Consumer medicine information

Saflutan

Tafluprost

BRAND INFORMATION

Brand name

Saflutan

Active ingredient

Tafluprost

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Saflutan.

What is in this leaflet

This leaflet answers some common questions about SAFLUTAN.

It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor or pharmacist has weighed the risks of you using SAFLUTAN against the benefits they expect it will have for you.

If you have any concerns about using this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What SAFLUTAN is used for

SAFLUTAN belongs to a group of medicines called prostaglandin analogues. It is used to lower raised pressure in the eye and to treat glaucoma. Glaucoma is a condition in which the pressure of fluid in the eye may be high. However, some people with glaucoma may have normal eye pressure. Also, some people with raised eye pressure may not have glaucoma.

Glaucoma is usually caused by a build-up of the fluid which flows through the eye. This build up occurs because the fluid drains out of your eye more slowly than it is being pumped in. Since new fluid continues to enter the eye, joining the fluid already there, the pressure continues to rise. This raised pressure may damage the back of the eye resulting in gradual loss of sight. Damage can progress so slowly that the person is not aware of this gradual loss of sight. Sometimes even normal eye pressure is associated with damage to the back of the eye. There are usually no symptoms of glaucoma. The only way of knowing that you have glaucoma is to have your eye pressure, optic nerve and visual field checked by an eye specialist or optometrist. If glaucoma is not treated it can lead to serious problems, including total blindness. In fact, untreated glaucoma is one of the most common causes of blindness.

Although SAFLUTAN helps control your glaucoma it does not cure it so you must keep using SAFLUTAN until your doctor tells you to stop.

For more information about glaucoma, contact Glaucoma Australia Inc., PO Box 420, Crows Nest 1585, telephone 1800 500 880.

SAFLUTAN lowers pressure in the eye by allowing more fluid to flow out from within your eye.

SAFLUTAN is used, either alone or in combination with other eye drops or medicines, to lower raised pressure within your eye(s).

SAFLUTAN is not addictive.

Before you use SAFLUTAN

When you must not use it

Do not use SAFLUTAN if:

  • You have an allergy to tafluprost or any of the ingredients listed at the end of this leaflet.
  • The packaging shows signs of tampering
  • The expiry date (EXP) printed on the pack has passed.
    If you use this medicine after the expiry date has passed, it may not work.

If you are not sure whether you should start using/taking SAFLUTAN, talk to your doctor.

The safety and effectiveness of SAFLUTAN in children have not been established. SAFLUTAN is not recommended for use in children.

Before you start to use it

Tell your doctor or pharmacist if you have allergies to:

  • any other medicines
  • any other substances, such as foods, preservatives or dyes

Tell your doctor or pharmacist if you are pregnant or intend to become pregnant. If you are a woman of childbearing age, you should use an effective method of birth control when using SAFLUTAN.

If you become pregnant, talk to your doctor immediately to determine if you should use SAFLUTAN.

Tell your doctor or pharmacist if you are breast-feeding or plan to breast-feed. Your doctor or pharmacist will discuss the possible risks and benefits of using SAFLUTAN during breastfeeding.

Tell your doctor or pharmacist if you have or have had any medical conditions, especially the following:

  • other eye diseases
  • kidney disease
  • liver disease
  • lung disease, including asthma, chronic obstructive lung disease or other breathing problems.

If you have not told your doctor or pharmacist about any of the above, tell them before you start using SAFLUTAN.

You may experience the following side effects, some of which may be permanent. These effects may occur slowly and it may be several months before you notice them. SAFLUTAN may:

  • increase the length, thickness, colour and/or number of your eyelashes and may cause unusual hair growth around your eyelids
  • cause darkening of the colour of the skin around the eyes. Wipe off any excess solution from the skin. This will reduce the risk of skin darkening.
  • Change the colour of your iris (the coloured part of your eye). If SAFLUTAN is used in one eye only, the colour of the treated eye may permanently become different from the colour of the other eye.

Taking other medicines

Tell your doctor or pharmacist if you are taking or using any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

If you use other medicines in the eye, leave at least 5 minutes between using SAFLUTAN and the other medication.

How to use SAFLUTAN

Use SAFLUTAN only when prescribed by your doctor.

Follow all directions given to you by your doctor carefully.

How much to use

The dose is one drop of SAFLUTAN in the eye or eyes, once daily in the evening. Only use SAFLUTAN in both eyes if your doctor has told you to do so.

Do not instil more drops or use more often than as instructed by your doctor. This may make SAFLUTAN less effective.

Do not stop using SAFLUTAN without asking your doctor. If you stop using SAFLUTAN, the pressure in the eye will increase again. This may result in permanent damage to the eye.

If you use other medicines in the eye, leave at least 5 minutes between putting in SAFLUTAN and the other medication.

Follow all directions given to you by your doctor and pharmacist carefully. These directions may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

If you are being changed from one eye drop to another, follow your doctor's instructions carefully as to when to stop the old drops and when to start the new drops.

How to use it

You may find it easier to put eye drops in your eye while you are sitting or lying down.

If you are wearing soft contact lenses, remove them before putting the drops in your eye.

When starting a new pouch:

Do not use the single-dose containers if the pouch is broken. Open the pouch along the dotted line. Write the date of opening on the space reserved for this on the pouch.

When using SAFLUTAN:

  1. Wash your hands well with soap and water.
  2. Take the strip of containers from the pouch.
  3. Detach one single dose container from the strip.
  4. Put the remaining strip back in the pouch and fold down the edge to close the pouch.
  5. Make sure that the solution is in the bottom part of the single-dose container.
  6. To open the container, twist off the tab.
  7. Tilt your head backwards. If you are unable to tilt your head, lie down.
  8. Place the tip of the container close to your eye. Be careful not to touch the tip of the container to the eye itself.
  9. Pull the lower eye lid downwards and look up.
  10. Gently squeeze the container and let one drop fall into the space between the lower eyelid and the eye.
  11. Close your eye for a moment and press the inner corner of the eye with your finger for about one minute. This helps prevent the eye drop from draining down the tear duct. Do not blink or rub your eye.
  12. Blot off any excess solution from the skin around the eye with a tissue.

If a drop misses your eye, try again.

If your doctor has told you to use drops in both eyes, repeat steps 7 to 12 for your other eye.

The contents of one single-dose container of SAFLUTAN are sufficient for both eyes. After dosing, discard the single-dose container even if there is solution remaining. Wash your hands with soap and water to remove any residue.

If you are not sure how to use eye drops, ask your doctor or pharmacist.

If you are not sure what to do, ask your doctor or pharmacist.

How long to use it

SAFLUTAN helps control your condition, but does not cure it. Therefore you must use SAFLUTAN every day.

Do not stop using it unless your doctor or pharmacist tells you to stop.

If you forget to use it

If it is almost time for your next dose, skip the dose you missed and use your next dose when you are meant to.

Otherwise, use it as soon as you remember, and then go back to using your medicine as you would normally at the usual time.

Do not use a double dose to make up for the dose that you missed.

If you have trouble remembering to use your eye drops, ask your pharmacist for some hints.

If you use too much (overdose)

If you accidentally put several drops in your eye(s), immediately rinse your eye(s) with warm water.

If you think that you or anyone else may have swallowed any or all of the contents of a single-dose container of SAFLUTAN immediately telephone your doctor or pharmacist or the Poisons Information Centre (telephone 13 11 26), or go to accident and emergency at your nearest hospital.

Do this even if there are no signs of discomfort or poisoning.

While you are using SAFLUTAN

Things you must do

Have your eye pressure checked when your eye specialist says, to make sure SAFLUTAN is working.

If you develop an eye infection, receive an eye injury, or have eye surgery, tell your doctor. Your doctor may advise you to stop your treatment with SAFLUTAN.

If you become pregnant while using SAFLUTAN, tell your doctor immediately.

After opening a single-dose container of SAFLUTAN, immediately use it in one or both eyes and then discard the single-dose container, even if there is some solution remaining.

SAFLUTAN does not contain any preservatives. Therefore, if you keep the remaining solution for your next dose, there is a risk that it may be contaminated with germs and cause an eye infection.

Tell any other doctors, dentists, and pharmacists who are treating you that you are using SAFLUTAN.

If you are about to be started on any new medicine, tell your doctor, dentist or pharmacist that you are using SAFLUTAN.

Things you must not do

Do not give SAFLUTAN to anyone else, even if they have the same condition as you.

Do not give SAFLUTAN to a child under 18 years. The safety and effectiveness of SAFLUTAN in children have not been established. SAFLUTAN is not recommended for use in children.

Do not stop using SAFLUTAN without first talking to your doctor or pharmacist. If you stop using your eye drops, your eye pressures may rise again and damage to your eye may occur.

Things to be careful of

Be careful driving or operating machinery until you know how SAFLUTAN affects you. SAFLUTAN generally does not cause any problems with your ability to drive a car or operate machinery. However, SAFLUTAN may cause blurred vision in some people. Make sure you know how you react to SAFLUTAN or that your vision is clear before driving a car or operating machinery.

Side effects

Check with your doctor as soon as possible if you have any problems while using SAFLUTAN, even if you do not think the problems are connected with the medicine or are not listed in this leaflet. SAFLUTAN helps most people with glaucoma, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • redness, itching, or irritation of the eye(s)
  • eye pain
  • feeling that something is in the eye(s)
  • dry eye
  • watery eye(s) or eye discharge
  • Redness or puffy eyelid(s)
  • blurred vision or sharpness of your vision reduced
  • sensitivity to light
  • headache
  • cataract

Patients also experience the following side effects:

  • Change of colour of the iris (may be permanent)
  • Changes in the length, thickness, or number of eyelashes, discolouration of eyelashes
  • Change in the colour of the skin around the eye
  • Deepening of the eye-lid crease (eyes appear sunken)
  • Worsening of asthma
  • Shortness of breath

These are the more common side effects seen in studies of SAFLUTAN. Mostly these are mild and short-lived.

Other side effects not listed above may occur in some patients. Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After using SAFLUTAN

Storage

Keep your unopened single-dose containers in the foil pouch and store them at (2°C - 8°C). Refrigerate. Do not freeze. Do not open the pouch until you are about to start using the eye drops.

Do not store the eye drops out of the foil pouches.

After opening the foil pouch:

  • Keep the remaining single-dose containers in the original foil pouch.
  • Store below 25°C.
  • Discard unused single-dose containers after 28 days from date of first opening the foil pouch.
  • Discard any opened single-dose containers with any remaining solution immediately after use.

Do not store SAFLUTAN or any other medicine in the bathroom or near a sink.

Do not leave it in the car on hot days or on window sills.

Do not carry the eye drops in pockets of your clothes. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

Do not use this medicine after the expiry date stated on the single-dose container, pouch and the outer carton.

If your doctor or pharmacist tells you to stop using SAFLUTAN, or it has passed its expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

SAFLUTAN is a clear, colourless liquid (solution) supplied in single-dose plastic containers, each containing 0.3mL of solution. Ten (10) single-dose containers are provided in one foil pouch.

Ingredients

Active ingredient:

The active ingredient in SAFLUTAN is tafluprost. Each single-dose container (0.3 mL) contains 4.5 micrograms of tafluprost.

Inactive ingredients:

  • glycerol
  • monobasic sodium phosphate dihydrate
  • disodium edetate
  • polysorbate 80
  • hydrochloric acid and/or sodium hydroxide (to adjust pH)
  • Water for injections

Supplier

SAFLUTAN is supplied in Australia by:

Mundipharma Pty Limited
ABN 87 081 322 509
10 Carrington Street
Sydney NSW 2000 AUSTRALIA
Phone: 1800 188 009

Australian Register Number:
AUST R 168803

This leaflet was prepared in May 2022

SAFLUTAN-CMI-v1 (CCDSv2)

Published by MIMS July 2022

BRAND INFORMATION

Brand name

Saflutan

Active ingredient

Tafluprost

Schedule

S4

 

1 Name of Medicine

Tafluprost.

2 Qualitative and Quantitative Composition

Saflutan is available as an ophthalmic solution (eye drops) containing 15 micrograms of tafluprost per mL. One single-dose container (0.3 mL) contains 4.5 micrograms of tafluprost. Saflutan does not contain preservatives such as benzalkonium chloride.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Eye drops.
Clear and colourless solution.

4 Clinical Particulars

4.1 Therapeutic Indications

Saflutan is indicated for the reduction of elevated intraocular pressure in open angle glaucoma or ocular hypertension, as monotherapy or as adjunctive therapy to beta-blockers.

4.2 Dose and Method of Administration

The recommended dose is one drop of Saflutan 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.
Saflutan is a sterile solution that does not contain a preservative. For single use only, one container is sufficient to treat both eyes. Any unused solution should be discarded immediately after use.
If more than one topical ophthalmic product is being used, each one should be administered at least 5 minutes apart.
To reduce the risk of darkening of the eyelid skin, patients should blot 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 products administered via the ocular route.

Use in elderly patients.

No dosage adjustment is required for elderly patients.

4.3 Contraindications

Hypersensitivity to tafluprost or to any of the excipients.

4.4 Special Warnings and Precautions for Use

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. blue-brown, grey-brown, yellow-brown and green-brown. Unilateral treatment can result in permanent heterochromia.
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.
Macular oedema, including cystoid macular oedema, has been reported during treatment with prostaglandin F2α analogues. These reports have mainly occurred in aphakic patients, pseudophakic patients with a torn posterior lens capsule or anterior chamber lenses, or in patients with known risk factors for macular oedema. Therefore, caution is recommended when using tafluprost in these patients. Caution is also recommended in patients with known risk factors for iritis/ uveitis.
Tafluprost has not been studied in patients with compromised lung function and should therefore be used with caution in these patients. Cases of dyspnoea and the worsening of asthma have been observed in post-marketing experience.

Use in hepatic impairment.

Tafluprost has not been studied in patients with hepatic insufficiency and should therefore be used with caution in such patients.

Use in renal impairment.

Tafluprost has not been studied in patients with renal insufficiency and should therefore be used with caution in such patients.

Pulmonary insufficiency.

Tafluprost has not been systematically studied in patients with pulmonary insufficiency and should therefore be used with caution in such patients.

Use in the elderly.

No differences in efficacy or adverse events profile have been observed between elderly (> 65 years) and nonelderly (≤ 65 years) patients. Therefore, no dosage adjustment is required for elderly patients.

Paediatric use.

Safety and effectiveness of Saflutan in paediatric patients have not been established. Therefore, treatment with Saflutan is not recommended.

Effects on laboratory tests.

Saflutan was not associated with clinically meaningful electrolyte disturbances. Clinical laboratory investigations were performed in pivotal phase-III clinical trials. No clear-cut trends of shifts in the clinical laboratory variables, or obvious pathological values linked to the treatment could be observed during 6 months of treatment.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No interactions are anticipated in humans, since systemic concentrations of tafluprost are extremely low following ocular dosing. Therefore, specific drug interaction studies have not been performed with tafluprost.
In clinical studies tafluprost was used concomitantly with timolol without evidence of an increase in incidence of adverse events.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

In male and female rats, no adverse effects on mating performance, fertility or early embryonic development were observed with intravenous dosing of tafluprost at up to 100 microgram/kg/day, yielding systemic exposure to tafluprost acid over 14000 times the maximum clinical exposure based on Cmax or greater than 3600 times based on AUC.
(Category B3)
There are no adequate and well controlled studies with Saflutan in pregnant women.
In embryofetal development studies, tafluprost administered intravenously caused increases in postimplantation losses in rats and rabbits and reductions in fetal bodyweights in rats. Tafluprost also increased the incidence of spine malformations and vertebral skeletal variations in rats and the incidence of skull, brain and spine malformations in rabbits. In the rats, there were no adverse effects on embryofetal development at 3 microgram/kg/day, yielding maternal plasma levels of tafluprost acid that were 343 times the maximum clinical exposure based on Cmax. In rabbits, effects were seen at doses ≥ 0.03 microgram/kg/day, producing maternal plasma levels of tafluprost acid during the critical period of development that were 5.3 times higher than the clinical exposure based on Cmax. At the no effect dose in rabbits, maternal plasma levels of tafluprost acid were below the lower limit of quantification (20 picogram/mL) and less than the clinical Cmax.
In a pre- and postnatal development study in rats, increased mortality of newborns were observed with tafluprost at ≥ 1 microgram/kg/day by intravenous administration (yielding 114 times the clinical Cmax) and decreased birthweights and delayed development (pinna unfolding) were observed at 10 microgram/kg/day.
Although animal reproduction studies are not always predictive of human response, Saflutan 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 radiolabeled tafluprost and/or its metabolites (0.1% of the dose) 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 Saflutan is administered to a nursing woman.

4.7 Effects on Ability to Drive and Use Machines

As with any ocular treatment, if transient blurred vision occurs at instillation, the patient should wait until the vision clears before driving or using machinery.

4.8 Adverse Effects (Undesirable Effects)

Multiple dose strengths of tafluprost have been studied in over 1110 patients in U.S. and multinational phase II and phase III studies either as monotherapy or as adjunctive therapy to timolol 0.5%, primarily using preservative containing formulations. The clinical dose strength of tafluprost 0.0015% has been studied in 724 patients in U.S. and multinational masked phase II and phase III trials. The most common drug related adverse reaction in these patients treated with tafluprost 0.0015% was ocular hyperaemia, which was reported in 14.2% of patients. Most adverse reactions in this population were mild and led to discontinuation in 2.1% of patients participating in these studies.
The following additional drug related adverse reactions were reported during treatment up to 24 months (within each frequency grouping, adverse reactions are presented in order of decreasing frequency).

Eye disorders.

Common (≥ 1%, < 10%): eye pruritus, eye irritation, eye pain, growth of eyelashes, dry eye, eyelash discolouration, lacrimation increased, erythema of eyelid, foreign body sensation in eyes, vision blurred, photophobia, visual acuity reduced, eyelash thickening, cataracts, punctate keratitis, eye discharge, eyelid oedema and iris hyperpigmentation.
Uncommon (≥ 0.1%, < 1%): blepharal pigmentation.

Nervous system disorders.

Common (≥ 1%, < 10%): headache.

Post-marketing experience.

The following adverse reactions have been identified during post approval use of Saflutan.

Eye disorders.

Allergic conjunctivitis, deepening of the eyelid sulcus, iritis/ uveitis.

Respiratory disorders.

Exacerbation of asthma, dyspnoea.

Corneal calcification.

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.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Overdose is unlikely to occur after ocular administration. If overdose occurs, treatment should be symptomatic.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Tafluprost in clinical doses has not been found to have any significant pharmacological effects on the cardiovascular system.

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 subnanomolar affinity for the FP receptor (Ki, 0.4 nanoM), 12 times higher than that of latanoprost acid.
Reduction of the intraocular pressure in humans starts about 2 to 4 hours after administration and maximum effect is reached 12 hours after instillation. The effect is maintained for at least 24 hours.
Pharmacodynamic studies in monkeys indicate that tafluprost reduces intraocular pressure by increasing the uveoscleral outflow of aqueous humour.

Clinical trials.

Clinical effects on intraocular pressure.

The efficacy of tafluprost as monotherapy, or as adjunctive therapy to timolol, was investigated in clinical studies of up to two years duration in patients with primary open angle glaucoma or ocular hypertension.
Reduction of intraocular pressure (IOP) 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 has an additive effect when administered as adjunctive therapy to timolol.

Monotherapy versus active comparator.

The efficacy of tafluprost as monotherapy in patients with primary open angle glaucoma or ocular hypertension (baseline IOP ≥ 22 mmHg) was demonstrated in two large clinical studies of up to two years duration. The IOP lowering effect of tafluprost was demonstrated throughout the day and this effect was maintained during long-term administration.
A randomised, double masked, active controlled, parallel group, multicentre phase III study compared the efficacy and safety of tafluprost 0.0015% q.d. (N = 269) eye drops with that of latanoprost 0.005% q.d. (N = 264) eye drops in patients with open angle glaucoma or ocular hypertension. The protocol specified primary outcome measure was the difference in diurnal IOP reduction at 6 months from baseline. The primary efficacy endpoint was the change from baseline in the overall diurnal IOP at month 6 and the noninferiority was determined if the 95% CI of the treatment difference did not exceed 1.5 mmHg. The primary efficacy analysis, change from baseline to 6 months in the diurnal IOP, used a repeated measurements analysis of covariance (RM ANCOVA) model which included fixed effects for baseline, pooled centre, treatment, visit and time, and all interactions among treatment, visit and time. A sensitivity analysis without baseline IOP as a covariate (RM ANOVA) was also performed. The study was continued for up to 24 months. The IOP lowering effects over 24 months and the treatment difference based ITT (intent to treat) dataset are presented in Tables 1 and 2. ITT dataset included all randomised patients who had received at least one dose of study treatment and had at least one efficacy measurement available.
Tafluprost 0.0015% once daily showed a significant IOP lowering effect from baseline of 6 to 8 mmHg as compared to 7 to 9 mmHg with latanoprost 0.005%. At the primary endpoint following 6 months treatment, noninferiority was not demonstrated. However, at the 3 month, 18 month and 24 month (RM ANOVA; unadjusted for baseline IOP) time points and the 3 month and 18 month (RM ANCOVA; adjusted for baseline IOP) time points, noninferiority was demonstrated. The IOP lowering effect of tafluprost was sustained throughout this study up to 24 months.
A randomised, double masked, active controlled, parallel group, multicentre phase III clinical study compared the efficacy and safety of tafluprost 0.0015% with timolol 0.5% in patients with open angle glaucoma or ocular hypertension. The primary efficacy endpoint was the change from baseline in the overall diurnal IOP at month 6 and the noninferiority was determined if the 95% CI did not exceed 1.5 mmHg. At the 6 month timepoint, there was a mean change of 5 to 7 mmHg in the tafluprost 0.0015% q.d. group (N = 267) and 4 to 6 mmHg in the 0.5% timolol b.i.d. group (N = 191). Noninferiority to timolol was demonstrated. The IOP lowering effect of tafluprost was sustained in the extension of this study up to 12 months.
The treatment difference based on ITT (intent to treat) dataset are presented in Tables 3 and 4. ITT dataset included all randomised patients who had received at least one dose of study treatment and had at least one efficacy measurement available.

Adjunctive therapy to beta-blocker.

The efficacy of tafluprost as adjunctive therapy to timolol in patients with primary open angle glaucoma or ocular hypertension (baseline IOP ≥ 23 mmHg) was demonstrated in a 6 week randomised, double masked, placebo controlled, parallel group, multinational study. The diurnal IOP lowering effect of tafluprost 0.0015% q.d. (N = 96) was compared to vehicle q.d. (N = 89) when used adjunctively with timolol 0.5% administered b.i.d. Compared to baseline values (measured after a 4 week run in on timolol), the IOP lowering effects were 5 to 6 mmHg in the timolol-tafluprost group and 3 to 4 mmHg in the timolol-vehicle group.

Preservative free versus preservative containing.

In a small 4 week randomised, investigator masked, multinational crossover study, the diurnal IOP lowering effect of preservative free tafluprost 0.0015% q.d. was compared with the preservative containing formulation (N = 43). Patients were dosed for 4 weeks with the preservative free and for 4 weeks with the preservative containing formulation in crossover fashion, with an intervening washout period. Compared to baseline values, the preservative containing and the preservative free formulations of tafluprost showed a similar IOP lowering effect of approximately 5 mmHg. Both the preservative free and preservative containing formulations were generally well tolerated.

Open label preservative free crossover.

The tolerability and IOP reducing effect of preservative free tafluprost was investigated in an open label, phase IIIb study of 158 patients exhibiting ocular surface signs or symptoms during latanoprost 0.005% treatment. Preservative free tafluprost 0.0015% maintained IOP at the same level after 12 weeks treatment as latanoprost at baseline. After switching to tafluprost, the number of patients with abnormal Schirmer's test was significantly reduced, and tear break up time improved significantly. A reduction in the number of patients with abnormal conjunctival cells based on HLA-DR and MUC5AC was also detected. Patients had fewer ocular signs or symptoms while taking preservative free tafluprost than while taking latanoprost.

5.2 Pharmacokinetic Properties

Absorption.

Tafluprost is absorbed through the cornea where the isopropyl ester is hydrolysed to the biologically active acid metabolite. Pharmacokinetics of tafluprost acid were obtained from a study comparing preservative containing and preservative free ophthalmic solutions. The preservative free formulation showed similar pharmacokinetic properties to the preservative containing formulation. Mean plasma Cmax for the preservative containing and preservative free formulations were 24 picogram/mL and 26 picogram/mL respectively on day 1, and 31 picogram/mL and 27 picogram/mL respectively on day 8. Mean plasma AUC0-last for the preservative containing and preservative free formulations were 406 picogram.min/mL and 394 picogram.min/mL respectively on day 1, and 581 picogram.min/mL and 432 picogram.min/mL respectively on day 8. Mean plasma concentrations were below the limit of quantification at 30 minutes for both formulations.
In a rabbit study, the absorption of tafluprost into the aqueous humour was comparable after a single ocular instillation of preservative free or preservative containing tafluprost 0.0015% ophthalmic solution.

Distribution.

After topical administration of 1 microgram 3H-tafluprost on the monkey eye, the maximum radioactivity in the aqueous humour was detected at 2 hours (21-30 nanogram equivalents/mL) and declined to 0.3-0.4 nanogram equivalents/mL at 24 hours. Lower levels of drug related radioactivity were observed in tissues outside the eye and also declined over 24 hours.
The binding of tafluprost acid to human serum albumin was > 99%. It is anticipated that tafluprost acid will be highly protein bound in human plasma.

Metabolism.

Tafluprost, an ester prodrug, is hydrolysed to its biologically active acid metabolite in the eye. The acid metabolite is further metabolised via fatty acid β-oxidation and phase II conjugation.
Cytochrome P450 (CYP) enzyme system is not involved in the metabolism of tafluprost acid.

Excretion.

In two clinical studies, mean tafluprost acid metabolite concentrations fell below the limit of quantification in plasma (10 picogram/mL) 30 minutes after administration, indicating rapid elimination.

5.3 Preclinical Safety Data

Genotoxicity.

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.

Carcinogenicity.

Tafluprost was not carcinogenic when administered subcutaneously daily for 24 months at doses up to 30 microgram/kg/day in rats and for 18 months at doses up to 100 microgram/kg/day in mice (over 1600 and 1300 times, respectively, the maximum clinical exposure based on plasma AUC).

6 Pharmaceutical Particulars

6.1 List of Excipients

Glycerol, monobasic sodium phosphate dihydrate, disodium edetate, polysorbate 80, sodium hydroxide and/or hydrochloric acid, and water for injections.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store the unopened foil pouches at 2°C-8°C. Refrigerate. Do not freeze.

After opening the foil pouch.

Keep the single dose containers in the original foil pouch.
Store below 25°C.
Discard unused single dose containers after 28 days from date of first opening of the foil pouch.
Discard an opened single dose container with any remaining solution immediately after use.

6.5 Nature and Contents of Container

Saflutan Eye Drops are supplied in low density polyethylene (without additives) unit dose containers packed in a foil pouch. Each single dose container has a fill volume of 0.3 mL and there are 10 individual containers in each foil pouch.
The following pack sizes are available: 30 x 0.3 mL single dose containers and 10 x 0.3 mL single dose containers (Starter pack).

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

The chemical name for tafluprost is 2-Propyl (5Z)-7-[(1R, 2R, 3R, 5S)-2-[(1E)-3,3-difluoro-4-phenoxybut-1-enyl]-3,5-dihydroxycyclopentyl]hept-5-enoate. The empirical formula of tafluprost is C25H34F2O5 and its molecular weight is 452.53.
Tafluprost is a colourless to light yellow viscous liquid that is practically insoluble in water.

CAS number.

209860-87-7.

7 Medicine Schedule (Poisons Standard)

Prescription only medicine (S4).

Summary Table of Changes