BRINZOLAMIDE/TIMOLOL ACCORD

Posology Use in adults, including the elderly:

The dose is one drop of Brinzolamide/Timolol in the conjunctival sac of the affected eye(s) twice daily. When using nasolacrimal occlusion or closing the eyelids, the systemic absorption is reduced. 4). If a dose is missed, treatment should be continued with the next dose as planned.

The dose should not exceed one drop in the affected eye(s) twice daily. When substituting another ophthalmic antiglaucoma medicinal product with Brinzolamide/Timolol, the other medicinal product should be discontinued and Brinzolamide/Timolol should be started the following day.

Special populations Paediatric population The safety and efficacy of Brinzolamide/Timolol in children and adolescents aged 0 to 18 years has not yet been established. No data is available. Hepatic and renal impairment No studies have been conducted with Brinzolamide/Timolol or with timolol 5mg/ml eye drops in patients with hepatic or renal impairment.

No dosage adjustment is necessary in patients with hepatic impairment or in patients with mild to moderate renal impairment. 3). 3). 4). Method of administration For ocular use. Patients should be instructed to shake the bottle well before use.

After cap is removed, if tamper evident snap collar is loose, remove before using product. To prevent contamination of the dropper tip and the suspension, care must be taken not to touch the eyelids, surrounding areas or other surfaces with the dropper tip of the bottle.

Instruct patients to keep the bottle tightly closed when not in use. If more than one topical ophthalmic medicinal product is being used, the medicinal products must be administered at least 5 minutes apart. Eye ointments should be administered last.

Summary of the safety profile In clinical trials, the most common adverse reactions were blurred vision, eye irritation and eye pain, occurring in approximately 2% to 7% of patients. Tabulated summary of adverse reactions The following adverse reactions have been reported during clinical studies and post- marketing surveillance with Brinzolamide/Timolol and the individual components brinzolamide and timolol.

They 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).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. System Organ Classification MedDRA Preferred Term (v. 4) Musculoskeletal and connective tissue disorders Not known: myalgia1, muscle spasms3, arthralgia3, back pain3, pain in extremity3 Renal and urinary disorders Uncommon: blood urine present1 Not known: renal pain3, pollakiuria3 Reproductive system and breast disorders Not known: erectile dysfunction3, sexual dysfunction2, decreased libido2 General disorders and administration site conditions Uncommon: malaise1,3 Not known: chest pain1, pain3, fatigue1, asthenia2,3, chest discomfort3, feeling jittery3, irritability3, peripheral oedema3, medication residue3 Investigations Uncommon: blood potassium increase1, blood lactate dehydrogenase increased1 1 adverse reaction observed for Brinzolamide/Timolol 2 additional adverse reactions observed with timolol monotherapy 3 additional adverse reactions observed with brinzolamide monotherapy Description of selected adverse reactions Dysgeusia (bitter or unusual taste in the mouth following instillation) was a frequently reported systemic adverse reaction associated with the use of Brinzolamide/Timolol during clinical trials.

It is likely to be caused by passage of the eye drops in the nasopharynx via the nasolacrimal canal and is attributable to brinzolamide. 2). Brinzolamide/Timolol contains brinzolamide which is a sulphonamide inhibitor of carbonic anhydrase with systemic absorption.

Systemic effects − Brinzolamide and timolol are absorbed systemically. Due to the beta- adrenergic blocking component, timolol, the same types of cardiovascular, pulmonary and other adverse reactions seen with systemic beta-adrenergic blocking agents may occur.

The incidence of systemic adverse reactions after topical ophthalmic administration is lower than for systemic administration. 2. − Hypersensitivity reactions common to all sulphonamide derivates can occur in patients receiving Brinzolamide/Timolol including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).

At the time of prescription, patients should be advised of the signs and symptoms and monitored closely for skin reactions as it is absorbed systemically. If signs of serious reactions or hypersensitivity occur, brinzolamide should be withdrawn immediately.

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. Hyperthyroidism Beta-blockers may also mask the signs of hyperthyroidism.

g. diplopia, ptosis and generalised weakness). Respiratory disorders Respiratory reactions, including death due to bronchospasm in patients with asthma have been reported following administration of some ophthalmic beta-blockers. Brinzolamide/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.

1. − Hypersensitivity to other beta-blockers. 4). − 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. 2). − Severe renal impairment.