Included as part of the PRECAUTIONS section.
Tafluprost ophthalmic solution has been reported to cause
changes to pigmented tissues. The most frequently reported changes have been
increased pigmentation of the iris, periorbital tissue (eyelid) and eyelashes.
Pigmentation is expected to increase as long as tafluprost is administered. The
pigmentation change is due to increased melanin content in the melanocytes
rather than to an increase in the number of melanocytes. After discontinuation
of tafluprost, pigmentation of the iris is likely to be permanent, while
pigmentation of the periorbital tissue and eyelash changes have been reported
to be reversible in some patients. Patients who receive treatment should be
informed of the possibility of increased pigmentation. The long term effects of
increased pigmentation are not known.
Iris color change may not be noticeable for several
months to years. 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 ZIOPTAN® can be
continued in patients who develop noticeably increased iris pigmentation, these
patients should be examined regularly. [See PATIENT INFORMATION].
ZIOPTAN® may gradually change eyelashes and
vellus hair in the treated eye. These changes include increased length, color,
thickness, shape and number of lashes. Eyelash changes are usually reversible
upon discontinuation of treatment.
ZIOPTAN® should be used with caution in
patients with active intraocular inflammation (e.g., iritis/uveitis) because
the inflammation may be exacerbated.
Macular edema, including cystoid macular edema, has been
reported during treatment with prostaglandin F2α analogs. ZIOPTAN® should
be used with caution in aphakic patients, in pseudophakic patients with a torn
posterior lens capsule, or in patients with known risk factors for macular
Patient Counseling Information
See FDA-Approved Patient Labeling (PATIENT INFORMATION).
Advise patients to not exceed once daily dosing since
more frequent administration may decrease the intraocular pressure lowering
effect of ZIOPTAN®.
Handling The Single-Use Container
Advise patients that ZIOPTAN® is a sterile
solution that does not contain a preservative. The solution from one individual
unit is to be used immediately after opening for administration to one or both
eyes. Since sterility cannot be maintained after the individual unit is opened,
the remaining contents should be discarded immediately after administration.
Potential For Pigmentation
Advise patients about the potential for increased brown
pigmentation of the iris, which may be permanent. Also inform patients about
the possibility of eyelid skin darkening, which may be reversible after
discontinuation of ZIOPTAN®.
Potential For Eyelash Changes
Inform patients of the possibility of eyelash and vellus
hair changes in the treated eye during treatment with ZIOPTAN®.
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
When To Seek Physician Advice
Advise patients that if they develop a new ocular
condition (e.g., trauma or infection), experience a sudden decrease in visual
acuity, have ocular surgery, or develop any ocular reactions, particularly
conjunctivitis and eyelid reactions, they should immediately seek their
physician's advice concerning the continued use of ZIOPTAN®.
Use With Other Ophthalmic Drugs
If more than one topical ophthalmic drug is being used,
the drugs should be administered at least five (5) minutes between applications.
Instruct patients on proper storage of cartons, unopened
foil pouches, and opened foil pouches [see HOW SUPPLIED/Storage and
Handling]. Recommended storage for cartons and unopened foil pouches is to
store refrigerated at 2° to 8°C (36° to 46°F). After the pouch is opened, the
single-use containers may be stored in the opened foil pouch for up to 28 days
at room temperature 20° to 25°C (68° to 77°F). Protect from moisture.
Impairment Of Fertility
Tafluprost was not carcinogenic
when administered subcutaneously daily for 24 months at doses up to 30
mcg/kg/day in rats and for 18 months at doses up to 100 mcg/kg/day in mice
(over 1600 and 1300 times, respectively, the maximum clinical exposure based on
Tafluprost was not mutagenic or
clastogenic in a battery of genetic toxicology studies, including an in vitro microbial
mutagenesis assay, an in vitro chromosomal aberration assay in Chinese hamster
lung cells, and an in vivo mouse micronucleus assay in bone marrow.
In rats, no adverse effects on mating performance or
fertility were observed with intravenous dosing of tafluprost at a dose of 100
mcg/kg/day (over 14000 times the maximum clinical exposure based on plasma Cmax
or over 3600 times based on plasma AUC).
Use In Specific Populations
Pregnancy Category C.
In embryo-fetal development studies in rats and rabbits,
tafluprost administered intravenously was teratogenic. Tafluprost caused
increases in post-implantation losses in rats and rabbits and reductions in
fetal body weights in rats. Tafluprost also increased the incidence of
vertebral skeletal abnormalities in rats and the incidence of skull, brain and
spine malformations in rabbits. In rats, there were no adverse effects on
embryo-fetal development at a dose of 3 mcg/kg/day corresponding to maternal
plasma levels of tafluprost acid that were 343 times the maximum clinical
exposure based on Cmax. In rabbits, effects were seen at a tafluprost dose of
0.03 mcg/kg/day corresponding to maternal plasma levels of tafluprost acid
during organogenesis that were approximately 5 times higher than the clinical
exposure based on Cmax. At the no-effect dose in rabbits (0.01 mcg/kg/day),
maternal plasma levels of tafluprost acid were below the lower level of
quantification (20 pg/mL).
In a pre-and postnatal development study in rats,
increased mortality of newborns, decreased body weights and delayed pinna
unfolding were observed in offsprings. The no observed adverse effect level was
at a tafluprost intravenous dose of 0.3 mcg/kg/day which is greater than 3
times the maximum recommended clinical dose based on body surface area
There are no adequate and well-controlled studies in
pregnant woman. Although animal reproduction studies are not always predictive
of human response, ZIOPTAN should not be used during pregnancy unless the
potential benefit justifies the potential risk to the fetus.
Women of childbearing age/potential should have adequate
contraceptive measures in place.
A study in lactating rats demonstrated that radio-labeled
tafluprost and/or its metabolites were excreted in milk. 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 ZIOPTAN® is administered to a nursing woman.
Use in pediatric patients is not recommended because of
potential safety concerns related to increased pigmentation following long-term
No overall clinical differences in safety or
effectiveness have been observed between elderly and other adult patients.