Travapress Duo eye drops 5mg/ml+0.04mg/ml vials, 2.5ml

Composition

Composition per 1 ml of the drug:

active ingredients: travoprost 0,040 mg timolol 5,000 mg (in the form of timolol maleate 6,800 mg);

inactive ingredients: boric acid 3,000 mg, sodium chloride 2,500 mg, mannitol 3,000 mg, macrogol glycerylmonostearate (Califor RH40) 1,000 mg, propylene glycol 7,500 mg,1 M hydrochloric acid or 1 M sodium hydroxide solution to pH of 6.8 ± 0,1, purified water to 1.0 ml.

Pharmacological properties

Pharmacotherapeutic group: Combined anti-glaucoma agent (prostaglandin F2-alpha analog synthetic + beta-adrenoblocker).

ATX code: S01ED51.

Pharmacological properties

Pharmacodynamics

Travapress Duo contains two active ingredients: timolol and travoprost. Both components reduce intraocular pressure. Due to the complementary mechanisms of their action, the decrease in intraocular pressure under the influence of the combination is more significant than with the action of each of these components separately.

Timolol

Timolol is a non-selective beta-adrenergic blocker with no sympathomimetic activity, has no direct depressive effect on the myocardium, and has no membrane-stabilizing activity.

When applied topically, it reduces intraocular pressure by reducing the formation of watery moisture and slightly increasing its outflow.

Travoprost

Travoprost, an analog of prostaglandin F2-alpha, 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 travoprost is associated with an increase in uveoscleral outflow. It does not significantly affect the production of watery moisture.

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

Pharmacokinetics

Absorption anddistribution

Travoprost and timolol are absorbed through the cornea of the eye. In the cornea, travoprost is hydrolyzed to a biologically active form-free travoprost acid. Travoprost free acid is rapidly eliminated from the plasma within one hour – the concentration in the blood plasma decreases below the detection threshold-less than 0.01 ng / ml (can vary from 0.01 to 0.03 ng/ml). The maximum concentration (Cmax) of timolol in blood plasma is 1.34 ng/ml and persists to the detection threshold for 12 hours, and the time to reach the maximum concentration (Tmax) of timolol is reached within 0.69 hours after topical application. The half-life (T 1/2) of timolol is 4 hours after topical application of timolol+travoprost.

Metabolism and elimination

Metabolism is the main route of elimination of travoprost and travoprost free acid. The pathways of systemic metabolism are parallel to the pathways of endogenous prostaglandin F2a metabolism, which are characterized by the reduction of double bond 13-14, oxidation of the 15-hydroxyl group, and P-oxidative cleavage of the upper side chain link. Travoprost free acid and its metabolites are mainly excreted by the kidneys. Less than 2% of travoprost is found in the urine as free acid.

Timolol and the resulting metabolites are mainly excreted by the kidneys. About 20% of timolol is excreted unchanged, with the remainder as metabolites.

Indications

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

Use during pregnancy and lactation

Pregnancy

Travoprost has a negative pharmacological effect both on the course of pregnancy and on the fetus or newborn. Data on the use of a combination of travoprost + timolol or its individual components in pregnant women are absent or limited.

The results of animal studies of travoprost showed reproductive toxicity. Epidemiological studies with oral use of beta-blockers have not revealed effects associated with malformations, but indicate a risk of intrauterine development delay. In addition, signs and symptoms of beta-adrenergic blocking (e. g., bradycardia, hypotension, respiratory depression, and hypoglycemia) have been reported in newborns with the use of systemic beta-blockers by the mother prior to delivery.

The use of Travapress Duo is contraindicated during pregnancy. If Travapress Duo is used before delivery, the condition of the newborn should be carefully monitored in the first days of life.

Breast-feeding period

It is not known whether travoprost in the medicinal form of eye drops penetrates into human breast milk. Animal studies have shown that travoprost and its metabolites are excreted in breast milk. Timolol passes into breast milk, which can potentially lead to the development of serious adverse reactions (HP) in an children who is breastfed. However, when using timolol in therapeutic doses, it is unlikely that there will be enough of it in breast milk to develop symptoms of beta-adrenergic blockade in the child.

The use of the drug Travapress Duo during breastfeeding is contraindicated.

Fertility

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

Women with preserved reproductive potential/contraception

Travapress Duo is not recommended for women with preserved reproductive potential, except when using reliable contraceptives.

Contraindications

• Hypersensitivity to active substances or to any of the excipients.
• Hypersensitivity to other beta-blockers.
• Reactive airway diseases, including a history of bronchial asthma, as well as severe chronic obstructive pulmonary disease (COPD).
• Sinus bradycardia, sinus node weakness syndrome, including sinoatrial block, grade II or III atrioventricular block without a pacemaker.
• Decompensated chronic heart failure.
• Cardiogenic shock.
• Severe allergic rhinitis.
• Corneal dystrophy.
• Pregnancy and breast-feeding period.
• Children under 18 years of age (safety and efficacy have not been established).

With caution

Neovascular, closed-angle, narrow-angle glaucoma; pigmented and congenital glaucoma; open-angle glaucoma with pseudoaphakia; pseudoexfoliative glaucoma; acute inflammatory diseases of the visual organ; in patients with pseudoaphakia when the posterior lens capsule is torn or in patients with an anterior chamber intraocular lens; in patients at risk of developing cystic macular edema, iritis, uveitis; in patients with atopy or with severe anaphylactic reactions to various allergens in the anamnesis; in patients with labile diabetes mellitus and a tendency to hypoglycemia; in patients with hyperthyroidism, Prinzmetal angina pectoris; in patients who are planning to undergo surgery.

Side effects

General information about the safety profile of timolol + travoprost

In clinical trials involving 2,170 patients treated with a fixed combination of timolol+travoprost, the most common adverse event was conjunctival injection (12.0%).

Data on undesirable events

The following adverse events were reported in clinical trials and post-marketing use of a fixed combination of timolol+travoprost and are classified according to the following gradation of the frequency of adverse events: very common (≥1/10), common (≥1/100 to <1/10), infrequent (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare ( In each group, adverse events are listed in descending order of severity.

Immune system disorders infrequently hypersensitivity

Mental disorders rare Nervousness: frequency unknown depression

Nervous system disorders: infrequently dizziness, headache, frequency unknown stroke, syncope, paresthesia

Disorders of the visual organ very often conjunctival hyperemia:

• often point keratitis, eye pain, visual disturbances, blurred vision syndrome, dry eyes, itchy eyes, discomfort in the eye, eye irritation
• infrequently keratitis, iritis, conjunctivitis, inflammation of the anterior chamber of the eye, blepharitis, photophobia (photophobia), reduced visual acuity, asthenopia, eye swelling, tearing, eyelid erythema, increased eyelash growth, allergic phenomena for the eyes, swelling of the conjunctiva, swelling of the eyelids
• is rare corneal erosion, mabait, subconjunctival hemorrhage, formation of crusts on the eyelids, trichiasis distichus
• frequency unknown macular edema, ptosis, corneal pathology

Cardiac disorders infrequently bradycardia:

• rare arrhythmia, cardiac arrhythmia
• frequency unknown heart failure, tachycardia, chest pain, palpitation sensation

Vascular disorders infrequently arterial hypertension, hypotension: frequency unknown peripheral edema

Respiratory, thoracic and mediastinal disorders:

• infrequently dyspnea, postnasal syndrome
• rarely dysphonia, bronchospasm, cough, throat irritation, pharyngopharyngeal pain, nasal discomfort
• frequency unknown bronchial asthma

Gastrointestinal disorders: frequency unknown dysgeusia

Disorders of the hepatobiliary system: rarely increased activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST)

Skin and subcutaneous tissue disorders:

• infrequently contact dermatitis, hypertrichosis
• rarely urticaria, skin discoloration, alopecia, periocular hyperpigmentation of the skin
• frequency unknown skin rash

Musculoskeletal and connective tissue disorders: rarely pain in the extremities

Renal and urinary tract disorders: rarely chromaturia

General disorders and disorders at the injection site: rarely thirst, increased fatigue

Additional adverse events that were observed during therapy with monocomponents separately may be noted during therapy with a fixed combination of timolol+travoprost.

Travoprost

Visual disorders uveitis, conjunctival disorders, conjunctival folliculosis, hyperpigmentation of the iris

Skin and subcutaneous tissue disorders skin peeling

Timolol

Like other topical ophthalmic medications, timolol is absorbed into the systemic circulation. This can cause the same spectrum of adverse events as with oral forms of beta-blockers.

Interaction

Interaction studies with other drugs have not been conducted.

During the combined use of cytochrome CYP2D6 inhibitors (for example, quinidine, fluoxetine, paroxetine) and timolol, cases of increased systemic action of beta-blockers (for example, decreased heart rate, depression) were noted.

When combined with the use of eye drops containing timolol, with blockers of “slow” calcium channels, guanethidine, beta-blockers, antiarrhythmic agents (including amiodarone), parasympathomimetics and cardiac glycosides, additive effects may develop, leading to the development of arterial hypotension and (or) severe bradycardia.

Against the background of the combined use of beta-blockers and clonidine, “rebound” arterial hypertension may develop after abrupt withdrawal of the latter.

Beta-blockers may reduce the response to epinephrine (epinephrine) used in the treatment of anaphylactic reactions. Special care should be taken in patients with a history of atopy and anaphylaxis (see section “Special instructions”).

Concomitant use of two local beta-blockers or two local prostaglandin analogues is not recommended!

There have been reports of the development of mydriasis (dilated pupils) with the combined use of ophthalmic beta-blockers and epinephrine (epinephrine).

Beta-blockers may increase the effect of hypoglycemic medications.

How to take, course of use and dosage

For topical application.

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

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

If a dose of the drug was missed, then 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 a day.

Travapress Duo can be used in combination with other topical ophthalmic medications 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 bottle and its contents. The bottle must be closed after each use.

Special patient groups

Use in hepatic and renal insufficiency

Studies on the use of timolol+travoprost eye drops or timolol 5 mg/ml eye drops in patients with hepatic or renal insufficiency have not been conducted.

The use of travoprost has been studied in patients with mild to severe hepatic insufficiency and mild to severe renal insufficiency (with a creatinine clearance of no more than 14 ml / min). No dose adjustment is required in these groups of patients.

Dose adjustment of timolol+travoprost eye drops in patients with hepatic or renal insufficiency is most likely not required.

Use in children

The safety and efficacy of timolol+travoprost eye drops in children and adolescents under 18 years of age have not been established. No data available.

Overdose

In case of overdose with local ophthalmic application, no toxic effects from the visual organ are expected. Immediate eye rinsing with water is recommended.

Symptoms

If accidentally ingested, symptoms of overdose resulting from systemic exposure to beta-blockers may include bradycardia, hypotension, heart failure and bronchospasm, and cardiac arrest.

Treatment

Treatment in case of accidental ingestion of timolol+travoprost eye drops should include symptomatic and supportive therapy. Hemodialysis is ineffective in the elimination of timolol.

Description

Transparent colorless solution.

Special instructions

System effects

Like other topical ophthalmic medications, timolol and travoprost are absorbed into the systemic circulation.

Due to the beta-adrenergic effect of the Active ingredient – timolol-the same cardiovascular and respiratory disorders may occur as with the use of systemic beta-blockers.

Cardiac disorders

In patients with diseases of the cardiovascular system (for example, coronary heart disease, Prinzmetal angina, heart failure) and arterial hypotension, treatment with beta-blockers should be critically evaluated and other medications should be considered. Patients with diseases of the cardiovascular system should be evaluated for signs of worsening of these diseases and the development of HP. Since beta-blockers negatively affect the duration of treatment, they should be used with caution in patients with grade I atrioventricular block.

Vascular disorders

Patients with severe peripheral circulatory disorders (including severe forms of Raynaud’s disease or syndrome) should be treated with caution.

Respiratory disorders

The patient’s condition should be monitored before and during timolol therapy. Cases of respiratory reactions, including death from bronchospasm in patients with bronchial asthma, have been reported following the use of certain ophthalmic drugs from the beta – blockers group.

In patients with mild to moderate COPD, the combination of timolol+travoprost should be used with caution and only if the intended benefit outweighs the possible risk.

Hypoglycemia / diabetes mellitus

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

Hyperthyroidism

Beta-blockers can mask the symptoms of hyperthyroidism.

Muscle weakness

Beta-blockers can potentiate muscle weakness, which is consistent with certain symptoms of myasthenia gravis (for example, diplopia, ptosis, and generalized muscle weakness).

Corneal diseases

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 of the eye

In patients who used drugs that inhibit the production of aqueous humor (for example, timolol and acetazolamide), after fistulizing operations of the visual organ, cases of vascular detachment were noted.

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 such patients should be carefully monitored. The use of two beta-blockers for topical use is not recommended (see the section “Interaction with other drugs”).

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 pregnancy, should take appropriate precautions to prevent direct contact of the contents of the bottle on the skin. If a significant part of the contents of the bottle still gets on the skin (which is unlikely), the area of skin on which the drug has got, should be immediately rinsed with water.

Anaphylactic reactions

The use of timolol in patients with a history of atopic or severe anaphylactic reactions to various allergens may provoke more severe reactions in response to allergen management. Such patients may not respond well to regular doses of epinephrine (epinephrine) to relieve anaphylactic reactions.

Ophthalmic effects

When using travoprost, there may be a gradual change in eye color due to an increase in the number of melanosomes (pigment granules) in melanocytes. Before starting treatment, the patient should be informed about the possibility of irreversible changes in eye color. Treating only one eye can lead to irreversible heterochromia. The long-term effect on melanocytes and the consequences of this effect are currently unknown. The change in color of the iris is slow and may not be noticeable for months or years. Color change is more often observed in patients with mixed iris color (blue-brown, gray-brown, yellow-brown and 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, and therefore the entire iris or parts of it become more brown. At the end of therapy, further accumulation of brown pigment in the iris does not occur.

Darkening of the skin of the periorbital area 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 the length, thickness, pigmentation and / or number of eyelashes. The mechanism for these changes is not currently established.

_{Macular edema has been reported during treatment with prostaglandin f2a analogues}.

Travoprost should be used with caution in patients with neovascular, closed-angle, narrow-angle, pigmented and congenital glaucoma; open-angle glaucoma with pseudophakia, pseudoexfoliative glaucoma, inflammatory diseases of the visual organ, aphakia, pseudophakia with rupture of the posterior lens capsule or anterior chamber intraocular lens, as well as in patients with risk factors for macular edema, iritis, uveitis.

When using prostaglandin analogues, changes in the periorbital region and eyelids were noted. The deepening of the eyelid groove was observed only in studies in monkeys, while no data on this effect was obtained in clinical studies in humans, which made it possible to consider it species-specific.

Anesthesia during surgical procedures

Ophthalmic drugs from the group of beta-blockers can suppress the beta-agonist effects of, for example, epinephrine. Inform the anaesthetist if the patient is using timolol. Auxiliary substances

Travapress Duo eye drops contain propylene glycol, which can cause skin irritation.

Travapress Duo eye drops contain macrogol glycerylhydroxystearate, which can cause skin reactions.

Contact Lenses

The patient should be warned about the need to remove contact lenses before instilling the drug Travapress Duo and do not put them on for 15 minutes after that.

Influence on the ability to drive vehicles and mechanisms

Temporary blurred vision or other visual disturbances after using the drug may affect the ability to drive vehicles or mechanisms. If blurred vision is observed after instillation, then the patient should wait for the restoration of visual clarity before driving vehicles or mechanisms.

Form of production

Eye drops (5 mg + 0.04 mg / ml) /ml.

2.5 ml of the drug is placed in a polyethylene bottle with a capacity of 5 ml, equipped with a closing system (a dropper plug and a polyethylene lid that ensures tightness).

One bottle together with the instructions for use is placed in a cardboard pack.

Storage conditions

At a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 3 years. After opening the bottle, the drops should be used for 4 weeks. Do not use after the expiration date.

Active ingredient

Travoprost

Conditions of release from pharmacies

By prescription

Dosage form

eye drops