Reduction of elevated intraocular pressure in open angle glaucoma and ocular hypertension.
As monotherapy in patients:
 who would benefit from preservative free eye drops
 insufficiently responsive to first line therapy
 intolerant or contra-indicated to first line therapy
As adjunctive therapy to beta-blockers. Tafluprost is indicated in adults ≥ 18 years.

Posology
The recommended dose is one drop of Tafluprost in the conjunctival sac of the affected eye(s) once
daily in the evening.
The dose should not exceed once daily as more frequent administration may lessen the intraocular
pressure lowering effect.
For single use only, one container is sufficient to treat both eyes. Any unused solution should be
discarded immediately after use.
Use in elderly
No dosage alteration in elderly patients is necessary.
Paediatric population
The safety and efficacy of tafluprost in children below age 18 has not yet been established. No data
are available.
Use in renal/hepatic impairment 

Tafluprost has not been studied in patients with renal/hepatic impairment and should therefore be
used with caution in such patients.
Method of administration
To reduce the risk of darkening of the eyelid skin the patients should wipe off any excess solution
from the skin. As with any other eye drops, nasolacrimal occlusion or gently closing the eyelid after
administration is recommended. This may reduce the systemic absorption of medicinal products
administered via the ocular route.
If more than one topical ophthalmic medicinal product is being used, each one should be administered
at least 5 minutes apart.

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.
The change in iris pigmentation occurs slowly and may not be noticeable for several months. The
change in eye colour has predominantly been seen in patients with mixed coloured irises, e.g. bluebrown,
grey-brown, yellow-brown and green-brown. The risk of lifelong heterochromia between the
eyes in unilateral cases is obvious.
There is a potential for hair growth to occur in areas where tafluprost solution comes repeatedly in
contact with the skin surface.
There is no experience with tafluprost in neovascular, angle-closure, narrow-angle or congenital
glaucoma. There is only limited experience with tafluprost in aphakic patients and in pigmentary or
pseudoexfoliative glaucoma.
Caution is recommended when using tafluprost in aphakic patients, pseudophakic patients with torn
posterior lens capsule or anterior chamber lenses, or in patients with known risk factors for cystoid
macular oedema or iritis/uveitis.
There is no experience in patients with severe asthma. Such patients should therefore be treated with
caution.

No interactions are anticipated in humans since systemic concentrations of Tafluprost are extremely
low following ocular dosing. Therefore, specific interaction studies with other medicinal products
have not been performed with Tafluprost.
In clinical studies Tafluprost was used concomitantly with timolol without evidence of interaction.

Women of childbearing potential/contraception
Tafluprost must not be used in women of childbearing age/potential unless adequate contraceptive
measures are in place (see section 5.3).

Pregnancy
There are no adequate data from the use of tafluprost in pregnant women.
Tafluprost can have harmful pharmacologic effects on pregnancy and/or the fetus/newborn child.
Studies in animals have shown reproductive toxicity (see section 5.3). Therefore, Tafluprost should
not be used during pregnancy unless clearly necessary (in case no other treatment options are
available).
Breastfeeding
It is unknown whether tafluprost and/or its metabolites are excreted in human milk. A study in rats
has shown excretion of tafluprost and/or its metabolites in breast milk after topical administration
(see section 5.3).
Therefore tafluprost should not be used during breastfeeding.
Fertility
In female and male rats, mating performance and fertility was unaffected by intravenous tafluprost
doses up to 100 microg/kg/day.

Tafluprost has minor influence on the ability to drive and use machines. If transient blurred vision
occurs at instillation, the patient should wait until the vision clears before driving or using machinery.

In clinical studies, over 1,400 patients have been treated with preserved tafluprost either as
monotherapy or as adjunctive therapy to timolol 0.5%. The most frequently reported treatmentrelated
adverse event was ocular hyperaemia. It occurred in approximately 13% of the patients
participating in the clinical studies with preserved tafluprost in Europe and the US. It was mild in
most cases and led to discontinuation on an average in 0.4% of patients participating in the pivotal
studies. In a 3-month, phase III study in the US comparing the non-preserved formulation of
tafluprost with the non-preserved timolol formulation, ocular hyperemia occurred in 4.1% (13/320) of
patients treated with tafluprost.
The following undesirable effects related to treatment were reported during clinical trials with
tafluprost in Europe and the US after a maximum follow-up of 24 months:
Within each frequency grouping, adverse reactions are presented in order of decreasing frequency. 

Nervous system disorders
Common (≥1/100 to <1/10): headache 

Eye disorders
Common (≥1/100 to <1/10): eye pruritus, eye irritation, eye pain, conjunctival/ocular hyperaemia,
changes in eyelashes (increased length, thickness and number of lashes), dry eye, foreign body
sensation in eyes, eyelash discolouration, erythema of eyelid, superficial punctate keratitis (SPK),
photophobia, increased lacrimation, blurred vision, reduced visual acuity and increased iris
pigmentation.
Uncommon (≥1/1,000 to <1/100): blepharal pigmentation, eyelid oedema, asthenopia, conjunctival
oedema, eye discharge, blepharitis, anterior chamber cells, ocular discomfort, anterior chamber flare,
conjunctival pigmentation, conjunctival follicles, allergic conjunctivitis and abnormal sensation in
eye.
Not known (cannot be estimated from the available data): iritis/uveitis, lid sulcus deepened, macular
oedema/cystoid macular oedema.
Cases of corneal calcification have been reported very rarely in association with the use of phosphate
containing eye drops in some patients with significantly damaged corneas.
Respiratory, thoracic, and mediastinal disorders
Not known (cannot be estimated from the available data): exacerbation of asthma, dyspnea
Skin and subcutaneous tissue disorders
Uncommon (≥1/1,000 to <1/100): hypertrichosis of eyelid
Reporting of suspected adverse reactions
• Saudi Arabia:
The National Pharmacovigilance and Drug Safety Centre (NPC)
Fax: +966-11-205-7662
Call NPC at +966-11-2038222,
Ext: 2317-2356-2340.
Toll free phone: 19999
E-mail: npc.drug@sfda.gov.sa

Website: www.sfda.gov.sa/npc
• Other GCC States:
− Please contact the relevant competent authority.

Overdose is unlikely to occur after ocular administration.
If overdose occurs, treatment should be symptomatic.

Pharmacotherapeutic group: Antiglaucoma preparations and miotics, prostaglandin analogues
ATC code: S01EE05
Mechanism of action
Tafluprost is a fluorinated analogue of prostaglandin F2α. Tafluprost acid, the biologically active
metabolite of tafluprost, is a highly potent and selective agonist of the human prostanoid FP receptor.
Tafluprost acid has a 12-fold higher affinity for the FP receptor than latanoprost. Pharmacodynamic
studies in monkeys indicate that tafluprost reduces intraocular pressure by increasing the uveoscleral
outflow of aqueous humour.
Pharmacodynamic effects
The experiments in normotensive and ocular hypertensive monkeys showed that tafluprost is an
effective IOP-lowering compound. In the study investigating IOP-reducing effect of tafluprost
metabolites only tafluprost acid reduced IOP significantly.
When rabbits were treated for 4 weeks with a tafluprost 0.0015% ophthalmic solution once daily, the
optic nerve head blood flow was significantly (15%) increased compared to baseline when measured
by the laser speckle flowgraphy on Days 14 and 28.
Clinical efficacy
Reduction of the intraocular pressure starts between 2 and 4 hours after the first administration and
maximum effect is reached at around 12 hours after instillation. The duration of effect is maintained
for at least 24 hours. Pivotal studies with a tafluprost formulation containing the preservative
benzalkonium chloride have demonstrated that tafluprost is effective as monotherapy and showedan additive effect when administered as adjunctive therapy to timolol: In a 6-month study, tafluprost
showed a significant IOP-lowering effect of 6 to 8 mmHg at different time points of the day as
compared to 7 to 9 mmHg with latanoprost. In a second 6-month clinical study, tafluprost reduced
IOP by 5 to 7 mmHg as compared to 4 to 6 mmHg with timolol. The IOP-lowering effect of
tafluprost was maintained in the extension of these studies up to 12 months. In a 6-week study, the
IOP-lowering effect of tafluprost was compared with its vehicle when used adjunctively with timolol.
Compared to baseline values (measured after a 4-week run in on timolol), the additional IOPlowering
effects were 5 to 6 mmHg in the timolol-tafluprost group and 3 to 4 mmHg in the timololvehicle
group. The preserved and the non-preserved formulations of tafluprost showed a similar IOPlowering
effect of over 5 mmHg in a small cross-over study with a 4-week treatment period.
Furthermore, in a 3-month study in the US comparing the non-preserved formulation of tafluprost
with the non-preserved formulation of timolol, the IOP-lowering effect of tafluprost was between 6.2
and 7.4 mmHg at different timepoints whereas that of timolol varied between 5.3 and 7.5 mmHg.

Absorption
After once daily administration of one drop of unpreserved tafluprost 0.0015% eye drops to both eyes
for 8 days, plasma concentrations of tafluprost acid were low and had similar profiles on days 1 and
8. The plasma concentrations peaked at 10 minutes after dosing and declined to below the lower limit
of detection (10 pg/ml) before one hour after dosing. Mean Cmax (26.2 and 26.6 pg/ml) and AUC0-
last (394.3 and 431.9 pg*min/ml) values were similar on days 1 and 8, indicating that a steady drug
concentration was reached during the first week of ocular dosing. No statistically significant
differences in the systemic bioavailability between the preserved and unpreserved formulation were
detected.
In a rabbit study, the absorption of tafluprost into the aqueous humour was comparable after a single
ocular instillation of unpreserved or preserved tafluprost 0.0015% ophthalmic solution.

Distribution
In monkeys, there was no specific distribution of radiolabelled tafluprost in the iris-ciliary body or
choroid including retinal pigment epithelium, which suggested low affinity for melanin pigment. In a
whole body autoradiography study in rats, the highest concentration of radioactivity was observed in
the cornea followed by the eyelids, sclera and the iris. Outside the eye radioactivity was distributed to
the lacrimal apparatus, palate, oesophagus and gastrointestinal tract, kidney, liver, gall bladder and
urinary bladder.
The binding of tafluprost acid to human serum albumin in vitro was 99% at 500 ng/ml tafluprost acid.

Biotransformation
The principal metabolic pathway of tafluprost in human, which was tested in vitro, is the hydrolysis
to the pharmacologically active metabolite, tafluprost acid, which is further metabolized by
glucuronidation or beta-oxidation. Products of beta-oxidation, 1,2-dinor and 1,2,3,4-tetranor
tafluprost acids, which are pharmacologically inactive, may be glucuronidated or hydroxylated.
Cytochrome P450 (CYP) enzyme system is not involved in the metabolism of tafluprost acid. Based
on the study in rabbit corneal tissue and with purified enzymes, the main esterase responsible for the
ester hydrolysis to tafluprost acid is carboxyl esterase. Butylcholine esterase but not acetylcholine
esterase may also contribute to the hydrolysis.
Elimination
Following once daily administration of 3H-tafluprost (0.005% ophthalmic solution; 5 microl/eye) for
21 days to both eyes in rats, approximately 87% of the total radioactive dose was recovered in the
excreta. Percent of the total dose excreted in urine was approximately 27-38% and approximately 44-
58% of the dose was excreted in the feces.
 

Non-clinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, systemic repeated dose toxicity, genotoxicity and carcinogenic potential. As with
other PGF2 agonists, repeated dose topical ocular administration of tafluprost to monkeys produced
irreversible effects on iris pigmentation and reversible enlargement of the palpebral fissure.
Increased contraction of rat and rabbit uteri in vitro was observed at tafluprost acid concentrations
that exceeded 4 to 40 times, respectively, the maximum plasma concentrations of tafluprost acid in
humans. Uterotonic activity of tafluprost has not been tested in human uterus preparations.
Reproduction toxicity studies were performed in the rat and rabbit with intravenous administration. In
rats, no adverse effects on fertility or early embryonic development were observed at systemic
exposure over 12,000 times the maximum clinical exposure based on Cmax or greater than 2,200
times based on AUC.
In conventional embryo-foetal development studies, tafluprost caused reductions in foetal body
weights and increases in post-implantation losses. Tafluprost increased the incidence of skeletal
abnormalities in rats as well as the incidence of skull, brain and spine malformations in rabbits. In the
rabbit study, plasma levels of tafluprost and its metabolites were below the level of quantification.
In a pre- and postnatal development study in rats, increased mortality of newborns, decreased body
weights and delayed pinna unfolding were observed in offspring at tafluprost doses greater than 20
times the clinical dose.
The experiments in rats with radiolabelled tafluprost showed that around 0.1% of the topically
applied dose on eyes was transferred into milk. As the half-life of active metabolite (tafluprost acid)
in plasma is very short (not detectable after 30 minutes in humans), most of the radioactivity probably represented metabolites with little, or no pharmacologic activity. Based on metabolism of the drug
and natural prostaglandins, the oral bioavailability is expected to be very low.

Glycerol
Edetate Disodium(EDTA)
Sodium dihydrogen phosphate dihydrate
Polysorbate 80
Hydrochloric acid and/or sodium hydroxide (for pH adjustment)
Water for injections

Not applicable

Store in a refrigerator (2°C -8°C).
For storage conditions after first opening of the foil pouch, see section 6.3.
After opening the foil pouch:
• Keep the single-dose containers in the original foil pouch
• Do not store above 25°C
• Discard an opened single-dose container with any remaining solution immediately after use.

Low-density polyethylene (LDPE) single-dose containers packed in foil pouch. Each single-dose
container has a fill volume of 0.3 ml
The following pack size is available: 30 x 0.3 ml single-dose containers.

Any unused medicinal product or waste material should be disposed of in accordance with local
requirements.