Therapeutic indications
Reduction of elevated intraocular pressure in conditions such as:
- Ocular hypertension
- Chronic open ' angle glaucoma (including aphakic patients)
- Some cases of secondary glaucoma
Posology and method of administration
Adults and children over 12 years; recommended therapy is one drop of Timolol Eye Drops in the affected eye(s) twice a day.
Elderly: Dosage need not be modified for the elderly as there has been wide experience with the use of Timolol Eye Drops in elderly patients.
Children below the age of 12 years: This product is currently not recommended for use.
Intraocular pressure should be reassessed approximately four weeks after starting treatment because response to Timolol Eye Drops may take a few weeks to stabilize. Provided that intraocular pressure is maintained at satisfactory levels, many patients can then be placed on once daily therapy.
If clinical response is not adequate, dosage may be increased to one drop of Timolol Eye drops in each affected eye twice daily.
If necessary, concomitant treatment with miotics, epinephrine and/or carbonic anhydrase inhibitors can be instituted. In order to prevent the active substance(s) from being washed out when additional ophthalmic medication is used, an interval of at least 10 minutes between each application is recommended. The use of two topical beta ' adrenergic agents is not recommended.
Transfer from other topical beta ' blocking agents: Discontinue use after a full day of therapy and start treatment with Timolol Eye Drops the next day, with one drop in each affected eye twice daily.
Transfer form a single antiglaucoma agent other than a topical beta ' blocking agent: Continue the agent and add one drop of Timolol Eye Drops in each affected eye twice daily. On the following day, discontinue the previous agent completely, and continue with Timolol Eye Drops.
Patients should be instructed to remove soft contact lenses before using timolol.
Contraindications
Timolol Eye Drop is contraindicated in patients with:
- Cardiogenic shock;
- Over cardiac failure;
- Second and third degree AV block;
- Sinus bradycardia;
- Presence or history of bronchial asthma;
- Presence or history of severe chronic obstructive pulmonary disease;
- Severe peripheral circulatory disturbances (Raynaud disease);
- Hypersensitivity to any component of this product or other beta ' blocking agents.
Special warnings and precautions for use
Like other topically applied ophthalmic drugs, Timolol Eye Drops may be absorbed systemically and adverse reactions seen with oral beta ' blockers may occur. Patients who are receiving a beta ' adrenergic blocking agent orally and Timolol Eye Drops should be observed for a potential additive effect either on the intraocular pressure or on the known systematic effects of beta blockage.
Patients should not receive two topical ophthalmic beta ' adrenergic blocking agents concurrently.
Cardiac failure should be adequately controlled before beginning therapy with Timolol Eye Drops. Patients with a history of severe cardiac disease should be watched for signs of cardiac failure. Respiratory and cardiac reactions, including death due to bronchospasm in patients with asthma and rarely, death associated with cardiac failure have been reported.
Timolol Eye Drops should be used with caution in patients with sick sinus syndrome, Prinzmetal's angina, untreated phaeochromocytoma, metabolic acidosis, hypertension and diabetics under treatment (timolol may mask the signs of and response to hypoglycemia).
Risk from 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, accidental, diagnostic or therapeutic. Such patients may be unresponsive to the usual dose of adrenaline used to treat anaphylactic reactions.
This formulation of Timolol Eye Drops contains benzalkonium chloride as a preservative which may be deposited in soft contact lenses. Hence, Timolol Eye Drops should not be used while wearing these lenses. The lenses should be removed before instillation of the drops and not reinserted earlier than 15 minutes after use.
When timolol Eye Drops is used to reduce intraocular pressure in angle ' closure glaucoma, it should be used with a miotic and not alone.
A reduction in ocular hypotensive response has been reported in some patients following prolonged therapy with timolol Maleate eye drops.
Muscle weakness: Beta ' adrenergic blockade has been reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g. diplopia, ptosis, and generalized weakness). Timolol Eye Drops have been reported rarely to increase muscle weakness in some patients with myasthenia gravis or myasthenic symptoms.
Choroidal detachment has been reported with administrative of aqueous suppressant therapy (e.g. timolol, acetazolamide) after filtration procedures.
Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures.
Patients should also be instructed that ocular solutions, if handled improperly can become contaminated by common bacteria know to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.
Patients should also be advised that if they develop any intercurrent ocular condition (e.g. trauma, ocular surgery or infection),they should immediately seek their physician's advice concerning the continued use of present multi ' dose container.
There have been reports of bacteria keratitis associated with the use of topical ophthalmic products.
Interaction with other medicinal products and other forms of interaction
Although Timolol Eye Drops alone has little or no effect on pupil size, mydriasis has occasionally been reported when Timolol is given with adrenaline.
The effect on intraocular pressure or the known effects of systemic beta ' blocking agent. The response of these patients should be closely monitored.
As Timolol Eye Drops may be absorbed systemically, the following interactions seen with oral beta blockers may occur.
Calcium channel blockers (verapamil and diltiazem): negative effect on contractility and atrio-ventricular conduction can lead to cardiac failure and hypotension.
Digitalis glycosides: in association with calcium channel blockers may increase atrio-ventricular conduction time.
Catecholamine ' depleting drugs (rauwolfia alkaloids, reserpine etc): potentiation of hypotension and /or marked bradycardia.
Clonidine: increased risk of 'rebound hypertension' on discontinuation of clonidine.
Class I anti ' arrhythmic drugs (e.g. disopyramide, quinidine) and amiodarone: potentiation of bradycardia, sinus arrest and AV block.
Anaesthetic drugs: increased risk of myocardial depression and hypotension due to blockage of cardiac response to reflex sympathetic stimuli.
Cimetidine, hydralazine, phenothiazines and alcohol: may increase plasma level of timolol.
Pregnancy and lactation
Timolol Eye Drops has not been studied in human pregnancy. However, timolol may cross the placenta with the potential to cause adverse effects of beta ' blockade e.g. bradycardia in the foetus and neonate. Timolol Eye Drops should therefore not be used in pregnancy unless the potential benefit to the pregnant woman justifies the potential risk to the foetus.
Timolol Eye Drops may be systemically absorbed and excreted in the breast milk, with the potential to cause adverse effects related to beta 'blockade in the infant. Treatment during breast feeding is therefore not recommended unless the potential benefit to the nursing mother justifies the potential risk both to the infant and to the mother.
Effects on ability to drive and use machines
There are currently no data available on the effects of Timolol Eye Drops on the ability to drive or use machinery. IT has to be taken into account that dizziness, fatigue, transient ocular irritation, blurred vision and lacrimation may occur occasionally.
Undesirable effects
Timolol Eye drops are usually well tolerated. The following adverse reactions have been reported either in clinical trials or since the drug has been marketed:
Body as whole: Headache, asthenia, fatigue, chest pain.
Nervous system/Psychiatric:
Dizziness, depression, insomnia, nightmares, memory loss, increase in signs and symptoms of myasthenia gravis, paraesthesia.
Skin:
Hypersensitivity including localised and generalized rash, urticaria, alopecia, exacerbation of psoriasis.
Respiratory:
Bronchospasm (predominantly in patients with pre ' existing bronchospastic disease), respiratory failure, dyspnoea, nasal congestion, cough.
Endocrine:
Masked symptoms of hypoglycemia in insulin ' dependant diabetics.
Special senses:
Signs and symptoms of ocular irritation, including burning and stinging, conjunctivitis, blepharitis, keratitis, blepharoptosis, decreased corneal sensitivity, visual disturbances including refractive changes (due to withdrawal of miotic therapy in some cases), diplopia, ptosis, choroidal detachment following filtration surgery.
Casual relationship unknown:
The following adverse effects have been reported, and a causal relationship to therapy with Timolol eye drops has not been established.
Cardiovascular:
Hypertension, pulmonary edema, worsening of angina pectoris;
Digestive:
anorexia
Nervous System/Psychiatric :
Behavioral changes including confusion, hallucinations, anxiety, disorientation, nervousness, somnolence and other psychic disturbances.
The following additional adverse effects have been reported in clinical experience with oral Timolol Maleate, and may be considered potential effects of ophthalmic Timolol Maleate.
Body as a whole: Extremity pain, decreased exercise tolerance, weight loss, Cardiovascular: Oedema, Worsening of arterial insufficiency, Raynaud's phenomenon, vasodilatation; Digestive Gastrointestinal pain, hepatomegaly, vomiting; Haematologic: Nonthrombocytopenic purpura; Endocrine: Hyperglycaemia; Hypoglycaemia; skin: Pruritis, skin irritation, increased pigmentation, sweating, cold hands and feet: Musculoskeletal: Arthralgia, claudication; Nervous System/Psychiatric: Vertigo, local weakness, decreased libido, nightmares, insomnia, diminished concentration; Respiratory: Rales, bronchial obstruction; Special Senses: Tinnitus, dry eyes; Urogential: Urination difficulties.
Potential adverse effects: In addition, a variety of adverse effects have been reported with other beta-adrenergic blocking agents and may be considered potential effects of ophthalmic Timolol Maleate: Digestive: Mesenteric arterial thrombosis, ischaemic colitis; Haematologic: Agranulocytosis , thrombocytopenic purpura; Nervous system: reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation for time and place, short ' term memory loss, emotional liability, slightly clouded sensorium and decreased performance on neuropsychometrics; Allergic: Erythematous rash, fever combined with aching and sore throat, layngospasm with respiratory distress; Urogenital: Peyronie's disease.
There have been reports of a syndrome comprising psoriasiform skin rash, conjunctivitis sicca, otitis and sclerosing serositis attributed to the beta ' adrenergic receptor blocking agent, practolol. This syndrome has been reported with Timolol Maleate.
