No information provided.
None
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in one clinical trial of a drug cannot be directly compared with the rates in the clinical trials of the same or another drug and may not reflect the rates observed in practice.
The data described below reflect exposure to Besiflox in approximately 1,000 patients between 1 and 98 years old with clinical signs and symptoms of bacterial conjunctivitis.
The most frequently reported ocular adverse reaction was conjunctival redness, reported in approximately 2% of patients.
Other adverse reactions reported in patients receiving Besiflox occurring in approximately 1-2% of patients included: blurred vision, eye pain, eye irritation, eye pruritus and headache.
Besiflox® (besifloxacin ophthalmic suspension) 0.6%, is indicated for the treatment of bacterial conjunctivitis caused by susceptible isolates of the following bacteria:
Aerococcus viridans*
CDC coryneform group G
Corynebacterium pseudodiphtheriticum*
Corynebacterium striatum*
Haemophilus influenzae
Moraxella catarrhalis*
Moraxella lacunata*
Pseudomonas aeruginosa*
Staphylococcus aureus
Staphylococcus epidermidis
Staphylococcus hominis*
Staphylococcus lugdunensis*
Staphylococcus warneri*
Streptococcus mitis group
Streptococcus oralis
Streptococcus pneumoniae
Streptococcus salivarius*
*Efficacy for this organism was studied in fewer than 10 infections.
Plasma concentrations of besifloxacin were measured in adult patients with suspected bacterial conjunctivitis who received Besiflox bilaterally three times a day (16 doses total). Following the first and last dose, the maximum plasma besifloxacin concentration in each patient was less than 1.3 ng/mL. The mean besifloxacin Cmax was 0.37 ng/mL on day 1 and 0.43 ng/mL on day 6. The average elimination half-life of besifloxacin in plasma following multiple dosing was estimated to be 7 hours.
Included as part of the PRECAUTIONS section.
PRECAUTIONS Topical Ophthalmic Use OnlyNOT FOR INJECTION INTO THE EYE.
Besiflox is for topical ophthalmic use only, and should not be injected subconjunctivally, nor should it be introduced directly into the anterior chamber of the eye.
Growth Of Resistant Organisms With Prolonged UseAs with other anti-infectives, prolonged use of Besiflox (besifloxacin ophthalmic suspension) 0.6% may result in overgrowth of non-susceptible organisms, including fungi. If super-infection occurs, discontinue use and institute alternative therapy. Whenever clinical judgment dictates, the patient should be examined with the aid of magnification, such as slit-lamp biomicroscopy, and, where appropriate, fluorescein staining.
Avoidance Of Contact LensesPatients should not wear contact lenses if they have signs or symptoms of bacterial conjunctivitis or during the course of therapy with Besiflox.
Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of FertilityLong-term studies in animals to determine the carcinogenic potential of besifloxacin have not been performed.
No in vitro mutagenic activity of besifloxacin was observed in an Ames test (up to 3.33 mcg/plate) on bacterial tester strains Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA. However, it was mutagenic in S. typhimurium strain TA102 and E. coli strain WP2(pKM101).
Positive responses in these strains have been observed with other quinolones and are likely related to topoisomerase inhibition.
Besifloxacin induced chromosomal aberrations in CHO cells in vitro and it was positive in an in vivo mouse micronucleus assay at oral doses ≥ 1500 mg/kg. Besifloxacin did not induce unscheduled DNA synthesis in hepatocytes cultured from rats given the test compound up to 2,000 mg/kg by the oral route. In a fertility and early embryonic development study in rats, besifloxacin did not impair the fertility of male or female rats at oral doses of up to 500 mg/kg/day. This is over 10,000 times higher than the recommended total daily human ophthalmic dose.
Use In Specific Populations PregnancyPregnancy Category C. Oral doses of besifloxacin up to 1000 mg/kg/day were not associated with visceral or skeletal malformations in rat pups in a study of embryo-fetal development, although this dose was associated with maternal toxicity (reduced body weight gain and food consumption) and maternal mortality. Increased post-implantation loss, decreased fetal body weights, and decreased fetal ossification were also observed. At this dose, the mean Cmax in the rat dams was approximately 20 mcg/mL, > 45,000 times the mean plasma concentrations measured in humans. The No Observed Adverse Effect Level (NOAEL) for this embryo-fetal development study was 100 mg/kg/day (Cmax, 5 mcg/mL, > 11,000 times the mean plasma concentrations measured in humans).
In a prenatal and postnatal development study in rats, the NOAELs for both fetal and maternal toxicity were also 100 mg/kg/day. At 1000 mg/kg/day, the pups weighed significantly less than controls and had a reduced neonatal survival rate. Attainment of developmental landmarks and sexual maturation were delayed, although surviving pups from this dose group that were reared to maturity did not demonstrate deficits in behavior, including activity, learning and memory, and their reproductive capacity appeared normal.
Since there are no adequate and well-controlled studies in pregnant women, Besiflox should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing MothersBesifloxacin has not been measured in human milk, although it can be presumed to be excreted in human milk. Caution should be exercised when Besiflox is administered to a nursing mother.
Pediatric UseThe safety and effectiveness of Besiflox in infants below one year of age have not been established. The efficacy of Besiflox in treating bacterial conjunctivitis in pediatric patients one year or older has been demonstrated in controlled clinical trials.
There is no evidence that the ophthalmic administration of quinolones has any effect on weight bearing joints, even though systemic administration of some quinolones has been shown to cause arthropathy in immature animals.
Geriatric UseNo overall differences in safety and effectiveness have been observed between elderly and younger patients.
Invert closed bottle and shake once before use.
Instill one drop in the affected eye(s) 3 times a day, four to twelve hours apart for 7 days.
