qanastek/EMEA-V3 huggingface dataset:
Important information about some of the ingredients of DaTSCAN
Tagħrif importanti dwar xi wħud mis- sustanzi ta ’ DaTSCAN
When DaTSCAN is used, you are exposed to small amounts of radioactivity. his exposure is less than in some types of X-ray investigation.
Din l- espożizzjoni hija inqas minn ċerti tipi ta 'investigazzjoni bl- X- ray.
Your doctor will always consider the possible risks and benefits of DaTSCAN.
It- tabib tiegħek dejjem iqis ir- riskji u l - benifiċċji ta ’ DaTSCAN.
DaTSCAN contains alcohol (ethanol).
DaTSCAN fih l- alkoħol.
This is about the same as 5 ml beer, or 2 ml wine.
Kull doża fiha sa 197 mg ta ’ alkoħol. Dan hu ekwivalenti għal 5 ml ta ’ birra jew 2 ml inbid.
This is harmful for people with alcoholism, liver disease or epilepsy.
Dan hu ta ’ ħsara għal persuni li jbatu mill- alkoħoliżmu, il- mard tal- fwied jew l- epilessija.
Tell your doctor if any of these apply to you.
Għid lit- tabib tiegħek jekk dan japplika għalik.
HOW DaTSCAN IS USED
KIF GĦANDEK TUŻA DaTSCAN
Your doctor will decide the dose that is best for you.
It- tabib tiegħek ser jiddeċiedi liema doża hija l- aħjar għalik.
Before you receive DaTSCAN, your doctor will ask you to take some tablets or liquid that contain iodine.
Qabel ma tieħu DaTSCAN it- tabib tiegħek jgħidlek biex tieħu pilloli jew likwidu li jkun fih il- jodju.
These stop the radioactivity building-up in your thyroid gland.
Dawn iwaqqfu r- radjoattività milli takkumula fil- glandola tat- tirojde.
It is important that you take the tablets or liquid as the doctor tells you.
Huwa importanti li tieħu l- pilloli jew il- likwidu kif jgħidlek it- tabib.
DaTSCAN is given to you as an injection, usually into a vein in your arm.
DaTSCAN tingħatalek bħala injezzjoni, ġeneralment f’ xi vina fi driegħek.
A single injection is enough.
Injezzjoni waħda hija biżżejjed.
The camera pictures are usually taken 3 to 6 hours after the injection of DaTSCAN.
Ir- ritratti tal- kamera ġeneralment jittieħdu bejn 3 u 6 sigħat wara l- injezzjoni ta 'DaTSCAN.
If you get more DaTSCAN than you should
Jekk tieħu DaTSCAN aktar milli suppost:
Since DaTSCAN is given by a doctor under controlled conditions, it is unlikely that you will get an overdose.
Billi DaTSCAN jingħata mit- tabib f' kondizzjonijiet ikkontrollati, qajla hemm ċans li tingħata xi doża eċċessiva.
Your doctor will suggest that you drink plenty of fluids to help the body get rid of the medicine.
It- tabib tiegħek ser jissuġerixxilek li tixrob ħafna fluwidi biex iħaffef l - eliminazzjoni tal- mediċina minn ġismek.
You will need to be careful with the water (urine) that you pass - your doctor will tell you what to do.
Għandek toqgħod attent bl- ilma (l- awrina) li tgħaddi – it- tabib tiegħek ser jgħidlek x’ għandek tagħmel.
This is normal practice with medicines like DaTSCAN.
Din hija prattika normali b’ mediċini bħal DaTSCAN.
Any ioflupane (123I) which remains in your body will naturally lose its radioactivity.
Jekk jibqa 'ioflupane (123I) f' ġismek dan jitlef ir- radjoattivita` tiegħu b' mod naturali.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Jekk għandek aktar mistoqsijiet dwar l- użu ta ’ din il- mediċina, staqsi lit- tabib jew lill- ispiżjar tiegħek.
POSSIBLE SIDE-EFFECTS
EFFETTI SEKONDARJI LI JISTA ’ JKOLLU
Like all medicines, DaTSCAN can cause side effects, although not everybody gets them.
Bħal kull mediċina oħra, DaTSCAN jista ’ jkollu effetti sekondarji, għalkemm ma jidhrux fuq kulħadd.
Common side- effects (affecting less than 1 person in 10) are headache, dizziness (vertigo), increased appetite and a brief irritating feeling similar to ants crawling over your skin (formication).
Effetti sekondarji komuni (li jaffettwaw anqas minn persuna 1 f’ 10) huma l- uġigħ ta 'ras, vertigo (sturdament), żieda fl- aptit u sensazzjoni qasira ta ’ irritazzjoni bħal nemel mixjin fuq il- ġilda (formikazzjoni).
An uncommon side effect (affecting less than 1 person in 100) is intense pain on injection.
Effett sekondarju mhux komuni (li jaffettwa inqas minn persuna 1 f’ 100) hija uġigħ qawwi ma 'l- injezzjoni.
This has been reported among patients receiving DaTSCAN into a small vein.
Dan ġie rapportat fost pazjenti li jirċievu DatSCAN f' vini żgħar.
The amount of radioactivity in the body from DaTSCAN is very small.
22 L- ammont ta 'radjoattività fil- ġisem minn DaTSCAN huwa żgħir ħafna.
It will be passed out of the body in a few days without need for you to take special precautions.
Huwa jiġi eliminat mill- ġisem wara ftit jiem mingħajr il- bżonn li int tieħu xi prekawzjonijiet speċjali.
HOW DaTSCAN IS STORED
KIF TAĦŻEN DaTSCAN
• Keep out of the reach and sight of children. • Do not store above 25°C.
• Żommu fejn ma jintlaħaqx u ma jidhirx mit- tfal. • Taħżinx f' temperatura 'l fuq minn 25°C. • Tagħmlux fil- friża.
The product label includes the correct storage conditions and the expiry date for the batch.
It- tikketta tal- prodott tinkludi l- kondizzjonijiet xierqa għall- ħażna u d- data ta 'meta jiskadi l- lott tal- prodott.
Hospital staff will ensure that the product is stored and thrown away correctly and not used after the expiry date stated on the label.
L- istaff ta 'l- isptar jaċcertaw li l- prodott jinħażen u jintrema sew u li ma jintużax wara- data ta' skadenza dikjarata fuq it- tikketta.
What DaTSCAN contains
X’ fih DaTSCAN
• The active substance is ioflupane (123I). • The other ingredients are acetic acid, sodium acetate, ethanol and water for injections.
- Is- sustanzi l- oħra huma acetic acid, sodium acetate, ethanol u ilma għall- injezzjonijiet.
What DaTSCAN looks like and contents of the pack
Id- dehra tal- prodott u d- daqs tal- pakkett:
DaTSCAN is supplied as a single, colourless, 10 ml glass vial containing either: • 185 MBq (Megabecquerel – the unit in which radioactivity is measured) of the active substance ioflupane (123I) in 2.5 ml of a sterile solution for intravenous injection, or • 370 MBq of ioflupane (123I) in 5.0 ml of a sterile solution for intravenous injection.
DaTSCAN jiġi fi fjala waħda ta ’ 10ml mingħajr kulur li jkun fih jew: − 185 MBq (Megabecquerel – l- unità li biha titkejjel ir- radjuattività) tas- sustanza attiva ioflupane (123I) f' soluzzjoni sterili ta '2. 5 ml għall- injezzjoni fil- vina, jew − 370 MBq of ioflupane (123I) f' soluzzjoni sterili ta' 5. 0 ml għall- injezzjoni fil- vina.
Marketing Authorisation Holder and Manufacturer
Sid l- Awtorizazzjoni għall- kummerċ u l- Manifattur:
Marketing Authorisation Holder:
Sid l- Awtorizzazzjoni tal- Kummerċ:
For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
Għal kull tagħrif dwar dan il- prodott mediċinali, jekk jogħġbok għamel kuntatt mar - rappreżentant lokali tas- Sid ta ’ l- Awtorizzazzjoni għall- Kummerċ.
United Kingdom GE Healthcare Limited Amersham Place Little Chalfont HP7 9NA-UK Tel: +44 (0) 1494 54 40 00
25 United Kingdom GE Healthcare Limited Amersham Place Little Chalfont HP7 9NA- UK Tel: +44 (0) 1494 54 40 00
This leaflet was last approved in MM/ YYYY
Dan il- fuljett kien approvat l- aħħar f ’ {XX/ SSSS}
What is DepoCyte?
X’ inhu DepoCyte?
DepoCyte is a suspension for injection that contains 50 mg of the active substance, cytarabine.
DepoCyte hija sospensjoni għall- injezzjoni li fiha 50 mg ta ’ sustanza attiva cytarabine.
What is DepoCyte used for?
Għal x' hiex jintuża DepoCyte?
DepoCyte is used to treat lymphomatous meningitis: this is a condition where lymphoma tumour cells have spread to the spinal fluid and the membranes that surround the brain and spinal cord (meninges).
DepoCyte huwa wżat sabiex tiġi ttrattata l- meninġite limfatika: din hija kondizzjoni fejn iċ- ċelluli ta ’ tumur limfoma jkunu infirxu fil- likwidu tax- xewka tad- dahar u l- membrani ta ’ madwar il- moħħ u s - sinsla tad- dahar (meninġi).
DepoCyte helps control the symptoms of the disease.
DepoCyte jgħin fil- kontroll tas- sintomi tal- marda.
How is DepoCyte used?
Kif jintuża DeopCyte?
DepoCyte should only be given by a doctor who has experience in the use of anti-cancer medicines.
DepoCyte għandha tingħata biss minn tabib li għandu esperjenza fl- użu ta ’ mediċini antikarċeroġini.
DepoCyte is a ‘ depot’ injection (a type of injection where the medicine is prepared in such a way that it is absorbed by the body very slowly).
DepoCyte hija injezzjoni depot (tip ta ’ injezzjoni fejn il- mediċina hija preparata b’ mod li tiġi assorbita mill- ġisem bil- mod ħafna).
The medicine must be injected directly into the spinal fluid (intrathecal injection: injection into the space that surrounds the spinal cord and the brain).
Il- mediċina għandha tiġi injettata direttament fil- likwidu tax- xewka tad - dahar (injezzjoni intratekali: injezzjoni fl- ispazju li jdawwar is- sinsla tad- dahar u l- moħħ).
The patient should also receive a steroid medicine (dexamethasone) at the same time to help control some of the side effects of the medicine.
Il- pazjent għandu jirċievi wkoll mediċina sterojde (dexamethasone) fl- istess waqt sabiex jikkontrolla l- effetti mhux mixtieqa tal- mediċina.
DepoCyte is first given as a 50 mg injection every two weeks for the first 5 doses, followed by a further 50 mg dose 4 weeks later.
DepoCyte tingħata fil- bidu f’ injezzjoni ta ’ 50 mg kull ġimgħatejn għall- ewwel 5 dożi, segwiti minn doża ta ’ 50 mg oħra għall- 4 ġimgħat ta ’ wara.
This is then followed by maintenance doses of 50 mg every 4 weeks for a further 4 doses.
Dan huwa segwit minn dożi ta ’ żamma ta ’ 50 mg kull 4 ġimgħat għal 4 dożi oħrajn.
The dose can be decreased to 25 mg if the patient shows signs of neurotoxicity (such as headache, abnormal vision, or muscle weakness or pains).
Din id- doża tista ’ tiġi mnaqqsa għal 25 mg jekk il- pazjent juri sinjali ta ’ newrotiċità (bħal uġiegħ ta ’ ras, viżjoni mhux normali jew dgħjufija fil- muskoli jew uġiegħ).
How does DepoCyte work?
Kif jaħdem DepoCyte?
The active substance in DepoCyte, cytarabine (also known as ara-C), is an anti-cancer agent that has been used since the 1970s.
Is- sustanza attiva fid- DepoCyte, cytarabine (magħrufa wkoll bħala ara- C), hija aġent anti- karċeroġenu li ilu jintuża mis- snin sebgħin.
It is a cytotoxic (a medicine that kills cells that are dividing, such as cancer cells) that belongs to the groups of the anti-metabolites.
Hi ċitotossika (mediċina li toqtol iċ- ċelloli li jkunu qed jinqasmu bħaċ - ċelloli tal- kanċer) li jkunu parti mill- grupp ta ’ anti- metaboliti.
Cytarabine is an analogue of pyrimidine.
Cytarabine huwa analogu għal pyrimidine.
Pyrimidine is part of the genetic material of cells (DNA and RNA).
Pyrimidine hu parti mill- materjal ġenetiku taċ- ċelloli (DNA u RNA).
In the body, cytarabine takes the place of pyrimidine and interferes with the enzymes involved in the synthesis of DNA.
Fil- ġisem, cytarabine jieħu post il- pyrimidine u jinterferixxi ma ’ l- enzimi li jieħdu sehem fis- sintesi tad- DNA.
As a result, cytarabine inhibits growth of tumour cells and eventually kills them.
Minħabba f’ hekk, cytarabine jinibixxi t- tkabbir taċ- ċelloli tat- tumur u eventwalment joqtolhom.
In DepoCyte, cytarabine is in a special formulation: the active substance is contained in liposomes (small fatty particles) from which it is slowly released.
Fid- DepoCyte, cytarabine huwa f’ format speċjali: is- sustanza attiva tinsab fil- lipożomi (partiċelli xaħmin żgħir) minn fejn tiġi rilaxxata bil- mod il- mod.
(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 How has DepoCyte been studied?
(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 Kif ġie studjat DepoCyte?
The effects of DepoCyte were first tested in experimental models before being studied in humans.
L- effetti ta ’ DepoCyte għall- ewwel ġew ittestjati f’ mudelli sperimentali qabel ma ’ ġew studjati fil - bniedem.
The main study was carried out in 35 patients and compared the intrathecal administration of DepoCyte with that of a standard formulation of cytarabine.
L- istudju prinċipali sar fuq 35 pazjent u kkumpara l- amministrazzjoni intratekali tad- DepoCyte ma ’ dik tal- format standard tas- cytarabine.
The study measured how the patient responded to the treatment (no more cancer cells in the spinal fluid after treatment) and how their nerve disease (symptoms from their nervous system) progressed.
L- istudju kejjel ir- rispons ta ’ kif il- pazjent irrisponda għat - trattament (qtil taċ- ċelluli kanċeroġeni kollha fil- likwidu tax- xewka tad- dahar wara t- trattament) u kif il- marda tan- nervaturi tagħhom (sintomi mis- sistema tan- nervaturi tagħhom) tiggrava.
What benefit has DepoCyte shown during the studies?
Liema benefiċċju wera DepoCyte waqt l- istudji li ġew mwettqa?
13 of the 18 patients treated with DepoCyte responded to treatment as shown through elimination of cancer cells from their spinal fluid.
13 minn kull 18 – il pazjent trattat bid- DepoCyte irrisponda għat- trattament kif jidher mill - eliminazzjoni taċ- ċelloli kanċeroġeni mill- likwidu tax- xewka tad- dahar.
Among the 17 patients who received the standard formulation, 3 responded to treatment.
3 mis- 17 – il pazjent li rċevew it- trattament f’ format standard irrispondew għat- trattament.
However, there was no difference between the two medicines with regards to the time before the patient experienced a worsening of their nerve disease.
Minkejja dan, ma kienx hemm differenza bejn iż- żewġ mediċini rigward iż- żmien qabel ma ’ l- pazjenti esperjenzaw aggravazzjoni tal- marda tan - nervaturi tagħhom.
What is the risk associated with DepoCyte?
X’ inhu r- riskju assoċjat ma ’ DepoCyte?
The most common side effects (seen in between 1 in 10 and 1 in 4 treatment cycles) are headache, nausea (feeling sick), vomiting, fever, and back pain.
L- aktar effetti sekondarji komuni fil- pazjenti (kif muri f’ 1 minn 10 f’ ċikli ta ’ 1 minn kull 4 trattamenti) huma uġiegħ ta ’ ras, tqalligħ (tħossok ma tiflaħx), remettar, deni u uġiegħ fid- dahar.
DepoCyte can cause arachnoiditis (an inflammation of the arachnoid, one of the membranes protecting the spine and the brain).
DepoCyte jista ’ jikkawża arachnoiditis (infjammazzjoni tal- arachnoid, waħda mill- membrani li tipproteġi x- xewka tad- dahar u l- moħħ).
To minimise these side effects, patients should receive a steroid (either orally or by injection) at the same time as the DepoCyte injection and they must also be closely monitored.
Il- pazjenti għandhom jirċievu sterojdi sabiex jitnaqqsu l - effetti sekondarji (jew oralment jew b’ injezzjoni) fl- istess waqt li l- injezzjoni tad- DepoCyte u għandhom jiġu monitorjati mill- qrib ukoll.
For the full list of all side effects reported with DepoCyte, see the Package Leaflet.
Għal- lista sħiħa ta 'l- effetti sekondarji rrapportati tad - DepoCyte, ara l- Fuljett ta' Tagħrif.
DepoCyte should not be given to people who may be hypersensitive (allergic) to cytarabine or any other ingredient.
DepoCyte m’ għandux jingħata lil nies li jistgħu jkunu ipersensittivi (allerġiċi) għas- cytarabine jew xi ingredjent ieħor.
It should not be used in patients who have an active infection of the meninges.
M’ għandux jintuża f’ pazjenti li għandhom infezzjoni tal- meninġi attiva.
Why has DepoCyte been approved?
Għaliex ġie approvat DepoCyte?
The Committee for Medicinal Products for Human use (CHMP) concluded that DepoCyte has shown effectiveness in lymphomatous meningitis when compared with the standard formulation of cytarabine, and that its administration schedule, with fewer intrathecal injections, can be of benefit to the patient ’ s quality of life.
Il- Kumitat għall- Prodotti Mediċinali għall- Użu mill- Bniedem (CHMP) ikkonkluda li d- DepoCyte wera li huwa effettiv f’ meninġite limfomatika meta kumparat mal- format standard tas- cytarabine, u l - iskeda ta ’ l- amministrazzjoni tiegħu, b’ anqas injezzjonijiet intratekali tista ’ tkun benefika għal kwalità tal- ħajja tal- pazjent.
They concluded that DepoCyte’ s benefits outweigh its risks and recommended that the medicine be given marketing authorisation.
Huma kkonkludew li l- effetti tad- DepoCyte huma akbar mir- riskji u jirrakkommandaw li din il- mediċina tingħata awtorizzazzjoni għat- tqegħid fis- suq.
Other information about DepoCyte:
Informazzjoni oħra dwar DepoCyte:
The European Commission granted a marketing authorisation valid throughout the European Union, for DepoCyte on 11 July 2001.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fuq is- suq madwar l- Unjoni Ewropea, għal DepoCyte fil- 11 ta ’ Lulju 2001.
The marketing authorisation was renewed on 11 July 2006.
L- awtorizzazzjoni għat- tqegħid fis- suq ġiet mġedda fil- 11 ta ’ Lulju 2006.
The marketing authorisation holder is Pacira Limited
Is- sid ta ’ l- awtorizzazzjoni għat- tqegħid fis- suq huwa Pacira Limited.
The full EPAR for DepoCyte can be found here.
L- EPAR sħiħ għal DepoCyte jista ’ jinstab hawnhekk
This summary was last updated in 07-2007.
Dan is- sommarju kien aġġornat l- aħħar f’ 07- 2007.
ANNEX 1
ANNESS I
DepoCyte 50 mg suspension for injection
DepoCyte 50 mg suspensjoni għall- injezzjoni
Each 5 ml vial contains 50 mg cytarabine (10 mg/ ml).
Kull kunjett ta ’ 5 ml fih 50 mg ta ’ cytarabine (10 mg/ ml).
For a full list of excipients, see section 6.1.
Għal lista sħiħa ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1.
A white to off-white suspension for injection.
Suspensjoni għall- injezzjoni ta ’ lewn abjad sa offwajt.
Intrathecal treatment of lymphomatous meningitis.
Trattament ġot- teka ta ’ meninġite limfomatuża.
In the majority of patients such treatment will be part of symptomatic palliation of the disease.
Fil- biċċa l- kbira tal- pazjenti trattament bħal dan ikun parti minn taffija sintomatika tal- marda.
DepoCyte should be administered only under the supervision of a physician experienced in the use of cancer chemotherapeutic agents.
DepoCyte għandu jingħata biss taħt is- superviżjoni ta ’ tabib b’ esperjenza fl- użu ta ’ mediċini kimoterapewtiċi tal- kanċer.
Adults and the elderly
Adulti u l- anzjani
For the treatment of lymphomatous meningitis, the dose for adults is 50 mg (one vial) administered intrathecally (lumbar puncture or intraventricularly via an Ommaya reservoir).
Għat- trattament ta ’ meninġite limfomatuża, id- doża għall- adulti hi ta ’ 50 mg (kunjett wieħed) mogħti minn ġot- teka (tneħħija tal- likwidu mill- bażi tas- sinsla permezz ta ’ labra tas- siringa jew intraventrikularment permezz tal- ħażna ta ’ Ommaya).
The following regimen of induction, consolidation and maintenance therapy is recommended:
Il- kors tal- bidu, tal- konsolidazzjoni u tal - manteniment tat- terapija li jidher hawn taħt hu rakkomandat:
Induction therapy:
Terapija tal- bidu:
50 mg administered every 14 days for 2 doses (weeks 1 and 3).
50 mg mogħtija kull 14- il jum għal 2 dożi (ġimgħa 1 u 3).
Consolidation therapy:
Terapija ta ’ konsolidazzjoni:
50 mg administered every 14 days for 3 doses (weeks 5, 7 and 9) followed by an additional dose of 50 mg at week 13.
50 mg mogħtija kull 14- il jum għal 3 dożi (ġimgħat 5, 7 u 9) segwiti minn doża addizzjonali ta ’ 50 mg f’ ġimgħa 13.
Maintenance therapy:
Terapija ta ’ manteniment:
50 mg administered every 28 days for 4 doses (weeks 17, 21, 25 and 29).
50 mg mogħtija kull 28 jum għal 4 dożi (ġimgħat 17, 21, 25 u 29).
Method of administration:
Kif jingħata:
DepoCyte is to be administered by slow injection over a period of 1-5 minutes directly into the cerebrospinal fluid (CSF) via either an intraventricular reservoir or by direct injection into the lumbar sac.
DepoCyte għandu jingħata b’ injezzjoni bil- mod fuq perjodu ta ’ 1- 5 minuti direttament fil - fluwidu ċerebrospinali (CSF) jew permezz ta ’ ħażna intraventrikulari jew b’ injezzjoni diretta ġor - rita tal- bażi tas- sinsla.
Following administration by lumbar puncture, it is recommended that the patient should be instructed to lie flat for one hour.
Wara l- għoti b’ titqiba fil- bażi tas- sinsla, huwa rakkomandat li l- pazjent għandu jingħata struzzjonijiet biex jimtedd għal siegħa.
Patients should be started on dexamethasone 4 mg twice daily orally or intravenously for 5 days beginning on the day of injection of DepoCyte.
Il- pazjenti għandhom jinbdew fuq 4 mg ta ’ dexamethasone darbtejn kuljum mill- ħalq jew ġol- vina għal 5 ijiem li jibdew fil- jum ta ’ l- injezzjoni ta ’ DepoCyte.
DepoCyte must not be administered by any other route of administration.
DepoCyte m’ għandux jingħata minn xi post ieħor ta ’ l- għoti.
DepoCyte must be used as supplied; do not dilute (see section 6.2).
DepoCyte għandu jintuża kif ipprovdut; tiddilwix (ara sezzjoni 6. 2).
Patients should be observed by the physician for immediate toxic reactions.
Il- pazjenti għandhom ikunu osservati mit- tabib għal reazzjonijiet tossiċi immedjati.
If neurotoxicity develops, the dose should be reduced to 25 mg.
2 Jekk tiżviluppa newrotossiċità, id- doża għandha titnaqqas għal 25 mg.
If it persists, treatment with DepoCyte should be discontinued.
Jekk tippersisti, it- trattament b’ DepoCyte għandu jitwaqqaf.
2 Children and adolescents
Tfal u adoloxxenti
Safety and efficacy in children have not been adequately demonstrated (see section 5.1).
Is- sigurtà u l- effikaċja fit- tfal ma ġietx ippruvata b’ mod adegwat (ara sezzjoni 5. 1).
DepoCyte is not recommended for use in children and adolescents until further data become available.
DepoCyte mhuwiex irrakkomandat biex jintuża fit- tfal u adoloxxenti sakemm aktar tagħrif ikun disponibbli.
Patients with active meningeal infection.
Pazjenti b’ infezzjoni meninġeali attiva.
Patients receiving DepoCyte should be concurrently treated with corticosteroids (e. g. dexamethasone) to mitigate the symptoms of arachnoiditis (see section 4.8), which is a common adverse reaction.
(eż. dexamethasone) biex jittaffew is- sintomi ta ’ l- araknojdite (ara sezzjoni 4. 8), li hi reazzjoni avversa komuni.
Arachnoiditis is a syndrome manifested primarily by nausea, vomiting, headache and fever.
L- araknojdite hi sindrome li tintwera primarjament permezz tad- dardir, rimettar, uġigħ ta ’ ras u deni.
If left untreated, chemical arachnoiditis may be fatal.
Jekk ma tiġix ittrattata, l- araknojdite kimika tista ’ tkun fatali.
Patients should be informed about the expected adverse reactions of headache, nausea, vomiting and fever, and about the early signs and symptoms of neurotoxicity.
Il- pazjenti għandhom ikunu infurmati dwar ir- reazzjonijiet avversi mistennija ta ’ uġigħ ta ’ ras, dardir, rimettar u deni, u dwar is- sinjali bikrija u s- sintomi tan- newrotossiċità.
The importance of concurrent dexamethasone administration should be emphasised at the initiation of each cycle of DepoCyte treatment.
L- importanza ta ’ l- għoti flimkien ma ’ dexamethasone għandha tkun enfasizzata fil- bidu ta ’ kull ċiklu ta ’ trattament b’ DepoCyte.
Patients should be instructed to seek medical attention if signs or symptoms of neurotoxicity develop, or if oral dexamethasone is not well tolerated.
Il- pazjenti għandhom jingħataw parir biex jitolbu għajnuna medika jekk sinjali jew sintomi ta ’ newrotossiċità jiżviluppaw, jew jekk dexamethasone li jittieħed mill- ħalq ma jkunx ittollerat sew.
Cytarabine, when administered intrathecally, has been associated with nausea, vomiting and serious central nervous system toxicity including blindness, myelopathy and other neurological toxicity sometimes leading to a permanent neurological deficit.
Cytarabine, meta mogħti minn ġot- teka, kien assoċjat ma ’ dardir, rimettar, u tossiċità serja tas- sistema nervuża ċentrali li mjelopatija u tossiċità newroloġika oħra li kultant iwasslu għal żbilanċ newroloġiku permanenti.
Administration of DepoCyte in combination with other neurotoxic chemotherapeutic agents or with cranial/ spinal irradiation may increase the risk of neurotoxicity.
L- għoti flimkien ta ’ DepoCyte ma ’ mediċini kimoterapewtiċi newrotossiċi oħrajn jew ma ’ irradjazzjoni kranjali/ tas- sinsla tad- dahar jista ’ jżid ir- riskju ta ’ newrotossiċità.
Infectious meningitis may be associated with intrathecal administration.
Meninġite infettiva tista ’ tkun assoċjata ma ’ l- għoti ġot- teka.
Hydrocephalus has also been reported, possibly precipitated by arachnoiditis.
L- idroċefalu kien irrappurtat ukoll, possibbilment ikkawżat mill- araknojdite.
Blockage of CSF flow may result in increased free cytarabine concentrations in the CSF with increased risk of neurotoxicity.
L- imblukkar tat- tnixxija ta ’ CSF jista ’ jirriżulta f’ żieda f’ konċentrazzjonijiet ta ’ cytarabine ħieles f ’ - CSF b’ riskju miżjud ta ’ newrotossiċità.
Although significant systemic exposure to free cytarabine is not expected following intrathecal treatment, some effects on bone marrow function cannot be excluded.
Għalkemm espożizzjoni sistemika sinifikantib’ mod sinifikattiv għal cytarabine ħieles ma tkunx mistennija wara trattament ġot- teka, xi effetti fuq il- funzjoni tal- mudullun ma jistgħux ikunu esklużi.
Systemic toxicity due to intravenous administration of cytarabine consists primarily of bone marrow suppression with leucopenia, thrombocytopenia and anaemia.
Tossiċità sistemika minħabba l- għoti minn ġol- vina ta ’ cytarabine tikkonsisti primarjament mit- trażżin tal- mudullun bil- lewkopenja, tromboċitopenja u anemija.
Therefore monitoring of the haemopoietic system is advised.
Għalhekk il- monitoraġġ tas- sistema emopojetika huwa meħtieġ.
Anaphylactic reactions following intravenous administration of free cytarabine have been rarely reported.
Reazzjonijiet anafilattiċi wara l- għoti minn ġol- vina ta ’ cytarabine libera rarament kienu rrappurtati.
Since DepoCyte’ s particles are similar in size and appearance to white blood cells, care must be taken in interpreting CSF examination following DepoCyte administration.
Billi l- partikuli ta ’ DepoCyte huma simili fid- daqs u fid- dehra għaċ- ċelluli bojod tad- demm, attenzjoni għandha tingħata fl- interpretazzjoni ta ’ l- eżami tas- CSF wara l- għoti ta ’ DepoCyte.
No definite interactions between DepoCyte delivered intrathecally and other medicinal products have been established.
L- ebda interazzjonijiet definiti bejn DepoCyte mogħti minn ġot- teka u prodotti mediċinali oħrajn ma kienu stabbiliti.
3 Concomitant administration of DepoCyte with other antineoplastic agents administered by the intrathecal route has not been studied.
L- għoti flimkien ta ’ DepoCyte ma ’ mediċini anti- neoplastiċi oħrajn mogħtija minn ġot- teka ma kienx studjat.
Intrathecal co-administration of cytarabine with other cytotoxic agents may increase the risk of neurotoxicity.
L- għoti ġot- teka ta ’ cytarabine flimkien ma ’ mediċini ċitotossiċi oħrajn jista ’ jżid ir- riskju ta ’ newrotossiċità.
Teratology studies in animals have not been conducted with DepoCyte and there are no adequate and well controlled studies in pregnant women; however cytarabine can cause foetal harm when administered during pregnancy.
Studji dwar it- teratoloġija fl- annimali ma sarux b’ DepoCyte u m’ hemmx studji adegwati u kkontrollati tajjeb f’ nisa tqal; madankollu, cytarabine jista ’ jikkaġuna ħsara lill- fetu meta jingħata waqt it- tqala.
Therefore, women of childbearing potential should not receive the treatment until pregnancy is excluded and should be advised to use a reliable contraceptive method.
Għalhekk, nisa li potenzjalment jista ’ jkollhom it- tfal m’ għandhomx jirċievu t- trattament sakemm it - tqala tkun eskluża u għandhom jingħataw il- parir biex jużaw metodu ta ’ kontraċezzjoni li tista ’ torbot fuqu.
Given that cytarabine has a mutagenic potential which could induce chromosomal damage in the human spermatozoa, males undergoing DepoCyte treatment and their partner should be advised to use a reliable contraceptive method.
Billi cytarabine għandha potenzjal mutaġeniku li jista jikkaġuna ħsara fil- kromosomi fl- isperma umana, irġiel li qed jirċievu t- trattament b’ DepoCyte u s- sieħba tagħhom għandhom jingħataw il- parir biex jużaw metodu ta ’ kontraċezzjoni li tista ’ torbot fuqu.
It is not known whether cytarabine is excreted in human milk following intrathecal administration.
Mhuwiex magħruf jekk cytarabine joħroġhix imneħħija fil- ħalib tal- bniedem wara l- għoti ġot- teka.
The systemic exposure to free cytarabine following intrathecal treatment with DepoCyte was negligible.
L - espożizzjoni sistemika għal cytarabine ħieles wara trattament ġot- teka b’ DepoCyte kienet negliġibbli.
Because of possible excretion in human milk and because of the potential for serious adverse reactions in nursing infants, the use of DepoCyte is not recommended in breast-feeding women.
Minħabba t- tneħħija possibbli fil- ħalib uman u minħabba l- potenzjal għal reazzjonijiet avversi serji fit - trabi li jkunu qed jerdgħu, l- użu ta ’ DepoCyte mhuwiex rakkomandat f’ nisa li qed ireddgħu.
There have been no reports explicitly relating to effects of DepoCyte treatment on the ability to drive or use machines.
Ma kien hemm l- ebda rapporti li espliċitament għamlu konnessjoni bejn l- effetti tat- trattament b’ DepoCyte u l- ħila biex issuq u tħaddem il- magni.
However, on the basis of reported adverse reactions, patients should be advised against driving or using machines during treatment.
Madankollu, fuq il- bażi ta ’ reazzjonijiet avversi rrappurtati, il- pazjenti għandhom jingħataw parir biex ma jsuqux u ma jużawx magni waqt it - trattament.
DepoCyte has the potential of producing serious toxicity.
DepoCyte għandu l- potenzjal li jipproduċi tossiċità serja.
All patients receiving DepoCyte should be treated concurrently with corticosteroids (e. g., dexamethasone) to mitigate the symptoms of arachnoiditis.
Il- pazjenti kollha li qed jirċievu DepoCyte għandhom ikunu ttrattati fl- istess ħin bil- kortikosterojdi (eż. dexamethasone) biex is- sintomi ta ’ l- araknojdite jittaffew.
Toxic effects may be related to a single dose or to cumulative doses.
Effetti tossiċi jistgħu jkunu marbuta ma ’ doża waħda jew ma ’ dożi kumulattivi.
Because toxic effects can occur at any time during therapy (although they are most likely within 5 days of administration), patients receiving DepoCyte therapy should be monitored continuously for the development of neurotoxicity.
Minħabba li effetti tossiċi jistgħu jseħħu fi kwalunkwe ħin waqt it- terapija (għalkemm li x’ aktarx li jseħħu l- aktar sa 5 ijiem mill- għoti), pazjenti li qed jirċievu t - terapija b’ DepoCyte għandhom ikunu mmonitorjati l- ħin kollu għall- iżvilupp ta ’ newrotossiċità.
If patients develop neurotoxicity, subsequent doses of DepoCyte should be reduced, and DepoCyte should be discontinued if toxicity persists.
Jekk il- pazjenti jiżviluppaw newrotossiċità, dożi sussegwenti ta ’ DepoCyte għandhom jitnaqqsu, u DepoCyte għandu jitwaqqaf jekk it- tossiċità tippersisti.
Arachnoiditis, a syndrome manifested primarily by headache, nausea, vomiting, fever, neck rigidity, neck or back pain, meningism, convulsions, hydrocephalus, CSF pleocytosis, with or without altered state of consciousness, is a common adverse reaction.
L- araknojdite, sindrome li tintwera primarjament permezz ta ’ uġigħ ta ’ ras, dardir, rimettar, deni, ebusija ta ’ l- għonq, uġigħ ta ’ l- għonq jew uġigħ tad- dahar, meninġiżmu, konvulżjonijiet, idroċefalu, plewċitożi tas- CSF, bi jew mingħajr stat mibdul ta ’ koxjenza, hi reazzjoni avversa komuni.
Arachnoiditis can be fatal if left untreated.
L - araknojdite tista ’ tkun fatali jekk ma tkunx ittrattata.
The incidence of adverse reactions possibly reflecting meningeal irritation determined from all the patients treated with 50 mg DepoCyte in the Phase II-IV clinical trials is given in Table 1 below:
4 L- inċidenza ta ’ reazzjonijiet avversi li possibbilment jirriflettu irritazzjoni meninġeali ddeterminata mill- pazjenti kollha li ngħataw 50 mg ta ’ DepoCyte fil- provi kliniċi ta ’ Fażi II- IV hi mogħtija f’ Tabella 1 hawn taħt:
4 Table 1:
Tabella 1:
Adverse reactions possibly reflecting meningeal irritation in Phase II, III, and IV patients (n [%] of cycles* of therapy)
Reazzjonijiet avversi li possibbilment jirriflettu irritazzjoni meninġeali fil - pazjenti ta ’ Fażi II, III u IV (n [%] ta ’ ċikli * ta ’ terapija)
MedDRA preferred term
Terminu ppreferut MedDRA
Headache NOS Nausea Vomiting NOS Arachnoiditis Pyrexia Back pain Convulsions NOS Neck pain Neck stiffness Hydrocephalus acquired CSF Pleocytosis Meningism
Uġigħ ta ’ ras mhux speċifiku Dardir Rimettar mhux speċifiku Araknojdite Deni Uġigħ fid- dahar Konvulżjonijiet mhux speċifiċi
(n = 929 cycles) 24% 18% 17% 16% 12% 7% 6% 4% 3% 2% 1% < 1%
(n = 929 ċikli) 24% 18% 17% 16% 12% 7% 6%
(n = 258 cycles) 16% 12% 11% 7% 7% 7% 5% 3% < 1% 1% 0% 1%
258 ċikli) 16% 12% 11% 7% 7% 7% 5%
(n =
(n = 99 ċikli) 14% 15% 11% 13% 16% 6% 2%
99 cycles) 14% 15% 11% 13% 16% 6% 2% 3% 4% 0% 0% 1%
3% 4% 0% 0% 1%
*Cycle length was 2 weeks during which the patient received either 1 dose of DepoCyte or 4 doses of cytarabine or methotrexate.
* It- tul taċ- ċiklu kien ta ’ ġimagħtejn li matulhom il- pazjent irċieva jew doża waħda ta ’ DepoCyte jew 4 dożi ta ’ cytarabine jew methotrexate.
Cytarabine and methotrexate patients not completing all 4 doses are counted as a fraction of a cycle.
Il- pazjenti fuq cytarabine jew methotrexate li ma jkomplux l- 4 dożi kollha huma magħduda bħala porzjon ta ’ ċiklu.
The incidence of all adverse reactions occurring in > 10% of cycles in either treatment group in Phase 1-4 studies in patients with lymphomatous meningitis receiving DepoCyte or cytarabine is given in Table 2 below:
L- inċidenza tar- reazzjonijiet avversi kollha li seħħew f ’ > 10% taċ- ċikli fi kwalunkwe grupp tat - trattament f’ pazjenti fl- istudji ta ’ Fażi 1- 4 b’ meninġite limfomatuża li kienu qed jirċievu DepoCyte jew cytarabine huma mogħtija f’ Tabella 2 hawn taħt:
Adverse reactions occurring in > 10% of cycles in either treatment group in Phase 1- 4 study patients with lymphomatous meningitis receiving DepoCyte 50 mg or cytarabine (% of cycles* of therapy) Number of cycles
Reazzjonijiet avversi li seħħew f ’ > 10% taċ- ċikli fi kwalunkwe grupp tat- trattament tal- pazjenti fl- istudju ta ’ Fażi 1- 4 b’ meninġite limfomatuża li kienu qed jirċievu 50 mg ta ’ DepoCyte jew cytarabine (% ta ’ ċikli * ta ’ terapija) Numru ta ’ ċikli
System Organ Class
Klassi ta ’ l- Organu tas- Sistema
MedDRA Preferred Term
Terminu ppreferut MedDRA
(n=151 cycles)
(n=151 ċikli)
(n=99 cycles)
(n=99 ċikli)
Nervous System Disorders
Disturbi tas- Sistema Nervuża
Headache NOS Arachnoiditis Confusion
Uġigħ ta ’ ras mhux speċifikat Araknojdite Konfużjoni
Gastrointestinal Disorders
Disturbi Gastrointestinali
Nausea Vomiting NOS Diarrhoea NOS
Dardir Rimettar mhux speċifiku Dijarrea mhux speċifika
General Disorders and Administrative Site Conditions
Disturbi Ġenerali u Kundizzjonijiet ta ’ Mnejn Jingħata
Weakness Pyrexia Fatigue
Dgħjufija Deni Għeja kbira
Blood and Lymphatic System Disorders
Disturbi tad- Demm u tas- Sistema Limfatika
Thrombocytopenia
Tromboċitopenja
*Induction and Maintenance cycle lengths were 2 and 4 weeks, respectively, during which the patient received either 1 dose of DepoCyte or 4 doses of cytarabine.
* It- tul taċ- Ċiklu tal- Bidu u tal- Manteniment kien ta ’ ġimagħtejn u 4 ġimgħat rispettivament, li matulhom il- pazjent irċieva jew doża waħda ta ’ DepoCyte jew 4 dożi ta ’ cytarabine.
Cytarabine patients not completing all 4 doses within a cycle are counted as a complete cycle.
Il- pazjenti fuq cytarabine li ma jkomplux l- 4 dożi kollha f’ ċiklu wieħed huma magħduda bħala ċiklu sħiħ.
Intrathecal administration of cytarabine may cause myelopathy and other neurologic toxicity sometimes leading to a permanent neurological deficit.
5 L- għoti ġot- teka ta ’ cytarabine jista ’ jikkawża mjelopatija u tossiċitajiet newroloġiċi oħra li kultant jistgħu jwasslu għal żbilanċ newroloġiku permanenti.
Following intrathecal administration of DepoCyte, serious central nervous system toxicity, including persistent extreme somnolence, confusion, hemiplegia, visual disturbances including blindness, deafness and cranial nerve palsies have been reported.
Wara l- għoti ġot- teka ta ’ DepoCyte, tossiċità serja tas- sistema nervuża ċentrali, li tinkludi ngħas persistenti estrem, konfużjoni, emipleġja, disturbi fil- vista li jinkludu l- għama, li wieħed jittarrax, u paralisi tan- nerv kranjali, kienu rrappurtati.
Symptoms and signs of peripheral neuropathy, such as pain, numbness, paresthesia, hypoaesthesia, weakness, and impaired bowel and bladder control (incontinence) have also been observed.
Sintomi u sinjali ta ’ newropatija periferali, bħal uġigħ, tirżiħ, parestesija, ipoestesija, dgħjufija, u indeboliment fil- kontroll ta ’ l- imsaren u tal- bużżieqa ta ’ l- awrina (inkontinenza) kienu wkoll osservati.
5 Adverse reactions more commonly associated with DepoCyte are headache, arachnoiditis and confusion.
Reazzjonijiet avversi li kienu aktar komunement assoċjati ma ’ DepoCyte huma l- uġigħ ta ’ ras, l - araknojdite u l- konfużjoni.
In addition, in Phase 1-4 studies, the patient incidence of convulsions was higher in the DepoCyte group (7/ 33, 21%) than in the cytarabine group (1/ 28, 4%).
Flimkien ma ’ dan, fl- istudji ta ’ Fażi 1- 4, l- inċidenza ta ’ pazjenti b’ konvulżjonijiet kienet ogħla fil- grupp ta ’ DepoCyte (7/ 33, 21%) milli fil- grupp ta ’ cytarabine (1/ 28, 4%).
Transient elevations in CSF protein and white blood cells have also been observed in patients following DepoCyte administration and also been noted after intrathecal treatment with methotrexate or cytarabine.
Elevazzjonijiet temporanji fil- proteina tas- CSF u fiċ- ċelluli bojod tad- demm kienu wkoll osservati f’ pazjenti wara l- għoti ta ’ DepoCyte u kienu nnutati wkoll wara trattament ġot- teka b’ methotrexate jew b’ cytarabine.
No overdoses with DepoCyte have been reported.
L- ebda każ ta ’ doża eċċessiva b’ DepoCyte ma ġie rrapurtat.
An overdose with DepoCyte may be associated with severe arachnoiditis including encephalopathy.
Doża eċċessiva b’ DepoCyte tista ’ tkun assoċjata ma ’ araknojdite serja li tinkludi l- enċefalopatija.
In an early uncontrolled study without dexamethasone prophylaxis, single doses up to 125 mg were administered.
Fi studju bikri mhux ikkontrollat mingħajr profilassi ta ’ dexamethasone, dożi waħidhom sa 125 mg kienu mogħtija.
One patient at the 125 mg dose level died of encephalopathy 36 hours after receiving DepoCyte intraventricularly.
Pazjent wieħed fil- livell tad- doża ta ’ 125 mg miet bl- enċefalopatija 36 siegħa wara li rċieva DepoCyte intraventrikularment.
This patient, however, was also receiving concomitant whole brain irradiation and had previously received intraventricular methotrexate.
Madankollu, dan il- pazjent kien qed jirċievi wkoll irradjazzjoni tal- moħħ kollu fl- istess ħin, u qabel kien irċieva methotrexate intraventrikulari.
There is no antidote for intrathecal DepoCyte or unencapsulated cytarabine released from DepoCyte.
M’ hemm l- ebda antidot għal DepoCyte mogħti ġot- teka jew għal cytarabine li mhux f’ kapsuli li tintreħa minn DepoCyte.
Exchange of cerebrospinal fluid with isotonic saline has been carried out in a case of intrathecal overdose of free cytarabine and such a procedure may be considered in the case of DepoCyte overdose.
Il- bdil ta ’ fluwidu ċerebrospinali ma ’ likwidu li fih il- melħ isotoniku sar f’ każ ta ’ doża eċċessiva ta ’ cytarabine ħieles ġot- teka, u proċedura bħal din tista ’ tkun ikkunsidrata f’ każ ta ’ doża eċċessiva ta ’ DepoCyte.
Management of overdose should be directed at maintaining vital functions.
L- immaniġġjar ta ’ doża eċċessiva għandu jkun immirat biex imantni l- funzjonijiet vitali.
DepoCyte is a sustained-release formulation of cytarabine, designed for direct administration into the cerebrospinal fluid (CSF).
DepoCyte huwa formulazzjoni ta ’ cytarabine li terħi l- mediċina b’ mod sostnut, magħmul għall- għoti dirett ġol- fluwidu ċerebrospinali (CSF).
Cytarabine is a cell-cycle phase specific antineoplastic agent, affecting cells only during the S-phase of cell division.
Cytarabine hi mediċina anti- neoplastika speċifika tal- fażi taċ- ċiklu taċ- ċellula, li taffettwa liċ- ċelluli biss waqt il- fażi S tad- diviżjoni taċ- ċellula.
Intracellularly, cytarabine is converted into cytarabine-5’ -triphosphate (ara-CTP), which is the active metabolite.
Fiċ- ċelluli, cytarabine tinbidel f’ cytarabine- 5 ’ - triphosphate (ara- CTP), li huwa l- metabolit attiv.
The mechanism of action is not completely understood, but it appears that ara-CTP acts primarily through inhibition of DNA synthesis.
Il- mekkaniżmu ta ’ l- azzjoni mhuwiex mifhum għal kollox, iżda jidher li ara- CTP jaġixxi primarjament permezz ta ’ l- inibizzjoni tas- sintesi ta ’ DNA.
Incorporation into DNA and RNA may also contribute to cytarabine cytotoxicity.
L - inkorporazzjoni f’ DNA u RNA tista ’ wkoll tikkontribwixxi għaċ- ċitotossiċità ta ’ cytarabine.
Cytarabine is cytotoxic to a wide variety of proliferating mammalian cells in culture.
Cytarabine hu ċitotossiċiku għal varjetà wiesgħa ta ’ ċelluli mammiferi li jkunu qed jikbru b’ mod mgħaġġel fil- koltura.
For cell-cycle phase specific antimetabolites the duration of exposure of neoplastic cells to cytotoxic concentrations is an important determination of drug efficacy.
Għal antimetaboliti speċifiċi tal- fażi taċ- ċiklu taċ- ċellula, it- tul ta ’ l- espożizzjoni taċ- ċelluli neoplastiċi għal konċentrazzjonijiet ċitossiċi hu determinazzjoni importanti ta ’ l- effikaċja tal- prodott mediċinali.
In vitro studies, examining more than 60 cell lines, demonstrated that the median cytarabine concentration resulting in 50% growth inhibition (IC50) was approximately 10 μ M (2.4 μ g/ ml) for two days of exposure and 0.1 μ M (0.024 μ g/ ml) for 6 days of exposure.
Studji in vitro, li eżaminaw aktar minn 60 razza ta ’ ċelluli, urew li l- medjan tal- konċentrazzjoni ta ’ cytarabine li irriżulta f’ inibizzjoni tat- tkabbir ta ’ 50% (IC50) kien ta ’ madwar 10 μM (2. 4 μg/ ml) għal jumejn ta ’ espożizzjoni, u ta ’ 0. 1 μM (0. 024 μg/ ml) għal 6 ijiem ta ’ espożizzjoni.
The studies also demonstrated susceptibility of many solid tumour cell lines to cytarabine, particularly after longer periods of exposure to cytarabine.
L- istudji wrew ukoll suxxettibbilità ta ’ ħafna razez ta ’ ċelluli ta ’ tumur solidu għal cytarabine, partikularment wara perijodi
In an open-label, active-controlled, multicentre clinical study, 35 patients with lymphomatous meningitis (with malignant cells found on CSF cytology) were randomised to intrathecal therapy with either DepoCyte (n=18) or unencapsulated cytarabine (n=17).
Fi studju kliniku open label, ikkontrollat attivatament, u multiċentriku, 35 pazjent b’ meninġite limfomatuża (b’ ċelluli malinni misjuba fiċ- ċitoloġija tas- CSF) kienu magħżula bl- addoċċ għat- terapija ġot- teka b’ DepoCyte (n=18) jew b’ cytarabine li mhux f’ kapsuli (n=17).
During the 1 month Induction phase of treatment, DepoCyte was administered intrathecally as 50 mg every 2 weeks, and unencapsulated cytarabine as 50 mg twice a week.
Matul ix- xahar tal- fażi tat - Trattament tal- Bidu, DepoCyte kien mogħti minn ġot- teka bħal 50 mg kull ġimgħatejn, u cytarabine li mhux f’ kapsuli bħal 50 mg darbtejn kull ġimgħa.
Patients who did not respond discontinued protocol treatment after 4 weeks.
Pazjenti li ma rrispondewx waqqfu t- trattament tal - protokoll wara 4 ġimgħat.
6 absence of progression of neurological symptoms) went on to receive Consolidation and Maintenance therapy for up to 29 weeks.
Pazjenti li rnexxielhom jirrispondu (ir- respons kien definit bħala l- ikklirjar tas- CSF ta ’ ċelluli malinni fin- nuqqas ta ’ progressjoni ta ’ sintomi newroloġiċi) komplew it- trattament u rċivew it- Terapija ta ’ Konsolidazzjoni u ta ’ Manteniment sa 29 ġimgħa.
Responses were observed in 13/ 18 (72%, 95% confidence intervals:
Responsi kienu osservati fi 13/ 18 (72%, 95% intervalli ta ’ kunfidenza:
47, 90) of DepoCyte patients versus 3/ 17 (18% patients, 95% confidence intervals:
47, 90) ta ’ pazjenti fuq DepoCyte kontra 3/ 17 (18% tal- pazjenti, 95% intervalli ta ’ kunfidenza:
4, 43) in the unencapsulated cytarabine arm.
4, 43) fil- parti ta ’ l- istudju b’ cytarabine li mhux f’ kapsuli.
A statistically significant association between treatment and response was observed (Fisher’ s exact test p-value = 0.002).
Assoċjazzjoni statistikament sinifikanti bejn it- trattament u r- respons kienet osservata (il- valur p tat- test eżatt ta ’ Fisher = 0. 002).
The majority of DepoCyte patients went on beyond Induction to receive additional therapy.
Il- maġġoranza tal- pazjenti fuq DepoCyte komplew it- trattament wara l- Fażi tal- Bidu u rċivew terapija addizzjonali.
DepoCyte patients received a median of 5 cycles (doses) per patient (range 1 to 10 doses) with a median time on therapy of 90 days (range 1 to 207 days).
Pazjenti fuq DepoCyte irċivew medjan ta ’ 5 ċikli (dożi) kull pazjent (medda ta ’ 1 sa 10 dożi) bi żmien medjan fuq it- terapija ta ’ 90 jum (medda ta ’ 1 sa 207 jiem).
No statistically significant differences were noted in secondary endpoints such as duration of response, progression-free survival, neurological signs and symptoms, Karnofsky performance status, quality of life and overall survival.
L- ebda differenzi statistikament sinifikanti ma kienu nnutati f’ endpoints sekondarji bħat- tul tar - respons, is- sopravivenza mingħajr progressjoni, is- sinjali u sintomi newroloġiċi, l- istat tal- prestazzjoni ta ’ Karnofsky, il- kwalità tal- ħajja u sopravivenza totali.
Median progression-free survival (defined as time to neurological progression or death) for all treated patients was 77 versus 48 days for DepoCyte versus unencapsulated cytarabine, respectively.
Il- medjan tas- sopravivenza mingħajr progressjoni (definit bħala ż- żmien għall- progressjoni newroloġika jew il- mewt) għall- pazjenti kollha ttrattati kien ta ’ 77 kontra 48 jum għal DepoCyte kontra cytarabine li mhux f’ kapsuli, rispettivament.
The proportion of patients alive at 12 months was 24% for DepoCyte versus 19% for unencapsulated cytarabine.
Il- proporzjon ta ’ pazjenti ħajjin wara 12- il xahar kien ta ’ 24% għal DepoCyte kontra 19% għal cytarabine li mhux f’ kapsuli.
In an open-label non-comparative dose escalation study in 18 paediatric patients (4 to 19 years) with leukaemic meningitis or neoplastic meningitis due to primary brain tumour, an intrathecal dose of 35 mg was identified as the maximum tolerated dose.
Fi studju eskalat open- label dwar doża mhux komparattiv fuq 18- il pazjent pedjatriku (bejn 4 sa 19- il sena) li kellhom il- meninġite lewkemika jew meninġite neoplastika minħabba tumur primarju fil - moħħ, doża ġot- teka ta ’ 35 mg kinet identifikata bħala d- doża massima ttolerata.
Analysis of the available pharmacokinetic data shows that following intrathecal DepoCyte administration in patients, either via the lumbar sac or by intraventricular reservoir, peaks of free cytarabine were observed within 5 hours in both the ventricle and lumbar sac.
Analiżi tat- tagħrif farmakokinetiku disponsibbli turi li wara l- għoti ta ’ DepoCyte ġot- teka fil- pazjenti, jew minn ġor- rita tal- bażi tas- sinsla jew minn ġol- ħażna intraventrikulari, l- ogħla ammonti ta ’ cytarabine ħieles kienu osservati sa 5 sigħat kemm fil- ventriklu u kemm fir- rita tal- bażi tas- sinsla.
These peaks were followed by a biphasic elimination profile consisting of an initial sharp decline and subsequent slow decline with a terminal phase half-life of 100 to 263 hours over a dose-range of 12.5 mg to 75 mg.
Dawn l- ogħla ammonti kienu segwiti minn profil ta ’ eliminazzjoni bifażika li tikkonsisti fi tnaqqis qawwi inizjali u tnaqqis sussegwenti bil- mod b’ half- life tal- fażi terminali ta ’ 100 sa 263 siegħa fuq medda ta ’ doża ta ’ 12. 5 mg sa 75 mg.
In contrast, intrathecal administration of 30 mg free cytarabine has shown a biphasic CSF concentration profile with a terminal phase half-life of about 3.4 hours.
B' kuntrast, l- għoti ġot- teka ta ’ 30 mg ta ’ cytarabine ħieles wera profil ta ’ konċentrazzjoni bifażiku tas- CSF b’ half- life tal- fażi terminali ta ’ madwar 3. 4 sigħat.