Consumer medicine information

Trusamide

Dorzolamide

BRAND INFORMATION

Brand name

Trusamide

Active ingredient

Dorzolamide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Trusamide.

What is in this leaflet

This leaflet answers some common questions about TRUSAMIDE. 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 using TRUSAMIDE 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 TRUSAMIDE is used for

TRUSAMIDE is used to lower raised pressure in the eye and to treat glaucoma. Glaucoma is a condition in which the pressure of fluid in the eye may be high. However, some people with glaucoma may have normal eye pressure. Also, some people with raised eye pressure may not have glaucoma.

Glaucoma is caused by a build-up of the fluid which flows through the eye. This build-up occurs because the fluid drains out of your eye more slowly than it is being pumped in. Since new fluid continues to enter the eye, joining the fluid already there, the pressure continues to rise. This raised pressure may damage the back of the eye resulting in gradual loss of sight. Damage can progress so slowly that the person is not aware of this gradual loss of sight.

Sometimes even normal eye pressure is associated with damage to the back of the eye.

There are usually no symptoms of glaucoma. The only way of knowing that you have glaucoma is to have your eye pressure, optic nerve and visual field checked by an eye specialist or optometrist. If glaucoma is not treated it can lead to serious problems. You may have no symptoms but eventually glaucoma can lead to total blindness. In fact, untreated glaucoma is one of the most common causes of blindness.

Although TRUSAMIDE helps control your glaucoma it does not cure it.

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

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

TRUSAMIDE lowers pressure in the eye by reducing the production of fluid.

TRUSAMIDE belongs to a family of medicines called carbonic anhydrase inhibitors.

TRUSAMIDE is not addictive.

Before you use TRUSAMIDE

When you must not take it

Do not use TRUSAMIDE if:

  • you have an allergy to TRUSAMIDE or any of the ingredients listed at the end of this leaflet
  • you are breast-feeding or intend to breast-feed
    It is not known whether TRUSAMIDE passes into breast milk.

Do not put the eye drops into your eye(s) while you are wearing soft contact lenses. The preservative in TRUSAMIDE (benzalkonium chloride) may be deposited in soft contact lenses. You can put your soft contact lenses back into your eyes at least 15 minutes after you have used TRUSAMIDE.

Do not use TRUSAMIDE if:

  • the seal around the cap is broken
  • the bottle shows signs of tampering
  • the expiry date on the pack has passed.
    If you use this medicine after the expiry date has passed, it may not work.

If you are not sure whether you should start using TRUSAMIDE, talk to your doctor.

Do not give TRUSAMIDE to a child. The safety and effectiveness of TRUSAMIDE in children have not been established.

Before you start to use it

Tell your doctor if:

  1. you are pregnant or intend to become pregnant
Your doctor will discuss the risks and benefits of using TRUSAMIDE during pregnancy and a decision can be made if you should or should not use it.
  1. you have now or have had in the past any medical conditions, especially the following:
  • kidney disease
  • liver disease
  1. you have an allergy to sulfonamide medicines
The active ingredient of TRUSAMIDE, dorzolamide hydrochloride, is a sulfonamide-related compound. Therefore, if you are allergic to sulfonamide medicines you may be allergic to TRUSAMIDE. Check with your doctor or pharmacist if you are not sure whether you are allergic to sulfonamides.
  1. you have any allergies to any other medicines or any other substances, such as foods, preservatives or dyes.

If you have not told your doctor about any of the above, tell them before you use TRUSAMIDE.

Taking other medicines

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

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

  • tablets used to treat glaucoma
  • large amounts of aspirin or salicylates

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

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

How to use TRUSAMIDE

How much to use

Your doctor will tell you how many drops you need to use each day.

Use TRUSAMIDE only when prescribed by your doctor.

When TRUSAMIDE is used alone, the usual dose for adults is one drop three times a day, in either one or both eyes.

If your doctor has recommended that you use TRUSAMIDE with a beta-blocker eye drop, then the usual dose for adults is one drop of TRUSAMIDE twice a day, in either one or both eyes.

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

After using TRUSAMIDE, wait at least 10 minutes before putting any other eye drops in your eye(s).

When to use it

If you are using TRUSAMIDE three times a day, use the drops first thing in the morning, in the early afternoon and at bedtime (i.e. approximately 8 hours apart). If you are using TRUSAMIDE twice a day, use the drops in the morning and in the evening (i.e. approximately 12 hours apart).

Use TRUSAMIDE every day, at about the same time each day, 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 to use it

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

Before opening the bottle for the first time, make sure the two safety seals joining the cap to the bottle are not broken. If they are, do not use the bottle and return it to your pharmacist. You will notice a small space between the cap and the bottle - this is normal.

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

  1. Wash your hands well with soap and water.
  2. To open the bottle for the first time, hold the bottle upright and turn the cap in the direction of the arrows until you can lift it off. This will break the two safety seals.
  3. Place the cap upside down (arrows face down) on a flat surface. Do not touch the inside of the cap. This will help keep the inside of the cap clean and keep germs out of the eye drops.
  4. Hold the bottle upside down in one hand, with your thumb or index finger over the "finger push" area.
  5. Using your other hand, gently pull down your lower eyelid to form a pouch.
  6. Tilt your head back and look up.
  7. Put the tip of the bottle close to your lower eyelid. Do not let it touch your eye.
  8. Release one drop into the pouch formed between your eye and eyelid by gently squeezing the bottle.
  9. Close your eye and keep it closed. Do not blink or rub your eye.
  10. While your eye is still closed, place your index finger against the inside corner of your eye and press against your nose for about two minutes.
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. Ask your doctor for more specific instructions on this technique.
  1. Replace the cap, sealing it tightly. Do not overtighten the cap.
  2. Wash your hands again with soap and water to remove any residue.

Wait at least 15 minutes before replacing your contact lenses.

Be careful not to touch the dropper tip against your eye, eyelid or anything else to avoid contaminating the eye drops. Contaminated eye drops may give you an eye infection.

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.

How long to use it

TRUSAMIDE helps control your condition but does not cure it. Therefore, TRUSAMIDE must be used every day. Continue using TRUSAMIDE for as long as your doctor prescribes.

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 them as you would normally.

If you are not sure whether to skip the dose, talk to your doctor or pharmacist.

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

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

If you use too much (overdose)

If you think that you or anyone else may have swallowed any or all of the contents of a bottle of TRUSAMIDE, or used too many drops, immediately telephone your doctor or Poisons Information Centre (telephone 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 TRUSAMIDE

Things you must do

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

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 TRUSAMIDE because of possible contamination of the old one, or may advise you to stop your treatment with TRUSAMIDE.

If you become pregnant while using TRUSAMIDE tell your doctor.

If you are about to be started on any new medicine tell your doctor and pharmacist that you are using TRUSAMIDE.

Things you must not do

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

Do not stop using TRUSAMIDE without first talking to 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 TRUSAMIDE affects you. TRUSAMIDE generally does not cause any problems with your ability to drive a car or operate machinery. However, it may cause certain side effects in some people, including blurred vision and dizziness. Make sure you know how you react to TRUSAMIDE before you drive a car or operate machinery.

Side effects

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

TRUSAMIDE helps most people with high eye pressure and glaucoma, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

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

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

  • eye problems such as burning, stinging, itching, conjunctivitis, watering of the eye(s), redness of the eye(s), swelling or crusting of the eyelids(s), eye pain, blurred vision
  • feeling sick
  • bitter taste, dry mouth
  • nose bleeds
  • throat irritation
  • headache, dizziness
  • tiredness, weakness
  • kidney stones
  • numbness or tingling in fingers or toes

These are usually mild side effects of TRUSAMIDE.

If any of the following happen, stop using TRUSAMIDE and tell your doctor immediately or go to accident and emergency at your nearest hospital:

  • wheezing, difficulty in breathing, shortness of breath
  • swelling of the face, lips, mouth, tongue or throat which may cause difficulty in breathing or swallowing
  • severe and sudden onset of pinkish, itchy swellings on the skin, also called hives or nettlerash
  • skin rash, itchiness

These may be serious side effects. You may have an allergic reaction to TRUSAMIDE. You may need urgent medical attention. Serious side effects are rare.

Other side effects not listed above may also occur in some patients. Tell your doctor if you notice any other effects.

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

After using TRUSAMIDE

Storage

Keep your eye drops in a cool dry place where the temperature stays below 30°C.

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

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

Do not carry the eye drops in pockets of your clothes.

Heat and dampness can destroy some medicines.

Keep the eye drops away from light.

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.

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

Disposal

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

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

TRUSAMIDE comes as eye drops in a 5 mL bottle.

Ingredients

Active ingredient:

  • dorzolamide hydrochloride, equivalent to dorzolamide 2%

Inactive ingredients:

  • hydroxyethylcellulose
  • mannitol
  • sodium citrate
  • sodium hydroxide
  • benzalkonium chloride as preservative

Supplier

TRUSAMIDE is supplied in Australia by:

Alphapharm Pty Ltd trading as Viatris
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.viatris.com.au
Phone: 1800 274 276

This leaflet was prepared in April 2022.

Australia registration numbers:
AUST R 217251

TRUSAMIDE_cmi\Apr22/00

Published by MIMS May 2022

BRAND INFORMATION

Brand name

Trusamide

Active ingredient

Dorzolamide

Schedule

S4

 

1 Name of Medicine

Dorzolamide hydrochloride.

2 Qualitative and Quantitative Composition

Each mL of Trusamide contains 20 mg (2%) dorzolamide (22.3 mg of dorzolamide hydrochloride).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Eye drops, solution.
Clear, slightly viscous, colourless aqueous solution.

4 Clinical Particulars

4.1 Therapeutic Indications

Trusamide eye drops are indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open angle glaucoma.

4.2 Dose and Method of Administration

For individual patient use only.
When used as monotherapy, the dose is one drop of Trusamide in the affected eye(s) three times daily.
When used as adjunctive therapy with an ophthalmic beta-blocker, the dose is one drop of Trusamide in the affected eye(s) two times daily.
When substituting Trusamide for another ophthalmic antiglaucoma agent, discontinue the other agent after usual dosing on one day, and start Trusamide on the next day.
If more than one topical ophthalmic drug is being used, the drugs should be administered at least ten minutes apart.
Systemic absorption of drugs from ophthalmic solutions may be minimised by pressure on the tear duct immediately after application.

4.3 Contraindications

Trusamide is contraindicated in patients who are hypersensitive to any component of this product.

4.4 Special Warnings and Precautions for Use

General.

The management of patients with acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents. Dorzolamide hydrochloride eye drops has not been studied in patients with acute angle-closure glaucoma.
Dorzolamide hydrochloride eye drops is a sulphonamide and although administered topically, is absorbed systemically. Therefore the same types of adverse reactions that are attributable to sulphonamides may occur with topical administration, including severe reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. The safety of dorzolamide hydrochloride eye drops has not been demonstrated in patients with known hypersensitivity to sulphonamides. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation.
In clinical studies, local ocular adverse effects, primarily conjunctivitis and lid reactions, were reported with chronic administration of dorzolamide hydrochloride eye drops. Some of these reactions had the clinical appearance and course of an allergic type reaction that resolved upon discontinuation of drug therapy. If such reactions are observed, discontinuation of treatment with dorzolamide hydrochloride eye drops should be considered.
There is a potential for an additive effect on the known systemic effects of carbonic anhydrase inhibition in patients receiving an oral carbonic anhydrase inhibitor and dorzolamide hydrochloride eye drops. The concomitant administration of dorzolamide hydrochloride eye drops and oral carbonic anhydrase inhibitors has not been studied and is not recommended.
Choroidal detachment has been reported with administration of dorzolamide after filtration procedures.
Dorzolamide hydrochloride eye drops contains the preservative benzalkonium chloride, which may be absorbed by soft contact lenses. Therefore, dorzolamide hydrochloride eye drops should not be administered while wearing soft contact lenses. The contact lenses should be removed before application of the drops and not be reinserted earlier than 15 minutes after use.
There is an increased potential for developing corneal oedema in patients with low endothelial cell counts. Precautions should be used when prescribing dorzolamide hydrochloride eye drops to this group of patients.
There have been reports of bacterial keratitis associated with the use of multiple dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface.
Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures.
Patients should also be instructed that ocular solutions, if handled improperly, can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.
Patients should also be advised that if they develop an intercurrent ocular condition (e.g. trauma, ocular surgery or infection), or any ocular reactions, particularly conjunctivitis and lid reactions, they should immediately seek their physician's advice concerning the continued use of the product.
If more than one topical ophthalmic drug is being utilised, the drugs should be administered at least ten minutes apart.

Contact lens use.

Trusamide contains the preservative benzalkonium chloride, which may be absorbed by soft contact lenses. Therefore, Trusamide should not be administered while wearing soft contact lenses. The contact lenses should be removed before application of the drops and not be reinserted earlier than 15 minutes after use.

Use in hepatic impairment.

Dorzolamide hydrochloride eye drops has not been studied in patients with hepatic impairment and should therefore be used with caution in such patients.

Use in renal impairment.

Dorzolamide hydrochloride eye drops has not been studied in patients with severe renal impairment (CrCl < 30 mL/min). Because dorzolamide hydrochloride eye drops and its metabolite are excreted predominantly by the kidney, dorzolamide hydrochloride eye drops is not recommended in such patients.

Use in the elderly.

Of the total number of patients in clinical studies of dorzolamide hydrochloride eye drops, 44% were 65 years of age and over, while 10% were 75 years of age and over. No overall differences in effectiveness or safety were observed between these patients and younger patients, but greater sensitivity of some older individuals to the product cannot be ruled out.

Paediatric use.

Safety and effectiveness in children have not been established as there have been no trials in children.

Effects on laboratory tests.

Dorzolamide hydrochloride eye drops was not associated with clinically meaningful electrolyte disturbances.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Specific drug interaction studies have not been performed with dorzolamide hydrochloride eye drops. In clinical studies, dorzolamide hydrochloride eye drops was used concomitantly with the following medications without evidence of adverse interactions: timolol ophthalmic solution, betaxolol ophthalmic solution and systemic medications, including ACE inhibitors, calcium channel blockers, diuretics, nonsteroidal anti-inflammatory drugs including aspirin, and hormones (e.g. estrogen, insulin, thyroxine).
Dorzolamide hydrochloride eye drops is a carbonic anhydrase inhibitor and although administered topically, is absorbed systemically. Dorzolamide hydrochloride eye drops should not be used concomitantly with oral carbonic anhydrase inhibitors.
In clinical studies, dorzolamide hydrochloride eye drops was not associated with acid-base disturbances. However, these disturbances have been reported with oral carbonic anhydrase inhibitors and have in some instances, resulted in drug interactions (e.g. toxicity associated with high dose salicylate therapy). Therefore, the potential for such drug interactions should be considered in patients receiving dorzolamide hydrochloride eye drops.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

In reproduction studies of dorzolamide hydrochloride in rats, there were no adverse effects on the reproductive capacity of males or females at oral doses up to 15 and 7.5 mg/kg/day, respectively.
(Category B3)
There are no adequate and well controlled studies in pregnant women. Dorzolamide hydrochloride eye drops should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Developmental toxicity studies with dorzolamide hydrochloride in rabbits at oral doses of ≥ 2.5 mg/kg/day (fetal red blood cell Cmax was approximately twice the maternal red blood cell Cmax after the recommended human ophthalmic dose) revealed malformations of the vertebral bodies. These malformations occurred at doses that caused metabolic acidosis with decreased body weight gain in dams and decreased fetal weights. No treatment related malformations were seen at 1 mg/kg/day. There were no treatment related fetal malformations in developmental toxicity studies with dorzolamide hydrochloride in rats at oral doses up to 10 mg/kg/day.
In a study of dorzolamide hydrochloride in lactating rats, decreases in body weight gain in offspring were seen during lactation after an oral dose of 7.5 mg/kg/day. A slight delay in postnatal development (incisor eruption, vaginal canalization and eye opening), secondary to lower fetal body weight, was noted.
It is not known whether this drug is excreted in human milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

4.7 Effects on Ability to Drive and Use Machines

There are potential side effects of dorzolamide hydrochloride eye drops that may affect some patients' ability to drive and use machines (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.8 Adverse Effects (Undesirable Effects)

Dorzolamide hydrochloride eye drops were evaluated in more than 1400 individuals in controlled and uncontrolled clinical studies. In long-term studies of 1108 patients treated with dorzolamide hydrochloride eye drops as monotherapy or as adjunctive therapy with an ophthalmic beta-blocker, the most frequent cause of discontinuation (approximately 3%) from treatment with dorzolamide hydrochloride eye drops was drug related ocular adverse effects consistent with allergic type reactions, primarily conjunctivitis and lid reactions (see Section 4.4 Special Warnings and Precautions for Use). Such reactions occurred approximately 7% overall in the clinical trials.
In clinical studies, the most common ocular complaints were burning and stinging, blurred vision, itching and tearing. Bitter taste was also frequently reported. Local symptoms considered clinically important by investigators appear as adverse experiences in the listing below.
Adverse experiences reported during clinical studies as drug related (possibly, probably, or definitely) in 1-5% of patients on dorzolamide hydrochloride eye drops were (in decreasing order of frequency):

Ocular.

Burning and stinging, conjunctivitis, eyelid inflammation, eye itching, eyelid irritation.

Systemic.

Headache, bitter taste, nausea, asthenia/ fatigue.
In addition, iridocyclitis and rash were each reported rarely. Also, there was one report of urolithiasis.
The following adverse reactions have been reported in post-marketing experience:

Hypersensitivity.

Signs and symptoms of local reactions including palpebral reactions and systemic allergic reactions including angioedema, bronchospasm, urticaria and pruritus.

Nervous system.

Dizziness, paraesthesia.

Ocular.

Pain, redness, transient myopia (which resolved upon discontinuation of therapy), superficial punctate keratitis, eyelid crusting, choroidal detachment following filtration surgery.

Skin/ mucous membranes.

Contact dermatitis, epistaxis, throat irritation, dry mouth, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Respiratory.

Dyspnoea.

Urogenital.

Urolithiasis.

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

Treatment should be symptomatic and supportive. Electrolyte imbalance, development of an acidotic state, and possible central nervous system effects may occur. Serum electrolyte levels (particularly potassium) and blood pH levels should be monitored.
Significant lethality was observed in female rats and mice after single oral doses of dorzolamide hydrochloride of 11,369 mg/m2 (1927 mg/kg) and 3960 mg/m2 (1320 mg/kg), respectively.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Trusamide eye drops contain dorzolamide hydrochloride, which is a novel carbonic anhydrase inhibitor formulated for topical ophthalmic use. Unlike oral carbonic anhydrase inhibitors, Trusamide, which is administered topically, exerts its effects directly in the eye.
Unlike oral carbonic anhydrase inhibitors, topical administration of dorzolamide hydrochloride allows for the drug to exert its effects directly in the eye at substantially lower doses and therefore with less systemic exposure. In clinical trials, this resulted in a reduction in IOP without the acid-base disturbances or alterations in electrolytes characteristic of oral carbonic anhydrase inhibitors.

Mechanism of action.

Carbonic anhydrase (CA) is an enzyme found in many tissues of the body including the eye. It catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid. In humans, carbonic anhydrase exists as a number of isoenzymes, the most active being carbonic anhydrase II (CA-II) found primarily in red blood cells (RBCs) but also in other tissues. Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. The result is a reduction in intraocular pressure (IOP).
Trusamide eye drops contain dorzolamide hydrochloride, a potent inhibitor of human carbonic anhydrase II. Following topical ocular administration, dorzolamide hydrochloride eye drops reduces elevated intraocular pressure, whether or not associated with glaucoma. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss. Dorzolamide hydrochloride eye drops does not cause pupillary constriction and reduces intraocular pressure without the side effects such as night blindness and accommodative spasm. Dorzolamide hydrochloride eye drops has minimal or no effect on pulse rate or blood pressure.
Topically applied beta-adrenergic blocking agents also reduce IOP by decreasing aqueous humour secretion but by a different mechanism of action. Studies have shown that when dorzolamide hydrochloride eye drops is added to a topical beta-blocker, additional reduction in IOP is observed; this finding is consistent with the reported additive effects of beta-blockers and oral carbonic anhydrase inhibitors.

Clinical trials.

In clinical studies for up to one year in patients with glaucoma or ocular hypertension (baseline IOP ≥ 23 mmHg), the IOP-lowering effect of dorzolamide hydrochloride eye drops was approximately 3 to 5 mmHg throughout the day. However, as with other IOP lowering drugs, diminished responsiveness after prolonged therapy has been observed in some patients.

5.2 Pharmacokinetic Properties

When topically applied, dorzolamide reaches the systemic circulation. To assess the potential for systemic carbonic anhydrase inhibition following topical administration, drug and metabolite concentrations in RBCs and plasma and carbonic anhydrase inhibition in RBCs were measured. Dorzolamide accumulates in RBCs during chronic dosing as a result of selective binding to CA-II while extremely low concentrations of free drug in plasma are maintained. The parent drug forms a single N-desethyl metabolite that inhibits CA-II less potently than the parent drug but also inhibits a less active isoenzyme (CA-I). The metabolite also accumulates in RBCs where it binds primarily to CA-I. Dorzolamide binds moderately to plasma proteins (approximately 33%). Dorzolamide is primarily excreted unchanged in the urine; the metabolite is also excreted in urine. After dosing ends, dorzolamide washes out of RBCs nonlinearly, resulting in a rapid decline of drug concentration initially, followed by a slower elimination phase with a half-life of about four months.
To simulate the maximum systemic exposure after long-term topical ocular administration, dorzolamide hydrochloride eye drops was given orally to eight healthy subjects for up to 20 weeks. The oral dose of 4 mg/day closely approximates the maximum amount of drug delivered by topical ocular administration of dorzolamide hydrochloride eye drops 2% t.i.d. Steady state was reached within 13 weeks, and the following observations were noted:
in plasma, concentrations of dorzolamide and metabolite were generally below the assay limit of quantitation (15 nanoM) indicating almost no free drug or metabolite;
in RBCs, dorzolamide concentrations approached the binding capacity of CA-II (20-25 microM) and metabolite concentrations approached 12-15 microM, well below the binding capacity of CA-I (125-155 microM);
in RBCs, CA-II activity was inhibited 94-96% and total carbonic anhydrase activity was inhibited 81-88%. This was below the > 99% inhibition of CA-II activity and 96% inhibition of total carbonic anhydrase activity in RBCs that are anticipated to be necessary for a pharmacological effect on renal function and respiration, respectively.
In a subset of 71 patients in a large clinical study (N = 333) of dorzolamide hydrochloride eye drops t.i.d. in patients with elevated IOP, dorzolamide and metabolite concentrations and carbonic anhydrase inhibition in RBCs were measured after approximately six and twelve months of treatment. The pharmacokinetic results were consistent with those observed at steady state in the oral pharmacokinetic study in terms of CA-II inhibition. Although in this study several patients 65 years of age and older with renal impairment (estimated CrCl 30-60 mL/min) had higher metabolite concentrations in RBCs, no meaningful differences in carbonic anhydrase inhibition and no clinically significant systemic side effects were directly attributable to this finding.

5.3 Preclinical Safety Data

Genotoxicity.

Dorzolamide showed no mutagenic potential in a series of standard assays for gene mutations, chromosomal damage and DNA damage.

Carcinogenicity.

In a 2 year study of dorzolamide administered orally to male and female Sprague-Dawley rats, urinary bladder papillomas were seen in male rats in the highest dosage group of 20 mg/kg/day. No treatment related tumours were seen in a 21 month study in male and female mice given oral doses up to 75 and 37.5 mg/kg/day, respectively.
The increased incidence of urinary bladder papillomas seen in the high dose male rats appears to be a class effect of carbonic anhydrase inhibitors in rats. Rats are particularly prone to developing papillomas in response to foreign bodies, compounds causing crystalluria and diverse sodium salts.
No changes in bladder urothelium were seen in dogs given oral dorzolamide hydrochloride for 1 year at doses of 2 mg/kg/day or in monkeys given 20 microL of 3% dorzolamide hydrochloride topically to the eye b.i.d for 1 year.

6 Pharmaceutical Particulars

6.1 List of Excipients

Trusamide contains the following inactive ingredients: sodium citrate dihydrate, hyetellose, sodium hydroxide, mannitol and water for injections. Benzalkonium chloride (0.0075%) is added as preservative.

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 Trusamide eye drops below 30°C. Protect from light. To be used within 4 weeks after opening.

6.5 Nature and Contents of Container

Trusamide eye drops is available in a polyethylene dispensing bottle. Each bottle contains 5 mL of solution and is supplied in 1 x 5 mL bottle packs.

Australian register of therapeutic goods (ARTG).

AUST R 217251 - Trusamide dorzolamide (as hydrochloride) 20 mg/mL eye drops bottle.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Dorzolamide hydrochloride is optically active.
The specific rotation is α 25°405 (C = 1, water) = ~ -17°.
Dorzolamide hydrochloride has a molecular weight of 360.9 and a melting point of about 275°C. It is a white to off-white, free flowing crystalline powder, which is soluble in water and slightly soluble in methanol and ethanol.

Chemical structure.

Dorzolamide hydrochloride is described chemically as: (4S, 6S)-4-ethylamino-5,6-dihydro-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide monohydrochloride.
Its empirical formula is C10H17N2O4S3Cl and its structural formula is:

CAS number.

130693-82-2.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes