Gemifloxacin Mesylate

Trade Names:Factive- Tablets 320 mg

Pharmacology

Interferes with microbial DNA synthesis.

Pharmacokinetics

Absorption

Rapidly absorbed from the GI tract. Bioavailability is approximately 71%. C _max is about 1.61 mcg/mL, and the AUC is about 9.93 mcg•h/mL.

Distribution

Protein binding ranges from 55% to 73%. Mean Vd _ss is 4.18 L/kg.

Metabolism

Metabolized to a limited extent by the liver.

Elimination

61% in the feces and 36% in the urine as unchanged drug and metabolites. The half-life is approximately 7 h. The mean renal Cl following multiple doses was approximately 11.6 L/h.

Special Populations

Average increase in AUC of approximately 70% in patients with renal insufficiency. Dosage modification is recommended for patients with CrCl of 40 mL/min or less.

No dosage adjustment is recommended in patients with mild, moderate, or severe hepatic impairment.

Indications and Usage

Treatment of acute bacterial exacerbation of chronic bronchitis and community-acquired pneumonia (mild to moderate) caused by susceptible strains of designated microorganisms.

Contraindications

Hypersensitivity to gemifloxacin, any member of the quinolone class of antimicrobial agents, or any component of the product.

Dosage and Administration

PO 320 mg/day for 5 days.

PO 320 mg/day for 5 to 7 days.

PO 160 mg every 24 h. Patients requiring routine hemodialysis or continuous ambulatory peritoneal dialysis should receive 160 mg every 24 h.

General Advice

• Administer gemifloxacin 3 h before or 2 h after sucralfate, antacids containing magnesium or aluminum, didanosine chewable buffered tablets or pediatric powder, or other products containing iron or zinc.
• Administer prescribed dose with a full glass of water.
• Administer without regard to meals, but administer with food if GI upset occurs.

Storage/Stability

Store tablets at room temperature (59° to 86°F). Protect from light.

Drug Interactions

May decrease the bioavailability of gemifloxacin. Do not take within 3 h before or 2 h after gemifloxacin.

The renal Cl of gemifloxacin may be decreased, increasing the bioavailability and AUC.

May decrease the bioavailability of gemifloxacin. Take at least 2 h before sucralfate.

Anticoagulant effect may be increased.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Prolonged QT, supraventricular tachycardia, syncope, transient ischemic attack (postmarketing).

CNS

Headache (4%); dizziness (2%).

Dermatologic

Rash (4%); erythema multiforme, skin exfoliation (postmarketing).

EENT

Retinal hemorrhage (postmarketing).

GI

Diarrhea (5%); nausea (4%); abdominal pain, vomiting (2%); pseudomembranous colitis (postmarketing).

Genitourinary

Renal failure (postmarketing).

Hematologic-Lymphatic

Hemorrhage, increased INR (postmarketing).

Lab Tests

Increased ALT (2%); increased AST, platelets (1%).

Musculoskeletal

Tendon rupture (postmarketing).

Miscellaneous

Anaphylactic reaction, facial swelling, peripheral edema, photosensitivity/phototoxicity reaction (postmarketing).

Precautions

Pregnancy

Category C .

Lactation

Undetermined; however, other fluoroquinolones have been shown to be excreted in breast milk.

Children

Safety and efficacy not established.

Hypersensitivity

Mild to life-threatening. Discontinue drug at first sign of hypersensitivity reaction.

Renal Function

Reduced Cl may occur; decrease the dose in patients with CrCl of 40 mL/min or less.

Superinfection

Use of antibiotics may result in bacterial or fungal overgrowth.

Photosensitivity

Photosensitivity reaction may occur.

CNS effects

Use with caution in patients with CNS disease (eg, epilepsy) or patients predisposed to convulsions.

Peripheral nephropathy

Sensory or sensorimotor axonal polyneuropathy, resulting in paresthesias, hypesthesia, dysesthesias, and weakness, has been reported in patients taking quinolones.

Clostridium difficile –associated diarrhea

Consider possibility in patients with diarrhea.

QT effects

Gemifloxacin may prolong the QT interval in some patients; avoid in patients with a history of prolongation of the QTc interval, patients with uncorrected electrolyte disorder (eg, hypokalemia or hypomagnesemia), and patients receiving class IA (eg, quinidine, procainamide) or class III (eg, amiodarone, sotalol) antiarrhythmic agents. Use gemifloxacin with caution in patients receiving drugs that prolong the QTc interval (eg, erythromycin, tricyclic antidepressants, antipsychotics) and in patients with ongoing proarrhythmic conditions (eg, clinically important bradycardia, acute MI).

Serious reactions

Clinical manifestations of serious and sometimes fatal reactions that have been reported with gemifloxacin include acute hepatic necrosis or failure, acute renal insufficiency or failure, agranulocytosis, allergic pneumonitis, anemia (including hemolytic and aplastic), arthralgia, fever, hepatitis, interstitial nephritis, jaundice, leukopenia, myalgia, pancytopenia, rash, serum sickness, Stevens-Johnson syndrome, thrombocytopenia (including thrombotic thrombocytopenic purpura), toxic epidermal necrolysis, and vasculitis.

Tendon and cartilage effects

Tendonitis and rupture of the shoulder, hand, and Achilles tendons, requiring surgical repair and resulting in prolonged disability, have been reported in patients receiving fluoroquinolones. The risk may be increased in patients receiving corticosteroids, especially in elderly patients.

Overdosage

Symptoms

Possible QTc prolongation.

Patient Information

• Advise patient to read patient information leaflet before starting therapy and with each refill.
• Review dosing schedule and prescribed length of therapy with patient.
• Instruct patient to take each dose with a full glass of water.
• Advise patient that medication can be taken without regard to meals, but to take with food if GI upset occurs.
• Advise patient that if a dose is missed to take as soon as remembered. However, if it is nearing the time for the next dose, they should skip the dose and take the next dose at the regularly scheduled time. Caution patient not to take more than 1 dose of medication in a day.
• Remind patient to complete entire course of therapy, even if symptoms of infection have disappeared.
• Advise patient to inform health care provider if infection does not improve or worsens.
• Advise patient to drink fluids liberally (eg, eight 8 oz glasses of water daily) while taking this medication.
• Advise patient to discontinue therapy and contact health care provider immediately if skin rash, hives, itching, shortness of breath, palpitations, fainting, pain, tenderness, or rupture of tendon occur.
• Warn patient that diarrhea containing blood or pus may be a sign of a serious disorder and to seek medical care if noted and not to treat at home.
• Caution patient that drug may cause dizziness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
• Advise patient to avoid unnecessary exposure to direct and indirect sunlight or tanning lamps, and to use sunscreen and wear protective clothing to avoid photosensitivity reactions during therapy and for several days after stopping medication. Advise patient to discontinue therapy and notify health care provider if any of the following occur following exposure to sunlight or artificial UV light (eg, sunlamp): sensation of skin burning, redness, swelling, blistering, rash, or itching.
• Inform patient not to take antacids containing magnesium and/or aluminum or products containing ferrous sulfate (iron), multivitamins containing zinc or other metal cations, or didanosine chewable buffered tablets or pediatric powder within 3 h before or 2 h after taking gemifloxacin.
• Inform patient that gemifloxacin may produce prolongation of the QTc interval on an ECG.
• Instruct patient to inform health care provider of any personal or family history of QTc prolongation or proarrhythmic conditions such as recent hypokalemia, significant bradycardia, or acute MI, or history of convulsions.

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