Gemifloxacin Mesylate

Class: Quinolones
VA Class: AM900
Chemical Name: (Z - 7 - [3 - (Aminomethyl) - 4 - (methoxyimino) - 1 - pyrrolidinyl] - 1 - cyclopropyl - 6 - fluoro - 1,4 - dihydro - 4 - oxo - 1,8 - naphthyridine - 3 - carboxylic acid monomethanesulfonate
Molecular Formula: C18H20FN5O4•CH4O3S
CAS Number: 204519-65-3
Brands: Factive

Warning(s)

Special Alerts:

[Posted 08/15/2013] ISSUE: ISSUE: FDA has required the drug labels and Medication Guides for all fluoroquinolone antibacterial drugs be updated to better describe the serious side effect of peripheral neuropathy. This serious nerve damage potentially caused by fluoroquinolones may occur soon after these drugs are taken and may be permanent.

BACKGROUND: The risk of peripheral neuropathy occurs only with fluoroquinolones that are taken by mouth or by injection. Approved fluoroquinolone drugs include levofloxacin (Levaquin), ciprofloxacin (Cipro), moxifloxacin (Avelox), norfloxacin (Noroxin), ofloxacin (Floxin), and gemifloxacin (Factive). The topical formulations of fluoroquinolones, applied to the ears or eyes, are not known to be associated with this risk.

RECOMMENDATION: Make sure your patients know to contact you if they develop symptoms of peripheral neuropathy. Make sure your patients receive the Medication Guide with every prescription. If a patient develops symptoms of peripheral neuropathy, the fluoroquinolone should be stopped, and the patient should be switched to another, non-fluoroquinolone antibacterial drug, unless the benefit of continued treatment with a fluoroquinolone outweighs the risk. Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program.

For more information visit the FDA website at: and .

REMS:

FDA approved a REMS for gemifloxacin mesylate to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

Warning(s)

  • Fluoroquinolones, including gemifloxacin, are associated with an increased risk of tendinitis and tendon rupture in all age groups.1 55 56 This risk is further increased in older adults (usually those >60 years of age), individuals receiving concomitant corticosteroids, and kidney, heart, or lung transplant recipients.1 55 56 (See Tendinopathy and Tendon Rupture under Cautions.)

Introduction

Antibacterial; naphthyridine derivative; fluoroquinolone.1 4 12 23

Uses for Gemifloxacin Mesylate

Respiratory Tract Infections

Treatment of acute bacterial exacerbations of chronic bronchitis caused by susceptible Streptococcus pneumoniae, Haemophilus influenzae, H. parainfluenzae, or Moraxella catarrhalis.1 2 3 28

Treatment of mild to moderate community-acquired pneumonia (CAP) caused by susceptible S. pneumoniae (including multidrug-resistant strains), H. influenzae, M. catarrhalis, Mycoplasma pneumoniae, Chlamydophila pneumoniae (formerly Chlamydia pneumoniae), or Klebsiella pneumoniae.1 29 43

Slideshow: Prescription Drug Addiction - Are You at Risk?

Select regimen for empiric treatment of CAP based on most likely pathogens and local susceptibility patterns; after pathogen is identified, modify to provide more specific therapy (pathogen-directed therapy).6 Do not use a fluoroquinolone alone for empiric treatment of CAP in inpatients requiring treatment in an intensive care unit (ICU).6

For empiric outpatient treatment of CAP in previously healthy adults without risk factors for drug-resistant S. pneumoniae (DRSP), IDSA and ATS recommend monotherapy with a macrolide (azithromycin, clarithromycin, erythromycin) or, alternatively, doxycycline.6 If risk factors for DRSP are present (e.g., chronic heart, lung, liver, or renal disease, diabetes mellitus, alcoholism, malignancy, asplenia, immunosuppression, history of anti-infective treatment within the last 3 months), IDSA and ATS recommend monotherapy with a fluoroquinolone with enhanced activity against S. pneumoniae (gemifloxacin, levofloxacin, moxifloxacin) or, alternatively, a combination regimen that includes a β-lactam active against S. pneumoniae (high-dose amoxicillin or fixed combination of amoxicillin and clavulanic acid or, alternatively, ceftriaxone, cefpodoxime, or cefuroxime) given in conjunction with a macrolide or doxycycline.6

For empiric inpatient treatment of CAP in non-ICU patients, IDSA and ATS recommend adults receive monotherapy with a fluoroquinolone with enhanced activity against S. pneumoniae (gemifloxacin, levofloxacin, moxifloxacin) or, alternatively, a combination regimen that includes a β-lactam (usually cefotaxime, ceftriaxone, or ampicillin) given in conjunction with a macrolide (azithromycin, clarithromycin, erythromycin) or doxycycline.6 For empiric inpatient treatment of CAP in ICU patients when Pseudomonas and oxacillin-resistant (methicillin-resistant) Staphylococcus aureus are not suspected, IDSA and ATS recommend a combination regimen that includes a β-lactam (cefotaxime, ceftriaxone, fixed combination of ampicillin and sulbactam) given in conjunction with either azithromycin or a fluoroquinolone (gemifloxacin, levofloxacin, moxifloxacin).6

Gemifloxacin Mesylate Dosage and Administration

Administration

Oral Administration

Administer orally once daily without regard to meals.1 14

Take with copious amounts (≥100 mL) of fluids to prevent formation of highly concentrated urine.1

Tablets should be swallowed intact and should not be chewed or crushed.1 23

Dosage

Available as gemifloxacin mesylate; dosage expressed in terms of gemifloxacin.1

Adults

Respiratory Tract Infections
Acute Exacerbations of Chronic Bronchitis
Oral

320 mg once daily for 5 days.1

Mild to Moderate Community-acquired Pneumonia (CAP)
Oral

Known or suspected to be caused by S. pneumoniae, H. influenzae, M. pneumoniae, or C. pneumoniae: 320 mg once daily for 5 days.1

Known or suspected to be caused by multidrug-resistant S. pneumoniae, K. pneumoniae, or M. catarrhalis: 320 mg once daily for 7 days.1

Manufacturer recommends that results of initial sputum cultures be used to guide clinical decisions regarding use of a 5- or 7-day regimen.1 IDSA and ATS state that CAP should be treated for a minimum of 5 days and patients should be afebrile for 48–72 hours before discontinuing anti-infective therapy.6

Prescribing Limits

Adults

Do not exceed recommended dosage or duration of therapy.1

Special Populations

Hepatic Impairment

Dosage adjustments not required in adults with mild, moderate, or severe hepatic impairment (Child Pugh class A, B, or C).1

Renal Impairment

Reduce dosage to 160 mg once daily in adults with Clcr ≤40 mL/minute, including those on hemodialysis or CAPD.1

Gemifloxacin partially removed by hemodialysis;1 administer dose after hemodialysis.23

Geriatric Patients

No dosage adjustments except those related to renal impairment.1 (See Renal Impairment under Dosage and Administration.)

Cautions for Gemifloxacin Mesylate

Contraindications

  • Known hypersensitivity to gemifloxacin, other fluoroquinolones, or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Tendinopathy and Tendon Rupture

Fluoroquinolones, including gemifloxacin, are associated with increased risk of tendinitis and tendon rupture in all age groups.1 55 56 This risk is further increased in older adults (usually those >60 years of age), individuals receiving concomitant corticosteroids, and kidney, heart, or lung transplant recipients.1 55 56 (See Geriatric Use under Cautions.)

Other factors that may independently increase risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis.1 55 56 Tendinitis and tendon rupture have been reported in patients receiving fluoroquinolones who did not have any of these risk factors.1

Fluoroquinolone-associated tendinitis and tendon rupture most frequently involve the Achilles tendon and may require surgical repair.1 Tendinitis and tendon rupture in the rotator cuff (shoulder), hand, biceps, thumb, and other tendon sites also reported.1

Tendon rupture can occur during or following fluoroquinolone therapy and has been reported up to several months after completion of therapy.1

Discontinue if pain, swelling, inflammation, or rupture of a tendon occurs.1 55 56 Advise patients to rest and refrain from exercise and contact a clinician at the first sign of tendinitis or tendon rupture (e.g., pain, swelling, or inflammation of a tendon; weakness or inability to use a joint).1 55 56 (See Advice to Patients.)

Prolongation of QT Interval

Prolonged QT interval and increased risk of ventricular arrhythmias, including torsades de pointes, reported with some fluoroquinolones, including gemifloxacin.1 24

Do not exceed usual recommended dosage since this may increase risk of prolonged QT interval, especially in those with renal or hepatic impairment.1

Avoid use in patients with a history of prolonged QT interval, in those with uncorrected electrolyte disorders (e.g., hypokalemia, hypomagnesemia), and in those receiving class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents.1

Use with caution in patients receiving drugs that prolong QT interval (e.g., cisapride [available in the US only under a limited-access protocol], erythromycin, antipsychotic agents, tricyclic antidepressants) and in those with ongoing proarrhythmic conditions, such as clinically important bradycardia or acute myocardial ischemia.1

Musculoskeletal Effects

Fluoroquinolones, including gemifloxacin, cause arthropathy and osteochondrosis in immature animals of various species;1 12 45 46 47 48 49 52 53 relevance of these adverse effects in immature animals to use in humans unknown.50 51 Safety and efficacy of gemifloxacin not established in children and adolescents <18 years of age (see Pediatric Use under Cautions) or in pregnant or lactating women (see Pregnancy and see Lactation under Cautions).1

CNS Effects

Seizures, toxic psychoses, and increased intracranial pressure and CNS stimulation, which may lead to tremor, restlessness, anxiety, lightheadedness, confusion, hallucinations, paranoia, depression, insomnia, and rarely, suicidal thoughts or acts, have been reported with fluoroquinolones.1

Use with caution in patients with known or suspected CNS disorders (e.g., seizure disorders) or other risk factors that predispose to seizures.1

If nervous system effects occur, discontinue gemifloxacin and institute appropriate measures.1

Peripheral Neuropathy

Sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias, and weakness have been reported rarely in patients receiving quinolones.1

Superinfection/Clostridium difficile-associated Diarrhea and Colitis (CDAD)

Possible emergence and overgrowth of nonsusceptible organism.1 Institute appropriate therapy if superinfection occurs.1

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.1 31 32 33 34 35 C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) has been reported with nearly all anti-infectives, including gemifloxacin, and may range in severity from mild diarrhea to fatal colitis.1 37 41 42 Outbreaks of severe CDAD caused by fluoroquinolone-resistant C. difficile have been reported with increasing frequency over the past several years.36 37 38 39 41 Hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.1

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.1 31 32 33 34 35 40 Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.1

If CDAD is suspected or confirmed, discontinuance of gemifloxacin may be needed.1 Some mild cases of CDAD may respond to discontinuance alone.31 32 33 34 35 Manage moderate to severe cases with fluid, electrolyte, and protein supplementation, appropriate anti-infective therapy active against C. difficile (e.g., oral metronidazole or vancomycin), and surgical evaluation when clinically indicated.1 31 32 33 34 35

Sensitivity Reactions

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions reported in patients receiving fluoroquinolones.1 These reactions may occur with first dose.1

Some reactions have been accompanied by cardiovascular collapse, hypotension or shock, seizures, loss of consciousness, tingling, angioedema (e.g., edema or swelling of the tongue, larynx, throat, or face), airway obstruction (e.g., bronchospasm, shortness of breath, acute respiratory distress), urticaria, pruritus, and other severe skin reactions.1

Discontinue gemifloxacin at first appearance of rash, jaundice, or any other sign of hypersensitivity.1 23 Institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).1

Photosensitivity Reactions

Moderate to severe photosensitivity/phototoxicity reactions reported rarely with fluoroquinolones, including gemifloxacin.1

Phototoxicity may manifest as exaggerated sunburn reactions (e.g., burning, erythema, exudation, vesicles, blistering, edema) on areas exposed to sun or artificial ultraviolet (UV) light (usually the face, neck, extensor surfaces of forearms, dorsa of hands).1

Relative potential of the various fluoroquinolones to cause photosensitivity/phototoxicity unclear.1 Factors that contribute to susceptibility to this adverse effect during fluoroquinolone therapy include patient’s skin pigmentation, frequency and duration of exposure to sun and UV light, use of protective clothing and sunscreen, concomitant use of other drugs, and dosage and duration of fluoroquinolone therapy.1

Avoid unnecessary or excessive exposure to sunlight or artificial UV light (tanning beds, UVA/UVB treatment) while receiving gemifloxacin.1 If patient needs to be outdoors, they should wear loose-fitting clothing that protects skin from sun exposure and use other sun protection measures (sunscreen).1

Discontinue gemifloxacin if photosensitivity or phototoxicity (sunburn-like reaction, skin eruption) occurs.1

General Precautions

Selection and Use of Anti-infectives

When prescribing a fluoroquinolone, consider potential benefits and risks for the individual patient.55 56 Most patients tolerate the drugs, but serious adverse reactions (e.g., CNS effects, QT prolongation, C. difficile-associated diarrhea and colitis, damage to liver, kidneys, or bone marrow, alterations in glucose homeostatis) may occur rarely.55 56

To reduce development of drug-resistant bacteria and maintain effectiveness of gemifloxacin and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.1

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.1 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.1

Dermatologic Reactions

Rash (maculopapular, urticarial) reported;1 5 12 usually resolves within 14 days.1

Rash reported most frequently in patients <40 years of age (especially women), in women receiving hormone replacement therapy, and in patients who received gemifloxacin for >7 days (although this was not evident in men ≥40 years of age).1

Discontinue gemifloxacin at first appearance of rash.1

Specific Populations

Pregnancy

Category C.1

Lactation

Distributed into milk in rats.1 Do not use in nursing women unless possible benefits outweigh potential risks.1

Pediatric Use

Safety and efficacy not established in children or adolescents <18 years of age.1 Like other fluoroquinolones, gemifloxacin causes arthropathy and osteochondrosis in juvenile animals.1 (See Musculoskeletal Effects under Cautions.)

AAP states use of fluoroquinolones may be justified in children <18 years of age in special circumstances after careful assessment of the risks and benefits for the individual patient and after these benefits and risks have been explained to the parents or caregivers.26

Geriatric Use

No overall differences in safety or efficacy relative to younger adults.1

Risk of severe tendon disorders, including tendon rupture, is increased in older adults (usually those >60 years of age).1 55 56 This risk is further increased in those receiving concomitant corticosteroids.1 55 56 (See Tendinopathy and Tendon Rupture under Cautions.) Use caution in geriatric adults, especially those receiving concomitant corticosteroids.1

Risk of QT interval prolongation may be increased in geriatric patients.1 (See Prolongation of QT Interval under Cautions.)

Consider age-related decreases in renal function when selecting dosage.1 (See Renal Impairment under Dosage and Administration.)

Hepatic Impairment

Serum concentrations and AUC may be increased; dosage adjustments not considered necessary.1

Renal Impairment

Decreased renal clearance and prolonged half-life; reduce dosage in those with Clcr ≤40 mL/minute.1 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI effects (diarrhea, nausea, abdominal pain, vomiting); rash; headache; dizziness.1

Interactions for Gemifloxacin Mesylate

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 the US only under a limited-access protocol], erythromycin, antipsychotic agents, tricyclic antidepressants).1 (See Prolongation of QT Interval under Cautions.)

Specific Drugs

Drug

Interaction

Comments

Antacids (aluminum- or magnesium-containing)

Decreased absorption of gemifloxacin1

Administer antacids containing aluminum or magnesium at least 3 hours before or 2 hours after gemifloxacin1

Antacids (calcium-containing); calcium supplements

No clinically important pharmacokinetic interactions 1

Anticoagulants, oral (warfarin)

Increased PT, INR, and/or bleeding reported1

Closely monitor PT, INR, or other suitable coagulation test1

Consider that infectious disease and its accompanying inflammatory process, age, and general patient status also are risk factors for increased anticoagulation activity1

Cimetidine

Slightly increased gemifloxacin concentrations1

Not considered clinically important1

Corticosteroids

Increased risk of tendinitis or tendon rupture, especially in patients >60 years of age1 55 56

Didanosine

Decreased absorption of gemifloxacin with buffered didanosine preparations1

Administer buffered didanosine (pediatric oral solution admixed with antacid) at least 3 hours before or 2 hours after gemifloxacin1

Digoxin

No evidence of effect on digoxin pharmacokinetics1

Hormonal contraceptives

Possible decreased gemifloxacin concentrations;1 no evidence of effect on pharmacokinetics of ethinyl estradiol/levonorgestrel oral contraceptives1

Not considered clinically important1

Iron preparations

Decreased absorption of gemifloxacin1 15

Administer ferrous sulfate and dietary supplements containing iron at least 3 hours before or 2 hours after gemifloxacin1 15

Multivitamins and mineral supplements

Decreased absorption of gemifloxacin1

Administer supplements containing zinc, magnesium, or iron at least 3 hours before or 2 hours after gemifloxacin1

Omeprazole

Possible increased gemifloxacin concentrations1

Not considered clinically important1

Probenecid

Increased gemifloxacin concentrations1

Sucralfate

Decreased absorption of gemifloxacin1 15

Administer gemifloxacin at least 2 hours before sucralfate1 15

Theophylline

No evidence of effect on theophylline pharmacokinetics 1

Gemifloxacin Mesylate Pharmacokinetics

Absorption

Bioavailability

71%.1

Rapidly absorbed from GI tract;1 21 30 peak plasma concentrations attained within 0.5 –2 hours.1 21 30

Food

Administration of 320-mg dose with a standard high-fat breakfast (2 eggs cooked in butter, 2 strips of bacon, hash brown potatoes, 2 slices of toast with butter, 300 mL whole milk) reduces peak plasma concentration and AUC by 12 and 3%, respectively;14 this reduction in systemic exposure not considered clinically important.1 14

Distribution

Extent

Widely distributed into body tissues and fluids, including lung tissue and fluids.1

Distributed into milk in rats.1

Plasma Protein Binding

60–70%.1

Elimination

Metabolism

Metabolized to a limited extent in liver.1 Not metabolized by CYP isoenzymes.1

Elimination Route

Eliminated by renal and nonrenal mechanisms.1

36% of a dose eliminated in urine and 61% excreted in feces as unchanged drug and metabolites.1

Half-life

7 hours (range 4–12 hours).1 21 30

Special Populations

Pharmacokinetics in geriatric patients similar to that in younger adults.1

Adults with hepatic impairment: Peak plasma concentrations increased 25% in those with mild to moderate hepatic impairment (Child-Pugh class A or B) and increased 41% in those with severe hepatic impairment (Child-Pugh class C); no substantial change in plasma half-life.1 Increased serum concentrations not considered clinically important.1

Adults with renal impairment: Decreased clearance and prolonged half-life.1

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).1 Protect from light.1

Actions and Spectrum

  • 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

Advice to Patients

  • Advise patients that antibacterials (including gemifloxacin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1

  • Importance of completing full course of therapy, even if feeling better after a few days.1

  • Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with gemifloxacin or other antibacterials in the future.1

  • May be taken without regard to meals,1 but should be taken with copious amounts (≥100 mL) of fluids to prevent formation of highly concentrated urine.1

  • Importance of taking gemifloxacin at least 2 hours before or 3 hours after multivitamins containing iron, magnesium, or zinc; aluminum- or magnesium-containing antacids; or buffered didanosine (pediatric oral solution admixed with antacid).1 Importance of taking gemifloxacin at least 2 hours before sucralfate.1

  • Increased risk of tendinitis and tendon rupture in all age groups and further increased risk in adults >60 years of age, individuals receiving corticosteroids, and kidney, heart, or lung transplant recipients.1 55 56 Importance of resting and refraining from exercise at the first sign of tendinitis or tendon rupture (e.g., pain, swelling, or inflammation of a tendon; weakness or inability to use a joint), discontinuing the drug, and contacting a clinician regarding changing to an anti-infective that is not a fluoroquinolone.1 55 56 (See Tendinopathy and Tendon Rupture under Cautions.)

  • Potential for gemifloxacin to cause dizziness and lightheadedness; need for caution when operating machinery or driving a motor vehicle until effects of drug on individual are known.1

  • Importance of informing clinician if medical history includes palpitations, seizures, or fainting spells or if any of these occur during therapy.1

  • Advise patient that gemifloxacin has been associated with rash or hives and that rash occurs most frequently in patients <40 years of age (especially women), in postmenopausal women receiving hormone replacement therapy, and in patients who receive gemifloxacin for >5 days (especially when given for >7 days).1 Importance of discontinuing gemifloxacin and informing clinician if rash occurs.1

  • May be associated with hypersensitivity reactions (including anaphylactic reactions), even following the first dose.1 Importance of immediately discontinuing gemifloxacin and informing clinician at the first sign of rash, jaundice, or any other sign of hypersensitivity.1

  • Risk of photosensitivity/phototoxicity reactions following exposure to sun or UV light while receiving fluoroquinolones.1 Importance of avoiding or minimizing exposure to sunlight or artificial UV light (e.g., tanning beds, UVA/UVB treatment) and using protective measures (e.g., wearing loose-fitting clothes, sunscreen) if outdoors during gemifloxacin therapy.1 Discontinue gemifloxacin and inform a clinician if a sunburn-like reaction or skin eruption occurs.

  • Advise patient that gemifloxacin may prolong QT interval and should be avoided in those receiving class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents and used with caution in those receiving drugs that prolong QT interval (e.g., cisapride [available in the US only under a limited-access protocol], erythromycin, antipsychotic agents, tricyclic antidepressants).1

  • Importance of informing clinician of personal or family history of QT interval prolongation or proarrhythmic conditions (e.g., recent hypokalemia, bradycardia, recent myocardial ischemia).1

  • Advise patients that seizures have been reported and importance of informing clinician about any history of convulsions, seizures, or epilepsy before taking gemifloxacin.1

  • Advise patients of risk of other CNS problems (e.g., tremors, restlessness, confusion, hallucinations).1

  • Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.1 Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.1

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, especially drugs that may affect QT interval (e.g., cisapride [available in the US only under a limited-access protocol], erythromycin, antipsychotic agents, tricyclic antidepressants).1 Importance of informing clinicians of concomitant therapy with warfarin or its derivatives.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Gemifloxacin Mesylate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

320 mg (of gemifloxacin)

Factive ()

Oscient

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Factive 320MG Tablets (CORNERSTONE BIOPHARMA): 5/$219.99 or 15/$629.98

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 4, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Oscient Pharmaceuticals. Factive (gemifloxacin mesylate) tablets prescribing information. Waltham, MA; 2008 Oct

2. File T, Schlemmer B, Garau J et al. Gemifloxacin versus amoxicillin/clavulanate in the treatment of acute exacerbations of chronic bronchitis. J Chemother. 2000; 12:314-25. [PubMed 10949981]

3. Wilson R, Schentag JJ, Ball P et al. A comparison of gemifloxacin and clarithromycin in acute exacerbations of chronic bronchitis and long-term clinical outcomes. Clin Ther. 2002; 24:639-52. [IDIS 485250] [PubMed 12017408]

4. Lowe MN, Lamb HM. Gemifloxacin. Drugs. 2000; 59:1137-47. [PubMed 10852645]

5. File TM, Schlemmer B, Garau J et al. Efficacy and safety of gemifloxacin in the treatment of community-acquired pneumonia: a randomized, double-blind comparison with trovafloxacin. J Antimicrob Chemother. 2001; 48:67-74. [IDIS 467735] [PubMed 11474633]

6. 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:S27-72. [PubMed 17278083]

7. Heffelfinger JD, Dowell SF, Jorgensen JH et al. Management of community-acquired pneumonia in the era of pneumococcal resistance: a report from the drug-resistance streptococcus pneumoniae therapeutic working group. Arch Intern Med. 2000; 160:1399-1408. [IDIS 448719] [PubMed 10826451]

9. Bishai W. Current issues on resistance, treatment guidelines, and the appropriate use of fluoroquinolones for respiratory tract infections. Clin Ther. 2002; 24:838-50. [IDIS 483635] [PubMed 12117077]

10. Schering-Plough. Avelox (moxifloxacin hydrochloride) tablets and Avelox I.V. (moxifloxacin hydrochloride in sodium chloride injection) prescribing information. Kenilworth, NJ; 2008 Oct.

12. Zhanel GG, Ennis K, Vercaigne L et al. A critical review of the fluoroquinolones: focus on respiratory tract infections. Drugs. 2002; 62:13-59. [PubMed 11790155]

13. Ball P. Quinolone generations: natural history or natural selection?. J Antimicrob Chemother. 2000; 46:17-24. [IDIS 450996] [PubMed 10997595]

14. Allen A, Bygate E, Clark D et al. The effect of food on the bioavailability of oral gemifloxacin in healthy volunteers. Int J Antimicrob Agents. 2000; 16:45-50. [PubMed 11185412]

15. Allen A, Bygate E, Faessel H et al. The effect of ferrous sulphate and sucralfate on the bioavailability of oral gemifloxacin in healthy volunteers. Int J Antimicrob Agents. 2000; 16:283-9.

16. Allen A, Vousden M, Porter A et al. Effect of Maalox on the bioavailability of oral gemifloxacin in healthy volunteers. Chemotherapy. 1999; 45:504-11. [IDIS 439831] [PubMed 10567782]

17. Davy M, Allen A, Bird N et al. Lack of effect of gemifloxacin on the steady-state pharmacokinetics of theophylline in healthy volunteers. Chemotherapy. 1999; 45:478-84. [IDIS 439827] [PubMed 10567778]

18. Vousden M, Allen A, Lewis A et al. Lack of pharmacokinetic interaction between gemifloxacin and digoxin in healthy elderly volunteers. Chemotherapy. 1999; 45:485-90. [IDIS 439828] [PubMed 10567779]

19. Davy M, Bird N, Rost KL et al. Lack of effect of gemifloxacin on the steady-state pharmacodynamics of warfarin in healthy volunteers. Chemotherapy. 1999; 45:491-5. [IDIS 439829] [PubMed 10567780]

20. Allen A, Vousden M, Lewis A et al. Effect of omeprazole on the pharmacokinetics of oral gemifloxacin in healthy volunteers. Chemotherapy. 1999; 45:496-503. [IDIS 439830] [PubMed 10567781]

21. Allen A, Bygate E, Vousden M et al. Multiple-dose pharmacokinetics and tolerability of gemifloxacin administered orally to healthy volunteers. Antimicrob Agents Chemother. 2001; 45:540-5. [IDIS 458566] [PubMed 11158752]

22. Boswell FJ, Andrews JM, Jevons G et al. Comparison of the in vitro activities of several new fluoroquinolones against respiratory pathogens and their abilities to select fluoroquinolone resistance. J Antimicrob Chemother. 2002; 50:495-502. [PubMed 12356793]

23. Genesoft, Inc, South San Francisco, CA: Personal communication.

24. Ortho-McNeil Pharmaceutical. Levaquin (levofloxacin) tablets, oral solution, injection for intravenous use, and injection in 5% dextrose for intravenous use prescribing information. Raritan, NJ; 2008 Oct.

26. American Academy of Pediatrics. 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006.

27. Ruiz-Serrano MJ, Alcala L, Martinez L et al. In vitro activities of six fluoroquinolones against 250 clinical isolates of Mycobacterium tuberculosis susceptible or resistant to first-line antituberculosis drugs. Antimicrob Agents Chemother. 2000; 44:2567-8.

28. Sethi S, Fogarty C, Fulambarker A. A randomized, double-blind study comparing 5 days oral gemifloxacin with 7 days of levofloxacin in patients with acute exacerbation of chronic bronchitis. Respir Med. 2004; 98:697-707. [PubMed 15303633]

29. Leophonte P, File T, Feldman C. Gemifloxacin once daily for 7 days compared to amoxicillin/clavulanic acid thrice daily for 10 days for the treatment of community-acquired pneumonia of suspected pneumococcal origin. Respir Med. 2004; 98:708-20. [PubMed 15303634]

30. Allen A, Bygate E, Oliver S et al. Pharmacokinetics and tolerability of gemifloxacin (SB-265805) after administration of single oral doses to healthy volunteers. Antimicrob Agents Chemother. 2000; 44:1604-8. [PubMed 10817716]

31. Johnson S, Gerding DN. Clostridium difficile-associated diarrhea. Clin Infect Dis. 1998; 26:1027-36. [IDIS 407733] [PubMed 9597221]

32. Gerding DN, Johnson S, Peterson LR et al for the Society for Healthcare Epidemiology of America. Position paper on Clostridium difficile-associated diarrhea and colitis. Infect Control Hosp Epidemiol. 1995; 16:459-77. [PubMed 7594392]

33. Fekety R for the American College of Gastroenterology Practice Parameters Committee. Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis. Am J Gastroenterol. 1997; 92:739-50. [IDIS 386628] [PubMed 9149180]

34. American Society of Health-System Pharmacists Commission on Therapeutics. ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile-associated disease. Am J Health-Syst Pharm. 1998; 55:1407-11. [IDIS 407213] [PubMed 9659970]

35. Wilcox MH. Treatment of Clostridium difficile infection. J Antimicrob Chemother. 1998; 41(Suppl C)::41-6.

36. McDonald LC, Killgore GE, Thompson A et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med. 2005; 353:2433-41. [PubMed 16322603]

37. Loo VG, Poirier L, Miller MA et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med. 2005; 353:2442-9. [PubMed 16322602]

38. McDonald LC, Owings M, Jernigan DB. Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996-2003. Emerg Infect Dis. 2006; 12:409-15. [PubMed 16704777]

39. Bartlett JG, Peri TM. The new Clostridium difficile–what does it mean? N Engl J Med. 2005; 353:2503-5.

40. Centers for Disease Control and Prevention. Severe Clostridium difficile-associated disease in populations previously at low risk–four states, 2005. MMWR. 2005; 54:1201-5. [PubMed 16319813]

41. Kazakova SV, Ware K, Baughman B et al. A hospital outbreak of diarrhea due to an emerging epidemic strains of Clostridium difficile. Arch Intern Med. 2006; 166:2518-24. [PubMed 17159019]

42. Dhalla IA, Mamdani MM, Simor AE et al. Are broad-spectrum fluoroquinolones more likely to cause Clostridium difficile-associated disease? Antimicrob Agents Chemother. 2006; 50:3216-9.

43. File TM Jr, Mandell LA, Tillotson G et al. Gemifloxacin once daily for 5 days versus 7 days for the treatment of community-acquired pneumonia: a randomized, multicentre, double-blind study. J Antimicrob Chemother. 2007; 60:112-20. [PubMed 17537866]

44. Ball P. Long-term use of quinolones and their safety. Rev Infect Dis. 1989; 11(Suppl 5):S1365-9. [IDIS 307993] [PubMed 2672258]

45. Davis GJ, McKenzie ME. Toxicologic evaluation of ofloxacin. Am J Med. 1989; 87(Suppl 6C):43S-46S. [PubMed 2690619]

46. Mayer DG. Overview of toxicological studies. Drugs. 1987; 34(Suppl 1):150-3. [PubMed 3325258]

47. Kato M, Onodera T. Morphological investigation of cavity formation in articular cartilage induced by ofloxacin in rats. Fund Appl Toxicol. 1988; 11:110-9.

48. Hooper DC, Wolfson JS. Fluoroquinolone antimicrobial agents. N Engl J Med. 1991; 324:384-94. [IDIS 277079] [PubMed 1987461]

49. Paton JH, Reeves DS. Fluoroquinolone antibiotics: microbiology, pharmacokinetics and clinical uses. Drugs. 1988; 36:193-228. [IDIS 245416] [PubMed 3053126]

50. Maggiolo F, Caprioli S, Suter F. Risk/benefit analysis of quinolone use in children: the effect on diarthrodial joints. J Antimicrob Chemother. 1990; 26:469-71. [PubMed 2254219]

51. Pfister K, Mazur D, Vormann J et al. Diminished ciprofloxacin-induced chondrotoxicity by supplementation with magnesium and vitamin E in immature rats. Antimicrob Agents Chemother. 2007; 51:1022-7. [PubMed 17210779]

52. Stahlmann R. Safety profile of the quinolones. J Antimicrob Chemother. 1990; 26(Suppl D):31-44. [PubMed 2286589]

53. Christ W, Lehnert T, Ulbrich B. Specific toxicologic aspects of the quinolones. Rev Infect Dis. 1988; 10(Suppl 1):S141-6. [IDIS 311600] [PubMed 3279489]

55. Food and Drug Administration. FDA news. FDA requests boxed warnings on fluoroquinolone antimicrobial drugs. 2008 Jul 8. From FDA website.

56. Food and Drug Administration. Information for healthcare professionals: Fluoroquinolone antimicrobial drugs. 2008 Jul 8. From FDA website.

Hide
(web3)