Duoprost eye drops, 2.5ml

Reduction of increased intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension with insufficient effectiveness of monotherapy with individual components of the drug

Adults (including the elderly) - 1 drop in the affected eye (s) 1 time / day.

As with the use of any eye drops, in order to reduce the possible systemic effect of the drug, immediately after instillation of each drop, it is recommended to press on the lower lacrimal opening located at the inner corner of the eye on the lower eyelid. This must be done within 2 minutes. If one dose is missed, treatment should be continued with the next dose as scheduled. Do not instill more than 1 drop per day into the affected eye. In the case of the combined use of Duoprost with another ophthalmic drug, an interval of at least 5 minutes should be observed between use. You should remove contact lenses before instilling the drug and put them on again only after 15 minutes.

Eye drops in the form of a clear, colorless solution.

1 ml

latanoprost 50 mcg

timolol (in the form of maleate) 5 mg

Excipients: disodium hydrogen phosphate dodecahydrate - 11.85 mg, sodium dihydrogen phosphate dihydrate - 5.2 mg, sodium chloride - 4.1 mg, benzalkonium chloride - 0.2 mg, sodium hydroxide solution 1M / hydrochloric acid solution 1M - up to pH 6.0 ± 0.1, purified water - up to 1 ml.

• Reactive diseases of the respiratory tract, incl. bronchial asthma, or an indication of a history of bronchial asthma;

• Severe COPD; sinus bradycardia;

• SSSU;

• sinoatrial blockade;

• AV block II-III degree without a control artificial pacemaker;

• clinically significant heart failure;

• cardiogenic shock; age under 18;

• hypersensitivity to latanoprost, timolol or other components of the drug.

With care: inflammatory, neovascular, angle-closure glaucoma, open-angle glaucoma in combination with pseudophakia, pigmentary glaucoma (due to lack of sufficient experience with the drug); aphakia, pseudoaphakia with rupture of the posterior lens capsule, patients with known risk factors for macular edema (cases of macular edema, including cystoid edema, have been described in the treatment with latanoprost); history of herpetic keratitis; AV blockade of the I degree (beta-blockers negatively affect the time of the impulse in the heart muscle); disorders of peripheral circulation (for example, severe forms of Raynaud's syndrome or Raynaud's disease). The use of Duoprost should be avoided in patients with active herpetic keratitis and recurrent herpetic keratitis,especially associated with the intake of analogs of prostaglandin F2 ?. Timolol should be used with caution in patients with COPD and only in cases where the potential benefit from the drug to the patient outweighs the risk. Duoprost should be used with caution in patients with corneal diseases, because the drug may cause dryness of the mucous membrane of the eyes.

pharmachologic effect

Duoprost contains two active ingredients - latanoprost and timolol. The mechanism for lowering increased intraocular pressure (IOP) is different for these components, which provides an additional decrease in IOP compared to the effect achieved with the use of each of these components in the form of monotherapy.

Latanoprost - an analogue of prostaglandin F2? - is a selective agonist of prostaglandin FP receptors and reduces IOP by increasing the outflow of aqueous humor, mainly by the uveoscleral route, as well as through the trabecular network. It was found that latanoprost has no significant effect on the production of aqueous humor and the permeability of the blood-ophthalmic barrier. During short-term treatment, latanoprost does not cause fluorescein leakage into the posterior segment of the eye in pseudophakia. When used in therapeutic doses, latanoprost does not have a significant pharmacological effect on the cardiovascular and respiratory systems.

Timolol is a non-selective beta1- and beta2-adrenergic blocker, which does not have significant internal sympathomimetic activity, does not have a direct inhibitory effect on the myocardium or a local anesthetic (membrane stabilizing) effect.

Blockade of ?-adrenergic receptors causes a decrease in cardiac output in healthy people and patients with heart disease. In patients with severe myocardial dysfunction, beta-blockers can inhibit the stimulating effect of the sympathetic nervous system, which is necessary for adequate heart function.

The blockade of ?-adrenergic receptors in the bronchi and bronchioles leads to an increase in airway resistance under the influence of the parasympathetic nervous system. A similar effect can be dangerous for patients with bronchial asthma and other bronchospastic diseases.

The use of timolol in the form of eye drops causes a decrease in elevated and normal IOP regardless of the presence or absence of glaucoma.

Elevated IOP is a major risk factor for glaucomatous visual field loss. The higher the IOP, the higher the risk of glaucomatous loss of visual fields and damage to the optic nerve. The exact mechanism of lowering IOP by timolol has not been established. The results of tonography and fluorophotometry indicate that the main mechanism of action may be associated with a decrease in the formation of aqueous humor. However, some studies have also noted a slight increase in churn. In addition, the mechanism of inhibition of the increased synthesis of cyclic AMP caused by endogenous stimulation of ?-adrenergic receptors is also possible. There was no evidence of any effect of timolol on the permeability of the blood-ophthalmic barrier.

The action of the combination of latanoprost and timolol begins within an hour, the maximum effect is observed within 6-8 hours. With repeated use, an adequate decrease in IOP persists for 24 hours after administration.

Pharmacokinetics

The pharmacokinetic interaction between latanoprost and timolol has not been established, although 1-4 hours after using the combined preparation, the concentration of latanoprost acid in aqueous humor was approximately 2 times higher than with monotherapy.

Latanoprost

Suction

Latanoprost, a prodrug, is absorbed through the cornea, where it is hydrolyzed to a biologically active acid. It was found that the concentration in aqueous humor reaches a maximum approximately 2 hours after topical application.

Distribution

Vd is 0/16 ± 0/02 l / kg. Latanoprost acid is distributed in aqueous humor within 4 hours, and in plasma - only within the first hour after topical application.

Metabolism

Latanoprost undergoes hydrolysis in the cornea under the action of esterases to form a biologically active acid. Latanoprost acid, entering the systemic circulation, is metabolized mainly in the liver by ?-oxidation of fatty acids with the formation of 1,2-dinor- and 1,2,3,4-tetranor-metabolites.

Withdrawal

Latanoprost acid is rapidly excreted from the plasma - T1 / 2 is 17 minutes. Plasma clearance is 0.40 l / h / kg. Systemic clearance is approximately 7 ml / min / kg.

After topical application of eye drops, the systemic bioavailability of latanoprost acid is 45%. The connection with blood plasma proteins is 87%. Metabolites are excreted mainly by the kidneys: after topical application, approximately 88% of the administered dose is excreted in the urine.

Timolol

The concentration of timolol in aqueous humor reaches a maximum approximately 1 hour after the application of eye drops. Part of the dose undergoes systemic absorption, and Cmax in plasma, which is 1 ng / ml, is achieved 10-20 minutes after the drug is applied, 1 drop in each eye 1 time / day (300 ?g / day). T1 / 2 of timolol from plasma is about 6 hours. Timolol is actively metabolized in the liver. Metabolites, as well as some unchanged timolol, are excreted in the urine.

Side effect

From the side of the organ of vision: very often - increased pigmentation of the iris; often - visual impairment, blepharitis, conjunctivitis, conjunctival lesions (including follicles, papillary reactions of the conjunctiva, punctate hemorrhages), corneal lesions (including erosion, pigmentation, keratitis, punctate keratitis), refractive errors, hyperemia , eye irritation (including burning sensation and itching in the eyes), eye pain, photophobia, loss of visual fields, increased tear formation; infrequently - hypertrichosis (changes in eyelashes and vellus hair, lengthening, thickening, increased pigmentation, increased density and change in the direction of eyelash growth); frequency unknown - changes in refraction.

Infectious and parasitic diseases: frequency unknown - sinusitis, upper respiratory tract infections and other infections.

From the side of metabolism and nutrition: often diabetes mellitus, hypercholesterolemia.

From the side of the psyche: the frequency is unknown - depression.

From the nervous system: frequent - headache.

From the side of the cardiovascular system: often - increased blood pressure.

On the part of the skin and subcutaneous tissues: often - rash, itching and skin changes (irritation, dermatochalasion, etc.), skin diseases.

From the musculoskeletal system: the frequency is unknown - arthritis.

Listed below are other undesirable effects that were observed with monotherapy with the individual components of Duoprost (in addition to those mentioned above).

Latanoprost

From the side of the organ of vision: eye irritation (burning sensation, feeling of sand in the eyes, itching, tingling and foreign body sensation); transient punctate erosion of the corneal epithelium, eyelid edema, keratitis, punctate keratitis, corneal edema; lengthening, thickening, increasing the number and increasing pigmentation of eyelashes and vellus hair; iritis / uveitis; macular edema (in patients with aphakia, in patients with pseudophakia with rupture of the posterior lens capsule, or in patients with risk factors for the development of macular edema), incl. cystoid; trichiasis; blurred vision, photophobia, changes in the periorbital region and eyelids, leading to a deepening of the groove of the upper eyelid, periorbital edema, iris cysts.

From the side of the cardiovascular system: exacerbation of angina pectoris in patients with coronary artery disease, angina pectoris, unstable angina pectoris, palpitations.

Skin and subcutaneous tissue disorders: skin rash, itching, darkening of the eyelid skin and local skin reactions on the eyelids.

From the nervous system: dizziness.

From the respiratory system: asthma (including acute attacks or exacerbation of the disease in patients with a history of bronchial asthma), shortness of breath.

From the musculoskeletal system: myalgia, arthralgia.

General disorders and disorders at the injection site: nonspecific chest pain.

Infections: herpetic keratitis.

Timolol (in the form of eye drops)

From the immune system: systemic allergic reactions, incl. anaphylaxis, angioedema, anaphylactic reactions, urticaria, pruritus, localized and generalized rash.

From the side of metabolism and nutrition: anorexia, latent symptoms of hypoglycemia in patients with diabetes mellitus.

From the side of the psyche: behavioral changes and mental disorders, incl. confusion, hallucinations, anxiety, disorientation, nervousness, memory loss, insomnia, depression, and nightmares.

From the nervous system: cerebral ischemia, acute cerebrovascular accident, dizziness, increased symptoms of miastenia gravis, paresthesia, drowsiness, headache, fainting.

From the side of the organ of vision: cystoid macular edema, decreased sensitivity of the cornea; symptoms and signs of eye irritation (eg, burning sensation, itching, gritty eyes, increased lacrimation, redness), blepharitis, keratitis, blurred vision, dry eye mucosa, corneal erosion, choroid detachment after filtration surgery; ptosis, visual impairment, incl. change in refraction and diplopia.

On the part of the organ of hearing and labyrinthine disorders: tinnitus.

From the side of the cardiovascular system: arrhythmia, bradycardia, AV block, heart failure, chronic heart failure, cardiac arrest, blockade of intracardiac conduction, palpitations, progression of angina pectoris; intermittent claudication, cold hands and feet, lowering blood pressure, Raynaud's syndrome.

From the respiratory system: bronchospasm (mainly in patients with previous bronchospastic diseases), cough, shortness of breath, nasal congestion, pulmonary edema and respiratory failure.

From the digestive system: diarrhea, dryness of the oral mucosa, impaired taste, dyspepsia, nausea, vomiting, abdominal pain, retroperitoneal fibrosis.

Skin and subcutaneous tissue disorders: alopecia, pseudopemphigoid, skin rash, psoriasis-like rash or exacerbation of psoriasis.

From the musculoskeletal system: systemic lupus erythematosus and myalgia.

On the part of the genitals and breast: decreased libido, impotence, impaired sexual function and Peyronie's disease.

General disorders and disorders together introduction: asthenia / fatigue, chest pain, edema.

In some patients with significant corneal damage, very rare cases of corneal calcification have been reported due to the use of phosphate-containing eye drops.

Application during pregnancy and lactation

There have been no adequate controlled studies in pregnant women.

When conducting epidemiological studies with the use of beta-blockers inside, there were no cases of fetal malformations, however, the risk of intrauterine growth retardation was increased. In addition, symptoms of beta-blocking action (such as bradycardia, decreased blood pressure, impaired respiratory function and hypoglycemia) were detected in newborns whose mothers took beta-blockers during pregnancy. If a pregnant woman received beta-blocker therapy, careful monitoring of the condition of the newborn should be carried out in the first days after birth. In this regard, the use of the drug Duoprost during pregnancy is possible only in cases where the expected benefit to the mother outweighs the potential risk to the fetus or child.

Latanoprost and its metabolites may be excreted in breast milk. Timolol, when taken in the form of eye drops, has also been found in breast milk. Given the risk of serious adverse reactions in breastfed newborns, and the importance of using the drug for the mother, either breastfeeding should be discontinued or the drug should be discontinued.

Application in children

The use of the drug under the age of 18 is contraindicated.

special instructions

The drug Duoprost should be used no more than 1 time / day, because more frequent administration of latanoprost leads to a weakening of the IOP-lowering effect.

If one dose is missed, the next dose should be given at the usual time.

If the patient is using other eye drops at the same time, then they should be applied at intervals of at least 5 minutes.

The composition of the drug Duoprost contains benzalkonium chloride, which is usually used as a preservative in ophthalmic preparations and can be absorbed by contact lenses. Benzalkonium chloride is known to cause punctate keratopathy and / or toxic ulcerative keratopathy and can cause eye irritation and discoloration of soft contact lenses. It is recommended to carefully monitor the condition of patients using Duoprost frequently or for a long time, and who have dryness of the mucous membrane of the eyes or conditions that damage the cornea. Before instilling drops, contact lenses must be removed and reinstalled after 15 minutes.

Latanoprost

Change in brown pigment content

Latanoprost can cause a gradual increase in the brown pigment content in the iris. The change in eye color is due to an increase in the content of melanin in the stromal melanocytes of the iris, and not an increase in the number of melanocytes themselves. Typically, brown pigmentation appears around the pupil and spreads concentrically to the periphery of the iris. In this case, the entire iris or parts of it become brown. In most cases, discoloration is minor and may not be clinically apparent. Increased pigmentation in the iris of one or both eyes is observed mainly in patients with a mixed iris color with a brown base. The drug has no effect on nevi and iris lentigo: pigment accumulation in the trabecular meshwork or in the anterior chamber of the eye was not observed.

When determining the degree of pigmentation of the iris for more than 5 years, no undesirable consequences of increased pigmentation were revealed even with continued therapy with latanoprost. In patients, the degree of IOP reduction was the same regardless of the presence or absence of increased iris pigmentation. Therefore, treatment with latanoprost can be continued in cases of increased iris pigmentation. Such patients should be monitored regularly, depending on the clinical situation, treatment may be discontinued.

Increased iris pigmentation is usually observed within the first year after starting treatment, rarely during the second or third year. After the fourth year of treatment, this effect was not observed. The rate of progression of pigmentation decreases over time and stabilizes after 5 years. In more distant terms, the effects of increased iris pigmentation have not been studied. After stopping treatment, there was no increase in brown pigmentation of the iris, but the change in eye color may be irreversible.

In patients using drops in only one eye, heterochromia may develop, which can also be irreversible.

Eyelash and vellus hair changes

In connection with the use of latanoprost, cases of darkening of the eyelid skin have been described, which can be reversible.

Latanoprost can cause gradual changes in eyelashes and vellus hair, such as lengthening, thickening, increased pigmentation, increased density and a change in the direction of eyelash growth. Eyelash changes are reversible and disappear after stopping treatment.

Latanoprost should be used with caution in patients with a history of herpetic keratitis. Latanoprost should not be used in the case of active keratitis caused by herpes simplex, as well as in patients who have a history of recurrent herpetic keratitis, especially caused by prostaglandin analogues.

Cases of macular edema have been reported, incl. cystic macular edema, when treated with latanoprost. These events have mainly occurred in patients with aphakia, in those with pseudophakia and rupture of the posterior lens capsule, or in patients with known risk factors for cystic macular edema. Therefore, Duoprost should be used with caution in these patients.

There are no documented data on the use of latanoprost in inflammatory, neovascular or chronic angle-closure glaucoma, in open-angle glaucoma in patients with pseudophakic eye and in pigmentary glaucoma.

Timolol

ѕри местном применении бета-адреноблокаторов могут наблюдатьс¤ такие же нежелательные реакции, как и при их системном применении. ѕациентов с т¤желыми заболевани¤ми сердца в анамнезе следует посто¤нно наблюдать с целью своевременного вы¤влени¤ симптомов сердечной недостаточности. ѕри местном применении тимолола могут возникнуть следующие реакции со стороны сердца и системы дыхани¤: прогрессирование »Ѕ—, стенокардии ѕринцметала, а также периферических (т¤желой формы болезни –ейно или синдрома –ейно) и центральных нарушений кровообращени¤, гипотензи¤, сердечна¤ недостаточность с летальным исходом, т¤желые реакции со стороны дыхательной системы, в т.ч. бронхоспазм с летальным исходом у больных астмой, брадикарди¤. — осторожностью следует примен¤ть у пациентов с ’ќЅЋ легкой и умеренной степени и только в том случае, если потенциальна¤ польза превосходит потенциальный риск.

¬ св¤зи с негативным вли¤нием тимолола на врем¤ проведени¤ импульса бета-адреноблокаторы следует примен¤ть с осторожностью у пациентов с блокадой сердца первой степени.

ѕеред проведением обширного хирургического вмешательства следует обсудить целесообразность постепенной отмены бета-адреноблокаторов. ѕрепараты этой группы нарушают способность сердца к ответной реакции на рефлекторную стимул¤цию ?-адренорецепторов, что может повысить риск при общем наркозе. ќписаны случаи зат¤жного т¤желого снижени¤ ј? во врем¤ наркоза и трудности при восстановлении и поддержании сердечных сокращений. ¬о врем¤ операции эффекты бета-адреноблокаторов могут быть ликвидированы с помощью достаточных доз бета-адреномиметиков.

Ћекарственные средства с бета-адреноблокирующим эффектом могут заблокировать системный агонистический эффект, например, эпинефрина. Ќеобходимо предупредить анестезиолога о том, что пациент получает тимолол.

Ѕета-адреноблокаторы могут усилить гипогликемическое действие противодиабетических средств и маскировать симптомы и про¤влени¤ гипогликемии. »х следует примен¤ть с осторожностью у больных со спонтанной гипогликемией или сахарным диабетом (особенно лабильного течени¤), получающих инсулин или гипогликемические средства дл¤ приема внутрь.

“ерапи¤ бета-адреноблокаторами может маскировать некоторые основные симптомы и про¤влени¤ гипертиреоза. –езкое прекращение лечени¤ может вызвать обострение этого заболевани¤.

ѕри лечении бета-адреноблокаторами у больных с атопией или т¤желыми анафилактическими реакци¤ми на различные аллергены в анамнезе возможно усиление ответа при повторном контакте с этими аллергенами. ѕри этом эпинефрин в обычных дозах, примен¤ющихс¤ дл¤ купировани¤ анафилактических реакций, может оказатьс¤ неэффективным.

¬ редких случа¤х тимолол вызывал усиление мышечной слабости у пациентов с miastenia gravis или миастеническими симптомами (например, диплопией, птозом, генерализованной слабостью).

ѕри применении средств, снижающих ¬v?, описаны случаи отслойки сосудистой оболочки после фильтрационных процедур - фистулизирующих операций (трабекулэктоми¤ и ее модификации, синусотоми¤ с диатермотрабекулоспазисом, непроникающа¤ глубока¤ склерэктоми¤ и другие фистулизирующие операции, которые создают новые или стимулируют существующие пути оттока внутриглазной жидкости).

ќфтальмологические препараты из группы бета-адреноблокаторов могут вызывать сухость глаз. —ледует про¤вл¤ть осторожность при применении у пациентов с заболевани¤ми роговицы.

¬ли¤ние на способность к вождению автотранспорта и управлению механизмами

ѕрименение глазных капель может вызвать преход¤щее затуманивание зрени¤. ѕока этот эффект не исчезнет, пациентам не следует управл¤ть транспортным средством или потенциально опасными механизмами.

ѕередозировка

—имптомы: обусловленные латанопростом - раздражение глаз, конъюнктивальна¤ или эписклеральна¤ гипереми¤, головокружение; обусловленные тимололом - головна¤ боль, аритми¤, брадикарди¤, бронхоспазм, тошнота, рвота.

Ћечение: немедленно промыть глаза водой или 0.9% раствором натри¤ хлорида. ѕроведение симптоматической терапии.

Ћекарственное взаимодействие

¬заимодействие препарата ?уопрост с другими препаратами специально не изучалось.

ѕри применении препарата ?уопрост у пациентов, получающих бета-адреноблокатор внутрь, возможно более выраженное снижение ¬v? или усиление системных про¤влений бета-адреноблокаторов, поэтому одновременное местное применение двух и более бета-адреноблокаторов не рекомендуетс¤.

ѕри одновременном закапывании в глаза двух аналогов простагландинов описано парадоксальное повышение ¬v?, поэтому одновременное применение двух и более простагландинов, их аналогов или производных не рекомендуетс¤.

ѕри одновременном применении тимолола с эпинефрином иногда развивалс¤ мидриаз.

ѕри сочетании тимолола с перечисленными ниже препаратами возможно аддитивное действие со снижением ј? и/или выраженной брадикардией:

• блокаторы медленных кальциевых каналов;

• средства, вызывающие снижение содержани¤ катехоламинов, или бета-адреноблокаторы;

• антиаритмические средства (в т.ч. амиодарон);

• парасимпатомиметические средства;

• симпатолитические средства (включа¤ гуанетидин);

• сердечные гликозиды.

An increase in the action of systemic beta-blockers (eg, decreased heart rate, depression) has been reported with the simultaneous use of inhibitors of the CYP2D6 isoenzyme (eg, quinidine, fluoxetine, paroxetine) and timolol.

Beta-blockers can enhance the effect of hypoglycemic drugs.

With a sudden cancellation of clonidine, an increase in blood pressure is noted. This reaction can be enhanced by simultaneous use with beta-blockers.