qanastek/EMEA-V3 huggingface dataset:
Another patient accidentally received an overdose of the medicinal product (3000 mg instead of 1580 mg).
Pazjent ieħor aċċidentalment irċieva doża eċċessiva tal- prodott mediċinali (3000 mg minflok 1580 mg).
Respiratory insufficiency, which was reported in this patient, was managed by adaptation of ventilation and resolved completely.
L- insuffiċjenza respiratorja, li ġiet irrappurtata f’ dan il- pazjent, kienet ġestita b’ adattament tal- ventilazzjoni u telqet kompletament.
A more pronounced transient increase of liver enzymes without clinical symptoms was observed in the 5-ALA HCl- treated patients.
Żieda għaddiena aktar evidenti ta ’ enzimi tal- fwied kienet osservata fil- pazjenti trattati bi 5- ALA HCl.
Peak values occurred between 7 and 14 days after administration.
L- ogħla valuri seħħew bejn 7 u 14- il jum wara l- għoti.
Increased levels of amylase, total bilirubin, and leukocytes, but decreased levels of thrombocytes and erythrocytes were observed, however differences between treatment groups were not statistically significant.
Kienu osservati żidiet fil- livelli ta ’ amylase, bilirubin totali u lewkoċiti, iżda tnaqqis fil- livelli tat- tromboċiti u ta ’ l- eritroċiti, madankollu d - differenzi bejn il- gruppi ta ’ kura ma kinux statistikament sinifikanti.
Within a clinical trial, a 63-year old patient with known cardiovascular disease was accidentally given an overdose of 5-ALA HCl (3000 mg instead of 1580 mg).
Fi prova klinika, pazjent ta ’ 63 sena b’ mard kardjovaskulari magħruf aċċidentalment ingħata doża eċċessiva ta ’ 5- ALA HCl (3000 mg minflok 1580 mg).
During surgery he developed respiratory insufficiency, which was managed by adaptation of ventilation.
Waqt l- operazzjoni huwa żviluppa insuffiċjenza respiratorja, li kienet ġestita bl- adattament tal- ventilazzjoni.
After surgery the patient also displayed facial erythema.
Wara l- kirurġija l- pazjent wera wkoll eritema fil- wiċċ.
It was stated that the patient had been exposed to more light than permitted for the trial.
Intqal li l- pazjent kien ġie espost għal aktar dawl milli permess għall - prova.
Respiratory insufficiency and erythema completely resolved.
L- insuffiċjenza respiratorja u l- eritema telqu kompletament.
In the event of overdose, supportive measures should be provided as necessary, including sufficient protection from strong light sources (e. g. direct sunlight).
F’ każ ta ’ doża eċċessiva, għandhom jiġu pprovduti miżuri ta ’ sostenn kif meħtieġ, fosthom protezzjoni suffiċjenti minn sorsi ta ’ dawl qawwija (eż. dawl tax- xemx dirett).
Pharmacotherapeutic group: sensitisers used in photodynamic therapy, ATC code:
Kategorija farmakoterapewtika: sensitizzaturi użati f’ terapija fotodinamika, kodiċi ATC:
5-aminolevulinic acid (5-ALA), the active substance of Gliolan, is a natural biochemical precursor of heme that is metabolised in a series of enzymatic reactions to fluorescent porphyrins, particularly protoporphyrin IX (PPIX).
5- aminolevulinic acid (5- ALA), is- sustanza attiva ta ’ Gliolan, huwa prekursur bijokimiku naturali ta ’ heme li jiġi metabolizzat f’ sensiela ta ’ reazzjonijiet enzimatiċi għal porphyrins fluworexxenti, b’ mod partikulari l- protoporphyrin IX (PPIX).
5-ALA synthesis is regulated by an intracellular pool of free heme via a negative feedback mechanism.
Is- sinteżi tal- 5- ALA hija regolata minn għadira intraċellulari ta ’ heme liberu permezz ta ’ mekkaniżmu ta ’ rispons negattiv.
Systemic administration of 5-ALA results in an overload of the cellular porphyrin metabolism and accumulation of PPIX in various epithelia and cancer tissues.
L- għoti sistemiku ta ’ 5- ALA jirriżulta f’ tagħbija eċċessiva tal- metaboliżmu ċellulari tal- porphyrin u l - akkumulazzjoni ta ’ PPIX f’ diversi epitelji u tessuti tal- kanċer.
Malignant glioma tissue (WHO-grade III and IV, e. g. glioblastoma multiforme, gliosarcoma or anaplastic astrocytoma) has also been demonstrated to synthesise and accumulate porphyrins in response to 5-ALA administration.
It- tessut ta ’ glijomi malinni (WHO- grad III u IV, eż. glioblastoma multiformi, gliosarcoma jew astrocytoma anaplastika) ġie muri li jissintetizza u jakkumula porphyrins b’ reazzjoni għall- għoti ta ’ 5- ALA.
The concentration of PPIX is significantly lower in white matter than in cortex and tumour.
Il- konċentrazzjoni ta ’ PPIX hija sinifikattivament aktar baxxa fil- materja bajda milli fil- kortiċi u t- tumur.
Tissue surrounding the tumour and normal brain may also be affected.
It- tessut li jdawwar it - tumur u l- moħħ normali jista ’ jiġi wkoll affettwat.
However, 5-ALA induced PPIX formation is significantly higher in malignant tissue than in normal brain.
Madankollu, il- formazzjoni ta ’ PPIX indotta mill- 5 - ALA hija sinifikattivament ogħla fit- tessut malinn milli fil- moħħ normali.
In contrast, in low-grade tumours (WHO-grade I and II, e. g. medulloblastoma, oligodendroglioma) no fluorescence could be observed after application of the active substance.
B’ kuntrast, fit- tumuri ta ’ grad baxx (WHO- grad I u II, eż. medulloblastoma, oligodendroglijoma) ma setgħet tiġi osservata l- ebda fluworexxenza wara l- applikazzjoni tas- sustanza attiva.
Brain metastases revealed inconsistent or no fluorescence.
Il- metastasi ċerebrali żvelaw fluworexxenza inkonsistenti jew l- ebda fluworexxenza.
The phenomenon of PPIX accumulation in WHO grade III and IV malignant gliomas may be explained by higher 5-ALA uptake into the tumour tissue or an altered pattern of expression or activity of enzymes (e. g.
5 Il- fenomenu ta ’ l- akkumulazzjoni ta ’ PPIX fi glijomi malinni ta ’ WHO grad III u IV jista ’ jiġi spjegat mit- teħid akbar ta ’ 5- ALA fit- tessut ta ’ tumur jew mudell mibdul ta ’ l- espressjoni jew attività ta ’ l- enzimi (eż. ferrochelatase) involuti fil- bijosinteżi ta ’ l- emoglobina fiċ- ċelloli ta ’ tumur.
Explanations for higher 5-ALA uptake include a disrupted blood-brain barrier, increased neo-vascularisation, and the overexpression of membrane transporters in glioma tissue.
L- ispjegazzjonijiet għat- teħid akbar ta ’ 5- ALA jinkludu barriera sfaxxata bejn il- moħħ u d- demm, żieda fin- neovaskularizzazzjoni, u l- espressjoni eċċessiva ta ’ trasportaturi tal- membrana fit- tessut ta ’ glijoma.
After excitation with blue light (λ =400-410 nm), PPIX is strongly fluorescent (peak at λ =635 nm) and can be visualised after appropriate modifications to a standard neurosurgical microscope.
Wara stimulazzjoni b’ dawl blu (λ=400- 410 nm), il- PPIX ikun fluworexxenti ħafna (l- ogħla punt f’ λ=635 nm) u jkun jista ’ jidher wara li jsiru modifikazzjonijiet xierqa għal mikroskopju newroloġiku standard.
5 Fluorescence emission can be classified as intense (solid) red fluorescence (corresponds to vital, solid tumour tissue) and vague pink fluorescence (corresponds to infiltrating tumour cells), whereas normal brain tissue lacking enhanced PPIX levels reflects the violet-blue light and appears blue.
L- emissjoni ta ’ fluworexxenza tista ’ tiġi kklassifikata bħala fluworexxenza ħamra intensa (solida) (li tikkorrispondi ma ’ tessut ta ’ tumur solidu, vitali) u fluworexxenza roża mhux ċara (li tikkorrispondi ma ’ ċelloli ta ’ tumur infiltranti), filwaqt li t- tessut tal- moħħ normali nieqes mil- livelli akbar ta ’ PPIX jirrifletti d- dawl ultra- vjola u jidher blu.
In a phase I/ II-trial including 21 patients, a dose-efficacy relationship between the dose levels and the extent and quality of fluorescence in the tumour core was detected:
Fi prova klinika ta ’ fażi I/ II li kienet tinkludi 21 pazjent, kienet rilevata relazzjoni ta ’ l- effikaċja tad - doża bejn il- livelli tad- doża u l- firxa u l- kwalità tal- fluworexxenza fil- qalba tat- tumur:
Higher doses of 5-ALA HCl enhanced the fluorescence quality and the fluorescence extent of the tumour core compared to demarcation of the tumour core under standard white illumination in a monotone, non-falling fashion.
Dożi akbar ta ’ 5- ALA HCl tejbu l- kwalità tal- fluworexxenza u l- miżura ta ’ fluworexxenza tal- qalba tat- tumur meta mqabbel mad- demarkazzjoni tal- qalba tat- tumur taħt dawl abjad standard b’ ton wieħed, non- falling.
The highest dose (20 mg/ kg body weight) was determined to be the most efficient.
L- ogħla doża (20 mg/ kilogramm ta ’ piż tal- ġisem) kienet stabbilita li hija l- aktar effiċjenti.
A positive predictive value of tissue fluorescence of 84.8% (90% CI:
Instab valur ta ’ previżjoni pożittiva ta ’ fluworexxenza tat- tessut ta ’ 84. 8% (90% CI:
70.7 %-93.8%) was found.
70. 7% - 93. 8%).
This value was defined as the percentage of patients with positive tumour cell identification in all biopsies taken from areas of weak and strong fluorescence.
Dan il- valur kien definit bħala l- perċentwal ta ’ pazjenti b’ identifikazzjoni pożittiva ta ’ ċelloli ta ’ tumur fil- bijopsiji kollha meħuda minn żoni ta ’ fluworexxenza dgħajfa u qawwija.
The positive predictive value of strong fluorescence was higher (100.0%; 90% CI:
Il- valur ta ’ previżjoni pożittiv tal- fluworexxenza qawwija kien ogħla (100. 0%; 90% CI:
91.1 %-100.0%) than of weak fluorescence (83.3%; 90% CI:
91. 1% - 100. 0%) minn tal - fluworexxenza dgħajfa (83. 3%; 90% CI:
68.1 %-93.2%).
68. 1% - 93. 2%).
Results were based on a phase-II trial including 33 patients receiving 5- ALA HCl in a dose of 20 mg/ kg body weight.
Ir- riżultati kienu bbażati fuq prova klinika ta ’ fażi II li kienet tinkludi 33 pazjent li rċevew 5- ALA HCl f’ doża ta ’ 20 mg/ kilogramm ta ’ piż tal- ġisem.
The resulting fluorescence was used as an intraoperative marker for malignant glioma tissue with the aim of improving the surgical resection of these tumours.
Il- fluworexxenza li rriżultat kienet użata bħala marker waqt l- operazzjoni għal tessut ta ’ glijomi malinni bil- għan li tittejjeb ir- risezzjoni kirurġika ta ’ dawn it- tumuri.
In a phase-III trial with 349 patients with suspected malignant glioma amenable to complete resection of contrast-enhancing tumour were randomised to fluorescence-guided resection after administration of 20 mg/ kg body weight 5-ALA HCl or conventional resection under white light.
Fi prova klinika ta ’ fażi III bi 349 pazjent suspettati bi glijoma malinna li toqgħod għal tneħħija kompleta ta ’ tumur li jkabbar il- kuntrast, il- pazjenti ntgħażlu b’ mod każwali għal tneħħija ggwidata bil- fluworexxenza wara l- għoti ta ’ 20 mg/ kilogramm ta ’ piż tal- ġisem 5- ALA HCl jew tneħħija konvenzjonali taħt dawl abjad.
Contrast-enhancing tumour was resected in 64% of patients in the experimental group compared to 38% in the control- group (p < 0.001).
Tumur li jkabbar il- kuntrast ġie mneħħi f’ 64% tal- pazjenti fil- grupp sperimentali meta mqabbel mat- 38% tal- grupp ta ’ kontroll (p < 0. 001).
At the visit six months after tumour resection, 20.5% of 5-ALA-treated-patients and 11% of patients who underwent standard surgery were alive at the six-month visit without progression.
Fil- viżta sitt xhur wara r- risezzjoni tat- tumur, 20. 5% tal- pazjenti trattati bil- 5- ALA u 11% tal- pazjenti li għamlu operazzjoni standard kienu ħajjin fil- viżta tas- sitt xahar mingħajr progressjoni.
The difference was statistically significant using the chi-square test (p=0.015).
Id- differenza kienet statistikament sinifikanti bl- użu tat- test chi- square (p=0. 015).
No significant increase in overall survival has been observed in this study, however, the trial was not powered to detect such a difference.
Ma kienet osservata l- ebda żieda sinifikanti fis- sopravivenza globali f’ dan l- istudju, madankollu, il - prova ma kinetx potenzjata biex issib tali differenza.
General characteristics This medicinal product shows good solubility in aqueous solutions.
Karatteristiċi ġenerali Dan il- prodott mediċinali juri solubilità tajba f’ soluzzjonijiet akweji.
After ingestion, 5-ALA itself is not fluorescent but is taken up by tumour tissue (see section 5.1) and is intracellularily metabolised to fluorescent porphyrins, predominantly protoporphyrin IX (PPIX).
Wara l- inġestjoni, 5- ALA nnifsu ma jkunx fluworexxenti iżda jiġi assorbit mit- tessut tat- tumur (ara sezzjoni 5. 1) u jiġi metabolizzat b’ mod intraċellulari għal porphyrins fluworexxenti, l- aktar protoporphyrin IX (PPIX).
Absorption 5-ALA HCl as drinking solution is rapidly and completely absorbed and peak plasma levels of 5-ALA are reached 0.5– 2 hours after oral administration of 20 mg/ kg body weight.
Assorbiment 5- ALA HCl bħala soluzzjoni li tinxtorob tiġi assorbita malajr u kompletament u l- ogħla livelli fil - plażma ta ’ 5- ALA jintlaħqu 0. 5– 2 sigħat wara l- għoti b’ mod orali ta ’ 20 mg/ kilogramm ta ’ piż tal - ġisem.
Plasma levels return to baseline values 24 hours after administration of an oral dose of 20 mg/ kg body weight.
Il- livelli fil- plażma jirritornaw għall- valuri tal- linja bażi 24 siegħa wara l- għoti ta ’ doża orali ta ’ 20 mg/ kilogramm ta ’ piż tal- ġisem.
The influence of food has not been investigated because this medicinal product is generally given on empty stomach prior to induction of anaesthesia.
L- effett ta ’ l- ikel ma ġiex investigat minħabba li dan il- prodott mediċinali ġeneralment jingħata fuq stonku vojt qabel l- induzzjoni ta ’ l- anestesija.
Distribution and Biotransformation 5-ALA is preferentially taken up by the liver, kidney, endothelials and skin as well as by malignant gliomas (WHO grade III and IV) and metabolised to fluorescent PPIX.
6 Distribuzzjoni u Bijotrasformazzjoni 5- ALA huwa assorbit b’ mod preferenzjali mill- fwied, il- kliewi, l- endotelji u l- ġilda kif ukoll minn glijomi malinni (WHO grad III u IV) u jiġi metabolizzat għal PPIX fluworexxenti.
Four hours after oral administration of 20 mg/ kg body weight 5-ALA HCl, the maximum PPIX plasma level is reached.
Erba ’ sigħat wara l- għoti orali ta ’ 20 mg/ kilogramm ta ’ piż tal- ġisem 5- ALA HCl, il- livell massimu ta ’ PPIX fil- plażma jintlaħaq.
PPIX plasma levels rapidly decline during the subsequent 20 hours and are not detectable anymore 48 hours after administration.
Il- livelli ta ’ PPIX fil- plażma jonqsu malajr matul l- 20 siegħa suċċessivi u ma tistax tidditektjhom 48 siegħa wara l- għoti.
At the recommended oral dose of 20 mg/ kg body weight, tumour to normal brain fluorescence ratios are usually high and offer lucid contrast for visual perception of tumour tissue under violet-blue light for at least 9 hours.
Bid- doża orali rakkomandata ta ’ 20 mg/ kilogramm ta ’ piż tal - ġisem, il- proporzjonijiet ta ’ fluworexxenza tat- tumur għall- moħħ normali huma ġeneralment għoljin u joffru kuntrast luċidu għall- perċezzjoni viżwali tat- tessut ta ’ tumur taħt dawl ultra- vjola għal mill - anqas 9 sigħat.
6 Besides tumour tissue, faint fluorescence of the choroid plexus was reported.
Minbarra t- tessut ta ’ tumur, kienet irrappurtata fluworexxenza dgħajfa tal- choroid plexus.
5-ALA is also taken up and metabolised to PPIX by other tissues, e. g. liver, kidneys or skin (see section 4.4).
5- ALA jiġi wkoll assorbit u metabolizzat għal PPIX minn tessuti oħra, eż. il- fwied, il- kliewi jew il- ġilda (ara sezzjoni 4. 4).
Plasma protein binding of 5-ALA is unknown.
Mhux magħruf it- twaħħil ta ’ 5- ALA mal- proteini tal- plażma.
Elimination 5-ALA is eliminated quickly with a terminal half-life of 1-3 hours.
Eliminazzjoni 5- ALA huwa eliminat malajr b’ half- life terminali ta ’ 1- 3 sigħat.
Approximately 30% of an orally administered dose of 20 mg/ kg body weight are excreted unchanged in urine within 12 hours.
Madwar 30% ta ’ doża ta ’ 20 mg/ kilogramm ta ’ piż tal- ġisem mogħtija b’ mod orali jitneħħew mhux mibdula fl- awrina fi żmien 12- il siegħa.
Linearity/ non-linearity There is dose proportionality between AUC0-inf. of 5-ALA values and different oral doses of this medicinal product.
Lineari/ mhux lineari Hemm proporzjonalità tad- doża bejn l- AUC0- inf. tal- valuri ta ’ 5- ALA u dożi orali differenti ta ’ dan il - prodott mediċinali.
Patients with renal or hepatic impairment Pharmacokinetics of 5-ALA in patients with renal or liver impairment has not been investigated.
Pazjenti b’ indeboliment tal- kliewi jew tal- fwied Il- farmakokinetika ta ’ 5- ALA f’ pazjenti b’ indeboliment tal- kliewi jew tal- fwied ma ġietx investigata.
Standard safety pharmacology experiments were performed under light protection in the mouse, rat and dog.
Esperimenti standard ta ’ sigurtà farmakoloġika ġew imwettqa taħt protezzjoni mid- dawl fil- ġurdien, il - far u l- kelb.
5-ALA HCl administration does not influence the function of the gastro-intestinal and central nervous systems.
L- għoti ta ’ 5- ALA HCl ma jaffettwax il- funzjoni tas- sistema gastro- intestinali u tas - sistema nervuża ċentrali.
A slight increase in saluresis cannot be excluded.
Żieda żgħira fis- saluresis ma tistax tiġi eskluża.
Single administration of high doses of 5-ALA HCl to mice or rats leads to unspecific findings of intolerance without macroscopic abnormalities or signs of delayed toxicity.
L- għoti ta ’ darba ta ’ dożi għoljin ta ’ 5- ALA HCl lil ġrieden jew firien iwassal għal sejbiet mhux speċifikati ta ’ intolleranza mingħajr abnormalitajiet makroskopiċi jew sinjali ta ’ tossiċità ttardjata.
Repeat-dose toxicity studies performed in rats and dogs demonstrate dose-dependent adverse reactions affecting changes in bile duct histology (non-reversible within a 14 day recovery period), transient increase in transaminases, LDH, total bilirubin, total cholesterin, creatinine, urea and vomiting (only in dogs).
Studji tat- tossiċità minn dożi ripetuti li twettqu fuq il- firien u l- klieb juru reazzjonijiet avversi dipendenti fuq id- doża li jaffettwaw bidliet fl- istoloġija tal- kanal tal- bile (mhux riversibbli sa perjodu ta ’ rkupru ta ’ 14- il jum), żieda għaddiena fit- transaminases, LDH, bilirubin totali, cholesterin totali, kreatinina, urea u rimettar (fil- klieb biss).
Signs of systemic toxicity (cardiovascular and respiratory parameters) occurred at higher doses in the anaesthetised dog: at 45 mg/ kg body weight intravenously a slight decrease in peripheral arterial blood pressure and systolic left ventricular pressure was recorded.
Is- sinjali ta ’ tossiċità sistemika (parametri kardjovaskulari u respiratorji) seħħew b’ dożi aktar gholjin fil- kelb anestetizzat: b’ 45 mg/ kilogramm ta ’ piż tal- ġisem minn ġol- vina ġie rreġistrat tnaqqis żgħir fil- pressjoni tad- demm ta ’ l- arterji periferali u l- pressjoni sistolika fil- ventrikolu tax- xellug.
Five minutes after administration, the baseline values had been reached again.
Ħames minuti wara l- għoti, il- valuri tal- linja bażi kienu reġgħu ntlaħqu mill- ġdid.
The cardiovascular effects seen are considered to be related to the intravenous route of administration.
L- effetti kardjovaskulari li dehru huma meqjusa bħala relatati ma ’ l- għoti minn ġol - vina.
Phototoxicity observed after 5-ALA HCl treatment in vitro and in vivo is obviously closely related to dose- and time- dependent induction of PPIX synthesis in the irradiated cells or tissues.
Il- fototossiċità osservata wara trattament bil- 5- ALA HCl in vitro u in vivo hija ovvjament marbuta mill- qrib ma ’ l- induzzjoni dipendenti fuq id- doża u l- ħin tas- sinteżi tal- PPIX fiċ- ċelloli jew it- tessuti mdawla.
Destruction of sebaceous cells, focal epidermal necrosis with a transient acute inflammation and diffuse reactive changes in the keratinocytes as well as transient secondary oedema and inflammation of dermis are observed.
Qerda taċ- ċelloli sebaċi, nekrosi epidermika fokali b’ infjammazzjoni akuta li tgħaddi u bidliet reattivi mxerrda fil- keratinoċiti kif ukoll edema sekondarja li tgħaddi u infjammazzjoni tad - dermis huma osservati.
Light exposed skin recovered completely except for a persistent reduction in the number of hair follicles.
Il- ġilda esposta għad- dawl irkuprat kompletament għajr għal tnaqqis persistenti fl- għadd ta ’ follikuli tax- xagħar.
Accordingly, general light protective measures of eyes and skin are recommended for at least 24 hours after administration of this medicinal product.
Għalhekk, huma rakkomandati miżuri ġenerali għall - protezzjoni ta ’ l- għajnejn u l- ġilda mid- dawl għal mill- anqas 24 siegħa wara l- għoti ta ’ dan il- prodott mediċinali.
Although pivotal studies on the reproductive and developmental behaviour of 5-ALA have not been performed, it can be concluded that 5-ALA induced porphyrin synthesis may lead to embryotoxic activity in mouse, rat and chick embryos only under the condition of direct concomitant light exposure.
Għalkemm ma sarux studji pivotali dwar il- komportament riproduttiv u fuq l- iżvilupp ta ’ 5- ALA, wieħed jista ’ jikkonkludi li s- sinteżi ta ’ porphyrin indotta mill- 5- ALA tista ’ twassal għal attività embrijutossika fil- ġurdien, il- far u l- embriji tal- fellus biss fil- kundizzjoni ta ’ esponiment simultanju dirett għad- dawl.
This medicinal product should, therefore, not be administered to pregnant women.
It- trattament
Excessive single dose treatment of rats with 5-ALA reversibly impaired male fertility for two weeks after dosing.
7 b’ doża waħda eċċessiva ta ’ firien b’ 5- ALA indebolixxa b’ mod riversibbli l- fertilità tar- raġel għal ġimagħtejn wara d- dożaġġ.
The majority of genotoxicity studies performed in the dark do not reveal a genotoxic potential of 5-ALA.
Il- maġġoranza ta ’ l- istudji dwar l- effett ġenotossiku li twettqu fid- dlam ma jurux potenzjal ġenotossiku ta ’ 5- ALA.
The compound potentially induces photogenotoxicity after subsequent irradiation or light exposure which is obviously related to the induction of porphyrin synthesis.
Il- kompost potenzjalment jikkawża fotoġenotossiċità wara l- irradjazzjoni jew l- esponiment sussegwenti għad- dawl li jkun ovvjament relatat ma ’ l- induzzjoni tas- sinteżi tal - porphyrin.
Long-term in vivo carcinogenicity studies have not been conducted.
Ma sarux studji in vivo fuq perjodu fit- tul dwar ir- riskju ta ’ kanċer.
However, considering the therapeutic indication, a single oral treatment with 5-ALA HCl might not be related to any serious potential carcinogenic risk.
Madankollu, meta titqies l- indikazzjoni terapewtika, trattament orali wieħed b’ 5- ALA HCl jista ’ ma jkunx relatat ma ’ xi riskju karċinoġeniku potenzjali serju.
The reconstituted solution is physically-chemically stable for 24 hours at 25ºC.
Is- soluzzjoni rikostitwita hija fiżikament u kimikament stabbli għal 24 siegħa f’ 25ºC.
For storage conditions of the reconstituted product see section 6.3.
Għall- kundizzjonijiet ta ’ ħażna tal- prodott rikostitwit ara sezzjoni 6. 3.
Colourless type II glass vial, with rubber stopper.
Kunjett tal- ħġieġ ta ’ tip II bla kulur, b’ tapp tal- lastku.
Pack sizes:
Daqsijiet tal- pakkett:
1, 2 and 10 vials of powder.
1, 2 u 10 kunjetti ta ’ trab.
Not all pack sizes may be marketed.
Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għal- skop kummerċjali.
The oral solution is prepared by dissolving the amount of powder of one vial in 50 ml of tap water.
Is- soluzzjoni orali tiġi ppreparata billi jinħall l- ammont tat- trab ta ’ kunjett wieħed f’ 50 ml ta ’ ilma.
The reconstituted solution is a clear and colourless to slightly yellowish fluid.
Is - soluzzjoni rikostitwita hija fluwidu ċar u mingħajr lewn għal daqsxejn fl- isfar.
Single use vial – discard any content remaining after first use.
Kunjett jintuża darba biss – armi kwalunkwe kontenut li jifdal wara l- ewwel użu.
medac Gesellschaft für klinische Spezialpräparate mbH Fehlandtstraße 3 D-20354 Hamburg, Germany Tel. + 49 4103 8006 0 Fax: +49 4103 8006 100
medac Gesellschaft für klinische Spezialpräparate mbH Fehlandtstraße 3 D- 20354 Hamburg, Il- Ġermanja Tel. + 49 4103 8006 0 Fax: +49 4103 8006 100
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE
DATA TA ’ L- EWWEL AWTORIZZAZZJONI/ TIĠDID TA ’ L- AWTORIZZAZZJONI
9 A.
9 ANNESS II
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE
KUNDIZZJONIJIET TA 'L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS - SUQ
Name and address of the manufacturer responsible for batch release
DETENTUR TA ’ L- AWTORIZZAZZJONI TAL- MANIFATTURA RESPONSABBLI GĦALL- ĦRUĠ TAL- LOTT
medac Gesellschaft für klinische Spezialpräparate mbH Theaterstraße 6 D-22880 Wedel Germany
medac Gesellschaft für klinische Spezialpräparate mbH Theaterstraße 6 D- 22880 Wedel Il- Ġermanja
The Marketing Authorisation Holder in agreement with the competent authorities in the Member States shall implement, prior to launch:
Id- Detentur ta ’ l- Awtorizzazzjoni Għat- Tqegħid fis- Suq bi ftehim ma ’ l- awtoritajiet kompetenti fl- Istati Membri għandu jimplimenta, qabel it- tnedija:
− A training course for neurosurgeons which is aimed at risk minimisation and to support safe and effective use for the product.
− Kors ta ’ taħriġ għal newrokirurgi li huwa mmirat għall- minimizzazzjoni tar- riskji u biex jiġi appoġġjat l- użu sikur u effettiv għall- prodott.
a) Theory and core principles of Gliolan-fluorescence-guided surgery and malignant glioma resection, including methods of eloquent sites identification; b) On-site instructions on the use of the fluorescence-microscope, including pitfalls and recognition of problems; c) Differentiation of fluorescence intensity, maintaining safety distances from eloquent areas, etc. d) The practice of Gliolan-fluorescence-guided surgery (including participation in at least one cases using Gliolan-fluorescence-guided surgery in the operating room with on-site instructions on the use of the microscope or demonstration of a fluorescence-guided resection by video); e) The current understanding of the benefits and risks of cytoreductive surgery in the management of patients with malignant gliomas; f) The theoretical base for porphyrin accumulation in malignant gliomas; g) The technical principles behind fluorescence-guided resections using Gliolan; h) How to identify suitable candidates for fluorescence-guided resections using Gliolan; i) How to apply Gliolan in the correct dosage and timing regimen, and to understand the importance of concurrent corticosteroids; j) How to identify patients at risk for neurological deficits using fluorescence-guided resections with Gliolan with special focus on aphasias and other critical focal deficits;
a) It- teorija u l- prinċipji ewlenin tal- kirurġija ggwidata bil- fluworexxenza ta ’ Gliolan u risezzjoni ta ’ glijoma malinna, inkluż metodi ta ’ identifikazzjoni ta ’ siti elokwenti; b) Struzzjonijiet fuq is- sit dwar l- użu tal- mikroskopju tal- fluworexxenza, inkluż il- perikli u l- għarfien tal- problemi; c) Id- differenzazzjoni ta ’ l- intensità tal- fluworexxenza, filwaqt li jinżammu d- distanzi ta ’ sigurtà minn żoni elokwenti, eċċ. d) Il- prattika tal- kirurġija ggwidata bil- fluworexxenza ta ’ Gliolan (inkluż il- parteċipazzjoni f’ għallinqas każ wieħed ta ’ użu ta ’ kirurġija ggwidata bil- fluworexxenza ta ’ Gliolan fis- sala ta ’ l- operazzjonijiet bi struzzjonijiet fuq is- sit fuq l- użu ta ’ mikroskopju jew demostrazzjoni ta ’ risezzjoni ggwidata bil- fluworexxenza permezz ta ’ vidjo); e) L- għarfien preżenti fuq il- benefiċċji u r- riskji ta ’ kirurġija ċitoreduttiva fil - maniġġar ta ’ pazjenti bi glijomi malinni; f) Il- bażi teoretika għall- akkumulazzjoni ta ’ porphyrin fi glijomi malinni; g) Il- prinċipji tekniċi wara r- risezzjonijiet iggwidati bil- fluworexxenza li jużaw Gliolan; h) Kif għandhom jiġu identifikati kandidati xierqa għar- risezzjonijiet iggwidati bil - fluworexxenza li jużaw Gliolan; i) Kif għandu jiġi applikat Gliolan fid- dożaġġ korrett u reġimen ta ’ żmien, u kif għandha tiġi mifhuma l- importanza ta ’ kortikosterojdi li jkunu preżenti fl- istess ħin;
10 k) Techniques for intraoperative risk reduction (microsurgical technique, neurophysiological monitoring, choice of approach) and how to implement them; l) How to identify fluorescence for resection through using the operating microscope in a hands- on setting in the operating room; m) The benefits and risks of fluorescence-guided resections using Gliolan;
11 j) Kif għandhom jiġu identifikati pazjenti b’ riskju ta ’ defiċit newroloġiku li jużaw risezzjonijiet iggwidati bil- fluworexxenza li jużaw Gliolan b’ fokus speċjali fuq afasji u defiċit fokali kritiku ieħor; k) Tekniki għat- tnaqqis inter- operattiv tar- riskji (teknika tal- mikro- kirurġija, monitoraġġ newrofiżjoloġiku, għażla tal- metodu) u kif dawn għandhom jiġu implimentati; l) Kif għandha tiġi identifikata l- fluworexxenza għar- risezzjoni permezz ta ’ l- użu ta ’ mikroskopju ta ’ tħaddim f’ ambjent prattiku fis- sala ta ’ l- operazzjonijiet; m) Il- benefiċċji u r- riskji ta ’ risezzjonijiet iggwidati bil- fluworexxenza li jużaw Gliolan;
- Sufficient case load (at least 10 patients per year) of malignant gliomas (WHO grade III and
- Ammont adegwat ta ’ pazjenti (għallinqas 10 kull sena) ta ’ glijomi malinni (grad III u IV ta ’
IV);
WHO);
- Neurophysiological monitoring techniques for surgery in eloquent brain regions.
- Tekniki ta ’ monitoraġġ newrofiżjoloġiċi għall- kirurġija f’ oqsma tal- moħħ elokwenti.
Pharmacovigilance system The MAH must ensure that the system of pharmacovigilance, as described in version 2 presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and whilst the product is on the market.
Sistema ta ’ farmakoviġilanza Id- detentur ta ’ l- awtorizzazzjoni għat- tqegħid fis- suq għandu jiżgura li s- sistema ta ’ farmakoviġilanza, kif deskritta fil- verżjoni 2 ippreżentata fil- Modulu 1. 8. 1. ta ’ l- Applikazzjoni ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq, tkun fis- seħħ u li din tkun qegħda taħdem qabel u waqt li l- prodott ikun fis- suq.
Risk Management Plan The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan, as agreed in version 5 of the Risk Management Plan (RMP) presented in Module 1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP agreed by the CHMP.
Pjan ta ’ Ġestjoni tar- Riskju Id- detentur ta ’ l- awtorizzazzjoni għat- tqegħid fis- suq jimpenja ruħu li jwettaq l- istudji u l- attivitajiet ta ’ farmakoviġilanza mogħtija fid- dettall fil- Pjan ta ’ Farmakoviġilanza, kif miftiehem fil- verżjoni 5 tal- Pjan ta ’ Ġestjoni tar- Riskji (RMP) ippreżentat fil- Modulu 1. 8. 2. ta ’ l- Applikazzjoni ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq u kwalunkwe aġġornament sussegwenti tal- RMP li jkun qabel fuqu l- CHMP.
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the updated RMP should be submitted at the same time as the next Periodic Safety Update Report (PSUR).
Skond il- Linja gwida tal- CHMP dwar is- Sistemi ta ’ Ġestjoni tar- Riskji għal prodotti mediċinali għal użu mill- bniedem, l- RMP aġġornat għandu jiġi ppreżentat fl- istess ħin tar- Rapport Perjodiku ta ’ Aġġornament dwar is- Sigurtà (PSUR).
In addition, an updated RMP should be submitted • When new information is received that may impact on the current Safety Specification, Pharmacovigilance Plan or risk minimisation activities • Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being reached • At the request of the EMEA
Barra minn hekk, għandu jiġi ppreżentat RMP aġġornat • Meta tiġi rċevuta informazzjoni ġdida li jista ’ jkollha impatt fuq l- Ispeċifikazzjoni tas- Sigurtà, il- Pjan ta ’ Farmakoviġilanza jew attivitajiet ta ’ minimizzazzjoni tar- riskji kurrenti • Fi żmien 60 jum minn meta tkun intlaħqet mira importanti (farmakoviġilanza jew minimizzazzjoni tar- riskji) • Fuq it- talba ta ’ l- EMEA
Outer carton/ Vial label
Kartuna ta ’ barra/ Tikketta tal- kunjett
Gliolan 30 mg/ ml powder for oral solution 5-aminolevulinic acid hydrochloride
Gliolan 30 mg/ ml trab għal soluzzjoni orali 5- aminolevulinic acid hydrochloride
One ml of reconstituted solution contains 23.4 mg of 5-aminolevulinic acid, corresponding to 30 mg 5-aminolevulinic acid hydrochloride (5-ALA HCl).
1 ml tas- soluzzjoni rikostitwita fih 23. 4 mg ta ’ 5- aminolevulinic acid, li jikkorrispondu għal 30 mg ta ’ 5- aminolevulinic acid hydrochloride (5- ALA HCl).
Powder for oral solution
Trab għal soluzzjoni orali
Vial only:
Kunjett biss:
1.5 g 5-aminolevulinic acid hydrochloride
1. 5 g 5- aminolevulinic acid hydrochloride
Outer carton only:
Kartuna ta ’ barra biss:
1 vial 2 vials 10 vials
1 kunjett 2 kunjetti 10 kunjetti
For oral use after reconstitution.
Għal użu orali wara rikostituzzjoni.
14 EXP:
15 JIS:
medac Gesellschaft für klinische Spezialpräparate mbH Fehlandtstraße 3 D-20354 Hamburg Germany
medac Gesellschaft für klinische Spezialpräparate mbH Fehlandtstraße 3 D- 20354 Hamburg Il- Ġermanja
What Gliolan is and what it is used for 2.
X’ inhu Gliolan u għalxiex jintuża 2.
Before you take Gliolan 3.
Qabel ma tieħu Gliolan 3.
How to take Gliolan 4.
Kif għandek tieħu Gliolan 4.
How to store Gliolan 6.
Kif taħżen Gliolan 6.
WHAT GLIOLAN IS AND WHAT IT IS USED FOR
X’ INHU GLIOLAN U GĦALXIEX JINTUŻA
Gliolan is used for the visualisation of certain brain tumours (called malignant glioma) during tumour surgery.
Gliolan jintuża għall- viżwalizzazzjoni ta ’ ċerti tumuri tal- moħħ (imsejħa glijomi malinni) matul kirurġija tat- tumuri.
Gliolan contains a substance called aminolevulinic acid hydrochloride (5-ALA).
Gliolan fih sustanza imsejħa aminolevulinic acid hydrochloride (5- ALA).
5-ALA is taken up more by tumour cells where it is transformed into another similar substance.
5- ALA jittieħed aktar minn ċelloli ta ’ tumuri fejn imbagħad jiġi ttrasformat f’ sustanza simili oħra.
If then the tumour is put under blue light exposure this new substance emits a red-violet light which helps to see better what normal tissue is and what tumour tissue is.
Jekk imbagħad it- tumur jitpoġġa taħt espożizzjoni ta ’ dawl blu, din is- sustanza ġdida temetti dawl aħmar- vjola li jgħin biex wieħed jara aħjar liema huwa t- tessut normali u liema huwa t- tessut b’ tumur.
This helps the surgeon to remove the tumour more completely while sparing healthy tissue.
Dan jgħin lill- kirurgu jneħħi t- tumur għal kollox filwaqt li jibża għat- tessut b’ saħħtu.
BEFORE YOU TAKE GLIOLAN
QABEL MA TIEĦU GLIOLAN
Do not take Gliolan
Tiħux Gliolan
- If you are allergic (hypersensitive) to 5-aminolevulinic acid hydrochloride or porphyrins.
- Jekk int allerġiku/ a (tbati minn sensittività eċċessiva) għal 5- aminolevulinic acid jew porphyrins
- In case of known or suspected acute or chronic types of porphyria (i. e. inherited or acquired
- Jekk huwa magħruf jew hemm suspett li għandek tipi akuti jew kroniċi ta ’ porfirja (jiġifieri
disorders of certain enzymes in the synthesis pathway of red blood pigment).
disturbi li jintirtu jew jiġu akkwiżiti ta ’ ċerti enzimi fil- passaġġ tas- sinteżi tal- pigment tad- demm aħmar).
- In case of known or suspected pregnancy.
- Jekk taf jew tissuspetta li inti tqila.
Take special care with Gliolan After administration of this medicine, avoid that your eyes and skin are under strong light (for example operating illumination, direct sunlight or brightly focused indoor light) for 24 hours.
Oqgħod attent ħafna bi Gliolan Wara l- għoti ta ’ din il- mediċina, evita li għajnejk u l- ġilda tiegħek ikunu esposti għal dawk qawwi (eż. mixegħla ta ’ l- operazzjoni, dawl tax- xemx dirett jew dawl ta ’ ġewwa ffukat qawwi ħafna) għal 24 siegħa.
If you have a heart disease or had heart disease in the past, you should tell your doctor.
Jekk għandek xi mard tal- qalb jew jekk kellek xi mard tal- qalb, inti għandek tinforma lit- tabib tiegħek.
In this case, this medicine should be used with caution because the blood pressure may be decreased.
F’ dan il- każ, din il- mediċina għandha tintuża b’ kawtela minħabba li l- pressjoni tad- demm tista ’ titbaxxa.
Patients with renal or hepatic impairment No studies have been performed in patients with poor liver or kidney function.
Pazjenti b’ indeboliment tal- kliewi jew tal- fwied Ma sar ebda studju fuq pazjenti b’ funzjoni indebolita tal- fwied jew tal- kliewi.
Therefore, this medicine should be used with caution in such patients.
Għalhekk, din il - mediċina għandha tintuża b’ kawtela f’ dawn il- pazjenti.
Children and adolescents (< 18 years) There is no experience with Gliolan in children.
18 Tfal u adoloxxenti (< 18 sena) M’ hemm ebda esperjenza b’ Gliolan fuq it- tfal.
Therefore this medicine is not recommended in this age group.
Għalhekk, din il- mediċina m’ hijiex irrikmandata f’ dan il- grupp t’ età.
17 Elderly patients There are no special instructions for use in elderly patients with normal organ function.
Pazjenti anzjani M’ hemm ebda struzzjonijiet speċjali għal użu f’ pazjenti anzjani b’ funzjoni ta ’ l- organi normali.
Taking other medicines Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, particularly medicines that may cause skin problems when the skin comes under strong light (for example some types of medicines called antibiotics), but also medicines obtained without prescription (for example hypericin or Saint John’ s wort extracts).
Meta tieħu mediċini oħra Jekk jogħġbok għid lit- tabib jew lill- ispiżjar tiegħek jekk qiegħed tieħu jew ħadt dan l- aħħar xi mediċini oħra, b’ mod partikulari mediċini li jistgħu jikkawżaw problemi tal- ġilda meta tiġi taħt dawl qawwi (per eżempju xi tipi ta ’ mediċini msejħin antibijotiċi), iżda wkoll mediċini miksuba mingħajr riċetta (per eżempju estratti ta ’ hypericin jew estratti ta ’ Saint John’ s wort).
One case of severe sunburn lasting for 5 days has been reported in a patient after having taken this medicine and a hypericin extract.
Ġie rrappurtat każ wieħed ta ’ ħarqa tax- xemx severa li damet għal 5 ijiem f’ pazjent wara t- teħid ta ’ din il- mediċina ma ’ estratt ta ’ hypericin.
You should not take any such products up to 2 weeks after you have taken Gliolan.
M’ għandekx tieħu prodotti bħal dawn sa ġimagħtejn wara li tkun ħadt Gliolan.
Within 24 hours after having taken Gliolan, avoid any other medicines that may harm the liver.
Sa 24 siegħa wara t- teħid ta ’ Gliolan, evita kull mediċina oħra li tista ’ tagħmel ħsara lill- fwied.
Taking Gliolan with food and drink This medicine is generally used once only, namely 2-4 hours before anaesthesia for surgery for certain brain tumours called glioma.
Meta tieħu Gliolan ma ’ l- ikel u max- xorb Din il- mediċina ġeneralment tintuża darba biss, jiġifieri 2- 4 sigħat qabel l- anestesija għal operazzjoni għal ċerti tumuri tal- moħħ imsejħa glijomi.
You should not drink or eat for at least 6 hours before starting anaesthesia.
M’ għandekx tieħu ikel jew xorb għal mill- inqas 6 sigħat qabel ma tinbeda l- anestesija.
Pregnancy and breast-feeding Use in pregnancy It is not known whether Gliolan will harm an unborn baby.
Tqala u treddigħ L- użu fit- tqala Mhux magħruf jekk Gliolan jagħmilx ħsara lil tarbija mhux imwielda.
Do not use this medicine if you are pregnant.
Tużax din il- mediċina jekk inti tqila.
Use in lactation It is not known whether this medicine enters breast milk.
L- użu waqt it- treddigħ Mhux magħruf jekk din il- mediċina tidħolx fil- ħalib tas- sider.
Breast-feeding mothers should not breast- feed for 24 hours after treatment with this medicine.
L- ommijiet li jkunu qegħdin ireddgħu ma għandhomx ireddgħu għal 24 siegħa wara t- trattament b’ din il- mediċina.
Driving and using machines This medicine itself has no influence on the ability to drive and use machines.
Sewqan u tħaddim ta ’ magni Din il- mediċina fiha nnifisha m’ għandha l- ebda effett fuq il- ħila ta ’ sewqan u l- użu ta ’ magni.
HOW TO TAKE GLIOLAN
KIF GĦANDEK TIEĦU GLIOLAN
This medicine is a powder that must be first mixed with drinking water before use.
Din il- mediċina hija trab għal soluzzjoni li l- ewwel irid jitħallat ma ’ l- ilma tax- xorb qabel l- użu.
This is always done by a pharmacist or a nurse and not by yourself.
Dan għandu dejjem isir minn spiżjar jew infermier u mhux minnek stess.
The usual dose is 20 mg per kilogram body weight.
Id- doża normali hija 20 mg għal kull kilogramm ta ’ piż tal- ġisem.
The pharmacist or nurse will calculate the exact dose you need.
L- ispiżjar jew infermier jikkalkula d- doża eżatta li għandek bżonn.
You have to drink the prepared solution 2-4 hours before start of anesthesia.
Inti trid tixrob is- soluzzjoni ppreparata 2- 4 sigħat qabel il- bidu ta ’ l- anestesija.
If the anesthesia/ surgery is delayed by some hours, additional doses of this medicine must not be given.
Jekk l- anestesija/ kirurġija tittardja b’ xi sigħat, ma jridux jingħataw dożi addizzjonali ta ’ din il - mediċina.
If the surgery is delayed by one or more days, another dose of this medicine can be taken 2-4 hours before start of anesthesia.
Jekk l- operazzjoni tittardja b’ ġurnata jew aktar, tista ’ tittieħed doża oħra ta ’ din il- mediċina 2- 4 sigħat qabel il- bidu ta ’ l- anestesija.
If you take more Gliolan than you should If you have taken more Gliolan than you should, your doctor will decide on any necessary measures to avoid any problems, including sufficient protection from strong light (for example direct sunlight).
Jekk tieħu Gliolan aktar milli suppost Jekk ħadt aktar Gliolan milli suppost, it- tabib tiegħek jiddeċiedi fuq il- miżuri meħtieġa biex jiġu evitati xi problemi, fosthom protezzjoni suffiċjenti minn sorsi ta ’ dawl qawwija (per eżempju, dawl tax- xemx dirett).
If you forget to take Gliolan This medicine is given once only at the day of surgery, 2-4 hours before start of anesthesia.
Jekk tinsa tieħu Gliolan Din il- mediċina tingħata darba biss fil- jum ta ’ l- operazzjoni, 2- 4 sigħat qabel il- bidu ta ’ l- anestesija.
If you have forgotten to take this medicine during this time period, it is not advisable to take it just before start of anesthesia.
Jekk tkun insejt tieħu din il- mediċina matul dan il- perjodu ta ’ ħin, mhuwiex rakkomandabbli li
In this case, anesthesia and surgery must be postponed for at least 2 hours, if possible.
F’ dan il- każ, l- anestesija u l- operazzjoni jridu jiġu posposti għal mill- anqas sagħtejn, jekk ikun possibbli.
18 Like all medicines, Gliolan can cause side effects, although not everybody gets them.
Bħal kull mediċina oħra, Gliolan jista ’ jkollu effetti sekondarji, għalkemm ma jidhrux fuq kulħadd.
After having taken Gliolan and before start of anaesthesia, the following side effects may occur:
Wara li tkun ħadt Gliolan u qabel il- bidu ta ’ l- anestesija, jistgħu jseħħu l- effetti sekondarji li ġejjin:
Uncommon side effects (likely to occur in more than 1 of 1,000 patients but less than 1 of 100 patients):
Effetti sekondarji mhux komuni (probabbli li jseħħu f’ aktar minn 1 minn kull 1, 000 pazjent iżda f’ anqas minn 1 minn kull 100 pazjent:
Nausea (unsettled stomach), decrease of blood pressure, skin reactions (for example rash, looking like sunburn).
Dardir (stonku mqalleb), tnaqqis fil- pressjoni tad- demm, reazzjonijiet tal- ġilda (per eżempju raxx, jidher qisu reazzjoni ta ’ ħarqa tax- xemx).
In combination with anaesthesia and tumour resection further side effects may occur:
Flimkien ma ’ l- anestesija u r- risezzjoni tat- tumur, jistgħu jseħħu aktar effetti sekondarji:
Very common side effects (likely to occur in more than 1 of 10 patients):
Effetti sekondarji komuni ħafna (probabbli li jseħħu f’ aktar minn 1 minn kull 10 pazjenti):
Mild alterations of blood cell counts (red and white cells, platelets), slight increase of some enzymes (transaminases, γ -GT, amylase) or bilirubin (a bile pigment produced in the liver by breakdown of red blood pigment) in the blood.
Bidliet ħfief fl- għadd ta ’ ċelloli tad- demm (ċelloli ħomor u bojod, pjastrini), żieda ħafifa ta ’ xi enzimi (transaminases, γ- GT, amylase) jew bilirubin (pigment tal- bile prodott fil- fwied bit- tkissir ta ’ pigment tad- demm aħmar) fid- demm.
These changes peak between 7 and 14 days after surgery.
Dawn il- bidliet jilħqu l- massimu bejn 7 u 14- il jum wara l- operazzjoni.
The changes will completely resolve within a few weeks.
Il- bidliet jgħaddu għal kollox fi żmien ftit ġimgħat.
Usually you will not experience any symptoms when these changes occur.
Normalment, inti ma tesperjenza ebda sintomu meta jseħħu dawn il- bidliet.
Common side effects (likely to occur in more than 1 of 100 patients but less than 1 of 10 patients):
Effetti sekondarji komuni (probabbli li jseħħu f’ aktar minn 1 minn kull 100 pazjent iżda f’ anqas minn 1 minn kull 10 pazjenti):
Nausea (unsettled stomach), vomiting (sickness), neurological disorders (disorders that affect the nervous system like hemiparesis (partial paralysis of one side of the body), aphasia (total or partial loss of ability to use or understand language), convulsions (seizures) and hemianopsia (blindness for half the field of vision in one or both eyes), thromboembolism (blood clots that may obstruct blood vessels).
Dardir (stonku mqalleb), rimettar (tħossok ħa taqla), disturbi newroloġiċi (distrubi li jaffettwaw is- sistema nervuża bħal emipareżi (paraliżi parzjali ta ’ naħa tal- ġisem), afasja (telf totali jew parzjali tal- kapaċità li tipproduċi jew tifhem il- lingwa), konvulżjonijiet, emianopsija (għama għal nofs il- kamp viżiv f’ għajn waħda jew fl- għajnejn), tromboemboliżmu (emboli li jistgħu jimblokkaw il- vini u l- arterji).
Uncommon side effects (likely to occur in more than 1 of 1,000 patients but less than 1 of 100 patients):
Effetti sekondarji mhux komuni (probabbli li jseħħu f’ aktar minn 1 minn kull 1, 000 pazjent iżda f’ anqas minn 1 minn kull 100 pazjent):
Decrease of blood pressure.
Tnaqqis fil- pressjoni tad- demm.
Very rare side effects (likely to occur in less than 1 of 10,000 patients), including isolated reports:
Effetti sekondarji rari ħafna (probabbli li jseħħu f’ anqas minn 1 minn kull 10, 000 pazjent), inklużi rapporti iżolati:
Hypesthesia (i. e. decrease of your sense of touch); diarrhoea (loose or watery stools).
Ipoestesija (per eżempju tnaqqis tas- sens ta ’ ħass tiegħek); dijarea (ippurgar mimli ilma jew laxk)
HOW TO STORE GLIOLAN
KIF TAĦŻEN GLIOLAN
Do not use this medicine after the expiry date which is stated on the carton.
Tużax din il- mediċina wara d- data ta ’ skadenza li tidher fuq il- kartuna.
Medicines should not be disposed of via wastewater or household waste.
20 Il- mediċini m’ għandhomx jintremew ma ’ l- ilma tad- dranaġġ jew ma ’ l- iskart domestiku.
What Gliolan contains The active substance is 5-aminolevulinic acid hydrochloride.
X’ fih Gliolan Is- sustanza attiva hija 5- aminolevulinic acid hydrochloride.
One vial contains 1.17 g of 5-aminolevulinic acid, corresponding to 1.5 g 5-aminolevulinic acid hydrochloride (5-ALA HCl).
Kunjett wieħed fih 1. 17 g ta ’ 5 - aminolevulinic acid, li jikkorrispondi għal 1. 5 g ta ’ 5- aminolevulinic acid hydrochloride (5- ALA HCI).
One ml of reconstituted solution contains 23.4 mg of 5-aminolevulinic acid, corresponding to 30 mg 5-aminolevulinic acid hydrochloride (5-ALA HCl).
1 ml tas- soluzzjoni rikostitwita fih 23. 4 mg ta ’ 5- aminolevulinic acid, li jikkorrispondu għal 30 mg ta ’ 5- aminolevulinic acid hydrochloride (5- ALA HCI).
19 What Gliolan looks like and contents of the pack This medicine is a powder for oral solution.
Id- dehra tal- prodott u d- daqs tal- pakkett Din il- mediċina hija trab għal soluzzjoni orali.
The reconstituted solution is a clear and colourless to slightly yellowish fluid.
Is- soluzzjoni rikostitwita hija fluwidu ċar u mingħajr lewn għal daqsxejn fl- isfar.
Gliolan is presented in packs of 1, 2 and 10 vials.
Gliolan huwa ppreżentat f’ pakketti ta ’ 1, 2 u 10 kunjetti.
Not all pack size may be marketed.
Id- Detentur ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq
Marketing Authorisation Holder medac Gesellschaft für klinische Spezialpräparate mbH Fehlandtstraße 3 D-20354 Hamburg, Germany Tel. + 49 4103 8006 0 Fax: + 49 4103 8006 100
medac Gesellschaft für klinische Spezialpräparate mbH Fehlandtstraße 3 D- 20354 Hamburg, Il- Ġermanja Tel. + 49 4103 8006 0 Fax: + 49 4103 8006 100
Manufacturer medac Gesellschaft für klinische Spezialpräparate mbH Theaterstraße 6 D-22880 Wedel, Germany Tel. + 49 4103 8006 0 Fax: + 49 4103 8006 100
medac Gesellschaft für klinische Spezialpräparate mbH Theaterstraße 6 D- 22880 Wedel, Il- Ġermanja Tel. + 49 4103 8006 0 Fax: + 49 4103 8006 100
Capsule, hard Capsule, hard Capsule, hard Capsule, hard Capsule, hard Capsule, hard Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet
Kapsula, iebsa Kapsula, iebsa Kapsula, iebsa Kapsula, iebsa Kapsula, iebsa Kapsula, iebsa Pillola miksija b’ rita Pillola miksija b’ rita Pillola miksija b’ rita Pillola miksija b’ rita Pillola miksija b’ rita Pillola miksija b’ rita Pillola miksija b’ rita
Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use
Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali