community-Acquired Pneumonia: A Randomized, Open-Label, Multicenter Study of Clinical Efficacy and Tolerability. 185 Gemifloxacin Study Group,” Clin Ther, 2002, 24(11):1915-36.
Malone RS, Fish DN, Abraham E, et al, “Pharmacokinetics of Levofloxacin and Ciprofloxacin During Continuous Renal Replacement Therapy in Critically Ill Patients,” Antimicrob Agents Chemother, 2001, 45(10):2949-54.
Mandell LA, Wunderink RG, Anzueto A, et al, “Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults,” Clin Infect Dis, 2007, 44 (Suppl 2):27-72.
Mohr JF, McKinnon PS, Peymann PJ, et al, “A Retrospective, Comparative Evaluation of Dysglycemias in Hospitalized Patients Receiving Gatifloxacin, Levofloxacin, Ciprofloxacin, or Ceftriaxone,” Pharmacotherapy, 2005, 25(10):1303-9.
Park-Wyllie LY, Juurlink DN, Kopp A, et al, “Outpatient Gatifloxacin Therapy and Dysglycemia in Older Adults,” N Engl J Med, 2006, 354(13):1352-61.
Szarfman A, Chen M, and Blum MD, “More on Fluoroquinolone Antibiotics and Tendon Rupture,” N Engl J Med, 1995, 332(3):193.
Trotman RL, Williamson JC, Shoemaker DM, et al, “Antibiotic Dosing in Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy,” Clin Infect Dis, 2005, 41(8):1159-66.
Wang S and Rizvi AA, “Levofloxacin-Induced Hypoglycemia in a Nondiabetic Patient,” Am J Med Sci, 2006, 331(6):334-5.
Wilson R, Langan C, Ball P, et al, “Oral Gemifloxacin Once Daily for 5 Days Compared With Sequential Therapy With I.V. Ceftriaxone/Oral Cefuroxime (Maximum of 10 Days) in the Treatment of Hospitalized Patients With Acute Exacerbations of Chronic Bronchitis. Gemifloxacin 207 Clinical Study Group,” Respir Med, 2003, 97(3):242-9.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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