TAFLUTAN

 

Tafluprost 0.0015% is a prostaglandin analogue which was co-developed by Santen with Asahi Glass Co., Ltd (Tokyo, Japan) for the treatment of glaucoma and elevated intraocular pressure (IOP). Unit-dose, preservative- free eyedrops and in combination with timolol are now also available.  

The recommended dose is one drop of tafluprost in the conjunctival sac of the affected eye(s) once daily in the evening.

PHARMACOLOGY:

Mechanism of action=

Tafluprost acid is a fluorinated prostaglandin F2α (PGF2α) analogue. Tafluprost is a prodrug of the active substance, tafluprost acid, a structural and functional analogue of PGF2α. Tafluprost acid is a selective agonist at the prostaglandin F-receptor, increasing outflow of aqueous humor via the uveoscleral pathway and thus lowering IOP.

Other PGF2α analogues with the same mechanism of action include latanoprost and travoprost.

Pharmacokinetics=

Tafluprost is a prodrug ester prostaglandin F2α-analog designed to expedite the corneal penetration of the drug, which is then hydrolyzed by corneal esterases to produce the carboxylic acid active metabolite. The product, tafluprost acid, can then be taken up by the aqueous humor to therapeutically relevant levels.

Onset of action is 2 to 4 hours after application, the maximal effect is reached after 12 hours, and ocular pressure remains lowered for at least 24 hours.

Tafluprost acid is inactivated by beta oxidation to 1,2-dinortafluprost acid, 1,2,3,4-tetranortafluprost acid, and its lactone, which are subsequently glucuronidated or hydroxylated. The cytochrome P450 liver enzymes play no role in the metabolism.

ADVERSE EFFECTS:

The most common side effect of tafluprost is conjunctival hyperemia, which occurs in 4 to 20% of patients. Less common side effects include stinging of the eyes, headache, and respiratory infections. Rare side effects are dyspnea (breathing difficulties), worsening of asthma, and macular oedema.

Tafluprost causes changes to pigmented tissues, leading to increased pigmentation of the iris, periorbital tissue (eyelid) and eyelashes. Before treatment is initiated, patients should be informed of the possibility of eyelash growth, darkening of the eyelid skin and increased iris pigmentation. Some of these changes may be permanent, and may lead to differences in appearance between the eyes when only one eye is treated.

Usually, the eyelash and pigmentary changes resolve after discontinuation of the drug.

To reduce the risk of darkening of the eyelid skin patients should blot off any excess solution from the skin. Nasolacrimal outflow occlusion or gently closing the eyelid after administration may reduce the systemic absorption of products administered via the ocular route.

Contact lenses should be removed prior to the administration of tafluprost, and may be reinserted 15 minutes following administration.

Caution is recommended in patients with known risk factors for 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 prostaglandin F2α analogues. These side-effects usually occur in aphakic patients, pseudophakic patients with a torn posterior lens capsule or anterior chamber lenses, or in patients with known risk factors for macular edema. Therefore, caution is recommended when using tafluprost in these patients.

STUDIES:

In a review performed by Keating, tafluprost was at least as effective as latanoprost ophthalmic solution 0.005 % in Asian patients with primary open-angle glaucoma or ocular hypertension. The efficacy of tafluprost ophthalmic solution 0.0015 % was maintained in the longer term. [1]

A study by the Tafluprost Multi-center Study Group and others, found the agent to be effective in lowering IOP in normal-tension glaucoma (NTG) patients. Mean IOP changes from baseline were -4.0 +/- 1.7 mmHg in tafluprost administered patients and -1.4 +/- 1.8 mmHg in Placebo administered patients at 4 weeks, with a statistically significant difference (p<0.001). [2]

A study by Nakano et al., to evaluate the efficacy and safety of tafluprost in NTG with IOP of 16 mmHg or less, found the IOP in the study eyes versus fellow eyes were 10.2 ± 1.6 versus 12.1 ± 1.5 mmHg at week 12 of treatment. The IOP difference between the study eyes and the fellow eyes was statistically significant (P < 0.0001, Student's t test). [3]

Hoy has reported good IOP control with the tafluprost/timolol combination (Taptiqom). [4]

REFERENCES:

1. Keating GM. Tafluprost Ophthalmic Solution 0.0015 %: A Review in Glaucoma and Ocular Hypertension. Clin Drug Investig. 2016 Jun;36(6):499-508. doi: 10.1007/s40261-016-0413-z. PMID: 27225879.
2. Kuwayama Y, Komemushi S; Tafluprost Multi-center Study Group. [Intraocular pressure lowering effect of 0.0015% tafluprost as compared to placebo in patients with normal tension glaucoma: randomized, double-blind, multicenter, phase III study]. Nippon Ganka Gakkai Zasshi. 2010 May;114(5):436-43. Japanese. PMID: 20545217.
3. Nakano T, Yoshikawa K, Kimura T, Suzumura H, Nanno M, Noro T. Efficacy and safety of tafluprost in normal-tension glaucoma with intraocular pressure of 16 mmHg or less. Jpn J Ophthalmol. 2011 Nov;55(6):605-13. doi: 10.1007/s10384-011-0082-7. Epub 2011 Aug 27. PMID: 21874307.
4. Hoy SM. Tafluprost/Timolol: A Review in Open-Angle Glaucoma or Ocular Hypertension. Drugs. 2015 Oct;75(15):1807-13. doi: 10.1007/s40265-015-0476-9. PMID: 26431840.