Consumer medicine information

Iopidine Eye Drops 0.5%

Apraclonidine hydrochloride

BRAND INFORMATION

Brand name

Iopidine Eye Drops

Active ingredient

Apraclonidine hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Iopidine Eye Drops 0.5%.

What is in this leaflet

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

This leaflet answers some common questions about Iopidine 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 Iopidine Eye Drops against the risks this medicine could have for you.

The information in this leaflet applies to Iopidine 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 Iopidine is used for

Iopidine Eye Drops are used to lower raised pressure in the eye and to treat 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. If glaucoma is not treated, it can lead to serious problems, including total blindness. Untreated glaucoma is one of the most common causes of blindness.

Iopidine Eye Drops contain the active ingredient apraclonidine hydrochloride. Apraclonidine hydrochloride belongs to a class of medicines known as alpha-adrenergic agonists.

Iopidine Eye Drops are used, in conjunction with other medications, to lower raised pressure within your eyes. Iopidine Eye Drops do this by reducing the amount of fluid produced within your eyes.

Ask your doctor if you have questions about why this medicine has been prescribed for you.

Your doctor may have prescribed it for another reason.

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

For more information about glaucoma, contact Glaucoma Australia (telephone 1800 500 880).

There is no evidence that Iopidine is addictive.

Use in Children

Iopidine Eye Drops are not recommended in children and infants due to the risk of serious side effects.

Before you use Iopidine

When you must not use it

Do not use this medicine if you:

  • are allergic to apraclonidine hydrochloride, clonidine, or to any of the other ingredients in Iopidine Eye Drops. These are listed at the end of this leaflet under "Product description."

Some of the symptoms of an allergic reaction 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.

  • are currently taking any monoamine oxidase inhibitors (MAOI) which are used to treat depression.
  • are currently taking a tricyclic antidepressant for depression.
  • are currently taking any sympathomimetic medications which are used to treat asthma, severe headaches, or coughs and colds.

If you are unsure if you are taking any of these medicines ask your doctor or pharmacist.

Do not use this medicine if the expiry date printed on the pack has passed, the packaging is torn, the safety seal around the closure and neck area is broken or the bottle/packaging shows signs of tampering.

If this medicine has expired or is damaged, return 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 Iodipine, talk to your doctor.

Before you start to use it

Tell your doctor if:

You are pregnant, or intend to become pregnant. Iopidine is not recommended for use in pregnancy.

Your doctor will discuss the possible risks and benefits of using Iopidine during pregnancy.

You are breastfeeding or intend to breastfeed.

You should stop breastfeeding while you are using this medicine as Iopidine is not recommended whilst breastfeeding.

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

  • Heart problems. These include coronary heart disease (symptoms can include chest pain or tightness, breathlessness or choking), heart failure, a recent heart attack
  • Circulation conditions. These include Raynaud's disease, thromboangiitis obliterans (Buerger disease) where there is inflammation and clotting of the small and medium arteries and veins of the hands and feet, poor circulation of blood in the brain.
  • High blood pressure
  • Kidney problems
  • Liver problems
  • Depression
  • A type of glaucoma called angle-closure or narrow-angle glaucoma.

Taking or using other medicines

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

This is particularly important if you are currently using any type of beta-blocker medication, any medicine for the treatment of high blood pressure, any medicine for the treatment of a heart condition, any sedative-type medicine including alcohol and strong pain-killers, tricyclic antidepressants.

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

If you are unsure if you are taking these medicines speak to your doctor or pharmacist.

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

How to use Iopidine

Follow all directions given to you by your doctor carefully.

They may differ from the information contained in this leaflet.

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

How much to use

The usual dose of Iopidine Eye Drops is one drop in the affected eye(s) three times each day.

Do not put Iopidine Eye Drops into your eye(s) while you are wearing soft contact lenses.

You can insert soft contact lenses 15 minutes after you have used Iopidine Eye Drops.

Do not use Iopidine Eye Drops more often than your doctor or pharmacist has told you.

After using Iopidine Eye Drops, wait at least 5 minutes before putting any other eye drops in your eyes.

This ensures that you do not wash any of the eye drops from your eyes.

It is important to use Iopidine exactly as your doctor or pharmacist has told you. If you use the drops less often than prescribed, they may not work as well and the eye problem may not improve. Using the drops more often than prescribed may not improve the eye problem any faster and may cause increased side effects.

How to use Iopidine

Follow these steps to use Iopidine Eye Drops:

  1. Wash your hands well with soap and water.
  2. Immediately before using a bottle for the first time, break the safety seal around the neck area and throw the loose plastic ring away.
  3. Remove the cap.
  4. Hold the bottle upside down in one hand between your thumb and middle finger (see Diagram 1).
  1. Tilt you head back and look up.
  2. Using your other hand, gently pull down your lower eyelid to form a pouch/pocket.
  3. Place the dropper tip close to, but not touching, your eye. Release one drop into the pouch/pocket formed between your eye and eyelid by gently tapping or pressing the base of the bottle with your forefinger (see Diagrams 2 and 3).
  1. Close your eye. Do not blink or rub your eye.
  2. While your eye is closed, place your index finger against the inside corner of your eye and press against your nose for about two minutes.
  3. This will help to stop the medicine from draining through the tear duct to the nose and throat, from where it can be absorbed into other parts of your body.
  4. Replace the cap on the bottle, closing it tightly.
  5. Wash your hands again with soap and water to remove any residue.

You may feel a slight burning sensation in the eye shortly after using Iopidine Eye Drops.

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

Most people who use Iopidine Eye Drops will notice a whitening of the eye shortly after using the product.

Do not touch the tip of the dropper to your eye or to any other surface.

This will help to prevent your eye drops becoming dirty or contaminated.

How long to use it

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

This medicine helps control your condition, but does not cure it.

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

If you forget to use Iopidine

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise, use the drops as soon as you remember and then go back to using them as you would normally.

Never take a double dose to make up for the one that you missed.

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

Use in older adults

There are no special warnings or precautions regarding the use of Iopidine Eye Drops in older adults.

If you use too much (overdose)

If you accidentally put too many 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 bottle of Iopidine Eye Drops, immediately telephone your doctor or Poisons Information Centre on 13 11 26 for advice, 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 Iopidine

Things you must do

If you become pregnant while you are using Iopidine Eye Drops tell your doctor immediately.

If you are about to be started on any new medicines remind your doctor and pharmacist that you are using Iopidine Eye Drops.

Keep all your doctor's appointments so that your progress can be checked.

Your doctor will usually ask you to return regularly to make sure that Iopidine Eye Drops are working. It is very important that you return to see your doctor when instructed.

Things you must not do

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

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

Do not stop using Iopidine Eye Drops or lower the dose without first asking your doctor.

If you stop using your medicine your condition may worsen.

Do not let children handle Iopidine Eye Drops.

If a child accidentally swallows any of the Iopidine Eye Drops follow the instructions under the "If you use too much (overdose)" section above.

You should not drive, operate machinery or perform tasks requiring mental alertness and/or physical coordination as you may feel dizzy or tired after using Iopidine Eye Drops.

Side effects

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

This medicine helps most people with glaucoma, but it may have unwanted 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.

Most side effects from Iopidine Eye Drops occur in, or around, the eye. These include:

  • A feeling that the eye is dry or watery
  • Blurred vision and/or problems seeing clearly
  • Itchy eyes
  • Eye/eyelid redness
  • Discharge from the eye and/or crusty eyelashes
  • Discomfort, grittiness, irritation or pain in the eye(s)
  • Excessive sensitivity to bright light
  • Dilated pupils
  • Swelling to the front part of the eye
  • Difficult opening the eye
  • Eyelid swelling
  • Scales on or around the eyelid
  • Raising of the upper eyelid
  • Droopy eyelids
  • Conjunctiva (layer of skin between eyelid and eye) swelling.

It is also possible to experience an allergic-like reaction when using Iopidine Eye Drops. The allergic-like reaction may result in a redness and swelling of the eye(s), eyelid(s) and/or the areas surrounding the eye(s). The eye(s) may become watery, itchy and uncomfortable, as though something is in them.

If you think that you may be having an allergic-like reaction to Iopidine Eye Drops contact your doctor immediately.

Occasionally some people notice unwanted effects in the rest of their body as a result of using Iopidine Eye Drops. These effects may include:

  • Headache and/or feeling sick
  • Dizziness, tiredness, lack of co-ordination, fainting
  • Mood changes, such as depression, irritability or nervousness
  • Inability to sleep
  • Dry mouth
  • Sore throat and/or runny nose
  • Dry nose
  • Changes in the sensations of taste and/or smell
  • Chest pain
  • Irregular heartbeat
  • Wheezing, difficulty in breathing
  • Numbness or tingling in fingers or toes
  • Swelling of the face, hands or feet
  • Nausea and/or Constipation
  • Aching or painful muscles, not caused by exercise
  • Skin rash.

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

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

After using Iopidine

Storage

Keep Iopidine Eye Drops in a cool place where the temperature stays below 25°C. Do not freeze Iopidine Eye Drops.

Do not leave Iopidine Eye Drops or any other medicine in the bathroom, or near a sink or in other dark, warm places. Do not leave it on a window sill or in the car.

Heat and dampness can destroy some medicines.

Do not leave the top off the bottle for any length of time, to avoid contaminating the eye drops.

Keep Iopidine in a safe place 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.

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. A new bottle should then be used.

If your doctor tells you to stop using Iopidine or it has passed its expiry date, ask your pharmacist what to do with any remaining solution.

Product description

What it looks like

Iopidine is a sterile isotonic solution supplied in Drop-Tainer® bottles of 5 mL or 10 mL.

Ingredients

Iopidine contains the active ingredient apraclonidine hydrochloride 5 mg in 1 mL (0.5%).

Iopidine also contains the inactive ingredients:

  • benzalkonium chloride (as a preservative)
  • sodium acetate
  • sodium chloride
  • purified water.

Supplier

Iopidine 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
Telephone: 088 354 335
Web site: www.novartis.com.au

Date of preparation

This leaflet was prepared in August 2017.

Australian Registration Number

AUST R No. 51190

© Copyright Novartis Pharmaceuticals Australia Pty Limited 2017

® Registered Trademark

Internal document code:
(iop050717c) based on PI (iop050717i)

BRAND INFORMATION

Brand name

Iopidine Eye Drops

Active ingredient

Apraclonidine hydrochloride

Schedule

S4

 

Name of the medicine

Apraclonidine (as hydrochloride).

Excipients.

Benzalkonium chloride 0.1 mg/mL as preservative, sodium acetate, sodium chloride and purified water.

Description

Chemical name: 2[(4-amino-2,6-dichlorophenyl)imino] imidazolidine hydrochloride. Molecular formula: C9H10Cl2N4.HCl. MW: 281.6. Iopidine Eye Drops 0.5% contains apraclonidine hydrochloride, an alpha-adrenergic agonist, in a sterile isotonic solution for topical application to the eye. Apraclonidine hydrochloride is a white to off-white crystalline powder sparingly soluble in water (29.1 mg/mL). The pKa1 value is 1.16; the pKa2 value is 9.22.
Iopidine eye drops 0.5% contains 5.75 mg/mL apraclonidine hydrochloride equivalent to 5.0 mg of apraclonidine in a sterile isotonic base comprising benzalkonium chloride 0.1 mg/mL as preservative, sodium acetate, sodium chloride and purified water.

Pharmacology

Animal pharmacology.

Pharmacodynamics.

Apraclonidine is an α-adrenergic agonist with higher potency and affinity for α2 compared to α1-adrenoreceptors. It has been shown to produce a lowering of intraocular pressure (IOP) in rabbits and monkeys with elevated IOP and in cats with normal IOP. The physicochemical properties of apraclonidine limit its rate of passage across the blood brain barrier to access the central nervous system. It produced a decrease in blood pressure in rats when given intracerebroventricularly but not intravenously. Topical ocular administration to dogs did not change cardiovascular parameters, but intravenous administration to rats and dogs produced a transient elevation of blood pressure and a slight decrease in heart rate.
Administration of apraclonidine intravenously to cats and via the topical ocular route to monkeys resulted in a reduced anterior segment blood flow, whereas flow to the posterior segment, i.e. retina, choroid or optic nerve head, was not affected. Chronic treatment of primates with apraclonidine 1.5% ocularly three times a day for one year did not result in morphological effects which would be indicative of vasoconstriction of the anterior or posterior segments of the eye. Although ocular blood flow studies have not been conducted in humans, the animal studies provide a basis for the safe use of this drug in the treatment of ocular hypertension and open angle glaucoma.

Pharmacokinetics.

Following topical ocular administration to New Zealand white rabbits, apraclonidine reached peak concentrations after two hours in the aqueous humour, iris, ciliary body and lens. The cornea exhibited the greatest concentration and peaked at the earliest time point (20 minutes). The tissue distribution of apraclonidine from the highest to lowest concentration in microgram equivalents of tissue was cornea, iris/ ciliary body, aqueous humour, lens and vitreous humour. The elimination half-life of apraclonidine from the aqueous humour was determined to be approximately two hours.
Following IV administration, the plasma half-life of parent apraclonidine was 9 hours in cynomolgus monkeys and 3 hours in the rat. In both species, the half-life of the radioactivity from 3H-apraclonidine was longer than that of the parent drug and urinary excretion was the primary route of elimination (65-75% of dose) with the balance excreted in the faeces.

Clinical pharmacology.

Pharmacodynamics.

Optic nerve head damage and visual field loss are the result of sustained elevated intraocular pressure and poor ocular perfusion. When instilled in the eye, Iopidine Eye Drops 0.5% have the action of reducing elevated as well as normal IOP, whether or not accompanied by glaucoma. The onset of the ocular hypotensive action of apraclonidine usually occurs within one hour and the peak pressure reduction can usually be seen three to five hours after administration of a single dose. Repeated dose response and comparative studies (with 0.125%-1% apraclonidine) demonstrate that apraclonidine 0.5% is at the top of the dose response IOP reduction curve.
Aqueous fluorophotometry studies demonstrate that apraclonidine's predominant mechanism of action is reduction of aqueous flow via stimulation of the α-adrenergic system.
Unlike β-blockers and adrenaline, apraclonidine reduces aqueous flow during the day and also at night during sleep. Apraclonidine's mechanism of action may account for the additional IOP reductions observed after instillation of apraclonidine in patients receiving maximally tolerated medical therapy.
The clinical utility of Iopidine 0.5% is most apparent for those glaucoma patients on maximally tolerated medical therapy who require additional short-term IOP reduction. Clinical studies have shown that Iopidine 0.5% is effective in combination with topical β-blockers, sympathomimetics, parasympathomimetics and oral carbonic anhydrase inhibitors. However, the IOP lowering efficacy of Iopidine 0.5% diminishes over time in some patients. This loss of effect appears to be an individual occurrence with a variable time of onset and should be closely monitored (see Indications).
Ophthalmic apraclonidine has minimal effect on cardiovascular parameters.

Pharmacokinetics.

Studies of Iopidine 0.5% dosed at one drop three times a day for both eyes for 10 days in 12 normal volunteers yielded a peak plasma concentration of less than 1.0 nanogram/mL (range 0.6-0.9 nanogram/mL) with a trough concentration of 0.5 nanogram/mL. The plasma half-life was estimated to be 8 hours with an elimination rate constant of 0.083 ± 0.048 hours-1.

Indications

Iopidine 0.5% is indicated to control of intraocular pressure (IOP) in glaucoma patients on maximally tolerated glaucoma therapy for a period of 3 months.
In clinical studies, the drop in IOP appeared to decrease after day 60, which may be associated with a progression of the disease or loss of effect of the drug. This phenomenon appears to be an individual occurrence with a variable time of onset.
As with any patient on maximally tolerated therapy (see Dosage and Administration), patients using Iopidine 0.5% to delay surgery should have frequent follow-up examinations, and treatment with Iopidine 0.5% should be discontinued if IOP rises significantly.
In patients who have maintained a response to Iopidine 0.5% for 3 months and a decision is made to continue treatment, safety aspects, including any evidence of corneal changes (see Precautions), and IOP control should be closely monitored.

Contraindications

Iopidine 0.5% is contraindicated in patients with hypersensitivity to any component of the formulation or to systemic clonidine; patients receiving monoamine oxidase inhibitors (MAOIs), systemic sympathomimetics or tricyclic antidepressants.

Precautions

Not for injection or oral ingestion. Since apraclonidine is a potent depressor of IOP, patients who develop an exaggerated reduction in IOP should be closely monitored.
Iopidine 0.5% should be used with caution in patients with coronary insufficiency, recent myocardial infarction, cerebrovascular disease, chronic renal failure, Raynaud's disease or thromboangiitis obliterans.
While the topical administration of Iopidine 0.5% had minimal effect on heart rate or blood pressure in clinical studies evaluating glaucoma patients, the preclinical pharmacological profile of this drug suggests that caution should be observed in treating patients with severe, uncontrolled cardiovascular disease, including hypertension. The possibility of a vasovagal attack should be considered and caution should be exercised in patients with a history of such episodes.
Although the topical use of Iopidine 0.5% has not been studied in renal failure patients, structurally related clonidine undergoes a significant increase in half life in patients with severe renal impairment. Caution is advised in patients with renal failure. Close monitoring of cardiovascular parameters in patients with impaired renal function is advised if they are candidates for topical therapy with Iopidine 0.5%. Close monitoring of cardiovascular parameters in patients with impaired hepatic function is also advised as the systemic dosage form of clonidine is partly metabolised in the liver.
Caution and monitoring of depressed patients are advised since apraclonidine has been infrequently associated with depression (see Interactions with Other Medicines).
Topical apraclonidine can lead to an allergic-like reaction requiring discontinuation of therapy with Iopidine 0.5% (see Adverse Effects); the overall discontinuation rate in clinical studies was 15%.
Apraclonidine can cause dizziness or somnolence. Patients should be warned of the potential for decreased mental alertness while using Iopidine 0.5% and advised not to drive or operate machinery.
Where the decision is made to continue treatment with Iopidine 0.5% beyond three months, patients should be closely monitored for any evidence of corneal changes. No adverse ocular effects were observed in cynomolgus monkeys treated with apraclonidine 1.5%, 2 drops three times daily for 15 months. Repeated ocular dosing to rabbit eyes of apraclonidine 0.5%, 2 drops three times daily for one month showed minimal to moderate congestion and discharge of the conjunctiva, minimal corneal cloudiness and impaired pupillary response although there were no accompanying histological changes. Following oral administration to rats and mice for 2 years, corneal lesions (inflammation, vascularisation and mineralisation) were reported. These changes appear to be species related and were not observed in systemic or topical studies in primates or reported clinically. Adequate data on the efficacy and safety of the use of apraclonidine beyond 3 months have not been presented.
In patients with angle closure glaucoma, the immediate treatment objective is to reopen the angle by constriction of the pupil with a miotic agent. Iopidine 0.5% has not been demonstrated to be effective in cases of angle closure glaucoma.
Iopidine 0.5% eye drops contain benzalkonium chloride which may cause eye irritation and is known to discolour soft contact lenses. Avoid contact with soft contact lenses. Patients must be instructed to remove contact lenses prior to the application of Iopidine 0.5% eye drops and wait at least 15 minutes before reinsertion.

Effects on fertility.

Studies have not been performed to evaluate the effect of topical ocular administration of Iopidine 0.5% on human fertility. The fertility of male and female rats was not affected by the apraclonidine administered at oral doses up to 0.5 mg/kg/day.

Use in pregnancy.

(Category B3)
There are no well controlled studies of Iopidine 0.5% in pregnant women.
Iopidine 0.5% is not recommended during pregnancy.
Iopidine 0.5% should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.
Apraclonidine was not teratogenic in rats or rabbits when given orally during the period of organogenesis at doses of up to 0.3 and 3.0 mg/kg/day respectively, but was embryotoxic in rabbits at a dose of 3.0 mg/kg/day. Dose related maternal toxicity was evident in both the rat and the rabbit studies.

Use in lactation.

It is not known if topically applied apraclonidine is excreted in human milk. A risk to the suckling child cannot be excluded. Breastfeeding should be discontinued during treatment with Iopidine 0.5%.

Paediatric use.

Iopidine 0.5% is not recommended for use in children; especially in infants under the age of 1 year due to the risk of serious systemic adverse reactions that could occur even with a single dose (see Adverse Effects and Overdosage).

Carcinogenicity and mutagenicity.

Apraclonidine was not genotoxic in a series of assays for gene mutations and chromosomal damage. Apraclonidine showed no evidence of carcinogenicity when administered orally to rats and mice at doses up to 1 and 0.6 mg/kg/day, respectively.

Interactions

Iopidine 0.5% should not be used in patients receiving MAOIs (see Contraindications).
No specific drug interactions with topical glaucoma products (betaxolol, carbachol, dipivefrin, ecothiopate, adrenaline, levobunolol, pilocarpine, timolol) or systemic medication (acetazolamide, methazolamide) were identified in the clinical studies with Iopidine 0.5%.
However, since apraclonidine may reduce pulse and blood pressure, caution in concomitant use of drugs such as β-blockers (ophthalmic and systemic), antihypertensives and cardiac glycosides is advised. Patients using cardiovascular drugs concurrently with apraclonidine should have their pulse and blood pressure monitored frequently. Caution should be exercised with simultaneous use of clonidine and other similar pharmacologic agents.
The possibility exists for an additive or potentiating effect with CNS depressants (alcohol, barbiturates, opiates, sedatives, anaesthetics). Tricyclic antidepressants have been reported to blunt the hypotensive effect of systemic clonidine. It is not known whether the concurrent use of these agents with Iopidine 0.5% can lead to a reduction in the IOP lowering effect. No data on the level of circulating catecholamines after apraclonidine withdrawal are available. Caution is advised, however, in patients taking tricyclic antidepressants, which can affect the metabolism and uptake of circulating amines (see Contraindications).

Adverse Effects

Iopidine 0.5% is generally well tolerated at the recommended dosage for up to 3 months (see Indications) for control of IOP in glaucoma patients. The most frequently observed effects were ocular.
Use of Iopidine 0.5% can lead to an allergic-like reaction characterised wholly or in part by the symptoms of hyperaemia, pruritus, discomfort, tearing, foreign body sensation, oedema of the lids and conjunctiva. If allergic-like symptoms occur, therapy with Iopidine 0.5% should be discontinued.
In clinical studies (n = 458 patients) the overall discontinuation rate related to Iopidine 0.5% was 15%. The most commonly reported events leading to discontinuation were hyperaemia, pruritus, tearing, discomfort, lid oedema, dry mouth and foreign body sensation. Other adverse reactions related to apraclonidine were generally mild to moderate, nonserious and did not result in sequelae.
The following adverse reactions (incidence) were reported in clinical studies with Iopidine 0.5% as being related to therapy.

Ocular.

Hyperaemia (13%), pruritus (10%), discomfort (6%), tearing (4%).

< 3% of patients.

Lid oedema, blurred vision, foreign body sensation, dry eye, conjunctivitis, discharge, blanching.

< 1% of patients.

Lid margin crusting, conjunctival follicles, conjunctival oedema, oedema, abnormal vision, lid disorder, keratitis, blepharitis, photophobia, corneal staining, lid erythema, blepharoconjunctivitis, irritation, corneal erosion, corneal infiltrate, keratopathy, lid scales, lid retraction.

Systemic.

Body as a whole.

< 3% of patients.

Headache, asthenia, chest pain, abnormal coordination, malaise.

Cardiovascular.

< 1% of patients.

Peripheral oedema, arrhythmia.

CNS.

< 1% of patients.

Somnolence, dizziness, nervousness, depression, insomnia, paraesthesia.

Digestive system.

Dry mouth (10.3%).

< 1% of patients.

Constipation, nausea.

Musculoskeletal.

< 1% of patients.

Myalgia.

Respiratory.

Dry nose (2%).

< 1% of patients.

Rhinitis, dyspnoea, pharyngitis, asthma.

Dermatological.

< 1% of patients.

Contact dermatitis, dermatitis.

Special senses.

Taste perversion (3%), parosmia (< 1%).

Postmarketing events.

The following adverse reactions are classified according to the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), or not known (cannot be estimated from the available data) according to system organ classes. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The adverse reactions have been observed during clinical trials and postmarketing experience with Iopidine 0.5%.

Eye disorders.

Very common (≥ 10%): conjunctivitis, eye pruritus, ocular hyperaemia.
Common (≥ 1% to < 10%): eyelid oedema, dry eye, conjunctival follicles, foreign body sensation in eyes, eyelid margin crusting, lacrimation increased, ocular discomfort.
Uncommon (≥ 0.1% to < 1%): mydriasis, keratitis, keratopathy, visual impairment, visual acuity reduced, photophobia, vision blurred, corneal infiltrates, blepharospasm, blepharitis, eyelid ptosis, erythema of eyelid, eyelid disorders, eye pain, eye oedema, conjunctival vascular disorders, conjunctival oedema, eye discharge, eye irritation.

Infections and infestations.

Common (≥ 1% to < 10%): rhinitis.

Psychiatric disorders.

Uncommon (≥ 0.1% to < 1%): depression, nervousness.

Nervous system disorders.

Common (≥ 1% to < 10%): headache, dysgeusia.
Uncommon (≥ 0.1% to < 1%): dizziness, coordination abnormal, somnolence.

Vascular disorders.

Uncommon (≥ 0.1% to < 1%): vasodilation.

Respiratory, thoracic and mediastinal disorders.

Common (≥ 1% to < 10%): nasal dryness.
Uncommon (≥ 0.1% to < 1%): dyspnoea, rhinorrhoea, throat irritation.

Gastrointestinal disorders.

Common (≥ 1% to < 10%): dry mouth.
Uncommon (≥ 0.1% to < 1%): nausea, constipation.

Skin and subcutaneous tissue disorders.

Common (≥ 1% to < 10%): dermatitis.
Uncommon (≥ 0.1% to < 1%): dermatitis contact.

General disorders and administration site conditions.

Common (≥ 1% to < 10%): asthenia.
Uncommon (≥ 0.1% to < 1%): chest pain, malaise, fatigue, irritability.
Additional adverse reactions identified from post-marketing surveillance include the following (see Table 1). Frequencies cannot be estimated from the available data.

Paediatric population.

Iopidine 0.5% is not recommended for use in children. Reactions including lethargy, bradycardia and decreased oxygen saturation have been reported in neonates and infants under 1 year of age even when a single dose of apraclonidine was administered.

Dosage and Administration

One drop of Iopidine 0.5% should be instilled into the affected eye(s) three times per day. Since Iopidine 0.5% will be used with other ocular glaucoma therapies, an approximate five minute interval between instillation of each medication should be observed to prevent washout of the previous dose (see Indications).
Clinical studies to establish safety and efficacy in children have not been conducted and therefore Iopidine 0.5% is not recommended for use in children.
There are no special precautions for administration to the elderly.
Patients with impaired renal and/or hepatic function should be carefully monitored (see Precautions).
In order to minimise systemic absorption, apply pressure to the tear duct for two minutes immediately after administration.

Overdosage

No information on overdosage with Iopidine 0.5% is available in humans. Based on information with clonidine, signs of a topical or oral overdose with apraclonidine may include hypotension, lethargy, somnolence, bradycardia, hypoventilation, and seizure, particularly in children. A topical overdose of Iopidine 0.5% may be flushed from the eyes with warm tap water. Following accidental overdosage per ora, treatment should include drug removal by emesis or activated charcoal as well as symptomatic treatment.
Contact Poisons Information Centre on 131 126 (Australia) for advice on management.

Presentation

Eye drops (sterile isotonic solution), 0.5% (5.0 mg apraclonidine ≡ 5.75 mg/mL apraclonidine hydrochloride): 5 mL, 10 mL (Drop-Tainer dispenser, AUST R 51190).
Consumer product information is supplied with this product.

Storage

Store below 25°C. Protect from light.

Poison Schedule

S4.