Factive

Factive

gemifloxacin

Manufacturer:

LG Chem

Distributor:

Pahang Pharmacy
Full Prescribing Info
Contents
Gemifloxacin mesylate.
Description
Each tablet contains gemifloxacin mesylate equivalent to 320 mg gemifloxacin.
Excipients/Inactive Ingredients: Povidone, Microcrystalline cellulose, Crospovidone, Magnesium stearate, Titanium dioxide, Hypromellose, Polyethylene glycol.
Action
ATC code: J01MA.
Pharmacology: Pharmacodynamics:
General Properties: Gemifloxacin is a synthetic antibacterial agent. Gemifloxacin is a fluoroquinolone antibiotic with a wide range of Gram-positive and Gramnegative pathogens.
Mode of Action: The mode of action is by inhibiting DNA synthesis through the inhibition of both bacterial DNA gyrase and topoisomerase. Gemifloxacin is highly selective for bacterial rather than human topoisomerase II, having strong affinity for bacterial topoisomerases II (DNA gyrase) and IV, which are essential enzymes that play a decisive part in the replication, transcription and repair of bacterial DNA.
Susceptible Micro-organisms: Aerobic Gram-positive: Streptococcus pneumoniae (including penicillin, macrolide and most ofloxacin/levofloxacin resistant and MDRSP*); Streptoccocus pyogenes (including macrolide resistant); Streptococcus viridans; Streptococcus agalactiae; Streptococcus milleri; Streptococcus anginosius; Streptococcus constellatus; Streptococcus mitis; etc., Streptococcus species; Staphylococcus aureus (methicillin sensitive); Staphylococcus epidermidis; Staphylococcus saprophyticus; Staphylococcus haemolyticus; etc., Staphylococcus species; Enterococcus faecalis; Enterococcus faecium; etc., Enterococcus species.
*MDRSP, Multi-drug resistant Streptococcus pneumoniae includes isolates previously known as PRSP (penicillin-resistant Streptococcus pneumoniae), and are strains resistant to two or more of the following antibiotics: penicillin, 2nd generation cephalosporins, e.g., cefuroxime, macrolides, tetracyclines and trimethoprim/sulfamethoxazole.
Aerobic Gram-negative: Haemophilus influenzae (beta lactamase positive and negative); Haemophilus parainfluenzae; etc., Haemophilus species; Moraxella catarrhalis (beta lactamase positive and negative); etc., Moraxella species; Klebsiella pneumoniae; Klebsiella oxytoca; etc., Klebsiella species; Escherichia coli; Neisseria gonorrhoeae; etc., Neisseria species; Acinetobacter lwoffi; Acinetobacter anitratus; Acinetobacter calcoaceticus; Acinetobacter haemolyticus; etc., Acinetobacter species; Citrobacter freundii; Citrobacter koseri; etc., Citrobacter species; Salmonella species; Shigella species; Enterobacter cloacae; Enterobacter aerogenes; etc., Enterobacter species; Serratia marcescens; etc., Serratia species; Proteus mirabilis; Proteus vulgaris; etc., Proteus species; Providencia species; Morganella morganii; etc., Morganella species; Yersinia species; Pseudomonas aeruginosa; etc., Pseudomonas species; Bordetella pertussis; etc., Bordetella species.
Atypicals: Coxiella burnetti; etc., Coxiella species; Mycoplasma pneumoniae; etc., Mycoplasma species; Legionella pneumophila; etc., Legionella species; Chlamydia pneumoniae; etc., Chlamydia species.
Anaerobes: Peptostreptococcus species; Clostridium non-perfringens; Clostridium perfringens; etc., Clostridium species; Fusobacterium species; Porphyromonas species; Prevotella species.
Pharmacokinetics: The pharmacokinetics of gemifloxacin are approximately linear over the dose range from 40 mg to 640 mg. There was minimal accumulation of gemifloxacin following multiple oral doses up to 640 mg a day for 7 days (mean accumulation <20%). Following repeat oral administration of 320 mg gemifloxacin once daily, steady-state is achieved by the third day of dosing.
Absorption and Bioavailability: Gemifloxacin, given as an oral tablet, is rapidly absorbed from the gastrointestinal tract. Peak plasma concentrations of gemifloxacin were observed between 0.5 and 2 hours following oral tablet administration and the absolute bioavailability of the 320 mg tablet averaged approximately 71% (95% CI 60%-84%). Following repeat oral doses of 320 mg to healthy subjects, the mean ± SD maximal gemifloxacin plasma concentrations (Cmax) and systemic drug exposure (AUC (0-24)) were 1.61 ± 0.51 μg/mL (range 0.70-2.62 μg/mL) and 9.93 ± 3.07 μg·hr/mL (range 4.71-20.1 μg·hr/mL), respectively. In patients with respiratory and urinary tract infections (n=1423), similar estimates of systemic drug exposure were determined using a population pharmacokinetics analysis (geometric mean AUC (0-24), 8.36 μg·hr/mL; range 3.2-47.7 μg·hr/mL. The pharmacokinetics of gemifloxacin was not significantly altered when a 320 mg dose was administered with a high-fat meal. Therefore Factive may be administered without regard to meals.
Distribution: In vitro binding of gemifloxacin to plasma proteins in healthy subjects is approximately 60 to 70% and is concentration independent. After repeated doses, the in vivo plasma protein binding in healthy elderly and young subjects ranged from 55% to 73% and was unaffected by age. Renal impairment does not significantly affect the protein binding of gemifloxacin. The blood-to-plasma concentration ratio of gemifloxacin was 1.2:1. The geometric mean for Vdss/F is 4.18 L/kg (range, 1.66-12.12 L/kg). Gemifloxacin is widely distributed throughout the body after oral administration. Concentrations of gemifloxacin in bronchoalveolar lavage fluid exceed those in the plasma. Gemifloxacin penetrates well into lung tissue and fluids. After five daily doses of 320 mg gemifloxacin, concentrations in plasma, bronchoalveolar macrophages, epithelial lining fluid and bronchial mucosa at approximately 2 hours are indicated in Table 1. (See Table 1.)

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Metabolism: Gemifloxacin is metabolized to a limited extent by the liver. The unchanged compound is the predominant drug-related component detected in plasma (approximately 65%) up to 4 hours after dosing. All metabolites formed are minor (<10% of the administered oral dose); the principal ones are N-acetyl gemifloxacin, the E-isomer of gemifloxacin and the carbamyl glucuronide of gemifloxacin. Cytochrome P450 enzymes do not play an important role in gemifloxacin metabolism, and the metabolic activity of these enzymes is not significantly inhibited by gemifloxacin.
Elimination: Gemifloxacin and its metabolites are excreted via dual routes of excretion. Following oral administration of gemifloxacin to healthy subjects, a mean (± SD) of 61± 9.5% of the dose was excreted in the feces and 36 ± 9.3% in the urine as unchanged drug and metabolites. The mean (± SD) renal clearance following repeat doses of 320 mg was approximately 11.6± 3.9 L/hr (range 4.6-17.6 L/hr), which indicates active secretion is involved in the renal excretion of gemifloxacin. The mean (± SD) plasma elimination half-life at steady state following 320 mg to healthy subjects was approximately 7± 2 hours (range 4-12 hours).
Photosensitivity Potential: In a study of the skin response to ultraviolet and visible radiation conducted in 40 healthy volunteers, the minimum erythematous dose (MED) was assessed following administration of either gemifloxacin 160 mg once daily, gemifloxacin 320 mg once daily, ciprofloxacin 500 mg BID, or placebo for 7 days. At 5 of the 6 wavelengths tested (295-430 nm), the photosensitivity potential of gemifloxacin was not statistically different from placebo. At 365 nm (UVA region), gemifloxacin showed a photosensitivity potential similar to that of ciprofloxacin 500 mg BID and the photosensitivity potential for both drugs were statistically greater than that of placebo. Photosensitivity reactions were reported rarely in clinical trials with gemifloxacin (0.039%).
It is difficult to ascribe relative photosensitivity/phototoxicity among various fluoroquinolones during actual patient use because other factors play a role in determining a subject’s susceptibility to this adverse event such as: a patient's skin pigmentation, frequency and duration of sun and artificial ultraviolet light (UV) exposure, wearing of sun screen and protective clothing, the use of other concomitant drugs and the dosage and duration of fluoroquinolone therapy.
Special Population: Geriatric: In adult subjects, the pharmacokinetics of gemifloxacin are not affected by age.
Gender: There are no significant differences between gemifloxacin pharmacokinetics in males and females when differences in body weight are taken into account. Population pharmacokinetic studies indicated that following administration of 320 mg gemifloxacin, AUC values were approximately 10% higher in healthy female patients compared to males. No gemifloxacin dosage adjustment based on gender is necessary.
Renal Insufficiency: Results from population pharmacokinetic and clinical pharmacology studies with repeated 320 mg doses indicate the clearance of gemifloxacin is reduced and the plasma elimination is prolonged, leading to an average increase in AUC values of approximately 70% in patients with renal insufficiency. In the pharmacokinetic studies, gemifloxacin Cmax was not significantly altered in subjects with renal insufficiency. Dose adjustment in patients with creatinine clearance ≥40 mL/min is not required. Modification of the dosage is recommended for patients with creatinine clearance <40 mL/min.
Hepatic Insufficiency: The pharmacokinetics following a single 320 mg dose of gemifloxacin were studied in patients with mild to severe hepatic impairments. There was a mean increase in AUC and in Cmax in these subjects with hepatic imparement compared to healthy volunteers. These average pharmacokinetic increases are not considered to be clinically significant. There was no significant change in plasma elimination half-life in the mild, moderate or severe hepatic impairment patients. No dosage adjustment is recommended in patients with mild, moderate or severe hepatic impairment (Child-Pugh A, B and C).
Toxicology: Preclinical safety data: Genotoxicity: Gemifloxacin was not mutagenic in the bacterial strains used in an Ames Salmonella reversion assay. It did not induce either micronuclei in the bone marrow of mice following intraperitoneal doses nor unscheduled DNA synthesis in hepatocytes from rats. Gemifloxacin was clastogenic in vitro in the mouse lymphoma and human lymphocyte chromosome aberration assays. It was clastogenic in vivo in the rat micronucleus assay at oral and intravenous dose levels that produced bone marrow toxicity.
Carcinogenesis: Long term studies in animals to determine the carcinogenic potential of gemifloxacin have not been conducted.
Gemifloxacin was administered orally, by gavage, 5 days per week for 12 months, to hairless mice at doses up to 100 mg/kg/day and mice were exposed to UV radiation. Gemifloxacin did not induce development of UVR-induced skin tumor. In phototoxicity studies, gemifloxacin demonstrated either the least or no phototoxic effects.
Gemifloxacin was reported to have antigenic potential in animal studies.
Impairment of Fertility: Gemifloxacin did not affect the fertility of male or female rats at AUC levels following oral administration that were approximately 3- to 4-fold higher than the AUC levels at the clinically recommended dose.
Indications/Uses
Factive is indicated for the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions listed as follows.
Community-acquired pneumonia (of mild to moderate severity) caused by Streptococcus pneumoniae (including multi-drug resistant strains [MDRSP])*, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumonia, or Klebsiella pneumonia.
*MDRSP: multi-drug resistant Streptococcus pneumoniae, includes isolates previously known as PRSP (penicillin resistant Streptococcus pneumonia), and are strains resistant to two or more of the following antibiotics: penicillin (MIC ≥2 μg/mL), 2nd generation cephalosporins (e.g., cefuroxime), macrolides, tetracyclines and trimethoprim/sulfamethoxazole.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Factive and other antibacterial drugs, Factive should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Dosage/Direction for Use
Factive can be taken with or without food and should be swallowed whole with a liberal amount of liquid. The recommended dose of Factive is 320 mg daily, according to following indication. (See Table 2.)

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Table as follows provide dosage guidelines for use in renal impaired patients. (See Table 3.)

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Overdosage
In the event of acute oral overdosage, the stomach should be emptied by inducing vomiting or by gastric lavage; the patient should be carefully observed and treated symptomatically. Adequate hydration should be maintained and hemodialysis does not remove gemifloxacin sufficiently to be useful in overdosage. No specific antidote is known.
Contraindications
Known hypersensitivity to Factive or other quinolones; patients with a history of Factive or other quinolone-associated tendonitis and tendon rupture; children or growing adolescents under 18 years of age; pregnant or lactating women.
Warnings
Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and Tendon Rupture, Peripheral Neuropathy, and Central Nervous System Effects: Fluoroquinolones, including Factive have been associated with disabling and potentially irreversible serious adverse reactions from different body systems that can occur together in the same patient. Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion). These reactions can occur within hours to weeks after starting Factive. Patients of any age or without pre-existing risk factors have experienced these adverse reactions (See Tendinopathy and Tendon Rupture, Peripheral Neuropathy and CNS Effects as follows).
Discontinue Factive immediately at the first signs or symptoms of any serious adverse reaction. In addition, avoid the use of fluoroquinolones, including Factive, in patients who have experienced any of these serious adverse reactions associated with fluoroquinolones.
Tendinopathy and Tendon Rupture: Fluoroquinolones, including Factive, are associated with an increased risk of tendinitis and tendon rupture in all ages. This adverse reaction most frequently involves the Achilles tendon, and rupture of the Achilles tendon may require surgical repair. Tendinitis and tendon rupture in the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendon sites have also been reported. The risk of developing fluoroquinolone associated tendinitis and tendon rupture is further increased in older patients usually over 60 years of age, in those taking corticosteroid drugs, and in patients with kidney, heart or lung transplants. Factors, in addition to age and corticosteroid use, that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. Tendinitis and tendon rupture have also occurred in patients taking fluoroquinolones who do not have the above risk factors. Tendon rupture can occur during or after completion of therapy; cases occurring up to several months after completion of therapy have been reported. Factive should be discontinued if the patient experiences pain, swelling, inflammation or rupture of a tendon. Patients should be advised to rest at the first sign of tendinitis or tendon rupture, and to contact their healthcare provider regarding changing to a non-quinolone antimicrobial drug.
Peripheral Neuropathy: Fluoroquinolones, including Factive, have been associated with an increased risk of peripheral neuropathy. Cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving fluoroquinolones, including Factive. Symptoms may occur soon after initiation of Factive and may be irreversible. Factive should be discontinued immediately if the patient experiences symptoms of peripheral neuropathy, including pain, burning, tingling, numbness, and/or weakness or other alterations in sensations including light touch, pain, temperature, position sense, and vibratory sensation.
CNS Effects: Fluoroquinolones, including Factive, have been associated with an increased risk of central nervous system (CNS) effects, including convulsions, increased intracranial pressure (including pseudotumor cerebri), and toxic psychosis. In clinical studies with Factive, central nervous system (CNS) effects have been reported infrequently. As with other fluoroquinolones, Factive should be used with caution in patients with CNS diseases such as epilepsy or patients predisposed to convulsions. CNS stimulation which may lead to tremors, restlessness, anxiety, lightheadedness, confusion, hallucinations, paranoia, depression, insomnia, and rarely suicidal thoughts or acts may also be caused by other fluoroquinolones. If these reactions occur in patients receiving Factive, discontinue Factive immediately and institute appropriate measures.
THE SAFETY AND EFFECTIVENESS OF FACTIVE IN CHILDREN, ADOLESCENTS (LESS THAN 18 YEARS OF AGE), PREGNANT WOMEN, AND LACTATING WOMEN HAVE NOT BEEN ESTABLISHED.
Exacerbation of Myasthenia Gravis: Fluoroquinolones, including Factive, have neuromuscular blocking activity and may exacerbate muscle weakness in persons with myasthenia gravis. Postmarketing serious adverse events, including deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in persons with myasthenia gravis. Avoid Factive in patients with known history of myasthenia gravis.
QT Effects: Fluoroquinolones may prolong the QT interval in some patients. Factive should be avoided in patients with a history of prolongation of the QTc interval, patients with uncorrected electrolyte disorders (hypokalemia or hypomagnesemia), and patients receiving Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic agents.
Pharmacokinetic studies between gemifloxacin and drugs that prolong the QTc interval such as erythromycin, antipsychotics, and tricyclic antidepressants have not been performed. Factive should be used with caution when given concurrently with these drugs, as well as in patients with ongoing proarrhythmic conditions, such as clinically significant bradycardia or acute myocardial ischemia. No cardiovascular morbidity or mortality attributable to QTc prolongation occurred with Factive treatment in over 8119 patients, including 707 patients concurrently receiving drugs known to prolong the QTc interval and 7 patients with hypokalemia.
The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher. QTc prolongation may lead to an increased risk for ventricular arrhythmias including torsades de pointes. The maximal change in the QTc interval occurs approximately 5-10 hours following oral administration of gemifloxacin.
Hypersensitivity Reactions: Serious hypersensitivity and/or anaphylactic reactions have been reported in patients receiving fluoroquinolone therapy, including Factive. Hypersensitivity reactions reported in patients receiving fluoroquinolone therapy have occasionally been fatal. These reactions may occur following the first dose. Some reactions have been accompanied by cardiovascular collapse, hypotension/shock, seizure, loss of consciousness, tingling, angioedema (including tongue, laryngeal, throat or facial edema/swelling), airway obstruction (including bronchospasm, shortness of breath and acute respiratory distress), dyspnea, urticaria, itching and other serious skin reactions. Factive should be discontinued immediately at the appearance of any sign of an immediate type I hypersensitivity skin rash or any other manifestation of a hypersensitivity reaction; the need for continued fluoroquinolone therapy should be evaluated. As with other drugs, serious acute hypersensitivity reactions may require treatment with epinephrine and other resuscitative measures, including oxygen, intravenous fluids, antihistamines, corticosteroids, pressor amines and airway management as clinically indicated.
Other serious and sometimes fatal events, some due to hypersensitivity and some due to uncertain etiology, have been reported rarely in patients receiving therapy with quinolones, including Factive. These events may be severe and generally occur following the administration of multiple doses. Clinical manifestations may include one or more of the following: fever, rash or severe dermatologic reactions (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; thrombocytopenia, including thrombotic thrombocytopenic purpura; leukopenia agranulocytosis; pancytopenia; and/or other hematologic abnormalities.
The drug should be discontinued immediately at the first appearance of a skin rash, jaundice, or any other sign of hypersensitivity and supportive measures instituted.
Clostridium difficile Associated Diarrhea
: Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Factive, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile
produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
Special Precautions
General: Prescribing Factive in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Rash: In clinical studies, rash occurred more often with Factive than with therapy with comparator agents (2.7% vs. 0.6%). Increasing incidence of rash was associated with younger age (especially below 40), female gender, use of hormone replacement therapy and longer durations of therapy (see Table 4). Urticarial reactions, some of which were not classified as rash, were more common in Factive patients than in comparator patients (0.6% vs. 0.2%). Factive should be discontinued in patients developing a rash or urticaria while on treatment. (See Table 4.)

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The most common form of rash associated with Factive was described as maculopapular and mild to moderate in severity. Eighty percent of rashes resolved within 14 days. Approximately 10% of the rashes (0.5% of all patients) were described as of severe intensity and approximately 10% of those with rash were treated with systemic steroids. There were no documented cases in the clinical trials of more serious skin reactions known to be associated with significant morbidity or mortality.
Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions (e.g., burning, erythema, exudation, vesicles, blistering, edema) involving areas exposed to light (typically the face, "V" area of the neck, extensor surfaces of the forearms, dorsa of the hands), can be associated with use of quinolones after sun or UV light exposure. Therefore excessive exposure to these sources of light should be avoided. Drug therapy should be discontinued if phototoxicity occurs.
Hepatic Effects: Liver enzyme elevations (increased ALT and/or AST) occurred at similar rates in patients receiving Factive 320 mg daily relative to comparator antimicrobial agents (ciprofloxacin, levofloxacin, clarithromycin/cefuroxime axetil, amoxicillin/clavulanate potassium, and ofloxacin). In patients who received gemifloxacin at doses of 480 mg per day or greater there was an increased incidence of elevations in liver enzymes.
There were no clinical symptoms associated with these liver enzyme elevations. The liver enzyme elevations resolved following cessation of therapy. The recommended dose of Factive 320 mg daily should not be exceeded and the recommended length of therapy should not be exceeded.
Renal Effects: Alteration of the dosage regimen is necessary for patients with impairment of renal function (creatinine clearance ≤40 mL/min). Adequate hydration of patients receiving Factive should be maintained to prevent the formation of a highly concentrated urine.
Serious Adverse Reactions: Advise patients to stop taking Factive if they experience an adverse reaction and to call their healthcare provider for advice on completing the full course of treatment with another antibacterial drug.
Inform patients of the following serious adverse reactions that have been associated with Factive or other fluoroquinolone use: Disabling and potentially irreversible serious adverse reactions that may occur together, including tendinitis and tendon rupture, peripheral neuropathies, and central nervous system effects, have been associated with use of Factive and may occur together in the same patient. Inform patients to stop taking Factive immediately if they experience an adverse reaction and to call their healthcare provider
Tendinitis and tendon rupture: instruct patients to contact their healthcare provider if they experience pain, swelling, or inflammation of a tendon, or weakness or inability to use one of their joints; rest and refrain from exercise; and discontinue Factive treatment. The risk of severe tendon disorders with fluoroquinolones is higher in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants;
Peripheral neuropathies: Inform patients that peripheral neuropathies have been associated with the use of Factive, that symptoms may occur soon after initiation of therapy and may be irreversible. If symptoms of peripheral neuropathy including pain, burning, tingling, numbness and/or weakness develop, patients should immediately discontinue Factive and contact their physician;
Central nervous system effects (for example, convulsions, dizziness, lightheadedness, increased intracranial pressure): Inform patients that convulsions have been reported in patients receiving fluoroquinolones, including Factive. Patients should notify their physician before taking Factive if they have a history of convulsions, seizures, or epilepsy; Inform patients that other central nervous system problems such as tremors, restlessness, lightheadedness, confusion and hallucinations may occur rarely;
Exacerbation of Myasthenia Gravis: Inform patients that fluoroquinolones like Factive may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Patients should call their healthcare provider right away if they have any worsening muscle weakness or breathing problems;
Hypersensitivity Reactions: Inform patients that Factive may be associated with hypersensitivity reactions, including anaphylactic reactions, even following a single dose; patients should immediately discontinue the drug at the sign of a rash or other allergic reaction and seek medical care; Inform patients that Factive has been associated with rash and hives. Rash occurs more commonly in those under 40, especially women and in women on hormone replacement therapy. The incidence of rash increases with duration more than 5 days and particularly longer than 7 days. Patients should discontinue Factive and call their healthcare provider if they develop a rash;
Diarrhea: Inform patients that diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible;
Prolongation of the QT interval: inform patients of the following: that Factive may cause changes in the electrocardiogram (QTc interval prolongation); that Factive should be avoided in patients receiving Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic agents; that Factive should be used with caution in patients receiving drugs that affect the QTc interval such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants; to inform their physician of any personal or family history of QTc prolongation or proarrhythmic conditions such as hypokalemia, bradycardia, or recent myocardial ischemia; to contact their physician if they experience palpitations or fainting spells while taking Factive; that Factive may cause dizziness; if this occurs, patients should not operate an automobile or machinery or engage in activities requiring mental alertness or coordination.
Photosensitivity/Phototoxicity: Inform patients that photosensitivity/phototoxicity has been reported in patients receiving quinolones. Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while taking quinolones. If patients need to be outdoors while using quinolones, they should wear loose-fitting clothes that protect skin from sun exposure and discuss other sun protection measures with their physician. If a sunburn-like reaction or skin eruption occurs, patients should contact their physician.
Other Information: Advise Patients: that increases of the International Normalized Ratio (INR), or prothrombin time (PT), and/or clinical episodes of bleeding have been noted with concurrent administration of warfarin or its derivatives, and Factive. Patients should notify their physicians if they are taking warfarin or its derivatives; to inform their physician of any other medications when taken concurrently with Factive, including over-the-counter medications and dietary supplements; that Factive may be taken with or without meals to drink fluids liberally; not to take antacids containing magnesium and/or aluminum or products containing ferrous sulfate (iron), multivitamin preparations containing zinc or other metal cations, or Videx (didanosine) chewable/buffered tablets or the pediatric powder for oral solution within 3 hours before or 2 hours after taking Factive tablets; that Factive should be taken at least 2 hours before sucralfate; that antibacterial drugs including Factive should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Factive is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Factive or other antibacterial drugs in the future.
Effects on ability to drive and use machines: CNS effects have been seen rarely in clinical trials with Factive. However, as with all drugs, patients should observe their reaction to Factive and, if affected, should not drive or operate machinery.
Use In Pregnancy & Lactation
Gemifloxacin treatment during organogenesis caused fetal growth retardation in mice (oral dosing at 450 mg/kg/day), rats (oral dosing at 750 mg/kg/day) and rabbits (IV dosing at 40 mg/kg/day). Treatment of pregnant rats at 750 mg/kg/day caused fetal brain and ocular malformations (unilateral microphthalmia, anophthalmia, and dome shaped head) in the presence of maternal toxicity.
Factive should not be used in pregnant women because the safety of Factive in pregnant women has not been established.
Stop breast-feeding during the administration of Factive because animal studies have shown gemifloxacin-related material is excreted in the breast milk of rats.
Adverse Reactions
Shock: Anaphylactic shock or anaphylactic reactions may occur rarely. Closely monitor patients' reaction to the drug. If patients experience trouble breathing, decreased blood pressure or dyspnea while receiving Factive, the drug should be discontinued immediately and appropriate measures instituted.
Central Nervous System: Quinolone family of antibiotics may lead to increase in intracranial pressure and CNS stimulation which eventually lead to tremor, anxiety, lightheadedness, confusion, hallucination, paranoia, depression, nightmares, insomnia or rarely suicidal thoughts or acts. Dizziness can occur occasionally, tremor rarely and headache might also occur.
Gastrointestinal: Rarely, patients can develop fatal pseudomembraneous colitis or colitis associated with bloody stool. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Factive. If the patient experiences stomach cramps, frequent diarrhea or symptoms of colitis after administration of Factive, tests to confirm CDAD should be conducted and appropriate measures instituted. Abdominal pains, vomiting, constipation, dry mouth, dyspepsia, flatulence, gastritis, and hyperglycemia can sometimes occur, gastroenteritis rarely, and anorexia and diarrrhea might also occur. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
Hepatic: Patients can develop asymptomatic transient elevation of liver enzyme (AST/ALT) occasionally, bilirubinemia, γ-GTP elevation and increased GGT rarely.
Hypersensitive Reaction: Rash, hives and itching can occur occasionally, photosensitivity rarely. Diffuse maculopapular or erythematous skin rash was reported in clinical trials with Factive. The incidences of rash were observed approximately after 7 days since the initiation of the treatment and eighty percent of rashes resolved within 14 days. The rashes were generally considered to be mild to moderate reversible hypersensitive reaction (type IV). Factive should be discontinued immediately at the appearance of any sign of an immediate type I hypersensitivity skin rash or any other manifestation of a hypersensitivity reaction.
Dermatologic: Patients can experience Stevens-Johnson syndrome and Lyell's Syndrome while receiving therapy with quinolones. Closely monitor patients' reaction to the drug. If these symptoms occur, Factive should be discontinued and appropriate measures instituted. Patients can develop dermatitis, fungal infection of reproductive organs, genital pruritus and vaginitis occasionally, eczema rarely.
Musculoskeletal: Arthralgia can occur, tendonitis and increased creatine phosphokinase occasionally, and back pain and leg cramps rarely.
Hematology: Decreased and increased platelets and decreased leucopenia can occur occasionally, anemia, eosinophilia and granulocytopenia rarely.
Respiratory: Trouble breathing and pneumonia can occur rarely.
Peripheral Nervous System: Quinolones may rarely cause sensorimotor axonal polyneuropathy or affect axons which results in paresthesia, hypoesthesia, dysesthesias or weakness.
Other: Fungal overgrowth, fatigue and taste perversion can occur occasionally, hot flashes, flushing, restlessness, pharyngitis and abnormal vision rarely.
Post-Market Experience: Exacerbation of myasthenia gravis was reported from the post-market.
Drug Interactions
Gemifloxacin absorption is significantly reduced and its efficacy may be lowered when aluminium- and/or magnesium-containing antacids, ferrous sulphate (iron), calcium preparation, multivitamins preparation containing zinc or iron are concomitantly administered. Factive should not be taken within 3 hours before and after taking these agents. These agents should not be taken within 3 hours before or 2 hours after taking Factive.
Didanosine should not be taken within 3 hours before or after taking Factive.
Sucralfate and calcium carbonate should not be taken within 2 hours before or after taking Factive.
No clinically significant interactions have been observed when gemifloxacin was coadministered with omeprazole, theophylline, digoxin, warfarin, oral contraceptives, or cimetidine.
Factive had no significant effect on the anticoagulant effect of warfarin in healthy subjects on stable warfarin therapy. However, increases in the INR (International Normalized Ratio), or PT (prothrombin time), and/or clinical episodes of bleeding in patients have been noted with the use of quinolones, including Factive, and warfarin, or its derivatives. Therefore, the PT, INR or other suitable coagulation test should be closely monitored if a quinolone antimicrobial, including Factive, is administered concomitantly with warfarin or its derivatives.
Caution For Usage
Special precautions for disposal and other handling: Not applicable.
Incompatibilities: Not applicable.
Storage
Do not store above 30°C.
Shelf-Life: 48 months.
MIMS Class
ATC Classification
J01MA15 - gemifloxacin ; Belongs to the class of fluoroquinolones. Used in the systemic treatment of infections.
Presentation/Packing
FC tab 320 mg (white to off-white oval-shaped with breaklines on both faces debossed with LG 320 on both faces) x 1 x 5's, 1 x 7's.
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