Cosopt eye drops, 5ml

Increased intraocular pressure:

• with open-angle glaucoma;

• with pseudoexfoliative glaucoma with insufficient effectiveness of monotherapy.

Cosopt is prescribed 1 drop into the conjunctival sac of the affected eye (or both eyes) 2 times / day. If Cosopt is prescribed as a replacement for another ophthalmic drug for the treatment of glaucoma, the latter should be canceled the day before Cosopt therapy begins.

In the case of joint use with another local ophthalmic drug, Cosopt should be used with an interval of at least 10 minutes. With nasolacrimal occlusion (closing the eyelids) for 2 minutes after instillation of the drug, its systemic absorption decreases, which can lead to an increase in local action. Rules for using the drug Cosopt is a sterile solution, therefore, patients should be instructed on how to use the bottle correctly.

1. Before using the drug for the first time, make sure that the protective strip on the outside of the bottle is not damaged. Unopened vials may have a gap between the vial and the 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 the direction arrows on the top surface of the cap.

4. Tilt your head back and pull the lower eyelid slightly downward to create a space between the eyelid and the eye.

5. Turn the bottle over, lightly press with thumb or forefinger in the place specially marked on the bottle so that one drop gets into the eye. Do not touch the surface of the eye or eyelid with the tip of the bottle. If used improperly, the vial can become infected and cause serious infection of the eye and subsequent loss of vision.

6. After instillation of the drug, you should close your eyes and press your finger on the inner corner of the eye, pressing it to the bridge of the nose for 2 minutes. This helps to keep the drug in the eye.

7. Repeat steps 4 and 5 for the other eye, if necessary.

8. Close the bottle with a cap by twisting it until tight contact with the bottle. When properly closed, the arrow on the vial cap should line up with the arrow on the vial label. Do not tighten the cap too tightly, otherwise the bottle or cap may be damaged.

9. Do not enlarge the opening of the specially designed dispensing tip.

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

1 ml

dorzolamide hydrochloride 22.26 mg,

which corresponds to the content of dorzolamide base 20 mg

timolol maleate 6.83 mg,

which corresponds to the content of timolol base 5 mg

Excipients: benzalkonium chloride (in the form of a 50% solution of benzalkonium chloride) - 0.075 mg (0.15 mg), sodium citrate - 2.94 mg, mannitol - 16 mg, hyetellose (hydroxyethyl cellulose) - 4.75 mg, 1M sodium hydroxide solution - qs to pH 5.6 , water d / i - qs up to 1 ml.

• Airway hyperresponsiveness;

• bronchial asthma (including history);

• severe COPD;

• sinus bradycardia;

• SSSU;

• AV block II and III degree without a pacemaker;

• severe heart failure;

• cardiogenic shock;

• severe renal failure (CC <30 ml / min);

• hyperchloremic acidosis;

• dystrophic processes in the cornea; pregnancy;

• lactation period (breastfeeding);

• children and adolescents up to 18 years of age (due to insufficient knowledge of the effectiveness and safety);

• hypersensitivity to the components of the drug.

pharmachologic effect

Combined antiglaucoma drug. Contains two active ingredients: dorzolamide hydrochloride and timolol maleate, each of which reduces increased intraocular pressure by reducing the secretion of intraocular fluid. The combined action of these substances in the composition of the drug leads to a more pronounced decrease in intraocular pressure. Dorzolamide hydrochloride is a selective type II carbonic anhydrase inhibitor. Inhibition of carbonic anhydrase of the ciliary body leads to a decrease in the secretion of intraocular fluid, presumably due to a decrease in the formation of bicarbonate ions, which in turn leads to a slowdown in the transport of sodium and fluid. Timolol maleate is a non-selective beta-blocker. Although the exact mechanism of action of timolol maleate in lowering intraocular pressure has not yet been established,a number of studies have shown a predominant decrease in education, as well as a slight increase in fluid outflow.

Pharmacokinetics

Dorzolamide hydrochloride

Absorption and distribution

When applied topically, dorzolamide enters the systemic circulation. With prolonged use, dorzolamide accumulates in erythrocytes as a result of selective binding to type II carbonic anhydrase, maintaining extremely low plasma concentrations of the free drug. About 33% of dorzolamide binds to blood plasma proteins.

Metabolism and excretion

As a result of the metabolism of dorzolamide, a single N-deethyl metabolite is formed, which less pronouncedly blocks type II carbonic anhydrase compared to its initial form, but at the same time inhibits type I carbonic anhydrase - a less active isoenzyme. The metabolite also accumulates in erythrocytes, where it binds mainly to type I carbonic anhydrase. Dorzolamide is excreted in the urine unchanged and as a metabolite. After discontinuation of the drug, dorzolamide is nonlinearly washed out of erythrocytes, which first leads to a rapid decrease in its concentration, and then elimination slows down. T1 / 2 is about 4 months old. When dorzolamide was taken orally, in order to simulate the maximum systemic exposure during its topical application, a stable state was achieved after 13 weeks.At the same time, virtually no free drug or its metabolites were found in plasma. Inhibition of erythrocyte carbonic anhydrase was insufficient to achieve a pharmacological effect on renal and respiratory function. Similar pharmacokinetic results were observed with long-term topical administration of dorzolamide hydrochloride. Nevertheless, in some elderly patients with renal insufficiency (CC 30-60 ml / min), higher concentrations of the metabolite in erythrocytes were detected, however, this had no clinical significance.in some elderly patients with renal insufficiency (CC 30-60 ml / min), higher concentrations of the metabolite in erythrocytes were detected, but this had no clinical significance.in some elderly patients with renal insufficiency (CC 30-60 ml / min), higher concentrations of the metabolite in erythrocytes were detected, but this had no clinical significance.

Timolol maleate

When applied topically, timolol maleate enters the systemic circulation. The concentration of timolol in plasma was studied in 6 patients with topical application of eye drops of timolol maleate 0.5% 2 times / day. The average Cmax after the morning dose was 0.46 ng / ml, after the daily dose - 0.35 ng / ml. The antihypertensive effect occurs 20 minutes after instillation, reaches a maximum after 2 hours and lasts for at least 24 hours.

Side effect

Cosopt is generally well tolerated. In clinical studies, side effects unique to this combination drug were not observed. Adverse reactions 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 discontinuation of the drug. In clinical studies, Cosopt was prescribed to 1035 patients. In about 2.4% of patients, the drug was discontinued due to local ocular adverse reactions. In about 1.2% of patients, the drug was discontinued due to local adverse allergic reactions. The most common side effects from the organ of vision were: burning or itching in the eye, taste distortion, corneal erosion, conjunctival injections, blurred vision, lacrimation.In the post-registration period of observation, the following adverse events were noted: shortness of breath, respiratory failure, contact dermatitis, bradycardia, AV blockade, detachment of the choroid, nausea, Stevens-Johnson syndrome and toxic epidermal necrolysis. Cases of edema and irreversible destruction of the cornea have been reported in patients with chronic corneal defects and / or undergoing intraocular surgery.

Below are the possible side effects of the components of the drug.

Dorzolamide hydrochloride

From the side of the organ of vision: inflammation of the eyelid, irritation and peeling of the eyelid, iridocyclitis, punctate keratitis, transient myopia (passing after drug withdrawal). From the nervous system: headache, dizziness, paresthesia. Allergic reactions: angioedema, bronchospasm, itching, urticaria.

Others: asthenia / fatigue, nosebleeds, throat irritation, dry mouth, rash.

Timolol maleate (topical application)

From the side of the organ of vision: conjunctivitis, blepharitis, keratitis, decreased sensitivity of the cornea, dryness; visual disorders, including changes in the refractive power of the eye (in some cases due to the cancellation of miotics), diplopia, ptosis. From the side of the cardiovascular system: arrhythmia, hypotension, fainting, cardiovascular disorders, rhythm disturbances, cardiac arrest, edema, paresthesia, Raynaud's phenomenon. From the respiratory system: bronchospasm (mainly in patients with previous broncho-obstructive pathology), cough. Dermatological reactions: alopecia, psoriasis-like rashes or exacerbation of psoriasis. Allergic reactions: anaphylaxis, angioedema, urticaria, local or generalized rash. From the nervous system: headache, dizziness; paresthesia, depression, insomnia, nightmares,memory loss, an increase in myasthenia gravis symptoms. From the digestive system: diarrhea, dyspepsia, dry mouth. Others: ringing in the ears, asthenia, fatigue, chest pain, abdominal pain, decreased libido, Peyronie's disease, sexual dysfunction, systemic lupus erythematosus, myalgia, lameness, decreased temperature of hands and feet, edema. Timolol maleate (systemic use) From the side of the cardiovascular system: AV block II and III degree, sinoauricular block, worsening arterial insufficiency, worsening angina pectoris, vasodilation. From the side of metabolism: hyperglycemia, hypoglycemia. From the nervous system: dizziness, decreased concentration, increased drowsiness. Dermatological reactions: itching of the skin, increased sweating, exfoliative dermatitis. Others: pain in the limbs,decreased exercise tolerance, pulmonary edema, vomiting, arthralgia, weakness, non-thrombocytopenic purpura, wheezing, impotence, urinary disorders. With the systemic use of timolol maleate, clinically significant changes in standard laboratory parameters were observed extremely rarely. A slight increase in residual nitrogen, potassium, uric acid and plasma triglycerides is described; a slight decrease in hemoglobin, hematocrit, high-density lipoprotein cholesterol (HDL-C), however, these changes did not progress and did not appear clinically. The use of beta-blockers can exacerbate pseudoparalytic myasthenia gravis.With the systemic use of timolol maleate, clinically significant changes in standard laboratory parameters were observed extremely rarely. A slight increase in residual nitrogen, potassium, uric acid and plasma triglycerides is described; a slight decrease in hemoglobin, hematocrit, high-density lipoprotein cholesterol (HDL-C), however, these changes did not progress and did not appear clinically. The use of beta-blockers can exacerbate pseudoparalytic myasthenia gravis.With the systemic use of timolol maleate, clinically significant changes in standard laboratory parameters were observed extremely rarely. A slight increase in residual nitrogen, potassium, uric acid and plasma triglycerides is described; a slight decrease in hemoglobin, hematocrit, high-density lipoprotein cholesterol (HDL-C), however, these changes did not progress and did not appear clinically. The use of beta-blockers can exacerbate pseudoparalytic myasthenia gravis.however, these changes did not progress and did not manifest themselves clinically. The use of beta-blockers can exacerbate pseudoparalytic myasthenia gravis.however, these changes did not progress and did not manifest themselves clinically. The use of beta-blockers can exacerbate pseudoparalytic myasthenia gravis.

Application during pregnancy and lactation

You should not take Cosopt during pregnancy and breastfeeding. Dorzolamide There is insufficient information on the use of dorzolamide in pregnant women. It is not known whether dorzolamide passes into the breast milk of lactating women. In studies on rats, the teratogenic effect of dorzolomide in doses toxic to pregnant females was revealed. In pups of lactating female rats treated with dorzolamide, a decrease in body weight gain was found. Timolol There is insufficient information on the use of timolol in pregnant women. Timolol should not be taken during pregnancy unless the use of timolol is essential. Epidemiological studies have not found the effect of oral beta-blockers on the development of congenital malformations, but the risk of intrauterine growth retardation has been identified. Besides,in newborns, signs and symptoms of ?-adrenergic receptor blockade (bradycardia, hypotension, respiratory failure and hypoglycemia) were found when beta-blockers were used before delivery. If the drug was used before childbirth, you should carefully monitor the condition of the newborn in the first days of life. Beta-blockers pass into breast milk. The healthcare provider must decide whether to stop breastfeeding or stop taking the drug, taking into account the potential serious side effects for the breastfed baby and the benefits of the drug for the mother.the condition of newborns should be carefully monitored in the first days of life. Beta-blockers pass into breast milk. The healthcare provider must decide whether to stop breastfeeding or stop taking the drug, taking into account the potential serious side effects for the breastfed baby and the benefits of the drug for the mother.the condition of newborns should be carefully monitored in the first days of life. Beta-blockers pass into breast milk. The healthcare provider should make a decision about whether to stop breastfeeding or stop taking the drug, taking into account the potential serious side effects for the breastfed baby and the benefits of the drug for the mother.

Application for violations of liver function

There have been no studies of the use of the drug Cosopt in patients with hepatic insufficiency, and therefore the drug in such patients should be used with caution.

Application for impaired renal function

Contraindication: severe renal failure (CC <30 ml / min).

Application in children

Contraindicated in children and adolescents under 18 years of age.

Use in elderly patients

The possibility of a higher sensitivity to the drug in some elderly patients should not be ruled out.

special instructions

Like other topical ophthalmic drugs, Cosopt can be absorbed into the systemic circulation. Since timolol, which is part of the drug, is a beta-blocker, adverse reactions that develop with the systemic use of beta-blockers can be observed with local application of the drug. When the first signs or symptoms of heart failure appear, the use of Cosopt should be discontinued. Cardiovascular and Respiratory Reactions Patients with a history of cardiovascular disease, including heart failure, should be closely monitored for signs of worsening of these conditions. In such patients, it is necessary to monitor the pulse.Patients with grade I heart block should be given beta-blockers with caution due to their ability to slow impulse conduction. There have been reports of cases of fatal bronchospasm in patients with bronchial asthma and cases of fatal heart failure during the use of timolol maleate eye drops. For patients with mild to moderate COPD, Cosopt should be prescribed with caution and only if the intended benefit of treatment outweighs the potential risk. The drug should be used with caution in patients with severe peripheral circulatory disorders (severe forms of Raynaud's disease or Raynaud's syndrome). Hypoglycemia in patients with diabetes mellitus Beta-blockers should be used with caution in patientspredisposed to spontaneous hypoglycemia or patients with diabetes mellitus (especially a labile course of diabetes mellitus), while taking insulin or oral hypoglycemic drugs. Beta-blockers can mask the signs and symptoms of acute hypoglycemia. Thyrotoxicosis Beta-blockers can mask some clinical signs of hyperthyroidism (eg, tachycardia). If you suspect the development of thyrotoxicosis, patients should be closely monitored. It is necessary to avoid abrupt withdrawal of beta-blockers because of the risk of developing a thyrotoxic crisis. Anesthesia in surgery The need to cancel beta-blockers in the event of an upcoming major surgical intervention has not been proven.If necessary, during the operation, the effects of beta-blockers can be eliminated by using sufficient doses of adrenergic agonists. Liver dysfunction There have been no studies of the use of the drug Cosopt in patients with hepatic insufficiency, and therefore the drug in such patients should be used with caution. Allergies and hypersensitivity Like other topical ophthalmic preparations, Cosopt can enter the systemic circulation. Dorzolamide, which is part of the drug, is sulfonamide. Thus, adverse reactions identified with the systemic use of sulfonamides can be observed with topical application of the drug (Stevens-Johnson syndrome and toxic epidermal necrolysis). If signs of serious hypersensitivity reactions appear, the drug should be discontinued.When treating with beta-blockers in patients with atopy or severe anaphylactic reactions to various allergens in history, it is possible to increase the response with repeated contact with these allergens. In this group of patients, administration of epinephrine at the standard therapeutic dose used to relieve allergic reactions may be ineffective. Concomitant therapy When using the drug Cosopt in patients who are taking systemic beta-blockers, it is necessary to take into account the possible mutual enhancement of the pharmacological action of the drugs both with respect to the known systemic effects of beta-blockers and with respect to reducing intraocular pressure. The combined use of the drug Cosopt with other beta-blockers is not recommended. Termination of treatment If necessary, the cancellation of local use of timolol,as in the case of systemic beta-blockers, discontinuation of therapy in patients with coronary artery disease should be carried out gradually. Corneal disorders Beta-blockers used in ophthalmology can cause dry eyes. For patients with corneal disorders, the drug should be administered with caution. Patients with low endothelial cell counts have an increased risk of developing corneal edema. Urolithiasis The use of systemic carbonic anhydrase inhibitors can lead to acid-base imbalance and be accompanied by urolithiasis, especially in patients with a history of urolithiasis. During the use of the drug Cosopt, such violations were not observed, reports of urolithiasis were rare. Because Cosopt contains a carbonic anhydrase inhibitor,which, when applied topically, can be absorbed and penetrate into the systemic circulation, during treatment with the drug, the risk of developing urolithiasis in patients with a history of urolithiasis may increase. Miscellaneous Patients with acute angle-closure glaucoma, in addition to prescribing drugs that reduce intraocular pressure, require other therapeutic measures. Studies of the effect of the drug Cosopt in patients with acute angle-closure glaucoma have not been conducted. Use in the elderly 49% of patients in clinical trials of Cosopt were 65 years of age and older, 13% of patients were 75 years of age and older. There were no differences in the effectiveness and safety of the drug in these age groups compared with younger patients. Nonetheless,the possibility of a higher sensitivity to the drug in some elderly patients should not be ruled out. Using contact lenses Cosopt contains the preservative benzalkonium chloride, which can cause eye irritation. Before using the drug, the lenses must be removed and reinstalled no earlier than 15 minutes after the instillation of the drug. Benzalkonium chloride can discolor soft contact lenses.

Influence on the ability to drive vehicles and use mechanisms

When using the drug Cosopt, side effects may develop, which in some patients may make it difficult to drive or work with complex mechanisms.

Overdose

There are no data on accidental or intentional overdose of Cosopt. Symptoms: cases of unintentional overdose of eye drops containing timolol maleate have been described, with the development of systemic effects of an overdose of beta-blockers taken by mouth: dizziness, headache, shortness of breath, bradycardia, bronchospasm, cardiac arrest. The most expected symptoms of an overdose of dorzolamide are electrolyte imbalance, the development of acidosis, and possible side effects from the central nervous system. Treatment: symptomatic and supportive therapy. The level of electrolytes (primarily potassium) and blood plasma pH should be monitored. Timolol is not removed by dialysis.

Drug interactions

Specific studies of the interaction of the drug Cosopt with other drugs have not been conducted. Nevertheless, there is a possibility of an increase in the hypotensive effect and / or severe bradycardia with the combined use of eye drops of timolol maleate and systemic calcium channel blockers, catecholamine-depleting drugs, beta-blockers, antiarrhythmics (including amiodarone), digitalis glycosides, parasympathomimetics, opioids and MAO inhibitors. With the combined use of timolol and inhibitors of the isoenzyme CYP2D6 (for example, quinidine or selective serotonin reuptake inhibitors), a potentiated effect of systemic blockade of ?-adrenergic receptors has been reported (for example, decreased heart rate, depression). As a consequence, the possibility of such an interaction must be taken into account in patients,receiving Cosopt. Systemic beta-blockers can increase the hypoglycemic effect of antidiabetic drugs and hypertension, which is the effect of clonidine (clonidine) withdrawal. Despite the fact that with monotherapy with Cosopt, the effect on the pupil is minimal or absent, there are isolated descriptions of the development of mydriasis with the combined use of timolol maleate and adrenaline. There is a possibility of enhancing the known systemic effects of carbonic anhydrase inhibition with the combined use of local and systemic carbonic anhydrase inhibitors. Because there are no data on the use of such a combination; the combined use of Cosopt and systemic carbonic anhydrase inhibitors is not recommended.which is the effect of withdrawal of clonidine (clonidine). Despite the fact that with monotherapy with Cosopt, the effect on the pupil is minimal or absent, there are isolated descriptions of the development of mydriasis with the combined use of timolol maleate and adrenaline. There is a possibility of enhancing the known systemic effects of carbonic anhydrase inhibition with the combined use of local and systemic carbonic anhydrase inhibitors. Because there are no data on the use of such a combination; the combined use of Cosopt and systemic carbonic anhydrase inhibitors is not recommended.which is the effect of withdrawal of clonidine (clonidine). Despite the fact that with monotherapy with Cosopt, the effect on the pupil is minimal or absent, there are isolated descriptions of the development of mydriasis with the combined use of timolol maleate and adrenaline. There is a possibility of enhancing the known systemic effects of carbonic anhydrase inhibition with the combined use of local and systemic carbonic anhydrase inhibitors. Because there are no data on the use of such a combination; the combined use of Cosopt and systemic carbonic anhydrase inhibitors is not recommended.There is a possibility of enhancing the known systemic effects of carbonic anhydrase inhibition with the combined use of local and systemic carbonic anhydrase inhibitors. Because there are no data on the use of such a combination; the combined use of Cosopt and systemic carbonic anhydrase inhibitors is not recommended.There is a possibility of enhancing the known systemic effects of carbonic anhydrase inhibition with the combined use of local and systemic carbonic anhydrase inhibitors. Because there are no data on the use of such a combination; the combined use of Cosopt and systemic carbonic anhydrase inhibitors is not recommended.