qanastek/EMEA-V3 huggingface dataset:
- Decrease in the normal amounts of different blood cells, which can result in increased risk of
- Tnaqqis fl- ammonti normali ta ’ ċelluli ta ’ demm differenti, li jista ’ jirriżulta f’ riskju ogħla ta ’
infections, bruising, swollen glands
infezzjonijiet, tbenġil, emorraġija, glandoli minfuħin
- Tingling or numbness feeling, flushing (becoming red in the skin), impaired concentration,
- Tnemnim jew mewt, fwawar (il- ġilda ssir ħamra), konċentrazzjoni indebolita, rogħda
- Abnormal vision, conjunctivitis, eye pain, swollen glands on the eyelids
- Vista mhix normali, konġuntivite, uġigħ fl- għajnejn, glandoli minfuħin tal- kpiepel għal għajnejn
- Breathing difficulties, blocked, runny or irritated nose, sneezing, nosebleed, problems with your
- Diffikultajiet biex tieħu n- nifs, imnieħer imblukkat, inixxi jew irritat, għatis, imnieħer jinfaraġ,
oral cavity, inflammation of the tongue or gums, mouth ulcers, toothache or tooth abscess
problemi bil- kavità orali tiegħek, infjammazzjoni tal- ilsien jew il- ħanek, ulċeri tal- ħalq, uġigħ fis- snien jew tinwir fis- snien Emorraġija rapida, stitikezza, indiġestjoni, aċidu fl- istonku, tqalligħ, remettar, uġigħ
- Rapid breathing, constipation, indigestion, heartburn, nausea, vomiting, abdominal pain,
-
diarrhoea, Pain on the right side around the ribs
addomainali, dijarea, Uġigħ fuq in- naħa leminija tal- kustilji
- Unusual, increased or altered sensitivity to sensory stimulation, sun allergy, eczema, increased
- Sensittivita mhux tas- soltu, ogħla jew mibdula għal stimulazzjoni sensorjali, allerġija tax- xemx,
sweating, itching and dry skin, skin and nail disorders
ekżema, żieda fl- għaraq, ħakk u ġilda xotta, disturbi fil- ġilda u fid- dwiefer
- Overactive thyroid gland has been reported, abnormal development of secondary male sexual
- Glandola aktar attiva milli suppost ġiet rapportata, żvilupp mhux normali tal- karatteristiċi
characteristics, such as facial hair
sekondarji tar- raġel, bħal xagħar fil- wiċċ
- Abnormally high level of uric acid in the blood.
- Livelli mhux normali għoljin ta ’ aċidu uriku fid- demm.
Can cause gout or kidney stones, increased
Jista ’ jirriżulta f’ gotta jew ħaġar renali,
appetite, hyperactive, excess of triglycerides (a type of fat) in the blood
żieda fl- aptit, iperattiv, livelli għolja ħafna ta ’ trigliċeridi (tip ta ’ grass) fid- demm
- Cold sores, fungal infection, bacterial and urinary tract infection, build up of fluid in the ear, lung
- Uġigħ minħabba l- kesħa, infezzjoni fungali, infezzjoni batterika u tal- passaġġ awrinarju,
infection, coughing, gastric or stomach flu
jinġabara il- fluwidu fil- widna, infezzjoni fil- pulmun, sogħla, influwenza gastrika jew tal- istonku
- Pain in the testis, pain at the site of injection, lethargy, chest pain
Uġigħ fit- testikoli, uġigħ fis- sit mnejn tingħata l- injezzjoni, ritensjoni ta ’ ilma, letarġija, uġigħ
- Abnormal liver function
- Funzjoni mhix normali tal- fwied
- Incontinence, water retention, uncontrolled urination, abnormal menstruation, disorder of the
- Inkontinenza, ritensjoni tal- ilma, awrinazzjoni mhix kontrollata, menstruwazzjoni mhix normali,
vagina
disturbi fil- vaġina
- Feeling agitated or nervous, aggressive behaviour, feelings of apathy, confusion, altered sleeping
- Tħossok aġitat jew nervuż, mġieba aggressiva, tħossok b’ apatija, konfużjoni, xejriet mibdula
patterns, unusual dreams, suicidal thoughts, sleep walking
fl- irqad, ħolm mhux tas- soltu, ħsibijiet suwiċidali, ħmar il- lejl
41 The following side effects may also occur:
L- effetti sekondarji li ġejjin jistgħu jseħħu wkoll:
Aplastic anaemia, pure red cell aplasia (the failure of bone marrow to produce sufficient blood cells for the circulation); this can cause weakness, bruising or make infections more likely, seizures (fits), inflammation of the pancreas, which causes severe pain in the abdomen and back, redness of the skin and blistering of the skin, mouth, eyes and genitals.
Anemija aplastika, aplasja pura taċ- ċelluli ħomor (in- nuqqas tal- mudullun biex jipproduċi biżżejjed ċelluli ħomor għaċ- ċirkolazzjoni); dan jista ’ jikkawża dgħufija, tbenġil jew iwassal biex infezzjonijiet ikunu aktar probabbli, attakki ta ’ puplesija, infjammazzjoni tal- frixa, li jikkawża uġigħ sever fl - addome u fid- dahar, ħmura fil- ġilda u nfafaet fil- ġilda, il- ħalq, l- għajnejn u l- partijiet ġenitali.
Intense pain in an appendage, loss of range of motion, stiffness, abnormal thoughts, hearing or seeing images that are not present, altered mental status, disorientation, leg or thigh pain, constant cough, trouble having bowel movement or painful bowel movement, bruises, heartburn, enlarged abdominal area, acute hypersensitivity reactions including urticaria (hives), angioedema (swelling of the hands, feet, ankles, face, lips, mouth, or throat which may cause difficulty in swallowing or breathing), bronchoconstriction and anaphylaxis (a severe, whole-body allergic reaction) have been reported.
Uġigħ intensiv fl- appendiċi, telf fil- medda ta ’ ċaqlieq, ebusija, ħsibijiet mhux normali, smigħ jew tara oġġetti li ma jkunux hemm, stat mentali mibdul, diżorjentazzjoni, uġigħ fir- riġel jew il- koxxa, sogħla kostanti, problemi biċ- ċaqlieq fl- imsaren jew uġigħ biċ- ċaqlieq fl- imsaren, tbenġil, ħruq fl- istonku, iż- żaqq tikber, reazzjonijiet ta ’ sensittività eċċessiva akuta li jinkludu urtikarja (ħorriqija), anġjodema (nefħa tal- idejn, is- saqajn, l- għekiesi, wiċċ, xofftejn, ħalq, jew griżmejn li tista ’ toħloq diffikultajiet biex tibla ’ jew tieħu n- nifs), jidjiequ l- bronki u anafilassi (reazzjoni severa u allerġika mal- ġisem kollu) ġew rapportati.
Additionally, Vogt-Koyanagi-Harada syndrome (an autoimmune inflammatory disorder affecting the eyes, skin and the membranes of the ears, brain and spinal cord) has been reported.
Barra dan, kien hemm rapporti tas- sindromu ta ’ Vogt- Koyangi (disturb infjammatorju awtoimmuni li jaffettwa l- għajnejn, il- ġilda u r- riti tal- widnejn, il- moħħ u l- korda spinali).
Sarcoidosis, (a disease characterised by persistent fever, weight loss, joint pain and swelling, skin lesions and swollen glands) has been reported.
Sarkojdosi (marda karatterizzata b’ deni persistenti, telf fil- piż, uġigħ fil- ġogi u nefħa, ġrieħi fil- ġilda u glandoli minfuħin) ġiet rapportata.
Cases of stroke (cerebrovascular events) have been reported.
Każijiet ta ’ puplesija (każijiet ċerebrovaskulari) ġiet rapportata.
Ribavirin Teva in combination with peginterferon alfa-2b or interferon alfa-2b may also cause: loss of use, drooping or loss of power of facial muscles, loss of feeling sensation, loss of consciousness, loss of vision, difficulty breathing, changes in the way your heart beats, chest pain, pain down left arm, jaw pain, dark, cloudy or abnormally coloured urine.
Ribavirin Teva flimkien ma ’ peginterferon alfa- 2b jew interferon alfa- 2b jistgħu jikkawżaw ukoll: telf fl- użu, il- waqgħa ’ jew t- telf tal- muskoli tal- wiċċ, telf mis- sensittività ta ’ dak li tħoss, inkoxjenza, telf fil- vista tal- għajnejn, diffikultà biex tieħu n- nifs, bidliet fil- mod kif tħabbat qalbek, uġigħ fi- sider, uġigħ fin- naħa t’ isfel ta ’ dirgħajk, uġigħ fix- xedaq, awrina skura, mċajpra jew mhix ta ’ kulur normali.
You or your caregiver should call your doctor immediately if you have any of these symptoms.
Int jew il- persuna li qed tieħu ħsiebek għandhom isejħu lit- tabib tiegħek minnufih jekk ikollok xi wieħed minn dawn is- sintomi.
Diabetes and pneumonia have been reported rarely.
Id- dijabete u l- pnewmonja ġew rapportati b’ mod rari.
Suicide has been reported very rarely.
Is- suwiċidju ġie rapportat b’ mod rari ħafna.
For HCV/HIV co-infected patients receiving Ribavirin Teva in combination with peginterferon alfa- 2b, there is an increased risk of lactic acidosis, liver failure and blood abnormalities (reduction in red or white blood cells that fight infection, and blood clotting cells called platelets).
Għal pazjenti koinfettati b’ HCV/ HIV li qed jirċievu Ribavirin f’ kombinazzjoni ma ’ peginterferon alfa - 2b, hemm riskju ogħla ta ’ aċidosi lattika, insuffiċjenza epatika u abnormalitajiet tad- demm (reduction in red or white blood cells that fight infection, and blood clotting cells called platelets).
The following additional side effects have occurred in HCV/HIV co-infected patients receiving Ribavirin in combination with peginterferon alfa-2b: oral thrush, changes in the amount and distribution of body fat, reduction in the amount of white blood cells, decreased appetite, increase in gamma-glutamyltransferase (an enzyme produced by the liver, associated with early liver cell damage), back pain, increase amounts of amylase (an enzyme present in the blood) and lactic acid, hepatitis, increased lipase (the enzyme necessary for the absorption and digestion of nutrients in the intestines) and limb pain.
L- effeti sekondarji addizzjonali li ġejjin seħħew f’ pazjenti li kienu ko- infettati b’ HCV/ HIV li kienu qed jirċievu Ribavirin flimkien ma ’ peginterferon alfa- 2b: kandidjasi orali, bidliet fl- ammont u d- distribuzzjoni tax- xaħam fil- ġisem, tnaqqis fl- ammont ta ’ ċelluli bojod tad- demm, tnaqqis fl- aptit, żieda fil- gamma- glutamyltransferase (enżim prodott mill- fwied li hu assoċjat ma ’ ħsara bikrija fiċ- ċelluli tal- fwied), uġigħ fid- dahar, żieda fl- ammont ta ’ amylase (enżima preżenti fid- demm) u aċidu lattiku, epatite, żieda fil- lipase (enżim meħtieġ għall- assorbiment u d- diġestjoni ta ’ nutrimenti fl- imsaren) u uġigħ fid- driegħ/ riġel.
HOW TO STORE RIBAVIRIN TEVA
KIF TAĦŻEN RIBAVIRIN TEVA
Do not use Ribavirin Teva after the expiry date which is stated on the outer packaging.
Tużax Ribavirin Teva wara d- data ta ’ skadenza li tidher fuq il- kartuna ta ’ barra.
Do not use Ribavirin Teva if you notice any change in the appearance of the capsules.
43 M’ għandekx tuża Ribavirin jekk tara tibdil fid- dehra tal- kapsuli.
What Ribavirin Teva contains
X’ fih Ribavirin Teva
The active substance is Ribavirin 200 mg The other ingredients are calcium hydrogen phosphate, croscarmellose sodium, povidone, magnesium stearate.
Is- sustanza attiva hi Ribavirin 200 mg Is- sustazi l- oħra huma calcium hydrogen phosphate, croscarmellose sodium, povidone, magnesium stearate.
The capsule shell contains titanium dioxide (E171) and gelatin.
Il- qoxra tal- kapsula fiha titanium dioxide (E171) u gelatin.
The capsule shell imprint contains shellac, titanium dioxide (E171) and indigo carmine
L- intaljar fuq il- qoxra ta ’ barra jikkonsisti minn shellac, titanium dioxide (E171) u indigo carmine
What Ribavirin Teva looks like and contents of the pack
Id- dehra ta ’ Ribavirin Teva u l- kontenuti tal- pakkett
Ribavirin Teva is a white, opaque, hard capsule imprinted with blue ink.
Ribavirin Teva hija kapsula iebsa bajda, opaka immarkata b’ linka blu.
Ribavirin Teva is available in different pack sizes containing 84, 112, 140 or 168 capsules to be swallowed.
Ribavirin Teva jiġi f’ daqsijiet ta ’ pakketti differenti ta ’ 84, 112, 140 jew 168 kapsula li għandhom jinbelgħu.
Teva Pharmaceutical Works Private Limited Company Pallagi út 13 Debrecen H-4042 Hungary
Teva Pharmaceutical Works Private Limited Company Pallagi út 13 Debrecen H- 4042 L- Ungerija
TEVA Pharmaceutical Works Private Limited Company H-2100 Gödöllö Táncsics Mihály út 82 Hungary
TEVA Pharmaceutical Works Private Limited Company H- 2100 Gödöllö Táncsics Mihály út 82 L- Ungerija
44
44 TEVA Santé SA Rue Bellocier 89107 Sens Franza
European Medicines Agency
Europeans Medicines Agency
What is RILUTEK?
X’ inhu RILUTEK?
RILUTEK is a medicine containing the active substance riluzole.
RILUTEK hija mediċina li fiha s- sustanza attiva riluzole.
It is available as white, capsule- shaped 50 mg tablets.
Hija tiġi bħala pillola bajdanija ta ’ 50 mg f’ għamla ta ’ kapsula.
What is RILUTEK used for?
Għalxiex jintuża RILUTEK?
RILUTEK is used in patients with amyotrophic lateral sclerosis (ALS).
RILUTEK jintuża f’ pazjenti li għandhom sklerosi amijotrofika laterali (ALS).
ALS is a form of motor neurone disease where attacks of the nerve cells responsible for sending instructions to the muscles lead to weakness, muscle waste and paralysis.
ALS hija forma ta ’ marda tan- newroni motorili meta attakki fuq iċ- ċelloli tan- nervituri responsabbli biex jibagħtu messaġġi lill- muskoli jwasslu għal dgħjufija, tpaħpiħ muskolari u paraliżi.
RILUTEK is used to extend the patient ’ s life, or the time before they need to use mechanical ventilation.
RILUTEK jintuża biex idewwem ħajjet il- pazjent, jew iż- żmien li jeħtieġ biex juża ventilazzjoni mekkanika.
RILUTEK should not be used in patients with any other form of motor neurone disease.
RILUTEK m’ għandux jintuża f’ pazjenti li għandhom xi forma ta ’ marda tan- newroni motorili oħra.
How is RILUTEK used?
Kif jintuża RILUTEK?
Treatment with RILUTEK should only be started by a specialist doctor with experience in the management of motor neurone diseases.
It- trattament b’ RILUTEK għandu jinbeda biss minn tabib speċjalista li għandu esperjenza fil- ġestjoni ta ’ mard tan- newroni motorili.
In adult and elderly patients, it is given as 100 mg a day (50 mg every 12 hours).
F’ adulti u pazjenti anzjani, huwa jingħata bħala 100 mg kuljum (50 mg kull 12- il siegħa).
RILUTEK is not recommended for children or patients with kidney disease and should not be given to patients with liver disease.
RILUTEK mhux rakkomandat fi tfal b’ mard tal- kliewi u m’ għandux jingħata lil pazjenti b’ mard tal- fwied.
For more information please see the Package Leaflet.
Għal aktar tagħrif jekk jogħġbok ara l- Fuljett tat- Tagħrif.
How does RILUTEK work?
Kif jaħdem RILUTEK?
The active substance in RILUTEK, riluzole, acts on the nervous system.
Is- sustanza attiva f’ RILUTEK, riluzole, taġixxi fuq is- sistema nervuża.
The exact way in which it works in ALS is not known.
Il- mod eżatt kif taħdem fuq l- ALS għadu mhux magħruf.
It is thought that the destruction of nerve cells in motor neurone disease may be caused by too much glutamate, a neurotransmitter (chemical messenger).
Huwa maħsub li l- qerda ta ’ ċelloli fil- mard tan- newroni motorili jista ’ jiġi kkawżat minn aktar glutamate, newrotrasmettitur (messaġġier kemikali), milli meħtieġ.
Riluzole stops the release of glutamate and this may help in preventing the nerve cells being damaged.
Riluzole iwaqqaf ir- rilaxx ta ’ glutamate u dan jgħin jevita milli ċ- ċelloli tan- nervituri tiġrilhom ħsara.
How has RILUTEK been studied?
Kif ġie studjat RILUTEK?
The effectiveness of RILUTEK has been compared with that of placebo (a dummy treatment) in three studies involving a total of 1,282 patients.
L- effikaċja ta ’ RILUTEK ġiet imqabbla ma ’ dik ta ’ plaċebo (trattament finta) fi tliet studji li kienu jinvolvu total ta ’ 1, 282 pazjent.
One of these studies was in older patients (over 75) and in patients with advanced disease.
Wieħed minn dawn l- istudji kien f’ pazjenti aktar anzjani (’ il fuq minn 75 sena) u f’ pazjenti bil- marda f’ fażi avvanzata.
Across the studies, RILUTEK was given as 50, 100 or 200 mg per day, and for up to 18 months.
Waqt l- istudju, RILUTEK ingħata bħala 50, 100 jew 200 mg kuljum, u sa 18- il xahar.
The main measure of effectiveness was the average survival time.
Il- miżura ewlenija ta ’ effikaċja kienet iż- żmien medju ta ’ sopravivenza.
(44-20) 74 18 84 00 Fax (44-20) 74 18 84 16 E-mail: mail@emea. europa. eu http: / /www. emea. europa. eu ©EMEA 2007 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged What benefit has RILUTEK shown during the studies?
(44- 20) 74 18 84 00 Fax (44- 20) 74 18 86 68 E- mail: mail@ emea. europa. eu http: // www. emea. europa. eu ©EMEA 2007 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged X’ benefiċċju wera RILUTEK matul l- istudji?
The average survival time was significantly longer for patients who received RILUTEK compared with patients who received placebo.
Iż- żmien medju ta ’ sopravivenza kien ferm ogħla għal pazjenti li rċevew RILUTEK meta mqabbel ma ’ pazjenti li rċevew plaċebo.
Looking at the results of the three studies together, over 18 months, patients who received RILUTEK 100 mg/ day had an average survival time that was about 2 months longer than the survival time for patients who received placebo.
Meta wieħed jara r- riżultati tat- tliet studji flimkien, fuq 18- il xahar, pazjenti li rċevew 100 mg/ kuljum RILUTEK kellhom żmien medju ta ’ sopravivenza ta ’ madwar xahrejn aktar miż- żmien ta ’ sopravivenza għal pazjenti li rċevew il- plaċebo.
RILUTEK 50 mg/ day was no more effective than placebo and 200 mg/ day was no more effective than 100 mg/ day.
RILUTEK 50 mg/ kuljum ma kienx aktar effettiv mill- plaċebo u 200 mg/ kuljum ma kienx aktar effettiv minn 100 mg/ kuljum.
The medicine was not more effective than placebo in the late stages of ALS.
Il- mediċina ma kinetx aktar effettiva mill- plaċebo fl- aħħar stadji ta ’ ALS.
What is the risk associated with RILUTEK?
X’ inhu r- riskju assoċjat b’ RILUTEK?
The most common side effects seen with RILUTEK (in more than 1 patient in 10) are nausea (feeling sick), asthenia (weakness) and abnormal liver tests (increased in liver enzymes levels).
L- aktar effetti sekondarji komuni li dehru b’ RILUTEK (f’ aktar minn pazjent 1 f’ 10) huma dardir (tħossok ma tiflaħx), astenja (debolezza) u test tal- fwied anormali (żieda fil- livelli ta ’ enzimi tal- fwied).
For the full list of all side effects reported with RILUTEK, see the Package Leaflet.
Għal- lista sħiħa ta ’ effetti sekondarji rrapportati b’ RILUTEK, ara l- Fuljett ta ’ Tagħrif.
RILUTEK should not be used in people who may be hypersensitive (allergic) to riluzole or any of the other ingredients.
RILUTEK m’ għandux jintuża fuq persuni li għandhom sensittività eċċessiva (allerġika) għal riluzole jew xi wieħed mis- sustanzi l- oħra.
RILUTEK should not be used in patients who have liver disease or who have abnormally high levels of liver enzymes.
RILUTEK m’ għandux jintuża f’ pazjenti li għandhom il- mard tal - fwied jew li għandhom livelli għoljin b’ mod anormali ta ’ enzimi tal- fwied.
RILUTEK should also not be given to women who are pregnant or breast-feeding.
RILUTEK m’ għandux jingħata lil nisa li huma tqal jew li qed ireddgħu.
Why has RILUTEK been approved?
Għaliex ġie approvat RILUTEK?
The Committee for Medicinal products for Human Use (CHMP) decided that RILUTEK’ s benefits are greater than its risks to extend life or the time to mechanical ventilation for patients with amyotrophic lateral sclerosis.
Il- Kumitat dwar il- Prodotti Mediċini għal Użu mill- Bniedem (CHMP) iddeċieda li l- benefiċċji ta ’ RILUTEK huma akbar mir- riskji biex il- ħajja tiġi estiża jew għaż- żmien ta ’ ventilazzjoni mekkanika għal pazjenti bi sklerożi amijotrofika laterali.
They noted that there is no evidence that RILUTEK exerts a therapeutic effect on motor function, lung function, fasciculations, muscle strength and motor symptoms, and that it has not been shown to be effective in the late stages of ALS.
Hu nnota li m’ hemmx evidenza li RILUTEK jeżerċita effett terapewtiku fuq funzjoni motorili, funzjoni tal- pulmun, faxxikulazzjonijiet, saħħa muskolari u sintomi motorili u li ma ntweriex li hu effettiv fl- aħħar stadji ta ’ ALS.
The committee recommended that RILUTEK be given marketing authorisation.
Il- kumitat irrakkomanda li RILUTEK għandu jingħata awtorizzazzjoni għat- tqegħid fis- suq.
Other information about RILUTEK:
Aktar tagħrif dwar RILUTEK:
The European Commission granted a marketing authorisation valid throughout the European Union for RILUTEK to Aventis Pharma S. A. on 10 June 1996.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fis- suq valida madwar l- Unjoni Ewropea kollha għal RILUTEK lil Aventis Pharma S. A. fl- 10 ta ’ Ġunju 1996.
The marketing authorisation was renewed on 10 June 2001 and 10 June 2006.
L- awtorizzazzjoni għat- tqegħid fis- suq ġiet riveduta fl- 10 ta ’ Ġunju 2001 u fl- 10 ta ’ Ġunju 2006.
The full EPAR for RILUTEK is available here.
L- EPAR sħiħ dwar RILUTEK huwa disponibbli minn hawnhekk.
This summary was last updated in 03-2007.
Dan is- sommarju ġie aġġornat fit- 03- 2007.
RILUTEK 50 mg film-coated tablets
RILUTEK 50 mg pilloli miksija b’ rita
Each film-coated tablet contains 50 mg of riluzole
Kull pillola miksija b’ rita fiha 50 mg ta ’ riluzole.
Film-coated tablet The tablets are capsule-shaped, white and engraved with “ RPR 202 ” on one side.
Il- pilloli huma taħt għamla ta ’ kapsuli bojod b ’ “ RPR 202 ” imnaqqax fuq naħa waħda.
RILUTEK is indicated to extend life or the time to mechanical ventilation for patients with amyotrophic lateral sclerosis (ALS).
RILUTEK huwa indikat biex itawwal il- ħajja, jew iż- żmien li pazjent jista ’ jdum ventilat mekkanikament, għal dawk li qed ibatu minn atrofija tal- muskoli dovuta għall- isklerożi laterali (ALS).
Clinical trials have demonstrated that RILUTEK extends survival for patients with ALS (see section 5.1).
Studji kliniċi wrew li RILUTEK itawwal il- ħajja ta ’ pazjenti bl- ALS (ara sezzjoni 5. 1).
Survival was defined as patients who were alive, not intubated for mechanical ventilation and tracheotomy-free.
Il- ħajja mtawwla kienet definita bħala każi fejn il- pazjenti li baqgħu ħajjin, ma kienux intubati għal ventilazzjoni mekkanika u ma kellhomx bżonn ta ’ trakejotomija.
There is no evidence that RILUTEK exerts a therapeutic effect on motor function, lung function, fasciculations, muscle strength and motor symptoms.
M’ hemm l- ebda evidenza li RILUTEK jeżerċita effett terapewtiku fuq il- movimenti tal- persuna, il - funzjoni tal- pulmuni, kontrazzjonijiet involontarji tal- muskoli, s- saħħa tal- muskoli jew sintomi riferibbli għall- moviment.
RILUTEK has not been shown to be effective in the late stages of ALS.
RILUTEK ma ntweriex li kien effettiv fi stadji avanzati ta ’ ALS.
Safety and efficacy of RILUTEK has only been studied in ALS.
Is- sigurtà u l- effikaċja ta ’ RILUTEK kienu studjati biss f’ dawk li jbatu minn ALS.
Therefore, RILUTEK should not be used in patients with any other form of motor neurone disease.
Għalhekk, RILUTEK m’ għandux jintuża f’ pazjenti li qed ibatu minn xi forma oħra ta ’ mard tan- newroni, relatat maċ- ċaqlieq tal- muskoli.
Treatment with RILUTEK should only be initiated by specialist physicians with experience in the management of motor neurone diseases.
Il- kura b’ RILUTEK għandha tinbeda biss minn tobba speċjalisti b’ esperjenza fil- kura ta ’ mard tan - newroni relatat mac- ċaqlieq tal- muskoli.
The recommended daily dose in adults or elderly is 100 mg (50 mg every 12 hours).
Id- doża rrakkomandata fl- adulti u l- anzjani hija ta ’ 100 mg kuljum (50 mg kull 12- il siegħa).
No significant increased benefit can be expected from higher daily doses.
Mhux mistenni li jkun hemm benefiċju miżjud u sinifikanti b’ dożi akbar ta ’ kuljum.
Special populations
Gruppi ta ’ pazjenti speċjali
RILUTEK is not recommended for use in children, due to a lack of data on the safety and efficacy of riluzole in any neurodegenerative diseases occurring in children or adolescents.
RILUTEK mhux irrakkomandat għall- użu fit- tfal, dovut għan- nuqqas ta ’ data dwar is- sigurtà u l - effikaċja ta ’ riluzole, f’ kull kundizzjoni newrodeġenerattiva fit- tfal u fl- adoloxxenti.
Patients with impaired renal function:
Pazjenti b’ indeboliment renali:
RILUTEK is not recommended for use in patients with impaired renal function, as studies at repeated doses have not been conducted in this population (see section 4.4).
RILUTEK mhux irrakkomandat f’ pazjenti li għandhom indeboliment renali, peress li qatt ma saru studji b’ dożi repetuti f’ dawn il- pazjenti (ara sezzjoni 4. 4).
Elderly: based on pharmacokinetic data, there are no special instructions for the use of RILUTEK in this population.
Anzjani: skond it- tagħrif farmakokinetiku, m’ hemmx struzzjonijiet speċjali fl- użu ta ’ RILUTEK f’ dawn il- pazjenti.
Patients with impaired hepatic function:
Pazjenti b’ indeboliment tal- fwied:
(see section 4.3, section 4.4, and section 5.2).
(ara sezzjoni 4. 3, sezzjoni 4. 4, u sezzjoni 5. 2).
Hepatic disease or baseline transaminases greater than 3 times the upper limit of normal.
Mard tal- fwied, jew meta l- livelli ta ’ transaminases fil- linja bażi jkunu aktar minn 3 darbiet iżjed mill - ogħla limitu tal- firxa normali.
Patients who are pregnant or breast-feeding.
Pazjenti li huma tqal jew li qegħdin ireddgħu.
Liver impairment:
Indeboliment tal- fwied:
Riluzole should be prescribed with care in patients with a history of abnormal liver function, or in patients with slightly elevated serum transaminases (ALT/ SGPT; AST/ SGOT up to 3 times the upper limit of the normal range (ULN)), bilirubin and/ or gamma-glutamyl transferase (GGT) levels.
Riluzole għandu jintuża b’ kawtela f’ pazjenti li għandhom passat mediku ta ’ funzjoni abnormali tal - fwied, jew f’ dawk il- pazjenti li għandhom livelli kemmxejn għoljin ta ’ l- enżimi transaminases fis - serum (ALT/ SGPT u AST/ SGOT, sa 3 darbiet aktar mill- ogħla livell fil- firxa normali (ULN)); tal - bilirubina u/ jew tal- livelli ta ’ gamma- glutamyl transferase (GGT).
Baseline elevations of several liver function tests (especially elevated bilirubin) should preclude the use of riluzole (see section 4.8).
Żieda fil- linja bażi ta ’ diversi testijiet tal- funzjoni tal- fwied (speċjalment livelli għoljin ta ’ bilirubina) jipprekludi l- użu ta ’ riluzole (ara sezzjoni 4. 8).
Because of the risk of hepatitis, serum transaminases, including ALT, should be measured before and during therapy with riluzole.
Dovut għar- riskju ta ’ epatite, l- livell tat- transaminases fis- serum, inkluż ALT, għandhom jitkejjlu qabel u waqt it- terapija b’ riluzole.
ALT should be measured every month during the first 3 months of treatment, every 3 months during the remainder of the first year, and periodically thereafter.
L- ALT għandu jitkejjel kull xahar waqt l- ewwel 3 xhur tal- kura, kull 3 xhur għall- bqija ta ’ l- ewwel sena, u mbagħad, perjodikament.
ALT levels should be measured more frequently in patients who develop elevated ALT levels.
Il- livelli ta ’ l- ALT iridu jkunu mkejjla aktar spiss f’ pazjenti li juru livelli għoljin ta ’ l- ALT.
Riluzole should be discontinued if the ALT levels increase to 5 times the ULN.
Riluzole għandu jitwaqqaf jekk il- livelli ta ’ l- ALT jiżdiedu b’ ħames darbiet dak ta ’ l- ULN.
There is no experience with dose reduction or rechallenge in patients who have developed an increase of ALT to 5 times ULN.
M’ hemm l- ebda esperjenza b’ dożi inqas jew teħid mill- ġdid tal- mediċina f’ pazjenti li żvillupaw żieda ta ’ livelli ta ’ ALT b’ ħames darbiet dak ta ’ ULN.
Readministration of riluzole to patients in this situation cannot be recommended.
It- teħid mill- ġdid ta ’ riluzole f’ pazjenti f’ din il- qagħda mhux irrakkomandat.
Neutropenia:
Newtropenja:
Patients should be warned to report any febrile illness to their physicians.
Il- pazjenti għandhom ikunu mwissjia li għandhom jgħarrfu lit- tabib jekk ikollhom xi mard bid- deni.
The report of a febrile illness should prompt physicians to check white blood cell counts and to discontinue riluzole in case of neutropenia (see section 4.8).
Fdan il- każ it- tobba għandhom jiċċekkjaw l- għadd taċ- ċelluli bojod tad- demm mill- ewwel u f’ każ li jkun hemm newtropenja, għandha titwaqqaf il- kura b’ riluzole (ara sezzjoni 4. 8).
Studies at repeated doses have not been conducted in patients with impaired renal function (see section 4.2).
Studji b’ dożi repetuti ma sarux f’ pazjenti b’ indeboliment fil- funzjoni renali (ara sezzjoni 4. 2).
4.5 Interaction with other medicinal products and other forms of interaction
4. 5 Prodotti mediċinali oħra li ma jablux ma ’ dan il- prodott u affarijiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
There have been no clinical studies to evaluate the interactions of riluzole with other medicinal products.
Ma sarux studji kliniċi biex jevalwaw l- interazzjonijiet ta ’ riluzole ma ’ prodotti mediċinali oħra.
In vitro studies using human liver microsomal preparations suggest that CYP 1A2 is the principal isozyme involved in the initial oxidative metabolism of riluzole.
Studji in vitro, fejn intużaw preparati ta ’ mikrożomi mill- fwied tal- bniedem, jindikaw li l- CYP 1A2 hija l- iżożima prinċipali involuta fil- metaboliżmu ossidattiv inizjali ta ’ riluzole.
Inhibitors of CYP 1A2 (e. g. caffeine, diclofenac, diazepam, nicergoline, clomipramine, imipramine, fluvoxamine, phenacetin, theophylline, amitriptyline and quinolones) could potentially decrease the rate of riluzole elimination, while inducers of CYP 1A2 (e. g. cigarette smoke, charcoal-broiled food, rifampicin and omeprazole) could increase the rate of riluzole elimination.
Inibituri ta ’ CYP 1A2 (eż. caffeine, diclofenac, diazepam, nicergoline, clomipramine, imipramine, fluvoxamine, phenacetin, theophylline, amitriptyline u quinolones) potenzjalment jistgħu jnaqqsu r- rata tat- tneħħija ta ’ riluzole, fil- waqt li indutturi ta ’ CYP 1A2 (e. g. id- duħħan tas- sigaretti, ikel mixwi fuq il- faħam, rifampicin u omeprazole) jistgħu jżidu r- rata tat- tneħħija ta ’ riluzole.
RILUTEK is contraindicated (see section 4.3) in pregnancy (see section 5.3).
RILUTEK huwa kontra- indikat (ara sezzjoni 4. 3) waqt it- tqala (ara sezzjoni 5. 3).
Clinical experience with riluzole in pregnant women is lacking.
L- esperjenza klinika fuq l- użu ta ’ riluzole fit- tqala hija nieqsa.
RILUTEK is contraindicated (see section 4.3) in breast-feeding women (see section 5.3).
RILUTEK huwa kontra- indikat (ara sezzjoni 4. 3) waqt it- treddigħ (ara sezzjoni 5. 3).
It is not known whether riluzole is excreted in human milk.
Mhux magħruf jekk riluzole joħroġx fil- ħalibtal- bniedem.
Patients should be warned about the potential for dizziness or vertigo, and advised not to drive or operate machinery if these symptoms occur.
Il- pazjenti għandhom ikunu mwissija fuq il- possibbiltà li jkollhom sturdamenti jew il- vertigo, u għandhom jingħataw il- parir biex la jsuqu u l- anqas iħaddmu makkinarju jekk iħossu dawn is- sintomi.
In phase III clinical studies conducted in ALS patients treated with riluzole, the most commonly reported adverse reactions were asthenia, nausea and abnormal liver function tests.
Fil- fażi III ta ’ l- istudji kliniċi magħmulin fuq pazjenti b’ ALS ittrattati b’ riluzole, r- reazzjonijiet avversi li kienu rrapurtati l- aktar kienu astenja, tqalligħ u riżultati abnormali fit- testijiet dwar il - funzjoni tal- fwied.
Undesirable effects ranked under headings of frequency are listed below, using 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/ 1,000), very rare (< 1/ 10,000), not known (cannot be estimated from the available data).
L- effetti mhux mixtieqa miġburin,, huma mniżżlin skond il- frekwenza tagħhom, skond din il - konvenzjoni: komuni ħafna (≥1/ 10), komuni (minn ≥1/ 100 sa < 1/ 10), mhux komuni (minn ≥1/ 1, 000 sa < 1/ 100), rari (minn ≥1/ 10, 000 sa < 1/ 1, 000), rari ħafna (< 1/ 10, 000), mhux magħruf (ma tistax tittieħed stima mid- data disponibbli).
Blood and the lymphatic system disorders Uncommon: anaemia Not known: severe neutropenia (see section 4.4)
Disturbi tad- demm u tas- sistema limfatika Mhux komuni: anemija Mhux magħruf: newtropenja severa (ara sezzjoni 4. 4)
Immune system disorders Uncommon: anaphylactoid reaction, angioedema
Disturbi fis- sistema immuni Mhux komuni: reazzjoni anafilojdi, angjoedema
Nervous system disorder Common: headache, dizziness, oral paraesthesia and somnolence
Disturbi fis- sistema nervuża Komuni: uġigħ ta ’ ras, sturdament, parasteżija tal- ħalq u ngħas
Cardiac disorders Common: tachycardia
Disturbi fil- qalb Komuni: takikardja
Gastrointestinal disorders Very common: nausea Common: diarrhoea, abdominal pain, vomiting Uncommon: pancreatitis
Disturbi gastro- intestinali Komuni ħafna: tqalligħ Komuni: dijarea, uġigħ addominali, rimettar Mhux komuni: pankreatite
Hepato-biliary disorders Very common: abnormal liver function tests*.
Disturbi fil- fwied u fil- marrara Komuni ħafna: riżultati abnormali fit- testijiet tal- funzjoni tal- fwied *.
Increased alanine aminotransferase usually appeared within 3 months after the start of therapy with riluzole; they were usually transient and levels returned to below twice the ULN after 2 to 6 months while treatment was continued.
Żieda fil- livell ta ’ alanine aminotransferase normalment tfaċċat fi żmien 3 xhur mill- bidu tat- terapija b’ riluzole; dawn normalment għaddew u l- livelli ġew anqas minn darbtejn il- ULN wara perijodu ta ’ minn 2 sa 6 xhur, waqt li tkompliet il- kura.
These increases could be associated with jaundice.
Dawn iż- żidiet setgħu kienu assoċjati mas- suffejra.
In patients (n=20) from clinical studies with increases in ALT to more than 5 times the ULN, treatment was discontinued and the levels returned to less than 2 times the ULN within 2 to 4 months in most cases (see section 4.4) Not known: hepatitis
Mhux magħruf: epatite
General disorders and administration site conditions Very common: asthenia Common: pain
Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata Komuni ħafna: astenja Komuni: uġigħ
* study data indicate that Asian patients may be more susceptible to liver function test abnormalities - 3.2% (194/ 5995) of Asian patients and 1.8% (100/ 5641) of Caucasian patients.
* Id- dejta ta ’ l- istudju tindika li l- pazjenti Asjatiċi jistgħu ikunu aktar suxxettibbli għar- riżultati abnormali fit- testijiet dwar il- funzjoni tal- fwied - 3. 2% (194/ 5995) f’ pazjenti Asjatiċi u 1. 8% (100/ 5641) ta’ pazjenti Kawkasi.
Neurological and psychiatric symptoms, acute toxic encephalopathy with stupor, coma, and methemoglobinemia have been observed in isolated cases.
Kienu rapportati sintomi newroloġiċi u psikjatriċi, enċefalopatija tossika akuta bi sturdament, koma u metemoglobinimja f’ każijiet iżolati.
In case of overdose, treatment is symptomatic and supportive.
4 F’ każ ta ’ doża eċċessiva, l- kura hija sintomatika u supportiva.
PHARMACOLOGICAL PROPERTIES
5 TAGĦRIF FARMAKOLOĠIKU
Pharmacotherapeutic group: other nervous system drugs, ATC code:
Kategorija farmakoterapewtika: mediċini oħra għas- sistema nervuża, Kodiċi ATC:
Although the pathogenesis of ALS is not completely elucidated, it is suggested that glutamate (the primary excitatory neurotransmitter in the central nervous system) plays a role for cell death in the disease.
Għalkemm il- mod kif tiżviluppa l- marda ALS mhux magħruf kompletament, hemm il- possibbiltà li glutamate (stimulant prinċipali newrotransmittur fis- sistema ċentrali nervuża) għandu rwol fil- mewt taċ- ċelluli f’ din il- marda.
Riluzole is proposed to act by inhibiting glutamate processes.
Huwa suġġerit li riluzole jaġixxi billi jinibixxi il- proċessi dipendenti fuq glutamate.
The mode of action is unclear.
Il- mod kif jaħdem mhux ċar.
In a trial, 155 patients were randomised to riluzole 100 mg/ day (50 mg twice daily) or placebo and were followed-up for 12 to 21 months.
Fi prova waħda, 155 pazjent kienu allokati mingħajr għażla biex jieħdu jew riluzole 100 mg/ jum (50 mg darbtejn kuljum) jew il- plaċebo u kienu sorveljati għal 12 sa 21 xahar.
Survival, as defined in the second paragraph of section 4.1, was significantly extended for patients who received riluzole as compared to patients who received placebo.
Is- sopravivenza, kif definita fit- tieni paragrafu ta ’ taqsima 4. 1, kienet itwal b’ mod sinifikanti għall- pazjenti li ħadu riluzole meta mqabbla ma ’ dawk li ħadu l- plaċebo.
The median survival time was 17.7 months versus 14.9 months for riluzole and placebo, respectively.
Iż- żmien medjan ta ’ sopravivenza kien ta ’ 17. 7 xhur kontra 14. 9 xhur għal riluzole u l- plaċebo, rispettivament.
In a dose-ranging trial, 959 patients with ALS were randomised to one of four treatment groups: riluzole 50, 100, 200 mg/ day, or placebo and were followed-up for 18 months.
Fi prova fejn kienet investigata l- firxa tad- dożaġġi, 959 pazjent bl- ALS tqassmu, mingħajr għażla, f’ wieħed minn erba ’ gruppi ta ’ kura: riluzole 50, 100, 200 mg/ jum, jew plaċebo u kienu segwiti għal 18- il xahar.
In patients treated with riluzole 100 mg/ day, survival was significantly higher compared to patients who received placebo.
F’ pazjenti ttrattati b’ riluzole 100 mg/ jum, is- sopravivenza kienet aktar b’ mod sinifikant meta mqabbla mal- pazjenti li rċevew il- plaċebo.
The effect of riluzole 50 mg/ day was not statistically significant compared to placebo and the effect of 200 mg/ day was essentially comparable to that of 100 mg/ day.
L- effett ta ’ riluzole 50 mg/ jum ma kienx statistikament sinifikanti meta mqabbel mal- plaċebo, u l- effett ta ’ 200 mg/ jum kien essenzjalment komparabbli ma ’ dak ta ’ 100 mg/ jum.
The median survival time approached 16.5 months versus 13.5 months for riluzole 100 mg/ day and placebo, respectively.
Iż- żmien medjan ta ’ sopravivenza laħaq is- 16. 5 xhur kontra it - 13. 5 xhur, għal riluzole 100 mg/ jum u l- paċebo, rispettivament.
In a parallel group study designed to assess the efficacy and safety of riluzole in patients at a late stage of the disease, survival time and motor function under riluzole did not differ significantly from that of placebo.
Fi studju maqsum fi tnejn, immexxija simultanjament, biex jassessja l- effikaċja u s- sigurtà ta ’ riluzole f’ pazjenti li kienu fi stadju avvanzat tal- marda, ż- żmien ta ’ sopravivenza u l- funzjoni tal- moviment tal - ġisem b’ riluzole ma wrewx differenza sinifikanti minn dawk bil- plaċebo.
In this study the majority of patients had a vital capacity less than 60%.
F’ dan l- istudju, l - maġġoranza tal- pazjenti kellhom kapaċità vitali ta ’ inqas minn 60%.
In a double-blind placebo-controlled trial designed to assess the efficacy and safety of riluzole in Japanese patients, 204 patients were randomised to riluzole 100 mg/ day (50 mg twice daily) or placebo and were followed-up for 18 months.
Fi studji ikkontrollati permezz tal- plaċebo, tat- tip double blind, li sar biex jassessja l- effikaċja u s - sigurtà ta ’ riluzole f’ pazjenti Ġappuniżi, 204 pazjent kienu mqassmin, mingħajr għażla, biex jieħdu jew riluzole 100 mg/ jum (50 mg darbtejn kuljum) jew il- plaċebo, u dawn kienu segwiti għal 18- il xahar.
In this study, the efficacy was assessed on inability to walk alone, loss of upper limb function, tracheostomy, need for artificial ventilation, gastric tube feeding or death.
F’ dan l- istudju, l- effikaċja kienet assessjata fuq l- inabbiltà li wieħed jimxi waħdu, it- telf tal - funzjoni tad- driegħ, it- trakeostomija, il- bżonn ta ’ ventilazzjoni artifiċjali, il- bżonn li jingħata l- ikel permezz ta ’ tubu fl- istonku, jew il- mewt.
Tracheostomy-free survival in patients treated with riluzole did not differ significantly from placebo.
Is- sopravivenza ta ’ dawk il- pazjenti li ma kellhomx it - trakeostomija u li kienu ttrattati b’ riluzole ma kenitx differenti b’ mod sinifikanti minn dawk li ħadu l - plaċebo.
However, the power of this study to detect differences between treatment groups was low.
Madankollu, s- saħħa ta ’ dan l- istudju biex juri d- differenzi bejn il- gruppi li ħadu trattament differenti kien wieħed baxx.
Meta-analysis including this study and those described above showed a less striking effect on survival for riluzole as compared to placebo although the differences remained statistically significant.
Il- meta- analiżi f’ dan l- istudju, u fl- oħrajn deskritti hawn fuq, uriet impatt inqas fuq is- sopravivenza b’ riluzole, meta mqabbla mal- plaċebo, għalkemm id- differenzi baqgħu statistikament sinifikanti.
The pharmacokinetics of riluzole have been evaluated in healthy male volunteers after single oral administration of 25 to 300 mg and after multiple-dose oral administration of 25 to 100 mg bid.
Il- komportament farmakokinetiku ta ’ riluzole kien evalwat f’ irġiel voluntiera u b’ saħħithom wara li ttieħdet doża waħda orali ta ’ 25 sa 300 mg, kif ukoll dożi multipli orali minn 25 mg sa 100 mg bid.
Plasma levels increase linearly with the dose and the pharmacokinetic profile is dose-independent.
Il - livelli fil- plażma żdiedu linearment skond id- doża, u l- komportament farmakokinetiku kien indipendenti mid- doża wżata.
With multiple dose administration (10 day-treatment at 50 mg riluzole bid), unchanged riluzole accumulates in plasma by about 2 fold and steady-state is reached in less than 5 days.
Fil- każ ta ’ dożi multipli (kura ta ’ 10 ijiem b’ doża ta ’ 50 mg riluzole bid), riluzole mhux mibdul akkumula fil- plażma b’ bejn wieħed u ieħor id- doppju u intlaħaq stat stabbli u miżmum f’ inqas minn 5 ijiem.
Riluzole is rapidly absorbed after oral administration with maximal plasma concentrations occurring within 60 to 90 minutes (Cmax = 173 ± 72 (sd) ng/ ml).
5 Assorbiment Riluzole huwa assorbit malajr wara t- teħid orali b’ konċentrazzjonijiet massimi fil- plażma li jintlaħqu f’ 60 sa 90 minuta (Cmax = 173 ± 72 (sd) ng/ ml).
About 90% of the dose is absorbed and the absolute bioavailability is 60 ± 18%.
Madwar 90% tad- doża kienet assorbita u l - biodisponibilta` assoluta kienet ta ’ 60 ± 18%.
5 The rate and extent of absorption is reduced when riluzole is administered with high-fat meals (decrease in Cmax of 44%, decrease in AUC of 17%).
Ir- rata u l- grad ta ’ assorbiment tnaqqsu meta riluzole ittieħed ma ’ ikliet li kellhom kontenut għoli ta ’ xaħam (tnaqqis f’ Cmax ta ’ 44%, tnaqqis fl- AUC ta ’ 17%).
Riluzole is extensively distributed throughout the body and has been shown to cross the blood brain barrier.
Tqassim Riluzole jitqassam estensivament fil- ġisem u ntwera li jaqsam il- barriera ta ’ bejn id- demm u l- moħħ.
The volume of distribution of riluzole is about 245 ± 69 l (3.4 l/ kg).
Il- volum ta ’ distribuzzjoni ta ’ riluzole kien ta ’ madwar 245 ± 69 l (3. 4 l/ kg).
Riluzole is about 97% protein bound and it binds mainly to serum albumin and to lipoproteins.
Riluzole huwa madwar 97% marbut mal- proteini u jintrabat l- aktar ma ’ l- albumina tas- serum mal- lipoproteini.
Unchanged riluzole is the main component in plasma and is extensively metabolised by cytochrome P450 and subsequent glucuronidation.
Metaboliżmu Riluzole mhux mibdul huwa s- sustanza prinċipali fil- plażma u huwa estensivament metaboliżżat minn ċitokromju P450 u permezz tal- glukoronidazzjoni sussegwenti.
In vitro studies using human liver preparations demonstrated that cytochrome P450 1A2 is the principal isoenzyme involved in the metabolism of riluzole.
Studji in vitro, fejn intużaw preparati mill- fwied tal- bniedem, urew li ċitokromju P450 1A2 huwa l- iżoenżima prinċipali involuta fil - metaboliżmu ta ’ riluzole.
The metabolites identified in urine are three phenolic derivatives, one ureido-derivative and unchanged riluzole.
Il- prodotti metaboliċi identifikati fl- awrina huma tliet phenolic derivatives, wieħed tat- tip ureido u riluzole mhux mibdul.
The primary metabolic pathway for riluzole is initial oxidation by cytochrome P450 1A2 producing N- hydroxy-riluzole (RPR112512), the major active metabolite of riluzole.
Il- passaġġ metaboliku prinċipali ta ’ riluzole huwa l- ossidazzjoni inizjali permezz ta ’ ċitokromju P450 1A2 li tipproduċi N- hydroxy- riluzole (RPR112512), il- prodott metaboliku prinċipali attiv ta ’ riluzole.
This metabolite is rapidly glucuronoconjugated to O- and N-glucuronides.
Dan il- prodott huwa mibdul malajr f’ O u N- glucuronides.
The elimination half-life ranges from 9 to 15 hours.
Tneħħija mill- ġisem Il- half- life ta ’ l- eliminazzjoni hija bejn 9 u 15- il siegħa.
Riluzole is eliminated mainly in the urine.
Riluzole huwa prinċipalment imneħħi fl - awrina.
The overall urinary excretion accounts for about 90% of the dose.
L- ammont kollu li jitneħħa fl- awrina huwa ta ’ madwar 90% tad- doża.
Glucuronides accounted for more than 85% of the metabolites in the urine.
Il- glucuronides jammontaw għall- aktar minn 85% tal- prodotti metaboliċi fl- awrina.
Only 2% of a riluzole dose was recovered unchanged in the urine.
2% biss tad- doża ta ’ riluzole kienet irkuprata mhux mibdula fl- awrina.
Patients with impaired renal function: there is no significant difference in pharmacokinetic parameters between patients with moderate or severe chronic renal insufficiency (creatinine clearance between 10 and 50 ml. min-1) and healthy volunteers after a single oral dose of 50 mg riluzole.
Pazjenti b’ indeboliment fil- funzjoni renali: ma kienx hemm differenza sinifikanti fil- parametri farmakokinetiċi bejn pazjenti b’ insuffiċjenza kronika renali ta ’ grad moderat, jew sever, (il- clearance tal- krejatinina bejn 10 u 50 ml fil- minuta- 1) meta mqabbla ma ’ voluntiera b’ saħħithom, wara doża waħda orali ta ’ 50 mg ta ’ riluzole.
Elderly: the pharmacokinetic parameters of riluzole after multiple dose administration (4.5 days of treatment at 50 mg riluzole bid) are not affected in the elderly (> 70 years).
Anzjani: il- parametri farmakokinetiċi ta ’ riluzole wara t- teħid ta ’ dożi multipli (4. 5 jiem ta ’ kura b’ 50 mg riluzole bid) ma kienux effetwati fl- anzjani (> 70 sena).
Patients with impaired hepatic function: the AUC of riluzole after a single oral dose of 50 mg increases by about 1.7 fold in patients with mild chronic liver insufficiency and by about 3 fold in patients with moderate chronic liver insufficiency.
Pazjenti b’ indeboliment fil- funzjoni tal- fwied: l- AUC ta ’ riluzole wara doża waħda orali ta ’ 50 mg tiżdied b’ madwar 1. 7 drabi f’ pazjenti li għandhom insuffiċjenza kronika ħafifa tal- fwied, u b’ madwar 3 darbiet f’ pazjenti li għandhom insuffiċjenza kronika moderata tal- fwied.
Race: a clinical study conducted to evaluate the pharmacokinetics of riluzole and its metabolite N- hydroxyriluzole following repeated oral administration twice daily for 8 days in 16 healthy Japanese and 16 Caucasian adult males showed in the Japanese group a lower exposure of riluzole (Cmax 0.85 [90% CI 0.68-1.08] and AUC inf.
Il- grupp Ġappuniż wera espożizzjoni anqas ta ’ riluzole (Cmax 0. 85 [90% CI 0. 68– 1. 08] u AUC inf.
0.88 [90% CI 0.69-1.13]) and similar exposure to the metabolite.
0. 88 [90% CI 0. 69- 1. 13] u espożizzjoni simili tal- prodott metaboliku.
The clinical significance of these results is not known.
Is- sinifikat kliniku ta ’ dawn ir- riżultati mhux magħruf.
Riluzole did not show any carcinogenicity potential in either rats or mice.
Riluzole ma weriex potenzjal li jikkawża l- kanċer, kemm fil- firien kif ukoll fil- ġrieden.
Standard tests for genotoxicity performed with riluzole were negative.
Testijiet standard għall- ġenotossiċita b’ riluzole kienu negattivi.
Tests on the major active metabolite of riluzole gave positive results in two in vitro tests.
Studji fuq il- prodott metaboliku principali u attiv ta ’ riluzole ta riżultati pożittivi f’ żewġ testijiet in vitro.
On the basis
L- ittestjar intensiv b’ seba ’
6 of these data, and taking into consideration the negative studies on the carcinogenesis of riluzole in the mouse and rat, the genotoxic effect of this metabolite is not considered to be of relevance in humans.
Fuq il- bażi ta ’ dan it- tagħrif, u wara li ttieħdu f’ konsiderazzjoni l- istudji negattivi fuq l - effett ta ’ riluzole biex jikkaguna l- kanċer fil- ġurdien u l- far, l- effett ġenotossiku ta ’ dan il- prodott metaboliku mhux meqjus li huwa rilevanti fil- bniedem.
Reductions in red blood cell parameters and/ or alterations in liver parameters were noted inconsistently in subacute and chronic toxicity studies in rats and monkeys.
Tnaqqis fil- parametri taċ- ċelluli ħomor tad- demm u/ jew tibdiliet fil- parametri tal- fwied kienu innotati b’ mod inkonsistenti fi studji dwar it- tossiċità, kemm subakuta kif ukoll kronika, fil- firien u x- xadini.
In dogs, haemolytic anaemia was observed.
Fil- klieb, l- anemija emolitika kienet innotata.
In a single toxicity study, the absence of corpora lutea was noted at a higher incidence in the ovary of treated compared to control female rats.
Fi studju wieħed dwar it- tossiċità, l- assenza tal- corpora lutea kienet ta ’ inċidenza ogħla fl- ovaji tal - firien femminili ttrattati, meta mqabbla ma ’ dawk li kienu fil- grupp tal- plaċebo.
This isolated finding was not noted in any other study or species.
Din is- sejba waħdanija ma kenitx innotata f’ ebda studju ieħor jew fi speċi oħra.
All these findings were noted at doses which were 2-10 times higher than the human dose of 100 mg/ day.
Dawn ir- reperti kollha kienu innotati f’ dożi li kienu minn 2 sa 10 darbiet akbar mid- doża ta ’ 100 mg/ jum li tingħata lill- bniedem.