qanastek/EMEA-V3 huggingface dataset:
Pharmacokinetic parameters of DepoCyte (75 mg) in neoplastic meningitis patients in whom the drug was administered either intraventricularly or by lumbar puncture suggest that exposure to the drug in the ventricular or lumbar spaces is similar regardless of the route of administration.
Il- parametri farmakokinetiċi ta ’ DepoCyte (75 mg) f’ pazjenti b’ meninġite neoplastika li ngħataw il - prodott mediċinali intraventrikularment jew b’ titqiba fil- bażi tas- sinsla, jissuġġerixxu li l- espożizzjoni għall- prodott mediċinali fl- ispazji ventrikulari jew fil- bażi tas- sinsla hi simili mingħajr ma wieħed jagħti kas minn fejn jingħata.
In addition, compared with free cytarabine, the formulation increases the biological half-life by a factor of 27 to 71 depending upon the route of administration and the compartment sampled.
Flimkien ma ’ dan, meta mqabbla ma ’ cytarabine ħieles, il- formulazzjoni żżid il- half- life bijoloġika b’ fattur ta ’ 27 sa 71, li jiddependi fuq minn fejn jingħata u l- kumpartiment li minnu jittieħed il- kampjun.
Encapsulated cytarabine concentrations and the counts of the lipid particles in which the cytarabine is encapsulated in DepoCyte followed a similar distribution pattern.
Konċentrazzjonijiet ta ’ cytarabine inkapsulat u l- għadd tal- partikuli tal - lipidi li fihom cytarabine hu inkapsulat f’ DepoCyte, segwew mod ta ’ distribuzzjoni simili.
AUCs of free and encapsulated cytarabine after ventricular injection of DepoCyte appeared to increase linearly with increasing dose, indicating that the release of cytarabine from DepoCyte and the pharmacokinetics of cytarabine are linear in human CSF.
L- AUCs ta ’ cytarabine ħieles u inkapsulat wara injezzjoni ventrikulari ta ’ DepoCyte dehru li żdiedu b’ mod lineari ma ’ żjieda fid- doża, li jindika li l- ħruġ ta ’ cytarabine minn DepoCyte u l- farmakokinetiċità ta ’ cytarabine huma lineari fis- CSF uman.
The transfer rate of cytarabine from CSF to plasma is slow and the conversion to uracil arabinoside (ara-U), the inactive metabolite, in the plasma is fast.
Ir- rata ta ’ trasferiment ta ’ cytarabine mis- CSF għall- plażma hi bil- mod u l- bidla għal uracil arabinoside (ara- U), il- metabolit inattiv, fil- plażma hi mgħaġġla.
Systemic exposure to cytarabine was determined to be negligible following intrathecal administration of 50 mg and 75 mg of DepoCyte.
Kien iddeterminat li l- espożizzjoni sistemika għal cytarabine hi negliġibbli wara l- għoti ġot- teka ta ’ 50 mg u 75 mg ta ’ DepoCyte.
Metabolism and elimination The primary route of elimination of cytarabine is metabolism to the inactive compound ara-U, (1-β -D- arabinofuranosyluracil or uracil arabinoside) followed by urinary excretion of ara-U.
7 Metaboliżmu u eliminazzjoni Ir- rotta primarja ta ’ l- eliminazzjoni ta ’ cytarabine hi l- metaboliżmu għall- kompost inattiv ara- U, (1- β - D- arabinofuranosyluracil jew uracil arabinoside) segwit minn eskrezzjoni fl- awrina ta ’ ara- U.
In contrast with systemically administered cytarabine which is rapidly metabolised to ara-U, conversion to ara-U in the CSF is negligible after intrathecal administration because of the significantly lower cytidine deaminase activity in the CNS tissues and CSF.
B’ kuntrast ma ’ cytarabine mogħti sistemikament li hu metabolizzat malajr għal ara- U, il- bidla għal ara- U fis- CSF hi negliġibbli wara l- għoti ġot- teka minħabba l- attività mnaqqsa sinifikanti ta ’ cytidine deaminase fit- tessuti tas- CNS u s- CSF.
The CSF clearance rate of cytarabine is similar to the CSF bulk flow rate of 0.24 ml/ min.
Ir- rata ta ’ tneħħija tas- CSF ta ’ cytarabine hi simili għar- rata tat- tnixxija totali tas- CSF ta ’ 0. 24 ml/ min.
The distribution and clearance of cytarabine and of the predominant phospholipid component of the lipid particle (DOPC) following intrathecal administration of DepoCyte was evaluated in rodents.
Id- distribuzzjoni u t- tneħħija ta ’ cytarabine u tal- komponent fosfolipidu predominanti tal- partikula tal - lipidu (DOPC) wara l- għoti ġot- teka ta ’ DepoCyte kien evalwat f’ annimali gerriema.
More than
Radiolabels għal cytarabine u DOPC kienu distribwiti malajr f’ kull parti tan- newroassi.
7 90% of cytarabine was excreted by day 4 and an additional 2.7% by 21 days.
Iktar minn 90% ta ’ cytarabine tneħħa mil- ġisem sar- 4 jum u 2. 7% addizzjonali sal- 21 jum.
The results suggest that the lipid components undergo hydrolysis and are largely incorporated in the tissues following breakdown in the intrathecal space.
Ir- riżultati jissuġġerixxu li l- komponenti tal- lipidi jġarrbu idrolisi u fil- parti l- kbira jkunu inkorporati fit- tessuti wara t- tkissir tagħhom fl- ispazju intratekali.
A review of the toxicological data available for the constituent lipids (DOPC and DPPG) or similar phospholipids to those in DepoCyte indicates that such lipids are well tolerated in various animal species even when administered for prolonged periods at doses in the g/ kg range.
Reviżjoni tat- tagħrif tossikoloġiku disponibbli għal- lipidi kostitwenti (DOPC u DPPG) jew fosfolipidi simili għal dawk f’ DepoCyte tindika li lipidi bħal dawn huma ttollerati tajjeb fi speċi ta ’ annimali differenti anki meta jingħataw għall- perijodi twal ta ’ żmien f’ dożi fil- medda ta ’ g/ kg.
The results of acute and subacute toxicity studies performed in monkeys suggested that intrathecal DepoCyte was tolerated up to a dose of 10 mg (comparable to a human dose of 100 mg).
Ir- riżultati ta ’ studji dwar tossiċità akuta u subakuta li saru fuq ix- xadini ssuġġerixxew li DepoCyte ġot- teka kien ittolerat sa doża ta ’ 10 mg (komparabbli ma ’ doża fil- bniedem ta ’ 100 mg).
Slight to moderate inflammation of the meninges in the spinal cord and brain and/ or astrocytic activation were observed in animals receiving intrathecal DepoCyte.
Infjammazzjoni ħafifa sa moderata tal- meninġe fin- nerv qawwi li jgħaddi minn ġos- sinsla u fil- moħħ u/ jew attivazzjoni astroċitika kienu osservati f’ annimali li kienu qed jirċievu DepoCyte ġot- teka.
These changes were believed to be consistent with the toxic effects of other intrathecal agents such as unencapsulated cytarabine.
Huwa maħsub li dawn it- tibdiliet huma konsistenti ma ’ l- effetti tossiċi ta ’ sustanzi oħra mogħtija ġot - teka bħal cytarabine li mhux inkapsulat.
Similar changes (generally described as minimal to slight) were also observed in some animals receiving DepoFoam alone (DepoCyte vesicles without cytarabine) but not in saline control animals.
Tibdiliet simili (ġeneralment deskritti bħala minimali sa ħfief) kienu osservati wkoll f’ xi annimali li kienu qed jirċievu DepoFoam waħdu (bżieżaq żgħar ta ’ DepoCyte mingħajr cytarabine) imma mhux f’ annimali tal- kontroll tal- melħ.
Mouse, rat and dog studies have shown that free cytarabine is highly toxic for the haemopoietic system.
Studji fil- ġrieden, firien u klieb urew li cytarabine ħieles huwa tossikua b’ mod qawwi għas- sistema emopojetika.
No carcinogenicity, mutagenicity or impairment of fertility studies have been conducted with DepoCyte.
Ma saru l- ebda studji b’ DepoCyte dwar il- karċinoġeneċità, il- mutaġeniċità jew il- ħsara fil- fertilità.
The active ingredient of DepoCyte, cytarabine, was mutagenic in in vitro tests and was clastogenic in vitro (chromosome aberrations and sister chromatid exchange in human leukocytes) and in vivo (chromosome aberrations and sister chromatid exchange assay in rodent bone marrow, mouse micronucleus assay).
L - ingredjent attiv ta ’ DepoCyte, cytarabine, kien mutaġeniku f’ testijiet in vitro u kien klastoġeniku in vitro (aberrazzjonijiet tal- kromosomi u skambju tal- kromatid- oħt f’ lewkoċiti umani) u in vivo (aberrazzjonijiet tal- kromosomi u assay ta ’ l- iskambju tal- kromatid- oħt fil- mudullun ta ’ annimali gerriema, assay mikronuklejari tal- ġrieden).
Cytarabine caused the transformation of hamster embryo cells and rat H43 cells in vitro.
Cytarabine ikkawżat it- trasformazzjoni taċ- ċelluli ta ’ l - embriju tal- ħamster u taċ- ċelluli H43 tal- firien in vitro.
Cytarabine was clastogenic to meiotic cells; a dose-dependent increase in sperm-head abnormalities and chromosomal aberrations occurred in mice given i. p. cytarabine.
Cytarabine kien klastoġeniku għal ċelluli mejotiċi; żjieda li tiddependi mid- doża, ta ’ anormalitajiet fl- irjus ta ’ l- isperma u aberrazzjonijiet tal - kromosomi seħħet fil- ġrieden li ngħataw cytarabine i. p.
No studies assessing the impact of cytarabine on fertility are available in the literature.
M’ hemm l- ebda studji disponibbli fil - letteratura li jassessjaw l- impatt ta ’ cytarabine fuq il- fertilità.
Because the systemic exposure to free cytarabine following intrathecal treatment with DepoCyte was negligible, the risk of impaired fertility is likely to be low.
Minħabba li l- espożizzjoni sistemika għal cytarabine ħieles wara trattament ġot- teka b’ DepoCyte kienet negliġibbli, ir- riskju ta ’ ħsara fil - fertilità aktarx li jkun baxx.
Cholesterol Triolein Dioleoylphosphatidylcholine (DOPC) Dipalmitoylphosphatidylglycerol (DPPG) Sodium chloride Water for injections
Cholesterol Triolein Dioleoylphosphatidylcholine (DOPC) Dipalmitoylphosphatidylglycerol (DPPG) Sodium chloride Ilma ghall- injezzjonijiet
No formal assessments of pharmacokinetic drug-drug interactions between DepoCyte and other agents have been conducted.
Ma saru l- ebda evalwazzjonijiet formali dwar il- farmakokinetiċità ta ’ interazzjonijiet bejn DepoCyte u mediċini oħrajn.
DepoCyte should not be diluted or mixed with any other medicinal products, as any change in concentration or pH may affect the stability of the microparticles.
DepoCyte m’ għandux ikun dilwit jew imħallat ma ’ l- ebda prodott mediċinali ieħor, għax kwalunkwe bidla fil- konċentrazzjoni jew pH tista ’ taffettwa l- istabilità tal- mikropartikuli.
6.3 Shelf life
Żmien kemm idum tajjeb il- prodott mediċinali 6. 3
18 months
18- il xahar
Store in a refrigerator (2°C - 8°C).
Aħżen fil- friġġ (2oC - 8oC).
8 6.5 Nature and contents of container
In- natura tal- kontenitur u ta ’ dak li hemm ġo fih 6. 5
DepoCyte is supplied in individual cartons each containing one single-dose Type I glass vial containing 50 mg (in 5 ml), closed with a fluororesin faced butyl rubber stopper and sealed with an aluminium flip-off seal.
DepoCyte hu fornut f’ kartun individwali li kull waħda jkun fiha kunjett wieħed tal- ħġieġ ta ’ Tip I ta ’ doża waħda, li fih 50 mg (f’ 5 ml), magħluq b’ tapp tal- gomma butyl b’ wiċċ ta ’ fluororesin issiġillat b’ siġill li jinqala ’ ta ’ l- aluminju.
Preparation of DepoCyte
Preparazzjoni ta 'DepoCyte
Given its toxic nature, special precautions should be taken in handling DepoCyte.
Minħabba n- natura tossika tiegħu, prekawzjonijiet speċjali għandhom jittieħdu meta tuża DepoCyte.
See ‘ Precautions for the handling and disposal of DepoCyte’ below.
Ara ‘ Prekawzjonijiet dwar l- immaniġġjar u r- rimi ta ’ DepoCyte ’ hawn taħt.
Vials should be allowed to warm to room temperature (18°C -22°C) for a minimum of 30 minutes and be gently inverted to resuspend the particles immediately prior to withdrawal from the vial.
Il- kunjetti għandhom jitħallew jisħnu sat- temperatura tal- kamra (18°C - 22°C) għal mill- inqas 30 minuta u għandhom jinqalbu bil- mod biex il- partikuli jerġgħu jiffurmaw suspensjoni immedjatament qabel il- ġbid mill- kunjett.
Avoid vigorous shaking.
Evita ċaqliq bil- goff.
No further reconstitution or dilution is required.
L- ebda rikostituzzjoni addizzjonali jew dilwizzjoni ma huma meħtieġa.
DepoCyte administration
L- għoti ta ’ DepoCyte
DepoCyte must only be administered by the intrathecal route.
DepoCyte għandu jingħata biss minn ġot- teka.
DepoCyte should be withdrawn from the vial immediately before administration.
DepoCyte għandu jinġibed mill- kunjett immedjatament qabel l- għoti.
Since it is a single use vial and does not contain any preservative, the drug should be used within 4 hours of withdrawal from the vial.
Billi DepoCyte huwa kunjett li jintuża darba u ma fih l- ebda preservattiv, il- prodott mediċinali għandu jintuża sa 4 sigħat mill- ġbid mill- kunjett.
Unused drug must be discarded and not used subsequently.
Il- prodott mediċinali li ma jintużax għandu jintrema u ma jintużax sussegwentement.
Do not mix DepoCyte with any other medicinal products (see section 6.2).
Tħallatx DepoCyte ma ’ xi prodotti mediċinali oħra (ara sezzjoni 6. 2).
Do not dilute the suspension.
Tiddilwix is- suspensjoni.
In-line filters must not be used when administering DepoCyte.
Il- filtri in- line m’ għandhomx jintużaw waqt l- għoti ta ’ DepoCyte.
DepoCyte is administered directly into the CSF via an intraventricular reservoir or by direct injection into the lumbar sac.
DepoCyte jingħata direttament ġos - CSF mill- ħażna intraventrikulari jew b’ injezzjoni diretta ġor- rita tal- bażi tas- sinsla.
DepoCyte should be injected slowly over a period of 1-5 minutes.
DepoCyte għandu jkun injettat bil- mod matul perijodu ta ’ 1- 5 minuti.
Following drug administration by lumbar puncture, the patient should be instructed to lie flat for one hour.
Wara l- għoti tal- prodott mediċinali b’ titqiba fil - bażi tas- sinsla, il- pazjent għandu jingħata istruzzjonijiet biex jimtedd għal siegħa.
Patients should be started on corticosteroids (e. g. dexamethasone 4 mg twice daily either orally or intravenously) for 5 days beginning on the day of DepoCyte injection.
4 mg ta ’ dexamethasone darbtejn kuljum mill - ħalq jew ġol- vina) għal 5 ijiem li jibdew fil- jum ta ’ l- injezzjoni ta ’ DepoCyte.
Precautions for the handling and disposal of DepoCyte
Prekawzjonijiet dwar l- immaniġġjar u r- rimi ta ’ DepoCyte
The following protective recommendations are given due to the toxic nature of this substance: • personnel should be trained in good technique for handling anticancer agents • male and female staff who are trying to conceive and female staff who are pregnant should be excluded from working with the substance • personnel must wear protective clothing: goggles, gowns, disposable gloves and masks • a designated area should be defined for preparation (preferably under a laminar flow system).
9 għandhom ikunu esklużi milli jaħdmu b’ din is- sustanza • il- personal irid jilbes ilbies protettiv: gogil, gawn, ingwanti u maskri li jintremew wara li jintużaw • żona speċifika għandha tkun definita għall- preparazzjoni (preferibbilment taħt sistema ta ’ tnixxija laminari).
The work surface should be protected by disposable, plastic backed, absorbent paper • all items used during administration or cleaning should be placed in high risk, waste-disposal bags for high temperature incineration • in the event of accidental contact with the skin, exposed areas should be washed immediately with soap and water • in the event of accidental contact with the mucous membranes, exposed areas should be treated immediately by copious lavage with water; medical attention should be sought.
Il- wiċċ fejn qed isir ix- xogħol għandu jkun protett minn karta li tassorbi u li jkun fiha dahar tal- plastik, li tintrema wara li tintuża • l- oġġetti kollha li jintużaw waqt l- għoti jew it- tindif, għandhom jitpoġġew f’ boroż għar- rimi ta ’ skart ta ’ riskju għoli, biex jinħarqu f’ temperatura għolja fl- inċineratur. • f’ każ ta ’ kuntatt aċċidentali mal- ġilda, il- partijiet esposti għandhom jinħaslu immedjatament bis- sapun u bl- ilma • f’ każ ta ’ kuntatt aċċidentali mal- membrani mukużi, il- partijiet esposti għandhom ikunu ttratati immedjatament b’ ħasil bi kwantitajiet kbar ta ’ ilma; għandha tintalab attenzjoni medika.
Pacira Limited West Forest Gate, Wellington Road Wokingham, Berkshire RG40 2AQ United Kingdom
Pacira Limited West Forest Gate, Wellington Road Wokingham, Berkshire RG40 2AQ Ir- Renju Unit
11 July 2001 Date of last renewal:
11 ta ’ Lulju, 2001 Data ta ’ l- aħħar tiġdid:
11 July 2006
11 ta ’ Lulju, 2006
DATE OF REVISION OF THE TEXT
DATA TA ’ META ĠIET RIVEDUTA L- KITBA 10.
10 ANNEX II
10 ANNESS II
11 A MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE
11 A DETENTUR TA ’ L- AWTORIZZAZZJONI TAL- MANIFATTURA RESPONSABBLI GĦALL- HRUĠ TAL- LOTT
Almac Pharma Services Limited 20 Seagoe Industrial Estate Craigavon, Co Armagh BT63 5QD United Kingdom
Almac Pharma Services Limited 20 Seagoe Industrial Estate Craigavon, Co Armagh BT63 5QD Ir- Renju Unit
The Marketing Authorisation Holder will continue to submit yearly PSURs unless otherwise specified by the CHMP.
Id- Detentur ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq għandu jkompli jibgħat il- PSURs kull sena, ħlief jekk mhux indikat mod ieħor mis- CHMP.
12 ANNEX III
12 ANNESS III
14 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
14 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA
BOX OF 1 VIAL
KAXXA B’ KUNJETT 1
DepoCyte 50 mg suspension for injection.
DepoCyte 50 mg suspensjoni għall- injezzjoni.
Each vial contains 50 mg cytarabine (10 mg/ ml).
Kull kunjett fih 50 mg ta ’ cytarabine (10 mg/ ml).
Also contains: cholesterol, triolein, dioleoylphosphatidylcholine, dipalmitoylphosphatidylglycerol, sodium chloride, water for injections.
Fih ukoll: cholesterol, triolein, dioleoylphosphatidylcholine, dipalmitoylphosphatidylglycerol, sodium chloride, ilma għall- injezzjonijiet.
Intrathecal use.
Użu għal ġot- teka.
Store in a refrigerator (2ºC - 8ºC) Do not freeze
Aħżen fil- friġġ (2oC - 8oC) Tiffriżax
14.
Lott
Medicinal product subject to medical prescription
KLASSIFIKAZZJONI ĠENERALI TA ’ KIF JINGĦATA 14.
INSTRUCTIONS ON USE
Prodott mediċinali jingħata bir- riċetta tat- tabib
INFORMATION IN BRAILLE
STRUZZJONIJIET DWAR L- UŻU
16 MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
INFORMAZZJONI BIL- BRAILLE
DepoCyte 50 mg suspension for injection Cytarabine
DepoCyte 50 mg suspensjoni għall- injezzjoni Cytarabine
Intrathecal use
Użu għal ġot- teka.
18 PACKAGE LEAFLET:
18 FULJETT TA ’ TAGĦRIF:
Read all of this leaflet carefully before you receive this medicine.
Aqra dan il- fuljett kollu qabel tieħu din il- mediċina.
- If you have further questions, please ask your doctor.
- Jekk ikollok aktar mistoqsijiet, jekk jogħġbok staqsi lit- tabib tiegħek.
What DepoCyte is and what it is given for 2.
X’ inhu DepoCyte u għalxiex jingħata 2.
Before you are given DepoCyte 3.
Qabel ma tingħata DepoCyte 3.
How DepoCyte is given 4.
Kif jingħata DepoCyte 4.
How to store DepoCyte 6.
Kif taħżen DepoCyte 6.
WHAT DEPOCYTE IS AND WHAT IT IS GIVEN FOR
X’ INHU DEPOCYTE U GĦALXIEX JINGĦATA
DepoCyte is used to treat lymphomatous meningitis.
DepoCyte jintuża għal kura tal- meninġite limfomatuża.
Lymphomatous meningitis is a condition in which tumour cells have invaded the fluid or membranes that surround the brain and spinal cord.
Meninġite limfomatuża hi kundizzjoni fejn ċelluli tat- tumur ikunu invadew il- fluwidu jew il - membrani li jinsabu madwar il- moħħ u n- nerv qawwi li jgħaddi minn ġos- sinsla.
DepoCyte is used in adults to kill lymphoma tumour cells.
DepoCyte jintuża fl- adulti biex joqtol iċ- ċelluli tat- tumur tal- limfoma.
BEFORE YOU ARE GIVEN DEPOCYTE
QABEL MA TINGĦATA DEPOCYTE
DepoCyte should not be given
DepoCyte m’ għandux jingħata
- If you are allergic (hypersensitive) to cytarabine or any of the other ingredients.
- Jekk int allerġiku/ a (tbagħti minn sensittività eċċessiva) għal cytarabine jew għal xi sustanzi
- If you have a meningeal infection.
- Jekk għandek infezzjoni meninġeali.
Taking other medicines Please inform your doctor or physician if you are taking or using any other medicines, including medicines obtained without a prescription.
Meta tieħu mediċini oħrajn Jekk jogħġbok għid lit- tabib tiegħek jekk qiegħed tieħu jew ħadt dan l- aħħar xi mediċini oħra, anki dawk mingħajr riċetta.
Pregnancy and breast-feeding DepoCyte should not be given to pregnant women as it may harm an unborn child.
Tqala u treddigħ DepoCyte m’ għandux jingħata lil nisa tqal għax jista ’ jagħmel ħsara lit- tarbija mhux imwielda.
Women of childbearing potential should use a reliable contraceptive to avoid pregnancy whilst being treated with DepoCyte.
Nisa li potenzjalment jista ’ jkollhom it- tfal għandhom jużaw metodu ta ’ kontraċezzjoni li tista ’ torbot fuqu waqt li jkunu qed jirċievu trattament b’ DepoCyte.
Male patients undergoing DepoCyte treatment should use a reliable contraceptive method.
Pazjenti rġiel li qed jirċievu t- trattament b’ DepoCyte għandhom jużaw metodu ta ’ kontraċezzjoni li tista ’ torbot fuqu.
Women should not breast-feed during treatment as DepoCyte may enter breast milk.
In- nisa m’ għandhomx ireddgħu waqt it- trattament għax DepoCyte jista ’ jidħol fil- ħalib tas- sider.
Driving and using machines Do not drive during treatment.
Sewqan u tħaddim ta ’ magni Issuqx matul it- trattament.
Do not operate any tools or machines during treatment.
Tħaddimx għodda jew magni matul it- trattament.
HOW DEPOCYTE IS GIVEN
KIF JINGĦATA DEPOCYTE
Before using DepoCyte, warm the vial to room temperature (18°C – 22°C) for at least 30 minutes.
Qabel ma tuża DepoCyte, saħħan il- fjala sakemm tilħaq temperatura ambjentali (18°C - 22°C) għal ta ’ lanqas 30 minuta.
Just before withdrawing DepoCyte, gently invert the vial to mix the particles evenly.
Qabel ma tiġbed DepoCyte, eqleb il- kunjett bil- mod biex tħallat il- partikuli b’ mod konsistenti.
Do not shake the vial vigorously.
Tħallatx il- funjett bil- qawwi.
A qualified and experienced doctor or physician in the treatment of cancer will inject DepoCyte in the spinal fluid or lumber sac.
Tabib kwalifikat u li għandu esperjenza fit- trattament tal- kanċer ser jinjetta DepoCyte fil- fluwidu tan - nerv qawwi li jgħaddi minn ġos- sinsla jew ġor- rita tal- bażi tas- sinsla.
DepoCyte must not be administered by any other way.
DepoCyte m’ għandux jingħata b’ xi mod ieħor.
Injections are given slowly over a few minutes and you may be asked to lie flat for one hour afterwards.
L- injezzjonijiet huma mogħtija bil- mod fuq perijodu ta ’ ftit minuti, u wara inti tista ’ tintalab biex timtedd għal siegħa.
You will also be given corticosteroids, such as dexamethasone, usually as tablets but possibly by intravenous injection for 5 days after you receive each DepoCyte dose to help reduce any side effects which might occur.
Inti ser tingħata wkoll il- kortikosterojdi, bħal dexamethasone, normalment bħala pilloli iżda possibbilment b’ injezzjoni ġol- vini għal 5 ijiem wara li tirċievi kull doża ta ’ DepoCyte biex jgħinuk tnaqqas xi effetti sekondarji li jistgħu jseħħu.
DepoCyte must be used as supplied without further dilution.
DepoCyte għandu jintuża kif fornut mingħajr dilwizzjoni addizzjonali.
The dose for adults is 50 mg (one vial of DepoCyte).
Id- doża għall- adulti hi ta ’ 50 mg (kunjett wieħed ta ’ DepoCyte).
For the treatment of lymphomatous meningitis, DepoCyte is given according to the following schedules:
Għat- trattament ta ’ meninġite limfomatuża, DepoCyte jingħata skond l- iskedi li ġejjin:
Start-up treatment: one vial of DepoCyte (50 mg) administered every 14 days for 2 doses (weeks 1 and 3).
Trattament tal- bidu: kunjett wieħed ta ’ DepoCyte (50 mg) mogħti kull 14- il jum għal 2 dożi (ġimgħa 1 u 3).
Follow-up treatment: one vial of DepoCyte (50 mg) administered every 14 days for 3 doses (weeks 5, 7 and 9) followed by an additional dose at week 13.
Trattament ta ’ wara: kunjett wieħed ta ’ DepoCyte (50 mg) mogħti kull 14- il jum għal 3 dożi (ġimgħat 5, 7 u 9) segwit minn doża addizzjonali f’ ġimgħa 13.
Maintenance treatment: one vial of DepoCyte (50 mg) administered every 28 days for 4 doses (weeks 17, 21, 25 and 29).
Trattament ta ’ manteniment: kunjett wieħed ta ’ DepoCyte (50 mg) mogħti kull 28 jum għal 4 dożi (ġimgħat 17, 21, 25 u 29).
If you are given more DepoCyte than you should The recommended dose will be given to you by the doctor or physician as necessary.
Jekk tingħata DepoCyte aktar milli suppost inti għandek Id- doża rrakkomandata ser tingħatalek mit- tabib kif meħtieġ.
There is no antidote for DepoCyte.
M’ hemmx antidot għal DepoCyte.
Management of overdose should be directed at maintaining vital functions.
L - immaniġġjar ta ’ doża eċċessiva għandu jkun immirat biex imantni l- funzjonijiet vitali.
Like all medicines, DepoCyte can cause side effects, although not everybody gets them.
Bħal kull mediċina oħra, DepoCyte jista ’ jkollu effetti sekondarji, għalkemm ma jidhrux fuq kulħadd.
Side effects may occur after each injection, usually within the first five days.
L- effetti sekondarji jistgħu jseħħu wara kull injezzjoni, normalment matul l- ewwel ħamest ijiem.
Tell the medical staff, who will be monitoring you during this time, if you suffer from:
Għid lill- membri ta ’ l- istaff mediku, li ser ikunu jagħmlulek il- monitoraġġ f’ dan iż- żmien, jekk int tbati minn:
• Pain, numbness or tingling (feeling of sensation of pins and needles) • Nausea and/ or vomiting • Weakness • Confusion • Fever • Headaches • Fatigue • Convulsion • Dizziness • Neck pain • A stiff or rigid neck • Partial paralysis • Blindness and other visual disturbances • Shaking • Back pain
• Uġigħ, tirżiħ jew tnemnim (tħoss sensazzjoni ta ’ tingis) • Tqallih u/ jew rimettar • Dgħjufija • Konfużjoni • Deni • Uġigħ ta ’ ras • Għeja • Konvulżjoni • Sturdament • Uġigħ fl- għonq • Għonq iebes jew riġidu • Paralisi parzjali • Għama jew disturbi oħrajn tal- vista • Rogħda
20 • Persistent or extreme sleepiness • Hearing loss • Infection of the meninges
20 • Uġigħ fid- dahar • Ngħas persistenti jew estrem • Nuqqas ta ’ smigħ • Infezzjoni tal- meninġe
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please inform the medical staff looking after you.
Jekk xi wieħed mill- effetti sekondarji jiggrava, jew jekk tinnota xi effetti sekondarji li mhumiex imsemmijin f’ dan il- fuljett, jekk jogħġbok informa lill- istaff mediku li jkun qed jieħu ħsiebek.
STORING DEPOCYTE
KIF TAĦŻEN DEPOCYTE
Do not use DepoCyte after the expiry date which is stated on the carton and on the vial.
Tużax DepoCyte wara d- data ta ’ skadenza li tidher fuq il- kaxxa u fuq il- kunjett.
Store in a refrigerator (2°C – 8°C).
Aħżen fil- friġġ (2°C – 8°C).
What DepoCyte contains
X’ fih DepoCyte
- The active substance is 50 mg cytarabine (10 mg/ ml)
- Is- sustanza attiva hi 50 mg ta ’ cytarabine (10 mg/ ml)
- The other ingredients are cholesterol, triolein, dioleoylphosphatidylcholine,
- L- ingredjenti l- oħra huma cholesterol, triolein, dioleoylphosphatidylcholine,
dipalmitoylphosphatidylglycerol, sodium chloride and water for injections.
dipalmitoylphosphatidylglycerol, sodium chloride u ilma għall- injezzjonijiet.
What DepoCyte looks like and contents of the pack
Kif jidher DepoCyte u l- kontenut tal- pakkett
DepoCyte is a vial containing a white to off-white-suspension for injection.
DepoCyte hu kunjett li fih suspensjoni għall- injezzjoni ta ’ lewn abjad sa offwajt.
Each vial contains 5 ml of suspension for a single injection.
Kull kunjett fih 5 ml ta ’ suspensjoni għal injezzjoni waħda.
Each pack contains a single vial.
Kull pakkett fih kunjett wieħed.
Marketing Authorisation Holder
Id- Detentur ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq
Pacira Limited, West Forest Gate, Wellington Road, Wokingham, Berkshire, RG40 2AQ, United Kingdom.
Pacira Limited, West Forest Gate, Wellington Road, Wokingham, Berkshire, RG40 2AQ, ir- Renju Unit.
Manufacturer Almac Pharma Services Limited, 20 Seagoe Industrial Estate, Craigavon, Co Armagh, BT63 5QD, United Kingdom.
Manifattur Almac Pharma Services Limited, 20 Seagoe Industrial Estate, Craigavon, Co Armagh, BT63 5QD, ir- Renju Unit
21 For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.
21 Għal kull tagħrif dwar dan il- prodott mediċinali, jekk jogħġbok ikkuntattja lir- rappreżentant lokali tad - detentur ta ’ l- awtorizzazzjoni għat- tqegħid fis- suq.
Eesti OÜ K-Büroo Marketing Kalevi 112/ 2 EE - 50104 Tartu Tel: +372 733 8080
OÜ K- Büroo Marketing Apollogasse 16- 18 Kalevi 112/ 2 A- 1072 Wien EE - 50104 Tartu Tel: + 43 (1) 523 25 05 Tel: +372 733 8080
Apollogasse 16-18 A-1072 Wien Tel: + 43 (1) 523 25 05
Kochanowskiego 49A 01- 864 Warszawa
EU/ 1/ 06/ 367/ 001 EU/ 1/ 06/ 367/ 002 EU/ 1/ 06/ 367/ 003 EU/ 1/ 06/ 367/ 004 EU/ 1/ 06/ 367/ 005 EU/ 1/ 06/ 367/ 006 EU/ 1/ 06/ 367/ 007 EU/ 1/ 06/ 367/ 008 EU/ 1/ 06/ 367/ 009 EU/ 1/ 06/ 367/ 010 EU/ 1/ 06/ 367/ 011 EU/ 1/ 06/ 367/ 012
Numru tal- proċedura ta ’ l- EMEA EMEA/ H/ C/ 664/ 001 EMEA/ H/ C/ 664/ 002 EMEA/ H/ C/ 664/ 003 EMEA/ H/ C/ 664/ 004 EMEA/ H/ C/ 664/ 005 EMEA/ H/ C/ 664/ 006 EMEA/ H/ C/ 664/ 007 EMEA/ H/ C/ 664/ 008 EMEA/ H/ C/ 664/ 009 EMEA/ H/ C/ 664/ 010 EMEA/ H/ C/ 664/ 011 EMEA/ H/ C/ 664/ 012
Diacomit Diacomit Diacomit Diacomit Diacomit Diacomit Diacomit Diacomit Diacomit Diacomit Diacomit Diacomit
Isem inventat Diacomit Diacomit Diacomit Diacomit Diacomit Diacomit Diacomit Diacomit Diacomit Diacomit Diacomit Diacomit
250 mg 250 mg 250 mg 500 mg 500 mg 500 mg 250 mg 250 mg 250 mg 500 mg 500 mg 500 mg
Qawwa 250 mg 250 mg 250 mg 500 mg 500 mg 500 mg 250 mg 250 mg 250 mg 500 mg 500 mg 500 mg
Capsule, hard Capsule, hard Capsule, hard Capsule, hard Capsule, hard Capsule, hard Powder for oral suspension Powder for oral suspension Powder for oral suspension Powder for oral suspension Powder for oral suspension Powder for oral suspension
Għamla Farmaċwewtika Capsule, hard Kapsula, iebsa, Kapsula, iebsa Kapsula, iebsa Kapsula, iebsa Kapsula, iebsa Trab għal suspensjoni orali Trab għal suspensjoni orali Trab għal suspensjoni orali Trab għal suspensjoni orali Trab għal suspensjoni orali Trab għal suspensjoni orali
Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use
Mnejn jingħata Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali
Bottle (PP) Bottle (PP) Bottle (PP) Bottle (PP) Bottle (PP) Bottle (PP) Sachet (paper/ Al/ PE) Sachet (paper/ Al/ PE) Sachet (paper/ Al/ PE) Sachet (paper/ Al/ PE) Sachet (paper/ Al/ PE) Sachet (paper/ Al/ PE)
Il- pakkett Fliexkun (PP) Fliexkun (PP) Fliexkun (PP) Fliexkun (PP) Fliexkun (PP) Fliexkun (PP) Qartas (karta/ Al/ PE) Qartas (karta/ Al/ PE) Qartas (karta/ Al/ PE) Qartas (karta/ Al/ PE) Qartas (karta/ Al/ PE) Qartas (karta/ Al/ PE)
30 capsules 60 capsules 90 capsules 30 capsules 60 capsules 90 capsules 30 sachets 60 sachets 90 sachets 30 sachets 60 sachets 90 sachets
Daqs tal- pakkett 30 kapsula 60 kapsula 90 kapsula 30 kapsula 60 kapsula 90 kapsula 30 qartas 60 qartas 90 qartas 30 qartas 60 qartas 90 qartas
Diacomit 250 mg hard capsules
Diacomit 250 mg kapsuli iebsin
Each capsule contains 250 mg of stiripentol
Kull kapsula fiha 250 mg ta ’ stiripentol
0.16 mg sodium per capsule.
0. 16 mg sodium għal kull kapsula.
Hard capsules
Kapsuli iebsin
Size 2 pink capsule
Daqs 2, kapsula roża
Diacomit is indicated for use in conjunction with clobazam and valproate as adjunctive therapy of refractory generalized tonic-clonic seizures in patients with severe myoclonic epilepsy in infancy (SMEI, Dravet’ s syndrome) whose seizures are not adequately controlled with clobazam and valproate.
Diacomit huwa indikat biex jintuża flimkien ma ’ clobazam u valproate bħala terapija miżjuda għal aċċessjonijiet toniċi- kloniċi ġeneralizzati refrattarji f’ pazjenti b’ epilessija mijoklonika severa fit- tfulija (SMEI, sindromu ta ’ Dravet) li l- aċċessjonijiet tagħhom m’ humiex ikontrollati adegwatament b’ clobazam u valproate.
Diacomit should only be administered under the supervision of a paediatrician / paediatric neurologist experienced in the diagnosis and management of epilepsy in infants and children.
Diacomit għandu jiġi amministrat biss taħt is- superviżjoni ta ’ tabib pedjatriku / newrologu pedjatriku li għandu esperjenza fid- dijanjosi u l- ġestjoni ta ’ epilessija fit- trabi u t- tfal.
The capsule should be swallowed whole with a glass of water during a meal.
Il- kapsula għandha tinbela ’ sħiħa b’ tazza mimlija ilma wara l- ikel.
The dose of Diacomit is calculated on a mg/ kg body weight basis.
Id- doża ta ’ Diacomit hija kkalkulata skond il- piż korporali b’ mg/ kgs.
The daily dosage may be administered in 2 or 3 divided doses.
Id- doża ta ’ kuljum tista tingħata f’ 2 jew 3 dożi separati kuljum.
The initiation of adjunctive therapy with Diacomit should be undertaken over 3 days using upwards dose escalation to reach the recommended dose of 50 mg/ kg/ day administered in conjunction with clobazam and valproate.
Il- bidu ta ’ terpaija miżjuda b’ Diacomit għandu jsir fuq 3 ijiem bl- użu ta ’ dożi li jitilgħu ’ l fuq biex jilħqu d- doża rrakomandata ta ’ 50 mg/ kg/ kuljum mogħtija flimkien ma ’ clobazam u valproate.
This recommended dose is based on the available clinical study findings and was the only dose of Diacomit evaluated in the pivotal studies.
Id- doża rakkomandata hija bbażata fuq ir- riżultati disponibbli fi studji kliniċi u kienet l- uniku doża ta ’ Diacomit evalwata fi studji pivitali.
(See, section 5.1)
(Ara, sezzjoni 5. 1).
There are no clinical study data to support the clinical safety of Diacomit administered at daily doses greater than 50mg/ kg/ day.
M’ hemmx tagħrif minn studji kliniċi li jissostanza s- sigurtà klinika ta ’ Diacomit li jingħata f’ dożi ta ’ kuljum ta ’ aktar minn 50mg/ kg/ day.
There are no clinical study data to support the use of Diacomit as monotherapy in Dravet’ s syndrome.
M’ hemm l- ebda tagħrif minn studju kliniku li jissostanza l- użu ta ’ Diacomit bħala monoterapija fis- sindromu ta ’ Dravet.
Dose adjustments of other antiepileptics used in combination with Diacomit Despite the absence of comprehensive pharmacology data on potential drug interactions, the following advice regarding modification of the dose and dosage schedules of other anti-epileptic medicinal products administered in conjunction with Diacomit is provided based on clinical experience.
Aġġustamenti fid- doża ta ’ antiepilettiċi oħrajn użati flimkien ma ’ Diacomit Minkejja n- nuqqas ta ’ tagħrif dwar farmakoloġija komprensiva dwar l- effetti potenzjali fuq mediċini, ir- rakkomandazzjonijiet li ġejjin fir- rigward ta ’ modifiċi fid- doża u l- iskedi tad- dożaġġ ta ’ prodotti mediċinali anti- epilettiċi mogħtija flimkien ma ’ Diacomit qed tiġi mogħtija skond l- esperjenza klinika.
In the pivotal studies, when the use of Diacomit was initiated, the daily dose of clobazam was 0.5 mg/ kg/ day usually administered in divided doses, twice daily.
Fi studji pivitali, meta jinbeda l- użu ta ’ Diacomit, id- doża ta ’ kuljum ta ’ clobazam kienet 0. 5mg/ kg/ kuljum ġeneralment mogħtija f’ żewġ dożi maqsuma, darbtejn kuljum.
In the event of clinical signs of side effects or overdosage of clobazam (i. e., drowsiness, hypotonia, and irritability in young children), this daily dose was reduced by 25% every week.
Fil- każ ta ’ sinjali kliniċi ta ’ effetti mhux mixtieqa jew dożaġġ eċċessiv ta ’ clobazam (i. e. ngħas, ipotonja, u irritabbilità fi tfal żgħar), din id- doża ta ’ kuljum kienet imnaqqsa b’ 25% kull ġimgħa.
Approximately two to three fold increases in clobazam and five fold increases in norclobazam plasma levels respectively have been reported with co- administration of Diacomit in children with Dravet’ s syndrome.
Żidiet fil- livelli tal- plażma ta ’ madwar tnejn sa tliet darbiet għal clobazam u ta ’ ħames darbiet għal norclobazam rispettivament ġew irrapportati b’ amministrazzjoni konkomitanti ta ’ Diacomit fi tfal bis- sindromu ta ’ Dravet.
- Valproate
- Valproate
The potential for metabolic interaction between Diacomit and valproate is considered modest and thus, no modification of valproate dosage should be needed when Diacomit is added, except for clinical safety reasons.
Il- potenzjal għall- interazzjoni metabolika bejn Diacomit u valproate hija konsidrata modesta u għalhekk, l- ebda modifikazzjoni tad- dożaġġ ta ’ valproate m’ għandu jkun meħtieġ meta Diacomit jiġi miżjud, ħlief għal raġunijiet ta ’ sigurtà klinika.
In the pivotal studies in the event of gastrointestinal adverse reactions such as loss of appetite, loss of weight, the daily dose of valproate was reduced by around 30% every week.
Fi studji pivitali fil- każ ta ’ reazzjonijiet avversi gastrointestinali bħal ma huma nuqqas t’ aptit, telf ta ’ piż, id- doża ta ’ kuljum ta ’ valproate kienet imnaqqsa b’ madwar 30% kull ġimgħa.
Abnormal Laboratory Findings In the event of an abnormal blood count or liver function test finding, the clinical decision for continuing use or adjusting the dose of Diacomit in conjunction with adjusting the doses of clobazam and valproate needs to be made on an individual patient basis taking into consideration the potential clinical benefits and risks (See, section 4.4).
Riżultati Abnormal ital- Laboratorju Fil- każ ta ’ riżultati abnormali fl- għadd tad- demm jew fit- test tal- funzjoni tal- fwied, id- deċizjoni klinika biex jitkompla l- użu jew l- aġġustament tad- doża ta ’ Diacomit flimkien ma ’ l- aġġustament tad - dożi ta ’ clobazam u valproate għandha tiġi magħmula fuq bażi individwali u għandhom jittieħdu in konsiderazzjoni l- benefiċċji u r- riskji kliniċi potenzjali (Ara, sezzjoni 4. 4).
Effects of food Diacomit must always be taken with food as it degrades rapidly in an acidic environment (e. g. exposure to gastric acid in an empty stomach).
Effetti ta ’ l- ikel Diacomit għandu dejjem jingħata ma ’ l- ikel billi jiddegrada malajr f’ ambjent aċiduż (e. g. espożizzjoni ta ’ aċidu gastriku fi stonku vojt).
Diacomit should not be taken with milk or dairy products (yoghurt, soft cream cheese, etc.), carbonated drinks, fruit juice or food and drinks that contain caffeine or theophylline.
Diacomit m’ għandux jittieħed ma ’ l- ikel jew prodotti tal- ħalib (jogurt, krema tal- ġobon ratba, eċċ.), xorb bl- ilma kkarbonat, meraq tal- frott jew ikel u xorb li fihom il- kaffeina jew theophylline.
Effect of formulation The sachet formulation has a slightly higher Cmax than the capsules and thus the formulations are not bioequivalent.
Effett ta ’ formulazzjoni Il- formulazzjoni fil- qartas għandha Cmax kemxejn ogħla mill- kapsuli u għalhekk il- formulazzjonijiet mhumiex bijoekwivalenti.
It is recommended that if a switch of formulations is required this is done under clinical supervision, in case of problems with tolerability (see section 5.2).
Huwa rakkomandat li jekk ikun hemm bżonn ta ’ bidla fil- formulazzjonijiet dan isir taħt superviżjoni klinika, f’ każ li jinqalgħu problemi ta ’ tollerabilità (ara sezzjoni 5. 2).
Children aged less than 3 years:
Tfal li għandhom inqas minn 3 snin:
The pivotal clinical evaluation of Diacomit was in children of 3 years of age and over with SMEI.
L- evalwazzjoni klinika ewlenija ta ’ Diacomit saret fi tfal ta ’ 3 snin jew akbar b’ SMEI.
The clinical decision for use of Diacomit in children with SMEI less than 3 years of age needs to be made on an individual patient basis taking into consideration the potential clinical benefits and risks.
Id- deċiżjoni klinika għall- użu ta ’ Diacomit fi tfal li għandhom inqas minn 3 snin bi SMEI jeħtieġ li tiġi magħmula fuq bażi individwali u tieħu inkonsiderazzjoni l- benefiċċji u r- riskji potenzjali.
In this younger group of patients, adjunctive therapy with Diacomit should only be started when the diagnosis of SMEI has been clinically confirmed (See, section 5.1).
F’ dan il- grupp ta ’ pazjenti iżgħar, it- terapija miżjuda b’ Diacomit għandha tinbeda biss meta d- djanjożi ta ’ SMEI tkun ġiet klinikament ikkonfermata (Ara, sezzjoni 5. 1).
Data are limited about the use of Diacomit under 12 months of age.
Hemm dejta ristretta dwar l- użu ta ’ Diacomit f’ età taħt it- 12- il xahar.
Patients with renal and hepatic impairment Diacomit is not recommended for use in patients with impaired hepatic and/ or renal function (See, section 4.4)
Pazjenti b’ indeboliment fil- kliewi u fil- fwied Diacomit mhux rakkomandat biex jintuża f’ pazjenti li għandhom indeboliment fil- funzjoni tal- fwied u/ jew tal- kliewi (Ara, sezzjoni 4. 4)
A past history of psychoses in the form of episodes of delirium.
Storja ta ’ psikosi fil- forma ta ’ episodji ta ’ dilirju.
3 4.4 Special warnings and precautions for use
3 4. 4 Twissijiet speċjali u prekawzjonijiet għall- użu
Carbamazepine, iphenytoin and phenobarbital should not be used in conjunction with Diacomit in the management of Dravet’ s syndrome.
Carbamazepine, iphenytoin u phenobarbital m’ għandomx jintużaw ma ’ Diacomit fis- sindromu ta ’ Dravet.
The daily dosage of clobazam and/ or valproate should be reduced according to the onset of side effects whilst on Diacomit therapy (See, section 4.2).
Id- dożaġġ ta ’ kuljum ta ’ clobazam u/ jew valproate għandu jiġi mnaqqas skond il- bidu ta ’ l - effetti mhux mixtieqa waqt terapija b’ Diacomit (Ara, sezzjoni 4. 2).
Given the frequency of gastrointestinal adverse reactions to treatment with Diacomit and valproate (anorexia, loss of appetite, nausea, vomiting), the growth rate of children under this combination of treatment should be carefully monitored.
Minħabba l- frekwenza ta ’ reazzjonijiet avversi gastrointestinali għat- trattament b’ Diacomit u valproate (anoressja, telf t’ aptit, dardir, remettar), ir- rata ta ’ l- iżvilupp tat- tfal taħt din il- kombinazzjoni tat- trattament għandha tkun sorveljata bir- reqqa.
Neutropenia may be associated with the administration of Diacomit, clobazam and valproate.
In- newtropenja tista ’ tkun assoċjata ma ’ l- amministrazzjoni ta ’ Diacomit, clobazam u valproate.
Blood counts should be assessed prior to starting treatment with Diacomit.
L - għadd tad- demm għandu jiġi assessjat qabel il- bidu ta ’ trattament b’ Diacomit.
Unless otherwise clinically indicated, blood counts should be checked every 6 months..
L- għadd tad- demm għandu jiġu ċċekkjat kull 6 xhur, sakemm ma jkunx klinikament indikat b’ mod ieħor.
Liver function should be assessed prior to starting treatment with Diacomit.
Il- funzjoni tal- fwied għandha tiġi assessjata qabel ma jinbeda trattament b’ Diacomit.
Unless otherwise clinically indicated, liver function should be checked every 6 months.
Il- funzjoni tal - fwied għandha tiġi ċċekkjata kull 6 xhur, sakemm ma jkunx klinikament indikat b’ mod ieħor.
In the absence of specific clinical data in patients with impaired hepatic or renal function, Diacomit is not recommended for use in patients with impaired hepatic and/ or renal function.
Fin- nuqqas ta ’ tagħrif kliniku speċifiku f’ pazjenti li għandhom il- funzjoni tal- fwied jew tal- kliewi indeboliti, Diacomit mhux rakkomandat għal użu f’ pazjenti li għandhom indeboliment fil- funzjoni tal - fwied u/ jew tal- kliewi.
Stiripentol is an inhibitor of the enzymes CYP2C19, CYP3A4 and CYP2D6 and may markedly increase the plasma concentrations of drugs metabolised by these enzymes and increase the risk of adverse effects (See, section 4.5.).
Stiripentol huwa inibitur ta ’ l- enzimi CYP2C19, CYP3A4 u CYP2D6 u jista ’ jżid bil- bosta l- konċentrazzjonijiet fil- plażma ta ’ mediċini metabolizzati minn dawn l- enżimi u jżid ir- riskju ta ’ reazzjonijiet avversi (Ara, sezzjoni 4. 5).
In vitro studies suggested that stiripentol phase 1 metabolism is catalyzed by CYP1A2, CYP2C19 and CYP3A4 and possibly other enzymes.
Studji in vitro issuġġerixxew li l- metaboliżmu ta ’ fażi 1 ta ’ stiripentol hu katalizzat minn CYP1A2, CYP2C19 u CYP3A4 u possibbilment minn enzimi oħrajn.
Caution is advised when combining stiripentol with other drugs that inhibit or induce one or more of these enzymes..
L - attenzjoni hi rakkomandata meta tħallat stiripentol ma ’ mediċini oħrajn li jinibixxu jew jinduċu wieħed jew aktar minn dawn l- enzimi..
The pivotal clinical studies did not include children below 3 years old.
L- istudji kliniċi pivitali ma inkludewx tfal taħt it- 3 snin.
As a consequence, it is recommended that children between 6 months and 3 years of age are carefully monitored whilst on Diacomit therapy.
B’ konsegwenza t’ hekk, huwa rakkomandat li tfal ta ’ etajiet ta ’ bejn 6 xhur u 3 snin ikunu sorveljati bir- reqqa waqt li jkunu fuq terapija b’ Diacomit.
Potential medicinal product interactions affecting stiripentol The influence of other antiepileptic medicinal products on stiripentol pharmacokinetics is not well established.
Interazzjonijiet potenzjali ta ’ prodotti mediċinalili jolqtu lil stiripentol L- influwenza ta ’ prodotti mediċinali antiepilettiċi oħra fuq il- farmakokinetiċi ta ’ stiripentol mhix stabbilita sew.
The impact of macrolides and azole antifungal agents on stiripentol metabolism, that are known to be inhibitors of CYP3A4 and substrates of the same enzyme, is not known.
L- impatt fuq il- metaboliżmu ta ’ stiripentol minn macrolides u mediċini kontra l- fungu tat- tip azole, li huma magħrufa bħala inibituri ta ’ CYP3A4 u sottostrati ta ’ l- istess enzima mhuwiex magħruf.
Likewise, the effect of stiripentol on their metabolism is not known.
Hekk ukoll l- effett ta ’ stripentol fuq il- metaboliżmu tagħhom mhuwiex magħruf.
Caution is advised when combining stiripentol with other drugs that inhibit or induce one or more of these enzymes
L- attenzjoni hi rakkomandata meta tħallat stiripentol ma ’ mediċini oħrajn li jinibixxu jew jinduċu wieħed jew aktar minn dawn l- enzimi.
Effect of stiripentol on cytochrome P450 enzymes.
L- effett ta ’ stiripentol fuq enżimi ta ’ cytochrome P450.
Many of these interactions have been partially confirmed by in vitro studies and in clinical trials.
Ħafna minn dawn l- interazzjonijiet ġew ikkonfermati parzjalment minn studji in vitro u provi kliniċi.
The increase in steady state levels with the combined use of Diacomit, valproate, and clobazam is similar in adults and children, though inter-individual variability is marked.
Iż- żieda fil- livelli ta ’ stat fiss kostanti bl- użu kkombinat ta ’ Diacomit, valproate, u clobazam huwa simili fl- adulti u fit- tfal, għalkemm l- varjabilità bejn l- individwi hija kbira.
At therapeutic concentrations, stiripentol significantly inhibits several CYP450 isoenzymes: for example, CYP2C19, CYP2D6 and CYP3A4.
F’ konċentrazzjonijiet terapewtiċi, stiripentol jinibixxi sinifikattivament bosta iżoenzimi CYP450, per eżempju, CYP2C19, CYP2D6 u CYP3A4.
As a result, pharmacokinetic interactions of metabolic origin with other medicines may be expected.
Bħala riżultat, l- interazzjonijiet farmakokinetiċi ta ’ oriġini metabolika ma ’ mediċini oħra jistgħu jkunu mistennija.
These interactions may result in increased systemic levels of these active substances that may lead to enhanced pharmacological effects and to an increase in side effects and adverse reactions.
Dawn l- interazzjonijiet jistgħu jirriżultaw fl - livelli sistemiċi miżjuda ta ’ dawn is- sustanzi attivi li jistgħu jirriżultaw f’ effetti farmakoloġiċi mqawwija u għal żieda fl- effetti mhux mixtieqa u reazzjonijiet avversi.
HIV protease inhibitors, antinistamines such as astemizole, chlorpheniramine, calcium channel blockers, statins, oral 4 contraceptives, codeine) due to the increased risk of adverse events (see further in this section for antiepileptic drugs).
4 Għandha tintuża l- kawtela jekk ċirkostanzi kliniċi jeħtieġu li stiripentol jiġi kkombinat ma ’ mediċini metabolizzati minn CYP2C19 (e. ż. citalopram, omeprazole) jew CYP3A4 (e. ż. inibituri HIV protease, antistaminiċi bħal astemizole, chlorpheniramine, imblokkaturi tal- kanali tal- kalċju, statins, kontraċettivi orali, kodeina) minħabba r- riskju akbar ta ’ reazzjonijiet avversi (ara aktar f’ din is - sezzjoni għal mediċini antiepilettiċi).
Monitoring of plasma concentrations or adverse effects is recommended.
Sorveljanza tal- konċentrazzjonijiet tal- plażma jew effetti avversi hija rrakkomandata.
A dose adjustment may be necessary.
Aġġustament fid- doza jista ’ jkun meħtieġ.
Co-administration with CYP3A4 substrates with a narrow therapeutic index should be avoided due to the markedly increased risk of severe adverse effects.
Għandha tiġi evitata l- amministrazzjoni konkomitanti ma ’ sottostrati CYP3A4 b’ indiċi terapewtiċi dojoq minħabba r- riskju bil- bosta miżjud ta ’ effetti avversi serji.
Data on the potential for inhibition of CYP1A2 are limited, and therefore, interactions with theophylline and caffeine cannot be excluded.
Dejta fuq il- potenzjal ta ’ inibizzjoni ta ’ CYP1A2 hija ristretta, u għaldaqstant, interazzjonijiet ma ’ theophylline u kaffeina ma jistgħux jiġu esklużi.
Use in combination with stiripentol is not recommended.
L- użu flimkien ma ’ stiripentol mhuwiex irrakomandat.
This warning is not only restricted to medicinal products but also to a considerable number of foods and nutritional products aimed at children, such as cola drinks, which contain significant quantities of caffeine or chocolate, which contains trace amounts of theophylline.
Din it- twissija mhix biss ristretta għal prodotti mediċinali iżda ukoll għal għadd konsiderevoli ta ’ ikel u prodotti ta ’ nutriment immirati lejn it- tfal, bħal ma ’ huma xarbiet tal- kola, li fihom kwantitajiet sinifikattivi ta ’ kaffeina jew ċikkulata, u traċċi ta ’ ammonti ta ’ theophylline.