CONTRAINDICATIONS
Known hypersensitivity to latanoprost, benzalkonium chloride or any other ingredients in
this product.
WARNINGS
Latanoprost has been reported to cause changes to pigmented tissues. The most
frequently reported changes have been increased pigmentation of the iris and
periorbital tissue (eyelid) and increased pigmentation and growth of eyelashes.
These changes may be permanent.
Latanoprost may gradually change eye color, increasing the amount of brown pigment in
the iris by increasing the number of melanosomes (pigment granules) in melanocytes. The
long-term effects on the melanocyles and the consequences of potential injury to the
melanocytes and/or deposition of pigment granules to other areas of the eye are currently
unknown. The change in iris color occurs slowly and may not be noticeable for several
months to years. Patients should be informed of the possibility of iris color change.
Eyelid skin darkening has also been repoted in association with the use of latanoprost.
Latanoprost may gradually change eyelashes; these changes include increased length,
thickness, pigmentation, and number of lashes.
Patients who are expected to receive treatment in only one eye should be informed about
the potential for increased brown pigmentation of the iris, periorbital tissue, and eyelashes
in the treated eye and thus, heterochromia between the eyes. They should also be
advised of the potential for a disparity between the eyes in length, thickness, and/or
number of eyelashes. These changes in pigmentation and lash growth may be permanent.
PRECAUTIONS
General
Latanoprost is hydrolyzed in the cornea. The effect of continued administration of
latanoprost on the corneal endothelium has not been fully evaluated.
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 Information for the Patient).
Patients may slowly develop increased brown pigmentation of the iris. 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 in affected
eyes, but the entire iris or parts of it may also become more brownish. Until more
information about increased brown pigmentation is available, patients should be examined
regularly and, depending on the clinical situation, treatment may be stopped if increased
pigmentation ensues. 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. Neither nevi nor freckles of the iris have been affected by
treatment.
Latanoprost should be used with caution in patients with active intraocular inflammation
(iritis/uveitis).
Macular edema, including cystoid macular edema, has been reported during treatment
with latanoprost. 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. Latanoprost should be used with caution in these patients.
There is limited experience with latanoprost in the treatment of angle closure,
inflammatory or neovascular glaucoma.
Latanoprost has not been studied in patients with renal or hepatic impairment and should
therefore be used with caution in such patients.
Latanoprost should not be administered while wearing contact lenses.
Information for the Patient
See also WARNINGS.
Patients should be informed about the possibility of iris color change due to an increase of
the brown pigment and resultant cosmetically different eye coloration that may occur
when only one eye is treated. Iris pigmentation changes may be more noticeable in
patients with green-brown, blue/gray-brown or yellow-brown irides.
Patients should also be informed of the possibility of eyelash changes in the treated eye,
which may result in a disparity between eyes in lash length, thickness, pigmentation,
and/or number.
Patients should also be informed about the possibility of eyelid skin darkening.
The increased pigmentation to the iris and eyelid, as well as the changes to the eyelashes,
may be permanent.
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 multidose 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 latanoprost 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 latanoprost. If more than one topical ophthalmic drug is being used, the
drugs should be administered at least 5 minutes apart.
Carcinogenesis, Mutagenesis, and 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 mg/kg/day (approximately 2800 times the
recommended 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. Latanoprost 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 latanoprost is
administered to a nursing woman.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.