Gemifloxacin has been discontinued in the US. Because this drug is no longer available in the US market, the material in this monograph is no longer updated by AHFS DI. If this drug is used in countries other than the U.S., it is essential that the manufacturers' labeling be consulted for more recently available information. |
Gemifloxacin, a naphthyridine derivative, is a fluoroquinolone anti-infective agent.1, 4, 12, 23
Acute Bacterial Exacerbation of Chronic Bronchitis
Gemifloxacin mesylate is used for the treatment of acute bacterial exacerbations of chronic bronchitis caused by susceptible Streptococcus pneumoniae , Haemophilus influenzae , H. parainfluenzae , or Moraxella catarrhalis .1, 2, 3, 28
Gemifloxacin should be used for the treatment of acute bacterial exacerbations of chronic bronchitis only when there are no other treatment options. 1, 140, 145Because systemic fluoroquinolones, including gemifloxacin, have been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that can occur together in the same patient (see Cautions)1, 140, 145and because acute bacterial exacerbations of chronic bronchitis may be self-limiting in some patients, 1the risks of serious adverse reactions outweigh the benefits of fluoroquinolones for patients with these infections. 140, 145
In several randomized, double-blind, active-controlled studies in patients with acute exacerbation of chronic bronchitis, clinical response (defined as sufficient improvement in or resolution of signs and symptoms at day 13-24 without further need for anti-infectives) was achieved in 86-94% of those receiving oral gemifloxacin (320 mg once daily for 5 days) and in 93, 85, or 85% of those receiving oral amoxicillin and clavulanate potassium (500 mg of amoxicillin 3 times daily for 7 days),2 oral clarithromycin (500 mg twice daily for 7 days),3 or oral levofloxacin (500 mg once daily for 7 days), respectively.1, 28
Gemifloxacin is used for the treatment of community-acquired pneumonia (CAP) of mild to moderate severity caused by susceptible S. pneumoniae (including multidrug-resistant strains; MDRSP), H. influenzae , M. catarrhalis , Mycoplasma pneumoniae , Chlamydophila pneumoniae (formerly Chlamydia pneumoniae ), or Klebsiella pneumoniae .1, 29, 43
Initial treatment of CAP generally involves use of an empiric anti-infective regimen based on the most likely pathogens and local susceptibility patterns;512 treatment may then be changed (if possible) to provide a more specific regimen (pathogen-directed therapy) based on results of in vitro culture and susceptibility testing.512 The most appropriate empiric regimen varies depending on the severity of illness at the time of presentation, whether outpatient treatment or hospitalization in or out of an intensive care unit (ICU) is indicated, and the presence or absence of cardiopulmonary disease and other modifying factors that increase the risk of certain pathogens (e.g., methicillin-resistant Staphylococcus aureus [MRSA; also known as oxacillin-resistant S. aureus or ORSA], penicillin-resistant S. pneumoniae , multidrug-resistant S. pneumoniae , enteric gram-negative bacilli, Pseudomonas aeruginosa ).512
For additional information on management of respiratory tract infections, the current clinical practice guidelines from the Infectious Diseases Society of America (IDSA) available at [Web] should be consulted.512
In several controlled and uncontrolled studies in patients with clinically and radiographically documented CAP, clinical response was achieved in 89-92% of patients receiving oral gemifloxacin (320 mg once daily for 7 days).1, 29, 43 In 35 patients with CAP caused by multidrug-resistant S. pneumoniae , clinical and bacteriologic response was achieved in 83% of patients treated with a 7-day regimen of the drug.1 The rate of clinical response reported with oral gemifloxacin (320 mg once daily for 7 days) is similar to that reported with oral amoxicillin and clavulanate potassium (1 g of amoxicillin 3 times daily for 10 days).1, 29
In studies evaluating a 7-day regimen of oral gemifloxacin in patients with mild to moderate CAP, the bacterial eradication rate was 87% in those with S. pneumoniae , 91% in those with H. influenzae , 92% in those with M. catarrhalis , 90% in those with K. pneumoniae , and 95-96% in those with C. pneumoniae or M. pneumoniae infection.1 In 35 patients with CAP caused by multidrug-resistant S. pneumoniae , the bacterial eradication rate was 94% in those with isolates resistant to penicillin; 91% in those with isolates resistant to second generation cephalosporins; 89% in those with isolates resistant to co-trimoxazole; 82% in those with isolates resistant to macrolides (i.e., clarithromycin, erythromycin); and 74% in those with isolates resistant to tetracycline.1
In a randomized, double-blind, active-controlled study evaluating a 5-day regimen of oral gemifloxacin (320 mg once daily for 5 days) in patients with clinically and radiographically documented mild to moderate CAP, clinical response was achieved in 95% of patients.1, 43 The bacterial eradication rate in those who received the 5-day regimen of oral gemifloxacin was 100% in those with S. pneumoniae , 96% in those with H. influenzae , 94% in those with C. pneumoniae , and 88% in those with M. pneumoniae infection.1, 43
Gemifloxacin mesylate is administered orally once daily1 without regard to meals.1, 14
Gemifloxacin tablets should be swallowed whole with a liberal amount of fluid and should not be chewed or crushed.1
Aluminum- or magnesium-containing antacids, dietary supplements containing metal cations such as zinc or iron (e.g., multivitamins, ferrous sulfate), or buffered didanosine preparations should be administered at least 3 hours before or 2 hours after gemifloxacin;1, 15, 16, 23 gemifloxacin should be administered at least 2 hours before sucralfate.1 These drugs may substantially interfere with absorption of gemifloxacin, resulting in systemic concentrations considerably lower than desired.1, 15, 16, 23 (See Drug Interactions.)
Patients receiving gemifloxacin should be adequately hydrated and instructed to drink fluids liberally to prevent highly concentrated urine.1
Dosage of gemifloxacin mesylate is expressed in terms of gemifloxacin.1
Dosage and duration of gemifloxacin therapy, particularly in patients with renal or hepatic impairment, should not exceed those recommended by the manufacturer.1 (See Cautions: Warnings/Precautions.)
Acute Exacerbations of Chronic Bronchitis
If oral gemifloxacin is used for the treatment of acute bacterial exacerbations of chronic bronchitis in adults (see Acute Bacterial Exacerbation of Chronic Bronchitis under Uses: Respiratory Tract Infections), the recommended dosage is 320 mg once daily for 5 days.1
Mild to Moderate Community-acquired Pneumonia
For the treatment of mild to moderate community-acquired pneumonia (CAP) known or suspected to be caused by Streptococcus pneumoniae , Haemophilus influenzae , Mycoplasma pneumoniae , or Chlamydophila pneumoniae (formerly Chlamydia pneumoniae ) in adults, the recommended dosage of oral gemifloxacin is 320 mg once daily for 5 days.1
For the treatment of mild to moderate CAP known or suspected to be caused by multidrug-resistant S. pneumoniae (MDRSP), Klebsiella pneumoniae , or Moraxella catarrhalis in adults, the recommended dosage of oral gemifloxacin is 320 mg once daily for 7 days.1
The manufacturer recommends that results of initial sputum cultures be used to guide clinical decisions regarding use of a 5- or 7-day gemifloxacin regimen in patients with CAP.1
Dosage adjustments are not necessary when gemifloxacin is used in adults with mild, moderate, or severe hepatic impairment (Child-Pugh class A, B, or C).1
Dosage adjustments are not necessary when gemifloxacin is used in adults with creatinine clearances greater than 40 mL/minute.1
Dosage of gemifloxacin should be reduced in adults with creatinine clearances of 40 mL/minute or less, including those receiving hemodialysis or chronic ambulatory peritoneal dialysis (CAPD).1 The recommended dosage of oral gemifloxacin for such patients is 160 mg once daily.1
Because gemifloxacin is partially removed by hemodialysis,1 the drug should be administered to patients undergoing hemodialysis after the end of the dialysis period.23
Adjustment of gemifloxacin dosage is not necessary in geriatric patients based solely on age.1 However, caution is advised since geriatric patients may be at increased risk for certain adverse effects associated with fluoroquinolones.1 (See Geriatric Use under Warnings/Precautions: Specific Populations, in Cautions.)
Gemifloxacin mesylate is contraindicated in patients with known hypersensitivity to gemifloxacin, other fluoroquinolones, or any ingredient in the formulation.1
Disabling and Potentially Irreversible Serious Adverse Reactions
Systemic fluoroquinolones, including gemifloxacin, have been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that can occur together in the same patient.1, 140, 145 These serious reactions may occur within hours to weeks after a systemic fluoroquinolone is initiated and have occurred in all age groups and in patients without preexisting risk factors for such adverse reactions.1
Gemifloxacin should be discontinued immediately at the first signs or symptoms of any serious adverse reactions.1, 140, 145
Systemic fluoroquinolones, including gemifloxacin, should be avoided in patients who have experienced any of the serious adverse reactions associated with fluoroquinolones.1, 140, 145
Systemic fluoroquinolones, including gemifloxacin, are associated with an increased risk of tendinitis and tendon rupture in all age groups.1, 128, 129
The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in older adults (usually those older than 60 years of age), individuals receiving concomitant corticosteroids, and kidney, heart, or lung transplant recipients.1 (See Geriatric Use under Warnings/Precautions: Specific Populations, in Cautions.)
Other factors that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis.1 Tendinitis and tendon rupture have been reported in patients receiving fluoroquinolones who did not have any risk factors for such adverse reactions.1
Fluoroquinolone-associated tendinitis and tendon rupture most frequently involve the Achilles tendon and have also been reported in the rotator cuff (shoulder), hand, biceps, thumb, and other tendon sites.1 Tendinitis or tendon rupture can occur within hours or days after gemifloxacin is initiated or as long as several months after completion of therapy and can occur bilaterally.1
Gemifloxacin should be discontinued immediately if pain, swelling, inflammation, or rupture of a tendon occurs.1 (See Advice to Patients.)
Systemic fluoroquinolones, including gemifloxacin, should be avoided in patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture.1
Systemic fluoroquinolones, including gemifloxacin, have been associated with an increased risk of peripheral neuropathy.1
Sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias, and weakness has been reported in patients receiving systemic fluoroquinolones, including gemifloxacin.1 Symptoms may occur soon after initiation of gemifloxacin and, in some patients, may be irreversible.1, 130
Gemifloxacin should be discontinued immediately if symptoms of peripheral neuropathy (e.g., pain, burning, tingling, numbness, and/or weakness) occur or if there are other alterations in sensations (e.g., light touch, pain, temperature, position sense, vibratory sensation).1, 130 (See Advice to Patients.)
Systemic fluoroquinolones, including gemifloxacin, should be avoided in patients who have previously experienced peripheral neuropathy.1
Systemic fluoroquinolones, including gemifloxacin, have been associated with an increased risk of adverse psychiatric effects, including toxic psychosis,1 hallucinations,1 paranoia,1 depression,1 suicidal thoughts or acts,1 anxiety,1 agitation,1, 171 nervousness,171 restlessness,1 confusion,1 delirium,1, 171 disorientation,1, 171 disturbances in attention,1, 171 insomnia,1 and memory impairment.1, 171 These adverse effects may occur after the first dose.1
Systemic fluoroquinolones, including gemifloxacin, have been associated with an increased risk of seizures (convulsions), increased intracranial pressure (pseudotumor cerebri), lightheadedness, and tremors.1 Gemifloxacin, like other fluoroquinolones, should be used with caution in patients with CNS disorders (e.g., epilepsy) or other risk factors that predispose to seizures.1
If psychiatric or other CNS effects occur, gemifloxacin should be discontinued immediately and appropriate measures initiated.1 (See Advice to Patients.)
Exacerbation of Myasthenia Gravis
Fluoroquinolones, including gemifloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in individuals with myasthenia gravis.1 Use of fluoroquinolones in myasthenia gravis patients has resulted in requirements for ventilatory support and in death.1
Gemifloxacin should be avoided in patients with a known history of myasthenia gravis.1 Patients should be advised to immediately contact their clinician if they have any worsening muscle weakness or breathing problems.1 (See Advice to Patients.)
Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions have been reported in patients receiving fluoroquinolones.1 These reactions may occur following the first dose.1
Some hypersensitivity reactions have been accompanied by cardiovascular collapse, hypotension or shock, seizure, 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), dyspnea, urticaria, pruritus, and other severe skin reactions.1
Other serious and sometimes fatal adverse effects that have been reported with fluoroquinolones, including gemifloxacin, and that may or may not be related to hypersensitivity reactions include one or more of the following: fever, rash or severe dermatologic reaction (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome); vasculitis, arthralgia, myalgia, serum sickness; allergic pneumonitis; interstitial nephritis, acute renal insufficiency or failure; hepatitis, jaundice, acute hepatic necrosis or failure; anemia (including hemolytic and aplastic anemia), thrombocytopenia (including thrombotic thrombocytopenic purpura), leukopenia, agranulocytosis, pancytopenia, and/or other hematologic abnormalities.1
Gemifloxacin should be discontinued immediately at the first appearance of rash, jaundice, or any other sign of hypersensitivity.1, 23 Appropriate therapy should be initiated as indicated (e.g., epinephrine, oxygen, antihistamines, corticosteroids, airway management).1 (See Advice to Patients.)
Moderate to severe photosensitivity/phototoxicity reactions have been 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
In clinical trials evaluating gemifloxacin, photosensitivity reactions were reported rarely (0.039%).1 In a study evaluating photosensitivity potential in healthy individuals, the incidence of photosensitivity reactions in those receiving gemifloxacin was similar to that reported with ciprofloxacin.1, 4 However, the relative potential of the various fluoroquinolones to cause photosensitivity/phototoxicity is 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
As with other fluoroquinolones, patients should be advised to avoid unnecessary or excessive exposure to sunlight or artificial UV light (e.g., tanning beds, UVA/UVB treatment) while receiving gemifloxacin.1 If a 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
Gemifloxacin should be discontinued if photosensitivity or phototoxicity (sunburn-like reaction, skin eruption) occurs.1
Other Warnings and Precautions
Risk of Aortic Aneurysm and Dissection
Rupture or dissection of aortic aneurysms has been reported in patients receiving systemic fluoroquinolones.172 Epidemiologic studies indicate an increased risk of aortic aneurysm and dissection within 2 months following use of systemic fluoroquinolones, particularly in elderly patients.1 The cause for this increased risk has not been identified.1, 172
Unless there are no other treatment options, systemic fluoroquinolones, including gemifloxacin, should not be used in patients who have an aortic aneurysm or are at increased risk for an aortic aneurysm.1, 172 This includes elderly patients and patients with peripheral atherosclerotic vascular disease, hypertension, or certain genetic conditions (e.g., Marfan syndrome, Ehlers-Danlos syndrome).172
If a patient reports adverse effects suggestive of aortic aneurysm or dissection, fluoroquinolone treatment should be discontinued immediately.172 (See Advice to Patients.)
Prolonged QT interval leading to ventricular arrhythmias, including torsades de pointes, has been reported with some fluoroquinolones, including gemifloxacin.1
Prolonged QT interval, supraventricular tachycardia, and syncope were reported during postmarketing surveillance of patients receiving gemifloxacin.1 Although the manufacturer states that no cardiovascular morbidity or mortality attributable to QT prolongation occurred with gemifloxacin treatment in premarketing clinical trials in over 8119 patients (including in 707 patients concurrently receiving drugs known to prolong the QT interval and 7 patients with uncorrected hypokalemia), gemifloxacin has the potential to prolong the QT interval and, if this happens, the maximal change in the QT interval occurs approximately 5-10 hours following administration of the drug.1
Gemifloxacin should be avoided 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 Caution is advised if gemifloxacin is used concomitantly with other drugs that prolong the QT interval (e.g., cisapride [available in the US only under a limited-access protocol], erythromycin, antipsychotic agents, tricyclic antidepressants).1
Caution is advised if gemifloxacin is used in patients with ongoing proarrhythmic conditions, such as clinically important bradycardia or acute myocardial ischemia.1
The recommended gemifloxacin dosage should not be exceeded, especially in patients with renal or hepatic impairment, since this may increase the risk of QT interval prolongation.1
The risk of prolonged QT interval may be increased in geriatric patients.1 (See Geriatric Use under Warnings/Precautions: Specific Populations, in Cautions.)
Systemic fluoroquinolones have been associated with alterations in blood glucose concentrations, including symptomatic hypoglycemia and hyperglycemia.1, 171 Blood glucose disturbances during fluoroquinolone therapy usually have occurred in patients with diabetes mellitus receiving an oral antidiabetic agent (e.g., glyburide) or insulin.1, 171
Severe cases of hypoglycemia resulting in coma or death have been reported with some systemic fluoroquinolones.1, 171 Although most reported cases of hypoglycemic coma have involved patients with risk factors for hypoglycemia (e.g., older age, diabetes mellitus, renal insufficiency, concomitant use of antidiabetic agents [especially sulfonylureas]), some cases have occurred in patients receiving a fluoroquinolone who were not diabetic and were not reported to be receiving an oral antidiabetic agent or insulin.171
Blood glucose concentrations should be carefully monitored when systemic fluoroquinolones, including gemifloxacin, are used in patients with diabetes mellitus receiving antidiabetic agents.1, 171
If a hypoglycemic reaction occurs, fluoroquinolone treatment should be discontinued and appropriate therapy initiated immediately.1 (See Advice to Patients.)
Rash1, 5, 12 has been reported in 0.4-4.9% of patients receiving gemifloxacin for up to 7 days in clinical studies.1 Urticarial reactions (some not classified as rash) were reported in approximately 0.6% of patients receiving gemifloxacin in clinical studies.1
The most common form of rash associated with gemifloxacin appears to be mild to moderate maculopapular rash;1 80% of rashes resolved within 14 days.1 Approximately 7-10% of reported rash cases were described as severe and approximately 10% of those with rash were treated with systemic corticosteroids.1 Histologic examination confirmed presence of uncomplicated exanthematous morbilliform eruptions.1
Rash has occurred most frequently in patients younger than 40 years of age (especially females), in women receiving hormone replacement therapy, and in patients who received gemifloxacin for longer than 7 days (although this was not evident in men 40 years of age and older);1 the reason for this observation has not been clearly elucidated.23
Gemifloxacin should be discontinued in patients who develop rash or urticaria.1 (See Hypersensitivity Reactions under Warnings/Precautions: Sensitivity Reactions, in Cautions.)
Increased serum concentrations of AST and/or ALT1, 5, 12 have been reported in approximately 1-2% of patients receiving the usually recommended gemifloxacin dosage in clinical studies.1 Such increases were not associated with clinical manifestations and resolved following discontinuance of the drug.1, 5 In a limited study in patients who received 640 mg of gemifloxacin once daily for 3 days, transient increases in ALT concentrations were reported in 4% of patients and, in 2 patients, were 8-10 times the upper limit of normal.1
Fluoroquinolones, including gemifloxacin, cause arthropathy and osteochondrosis in immature animals of various species.1, 12, 45, 46, 47, 48, 49, 52, 53 Degeneration of articular cartilage has been reported in juvenile dogs, but not in mature dogs.1 (See Pediatric Use under Warnings/Precautions: Specific Populations, in Cautions.)
C. difficile-associated Diarrhea and Colitis
Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridioides difficile (formerly known as Clostridium difficile ).1, 302, 303, 304 C. difficile infection (CDI) and C. difficile -associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) have been reported with nearly all anti-infectives, including gemifloxacin, and may range in severity from mild diarrhea to fatal colitis.1, 37, 41, 42, 302, 303, 304 C. difficile produces toxins A and B which contribute to development of CDAD;1, 302 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
CDAD should be considered in the differential diagnosis of patients who develop diarrhea during or after anti-infective therapy.1, 302, 303, 304 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, anti-infective therapy not directed against C. difficile should be discontinued as soon as possible.302 Patients should be managed with appropriate anti-infective therapy directed against C. difficile (e.g., vancomycin, fidaxomicin, metronidazole), supportive therapy (e.g., fluid and electrolyte management, protein supplementation), and surgical evaluation as clinically indicated.1, 302, 303, 304
Selection and Use of Anti-infectives
Gemifloxacin should be used for the treatment of acute bacterial exacerbations of chronic bronchitis only when no other treatment options are available.1, 140, 145 Because gemifloxacin, like other systemic fluoroquinolones, has been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that can occur together in the same patient, the risks of serious adverse reactions outweigh the benefits of gemifloxacin for patients with these infections.140, 145
To reduce development of drug-resistant bacteria and maintain effectiveness of gemifloxacin and other antibacterials, the drug should be used only for treatment of infections proven or strongly suspected to be caused by susceptible bacteria.1
When selecting or modifying anti-infective therapy, results of culture and in vitro susceptibility testing should be used.1 In the absence of such data, local epidemiology and susceptibility patterns should be considered when selecting anti-infectives for empiric therapy.1
Information on test methods and quality control standards for in vitro susceptibility testing of antibacterial agents and specific interpretive criteria for such testing recognized by FDA is available at [Web].1
Available data regarding use of gemifloxacin in pregnant women are insufficient to inform any drug-associated risk for miscarriages, major birth defects, and/or adverse maternal or fetal outcomes.1
Based on results of animal studies, gemifloxacin may cause fetal harm.1 Administration of gemifloxacin to pregnant mice or rabbits produced embryofetal toxicity (e.g., fetal growth retardation, reduced fetal body weight, delayed skeletal ossification) at exposures 2 or 3 times, respectively, the human exposure reported with the maximum recommended dosage of the drug.1
Pregnant women should be advised of the potential risk to the fetus.1
It is not known whether gemifloxacin is distributed into human milk, affects milk production, or affects the breast-fed infant.1 Gemifloxacin is distributed into milk in rats.1
The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for gemifloxacin and potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.1
Safety and efficacy of gemifloxacin have not been established in children or adolescents younger than 18 years of age.1 (See Musculoskeletal Effects under Warnings/Precautions: Warnings, in Cautions.)
Fluoroquinolones, including gemifloxacin, cause arthropathy and osteochondrosis in juvenile animals of various species.1, 12, 45, 46, 47, 48, 49, 52, 53 (See Musculoskeletal Effects under Warnings/Precautions: Warnings, in Cautions.)
The American Academy of Pediatrics (AAP) states that use of a systemic fluoroquinolone may be justified in children younger than 18 years of age in certain specific circumstances when there are no safe and effective alternatives and the drug is known to be effective.292, 293 For information regarding when fluoroquinolones may be a preferred option in children, see Cautions: Pediatric Precautions in Ciprofloxacin 8:12.18.
Approximately 29% of patients included in clinical studies of gemifloxacin were 65 years of age or older and 11% were 75 years of age or older.1 No overall differences in safety or efficacy were observed between geriatric individuals and younger adults.1 Although the incidence of rash appears to be lower in geriatric patients than in those younger than 40 years of age,1 the reason for this observation has not been clearly elucidated.23
The risk of developing severe tendon disorders, including tendon rupture, is increased in older adults (usually those older than 60 years of age).1, 128, 129 This risk is further increased in those receiving concomitant corticosteroids.1, 128, 129 (See Tendinitis and Tendon Rupture under Warnings/Precautions: Warnings, in Cautions.) Caution is advised if gemifloxacin is used in geriatric adults, especially those receiving concomitant corticosteroids.1
The risk of aortic aneurysm and dissection may be increased in geriatric patients.1 (See Risk of Aortic Aneurysm and Dissection under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)
The risk of QT interval prolongation may be increased in geriatric patients.1 Concomitant use of gemifloxacin and class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents and use in patients with risk factors for torsades de pointes (e.g., known QT prolongation, uncorrected hypokalemia) should be avoided.1 (See Prolongation of QT Interval under Warnings/Precautions: Warnings, in Cautions.)
The pharmacokinetics of gemifloxacin in adults are not affected by age.1
Following oral administration of a single 320-mg dose of gemifloxacin, peak plasma concentrations increased by 25 or 41% in patients with mild or moderate (Child-Pugh class A or B) or severe (Child-Pugh class C) hepatic impairment, respectively, and AUC increased by 34 or 45%, respectively.1 Dosage adjustments are not necessary in adults with hepatic impairment.1
Following oral administration of repeated doses of gemifloxacin (320 mg once daily) in patients with renal impairment, renal clearance of the drug was reduced and plasma elimination half-life prolonged, resulting in an average increase in area under the plasma concentration-time curve (AUC) of approximately 70%.1 Dosage adjustments are recommended in adults with creatinine clearances of 40 mL/minute or less.1 (See Renal Impairment under Dosage and Administration: Special Populations.)
Adverse effects occurring in 1% or more of patients receiving gemifloxacin in clinical studies include diarrhea (2.3-5.1%),1, 2, 3, 5, 12 rash (2.8-5.2%),1, 4, 5 nausea (2.6-4.3%),1, 2, 3 headache (1.2-4.2%),1, 4, 5, 12 dizziness (0.7-1.7%),1, 5 vomiting (0.7-1.6%),1, 2 and abdominal pain (0.7-2.2%).1, 2 Adverse effects occurring in up to 1% of patients receiving gemifloxacin include anorexia,1 constipation,1 dermatitis,1 dry mouth,1 dyspepsia,1, 2 fatigue,1 flatulence,1 fungal infection,1 gastritis,1 genital moniliasis,1 genital pruritus,1 hyperglycemia,1 insomnia,1 increased alkaline phosphatase,1 increased ALT,1 increased AST,1 increased creatine kinase (CK, creatinine phosphokinase, CPK),1 pruritus,1 somnolence,1 taste perversion,1 urticaria,1, 3 and vaginitis.1
Drugs that Prolong QT Interval
Potential pharmacologic interaction between gemifloxacin and drugs that prolong the QT interval (additive effect on QT interval prolongation).1, 23 Concomitant use of gemifloxacin and class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents should be avoided.1 Gemifloxacin should be used with caution in patients receiving other drugs that prolong the QT interval (e.g., cisapride [available in the US only under a limited-access protocol], erythromycin, antipsychotic agents, tricyclic antidepressants).1, 23 (See Prolongation of QT Interval under Warnings/Precautions: Warnings, in Cautions.)
Drugs Metabolized by Hepatic Microsomal Enzymes
Gemifloxacin is not metabolized by and is not an inhibitor of cytochrome P-450 (CYP) isoenzymes;1 pharmacokinetic interactions with drugs metabolized by CYP isoenzymes are unlikely.1
Pharmacokinetic interactions if gemifloxacin is used concomitantly with aluminum- or magnesium-containing antacids (decreased absorption of gemifloxacin).1, 16 Antacids containing aluminum or magnesium should be taken at least 3 hours before or 2 hours after gemifloxacin.1, 16 (See Dosage and Administration: Administration.)
Preparations containing calcium do not have a clinically important effect on absorption of gemifloxacin.1
Pharmacokinetic interaction between gemifloxacin and cimetidine (slightly increased serum gemifloxacin concentrations);1 not considered clinically important.1
Concomitant use of gemifloxacin and corticosteroids increases the risk of severe tendon disorders (e.g., tendinitis, tendon rupture), especially in geriatric patients older than 60 years of age.1
Gemifloxacin and corticosteroids should be used concomitantly with caution.1 (See Tendinitis and Tendon Rupture under Warnings/Precautions: Warnings, in Cautions.)
Possible pharmacokinetic interaction if gemifloxacin and buffered didanosine are used concomitantly (decreased gemifloxacin absorption).1
Buffered didanosine (pediatric oral solution admixed with antacid) should be taken at least 3 hours before or 2 hours after gemifloxacin.1, 23
Pharmacokinetic interactions between gemifloxacin and digoxin are unlikely.1, 18
Pharmacokinetic interactions if gemifloxacin and oral contraceptives containing ethinyl estradiol and levonorgestrel are used concomitantly (decreased serum gemifloxacin concentrations);1 not considered clinically important.1 Gemifloxacin has no effect on the pharmacokinetics of oral contraceptives containing ethinyl estradiol and levonorgestrel.1
Iron, Multivitamins, and Mineral Supplements
Possible pharmacokinetic interactions between gemifloxacin and iron, multivitamins, or mineral supplements containing iron, magnesium, or zinc (decreased absorption of gemifloxacin).1, 15
Multivitamins or dietary supplements containing iron, magnesium, zinc, or other metal cations should be taken at least 3 hours before or 2 hours after gemifloxacin.1, 15
Nonsteroidal Anti-inflammatory Agents
There is some evidence that nonsteroidal anti-inflammatory agents (NSAIAs) may increase the risk of CNS stimulation in patients receiving fluoroquinolones.1 In an animal study, convulsions did not occur when gemifloxacin was used with the active metabolite of an NSAIA.1
Pharmacokinetic interactions between gemifloxacin and omeprazole (slightly increased serum gemifloxacin concentrations);1 not considered clinically important.1, 4, 20
Pharmacokinetic interaction between gemifloxacin and probenecid (decreased clearance of gemifloxacin resulting in increased plasma concentrations and prolonged half-life of the fluoroquinolone).1
Pharmacokinetic interactions between gemifloxacin and sucralfate (decreased absorption of gemifloxacin)1, 15 when sucralfate administered 3 hours before gemifloxacin;1 no pharmacokinetic interaction when sucralfate was given 2 hours after gemifloxacin.1
Gemifloxacin should be taken at least 2 hours before sucralfate.1, 15
Pharmacokinetic interactions between gemifloxacin and theophylline are unlikely.1, 17
Concomitant use of gemifloxacin in patients receiving warfarin has resulted in increased prothrombin time [PT], international normalized ratio [INR], and/or bleeding.1 Consider that infectious disease and its accompanying inflammatory process, age, and general status of the patient also are risk factors for increased anticoagulation activity.1
Patients receiving gemifloxacin and warfarin concomitantly should be closely monitored using PT, INR, or other suitable coagulation tests.1
The absolute bioavailability of a single 320-mg oral dose of gemifloxacin is approximately 71%.1
The drug is rapidly absorbed from the GI tract,1, 21, 30 and peak plasma concentrations are attained within 0.5 -2 hours.1, 21, 30
When an oral dosage of 320 mg once daily is used, steady state is achieved by the third day.1
Administration of a 320-mg oral dose of gemifloxacin 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 the peak plasma concentration and area under the plasma concentration-time curve (AUC) by 12 and 3%, respectively;14 this reduction in systemic exposure is not considered clinically important.1, 14
Following oral administration, gemifloxacin is widely distributed into body tissues and fluids, including lung tissue and fluids.1
Gemifloxacin is distributed into milk in rats;1 it is not known whether the drug is distributed into human milk.1
Gemifloxacin is 60-70% bound to plasma proteins.1
Gemifloxacin is metabolized to a limited extent in the liver.1 The drug is not metabolized by cytochrome P-450 (CYP) isoenzymes.1
Gemifloxacin is eliminated by renal and nonrenal mechanisms.1
Following oral administration of gemifloxacin, 36% of a dose is eliminated in urine and 61% is excreted in feces as unchanged drug and metabolites.1
Approximately 20-30% of an oral dose of gemifloxacin is removed from plasma by hemodialysis.1
The mean plasma elimination half-life of gemifloxacin at steady state is approximately 7 hours (range 4-12 hours).1, 21, 30
Hepatic impairment: Peak plasma concentrations of gemifloxacin are increased 25% in adults 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); plasma half-life is not substantially changed.1 These increased serum concentrations are not considered clinically important.1
Renal impairment: Gemifloxacin clearance is reduced and the plasma elimination half-life of the drug is prolonged.1
Geriatric patients: Pharmacokinetics of gemifloxacin in adults are not affected by age.1
Gemifloxacin, a naphthyridine derivative, is a fluoroquinolone anti-infective agent.1, 4, 12, 23 Like other fluoroquinolones, gemifloxacin contains a fluorine at the C-6 position.12 However, gemifloxacin contains a naphthyridine nucleus rather than the quinolone nucleus contained in other commercially available fluoroquinolones (e.g., ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin).12 The pyrrolidine ring at the C-7 position and the 8-methoxyamino moiety on the naphthyridine nucleus of gemifloxacin appear to enhance activity against gram-positive organisms (e.g., Streptococcus pneumoniae );12, 13 however, the drug has reduced activity against Pseudomonas aeruginosa .12, 23
Like other fluoroquinolone anti-infectives, gemifloxacin inhibits DNA synthesis in susceptible organisms via inhibition of DNA gyrase and topoisomerase IV.1, 4, 12
Gemifloxacin is rapidly absorbed from the GI tract following oral administration.1, 21 The oral bioavailability of gemifloxacin is approximately 71%,1 and peak plasma concentrations of the drug generally are attained within 0.5 -2 hours.1, 21 Gemifloxacin has a mean elimination half-life of approximately 7 hours (range 4-12 hours) and may be administered once daily.1 Gemifloxacin is excreted in feces and urine; following oral administration of the drug in healthy individuals, approximately 61 or 36% of the dose was excreted in feces or urine, respectively, as unchanged drugs and metabolites.1
Gemifloxacin is active in vitro and in clinical infections against most strains of S. pneumoniae (including multidrug-resistant strains),1 Haemophilus influenzae ,1 H. parainfluenzae ,1 Klebsiella pneumoniae ,1 Moraxella catarrhalis ,1 Chlamydophila pneumoniae (formerly Chlamydia pneumoniae ),1 and Mycoplasma pneumoniae .1 Gemifloxacin also has in vitro activity against Staphylococcus aureus (methicillin-susceptible [oxacillin-susceptible] strains only),1 S. pyogenes (group A β-hemolytic streptococci; GAS),1 Acinetobacter lwoffi ,1 K. oxytoca ,1 Legionella pneumophila ,1 and Proteus vulgaris ;1 however, the safety and efficacy of the drug in infections caused by these bacteria have not been established in adequate and well-controlled clinical trials.1
Gemifloxacin has greater activity in vitro against S. pneumoniae (including penicillin- and macrolide-resistant strains) than many other fluoroquinolones (e.g., ciprofloxacin, levofloxacin, moxifloxacin).4, 12, 13, 22, 23 Although gemifloxacin may have in vitro activity against many gram-negative bacteria (e.g., H. influenzae , M. catarrhalis ) and the etiologic agents of atypical pneumonia (e.g., C. pneumoniae , M. pneumoniae , Legionella ) that is equal to or greater than that of these other fluoroquinolones,4, 12, 22 gemifloxacin is less active than ciprofloxacin in vitro against many Enterobacteriaceae and Ps. aeruginosa .4, 12 The relevance of these in vitro data to the treatment of clinical infections remains to be determined.1
Although gemifloxacin has some activity against Mycobacterium tuberculosis in vitro, the drug is considerably less active against mycobacteria than some other fluoroquinolones (e.g., ciprofloxacin, levofloxacin, ofloxacin).27
Resistance to fluoroquinolones can occur because of mutations in DNA gyrase and/or topoisomerase IV.1 Like other fluoroquinolones, resistance to gemifloxacin develops slowly via multiple-step mutations and efflux.1 S. pneumoniae with mutations in both DNA gyrase and topoisomerase IV (double mutants) are resistant to most fluoroquinolones.1 Although the clinical importance is unknown, some S. pneumoniae with double mutants may be susceptible to gemifloxacin in vitro.1
Cross-resistance can occur between gemifloxacin and other fluoroquinolones; however, gemifloxacin may be active against some bacteria (e.g., some strains of S. pneumoniae ) that are resistant to ciprofloxacin and other fluoroquinolones.1, 4, 12
Advise patients to read the manufacturer's patient information (medication guide) prior to initiating gemifloxacin therapy and each time the prescription is refilled.1
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
Advise patients that gemifloxacin tablets may be taken without regard to meals,1 but should be taken with liberal amounts of fluids.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
Inform patients that systemic fluoroquinolones, including gemifloxacin, have been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that may occur together in the same patient.1, 140, 145 Advise patients to immediately discontinue gemifloxacin and contact a clinician if they experience any signs or symptoms of serious adverse effects (e.g., unusual joint or tendon pain, muscle weakness, a “pins and needles” tingling or pricking sensation, numbness of the arms or legs, confusion, hallucinations) while taking the drug.1, 140, 145 Advise patients to talk with a clinician if they have any questions or concerns.1, 140, 145
Inform patients that systemic fluoroquinolones, including gemifloxacin, are associated with an increased risk of tendinitis and tendon rupture in all age groups and this risk is increased in adults older than 60 years of age, individuals receiving corticosteroids, and kidney, heart, or lung transplant recipients.1 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 or weakness or inability to use a joint) and importance of immediately discontinuing the drug and contacting a clinician.1 (See Tendinitis and Tendon Rupture under Warnings/Precautions: Warnings, in Cautions.)
Inform patients that peripheral neuropathies have been reported in patients receiving systemic fluoroquinolones, including gemifloxacin, and that symptoms may occur soon after initiation of the drug and may be irreversible.1 Importance of immediately discontinuing gemifloxacin and contacting a clinician if symptoms of peripheral neuropathy (e.g., pain, burning, tingling, numbness, and/or weakness) occur.1
Inform patients that systemic fluoroquinolones, including gemifloxacin, have been associated with CNS effects (e.g., convulsions, dizziness, lightheadedness, increased intracranial pressure, tremors, restlessness, lightheadedness, confusion, hallucinations) that can occur following the first dose.1 Importance of informing clinician of any history of convulsions, seizures, or epilepsy before initiating therapy with the drug.1
Advise patients that gemifloxacin may cause dizziness and lightheadedness;1 caution patients that they should not engage in activities requiring mental alertness and motor coordination (e.g., driving a vehicle, operating machinery) until the effects of the drug on the individual are known.1
Advise patients that systemic fluoroquinolones, including gemifloxacin, may worsen myasthenia gravis symptoms;1 importance of informing clinician of any history of myasthenia gravis.1 Importance of immediately contacting clinician if any symptoms of muscle weakness, including respiratory difficulties, occur.1
Inform patients that gemifloxacin may be associated with hypersensitivity reactions (including anaphylactic reactions), even following the first dose.1 Importance of immediately discontinuing gemifloxacin and contacting a clinician at the first sign of rash, jaundice, or any other sign of hypersensitivity.1
Advise patient that gemifloxacin has been associated with rash or hives and that rash occurs most frequently in patients younger than 40 years of age (especially women), in women receiving hormone replacement therapy, and in patients who received gemifloxacin for longer than 5 days (especially when given for longer than 7 days).1 Importance of discontinuing gemifloxacin and informing clinician if rash occurs.1
Inform patients that photosensitivity/phototoxicity reactions have been reported following exposure to sun or UV light in patients 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 Importance of discontinuing gemifloxacin and contacting a clinician if a sunburn-like reaction or skin eruption occurs.1
Inform patients that systemic fluoroquinolones may increase the risk of aortic aneurysm and dissection;172 importance of informing clinician of any history of aneurysms, blockages or hardening of the arteries, high blood pressure, or genetic conditions such as Marfan syndrome or Ehlers-Danlos syndrome.172 Advise patients to seek immediate medical treatment if they experience sudden, severe, and constant pain in the stomach, chest, or back.1, 172
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 should be used with caution in those 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
Importance of informing clinician of personal or family history of QT interval prolongation or proarrhythmic conditions (e.g., hypokalemia, bradycardia, recent myocardial ischemia).1 Importance of informing a clinician if palpitations or fainting spells occur.1
Inform patients that hypoglycemia has been reported when systemic fluoroquinolones were used in some patients receiving antidiabetic agents.171 Advise patients with diabetes mellitus receiving oral antidiabetic agents or insulin to discontinue gemifloxacin and contact a clinician if they experience hypoglycemia or symptoms of hypoglycemia.1, 171
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 (e.g., drugs that may affect QT interval, warfarin), as well as any concomitant illnesses.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.)
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 320 mg (of gemifloxacin)* | ||
Gemifloxacin Mesylate Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions April 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
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