Dorzolan Extra eye drops, 5 ml
Expiration Date: 05/2027
Russian Pharmacy name:
Дорзолан Экстра капли глазные, 5 мл
For topical use. Instill 1 drop into the conjunctival sac of the eye (or both eyes) 2 times / day.
If a drug containing this combination is prescribed as a replacement for another ophthalmic drug for the treatment of glaucoma, the latter must be canceled 1 day before starting therapy with a drug containing this combination.
In the case of joint use with other local ophthalmic drugs, the administration of the drug containing this combination should be carried out with an interval of 10 minutes.
With nasolacrimal occlusion (closing of the eyelids) for 2 minutes after instillation of the drug containing this combination, its systemic absorption decreases, which can lead to an increase in local action. The duration of treatment is determined by the doctor depending on the clinical condition of the patient.
Eye drops in the form of a transparent, colorless or almost colorless, slightly viscous liquid.
1 ml of dorzolamide hydrochloride 22.26 mg,
which corresponds to the content of dorzolamide 20 mg
timolol maleate 6.83 mg,
which corresponds to the content of timolol 5 mg
Excipients: sodium citrate dihydrate - 2.94 mg, sodium hyaluronate - 1.8 mg, mannitol - 16 mg, sodium hydroxide solution 1M - up to pH 5.6, water d / i - up to 1 ml.
Airway hyperresponsiveness;
bronchial asthma (including history);
severe COPD;
sinus bradycardia;
SSSU;
sinoatrial blockade;
AV block II-III degree;
severe heart failure;
cardiogenic shock;
severe renal failure (CC less than 30 ml / min);
hyperchloremic acidosis;
dystrophic processes in the cornea;
pregnancy;
lactation (breastfeeding);
children and adolescents up to 18 years old;
hypersensitivity to drug components.
Carefully
History of cardiovascular disease, including heart failure, 1st degree AV block; COPD of mild to moderate severity; severe peripheral circulatory disorders (severe forms of Raynaud's disease or Raynaud's syndrome); liver failure; diabetes; urolithiasis (including history); hyperthyroidism; disorders of the cornea; elderly patients.
pharmachologic effect
Combined antiglaucoma remedy.
Dorzolamide 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 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.
The combined action of these substances in the composition of the combined drug leads to a more pronounced decrease in intraocular pressure.
A decrease in intraocular pressure occurs 20 minutes after instillation, reaches a maximum after 2 hours and lasts for at least 24 hours.
Pharmacokinetics
Dorzolamide penetrates into the eye mainly through the cornea (to a lesser extent through the sclera or limbus). 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. Plasma protein binding is about 33%.
As a result of metabolism, it is transformed into an N-desethylated metabolite, less active in relation to carbonic anhydrase II, but capable of blocking type I carbonic anhydrase. The metabolite also accumulates in erythrocytes, where it binds mainly to type I carbonic anhydrase. It is excreted by the kidneys unchanged and in the form of metabolites. After stopping the use of the drug, dorzolamide is nonlinearly washed out of erythrocytes, which first leads to a rapid decrease in its concentration, then excretion slows down. T1 / 2 is about 4 months.
When dorzolamide was taken orally in order to simulate the maximum systemic exposure during its topical application, the equilibrium state was achieved after 13 weeks. At the same time, practically no free dorzolamide or its metabolites were found in blood plasma. Inhibition of erythrocyte carbonic anhydrase was insufficient to achieve a pharmacological effect on renal and respiratory function. Similar pharmacological results were observed with long-term topical use of dorzolamide. 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.
When applied topically, timolol enters 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 times / day. The average Cmax after application in the morning was 0.46 ng / ml, after application in the afternoon - 0.35 ng / ml
Side effect
The following possible undesirable reactions of the active components of the combination are known.
Dorzolamide
From the nervous system: headache, dizziness, asthenia / fatigue, paresthesia.
From the side 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).
Allergic reactions: angioedema, bronchospasm, urticaria, itching, rash.
From the respiratory system: epistaxis.
Timolol (topical application)
Mental Disorders: Depression.
From the immune system: anaphylaxis, angioedema, urticaria, local or generalized rash.
From the nervous system: ringing in the ears, paresthesia, headache, asthenia, fatigue, dizziness, insomnia, nightmares, memory loss, an increase in myasthenia gravis symptoms.
From the respiratory system: bronchospasm (mainly in patients with previous broncho-obstructive pathology), cough, chest pain.
From the side 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 cancellation of miotics), diplopia, ptosis.
From the side of the cardiovascular system: arrhythmia, cardiac arrest, decreased blood pressure, fainting, Raynaud's syndrome, decreased temperature of the hands and feet.
From the digestive system: diarrhea, dyspepsia, dry mouth, throat irritation, abdominal pain.
On the part of the skin and subcutaneous tissues: alopecia, psoriasis-like rash or exacerbation of psoriasis.
From the musculoskeletal system and connective tissue: lameness, systemic lupus erythematosus.
From the reproductive system: decreased libido, Peyronie's disease.
General disorders and disorders at the injection site: edema.
In the post-registration period, when using a combination of dorzolamide + timolol, the following adverse reactions were noted: shortness of breath, respiratory failure, bradycardia, AV block, choroidal detachment of the eye, nausea, contact dermatitis, 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.
Application during pregnancy and lactation
Use during pregnancy and lactation (breastfeeding) is contraindicated.
Application for violations of liver function
Use with caution in liver failure.
Application for impaired renal function
Contraindication: severe renal failure (CC less than 30 ml / min).
Application in children
Contraindicated for use in children and adolescents under the age of 18 years.
Use in elderly patients
It should be used with caution in elderly patients.
special instructions
The components of the combination drug can enter the systemic circulation. Since timolol is a beta-blocker, undesirable reactions that develop with the systemic use of beta-blockers can be observed with topical application of this combination.
Before starting use, it is necessary to ensure adequate control 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 (control of heart rate and blood pressure).
There have been reports of cases of fatal heart failure with the use of timolol in the form of eye drops.
When the first signs or symptoms of heart failure appear, this drug should be discontinued.
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 while using timolol in the form of eye drops.
In patients with mild to moderate COPD, m should be used 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 disease or Raynaud's 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 can mask the symptoms of hypoglycemia.
Beta-blockers can mask some of the clinical signs of hyperthyroidism (eg, tachycardia). Patients should be closely monitored if hyperthyroidism is suspected. It is necessary to avoid abrupt withdrawal of beta-blockers because of the risk of developing a thyrotoxic crisis.
Dorzolamide is a sulfonamide. Adverse reactions identified with the systemic use of sulfonamides can be observed 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 with beta-blockers of 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, the use of epinephrine in a standard therapeutic dose for the relief of allergic reactions may be ineffective.
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 reducing intraocular pressure. Combined use with other beta-blockers is not recommended.
If it is necessary to cancel the local use of timolol, as in the case of the cancellation 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 mucous membrane of the eye. In patients with disorders of the cornea, 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.
Influence on the ability to drive vehicles and mechanisms
During the period of application, it is necessary to refrain from driving vehicles and mechanisms and engaging in potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions.
Drug interactions
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, antiarrhythmics (including amiodarone), cardiac glycosides, parasympathomimetics, opioid analgesics 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).
Systemic beta-blockers can enhance the effect of hypoglycemic drugs.
Systemic beta-blockers can increase the severity of arterial hypertension, which is the effect of clonidine withdrawal.
There are sporadic data on the development of mydriasis with the combined use of timolol 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.