INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo GLAUCOSAN® 0,25% EYE DROPS.
GLAUCOSAN® 0,5% EYE DROPS.

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

GLAUCOSAN® 0,25% EYE DROPS.
GLAUCOSAN
® 0,5% EYE DROPS.

COMPOSITION:
0,25% Eye Drops - Each mL contains Timolol 2,5 mg (present as timolol maleate)
        Preservative: Benzalkonium chloride 0,01% m/v
0,5% Eye Drops - Each mL contains Timolol 5,0 mg (present as timolol maleate)
        Preservative: Benzalkonium chloride 0,01% m/v

PHARMACOLOGICAL CLASSIFICATION:
A 15.4 Ophthalmic Preparations, other.

PHARMACOLOGICAL ACTION:
Timolol maleate eye drops reduce elevated and normal intraocular pressure, whether or not associated with glaucoma. Timolol maleate is a short-acting, potent, non-selective, beta-adrenergic antagonist. It has no intrinsic sympathomimetic activity and no membrane stabilizing activity.
Timolol maleate eye drops reduce intraocular pressure with little or no effect on accommodation or pupil size.

INDICATIONS:
Timolol maleate eye drops are indicated for the reduction of elevated intraocular pressure.
Patients with ocular hypertension.
Patients with chronic open angle glaucoma.
Aphakic patients with glaucoma.
Some patients with secondary glaucoma.
Patients with narrow angles and a history of spontaneous or iatrogenically-induced narrow-angle closure in the opposite eye in whom reduction of intraocular pressure is necessary. (See Side Effects and Special Precautions)
Timolol maleate eye drops are also indicated as concomitant therapy in patients with paediatric glaucoma, who are inadequately controlled with other antiglaucoma therapy.

CONTRA-INDICATIONS:
Hypersensitivity to timolol maleate, or any of the other ingredients of this preparation.
Particular caution should be exercised with patients suffering from the following: asthma, bronchitis, chronic respiratory diseases, second and third degree heart block and sinus bradycardia less than 50 per minute, peripheral vascular diseases and Raynaud’s phenomenon.
Use in Pregnancy :
Safety in pregnancy has not been established. Administration to pregnant mothers shortly before birth or during labour may result in the newborn infants being born hypotonic, collapsed and hypoglycaemic.
In the perioperative period it is generally unwise to reduce the dosage. A patient’s normal tachycardiac response to hypovolaemia or blood loss may be obscured during or after surgery. Particular caution should be taken in this regard.

WARNINGS:
Caution should be exercised in the use of benzalkonium chloride preserved topical medication over an extended period in patients with extensive ocular surface disease.
As the possibility of an adverse effect on corneal permeability and the danger of disruption of the corneal epithelium with prolonged usage of benzalkonium chloride preserved ophthalmological preparations cannot be excluded, regular ophthalmic examination is required.

DOSAGE AND DIRECTIONS FOR USE:
Treatment can be initiated at one drop of 0,25% solution in each affected eye twice a day.
If clinical response is not adequate, dosage may be changed to one drop of 0,50% solution in each affected eye twice a day.
If needed concomitant therapy with miotics, epinephrine and systemically administered carbonic anhydrase inhibitors may be instituted in association with timolol maleate eye drops.
Since in some patients the pressure-lowering response to timolol maleate eye drops may require a few weeks to stabilize, evaluation should include a determination of intraocular pressure after approximately 4 weeks of treatment with timolol maleate eye drops
If the intraocular pressure is maintained at satisfactory levels, many patients can be maintained on once-a-day therapy. Because of naturally occurring diurnal variations in intraocular pressure, satisfactory response is best determined by measuring the intraocular pressure at different times during the day.
How to transfer patients from other therapy:
When a patient is transferred from another topical ophthalmic beta adrenergic blocking agent, that agent should be discontinued after proper dosing on one day and treatment with GLAUCOSAN, should be started on the following day, using the above mentioned dosing regimen.
When a patient is transferred from a single antiglaucoma agent, continue the agent already being used and add one drop of GLAUCOSAN in each affected eye, once a day. On the following day, discontinue the previously used antiglaucoma agent completely and continue with GLAUCOSAN. If a higher dose of GLAUCOSAN is required, substitute with one drop of solution in each affected eye twice a day.
When a patient is transferred from several concomitantly administered antiglaucoma agents, individualization is required. The physician may be able to discontinue some or all of the other antiglaucoma agents. Adjustments should involve one agent at a time.
Use in Children:
The usual starting dose is one drop of GLAUCOSAN 0,25% in the affected eye(s) every 12 hours, in addition to other antiglaucoma medication. The dosage may be increased to one drop of 0,50% solution in the affected eye(s) every 12 hours, if necessary.
The use of GLAUCOSAN eye drops is not recommended in premature infants or neonates.
The content of the GLAUCOSAN eye drops should be discarded after a period of 30 days after first opening container.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects:
Timolol maleate eye drops are usually well tolerated, the following adverse reactions have been reported.
Aphakic cystoid macular oedema has been reported, although a causal relationship to timolol maleate eye drops has not yet been established.
Eyes:
Signs and symptoms of ocular irritation, including conjunctivitis, blepharitis and keratitis and a decrease in corneal sensitivity, have been reported. Visual disturbances including refractive changes (due to withdrawal of miotic therapy in some cases), diplopia and ptosis have been reported.
Cardiovascular:
Bradycardia, arrhythmia, hypotension, syncope, heart block, cerebrovascular accident, cerebral ischaemia, congestive heart failure, palpitation, cardiac arrest.
Respiratory:
Bronchospasm (predominantly in patients with pre-existing bronchospastic disease), respiratory failure, dyspnoea.
Body as a whole:
Headache, asthenia, fatigue, chest pain.
Integumentary:
Hypersensitivity reactions, including localized and generalized rash, urticaria and alopecia.
Nervous system:
Dizziness, depression, increase in signs and symptoms of myasthenia gravis.
Digestive:
Nausea.
Special Precautions:
Although timolol maleate eye drops are applied topically, this medicine may be absorbed systemically.
The same adverse effects found with systemic administration of beta adrenergic blocking agents may occur with topical administration.
Timolol maleate eye drops should be used with caution in patients with known contra-indications to systemic use of beta adrenergic blocking agents.
These include sinus bradycardia and greater than first degree heart block, cardiogenic shock, diabetes, especially labile diabetes.
Cardiac failure should be adequately controlled before beginning treatment with timolol maleate eye drops.
In patients with a history of severe cardiac disease, signs of cardiac failure should be watched for and pulse rates should be checked.
Patients who are already receiving a beta adrenergic receptor blocking agent orally and who are given timolol maleate eye drops should be observed for potential additive effect, either on the intra - ocular pressure or on the known systemic effects of beta blockade.
In patients with angle closure glaucoma, the immediate objective of treatment is to reopen the angle. This requires constricting the pupil with a miotic. Timolol maleate eye drops have little or no effect on the pupil. When timolol maleate eye drops are used to reduce elevated intra-ocular pressure, in angle closure glaucoma it should be used with a miotic and not alone.
The preservative in GLAUCOSAN eye drops, may be deposited in soft contact lenses. GLAUCOSAN eye drops should not be used while wearing these lenses.
Lenses should be removed before application of the drops and should not be reinserted earlier than 15 minutes after use.
Risk from Anaphylactic Reaction
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, either accidental, diagnostic or therapeutic. Such patients may be unresponsive to the usual doses of adrenaline used to treat anaphylactic reactions.
Interactions
Timolol maleate eye drops have no effect on pupil size when used alone, midriasis resulting from concomitant therapy with adrenaline has been reported. The potential exists for additive effects and production of hypotension and/or marked bradycardia, when timolol maleate eye drops are administered together with an oral calcium channel blocker, catecholamine depleting drugs or beta adrenergic blocking drugs.
While no side effects of the oculo cutaneous syndrome type have been described, with use of this product the possibility of their development with prolonged usage has not been excluded and regular ophthalmic examination is required.
Bronchoconstriction may occur in patients suffering from asthma, bronchitis and other chronic pulmonary diseases. Congestive cardiac failure and marked bradycardia may occur.
A variety of neuropsychiatric disorders may occur, ranging from vague fatigue and malaise, sleeplessness, vivid dreams and nightmares, to overt psychosis.
The following may occur:
Exacerbation of peripheral vascular disease, or the development of Raynaud's phenomenon (due to unopposed arteriolar alpha-sympathetic activation), sexual impotence, hypoglycaemia, skeletal muscle weakness and gastro-intestinal disturbances. Severe peripheral vascular disease and even peripheral gangrene may be precipitated.
Safety in long term administration has not been demonstrated.
Adverse reactions are more common in patients with renal decompensation.
It can be dangerous to administer GLAUCOSAN eye drops concomitantly with the following medicines:
Hypoglycaemic agents, phenothiazines and various anti-arrhythmic agents.
N.B.        Such interactions can have life-threatening consequences.
Timolol maleate eye drops should be administered with care in patients suffering from myasthenia gravis. Deterioration in myasthenia has been reported following application of the eye drops.
Special Note: Digitalisation of patients receiving long-term beta-blocker therapy may be necessary if congestive cardiac failure is likely to develop. This combination can be considered despite the potentiation of negative chronotropic effects of the two medicines. Careful control of dosages and of the individual patients’ response (especially pulse rate) is essential in this situation.
Abrupt discontinuation of therapy may cause exacerbation of angina pectoris in patients suffering from ischaemic heart disease. Discontinuation of therapy should be gradual and patients should be advised to limit the extent of their physical activity during the period that the medicine is being discontinued.
Patients with phaeochromocytoma usually require treatment with alpha-adrenergic blocker.
Use in Pregnancy:
Safety in pregnancy has not been established. The use of timolol maleate eye drops requires that the anticipated benefit be weighed against possible hazards.
Nursing mothers:
Timolol maleate is detectable in human milk. Because of the potential for serious adverse reactions to timolol maleate in infants, a decision should be made whether to discontinue nursing or to discontinue the medication, taking into consideration the importance of the medication to the mother.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Overdosage may produce symptomatic bradycardia, hypotension, bronchospasm and acute cardiac failure. The following therapeutic measures should be considered:
Gastric lavage: If ingested - studies have shown that timolol maleate does not dialyse readily. Gastric lavage should be performed if within 4 hours of suspected overdose. Repeated activated charcoal is necessary in severe overdoses.
Symptomatic bradycardia: Use atropine sulphate intravenously in a dosage of 0,25 - 2 mg to induce vagal blockade. If bradycardia persists, intravenous isoproterenol hydrochloride should be administered, cautiously. In refractory cases the use of an intravenous pacemaker may be considered.
Hypotension : Use sympathomimetic pressor therapy e.g. dopamine, dobutamine or levarterenol. In refractory cases the use of glucagon hydrochloride has been reported to be useful.
Bronchospasm: Use isoproterenol hydrochloride. Additional therapy with aminophyline may be considered.
Acute cardiac failure: Conventional therapy with digitalis, diuretics and oxygen should be instituted immediately. In refractory cases the use of intravenous aminophyline is suggested. This may be followed if necessary by glucagon hydrochloride which has been reported to be useful.
Heart block (second or third degree): Use isoproterenol hydrochloride or a transvenous cardiac pacemaker.

IDENTIFICATION:
GLAUCOSAN 0,25% EYE DROPS         A clear and colourless solution
GLAUCOSAN 0,5% EYE DROPS         A clear and colourless solution

PRESENTATION:
GLAUCOSAN 0,25% EYE DROPS         Supplied in ocumeters containing 5 mL solution
GLAUCOSAN 0,5% EYE DROPS         Supplied in ocumeters containing 5 mL solution

STORAGE INSTRUCTIONS:
Store below 25°C. Protect from light.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
GLAUCOSAN 0,25% EYE DROPS         27/15.4/0312
GLAUCOSAN 0,5% EYE DROPS         27/15.4/0313

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Hexal Pharma (SA)(PTY) LTD
10 Fangio Road
Mahogany Ridge
Westmead
3610

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
26 April 1994

                        GAP1

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