FACTIVE- gemifloxacin mesylate tablet
Merus Labs International Inc.
WARNING: SERIOUS ADVERSE REACTIONS INCLUDING TENDINITIS, TENDON RUPTURE, PERIPHERAL NEUROPATHY, CENTRAL NERVOUS SYSTEM EFFECTS AND EXACERBATION OF MYASTHENIA GRAVIS
Fluoroquinolones, including FACTIVE � , have been associated with with disabling and potentially irreversible serious adverse reactions that have occurred together (See WARNINGS) including:
Tendinitis and tendon rupture
Peripheral neuropathy
Central nervous system effects
Discontinue FACTIVE immediately and avoid the use of fluoroquinolones, including FACTIVE, in patients who experience any of these serious adverse reactions (See WARNINGS ).
Fluoroquinolones, including FACTIVE, may exacerbate muscle weakness in persons with myasthenia gravis. Avoid FACTIVE in patients with known history of myasthenia gravis (See WARNINGS ).
Because fluoroquinolones, including FACTIVE, have been associated with serious adverse reactions (See WARNINGS), reserve FACTIVE for use in patients who have no alternative treatment options for acute bacterial exacerbation of chronic bronchitis (See INDICATIONS AND USAGE).
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 bacteria.
DESCRIPTION
FACTIVE (gemifloxacin mesylate) is a synthetic broad-spectrum antibacterial agent for oral administration. Gemifloxacin, a compound related to the fluoroquinolone class of antibiotics, is available as the mesylate salt in the sesquihydrate form. Chemically, gemifloxacin is (R,S)-7-[(4Z)-3-(aminomethyl)-4-(methoxyimino)-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid.
The mesylate salt is a white to light brown solid with a molecular weight of 485.49. Gemifloxacin is considered freely soluble at neutral pH (350 ?g/mL at 37�C, pH 7.0). Its empirical formula is C18 H20 FN5 O4 �CH4 O3 S and its chemical structure is:
Gemifloxacin Mesylate
(click image for full-size original)
Each white to off-white, oval, film-coated FACTIVE tablet has breaklines and GE 320 debossed on both faces and contains gemifloxacin mesylate equivalent to 320 mg gemifloxacin. The inactive ingredients are crospovidone, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, and titanium dioxide.
CLINICAL PHARMACOLOGY
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 ?g/mL (range 0.70-2.62 ?g/mL) and 9.93 � 3.07 ?g�hr/mL (range 4.71-20.1 ?g�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 ?g�hr/mL; range 3.2 � 47.7 ?g�hr/mL).
The pharmacokinetics of gemifloxacin were not significantly altered when a 320 mg dose was administered with a high-fat meal. Therefore FACTIVE tablets may be administered without regard to meals.