BRINZOLAMIDE / TIMOLOL

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 must 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 must be discontinued and Brinzolamide / Timolol must 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 have not yet been established. No data are available. Hepatic and renal impairment No studies have been conducted with Brinzolamide / Timolol or with timolol 5 mg/mL eye drops in patients with hepatic or renal impairment.

No dose 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), urticaria3, maculo-papular rash3, generalised pruritus3, skin tightness3, dermatitis3, alopecia1, psoriasiform rash or exacerbation of psoriasis2, rash1, erythema1 Musculoskeletal Not known: myalgia1, muscle spasms3, arthralgia3, back and connective tissue disorders 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 reactions 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.

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 including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) reported with sulphonamide derivates can occur in patients receiving Brinzolamide / Timolol as it is absorbed systemically.

At the time of prescription, patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs of serious reactions or hypersensitivity occur, Brinzolamide / Timolol 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 must 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.