

Antiglaucoma drug contains two active ingredients: dorzolamide and timolol, each of which reduces the increased intraocular pressure by reducing the secretion of intraocular fluid. The combined effect of these substances in the composition of the combined drug Dorzopt Plus leads to a more pronounced decrease in intraocular pressure.
Dorzolamide - selective type II carbonic anhydrase inhibitor. Inhibition of ciliary body carbonic anhydrase leads to a decrease in the secretion of intraocular fluid, presumably by reducing the formation of bicarbonate ions, which in turn leads to a slowdown in the transport of sodium and intraocular fluid.
Timolol - 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 reduction in the formation of intraocular fluid, as well as a slight increase in its outflow.
The reduction in intraocular pressure occurs 20 minutes after instillation, reaches a maximum after 2 hours and lasts at least 24 hours.
Pharmacokinetics
Dorzolamide
Suction and distribution
It penetrates inside the eye mainly through the cornea (to a lesser extent through the sclera or limb). Systemic absorption is low. After entering the blood, it rapidly penetrates red blood cells containing a significant amount of carbonic anhydrase II. Plasma protein binding - 33%.
Metabolism and excretion
It is transformed into an N-dezetilirovanny metabolite, less active in relation to carbonic anhydrase II, but capable of blocking carbonic anhydrase I. With prolonged use it accumulates in erythrocytes. Excreted by the kidneys unchanged and in the form of metabolites. After the abolition of the rapid phase of elimination is replaced by a slow, due to the gradual release of dorzolamide from red blood cells, with T1/2 about 4 months
Timolol
With topical application of timolol penetrates the systemic circulation. Plasma timolol concentration was studied in 6 patients with topical timolol in the form of 0.5% eye drops 2 times / day. Average Cmax after morning use it was 0.46 ng / ml, after applying during the day it was 0.35 ng / ml.
Increased intraocular pressure with:
1 ml of solution contains:
Active substances: 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: hyetillosis - 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 / acid hydrochloric solution 1M - to pH 5.6 ± 0.1 , purified water - up to 1 ml.
Dorzolamide, Timolol is marketed under different brands and generic names, and comes in different dosage forms:
Brand name | Manufacturer | Country | Dosage form |
---|---|---|---|
Dorzopt plus | K.O.Romparm Company S.R.L | Romania | eye drops |
Kosopt | Merck Sharp & Dohme | USA | eye drops |
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Instill 1 drop in the conjunctival sac 2 times / day.
If several local ophthalmic drugs are used in the treatment, they should be administered at intervals of 10 minutes.
The duration of treatment is determined by the doctor depending on the clinical condition of the patient.
Dorzolamide
On the part of the organ of vision: eyelid inflammation, lacrimation, eyelid irritation and desquamation, iridocyclitis, punctate keratitis, transient myopia (passing after drug withdrawal).
From the side of the central nervous system and peripheral nervous system: headache, asthenia / fatigue, paresthesias.
Allergic reactions: angioedema, bronchospasm, urticaria, pruritus.
Other: nasal bleeding, pharyngeal irritation, dry mouth, rash.
Timolol
On the part of the organ of vision: conjunctivitis, blepharitis, keratitis, decreased corneal sensitivity, dry eye syndrome; visual disturbances, including changes in the refractive ability of the eye (in some cases due to the abolition of miotics), diplopia, ptosis.
From the side of the central nervous system and peripheral nervous system: tinnitus, paresthesia, headache, asthenia, fatigue, dizziness, depression, insomnia, nightmares, loss of memory, increased symptoms of myasthenia.
Since the cardiovascular system: arrhythmia, decrease in blood pressure, fainting, arrhythmias, cardiac arrest, edema, Raynaud's syndrome, decrease in temperature of hands and feet.
On the part of 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.
Carefully: liver failure, advanced age, diabetes.
Research interaction Dorzopt Plus with other drugs was not conducted.
Nevertheless, there is a possibility of enhancing the 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, antiarrhythmic drugs (including amiodarone), cardiac glycosides, parasympathomimetics, opioid analgesics and MAO inhibitors .
With the combined use of timolol and CYP2D6 isoenzyme inhibitors (for example, quinidine or selective serotonin reuptake inhibitors), the potentiated effect of systemic blockade of β-adrenoreceptors (for example, decrease in heart rate, depression) has been reported.
Despite the fact that the dorzolamide carbonic anhydrase inhibitor, which is part of Dorzopt Plus, is used topically, it can penetrate the systemic circulation. In clinical studies of the use of dorzolamide ophthalmic solution, no acid-base balance disorders were detected. However, with systemic use of carbonic anhydrase inhibitors, these disorders are known, and in some cases they can affect the interaction with other drugs (for example, enhance toxic reactions when using salicylates in high doses).
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. Since data on the use of such a combination are not available, the combined use of Dorzopt Plus and systemic carbonic anhydrase inhibitors is not recommended.
Dorzopt Plus drug is contraindicated for use during pregnancy and lactation (breastfeeding).
Before using Dorzopt Plus, it is necessary to ensure adequate monitoring of the cardiovascular system. Patients with a history of severe heart disease and signs of heart failure should be closely monitored.
Dorzopt Plus contains a preservative benzalkonium chloride, which can be deposited in soft contact lenses and have a damaging effect on the tissue of the eye. Therefore, patients wearing soft contact lenses should remove them before using the drops and install them back no more 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 planned surgery, the drug should be gradually discontinued 48 hours before general anesthesia, since beta-blockers enhance the action of muscle relaxants and agents for general anesthesia.
Impact on the ability to drive vehicles and other mechanisms that require high concentration of attention
During the treatment period, it is necessary to refrain from driving vehicles and practicing potentially hazardous activities that require increased concentration and psychomotor speed.
Symptoms: non-intentional overdose of timolol in the form of eye drops with the development of systemic effects of beta-blockers for systemic use — dizziness, headache, shortness of breath, bradycardia, bronchospasm, cardiac arrest.
The most expected symptoms of dorzolamide overdose are electrolyte imbalance, acidosis, headache, asthenia / fatigue, paresthesia.
Treatment: conduct symptomatic and supportive therapy. The concentration of electrolytes (primarily sodium) and the pH of the blood plasma should be controlled. Studies have also shown that timolol is not eliminated during dialysis.