Tafluprost

• Solution, Ophthalmic; 0.0015%: Zioptan or Generic (0.3 mL single use vials)

• Adults: One drop in the affected eye(s) once daily in the evening.

• Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. Latanoprostene bunod should be used with caution in patients with hepatic impairment; data are lacking in these patients.

• Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. Latanoprostene bunod should be used with caution in patients with renal impairment; data are lacking in these patients. For intermittent hemodialysis, no dosage adjustment is needed.

Pediatric

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

Pregnancy

• Pregnancy Category C
• Teratogenic effects: 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 C_max . 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 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 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 comparison. 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.

Breast Feeding

• 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.

Geriatric

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

• Intraocular pressure
• Ocular pigmentation changes

• None

• Increased pigmentation of the iris and periorbital tissue (eyelid) can occur. Iris pigmentation is likely to be permanent.

• Gradual changes to eyelashes including increased length, increased thickness and number of eyelashes. Usually reversible upon discontinuation of treatment.

• Most common ocular adverse reaction is conjunctival hyperemia (range 4% to 20%).

• Absorption

• Following instillation, tafluprost is absorbed through the cornea and is hydrolyzed to the biologically active acid metabolite, tafluprost acid. Following instillation of one drop of the 0.0015% solution once daily into each eye of healthy volunteers, the plasma concentrations of tafluprost acid peaked at a median time of 10 minutes on both Days 1 and 8. The mean plasma Cmax of tafluprost acid were 26 pg/mL and 27 pg/mL on Day 1, and Day 8, respectively. The mean plasma AUC estimates of tafluprost acid were 394 pg*min/mL and 432 pg*min/mL on day 1 and 8, respectively.

• Metabolism

• Tafluprost, an ester prodrug, is hydrolyzed to its biologically active acid metabolite in the eye. The acid metabolite is further metabolized via fatty acid β-oxidation and phase II conjugation.

• Elimination

• Mean plasma tafluprost acid concentrations were below the limit of quantification of the bioanalytical assay (10 pg/mL) at 30 minutes following topical ocular administration of tafluprost 0.0015% ophthalmic solution.

• Carcinogenesis

• 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 plasma AUC).

• Mutagenesis

• 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.

• Impairment of Fertility

• 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 C or over 3600 times based on plasma AUC).

Nightly Application

• 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 treatment.

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 with at least five (5) minutes between applications.

Storage Information

• Instruct patients on proper storage of cartons, unopened foil pouches, and opened foil pouches. 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 30 days at room temperature 20° to 25°C (68° to 77°F). Protect from moisture.

• Tafluprost ophthalmic solution 0.0015%

American Academy of Ophthalmology 2020

• Gedde SJ, Vinod K, Wright MM, et al. Primary Open-Angle Glaucoma Preferred Practice Pattern®. Ophthalmology. 2021;128(1):P71-P150. doi:10.1016/j.ophtha.2020.10.022