Consumer medicine information

Latanoprost Sandoz

Latanoprost

BRAND INFORMATION

Brand name

Latanoprost Sandoz

Active ingredient

Latanoprost

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Latanoprost Sandoz.

WHAT IS IN THIS LEAFLET

This leaflet answers some common questions about Latanoprost Sandoz.

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 has weighed the risks of you taking this medicine 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 LATANOPROST SANDOZ IS USED FOR

This medicine is used to treat 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.

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. 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.

How Latanoprost Sandoz works

It contains the active ingredient latanoprost. Latanoprost belongs to a group of medicines called prostaglandin agonists.

It works by lowering the pressure in the eye by allowing more fluid to flow out from within your eye.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

This medicine is not addictive.

This medicine is available only with a doctor's prescription.

Use in Children

Latanoprost Sandoz is not recommended for use in children. Safety and effectiveness in children has not been established.

BEFORE YOU USE LATANOPROST SANDOZ

When you must not use it

Do not use this medicine if you have an allergy to:

  • latanoprost, the active ingredient, or to any of the other ingredients listed at the end of this leaflet under Product Description
  • any other similar medicines.

Some of the symptoms of an allergic reaction may include:

  • asthma, wheezing or shortness of breath
  • swelling of the face, lips, tongue which may cause difficulty in swallowing or breathing
  • rash, itching or hives on the skin
  • fainting.

Do not use this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you are pregnant or intend to become pregnant: Your doctor can discuss the possible risks and benefits of using Latanoprost Sandoz during pregnancy.

Tell your doctor if you are breastfeeding or intend to breast-fed: Your doctor can discuss the possible risks and benefits of using Latanoprost Sandoz when breastfeeding.

Tell your doctor if you have or have had any medical conditions such as severe asthma, or any other types of glaucoma or eye conditions.

If you have not told your doctor about any of the above, tell him/her before you start using Latanoprost Sandoz.

Taking other medicines

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

Some medicines and Latanoprost Sandoz may interfere with each other. These include:

  • eye drops which contain an ingredient called thiomersal. If using such eye drops as well as Latanoprost Sandoz, you should wait at least 5 minutes between using these eye drops and Latanoprost Sandoz.
  • some other eye drops that contain a prostaglandin. The use of two or more prostaglandin eye drops at the same time is not recommended.

These medicines may be affected by Latanoprost Sandoz or may affect how well it works. You may need different amounts of your medicines, or you may need to use different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while using this medicine.

HOW TO USE LATANOPROST SANDOZ

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

If you do not understand the instructions, 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 much to use

The usual dose of Latanoprost Sandoz is one drop into the affected eye, or eyes, once daily.

Use Latanoprost every day, at about the same time each day, preferably in the evening, unless your doctor tells you otherwise.

Ask your doctor or pharmacist if you are unsure of the correct dose for you. They will tell you exactly how much to take.

Follow the instructions they give you. If you take the wrong dose, Latanoprost Sandoz may not work as well and your problem may not improve.

How to use it

If you are wearing soft contact lenses, remove them before putting the drops in your eye. The preservative in Latanoprost Sandoz (benzalkonium chloride) may be deposited in soft contact lenses. You can put your soft contact lenses back into your eyes 15 minutes after you have used Latanoprost Sandoz.

Be careful not to touch the dropper tip against your eye, eyelid or anything else. Touching the dropper tip against something may contaminate the eye drops and give you an eye infection. You may find it easier to put drops in your eye while you are sitting or lying down.

Instructions for use

The DROP-TAINER® bottle is designed to assure the delivery of a precise dose of medication. Before using your DROP-TAINER® bottle, read the complete instructions carefully.

  1. If you use other topically applied ophthalmic medications, they should be administered at least 10 minutes before or after Latanoprost Sandoz
  2. Wash your hands well with soap and water.
  3. Before using the medication for the first time. Be sure the safety Seal on the bottle is unbroken.
  4. Tear off the Safety Seal to break the seal.
  5. Before each use, shake once and remove the screw cap.
  6. Invert the bottle and hold the bottle between your thumb and middle finger, with the tips of the fingers pointing towards you.

  1. Tilt your head back and position the bottle above the affected eye.
  2. With the opposite hand, place a finger under the eye. Gently pull down until a “V” pocket is made between your eye and lower lid. Do not touch the eye with the tip of the dropper.
  3. With the hand holding the bottle, place your index finger on the bottom of the bottle. Push the bottom of the bottle to dispense one drop of medication. Do not squeeze the sides of the bottle. Keep your head tilted backward and close your eye to allow absorption of the medication into the eye.
  4. Repeat steps 6 to 9 with other eye if instructed to do so.
  5. Replace screw cap by turning until firmly touching the bottle.

You may feel a slight burning sensation in the eye shortly after using the eye drops.

If this persists, or is very uncomfortable, contact your doctor or pharmacist

When to take Latanoprost Sandoz

Use your medicine at about the same time each day preferably in the evening, unless your doctor tells you otherwise. Using your eye drops at the same time each day will have the best effect on your eye pressure. It will also help you remember when to use the eye drops.

How long to use Latanoprost Sandoz

Continue using your medicine for as long as your doctor tells you.

This medicine helps to control your condition, but does not cure it. It is important to keep taking your medicine even if you feel well.

If you forget to use it

Take your dose as soon as you remember, and continue to take it as you would normally.

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

Do not use double the amount to make up for the dose that you missed. This may increase the chance of you getting an unwanted side effect.

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

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you use too much (overdose)

If you accidentally put several drops in your eye, immediately rinse your eye in warm water.

Immediately telephone your doctor or the Poisons Information Centre (telephone Australia 13 11 26 or New Zealand 0800 POISON or 0800 764766) for advice, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much Latanoprost Sandoz. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

WHILE YOU ARE USING LATANOPROST SANDOZ

Things you must do

To make sure Latanoprost Sandoz is working properly, have your eye pressure checked regularly.

Have your eyes checked regularly for any other changes, including a change in eye colour. A slow change in eye colour, which may be permanent, has been reported to occur in some patients who use Latanoprost Sandoz. Your doctor will decide whether you should continue using Latanoprost Sandoz.

If you develop an eye infection, receive an eye injury, or have eye surgery tell your doctor. Your doctor may tell you to use a new container of Latanoprost Sandoz because of possible contamination of the old one, or may advise you to stop your treatment with Latanoprost

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are using Latanoprost Sandoz.

Tell any other doctors, dentists, and pharmacists who treat you that you are taking this medicine.

If you become pregnant while taking this medicine, tell your doctor immediately.

Things you must not do

Do not use Latanoprost Sandoz to treat any other complaints unless your doctor tells you to.

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

Do not stop using your medicine without checking with your doctor. 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 Latanoprost Sandoz affects you. Latanoprost Sandoz generally does not cause any problems with your ability to drive a car or operate machinery. However, it may cause blurred vision in some people. Make sure you know how you react to Latanoprost Sandoz or that your vision is clear before driving a car or operating machinery.

SIDE EFFECTS

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Latanoprost Sandoz.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

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:

  • a slow change in eye colour over a period of time. The iris may become more brown in colour and appear darker. This change may be permanent and more noticeable if you are only being treated in one eye
  • blurred vision, double vision or other visual problems
  • irritation or feeling of having something in the eye. This may be worse during the first two or three days of using Latanoprost Sandoz.
  • eye pain
  • dry eye
  • redness, burning or watering of the eye/s
  • discharge, itching of the eye/s, crusty eyelashes
  • darkening, thickening, lengthening or an increase in the number of eye lashes and the fine hair on the eyelids.
  • misdirected eyelashes sometimes causing eye irritation
  • darkening of the skin of the eyelids
  • crusting, redness, thickening, itching or burning of the eyelids
  • sensitivity to light
  • skin rash
  • headache
  • muscle/joint pain
  • painful, urgent or frequent urination.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • wheezing, difficulty in breathing (asthma or worsening of asthma)
  • shortness of breath
  • chest pain
  • you notice strong, rapid or irregular heartbeats
  • dizziness
  • swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing
  • white deposits or plaque in the cornea causing the transparent front part of your eye to look white or cloudy.

The above list includes serious side effects that may require urgent medical attention. Serious side effects are rare.

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

AFTER USING LATANOPROST SANDOZ

Storage

Keep your medicine in the original container.

Before opening Latanoprost Sandoz, keep your medicine in its box in a refrigerator (2°C - 8°C) protected from light.

After opening Latanoprost Sandoz, keep your medicine in its box in a cool place where the temperature stays below 25°C, but do not refrigerate. Keep the box properly closed and protected from light.

Do not store Latanoprost Sandoz or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car.

Heat and dampness can destroy some medicines.

Put the top back on the bottle right away after use to avoid contaminating the eye drops.

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

Write the date on the bottle when you open the eye drops and throw out any remaining solution after four weeks.

Open a new bottle every 4 weeks. Eye drops contain a preservative, which helps prevent germs growing in the solution for the first four weeks after opening the bottle. After this time there is a greater risk that the drops may become contaminated and cause an eye infection.

If your doctor tells you to stop using this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

PRODUCT DESCRIPTION

What it looks like

Your Latanoprost Sandoz eye drops come in a plastic bottle with a dropper and screw cap inside a protective overcap. Remove the overcap before use.

When you first receive your Latanoprost Sandoz bottle, it will appear half full. This corresponds to 2.5mL of clear colourless eye drop solution, giving a minimum of 80 drops. This volume is enough to last 4 weeks if used in both eyes.

Ingredients

Active ingredients:

  • Latanoprost Sandoz 50 micrograms/mL - 50 micrograms latanoprost

Each drop contains about 1.5 micrograms of latanoprost.

Inactive ingredients:

  • sodium chloride
  • monobasic sodium phosphate monohydrate
  • dibasic sodium phosphate
  • water for injections
  • benzalkonium chloride (as a preservative).

This medicine does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Supplier

Sandoz Pty Ltd
ABN 60 075 449 553
54 Waterloo Road
Macquarie Park, NSW 2113
Tel: 1800 726 369

This leaflet was revised in April 2020.

Australian Register Number(s)

50 microgram/mL Eye Drops: AUST R 290733

Published by MIMS June 2020

BRAND INFORMATION

Brand name

Latanoprost Sandoz

Active ingredient

Latanoprost

Schedule

S4

 

1 Name of Medicine

Latanoprost.

6.7 Physicochemical Properties

The active ingredient latanoprost is a prostaglandin F analogue. Latanoprost is a viscous oil which is practically insoluble in water, freely soluble in ethanol, ethyl acetate, isopropanol, methanol, acetone and octanol, and very soluble in acetonitrile.
Sixty four isomers of latanoprost are possible, however, for Latanoprost Sandoz it is purified as a single isomer.

Chemical structure.


Chemical name: Isopropyl-(Z)-7[(1R,2R,3R,5S) 3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenyl-1-pentyl]cyclopentyl]-5-heptenoate.
Molecular formula: C26H40O5.
Molecular weight: 432.593.

CAS number.

130209-82-4.

2 Qualitative and Quantitative Composition

Latanoprost Sandoz Eye Drops is a sterile, isotonic solution containing 50 micrograms/mL of latanoprost in an aqueous solution of pH 6.7.
Each 5 mL polyethylene bottle contains 2.5 mL clear colourless eye drop solution corresponding to a minimum of 80 drops of solution. One drop contains approximately 1.5 micrograms latanoprost.

Excipients with known effect.

Benzalkonium chloride.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Eye drops, solution.
The solution is a clear and colourless liquid, filled in a polyethylene container.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Latanoprost, a selective prostaglandin F analogue, is a selective prostanoid FP receptor agonist which reduces the intraocular pressure by increasing the outflow of aqueous humour. Reduction of the intraocular pressure in man starts about three to four hours after administration and maximum effect is reached after 8 to 12 hours. Pressure reduction is maintained for at least 24 hours. Studies in animals and man indicate that the main mechanism of action is increased uveoscleral outflow, although some increase in outflow facility (decrease in outflow resistance) has been reported in man.
Clinical trials have shown that latanoprost has no significant effect on the production of aqueous humour. Latanoprost has not been found to have any effect on the blood-aqueous barrier.
Latanoprost has no or negligible effects on the intraocular blood circulation when used at the human clinical dose, as studied in monkeys. However, mild to moderate conjunctival or episcleral hyperaemia may occur during topical treatment.
Chronic treatment with latanoprost in monkey eyes which had undergone extracapsular lens extraction did not affect the retinal blood vessels as determined by fluorescein angiography.
Latanoprost has not induced fluorescein leakage in the posterior segment of pseudophakic human eyes during short-term treatment.
Latanoprost in clinical doses has not been found to have any significant pharmacological effects on the cardiovascular or respiratory systems.

Clinical trials.

Efficacy.

In three pivotal, randomised, double blind, parallel group trials latanoprost 50 microgram/mL once a day was compared with timolol 5 mg/mL twice a day. Across the three trials, 460 patients received latanoprost and 369 received timolol. At 6 months latanoprost reduced intraocular pressure (IOP) by 27-34% from the untreated baseline of 24.4-25.2 mmHg and timolol reduced IOP by 20-33% from a baseline of 24.1-25.4 mmHg. In one of these three studies, the difference between the reduction in IOP by latanoprost versus timolol was statistically significant (p < 0.001). A meta-analysis of the three trials demonstrated that of the intention-to-treat population, 61% of latanoprost treated patients, compared with 40% of timolol treated patients, reached a 30% reduction in diurnal IOP after 6 months. No tolerance to the effect of latanoprost was seen after 12 months in these trials.
The pivotal studies have demonstrated that latanoprost is effective as monotherapy. In addition, latanoprost is effective as adjunctive therapy in reduction of IOP. Short-term (1 or 2 week) studies suggest the effect of latanoprost is additive in combination with adrenergic agonists (dipivefrine hydrochloride), carbonic anhydrase inhibitors (acetazolamide) and at least partly additive with cholinergic agonists (pilocarpine). Although intended primarily as a safety study, IOP reduction was effectively maintained over 48 months in a clinical trial of 356 patients receiving latanoprost as adjunctive therapy to various medications including β-adrenergic antagonists, adrenergic agonists, cholinergic agonists and carbonic anhydrase inhibitors. Out of 519 patients at study start, only 7 patients were withdrawn from the study due to uncontrolled IOP.
Clinical trials involving a fixed combination of latanoprost 50 microgram/mL and timolol 5 mg/mL given once daily have also been conducted. The mean diurnal IOP-lowering effect of the combination was greater than that produced by monotherapy with either latanoprost 50 microgram/mL once daily or timolol 5 mg/mL twice a day.
Clinical studies to demonstrate non-inferiority to the Australian innovator product have not been conducted. Comparisons with the innovator's product were made on the basis of physiochemical tests. No clinical studies have been conducted using Latanoprost Sandoz Eye drops.

Safety.

Long-term safety of latanoprost has been investigated in an open label, multicentre, safety study. This trial enrolled 519 patients, 356 of whom continued for 48 months. Iris pigmentation changes have been observed in patients of the pivotal clinical trials of latanoprost (also see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)). The long-term safety study has shown that this change is not associated with any increased risk of clinically significant ocular or systemic effects, nor is it considered to have any long-term consequences.
In those patients experiencing colour change, the time to onset of increased iris pigmentation usually occurred within 8 months of starting treatment. Within 24 months, onset had occurred in almost all of these cases. Onset after 36 months of treatment was very rare. Using iris photography, the increase in iris pigmentation was graded as "weak" in 75 out of 124 patients (60.5%) during the first year of onset. A weak grading was maintained in 42 of these patients (33.9%) over 48 months of treatment. In those patients showing iris pigmentation progression, there was no apparent increase in iris pigmentation during the fourth year of treatment, indicating a plateau in pigmentation had been reached. A separate safety study has also shown that reintroduction of latanoprost to patients with increased iris pigmentation will not necessarily lead to a further increase in iris pigmentation severity.
IOP reduction between patients who developed iris pigmentation, and those who did not, was shown to be comparable over 48 months. Table 2 shows the mean IOP and change from baseline in patients experiencing increased iris pigmentation (IIP) and those not experiencing increased iris pigmentation (NIIP).

5.2 Pharmacokinetic Properties

Latanoprost is an isopropyl ester prodrug which is inactive, but after hydrolysis to the acid of latanoprost, becomes biologically active.

Absorption.

The prodrug is well absorbed through the cornea and all drug that enters the aqueous humour is hydrolysed during the passage through the cornea.

Distribution.

Studies in man indicate that the peak concentration in the aqueous humour is reached about two hours after topical administration. After topical application in monkeys, latanoprost is distributed primarily in the anterior segment, the conjunctivae and the eyelids. Only minute quantities of the drug reach the posterior segment.
Following an ocular dose of latanoprost, 45% of latanoprost acid is absorbed systemically, with 90% being bound to plasma proteins.

Metabolism.

There is practically no metabolism of the acid of latanoprost in the eye. The main metabolism occurs in the liver. Following intravenous administration in man, the half-life in plasma is 17 minutes.

Excretion.

The main metabolites, the 1,2-dinor and 1,2,3,4-tetranor metabolites, exert no or only weak biological activity in animal studies and are excreted primarily in the urine.

5.3 Preclinical Safety Data

Genotoxicity.

Latanoprost was not mutagenic in gene mutation assays in bacteria and mouse lymphoma L5178Y cells and was negative in studies of unscheduled DNA synthesis. Chromosome aberrations were observed with human lymphocytes in vitro but latanoprost did not induce micronucleus formation in vivo.

Carcinogenicity.

Latanoprost was not carcinogenic in either rats or mice when administered by oral gavage at doses up to 170 microgram/kg/day for 24 and 20 months respectively.

Animal toxicity.

The ocular, as well as systemic toxicity of latanoprost has been investigated in several animal species. Intravenous acute toxicity studies (2 mg/kg) and oral acute toxicity studies (50 mg/kg) in rats and mice resulted in no mortality. Latanoprost, 2-6 micrograms/kg body weight, administered intravenously to unanaesthetised monkeys have been shown to increase the respiration rate probably reflecting bronchoconstriction of short duration.
In animal studies latanoprost has not been found to have sensitising properties.
In the eye no significant toxic effects have been detected with doses of up to 100 micrograms/eye/day in rabbits or monkeys (clinical dose is approximately 1.5 micrograms/eye/day). In monkeys, however, latanoprost has been shown to induce increased pigmentation of the iris. The mechanism of increased pigmentation seems to be stimulation of melanin production in melanocytes of the iris with no proliferative changes observed. The change in iris colour may be permanent.
In chronic ocular toxicity studies, administration of latanoprost at 6 micrograms/eye/day has also been shown to induce increased palpebral fissure. This effect is reversible and occurs at doses above the clinical dose level. The effect has not been seen in humans.

4 Clinical Particulars

4.1 Therapeutic Indications

Reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension.

4.3 Contraindications

Known hypersensitivity to latanoprost or to any component in Latanoprost Sandoz.

4.4 Special Warnings and Precautions for Use

Iris pigmentation changes.

Latanoprost may gradually change eye colour by increasing the amount of brown pigment in the iris. Before treatment is instituted, patients should be informed of the possibility of a permanent change in eye colour. Unilateral treatment can result in heterochromia.
This change in eye colour has predominantly been seen in patients with mixed colour irides, i.e. blue-brown, grey-brown, green-brown or yellow-brown. The highest incidence was found in patients with green-brown and yellow-brown irides. In patients with homogeneously blue eyes, no change has been observed and in patients with homogenously grey, green or brown eyes, the change has only rarely been seen. The onset of the change is usually within the first eight months of treatment, but may occur later in a small number of patients (see Section 5.1 Pharmacodynamic Properties, Clinical trials).
The colour change is due to increased melanin content in the stromal melanocytes of the iris and not to an increase in the number of melanocytes. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery in affected eyes, but the entire iris or parts of it may become more brownish. Patients who develop increased iris pigmentation should be examined regularly and, depending on the clinical situation, treatment may be stopped. No further increase in brown iris pigment has been observed after discontinuation of treatment, but the resultant colour change may be permanent. It has not been associated with any symptom or pathological changes in clinical trials of up to 48 months duration.
Naevi or freckles of the iris have not been affected by treatment. Accumulation of pigment in the trabecular meshwork or elsewhere in the anterior chamber has not been observed in long-term clinical trials.

Eyelid and eyelash changes.

Eyelid skin darkening, which may be reversible, has been reported in association with the use of latanoprost.
Latanoprost may gradually change eyelashes and vellus hair in the treated eye and surrounding areas; these changes include increased length, thickness, pigmentation and number of lashes or hairs, and misdirected growth of eyelashes. Eyelash changes are reversible upon discontinuation of treatment.

Use with caution in the following circumstances.

Macular oedema.

Macular oedema, including cystoid macular oedema, has been reported uncommonly during treatment with latanoprost. These reports have mainly occurred in patients with aphakia or pseudophakia with anterior chamber lenses and/or torn posterior lens capsule, or in patients with known risk factors for macular oedema (such as diabetic retinopathy and retinal vein occlusion). Caution is recommended when using latanoprost in these patients. Upon discontinuation of latanoprost treatment, visual acuity has improved, in some cases with concurrent treatment with topical steroidal and non-steroidal anti-inflammatory drugs.

Glaucoma.

There is no experience with latanoprost in inflammatory and neovascular glaucoma, inflammatory ocular conditions or congenital glaucoma. There is limited experience with latanoprost in chronic angle closure glaucoma (one 12 week study), open angle glaucoma of pseudophakic patients (4 out of 519 patients enrolled in the long-term safety study were pseudophakic patients) and in pigmentary glaucoma (one 12 month study). Latanoprost has no or little effect on the pupil, but there is no experience in acute attacks of closed angle glaucoma. Latanoprost should be used with caution in these conditions until more experience is obtained.

Cataract surgery.

There are limited study data on the use of latanoprost during the peri-operative period of cataract surgery. Latanoprost should be used with caution in these patients.

Iritis/uveitis.

In patients with known predisposing risk factors for iritis/uveitis, latanoprost can be used with caution.

Use with contact lenses.

Latanoprost Sandoz contains benzalkonium chloride which may be absorbed by contact lenses. Benzalkonium chloride has been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy, may cause eye irritation and is known to discolour soft contact lenses. Close monitoring is required with frequent or prolonged use of latanoprost in dry-eye patients, or in conditions where the cornea is compromised. The contact lenses should be removed before instillation of the eye drops and may be reinserted after 15 minutes.

Asthma.

There is no experience in patients with severe or brittle asthma. There is limited experience from patients with asthma, but some cases of exacerbation of asthma and/or dyspnea were reported in post-marketing experience. Asthmatic patients should therefore be treated with caution until there is sufficient experience (see Section 4.8 Adverse Effects (Undesirable Effects)).

Herpetic keratitis.

Use with caution in patients with a history of herpetic keratitis, it should be avoided in cases of active herpes simplex keratitis and in patients with a history of recurrent herpetic keratitis specifically associated with prostaglandin analogues.

Periorbital skin discolouration.

Periorbital skin discolouration has been observed, the majority of reports being in Japanese patients. Experience to date shows that periorbital skin discolouration is not permanent and in some cases has reversed on continued treatment with latanoprost.

Use in the elderly.

No data available. See Section 4.2 Dose and Method of Administration.

Paediatric use.

Latanoprost is not recommended for use in children. Use in children has not been studied.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Interactions with other medications than those described (see Section 5.1 Pharmacodynamic Properties, Clinical trials) have not been investigated.
There have been reports of paradoxical elevations in IOP following the concomitant ophthalmic administration of two prostaglandin analogues. Therefore, the use of two or more prostaglandins, prostaglandin analogues, or prostaglandin derivatives is not recommended.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Latanoprost had no effect on male or female fertility studies in rats when administered intravenously with 250 microgram/kg.
(Category B3)
The safety of latanoprost for use in human pregnancy has not been established. Reproductive studies have been performed in rats and rabbits and no malformations or structural variations were observed in the fetuses at any doses of latanoprost. In rabbits given latanoprost IV at 5 microgram/kg/day, a slight increase of litter resorption occurred and at doses of 50 or 300 microgram/kg/day, total litter resorption (100%) in all animals was recorded. A dose of 1 microgram/kg/day was well tolerated in rabbits.
In pregnant rats dosed with tritium labelled latanoprost intravenously, the radioactivity was detected in all maternal tissues, placenta and fetus. It has potential hazardous pharmacological effects with respect to the course of pregnancy and to the unborn or the neonate.
Therefore, latanoprost should not be used during pregnancy.
There are limited experimental animal and no human data available on the pharmacokinetics of latanoprost in lactation. The active substance, latanoprost and its metabolites may pass into breast milk and latanoprost should therefore not be used by nursing women, or breast-feeding should be stopped.
The benefits of treatment with latanoprost should clearly outweigh the possible risks for use in nursing mothers.

4.8 Adverse Effects (Undesirable Effects)

Short-term treatment.

Adverse events occurring at a frequency of > 1% in 6 month comparative trials are presented in Table 1.
(See Section 4.4 Special Warnings and Precautions for Use.)

Chronic treatment (> 6 months).

The majority of adverse effects relate to the ocular system.
Adverse effects are categorised by frequency as follows.
Very common (≥ 1/10); Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1000 to < 1/100); Rare (≥ 1/10,000 to < 1/1000); Very rare (< 1/10,000); Not known (cannot be estimated from the available data).

Very common.

Eye disorders.

Increased iris pigmentation; mild to moderate conjunctival hyperaemia; eye irritation (burning, grittiness, itching, stinging and foreign body sensation); eyelash and vellus hair changes (darkening, thickening, lengthening, increased number) (vast majority of reports in Japanese population).

Common.

Eye disorders.

Transient punctate epithelial erosions, mostly without symptoms; blepharitis; eye pain; conjunctivitis; vision blurred; eyelid oedema.

Musculoskeletal and connective tissue disorders.

Muscle/joint pain.

Nervous system disorders.

Dizziness; headache.

Skin and subcutaneous tissue disorders.

Localised skin reaction on the eyelids; skin rash.

Uncommon.

Eye disorders.

Iritis/uveitis (the majority of reports in patients with concomitant predisposing factors); dry eye; keratitis; macular oedema including cystoid macular oedema.

General disorders and administration site conditions.

Non-specific chest pain.

Respiratory, thoracic and mediastinal disorders.

Asthma; dyspnoea.

Rare.

Eye disorders.

Symptomatic corneal oedema and erosions; periorbital oedema; darkening of the palpebral skin; misdirected eyelashes sometimes resulting in eye irritation; extra row of cilia at the aperture of the meibomian glands (distichiasis); photophobia.

Respiratory, thoracic and mediastinal disorders.

Asthma aggravation; acute asthma attacks.

Very rare.

Eye disorders.

Periorbital and lid changes resulting in deepening of the eyelid sulcus.

Cardiac disorders.

Aggravation of angina in patients with pre-existing disease.

Not known.

Eye disorders.

Iris cyst.

Cardiac disorders.

Palpitations.

Infections and infestations.

Herpetic keratitis.

Additional information for selected adverse reactions.

Iris pigmentation changes.

Latanoprost may cause an increase in brown pigmentation of the iris, predominantly in patients with mixed coloured irides, (i.e. blue-brown, grey-brown, green-brown, yellow-brown). This is due to increased melanin content in the stromal melanocytes of the iris (see Section 4.4 Special Warnings and Precautions for Use).

Macular oedema.

Macular oedema has been reported uncommonly during latanoprost treatment. These reports have mainly occurred in aphakic patients, in pseudophakic patients with torn posterior lens capsule or anterior chamber lens, or in patients with known risk factors for cystoid macular oedema (such as diabetic retinopathy and retinal vein occlusion). An association between the use of latanoprost and unexplained macular oedema cannot be excluded (see Section 4.4 Special Warnings and Precautions for Use).

Iritis/uveitis.

Cases of iritis/uveitis have been uncommonly reported. The majority of patients in these cases had concomitant predisposing factors for developing iritis/uveitis.

Asthma/dyspnoea.

Cases of asthma and dyspnoea have been uncommonly reported. Rare cases of asthma aggravation and acute asthma attacks have also been reported. There is limited experience from patients with asthma, but latanoprost has not been found to affect the pulmonary function when studied in a small number of steroid and non-steroid treated patients suffering from moderate asthma. There is no experience in patients with severe or brittle asthma and such patients should therefore be treated with caution until there is sufficient experience.

Post-marketing experience.

Eye disorders.

Pseudopemphigoid of ocular conjunctiva, iris cyst.

Cardiac disorders.

Angina, palpitations, angina unstable.

Skin and subcutaneous tissue disorders.

Pruritus.

Adverse reaction for eye drops containing phosphate buffers.

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.

4.2 Dose and Method of Administration

Dosage.

Recommended dosage for adults (including the elderly).

Recommended therapy is one eye drop in the affected eye(s) once daily. Optimal effect is obtained if Latanoprost Sandoz is administered in the evening. Systemic absorption can be minimised by pressure on the tear duct immediately after application of the eye drop.
If one dose is missed, treatment should continue with the next dose as normal.
The dosage of Latanoprost Sandoz should not exceed once daily since it has been shown that more frequent administration decreases the intraocular pressure lowering effect.

Method of administration.

Latanoprost Sandoz is effective as a single drug therapy but can also be used in combination with beta-adrenergic antagonists (timolol), adrenergic agonists (dipivefrine hydrochloride), cholinergic agonists (pilocarpine) and carbonic anhydrase inhibitors (acetazolamide) to achieve an additive effect. In case of combined therapy the eye drop products should be administered with an interval of at least five minutes.

Use with contact lenses.

The contact lenses should be removed before instillation of the eye drops and may be reinserted after 15 minutes (see Section 4.4 Special Warnings and Precautions for Use).

4.7 Effects on Ability to Drive and Use Machines

In common with other eye preparations, instillation of eye drops may cause transient blurring of vision. Until this has resolved, patients should not drive or use machines.
Adverse effects of this medicine also include dizziness which could affect the ability to drive or use machines (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.9 Overdose

Symptoms.

Apart from ocular irritation and conjunctival or episceral hyperaemia, the ocular effects of latanoprost administered at high doses are not known.

Treatment.

If overdosage with Latanoprost Sandoz occurs, treatment should be symptomatic and supportive.
If Latanoprost Sandoz is accidentally ingested the following information may be useful: one bottle contains 125 micrograms latanoprost. More than 90% is metabolised during the first pass through the liver. Intravenous infusion of 3 micrograms/kg in healthy volunteers induced no symptoms, but a dose of 5.5-10 micrograms/kg caused nausea, abdominal pain, dizziness, fatigue, hot flushes and sweating.
Intravenous administration of latanoprost in monkeys has been associated with transient bronchoconstriction. However, in patients with bronchial asthma, bronchoconstriction was not induced by latanoprost when applied topically on the eyes in a dose of seven times the clinical dose of latanoprost.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

7 Medicine Schedule (Poisons Standard)

Schedule 4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium chloride, monobasic sodium phosphate monohydrate, dibasic sodium phosphate, water for injections and benzalkonium chloride (0.20 mg/mL) as a preservative agent.

6.2 Incompatibilities

In vitro studies have shown that precipitation occurs when eye drops containing thiomersal are mixed with latanoprost. If such drugs are used, the eye drops should be administered with an interval of at least five minutes.
For information about interactions with medicines and other forms of interactions, see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

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 at 2°C-8°C. Refrigerate. Do not freeze.
Store opened bottle below 25°C. Replace the cover firmly after use. Store in the outer cardboard carton. To be used within 4 weeks after opening.
Protect from light.

6.5 Nature and Contents of Container

Latanoprost Sandoz eye drops are supplied in LDPE bottles; pack size: 1 bottle.

6.6 Special Precautions for Disposal

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

Summary Table of Changes