DuoTrav® (DuoTrav®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Dosage form: & nbspTOApli eye.
Composition:

In 1 ml of the solution:

Active substances: travoprost 0.04 mg, timolol 5 mg (in the form of timolol maleate 6.8 mg).

Excipients: macrogol glitserilgidroksistearat 1 mg, 7.5 mg propylene glycol, boric acid 3 mg, 3 mg mannitol, 2.5 mg sodium chloride, 0.01 mg polidroniya chloride, sodium hydroxide and / or hydrochloric acid to adjust pH, purified water to 1 ml .

Description:

The clear or slightly opalescent solution from colorless to pale yellow.

Pharmacotherapeutic group:antiglaucoma agents combined (prostaglandin F2-alpha analogue synthetic + beta-blocker)
ATX: & nbsp
  • Timolol in combination with other drugs
    • Pharmacodynamics:

    Travoprost - synthetic analogue of prostaglandin F2-alpha is highly selective prostaglandin agonist FPreceptors and lowers intraocular pressure by increasing the outflow of aqueous humor. The main mechanism of action of the drug is associated with an increase in out-scleral outflow. Has no significant effect on the production of aqueous humor.

    Timolol - a non-selective beta-adrenergic blocker without sympathomimetic activity, does not have a direct depressive effect on the myocardium, does not have membrane-stabilizing activity.With topical application reduces intraocular pressure by reducing the formation of watery moisture and a slight increase in its outflow.

    Intraocular pressure decreases approximately 2 hours after application, and the maximum effect is achieved after 12 hours. A significant decrease in intraocular pressure can persist for 24 hours after a single application of the drug.

    Pharmacokinetics:

    Travoprost and timolol absorbed through the cornea of ​​the eye. In the cornea hydrolysis of travoprost to the biologically active form - free acid travoprost. The free acid of travoprost is rapidly excreted from the plasma for an hour - the concentration in the blood plasma drops below the detection threshold - less than 0.01 ng / ml (it can vary from 0.01 to 0.03 ng / ml). The maximum concentration (CmOh) of timolol in blood plasma is 1.34 ng / ml and is kept to the detection threshold for 12 hours, and TmOh Timolol is reached within 0.69 hours after topical application. T1/2 timolol is 4 hours after topical application of the preparation DuoTra®.

    Metabolism is the main way of eliminating travoprost and free acid travoprost. The pathways of systemic metabolism are parallel to the pathways of the metabolism of endogenous prostaglandin F2α, which are characterized by the reduction of the double bond 13-14, the oxidation of the 15-hydroxyl group and the β-oxidative cleavage of the link of the upper side chain. The free acid of travoprost and its metabolites are mainly excreted by the kidneys. Less than 2% of travoprost is found in the urine as a free acid.

    Timolol and the resulting metabolites are excreted mainly by the kidneys. About 20% of timolol is excreted unchanged, the rest - in the form of metabolites.

    Indications:

    Decreased elevated intraocular pressure in open-angle glaucoma and intraocular hypertension in patients with beta-blockers or analogues of prostaglandin resistant to monotherapy.

    Contraindications:

    Hypersensitivity to the components of the drug.

    Reactive airways disease, including bronchial asthma (or history of asthma), and severe chronic obstructive pulmonary disease.

    Sinus bradycardia, syndrome of weakness of the sinus node, including sinoatrial block, atrioventricular blockade of the second or third degree without a pacemaker, decompensated chronic heart failure,cardiogenic shock, severe allergic rhinitis, corneal dystrophy, hypersensitivity to a group of beta-blockers, pregnancy, the period of breastfeeding, children under 18 years of age.

    Carefully:

    Neovascular, closed-angle, narrow-angle glaucoma, pigmented and congenital glaucoma, open-angle glaucoma with pseudo-phacia, pseudoexfoliative glaucoma, acute inflammatory diseases of the eye, patients with pseudoafacies at rupture of the posterior capsular lens or in patients with anterocular intraocular lens, in patients at risk of developing cystoid macular edema, iritis, uveitis; in patients with atopy or with severe anaphylactic reactions to various allergens in the anamnesis; in patients with diabetes mellitus and a tendency to hypoglycemia; in patients with hyperthyroidism, prinzmetal angina; in patients who are planning surgical interventions.

    Pregnancy and lactation:

    Fertility

    There is no information on the effect of Duotra® on human fertility. Studies in animals showed no effect of travoprost or timolol on fertility in doses,which more than 250 times exceeded the maximum recommended dose for ophthalmic use in humans.

    BVariability

    Travoprost has a negative pharmacological effect both on the course of pregnancy, and on the fetus or newborn.

    Data on the use of DuoTra® or the components of the drug in pregnant women are not available or limited.

    The results of animal travoprost studies have shown reproductive toxicity. Epidemiological studies using oral beta-blockers did not reveal effects associated with malformations, but indicate a risk of intrauterine growth retardation. In addition, with the use of systemic beta-blockers by the mother before the birth in newborns, signs and symptoms of beta-adrenergic blocking (for example, bradycardia, hypotension, respiratory depression and hypoglycemia) were noted.

    DuoTrav® is not recommended for use during pregnancy. In the case of the use of the drug DuoTra® prior to delivery, careful monitoring of the condition of the newborn in the first days of life should be carried out.

    Breastfeeding period

    It is not known whether the blood is excreted travoprost in the form of a drop of ocular drops into human milk. According to the results of animal studies, it is shown that travoprost and its metabolites are excreted into breast milk. Timolol is excreted in breast milk, which can potentially lead to the development of serious adverse reactions in the infant who is breastfed. However, when timolol is used in therapeutic doses, it is unlikely that sufficient amounts of the drug will be present in breast milk for the development of symptoms of beta-adrenoreceptor blockade in a child. The use of the drug DuoTrav® during breastfeeding is not recommended.

    Dosing and Administration:

    The drug is instilled in 1 drop in the conjunctival sac of the eye 1 time per day, in the evening or in the morning at the same time.

    To reduce the risk of developing systemic side effects, it is recommended after the instillation of the drug to squeeze the nasolacrimal canal by pressing in the area of ​​its projection at the inner corner of the eye.

    If the dose has been missed, then the treatment should be continued with the next dose.The daily dose of the drug should not exceed 1 drop in the conjunctival sac of the eye 1 time per day.

    DuoTrav® can be used in combination with other local ophthalmic drugs to reduce intraocular pressure. In this case, the interval between their use should be at least 5 minutes.

    Do not touch the tip of the dropper bottle to any surface to avoid contamination of the dropper and its contents.

    The bottle must be closed after each use.

    Side effects:

    General information about the drug safety profile

    In clinical trials involving 2170 patients who received therapy with Duotv®, the most common adverse event was conjunctival injection (12.0%).

    Table data on undesirable phenomena

    The following undesirable phenomena were noted during clinical trials and post-marketing use of the drug and classified according to the following gradation of incidence of adverse events: very often (> 1/10), often (from ≥1 / 100 to <1/10), infrequently ≥1 / 1000 to <1/100),rarely (from ≥1 / 10,000 to <1/1000); very rarely (≥1 / 10,000); with an unknown frequency (can not be established based on available data). In each group, adverse events are listed in descending order of severity.

    System-Organ Class

    Frequency of occurrence

    Unwanted reaction

    Immune system disorders

    Infrequently

    Hypersensitivity

    Mental disorders

    Rarely

    Nervousness

    With unknown frequency

    Depression

    Disturbances from the nervous system

    Infrequently

    Dizziness, headache

    With unknown frequency

    Violation of cerebral circulation, syncope, paresthesia

    Disturbances on the part of the organ of sight

    Often

    Conjunctival injection

    Often

    Punctate keratitis, eye pain, blurred vision, visual disturbances, a syndrome of "dry" eyes, itchy eyes, eye discomfort, eye irritation

    Infrequently

    Keratitis, iritis, conjunctivitis, inflammation of the anterior chamber of moisture, blepharitis, photophobia, blurred vision, asthenopia, eye edema, tearing, erythema eyelid, eyelash growth enhancement, allergic conditions of the eyes, conjunctival edema, eyelid edema

    Rarely

    Erosion of the cornea, meibomite, subconjunctival hemorrhage, formation of crusts on the edges of the eyelids, trichiasis, distichiasis

    With unknown frequency

    Macular edema, ptosis, disorders of the cornea

    Heart Disease

    Infrequently

    Bradycardia

    Rarely

    Arrhythmia, heart rhythm disturbance

    With unknown frequency

    Heart failure, tachycardia, chest pain, palpitation

    Vascular disorders

    Infrequently

    Hypertension, hypotension

    With unknown frequency

    Peripheral edema

    Disturbances from the respiratory system, chest and mediastinal organs

    Infrequently

    Dispno, postnatal syndrome

    Rarely

    Dysphonia, bronchospasm, cough, irritation in the throat, pharyngeal-laryngeal pain, discomfort in the nose

    With unknown frequency

    Asthma

    Disorders from the gastrointestinal tract

    With unknown frequency

    Dysgeusia

    Disorders from the hepatobiliary system

    Rarely

    Increase in ALT and ACT

    Disturbances from the skin and subcutaneous fat

    Infrequently

    Contact dermatitis, hypertrichosis

    Rarely

    Urticaria, skin discoloration, alopecia, periocular hyperpigmentation of the skin

    With unknown frequency

    Rash

    Impaired kidney and urinary system

    Rarely

    Chromaturia

    Disturbances from musculoskeletal system and connective tissue

    Rarely

    Pain in the extremities

    Common violations

    Rarely

    Thirst, increased fatigue

    Additional adverse events that were noted during the therapy with monocomponents of the drug and can be noted during therapy with Duotrav®.

    Travoprost

    System-Organ Class

    Preferred term (according to classification MedDRA)

    Disturbances on the part of the organ of sight

    Uveitis, disorders of the conjunctiva, conjunctival follicles, hyperpigmentation of the iris

    Disturbances from the skin and subcutaneous fat

    Skin peeling

    Timolol

    Like other drugs for topical application in ophthalmology, timolol absorbed into the systemic circulation. This can cause the same range of adverse events as with the use of oral forms of beta-blockers. In addition, undesirable phenomena specific to the pharmacotherapeutic group of beta-blockers are presented. The incidence of systemic adverse events after local ophthalmic use is lower than in systemic use.Measures to reduce systemic absorption are presented in the section "Method of administration and dose".

    System-Organ Class

    Preferred term MedDRA

    Immune system disorders

    Systemic allergic reactions, including angioedema, hives, local and generalized rash, itching, anaphylactic shock

    Disorders from nutrition and metabolism

    Hypoglycaemia

    Mental disorders

    Insomnia, nightmarish dreams, memory loss

    Disturbances from the nervous system

    Cerebral ischemia, weighting of signs and symptoms of myasthenia gravis gravis

    Disturbances on the part of the organ of sight

    Symptoms of eye irritation (burning sensation, stitching sensation, itching, lacrimation, conjunctival injection), vitreous detachment in the postoperative period of fistulatory operations of the organ of vision (see section Special instructions), decrease in corneal sensitivity, diplopia

    Heart Disease

    Chest pain, palpitations, swelling, congestive heart failure, atrioventricular block, cardiac arrest

    Vascular disorders

    The phenomenon of Raynaud, cold extremities

    Disturbances from the respiratory, thoracic and mediastinal organs

    Bronchospasm (mainly in patients with existing bronchospastic diseases)

    Disorders from the gastrointestinal tract

    Dysgeusia, nausea, dyspepsia, diarrhea, dry mouth, abdominal pain, vomiting

    Disturbances from the skin and subcutaneous fat

    Psoriasisiform rash or weighting of psoriasis

    Muscular and connective tissue disorders

    Myalgia

    Disorders from the reproductive system

    Sexual dysfunction, decreased libido

    Common violations

    Asthenia
    Overdose:

    In the case of an overdose of the drug with a local ophthalmological application, toxic effects on the part of the eye are not expected. It is recommended that eyes be washed immediately with water.

    Inadvertently ingestion symptoms of overdose as a result of systemic effects of beta-blockers may include bradycardia, hypotension, heart failure and bronchospasm, cardiac arrest.

    Treatment In case of accidental ingestion of the drug inside should include symptomatic and supportive therapy.Hemodialysis is ineffective in removing timolol.

    Interaction:

    Studies on interactions with other drugs have not been conducted.

    During combined treatment with cytochrome inhibitors CYP2D6 (e.g., quinidine, fluoxetine, paroxetine) and timolol, there have been cases of increased systemic effect of beta-blockers (eg, reduction in heart rate, depression).

    When using an ophthalmic solution of the beta-blocker simultaneously with calcium channel blockers, beta-blockers, antiarrhythmics (including amiodarone), cardiac glycosides and parasympathomimetics, the development of additive effects leading to hypotension and / or severe bradycardia is possible.

    Against a background of joint application of beta-blockers and clonidine, ricochetial hypertension can develop after a sharp abolition of the latter.

    Beta-blockers can reduce the response to adrenaline used in the treatment of anaphylactic reactions. Particular care should be taken in patients with a history of atopy and anaphylaxis (see section "Special instructions").

    It is not recommended simultaneous use of two local beta-blockers or two local analogues of prostaglandins!

    Sometimes reported on the development of mydriasis, while the use of ophthalmic beta-blockers and adrenaline.

    Special instructions:

    General information

    Like other ophthalmic drugs for topical use, travoprost and timolol are absorbed into the systemic circulation. Due to the presence of an ophthalmic drug timolol having beta-adrenoceptor blocking action may develop the same types of adverse reactions to the cardiovascular system, lungs and other organs, and that by using systemic beta-blockers.

    Heart Disease

    In patients with diseases of the cardiovascular system (eg, coronary heart disease, Prinzmetal angina, heart failure) and hypotension, it is necessary to critically evaluate the feasibility of using beta-blockers and consider the possibility of using other active substances. Patients with diseases of the cardiovascular system should be assessed for signs of worsening of the course of these diseases and development of undesirable reactions.

    Since beta-blockers have a negative effect on the timing, they should be used with caution in patients with stage I atrioventricular block.

    Vascular disorders

    In patients with severe impairment or diseases of peripheral circulation (ie severe forms of the disease or Reynaud's syndrome), treatment should be conducted with caution.

    Breathing disorders

    It is necessary to monitor the patient's condition before and during therapy with timolol. After using some ophthalmic drugs from the group of beta-blockers, cases of respiratory reactions, including death from bronchospasm in patients suffering from bronchial asthma, are described.

    In patients with chronic obstructive pulmonary disease (COPD) of mild to moderate severity, DuoTra® should be used with caution and only if the intended benefit exceeds the possible risk.

    Hypoglycemia / diabetes mellitus

    In patients prone to the development of spontaneous hypoglycemia, as well as in patients with a labile course of diabetes mellitus, beta-blockers should be used with caution, as they can mask the signs and symptoms of acute hypoglycemia.

    Hyperthyroidism

    Beta-blockers can mask the signs of hyperthyroidism.

    Muscle weakness

    It was reported that beta-adrenoblockers can potentiate muscle weakness, which is consistent with certain symptoms of myasthenia gravis (eg, diplopia, ptosis and generalized muscle weakness).

    Diseases of the cornea

    Beta-blockers for ophthalmic use can cause dry eyes. The drug should be used with caution in patients with corneal disease.

    Vascular wall detachment

    In patients who used drugs that inhibit the production of aqueous humor (eg, timolol and acetazolamide), after the fistulaizing operations of the organ of vision, there were cases of detachment of the choroid.

    Other beta blockers

    When using timolol in patients who already use systemic beta-blockers, it is possible to increase the effect on intraocular pressure or other known effects of systemic beta-blockers. The response to therapy in such patients should be carefully monitored. The use of two beta-blockers for topical application is not recommended (see.section Interaction with other medicinal products).

    Skin contact

    Prostaglandins and prostaglandin analogues are biologically active substances that can be absorbed through the skin. Women during pregnancy, as well as women planning a pregnancy, should take appropriate precautions to prevent the contents of the vial from getting directly onto the skin. If a significant part of the contents of the vial is still on the skin (which is unlikely), the area of ​​skin that the preparation has got should be washed immediately with water.

    Anaphylactic reactions

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

    Effects on the eyes

    Travoprost can gradually change the color of the eyes, increasing the amount of melanosomes (pigment granules) in melanocytes. Before starting treatment, patients should be informed of the possibility of a permanent change in eye color.Treatment of only one eye can lead to permanent heterochromia. Long-term effects on melanocytes and the effects of this effect are currently unknown.

    The change in the color of the iris occurs slowly and may not be noticeable for several months or years.

    The change in eye color is predominantly observed in patients with mixed color of the iris (blue-brown, gray-brown, yellow-brown or green-brown), a similar effect was observed in patients with brown eyes. In typical cases, brown pigmentation around the pupil extends concentrically to the periphery of the iris of the eye; in connection with which the entire iris or its parts become more brown. After the termination of therapy, no further accumulation of brown pigment in the iris was noted.

    When using travoprost was reported on the darkening of the skin of the periorbital region and (or) eyelids.

    Travoprost can gradually change the state of the eyelashes in the treated eye (s); These changes include changes in length, thickness, pigmentation, and (or) the number of eyelashes.

    The mechanism of these changes is not currently established.

    The drug contains propylene glycol, which can cause irritation of the skin!

    The drug contains macrogol glyceryl hydroxy stearate, which can cause reactions from the skin.

    During treatment with prostaglandin analogues F2α marked macular edema.

    Travoprost should be used with caution in patients with neovascular, occlusive, narrow-angle glaucoma, pigmented and congenital glaucoma, open-angle glaucoma with pseudophakia, pseudoexfoliation glaucoma, inflammatory diseases of the eye, aphakia, pseudophakia with ruptured posterior lens capsule or anterocular intraocular lens, as well as in patients with risk factors for macular edema, iritis, uveitis.

    When using analogues of prostaglandin, periorbital area and eyelid changes were noted. Deepening of the groove of the eyelids was noted only in the course of studies in monkeys, while in the course of clinical studies, the person did not receive data on this effect, which made it possible to consider it species-specific.

    Anesthesia during surgical interventions

    Ophthalmic drugs from the group of beta-blockers can suppress beta-agonistic effects, for example, adrenaline. Inform an anesthetist if the patient receives timolol.

    Contact lenses

    Patients should be instructed to remove contact lenses before using DuoTrav® and wait at least 15 minutes before re-use.

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

    Temporary blurring of vision or other visual impairment after application of the drug may affect the ability to drive a car or use mechanisms. If blurring of vision occurs after instillation of the drug, then before driving a vehicle or controlling the mechanisms, the patient must wait for the restoration of the clearness of vision.

    Form release / dosage:Eye drops.
    Packaging:

    For 2.5 ml per dropper of polypropylene.

    For 1 or 3 bottles in individual bags of foil with instructions for use in a pack of cardboard.

    Storage conditions:

    At a temperature of 2 to 30 ° C, out of the reach of children.

    Shelf life:

    2 years.

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

    Use within 4 weeks after opening the vial.

    Terms of leave from pharmacies:On prescription
    Registration number:LSR-007704/09
    Date of registration:01.10.2009 / 19.09.2013
    Expiration Date:Unlimited
    The owner of the registration certificate:Alkon-Kouvreur N.V. S.A.Alkon-Kouvreur N.V. S.A. Belgium
    Manufacturer: & nbsp
    Representation: & nbspALKON PHARMACEUTICS LLCALKON PHARMACEUTICS LLCRussia
    Information update date: & nbsp21.11.2016
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