Composition, form of production and packaging
Eye drops 1 ml
Brenzolamide 10 mg
timolol (in the form of maleate) 5 mg
Excipients: mannitol, disodium edetate, sodium chloride, purified water, benzalkonium chloride 50%, sodium hydroxide, tyloxapol.
5 ml - a dropper bottle (1) a drop-toyer made from low-density polyethylene - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2010.
PHARMACHOLOGIC EFFECT
Brinzolamide is an inhibitor of carbonic anhydrase II. Due to inhibition of carbonic anhydrase II, the formation of bicarbonate ions slows down, followed by a decrease in the transport of sodium and liquid, which leads to a decrease in the production of intraocular fluid in the ciliary body of the eye. As a result, there is a decrease in intraocular pressure (IOP).
Timolol is a non-selective beta-adrenergic blocker without sympathomimetic activity, does not have a direct depressive effect on the myocardium, does not have membrane-stabilizing activity. With topical application reduces intraocular pressure by reducing the formation of watery moisture and a slight increase in its outflow.
The combined action of Brinzolamide and Timolol exceeds the effect of each substance separately.
PHARMACOKINETICS
With topical application, brinzolamide and timolol penetrate the systemic bloodstream. Brinzolamide is absorbed in erythrocytes as a result of selective binding mainly with carbonic anhydrase II. C max of brinzolamide in erythrocytes is about 18.4? M. The binding with plasma proteins is about 60%.
The metabolism of Brinzolamide takes place by N-dealkylation, O-dealkylation and oxidation of the N-propyl side chain. The main metabolite, N-desethylbenzenamide, binds predominantly to carbonic anhydrase I in the presence of Brinzolamide and also accumulates in erythrocytes. In vitro studies show that the benzoamide metabolism is mainly responsible for the isozyme CYP3A4, as well as the isozymes CYP2A6, CYP2B6, CYP2C8 and CYP2C9. Brinzolamide is excreted mainly by the kidneys in an unchanged form - about 60%. About 20% is excreted in the form of metabolites: the main metabolite (N-desethylbenzenamide) and trace concentrations of other metabolites (N-demethoxypropyl and O-desmethyl).
C max timolol in blood plasma is about 0.824 ng / ml and is kept to the detection threshold for 12 hours. T 1/2 of timolol is 4.8 hours after topical application of Azarga. Metabolism of timolol occurs in two ways: with the formation of ethanolamine side chain on the thiadiazole ring and with the formation of an ethanol side chain in morpholine nitrogen and a similar side chain with a carbonyl group connected to nitrogen. Metabolism of timolol is mainly carried out by the isoenzyme CYP2D6. Timolol and the resulting metabolites are mainly excreted by the kidneys. About 20% of timolol is excreted unchanged, the rest - in the form of metabolites.
INDICATIONS
- Decreased increased intraocular pressure in open-angle glaucoma and intraocular hypertension in patients in whom monotherapy was insufficient to reduce intraocular pressure.
DOSING MODE
Locally. Vial before use shake.
1 drop in the conjunctival sac of the eye 2 times / day.
After applying the drug to reduce the risk of systemic side effects, it is recommended to lightly press the finger onto the projection area of ​​lacrimal sacs at the inner corner of the eye within 1-2 minutes after the drug is installed - this reduces the systemic absorption of the drug.
If the dose was missed, then the treatment should be continued from the next dose on schedule. The dose should not exceed 1 drop in the conjunctival sac of the eye 2 times / day.
If you replace an antiglaucoma drug with Azarga, you should start using Azarga the day after the previous drug was discontinued.
SIDE EFFECT
Local reactions: 1-10% of cases - blurred vision, pain in the eye, eye irritation, foreign body sensation; 0.1-1% of cases - corneal erosion, pinpoint keratitis, dry eye syndrome, eye discharge, pruritus in the eye, blepharitis, allergic conjunctivitis, effusion to the anterior chamber of the eye, conjunctival hyperemia, crust formation on the eyelid, asthenopia, discomfort in the eyes , itching, erythema eyelids, allergic blepharitis.
Systemic side effects: 1-10% of cases - dysgeusia; 0.1-1% of cases - insomnia, decreased blood pressure, chronic obstructive pulmonary disease, pain in the oropharynx, rhinorrhea, cough, hair growth disorder, flat lichen.
Brinzolamide
Local reactions: keratitis, keratopathy, increased excavation of the optic nerve disc, defective epithelium of the cornea, increased intraocular pressure, corneal deposits, corneal defects, corneal edema, conjunctivitis, inflammation of the meibomian glands, diplopia, photophobia, photopsy, decreased visual acuity, pterygium, dry keratoconjunctivitis, eye hypoesthesia, scleral pigmentation, subconjunctival cyst, increased lacrimation, visual impairment, eye swelling, allergic reactions of the eye, mydriasis, edema of the eyelids.
Systemic side effects: apathy, depression, decreased libido, nightmares, nervousness, drowsiness, motor dysfunctions, amnesia, memory impairment, CNS disorders.
Treatment: immediately flush eyes with water. Symptomatic and supportive therapy. The level of electrolytes and the pH of the blood should be monitored. Hemodialysis is ineffective.
CONTRAINDICATIONS
- bronchial asthma (including in the anamnesis);
- chronic obstructive pulmonary disease of the severe course;
- hyperreactivity of the bronchi;
- sinus bradycardia;
- AV-blockade of II-III degree;
- severe heart failure;
- cardiogenic shock;
- Allergic rhinitis of severe course;
- severe renal failure (creatinine clearance <30 ml / min);
- an angle-closure glaucoma;
- simultaneous use with oral inhibitors of carbonic anhydrase;
- Pregnancy;
- lactation period;
- children's age till 18 years;
- Hypersensitivity to a group of beta-blockers, hyperchloremic acidosis;
- hypersensitivity to sulfonamides;
- Hypersensitivity to the components of the drug.
With caution: patients with hyperthyroidism, Prinzmetal angina, peripheral and central circulation disorders and arterial hypotension.
The experience of using Azarga for the treatment of patients with pseudoexfoliation glaucoma, pigmentary glaucoma is limited: in these cases, use the drug with caution and constantly monitor the intraocular pressure.
Anaphylactic reactions. Patients with atopy or with severe anaphylactic reactions to various allergens in a history who receive beta-blockers may be resistant to conventional doses of epinephrine in the treatment of anaphylactic reactions.
System effects. Brinzolamide and timolol can undergo systemic absorption. Timolol with local use can cause the same side effects from the cardiovascular and respiratory systems, as well as systemic beta-blockers. It is necessary to monitor the patient's condition before and during therapy with timolol. Cases of severe respiratory and cardiovascular disorders, including death from bronchospasm in patients with bronchial asthma and death from heart failure with timolol, are described.
Beta-blockers should be used with caution in patients with a tendency to hypoglycemia or diabetes (especially with diabetes mellitus), because these drugs can mask the symptoms of acute hypoglycemia.
Prior to the planned operation, beta-blockers should be gradually (not simultaneously) canceled 48 hours before the general anesthesia, tk. during general anesthesia, they can reduce the sensitivity of the myocardium to sympathetic stimulation, the necessary day of the heart.
Azarga contains Brinzolamide, which is a sulfonamide. Because When topical application occurs systemic absorption of the drug, there may be side reactions, characteristic of sulfonamides. The development of a violation of acid-base balance with the use of oral forms of inhibitors of carbonic anhydrase is described.
PREGNANCY AND LACTATION
The drug is contraindicated for use in pregnancy and lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
The drug is contraindicated in severe renal failure (creatinine clearance less than 30 ml / min).
APPLICATION FOR CHILDREN
Contraindicated in children under 18 years.
APPLICATION IN ELDERLY PATIENTS
In older patients, carbonic anhydrase inhibitors administered orally may affect the ability to engage in activities requiring increased attention or coordination. This effect should be considered when assigning Azarga, tk. at local application the preparation gets into the systemic bloodstream.
SPECIAL INSTRUCTIONS
In older patients, carbonic anhydrase inhibitors administered orally may affect the ability to engage in activities requiring increased attention or coordination. This effect should be considered when assigning Azarga, tk. at local application the preparation gets into the systemic bloodstream.
When using brinzolamide in patients wearing contact lenses, the condition of the cornea should be monitored, since carbonic anhydrase inhibitors can lead to a disruption of its hydration. It is recommended to carefully monitor patients with corneal abnormalities, diabetes mellitus, or corneal dystrophy.
Benzalkonium chloride, which is part of the Azarga preparation, can cause point keratopathy and / or toxic ulcer keratopathy. With prolonged use of the drug, careful monitoring of patients is recommended. Benzalkonium chloride can be absorbed by contact lenses. Before using the drug, the lenses should be removed and installed back no earlier than 15 minutes after the drug is used.
Do not touch the tip of the dropper bottle to any surface to avoid contamination of the dropper and its contents. The bottle must be closed after each use.
Impact on the ability to drive vehicles and manage mechanisms
After applying the drug, vision sharpness may temporarily decrease, and it is not recommended to drive and engage in activities requiring increased attention before recovery.
DRUG INTERACTION
Studies on interactions with other drugs have not been conducted. It is not recommended simultaneous use with oral inhibitors of carbonic anhydrase, t. there is a possibility of increasing systemic adverse reactions.
For the metabolism of Brinzolamide, cytochrome P450 isoenzymes: CYP3A4 (mostly), CYP2A6, CYP2B6, CYP2C8 and CYP2C9 are responsible. CYP3A4 isoenzyme inhibitors such as ketoconazole, itraconazole, clotrimazole, ritonavir and trolleandomycin should be used with caution, due to the possible inhibition of the metabolism of brenzolamide. Caution should be exercised when co-administration of inhibitors of the isoenzyme CYP3A4. However, the accumulation of Brinzolamide is unlikely. it is excreted by the kidneys. Brinzolamide is not an inhibitor of cytochrome P450 isoenzymes.
There is a possibility of intensifying the hypotensive effect and / or development of severe bradycardia with simultaneous use of timolol with calcium channel blockers for oral administration, guanethidine, beta-adrenoblockers, antiarrhythmics, cardiac glycosides and parasympathomimetics.
The development of hypertension after a sharp abolition of clonidine can be enhanced with simultaneous reception of beta-blockers.
Enhancement of the systemic action of beta-blockers (reduction in heart rate) can develop with the simultaneous use of inhibitors of CYP2D6 (quinidine, cimetidine) and timolol.
Beta-blockers can increase the hypoglycemic effect of antidiabetics. Beta-blockers can mask symptoms of hypoglycemia.
In case of use with other local ophthalmic preparations, the interval between their use should be at least 15 minutes.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug is stored at a temperature of 2 В° to 30 В° C, out of reach of children. Shelf life - 2 years. Do not use after the expiry date printed on the package. Use within 4 weeks after opening the vial.
