KOSOPT

Active material: Dorzolamid, Timolol
When ATH: S01ED51
CCF: Antiglaucoma drug
ICD-10 codes (testimony): H40.1
When CSF: 26.01.01.09
Manufacturer: MERCK SHARP & DOHME B.V.. (Netherlands)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Eye drops in the form of a transparent, colorless or nearly colorless, slightly viscous liquid.

Excipients: benzalkonium chloride, sodium citrate, mannitol, gietelloza (hydroxyethyl), Sodium hydroxide, water d / and.

5 ml – bottles plastic type “Okumeter Plus” (1) – packs cardboard.

Pharmacological action

Antiglaucoma drug, contains two active components: dorzolamida hydrochloride and timolola maleate, each of which reduces the elevated intraocular pressure by lowering the secretion of fluid vnutriglazna. The combined effect of these substances combined drug Kosopt leads to a more pronounced reduction of intraocular pressure.

Dorzolamida hydrochloride – selective inhibitor of carbonic anhydrase type II. Inhibition of carbonic anhydrase ciliary body leads to a decrease in the secretion of fluid vnutriglazna, presumably due to reduce the formation of bicarbonate ions, that in turn leads to a slow transport of sodium and fluid.

Timolola maleate – selective beta-8th. Although the exact mechanism of action of timolola maleate in lowering intraocular pressure is still not installed, a number of studies have shown preemptive reduction education, as well as slight increased outflow of fluid.

Pharmacokinetics

Dorzolamida hydrochloride

The local application dorzolamid penetrates into the bloodstream. With long-term use, dorzolamid accumulates in erythrocytes as a result of the selective binding with type II karboangidrazoj, maintaining extremely low concentrations of free drug plasma. As a result of the metabolism of dorzolamida formed the only N-desètil′nyj metabolite, which is less explicitly blocks the carbonic anhydrase type II compared to the reference substance, at the same time, however, ingibiruet carboangidrazou type I (less active CYP). Metabolite also accumulates in erythrocytes, where is associated mainly with type I karboangidrazoj. About 33% dorzolamida associated with blood plasma proteins. Dorzolamid return with urine in an unmodified form and in the form of metabolita. After discontinuation of the drug dorzolamid nonlinear washed from erythrocytes, that leads to a rapid decline in its concentration, and then off to slow down. T_1/2 is about 4 Months.

When taking dorzolamida inside, to simulate the maximum system impact during it topical application, equilibrium was able to achieve through the 13 weeks. When the plasma actually was found free of the drug or its metabolites. Inhibition of erythrocyte carbonic anhydrase was not sufficient for the, to achieve a pharmacological effect on the kidneys and respiratory. Similar pharmacokinetic results were observed in long-term topical application of dorzolamide hydrochloride. Nonetheless, in some elderly patients with renal insufficiency (CC 30-60 ml / min) We showed higher concentrations of metabolite in erythrocytes, however it had no clinical significance.

Timolola maleate

The local application of timolol maleate penetrates into the systemic circulation. The concentration of timolol in plasma was studied in 6 patients with local application of timolola maleate in the form 0.5% eye drops 2 times / day. Average C_max After a morning of use was 0.46 ng / ml, After applying the day – 0.35 ng / ml. Decline vnutriglaznogo pressure comes through 20 min after instillation, reaches through 2 hours and lasts not less than 24 no.

Testimony

For the treatment of elevated intraocular pressure:

-Open-glaucome;

— psevdoèksfoliativnoj glaucoma.

Dosage regimen

The drug is prescribed for 1 drop into the conjunctival sac of the affected eye (or in both eyes) 2 times / day.

If Kosopt is prescribed as a substitute for other ophthalmic drug for treatment of glaucoma, the latter should cancel the day before applying Kosopta.

In the case of a joint application with other eye drops Kosopt should be assigned at intervals of not less than 10 m.

Kosopt is a sterile solution, Therefore, patients should be instructed to, How to use a bottle.

Instructions for use

1. Before using the product to make sure, that the protective Strip on the outside of the vial is not damaged. From sealed bottles there may be a gap between the bottle and the CAP.

2. Remove the protective Strip for, to open the CAP.

3. To open the bottle, unscrew the cap, by turning it in the direction of arrows pointing at the upper surface of the cap.

4. Tilt your head back slightly and pull the lower eyelid down to the appearance of the space between the eyelid and the eye.

5. Turn the bottle, thumb or finger lightly press into place, specially marked on the bottle so, to a drop hit the eye. Do not touch the surface of the eye, or the tip of the vial century. If used improperly, the bottle can become infected and cause serious infectious damage to the eye and subsequent vision loss.

6. Repeat items 4 and 5 for each eye, If the drug should be instilled into both eyes.

7. Close the bottle cap, twisting to tight contact with the bottle. Do not press on the lid too hard or you may damage the bottle or Cap.

8. There should be no increase in the hole specifically designed dosing devices as well as tip.

Side effect

The drug is generally well tolerated. In clinical studies, side effects, inherent in this drug combination exclusively, not observed. Side effects were limited to the already known side effects of dorzolamida hydrochloride and/or timolola maleate. Total systemic side effects were mild and did not result in withdrawal. In clinical studies was appointed Kosopt 1035 patients. At approximately 2.4% patients medication was cancelled in connection with local adverse reactions on the part of the organ of vision. Approximately 1.2% patients drug was canceled due to local adverse reactions of hypersensitivity or allergies.

Among the most frequent side effects experienced a burning sensation or itching in the eye, distortion of taste, corneal erosion, conjunctival injection, blurred vision, lacrimation.

IN post-marketing surveillance period The following adverse events were noted: breathlessness, respiratory insufficiency, contact dermatitis, bradycardia, AV блокада, choroidal detachment shell eyes, nausea. Describes cases of edema and irreversible destruction of the cornea in patients with chronic corneal defects and/or undergoing producing intraocular surgery.

Known possible side effects of the drug:

Dorzolamida hydrochloride

On the part of the organ of vision: inflammation of eyelid, irritation and peeling of the century, iridocyclitis, punctate keratitis, transient myopia (passing after drug withdrawal),

From the central and peripheral nervous system: headache, fatigue/tiredness, paresthesia.

Allergic reaction: angioedema, bronchospasm, hives, itch.

Other: nose bleed, throat irritation, dry mouth, rash.

Timolola maleate

When applied topically

On the part of the organ of vision: conjunctivitis, .Aloe, keratit, reduced corneal sensitivity, dryness; visual disturbances, include revisions of the refractive power of the eye (in some cases, due to the cancellation of miotikov), diplopia, ptosis.

From the central and peripheral nervous system: Tinnitus paresthesia, headache, asthenia, fatigue, dizziness; depression, insomnia, nightmares, memory decline, increase symptoms of myasthenia.

Cardio-vascular system: arrhythmia, gipotenziya, fainting, cardiovascular disorders, arrhythmias, cardiac arrest, swelling, Raynaud's syndrome, reducing the temperature of hands and feet.

The respiratory system: bronchospasm (mainly in patients with previous bronhoobstruktivnoj pathology), cough, chest pain.

Dermatological reactions: alopecia, psoriasiform rash or worsening of psoriasis.

Allergic reactions: anaphylaxis, angioedema, hives, local or generalized rash.

From the digestive system: diarrhea, dyspepsia, dry mouth.

Other: decreased libido, Peyronie's disease, SLE.

When administered systemically

Cardio-vascular system: reduced tolerance for endurance, AV блокада 2 and 3 degrees, sinoaurikuliarnaya blockade, pulmonary edema, worsening of violations of peripheral blood circulation, worsening of angina, vasodilation.

Dermatological reactions: scabies, increased perspiration, exfoliative dermatitis.

CNS: dizziness, weakness, poor concentration, hypersomnia.

Other: pain in the extremities, vomiting, giperglikemiâ, gipoglikemiâ, netrombocitopeničeskaâ Purpura, crepitation, arthralgia, impotence, voiding.

From the laboratory parameters: clinically significant changes in systemic application of timolola maleate occurred very rarely. Describes an easy increase in magnitude of residual nitrogen, potassium level, uric acid and triglycerides blood plasma; a slight decrease in hemoglobin, gematokrita, cholesterol, HDL, However, these changes have not progressed and not clinically manifested.

Application of beta-adrenoblokatorov could exacerbate myasthenia psevdoparalitičeskoj.

Contraindications

- Bronchial asthma (incl. history);

-severe COPD;

— sinusova aetiology;

— AV-blockade II and III degrees;

- Severe heart failure;

- Cardiogenic shock;

- Severe renal insufficiency (CC less than 30 ml / min);

-Dystrophic processes in the cornea;

- Pregnancy;

- Lactation (breast-feeding);

- Childhood and adolescence up 18 years (tk. efficacy and safety were studied is not enough);

- Hypersensitivity to the drug.

Pregnancy and lactation

The drug is contraindicated during pregnancy and lactation (breast-feeding).

Cautions

In clinical trials Kosopta 49% patients were aged 65 and older, 13% patients – aged 75 and older. The difference in efficacy and safety of drugs in these age groups compared with younger patients has not been. Nonetheless, You should not exclude the possibility of a higher sensitivity to the drug among some older patients.

Like other ophthalmic drugs for topical application, Kosopt can be absorbed in the blood system. Of the drug is a beta adrenoblokatorom timolol, thus, Adverse Reactions, systems use known beta-adrenoblokatorov, may occur when a local drug Kosopt, incl. exacerbation of vasospastic angina (Prinzmetal angina), violations of peripheral and Central circulatory system, hypotension. Before applying the product Kosopt it is necessary to ensure adequate control of cardiac insufficiency. Patients with severe pathologies of heart disorder and signs of congestive heart failure should be under close supervision (You must follow the CURVES in these patients).

Registered reports of fatality as a result of bronchospasm in patients with bronchial asthma and heart failure with the use of eye drops, containing timolola maleate.

No studies of the application of Kosopta in patients with liver failure, Therefore the drug in these patients should be used with caution.

Systemic carbonic anhydrase inhibitors may lead to violation of KHR and urolithiasis, especially in patients with urolithiasis in history. During the application Kosopta such violations were observed, urolitiaze messages were rare. The risk of urolitiaza in patients with urolithiasis in history may increase when applying Kosopta, tk. It includes an inhibitor of carbonic anhydrase, which when applied topically can be absorbed into the bloodstream.

Therapy with beta-adrenoblokatorami can distort some of the symptoms of hypoglycemia in patients with diabetes or hypoglycemia.

Beta-adrenoblokatora may smooth over hyperthyroidism. Stopping beta blockers may be the cause of the deterioration of the.

When the first signs or symptoms of heart failure use Kosopta should stop.

In the case of the upcoming surgery using general anesthesia should stop the drug for 48 hours before the operation, tk. timolol enhances the effect miorelaksantov and general anesthetics.

The composition of the Kosopta includes the preservative benzalkonium chloride, that can cause irritation of the eyes. Contact lenses before instillation of drug should be remove and install them again no earlier than 15 minutes after instillation. Benzalconia chloride is capable of discoloring soft contact lenses.

Effects on ability to drive vehicles and management mechanisms

In applying Kosopta possible side effects, that some patients can make driving a car or work with complex mechanisms.

Overdose

Data on accidental or intentional overdose Kosopta lacking.

Cases of unintentional overdose of timolola maleate in the form of eye drops with the development of systemic effects overdose beta-adrenoblokatorov for systemic use: dizziness, headache, breathlessness, bradycardia, bronchospasm, cardiac arrest.

Most expected symptoms dorzolamida overdose are violation of elektrolitnogo balance, development of acidosis, possible side effects of the central nervous system.

Treatment: symptomatic and supportive therapy. It should monitor the level of electrolytes (primarily sodium) and pH of blood plasma. Studies have also shown, that appears when no dialysis timolol.

Drug Interactions

Specific Kosopta interaction studies with other drugs had not been. Nonetheless, There is a possibility of strengthening gipotenzivnogo effect and/or development of bradycardia with a joint application of the ophthalmic solution timolola maleate and calcium channel blockers, kateholamin-exhausting funds, beta-blockers, antiarrhythmics (including amiodarone), Digitalis glycosides, parasimpatomimetikov, opioid analgesics and MAO inhibitors.

When timolola and inhibitors of CYP2D6 (eg, quinidine or selective serotonin reuptake inhibitors) It was reported on potencirovannom effect of systemic Beta-Adrenergic blockade (eg, reduction of frequency CURVES, depression).

Despite, that is part of the Kosopta inhibitor of carbonic anhydrase dorzolamid used locally, It can seep into the bloodstream. In clinical studies of the use of the ophthalmic solution dorzolamida hydrochloride have been detected disorders KHR. Nonetheless, the systems use carbonic anhydrase inhibitors, these disorders are known, and in some cases, they can affect the interaction with other drugs (eg, strengthen the toxic reaction when applied in high doses of salicylates). The possibility of such interactions must be taken into account in patients, receiving Kosopt.

Systemic beta-adrenoblokatora may increase gipoglikemiceski effect protivodiabeticakih drugs and arterial hypertension, that is the effect of the abolition of clonidine (clofelina).

Despite, that alone Kosoptom effect on the pupil is minimal or non-existent, There are individual descriptions of kid development in the sharing of timolola maleate and adrenaline.

There is a possibility of strengthening known systemic effects of inhibition of carbonic anhydrase in the combined application of local and systemic carbonic anhydrase inhibitors. Unnecessarily. data on the use of such combinations is missing, combined use of Kosopta and systemic carbonic anhydrase inhibitors is not recommended.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children, dark place at a temperature no higher than 25 ° C. Shelf life – 2 year. After first opening the vial Kosopt should not be used for longer 4 weeks.