Instructions Dorzitim eye drops solution 20 mg/ml + 5 mg/ml bottle with dropper 5 ml
Composition
active ingredients: dorzolamide; timolol;
1 ml of solution contains 20 mg of dorzolamide as 22.26 mg of dorzolamide hydrochloride and 5 mg of timolol as 6.830 mg of timolol maleate;
Excipients: benzalkonium chloride, mannitol (E 421), sodium citrate dihydrate, 1 M sodium hydroxide solution, hydroxyethylcellulose, water for injections.
Dosage form
Eye drops, solution.
Main physicochemical properties: almost colorless, slightly viscous, opalescent solution.
Pharmacotherapeutic group
Drugs used in ophthalmology. Antiglaucoma drugs and miotics. Beta-adrenergic blockers. ATC code S01E D51.
Pharmacological properties
Pharmacodynamics
The drug contains two active ingredients: dorzolamide hydrochloride and timolol maleate. Each of these components reduces elevated intraocular pressure by reducing the secretion of intraocular fluid, but by a different mechanism of action.
Dorzolamide hydrochloride is a potent inhibitor of type II carbonic anhydrase. Inhibition of miliary carbonic anhydrase results in a decrease in aqueous humor secretion by slowing the formation of bicarbonate ions, which in turn leads to a decrease in sodium and fluid transport.
Timolol maleate is a non-selective beta-adrenergic receptor blocker. The exact mechanism of action of timolol, which is manifested in the reduction of intraocular pressure, is still unknown. Fluorimetric and tonographic studies indicate that the effect of timolol is due to a decrease in the secretion of humoral fluid. In addition, timolol may increase the outflow of moisture.
The combined effect of the two components leads to a more pronounced reduction in intraocular pressure than monotherapy with these drugs.
After topical application, Dorzitim® reduces intraocular pressure, regardless of whether its increase is associated with glaucoma. Elevated intraocular pressure plays a significant role in the pathogenesis of optic nerve damage and visual field loss in glaucoma.
Dorzitim® reduces intraocular pressure without the development of side effects typical of miotic agents, such as night blindness, accommodation spasm, and pupil constriction.
Pharmacokinetics
Dorzolamide hydrochloride. When applied topically, dorzolamide penetrates the systemic circulation. With prolonged use, dorzolamide accumulates in erythrocytes as a result of binding to carbonic anhydrase type II, maintaining very low concentrations of the free drug in plasma. As a result of metabolism, dorzolamide forms a single N-desethyl metabolite, which blocks carbonic anhydrase type II less strongly than its original form, but also inhibits carbonic anhydrase type I, a less active isoenzyme. The metabolite also accumulates in erythrocytes, where it binds mainly to carbonic anhydrase type I. Approximately 33% of dorzolamide binds to plasma proteins. Dorzolamide is excreted in the urine in unchanged form and as a metabolite. After discontinuation of the drug, dorzolamide is eliminated non-linearly from erythrocytes, characterized by an initial rapid decline in concentration and a subsequent phase of slow elimination with a half-life of approximately 4 months.
Timolol maleate. Timolol is absorbed systemically after topical ocular administration. Systemic exposure to timolol was determined after topical application of a 0.5% ophthalmic solution twice daily. Peak plasma concentrations were 0.46 ng/mL after the morning dose and 0.35 ng/mL after the evening dose.
Indication
Increased intraocular pressure in patients with open-angle glaucoma or pseudoexfoliative glaucoma when topical beta-blockers alone are insufficient.
Contraindication
Hypersensitivity to one or both active substances or to any of the excipients of the drug; respiratory tract diseases, including bronchial asthma and severe chronic obstructive pulmonary disease; sinus bradycardia, atrioventricular block II or III degree, severe heart failure, cardiogenic shock; severe renal dysfunction (creatinine clearance less than 30 ml/min) or hyperchloremic acidosis; pregnancy and breastfeeding, children's age.
Interaction with other medicinal products and other types of interactions
In case of concomitant use of other topical ophthalmic medications, Dorzitim® should be applied with an interval of at least 10 minutes.
However, there is a possibility of additive effects and hypotension and/or marked bradycardia when timolol maleate is used concomitantly with oral calcium channel blockers, drugs that reduce catecholamine production or beta-adrenergic receptor blockers, antiarrhythmic drugs (including amiodarone), digitalis glycosides, parasympathomimetics, narcotics and MAO inhibitors.
Potentiation of systemic beta-blockade (decreased heart rate, depression) has been reported with concomitant use of CYP2D6 inhibitors (e.g. quinidine-type selective serotonin reuptake inhibitors) and timolol.
Although Dorzitem® as monotherapy has little effect on pupil size, mydriasis has occasionally been reported following concomitant use of topical timolol maleate and epinephrine (adrenaline).
Beta-blockers may enhance the hypoglycemic effects of antidiabetic drugs.
Oral beta-blockers may provoke the development of "ricochet" arterial hypertension upon withdrawal of clonidine.
Application features
Before using the medicine, wash your hands thoroughly.
Cardiovascular and respiratory reactions. Like other topical agents, Dorzitem® may be absorbed systemically. Since timolol is a beta-blocker, the side effects associated with systemic use of such agents may occur, including worsening of Prinzmetal's angina, severe central and peripheral circulatory disorders, and hypotension. Appropriate monitoring should be performed before prescribing Dorzitem® in patients with heart failure. Patients with a history of severe heart disease should be monitored for symptoms of heart failure and their pulse should be checked. Respiratory and cardiac reactions, including death due to bronchospasm and rarely death due to heart failure, have been reported following the use of timolol maleate.
Hepatic impairment: Since there are no data on the use of the drug in patients with hepatic impairment, caution should be exercised when prescribing the drug to such patients.
Immunological and hypersensitivity reactions. Like other topical medications, Dorzolamide® may be absorbed systemically. Dorzolamide, like sulfonamides, contains a sulfonamide group, therefore, the development of adverse reactions observed with systemic use of sulfonamide drugs is possible. If signs of serious reactions or hypersensitivity reactions appear, the drug should be discontinued.
Local adverse reactions from the organs of vision, similar to those observed with dorzolamide hydrochloride, have been observed with the use of the drug. If such reactions develop, the question of discontinuing Dorzolamide® should be considered.
Patients with a history of atopy or anaphylactic reactions to multiple allergens may be more sensitive to these allergens upon accidental, diagnostic, or therapeutic re-exposure while taking beta-blockers. In such patients, usual doses of epinephrine for the treatment of allergic reactions may be ineffective.
Discontinuation of treatment: As with systemic beta-blockers, ophthalmic timolol should be gradually discontinued if the drug is to be discontinued in patients with coronary artery disease.
Additional effects of beta-blockers. Beta-blockers may mask certain symptoms of hypoglycemia in patients with diabetes or hypoglycemia, as well as symptoms of hyperthyroidism. Abrupt discontinuation of beta-blockers may lead to worsening of symptoms. Beta-blocker treatment may exacerbate symptoms in myasthenia gravis.
Additional effects of carbonic anhydrase inhibition. The use of carbonic anhydrase inhibitors has been associated with the development of urolithiasis as a result of acid-base disturbances, especially in patients with a history of urolithiasis. Although acid-base disturbances have not been observed with Dorzitem®, urolithiasis has been reported rarely. Since a topical carbonic anhydrase inhibitor is absorbed systemically, patients with a history of urolithiasis may be at higher risk of developing urolithiasis when using Dorzitem®.
Other features. Treatment of patients with acute open-angle glaucoma requires the use of other therapeutic agents in addition to drugs that lower intraocular pressure. The use of Dorzitim® in patients with acute open-angle glaucoma has not been studied.
Corneal edema and irreversible corneal decompensation have been reported with dorzolamide in patients with pre-existing chronic corneal defects and/or a history of intraocular surgery. Dorzolamide topical should be used with caution in such patients.
Use of contact lenses. The drug contains benzalkonium chloride, which may cause eye irritation. Contact lenses should be removed before instillation of the drug and put on at least 15 minutes after application of the drug. Benzalkonium chloride is known to discolor soft contact lenses.
As with other antiglaucoma agents, decreased sensitivity to topical timolol maleate has been reported with prolonged treatment. It is known that patients did not experience a significant difference in mean intraocular pressure after initial stabilization of pressure.
Ability to influence reaction speed when driving vehicles or other mechanisms
Studies on the effect of the drug on the ability to drive or use machines have not been conducted. However, taking into account the listed adverse reactions, driving or using machines should be avoided.
Use during pregnancy or breastfeeding
The medicine is not used during pregnancy.
It is not known whether dorzolamide is excreted in human milk. Timolol is excreted in human milk. Therefore, breastfeeding should be discontinued during treatment.
Method of administration and doses
Dorzitim® is prescribed 1 drop into the conjunctival sac twice a day.
1. Before using the medicine for the first time, make sure that the cap is not damaged.
2. To open the bottle, unscrew the cap by turning it counterclockwise.
3. Tilt your head back and pull the lower eyelid down to create space between the eyelid and the eye.
4. Turn the bottle upside down and gently press the walls of the bottle with your thumb and forefinger until one drop falls into the space between the eyelid and the eye.
DO NOT TOUCH THE SURFACE OF THE EYE OR EYELIDS WITH THE TIP OF THE BOTTLE.
If used incorrectly, the bottle can become infected and cause serious eye infections with subsequent loss of vision.
5. Repeat steps 3 and 4 for both eyes, if prescribed by your doctor.
6. Close the bottle with the cap and screw it on tightly. Do not press the cap too hard, as this may damage the bottle or the cap.
The drug can be used for a long time. It is known that, after the initial stabilization of intraocular pressure, no significant changes in the average pressure were observed in patients, which would indicate a decrease in sensitivity to the drug.
Children
Not used.
Overdose
In case of overdose of timolol, the development of systemic effects of overdose of systemic beta-blockers is possible: dizziness, headache, shortness of breath, bradycardia, bronchospasm and cardiac arrest. The most expected symptoms of overdose of dorzolamide are electrolyte imbalance, development of acidosis and possible effects on the central nervous system.
There is limited information on accidental or intentional overdose of dorzolamide hydrochloride. Drowsiness has been reported after oral administration. Nausea, dizziness, headache, weakness, abnormal dreams, dysphagia have been observed with topical administration.
Treatment: symptomatic and supportive.
Monitoring of serum electrolyte levels (mainly potassium) and blood pH. Timolol is not completely removed by dialysis.
Adverse reactions
Musculoskeletal and connective tissue disorders: timolol maleate eye drops: systemic lupus erythematosus.
Nervous system disorders: Dorzolamide hydrochloride eye drops: headache*; dizziness*, paresthesia*;
Timolol maleate, eye drops: headache*; dizziness*, depression*; insomnia*, nightmares*, memory loss, paresthesia*, increased symptoms of myasthenia gravis, decreased libido*, stroke*.
On the part of the organs of vision: Dorzitim®: burning and tingling; conjunctival injection, blurred vision, corneal erosion, itching in the eye, tearing;
Dorzolamide hydrochloride eye drops: eyelid inflammation*, eyelid irritation*; iridocyclitis*; eye irritation including redness*, eye pain*, eyelid peeling*, transient myopia (reversible upon discontinuation of treatment), corneal edema*, decreased intraocular pressure*, choroid plexus detachment (with subsequent filtering surgery)*;
Timolol maleate, eye drops: symptoms of eye irritation, including blepharitis*, keratitis*, decreased corneal sensitivity, dry eye*; visual disturbances, including changes in refraction (in some cases due to withdrawal of miotics)*; ptosis, diplopia, choroid detachment (with subsequent filtering surgery)*.
From the auditory system: timolol maleate, eye drops: tinnitus*.
Cardiovascular system: timolol maleate, eye drops: bradycardia*, syncope*; hypotension*, chest pain*, palpitations*, edema*, arrhythmia*, congestive heart failure*, heart block*, cardiac arrest*, cerebral ischemia, intermittent claudication, Raynaud's phenomenon*, coldness in the hands and feet*.
From the respiratory system, chest organs and mediastinum: Dorzitim®: sinusitis; shortness of breath, respiratory failure, rhinitis;
Timolol maleate eye drops: dyspnea*; bronchospasm (predominantly in patients with pre-existing bronchospastic disease)*, cough*.
Gastrointestinal: Dorzitim®: change in taste;
Dorzolamide hydrochloride eye drops: nausea*; throat irritation, dry mouth*;
Timolol maleate eye drops: nausea*, dyspepsia*; diarrhea, dry mouth*.
Skin: Dorzitim®: contact dermatitis;
dorzolamide hydrochloride eye drops: rash*;
Timolol maleate eye drops: alopecia*, psoriatic rash or exacerbation of psoriasis*.
From the kidneys and urinary tract: Dorzitim®: urolithiasis.
Reproductive system and breast disorders: timolol maleate eye drops: Peyronie's disease*.
General condition disorders and disorders related to the method of administration of the medicinal product.
Dorzitim®: symptoms of allergic reactions, including angioedema, urticaria, itching, rash, anaphylaxis, bronchospasm;
Dorzolamide hydrochloride eye drops: asthenia/weakness*.
* Adverse reactions also observed with Dorzitim®.
Laboratory indicators. The use of the drug was not accompanied by significant disturbances in electrolyte balance.
Expiration date
2 years.
After opening the bottle, the shelf life is no more than 4 weeks.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
5 ml in a polyethylene bottle with a dropper and tamper-evident cap, 1 bottle in a pack.
Vacation category
According to the recipe.
Producer
JSC "KYIV VITAMIN FACTORY" (production from bulk products of "Rafarm S.A.", Greece).
Location of the manufacturer and its business address
04073, Ukraine, Kyiv, Kopylivska St., 38.
