qanastek/EMEA-V3 huggingface dataset:
However, in combining with platinum agents, there is a distinct sequence-dependent interaction depending on whether the platinum agent is given on day 1 or 5 of the topotecan dosing.
Madanakollu, meta jiġu użati ukoll mediċini li għandhom il- platinum, hemm interazzjoni distinta li tiddependi fuq is - sekwenza tal- mediċini, tiddependi fuq jekk il- mediċina li fiha l- platinum tingħatax fl- ewwel jew fil - ħames jum waqt li qed jingħata topotecan.
If either cisplatin or carboplatin is given on day 1 of the topotecan dosing, a lower dose of each agent must be given to improve tolerability compared to the dose of each agent which can be given if the platinum agent is given on day 5 of the topotecan dosing.
Jekk cisplatin jew carboplatin jingħataw lill- pazjent fl - ewwel ġurnata tad- dożaġġ ta ’ topotecan, trid tingħata doża iktar baxxa ta ’ kull prodott, biex tkun tista ’ titjieb it- tollerabilità tagħhom.
When topotecan (0.75 mg/ m2/ day for 5 consecutive days) and cisplatin (60 mg/ m2/ day on Day 1) were administered in 13 patients with ovarian cancer, a slight increase in AUC (12%, n=9) and Cmax (23%, n=11) was noted on day 5.
Meta topotecan (0. 75 mg/ m2 / ġurnata għal ħamest ijiem konsekuttivi) u cisplatin (60 mg/ m2 / ġurnata fil- ġurnata 1) ġew amministrati lil 13- il pazjent b’ kanċer ta ’ l- ovarji, żjieda żgħira fl- AUC (12%, n=9) u Cmax (23%, n=11) kienet innutata fil- ġurnata 5.
This increase is considered unlikely to be of clinical relevance.
Din iż- żjieda hija kkunsidrata li x’ aktarx m’ hijiex ta ’ rilevanza klinika.
As with all cytotoxic chemotherapy, effective contraceptive methods must be advised when either partner is treated with topotecan.
Bħal fil- każ ta ’ kull kemoterapija ċitotossika, għandha tingħata rakkomandazzjoni li jintużaw metodi effettivi ta ’ kontraċezzjoni meta l- mara jew ir- raġel qed jirċievu trattament b’ topotecan.
Topotecan has been shown to cause embryo-foetal lethality and malformations in preclinical studies (see section 5.3).
Minn studji pre- kliniċi li saru, topotecan ġie ippruvat li jikkawża il- mewt jew malformazzjoni ta ’ l - embrju jew fetu (ara sezzjoni 5. 3).
As with other cytotoxic medicinal products, topotecan may cause foetal harm and therefore women of child bearing potential should be advised to avoid becoming pregnant during therapy with topotecan.
Bħal fil- każ ta ’ prodotti mediċinali ċitotossiċi oħra, topotecan jista jagħmel ħsara lil- fetu w għalhekk għandu jingħata parir lin- nisa li jistgħu jinqabdu tqal biex jevitaw it - tqala waqt il- kura b’ topotecan.
If topotecan is used during pregnancy, or if the patient becomes pregnant during therapy with topotecan, the patient must be warned of the potential hazards to the foetus.
Fil- każ li topotecan jintuża waqt it- tqala jew il- mara tinqabad tqila waqt il- kura b’ topotecan, din għandha tiġi avżata dwar il- periklu potenzjali għal- fetu.
Topotecan is contra-indicated during breast-feeding (see section 4.3).
Topotecan huwa kontra- indikat waqt it- treddigħ (ara sezzjoni 4. 3).
Although it is not known whether topotecan is excreted in human breast milk, breast-feeding should be discontinued at the start of therapy.
Għalkemm mhux magħruf jekk topotecan jgħaddix fil- ħalib tas- sider, it- treddigħ irid jieqaf meta tibda t- terapija.
No effects on male or female fertility have been observed in reproductive toxicity studies in rats (see section 5.3).
F’ studji dwar it- tossiċita riprodduttiva fil- firien, ma ġew osservati l- ebda effetti fuq il- fertilità tal- firien nisa jew irġiel (ara sezzjoni 5. 3).
However, as with other cytotoxic medicinal products topotecan is genotoxic and effects on fertility, including male fertility, cannot be excluded.
Madankollu, bħal prodotti mediċinali ċitotossiċi oħra topotecan huwa ġenotossiku w effetti fuq il- fertilità, inkluż fuq il- fertilità tar- raġel, ma jistgħux jiġu esklużi.
However, caution should be observed when driving or operating machines if fatigue and asthenia persist.
Madanakollu, għandu jkun hemm attenzjoni fis- sewqan jew it- tħaddim ta ’ magni jekk l- għeja jew it- telqa jippersistu.
In dose-finding trials involving 523 patients with relapsed ovarian cancer and 631 patients with relapsed small cell lung cancer, the dose limiting toxicity of topotecan monotherapy was found to be haematological.
Fi studji fejn tiġi stabbilita d- doża rakkomandata, li kienu jinvolvu 523 pazjent b’ kanċer ta ’ l- ovarji li reġa ’ feġġ u 631 pazjent b’ kanċer taċ- ċelluli ż- żgħar tal- pulmun li reġa ’ feġġ, instab li l- effett tossiku ematoloġiku huwa dak li jillimita d- doża ta ’ monoterapija b’ topotecan.
Toxicity was predictable and reversible.
It- tossiċità kienet prevedibbli u wkoll riversibbli.
There were no signs of cumulative haematological or non-haematological toxicity.
Ma kien hemm l- ebda indikazzjoni ta ’ tossiċità kumulattiva ematoloġika jew mhux ematoloġika.
The adverse event profile for topotecan when given in combination with cisplatin in the cervical cancer clinical trials is consistent with that seen with topotecan monotherapy.
Il- profil ta ’ l- effetti avversi għal topotecan meta jingħata flimkien ma cisplatin fi provi kliniċi tal - kanċer taċ- ċerviċi huwa konsistenti ma dak li ntwera b’ monoterapija ta ’ topotecan.
The overall haematological toxicity is lower in patients treated with topotecan in combination with cisplatin compared to topotecan monotherapy, but higher than with cisplatin alone.
It- tossiċità ematoloġika totali hija anqas f’ pazjenti trattati b’ topotecan flimkien ma ’ cisplatin meta mqabbla ma ’ monoterapija b ’ topotecan, iżda ogħla milli b’ cisplatin waħdu.
Additional adverse events were seen when topotecan was given in combination with cisplatin, however, these events were seen with cisplatin monotherapy and not attributable to topotecan.
Aktar ġrajjiet avversi intwerew meta topotecan ingħata flimkien ma cisplatin, madanakollu, dawn il - ġrajjiet intwerew b’ monoterapija b’ cisplatin u m’ humiex attribwiti għal topotecan.
The prescribing information for cisplatin should be consulted for a full list of adverse events associated cisplatin use.
L- informazzjoni ta ’ kif għandu jiġi preskritt cisplatin għandha tiġi kkonsultata għall- lista kompleta ta ’ reazzjonijiet avversi assoċjati ma ’ l- użu ta ’ cisplatin.
5 The integrated safety data for topotecan monotherapy are presented below.
6 It- tagħrif integrat ta ’ sigurtà għal monoterapija b’ topotecan huma ppreżentati hawn taħt.
Adverse reactions are listed below, by system organ class and absolute frequency (all reported events).
Reazzjonijiet avversi huma elenkati hawn taħt, ikklassifikati skond is- sistema tal- ġisem u l- frekwenza assoluta (il- ġrajjiet kollha rappuratati).
Frequencies are defined as: very common (≥ 1/ 10), common (≥ 1/ 100, < 1/ 10); uncommon (≥ 1/ 1,000, < 1/ 100); rare (≥ 1/ 10,000, < 1/ 1,000); very rare (< 1/ 10,000), including isolated reports and not known (cannot be estimated from the available data).
Il- frekwenzi huma definiti bħala: komuni ħafna (> 1/ 10), komuni (> 1/ 100, < 1/ 10); mhux komuni (> 1/ 1, 000, < 1/ 100); rari (> 1/ 10, 000, < 1/ 1, 000); rari ħafna (< 1/ 10, 000) inklużi rapporti iżolati u mhux magħrufa (ma jistgħux jiġu kkalkolati mit- tagħrif eżistenti).
Blood and lymphatic system disorders Very common: febrile neutropenia, neutropenia (see Gastrointestinal disorders), thrombocytopenia, anaemia, leucopenia.
Disturbi tad- demm u tas- sistema limfatika Komuni ħafna: newtropenja bid- deni, newtropenja (ara Disturbi gastro- intestinali), tromboċitopenja, anemija, lewkopenja.
Respiratory, thoracic and mediastinal disorders Rare: interstitial lung disease
Disturbi respiratorji, toraċiċi u medjastinali Rari: mard fiċ- ċelluli interstitial tal- pulmun
Nausea, vomiting and diarrhoea (all of which may be severe), constipation, abdominal pain* and mucositis. *Neutropenic colitis, including fatal neutropenic colitis, has been reported to occur as a complication of topotecan-induced neutropenia (see section 4.4).
Dardir, rimettar, u dijarrea (li kollha jistgħu jkunu serji), stitikezza, uġigħ ta ’ żaqq * u mukosite. * Kolite tan- newtropenja, inkluża l- kolite tan- newtropenja fatali, ġiet irrappurtata bħala kumplikazzjoni tan- newtropenja kkawżata minn topotecan (ara sezzjoni 4. 4).
Skin and subcutaneous tissue disorders Very common: alopecia.
Disturbi fill- ġilda u fit- tessuti ta ’ taħt il- ġilda Komuni ħafna: alopeċja.
Common: pruritus.
Komuni: ħakk.
Metabolism and nutrition disorders Very common: anorexia (which may be severe).
Disturbi fil- metaboliżmu u n- nutrizzjoni Komuni ħafna: anoreksja (li tista ’ tkun serja)
Infections and infestations Very common: infection Common: sepsis
Infezzjonijiet u infestazzjonijiet Komuni ħafna: infezzjoni Komuni: sepsis
General disorders and administration site conditions Very common: pyrexia, asthenia, fatigue.
Disturbi ġenerali u kundizzjonijiet ta 'mnejn jingħata Komuni ħafna: deni, astenja, għeja.
Common: malaise.
Komuni: telqa.
Very rare: extravasation*. *Extravasation has been reported very rarely.
Rari: estravażazzjoni *. * Estravażazzjoni ġiet irrappurtata b’ mod rari ħafna.
Reactions have been mild and have not generally required specific therapy.
Reazzjonijiet kienu ħfief u ma ’ kellhomx bżonn terapija speċifika li ġeneralment ikun hemm bżonnha.
Immune system disorders Common: hypersensitivity reaction including rash Rare: anaphylactic reaction, angioedema, urticaria.
Disturbi fis- sistema immuni Komuni: reazzjoni ta ’ sensittività eċċessiva inkluż raxx Rari: reazzjoni anafilattika, anġoedima, urtikarja.
Hepato-biliary disorders Common: hyperbilirubinaemia.
Disturbi fil- fwied u fil- marrara Komuni: iperbilirubinimja.
The incidence of adverse events listed above have the potential to occur with a higher frequency in patients who have a poor performance status (see section 4.4).
L- inċidenza ta ’ reazzjonijiet avversi elenkati hawn fuq għandhom il- potenzjal li jiġru bi frekwenza ogħla f’ dawk il- pazjenti bi stat ta ’ saħħa ħażina (ara sezzjoni 4. 4).
The frequencies associated with the haematological and non-haematological adverse events listed below represent the adverse event reports considered to be related/ possibly related to topotecan therapy.
Il- frekwenzi assoċjati mal- ġrajjiet avversi ematoloġiċi u mhux ematoloġiċi elenkati hawn taħt jirrapreżentaw ir- rapporti ta ’ ġrajjiet avversiikkunsidrati li għandhom / jista ’ jkollhom x’ jaqsmu ma terapija b’ topotecan.
6 Haematological Neutropenia:
7 Ematoloġiċi Newtropenja:
Severe (neutrophil count < 0.5 x 109/ l) during course 1 was seen in 55% of the patients and with duration ≥ 7 days in 20% and overall in 77% of patients (39% of courses).
Serja (numru ta ’ newtrofili < 0. 5 x 109/ l) wara l- ewwel kors instabet f’ 55% tal- pazjenti li damet ≥ 7 ijiem f’ 20% u b’ kollox f’ 77% tal- pazjenti (39% tal- korsijiet).
In association with severe neutropenia, fever or infection occurred in 16% of patients during course 1 and overall in 23% of patients (6% of courses).
Flimkien ma newtropenja qawwija, kien hemm inċidenza ta ’ deni jew infezzjoni f’ 16% tal- pazjenti waqt l- ewwel kors u b’ kollox f’ 23% tal- pazjenti (6% tal- korsijiet).
Median time to onset of severe neutropenia was 9 days and the median duration was 7 days.
Iż- żmien medju għal bidu ta ’ newtropenja qawwija kien 9 ijiem u ħadet medja ta ’ 7 ijiem.
Severe neutropenia lasted beyond 7 days in 11% of courses overall.
Newtropenja qawwija damet iktar minn 7 ijiem fi 11% tat- total tal- korsijiet.
Among all patients treated in clinical trials (including both those with severe neutropenia and those who did not develop severe neutropenia), 11% (4% of courses) developed fever and 26% (9% of courses) developed infection.
Fost il- pazjenti kollha li kienu kkurati fi studji kliniċi (inklużi kemm dawk b’ newtropenja qawwija kif ukoll dawk li ma żviluppawx newtropenja qawwija), 11% (4% tal- korsijiet) kellhom d- deni u 26% (9% tal- korsijiet) qabdithom infezzjoni.
In addition, 5% of all patients treated (1% of courses) developed sepsis (see section 4.4).
5% tal- pazjenti kkurati (1% tal- korsijiet) kellhom sepsis (ara sezzjoni 4. 4).
Thrombocytopenia:
Tromboċitopenja:
Severe (platelets less than 25 x 109/ l) in 25% of patients (8% of courses); moderate (platelets between 25.0 and 50.0 x 109/ l) in 25% of patients (15% of courses).
Serja (plejtlits inqas minn 25 x 109/ l) f’ 25% tal- pazjenti (8% tal- korsijiet); moderata (plejtlits bejn 25. 0 u 50. 0 x 109/ l) f’ 25% tal- pazjenti (15% tal- korsijiet).
Median time to onset of severe thrombocytopenia was Day 15 and the median duration was 5 days.
Iż- żmien medju għal bidu ta ’ tromboċitopenja qawwija kienet l- 15- il ġurnat u ħadet medja ta ’ 5 ijiem.
Platelet transfusions were given in 4% of courses.
Trasfużjonijiet ta ’ plejtlits ingħataw f’ 4% tal- korsijiet.
Reports of significant sequelae associated with thrombocytopenia including fatalities due to tumour bleeds have been infrequent.
Rapporti ta ’ konsegwenzi sinifikani assoċjati ma ’ tromboċitopenja inkluż fatalitajiet minħabba fsada tat- tumuri ma kienux frekwenti.
Moderate to severe (Hb ≤ 8.0 g/ dl) in 37% of patients (14% of courses).
Moderata sa qawwija (Hb ≤ 8. 0 g/ dl) f’ 37% tal- pazjenti (14% tal- korsijiet).
Red cell transfusions were given in 52% of patients (21% of courses).
Trasfużjonijiet ta ’ ċelluli ħomor ingħataw lil 52% tal- pazjenti (21% tal- korsijiet).
Non-haematological Frequently reported non-haematological effects were gastrointestinal such as nausea (52%), vomiting (32%), and diarrhoea (18%), constipation (9%) and mucositis (15%).
Mhux ematoloġiċi Effetti mhux ematoloġiċi li ġew irrappuratati b’ mod frekwenti kienu dawk gastro- intestinali bħal dardir (52%), rimettar (32%) u dijarrea (18%), stitikezza (9%) u mukosajtis (15%).
Severe (grade 3 or 4) nausea, vomiting, diarrhoea and mucositis incidence was 4, 3, 2 and 1% respectively.
Dardir qawwi (skala 3 jew 4), rimettar, dijarrea u inċidenza ta ’ mukosite kienet ta ’ 4, 3, 2 u 1% rispettivament.
Mild abdominal pain was also reported amongst 4% of patients.
Ġie irrappurtat ukoll uġigħ ta ’ żaqq ħafif f’ 4% tal- pazjenti.
Fatigue was observed in approximately 25% and asthenia in 16% of patients whilst receiving topotecan.
Għeja kienet irrappurtata bejn wieħed u ieħor f’ 25% tal- pazjenti u astenja f’ bejn wieħed u ieħor 16% tal- pazjenti waqt li kienu qed jieħdu topotecan.
Severe (grade 3 or 4) fatigue and asthenia incidence was 3 and 3% respectively.
Inċidenza ta ’ għeja u astenja serja (skala 3 jew 4) kienet ta ’ 3% u 3% rispettivament.
Total or pronounced alopecia was observed in 30% of patients and partial alopecia in 15% of patients.
Alopeċja kompleta jew serja ġiet osservata f’ 30% tal- pazjenti u alopeċja parzjali f’ 15% tal- pazjenti.
Other severe events occurring in patients that were recorded as related or possibly related to topotecan treatment were anorexia (12%), malaise (3%) and hyperbilirubinaemia (1%).
Anoreksja (12%), telqa (3%) u iperbilirubinimja (1%) kienu ġrajjiet serji oħra li ġew osservati f’ pazjenti u li kienu, jew setgħu kienu, assoċjati ma ’ kura b’ topotecan.
Hypersensitivity reactions including rash, urticaria, angioedema and anaphylactic reactions have been reported rarely.
Reazzjonijiet ta ’ sensittivita ’ eċċessiva, inkluż raxx, urtikarja, anġjoedima u reazjonijiet anafilattiċi ġew irrappurtati f’ każijiet rari.
In clinical trials, rash was reported in 4% of patients and pruritus in 1.5% of patients.
Fi provi kliniċi, ġie irrapurtat raxx f ’. 4% tal- pazjenti u ħakk f’ 1. 5% tal- pazjenti.
There is no known antidote for topotecan overdose.
M’ hemm l- ebda antidot għal doża eċċessiva ta ’ topotecan.
The primary complications of overdose are anticipated to be bone marrow suppression and mucositis.
Il- kumplikazzjonijiet ewlenin ta ’ doża eċċessiva x’ aktarx ikunu dipressjoni tal- mudullun u mukosite.
ATC code:
Prodotti antinejoplastiċi oħra: kodiċi ATC:
7 The anti-tumour activity of topotecan involves the inhibition of topoisomerase-I, an enzyme intimately involved in DNA replication as it relieves the torsional strain introduced ahead of the moving replication fork.
L- attività ta ’ topotecan kontra tumuri tikkonsisti fl- inibizzjoni ta ’ topoisomerase- I, li hija enżima partikolarment involuta fir- replikazzjoni ta ’ DNA waqt li jneħħi l- istrejn tat- tidwir ta ’ qabel il- moving replication fork.
Topotecan inhibits topoisomerase-I by stabilising the covalent complex of enzyme and strand-cleaved DNA which is an intermediate of the catalytic mechanism.
Topotecan jinibixxi topoisomerase- I billi jistabiliżża lill- kumpless kovalenti tal - 8 enżima u lid - DNA maqsum bl- istrand li huwa l- proċess intermedjarju tal- mekaniżmu katalitiku.
The cellular sequela of inhibition of topoisomerase-I by topotecan is the induction of protein-associated DNA single-strand breaks.
Il - konsegwenzi ċellulari ta ’ l- inibizzjoni ta ’ topoisomerase- I min- naħa ta ’ topotecan hija l- induzzjoni ta ’ qsim ta ’ strand waħda tad- DNA li hi assoċjata mall- proteina.
Relapsed Ovarian Cancer
Kanċer ta ’ l- Ovarji li reġa ’ feġġ
In a comparative study of topotecan and paclitaxel in patients previously treated for ovarian carcinoma with platinum based chemotherapy (n = 112 and 114, respectively), the response rate (95% CI) was 20.5% (13%, 28%) versus 14% (8%, 20%) and median time to progression 19 weeks versus 15 weeks (hazard ratio 0.7 [0.6, 1.0]), for topotecan and paclitaxel, respectively.
Fi studju kumparattiv bejn topotecan u paclitaxel f’ pazjenti li diġà ġew ikkurati għal karċinoma fl - ovarji permezz ta ’ kimoterapija ibbażata fuq il- platinum (n = 112 u 114, rispettivament,) ir- rata ta ’ rispons (95% CI) kienet ta ’ 20. 5% (13%, 28%) kontra 14% (8%, 20%) u ż- żmien medju għal kontinwazzjoni kienet ta ’ 19- il ġimgħa versu 15- il ġimgħa (proporzjon ta periklu 0. 7 [0. 6, 1. 0]), għal topotecan u paclitaxel rispettivament.
Median overall survival was 62 weeks for topotecan versus 53 weeks for paclitaxel (hazard ratio 0.9 [0.6, 1.3]).
Ir- rata medja totali ta ’ għejxien kienet ta ’ 62 ġimgħa għal topotecan, kontra 53 ġimgħa għal paclitaxel (proporzjon ta ’ periklu 0. 9 [0. 6, 1. 3]).
The response rate in the whole ovarian carcinoma programme (n = 392, all previously treated with cisplatin or cisplatin and paclitaxel) was 16%.
Ir- rata ta ’ rispons għal kura fl- istudju kollu tal- karċinoma fl- ovarji (n = 392, kollha preċedentement ikkurati b’ cisplatin jew cisplatin u paclitaxel) kienet ta ’ 16%.
The median time to response in clinical trials was 7.6- 11.6 weeks.
Iż- żmien medju ta ’ rispons ta ’ dawk li rrispondew għall- kura fi studji kliniċi kienet ta ’ bejn 7. 6 u 11. 6 ġimgħat.
In patients refractory to, or relapsing within 3 months after cisplatin therapy (n = 186), the response rate was 10%.
F’ pazjenti li ma rrispondewx għal kura jew fejn il- marda reġgħet feġġett fi żmien 3 xhur wara kura b’ cisplatin (n = 186), ir- rata ta ’ rispons kienet ta ’ 10%.
These data should be evaluated in the context of the overall safety profile of the medicinal product, in particular to the important haematological toxicity (see section 4.8).
Din l- informazzjoni trid tiġi evalwata fil- kuntest tal- profil tas- sigurtà ġenerali ta ’ din il- mediċina, partikolarment fil- kuntest tat- tossiċità ematologika importanti (ara sezzjoni 4. 8).
A supplementary retrospective analysis was conducted on data from 523 patients with relapsed ovarian cancer.
Saret analiżi supplementari retrospettiva f’ 523 pazjent li kellhom karċinoma ta ’ l- ovarji li reġa ’ feġġ.
Altogether, 87 complete and partial responses were observed, with 13 of these occurring during cycles 5 and 6 and 3 occurring thereafter.
Irriżulta illi b’ kollox, 87 pazjent irrispondew kompletament jew parzjalment, bi 13 minn dawn li ġraw waqt iċ- ċikli 5 u 6 u 3 li ġraw wara.
For patients administered more than 6 cycles of therapy, 91% completed the study as planned or were treated until disease progression with only 3% withdrawn for adverse events.
Għal pazjenti li ġew mgħotija iktar minn 6 ċikli ta ’ terpija, 91% spiċċaw l- istudju kif kien ippjanat jew ġew trattati sakkemm reġgħet feġġet il- marda, bi 3% biss li ma spiċċawx l- istudju minħabba effetti avversi.
Relapsed SCLC
SCLC li reġa ’ feġġ
A phase III trial compared oral topotecan plus Best Supportive Care [BSC] [n=71] with BSC alone [n=70] in patients who had relapsed following first line therapy [median time to progression [TTP] from first-line therapy:
Prova klinika tal- fażi III qabblet topotecan flimkien ma ’ l- Aħjar Kura ta ’ Appoġġ [BSC] [n=71] ma ’ BSC waħdu [n=70] f’ pazjenti li l- kanċer tagħhom reġa ’ feġġ wara t- terapija ewlenija [żmien medju għall- progressjoni [TTP] mit- terapija ewlenija:
84 days for oral topotecan + BSC, 90 days for BSC] and for whom retreatment with i. v chemotherapy was not considered appropriate.
84 ġurnata għal- terapija b’ topotecan + BSC, 90 ġurnata għal- BSC] u li għalihom trattament ieħor b’ kimoterapija li tingħata fil- vina ma kienx ikkunsidrat xieraq.
Oral topotecan plus BSC group had a statistically significant improvement in overall survival compared with the BSC alone group (Log- rank p=0.0104).
(Log- rank p=0. 0104).
The unadjusted hazard ratio for oral topotecan plus BSC group relative to BSC alone group was 0.64 (95% CI:
Il- proporzjon ta ’ periklu (hazard ratio) mhux aġġustat għall- grupp ta ’ topotecan mill- ħalq flimkien ma ’ BSC mqabbel mal- grupp ta ’ BSC waħdu kien 0. 64 (95% CI:
0.45, 0.90).
0. 45, 0. 90).
The median survival for patients treated with topotecan + BSC was 25.9 weeks [95% C. I.
Is- sopravivenza medja għall- pazjenti trattati b’ topotecan + BSC kienet ta ’ 25. 9 ġimgħa [95% C. I.
18.3, 31.6] compared to 13.9 weeks [95% C. I.
18. 3, 31. 6] meta mqabbla ma’ 13. 9 ġimgħa [95% C. I.
11.1, 18.6] for patients receiving BSC alone [p=0.0104].
11. 1, 18. 6] għall- pazjenti li rċievew BSC waħdu [p=0. 0104].
Patient self-reports of symptoms using an unblinded assessment showed a consistent trend for symptom benefit for oral topotecan + BSC.
Rapporti miġbura mill- pazjenti stess permezz ta ’ assessjar unblinded urew benefiċju konsistenti fuq sintomi b ’ topotecan + BSC.
One Phase 2 study (Study 065) and one Phase 3 study (Study 396) were conducted to evaluate the efficacy of oral topotecan versus intravenous topotecan in patients who had relapsed ≥ 90 days after completion of one prior regimen of chemotherapy. (see Table 1).
Sar studju tal- fażi 2 (Studju 065) u studju tal- fażi 3 (Studju 396) biex l- effikaċja ta ’ topotecan mill - ħalq kontra topotecan mogħti ġol- vina tiġi evalwata f’ pazjenti li l- kanċer tagħhom reġa ’ feġġ ≥ 90 jum wara li spiċċaw kors wieħed ta ’ kemoterapija qabel ma bdew it- trattament (ara Tabella 1).
Oral and intravenous topotecan were associated with similar symptom palliation in patients with relapsed sensitive SCLC in patient self- reports on an unblinded symptom scale assessment in each of these two studies.
Topotecan mill- ħalq u topotecan ġol- vina kienu assoċjati ma ’ taffija mis- sintomi tixtiebaħ fil- pazjenti b’ SCLC sensittiv li reġa ’ feġġ, u dan ħareġ minn rapporti miġbura mill- pazjenti stess permezz ta ’ assessjar unblinded ta ’ skala ta ’ sintomi, f’ kull wieħed minn dawn iż- żewġ studji.
Summary of survival, response rate, and time to progression in SCLC patients treated with oral HYCAMTIN or intravenous HYCAMTIN
Sommarju ta ’ sopravivenza, rata ta ’ rispons u żmien għall- progressjoni f’ pazjenti b’ SCLC trattati b’ HYCAMTIN mill- ħalq jew HYCAMTIN ġol- vina.
Study 065
Studju 065
Study 396
Studju 396
Intravenous Oral topotecan topotecan
Topotecan Topotecan mill- ħalq ġol- vina (N = 52) (N = 54)
(N = 54) (N = 153)
Topotecan mill- ħalq (N = 153)
(N = 151)
Topotecan ġol- vina (N = 151)
Median survival (weeks) (95% CI) Hazard ratio (95% CI) Response rate (%) (95% CI)
Sopravivenza medja (ġimgħat)
32.3 (26.3, 40.9) 0.88 (0.59, 23.1 (11.6, 34.5)
Proporzjon ta ’ periklu (95% CI)
25.1 33.0 (21.1, 33.0) (29.1, 42.4) 1.31) 0.88 (0.7, 14.8 18.3 (5.3, 24.3) (12.2, 24.4)
0. 88 (0. 7, 1. 11)
35.0 (31.0, 37.1) 1.11) 21.9 (15.3, 28.5)
Rata ta ’ rispons (%)
Difference in response rate (95% CI)
Differenza fir- rata ta ’ rispons (95% CI)
8.3 (-6.6, 23.1)
8. 3 (- 6. 6, 23. 1)
-3.6 (-12.6, 5.5)
- 3. 6 (- 12. 6, 5. 5)
Median time to progression (weeks)
Żmien medju għall - progressjoni (ġimgħat)
11.9
11. 9
14.6
14. 6
(8.3, 21.3)
(8. 3, 21. 3)
(11.6, 18.3)
(11. 6, 18. 3)
(9.7, 14.1)
(9. 7, 14. 1)
(13.3, 18.9)
(13. 3, 18. 9)
Hazard ratio (95% CI) total number of patients treated.
Proporzjon ta ’ periklu (95% CI)
0.90 (0.60, 1.35)
0. 90 (0. 60, 1. 35)
1.21 (0.96, 1.53)
1. 21 (0. 96, 1. 53)
CI = Confidence interval.
CI = Confidence interval.
In another randomised phase III trial which compared IV topotecan to cyclophosphamide, Adriamycin (doxorubicin) and vincristine (CAV) in patients with relapsed, sensitive SCLC, the overall response rate was 24.3% for topotecan compared to 18.3% for the CAV group.
Fi prova oħra tal- fażi III randomised li qabblet topotecan IV ma cyclophosphamide, Adriamycin (doxorubicin) u vincristine (CAV) f’ pazjenti b’ SCLC sensittiv li reġa ’ feġġ, ir- rata totali ta ’ rispons kienet ta ’ 24. 3% għal topotecan meta mqabbla ma’ 18. 3% għall- grupp CAV.
Median time to progression was similar in the two groups (13.3 weeks and 12.3 weeks respectively).
Iż- żmien medju għall - progessjoni kien jixtiebah fiż- żewġ gruppi (13. 3 ġimgħat u 12. 3 ġimgħat rispettivament).
Median survivals for the two groups were 25.0 and 24.7 weeks respectively.
Sopravivenzi medji għaż- żewġ gruppi kienu 25. 0 u 24. 7 ġimgħat rispettivament.
The hazard ratio for survival of IV topotecan relative to CAV was 1.04 (95% CI 0.78 – 1.40).
Il- proporzjon ta ’ periklu għas - sopravivenza ta ’ topotecan li jingħata fil- vina meta mqabbel ma ’ CAV kien 1. 04 (95% CI 0. 78 - 1. 40).
The response rate to topotecan in the combined small cell lung cancer programme [n = 480] for patients with relapsed disease sensitive to first-line therapy, was 20.2%.
Ir- rata ta ’ rispons għal topotecan fil- programm ikkombinat tal- kanċer taċ- ċelluli ż- żgħar tal- pulmun [n=480] għall- pazjenti fejn reġgħet feġġet il- marda li kienet sensittiva għat- terapija ewlenija, kien ta ’ 20%.
The median survival was 30.3 weeks (95% CI:
Is- sopravivenza medja kienet ta ’ 30. 3 ġimgħat (95% CI:
27.6, 33.4).
26. 7, 33. 4).
In a population of patients with refractory SCLC (those not responding to first line therapy), the response rate to topotecan was 4.0%.
F’ popolazzjoni ta ’ pazjenti b’ SCLC refrattarju (dawk li ma jweġbux għat- terapija ewlenija), ir- rata ta ’ rispons għal- topotecan kienet ta ’ 4. 0%.
Cervical Carcinoma
Karċinoma taċ- Ċerviċi
In a randomised, comparative phase III trial conducted by the Gynaecological Oncology Group (GOG 0179), topotecan plus cisplatin (n=147) was compared with cisplatin alone (n=146) for the treatment of histologically confirmed persistent, recurrent or Stage IVB carcinoma of the cervix where curative treatment with surgery and/ or radiation was not considered appropriate.
Fi prova klinika randomised u kumparattiva tal- fażi III immexxija mill- Grupp Ġinekoloġiku ta ’ l - Onkoloġija (GOG 0179), topotecan flimkien ma ’ cisplatin (n=147) ġie mqabbel ma ’ cisplatin waħdu (n=146) għat- trattament ta ’ karċinoma taċ- ċerviċi, persistenti, li reġgħet feġġet jew fl- istat IVB, ikkonfermata istoloġikament fejn trattament kurattiv b’ kirurġija u/ jew radjazzjoni ma ’ kienx ikkunsidrat xieraq.
Topotecan plus cisplatin had a statistically significant benefit in overall survival relative to cisplatin monotherapy after adjusting for interim analyses (Log-rank p =0.033).
Topotecan flimkien ma cisplatin kellu benefiċċju fis- sopravivenza totali li kien statitstikament sinifikanti meta mqabbel ma monoterapija b’ cisplatin wara aġġustament għall- analiżi interim (Log- rank p=0. 033).
9 Study results Study GOG-0179
10 Riżultati ta ’ l- istudju Studju GOG- 0179
ITT population
Popolazzjoni ITT
1 + Topotecan 0.75mg/ m2 dx3 q21
0. 75mg/ m2 dx3 q21
Survival (months) Median (95% C. I.)
Sopravivenza (xhur)
Hazard ratio (95% C. I.) Log rank p-value
Proporzjon ta ’ periklu (95% C. I.) Valur p log rank
(0.59-0.98) 0.033
(0. 59- 0. 98) 0. 033
Patients without Prior Cisplatin Chemoradiotherapy
Pazjenti li ma ħadu l- ebda Kimoradjuterapija b’ Cisplatin qabel
Topotecan/ Cisplatin
Topotecan/ Cisplatin
Survival (months)
Sopravivenza (xhur)
Median (95% C. I.)
Medja (95% C. I.)
8.8 (6.4, 11.5)
8. 8 (6. 4, 11. 5)
15.7 (11.9, 17.7)
15. 7 (11. 9, 17. 7)
Hazard ratio (95% C. I.)
Proporzjon ta ’ periklu (95% C. I.)
0.51 (0.31, 0.82)
0. 51 (0. 31, 0. 82)
Patients with Prior Cisplatin Chemoradiotherapy
Pazjenti li qabel kienu ħadu Kimoradjuterapija b’ Cisplatin
Median (95% C. I) Hazard ratio (95% C. I.)
Medja (95% C. I)
5.9 (4.7, 8.8) 0.85 (0.59,
Proporzjon ta ’ periklu (95% C. I.)
2.9, 9.6) for the cisplatin arm with an hazard ratio of 1.15 (0.59, 2.23).
F’ pazjenti (n=39) b’ rikorrenza fi żmien 180 ġurnata wara kemoradjuterapija b’ cisplatin, il- medja ta ’ sopravivenza meta topotecan ingħata flimkien ma ’ cisplatin kienet ta ’ 4. 6 xhur (95% C. I.: 2. 6, 6. 1) versu 4. 5 xhur (95% C. I.: 2. 9, 9. 6) għal cisplatin bi proporzjon ta ’ periklu ta ’ 1. 15 (0. 59, 2. 23).
In those (n=102) with recurrence after 180 days, the median survival in the topotecan plus cisplatin arm was 9.9 months (95% C. I.:
F’ dawk (n=102) b’ rikorrenza wara 180 ġurnata, is- sopravivenza medja meta topotecan ingħata flimkien ma ’ cisplatin kienet ta ’ 9. 9 xhur (95% C. I.:
7, 12.6) versus 6.3 months (95%C. I.:
7, 12. 6) versu 6. 3 xhur (95% C. I.:
4.9, 9.5) for the cisplatin arm with an hazard ratio of 0.75 (0.49, 1.16).
4. 9, 9. 5) għal cisplatin bi proporzjoni ta ’ periklu ta ’ 0. 75 (0. 49, 1. 16).
Paediatrics
Pedjatriċi
Topotecan was also evaluated in the paediatric population; however, only limited data on efficacy and safety are available.
Topotecan kien ukoll evalwat fil- popolazzjoni pedjatrika; madanakollu, tagħrif limitat biss huwa disponibbli dwar l- effikaċja u s- sigurtà.
In an open-label trial involving children (n = 108, age range: infant to 16 years) with recurrent or progressive solid tumours, topotecan was administered at a starting dose of 2.0 mg/ m2 given as a 30- minute infusion for 5 days repeated every 3 weeks for up to one year depending on response to therapy.
Fi prova open- label li kienet tinvolvi t- tfal (n=108, varjazzoni fl- età: trabi sa 16- il sena) b’ tumuri li reġgħu feġġew jew kienu solidi progressivi, topotecan inbeda f’ doża ta ’ 2. 0 mg/ m2 mogħtija bħala infużjoni ta ’ 30 minuta għal 5 ijiem ripetuta kull 3 ġimgħat sa sena skond ir- rispons għat- terapija.
Tumour types included were Ewing's Sarcoma/ primitive neuroectodermal tumour, neuroblastoma, osteoblastoma, and rhabdomyosarcoma.
It - tipi ta ’ tumuri kienu jinkludu Sarkoma ta ’ Erwing / tumur newroektodermali primittiv, newroblastoma, osteoblastoma, u rabdomijosarkoma.
Antitumour activity was demonstrated primarily in patients with neuroblastoma.
Attività kontra t- tumur intweriet primarjament f’ pazjenti b’ newroblastoma.
Toxicities of topotecan in paediatric patients with recurrent and refractory solid tumours were similar to those historically seen in adult patients.
Tossiċitajiet ta ’ topotecan f’ pazjenti pedjatriċi b’ tumuri solidi rikorrenti jew refrattivi kienu jixbħu lill dak li s- soltu jidher fl- adulti.
In this study, forty-six (43%) patients received G-CSF over 192 (42.1%) courses; sixty-five (60%) received transfusions of Packed Red Blood Cells and fifty (46%) of platelets over 139 and 159 courses (30.5% and 34.9%) respectively.
F’ dan l- istudju, sitta u erbgħin (43%) pazjent irċevew G- CSF fuq medda ta ’ 192 (42. 1%) kors; ħamsa u sittin (60%) rċievew transfużjonijiet ta ’ Celluli Ħomor tad- Demm Ippakkjati u ħamsin (46%) irċevew plejtlits fuq medda ta ’ 139 u 159 kors (30. 5 u 34. 9%) rispettivament.
Based on the dose-limiting toxicity of myelosuppression, the maximum tolerated dose (MTD) was established at 2.0 mg/ m2/ day with G-CSF and 1.4 mg/ m2/ day without G- CSF in a pharmacokinetic study in paediatric patients with refractory solid tumours (see section 5.2).
Ibbażata fuq it- tossiċità ta ’ majelosuppressjoni li tillimita d- doża, id - doża massima tollerata (MTD) kienet stabbilita bħala 2. 0 mg/ m2 / ġurnata ma ’ G- CSF u 1. 4 mg/ m2 / ġurnata mingħajr G- CSF fi studju farmakokinetiku f’ pazjenti pedjatriċi b’ tumuri solidi refrattarji (ara sezzjoni 5. 2).
Following intravenous administration of topotecan at doses of 0.5 to 1.5 mg/ m2 as a 30 minute infusion daily for five days, topotecan demonstrated a high plasma clearance of 62 l/ h (SD 22), 10 corresponding to approximately 2/ 3 of liver blood flow.
Wara li topotecan ingħata ġol- vina f’ dożi ta ’ 0. 5 sa 1. 5 mg/ m2 bħala infużjoni ta ’ 30 minuta kuljum għal ħames tijiem, topotecan wera tneħħija għolja fil- plażma ta ’ 62 l/ h (SD 22), li tikkorrispondi għal 11 bejn wieħed u ieħor 2/ 3 taċ- ċirkolazjoni tad- demm fil- fwied.
Topotecan also had a high volume of distribution, about 132 l, (SD 57) and a relatively short half-life of 2-3 hours.
Topotecan kellu wkoll volum ta ’ distribuzzjoni għoli, ta ’ madwar 132 l, (SD 57) u half- life pjuttost qasira ta ’ 2- 3 sigħat.
Comparison of pharmacokinetic parameters did not suggest any change in pharmacokinetics over the 5 days of dosing.
Tqabbil ta ’ parametri farmakokinetiċi ma ssuġġerew l- ebda tibdil fil- farmakokinetika f’ perjodu ta ’ 5 ijiem ta ’ dożaġġ.
Area under the curve increased approximately in proportion to the increase in dose.
L- erja taħt il- kurva żdiedet bejn wieħed u ieħor fi proporzjoni maż- żjieda tad- doża.
There is little or no accumulation of topotecan with repeated daily dosing and there is no evidence of a change in the PK after multiple doses.
Hemm ftit li xejn akkumulazzjoni ta ’ topotecan wara dożi ripetuti ta ’ kuljum u m’ hemm l- ebda evidenza ta ’ bidla fil- PK wara ħafna dożi.
Preclinical studies indicate plasma protein binding of topotecan is low (35%) and distribution between blood cells and plasma was fairly homogeneous.
Studji pre- klinikali juru li r- rabta ta ’ topotecan ma ’ proteini tal- plażma huwa baxx (35%) u distribuzjoni bejn ċelluli tad- demm u plażma kienet pjuttost omoġeni.
The elimination of topotecan has only been partly investigated in man.
L- eliminazjoni ta ’ topotecan ġiet studjata biss parzjalment fil- bnedmin.
A major route of clearance of topotecan was by hydrolysis of the lactone ring to form the ring-opened carboxylate.
It- tneħħija ta ’ topotecan sseħħet l- aktar permezz ta ’ l- idroliżi tal- lactone ring biex jifforma r- ring- opened carboxylate.
Metabolism accounts for < 10% of the elimination of topotecan.
Il- metaboliżmu jispjega < 10% ta ’ l- eliminazzjoni ta ’ topotecan.
An N-desmethyl metabolite, which was shown to have similar or less activity than the parent in a cell-based assay, was found in urine, plasma, and faeces.
Sustanza iffurmata mill- metaboliżmu ta ’ N- desmethyl, li ntweriet li kellha attività tixtiebaħ jew anqas miinn dik tas- sustanza oriġinali f’ assay ibbażat fiċ- ċellula, instabet fl- awrina, fil- plasma u fil- ħmieġ.
The mean metabolite: parent AUC ratio was less than 10% for both total topotecan and topotecan lactone.
Il- medja ta ’ sustanza mill - metaboliżmu: proporżjon AUC tas- sustanza oriġinali kien ta ’ anqas minn 10% kemm għal topotecan kif ukoll għal topotecan lactone.
An O-glucuronidation metabolite of topotecan and N-desmethyl topotecan has been identified in the urine.
Is- sustanza mill- metaboliżmu ta ’ O- glucuronidation ta ’ topotecan u N- desmethyl topotecan ġew identifikati fl- awrina.
Overall recovery of medicinal product-related material following five daily doses of topotecan was 71 to 76% of the administered IV dose.
Il- ġbir totali ta ’ materjali li għandhom x’ jaqsmu mal- prodott mediċinali wara l- ħames dożi ta ’ topotecan li ingħataw darba kuljum kien ta ’ 71- 76% tad- doża amministrata fil- vina.
Approximately 51% was excreted as total topotecan and 3% was excreted as N-desmethyl topotecan in the urine.
Bejn wieħed u ieħor 51% tneħħa bħala topotecan totali u 3% tneħħa bħala N- desmethyl topotecan fl- awrina.
Faecal elimination of total topotecan accounted for 18% while faecal elimination of N-desmethyl topotecan was 1.7%.
Eliminazzjoni mal- ħmieġ ta ’ topotecan totali kienet ta ’ 18% filwaqt li eliminazzjoni mal- ħmieġ ta ’ N- desmethyl topotecan kienet ta ’ 1. 7%.
Overall, the N-desmethyl metabolite contributed a mean of less than 7% (range 4-9%) of the total medicinal product related material accounted for in the urine and faeces.
Globalment is- sustanza mill- metaboliżmu N- desmethyl ikkontribbwixxiet għal medja ta ’ anqas minn 7% (bejn 4- 9%) tat- total tal- materjali li għandhom x’ jaqsmu mal- prodott mediċinali li nstabu fl- awrina u fil - ħmieġ.
The topotecan-O-glucuronide and N-desmethyl topotecan-O-glucuronide in the urine were less than 2.0%.
L - O- glucuronide ta ’ topotecan u l - O- glucuronide ta ’ N- desmethyl topotecan fl- awrina kienu anqas minn 2. 0%.
In vitro data using human liver microsomes indicate the formation of small amounts of N- demethylated topotecan.
Informazzjoni in vitro, fejn intużaw il- mikrożomi li jinsabu fil- fwied tal- bniedem urew li jiġu magħmula ammonti ż- żgħar ta ’ N- demethylated topotecan.
In vitro, topotecan did not inhibit human P450 enzymes CYP1A2, CYP2A6, CYP2C8/ 9, CYP2C19, CYP2D6, CYP2E, CYP3A, or CYP4A nor did it inhibit the human cytosolic enzymes dihydropyrimidine or xanthine oxidase.
In vitro, topotecan ma wriex inibizzjoni tal- enżemi P450 umani CYP1A2, CYP2A6, CYP2C8/ 9, CYP2C19, CYP2D6, CYP2E, CYP3A, jew CYP4A u l- anqas inibizzjoni tal- enżemi sistoliċi umani dihydropyrimidine jew xanthine oxidase.
When given in combination with cisplatin (cisplatin day 1, topotecan days 1 to 5), the clearance of topotecan was reduced on day 5 compared to day 1 (19.1 L/ h/ m2 compared to 21.3 L/ h/ m2 [n=9]) (see section 4.5).
Meta mogħti flimkien ma ’ cisplatin (cisplatin fil- ġurnata 1, topotecan fil- ġranet 1- 5), it- tneħħija ta ’ topotecan kienet imnaqqsa fil- ġurnata 5 meta mqabbla ma ’ l- ġurnata 1 (19. 1 L/ s/ m2 meta mqabbel ma ’ 21. 3 L/ s/ m2 [n=9]) (ara sezzjoni 4. 5).
Plasma clearance in patients with hepatic impairment (serum bilirubin between 1.5 and 10 mg/ dl) decreased to about 67% when compared with a control group of patients.
It- tneħħija mill- plażma f’ pazjenti li għandhom indeboliment tal- fwied (bilirubin fis- serum bejn 1. 5 u 10 mg/ dl) naqset għal bejn wieħed u ieħor 67% meta ġiet imqabbla ma dik f’ pazjenti li kienu fi grupp ta ’ kontroll.
Topotecan half-life was increased by about 30% but no clear change in volume of distribution was observed.
Il- half- life tat- topotecan żdiedet b’ bejn wieħed u ieħor 30% iżda ma kienx hemm indikazzjoni ċara ta ’ xi tibdil fil- volum ta ’ distribuzzjoni.
Plasma clearance of total topotecan (active and inactive form) in patients with hepatic impairment only decreased by about 10% compared with the control group of patients.
Tneħħija fil- plażma ta ’ topotecan kollu (fil - forma attiva u inattiva) f’ pazjenti li għandhom indeboliment tal- fwied biss naqset b’ xi 10% meta ġiet imqabbla ma dik fil- pazjenti li kienu fi grupp ta ’ kontroll.
Plasma clearance in patients with renal impairment (creatinine clearance 41-60 ml/ min.) decreased to about 67% compared with control patients.
It- tneħħija mill- plażma f’ pazjenti li għandhom indeboliment tal- kliewi (tneħħija tal- krejatinina 41 - 60 ml/ min.) naqset għal bejn wieħed u ieħor 67% meta ġiet imqabbla ma dik f’ pazjenti li kienu fi grupp ta ’ kontroll.
Volume of distribution was slightly decreased and thus half-life only increased by 14%.
Il- volum ta ’ distribuzzjoni naqas ftit u b’ hekk il- half- life żdiedet biss b’ 14%.
In patients with moderate renal impairment topotecan plasma clearance was reduced to 34% of the value in control patients.
F’ pazjenti li għandhom indeboliment tal- kliewi moderat, it- tneħħija mill- plażma ġiet imnaqqsa għal 34% tal- valur fil- pazjenti li kienu fi grupp ta ’ kontroll.
Mean half-life increased from 1.9 hours to 4.9 hours.
Il- half- life medja żdiedet minn 1. 9 sigħat għal 4. 9 sigħat.
In a population study, a number of factors including age, weight and ascites had no significant effect on clearance of total topotecan (active and inactive form).
Fi studju ta ’ popolazzjoni, kien hemm numru ta ’ fatturi li jinkludu eta ’, piż u axxite li ma kellhomx effett sinifikanti fuq il- tneħħija totali ta ’ topotecan (fil- forma attiva u inattiva).
Paediatrics
12 Pedjatriċi
The pharmacokinetics of topotecan given as a 30-minute infusion for 5 days were evaluated in two studies.
Il- farmakokinetika ta ’ topotecan mogħti bħala infużjoni ta ’ 30 minuta għal 5 ijiem kienet evalwata f’ żewġ studji.
One study included a dose range of 1.4 mg/ m2 to 2.4 mg/ m2 in children (aged 2 up to 12 years, n = 18), adolescents (aged 12 up to 16 years, n = 9), and young adults (aged 16 to 21 years, n = 9) with
Studju wieħed inkluda limiti tad- doza bejn 1. 4mg/ m2 u 2. 4mg/ m2 fi tfal (età minn 2 sa 12- il sena, n=18), adoloxxenti (età minn 12 sa 16- il sena, n=9), u adulti ż- żgħar (età minn 16- il sena sa 21 sena, n=9) b’ tumuri solidi refrattarji.
The second study included a dose range of 2.0 mg/ m2 to 5.2 mg/ m2 in children (n = 8), adolescents (n = 3), and young adults (n = 3) with leukaemia.
It- tieni studju inkluda limiti tad- doża bejn 2. 0mg/ m2 u 5. 2mg/ m2 fi tfal (n=18), adoloxxenti (n=3) u adulti ż- żgħar (n=3) b’ lewkimja.
In these studies, there were no apparent differences in the pharmacokinetics of topotecan among children, adolescents, and young adult patients with solid tumours or leukaemia, but data are too limited to draw definite conclusions.
F’ dawn l- istudji, ma ’ kienu jidhru l- ebda differenzi fil- farmakokinetika ta ’ topotecan fost il- pazjenti tfal, adoloxxenti u adulti ż- żgħar b’ tumuri solidi jew lewkimja, iżda t- tagħrif huwa limitat wisq biex tasal għall - konklużjonijiet definiti.
5.3 Preclinical safety data
5. 3 Tagħrif ta’ qabel l- użu kiniku dwar is- sigurtà tal- mediċina
Resulting from its mechanism of action, topotecan is genotoxic to mammalian cells (mouse lymphoma cells and human lymphocytes) in vitro and mouse bone marrow cells in vivo.
Minnħabba l- mod ta ’ kif jaħdem, topotecan huwa ġenotossiku għal ċelluli mammiferi (ċelluli tal - limfoma tal- ġrieden u limfoċiti tal- bnedmin) in vitro u ċelluli tal- mudullun tal- ġrieden in vivo.
Topotecan was also shown to cause embryo-foetal lethality when given to rats and rabbits.
Ġie osservat ukoll li topotecan jikkawża l- mewt fl- embriji u fil- feti meta jiġi mogħti lill- ġrieden u lill - fniek.
In reproductive toxicity studies with topotecan in rats there was no effect on male or female fertility; however, in females super-ovulation and slightly increased pre-implantation loss were observed.
F’ studji dwar it- tossiċita riprodduttiva fil- firien, ma kien hemm l- ebda effett fuq il- fertilità tal- firien nisa jew irġiel; madankollu, fin- nisa ġew osservati super- ovulation u żjieda żgħira f’ telf tal- fetu qabel ma jeħel mal- ħajt tal- ġuf..
The carcinogenic potential of topotecan has not been studied.
Il- potenzjal karċinoġenu ta ’ topotecan ma ġiex studjat.
PHARMACEUTICAL PARTICULARS
TAGĦRIF FARMARĊEWTIKU
Tartaric acid (E334) Mannitol (E421) Hydrochloric acid (E507) Sodium hydroxide
Tartaric acid (E334) Mannitol (E421) Hydrochloric acid (E507) Sodium hydroxide
None known.
Ma jgħoddx f’ dan il- każ
Vials 3 years.
Fjali 3 snin.
Reconstituted and diluted solutions The product should be used immediately after reconstitution as it contains no antibacterial preservative.
Soluzzjonijiet rikostitwiti u dilwiti Il- prodott irid jintuża immedjatament wara r- rikostituzzjoni minħabba l- fatt li ma fihx preżervativi anti- batteriċi.
If reconstitution and dilution is performed under strict aseptic conditions (e. g. an LAF bench) the product should be used (infusion completed) within 12 hours at room temperature or 24 hours if stored at 2-8 0C after the first puncture of the vial.
Jekk ir- rikostituzzjoni u d- dilwizzjoni isiru f’ kundizzjonijiet asettiċi (per eżempju fuq bank LAF) il- prodott irid jintuża (l- infużjoni trid titlesta) fi żmien 12- il siegħa f’ temperatura tal- kamra jew fi żmien 24 siegħa jekk miżmum f’ temperaturi ta ’ bejn 2 0C u 8 0C minn meta l- fjala tinfetaħ għall- ewwel darba.
Keep the vial in the outer carton in order to protect from light.
Żomm il- kontenitur fil- pakkett ta ’ barra sabiex tipproteġih mid- dawl.
6.5 Nature and contents of container
13 6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
HYCAMTIN 1 mg is supplied in 5 ml type I flint glass vials, together with 13 mm grey butyl rubber stoppers and 13 mm aluminium seals with plastic flip-off caps.
HYCAMTIN 1 mg jiġi ġo fjali ta ’ 3 ml magħmulin minn ħġieġ tal- flint tat- tip I, flimkien ma ’ tappijiet griżi tal- gomma butyl ta ’ 13 mm u siġilli ta ’ l- aluminium ta ’ 13 mm b’ tapp tal- plastik li jinfetaħ b’ daqqa ta saba ’.
HYCAMTIN 1 mg is available in cartons containing 1 vial and 5 vials.
HYCAMTIN 1 mg jiġi f’ pakketti li fihom fjala waħda u pakketti ta ’ ħames fjali.
6.6 Special precautions for disposal and other handling 12 HYCAMTIN 1 mg vials must be reconstituted with 1.1 ml water for injections.
Fjali ta ’ HYCAMTIN ta ’ 1 mg iridu jiġu rikostitwiti b’ 1. 1 ml ta ’ ilma għal injezzjonijiet.
Since HYCAMTIN contains a 10% overage, the clear, reconstituted solution is yellow to yellow-green in colour and provides 1 mg per ml of topotecan.
Peress illi HYCAMTIN fih 10% żejjed, it- taħlita ċara rikkostitwita hija ta ’ kulur isfar għal isfar fl- aħdar u tipprovdi 1 mg għal kull ml ta ’ topotecan.
Further dilution of the appropriate volume of the reconstituted solution with either 0.9% w/ v sodium chloride intravenous infusion or 5% w/ v glucose intravenous infusion is required to a final concentration of between 25 and 50 microgram/ ml.
Il- volum approprjat tat- taħlita rikostitwita jrid jerġa ’ jiġi dilwit ma ’ 0. 9% w/ v sodium chloride għall- infużjoni fil- vina jew ma 5% w/ v glucose għall- infużjoni ġol- vina, għal konċentrazzjoni finali ta ’ bejn 25 bejn 50 mikrogramma/ ml.
The normal procedures for proper handling and disposal of anticancer medicinal products should be adopted, namely: − Personnel should be trained to reconstitute the medicinal product. − Pregnant staff should be excluded from working with this medicinal product. − Personnel handling this medicinal product during reconstitution should wear protective clothing including mask, goggles and gloves. − All items for administration or cleaning, including gloves, should be placed in high-risk, waste disposal bags for high-temperature incineration.
Iridu jiġu addotati l- proċeduri normali għal maniġġar u rimi ta ’ prodotti mediċinali kontra l- kanċer, speċifikament:
Liquid waste may be flushed with large amounts of water. − Accidental contact with the skin or eyes should be treated immediately with copious amounts of water.
- Jekk aċċidentalment il- mediċina tmiss mal- ġilda jew ma ’ l- għajnejn għandu jintuża ħafna ilma
SmithKline Beecham plc, 980 Great West Road, Brentford, Middlesex, TW8 9GS, United Kingdom.
SmithKline Beecham plc, 980 Great West Road, Brentford, Middlesex, TW8 9GS, Ir- Renju Unit.
1 mg vials:
Fjali ta ’ 1 mg:
5 vials 1 vial
5 fjali Fjala waħda
12/ 11/ 1996 Date of last renewal:
12/ 11/ 1996 Data ta ’ l- aħħar tiġdid:
HYCAMTIN 4 mg powder for concentrate for solution for infusion
HYCAMTIN 4 mg trab għall- konċentrat għal soluzzjoni għall- infużjoni.
Each vial contains 4 mg topotecan (as hydrochloride).
Kull fjala fiha 4 mg topotecan bħala (hydrochloride).
14 Subsequent doses Topotecan should not be re-administered unless the neutrophil count is ≥ 1 x 109/ l, the platelet count is ≥ 100 x 109/ l, and the haemoglobin level is ≥ 9g/ dl (after transfusion if necessary).
Jekk jiġi ttollerat mill- ġisem, il- kura tista ’ tkompla sakemm il - marda tmur għall- aħjar (ara sezzjonijiet 4. 8 u 5. 1) 15 Dożi sussegwenti Topotecan m’ għandux jerġa ’ jiġi amministrat ħlief jekk l- għadd tan- newtrofili jkun ≥ 1 x 109/ l, l - għadd ta ’ plejtlits ikun ≥ 100 x 109/ l, u l- livell ta ’ l- emoglobina jkun ≥ 9 g/ dl (wara trasfużjoni, jekk ikun hemm bżonn).