General: XALATAN Sterile Ophthalmic Solution may gradually increase the pigmentation
of the iris. The eye color change is due to increased melanin content in the stromal
melanocytes of the iris rather than to an increase in the number of melanocytes.
This change may not be noticeable for several months to years (see WARNINGS).
Typically, the brown pigmentation around the pupil spreads concentrically towards
the periphery of the iris and the entire iris or parts of the iris become more brownish.
Neither nevi nor freckles of the iris appear to be affected by treatment. While
treatment with XALATAN can be continued in patients who develop noticeably increased
iris pigmentation, these patients should be examined regularly.
During clinical trials, the increase in brown iris pigment has not been shown to
progress further upon discontinuation of treatment, but the resultant color change
may be permanent.
Eyelid skin darkening, which may be reversible, has been reported in association
with the use of XALATAN (see WARNINGS).
XALATAN may gradually change eyelashes and vellus hair in the treated eye; these
changes include increased length, thickness, pigmentation, the number of lashes
or hairs, and misdirected growth of eyelashes. Eyelash changes are usually reversible
upon discontinuation of treatment.
XALATAN should be used with caution in patients with a history of intraocular inflammation
(iritis/uveitis) and should generally not be used in patients with active intraocular
inflammation.
Macular edema, including cystoid macular edema, has been reported during treatment
with XALATAN. These reports have mainly occurred in aphakic patients, in pseudophakic
patients with a torn posterior lens capsule, or in patients with known risk factors
for macular edema. XALATAN should be used with caution in patients who do not have
an intact posterior capsule or who have known risk factors for macular edema.
There is limited experience with XALATAN in the treatment of angle closure, inflammatory
or neovascular glaucoma.
There have been reports of bacterial keratitis associated with the use of multiple-dose
containers of topical ophthalmic products. These containers had been inadvertently
contaminated by patients who, in most cases, had a concurrent corneal disease or
a disruption of the ocular epithelial surface (see PRECAUTIONS,Information
for Patients).
Contact lenses should be removed prior to the administration of XALATAN, and may
be reinserted 15 minutes after administration (see PRECAUTIONS,Information
for Patients).
Information for Patients (see WARNINGS and PRECAUTIONS): Patients
should be advised about the potential for increased brown pigmentation of the iris,
which may be permanent. Patients should also be informed about the possibility of
eyelid skin darkening, which may be reversible after discontinuation of XALATAN.
Patients should also be informed of the possibility of eyelash and vellus hair changes
in the treated eye during treatment with XALATAN. These changes may result in a
disparity between eyes in length, thickness, pigmentation, number of eyelashes or
vellus hairs, and/or direction of eyelash growth. Eyelash changes are usually reversible
upon discontinuation of treatment.
Patients should be instructed to avoid allowing the tip of the dispensing container
to contact the eye or surrounding structures because this could cause the tip to
become contaminated by common bacteria known to cause ocular infections. Serious
damage to the eye and subsequent loss of vision may result from using contaminated
solutions.
Patients also should be advised that if they develop an intercurrent ocular condition
(e.g., trauma, or infection) or have ocular surgery, they should immediately seek
their physician's advice concerning the continued use of the multiple-dose container.
Patients should be advised that if they develop any ocular reactions, particularly
conjunctivitis and lid reactions, they should immediately seek their physician's
advice.
Patients should also be advised that XALATAN contains benzalkonium chloride, which
may be absorbed by contact lenses. Contact lenses should be removed prior to administration
of the solution. Lenses may be reinserted 15 minutes following administration of
XALATAN.
If more than one topical ophthalmic drug is being used, the drugs should be administered
at least five (5) minutes apart.
Drug Interactions:In vitro studies have shown that precipitation occurs
when eye drops containing thimerosal are mixed with XALATAN. If such drugs are used
they should be administered at least five (5) minutes apart.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Latanoprost was not
mutagenic in bacteria, in mouse lymphoma or in mouse micronucleus tests.
Chromosome aberrations were observed in vitro with human lymphocytes.
Latanoprost was not carcinogenic in either mice or rats when administered by oral
gavage at doses of up to 170 µg/kg/day (approximately 2,800 times the recommended
maximum human dose) for up to 20 and 24 months, respectively.
Additional in vitro and in vivo studies on unscheduled DNA synthesis
in rats were negative. Latanoprost has not been found to have any effect on male
or female fertility in animal studies.
Pregnancy: Teratogenic Effects: Pregnancy Category C.
Reproduction studies have been performed in rats and rabbits. In rabbits an incidence
of 4 of 16 dams had no viable fetuses at a dose that was approximately 80 times
the maximum human dose, and the highest nonembryocidal dose in rabbits was approximately
15 times the maximum human dose. There are no adequate and well-controlled studies
in pregnant women. XALATAN should be used during pregnancy only if the potential
benefit justifies the potential risk to the fetus.
Nursing Mothers: It is not known whether this drug or its metabolites are
excreted in human milk. Because many drugs are excreted in human milk, caution should
be exercised when XALATAN is administered to a nursing woman.
Pediatric Use: Safety and effectiveness in pediatric patients have not been
established.
Geriatric Use: No overall differences in safety or effectiveness have been
observed between elderly and younger patients.