FrancophonIA/ELRC3.0 huggingface dataset:
English: When Ceplene is first given, the patient's blood pressure, heart rate and lung function must be checked.
Slovenian: Ob prvi uporabi zdravila Ceplene je treba spremljati bolnikov krvni tlak, srčni utrip in delovanje pljuč.
English: Ceplene is a medicine used in combination with interleukin-2 (a cancer medicine) as maintenance treatment in adults with acute myeloid leukaemia (AML), a type of cancer affecting the white blood cells.
Slovenian: Zdravilo Ceplene je zdravilo, ki se uporablja v kombinaciji z interlevkinom-2 (zdravilom za zdravljenje raka) za vzdrževalno zdravljenje pri odraslih bolnikih z akutno mieloično levkemijo (AML), vrsto raka, ki prizadene bele krvničke.
English: What information is still awaited for Ceplene?
Slovenian: Katere informacije o zdravilu Ceplene še pričakujemo?
English: It must also not be used in patients who have received a bone marrow transplant from a donor, or who are taking steroids (medicines used to reduce or prevent inflammation) given systemically (given by mouth or by injection), clonidine (used to reduce high blood pressure) or histamine H2 blockers (used to treat stomach ulcers, indigestion or heartburn).
Slovenian: Prav tako se ne sme uporabljati pri bolnikih, ki so jim presadili kostni mozeg, prejet od darovalca, ali ki jemljejo sistemske steroide (zdravila za ublažitev ali preprečevanje vnetij, prejete peroralno ali z injekcijo), klonidine (zdravila za zniževanje povišanega krvnega tlaka) ali zaviralce histaminskega receptorja H2 (zdravila za zdravljenje želodčnih razjed, slabe prebave ali zgage).
English: This improves the effectiveness of interleukin-2, a medicine that stimulates the immune system to attack cancerous cells.
Slovenian: To poveča učinkovitost interlevkina2, zdravila, ki spodbuja imunski sistem k uničevanju rakavih celic.
English: The most common side effects with Ceplene (seen in more than 1 patient in 10) are flushing (reddening), headache, tiredness, fever and inflammation or redness at the injection site.
Slovenian: Najpogostejši neželeni učinki zdravila Ceplene (opaženi pri 1 od 10 bolnikov) so zardevanje, glavobol, utrujenost, povišana telesna temperatura in vnetje ali rdečina na mestu injiciranja.
English: Ceplene and interleukin-2 are given for 10 cycles.
Slovenian: Zdravili Ceplene in interlevkin-2 se dajeta v 10 ciklih zdravljenja.
English: Each Ceplene injection must be given slowly over five to 15 minutes, in a different site from the interleukin-2 injection, and preferably in the thigh or abdomen (belly).
Slovenian: Vsak odmerek zdravila Ceplene je treba injicirati počasi, in sicer v 5-15 minutah, na mesto, ki se razlikuje od mesta injiciranja interlevkina-2, po možnosti v stegno ali abdomen (trebuh).
English: Every year, the Agency will review any new information that may become available and this summary will be updated as necessary.
Slovenian: Agencija za zdravila bo vsako leto ponovno pregledala vse nove podatke, ki bodo na voljo.
English: When Ceplene is given with interleukin-2, it helps the immune system to kill the leukaemia cells that may remain in the body during remission.
Slovenian: Če se zdravilo Ceplene daje skupaj z interlevkinom-2, pomaga imunskemu sistemu ubijati levkemične celice, ki ostanejo v telesu med remisijo.
English: In the treatment of AML, it is thought to work by protecting immune system cells from damage.
Slovenian: Domneva se, da histamin pri zdravljenju AML pomaga z zaščito celic imunskega sistema pred poškodbami.
English: Ceplene was given in combination with interleukin-2 and compared with no treatment.
Slovenian: Zdravilo je bilo dano v kombinaciji z interlevkinom-2, zdravljenje pa so primerjali s stanjem brez zdravljenja.
English: How does Ceplene work?
Slovenian: Kako zdravilo Ceplene deluje?
English: For the full list of side effects of Ceplene, see the package leaflet.
Slovenian: Za celoten seznam neželenih učinkov zdravila Ceplene glejte navodilo za uporabo.
English: The active substance in Ceplene, histamine dihydrochloride, is an immune modulator.
Slovenian: Učinkovina v zdravilu Ceplene, histaminijev diklorid, je imunomodulator.
English: How is Ceplene used?
Slovenian: Kako se zdravilo Ceplene uporablja?
English: Ceplene contains the active substance histamine dihydrochloride.
Slovenian: Zdravilo Ceplene vsebuje učinkovino histaminijev diklorid.
English: No effect of Ceplene and interleukin-2 was seen in patients in second or later remission.
Slovenian: Pri bolnikih v drugi ali poznejši remisiji ni bilo opaznega učinka zdravila Ceplene in interlevkina-2.
English: Hence no safety margin could be calculated.
Slovenian: Posledično ni bilo mogoče izračunati nobenega varnostnega faktorja.
English: • four cases of spontaneous abortion,
Slovenian: • štiri primere spontanega splava;
English: This DUS should be conducted over a three year period.
Slovenian: Študija mora trajati tri leta.
English: Carcinogenicity is an important potential risk.
Slovenian: Rakotvornost je pomembno možno tveganje.
English: Clinical Safety
Slovenian: Klinična varnost
English: A relevant summary is presented hereinafter.
Slovenian: Povzetek pregleda je predstavljen v nadaljevanju.
English: • Teratogenicity is classified as an important identified risk.
Slovenian: • Teratogenost je opredeljena kot pomembno znano tveganje.
English: However it is still controversial if aneuploidy is a contributing cause or merely a consequence of neoplastic transformation.
Slovenian: Še vedno pa je sporno vprašanje, ali je anevploidija eden od vzrokov za neoplastično transformacijo ali zgolj njena posledica.
English: Post marketing experience
Slovenian: Izkušnje v obdobju trženja
English: The CHMP was asked to give its opinion on whether the indication of TCC containing medicinal products should be restricted and/or other regulatory measures should be taken.
Slovenian: CHMP so zaprosili, naj poda svoje mnenje o tem, ali bi bilo treba omejiti indikacijo zdravil, ki vsebujejo tiokolhikozid, in/ali sprejeti druge ureditvene ukrepe.
English: The package size should be adapted to new recommended treatment-days.
Slovenian: Velikost pakiranja je treba spremeniti v skladu s priporočenim številom dni zdravljenja;
English: The CHMP also recommended further changes to the product information including information on fertility.
Slovenian: CHMP je priporočil tudi dodatne spremembe informacij o zdravilu, vključno z informacijami v zvezi s plodnostjo;
English: Subsequent safety assessments focusing on genotoxic potential were issued in 20012 and 20033 .
Slovenian: Leta 20012 in 20033 so bile objavljene naknadne ocene varnosti, ki so se osredotočile na genotoksični potencial.
English: • The CHMP also agreed on the need of a RMP.
Slovenian: • prav tako se je CHMP strinjal, da je potreben načrt za obvladovanje tveganja.
English: The CHMP also noted that the limited number of cases of malformations/embryo-foetal toxicities may be due to the fact that, in most of the Member States, the medicine is contraindicated in pregnancy.
Slovenian: CHMP je upošteval tudi, da bi majhno število primerov malformacij/embriofetalne toksičnosti lahko bilo posledica dejstva, da je v večini držav članic zdravilo v nosečnosti kontraindicirano.
English: In addition, the lack of evidence for the correlation between the use of TCC and cancer could be due to the difficulty of establishing a causal relationship between the medicine and the effect, which may occur years after intake.
Slovenian: Poleg tega bi lahko bilo pomanjkanje dokazov o povezavi med uporabo tiokolhikozida in rakom posledica dejstva, da je težko dokazati vzročno razmerje med zdravilom in učinkom, ki se lahko pojavi več let po jemanju.
English: Muscle relaxants are one of the many treatments currently employed in the management of non-specific low back pain.
Slovenian: Mišični relaksanti so ena od številnih vrst zdravljenja, ki se trenutno uporabljajo za obvladovanje nespecifične bolečine v križu.
English: In view of the above, on 15 February 2013, Italy requested the CHMP, under Article 31 of Directive 2001/83/EC, to assess the above concerns regarding aneuploidy and its impact on the benefit-risk balance for TCC containing medicinal products for systemic use.
Slovenian: Na podlagi zgoraj navedenega je Italija dne 15. februarja 2013 v skladu s členom 31 Direktive 2001/83/ES zaprosila odbor CHMP, da oceni omenjene zadržke v zvezi z anevploidijo in njen vpliv na razmerje med tveganji in koristmi zdravil za sistemsko uporabo, ki vsebujejo tiokolhikozid.
English: Case review reports from 2004 up to 29 April 2013 from the second database reported 23 cases secondary to exposure during pregnancy and / or exposition in utero:
Slovenian: Poročila o pregledu primerov med letom 2004 in 29. aprilom 2013 iz druge zbirke podatkov navajajo 23 primerov, ki so bili posledica izpostavljenosti med nosečnostjo in/ali intrauterine izpostavljenosti:
English: Overall summary of the scientific evaluation of thiocolchicoside containing medicinal products for systemic use (see Annex I)
Slovenian: Splošni povzetek znanstvenega vrednotenja zdravil za sistemsko uporabo, ki vsebujejo tiokolhikozid (glejte Prilogo I)
English: • Lastly, evidence for carcinogenicity of aneugens is limited.
Slovenian: • Dokazov o rakotvornosti anevgenov je malo.
English: Postmarketing spontaneous cases were collected based on the reports recorded in two MAHs' global pharmacovigilance databases (cut-off dates of 15 February 2013 and 29 April 2013 respectively).
Slovenian: Spontane primere v obdobju trženja so zbrali na podlagi poročil, ki so jih zabeležili v dveh zbirkah podatkov farmakovigilance po vsem svetu dveh imetnikov dovoljenja za promet z zdravilom (presečna datuma sta bila 15. februar 2013 oziroma 29. april 2013).
English: Taking the totality of data into account, the CHMP considered that causality cannot be excluded and that aneuploidy should be considered as a cancer risk factor on theoretical grounds.
Slovenian: Potem ko je proučil vse podatke, je CHMP menil, da vzročnosti ni mogoče izključiti in da bi morala anevploidija na podlagi teoretičnih spoznanj veljati za dejavnik tveganja za raka.
English: For the purpose of the review of this risk, the MAHs provided an analysis of this genotoxic potential for each systemic route of administration, together with an analysis of possible risk factors, including relevant criteria such as dose and duration of treatment.
Slovenian: Da bi omogočili pregled tega tveganja, so imetniki dovoljenja za promet z zdravilom predložili analizo genotoksičnega potenciala za vsako sistemsko pot uporabe, skupaj z analizo možnih dejavnikov tveganja, v katero so vključili pomembne faktorje, kot sta odmerek in trajanje zdravljenja.
English: • one case of threat of premature delivery.
Slovenian: • en primer grozečega prezgodnjega poroda.
English: In most cases the treatment is for short-term use and not associated with the perception of increased cancer risk for both physicians and patients, therefore a causal relationship between cancer occurrence and treatment is difficult to establish.
Slovenian: V večini primerov je zdravilo namenjeno kratkotrajni uporabi in ga zdravniki ter bolniki ne povezujejo s povečanim tveganjem za raka, tako da je vzročno razmerje med pojavom raka in zdravljenjem težko dokazati.
English: In the first database, 11 cases secondary to exposure during pregnancy were reported:
Slovenian: V prvi zbirki podatkov so zabeležili 11 primerov, ki so bili posledica izpostavljenosti med nosečnostjo:
English: • The Committee considered also that thiocolchicoside containing medicinal products for systemic use should be contraindicated during the entire pregnancy period.
Slovenian: • odbor je menil tudi, da je treba zdravila za sistemsko uporabo, ki vsebujejo tiokolhikozid, kontraindicirati med celotnim obdobjem nosečnosti.
English: • The Committee considered the procedure under Article 31 of Directive 2001/83/EC for thiocolchicoside containing medicinal products for systemic use (see annex I).
Slovenian: • odbor je obravnaval napotitveni postopek v skladu s členom 31 Direktive 2001/83/ES za zdravila za sistemsko uporabo, ki vsebujejo tiokolhikozid (glejte Prilogo I);
English: Grounds for the maintenance of the marketing authorisations
Slovenian: Podlaga za ohranitev dovoljenj za promet z zdravili
English: A risk management plan (RMP) will be submitted to national competent authorities in accordance with agreed timelines and periodic safety update reports (PSURs) will be submitted every 3 years.
Slovenian: Pristojnim nacionalnim organom se bo v dogovorjenih rokih predložil načrt za obvladovanje tveganja (RMP) in vsaka 3 leta tudi redno posodobljena poročila o varnosti zdravila (PSUR).
English: However, whether the exposure to M2 would be below a threshold of aneugenicity (including a sufficient safety margin) is unknown since M2 has not been analysed in the available clinical kinetic studies.
Slovenian: Vendar ni znano, ali bi bila izpostavljenost presnovku M2 pod mejno vrednostjo za anevgenost (ob upoštevanju zadostnega varnostnega faktorja), saj M2 v razpoložljivih kliničnih kinetičnih študijah niso analizirali.
English: Given the treatment conditions with TCC (short-term, potentially aneugenic at maximum doses) effects on male fertility will be low and a rapid recover to normal levels can be expected.
Slovenian: Glede na pogoje zdravljenja s tiokolhikozidom (kratkotrajno, potencialno anevgeno pri največjih odmerkih) bodo učinki na plodnost pri moških majhni, pričakuje pa se tudi hitra povrnitev normalnih ravni.
English: It was concluded that M1 (SL18.0740) is devoid of mutagenic (gene mutations) and clastogenic (structural chromosome damage) potential, but is able to induce aneuploidy (numerical chromosome damage).
Slovenian: Ugotovili so, da M1 (SL18.0740) nima mutagenega (mutacije genov) in klastogenega (strukturne poškodbe kromosomov) potenciala, lahko pa povzroči anevploidijo (številčne poškodbe kromosomov).
English: No case was registered for neonatal effects related to exposure occurred in late pregnancy or during childbirth.
Slovenian: Primerov neželenih učinkov na novorojenčke, povezanih z izpostavljenostjo v pozni nosečnosti ali med porodom, niso zabeležili.
English: Aneuploidy is a common characteristic of cancer cells.
Slovenian: Anevploidija je skupna lastnost rakavih celic.
English: Therefore, on the basis of the above-mentioned available data, the CHMP considered the safety margins and benefit/risk for TCC and SL18.0740 (M1) acceptable.
Slovenian: CHMP je zato na podlagi zgoraj omenjenih razpoložljivih podatkov menil, da so varnostni faktorji ter razmerje med tveganji in koristmi za tiokolhikozid in presnovek SL18.0740 (M1) sprejemljivi.
English: These products should also be contraindicated in women of childbearing potential not using contraception and during lactation.
Slovenian: Prav tako jih je treba kontraindicirati pri ženskah v rodni dobi, ki ne uporabljajo kontracepcije, in med dojenjem.
English: The study protocol should be provided within the RMP.
Slovenian: Protokol za študijo mora biti predložen v okviru načrta za obvladovanje tveganja.
English: Genotoxic mechanisms, such as aneuploidy, involving cell division and non-DNA targets, are known to occur above a certain threshold of exposure.
Slovenian: Genotoksični mehanizmi, kot je anevploidija, ki vključujejo delitev celic in tarčna mesta, ki niso DNA, se dokazano pojavijo nad določeno mejno vrednostjo izpostavljenosti.
English: In addition males and females showed only a slight gender difference in exposure.
Slovenian: Poleg tega so pri samcih in samicah zabeležili zelo majhne razlike v izpostavljenosti glede na spol.
English: However a follow-up study (in vivo micronucleus test) defined a no-effect level of 39.6 mg/kg.
Slovenian: Vendar pa je nadaljnja študija (mikronukleusni preskus in vivo) pokazala, da je odmerek do 39,6 mg/kg brez učinka.
English: After parenteral use, the plasma concentration of M2 is expected to be much lower as the M2 transformation occurs after oral administration mainly by intestinal metabolism.
Slovenian: Po parenteralni uporabi se pričakuje veliko manjša koncentracija M2 v plazmi, saj transformacija M2 po peroralnem dajanju v glavnem poteka s črevesno presnovo.
English: In addition, the CHMP was of the view that the package size should be restricted according to the new treatment-days scheme recommended (up to 30 tablets or capsules/4 mg pack, up to 14 tablets or capsules/8 mg pack and up to 10 vials/ampoules).
Slovenian: Poleg tega je CHMP menil, da je treba omejiti velikost pakiranja v skladu z novimi priporočili za omejitev zdravljenja na določeno število dni (največ 30 tablet ali kapsul/4-miligramsko pakiranje, največ 14 tablet ali kapsul/8-miligramsko pakiranje in največ 10 vial/ampul).
English: A significantly increased cancer risk would in general be dependent on long-term/chronic exposure/dosing with the aneugen.
Slovenian: Tveganje za raka bi se pri anevgenu običajno znatno povečalo zaradi dolgotrajne/kronične izpostavljenosti/odmerjanja.
English: Aneuploidy (variation in the number of chromosomes and loss of heterozygosity) is recognised as a potential risk factor for cancer when impacting somatic cells, and teratogenicity, embryotoxicity/spontaneous abortions and impaired male fertility when impacting germ cells1.
Slovenian: Anevploidija (sprememba števila kromosomov in izguba heterozigotnosti) je znan možni dejavnik tveganja za raka, kadar so prizadete somatske celice, in za teratogenost, embriotoksičnost/spontane splave ter zmanjšano plodnost moških, kadar so prizadete spolne celice1.
English: The preclinical development of TCC was mainly performed during the 1980s, and then complemented in the 1990s to be compliant with the European guidelines on the non-clinical documentation for mixed marketing authorisation applications (CPMP/SWP/799/95) and to investigate a new active metabolite SL18.0740 (M1) identified at that time.
Slovenian: Predklinični razvoj tiokolhikozida je v glavnem potekal v 80. letih prejšnjega stoletja, nato pa so ga v 90. letih dopolnili, da bi ga uskladili z evropskimi smernicami za predklinično dokumentacijo za mešane vloge za pridobitev dovoljenja za promet z zdravilom (CPMP/SWP/799/95) in raziskali aktivni presnovek SL18.0740 (M1), ki so ga v tistem času na novo odkrili.
English: • The Committee considered that thiocolchicoside containing medicinal products for systemic use remain an effective adjuvant treatment of painful muscle contractures in acute spinal pathology.
Slovenian: • odbor je menil, da so zdravila za sistemsko uporabo, ki vsebujejo tiokolhikozid, še vedno učinkovito adjuvantno zdravljenje pri bolečem krčenju mišic pri akutni patologiji hrbtenice.
English: • The Committee concluded that there was a need for further risk minimisation measures such as a drug utilisation study to characterise the prescribing practices during typical clinical use, as well as adequate educational materials to be developed for patients and prescribers.
Slovenian: • odbor je zaključil, da so potrebni dodatni ukrepi za zmanjšanje tveganja, kot sta študija o uporabi zdravila za razjasnitev prakse pri predpisovanju zdravila med običajno klinično uporabo in dovolj izčrpno izobraževalno gradivo, namenjeno bolnikom in zdravstvenim delavcem, ki predpisujejo zdravilo.
English: In the two in vitro and in vivo preclinical studies conducted, the findings (increase in the incidence of micronucleated cells) were observed at concentrations/exposures close to the exposures measured in human at therapeutic doses.
Slovenian: V obeh opravljenih predkliničnih študijah in vitro ter in vivo so opažanja (povečanje incidence celic z mikronukleusi) zabeležili pri koncentracijah/izpostavljenostih, ki so bile blizu izpostavljenostim, zabeleženim pri ljudeh po terapevtskih odmerkih.
English: Since no relevant genetic toxicology studies were previously performed with the aglycone metabolite SL59.0955, complementary studies (chromosome damage assays) were performed in order to investigate the genotoxic profile of this metabolite and its ability to induce aneuploidy in nonclinical in vitro (up to 600 µg/mL) and in vivo (up to 150 mg/kg):
Slovenian: Ker v preteklosti niso bile opravljene nobene ustrezne študije genotoksičnosti z aglikonskim presnovkom SL59.0955, so opravili komplementarni študiji (analizi poškodb kromosomov), da bi raziskali genotoksični profil tega presnovka in njegovo sposobnost povzročanja anevploidije v predkliničnih preskusih in vitro (do 600 µg/ml) ter in vivo (do 150 mg/kg):
English: To address the risks of teratogenicity and embryo-toxicity/spontaneous abortions the CHMP agreed on contraindicating TCC during the entire pregnancy period, during lactation, and in women of childbearing potential not using contraception.
Slovenian: Da bi zmanjšali tveganja za teratogenost in toksičnost za zarodek/spontani splav, se je CHMP dogovoril, da je treba tiokolhikozid kontraindicirati med celotnim obdobjem nosečnosti in dojenjem ter pri ženskah v rodni dobi, ki ne uporabljajo kontracepcije.
English: These measures are to be included in the RMP.
Slovenian: Ukrepi morajo biti vključeni v načrt za obvladovanje tveganja.
English: The use of the product should therefore be limited to acute conditions in patients over 16 years old; an updated SmPC with restriction for use and duration therapy was endorsed accordingly.
Slovenian: Uporabo zdravila je torej treba omejiti na uporabo pri akutnih stanjih pri bolnikih, starejših od 16 let; v skladu s tem je bil sprejet posodobljen povzetek glavnih značilnosti zdravila z omejitvami glede uporabe in trajanja zdravljenja.
English: The CHMP considered that a Direct healthcare professional communication (DHPC) was needed to inform on the outcome of the present review, including the updated indication, the clinical use for these products (short-term) and to highlight the genotoxic risk.
Slovenian: CHMP je menil, da je treba izdati neposredno obvestilo zdravstvenim delavcem (DHPC), da se jih seznani z izidom tega pregleda, vključno s spremenjeno indikacijo in klinično uporabo za ta zdravila (za kratek čas), ter da se jih opozori na tveganje za genotoksičnost.
English: The CHMP also considered that the use of TCC should be avoided during puberty (12 to 16-18 years) due to potential risk on fertility.
Slovenian: CHMP je prav tako menil, da se je treba zaradi možnih neželenih učinkov na plodnost uporabi tiokolhikozida izogibati med puberteto (med 12. in 16.-18. letom).
English: These PSURs should include a report compiling continuous monitoring of any safety signal correlated with aneuploidy and pregnancy on accidental exposure to the drug.
Slovenian: Ta morajo vsebovati poročilo, v katerem so zbrani podatki o rednem spremljanju kakršnih koli opozorilnih znakov, povezanih z anevploidijo, in nosečnosti z nenamerno izpostavitvijo zdravilu;
English: The aneugenic effect was observed at LOEL corresponding to only 1.6 x human Cmax and 4.1 x AUC (8mg bid, Per Os (PO)).
Slovenian: Anevgeni učinek so opazili pri LOEL, ki je ustrezal samo 1,6-kratni Cmax in 4,1-kratni AUC pri človeku (8 mg dvakrat na dan, skozi usta).
English: Continuous monitoring of any safety signal correlated with aneuploidy (i.e. teratogenicity, embryo-foetal toxicity / spontaneous abortion, impaired male fertility and cancer) and pregnancy reporting to collect structured data on accidental exposure to the drug should be performed.
Slovenian: Potrebna sta tudi redno spremljanje glede kakršnih koli opozorilnih znakov, povezanih z anevploidijo (tj. teratogenost, embriofetalna toksičnost/spontani splav, zmanjšana plodnost pri moških in rak), in poročanje o nosečnosti, da se zberejo strukturirani podatki o nenamerni izpostavljenosti zdravilu.
English: The in vitro MN test in human lymphocytes showed that M2 induced micronuclei in cultured human peripheral blood lymphocytes in all treatment conditions.
Slovenian: MN preskus in vitro na človeških limfocitih je pokazal, da je M2 spodbudil nastajanje mikronukleusov v gojenih človeških limfocitih periferne krvi v vseh pogojih zdravljenja.
English: Thiocolchicoside (TCC) is a semi-synthetic sulfurated colchicoside derivative with a muscle relaxant pharmacological activity.
Slovenian: Tiokolhikozid je žveplan polsintetični derivat kolhikozida, ki farmakološko deluje kot mišični relaksant.