DORZOLAMIDE/TIMOLOL

The dose is one drop in the conjunctival sac of the affected eye(s) two times daily. If another topical ophthalmic agent is being used, Dorzolamide / Timolol and the other agent 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.

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. Paediatric population Efficacy in paediatric patients has not been established.

Safety in paediatric patients below the age of two years has not been established. 1).

In clinical studies for dorzolamide timolol eye drops solution the observed adverse reactions have been consistent with those that were reported previously with dorzolamide hydrochloride and/or timolol maleate. During clinical studies, 1035 patients were treated with dorzolamide timolol eye drops solution.

2% of all patients discontinued because of local adverse reactions suggestive of allergy or hypersensitivity (such as lid inflammation and conjunctivitis). Like other topically applied ophthalmic drugs, timolol maleate is absorbed into the systemic circulation.

This may cause similar undesirable effects as seen with systemic beta-blocking agents. Incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration. The following adverse reactions have been reported with dorzolamide timolol eye drops solution or one of its components either during clinical trials or during post-marketing experience: [Very Common: ( 1/10), Common: ( 1/100 to <1/10), Uncommon: 1/1000 to <1/100), and Rare: ( 1/10,000 to <1/1000) , Not known (cannot be estimated from the available data)] Very Common Common Uncommon Rare Not Known** Immune system disorders dorzolamide timolol eye signs and symptoms of drops solution systemic allergic reactions, including angioedema, urticaria, pruritus, rash, anaphylaxis timolol maleate eye drops, solution signs and symptoms of systemic allergic reactions including angioedema, urticaria, localized and generalized rash, anaphylaxis pruritus Metabolism and nutrition disorders timolol maleate eye drops, solution hypoglycaemia Psychiatric disorders timolol maleate eye drops, solution depression* insomnia*, nightmares*, memory loss* hallucination Nervous system disorders dorzolamide hydrochloride eye drops, solution headache * dizziness*, paraesthesia* timolol maleate eye drops, solution headache * dizziness*, syncope* paraesthesia*, increase in signs and symptoms of myasthenia gravis, decreased libido*, cerebrovascul ar accident*, cerebral ischemia Eye disorders dorzolamide timolol eye drops solution burning and stinging conjunctiv al infection, blurred vision, corneal erosion, ocular itching, tearing dorzolamide hydrochloride eye drops, solution eyelid inflammati on*, eyelid irritation* iridocyclitis * irritation including redness*, pain*, eyelid crusting*, transient myopia (which resolved upon discontinuation of therapy), corneal oedema*, ocular hypotony*, choroidal detachment (following filtration surgery)* foreign body sensation in eye timolol maleate eye drops, solution signs and symptoms of ocular irritation, including blepharitis *, keratitis*, decreased corneal sensitivity, dry eyes* Ear and labyrinth disorders timolol maleate eye tinnitus* drops, solution Cardiac disorders timolol maleate eye drops, solution bradycardia * chest pain *, palpitations*, oedema, arrhythmia *, congestive heart failure*, cardiac arrest*, heart block atrioventricular block, cardiac failure dorzolamide hydrochloride eye drops, solution palpitations, Tachycardia Vascular disorders timolol maleate eye drops, solution hypotension*, claudication, Raynaud’s phenomenon*, cold hands and feet* dorzolamide hydrochloride eye drops, solution Hypertension Respiratory, thoracic, and mediastinal disorders dorzolamide timolol eye drops solution sinusitis shortness of breath, respiratory failure, rhinitis, rarely bronchospasm dorzolamide hydrochloride eye drops, solution epistaxis* timolol maleate eye drops, solution dyspnoea* bronchospasm (predominantl y in patients with pre- existing bronchospasti c disease)*, respiratory failure, cough*.

Gastro- intestinal disorders dorzolamide timolol eye drops solution dysgeusia dorzolamide hydrochloride eye drops solution nausea* throat irritation, dry mouth* timolol maleate eye drops, solution nausea*, dyspepsia* diarrhoea, dry mouth* dysgeusia, abdominal pain, vomiting Skin and subcutaneou s tissue disorders dorzolamide timolol eye drops solution contact dermatitis, Stevens- Johnson syndrome, toxic epidermal necrolysis rash* timolol maleate eye drops, solution alopecia*, psoriasi form rash or exacerbation of psoriasis* skin rash Musculoskel etal and connective tissue disorders timolol maleate eye drops, solution systemic lupus erythematosus myalgia Renal and urinary disorders dorzolamide timolol eye urolithiasis drops solution Reproductive system and breast disorders timolol maleate eye drops, solution Peyronie’s disease*, decreased libido sexual dysfunction General disorders and administratio n site conditions dorzolamide hydrochloride eye drops, solution asthenia/f atigue* timolol maleate eye drops, solution asthenia/fat igue* *These adverse reactions were also observed with dorzolamide timolol eye drops solution during post-marketing experience **Additional adverse reactions have been seen with ophthalmic beta-blockers and may potentially occur with Dorzolamide / Timolol Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Cardiovascular/Respiratory Reactions Like other topically applied ophthalmic agents Timolol maleate is absorbed systemically. Due to beta-adrenergic component, timolol maleate, the same types of cardiovascular, pulmonary and other adverse reactions seen with systemic beta- adrenergic blocking agents may occur.

Incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration. 2. g. coronary heart disease, Prinzmetal's angina and cardiac failure) and hypotension therapy with beta-blockers should be critically assessed and the therapy with other active substances should be considered.

Patients with cardiovascular diseases should be watched for signs of deterioration of these diseases and of adverse reactions. Due to its negative effect on conduction time, beta-blockers should only be given with caution to patients with first degree heart block.

e. severe forms of Raynaud’s disease or Raynaud’s syndrome) should be treated with caution. Respiratory Disorders Respiratory reactions, including death due to bronchospasm in patients with asthma have been reported following administration of some ophthalmic beta-blockers.

Dorzolamide / Timolol should be used with caution, in patients with mild/moderate chronic obstructive pulmonary disease (COPD) and only if the potential benefit outweighs the potential risk. Hepatic Impairment Dorzolamide / Timolol has not been studied in patients with hepatic impairment and should therefore be used with caution in such patients.

Immunology and Hypersensitivity As with other topically-applied ophthalmic agents, this medicinal product may be absorbed systemically. Dorzolamide contains a sulfonamido group, which also occurs in sulphonamides. Therefore, the same types of adverse reactions found with systemic administration of 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 use of this preparation. Local ocular adverse effects, similar to those observed with dorzolamide hydrochloride eye drops, have been seen with dorzolamide timolol eye drops solution.

If such reactions occur, discontinuation of Dorzolamide / Timolol should be considered. While taking beta-blockers, patients with a history of atopy or a history of severe anaphylactic reaction to a variety of allergens may be more reactive to accidental, diagnostic, or therapeutic repeated challenge with such allergens and may be unresponsive to the usual doses of adrenaline used to treat anaphylactic reactions.

Concomitant Therapy The effect on intra-ocular pressure or the known effects of systemic beta-blockade may be potentiated when timolol maleate is given to the patients already receiving a systemic beta-blocking agent. The response of these patients should be closely observed.

5). The use of dorzolamide and oral carbonic anhydrase inhibitors is not recommended. Withdrawal of Therapy As with systemic beta-blockers, if discontinuation of ophthalmic timolol is needed in patients with coronary heart disease, therapy should be withdrawn gradually.

Additional Effects of Beta-Blockade Hypoglycaemia/diabetes Beta-blockers should be administered with caution in patients subject to spontaneous hypoglycaemia or to patients with labile diabetes, as beta-blockers may mask the signs and symptoms of acute hypoglycaemia.

Beta-blockers may also mask the signs of hyperthyroidism. Abrupt withdrawal of beta-blocker therapy may precipitate a worsening of symptoms. Corneal diseases Ophthalmic β-blockers may induce dryness of eyes. Patients with corneal diseases should be treated with caution.

g. of adrenaline. The anaesthesiologist should be informed when the patient is receiving timolol maleate. Therapy with beta-blockers may aggravate symptoms of myasthenia gravis. Additional Effects of Carbonic Anhydrase Inhibition 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 / Timolol, urolithiasis has been reported infrequently. Because Dorzolamide / Timolol contains 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 / Timolol.

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

Corneal oedema and irreversible corneal decompensation have been reported in patients with pre-existing chronic corneal defects and/or a history of intraocular surgery while using dorzolamide. There is an increased potential for developing corneal oedema in patients with low endothelial cell counts.

Precautions should be used when prescribing Dorzolamide / Timolol to these groups of patients. g. timolol, acetazolamide) after filtration procedures. As with the use of other antiglaucoma drugs, diminished responsiveness to ophthalmic timolol maleate after prolonged therapy has been reported in some patients.

However, in clinical studies in which 164 patients have been followed for at least three years, no significant difference in mean intraocular pressure has been observed […]

Dorzolamide / Timolol is contraindicated in patients with: • reactive airway disease, including bronchial asthma or a history of bronchial asthma, or severe chronic obstructive pulmonary disease • sinus bradycardia, sick sinus syndrome, sino-atrial block, second or third degree atrioventricular block not controlled with pace-maker.

Overt cardiac failure, cardiogenic shock • severe renal impairment (CrCl < 30 ml/min) or hyperchloraemic acidosis • hypersensitivity to one or both active substances or to any of the excipients. The above are based on the components and are not unique to the combination.