Index of drugs

Reduction of intraocular pressure (IOP) in adult patients with open-angle glaucoma or ocular hypertension who were not adequately controlled with IOP by monotherapy.

1 ml suspension contains 10 mg brinzolamide and 5 mg Timolol as maleate (and 0.10 mg benzalkonium chloride).

The preparation contains two active substances that lower elevated intraocular pressure by reducing the secretion of aqueous humor through various mechanisms of action. The combined effects of both drugs cause an additional reduction in intraocular pressure compared to the treatment of each drug used separately. Brinzolamide is a potent inhibitor of carbonic anhydrase II (CA-II), an isoenzyme of CA predominant in the eye. Inhibition of carbonic anhydrase in the ciliary processes of the eye reduces the secretion of aqueous humor, presumably by slowing the production of bicarbonate ions and, consequently, reducing the transport of sodium and liquids. Timolol is a non-selective drug blocking β-adrenergic receptors, devoid of intrinsic sympathomimetic activity, direct inhibition of the heart and stabilizing cellular membranes. The main action of timolol is associated with a decrease in aqueous humor production and a slight increase in its outflow. After administration to the conjunctival sac, brinzolamide and timolol are absorbed through the cornea and penetrate into the systemic circulation. Bryznolamide binds to plasma proteins in approximately 60%. Due to its high affinity for CA-II and to a lesser degree for CA-I, brinzolamide extensively extends into erythrocytes. The main active metabolite of brinzolamide is N-desmethylbrinzolamide, which also accumulates in erythrocytes, where it is mainly associated with CA-I. The metabolism of brinzolamide is mainly mediated by CYP3A4 as well as at least four other isoenzymes (CYP2A6, CYP2B6, CYP2C8 and CYP2C9). The metabolism of timolol is mainly mediated by CYP2D6. Brynzolamide is eliminated mainly by renal excretion (approximately 60%). About 20% of the dose is excreted in the urine as metabolites. Timolol and its metabolites are mainly excreted by the kidneys. About 20% of the dose of timolol is excreted unchanged in the urine and the remainder in the form of metabolites. T_0,5 timolol after administration of the preparation is 4.8 hours.

Hypersensitivity to the active substances or to any of the excipients. Hypersensitivity to other β-blockers. Hypersensitivity to sulfonamides. Respiratory diseases with hyperreactivity, including bronchial asthma or bronchial asthma, severe obstructive pulmonary disease. Sinus bradycardia, sick sinus syndrome, atrio-ventricular block IIst. or IIIst. untreated with a pacemaker. Overt cardiac failure, cardiogenic shock. Severe allergic rhinitis. Hyperlloric acidosis. Severe renal impairment (creatinine clearance <30 ml / min).

Brinzolamide and timolol are absorbed systemically. Due to the content of Timolol, which is a beta-blocking agent, the same types of cardiovascular, pulmonary and other systems and orgasms as seen with beta-blockers with general effect may occur. The incidence of general adverse reactions after topical ocular administration is lower than after systemic administration. Patients receiving the preparation may experience hypersensitivity reactions typical of sulphonamides. In patients with cardiovascular disease (eg ischemic heart disease, Prinzmetal's angina and heart failure) and hypertension, beta-blockers should be evaluated with particular care and consideration should be given to the use of other active substances. Patients with cardiovascular disease should be monitored to detect signs of deterioration of these diseases and side effects.Due to the negative effect on the conduction time, β-blockers can be administered to patients with a heart block Ist. only with caution. Patients with severe peripheral circulation disorders (such as severe Raynaud's disease or Raynaud's syndrome) should be treated with caution. Β-blockers can also mask the symptoms of hyperthyroidism. Preparations containing β-blockers may increase muscle weakness coincident with some of the symptoms of myasthenia gravis (eg double vision, eyelid droop, generalized weakness). It should be used with caution in patients with mild or moderate chronic obstructive pulmonary disease (COPD) only if the expected benefit outweighs the potential risk. Β-blockers should be administered with caution in patients predisposed to spontaneous hypoglycaemia or patients with wobbly diabetes, because beta-blockers may mask the signs and symptoms of acute hypoglycaemia. After topical application of brinzolamide, the same types of side effects that are typical for sulphonamides may occur. When using oral carbonic anhydrase inhibitors, acid-base imbalance disorders have been reported. The drug should be used with caution in patients at risk of renal dysfunction, due to the possible risk of metabolic acidosis. If signs of severe reactions or hypersensitivity develop, discontinue use. Oral carbonic anhydrase inhibitors may interfere with the ability to perform tasks requiring increased attention and / or motor coordination (these disorders may also occur after topical administration). When using beta blockers, patients with a history of atopy or a history of severe anaphylactic reactions to a variety of allergens may be more sensitive to repeated allergen exposure or may not respond to the usual doses of adrenaline administered to treat anaphylactic reactions. During the administration of drugs that reduce the production of aqueous humor (eg, timolol, acetazolamide) cases of choroidal detachment after filtration have been reported. Β-blockers used for the eyes can block the systemic effects of β-agonists, e.g. adrenaline. The anesthetist should be informed about the use of timolol by the patient. The effect on intra-ocular pressure or known effects resulting from general blocking of β-adrenergic receptors may be increased when timolol is administered to patients already receiving general beta-blocking drugs. You should carefully monitor the response of these patients to treatment. Co-administration of two topical β-adrenergic blockers or two topical carbonic anhydrase inhibitors is not recommended. There is the possibility of an additive effect in the range of known systemic effects of carbonic anhydrase inhibition in patients receiving an oral carbonic anhydrase inhibitor and formulation. Co-administration of the preparation and oral carbonic anhydrase inhibitors has not been studied and is not recommended. The experience with the use of the preparation in the treatment of glaucoma in the course of pseudoexfoliation syndrome or pigment glaucoma is limited. Caution should be exercised when treating these patients; Careful monitoring of intraocular pressure is recommended. It is not recommended for patients with narrow-angle glaucoma (no studies). Β-blockers administered to the eye may cause dry eyes. Caution should be exercised in patients with corneal diseases. The possible effect of brinzolamide on corneal endothelial function in patients with damaged cornea (especially in patients with low endothelial cells) has not been studied. This is especially true for patients wearing contact lenses that have not been tested and should be carefully monitored when using brinzolamide, as carbonic anhydrase inhibitors may affect the degree of corneal hydration and the use of contact lenses may increase the risk for the cornea. Careful monitoring of patients with deteriorated corneal conditions, such as those with diabetes or corneal dystrophy, is recommended. The preparation contains benzalkonium chloride, which may cause eye irritation and is known to change the color of soft contact lenses.Avoid contact with soft contact lenses. The contact lenses should be removed before use, and wait 15 minutes before putting them on again. Benzalkonium chloride may cause punctate keratopathy and / or toxic ulcerative keratopathy; careful monitoring is required for patients who use the medicine frequently or for a long time.

Do not use the product during pregnancy unless clearly necessary. There are no adequate data on the use of brinzolamide or timolol in pregnant women. If the preparation is administered until delivery, the newborn should be carefully monitored during the first days of life. It is not known whether brinzolamide is excreted in human milk. In animal studies, it was demonstrated that brinzolamide was orally administered into milk. Β-blockers are excreted in human milk. However, when timolol eye drops are used in the form of eye drops, its milk concentrations should not be expected to cause clinical signs of blocking β-adrenergic receptors in the infant. However, the risk to a breastfed child can not be ruled out. A decision should be made whether to discontinue breast-feeding or discontinue the treatment taking into account the benefits of breastfeeding for the child and the benefits of treatment for the mother.

Common: taste disorders, blurred vision, eye pain, eye irritation. Uncommon: insomnia, corneal erosions, punctate keratitis, photophobia, dry eye, presence of secretion in the eye, pruritus of the eye, feeling of solid in the eye, congestion of the eye, hyperkeratosis, increased tearing, redness in the anterior chamber of the eye, conjunctival congestion, erythema of the eyelids, reduction of blood pressure, cough, increase in potassium in the blood, increase in LDH activity in the blood. Not known: nasopharyngitis, pharyngitis, sinusitis, rhinitis, red blood cell count, increase in blood chloride, anaphylactic reaction, systemic allergic reactions including angioneurotic edema, limited or generalized rash, hypersensitivity, urticaria, pruritus, hypoglycaemia , depression, memory loss, apathy, depressed mood, decreased libido, nightmares, nervousness, cerebral ischemia, cerebrovascular incident, fainting, worsening of subjective and subjective symptoms of muscle fatigue (myasthenia gravis), drowsiness, dysfunction, amnesia, memory impairment, paresthesia, tremor, hypoaesthesia, lack of taste, dizziness, headache, increased proportion of the size of the hollow to the size of the optic disc, choroidal detachment after filtration, keratitis, keratopathy, epithelial damage cornea, corneal epithelial disease, increased intraocular pressure, eye deposits, corneal staining, corneal edema, decreased corneal sensitivity, conjunctivitis, thyroid gland inflammation, diplopia, blindness, photopsy, reduced visual acuity, impaired vision, wings, discomfort in the eye , inflammation of the conjunctiva and cornea, weakness in the eye, scleral staining, subconjunctival cyst, blurred vision, swollen eye, eye allergy, eyelash loss, eyelid disease, eyelid edema, eyelid droop, dizziness, tinnitus, cardiac arrest, heart failure , congestive n heart failure, atrioventricular block, cardio-respiratory collapse, angina pectoris, bradycardia, irregular heart rate, arrhythmia, palpitations, tachycardia, increased heart rate, chest pain, edema, hypotension, hypertension, increased blood pressure, Raynaud, cold of the hands and feet, bronchospasm (mainly in patients with existing bronchospasm), dyspnoea, asthma, nosebleeds, bronchial hyperreactivity, throat irritation, nasal congestion, congestion of the upper respiratory tract, dripping from the nose, snoring , dryness of the nose, vomiting, epigastric pain, abdominal pain, diarrhea, dry mouth, nausea, oesophagitis, indigestion, epigastric discomfort, stomach discomfort, frequent movements of the large intestine, stomach and intestinal disease, impaired sensation in the cavity oral, paraesthesia in the mouth, bloating with the passing of winds, abnormal liver function tests, urticaria, maculopapular rash, pruritus pruritus,skin tightness, dermatitis, alopecia, psoriasis-like rash or exacerbation of psoriasis, skin rash, erythema, muscle pain, muscle cramps, arthralgia, back pain, pain in the extremities, kidney pain, pollakiuria, erectile dysfunction, sexual dysfunction, decreased libido, chest pain, pain, fatigue, muscle weakness, feeling unwell, chest discomfort, abnormal well-being, jittery feeling, irritability, peripheral edema, drug residues. The preparation contains brinzolamide, which is a sulfonamide inhibitor of carbonic anhydrase, which is absorbed in general. The use of general anhydrase inhibitors of general action is associated with gastro-intestinal, nervous, hematopoietic, renal and metabolic disorders. Local treatment with carbonic anhydrase inhibitors may include the same type of side effects as those with oral carbonic anhydrase inhibitors. Timolol is absorbed into the systemic circulation. This can cause similar side effects as seen with beta-adrenergic drugs administered systemically. The incidence of general adverse reactions after topical ocular administration is lower than after systemic administration.

Adults (also elderly patients). The conjunctival: 1 drop administered to the affected eye (eyes) 2 times a day. If a dose is missed, treatment should be continued with the Next scheduled dose. Do not exceed a dose of 1 drop in the affected eye (eyes) twice a day. If another ophthalmic antisecretory is replaced with another preparation, discontinue the other medicine and start administration the next day.Special groups of patients. No dose adjustment is required in patients with impaired hepatic function or in patients with mild or moderate renal impairment. The preparation should be used with caution in patients with severe hepatic impairment. The drug is contraindicated in patients with severe renal impairment (creatinine clearance <30 ml / min). The safety and efficacy of the medicine in children and adolescents aged 0 to 18 has not yet been established.Way of giving. Compression of the nasal-lacrimal channel or gentle closing of the eyelids for 2 min limits the systemic absorption of the preparation - this can reduce systemic side effects and increase the local effect of the drug. If the patient uses more than one topical eye medicine, each of the medicines should be administered separately, with at least a 5-minute break. Eye ointments should be given last.