Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Like other topically applied ophthalmic medicinal products, the active substances (timolol/bimatoprost) in GANFORT may be absorbed systemically. No enhancement of the systemic absorption of the individual active substances has been observed.
Due to the beta-adrenergic component, timolol, the same types of cardiovascular, pulmonary and other adverse reactions as seen with systemic beta-blockers 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
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 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.
GANFORT 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.


Endocrine disorders
Beta-adrenergic blocking medicinal products should be administered with caution in patients subject to spontaneous hypoglycemia or to patients with labile diabetes as beta- blockers may mask the signs and symptoms of acute hypoglycemia.
Beta-blockers may also mask the signs of hyperthyroidism.

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

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 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).

Anaphylactic reactions
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.

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

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

Hepatic
In patients with a history of mild liver disease or abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST) and/or bilirubin at baseline, bimatoprost had no adverse reactions on liver function over 24 months. There are no known adverse reactions of ocular timolol on liver function.

Ocular
Before treatment is initiated, patients should be informed of the possibility of eyelash growth, darkening of the eyelid or periocular skin and increased brown iris pigmentation since these have been observed during treatment with bimatoprost and GANFORT.
Increased iris pigmentation is likely to be permanent, and may lead to differences in appearance between the eyes if only one eye is treated. After discontinuation of GANFORT, pigmentation of iris may be permanent. After 12 months treatment with GANFORT, the incidence of iris pigmentation was 0.2%. After 12 months treatment with bimatoprost eye drops alone, the incidence was 1.5% and did not increase following 3 years treatment. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. The long-term effects of increased iridial pigmentation are not known. Iris colour changes seen with ophthalmic administration of bimatoprost may not be noticeable for several months to years. Neither nevi nor freckles of the iris appear to be affected by treatment. Periorbital tissue pigmentation has been reported to be reversible in some patients.

Macular oedema, including cystoid macular oedema has been reported with GANFORT.
Therefore, GANFORT should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular oedema (e.g. intraocular surgery, retinal vein occlusions, ocular inflammatory disease and diabetic retinopathy). GANFORT should be used with caution in patients with active intraocular inflammation (e.g. uveitis) because the inflammation may be exacerbated.

Skin
There is a potential for hair growth to occur in areas where GANFORT solution comes repeatedly in contact with the skin surface. Thus, it is important to apply GANFORT as instructed and avoid it running onto the cheek or other skin areas.

Excipients
The preservative in GANFORT, benzalkonium chloride, may cause eye irritation.
Contact lenses must be removed prior to application, with at least a 15-minute wait before reinsertion. Benzalkonium chloride is known to discolour soft contact lenses.
Contact with soft contact lenses must be avoided.
Benzalkonium chloride has been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. Therefore, monitoring is required with frequent or prolonged use of GANFORT in dry eye patients or where the cornea is compromised.

Other conditions
GANFORT has not been studied in patients with inflammatory ocular conditions, neovascular, inflammatory, angle-closure glaucoma, congenital glaucoma or narrow-angle glaucoma.
In studies of bimatoprost 0.3 mg/ml in patients with glaucoma or ocular hypertension, it has been shown that more frequent exposure of the eye to more than 1 dose of bimatoprost daily may decrease the IOP-lowering effect. Patients using GANFORT with other prostaglandin analogues should be monitored for changes to their intraocular pressure.

Effects on Driving

4.7   Effects on ability to drive and use machines
GANFORT has negligible influence on the ability to drive and use machines. As with any ocular treatment, if transient blurred vision occurs at instillation, the patient should wait until the vision clears before driving or using machines.