4.1. Therapeutic indications

Dorzolamide is indicated:

• as adjunctive therapy to beta-blockers,

• as monotherapy in patients unresponsive to beta-blockers or in whom beta-blockers are contraindicated,

in the treatment of elevated intraocular pressure in:

▪ ocular hypertension,

▪ open-angle glaucoma,

▪ pseudo-exfoliative glaucoma.

4.2. Posology and method of administration

Posology

When used as monotherapy, the dose is one drop of dorzolamide in the conjunctival sac of the affected eye(s), three times daily.

When used as adjunctive therapy with an ophthalmic beta-blocker, the dose is one drop of dorzolamide in the conjunctival sac of the affected eye(s), two times daily.

When substituting dorzolamide for another ophthalmic anti-glaucoma agent, discontinue the other agent after proper dosing on one day, and start dorzolamide on the next day.

If more than one topical ophthalmic medicinal product is being used, the medicinal products should be administered at least ten minutes apart.

Patients should be instructed to wash their hands before use and avoid allowing the tip of the container to come into contact with 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 be informed of the correct handling of the ophthalmic dispensers.

Paediatric population

Limited clinical data in paediatric patients with administration of dorzolamide three times a day are available. (For information regarding paediatric dosing see section 5.1).

Method of administration

1. The tamper-proof seal on the bottle neck must be unbroken before the product is being used for the first time. A gap between the bottle and the cap is normal for an unopened bottle.

2. The cap of the bottle should be taken off.

3. The patient's head must be tilted back and the lower eyelid must be pulled gently down to form a small pocket between the eyelid and the eye.

4. The bottle should be inverted and squeezed until a single drop is dispensed into the eye. THE EYE OR EYELID MUST NOT BE TOUCHED WITH THE DROPPER TIP.

5.When using nasolacrimal occlusion or closing the eyelids for 2 minutes, the systemic absorption is reduced. This may result in a decrease in systemic side effects and an increase in local activity.

6. Steps 3, 4 & 5 should be repeated with the other eye if it is necessary.

7. The cap must be put back on and the bottle must be closed straight after it has been used.

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Dorzolamide has not been studied in patients with severe renal impairment (creatinine clearance < 30 ml/min) or with hyperchloraemic acidosis. Because dorzolamide and its metabolites are excreted predominantly by the kidney, dorzolamide is therefore contraindicated in such patients.

4.4. Special warnings and precautions for use

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

The management of patients with acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents. Dorzolamide has not been studied in patients with acute angle-closure glaucoma.

Dorzolamide contains a sulphonamido group, which also occurs in sulphonamides 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. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation.

Therapy with oral carbonic anhydrase inhibitors has been associated with urolithiasis as a result of acid-base disturbances, especially in patients with a prior history of renal calculi. Although no acid-base disturbances have been observed with dorzolamide, urolithiasis has been reported infrequently. Because dorzolamide is a topical carbonic anhydrase inhibitor that is absorbed systemically, patients with a prior history of renal calculi may be at increased risk of urolithiasis while using dorzolamide.

If allergic reactions (e.g. conjunctivitis and eyelid reactions) are observed, discontinuation of treatment 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. The concomitant administration of dorzolamide and oral carbonic anhydrase inhibitors is not recommended.

Corneal oedemas and irreversible corneal decompensations have been reported in patients with pre-existing chronic corneal defects and/or a history of intraocular surgery while using dorzolamide. Topical dorzolamide should be used with caution in such patients.

Choroidal detachment concomitant with ocular hypotony have been reported after filtration procedures with administration of aqueous suppressant therapies.

Dorzolamide contains the preservative benzalkonium chloride, which is known to discolour soft contact lenses.

Contact lenses should be removed prior to application and wait at least 15 minutes before reinsertion.

Benzalkonium chloride has been reported to cause eye irritation, symptoms of dry eyes and may affect the tear film and corneal surface. Should be used with caution in dry eye patients and in patients where the cornea may be compromised.

Patients should be monitored in case of prolonged use.

Paediatric population

Dorzolamide has not been studied in patients less than 36 weeks gestational age and less than 1 week of age. Patients with significant renal tubular immaturity should only receive dorzolamide after careful consideration of the risk benefit balance because of the possible risk of metabolic acidosis.

4.5. Interaction with other medicinal products and other forms of interaction

No specific drug interaction studies have been performed.

In clinical studies, dorzolamide was used concomitantly with the following medicinal products without evidence of adverse interactions: timolol ophthalmic solution, betaxolol ophthalmic solution and systemic medicinal products, including ACE-inhibitors, calcium-channel blockers, diuretics, non-steroidal anti-inflammatory drugs including acetylsalicylic acid, and hormones (e.g. oestrogen, insulin, thyroxine).

Association between dorzolamide and miotics and adrenergic agonists has not been fully evaluated during glaucoma therapy.

4.6. Fertility, pregnancy and lactation

Pregnancy

Dorzolamide should not be used during pregnancy.

There are no or limited amount of data from the use of dorzolamide in pregnant women. In rabbits, dorzolamide produced teratogenic effects at maternotoxic doses (see section 5.3).

Breast-feeding

It is not known whether dorzolamide/metabolites are excreted in human milk. Available pharmacodynamic/toxicological data in animals have shown excretion of dorzolamide/metabolites in milk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from dorzolamide therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. A risk to the newborns/infants cannot be excluded.

Fertility

Animal data do not suggest an effect of treatment with dorzolamide on male and female fertility. Human data are lacking.

4.7. Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed. Possible adverse reactions such as dizziness and visual disturbances may affect the ability to drive and use machines.

4.8. Undesirable effects

Dorzolamide was evaluated in more than 1,400 individuals in controlled and uncontrolled clinical studies. In long-term studies of 1,108 patients treated with dorzolamide as monotherapy or as adjunctive therapy with an ophthalmic beta-blocker, the most frequent cause of discontinuation (approximately 3%) from treatment with dorzolamide was drug-related ocular adverse reactions, primarily conjunctivitis and lid reactions.

The following adverse reactions have been reported either during clinical trials or during post-marketing experience.

The frequency of adverse reactions listed below is defined using 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);Not known (frequency cannot be estimated from the available data).

Nervous system disorders:

Common:

headache

Rare:

dizziness, paraesthesia

Eye disorders:

Very common:

burning and stinging

Common:

superficial punctate keratitis, tearing, conjunctivitis, eyelid inflammation, eye itching, eyelid irritation, blurred vision

Uncommon:

Iridocyclitis

Rare:

irritation including redness, pain, eyelid crusting, transient myopia (which resolved upon discontinuation of therapy), corneal oedema, ocular hypotony, choroidal detachment following filtration surgery

Not known:

foreign body sensation in eye, photophobia

Cardiac disorders:

Not known:

palpitations, tachycardia

Vascular disorders:

Not known:

hypertension

Respiratory, thoracic and mediastinal disorders:

Rare:

Not known:

epistaxis

dyspnoea

Gastrointestinal disorders:

Common:

nausea, bitter taste

Rare:

throat irritation, dry mouth

Skin and subcutaneous tissue disorders:

Rare:

contact dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis

Renal and urinary disorders:

Rare:

urolithiasis

General disorders and administration site conditions:

Common:

asthenia/fatigue

Rare:

Hypersensitivity: signs and symptoms of local reactions (palpebral reactions) and systemic allergic reactions including angioedema, urticaria and pruritus, rash, shortness of breath, rarely bronchospasm

Investigations:

Dorzolamide was not associated with clinically meaningful electrolyte disturbances.

Paediatric population

See section 5.1.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme (website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store).

4.9. Overdose

Only limited information is available with regard to human overdose by accidental or deliberate ingestion of dorzolamide hydrochloride.

Symptoms

The following have been reported with oral ingestion: somnolence; topical application: nausea, dizziness, headache, fatigue, abnormal dreams and dysphagia.

Treatment

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.