Expiration date: 11/2025

Release form and composition: 

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

1 ml contains:

dorzolamide hydrochloride 22.6 mg, corresponds to the content of dorzolamide 20 mg

timolol maleate 6.83 mg, corresponds to the content of timolol 5 mg

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

5 ml - bottles, plastic-type Ocumeter Plus (1) - packs of cardboard.

Pharmacological action:

Antiglaucoma drug contains two active components: dorzolamide hydrochloride and timolol maleate, each of which reduces elevated intraocular pressure by reducing the secretion of intraocular fluid. The combined action of these substances in the combined drug Cosopt leads to a more pronounced reduction of intraocular pressure.

Dorzolamide hydrochloride is a selective inhibitor of carbonic anhydrase type II. Inhibition of carbonic anhydrase ciliary body leads to decreased secretion of intraocular fluid, presumably due to the decrease in the formation of bicarbonate ions, which in turn leads to a slow transport of sodium and fluid.

Timolol maleate is a nonselective beta-blocker. Although the exact mechanism of action of timolol maleate in lowering intraocular pressure is still not installed, a number of studies have shown a preferential reduction education, as well as a slight increase in the outflow of the liquid.

Pharmacokinetics:

Dorzolamide hydrochloride

The local application of dorzolamide enters the systemic circulation. With prolonged use of dorzolamide accumulates in red blood cells due to selective binding to carbonic anhydrase type II, supporting the extremely low concentrations of free drug in plasma. As a result of the metabolism of dorzolamide is formed only N-Desailly metabolite, which is less markedly inhibits carbonic anhydrase type II compared to the original substance, but at the same time inhibits carbonic anhydrase type I (less active isoenzyme). The metabolite also accumulates in RBCs where it binds mainly to carbonic anhydrase I type. About 33% of dorzolamide is associated with blood plasma proteins. Dorzolamide is excreted in the urine unchanged and as metabolites. After drug discontinuation nonlinear dorzolamide washes out of the red blood cells that initially leads to a rapid decrease in its concentration, and then elimination slows down.T1/2 is about 4 months.

When taking dorzolamide inside, to simulate the maximum systemic exposure during topical application, the equilibrium state was achieved in 13 weeks. In this case the plasma was not actually discovered the free drug or its metabolites. Inhibition of carbonic anhydrase of erythrocytes was insufficient in order to achieve a pharmacological effect in relation to renal function and respiration. Similar pharmacokinetic results were observed with long-term topical application of dorzolamide hydrochloride. However, in some elderly patients with renal insufficiency (QC 30-60 ml/min) showed a higher concentration of the metabolite in erythrocytes, however, this had no clinical significance.

Timolol maleate

The local application timolola maleate penetrates into the bloodstream. The concentration of timolol in plasma was studied in 6 patients the local application timolola maleate in the form of a 0.5% eye drops 2 times/day. The average Cmax after the morning use was 0.46 ng/ml, after the application of day - 0.35 ng/ml. the Reduction of intraocular pressure occurs within 20 minutes after instillation, reaching a maximum after 2 hours and lasts for at least 24 h.

Indications:

For the treatment of elevated intraocular pressure in:

• open angle glaucoma
  
• pseudoexfoliation glaucoma.
  

Dosing regimen:

The preparation appoint 1 drop in kongungualny bag the affected eye (or both eyes) 2 times/day.

If Cosopt appoint as a replacement another ophthalmic drug for glaucoma treatment, the latter should be abolished the day before the start of the application of Cosopt.

In the case of joint use with other eye drops Cosopt should be appointed at intervals of not less than 10 min.

Cosopt is a sterile solution, so patients should be instructed on how to properly use the bottle.

Instructions for use

1. Before the first use of the drug is necessary to make sure that the protective strip on the outside of the bottle is not damaged. Have unopened bottles you may have a gap between the bottle and cap.

2. Remove the protective strip in order to open the cap.

3. To open the bottle, Unscrew the cap by turning it in the direction of directional arrows on the upper surface of the cap.

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

5. Flip the bottle with your thumb or forefinger to lightly press in place, especially marked on the bottle so that one drop in your eye. Do not touch the surface of the eye or eyelid with the tip of the bottle. If used improperly, the bottle can become infected and cause serious infectious eye damage and subsequent loss of vision.

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

7. Close the bottle cap, twisting it until tight contact with the bottle. Do not press the cover too hard otherwise you can damage the bottle or the cap.

8. You should not enlarge the hole a specially designed dispenser tip.

Side effects:

The drug is generally well tolerated. In clinical studies, side effects, typical exclusively to this combination drug have been observed. Side effects were limited to the already known side effects of dorzolamide hydrochloride and/or timolol maleate. In General, systemic side effects were mild and did not lead to drug discontinuation. In clinical studies, Cosopt appointed 1035 patients. Approximately 2.4% of the patients the drug was withdrawn due to local adverse reactions from the body. Approximately 1.2% of patients the drug was withdrawn due to local adverse reactions, hypersensitivity or Allergy.

Among the most frequent side effects noted burning sensation or itching in the eye, distortion of taste, corneal erosion, conjunctival injection, blurred vision, watery eyes.

In post-marketing observation period was observed following adverse events: dyspnea, respiratory failure, contact dermatitis, bradycardia, AV-blockade, a detachment choroidal layer of the eye, nausea. Described cases of swelling and irreversible destruction of the cornea in patients with chronic corneal defects and/or undergoing intraocular surgery.

Known possible side effects of the drug's components:

Dorzolamide hydrochloride

On the part of the organ of vision: eyelid inflammation, irritation and flaking of the century, iridocyclitis, point keratitis, transient myopia (reversible after drug withdrawal),

CNS and peripheral nervous system: headache, asthenia/fatigue, paresthesia.

Allergic reactions: angioedema, bronchospasm, urticaria, itching.

Other: nasal bleeding, irritation of the pharynx, dry mouth, rash.

Timolol maleate

The local application

On the part of the organ of vision: conjunctivitis, blepharitis, keratitis, reduced corneal sensitivity, dry disturbances, including changes the refractive ability of the eye (in some cases due to the cancellation of miotikov), diplopia, ptosis.

CNS and peripheral nervous system: tinnitus, paresthesia, headache, asthenia, fatigue, dizziness, depression, insomnia, nightmares, memory loss, increase of symptoms of myasthenia gravis.

From the side of cardiovascular system: arrhythmia, hypotension, syncope, cardio-vascular disorders, arrhythmias, heart failure, edema, Raynaud's syndrome, temperature reduction of the hands and feet.

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

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

Allergic reactions: anaphylaxis, angioedema, urticaria, localized or generalized rash.

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

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

The systems use

From the side of cardiovascular system: reduced tolerance to physical stress, AV-blockade of 2nd and 3rd degree, sinoaurikuliarnaya blockade, pulmonary edema, poor peripheral circulatory disorders, worsening of angina pectoris, vasodilation.

Dermatological reactions: itching, sweating, exfoliative dermatitis.

CNS: dizziness, weakness, poor concentration, increased sleepiness.

Other: pain in extremities, vomiting, hyperglycemia, hypoglycemia, metropolitaines purpura, wheezing, arthralgia, impotence, voiding.

From the laboratory parameters: clinically important changes in systemic use of timolol maleate was observed very rarely. Described a slight increase in residual nitrogen levels of potassium, uric acid and triglycerides of blood plasma a slight decrease in hemoglobin, hematocrit, cholesterol, HDL, however, these changes are not progressed and not clinically manifested.

The use of beta-blockers may cause worsening of myasthenia gravis psevdoparalitichesky.

Contraindications:

• bronchial asthma (including in history)
  
• severe COPD
  
• sinus bradycardia
  
• AV blockade II and III degree
  
• expressed heart failure
  
• cardiogenic shock
  
• renal failure, severe (CC less than 30 ml/min)
  
• dystrophic processes in the cornea
  
• pregnancy
  
• lactation (breast feeding)
  
• child and adolescence to 18 years (because efficacy and safety have been insufficiently studied)
  
• hypersensitivity to the drug.
  

Pregnancy and lactation:

The drug is contraindicated during pregnancy and lactation (breastfeeding).

Special instructions:

In clinical studies of Cosopt 49% of patients were aged 65 years and older, 13% of patients aged 75 years and older. The difference in the efficiency and safety of the drug in these age groups compared to younger patients was not. However, one should not exclude the possibility of higher sensitivity to the drug in some older patients.

As with other ophthalmic drugs for topical application, Cosopt can be absorbed into the systemic circulation. Part of the drug timolol is a beta blocker, so adverse reactions known with systemic use of beta-blockers may occur with topical application of the drug Cosopt, including exacerbation of vasospastic angina (strokes Prinzmetala), disorders of the peripheral and Central circulation, hypotension. Before the drug Cosopt necessary to provide adequate control of heart failure. Patients with the severe cardiac pathology in anamnesis and signs of heart failure should be monitored carefully (monitor heart rate in these patients).

Recorded message about a lethal outcome as a result of bronchospasm in patients with bronchial asthma and heart failure on a background of application of eye drops containing timolol maleate.

Not been conducted studies of the use of Cosopt in patients with hepatic impairment, therefore such patients should be used with caution.

The use of systemic carbonic anhydrase inhibitors may lead to violation of AAR accompanied with urolithiasis, especially in patients with urolithiasis in history. During the application of Cosopt of such violations were observed, reports of urolithiasis was rare. The risk of urolithiasis in patients with urolithiasis in history may rise in the application of Cosopt, because it consists of a carbonic anhydrase inhibitor, which the local application may be absorbed and enter the systemic circulation.

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

Beta-blockers can make up for hyperthyroidism. Stopping beta-blockers can be the cause of deterioration.

When the first signs or symptoms of heart failure use of Cosopt should be discontinued.

In the case of the upcoming surgery with a General anaesthetic, you must stop the drug 48 hours before surgery, since timolol increases the effect of muscle relaxants and General anesthetics.

In Cosopt included the preservative benzalkonium chloride, which can be a cause of irritation to the eye. Contact lenses before instillation of drug should be removed and install them again no earlier than 15 minutes after backfilling. Benzalkonium chloride is able to discolour soft contact lenses.

Effects on ability to drive vehicles and management mechanisms

The application of Cosopt may develop side effects that some patients can make it difficult to control the car or work with complex mechanisms.

Overdose:

Data for accidental or intentional overdose of Cosopt do not exist.

Cases of unintentional overdose of timolol maleate in the form of eye drops to the development of systemic effects of overdose of beta-blockers for systemic use: dizziness, headache, shortness of breath, bradycardia, bronchospasm, cardiac arrest.

The most expected symptoms of overdosage of dorzolamide are electrolyte imbalance, development of acidosis, possible side effects from the CNS.

Treatment: symptomatic and supportive therapy. Should monitor the level of electrolytes (especially sodium) and the pH of the blood plasma. The studies also shown that timolol is not displayed by dialysis.

Drug interactions:

Specific studies of the interaction of Cosopt with other drugs have not been conducted. However, there is the possibility of increasing the hypotensive effect and/or the development of severe bradycardia when used together ophthalmic solution timolol maleate and calcium channel blockers, catecholamine-depleting means, beta-blockers, antiarrhythmics (including amiodarone), digitalis glycosides, parasympathomimetics, opioid analgesics and MAO inhibitors.

In a joint application of timolol and CYP2D6 inhibitors (e.g. quinidine or selective inhibitors of serotonin reuptake) was reported potentiated the effect of systemic blockade of beta-adrenergic receptors (e.g., reducing the frequency of heart rate, depression).

Despite the fact that part of Cosopt the carbonic anhydrase inhibitor dorzolamide is used topically, it can penetrate into the systemic circulation. In clinical studies use ophthalmic solution dorzolamide hydrochloride has not been identified disorders of the AAR. However, with systemic use of carbonic anhydrase inhibitors these disorders is known, and in some cases they can affect interaction with other drugs (for example, to strengthen the toxic reactions of salicylates in high doses). The possibility of such interactions must be considered in patients receiving Cosopt.

Systemic beta-blockers may enhance the hypoglycemic effect of antidiabetic drugs and arterial hypertension, which is the effect of the abolition of clonidine (clonidine).

Despite the fact that monotherapy Coopcom effect on the pupil is minimal or absent, there are few descriptions of the development of mydriasis in a joint application of timolol maleate and epinephrine.

There is probability gain known systemic effects of carbonic anhydrase inhibition by the combined use of local and systemic carbonic anhydrase inhibitors. Because data on the use of such combinations do not exist, the combined use of Cosopt and systemic carbonic anhydrase inhibitors is not recommended.

Terms and conditions of storage:

The drug should be stored out of the reach of children, protected from light place at temperature not exceeding 25°C. shelf Life - 2 years. After first opening of vial Cosopt should not be used longer than 4 weeks.