Timolol

Timolol

timolol

Manufacturer:

Novartis

Distributor:

Zuellig
/
Firma Chun Cheong
Full Prescribing Info
Contents
Timolol maleate.
Description
1 ml solution contains 5 mg timolol (as maleate).
Excipients with known effect: 1 ml solution contains 0.1 mg benzalkonium chloride.
Excipients/Inactive Ingredients: Benzalkonium chloride, Sodium dihydrogen phosphate dihydrate, Disodium phosphate dodecahydrate, Sodium hydroxide and/or concentrated hydrochloric acid, Purified water.
Action
Pharmacotherapeutic group: beta-blocking agents. ATC code: S01 ED 01.
Pharmacology: Pharmacodynamics: Mechanism of Action: The precise mechanism of the ocular hypotensive action of TIMOLOL MALEATE eye drops is not clearly established at this time. Tonography and fluorophotometry studies in man suggest that the predominant action may be related to reduced aqueous humour formation. However, in some studies a slight increase in outflow facility was also observed.
Pharmacodynamic effects: Timolol maleate is a non-selective beta-blocker without significant intrinsic sympathomimetic, direct myocardial depressant, or local anaesthetic (membrane-stabilising) activity.
Beta-adrenergic receptor blockade reduces the cardiac output both in healthy subjects and in patients with a heart disease. In patients with severe impairment of myocardial function, beta-adrenergic receptor blockade may inhibit the stimulatory effect of the sympathetic nervous system necessary to maintain an adequate cardiac function.
Beta-adrenergic receptor blockade in the bronchi and bronchioles results in an increased airway resistance through the unopposed parasympathetic activity. Such an effect is potentially dangerous in patients with asthma or other bronchospastic conditions.
TIMOLOL MALEATE eye drops, when applied topically in the eye, has the action of reducing elevated as well as normal intraocular pressure, whether or not accompanied by glaucoma. Elevated intraocular pressure is a major risk factor in the pathogenesis of glaucomatous visual field loss. The higher the level of intraocular pressure, the greater the likelihood of glaucomatous visual field loss and optic nerve damage.
Unlike miotics, TIMOLOL MALEATE eye drops reduces intraocular pressure with little or no effect on accommodation or pupil size.
Thus, changes in visual acuity due to increased accommodation are uncommon, and dim or blurred vision and night blindness produced by miotics are not evident. In addition, the inability to see around lenticular opacities when the pupil is constricted is avoided in patients with cataracts.
Clinical efficacy and safety: Clinical studies show that timolol eye drops reduce IOP in eyes with both normal and raised pressure.
Paediatric population: There is only very limited data available on the use of timolol (0.5% twice daily one drop) in the paediatric population for a treatment period up to 12 weeks. One small, double blinded, randomized, published clinical study conducted on 105 children (n=71 on timolol) aged 12 days - 5 years show to some extent evidence, that timolol in the indication primary congenital and primary juvenile glaucoma is effective in short term treatment.
Pharmacokinetics: Absorption: Following oral administration, maximum timolol plasma concentrations are achieved within 2 hours or less. Plasma concentrations decline with terminal half‑life of 4 to 5 hours.
80% of each eye drop passes through the nasolacrimal system where it may be rapidly absorbed into the systemic circulation via the nasal mucosa, conjunctiva, nasolacrimal duct, oropharynx and gut, or the skin from tear overflow.
In a clinical study in 16 volunteers dosed bilaterally with 0.5% timolol solution twice daily for 2 weeks (600 μg total dose per administration), peak steady‑state plasma concentrations ranged from below the 1 ng/mL quantitation limit to 5 ng/mL.
Distribution: Mean peak concentrations of about 870 ng/mL and 16 ng/mL in aqueous humor and plasma respectively, were achieved in 30 minutes after dosing. At 24 hours post‑dose, mean aqueous humor and plasma levels had declined to 6 ng/ml and 3 ng/ml respectively.
Studies in pigmented rabbits showed that timolol had prolonged retention and slow elimination from iris and ciliary body, indicating significant binding to melanin.
Timolol plasma protein binding is low (<10%).
Biotransformation: In humans, timolol is metabolized by cleavage of the morpholine ring to form two primary metabolites. These are an acetyl ethanol secondary amine derivative which undergoes subsequent loss of the acetyl side chain to form an ethanolic primary amine analog.
Hydroxylation of the terminal methyl group on the t‑butyl moiety to form an alcohol is a minor metabolic pathway in humans. Timolol is primarily metabolized in the liver by the CYP2D6 isozyme. Higher plasma concentrations were detected in CYP2D6 poor metabolizers compared with extensive metabolizers. Similar results have been obtained after the administration of ophthalmic timolol.
No timolol metabolism occurs within the eye.
Elimination: Following oral administration of radiolabelled timolol to human volunteers, approximately 72% of the dose was excreted within 84 hours, with 66% excreted in urine and 6% in feces.
Approximately 20% of the dose was excreted as unchanged drug in the urine.
Pharmacokinetic studies evaluating TIMOLOL MALEATE 0.5% solution (eye drops) in patients with hepatic and renal impairment and in geriatric patients have not been conducted. Since timolol is eliminated by liver metabolism by and urinary excretion, higher plasma levels of timolol may occur in patients with hepatic or renal impairment.
Linearity/non-linearity: Studies evaluating dose proportionality on systemic exposure following topical ocular doses have not been conducted.
Paediatric population: As already confirmed by adult data, 80% of each eye drop passes through the nasolacrymal system where it may be rapidly absorbed into the systemic circulation via the nasal mucosa, conjunctiva, nasolacrymal duct, oropharynx and gut, or the skin from tear overflow. Due to the fact that the blood volume in children is smaller than that in adults a higher circulation concentration has to be taken into account. In addition, neonates have immature metabolic enzyme pathways and it may result in an increase in elimination half‑life and potentiating adverse events.
Limited data show that plasma timolol levels in children after 0.25% greatly exceed those in adults after 0.5%, especially in infants and are presumed to increase the risk of side effects such as bronchospasm and bradycardia.
Toxicology: Preclinical safety data: Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the maximum human topical ocular exposure indicating little relevance to clinical use.
Teratogenicity studies with timolol in mice, rats, and rabbits at oral doses up to 50 mg/kg/day (7000 times the systemic exposure following the MRHOD) demonstrated no evidence of fetal malformations.
Although delayed ossification was observed at this dose in rats, there were no adverse effects on postnatal development of offspring. Doses of 1000 mg/kg/day (142,000 times the systemic exposure following the MRHOD) were maternotoxic in mice and resulted in an increased number of fetal resorptions. Increased fetal resorptions were also seen in rabbits at doses of 14,000 times the systemic exposure following the MRHOD, in this case without apparent maternotoxicity.
Beta-blockers are excreted in breast milk. However, at the therapeutic doses of timolol found in eye drops it is not likely that sufficient amounts would be present in breast milk to produce clinical symptoms of beta-blockade in the infant.
Indications/Uses
TIMOLOL MALEATE eye drops is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.
Dosage/Direction for Use
Posology: Apply 1 drop in the affected eye(s) twice daily.
Elderly: There are currently no clinical data indicating that dosage modifications are required for use in the elderly.
Hepatic and renal impairment: The safety and efficacy of TIMOLOL MALEATE EYE DROPS in patients with hepatic and renal impairment have not been established.
Method of administration: For ocular use.
The maximum dosage must be honoured. When administering too much and too frequently, too much of the drug may enter the systemic circulation, resulting in an increased risk on general side effects.
If a dose has been missed, it must be administered as soon as possible, unless the time for the next administration is near.
In case the intraocular pressure remains stable at an acceptable level, many patients can be treated with only one dose a day.
If a further control of intraocular pressure is required, a combination therapy should be considered; miotic drugs and orally administered carbonic anhydrase inhibitors are appropriate in this respect.
Simultaneous topical administration of two beta-blocking agents is not appropriate (see Precautions).
If more than one eye preparation is being used, the products must be administered at least 5 minutes apart. Eye ointments should be administered last.
When using nasolacrymal occlusion or closing the eyelids for 2 minutes, the systemic absorption is reduced. This may result in a decrease in systemic side effects and an increase in local activity.
To prevent contamination of the dropper tip and solution, care must be taken not to touch the eyelids, surrounding areas or other surfaces with the dropper tip. Keep the bottle tightly closed when not in use.
Paediatric population: Due to limited data, timolol could only be recommended for use in primary congenital and primary juvenile glaucoma for a transitional period while decision is made on a surgical approach, and in case of failed surgery while awaiting further options.
Posology: Clinicians should strongly evaluate the risks and benefits when considering medical therapy with timolol in paediatric patients. A detailed paediatric history and examination to determine the presence of systemic abnormalities should precede the use of timolol.
No specific dosage recommendation can be given as there is only limited clinical data (see also Pharmacology: Pharmacodynamics under Actions).
However, if benefit outweighs risk, it is recommended to use the lowest active agent concentration available once daily. If the intraocular pressure could not be sufficiently controlled, a careful up titration to a maximum of two drops daily per affected eye has to be considered. If applied twice daily, an interval of 12 hours should be preferred.
Furthermore the patients, especially neonates, should be strongly observed after the first dose for one to two hours in the office and closely monitored for ocular and systemic side effects until surgery is performed.
With regard to paediatric use, a 0.1% active agent concentration might already be sufficient.
Method of administration: To limit potential adverse effects only one drop should be instilled per dosing time.
Systemic absorption of topically administered β-blockers can be reduced by nasolacrymal occlusion and by keeping the eyes closed during 2 minutes after instillation of drops.
See also Precautions and Pharmacology: Pharmacokinetics under Actions.
Duration of treatment: For a transient treatment in the paediatric population.
Overdosage
A topical overdose with TIMOLOL MALEATE can be removed from the eye(s) by rinsing abundantly with warm water.
If overdose with TIMOLOL MALEATE occurs, treatment should be symptomatic and supportive.
Signs of overdose: No data specific to this preparation are available.
An overdose may lead to hypotension, cardiac failure, cardiogenic shock, bradycardia and to the extreme of cardiac arrest. In addition, respiratory difficulties, bronchospasms, vomiting, disturbed consciousness and generalised seizures may occur.
If overdosage occurs, the following measures should be considered: 1) Administration of activated charcoal, if the preparation has been taken orally. Studies have shown that timolol maleate cannot be removed by haemodialysis.
2) Symptomatic bradycardia: administration of atropine sulphate intravenously at a rate of 0.25 to 2 mg to initiate a vagal blockade. If the bradycardia persists, isoprenaline hydrochloride should carefully be administered intravenously. In difficult cases the use of a transvenous pacemaker could be considered.
3) AV block (second and third degree): administer isoprenaline hydrochloride or use a transvenous pacemaker.
4) Hypotension: A sympathomimetic agent such as dopamine, dobutamine or noradrenaline should be given. In refractory cases, the use of glucagon has been useful.
5) Acute heart decompensation: the normal treatment, based on the administration of digitalis, diuretics and oxygen has to be initiated immediately. In difficult cases, an intravenous administration of aminophylline is suggested. If necessary, this administration can be followed by an administration of glucagon, which has already been proven useful.
6) Bronchospasm: Isoprenaline hydrochloride should be given. Concomitant therapy with aminophylline may be considered.
Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in Description.
TIMOLOL MALEATE eye drops is contraindicated in patients with 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 or third degree atrioventricular block not controlled with pace-maker; overt cardiac failure; and cardiogenic shock.
Special Precautions
For ocular use only. Not for injection or ingestion.
After cap is removed, if tamper evident snap collar is loose, remove before using product.
Like other topically applied ophthalmic agents timolol is absorbed systemically. Due to its beta-adrenergic blocking component, timolol, the same types of cardiovascular, pulmonary and other adverse reactions seen with systemic beta-adrenergic blocking agents may occur. For example, severe respiratory reactions and cardiac reactions have been reported following administration of timolol eye drops, including death due to bronchospasm in patients with asthma, and in rare cases death in association with cardiac insufficiency. Incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration. To reduce the systemic absorption, see Dosage & Administration.
After application of the eye drops, following measures are useful to reduce systemic resorption: Keep the eyelid closed for 2 minutes; Close the lachrymal duct with the finger for 2 minutes.
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 the therapy with other active substances should be considered. Patients with cardiovascular diseases should be watched for signs of deterioration of these diseases and for 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 insufficiency should be checked adequately before starting a treatment with TIMOLOL MALEATE eye drops. In patients with a history of a severe cardiac disease, the potential occurrence of symptoms of cardiac insufficiency should be monitored carefully and the pulse should be checked.
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.
Because of the potential effects of beta-blocking agents relative to blood pressure and pulse, these agents should be used with great caution in patients with cerebrovascular insufficiency. If signs or symptoms suggesting reduced cerebral blood flow develop following initiation of therapy with TIMOLOL MALEATE eye drops, an alternative therapy should be considered.
Respiratory disorders: Respiratory reactions, including death due to bronchospasm in patients with asthma have been reported following administration of some ophthalmic beta-blockers.
TIMOLOL MALEATE should be used with caution, in patients with mild/moderate chronic obstructive pulmonary disease (COPD) and TIMOLOL MALEATE may only be used if the potential benefit outweighs the potential risk.
Hypoglycaemia/diabetes: 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, in particular tachycardia, palpitations and sweating. Diabetic patients should be advised to monitor their glycaemia carefully.
Corneal diseases: 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 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 Interactions).
Surgical anaesthesia: Beta-blocking ophthalmological preparations may block systemic beta-agonist effects e.g. of adrenaline. The anaesthesiologist should be informed when the patient is receiving timolol.
Before applying a general anaesthetic, a gradual decrease of the treatment with beta-adrenergic blocking agents could be appropriate because the beta-blockade reduces the capacity of the heart to respond to beta-adrenergic, sympathetic reflex stimuli.
Muscle weakness: Beta-adrenergic blocking agents have been reported to be able to potentiate certain symptoms of muscle weakness consistent with certain myasthenic symptoms (e.g. diplopia, ptosis and generalised weakness). Rare cases have been reported in which timolol eye drops increases muscle weakness in some patients with myasthenia gravis or myasthenic symptoms.
Choroidal detachment: Choroidal detachment has been reported with administration of aqueous suppressant therapy (e.g. timolol, acetazolamide) after filtration procedures.
Anaphylactic reactions: While taking beta-blockers, patients with 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.
Hyperthyroidism: Beta-blockers may also mask the signs of hyperthyroidism.
Contact lenses: TIMOLOL MALEATE eye drops should not be used when wearing contact lenses since the preservative benzalkonium chloride can be adsorbed by soft contact lenses, discolour them or cause eye irritation. Avoid contact with soft contact lenses. Patients should be advised to remove their lenses before instillation of TIMOLOL MALEATE and wait at least 15 minutes before putting their contact lenses back in.
In patients with angle-closure glaucoma, the first objective of the treatment is to reopen the angle. This requires constriction of the pupil with a miotic. TIMOLOL MALEATE eye drops has little or no effect on the pupil. When TIMOLOL MALEATE eye drops is used to reduce elevated intraocular pressure in angle-closure glaucoma, it should be used in combination with a miotic and not alone.
As with the use of other antiglaucoma drugs, a diminished responsiveness to timolol eye drops has been reported in some patients after prolonged therapy. However, in one long-term study in which 96 patients have been followed for at least 3 years, no significant difference in mean intraocular pressure has been observed after initial stabilisation.
Effects on ability to drive and use machines: No studies on the effect of this medicinal product on the ability to drive have been conducted. TIMOLOL MALEATE has no or negligible influence on the ability to drive and use machines. Temporary blurred vision or other visual disturbances may occur including refractive changes, diplopia, ptosis, frequent episodes of mild and transient blurred vision and occasional episodes of dizziness or fatigue.
If blurred vision occurs at instillation, the patient must wait until the vision clears before driving or using machinery.
Use in Children: Timolol solutions should generally be used cautiously in young glaucoma patients (see also Pharmacology: Pharmacokinetics under Actions). It is important to notify the parents of potential side effects so they can immediately discontinue the drug therapy. 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.
Use In Pregnancy & Lactation
Pregnancy: There are no adequate data for the use of timolol in pregnant women.
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. Studies in animals demonstrated no evidence of teratogencity (see Pharmacology: Toxicology: Preclinical safety data under Actions). Timolol should not be used during pregnancy unless clearly necessary.
However, if TIMOLOL MALEATE is administered until delivery, the neonate should be carefully monitored during the first days of life. To reduce systemic absorption, see Dosage & Administration.
Beta-blockers decrease placental perfusion, which can result in intrauterine embryofoetal death, immature delivery and premature delivery. In addition, undesirable effects (hypoglycaemia and bradycardia) may occur in the foetus and neonate. The likelihood of cardiac and pulmonary complications in the neonate in the post‑natal period is increased.
Breastfeeding: Beta-blockers are excreted in breast milk having the potential to cause serious undesirable effects in the breastfeeding infant. A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from TIMOLOL MALEATE therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. However, at therapeutic doses of timolol found in eye drops it is not likely that sufficient amounts would be present in breast milk to produce clinical symptoms of beta-blockade in the infant. To reduce the systemic absorption, see Dosage & Administration.
Fertility: There are no data on the effects of TIMOLOL MALEATE on human fertility.
Reproduction and fertility studies of timolol in rats demonstrated no adverse effects on male or female fertility (see Pharmacology: Toxicology: Preclinical safety data under Actions).
Adverse Reactions
Summary of safety profile: In clinical trials, the most common adverse drug reactions were ocular hyperaemia and eye irritation, occurring approximately in 5% and 2% of patients respectively.
The most frequently reported undesirable effects with timolol eye drops are local ocular reactions. 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 undesirable effects after topical ophthalmic administration is lower than for systemic administration. Listed adverse reactions include reactions seen within the class of ophthalmic beta-blockers.
The following adverse reactions are classified according to the following convention: very common (≥ 1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10000 to <1/1000), very rare (<1/10000), or not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The adverse reactions have been observed during clinical trials and post-marketing experience. (See table.)

Click on icon to see table/diagram/image

The following additional undesirable effects have been reported in clinical trials with orally administered timolol maleate and can be considered as potential side effects of ophthalmically administered timolol maleate: Blood and lymphatic system disorders: Non-thrombocytopenic purpura.
Endocrine disorders: Hyperglycaemia.
Psychiatric disorders: Decreased libido, increased dreaming frequency.
Nervous system disorders: Disturbance in attention (diminished concentration).
Ear and labyrinth disorders: Tinnitus.
Vascular disorders: Peripheral vascular disorder (arterial insufficiency), intermittent claudication, vasodilatation, sino-auricular block, deterioration of arterial insufficiency.
Respiratory, thoracic and mediastinal disorders: Rhonchi, bronchial obstruction.
Hepatobiliary disorders: Hepatomegaly.
Skin and subcutaneous tissue disorders: Pruritus, skin irritation, increased skin pigmentation, exfoliative dermatitis.
Musculoskeletal and connective tissue disorders: Arthralgia, pain in the limbs.
Renal and urinary disorders: Difficulty in micturation.
General disorders and administration site conditions: Weakness (local).
Investigations: Decreased exercise tolerance, decreased weight.
Laboratory parameters: In only a few cases, the oral administration of timolol maleate has been associated with significant clinical alterations of the laboratory parameters. Slight increase of urea, potassium, urinary acid and triglycerides in the blood has been observed, as well as slight decreases of haemoglobin, hematocrit and HDL cholesterol. However, these alterations were not evolutive and were not associated with clinical abnormalities.
Possible undesirable effects: In addition, a number of undesirable effects have been reported with other beta-adrenergic blocking agents and these may also be considered as potential undesirable effects of ophthalmically administered timolol maleate: Blood and lymphatic system disorders: Agranulocytosis, idiopathic thrombocytopenic purpura.
Immune system disorders: Pyrexia (with aching and sore throat).
Psychiatric disorders: Reversible mental depression leading to catatonia, an acute reversible syndrome characterised by disorientation in time and place, loss of short term memory, emotional instability, slightly clouded sensorium, decreased performance on neuropsychometrics.
Respiratory, thoracic and mediastinal disorders: Laryngospasms.
Gastrointestinal disorders: Mesenteric arterial insufficiency (arterial thrombosis), ischemic colitis.
Renal and urinary disorders: Peyronie's disease.
There have been reports of a syndrome comprising psoriasiform skin rash, conjunctivitis sicca, otitis and sclerosing serositis attributed to the beta-blocking agent, practolol. This syndrome has not been reported with timolol maleate.
Additional adverse reactions have been seen with ophthalmic beta-blockers and may potentially occur with TIMOLOL MALEATE: Immune system disorders: Systemic allergic reactions including pruritus, anaphylactic reaction.
Eye disorders: Decreased corneal sensitivity.
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.
Cardiac disorders: Chest pain.
Musculoskeletal and connective tissue disorders: Myalgia.
Reproductive system and breast disorders: Decreased libido.
Reporting of suspected adverse reactions: 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.
Drug Interactions
No interaction studies have been performed.
The interactions known for oral beta-blockers may also occur with the use of TIMOLOL MALEATE eye drops.
Mydriasis resulting from concomitant use of ophthalmic beta-blockers and adrenaline (epinephrine) has been reported occasionally.
Although TIMOLOL MALEATE eye drops, when used alone, has little or no effect on pupil size, mydriasis resulting from a combined therapy with timolol eye drops and adrenaline has been reported occasionally. The appearance of mydriasis following therapy with simultaneous usage of timolol eye drops and adrenaline cannot be ruled out.
There is a potential for additive effects resulting in hypotension and/or marked bradycardia when an ophthalmic beta-blocker solution is administered concomitantly with oral calcium channel blockers, beta-adrenergic blocking agents, antiarrhythmics (including amiodarone), digitalis glycosides, parasympathomimetics or guanethidine.
Close observation of the patient is necessary when beta-blockers are administered to patients receiving catecholamine-depleting drugs, such as reserpine, because of the potential additive effects and the occurrence of hypotension and/or marked bradycardia, which may cause dizziness, syncope, or postural hypotension.
Prudence is called for in the coadministration of beta-blocking agents, such as TIMOLOL MALEATE eye drops, in conjunction with oral or intravenous calcium antagonists, because of possible atrioventricular conduction disturbances, left ventricular failure, and hypotension. The nature of the undesired cardiovascular effect seems to depend on the type of calcium antagonist used. The derivatives of dihydropyridine, such as nifedipine, can cause hypotension, whereas verapamil or diltiazem, coadministered with a beta-adrenergic blocking agent, rather provoke atrioventricular conduction disturbances or an insufficiency of the left ventricle. Oral calcium antagonists can be combined with beta-adrenergic blocking agents when the heart function is normal.
In patients with impaired cardiac function, coadministration should be avoided.
The simultaneous use of beta-adrenergic blocking agents and digitalis with diltiazem or verapamil may have an additive effect in prolonging the atrioventricular conduction time.
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.
Patients who already use an oral beta-adrenergic blocking agent and who are administered TIMOLOL MALEATE as well, should be monitored because of the potential additive effect on the intraocular pressure and the known systemic effects of beta-adrenergic blockade. Known systemic effects of beta-adrenergic blockade are bradycardia, hypotension, bronchospasm and cardiac failure in susceptible patients (see also Precautions).
Oral beta-adrenergic blocking agents can enhance the rebound effect of hypertension which can occur when stopping the administration of clonidine. When the two substances are used simultaneously, the usage of the beta-adrenergic blocking agent should be stopped a few days before the progressive discontinuation of the clonidine therapy. When the treatment with the beta-adrenergic blocking agent replaces the clonidine therapy, it should be started a few days after the discontinuation of the clonidine therapy.
Beta-blocking ophthalmological preparations may block systemic beta-agonist effects e.g. of adrenaline (see Precautions).
In diabetics, simultaneous administration of timolol eye drops with insulin or oral antidiabetics can cause an increase of the hypoglycaemic effects and can mask the symptoms of acute hypoglycaemia. An extra check of the blood sugar level is necessary in these patients.
Simultaneous usage, systemic or topical, with steroids requires regular monitoring of the intraocular pressure.
Caution should be taken in case of a simultaneous administration with psychotropic adrenergics.
Beta-blockers can decrease the response to adrenaline used to treat anaphylactic reactions. Special caution should be exercised in patients with a history of atopy or anaphylaxis.
If more than one eye preparation is being used, the products must be administered at least 5 minutes apart. Eye ointments should be administered last. See Dosage & Administration.
Caution For Usage
Special precautions for disposal and other handling: No special requirements.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Incompatibilities: None known.
Storage
Shelf life: Discard one month after opening.
ATC Classification
S01ED01 - timolol ; Belongs to the class of beta blocking agents. Used in the treatment of glaucoma.
Presentation/Packing
Eye drops 0.5% x 5 mL.
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