Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use

Systemic effects
Like other topically applied ophthalmic agents, travoprost and timolol are absorbed systemically. Due to the beta-adrenergic component, timolol, the same types of cardiovascular, pulmonary and other adverse reactions seen with systemic beta- adrenergic blocking medicinal products may occur. The incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration. For information on how to reduce 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 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 their negative effect on conduction time, betablockers should only be given with caution to patients with first degree heart block.


Vascular disorders

DUO API DEC20 V3                                                                                EU SmPC Oct2020 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.
DuoTrav 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.


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


Muscle weakness
Beta- adrenergic blocking medicinal products have been reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g. diplopia, ptosis and generalised weakness).


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


Choroidal detachment
Choroidal detachment has been reported with administration of aqueous suppressant therapy (e.g. timolol, acetazolamide) after filtration procedures.


Other beta-blocking agents
The effect on intra ocular pressure or the known effects of systemic beta blockade may be potentiated when timolol is given to patients already receiving a systemic beta- blocking medicinal product. 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).


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


Hyperthyroidism
Beta blockers may mask the signs of hyperthyroidism.

Skin contact
Prostaglandins and prostaglandin analogues are biologically active substances that may be absorbed through the skin. Women who are pregnant or attempting to become pregnant should exercise appropriate precautions to avoid direct exposure to the contents of the bottle. In the unlikely event of coming in contact with a substantial portion of the contents of the bottle, thoroughly cleanse the exposed area immediately.


Anaphylactic reactions
DUO API DEC20 V3                                                                               EU SmPC Oct2020 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 unresponsive to the usual dose of adrenaline used to treat anaphylactic reactions.


Concomitant therapy
Timolol may interact with other medicinal products (see section 4.5). The use of two local prostaglandins is not recommended.

Ocular effects
Travoprost may gradually change the eye colour by increasing the number of melanosomes (pigment granules) in melanocytes. Before treatment is instituted, patients must be informed of the possibility of a permanent change in eye colour. Unilateral treatment can result in permanent heterochromia. The long term effects on the melanocytes and any consequences thereof are currently unknown. The change in iris colour occurs slowly and may not be noticeable for months to years. The change in eye colour has predominantly been seen in patients with mixed coloured irides, i.e. blue- brown, grey- brown, yellow- brown and green- brown; however, it has also been observed in patients with brown eyes. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery in affected eyes, but the entire iris or parts of it may become more brownish. After discontinuation of therapy, no further increase in brown iris pigment has been observed.
In controlled clinical trials, periorbital and/or eyelid skin darkening in association with the use of travoprost has been reported.

Periorbital and lid changes, including deepening of the eyelid sulcus have been observed with prostaglandin analogues.

Travoprost may gradually change eyelashes in the treated eye(s); these changes were observed in about half of the patients in clinical trials and include: increased length, thickness, pigmentation, and/or number of lashes. The mechanism of eyelash changes and their long-term consequences are currently unknown.

Travoprost has been shown to cause slight enlargement of the palpebral fissure in studies in the monkey.
However, this effect was not observed during the clinical trials and is considered to be species specific.

There is no experience of DuoTrav in inflammatory ocular conditions, nor in neovascular, angle- closure, narrow-angle or congenital glaucoma and only limited experience in thyroid eye disease, in open-angle glaucoma of pseudophakic patients and in pigmentary or pseudoexfoliative glaucoma.


Macular oedema has been reported during treatment with prostaglandin F2α analogues. Caution is recommended when using DuoTrav in aphakic patients, pseudophakic patients with a torn posterior lens capsule or anterior chamber lenses, or in patients with known risk factors for cystoid macular oedema.


In patients with known predisposing risk factors for iritis/uveitis, and in patients with active intraocular inflammation, DuoTrav can be used with caution.

Excipients
DuoTrav contains propylene glycol which may cause skin irritation.
DuoTrav contains polyoxyethylene hydrogenated castor oil 40 which may cause skin reactions.
Patients must be instructed to remove contact lenses prior to application of DuoTrav and wait 15 minutes after instillation of the dose before reinsertion (see section 4.2).

DUO API DEC20 V3                                                                                    EU SmPC Oct2020 

Effects on Driving

4.7 Effects on ability to drive and use machines
DuoTrav has minor influence on the ability to drive and use machines.
As with any eye drops, temporary blurred vision or other visual disturbances may occur. If blurred vision occurs at instillation, the patient must wait until the vision clears before driving or using machines.
DuoTrav may also cause hallucinations, dizziness, nervousness and/or fatigue (see section 4.8) which may affect the ability to drive and use machines. Patients should be advised not to drive and use machines if these symptoms occur.