Factive

Pregnancy Category: C

Lactation: excretion in milk unknown; do not use unless benefit to mother outweighs risk

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Get emergency medical help if you have any of these signs of an allergic reaction: hives, or the first sign of a skin rash; rapid heart rate, difficult breathing; swelling of your face, lips, tongue, or throat.

Gemifloxacin may cause swelling or tearing of (rupture) a tendon. Gemifloxacin can also have serious effects on your nerves, and may cause permanent nerve damage. Stop taking this medicine and call your doctor at once if you have:

• signs of tendon rupture--sudden pain, swelling, bruising, tenderness, stiffness, movement problems, or a snapping or popping sound in any of your joints (rest the joint until you receive medical care or instructions); or
• nerve symptoms--numbness, tingling, burning pain, or being more sensitive to temperature, light touch, or the sense of your body position.

Stop using gemifloxacin and call your doctor at once if you have:

• headache with chest pain and severe dizziness, fainting, fast or pounding heartbeats;
• upper stomach pain, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
• muscle weakness or trouble breathing;
• diarrhea that is watery or bloody;
• sudden weakness or ill feeling, fever, chills, sore throat, mouth sores, easy bruising or bleeding;
• depression, confusion, hallucinations, paranoia, tremors, feeling restless or anxious, insomnia, nightmares, thoughts of hurting yourself;
• seizure (convulsions); or
• increased pressure inside the skull-- severe headaches, ringing in your ears, dizziness, nausea, vision problems, pain behind your eyes.

Common side effects may include:

• nausea, vomiting, mild stomach pain, mild diarrhea;
• mild dizziness; or
• mild headache.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

You should not use this medicine if you are allergic to gemifloxacin or other fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin, norfloxacin, and others).

To make sure gemifloxacin is safe for you, tell your doctor if you have:

• tendon problems, arthritis or other joint problems;

• slow heartbeats or other heart rhythm disorder (especially if you take medication to treat it);

• a personal or family history of long QT syndrome;

• trouble swallowing pills;

• liver or kidney disease;

• a history of epilepsy or other seizure disorder;

• a nerve disorder;

• low levels of magnesium or potassium in your blood; or

• if you use a blood thinner (warfarin, Coumadin, Jantoven) and have "INR" or prothrombin time tests.

Gemifloxacin may cause swelling or tearing of a tendon (the fiber that connects bones to muscles in the body), especially in the Achilles' tendon of the heel. This can happen during treatment or up to several months after you stop taking gemifloxacin. Tendon problems may be more likely to occur if you are over 60, if you take steroid medication, or if you have had a kidney, heart, or lung transplant.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether gemifloxacin passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Gemifloxacin is not approved for use by anyone younger than 18 years old.

Do not take gemifloxacin with dairy products such as milk or yogurt, or with calcium-fortified juice. You may eat or drink these products as part of a regular meal, but do not use them alone when taking gemifloxacin. They could make the medication less effective.

Certain other medicines should not be taken at the same time as gemifloxacin. Avoid taking the following medicines within 3 hours before or 2 hours after you take gemifloxacin. These other medicines can make gemifloxacin much less effective when taken at the same time:

• antacids that contain magnesium or aluminum (such as Maalox, Mylanta, or Rolaids), or the ulcer medicine sucralfate (Carafate);

• didanosine (Videx) powder or chewable tablets; or

• vitamin or mineral supplements that contain iron or zinc.

Gemifloxacin may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Antibiotic medicines can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or bloody, call your doctor. Do not use anti-diarrhea medicine unless your doctor tells you to.

Avoid exposure to sunlight or tanning beds. Gemifloxacin can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors. Call your doctor if you have severe burning, redness, itching, rash, or swelling after being in the sun.

Get emergency medical help if you have signs of an allergic reaction: hives, or the first sign of a skin rash; fast heartbeat, difficult breathing; swelling of your face, lips, tongue, or throat.

Gemifloxacin may cause swelling or tearing of (rupture) a tendon. Gemifloxacin can also have serious effects on your nerves, and may cause permanent nerve damage.

Stop using gemifloxacin and call your doctor at once if you have:

• severe stomach pain, diarrhea that is watery or bloody;

• headache with chest pain and severe dizziness, fainting, fast or pounding heartbeats;

• a seizure (convulsions);

• signs of tendon rupture--sudden pain, swelling, bruising, tenderness, stiffness, movement problems, or a snapping or popping sound in any of your joints (rest the joint until you receive medical care or instructions);

• nerve symptoms--numbness, weakness, tingling, burning, pain, or being more sensitive to temperature, light touch, or the sense of your body position;

• changes in mood or behavior--depression, confusion, hallucinations, paranoia, tremors, feeling restless or anxious, unusual thoughts or behavior, insomnia, nightmares;

• liver problems--upper stomach pain, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or

• severe skin reaction--skin pain followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common side effects may include:

• nausea, vomiting, stomach pain, diarrhea;

• headache;

• dizziness; or

• rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Administration

Oral Administration

Administer orally once daily without regard to meals.1 14

Take with liberal amounts of fluids.1

Swallow tablets intact;1 do not chew or crush.1

Dosage

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

Adults

320 mg once daily for 5 days.1 (See Respiratory Tract Infections under Uses.)

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

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

Manufacturer recommends that results of initial sputum cultures be used to guide clinical decisions regarding use of a 5- or 7-day regimen.1

Prescribing Limits

Adults

Do not exceed recommended dosage or duration of therapy.1

Special Populations

Hepatic Impairment

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

Renal Impairment

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

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

Geriatric Patients

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

Contraindications

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

Warnings/Precautions

Warnings

Systemic fluoroquinolones, including gemifloxacin, 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 May occur within hours to weeks after a systemic fluoroquinolone is initiated;1 have occurred in all age groups and in patients without preexisting risk factors for such adverse reactions.1

Immediately discontinue gemifloxacin at first signs or symptoms of any serious adverse reactions.1 140 145

Avoid systemic fluoroquinolones, including gemifloxacin, 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

Risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in older adults (usually those >60 years of age), individuals receiving concomitant corticosteroids, and kidney, heart, or lung transplant recipients.1 (See Geriatric Use under 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;1 also reported in 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

Immediately discontinue gemifloxacin if pain, swelling, inflammation, or rupture of a tendon occurs.1 128 129 (See Advice to Patients.)

Avoid systemic fluoroquinolones, including gemifloxacin, in patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture.1

Systemic fluoroquinolones, including gemifloxacin, are 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 reported with systemic fluoroquinolones, including gemifloxacin.1 130 Symptoms may occur soon after initiation of the drug and, in some patients, may be irreversible.1 130

Immediately discontinue gemifloxacin 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.)

Avoid systemic fluoroquinolones, including gemifloxacin, in patients who have experienced peripheral neuropathy.1

Systemic fluoroquinolones, including gemifloxacin, are associated with an increased risk of CNS effects.1

Convulsions, increased intracranial pressure (including pseudotumor cerebri), and toxic psychosis reported in patients receiving fluoroquinolones.1 Fluoroquinolones may also cause CNS stimulation, which may lead to tremors, restlessness, anxiety, lightheadedness, confusion, hallucinations, paranoia, depression, insomnia, and rarely, suicidal thoughts or acts.1 These CNS effects may occur after first dose.1

If CNS effects occur, immediately discontinue gemifloxacin and institute appropriate measures.1 (See Advice to Patients.)

Use with caution in patients with a history of convulsions, seizures, or epilepsy or with other risk factors that predispose to convulsions.1

Avoid systemic fluoroquinolones, including gemifloxacin, in patients who have experienced CNS effects associated with fluoroquinolones.1

Fluoroquinolones, including gemifloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in myasthenia gravis patients;1 death or need for ventilatory support reported.1

Avoid use in patients with known history of myasthenia gravis.1 (See Advice to Patients.)

Prolonged QT interval leading to ventricular arrhythmias, including torsades de pointes, reported with some fluoroquinolones, including gemifloxacin.1

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

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

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

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

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 reported in juvenile dogs, but not in mature dogs.1 (See Pediatric Use under Cautions.)

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

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.1 96 98 99 C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives, including gemifloxacin, and may range in severity from mild diarrhea to fatal colitis.1 37 41 42 96 98 99 C. difficile produces toxins A and B which contribute to development of CDAD;1 96 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

Outbreaks of severe CDAD caused by fluoroquinolone-resistant C. difficile have been reported with increasing frequency over the past several years.36 37 38 39 41

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.1 96 98 99 Careful medical history necessary since CDAD may occur as late as 2 months or longer after anti-infective therapy is discontinued.1

If CDAD suspected or confirmed, discontinue anti-infectives not directed against C. difficile whenever possible.1 96 98 99 Initiate appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), appropriate anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.1 96 98 99

Sensitivity Reactions

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

Some hypersensitivity reactions have been accompanied by cardiovascular collapse, hypotension or shock, seizures, loss of consciousness, tingling, angioedema (e.g., edema or swelling of 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 reactions reported with fluoroquinolones, including gemifloxacin, that may or may not be related to hypersensitivity reactions include one or more of the following: fever, rash or other 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 effects.1

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

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

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

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

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

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

General Precautions

Rash (maculopapular, urticarial) reported;1 5 12 7–10% of rash cases were described as severe.1

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

Discontinue gemifloxacin at first appearance of rash or urticaria.1 (See Hypersensitivity Reactions under Cautions.)

Use for treatment of acute bacterial exacerbations of chronic bronchitis only when no other treatment options 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, risks of serious adverse reactions outweigh benefits for patients with these infections.140 145

When prescribing a fluoroquinolone, consider potential benefits and risks for the individual patient.128 129 Most patients tolerate the drugs, but serious adverse reactions (e.g., CNS effects, QT prolongation, C. difficile-associated diarrhea and colitis, damage to liver, kidneys, or bone marrow, alterations in glucose homeostasis) may occur rarely.128 129

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

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

Specific Populations

Category C.1

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

Safety and efficacy not established in children or adolescents <18 years of age.1 Like other fluoroquinolones, gemifloxacin causes arthropathy and osteochondrosis in juvenile animals.1 12 45 46 47 48 49 52 53 (See Musculoskeletal Effects under Cautions.)

AAP states use of systemic fluoroquinolones may be justified in children <18 years of age in special circumstances when there are no safe and effective alternatives and after careful assessment of risks and benefits for the individual patient.110 292

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

Risk of severe tendon disorders, including tendon rupture, is increased in older adults (usually those >60 years of age).1 128 129 This risk is further increased in those receiving concomitant corticosteroids.1 128 129 (See Tendinitis and Tendon Rupture under Cautions.) Use caution in geriatric adults, especially those receiving concomitant corticosteroids.1

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

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

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

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

Common Adverse Effects

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

Storage

Oral

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

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.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Use Factive (gemifloxacin) as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take this medicine at the same time of day.
• Take with or without food. Take with food if it causes an upset stomach.
• You may take with meals that have dairy products. Do not take with only dairy products.
• Swallow tablet whole. Do not chew, break, or crush.
• Do not take sucralfate, didanosine, antacids, multivitamins, or products that have magnesium, aluminum, iron, or zinc within 3 hours before or 2 hours after taking Factive.
• To gain the most benefit, do not miss doses.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take more than 1 dose of Factive in the same day.

Cartilage erosion and arthropathy have been observed in immature animals giving rise to concern over toxic effects in the developing joints of nursing infants; however, some studies suggest risk is low. Absorption of the small amounts of fluoroquinolones in milk may be blocked by the calcium in milk; data insufficient to prove or disprove. A nursing mother was administered a single 320 mg oral tablet. A single breast milk sample was collected 3 hours after dosing; milk drug level was about 0.9 mg/L.

LactMed: Use is considered acceptable with monitoring of the infant for possible effects on the gastrointestinal flora (e.g., diarrhea or candidiasis [thrush, diaper rash]); however, an alternate agent with safety information available is preferred. -According to some authorities: This drug should not be used unless the benefit to the mother outweighs the risk to the infant. Excreted into human milk: Yes (small amounts) Comments: -The effects in the nursing infant are unknown.

Substance Name

Gemifloxacin

CAS Registry Number

175463-14-6

Drug Class

Fluoroquinolones

Quinolones