Composition and release form
The drug Dorzopt plus is available in the form of eye drops, a colorless, transparent, somewhat viscous solution. Each milliliter of medicine contains two active substances:
- Dorzolamide (hydrochloride) 20 mg;
- Timolol (maleate) 5 mg.
Auxiliary components include mannitol, benzalkonium chloride, hydroxyethylcellulose, purified water, acidity stabilizers.
5 ml of solution are placed in dropper bottles made of polymer material.
Dorzopt Plus eye drops 20 mg/ml+5 mg/ml 5 ml fl-cap/pack card x1
DORZOPT PLUS Representative office: ROMFARM COMPANY S.R.L. ATX code: S01EX Registration certificate holder: SC ROMPHARM Company, SRL dorzolamide + timolol Release form, composition and packaging Eye drops in the form of a clear, colorless or almost colorless, slightly viscous solution. 1 ml of dorzolamide hydrochloride 22.26 mg, which corresponds to the content of dorzolamide 20 mg, timolol maleate 6.84 mg, which corresponds to the content of timolol 5 mg Excipients: hyethylose - 1 mg, citric acid monohydrate - 4 mg, sodium hydroxide solution 1M - 0.066 ml, mannitol - 20 mg, benzalkonium chloride - 0.075 mg, sodium hydroxide solution 1M/hydrochloric acid solution 1M - up to pH 5.6±0.1, purified water - up to 1 ml. 5 ml - polymer dropper bottle (1) - cardboard packs.
Clinical and pharmacological group: Antiglaucoma drug Registration No.: •eye drops 20 mg + 5 mg/1 ml: vial. 5 ml 1 - LP-000580, 09/08/11. Active. ——————————————————————————— The description of the drug DORZOPT PLUS is based on the officially approved instructions for use of the drug DORZOPT PLUS for specialists and approved by the manufacturer for 2013 edition. ——————————————————————————— Pharmacological action | Pharmacokinetics | Indications | Dosage regimen | Side effect | Contraindications | Pregnancy and lactation | Special instructions | Overdose | Drug interactions | Terms of release from pharmacies | Storage conditions and expiration dates —————————————————————————— Pharmacological action Antiglaucoma drug contains two active components: dorzolamide and timolol, each of which reduces increased intraocular pressure due to decreased secretion of intraocular fluid. The combined effect of these substances in the combined drug Dorzopt Plus leads to a more pronounced decrease in intraocular pressure. Dorzolamide is a selective type II carbonic anhydrase inhibitor. Inhibition of ciliary body carbonic anhydrase 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 intraocular fluid. Timolol is a non-selective beta blocker. Although the exact mechanism of action of timolol 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. A decrease in intraocular pressure occurs 20 minutes after installation, reaches a maximum after 2 hours and continues for at least 24 hours.
Pharmacokinetics Dorzolamide Absorption and distribution Penetrates into the eye mainly through the cornea (to a lesser extent through the sclera or limbus). Systemic absorption is low. After entering the blood, it quickly penetrates into red blood cells containing a significant amount of carbonic anhydrase II. Plasma protein binding - 33%. Metabolism and excretion Transforms into an N-desethylated metabolite, less active against carbonic anhydrase II, but capable of blocking carbonic anhydrase I. With long-term use, it accumulates in erythrocytes. It is excreted by the kidneys unchanged and in the form of metabolites. After discontinuation, the fast phase of elimination is replaced by a slow phase, caused by the gradual release of dorzolamide from red blood cells, with T1/2 of about 4 months. Timolol When applied topically, timolol penetrates into the systemic circulation. The concentration of timolol in plasma was studied in 6 patients with topical application of timolol in the form of eye drops 0.5% 2. The average Cmax after morning use was 0.46 ng/ml, after afternoon use - 0.35 ng/ml.
Indications for use of the drug DORZOPT PLUS Increased intraocular pressure in: - open-angle glaucoma, - pseudoexfoliative glaucoma.
Dosage regimen Instill 1 drop into the conjunctival sac 2 If several local ophthalmic drugs are used during treatment, then their administration should occur at intervals of 10 minutes. The duration of treatment is determined by the doctor depending on the clinical condition of the patient.
Side effects of Dorzolamide On the part of the organ of vision: inflammation of the eyelid, lacrimation, irritation and peeling of the eyelid, iridocyclitis, punctate keratitis, transient myopia (passing after discontinuation of the drug). From the central nervous system and peripheral nervous system: headache, asthenia/fatigue, paresthesia. Allergic reactions: angioedema, bronchospasm, urticaria, itching. Other: nosebleeds, throat irritation, dry mouth, rash. Timolol On the part of the organ of vision: conjunctivitis, blepharitis, keratitis, decreased sensitivity of the cornea, dry eye syndrome, visual disorders, including changes in the refractive power of the eye (in some cases due to the withdrawal of miotics), diplopia, ptosis. From the central nervous system and peripheral nervous system: tinnitus, paresthesia, headache, asthenia, fatigue, dizziness, depression, insomnia, nightmares, memory loss, increased symptoms of myasthenia gravis. From the cardiovascular system: arrhythmia, decreased blood pressure, fainting, rhythm disturbances, cardiac arrest, edema, Raynaud's syndrome, decreased temperature of the hands and feet. From the respiratory system: bronchospasm (mainly in patients with previous broncho-obstructive pathology), cough, chest pain. Dermatological reactions: alopecia, psoriasis-like rash or exacerbation of psoriasis. Allergic reactions: anaphylaxis, angioedema, urticaria, local or generalized rash. From the digestive system: diarrhea, dyspepsia, dry mouth. Other: decreased libido, Peyronie's disease, systemic lupus erythematosus.
Contraindications to the use of the drug DORZOPT PLUS - bronchial asthma (including a history), - severe chronic obstructive pulmonary disease (COPD), - sinus bradycardia, - AV block II and III degrees, - severe heart failure, - cardiogenic shock , - severe renal failure (creatinine clearance less than 30 ml/min), - dystrophic processes in the cornea, - pregnancy, - lactation (breastfeeding), - children and adolescents under 18 years of age (since the effectiveness and safety have not been sufficiently studied) , - hypersensitivity to the components of the drug.
With caution: liver failure, old age, diabetes mellitus.
Use of the drug DORZOPT PLUS during pregnancy and breastfeeding The drug Dorzopt Plus is contraindicated for use during pregnancy and lactation (breastfeeding).
Use for liver dysfunction Use with caution in liver failure.
Use for impaired renal function Contraindicated in severe renal failure (creatinine clearance less than 30 ml/min),
Use in elderly patients Use caution in elderly patients.
Use in children Contraindicated in children under 18 years of age.
Special instructions Before starting to use the drug Dorzopt Plus, it is necessary to ensure adequate monitoring of the state of the cardiovascular system. Patients with a history of severe cardiac disease and signs of heart failure should be closely monitored. Dorzopt Plus contains the preservative benzalkonium chloride, which can precipitate in soft contact lenses and cause damage to eye tissue. Therefore, patients wearing soft contact lenses should remove them before using drops and put them back no earlier than 20 minutes after instillation. The drug is prescribed with caution to patients with diabetes mellitus, since beta-blockers may mask the symptoms of acute hypoglycemia. Before a planned surgical operation, the drug should be gradually withdrawn 48 hours before general anesthesia, because beta-blockers enhance the effect of muscle relaxants and general anesthesia. Impact on the ability to drive vehicles and operate machinery During the treatment period, it is necessary to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Overdose Symptoms of an unintentional overdose of timolol in the form of eye drops with the development of systemic effects of an overdose of beta-blockers for systemic use: dizziness, headache, shortness of breath, bradycardia, bronchospasm, cardiac arrest. The most expected symptoms of a dorzolamide overdose are electrolyte imbalance, acidosis, headache, asthenia/fatigue, and paresthesia. Treatment: provide symptomatic and supportive therapy. The concentration of electrolytes (primarily sodium) and blood plasma pH should be monitored. Studies have also shown that timolol is not eliminated by dialysis.
Drug interactions No studies have been conducted on the interaction of Dorzopt Plus with other drugs. However, there is a possibility of increased hypotensive effect and/or the development of severe bradycardia with the combined use of timolol ophthalmic solution and slow calcium channel blockers, sympatholytics, beta-blockers, antiarrhythmics (including amiodarone), cardiac glycosides, parasympathomimetics, opioid analgesics and MAO inhibitors . When timolol is used concomitantly with inhibitors of the CYP2D6 isoenzyme (for example, quinidine or selective serotonin reuptake inhibitors), a potentiated effect of systemic beta-adrenergic receptor blockade (for example, decreased heart rate, depression) has been reported. Despite the fact that the carbonic anhydrase inhibitor dorzolamide, which is part of Dorzopt Plus, is used topically, it can penetrate into the systemic circulation. In clinical studies of the use of dorzolamide ophthalmic solution, no acid-base balance disorders were identified. However, with systemic use of carbonic anhydrase inhibitors, these disorders are known, and in some cases they may affect interactions with other drugs (for example, increase toxic reactions when using salicylates in high doses). There is a possibility that the known systemic effects of carbonic anhydrase inhibition may be enhanced by the combined use of topical and systemic carbonic anhydrase inhibitors. Because There are no data on the use of such a combination; the combined use of Dorzopt Plus and systemic carbonic anhydrase inhibitors is not recommended.
Conditions for dispensing from pharmacies The drug is dispensed with a prescription.
Conditions and periods of storage The drug should be stored out of the reach of children, in a dry place, protected from light, at a temperature not exceeding 25°C. Shelf life: 2 years.
pharmachologic effect
Dorzopt plus drops are an antiglaucoma drug that helps stabilize intraocular pressure by reducing the secretion of aqueous humor.
The action is based on two mechanisms. Dorzolamide is a carbonic anhydrase inhibitor and slows down the formation of bicarbonate, water and sodium transport. Timolol is a non-selective beta blocker and prevents catecholamines from stimulating receptors. At the same time, it not only inhibits the synthesis of aqueous humor, but also somewhat facilitates its outflow.
Contraindications
The use of Dorzopt plus is contraindicated for:
- Bronchial asthma;
- Heart rhythm disturbances (bradycardia, 2-3 degree AV block);
- Heart failure, including cardiogenic shock;
- Hyperchloremic acidosis;
- Severe renal failure, accompanied by a decrease in creatinine clearance less than 30 ml/min;
- Breastfeeding;
- Pregnancy;
- Hypersensitivity to the components of the drug.
Side effects
- Inflammation, irritation and peeling of the eyelids, iridocyclitis, myopia, which goes away when the drug is discontinued, punctate keratitis, conjunctivitis, keratitis, dry eye syndrome, diplopia, ptosis.
- Headache, asthenia, paresthesia, tinnitus, depression, memory loss.
- Angioedema, bronchospasm, itching, urticaria, alopecia, exacerbation of psoriasis.
- Nosebleeds, dry mouth, throat irritation, rash.
- Arrhythmia, fainting, decreased blood pressure, rhythm disturbances, decreased temperature of the extremities, edema, Raynaud's syndrome.
- Bronchospasm, cough and chest pain.
- Diarrhea, dry mouth, decreased libido, Peyronie's disease.
Interactions
No special studies have been conducted regarding the interaction of Dorzopt plus with other medications.
Increased hypotension, bradycardia and cardiac depression are possible with simultaneous use of systemic beta-blockers, antiarrhythmics, calcium blockers, glycosides, opioid analgesics, parasympathomimetics, MAO inhibitors.
With simultaneous administration of CYP2D6 inhibitors, the systemic effects of beta blockers (depression, bradycardia, etc.) may be enhanced.
Since Dorzopt plus can penetrate into the systemic circulation in some quantities, it may increase the toxic effects of large doses of salicylates.
It is not recommended to combine Dorzopt Plus with systemic carbonic anhydrase inhibitors.
Description of the drug DORZOPT PLUS
The components of the combination drug may enter the systemic circulation. Since timolol is a beta-blocker, adverse reactions that develop with systemic use of beta-blockers may occur with topical use of this combination.
Before starting use, it is necessary to ensure adequate monitoring of the state of the cardiovascular system.
Patients with a history of cardiovascular disease, including heart failure, should be closely monitored for signs of worsening of these diseases (monitoring heart rate and blood pressure).
Cases of fatal heart failure have been reported with the use of timolol eye drops.
When the first signs or symptoms of heart failure appear, this drug should be discontinued.
Patients with first-degree heart block should be prescribed 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 during the use of timolol in the form of eye drops.
In patients with mild to moderate COPD, use with caution and only if the expected 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 syndrome).
Use with caution in patients with spontaneous hypoglycemia or in patients with diabetes mellitus (especially with a labile course) while using insulin or oral hypoglycemic drugs, since beta-blockers may mask the symptoms of hypoglycemia.
Beta blockers may mask some clinical signs of hyperthyroidism (eg, tachycardia). If hyperthyroidism is suspected, patients should be closely monitored. Abrupt withdrawal of beta-blockers should be avoided due to the risk of developing thyrotoxic crisis.
Dorzolamide is a sulfonamide. Adverse reactions identified with systemic use of sulfonamides may occur with topical application (Stevens-Johnson syndrome and toxic epidermal necrolysis). If signs of serious hypersensitivity reactions appear, the use of the drug should be discontinued.
When treating patients with atopy or a history of severe anaphylactic reactions to various allergens with beta-blockers, the response may be enhanced upon repeated exposure to these allergens. In this group of patients, the use of epinephrine at a standard therapeutic dose to relieve allergic reactions may not be effective.
When used in patients taking systemic beta-blockers, it is necessary to take into account the possible mutual enhancement of the pharmacological action of the drugs, both in relation to the known systemic effects of beta-blockers and in relation to the reduction of intraocular pressure. Concomitant use with other beta-blockers is not recommended.
If it is necessary to discontinue topical use of timolol, as in the case of discontinuation of systemic beta-blockers, discontinuation of therapy in patients with coronary artery disease should be carried out gradually.
Beta-blockers used in ophthalmology can cause dryness of the eye mucosa. In patients with corneal disorders, the drug should be used with caution. Patients with low endothelial cell counts have an increased risk of developing corneal edema.
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.
Impact on the ability to drive vehicles and machinery
During the period of use, it is necessary to refrain from driving vehicles and machinery and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
special instructions
Prescribing Dorzopt plus to patients with liver dysfunction and diabetes mellitus requires caution.
When instilling other medications together, a 15-minute break must be observed. During treatment, monitoring of the electrolyte composition and acidity of blood plasma is required.
The drops contain benzalkonium chloride. This preservative can be deposited on the surface of contact lenses and cause irritation and toxic damage to the eyes. In this regard, the lenses must be removed.
During treatment with Dorzopt Plus, care must be taken when driving and operating dangerous machinery.
