Included as part of the "PRECAUTIONS" Section
Not For Injection Into The Eye
Growth Of Resistant Organisms With Prolonged Use
As with other anti-infectives, prolonged use of BESIVANCE (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 slitlamp
biomicroscopy, and, where appropriate, fluorescein staining.
Avoidance Of Contact Lenses
Patients should not wear contact lenses if they have signs or symptoms of bacterial conjunctivitis
or during the course of therapy with BESIVANCE.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term studies in animals to determine the carcinogenic potential of besifloxacin have not
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 ≥ 1,500 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 dose is approximately
26,500 times higher than the mean plasma concentration measured in humans at the
recommended human ophthalmic dose.
Use In Specific Populations
There are no available human data for the use of BESIVANCE during pregnancy to inform any
drug-associated risks; however, systemic exposure to besifloxacin from ocular administration is
low [see CLINICAL PHARMACOLOGY].
Oral administration of besifloxacin to pregnant rats during organogenesis or during the
pre/postnatal period did not produce adverse embryofetal or offspring effects at clinically
relevant systemic exposures [see Data].
In an embryofetal development study in rats, the administration of besifloxacin at oral doses up
to 1,000 mg/kg/day during organogenesis was not associated with visceral or skeletal
malformations in rat fetuses, 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, approximately 46,500 times
the mean plasma concentrations measured in humans at the recommended human ophthalmic
dose (RHOD). The No Observed Adverse Effect Level (NOAEL) for this embryofetal
development study was 100 mg/kg/day (Cmax, 5 mcg/mL, approximately 11,600 times the mean
plasma concentrations measured in humans at the RHOD).
In a prenatal and postnatal development study in rats, the NOAELs for both fetal/neonate and
maternal toxicity were 100 mg/kg/day. At 1,000 mg/kg/day, pups weighed significantly less than
controls and had a reduced neonatal survival rate. Attainment of developmental landmarks and
sexual maturation was 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.
There are no data on the presence of BESIVANCE in human milk, the effects on the breastfed
infant, or the effects on milk production. However, systemic exposure to besifloxacin following
topical ocular administration is low [see CLINICAL PHARMACOLOGY], and it is not known
whether measurable levels of besifloxacin would be present in maternal milk following topical
The developmental and health benefits of breastfeeding should be considered, along with the
mother’s clinical need for BESIVANCE, and any potential adverse effects on the breastfed infant
The safety and effectiveness of BESIVANCE in infants below one year of age have not been
established. The efficacy of BESIVANCE in treating bacterial conjunctivitis in pediatric patients
one year or older has been demonstrated in controlled clinical trials [see Clinical Studies].
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.
No overall differences in safety and effectiveness have been observed between elderly and