Kosopt - instructions for use, doses, side effects, contraindications

Active substanceDorzolamide + TimololDorzolamide + Timolol

Similar drugsTo uncover

Dorzopt Plus

drops d / eye

ROMFARMA, OOO Russia

Kosopt

drops d / eye

Santen, AO Finland

Dosage form: & nbspeye drops

Composition:

1 ml contains:

active substances: 20 mg of base dorzolamide (22.26 mg of dorzolamide hydrochloride) and 5 mg of timolol base (6.83 mg of timolol maleate);

Excipients: Benzalkonium chloride (as a 50% benzalkonium chloride solution) 0.075 mg (0.15 mg), sodium citrate 2.94 mg, mannitol 16.00 mg, hyethelose (hydroxyethyl cellulose) 4.75 mg, 1M sodium hydroxide solution q.s. to pH 5.6, water for injection q.s. up to 1 ml.

Description:Transparent, colorless or almost colorless, slightly viscous liquid.

Pharmacotherapeutic group:Antiglaucoma means

ATX: & nbsp

S.01.E.X Other antiglaucoma drugs

Pharmacodynamics:

COSOPT contains two active components: dorzolamide hydrochloride and timolol maleate, each of which reduces the increased intraocular pressure by decreasing the secretion of the aqueous humor. Joint action of these substances in the combined preparation of COSOPT leads to a more pronounced decrease in intraocular pressure.

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

Timolola maleate is a non-selective beta-blocker. Although the exact mechanism of action of timolol maleate in reducing intraocular pressure has not yet been established, a number of studies have shown a predominant decrease in the formation of intraocular fluid, as well as a slight increase in its outflow.

Pharmacokinetics:

Dorzolamide hydrochloride

With topical application dorzolamide penetrates into the systemic circulation. With prolonged use dorzolamide accumulates in erythrocytes as a result of selective binding to carbonic anhydrase type II, maintaining extremely low concentrations of free drug in plasma. As a result of the metabolism of dorzolamide, a single N-septic metabolite, which less severely blocks type II carbonic anhydrase in comparison with its initial form, but at the same time inhibits Type I carbonic anhydrase, a less active isoenzyme. The metabolite also accumulates in red blood cells, where it binds mainly to type I carbonic anhydrase.About 33% of dorzolamide binds to blood plasma proteins. Dorzolamide is excreted in the urine unchanged and in the form of a metabolite. After discontinuation of the drug dorzolamide is nonlinearly washed out of red blood cells, which first leads to a rapid decrease in its concentration, and then the elimination slows down. T_1/2is about 4 months.

When dorsolamide was taken internally, in order to simulate the maximum systemic exposure during its topical application, a stable state was achieved after 13 weeks. In this case, in fact, no free drug or its metabolites were found in the plasma. Inhibition of erythrocyte carbonic anhydrase was insufficient to achieve a pharmacological effect on renal function and respiration. Similar pharmacokinetic results were observed with long-term topical administration of dorzolamide hydrochloride. Nevertheless, in some elderly patients with renal insufficiency (creatinine clearance 30-60 ml / min), higher concentrations of metabolite in erythrocytes were detected, but this was not clinically significant.

Timolola maleate

With topical application of timolol, maleate enters the systemic circulation. The concentration of timolol in plasma was studied in 6 patients with topical application eye drops of timolol maleate 0.5% twice daily. The mean peak concentration after the morning dosage was 0.46 ng / ml, after daily dosing - 0.35 ng / ml. The hypotensive effect occurs 20 minutes after instillation, reaches a maximum after 2 hours and lasts at least 24 hours.

Indications:

COSOPT is used to treat increased intraocular pressure in open-angle glaucoma and pseudoexfoliation glaucoma with insufficient monotherapy or ophthalmic hypertension with an insufficient response to treatment with beta-blockers.

Contraindications:

- Hyperreactivity of the respiratory tract, bronchial asthma, history of bronchial asthma, severe chronic obstructive pulmonary disease;

- sinus bradycardia, syndrome of weakness of the sinus node, sinoatrial block, atrioventricular block II-III degree without a pacemaker, severe heart failure, cardiogenic shock;

- severe renal failure (CC less than 30 ml / min) or hyperchloremic acidosis;

- dystrophic processes in the cornea;

- pregnancy and the period of breastfeeding;

- hypersensitivity to any component of the drug;

- Children under 18 years of age (due to insufficient knowledge of effectiveness and safety).

Carefully:

Like other ophthalmic drugs used locally, COSOPT can be absorbed into the systemic circulation. As a part of the preparation timolol is a beta-adrenoblocker, adverse reactions that develop with systemic use of beta-blockers may be noted with topical application of the drug.

Reactions from the cardiovascular and respiratory system

Patients with a history of cardiovascular disease, including heart failure, should be carefully monitored for signs of worsening of these diseases. These patients need to monitor the pulse.

Patients with grade I blockade should be prescribed beta-blockers with caution because of their ability to slow the pulse.

Reported cases of bronchospasm with fatal outcome in patients with bronchial asthma and cases of heart failure with a lethal outcome on the background of the use of eye drops timolol maleate.

In patients with chronic obstructive pulmonary disease (COPD) of mild to moderate severity, COSOPT should be given with caution and only if the perceived benefit of treatment exceeds the potential risk.

The drug should be administered with caution to patients with severe impairment of peripheral circulation (severe Raynaud's disease or Raynaud's syndrome).

Hypoglycemia in patients with diabetes mellitus

Beta-blockers should be administered with caution to patients prone to spontaneous hypoglycemia or patients with diabetes mellitus (especially the labile course of diabetes mellitus), when taking insulin or oral hypoglycemic drugs. Beta-adrenoblockers can mask the signs and symptoms of acute hypoglycemia.

Thyrotoxicosis

Beta-blockers may mask some clinical signs of hyperthyroidism (eg, tachycardia).If suspected of developing thyrotoxicosis, patients should be closely monitored. It is necessary to avoid a sharp abolition of beta-blockers due to the risk of developing thyrotoxic crisis.

Anesthesia in surgery

The need to abolish beta-blockers in the case of the forthcoming extensive surgical intervention has not been proven. If necessary during the operation, the effects of beta-blockers can be eliminated by applying sufficient doses of adrenomimetics.

Impaired liver function

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

Allergy and hypersensitivity

Like other ophthalmic drugs for topical application, COSOPT can penetrate into the systemic bloodstream. Included in the preparation dorzolamide is sulfonamide. Thus, adverse reactions revealed in the systemic application of sulfonamides can be noted with topical application of the drug (Stevens-Johnson syndrome and toxic epidermal necrolysis).When signs of severe hypersensitivity reactions appear, the drug should be discontinued.

In the treatment of beta-adrenoblockers in patients with atopy or severe anaphylactic reactions to various allergens in an anamnesis, an enhancement of the response can occur upon repeated contact with these allergens. In this group of patients, the use of epinephrine in a standard therapeutic dose, used to stop allergic reactions, may not be effective.

Concomitant therapy

When using COSOPT by patients who take 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 COSOPT with other beta-blockers is not recommended.

Discontinuation of treatment

If it is necessary to cancel the local administration of timolol, as in the case of systemic beta-blockers, discontinuation of therapy in patients with coronary heart disease should be gradual.

Disturbances from the cornea

Used in ophthalmology, beta-blockers can cause dry eyes. Patients with disorders of the cornea should be administered with caution.

Patients with a low number of endothelial cells have an increased risk of developing corneal edema.

Urolithiasis disease

The use of systemic inhibitors of carbonic anhydrase can lead to a violation of acid-base balance and is accompanied by urolithiasis, especially in patients with a history of urolithiasis. During the use of COSOPT, no such disorders were observed, reports of urolithiasis were rare. Since the composition of the drug COSOPT includes an inhibitor of carbonic anhydrase, which, when applied topically, can be absorbed and enter the systemic bloodstream, the risk of urolithiasis in patients with urolithiasis in history may increase with treatment with COSOPT.

Miscellaneous

Patients with acute angle-closure glaucoma in addition to the appointment of funds that reduce intraocular pressure, requires other therapeutic measures. Studies of the effect of COSOPT in patients with acute closed-angle glaucoma were not conducted.

Application in the elderly

49% of patients in clinical trials of COSOPT were aged 65 years and older, and 13% of patients were 75 years of age or older. Differences in efficacy and safety of the drug in these age groups compared with younger patients were not. Nevertheless, the possibility of higher sensitivity to the drug in some elderly patients should not be ruled out.

Pregnancy and lactation:

Do not take COSOPT during pregnancy and breastfeeding.

Dorzolamide

Information on the use of dorzolamide in pregnant women is not enough. It is not known whether the dorzolamide in the breast milk of nursing women.

In studies on rats, the teratogenic effect of dorsolomide was detected in doses toxic to pregnant females. Young lactating females of rats receiving dorzolamide, a decrease in body weight gain was found.

Timolol

Information on the use of timolol in pregnant women is not enough. Timolol should not be taken during pregnancy, except when the use of timolol is vital.

In epidemiological studies, there was no effect of oral beta-blockers on the development of congenital malformations, but the risk of intrauterine growth retardation was identified. In addition, the newborns had signs and symptoms of beta-adrenergic blockade (bradycardia, hypotension, respiratory failure and hypoglycemia) in the case when beta-blockers were used before delivery. If the drug was used before delivery, you should carefully monitor the state of newborns in the first days of life.

Beta-blockers penetrate into breast milk. The attending physician must decide whether to stop breastfeeding or stop taking into account the potential serious side effects with regard to the infant breastfed and the benefit of the drug for the mother.

Dosing and Administration:

COSOPT is prescribed by one drop in the conjunctival sac of the affected eye (or both eyes) twice a day.

If the COSOPT is appointed as a replacement for another ophthalmic drug for the treatment of glaucoma, the latter should be canceled the day before the start of therapy with COSOPT.

In case of joint use with another local ophthalmic drug, COSOPT should be applied with an interval of at least 10 minutes.

With nasolacrimal occlusion (closing of the eyelids) for 2 minutes after instillation of the drug, its systemic absorption decreases, which may lead to an increase in local action.

COSOPT is a sterile solution, so patients should be instructed how to properly use the vial.

Side effects:

COSOPT is generally well tolerated. In clinical studies, the side effects peculiar to this combination drug alone 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 withdrawal of the drug. In clinical trials, COSOPT was administered to 1,035 patients. About 2.4% of the patients were withdrawn due to local side reactions from the side of the eye. Approximately in 1,2% of patients the drug was canceled due to local allergic reactions. Among the most common side effects there was a feelingburning or itching in the eye, distortion of taste, corneal erosion, conjunctiva injection, blurred vision, lacrimation.

During the post-registration period observed the following adverse events: shortness of breath, respiratory failure, contact dermatitis, bradycardia, atrioventricular blockade, choroidal ocular sheath detachment, 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. The following possible side effects of the drug components are known:

Dorzolamide hydrochloride:

Headache, inflammation of the eyelid, irritation and peeling of the eyelid, asthenia / fatigue, iridocyclitis, rash, dizziness, paresthesia, acne keratitis, transient myopia (after withdrawal), systemic allergic reactions including angioedema, bronchospasm, urticar rash and itching, nasal bleeding, irritation of the pharynx, dry mouth.

Timolola maleate (topical application):

From the side of the eyes there were conjunctivitis, blepharitis, keratitis,decreased sensitivity of the cornea, dryness; visual disturbances, including changes in refractive power of the eye (in some cases due to the cancellation miotikov), diplopia, ptosis; tinnitus, arrhythmia, hypotension, syncope, cardiovascular disorders, cardiac arrhythmias, heart failure, edema, claudication, paresthesia, Raynaud's phenomenon, decreased hand temperature and feet, bronchospasm (predominantly in patients with a prior broncho-obstructive pathology), cough, headache pain, asthenia, fatigue, chest pain, alopecia, psoriasiform rash or exacerbation of psoriasis; signs and symptoms of an allergic reaction, including anaphylaxis, angioedema, urticar rash, local or generalized rashes; dizziness; depression, insomnia, nightmares, memory loss, myasthenia gravis growth, diarrhea, dyspepsia, dry mouth, abdominal pain, decreased libido, Peyronie's disease, sexual dysfunction, systemic lupus erythematosus, myalgia.

Timolola maleate (systemic application):

Pain in the extremities, decreased exercise tolerance, atrioventricular block II and III degree sinoauricular block, pulmonary edema,deterioration of arterial insufficiency, worsening of angina, vasodilation, vomiting, hyperglycemia, hypoglycemia, skin itching, increased sweating, exfoliative dermatitis, arthralgia, dizziness, weakness, decreased concentration of attention, increased drowsiness, netrombotsitopenicheskaya purpura, wheezing, impotence, urination disorders.

When systemic administration of timolol maleate clinically relevant changes in standard laboratory parameters were observed very rarely. Described slight increase in residual nitrogen, potassium, uric acid and plasma triglycerides; a slight decrease in hemoglobin, hematocrit, high-density lipoprotein cholesterol (HDL cholesterol), but these changes did not progress and were not clinically manifested.

The use of beta-blockers can cause aggravation gravis.

Overdose:

Data on accidental or intentional overdose of the drug COSOPT are absent.

Cases of unintentional overdose of eye drops of timolol maleate with development of systemic effects of beta-blockers overdose of systemic use are described: dizziness, headache, dyspnea, bradycardia, bronchospasm, cardiac arrest.The most anticipated symptoms of an overdose of dorzolamide are a violation of electrolyte balance, development of acidosis, possible side effects from the central nervous system.

Treatment of overdose symptomatic and supportive. It is necessary to control the level of electrolytes (primarily potassium) and pH blood plasma. Timolol not output by dialysis.

Interaction:

Specific studies of the interaction of the drug COSOPT with other drugs have not been conducted. Nevertheless, it is possible to intensify the hypotensive effect and / or severe bradycardia when the ophthalmic solution of timolol maleate and systemic calcium channel blockers, catecholamine-depleting agents, beta-blockers, antiarrhythmics (including amiodarone), digitalis glycosides, parasympathomimetics, opioid analgesics and monoamine oxidase inhibitors (MAO).

With the simultaneous use of timolol and isoenzyme inhibitors CYP2D6 (e.g., quinidine or selective serotonin reuptake inhibitors) has been reported on the potentiated effect of systemic beta-adrenergic blockade (eg, reduction in heart rate, depression).

Despite the fact that the carbonic anhydrase inhibitor included in the composition of COSOPT dorzolamide It is used locally, it can penetrate into the systemic bloodstream. In clinical studies of the ophthalmic solution of dorzolamide hydrochloride, no acid-base equilibrium was found. Nevertheless, these disorders are known in the systemic use of carbonic anhydrase inhibitors and in a number of cases can affect the interaction with other drugs (eg, toxicity associated with salicylate therapy in high doses). As a consequence, the possibility of such interactions should be taken into account in patients receiving COSOPT.

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

Despite the fact that with monotherapy with COSOPT the effect on the pupil is minimal or absent, there are single descriptions of the development of mydriasis with the simultaneous use of timolol maleate and adrenaline.

There is a possibility of enhancing the known systemic effects of inhibiting carbonic anhydrase in the combined use of local and systemic inhibitors of carbonic anhydrase.Since there is no data on the use of such a combination, the combined use of COSOPT and systemic inhibitors of carbonic anhydrase is not recommended.

Special instructions:

When the first signs or symptoms of heart failure appear, use of COSOPT should be discontinued.

Use of contact lenses

The composition of the drug COSOPT includes a preservative benzalkonium chloride, which can be the cause of eye irritation. Before using the drug, the lenses must be removed and re-put them no earlier than 15 minutes after instillation of the drug. Benzalkonium chloride It is able to discolor soft contact lenses.

Instructions for use:

1. Before using the product for the first time, it must be ensured that the protective strip on the outside of the vial is intact. 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, it is necessary to unscrew the cap by turning it in the direction of the indicator arrows on the upper surface of the cap.

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

5. Turn the bottle over, use a thumb or forefinger lightly to press in a place specially marked on the bottle so that one drop gets into the eye.

DO NOT touch the surface of the eye or the eyelid by the VACUUM of the Vial (see Figure 5).

If not properly used, the vial may become infected and cause serious eye infections and subsequent reduction or loss of vision.

6. After instillation of a preparation it is necessary to close eyes and to press a finger on an internal corner of an eye, pressing it to a nose bridge within 2 minutes. This helps keep the drug in the eye.

7. Repeat steps 4 and 5 for the other eye, if prescribed by your doctor.

8. Close the bottle with a cap, tightening it until it comes into contact with the bottle.

If properly closed, the arrow on the bottle cap must match the arrow on the vial label. Do not tighten the cap too much, otherwise the bottle or cap may be damaged.

9. Do not enlarge the opening of a specially designed dispenser tip.

Effect on the ability to drive transp. cf. and fur:When using the COSOPT product, side effects may develop (see "Side Effects"), which in some patients may make it difficult to drive or work with complex mechanisms.

Form release / dosage:Eye drops, 20 mg / ml + 5 mg / ml.

Packaging:

5 ml in a plastic bottle type Okumeter Plus.

1 a bottle of Okumeter Plus type with instructions for use in a cardboard pack.

Storage conditions:

Store at a temperature of no higher than 25 ° C, in a place protected from light.

Keep out of the reach of children.

Shelf life:

2 of the year.

After the first opening of the vial, the COSOPT preparation should not be used for more than 4 weeks.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription