Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Santen Oy, Niittyhaankatu 20, 33720, Tampere, Finland
Reactive airway disease including bronchial asthma or a history of bronchial asthma, severe chronic obstructive pulmonary disease; sinus bradycardia, sick sinus syndrome sino-atrial block, second- and third-degree atrioventricular block not controlled with pace-maker, overt cardiac failure, cardiogenic shock.
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
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.
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.
Cardiac failure should be adequately controlled before beginning therapy with Timoptol. Patients with a history of severe cardiac disease should be watched for signs of cardiac failure and have their pulse rates monitored.
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 reactions, including death due to bronchospasm in patients with asthma have been reported following administration of some ophthalmic beta-blockers.
Timoptol 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.
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.
Ophthalmic beta-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).
There have been reports of skin rashes and/or dry eyes associated with the use of beta-adrenoreceptor blocking drugs. The reported incidence is small and in most cases the symptoms have cleared when treatment was withdrawn. Discontinuation of the drug should be considered if any such reaction is not otherwise explicable. Cessation of therapy involving beta-blockade should be gradual.
Choroidal detachment has been reported with administration of aqueous suppressant therapy (e.g. timolol, acetazolamide) after filtration procedures.
Beta-blocking ophthalmological preparations may block systemic beta-agonist effects e.g. of epinephrine (adrenaline). The anaesthesiologist should be informed when the patient is receiving timolol.
Timoptol has been generally well tolerated in glaucoma patients wearing conventional hard contact lenses. Timoptol has not been studied in patients wearing lenses made with material other than polymethylmethacrylate (PMMA), which is used to make hard contact lenses.
Timoptol Eye Drops Solution contains benzalkonium chloride as a preservative which may be deposited in soft contact lenses; therefore Timoptol should not be used while wearing these lenses. The lenses should be removed before application of the drops and not reinserted earlier than 15 minutes after use.
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.
In patients with angle-closure glaucoma, the immediate objective of treatment is to reopen the angle. This requires constricting the pupil with a miotic. Timoptol has little or no effect on the pupil. When Timoptol is used to reduce elevated intra-ocular pressure in angle-closure glaucoma it should be used with a miotic and not alone.
Patients should be advised that if they develop an intercurrent ocular condition (e.g. trauma, ocular surgery or infection), they should immediately seek their physician’s advice concerning the continued use of the present multidose container (see section 4.2).
There have been reports of bacterial keratitis associated with the use of multiple dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface.
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 epinephrine (adrenaline) used to treat anaphylactic reactions.
Timolol solutions should generally be used cautiously in young glaucoma patients (see also section 5.2).
It is important to notify the parents of potential side effects so they can immediately discontinue the drug therapy (see section 4.8). Signs to look for are, for example, coughing and wheezing.
Because of the possibility of apnoea and Cheyne-Stokes breathing, the drug should be used with extreme caution in neonates, infants and younger children. A portable apnoea monitor may also be helpful for neonates on Timolol.
No specific drug interaction studies have been performed with timolol maleate.
There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic beta-blockers solution is administered concomitantly with oral calcium-channel blockers, beta-adrenergic blocking agents, antiarrhythmics (including amiodarone), digitalis glycosides, rauwolfia alkaloids, parasympathomimetics, guanethidine.
Although Timoptol alone has little or no effect on pupil size, mydriasis resulting from concomitant use of ophthalmic beta-blockers and epinephrine (adrenaline) has been reported occasionally.
Potentiated systemic beta-blockade (e.g. decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors (e.g. quinidine, fluoxetine, paroxetine) and timolol.
Oral beta-adrenergic blocking agents may exacerbate the rebound hypertension which can follow the withdrawal of clonidine.
Close observation of the patient is recommended when a beta-blocker is administered to patients receiving catecholamine-depleting drugs such as reserpine, because of possible additive effects and the production of hypotension and/or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Oral calcium-channel antagonists may be used in combination with beta-adrenergic blocking agents when heart function is normal, but should be avoided in patients with impaired cardiac function.
The potential exists for hypotension, AV conduction disturbances and left ventricular failure to occur in patients receiving a beta-blocking agent when an oral calcium-channel blocker is added to the treatment regimen. The nature of any cardiovascular adverse effects tends to depend on the type of calcium-channel blocker used. Dihydropyridine derivatives, such as nifedipine, may lead to hypotension, whereas verapamil or diltiazem have a greater propensity to lead to AV conduction disturbances or left ventricular failure when used with a beta-blocker.
Intravenous calcium channel blockers should be used with caution in patients receiving beta-adrenergic blocking agents.
The concomitant use of beta-adrenergic blocking agents and digitalis with either diltiazem or verapamil may have additive effects in prolonging AV conduction time.
There are no adequate data for the use of timolol maleate in pregnant women. Timoptol should not be used during pregnancy unless clearly necessary. To reduce the systemic absorption, see section 4.2.
Epidemiological studies have not revealed malformative effects but show a risk for intra uterine growth retardation when beta-blockers are administered by the oral route. In addition, signs and symptoms of beta-blockade (e.g. bradycardia, hypotension, respiratory distress and hypoglycaemia) have been observed in the neonate when beta-blockers have been administered until delivery. If Timoptol is administered until delivery, the neonate should be carefully monitored during the first days of life.
Timolol is detectable in human milk. A decision for breastfeeding mothers, either to stop taking Timoptol or stop nursing, should be based on the importance of the drug to the mother.
Possible side effects such as dizziness, visual disturbances, refractive changes, diplopia, ptosis, frequent episodes of mild and transient blurred vision and fatigue may affect some patients' ability to drive or operate machinery.
Like other topically applied ophthalmic drugs, timolol is absorbed into the systemic circulation. This may cause similar undesirable effects as seen with systemic beta-blocking agents. Incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration. The following adverse reactions have been reported with ocular administration of this or other timolol maleate formulations, either in clinical trials or since the drug has been marketed. Additional side effects have been reported in clinical experiences with systemic timolol maleate, and may be considered potential effects of ophthalmic timolol maleate. Also listed are adverse reactions seen within the class of ophthalmic beta-blockers and may potentially occur with Timoptol.
ocular: signs and symptoms of ocular irritation, (e.g. burning, stinging, itching, tearing, redness), conjunctivitis, blepharitis, keratitis, dry eyes, decreased corneal sensitivity, blurred vision, corneal erosion. Visual disturbances, including refractive changes (due to withdrawal of miotic therapy in some cases), diplopia, ptosis and choroidal detachment following filtration surgery (see section 4.4). Cases of corneal calcification have been reported very rarely in association with the use of phosphate containing eye drops in some patients with significantly damaged corneas.
ocular: tinnitus
ocular: bradycardia, chest pain, arrhythmia, heart block, congestive heart failure, palpitations, cardiac arrest, cardiac failure, oedema.
systemic: atrioventricular block (second- or third-degree), sino-atrial block, pulmonary oedema, worsening of arterial insufficiency, worsening of angina pectoris, vasodilation.
ocular: claudication, hypotension, Raynaud’s phenomenon, cold hands and feet.
ocular: bronchospasm (predominantly in patients with pre-existing bronchospastic disease), respiratory failure, dyspnoea, cough.
systemic: rales.
ocular: asthenia, fatigue.
systemic: extremity pain, decreased exercise tolerance.
ocular: alopecia, psoriasiform rash or exacerbation of psoriasis, skin rash.
systemic: sweating, exfoliative dermatitis.
ocular: systemic lupus erythematosus, pruritus.
systemic: signs and symptoms of allergic reactions including anaphylaxis, angioedema, urticaria, localised and generalised rash, anaphylactic reaction.
ocular: depression, insomnia, nightmares, memory loss.
systemic: diminished concentration, increased dreaming.
ocular: syncope, cerebrovascular accident, cerebral ischemia, headache, dizziness, increase in signs and symptoms of myasthenia gravis, paraesthesia.
systemic: vertigo, local weakness.
ocular: nausea, diarrhoea, dyspepsia, dry mouth, dysgeusia, abdominal pain, vomiting.
ocular: decreased libido, Peyronie’s disease, sexual dysfunction such as impotence;
systemic: micturition difficulties.
ocular: hypoglycaemia.
systemic: hyperglycaemia.
ocular: myalgia.
systemic: arthralgia.
systemic: non-thrombocytopenic purpura.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, website www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
None known.
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