Consumer medicine information

Zaditen Eye Drops 1.0%

Ketotifen

BRAND INFORMATION

Brand name

Zaditen

Active ingredient

Ketotifen

Schedule

S2

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Zaditen Eye Drops 1.0%.

What is in this leaflet

Please read this leaflet carefully before you use Zaditen Eye Drops.

This leaflet answers some common questions about Zaditen Eye Drops. It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist.

The information in this leaflet was last updated on the date listed on the final page. More recent information on the medicine may be available.

You should ensure that you speak to your pharmacist or doctor to obtain the most up to date information on the medicine.

You can also download the most up to date leaflet from www.novartis.com.au.

The updates may contain important information about the medicine and its use of which you should be aware.

All medicines have risks and benefits. Your doctor has weighed the expected benefits of you using Zaditen Eye Drops against the risks this medicine could have for you.

The information in this leaflet applies to Zaditen only. This information does not apply to similar products, even if they contain the same ingredients.

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 ZADITEN is used for

Zaditen contains the active ingredient, ketotifen, which is an anti-inflammatory medicine. It works by blocking the allergic response and reducing inflammation.

This medicine is used for short term treatment of the symptoms of seasonal allergic conjunctivitis (itchy, watery or swollen eyes and/or eyelids).

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

This medicine is not addictive.

It is available from your pharmacy.

Use in children

Zaditen is not recommended for use in children under 3 years.

The safety and effectiveness of Zaditen in this age group has not been established.

Before you use ZADITEN

Do not use Zaditen Eye Drops if you have an allergy to:

  • Ketotifen
  • Other ingredients in Zaditen that are listed at the end of this leaflet under "Product description".

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

Do not use this medicine if the expiry date has passed, the packaging is torn or the seal around the closure of the multi-dose or single dose units and neck area is broken. If it has expired or is damaged, return it to your pharmacist for disposal.

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 Zaditen talk to your doctor or pharmacist.

Before you start to use it

Tell your doctor or pharmacist if:

  • You have an allergy to any other medicines or any other substances, such as foods, preservatives or dyes
  • You are pregnant, or intend to become pregnant
    Your doctor will discuss the possible risks and benefits of using Zaditen during pregnancy.
  • You are breastfeeding or intend to breastfeed
    Your doctor will discuss the possible risks and benefits of using Zaditen when you are breast-feeding.

If you have not told your doctor about any of the above, tell him/ her before you use Zaditen Eye Drops.

Do not put Zaditen Eye Drops into your eye(s) while you are wearing contact lenses. The preservative in Zaditen Eye Drops bottle, benzalkonium chloride, may be deposited in contact lenses that may cause irritation to your eyes.

You can put your contact lenses back into your eyes 15 minutes after you have used Zaditen Eye Drops.

Taking or using other medicines

Tell your doctor 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.

Some medicines and Zaditen Eye Drops may interfere with each other.

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

How to use ZADITEN

Carefully follow all directions given to you by your doctor and pharmacist. They 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.

How much to use

The usual dose of Zaditen Eye Drops is one drop in the affected eye(s) twice a day. This will normally be in the morning and at night.

After using Zaditen Eye Drops wait at least 5 minutes before putting any other eye drops in your eye(s).

If you wear soft contact lenses, remove them before using this medicine. Wait for 15 minutes after using Zaditen before reinserting the contact lenses. The preservative in Zaditen Eye Drops bottle can affect the contact lenses.

If you are unsure about when, or how, to stop using Zaditen Eye Drops you should talk to your doctor.

How to use

Follow these steps to use the single dose units:

  1. Wash your hands thoroughly with soap and water.
  2. Open the blister pack of the single dose units.
  3. Remove the strip of single dose units and tear off one strip. Hold the single dose unit by the tab with the nozzle pointing downwards and tap gently until all the air bubbles are above the solution.
  4. Twist the tab off the single dose unit.
  5. Make sure the tip of the single dose unit does not touch anything as this may contaminate the solution.
  6. Hold the single dose unit in one hand between the thumb and forefinger.
  7. With your head tilted back, use the forefinger of the other hand to pull down the lower lid of the eye to be treated.
  8. Place the single dose unit tip close to your eye but without touching your eye or eyelid, and squeeze unit gently so that one drop falls into the pouch between your lower lid and your eye, and then release your lower lid.
Only one drop is needed.
  1. Close your eyes and gently press the inner corner of your eye with your forefinger for one minute.
  2. Treat your other eye in the same way if it is also affected.
  3. Discard each single dose unit immediately after use. Keep the remaining single dose units at room temperature (below 25°C), preferably in the carton (See "After using Zaditen – Storage").

Follow these steps to use the multi-dose bottle:

  1. Wash your hands thoroughly with soap and water.
  2. Open the multi-dose bottle.
  3. Make sure the tip of the bottle does not touch anything as this may contaminate the solution.
  4. Hold the bottle in one hand between the thumb and forefinger.
  5. With your head tilted back, use the forefinger of the other hand to pull down the lower lid of the eye to be treated.
  6. Place the dropper close to your eye but without touching your eye or eyelid, and squeeze the bottle gently so that one drop falls into the pouch between your lower lid and your eye, and then release your lower lid.
Only one drop is needed.
  1. Close your eyes and gently press the inner corner of your eye with your forefinger for one minute.
  2. Treat your other eye in the same way if it is also affected.
  3. Close the bottle and keep it at room temperature (below 25°C). Discard the multi-dose bottle and remaining solution four (4) weeks after opening.

When to use it

Use Zaditen Eye Drops at about the same time every day unless your doctor or pharmacist tells you otherwise.

Using your eye drops at the same time each day will have the best effect in treating your allergic conjunctivitis. It will also help you remember when to use the eye drops.

How long to use it

You can stop using this medicine when the itching in your eye(s) has gone.

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 the drops as soon as you remember, and then go back to using your medicine as you would normally.

Do not use double the amount to make up for the dose that you missed. Using multiple doses may cause unwanted side effects.

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

If you use too much (overdose)

It is unlikely that you will experience symptoms or side effects if you accidently swallow Zaditen. Similarly, do not be concerned if more than one drop is accidently dropped into your eye.

If you have any doubts, speak to your doctor or pharmacist for advice or contact the Poisons Information Centre on 13 11 26.

While you are using Zaditen

Things you must do

Tell your pharmacist or doctor immediately if you become pregnant while using Zaditen.

If you are about to be started on any new medicine, remind your pharmacist or doctor that you are using Zaditen.

Tell any other doctors, dentists or pharmacists who treat you that you are using this medicine.

Things you must not do

Do not use Zaditen to treat any other complaints unless your pharmacist or doctor tells you to.

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

Things to be careful of

Be careful driving or operating machinery until you know how Zaditen affects you.

This medicine may cause blurred vision or tiredness in some people.

If you have either of these symptoms, do not drive, operate machinery or do anything else that could be dangerous. Children should be careful when riding bicycles or climbing trees.

Side effects

Tell your doctor as soon as possible if you do not feel well while you are using Zaditen.

This medicine helps most people with allergic conjunctivitis but may have unwanted side effects in some people.

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 pharmacist or doctor to answer any questions you may have.

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

  • burning, stinging or blurring of vision immediately after using the drops
  • eye irritation or a feeling of having something in your eye
  • swollen eyelid or other eyelid changes
  • unusual sensitivity of the eye to light
  • headache or tiredness
  • dry mouth.

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

Tell your pharmacist or doctor as soon as possible if you notice any of the following:

  • tiny breaks in the skin covering the eye
  • runny or sticky discharge from the eye with itching of the eye and crusty eyelids
  • pain in the eye
  • bleeding under the surface of the eye
  • skin rash
  • wheezing or difficulty breathing.

The above list includes serious side effects which may require medical condition.

Tell your doctor or pharmacist if you notice anything that is making you unwell.

Other side effects not listed above may also occur in some people.

After using Zaditen

Storage

Keep your eye drops in a cool place where the temperature stays below 25°C. Do not freeze the eye drops.

Do not store Zaditen Eye Drops or any other medicine in the car, bathroom, the window sill or in other warm, damp places. Heat and dampness can destroy some medicines.

Keep it out of the sight or reach of children. A locked cupboard at least one and a half metres above the ground is a good place to store medicines.

Multi-dose Bottle:

  • Keep the bottle sealed until it is time to use the eye drops.
  • After opening, write the date on the bottle.
  • Use the eye drops for four (4) weeks.
    These 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 you need to continue treatment get a new bottle of drops, even if there is some left in the old bottle.
  • Put the top back on the bottle right away after use to avoid contaminating the eye drops. Do not leave the top off the bottle for any length of time as the drops may not keep well.

Single Dose Units:

  • Keep the inner blisters sealed until it is time to use the eye drops.
    If you open the inner blisters, the eye drops may not keep well.
  • After opening the single dose unit, use the drops once and immediately discard any unused solution.
    These eye drops contain no preservative.
  • Keep the remaining single dose units at room temperature (below 25°C), preferably in the carton.

Disposal

If your doctor tells you to stop using the eye drops or they have passed their expiry date, ask your pharmacist what to do with any remaining solution.

Product description

What it looks like

Zaditen is a sterile solution containing ketotifen that is available in a multi-dose eye drop bottle in packs of 2.5 mL and 5 mL.

It is also available as single dose units in packs of 5 (1 x 5) and 20 (4 x 5).

Ingredients

Zaditen contains the active ingredient ketotifen 250 µg in 1mL.

Zaditen also contains:

  • Benzalkonium chloride (as a preservative) in the multi-dose bottles only
  • Glycerol
  • Sodium hydroxide
  • Water for Injections

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

Supplier

Zaditen is supplied in Australia by:

Novartis Pharmaceuticals Australia Pty Limited
ABN 18 004 244 160
54 Waterloo Road
Macquarie Park NSW 2113
Telephone: 1-800-671-203.
Web site: www.novartis.com.au

Date of preparation

This leaflet was prepared in February 2021.

Australian registration numbers

Multi-dose bottles: 99979.

Single dose units: 113770.

® Registered Trademark

© Novartis Pharmaceuticals Australia Pty Limited 2021.

Internal document code:
(zad280121c) based on PI (zad280121i)

Published by MIMS March 2021

BRAND INFORMATION

Brand name

Zaditen

Active ingredient

Ketotifen

Schedule

S2

 

1 Name of Medicine

Ketotifen as ketotifen fumarate.

2 Qualitative and Quantitative Composition

Zaditen is a sterile ophthalmic solution containing ketotifen for topical administration to the eye. Each 1.0 mL contains 345 microgram ketotifen fumarate corresponding to 250 microgram ketotifen.

Excipients with known effect.

Benzalkonium chloride (multidose bottle only).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Eye Drops - clear, colourless to faintly yellow, sterile ophthalmic solution for administration to the eye.

4 Clinical Particulars

4.1 Therapeutic Indications

Symptomatic short-term treatment of seasonal allergic conjunctivitis in adults and children 3 years or older.

4.2 Dose and Method of Administration

Adults, elderly and children (age 3 and older).

One drop of Zaditen into the conjunctival sac twice daily.

Instructions for use and handling.

Multidose bottle.

The contents and dispenser remain sterile until the original closure is broken. To avoid contamination, do not touch any surface with the dropper tip. The tip of the container should also not come into contact with the eye as this may cause injury to the eye. The multidose formulation of Zaditen eye drops contains benzalkonium chloride as a preservative, which may be deposited in soft contact lenses and may possibly discolor soft contact lenses (see Section 4.4 Special Warnings and Precautions for Use).
After opening, Zaditen should not be used for more than 4 weeks and any remaining contents should be discarded.
After cap is removed, if tamper evident snap collar is loose, remove before using the product.

Single dose units.

The contents remain sterile until the original closure is broken. To avoid contamination do not touch any surface with the tip of the container. The tip of the container should also not come into contact with the eye as this may cause injury to the eye. After opening, single dose units must be used immediately. Contains no antimicrobial agent. Use once only and discard any residue. After opening a blister, any unused single dose containers should be discarded after 4 weeks unless they have been stored in the outer carton, in which case they should be discarded after 3 months.

4.3 Contraindications

Hypersensitivity to ketotifen or to any of the excipients.

4.4 Special Warnings and Precautions for Use

For ocular use only.
The multidose formulation of Zaditen eye drops includes benzalkonium chloride as a preservative which may cause eye irritation. Since benzalkonium chloride may be deposited in soft contact lenses and since it has not been shown that soft contact lenses do not absorb ketotifen, Zaditen eye drops should not be instilled while the patient is wearing these lenses. The lenses should be removed before application of the drops and not reinserted earlier than 15 minutes after use.
All eye drops preserved with benzalkonium chloride may possibly discolour soft contact lenses.

Use in the elderly.

No data available.

Paediatric use (use in children under 3 years of age).

Safety and effectiveness in pediatric patients below 3 years of age have not been established.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

If Zaditen is used concomitantly with other eye medications, there must be an interval of at least 5 minutes between the two medications.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

In a fertility study in which male rats were treated with oral doses of ≥ 2 mg/kg/day, there was a trend for a decrease in fertility. Ketotifen had no effect on fertility of female rats at oral doses up to 50 mg/kg/day. These doses would have resulted in systemic ketotifen levels several orders of magnitude higher than the MRHOD.
There is no data available on the effect of ketotifen hydrogen fumarate on fertility in humans.
(Category B1)
Oral treatment of pregnant rats and rabbits during organogenesis with doses up to 100 and 45 mg/kg/day, respectively, did not result in any embryofoetal lethal effects or malformations. Animal studies using maternally toxic oral doses showed increased pre- and postnatal mortality, but no teratogenicity. In the offspring of rats that received ketotifen orally from day 15 of pregnancy to day 21 postpartum at the maternally toxic dose of 50 mg/kg/day, postnatal mortality was increased, and bodyweight gain during the first four days postpartum was slightly decreased. These doses would have resulted in systemic ketotifen levels several orders of magnitude higher than the MRHOD.
There are no adequate data from the use of ketotifen eye drops in pregnant women. Caution should be exercised when prescribing to pregnant women. When prescribing to pregnant woman, the benefits to the mother should be weighed against the risk to the fetus.
 Ketotifen has been identified in the milk of lactating rats following oral administration. It is not known whether topical ocular administration could result in sufficient systemic absorption to produce detectable quantities in human breast milk. Zaditen should be used with caution in breastfeeding women.

4.7 Effects on Ability to Drive and Use Machines

Any patient who experiences blurred vision or somnolence (see Section 4.8 Adverse Effects (Undesirable Effects) should not drive or operate machines.

4.8 Adverse Effects (Undesirable Effects)

Tabulated summary of adverse drug reactions from clinical trials [21,49].
Adverse drug reactions from clinical trials (Table 1) are listed by MedDRA system organ class. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse drug reaction is based on the following convention (CIOMS III): 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).

Adverse drug reactions from postmarketing experience (frequency not known).

The following adverse drug reactions have been derived from postmarketing experience with Zaditen eye drops. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency which is therefore categorized as not known.

Ocular adverse drug reactions.

Post marketing cases have been reported of localized allergic/ hypersensitivity reaction, including mostly contact dermatitis, eye swelling, and eyelid pruritus and oedema.

Systemic adverse drug reactions.

In addition, post marketing systemic hypersensitivity reactions have been reported including but not limited to facial swelling/ oedema (in some cases associated with contact dermatitis) and exacerbation of pre-existing allergic conditions such as asthma and eczema. Dizziness has also been reported.

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

No case of overdose has been reported.
Oral ingestion of the contents of a 5 mL bottle would be equivalent to 1.25 mg of ketotifen and oral ingestion of the contents of a single dose unit would be equivalent to 0.1 mg of ketotifen. Clinical results have shown no serious signs or symptoms after oral ingestion of up to 20 mg of ketotifen.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Ketotifen has a nonspecific anti-inflammatory action and is a mast cell stabiliser. Ketotifen also decreases chemotaxis, activation and degranulation of eosinophils. Increased cAMP levels by phosphodiesterase inhibition may contribute to the cell stabilising effect of ketotifen.

Clinical trials.

The efficacy of Zaditen was evaluated in 6 conjunctival allergen challenge studies in a total of 634 sensitised subjects (573 receiving Zaditen, including 133 paediatric subjects aged 8-16 years) and 2 four week environmental studies in a total of 1023 patients with seasonal allergic conjunctivitis (346 receiving Zaditen).
In conjunctival allergen challenge studies, Zaditen was significantly more effective than placebo in preventing ocular itching associated with allergic conjunctivitis. The action of ketotifen occurred rapidly with an effect seen within minutes after administration. The duration of action of a single dose was found to be 8 to 12 hours. In children the efficacy of Zaditen was superior to placebo and similar to that in adults.
The 2 environmental studies were identical in design, both double masked, parallel group, comparative studies. Results are summarised in Table 2.
In view of the high placebo response observed in study 2, an exploratory subgroup analysis was performed which included only those patients recruited during the peak pollen season. At day 5 to 8 the responder rates based on the patient assessment of global efficacy were 52.3% (ketotifen), 38.5% (vehicle) and 52.7% (levocabastine). Both levocabastine and ketotifen were significantly superior to vehicle (p = 0.048 and 0.045, respectively). This exploratory subgroup analysis cannot be used to support efficacy but might be useful in the design of another study.
The safety of Zaditen was evaluated in a total of 12 studies including 947 patients with an ocular pollen allergy who participated in efficacy studies and an additional 442 healthy volunteers (including 42 paediatric subjects aged 3-11 and 133 aged 8-16 years) who were enrolled in pharmacokinetic, local tolerance, safety and special studies. There were no significant findings noted on visual acuity, pupil size and reactivity or slit lamp examination. Dilated ophthalmoscopy and measurements of intraocular pressure revealed no abnormalities.

5.2 Pharmacokinetic Properties

Absorption.

In a pharmacokinetic study conducted in 18 healthy volunteers with Zaditen eye drops, plasma levels of ketotifen after ocular administration for 14 days were in most cases below the limit of quantitation (20 picogram/mL).

Biotransformation and elimination.

After oral administration, ketotifen is eliminated biphasically, with an initial half-life of 3 to 5 hours and a terminal half-life of 21 hours. About 1% of the substance is excreted unchanged in the urine within 48 hours and 60 to 70% as metabolites. The main metabolite is the practically inactive ketotifen-N-glucuronide.

5.3 Preclinical Safety Data

Genotoxicity.

See Section 4.6 Fertility, Pregnancy and Lactation.

Carcinogenicity.

Long-term studies in mice and rats revealed no evidence for carcinogenicity of ketotifen at dietary doses up to 93 and 71 mg/kg/day, respectively. These doses would have resulted in systemic ketotifen levels several orders of magnitude higher than those after administration of the maximum recommended human ocular dose (MRHOD). Ketotifen was not genotoxic in a battery of in vitro and in vivo assays including the Ames test, chromosomal aberration test with V79 Chinese hamster cells, micronucleus test in mice and mouse dominant lethal test.

6 Pharmaceutical Particulars

6.1 List of Excipients

Multidose bottle.

Benzalkonium chloride 0.1 mg/mL as preservative, glycerol, sodium hydroxide and water for injections.

Single dose units.

Glycerol, sodium hydroxide 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 below 25°C. (See Section 4.2 Dose and Method of Administration, Instructions for use and handling.)

6.5 Nature and Contents of Container

Multidose bottle.

2.5 mL and 5 mL.

Single dose units.

Blocks of 5 x 0.4 mL single dose units each packed in a blister and supplied in cartons containing 20 x 0.4 mL.

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

Ketotifen fumarate is a white to brownish yellow, fine crystalline powder. It is sparingly soluble in water, slightly soluble in methanol and very slightly soluble in acetonitrile.

Chemical structure.


Chemical name: 4-(1-methylpiperidin- 4-ylidene)-4,9-dihydro- 10H-benzo[4,5]cyclohepta [1,2-b]thiophen-10-one hydrogen- (E)-butenedioate.
Molecular formula: C19H19NOS.C4H4O4.
Molecular weight: 425.5.

CAS number.

34580-14-8.

7 Medicine Schedule (Poisons Standard)

Schedule 2 (Pharmacy Medicine).

Summary Table of Changes