DuoTrav eye drops, 2.5 ml

Reduction of increased intraocular pressure in open-angle glaucoma and intraocular hypertension in patients resistant to monotherapy with beta-blockers and or prostaglandin analogs.

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

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

If a dose of the drug has been missed, then treatment should be continued with the next dose. The daily dose of the drug should not exceed 1 drop into the conjunctival sac of the eye 1 time / day. DuoTravЃ can be used in combination with other topical ophthalmic drugs to reduce intraocular pressure. In this case, the interval between their application should be at least 5 minutes. Do not touch the tip of the dropper bottle to any surface to avoid contamination of the dropper bottle and its contents. The bottle must be closed after each use.

Eye drops in the form of a transparent or slightly opalescent solution from colorless to light yellow.

1 ml

travoprost 40 mcg

timolol maleate 6.8 mg,

which corresponds to the content of timolol 5 mg

Excipients: macrogol glyceryl hydroxystearate - 1 mg, propylene glycol - 7.5 mg, boric acid - 3 mg, mannitol - 3 mg, sodium chloride - 2.5 mg, polydronium chloride - 0.01 mg, sodium hydroxide and / or hydrochloric acid - to adjust the pH, water purified - up to 1 ml.

• Hypersensitivity to drug components; reactive airway disease, including bronchial asthma and severe COPD;

• sinus bradycardia;

• SSSU, including sinoatrial block, II or III degree AV block without a pacemaker;

• decompensated chronic heart failure;

• cardiogenic shock;

• severe allergic rhinitis; corneal dystrophy;

• hypersensitivity to the group of beta-blockers;

• pregnancy;

• breastfeeding period; children under 18 years of age.

  Carefully

• Neovascular, angle-closure (narrow-angle) glaucoma, pigmentary and congenital glaucoma, open-angle glaucoma with pseudophakia, pseudoexfoliative glaucoma, acute inflammatory diseases of the organ of vision, in patients with pseudoaphakia with rupture of the posterior lens capsule or in patients with an anterior cystic lens intraocular lens macular edema, iritis, uveitis; in patients with atopy or with severe anaphylactic reactions to various allergens in history; in patients with diabetes mellitus of a labile course and a tendency to hypoglycemia; in patients with hyperthyroidism, Prinzmetal's angina; in patients who are planned to undergo surgical interventions.

pharmachologic effect

Combined antiglaucoma drug. Travoprost, a synthetic analogue of prostaglandin F2?, is a highly selective agonist of prostaglandin FP receptors and reduces intraocular pressure by increasing the outflow of aqueous humor. The main mechanism of action of the drug is associated with an increase in uveoscleral outflow. Does not significantly affect the production of aqueous humor. Timolol is a non-selective blocker of ?-adrenergic receptors without sympathomimetic activity, does not have a direct depressive effect on the myocardium, and does not have membrane stabilizing activity. When applied topically, it reduces intraocular pressure by reducing the formation of aqueous humor 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 use of the drug.

Pharmacokinetics

Travoprost and timolol are absorbed through the cornea of ??the eye. In the cornea, travoprost is hydrolyzed to a biologically active form - travoprost freebord acid. The free acid of travoprost is rapidly excreted from the plasma within an hour - the concentration in the blood plasma decreases below the detection threshold - less than 0.01 ng / ml (it can vary from 0.01 to 0.03 ng / ml). Cmax of timolol in blood plasma is 1.34 ng / ml and remains up to the detection threshold for 12 hours, and Tmax of timolol is reached within 0.69 hours after topical application. T1 / 2 of timolol is 4 hours after topical administration of DuoTravЃ. Metabolism is the main pathway for the elimination of travoprost and free acid and travoprost. The pathways of systemic metabolism are parallel to the pathways of metabolism of endogenous prostaglandin F2?, which are characterized by the restoration of the double bond 13-14,oxidation of the 15-hydroxyl group and ?-oxidative cleavage of the upper side chain unit. The free acid of travoprost and its metabolites are excreted by the kidneys. Less than 2% of travoprost is found in urine as free acid. Timolol and the resulting metabolites are excreted mainly by the kidneys. About 20% of timolol is excreted unchanged, the rest as metabolites.

Application during pregnancy and lactation

Pregnancy Travoprost has a negative pharmacological effect both on the course of pregnancy and on the fetus or newborn. The results of studies of travoprost in animals have shown reproductive toxicity. Data on the use of DuoTravЃ or its components in pregnant women are absent or limited. Epidemiological studies with oral use of beta-blockers did not reveal effects associated with malformations, but indicate the risk of intrauterine growth retardation. In addition, signs and symptoms of beta-adrenergic receptor blocking (eg, bradycardia, hypotension, respiratory depression, and hypoglycemia) have been reported in newborns with the use of systemic beta-blockers by the mother before delivery. The use of DuoTravЃ during pregnancy is contraindicated.In the case of using the drug DuoTravЃ before delivery, careful monitoring of the condition of the newborn should be carried out in the first days of life.

Breastfeeding period

It is not known whether travoprost in the dosage form of eye drops is excreted in human breast milk. Animal studies have shown that travoprost and its metabolites are excreted in breast milk. Timolol is excreted in breast milk, which can potentially lead to the development of serious adverse reactions in a breastfed infant. However, when using timolol in therapeutic doses, it is unlikely that a sufficient amount of the drug will be present in breast milk for the development of symptoms of beta-adrenergic receptor blockade in a child. The use of the drug DuoTravЃ during breastfeeding is not recommended.

Fertility

There is no information on the effect of DuoTravЃ on human fertility. Animal studies have shown no effect of travoprost or timolol on fertility at doses more than 250 times the maximum recommended dose for ophthalmic use in humans.

Application in children

Contraindicated in children under 18 years of age.

special instructions

Like other topical ophthalmic drugs, travoprost and timolol are absorbed into the systemic circulation. Due to the presence in the ophthalmic drug timolol, which has a beta-adrenergic blocking effect, it is possible to develop the same types of adverse reactions from the cardiovascular system, lungs and other organs as when using systemic beta-blockers.

Heart disorders

In patients with diseases of the cardiovascular system (for example, ischemic heart disease, Prinzmetal angina pectoris, heart failure) and arterial hypotension, it is necessary to critically assess the feasibility of using beta-blockers and consider the use of other active substances. In patients with diseases of the cardiovascular system, the presence of signs of a worsening of the course of these diseases and the development of adverse reactions should be assessed. Since beta-blockers have a negative effect on the timing, they should be used with caution in patients with grade I AV block.

Vascular disorders

In patients with severe disorders or diseases of the peripheral circulation (i.e., severe forms of the disease or Raynaud's syndrome), treatment should be carried out with caution.

Breathing disorders

The patient's condition should be monitored before and during therapy with timolol. After using some ophthalmic drugs from the group of beta-blockers, cases of respiratory reactions have been described, including death from bronchospasm in patients suffering from bronchial asthma. In patients with mild to moderate COPD, DuoTravЃ should be used with caution and only if the intended benefit outweighs the potential 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, since they can mask the signs and symptoms of acute hypoglycemia.

Hyperthyroidism

Beta-blockers can mask the signs of hyperthyroidism.

Muscle weakness

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

Corneal disease

Beta-blockers for ophthalmic use can cause dry eyes. In patients with corneal diseases, the drug should be used with caution. Detachment of the choroid In patients who used drugs that suppress the production of aqueous humor (for example, timolol and acetazolamide), cases of detachment of the choroid were observed after fistulizing the organ of vision.

Other beta-blockers

When using timolol in patients who are already using 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 these patients must be carefully monitored. The use of two beta-blockers for topical use is not recommended (see the section 'Drug interactions').

Skin contact

Prostaglandins and prostaglandin analogs are biologically active substances that can be absorbed through the skin. Women during pregnancy, as well as women planning to become pregnant, should take appropriate precautions to prevent direct skin contact with the contents of the bottle. If a significant part of the contents of the vial nevertheless gets on the skin (which is unlikely), the area of ??the skin on which the drug has gotten should be immediately rinsed with water. Anaphylactic reactions

The use of timolol in patients with atopy or a history of severe pathological reactions to various allergens can provoke more severe reactions in response to the administration of various allergens. Such patients may be poorly responsive to the usual doses of epinephrine to control anaphylactic reactions. Effects on the eyes Travoprost can gradually change the color of the eyes by increasing the number of melanosomes (pigment granules) in the melanocytes. Before starting treatment, patients should be informed about the possibility of permanent changes in eye color. Treatment of only one eye can lead to permanent heterochromia. The long-term effects on melanocytes and the consequences of this effect are currently unknown. The color change in the iris is slow and may not be noticeable for months or years.Eye color changes are predominantly observed in patients with mixed iris color (blue-brown, gray-brown, yellow-brown or green-brown), a similar effect was observed in patients with brown eyes. Typically, brown pigmentation around the pupil extends concentrically to the periphery of the iris; in connection with which the entire iris or parts of it acquire a brownish color. After the end of therapy, no further accumulation of brown pigment in the iris was noted. Darkening of the skin of the periorbital region and / or eyelids has been reported with travoprost. Travoprost can gradually change the condition of the eyelashes in the treated eye (s); these changes include changes in length, thickness, pigmentation and / or number of eyelashes. The mechanism for these changes is currently not clear.The drug contains propylene glycol, which can irritate the skin. The drug contains macrogol glyceryl hydroxystearate, which can cause skin reactions. During treatment with prostaglandin F2 analogues? noted macular edema. Travoprost should be used with caution in patients with neovascular, angle-closure (narrow-angle) glaucoma, pigmentary and congenital glaucoma, open-angle glaucoma with pseudophakia, pseudoexfoliative glaucoma, inflammatory diseases of the organ of vision, aphakia, pseudophakia with rupture of the posterior lens capsule of the intracranial or anterior lens patients with risk factors for macular edema, iritis, uveitis. With the use of prostaglandin analogues, changes in the periorbital region and eyelids 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 in humans, no data on this effect was obtained, 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, of adrenaline. The anesthesiologist should be informed if the patient is receiving timolol. Contact lenses Patients should be instructed to remove contact lenses before using DuoTravЃ and wait at least 15 minutes before reusing them.Anesthesia during surgical interventions Ophthalmic drugs from the group of beta-blockers can suppress beta-agonistic effects, for example, of adrenaline. The anesthesiologist should be informed if the patient is receiving timolol. Contact lenses Patients should be instructed to remove contact lenses before using DuoTravЃ and wait at least 15 minutes before reusing them.Anesthesia during surgical interventions Ophthalmic drugs from the group of beta-blockers can suppress beta-agonistic effects, for example, of adrenaline. The anesthesiologist should be informed if the patient is receiving timolol. Contact lenses Patients should be instructed to remove contact lenses before using DuoTravЃ and wait at least 15 minutes before reusing them.

Influence on the ability to drive vehicles and mechanisms

Temporary blurred vision or other visual impairments after using the drug may affect the ability to drive a car or use machinery. If blurred vision occurs after instillation of the drug, then before driving a vehicle or operating machinery, the patient must wait until the clarity of vision is restored.

Overdose

Symptoms: in case of an overdose of the drug with local ophthalmological application, toxic effects on the part of the organ of vision are not expected. In case of accidental ingestion, symptoms of overdose as a result of systemic exposure to beta-blockers may include bradycardia, arterial hypotension, heart failure and bronchospasm, cardiac arrest. Treatment: in case of overdose with local ophthalmic application, immediate rinsing of the eyes with water is recommended. In case of accidental ingestion of the drug, symptomatic and supportive therapy is performed. Hemodialysis is ineffective in eliminating timolol.

Drug interactions

Interaction studies with other drugs have not been conducted. During combined treatment with inhibitors of the isoenzyme CYP2D6 (for example, quinidine, fluoxetine, paroxetine) and timolol, cases of increased systemic effect of beta-blockers (for example, decreased heart rate, depression) were observed. When using an ophthalmic solution of a beta-blocker simultaneously with calcium channel blockers, beta-blockers, antiarrhythmics (including amiodarone), cardiac glycosides and parasympathomimetics, additive effects may develop, leading to arterial hypotension and (or) severe bradycardia. Against the background of the combined use of beta-blockers and clonidine, rebound arterial hypertension may develop after the abrupt withdrawal of the latter. Beta-blockers can reduce the response to epinephrine,used in the treatment of anaphylactic reactions. Particular care should be taken in patients with a history of indications of atopy and anaphylaxis (see section 'Special instructions'). The simultaneous use of two local beta-blockers or two local analogs of prostaglandins is not recommended. Sometimes reported the development of mydriasis with the simultaneous use of ophthalmic beta-blockers and adrenaline.Sometimes reported the development of mydriasis with the simultaneous use of ophthalmic beta-blockers and adrenaline.Sometimes reported the development of mydriasis with the simultaneous use of ophthalmic beta-blockers and adrenaline.