Timolol - instructions for use, dose, side effects, contraindications

Excipients: benzalkopia chloride (50% solution) in terms of 100% substance - 0.1 mg, sodium dihydrogen phosphate dihydrate - 6.1 mg, sodium hydrogen phosphate dodecahydrate - 30.42 mg, sodium hydroxide - q.s. to pH 6.0-7.5, hydrochloric acid - q.s. up to pH 6.0-7.5, water for injection - up to 1 ml

Description:A clear, colorless or light yellow solution

Pharmacotherapeutic group:Antiglaucoma means β-blocker.

ATX: & nbsp

S.01.E.D. Beta-blockers

S.01.E.D.01 Timolol

Pharmacodynamics:

Timolol is a non-selective beta1 and beta2-adrenoblocker. Has no significant internal sympathomimetic, directly oppressing myocardium and local anesthetic (membrane-stabilizing) activity.

Blockade of beta-adrenergic receptors in the bronchi and bronchioles increases the resistance of the respiratory tract, due to the absence of antagonism to parasympathomimetic activity. This effect in patients with bronchial asthma or other bronchospastic states may pose a potential hazard.

Blockade of beta-adrenoreceptors reduces cardiac output in healthy subjects and patients with heart disease. In patients with severe myocardial dysfunction, beta-adrenergic blockade can weaken the stimulatory effect of the sympathetic nervous system necessary to maintain adequate cardiac function.

With topical application in the form of eye drops reduces both normal and increased intraocular pressure by reducing the formation of intraocular fluid. Increased intraocular pressure is the main risk factor in the pathogenesis of the development of glaucoma-specific damage to the optic nerve and narrowing the boundaries of the visual fields. Does not affect the width of the pupil and accommodation.

The exact mechanism for reducing intraocular pressure due to timolol is not known. According to the data of topography and fluorometry in humans, the action of timolol is mainly based on a decrease in the formation of intraocular fluid, however, in some studies, some improvement in the outflow of intraocular fluid has also been demonstrated.

The onset of decrease in intraocular pressure is observed 20 min after a single instillation of timolol.The maximum effect after a single instillation is observed after 1-2 hours, a significant decrease in intraocular pressure is maintained for 24 hours.

Pharmacokinetics:

Pharmacokinetics in the pediatric population:

As already confirmed by the study of pharmacokinetics in adults, 80% of eye drops enter the nasopharynx after instillation, where it is rapidly absorbed and enters the systemic circulation through conjunctiva, nasal mucosa, nasopharynx, oropharynx, skin (in case of transfusion over the edge of the eyelid).

Due to the fact that the volume of circulating blood in children is less than in adults, the higher systemic concentration of the drug should be taken into account.

Also immaturity of metabolic enzyme systems in newborns can lead to an increase in the half-life and potentiation of side effects.

According to limited data, plasma levels of timolol in children, especially in infants, after instillation of 0.25% solution of the drug are significantly higher than those in adults after instillation of a 0.5% solution of the drug, which presumably increases the risk of side effects such as bronchospasm and bradycardia.

Indications:

Decreased elevated intraocular pressure in patients with ophthalmic hypertension or open-angle glaucoma; as an aid: with secondary glaucoma, including

aphakic, with a closed-angle glaucoma (in combination with miotics), with congenital glaucoma (with ineffectiveness of other therapeutic measures).

Contraindications:

Hypersensitivity to timolol or other components of the drug; bronchial asthma (including anamnesis); severe chronic obstructive pulmonary disease; sinus bradycardia; atrioventricular blockade of II or III degree without a pacemaker; cardiogenic shock; decompensated chronic heart failure; syndrome of weakness of the sinus node.

Carefully:

Heart failure in the stage of compensation, mild and moderate severity of chronic obstructive pulmonary disease, extensive surgical interventions, diabetes, thyrotoxicosis.

Pregnancy and lactation:

Appropriate and well-controlled studies of the use of timolol in pregnant women have not been conducted. The drug should be used during pregnancy only if the expected benefit to the mother exceeds the possible risk to the fetus.It is known that beta-adrenoblokatory at ingestion can affect the fetal development of the fetus. In addition, neonates may have bradycardia, hypotension, respiratory failure and hypoglycemia with beta-blockers prior to delivery. Therefore, when the drug is used timolol During pregnancy, it is necessary to monitor the condition of newborns during the first days after birth.

Timolol excreted in breast milk after ingestion. However, when applying a therapeutic dose in the form of eye drops, it is unlikely that there will be enough timolol in breast milk to have clinically significant effects. Due to the possibility of developing serious adverse reactions in the child, it is necessary either to interrupt

breastfeeding, or refuse to use the drug (taking into account its importance for the mother).

Dosing and Administration:

Treatment begins with the application of 0.25% solution timolol 1 drop 2 times a day in the affected eye. In the absence of sufficient clinical effect, apply a 0.5% solution of timolol 1 drop 2 times a day to the affected eye.

Stable decrease in intraocular pressure on the background of drug use timolol occurs within a few weeks. Control of intraocular pressure is carried out within 4 weeks after the beginning of application of the preparation.

If a satisfactory level of intraocular pressure is achieved, the dosage regimen can be changed to 1 drop once a day in the affected eye. Doses exceeding 1 drop of 0.5% solution of timolol 2 times a day do not lead to an additional decrease in intraocular pressure. If thymolol is not able to achieve the required level of intraocular pressure, consideration should be given to the use of additional antihypertensive drugs. The simultaneous use of two beta-blockers for topical application is not recommended. In patients with significantly pigmented iris, a less pronounced decrease in intraocular pressure may be noted, as well as a longer period of achievement of intraocular pressure compensation. After discontinuation of treatment, the hypotensive effect of timolol may persist for several days, and in the case of prolonged prior treatment, the residual hypotensive effect may persist for 2 to 4 weeks.When carrying out therapy with timolol only in relation to one eye, an antihypertensive effect can also be observed with respect to the contralateral eye. To reduce systemic absorption, nasolacrimal occlusion is recommended - pressing the inner edges of the eyelids for 2-3 minutes after instillation of the drug.

Transition from another antihypertensive therapy:

when switching from therapy with a single beta blocker to therapy with another drug from the group of blockade runners, it is recommended to complete a full day of therapy with a previously used antihypertensive agent, and the next day to begin instillation of timolol 0.25% in each affected eye 1 drop 2 times a day.

In the absence of an adequate response to therapy, the dose may be increased to one drop of a 0.5% solution of timolol in each affected eye twice a day.

When switching to therapy with an antihypertensive drug of another group, in addition to beta-blockers, instillations of the previously prescribed drug continue with the addition of instillations of one drop of 0.25% solution of timolol into each affected eye twice a day. The next day, the earlier treatment is canceled and Timolol therapy continues.Use in the pediatric population

According to limited data, timolol can be recommended to reduce intraocular pressure in infantile and juvenile congenital glaucoma in the preoperative period or in the case of ineffective surgical treatment.

Before using the drug, you should carefully evaluate the risks and benefits of using timolol in the pediatric population by carefully collecting anamnesis regarding systemic disorders. In case the benefit outweighs the risk, it is recommended to use timolol in the lowest possible concentration. With insufficient control of IOP, it is necessary to switch to application 2 times a day with an interval between instillations of 12 hours. It is necessary to control eye and systemic side effects within 1-2 hours after the first instillation, especially in newborns, due to the possibility of developing apnea and breathing by type Cheyne-Stokes. It is necessary to warn the parents of the child receiving timolol treatment that the drug should be

Side effects

Undesirable reactions that occurred after administration of timolol and other beta-blockers,can be regarded as a potential adverse reaction and for timolol drugs in the form of eye drops.

Side effects:

The incidence of side effects, both in the course of research and in post-marketing surveillance, was assessed as follows: very often (> 1/10); often (> 1/100, <1/10); sometimes (> 1/1000 to <1/100); rarely (> 1/10000 to <1/1000); very rarely (<1 / 100,000), the frequency is unknown (the available data can not be estimated).

General reactions

With an unknown frequency: headache, asthenia / fatigue, chest pain.

From the side of the organ of vision

Common: blurred vision, eye pain, burning and itching in the eyes, discomfort in the eye, conjunctival injection.

Uncommon: blepharitis, punctate keratitis, keratitis, conjunctivitis, iritis, diplopia, corneal erosion, corneal ulcer, lacrimation or decrease in lacrimation, photophobia, sensation of "sand" in the eyes, eyelid edema, conjunctival edema, ptosis.

Rarely: uveitis, double vision, pigmentation of the cornea, erythema eyelids.

Very rarely: the development of calcification of the cornea with significant damage due to the presence of phosphates in the composition of drops.

With unknown frequency: decreased sensitivity of the cornea, detachment

vascular membrane in the postoperative period of antiglaucomatous surgery.

From the side of the cardiovascular system Infrequent: bradycardia, hypotension

Rarely: myocardial infarction, a decrease or increase in blood pressure, intermittent claudication.

With unknown frequency: cardiac arrest, atrioventricular block, arrhythmia, heart palpitations, congestive heart failure, Raynaud phenomenon.

From the side of the digestive system infrequently: dysgeusia

Rarely: dyspepsia, dryness of the oral mucosa, abdominal pain.

With an unknown frequency: nausea, vomiting, diarrhea.

From the immune system With an unknown frequency: systemic lupus erythematosus Mental disorders Rarely: depression

With an unknown frequency: insomnia, memory loss, nightmares. From the side of the nervous system Infrequently: a headache.

Rarely: cerebral ischemia, dizziness, migraine.

With unknown frequency: cerebral circulation, fainting, paresthesia, dizziness, aggravation of myasthenia gravis flow.

From the skin and subcutaneous tissues Rarely: edema of the face, erythema

With unknown frequency: psoriasis or worsening of psoriasis,

localized rash, alopecia.

From the connective tissue With an unknown frequency: arthropathy, muscle pain.

With unknown frequency: systemic allergic reactions, including anaphylaxis, angioedema, hives, local or generalized rash, itching.

From the respiratory system and mediastinal organs Infrequent: respiratory failure, dyspnea, bronchitis.

Rarely: bronchospasm (mainly in patients with already existing bronchospastic conditions), cough, nasal congestion, upper respiratory tract infection.

From the endocrine system

With unknown frequency: subclinical course of hypoglycemia in patients with diabetes mellitus (see section "Special instructions").

From the genitourinary system

With unknown frequency: retroperitoneal fibrosis, sexual

dysfunction (including impotence), decreased libido, Peyronie's disease.

From the side of ENT organs With an unknown frequency: ringing in the ears.

Undesirable reactions that occurred after taking timolol or other beta-adrenoblockers orally

Allergic reactions: erythematous rash, fever, accompanied by a bolo in the throat, laryngospasm accompanied by a distress syndrome.General reactions and reactions at the injection site: pain in the limbs, reduced exercise tolerance, weight loss.

From the cardiovascular system: aggravation of arterial insufficiency, vasodilation.

From the digestive system: gastrointestinal pain, hepatomegaly, vomiting, thrombosis of the mesenteric arteries, ischemic colitis.

On the part of the blood and lymphatic system: netrombotsitopenicheskaya purpura, thrombocytopenic purpura, agranulocytosis.

On the part of the endocrine system: hyperglycemia, hypoglycemia.

From the skin and subcutaneous tissues: itching, skin irritation,

increased pigmentation, sweating.

From the musculoskeletal system: arthralgia.

From the nervous system / mental disorders: vertigo, reduced concentration of attention, reversible suppression of mental functions, progressing to catatonia, acute reversible syndrome,

characterized by a violation of orientation in time and space, emotional lability, some difficulty in perception and a reduced ability to perform neuropsychiatric tests.

On the part of the respiratory system: wheezing, bronchial obstruction.

From the genitourinary system: difficulty urinating.

Overdose:

If the dosage regimen and application are observed, the development of an overdose is unlikely.

Cases of unintentional an overdose of timolol in

drug form eye drops, manifested systemic effects similar to the systemic effects of beta-adrenoblockers: dizziness, headache, dyspnea, bradycardia, hypotension, bronchospasm, generalized convulsions, loss of consciousness, cardiogenic shock and cardiac arrest.

When randomly administered timolol the reception is recommended

activated carbon. It was shown that timolol maleate can not be removed from the body by hemodialysis.

With the development of bradycardia and bradyarrhythmia (with atrioventricular block II and III degree), intravenous atropine sulfate at a dose of 0.25 to 2 mg is recommended; After partial relief of bradycardia, the administration of isoprenaline is indicated. When intractable bradycardia should consider the installation of a pacemaker.

When hypotension is recommended the reception of sympathomimetics, such as dopamine, dobutamine, noradrenaline.In the absence of effect - the introduction of glucagon. In the development of acute heart failure, the use of digitalis and diuretics, as well as oxygen therapy, with intravenous administration of aminophylline is recommended.

Interaction:

Joint use of timolol with epinephrine, pilocarpine, systemic beta-adrenoblockers leads to an intensification of hypotensive action of the latter.

Simultaneous use with eye drops containing epinephrine, can lead to mydriasis.

Strengthens the action of muscle relaxants and general anesthetics (48 hours before the general anesthesia, including with the use of peripheral muscle relaxants, it is necessary to stop taking the drug). Beta-blockers

In patients taking beta-adrenoblockers inside and timolol in the form of eye drops, systemic and local reactions due to beta-adrenergic blockade should be controlled. Blocks of "slow" calcium channels

In view of potential violations of atrioventricular conduction, left ventricular failure and reduction of blood pressure, simultaneous use of beta-blockers, including timolol, and slow calcium channel blockers (for oral or intravenous administration) should be administered with caution. In patients with impaired cardiac function, simultaneous use of these groups of drugs is not recommended.

Sympatholytics

With the simultaneous use of beta-blockers and sympatholytics, for example, reserpine, patients should be carefully monitored because of their mutual effects, lowering blood pressure and / or

severe bradycardia, which can lead to vertigo, syncope, and postural hypotension.

Cardiac glycosides

The simultaneous use of beta-blockers and cardiac glycosides can lead to disruption of atrioventricular conduction. Inhibitors of the isoenzyme CYP2D6

Simultaneous use of timolol with inhibitors of the isoenzyme CYP2D6 (for example, quinidine, selective serotonin reuptake inhibitors) can lead to an increase in the blockade of beta-adrenergic receptors (including a decrease in heart rhythm, depression).

Clonidine

Beta-adrenoblockers for oral administration may aggravate the "ricochet" hypertension that may occur after the withdrawal of clonidine.Information on the aggravation of "ricochet" hypertension against the background of the use of timolol in the dosage form "eye drops" is absent.

The neuromuscular blockade caused by tubocurarine can be enhanced by the action of the beta-blocker.

Special instructions:

Blockers of beta-adrenergic receptors, applied topically, can undergo systemic absorption. Thus, with topical application of the drug, the same adverse reactions are possible, as in the case of systemic use of beta-adrenoreceptor blockers. For example, after the use of timolol, serious reactions have been reported from the respiratory and cardiovascular systems, including fatal outcomes as a result of bronchospasm in patients with bronchial asthma and rarely due to heart failure.

Heart failure

To maintain circulation in people with impaired contractility of the myocardium requires sympathetic stimulation. The use of beta-blockers can aggravate the course of heart failure.

In patients without a history of heart failure, prolonged myocardial depression in some cases can lead to the development of heart failure.When the first signs of heart failure occur timolol necessary cancel.

Caution is needed when assigning timolol to patients with atrioventricular blockade of the 1st degree, Prinzmetal angina and peripheral circulatory disorders (Raynaud phenomenon).

Timolol should be used with caution in patients with chronic obstructive pulmonary disease (COPD) of mild to moderate severity, and only if the potential benefit of the treatment exceeds the possible risk. With prolonged use of timolol, weakening of the effect (tachyphylaxis) is possible.

Thyrotoxicosis

Beta-adrenoblockers are able to mask a number of clinical symptoms of hyperthyroidism (in particular, tachycardia). Care is required when using beta-blockers in patients with the possibility of developing thyrotoxicosis.

Diabetes

In patients with a tendency to spontaneous hypoglycemia or a labile course of diabetes that are treated with insulin or oral hypoglycemic agents, beta-blockers should be used with caution, as they can mask the signs and symptoms of acute hypoglycemia.

When using the drug Timolol can be obtained a positive result in doping control.

Diseases of the cornea

Patients with corneal disease should be careful in the course of therapy with beta-blockers in connection with their ability to provoke the development of dry eye syndrome.

In the course of therapy with timolol, it is necessary to monitor the function of tear and corneal conditions, as well as to assess the condition of the visual fields at least once every 6 months; monitor the hypotensive effect (measurement of intraocular pressure) at least once a month.

The use of timolol may increase muscle weakness in myasthenia gravis (for example, increase diplopia, ptosis and general weakness). In some patients with myasthenia gravis and other myasthenic diseases, there was an increase in muscle weakness with timolol.

The main pathogenetic aspect of the treatment of closed-angle glaucoma is the need to open the anterior chamber angle, which is achieved by narrowing the pupil with miotics. In connection with the lack of the influence of timolol on the diameter of the pupil in the treatment of closed-angle glaucoma, the drug can be used only in combination with miotics.

The use of timolol by patients with atopy or severe pathological reactions to various allergens in a history can provoke more severe reactions in response to accidental, diagnostic or therapeutic management of allergens. Such patients may respond poorly to the administration of conventional doses of epinephrine to relieve anaphylactic reactions.

Because of the possible effect of blockers of β-adrenergic receptors on blood pressure and heart rate, these agents should be used with caution in patients with cerebral circulatory insufficiency. If, after the initiation of therapy with timolol, signs or symptoms of a decrease in cerebral circulation develop, the need for therapy with local beta-blockers should be reviewed.

In the postoperative period of antiglaucomatous operations and with the use of drugs that reduce the secretion of intraocular fluid, the development of a detachment of the choroid of the eye is possible.

When used simultaneously with other drugs, the interval between instillations should be at least 15 minutes.

Preservative benzalkonium chloride, which is part of the preparation Timolol, can be adsorbed by soft contact lenses and cause a change in their color, so contact lenses should be removed before instillation and re-worn no earlier than 15 minutes.

Cases of development of bacterial keratitis in patients who used timolol in containers for multiple dosing of ophthalmic drugs. These containers were unintentionally contaminated with patients with concomitant diseases of the cornea.

When transferring patients to treatment with timolol, correction of refraction after the effects of previously used miotics may be necessary.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions within 30 minutes after instillation of the drug due to the profile of adverse reactions from the side of the eye.

Form release / dosage:

Drops of eye 0.5% m / vol. For 5 ml of the drug in the bottles-droppers of low-density polyethylene (PNP), sealed with a screw cap of high density polyethylene (PVP) with a point for piercing the dropper.One bottle together with the instruction for use is placed in a cardboard box.

Packaging:

. For 5 ml of the drug in the bottles-droppers of low-density polyethylene (PNP), sealed with a screw cap of high density polyethylene (PVP) with a point for piercing the dropper. One bottle together with the instruction for use is placed in a cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Shelf life after opening the bottle is 1 month.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002940

Date of registration:01.04.2015

The owner of the registration certificate:Micro Labs LimitedMicro Labs Limited India

Manufacturer: & nbsp

MICRO LABS, Limited India

Representation: & nbspMICRO LABS LIMITED MICRO LABS LIMITED India

Information update date: & nbsp31.08.2015

Illustrated instructions

Instructions

Timolol (Timolol)