Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use

Cardiovascular/Respiratory Reactions
Like other topically applied ophthalmic agents timolol is absorbed systemically. Due to beta-adrenergic component, timolol, 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. To reduce the systemic absorption, see section 4.2.

Cardiac Disorders:
In patients with cardiovascular diseases (e.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.

Vascular Disorders:
Patients with severe peripheral circulatory disturbance/disorders (i.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.
COSOPT 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

This medicinal product 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 sulfonamides.
Therefore, the same types of adverse reactions found with systemic administration of sulfonamides 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 this medicinal product. If such reactions occur, discontinuation of this medicinal product 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 repeated challenge with such allergens and may be unresponsive to the usual dose 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 is given to the patients already receiving a systemic beta-blocking agent. The response of these patients should be closely observed. The use of two topical beta-adrenergic blocking agents is not recommended (see section 4.5).

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 beta-blockers may induce dryness of eyes. Patients with corneal diseases should be treated with caution.

Surgical anaesthesia
Beta-blocking ophthalmological preparations may block systemic beta-agonist effects e.g. of adrenaline.
The anaesthesiologist should be informed when the patient is receiving timolol.

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 this medicinal product, urolithiasis has been reported infrequently.
Because COSOPT 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 this medicinal product.

Other

The management of patients with acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents. This medicinal product 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 COSOPT to these groups of patients.
Choroidal detachment has been reported with administration of aqueous suppressant therapies (e.g.
timolol, acetazolamide) after filtration procedures.
As with the use of other antiglaucoma medicines, 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 after initial stabilization.

Benzalkonium chloride
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.


Contact Lens Use
This medicinal product contains the preservative benzalkonium chloride, which may cause eye irritation.
Remove contact lenses prior to application and wait at least 15 minutes before reinsertion.
Benzalkonium chloride is known to discolour soft contact lenses.

Effects on Driving

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 side effects such as blurred vision may affect some patients’ ability to drive and/or operate machinery.