Tafluprost Opthalmic

Tafluprost ophthalmic solution is indicated for reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Tafluprost ophthalmic solution is a prostaglandin analog indicated for reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. ( 1 )

Ophthalmic solution: 0.0015% tafluprost in a single-dose container. Ophthalmic solution: 0.0015% tafluprost in a single-dose container. ( 3 )

None. None. ( 4 )

Pigmentation: Pigmentation of the iris, periorbital tissue (eyelid) and eyelashes can occur. Iris pigmentation is likely to be permanent. ( 5.1 ) Eyelash Changes: Gradual changes to eyelashes including increased length, thickness and number of lashes. Usually reversible. ( 5.2 )

5.1 Pigmentation 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 tafluprost ophthalmic solution can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly.

5.2 Eyelash Changes Tafluprost 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.

5.3 Intraocular Inflammation Tafluprost should be used with caution in patients with active intraocular inflammation (e.g., iritis/uveitis) because the inflammation may be exacerbated.

5.4 Macular Edema Macular edema, including cystoid macular edema, has been reported during treatment with prostaglandin F2α analogs. Tafluprost 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 edema.

5.5 Contact Lens Use Contact lenses should be removed prior to the administration of tafluprost ophthalmic solution and may be reinserted 15 minutes after administration.

Most common ocular adverse reaction is conjunctival hyperemia (4% to 20%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Micro Labs USA Inc., at 1-855-839-8195 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Preservative-containing or nonpreserved tafluprost 0.0015% was evaluated in 905 patients in five controlled clinical studies of up to 24-months duration. The most common adverse reaction observed in patients treated with tafluprost was conjunctival hyperemia which was reported in a range of 4% to 20% of patients. Approximately 1% of patients discontinued therapy due to ocular adverse reactions. Ocular adverse reactions reported at an incidence of ≥ 2% in these clinical studies included ocular stinging/irritation (7%), ocular pruritus including allergic conjunctivitis (5%), cataract (3%), dry eye (3%), ocular pain (3%), eyelash darkening (2%), growth of eyelashes (2%) and vision blurred (2%). Nonocular adverse reactions reported at an incidence of 2% to 6% in these clinical studies in patients treated with tafluprost 0.0015% were headache (6%), common cold (4%), cough (3%) and urinary tract infection (2%).

6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of tafluprost. Because postapproval adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Respiratory disorders: exacerbation of asthma, dyspnea Eye disorders: iritis/uveitis In postmarketing use with prostaglandin analogs, periorbital and lid changes including deepening of the eyelid sulcus have been observed.

Use in pediatric patients is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use. ( 8.4 )

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of tafluprost administration in pregnant women to inform of drug-associated risks. In animal reproduction studies, intravenous administration of tafluprost to pregnant rabbits and rats throughout organogenesis resulted in embryofetal toxicities at exposures ≥5-times the human dose in rabbit and ≥2362-times the human dose in rat. (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In embryo-fetal development studies, intravenous administration of tafluprost to pregnant rats and rabbits during organogenesis caused increases in post-implantation losses in both species and reductions in fetal body weights in rats (≥0.03 mcg/kg/day in rabbits, 5-times the maximum clinical exposure based on C max ; ≥10 mcg/kg/day in rats, 2362-times the maximum clinical exposure based on C max ). Tafluprost also increased the incidence of vertebral skeletal abnormalities in rats and the incidence of skull, brain and spine malformations in rabbits at these same doses. 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 C max . 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, intravenous administration of tafluprost to pregnant rats during organogenesis and through birth and lactation, caused increased mortality of newborns, decreased body weights and delayed pinna unfolding 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 comparison.

8.2 Lactation Risk Summary There are no data on the presence of tafluprost or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production following topical ocular administration. Tafluprost and/or its metabolites are present in rat milk following ocular administration. When a drug is present in animal milk, it is likely that the drug will be present in human milk.

8.4 Pediatric Use Use in pediatric patients is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use.

8.5 Geriatric Use No overall clinical differences in safety or effectiveness have been observed between elderly and other adult patients.

Tafluprost acid, a prostaglandin analog, is a selective FP prostanoid receptor agonist which is believed to reduce intraocular pressure by increasing uveoscleral outflow. The exact mechanism of action is unknown at this time.