Included as part of the "PRECAUTIONS" Section
Potential For Eye Injury And Contamination
To avoid the potential for eye injury and contamination, advise patients not to touch the vial tip
to the eye or other surfaces.
Use With Contact Lenses
CEQUA should not be administered while wearing contact lenses. If contact lenses are worn,
they should be removed prior to administration of the solution. Lenses may be reinserted 15
minutes following administration of CEQUA ophthalmic solution.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Systemic carcinogenicity studies were carried out in male and female mice and rats. In the
78-week oral (diet) mouse study, at doses of 1, 4, and 16 mg/kg/day, evidence of a statistically
significant trend was found for lymphocytic lymphomas in females, and the incidence of
hepatocellular carcinomas in mid-dose males significantly exceeded the control value.
In the 24-month oral (diet) rat study, conducted at 0.5, 2, and 8 mg/kg/day, pancreatic islet cell
adenomas significantly exceeded the control rate in the low dose level. The hepatocellular
carcinomas and pancreatic islet cell adenomas were not dose related. The low doses in mice and
rats are approximately 55 times higher than the maximum recommended human ophthalmic dose
(1.5 mcg/kg/day), normalized to body surface area.
In genetic toxicity tests, cyclosporine has not been found to be mutagenic/genotoxic in the Ames
Test, the V79-HGPRT Test, the micronucleus test in mice and Chinese hamsters, the
chromosome-aberration tests in Chinese hamster bone-marrow, the mouse dominant lethal assay,
and the DNA-repair test in sperm from treated mice. Cyclosporine was positive in an in vitro sister chromatid exchange (SCE) assay using human lymphocytes.
Impairment Of Fertility
Oral administration of cyclosporine to rats for 12 weeks (male) and 2 weeks (female) prior to
mating produced no adverse effects on fertility at doses up to 15 mg/kg/day (1620 times higher
than the maximum recommended human ophthalmic dose).
Use In Specific Populations
There are no adequate and well-controlled studies of CEQUA administration in pregnant women
to inform a drug-associated risk. Oral administration of cyclosporine to pregnant rats or rabbits
did not produce teratogenicity at clinically relevant doses [see Data].
Oral administration of cyclosporine oral solution (USP) to pregnant rats or rabbits was
teratogenic at maternally toxic doses of 30 mg/kg/day in rats and 100 mg/kg/day in rabbits, as
indicated by increased pre- and postnatal mortality, reduced fetal weight and skeletal
retardations. These doses (normalized to body weight) were approximately 3200 and 21000
times higher than the maximum recommended human ophthalmic dose (MRHOD) of
1.5 mcg/kg/day, respectively. No adverse embryofetal effects were observed in rats or rabbits
receiving cyclosporine during organogenesis at oral doses up to 17 mg/kg/day or 30 mg/kg/day,
respectively (approximately 1800 and 6400 times higher than the MRHOD, respectively).
An oral dose of 45 mg/kg/day cyclosporine (approximately 4800 times higher than MRHOD)
administered to rats from Day 15 of pregnancy until Day 21 postpartum produced maternal
toxicity and an increase in postnatal mortality in offspring. No adverse effects in dams or
offspring were observed at oral doses up to 15 mg/kg/day (approximately 1600 times greater
than the MRHOD).
Cyclosporine blood concentrations are low following topical ocular administration of CEQUA
[see CLINICAL PHARMACOLOGY]. There is no information regarding the presence of
cyclosporine in human milk following topical administration or on the effects of CEQUA on the
breastfed infants and milk production. Administration of oral cyclosporine to rats during
lactation did not produce adverse effects in offspring at clinically relevant doses [see Pregnancy]. The developmental and health benefits of breastfeeding should be considered along with
the mother’s clinical need for CEQUA and any potential adverse effects on the breast-fed child
The safety and efficacy of CEQUA ophthalmic solution have not been established in pediatric
patients below the age of 18.
No overall differences in safety or effectiveness have been observed between elderly and
younger adult patients.