Factive Warnings

The use of gemifloxacin should be avoided in patients who have experienced serious adverse reactions in the past when using fluoroquinolones containing products (see Adverse Reactions). Treatment of these patients with gemifloxacin should only be initiated in the absence of alternative treatment options and after careful benefit/risk assessment.
Aortic aneurysm and dissection: Epidemiologic studies report an increased risk of aortic aneurysm and dissection after intake of fluoroquinolones, particularly in the older population. Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other therapeutic options in patients with positive family history of aneurysm disease, or in patients diagnosed with pre-existing aortic aneurysm and/or aortic dissection, or in presence of other risk factors or conditions predisposing for aortic aneurysm and dissection (e.g. Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arteritis, Behcet's disease, hypertension, known atherosclerosis).
In case of sudden abdominal, chest or back pain, patients should be advised to immediately consult a physician in an emergency department.
Prolonged, Disabling and Potentially Irreversible Serious Adverse Drug Reactions: Very rare cases of prolonged (continuing months or year), disabling and potentially irreversible serious adverse reactions affecting different, sometimes multiple body systems (musculoskeletal, nervous, psychiatric and senses) have been reported in patients receiving fluoroquinolones irrespective of their age and pre-existing risk factors.
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 Tendinitis and tendon rupture, Peripheral Neuropathy and CNS Effects as follows). Factive should be discontinued immediately at the first signs or symptoms of any serious adverse reaction and patients should be advised to contact their prescriber for advice. In addition, avoid the use of fluoroquinolones, including Factive, in patients who have experienced any of these serious adverse reactions associated with fluoroquinolones.
Tendinitis and tendon rupture: Tendinitis and tendon rupture (especially but not limited to Achilles tendon), sometimes bilateral, may occur as early as within 48 hours of starting treatment with fluoroquinolones and have been reported to occur even up to several months after discontinuation of treatment. The risk of tendinitis and tendon rupture is increased in older patients (above 60 years of age), with renal impairment, patients with solid organ transplants, and those treated concurrently with corticosteroids. Therefore, concomitant use of corticosteroids should be avoided. At the first sign of tendinitis (e.g. painful swelling, inflammation) the treatment with Factive should be discontinued and alternative treatment should be considered. The affected limb(s) should be appropriately treated (e.g. immobilisation). Corticosteroids should not be used if signs of tendinopathy occur.
Peripheral Neuropathy: Cases of sensory or sensorimotor polyneuropathy resulting in paraesthesia, hypaesthesia, dysesthesia, or weakness have been reported in patients receiving quinolones and fluoroquinolones. Patients under treatment with Factive should be advised to inform their doctor and pharmacist prior to continuing treatment if symptoms of neuropathy such as pain, burning, tingling, numbness, or weakness develop in order to prevent the development of potentially irreversible condition. (See Adverse Reactions.)
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.
Exacerbation of Myasthenia Gravis: Fluoroquinolones, including Factive, have neuromuscular blocking activity and may exacerbate muscle weakness in persons with myasthenia gravis. Post marketing 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.
THE SAFETY AND EFFECTIVENESS OF FACTIVE IN CHILDREN, ADOLESCENTS (LESS THAN 18 YEARS OF AGE), PREGNANT WOMEN, AND LACTATING WOMEN HAVE NOT BEEN ESTABLISHED.
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.
Retinal detachment (RD): Some observational studies reported that using fluoroquinolones, including FACTIVE have been associated with an increased risk of RD. Patients should be advised to consult an ophthalmologist immediately if visual disturbances occur.
Fluoroquinolones have been associated with blood glucose disturbances, including symptomatic hyperglycemia or hypoglycemia, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent or with insulin. In these patients, careful monitoring of blood glucose is recommended. Severe cases of hypoglycemia resulting in coma or death have been reported from other fluoroquinolones. If a hypoglycemic reaction occurs a patient being treated with FACTIVE, the drug should be discontinued and initiate appropriate therapy immediately.
Glucose-6-Phosphate-dehydrogenase (G6PD) Deficiency: Fluoroquinolones have been associated with drug-induced hemolysis in patients with G6PD deficiency. FACTIVE should be used with caution in patients with G6PD deficiency or patient with positive family history of G6PD deficiency.
Heart Valve Regurgitation/Incompetence: Fluoroquinolones have been associated with an increased risk of mitral and aortic regurgitation. FACTIVE should be used after careful benefit-risk assessment and consideration of other therapeutic options in patients at risk for heart valve regurgitation/incompetence, or in presence of other risk factors or conditions predisposing for heart valve regurgitation/incompetence include congenital or preexisting heart valve disease, connective tissue disorders (e.g., Marfan syndrome or Ehlers-Danlos syndrome), Turner syndrome, Behcet's disease, hypertension, rheumatoid arthritis, and infective endocarditis. Patients should be advised to seek immediate medical attention in case of acute dyspnea, new onset of heart palpitations, or development of edema of the abdomen or lower extremities.
Photosensitivity Reaction: Fluoroquinolones, including FACTIVE have been associated with 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) after sun or UV light exposure. Excessive exposure to these sources of light should be avoided. Discontinue FACTIVE if phototoxicity (e.g., skin eruption) occurs.