qanastek/EMEA-V3 huggingface dataset:
The Committee decided that Azarga’ s benefits are greater than its risks for the decrease of IOP in adult patients with open-angle glaucoma or ocular hypertension for whom monotherapy provides insufficient IOP reduction.
Il - Kumitat iddeċieda li l- benefiċċji ta ’ Azarga huma ikbar mir- riskji tiegħu fit- tnaqqis tal- IOP f’ pazjenti adulti bil- glawkoma bl- angolu miftuħ jew bi pressjoni għolja fl- għajnejn li għalihom il- monoterapija ma tipprovdix biżżejjed tnaqqis fl- IOP.
The Committee recommended that Azarga be given marketing authorisation.
Il- Kumitat irrakkomanda li Azarga jingħata l- approvazzjoni għat- tqegħid fis- suq.
Other information about Azarga:
Tagħrif ieħor dwar Azarga:
The European Commission granted a marketing authorisation valid throughout the EU for Azarga to Alcon Laboratories (UK) Ltd. on 25 November 2008.
Il- Kummissjoni Ewropea tat l- awtorizzazzjoni għat- tqegħid fis- suq għal Azarga valida madwar l- UE kollha lil Alcon Laboratories (UK) Ltd. fil- 25 ta ’ Novembru 2008.
The full EPAR for Azarga can be found here.
L- EPAR għal Azarga jista ’ jinstab hawn.
This summary was last updated in 10-2008.
Dan is- sommarju ġie aġġornat l- aħħar fi: 10- 2008.
EU number
Numru ta ’ Proċedura ta ’ l - Isem inventat EU
name
Qawwa
EU/ 1/ 08/ 482/ 001
EU/ 1/ 08/ 482/ 001 AZARGA
Eye drops, suspension
qtar għall - għajnejn, suspensjoni
Ocular use
Użu għall- għajn
Bottle (PE)
Flixkun (LDPE)
EU/ 1/ 08/ 482/ 002
EU/ 1/ 08/ 482/ 002 AZARGA
3 bottles
3 Flixkun
AZARGA 10 mg/ ml + 5 mg/ ml eye drops, suspension
AZARGA 10 mg/ ml + 5 mg/ ml qtar għall- għajnejn, suspensjoni
One ml of suspension contains 10 mg brinzolamide and 5 mg timolol (as timolol maleate).
Ml ta ’ suspensjoni fiha 10 mg brinzolamide u 5 mg timolol (bħala timolol maleate).
One ml of suspension contains 0.10 mg benzalkonium chloride.
Ml ta ’ suspensjoni fiha 0. 10 mg benzalkonium chloride.
Eye drops, suspension (eye drops) White to off-white uniform suspension, pH 7.2 (approximately).
Qtar għall- għajnejn, suspensjoni (qtar għall- għajnejn) Suspensjoni uniformi, bajda sa off- white, pH 7. 2 (bejn wieħed u ieħor).
Decrease of intraocular pressure (IOP) in adult patients with open-angle glaucoma or ocular hypertension for whom monotherapy provides insufficient IOP reduction.
Tnaqqis tal- pressjoni ta ’ ġo l- għajn (IOP) f’ pazjenti adulti bi glawkoma tat- tip open- angle jew pressjoni ta ’ l- għajnejn għolja li għalihom monoterapija tipprovdi tnaqqis mhux suffiċjenti ta ’ l- IOP.
Use in adults, including the elderly The dose is one drop of AZARGA in the conjunctival sac of the affected eye(s) twice daily.
Użu f’ adulti, inkluż l- anzjani Id- doża hija qatra waħda ta ’ AZARGA darbtejn kuljum fil- borża konġuntivali tal- għajn( ejn) affettwata( i).
Nasolacrimal occlusion or gently closing the eyelid after instillation is recommended.
Huwa rrakkomandat li jkun hemm okklużjoni nasolakrimali jew li l- kappell tal- għajn jingħalaq bil - mod wara li jitqattar il- qtar.
This may reduce the systemic absorption of medicinal products administered via the ocular route and result in a decrease in systemic adverse reactions.
Dan jista ’ jnaqqas l- assorbiment sistemiku tal- prodotti mediċinali mogħtija mill- għajn u jirriżulta fi tnaqqis tar- reazzjonijiet avversi sistemiċi.
If more than one topical ophthalmic medicinal product is being used, the medicines must be administered at least 5 minutes apart.
Jekk ikun qed jintuża aktar minn prodott mediċinali topiku għall- għajnejn wieħed, il- mediċini għandhom jingħataw b’ interval ta ’ mill- inqas 5 minuti minn xulxin.
If a dose is missed, treatment should be continued with the next dose as planned.
Jekk tintnesa doża, l- kura għandha titkompla bid- doża li jmiss kif ippjanat.
The dose should not exceed one drop in the affected eye (s) twice daily.
Id- doża m’ għandhiex tkun aktar minn qatra waħda fl- għajn( ejn) affettwata( i) darbtejn kuljum.
When substituting another ophthalmic antiglaucoma agent with AZARGA, the other agent should be discontinued and AZARGA should be started the following day.
Meta qed tiġi sostitwita sustanza oħra għall- għajnejn kontra l- glawkoma b’ AZARGA, is- sustanza l - oħra għandha titwaqqaf u AZARGA għandu jinbeda l- ġurnata ta ’ wara.
Paediatric patients AZARGA is not recommended for use in children below 18 years due to a lack of data on safety and efficacy.
Pazjenti pedjatriċi AZARGA mhux irrakkomandat għall- użu fit- tfal taħt l- età ta ’ 18- il sena minħabba nuqqas ta ’ informazzjoni dwar is- sigurtà u l- effikaċja.
2 Use in hepatic and renal impairment No studies have been conducted with AZARGA or with timolol 5 mg/ ml eye drops in patients with hepatic or renal impairment.
2 Użu f’ indeboliment tal- fwied u tal- kliewi Ma sarux studji b' AZARGA jew timolol 5 mg/ ml qtar għall- għajnejn f’ pazjenti b’ indeboliment tal - fwied jew tal- kliewi.
No dosage adjustment is necessary in patients with hepatic impairment or in patients with mild to moderate renal impairment.
L- ebda aġġustament fid- doża ma huwa neċessarju f’ pazjenti b’ indeboliment tal - fwied jew f’ pazjenti b’ indeboliment ħafif sa moderat tal- kliewi.
AZARGA has not been studied in patients with severe renal impairment (creatinine clearance < 30 ml/ min) or in patients with hyperchloraemic acidosis.
AZARGA ma ’ ġiex studjat f’ pazjenti b’ indeboliment serju tal- kliewi (tneħħija tal- krejatinina ta ’ < 30 ml/ min) jew f’ pazjenti li għandhom aċidożi iperklorimika.
Since brinzolamide and its main metabolite are excreted predominantly by the kidney, AZARGA is therefore contraindicated in patients with severe renal impairment (see section 4.3).
Peress li brinzolamide u l- metabolit prinċipali tiegħu jitneħħew fil- biċċa l- kbira mill- kliewi, AZARGA huwa kontra- indikat f’ pazjenti b’ indeboliment sever tal- kliewi (ara sezzjoni 4. 3).
Instruct patients to shake the bottle well before use.
Għarraf lill- pazjenti biex iħawwdu il- flixkun sew qabel l- użu.
To prevent contamination of the dropper tip and solution, care must be taken not to touch the eyelids, surrounding areas or other surfaces with the dropper tip of the bottle.
Biex tevita ’ kontaminazzjoni tat- tarf tal- qattara u tas- soluzzjoni, għandu jkun hemm attenzjoni biex ma ’ jintmissux il- kappell ta ’ l- għajnejn, l- erja ta ’ madwar l- għajnenjn jew xi superfiċji oħra bit- tarf tal- qattara tal- flixkun.
Instruct patients to keep the bottle tightly closed when not in use.
Għarraf lill- pazjenti biex iżommu il- flixkun magħluq sewwa meta ma jkunx qed jintuża.
Hypersensitivity to the active substances, or to any of the excipients.
Ażżma tal- bronki, passat ta ’ ażżma tal- bronki, jew marda severa kronika ostruttiva tal- pulmun.
Bronchial asthma, a history of bronchial asthma, or severe chronic obstructive pulmonary disease.
Sinus bradikardja, blokk atrijoventrikolari tat- tieni jew tat- tielet grad, insuffiċjenza kardijaka ċara, jew xokk kardjovaskulari.
Sinus bradycardia, second or third degree atrioventricular block, overt cardiac failure, or cardiogenic shock.
Rinite allerġika severa u reattività eċċessiva tal- bronki; sensittività eċċesiva għall - imblokkaturi tar- riċetturi Beta oħra.
Hyperchloraemic acidosis (see section 4.2).
Aċidożi iperklorimika (ara sezzjoni 4. 2).
Severe renal impairment.
Indeboliment sever tal- kliewi.
Hypersensitivity to sulphonamides (see section 4.4).
Sensittività eċċessiva għal sulfonamides (ara sezzjoni 4. 4).
Systemic effects Like other topically applied ophthalmic agents, brinzolamide and timolol are absorbed systemically.
Effetti sistemiċi Bħal sustanzi għall- għajnejn applikata b’ mod topiku oħra, brinzolamide u timolol huma assorbiti b’ mod sistemiku.
Due to the beta-adrenergic component, timolol, the same types of cardiovascular and pulmonary adverse reactions as seen with systemic beta-adrenergic blocking agents may occur.
Minħabba l- komponent beta- adrenerġiku, timolol, jista ’ jkun hemm l- istess tipi ta ’ reazzjonijiet avversi kardovaskulari u pulmonari osservati b’ sustanzi imblokkaturi beta- adrenerġiċi sistemiċi.
Cardiac failure should be adequately controlled before beginning therapy with timolol.
Insuffiċjenza kardijaka għandha tiġi kkontrollata b’ mod suffiċjenti qabel tinbeda terapija b’ timolol.
Patients with a history of severe cardiac disease should be watched for signs of cardiac failure and have their pulse rates checked.
Pazjenti b’ passat ta ’ mard kardijaku sever għandhom jiġu sorveljati għal sinjali ta ’ insuffiċjenza kardijaka u jkollhom ir- rati tal- polz tagħhom iċċekkjati.
Respiratory reactions and cardiac reactions, including death due to bronchospasm in patients with asthma and, rarely, death in association with cardiac failure, have been reported following administration of timolol maleate.
Wara l- għoti ta ’ timolol maleate kienu irrapportati reazzjonijiet respiratorji u reazzjonijiet kardijaċi, inkluż mewt minħabba brokospażmu f’ pazjenti bl- ażżma u rari, mewt assoċjata ma ’ insuffiċjenza kardijaka.
Beta-adrenergic blocking agents should be administered with caution in patients subject to spontaneous hypoglycaemia or to patients with labile insulin-dependent diabetes as beta-adrenergic blocking agents may mask the signs and symptoms of acute hypoglycaemia.
Sustanzi imblokkaturi beta- adrenerġiċi għandhom jingħataw b’ kawtela f’ pazjenti soġġetti għal ipogliċemija spontanja jew lill- pazjenti b’ dijabete mhux stabbli dipendenti mill- insulina peress li sustanzi imblokkaturi beta- adrenerġiċi jistgħu jgħattu s- sinjali u s- sintomi ta ’ ipogliċemija akuta.
They may also mask the signs of hyperthyroidism and cause worsening of Prinzmetal angina, severe peripheral and central circulatory disorders and hypotension.
Huma jistgħu jgħattu wkoll is- sinjali ta ’ ipertirojdiżmu u jikkawżaw irkadar ta ’ l- anġina ta ’ Prinzmetal, disturbi ċirkulatorji periferali u ċentrali severi u pressjoni baxxa.
AZARGA contains brinzolamide, a sulphonamide.
AZARGA fih brinzolamide, sustanza sulphonamide.
The same types of undesirable effects that are attributable to sulphonamides may occur with topical administration.
Ma ’ l- għoti topika jistgħu jseħħu l- istess tipi ta ’ effetti mhux mixtieqa li huma attribwiti lis- sulfonamides.
Acid-base disturbances have been reported with oral carbonic anhydrase inhibitors.
Disturbi fl- aċidi u l- bażi kienu irrapportati b’ inibituri ta ’ carbonic anhydrase orali.
If signs of serious reactions or hypersensitivity occur, discontinue the use of this medicinal product.
Jekk iseħħu sinjali ta ’ reazzjonijiet serji jew sensittività eċċessiva, waqqaf l- użu ta ’ dan il- prodott mediċinali.
There is potential for an additive effect on the known systemic effects of carbonic anhydrase inhibition in patients receiving an oral carbonic anhydrase inhibitor and AZARGA.
3 F’ pazjenti li qed jirċievu inibituri ta ’ carbonic anhydrase orali u AZARGA, hemm potenzjal ta ’ effett addittiv fuq l- effetti sistemiċi magħrufa tal- inibizzjoni ta ’ carbonic anhydrase.
The concomitant administration of AZARGA and oral carbonic anhydrase inhibitors has not been studied and is not recommended (see section 4.5).
L- għoti ta ’ AZARGA flimkien ma ’ inibituri ta ’ carbonic anhydrase orali ma ’ ġietx studjata u mhux irrakkomandata (ara sezzjoni 4. 5).
3 Anaphylactic reactions While taking beta-adrenergic blocking agents, patients with a history of atopy or a history of severe anaphylactic reaction to a variety of allergens may be unresponsive to the usual doses of adrenaline used to treat anaphylactic reactions.
Reazzjonijiet anafilattiċi Waqt li qed jittieħdu sustanzi imblokkaturi beta- adrenerġiċi, pazjenti b’ passat ta ’ atopija jew passat ta ’ reazzjoni anafilattika severa għal varjetà ta ’ allerġeni jistgħu ma jirrispondux għad- dożi tas- soltu ta ’ adrenaline wżati għall- kura ta ’ reazzjonijiet anafilattiċi.
Concomitant therapy Timolol may interact with other medicinal products (see section 4.5).
Terapija fl- istess waqt Timolol jista ’ jkollu effett fuq prodotti mediċinali oħra (ara sezzjoni 4. 5).
The effect on intraocular pressure or the known effects of systemic beta blockade may be potentiated when AZARGA is given to patients already receiving an oral beta-adrenergic blocking agent.
L- effett fuq il- pressjoni ta ’ ġo l- għajn jew l- effetti magħrufa ta ’ l- imblukkar beta sistemiku jistgħu jkunu msaħħa meta AZARGA jingħata lill- pazjenti li diġà qed jieħdu sustanzi imblokkaturi beta - adrenerġiċi.
The use of two local beta-adrenergic blocking agents or two local carbonic anhydrase inhibitors is not recommended.
L- użu ta ’ żewġ sustanzi mblokkaturi beta- adrenerġiċi lokali jew ta ’ żewġ inibituri ta ’ carbonic anhydrase lokali mhux irrakkomandat.
Ocular effects There is limited experience with AZARGA in the treatment of patients with pseudoexfoliative glaucoma or pigmentary glaucoma.
Effetti fuq l- għajn Hemm esperjenza limitata b’ AZARGA fil- kura ta ’ pazjenti bi glawkoma psewdoeksfoljattiva jew glawkoma kkawżata minn akkumulazzjoni tal- pigment.
Caution should be utilised in treating these patients and close monitoring of IOP is recommended.
Għandu jkun hemm attenzjoni meta jiġu kkurati dawn il- pazjenti u hija rrakkomandata sorveljanza mill- qrib ta ’ l- IOP.
AZARGA has not been studied in patients with narrow-angle glaucoma and its use is not recommended in these patients.
AZARGA ma ’ ġiex studjat f’ pazjenti li għandhom glawkoma tat- tip narrow angle u l- użu tiegħu mhux irrakkomandat f’ dawn il- pazjenti.
Oral carbonic anhydrase inhibitors may impair the ability to perform tasks requiring mental alertness and/or physical coordination in elderly patients.
F’ pazjenti anzjani nibituri ta ’ carbonic anhydrase li jittieħdu mill- ħalq jistgħu jnaqqsu l- ħila biex jitwettqu azzjonijiet li jinħtieġu konċentrazzjoni mentali u/ jew ko- ordinazzjoni fiżika.
AZARGA is absorbed systemically and therefore this may occur with topical administration.
AZARGA huwa assorbit b’ mod sistemiku u għalhekk dan jista ’ jseħħ meta jingħata b’ mod topiku.
The possible role of brinzolamide on corneal endothelial function has not been investigated in patients with compromised corneas (particularly in patients with low endothelial cell count).
Ir- rwol possibli ta ’ brinzolamide fuq il- funzjoni ta ’ l- endotelju tal- korneja ma ’ ġiex investigat f’ pazjenti li għandhom il- korneji kompromessi (b’ mod partikolari f’ pazjenti li għandhom għadd baxx ta ’ ċelluli ta ’ l- endotelju).
Specifically, patients wearing contact lenses have not been studied and careful monitoring of these patients when using brinzolamide is recommended, since carbonic anhydrase inhibitors may affect corneal hydration and wearing contact lenses might increase the risk for the cornea.
Speċifikament, pazjenti li jilbsu l- lentijiet tal- kuntatt ma ’ ġewx studjati u huwa rrakkomandat li dawn il- pazjenti jkunu sorveljati tajjeb waqt l- użu ta ’ brinzolamide, peress li l - inibituri ta ’ carbonic anhydrase jistgħu jaffetwaw l- idratazzjoni tal- korneja u r- riskju għall- korneja jista ’ jiżdied jekk jintlibsu lentijiet tal- kuntatt.
Careful monitoring of patients with compromised corneas, such as patients with diabetes mellitus or corneal dystrophies, is recommended.
Hija rrakkomandata sorveljanza b’ attenzjoni ta ’ pazjenti b’ korneji kompromessi, bħal pazjenti b’ dijabete mellitus jew distrofiji tal- korneji.
Benzalkonium chloride, which is commonly used as a preservative in ophthalmic products, has been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy.
Benzalkonium chloride, li jintuża b’ mod komuni bħala preservattiv fi prodotti għall- għajnejn, kien irrapportat li jikkawza keratopatija bil- ponot u/ jew keratopatija ulċerattiva tossika.
Since AZARGA contains benzalkonium chloride, close monitoring is required with frequent or prolonged use
Peress li AZARGA fih benzalkonium chloride, hija meħtieġa sorveljanza mill- viċin jekk jintuża b’ mod frekwenti jew fit - tul.
AZARGA contains benzalkonium chloride which may cause eye irritation and is known to discolour soft contact lenses.
AZARGA fih benzalkonium chloride li jista ’ jikkawża irritazzjoni fl- għajn u huwa magħruf li jbiddel il- kulur ta ’ lentijiet tal- kuntatt rotob.
Patients must be instructed to remove contact lenses prior to the application of AZARGA and wait 15 minutes after instillation of the dose before reinsertion.
Il - pazjenti għandhom jiġu infurmati biex ineħħu l- lentijiet tal- kuntatt qabel l- applikazzjoni ta ’ AZARGA u jistennew 15- il minuta wara l- għoti tad- doża qabel jerġgħu jilbsuhom.
No interaction studies have been performed with AZARGA.
Ma sarux studji dwar l- effett ta ’ mediċini jew ta ’ affarijiet oħra fuq l- effett farmaċewtiku tal- prodott b’ AZARGA.
AZARGA contains brinzolamide, a carbonic anhydrase inhibitor and, although administered topically, is absorbed systemically.
4 AZARGA fih brinzolamide, inibitur ta ’ carbonic anhydrase, li għalkemm mogħti b’ mod topiku, huwa assorbit b’ mod sistemiku.
Acid-base disturbances have been reported with oral carbonic anhydrase inhibitors.
Kienu irrapportati disturbi fl- aċidi u l- bażi b’ inibituri ta ’ carbonic anhydrase orali.
The potential for interactions must be considered in patients receiving AZARGA.
F’ pazjenti li qed jirċievu AZARGA għandu jiġi kkunsidrat il- potenzjal ta ’ interazzjonijiet.
The cytochrome P-450 isozymes responsible for metabolism of brinzolamide include CYP3A4 (main), CYP2A6, CYP2B6, CYP2C8 and CYP2C9.
L- isożimi taċ- ċitokromju P- 450 responsabbli għall- metaboliżmu ta ’ brinzolamide jinkludu CYP3A4 (il- prinċipali), CYP2A6, CYP2C8 u CYP2C9.
It is expected that inhibitors of CYP3A4 such as ketoconazole, itraconazole, clotrimazole, ritonavir and troleandomycin will inhibit the metabolism of brinzolamide by CYP3A4.
Huwa mistenni li inibituri ta ’ CYP3A4 bħal ketoconazole, itraconazole, clortrimazole, ritonavir u troleandomycin jinibixxu il- metaboliżmu ta ’ brinzolamide permezz ta ’ CYP3A4.
Caution is advised if CYP3A 4 inhibitors are given concomitantly.
Hija rrakkomandata attenzjoni jekk inibituri ta ’ CYP3A4 jingħataw fl- istess waqt.
However, accumulation of brinzolamide is unlikely as renal elimination is the major route.
Madanakollu, mhux probabbli li jkun hemm akkumulazzjoni ta ’ brinzolamide peress li eliminazzjoni mill- kliewi hija r- rotta maġġuri.
Brinzolamide is not an inhibitor of cytochrome P-450 isozymes.
Brinzolamide mhux inibitur ta ’ isożimi taċ- citokromju P- 450.
4 There is a potential for additive effects resulting in hypotension and/or marked bradycardia when eye drops with timolol are administered concomitantly with oral calcium channel blockers, guanethidine or beta-blocking agents, antiarrhythmics, digitalis glycosides or parasympathomimetics.
Hemm il- potenzjal għall- effetti addittivi li jirriżultaw fi pressjoni baxxa u/ jew bradikardija qawwija meta qtar għall- għajnejn b’ timolol jingħataw fl- istess waqt ma ’ imblokkaturi tal- kanali tal- kalċju, guanethidine jew sustanżi li jimblukkaw ir- riċetturi Beta, sustanzi kontra l- arritmija, digitalis glycosides jew parasimpatomimetiċi.
The hypertensive reaction to sudden withdrawal of clonidine can be potentiated when taking beta-blockers.
Ir- reazzjoni ta ’ pressjoni għolja minħabba twaqqif f’ daqqa ta ’ clonidine tista ’ tkun imsaħħa meta jittieħdu imblokkaturi tar- riċetturi Beta.
Potentiated systemic beta-blockade (e.g. decreased heart rate) has been reported during combined treatment with CYP2D6 inhibitors (e.g. quinidine, cimetidine) and timolol.
Imblokk sistemiku imsaħħaħ tar- riċetturi Beta (e. ż. rata tal- qalb imnaqqsa) kien irrapportat waqt kura kombinata b’ inibituri ta ’ CYP2D6 (e. ż. quinidine, cimetidine) u timolol.
Beta-blockers may increase the hypoglycaemic effect of antidiabetic agents.
Imblokkaturi tar- riċetturi Beta jistgħu jżidu l- effett ipogliċemiku ta ’ sustanzi kontra d- dijabete.
Beta-blockers can mask the signs and symptoms of hypoglycaemia (see section 4.4).
Imblokkaturi tar- riċetturi Beta jistgħu jaħbu s- sinjali u s- sintomi ta ’ ipogliċemija (ara sezzjoni 4. 4).
Pregnancy There are no adequate data from the use of brinzolamide in pregnant women.
Tqala M’ hemmx tagħrif biżżejjed dwar l- użu ta ’ brinzolamide f’ nisa tqal.
Well-controlled epidemiological studies with systemic use of beta-blockers did not indicate malformative effects, but some pharmacological effects such as bradycardia have been observed in foetuses or neonates.
Studji epidemjoloġiċi kkontrollati tajjeb bl- użu sistemiku ta ’ mblokkaturi tar- riċetturi Beta ma tawx indikazzjoni ta ’ effetti malformattivi, iżda kienu osservati xi effetti farmakoloġiċi bħal bradikardija fil - feti jew fit- trabi tat- twelid.
Data on a limited number of exposed pregnancies indicate no adverse effects of timolol in eye drops on pregnancy or on the health of the foetus/newborn child but bradycardia and arrhythmia have been reported in one case in the foetus of a woman treated with timolol eye drops.
Tagħrif dwar numru limitat ta ’ użu waqt it- tqala ma jindikax effetti avversi ta ’ timolol fi qtar għall- għajnejn fuq it- tqala jew fuq is- saħħa tal- fetu/ tarbija tat- twelid iżda kien irrapportat każ wieħed ta ’ bradikardija u arritmija f’ fetu ta ’ mara kkurata b’ timolol qtar ta ’ l- għajnejn.
To date, no other relevant epidemiological data are available.
Sa llum, m’ hemm l- ebda tagħrif epidemjoloġiku rilevanti ieħor.
AZARGA should not be used during pregnancy unless clearly necessary.
AZARGA m’ għandux jintuża waqt it- tqala ħlief meta hemm bżonn speċifiku.
Lactation It is not known whether brinzolamide is excreted in human breast milk.
Treddigħ Mhux magħruf jekk brinzolamide jitneħhiex fil- ħalib tas- sider uman.
Animal studies have shown excretion of brinzolamide in breast milk.
Studji fuq il- bhejjem urew eskrezzjoni ta ’ brinzolamide fil- ħalib tas- sider.
Timolol does appear in human breast milk.
Timolol jidher fil- ħalib tas- sider uman.
However, at therapeutic doses of AZARGA, no effects on the breastfed newborns/infants are anticipated.
Iżda, f’ dożi terapewtiċi ta ’ AZARGA, mhux mistennija l- ebda effetti fuq it- trabi tat- twelid/ trabi li qed jerdgħu.
AZARGA can be used during breast-feeding.
AZARGA jista ’ jintuża waqt it- treddigħ.
As with any eye drops, temporary blurred vision or other visual disturbances may affect the ability to drive or use machines.
Bħal b’ kull qtar għall- għajnejn, vista temporanjament imċajpra jew disturbi oħra fil- vista jistgħu jaffetwaw il- ħila biex issuq jew tħaddem magni.
If blurred vision occurs at instillation, the patient must wait until the vision clears before driving or using machines.
Jekk ma ’ l- applikazzjoni jkun hemm vista mċajpra, il - pazjent għandu jistenna sakemm il- vista tiċċara qabel isuq jew iħaddem magni.
Oral carbonic anhydrase inhibitors may impair the ability of elderly patients to perform tasks requiring mental alertness and/or physical coordination (see section 4.4).
Inibituri ta ’ carbonic anhydrase orali jistgħu jtellfu l- ħila li pazjenti anżjani jwettqu azzjonijiet li jeħtieġu moħħ ċar u/ jew koordinazzjoni fiżika (ara sezzjoni 4. 4).
Summary of the safety profile In two clinical trials of 6 and 12 months duration involving 394 patients treated with AZARGA, the most frequently reported adverse reaction was transient blurred vision upon instillation (3.6%), lasting from a few seconds to a few minutes.
Sommarju tal- profil tas- sigurtà F’ żewġ provi kliniċi b’ tul ta ’ 6 xhur u 12- il xahar li nvolvew 394 pazjent ikkurat b’ AZARGA, l- aktar reazzjoni avversa rrapportata b’ mod frekwenti kienet vista temporanjament imċajpra ma ’ l - applikazzjoni (3. 6%), li damet ftit sekondi sa ftit minuti.
Tabulated summary of adverse reactions The following adverse reactions are classified according to the following convention: very common (≥1/10), common≥1/100 to < 1/10), uncommon (≥1/1,000 to < 1/100), rare (≥1/10,000 to < 1/1000), or very rare (< 1/10,000).
Sommarju tar- reazzjonijiet avversi f’ tabella Ir- reazzjonijiet avversi li ġejjin huma kklassifikati skond il- konvenzjoni li ġejja: komuni ħafna (≥1/ 10), komuni (≥1/ 100 sa < 1/ 10), mhux komuni (≥1/ 1, 000 sa < 1/ 100), rari (≥1/ 10, 000 sa < 1/ 1000), jew rari ħafna (< 1/ 10, 000).
5 System Organ Classification
Sistema tal- Klassifika tal- Organi
MedDRA Preferred Term
Terminu Ippreferut MedDRA
Psychiatric disorders Nervous system disorders Eye disorders
Disturbi psikjatriċi Disturbi fis- sistema nervuża Disturbi fl- għajnejn
Uncommon: insomnia Common: dysgeusia Common: blurred vision, eye pain, eye irritation, foreign body sensation in eyes Uncommon: corneal erosion, punctate keratitis, dry eye, eye discharge, eye pruritus, ocular hyperaemia, blepharitis, allergic conjunctivitis, corneal disorder, anterior chamber flare, conjunctival hyperaemia, eyelid margin crusting, astenopia, abnormal sensation in eye, eyelids pruritus, allergic blepharitis, erythema of eyelid
Mhux komuni: nuqqas ta ’ rqad Komuni: disġewżja Komuni: vista mċajpra, uġigħ fl- għajnejn, irritazzjoni fl - għajnejn, sensazzjoni ta ’ oġġett barrani fl- għajnejn Mhux komuni: erożjoni tal- korneja, keratite bil- ponot, għajn tinħass xotta, tnixxija mill- għajn, ħakk fl- għajn, iperimija ta ’ l- għajn, blefarite, konġuntivite allerġika, disturb fil- korneja, riflessjoni ta ’ dawl fil- kompartiment anterjuri, iperimija konġuntivali, qoxra fix- xifer tal- kappell ta ’ l- għajn, astenopija, sensazzjoni mhux normali fl- għajn, ħakk fil- kappell ta ’ l- għajn, blefarite allerġika, eritema tal - kappell ta ’ l- għajn
Vascular disorders Respiratory, thoracic and mediastinal disorders Skin and subcutaneous tissue disorders
Disturbi vaskulari Disturbi respiratorji, toraċiċi u medjastinali Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
Uncommon: decreased blood pressure Uncommon: chronic obstructive pulmonary disease, pharyngolaryngeal pain, rhinorrhoea, cough Uncommon: hair disorder, lichen planus
Mhux komuni: pressjoni tad- demm imnaqqsa Mhux komuni: marda kronika ta ’ ostruzzjoni pulmonari, uġigħ faringolarinġali, rinoreja, sogħla Mhux komuni: disturb fix- xagħar, lichen planus
Description of selected adverse reactions Dysgeusia (bitter or unusual taste in the mouth following instillation) was a frequently reported systemic adverse reaction associated with the use of AZARGA during clinical trials.
Disġewżja (togħma qarsa jew mhux tas- soltu fil- ħalq wara li jitqattar il- qtar) kienet reazzjoni sistemika avversa irrapportata b’ mod frekwenti assoċjata ma ’ l- użu ta ’ AZARGA waqt il- provi kliniċi.
It is likely to be caused by passage of the eye drops in the nasopharynx via the nasolacrimal canal and is attributable to brinzolamide.
X’ aktarx li hija kkawżata mill- passaġġ tal- qtar ta ’ l- għajnejn fin- nasofarinġi mill- kanal nasolakrimali u hija attribwita għal brinzolamide.
Nasolacrimal occlusion or gently closing the eyelid after instillation may help reduce the occurrence of this effect (see section 4.2).
Okklużjoni nasolakrimali jew għeluq bil- mod tal- kappell ta ’ l- għajn wara li jitqattar il- qtar jista ’ jgħin biex inaqqas l- inċidenza ta ’ dan l- effett (ara sezzjoni 4. 2).
AZARGA contains brinzolamide which is a sulphonamide inhibitor of carbonic anhydrase with systemic absorption.
AZARGA fih brinzolamide, inibitur sulphonamide ta ’ carbonic anhydrase li huwa assorbit b’ mod sistemiku.
Gastrointestinal, nervous system, haematological, renal and metabolic effects are generally associated with systemic carbonic anhydrase inhibitors.
Effetti gastro- intestinali, tas- sistema nervuża, ematoloġiċi, tal- kliewi u tal- metaboliżmu, ġeneralment huma assoċjati ma ’ inibituri sistemiċi ta ’ carbonic anhydrase.
The same type of adverse reactions attributable to oral carbonic anhydrase inhibitors may occur with topical administration.
L- istess tip ta ’ reazzjonijiet avversi li huma attribwiti lill- inibituri orali ta ’ carbonic anhydrase jistgħu jseħħu ma ’ għoti topika.
AZARGA contains brinzolamide and timolol (as timolol maleate).
AZARGA fih brinzolamide u timolol (bħala timolol maleate).
Additional adverse reactions associated with the use of the individual components observed in clinical trials and postmarketing experience that may potentially occur with AZARGA include:
Reazzjonijiet avversi addizzjonali assoċjati ma ’ l- użu tal- komponenti individwali osservati fil- provi kliniċi u l- esperjenza ta ’ wara t - tqegħid fis- suq li potenzjalment jistgħu jseħħu b’ AZARGA jinkludu:
Brinzolamide 10 mg/ml
Brinzolamide 10 mg/ ml
System Organ Classification
Sistema tal- Klassifika tal- Organi
Infections and infestations
farinġite, sinożite,
nasopharyngitis, pharyngitis, sinusitis, rhinitis
Disturbi tad- demm u tas- sistema limfatika
Blood and lymphatic system disorders Immune system disorders:
għadd ta ’ ċelluli ħomor tad- demm imnaqqas, chloride fid- demm miżjud
Metabolism and nutrition disorders
Disturbi fis- sistema immuni Disturbi fil- metaboliżmu u n - nutrizzjoni
decreased red blood cell count, increased blood chloride hypersensitivity
sensittività eċċessiva
hypoglycaemia
ipoġliċemija
apathy, depression, depressed mood, decreased libido, nightmare, nervousness
apatija, depressjoni, burdata depressa, tnaqqis fil- libido, inkubi, nervi
somnolence, motor dysfunction, amnesia, memory impairment, dizziness, paraesthesia, tremor,
ħedla ta ’ ngħas, disfunzjoni motorja, amnesija, tnaqqis tal - memorja, sturdament, paresteżija, rogħda, uġigħ ta ’ ras, ipoesteżija, aġewżja
cerebral ischaemia, cerebrovascular accident, syncope,
iskemija ċerebrali, inċident ċerebrovaskulari, sinkope, myasthenia gravis, paresteżija, uġigħ ta ’ ras, sturdament
headache, hypoaesthesia, ageusia myasthenia gravis, paresthesia, headache, dizziness Eye disorders
Disturbi fl- għajnejn
keratitis, keratopathy, increased optic nerve cup/disc ratio, corneal epithelium defect, corneal epithelium disorder, increased intraocular pressure, eye deposit, corneal staining, corneal oedema, conjunctivitis, meibomianitis, diplopia, glare, photophobia, photopsia, reduced visual acuity, pterygium, ocular discomfort, keratoconjunctivitis sicca, hypoaesthesia of the eye, scleral pigmentation, subconjunctival cyst, increased lacrimation, visual disturbance, eye swelling, eye allergy, madarosis, eyelid disorder, eyelid oedema
keratite, keratopatija, żjieda fil - proporzjon tat- tażża/ disk tan- nerv ottiku, difett fl- epitelju tal - korneja, disturb fl- epitelju tal - korneja, pressjoni ta ’ ġewwa l - għajn miżjuda, depożitu fl- għajn, tebgħa fil- korneja, edima fil - korneja, konġuntivite, meibomianitis, diplopja, leħħa,
conjunctivitis, diplopia, eyelid ptosis, keratitis, visual disturbance
konġuntivite, diplopja, ptosi tal- kappell ta ’ l - għajn, ketatite, disturb fil- vista
Ear and labyrinth disorders
fotofobija, fotopsija, akutezza tal - vista mnaqqsa, pteriġjum, skomdu fl- għajn, keratokonġuntivite xotta, ipoestesija ta ’ l- għajn, pigmentazzjoni ta ’ l- isklera, ċeste taħt il- konġuntiva, żjieda fid - dmugħ, disturb fil- vista, nefħa fl - għajn, allerġija fl- għajn, madarosi, disturb fil- kappell ta ’ l - għajn, edima fil- kappell ta ’ l - għajn Disturbi fil- widnejn u fis- sistema labirintika
tinnitus, vertigo
żanżin fil- widnejn, vertigo
cardio-respiratory distress, angina pectoris, bradycardia, irregular heart rate, arrhythmia, palpitations, tachycardia, increased heart rate
problemi kardjo- respiratorji, angina pectoris, bradikardija, rata tal- qalb irregolari, arritmija, palpitazzjonijiet, takikardija, rata tal- qalb miżjuda
cardiac arrest, cardiac failure, arrhythmia, atrioventricular block, bradycardia, palpitations
arrest kardijaku, insuffiċjenza tal- qalb, arritmija, blokk atrioventrikolari, bardikardija, palpitazzjonijiet
increased blood pressure, hypertension
żjieda fil- pressjoni tad- demm, pressjoni għolja
7 Gastrointestinal disorders
7 Disturbi respiratorji, toraċiċi u medjastinali
dry mouth, oesophagitis, vomiting, diarrhoea, nausea, dyspepsia, upper abdominal pain, abdominal discomfort, stomach discomfort, frequent bowel movements, gastrointestinal disorder, oral hypoaesthesia, oral paraesthesia, flatulence
ħalq xott, esofaġite, rimettar, dijarea, tqalligħ, dispepsja, uġigħ fin- naħa ta ’ fuq taż- żaqq, skomdu addominali, skomdu fl- istonku, purgar spiss, disturb gastro - intestinali, ipoestesija fil- ħalq, parestesija fil- ħalq, gass
diarrhoea, nausea
dijarea, tqalligħ
abnormal liver function test
test tal- funzjoni tal- fwied mhux normali
urticaria, maculo-papular rash, rash, generalised pruritus, alopecia, skin tightness, dermatitis, erythema
urtikarja, raxx makulo- papulari, raxx, ħakk ġeneralizzat, alopeċja, ġilda tinħass miġbuda, dermatite, eritema
alopecia, rash
alopeċja, raxx
back pain, muscle spasms, myalgia, arthralgia, pain in extremity
uġigħ fid- dahar, spażmi fil - muskoli, artralġja, uġigħ fl - estremitajiet
Renal and urinary disorders Reproductive system and breast disorders
Disturbi fil- kliewi u fis- sistema urinarja
renal pain, pollakiuria erectile dysfunction
uġigħ fil- kliewi, pollakurja
General disorders and administrative site conditions
Disturbi fis- sistema riproduttiva u fis- sider
pain, asthenia, chest discomfort, fatigue, feeling abnormal, feeling jittery, irritability, chest pain, peripheral oedema, malaise, medication residue
uġigħ, astenja, skomdu fis- sider, għeja, tħossok mhux normali, tħossok nervuż, irritabilità, uġigħ fis- sider, edima periferali, tħossok ma tiflaħx, fdal tal- mediċina
asthenia, chest pain
astenja, uġigħ fis- sider
foreign body in eye
oġġett barrani fl- għajn
AZARGA is not recommended for use in children below 18 years due to a lack of data on safety and efficacy.
AZARGA mhux irrakkomandat għall- użu fi tfal taħt 18- il sena minħabba nuqqas ta ’ tagħrif dwar is - sigurtà u l- effikaċja.
If overdose with AZARGA eye drops occurs, treatment should be symptomatic and supportive.
Jekk iseħħ doża eċċessiva b’ AZARGA qtar għall- għajnejn, il- kura għandha tkun sintomatika u ta ’ sapport.
Electrolyte imbalance, development of an acidotic state, and possibly central nervous system effects may occur.
Jista ’ jkun hemm żbilanċ ta ’ l- elettroliti, żvilupp ta ’ stat ta ’ aċidożi, u possibilment effetti fuq is- sistema nervuża ċentrali.
Serum electrolyte levels (particularly potassium) and blood pH levels should be monitored.
Il- livelli ta ’ l- elettroliti fis- serum (speċjalment tal- potassju) u l- livelli tal - pH fid- demm għandhom jiġu sorveljati.
Studies have shown that timolol does not dialyse readily.
Studji wrew li timolol ma jiġix dijalizzat malajr.
Antiglaucoma preparation and miotics ATC code:
Preparazzjoni kontra l- glawkoma u mijotiċi Kodiċi ATC:
Mechanism of action AZARGA contains two active substances: brinzolamide and timolol maleate.
Mekkaniżmu ta ’ azzjoni AZARGA fih żewġ sustanzi attiva: brinzolamide u timolol maleate.
These two components decrease elevated IOP primarily by reducing aqueous humour secretion, but do so by different mechanisms of action.
Dawn iż- żewġ komponenti jnaqqsu l- pressjoni elevata ġewwa l- għajn l- aktar billi jnaqqsu s- sekrezzjoni ta ’ l- aqueous humour iżda jagħmlu hekk b’ mekkaniżmi ta ’ azzjoni differenti.
The combined effect of these two active substances results in additional IOP reduction compared to either compound alone.
L- effett kombinat ta ’ dawn iż- żewġ sustanzi attivi jwassal għal tnaqqis addizzjonali tal- pressjoni ġewwa l- għajn (IOP) meta mqabbel mal- azzjoni ta ’ kull komponent waħdu.
8 Brinzolamide is a potent inhibitor of human carbonic anhydrase II (CA-II), the predominant iso-enzyme in the eye.
Brinzolamide huwa inibitur qawwi ta ’ carbonic anhydrase II (CA- II) uman, l- iso- enżima prinċipali fl - għajn.
Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humour secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport.
L- inibizzjoni ta ’ carbonic anhydrase fil- proċessi ċiljari ta ’ l- għajn tnaqqas is- sekrezzjoni ta ’ l - aqueous humour, preżumibbilment billi tnaqqas il- formazzjoni ta ’ ijoni ta ’ bicarbonate bi tnaqqis sussegwenti fit- trasport ta ’ sodju u ta ’ fluwidu.
Timolol is a non-selective adrenergic-blocking agent that has no intrinsic sympathomimetic, direct myocardial depressant or membrane-stabilising activity.
Timolol huwa mblokkatur adrinerġiku mhux selettiv li m’ għandux attività simpatomimetika intrinsika, attività ta ’ depressjoni mijokardijaka diretta jew attività ta ’ stabilizzazzjoni tal- membrana.
Pharmacodynamic effects Clinical effects:
Effetti farmkodinamiċi Effetti kliniċi:
In a twelve-month, controlled clinical trial in patients with open-angle glaucoma or ocular hypertension who, in the investigator’s opinion could benefit from a combination therapy, and who had baseline mean IOP of 25 to 27 mmHg, the mean IOP-lowering effect of AZARGA dosed twice daily was 7 to 9 mmHg.
Fi prova klinika kkontrollata ta ’ tnax il- xahar, f’ pazjenti bi glawkoma open- angle jew pressjoni għolja ta ’ l- għajnejn li fl- opinjoni ta ’ l- investigatur setgħu jibbenefikaw minn terapija kombinata, u li kellhom IOP medja fil- linja bażi ta ’ 25 sa 27 mmHg, il- medja tal- effett ta ’ tnaqqis fl- IOP ta ’ AZARGA mogħti darbtejn kuljum kien ta ’ 7 sa 9 mmHg.
The non-inferiority of AZARGA as compared to dorzolamide 20 mg/ml + timolol 5 mg/ml in the mean IOP reduction was demonstrated across all time-points at all visits.
In- nuqqas ta ’ inferjorità ta ’ AZARGA kif imqabbel ma ’ dorzolamide 20 mg/ ml + timolol 5 mg/ ml fit- tnaqqis medju tal- IOP kien dimostrat tul il - punti ta ’ ħin kollha, fil- visti kollha.
In a six-month, controlled clinical study in patients with open-angle glaucoma or ocular hypertension and baseline mean IOP of 25 to 27 mmHg, the mean IOP-lowering effect of AZARGA dosed twice daily was 7 to 9 mmHg, and was up to 3 mmHg greater than that of brinzolamide 10 mg/ml dosed twice daily and up to 2 mmHg greater than that of timolol 5 mg/ml dosed twice daily.
Fi studju kliniku kkontrollat ta ’ sitt xhur f’ pazjenti bi glawkoma open- angle jew pressjoni għolja ta ’ l - għajnejn u IOP medja fil- linja bażi ta ’ 25 sa 27 mmHg, il- medja tal- effett ta ’ tnaqqis fl- IOP ta ’ AZARGA mogħti darbtejn kuljum kien ta ’ 7 sa 9 mmHg, u kien sa 3 mmHg aktar minn dak ta ’ brinzolamide 10 mg/ ml mogħti darbtejn kuljum u sa 2 mmHg aktar minn dak ta ’ timolol 5 mg/ ml mogħti darbtejn kuljum.
A statistically superior reduction in mean IOP was observed compared to both brinzolamide and timolol at all time-points and visits throughout the study.
Kien osservat tnaqqis statistikament superjuri fl- IOP medja meta mqabbel kemm ma ’ brinzolamide kif ukoll ma ’ timolol tul il- punti ta ’ ħin u l- visti kollha tul l- istudju.
In three controlled clinic al trials, the ocular discomfort upon instillation of AZARGA was significantly lower than that of dorzolamide 20 mg/ml + timolol 5 mg/ml.
Fi tliet provi kliniċi kkontrollati, l- iskomdu fl- għajn mat- tqattir ta ’ AZARGA kien sinifikatament aktar baxx minn dak ta ’ dorzolamide 20 mg/ ml + timolol 5 mg/ ml.
In a pharmacokinetic study, healthy subjects received oral brinzolamide (1 mg) twice daily for 2 weeks to shorten the time to reach steady-state prior to starting AZARGA administration.
5. 2 Tagħrif farmakokinetiku
Following twice daily dosing of AZARGA for 13 weeks, red blood cell (RBC) concentrations of brinzolamide averaged 18.8 ± 3.29 µM, 18.1 ± 2.68 µM and 18.4 ± 3.01 µM at weeks 4, 10 and 15, respectively, indicating that steady-state RBC concentrations of brinzolamide were maintained
Wara għoti darbtejn kuljum ta ’ AZARGA għal 13- il ġimgħa, konċentrazzjonijiet fiċ- ċelluli ħomor tad- demm (RBC) ta ’ brinzolamide kellhom medja ta ’ 18. 8 ± 3. 29 µM, 18. 1 ± 2. 68 µM u 18. 4 ± 3. 01 µM f’ ġimgħat 4, 10 u 15, rispettivament, u dan jindika li l- konċentrazzjonijiet fl- RBC fi stat fiss ta ’ brinzolamide kienu sostnuti.
At steady state, following administration of AZARGA, the mean plasma Cmax and AUC0-12h of timolol were 27% and 28% lower (Cmax:
9 Fi stat fiss, wara għoti ta ’ AZARGA, Cmax u AUC0- 12h medja fil- plażma ta ’ timolol kienu 27% u 28% inqas (Cmax:
0.824 ± 0.453 ng/ml; AUC0-12h:
0. 824 ± 0. 453 ng/ ml; AUC0- 12h:
4.71 ± 4.29 ng·h/ml), respectively, in comparison to the administration of timolol 5 mg/ml (Cmax:
4. 71 ± 4. 29 ng h/ ml), rispettivament, meta mqabbel ma ’ l- għoti ta ’ timolol 5 mg/ ml (Cmax:
1.13 ± 0.494 ng/ml; AUC0-12h:
1. 13 ± 0. 494 ng/ ml; AUC0- 12h:
6.58 ± 3.18 ng·h/ml).
6. 58 ± 3. 18 ng· h/ ml).
The lower systemic exposure to timolol following AZARGA administration is not clinically relevant.
L- esponiment sistemiku aktar baxx ta ’ timolol wara l- għoti ta ’ AZARGA mhux klinikament rilevanti.
Following administration of AZARGA, mean Cmax of timolol was reached at 0.79 ± 0.45 hours.
Wara għoti ta ’ AZARGA, Cmax medja ta ’ timolol intlaħqet fi żmien 0. 79 ± 0. 45 sigħat.
Distribution Plasma protein binding of brinzolamide is moderate (about 60%).
Distribuzzjoni It- twaħħil mal- proteini fil- plażma ta ’ brinzolamide huwa moderat (madwar 60%).
Brinzolamide is sequestered in RBCs due to its high affinity binding to CA-II and to a lesser extent to CA-I.
Brinzolamide huwa sekwestrat fl- RBCs minħabba l- affinità għolja tiegħu li jeħel ma ’ CA- II u fi kwantità inqas ma ’ CA- I.
Its active N-desethyl metabolite also accumulates in RBCs where it binds primarily to CA-I.
Il- metabolit attiv N- desethyl tiegħu wkoll jakkumula fl- RBCs fejn jeħel primarjament ma ’ CA- I.
The affinity of brinzolamide and metabolite to RBC and tissue CA results in low plasma concentrations.
L - affinità ta ’ brinzolamide u tal- metaboli għal RBC u CA tat- tessut twassal għall- konċentrazzjonijiet baxxi fil- plażma.
Ocular tissue distribution data in rabbits showed that timolol can be measured in aqueous humour up to 48 hours after administration of AZARGA.
Tagħrif ta ’ distribuzzjoni fit- tessut ta ’ l- għajn fil- fniek juri li timolol jista ’ jitkejjel fl- aqueous humour sa 48 siegħa wara l- għoti ta ’ AZARGA.
At steady-state, timolol is detected in human plasma for up to 12 hours after administration of AZARGA.
Fi stat fiss, timolol jinstab fil- plażma umana sa 12- il siegħa wara l- għoti ta ’ AZARGA.
9 Metabolism The metabolic pathways for the metabolism of brinzolamide involve N-dealkylation, O-dealkylation and oxidation of its N-propyl side chain.
Metaboliżmu Ir- rotot metaboliċi għall- metaboliżmu ta ’ brinzolamide jinvolvi N- dealkylation, O- dealkylation u ossidazzjoni tal- katina N- propyl tat- tarf tiegħu.
N-desethyl brinzolamide is a major metabolite of brinzolamide formed in humans, which also binds to CA-I in the presence of brinzolamide and accumulates in RBCs.
N- desethyl brinzolamide huwa metabolit maġġuri ta ’ brinzolamide iffurmat fil- bnedmin, li jeħel ukoll ma ’ CA- I fil- preżenza ta ’ brinzolamide u jakkumula fl- RBCs.
In vitro studies show that the metabolism of brinzolamide mainly involves CYP3A4 as well as at least four other isozymes (CYP2A6, CYP2B6, CYP2C8 and CYP2C9).
Studji in vitro juru li l- metaboliżmu ta ’ brinzolamide jinvolvi prinċipalment lil CYP3A4 kif ukoll ta ’ l- inqas erba ’ isożimi oħra (CYP2A6, CYP2B6, CYP2C8 u CYP2C9).
Timolol is metabolised by two pathways.
Timolol huwa metabolizzat minn żewġ rotot.
Timolol metabolism is mediated primarily by CYP2D6.
Il- metaboliżmu ta ’ timolol huwa medjat primarjament minn CYP2D6.
Excretion Brinzolamide is eliminated primarily by renal excretion (approximately 60%).
Eskrezzjoni Brinzolamide huwa eliminat primarjament minn eskrezzjoni mill- kliewi (madwar 60%).
About 20% of the dose has been accounted for in urine as metabolite.
Madwar 20% tad- doża nstabet fl- awrina bħala metabolit.
Brinzolamide and N-desethyl-brinzolamide are the predominant components found in the urine along with trace levels (< 1%) of the N-desmethoxypropyl and O-desmethyl metabolites.
Brinzolamide u N- desethyl- brinzolamide huma l - komponenti predominanti li jinstabu fl- awrina flimkien ma ’ livelli traċċa (< 1%) tal- metaboliti N- desmethoxypropyl u O- desmethyl.
Approximately 20% of a timolol dose is excreted in the urine unchanged and the remainder excreted in urine as metabolites.
Madawar 20% tad- doża ta ’ timolol tiġi mneħħija mhux mibdula fl- awrina u l- bqija tiġi mneħħija fl- awrina bħala metaboliti.
The plasma t1/2 of timolol is 4.8 hours after administration of AZARGA.
It - t1/ 2 ta ’ timolol fil- plażma hija 4. 8 sigħat wara l- għoti ta ’ AZARGA.
Non-clinical data reveal no special hazard for humans with brinzolamide based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, and carcinogenic potential.
Informazzjoni mhux klinika, magħmula fuq studji konvenzjonali ta ’ sigurtà farmakoloġika, effett tossiku minn dożi ripetuti, effett tossiku fuq il- ġeni, u riskju ta ’ kanċer, ma turi l- ebda periklu speċjali għall- bnedmin bi brinzolamide.
Developmental toxicity studies in rabbits with oral doses of brinzolamide of up to 6 mg/kg/day (214 times the recommended daily clinical dose of 28 µg/kg/day) revealed no effect on foetal development despite significant maternal toxicity.
10 Studji dwar it- tossiċità fl- iżvilupp fil- fniek b’ dożi orali ta ’ brinzolamide sa 6 mg/ kg/ kuljum (214 darba d- doża klinika rrakkomandata kuljum ta ’ 28 µg/ kg/ kuljum) ma ’ wrew l- ebda effett fuq l- iżvilupp tal - fetu minkejja tossiċità sinifikanti għall- omm.
Similar studies in rats resulted in slightly reduced ossification of skull and sternebrae of foetuses of dams receiving brinzolamide at doses of 18 mg/kg/day (642 times the recommended daily clinical dose), but not 6 mg/kg/day.
Studji simili fil- firien wasslu għal tnaqqis żgħir fl - ossifikazzjoni tal- għadam tar- ras u ta ’ l- isternebrae tal- feti ta ’ ommijiet li rċevew brinzolamide b’ dożi ta ’ 18 mg/ kg/ kuljum (642 darba d- doża klinika rrakkomandata kuljum), iżda mhux b’ 6 mg/ kg/ kuljum.
These findings occurred at doses that caused metabolic acidosis with decreased body weight gain in dams and decreased foetal weights.
Dawn is- sejbiet seħħew b’ dożi li kkawżaw aċidożi metabolika bi tnaqqis fiż- żjieda tal- piż tal- ġisem ta ’ l- ommijiet u tnaqqis fil- piż tal- fetu.
Dose-related decreases in foetal weights were observed in pups of dams receiving brinzolamide orally ranging from a slight decrease (about 5-6%) at 2 mg/kg/day to nearly 14% at 18 mg/kg/day.
Fi friegħ ta ’ ommijiet li rċevew brinzolamide mill- ħalq, kien osservat tnaqqis relatat mad- doża fil- piż tal- fetu li varja minn tnaqqis żgħir (madwar 5- 6%) b’ doża ta ’ 2 mg/ kg/ kuljum sa kważi 14% b’ doża ta ’ 18 mg/ kg/ kuljum.
During lactation, the no adverse effect level in the offspring was 5 mg/kg/day.
Waqt it- treddigħ, il- livelli ta ’ l- ebda effett avvers kien 5 mg/ kg/ kuljum.
Non-clinical data reveal no special hazard for humans with timolol based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, and carcinogenic potential.
Informazzjoni li mhiex klinika, magħmula fuq studji konvenzjonali ta ’ sigurtà farmakoloġika, effett tossiku minn dożi ripetuti, effett tossiku fuq il- ġeni, u riskju ta ’ kanċer, ma turi l- ebda periklu speċjali għall- bnedmin b’ timolol.
Reproduction toxicity studies with timolol showed delayed foetal ossification in rats with no adverse effects on postnatal development (at 50 mg/kg/day or 3500 times the daily clinical dose of 14 μg/kg/day) and increased foetal resorptions in rabbits (at 90 mg/kg/day or 6400 times the daily clinical dose).
Studji dwar it- tossiċità fuq is- sistema riproduttiva b’ timolol urew ossifikazzjoni ttardjata tal- fetu fil- firien bl- ebda effetti avversi fuq l- iżvilupp wara t- twelid (b’ 50 mg/ kg/ kuljum jew 3500 darba d- doża klinika rrakkomandata kuljum ta ’ 14 μg / kg/ kuljum) u żjieda fl- assorbiment mill- ġdid tal- fetu fil- fniek (b’ 90 mg/ kg/ kuljum jew 6400 darba d- doża klinika ta ’ kuljum).
Benzalkonium chloride Mannitol (E421) Carbopol 974P Tyloxapol Disodium edetate Sodium chloride Hydrochloric acid and/or sodium hydroxide (for pH adjustment) Purified water
Benzalkonium chloride Mannitol (E421) Carbopol 974P Tyloxapol Disodium edetate Sodium chloride Hydrochloric acid u/ jew sodium hydroxide (għall- aġġustament tal- pH) Ilma ppurifikat
4 weeks after first opening
4 ġimgħat wara li jinfetaħ l- ewwel darba.
5 ml round opaque low density polyethylene bottles with a dispensing plug and white polypropylene screw cap (DROP-TAINER) containing 5 ml suspension.
Fliexken tal- polyethylene, tondi, opaki, ta ’ densità baxxa, ta ’ 5 ml, b’ tapp għall- għoti u b’ għatu bil - kamin abjad tal- polyethylene (DROP- TAINER) li fih 5 ml ta ’ suspensjoni.
Cartons containing 1 or 3 bottles.
11 Pakketti li fihom flixkun jew 3 fliexken.