qanastek/EMEA-V3 huggingface dataset:
If dose reduction is chosen for patients who experience severe neutropenia (neutrophil count < 0.5 x 109/ l) for 7 days or more, or severe neutropenia associated with fever or infection, or who have had treatment delayed due to neutropenia, the dose should be reduced by 0.25 mg/ m2/ day to 1.25 mg/ m2/ day (or subsequently down to 1.0 mg/ m2/ day if necessary)
Jekk it- tnaqqis fid- doża jiġi magħżul għal pazjenti li jġarrbu newtropenja qawwija (l- għadd ta ’ newtrofili < 0. 5 x 109/ l) għal 7 ijiem jew iktar, jew newtropenja qawwija bid- deni jew infezzjoni, jew li kellhom il- kura sospiża minħabba newtropenja, id- doża għandha titnaqqas b’ 0. 25mg/ m2/ jum għal 1. 25 mg/ m2/ ġurnata (jew sussegwentement imnaqqsa għal 1. 0 mg/ m2/ ġurnata jekk ikun hemm bżonn).
If dose reduction is chosen for patients who experience severe neutropenia (neutrophil count less than 0.5 x 109/ l) for 7 days or more, or severe neutropenia associated with fever or infection or who have had treatment delayed due to neutropenia, the dose should be reduced by 20% to 0.60 mg/ m2/ day for subsequent courses (or subsequently down to 0.45 mg/ m2/ day if necessary).
Jekk it- tnaqqis fid- doża jiġi magħżul għal pazjenti li jġarrbu newtropenja qawwija (l- għadd tan - newtrofils anqas minn 0. 5 x 109/ l) għal 7 ijiem jew aktar, jew newtropenja qawwija assoċċjata ma ’ deni jew infezzjoni jew li t- trattament kien ittardjat minħabba newtropenja, id- doża għandha titnaqqsilhom b’ 20% għal 0. 60 mg/ m2 / ġurnata għall- korsijiet sussegwenti (jew sussegwement titnaqqas għal 0. 45mg/ m2/ jum jekk ikun hemm bżonn)..
Doses should be similarly reduced if the platelet count falls below 25 x 109/ l.
Id- dożi għandhom jitnaqqsu bl- istess mod jekk il- għadd tal- plejtlits jinżel f’ livell anqas minn 25 x 109/ l.
The recommended monotherapy dose of topotecan in patients with ovarian or small cell lung cancer and a creatinine clearance between 20 and 39 ml/ min is 0.75 mg/ m2 / day for 5 consecutive days.
Id- doża ta ’ topotecan rakkomandata f’ monoterapija f’ pazjenti b’ karċinoma ta ’ l- ovarji jew taċ- ċelluli ż- żgħar tal- pulmun u li għandhom tneħħija tal- krejatinina ta ’ bejn l- 20 u d- 39 ml/ min hija ta ’ 0. 75 mg/ m2 / ġurnata għal ħamest ijiem konsekuttivi.
If, during topotecan/ cisplatin combination therapy serum creatinine exceeds 1.5 mg/ dL, it is recommended that the full prescribing information be consulted for any advice on cisplatin dose reduction/ continuation.
16 b’ topotecan flimkien ma ’ cisplatin il- krejatinina tas- serum taqbeż il- 1. 5mg/ dL, huwa rakkommandat li tiġi kkonsultata l- informazzjoni kompleta ta ’ kif jiġi preskritt cisplatin għall- parir dwar tnaqqis jew tkomplija tad- doża.
15 Paediatrics The experience in children is limited, therefore no recommendation for treatment of paediatric patients with HYCAMTIN can be given (see sections 5.1 and 5.2).
Pedjatrija L- esperjenza fit- tfal hija limitata u għalhekk ma tista ’ tingħata l- ebda rakkommandazzjoni għat - trattment ta ’ pazjenti pedjatriċi b’ HYCAMTIN (ara sezzjonijiet 5. 1 u 5. 2).
This should be taken into account, e. g. in case patients at increased risk for tumour bleeds are considered for therapy.
Din għandha tiġi kkunsidrata e. ż. f’ każ li pazjenti li għandhom riskju ogħla ta ’ fsada minn tumuri jiġu kkunsidrati għal terapija.
4.5 Interaction with other medicinal products and other forms of interaction
17 4. 5 Prodotti mediċinali oħra li ma ’ jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
Topotecan does not inhibit human P450 enzymes (see Section 5.2).
Topotecan ma jinibixxix l- enżimi umani P450 (ara sezzjoni 5. 2).
In a population study, the co- 16 administration of granisetron, ondansetron, morphine or corticosteroids did not appear to have a significant effect on the pharmacokinetics of total topotecan (active and inactive form).
Fi studju li sar fuq pazjenti, il- ko - amministrazzjoni ta ’ granisetron, ondansetron, morphine jew kortikosterojdi ma jidhirx li kellhom effetti sinifikant fuq il- farmakokinetika ta ’ topotecan totali (fil- forma attiva jew inattiva).
4.8 Undesirable effects
18 4. 8 Effetti mhux mixtieqa
17 The integrated safety data of topotecan monotherapy are presented below.
19 It- tagħrif integrat ta ’ sigurtà għal monoterapija b’ topotecan huma ppreżentati hawn taħt.
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..
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 18 therapy.
Il- frekwenzi assoċjati mal- ġrajjiet avversi ematoloġiċi u mhux ematoloġiċi elenkati hawn taħt jirrapreżentaw ir- rapporti ta ’ ġrajjiet avversi ikkunsidrati li għandhom / jista ’ jkollhom x’ jaqsmu ma terapija b’ topotecan.
Haematological Neutropenia:
20 Ematoloġiċi Newtropenja:
19 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 - 21 enżima u lid - DNA maqsum bl- istrand li huwa l- proċess intermedjarju tal- mekaniżmu katalitiku.
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 topotcan 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.
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 kkomparat mal- grupp ta ’ BSC waħdu kien 0. 64 (95% CI:
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 mqabbel ma’ 13. 9 ġimgħa [95% C. I.
21 Study results Study GOG-0179 ITT population
Popolazzjoni ITT
1 + Topotecan 0.75mg/ m2 dx3 q21
1 + Topotecan 0. 75mg/ m2 dx3 q21
Survival (months) Median (95% C. I.)
Sopravivenza (xhur) Medja( 95% C. I.)
(n= 146) 6.5 (5.8, 8.8)
(n= 146) 6. 5 (5. 8, 8. 8)
(n = 147) 9.4 (7.9, 11.9)
(n = 147) 9. 4 (7. 9, 11. 9)
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), 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 24 bejn wieħed u ieħor 2/ 3 taċ- ċirkolazjoni tad- demm fil- fwied.
Topotecan also had a high volume of 22 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.
23 Paediatrics
25 Pedjatriċi
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 refractory solid tumours.
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.
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 ta ’ topotecan 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.
Tartaric acid (E334) Mannitol (E421) Hydrochloric acid(E507) Sodium hydroxide
Tartaric acid (E334) Mannitol (E421) Hydrochloric acid (E507) Sodium hydroxide
6.5 Nature and contents of container
26 6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
HYCAMTIN 4 mg is supplied in 17 ml type I flint glass vials, together with 20 mm grey butyl rubber stoppers and 20 mm aluminium seals with plastic flip-off caps.
HYCAMTIN 4 mg jiġi ġo fjali ta ’ 17 ml magħmulin minn ħġieġ tal- flint tat- tip I, flimkien ma ’ tappijiet griżi tal- gomma butyl griża ta ’ 20 mm u siġilli ta ’ l- aluminium ta ’ 20 mm b’ tapp tal- plastik li jinfetaħ b’ daqqa ta saba ’.
24 HYCAMTIN 4 mg is available in cartons containing 1 vial and 5 vials.
HYCAMTIN 4 mg jiġi f’ pakketti li fihom fjala waħda u pakketti ta ’ ħames fjali.
HYCAMTIN 4 mg vials must be reconstituted with 4 ml water for injections.
Fjali ta ’ HYCAMTIN ta ’ 4 mg iridu jiġu rikostitwiti b’ 4 ml ta ’ ilma għal injezzjonijiet.
The clear, reconstituted solution is yellow to yellow-green in colour and provides 1 mg per ml of topotecan.
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.
4 mg vials:
Fjali ta ’ 4 mg:
HYCAMTIN 0.25 mg hard capsules
HYCAMTIN 0. 25mg kapsuli iebsin
Each capsule contains topotecan hydrochloride equivalent to 0.25 mg of topotecan.
Kull kapsula fiha topotecan hydrochloride ekwivalenti għal 0. 25 mg ta ’ topotecan.
The capsules are opaque white to yellowish white and imprinted with ‘ HYCAMTIN’ and ‘ 0.25 mg’.
Il- kapsuli huma trasparenti, bojod għal bojod fl- isfar u mmarkati b ’ ‘ HYCAMTIN ’ u ‘ 0. 25 mg ’.
HYCAMTIN capsules are indicated as monotherapy for the treatment of adult patients with relapsed small cell lung cancer (SCLC) for whom re-treatment with the first-line regimen is not considered appropriate (see section 5.1).
Il- kapsuli HYCAMTIN huma indikati bħala monoterapija, għat- trattament ta ’ pazjenti adulti b’ kanċer taċ- ċelluli ż- żgħar tal- pulmun (SCLC) li reġa ’ tfaċċa u li għalihom trattament mill- ġdid bit- terapija ewlenija m’ huwiex ikkunsidrat xieraq (ara sezzjoni 5. 1).
HYCAMTIN capsules should only be prescribed and therapy supervised by a physician experienced in the use of chemotherapeutic agents.
Il- kapsuli HYCAMTIN għandom jiġu preskritti u t- terapija għandha tiġi segwita biss minn tabib li għandu esperjenza fl- użu ta ’ sustanzi kimoterapewtiċi.
Initial dose The recommended dose of HYCAMTIN capsules is 2.3 mg/ m2 body surface area/ day administered for 5 consecutive days with a 3 week interval between the start of each course.
Doża inizjali Id- doża rakkomandata tal- kapsuli HYCAMTIN hija ta ’ 2. 3 mg/ m2 tal- erja tas- superfiċje tal- ġisem kuljum, mogħtija għal ħames ġranet konsekuttivi b’ intervall ta ’ 3 ġimgħat bejn il- bidu ta ’ kull kors.
If well tolerated, treatment may continue until disease progression (see sections 4.8 and 5.1).
Jekk jiġi ttollerat tajjeb mill- ġisem, it- trattament jista ’ jkompli sakemm il- marda tmur għall- agħar.
The capsule(s) must be swallowed whole, and must not be chewed crushed or divided.
Il- kapsula( i) għandha tinbela sħiħa u wieħed m’ għandux jomodha, jfarrakha jew jaqsamha.
Hycamtin capsules may be taken with or without food (see section 5.2).
Il- kapsuli ta ’ Hycamtin jistgħu jittieħdu ma ’ l- ikel jew mhux ma ’ l- ikel (ara sezzjoni 5. 2).
Prior to administration of the first course of topotecan, patients must have a baseline neutrophil count of ≥ 1.5 x 109/ l, a platelet count of ≥ 100 x 109/ l and a haemoglobin level of ≥ 9 g/ dl (after transfusion if necessary)..
Qabel ma jingħata l- ewwel kors ta ’ topotecan, il- pazjent irid ikollu linja bażi ta ’ l- għadd ta ’ newtrofili ta ’ ≥ 1. 5 x 109/ l, għadd ta ’ plejtlits ta ’ ≥ 100 x 109/ l u livell ta ’ emoglobina ta ’ ≥ 9g/ dl (jekk hemm bżonn wara trażfusjoni).
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 ≥ 9 g/ dl (after transfusion if necessary).
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).
If dose reduction is chosen for patients who experience severe neutropenia (neutrophil count < 0.5 x 109/ l) for 7 days or more, or severe neutropenia associated with fever or infection, or who have had treatment delayed due to neutropenia, the dose should be reduced by 0.4 mg/ m2/ day to 1.9 mg/ m2/ day (or subsequently down to 1.5 mg/ m2/ day if necessary).
Jekk it- tnaqqis fid- doża jiġi magħżul għal pazjenti li jġarrbu newtropenja qawwija (l- għadd ta ’ nutrofili < 0. 5 x 109/ l) għal 7 t’ ijiem jew iktar, jew newtropenja qawwija bid- deni jew infezzjoni, jew li kellhom il- kura sospiża minħabba newtropenja, id- doża għandha titnaqqas b’ 0. 4 mg / m2/ ġurnata 28 għal 1. 9 mg/ m2/ ġurnata (jew sussegwentement imnaqqsa għal 1. 5 mg/ m2/ ġurnata jekk ikun hemm bżonn).
26 Doses should be similarly reduced if the platelet count falls below 25 x 109/ l.
Id- dożi għandhom jitnaqqsu bl- istess mod jekk l- għadd ta ’ plejtlits jaqa ’ taħt 25 x 109/ l.
In clinical trials, topotecan was discontinued if the dose needed to be reduced below 1.5 mg/ m2.
Fi provi kliniċi, topotecan ma baqax jingħata jekk d- doża tnaqqset għal taħt 1. 5 mg/ m2.
Patients with Grade 2 diarrhoea may need to follow the same dose modification guidelines.
Id- doża għandha titnaqqas b’ 0. 4mg/ m2/ jum għal korsijiet ta ’ wara għal pazjenti li jkollhom dijarrea ta ’ Grad 3 jew 4 (ara sezzjoni 4. 4), Pazjenti bi Grad 2 ta ’ dijarrea jista ’ jkollhom bżonn isegwu l- istess linji ta ’ gwida għal tibdil fid- doża.
Dosage in renally impaired patients Patients with small cell lung carcinoma who participated in oral topotecan clinical trials had a serum creatinine less than or equal to 1.5 mg/ dl (133 µmol/ l) or a creatinine clearance of greater than or equal to 60 ml/ min.
Id- doża f’ pazjenti b’ indeboliment renali Pazjenti b’ karċinoma taċ- ċelluli ż- żgħar tal- pulmun li ħadu sehem fi provi kliniċi b’ topotecan mill - ħalq kellhom livell ta ’ krejatinina fis- serum anqas minn jew ta ’ 1. 5 mg/ dl (133 µmol/ l) jew tneħħija tal- krejatinina akbar minn jew ta ’ 60 ml/ min.
Dosing recommendations for patients receiving oral topotecan with Clcr less than 60 ml/ min have not been established (see section 4.4).
Rakkomandazzjonijiet ta ’ dożaġġ għal pazjenti li qed jirċievu topotecan mill- ħalq b’ Clcr ta ’ anqas minn 60 ml/ min ma ġewx stabbiliti (ara sezzjoni 4. 4.).
Dosage in hepatically impaired patients Pharmacokinetics of HYCAMTIN capsules have not been specifically studied in patients with impaired hepatic function.
Id- doża f’ pazjenti b’ indeboliment tal- fwied Il- farmakokinetika tal- kapsuli HYCAMTIN ma ġewx studjati speċifikament f’ pazjenti b’ indeboliment tal- fwied.
There are insufficient data available with HYCAMTIN capsules to make a dose recommendation for this patient group (see section 4.4).
M’ hemmx biżżejjed informazzjoni fuq il- kapsuli HYCAMTIN biex ikun hemm rakkomandazzjoni fuq id- dożaġġ f’ dan il- grupp ta ’ pazjenti (ara sezzjoni 4. 4).
Paediatrics The experience in children is limited, therefore no recommendation for treatment of paediatric patients with HYCAMTIN can be given (see section 5.1).
Pedjatrija L- esperjenza fit- tfal hija limitata u għalhekk ma tista ’ tingħata l- ebda rakkommandazzjoni għat - trattment ta ’ pazjenti pedjatriċi b’ HYCAMTIN (ara sezzjoni 5. 1).
Elderly No overall differences in effectiveness were observed between patients over 65 years and younger adult patients.
Ġerjatrija Ma ġew osservati l- ebda differenzi fl- effikaċja bejn pazjenti ta ’ fuq il- 65 sena u pazjenti adulti iżgħar.
However in the two studies administering both oral and intravenous topotecan, patients older than 65 years old receiving oral topotecan experienced an increase in drug related diarrhoea compared to those younger than 65 years of age (see section 4.4 and 4.8).
Madankollu fiż- żewġ studji fejn topotecan ingħata kemm mill- ħalq kif ukoll ġol- vina, pazjenti ta ’ fuq il- 65 sena li kienu qed jirċievu topotecan mill- ħalq kellhom żjieda f’ dijareja minħabba il- mediċina meta kkomparati ma ’ pazjenti ta ’ età iżgħar minn 65 sena (ara sezzjonijiet 4. 4 u 4. 8).
HYCAMTIN is contraindicated in patients who − have a history of hypersensitivity to the active substance or to any of the excipients − are breast feeding (see section 4.6) − already have severe bone marrow depression prior to starting first course, as evidenced by baseline neutrophils < 1.5 x 109/ l and/ or a platelet count of < 100 x 109/ l.
linja bażi ta ’ newtrofili ta ’ < 1. 5 x 109/ l u/ jew għadd ta ’ plejtlits ta ’ < 100 x 109/ l.
Topotecan-induced neutropenia can cause neutropenic colitis.
Newtropenja kkawżata minn topotecan tista twassal għal kolite tan- newtropenja.
Underlying risk factors include history of ILD, pulmonary fibrosis, lung cancer, thoracic exposure to radiation and use of pneumotoxic drugs and/ or colony stimulating factors.
Fatturi ta ’ riskju bażi jinkludu fil- passat ILD, fibrożi pulmonari, kanċer tal - 29 pulmun, espożizzjoni toraċika għal radjazzjoni u l- użu ta ’ mediċini pnewmotossiċi u/ jew fatturi li jistimulaw kolonji.
Patients should be monitored for pulmonary symptoms indicative of interstitial lung disease (e. g. cough, fever, dyspnoea and/ or hypoxia), and topotecan should be discontinued if a new diagnosis of 27 ILD is confirmed.
Il- pazjenti għandhom ikunu sorveljati għal sintomi pulmonari li jindikaw mard ta ’ l- interstizju tal- pulmun (e. ż. sogħla, deni, qtigħ ta 'nifs u/ jew nuqqas ta' ossiġenu), u topotecan għandu jitwaqqaf jekk tkun ikkonfermata dijanjożi ġdida ta ’ ILD.
Topotecan is partly eliminated via renal excretion and renal impairment might lead to increased exposure to topotecan.
Parti minn topotecan jitneħħa mill- kliewi u indeboliment tal- kliewi jista ’ jwassal għal esponiment akbar għal topotecan.
Dosing recommendations for patients receiving oral topotecan with Clcr less than 60 ml/ min have not been established.
Ma ġewx stabbiliti rakkomandazzjonijiet tad- dożaġġ f’ pazjenti li qed jirċievu topotecan mill- ħalq u li għandhom Clcr ta ’ anqas minn 60 ml/ min.
There is insufficient experience of the use of oral or intravenous topotecan in patients with severely impaired renal function (creatinine clearance < 20 ml/ min).
M’ hemmx biżżejjed esperjenza dwar l- użu ta ’ topotecan mill- ħalq jew ġol- vina f’ pazjenti b’ indeboliment serju tal- kliewi (tneħħija tal - krejatinina < 20 ml/ min).
Topotecan is not recommended to be used in these patients.
L- użu ta ’ topotecan f’ dawn il- pazjenti mhux rakkomandat.
A small number of hepatically impaired patients (serum bilirubin between 1.5 and 10 mg/ dl) were given intravenous topotecan at 1.5 mg/ m2 for five days every three weeks.
Numru żgħir ta ’ pazjenti b’ indeboliment tal- fwied ((bilirubin fis- serum bejn 1. 5 u 10 mg/ dl) ingħataw topotecan ġol- vina b’ doża ta ’ 1. 5 mg/ m2 għal ħamest ijiem kull tlett ġimgħat.
A reduction in topotecan clearance was observed however there are insufficient data available to make a dose recommendation for this patient group.
Ġie osservat tnaqqis fit - tneħħija ta ’ topotecan madankollu m’ hemmx tagħrif biżżejjed biex ikun hemm rakkomandazzjoni fuq id- dożaġġ f’ dan il- grupp ta ’ pazjenti.
There is insufficient experience of the use of topotecan in patients with severely impaired hepatic function (serum bilirubin ≥ 10 mg/ dl).
M’ hemmx biżżejjed esperjenza fl- użu ta ’ topotecan f’ pazjenti b’ indeboliment serju tal- fwied (bilirubin fis- serum ≥ 10 mg/ dl).
Diarrhoea, including severe diarrhoea requiring hospitalization, has been reported during treatment with oral topotecan.
Dijareja, inkluża d- dijareja serja li teħtieġ kura fl- isptar, ġiet irrappurtata waqt trattament b’ topotecan mill- ħalq.
Diarrhoea related to oral topotecan can occur at the same time as drug-related neutropenia and its sequelae.
Dijareja li għandha x’ taqsam ma ’ topotecan mill- ħalq tista ’ sseħħ fl- istess ħin man - newtropenja kkawżata mill- mediċina flimkien mal- konsegwenzi tagħha.
Communication with patients prior to drug administration regarding these side effects and proactive management of early and all signs and symptoms of diarrhoea is important.
Hija importanti l - komunikazzjoni mal- pazjenti qabel ma ’ tingħata l- mediċina, dwar dawn l- effetti avversi u huwa importanti l- maniġġjar pro- attiv ta ’ sinjali tal- bidu u ta ’ kull sinjal u sintomu ieħor ta ’ dijareja.
Cancer treatment-induced diarrhoea (CTID) is associated with significant morbidity and may be life-threatening.
Id - dijareja kkawżata mit- trattament tal- kanċer (CTID) hija assoċjata ma ’ morbidità sinifikanti u tista ’ twassal għal mewt.
Should diarrhoea occur during treatment with oral topotecan, physicians are advised to aggressively manage diarrhoea.
Jekk waqt it- trattament b’ topotecan mill- ħalq ikun hemm dijareja, l- parir lit- tobba huwa biex il- maniġġjar tad- dijareja jkun aggressiv.
Clinical guidelines describing the aggressive management of CTID includes specific recommendations on patient communication and awareness, recognition of early warning signs, use of anti-diarrhoeals and antibiotics, changes in fluid intake and diet, and need for hospitalization.
Gwidi klinikali li jiddeskrivu l- maniġġjar aggressiv ta ’ CTID jinkludu rakkomandazzjonijiet speċifiċi dwar il- komunikazzjoni mal- pazjent biex dan ikun jaf x’ inhu jiġri, biex jitlemħu s- sinjali tal- bidu tal- kundizzjoni, l- użu ta ’ mediċini kontra d - dijareja u ta ’ l- antibijotiċi, bidliet fil- konsum ta ’ likwidi u bidliet fid- dieta, u l- bżonn li wieħed jiddaħħal l- isptar.
Intravenous topotecan should be considered in the following clinical situations: uncontrolled emesis, swallowing disorders, uncontrolled diarrhoea, clinical conditions and medication that may alter gastrointestinal motility and drug absorption.
Topotecan ġol- vina għandu jiġi kkunsidrat f’ dawn il- każijiet kliniċi li ġejjin: rimettar mhux kontrollat, problemi biex tibla ’, dijareja mhux kontrollata, kundizzjonijiet kliniċi u mediċini li jistgħu jbidlu l - motilità gastro- intestinali u l- assorbiment ta ’ mediċini.
4.5 Interaction with other medicinal products and other forms of interaction
4. 5 Prodotti mediċinali oħra li ma ’ jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
In an intravenous population study, the co-administration of granisetron, ondansetron, morphine or corticosteroids did not appear to have a significant effect on the pharmacokinetics of total topotecan (active and inactive form).
Fi studju li sar fuq pazjenti li rċievew il- mediċina ġol- vina, il- ko- amministrazzjoni ta ’ granisetron, ondansetron, morfina jew kortikosterojdi ma jidhirx li kellha effett sinifikanti fuq il- farmakokinetika ta ’ topotecan totali (fil- forma attiva jew inattiva).
Topotecan is a substrate for both ABCB1 (P-glycoprotein) and ABCG2 (BCRP).
Topotecan huwa substrate kemm għal ABCB1 (P- glycoprotein) kif ukoll għal ABCG2 (BCRP).
Inhibitors of ABCB1 and ABCG2 administered with oral topotecan have been shown to increase topotecan exposure.
Intwera li inibituri ta ’ ABCB1 u ABCG2 li jittieħdu flimkien ma ’ topotecan mill- ħalq iwasslu għal - żieda fl- esponiment ta ’ topotecan.
Cyclosporin A (an inhibitor of ABCB1, ABCC1 [MRP-1], and CYP3A4) administered with oral topotecan increased topotecan AUC to approximately 2 - 2.5-fold of control.
30 Cyclosporin A (inibitur ta ’ ABCB1, ABCC1 [MRP- 1], u CYP3A4) meta ngħata flimkien ma ’ topotecan mill- ħalq wassal għal żjieda fl- AUC ta ’ topotecan ta ’ bejn wieħed u ieħor darbtejn sa darbtejn u nofs aktar mill- kontroll.
Patients should be carefully monitored for adverse reactions when oral topotecan is administered with a drug known to inhibit ABCB1 or ABCG2 (see section 5.2).
Il- pazjenti għandhom jiġu segwiti mill- qrib għal reazzjonijiet avversi meta topotecan mill- ħalq jingħata ma ’ xi mediċina li ssoltu tinibixxi ABCB1 or ABCG2 (ara sezzjoni 5. 2).
In combining topotecan with other chemotherapy agents, reduction of the doses of each medicinal 28 product may be required to improve tolerability.
Meta topotecan jiġi użat ma ’ prodotti kimoterapewtiċi oħra, jista ’ jkun hemm bżonn li titnaqqas id - doża ta ’ kull prodott mediċinali biex ittejjeb it- tollerabilità tagħhom.
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, meta kkomparat mad- doża ta ’ kull prodott li tista ’ tingħata jekk il- mediċina li fiha l- platinum tingħata fil- 5 jum tad- dożi ta ’ topotecan.
Currently there is only limited experience in combining oral topotecan with other chemotherapy agents.
Bħal issa hemm biss esperjenza limitata dwar l- użu ta ’ topotecan flimkien ma ’ sustanzi kimoterapewtiċi oħra.
The pharmacokinetics of topotecan was generally unchanged when coadministered with ranitidine.
Ġeneralment, il- farmakokinetika ta ’ topotecan ma tinbidilx meta topotecan jingħata flimkien ma ’ ranitidine.
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, din għandha tiġi avżata dwar il- periklu potenzjali għal- fetu.
In clinical trials involving patients with relapsed small cell lung cancer, the dose limiting toxicity of oral topotecan monotherapy was found to be haematological.
Fi provi kliniċi li kienu jinvolvu pazjenti b’ kanċer taċ- ċelluli ż- żgħar tal- pulmun li reġa ’ feġġ, instab li l- effett tossiku ematoloġiku kien dak li jillimita d- doża ta ’ monoterapija b’ topotecan.
29 The frequencies associated with the haematological and non-haematological adverse events presented are for adverse events considered to be related/ possibly related to oral topotecan therapy.
Il- frekwenzi assoċjati ma ’ l- effetti avversi ematoloġiċi u dawk mhux ematoloġiċi elenkati hawn taħt huma dawk ta ’ effetti avversi ikkunsidrati li għandhom / jista ’ jkollhom x’ jaqsmu mat- terapija ta ’ topotecan mill- ħalq.
Adverse reactions are listed below, by system organ class and absolute frequency.
Reazzjonijiet avversi huma elenkati hawn taħt, ikklassifikati skond is- sistema tal- ġisem u l- frekwenza assoluta.
Frequencies are defined as: very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10); uncommon (≥ 1/ 1,000 to < 1/ 100); rare (≥ 1/ 10,000 to < 1/ 1,000); very rare (< 1/ 10,000), 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 31 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 stabbiliti mit- tagħrif eżistenti).
Common: pancytopenia
Komuni: panċitopenja
Respiratory, thoracic and mediastinal disorders Rare: interstitial lung disease
Disturbi respiratorji, toraċiċi u medjastinali Rari: mard fl- interstizju tal- pulmun
Nausea, vomiting and diarrhoea (all of which may be severe), Common: abdominal pain*, constipation, stomatitis, dyspepsia *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 dijareja (li kollha jistgħu jkunu serji) Komuni: uġigħ ta ’ żaqq *, stitikezza, stomatite, dispepsja. * Kolite tan- newtropenja, inkluża l- kolite tan- newtropenja fatali, ġiet irrappurtata bħala kumplikazzjoni tan- newtropenja kkawżata minn topotecan (ara sezzjoni 4. 4).
Common: pruritis
Komuni: ħakk.
Common: asthenia, pyrexia, malaise.
Disturbi ġenerali u kundizzjonijiet ta 'mnejn jingħata Komuni ħafna: għeja Komuni: astenja, deni, telqa
Immune system disorders Common: hypersensitivity reaction including rash Not known: anaphylactic reaction, angioedema, urticaria.
Disturbi fis- sistema immuni Komuni: reazzjoni ta ’ sensittività eċċessiva inkluż raxx Mhux magħruf: reazzjoni anafilattika, anġoedima, urtikarja.
Hepato-biliary disorders Uncommon: hyperbilirubinaemia.
Disturbi fil- fwied u fil- marrara Mhux komuni: iperbilirubinimja.
Safety data are presented based on an integrated data set of 682 patients with relapsed lung cancer administered 2536 courses of oral topotecan monotherapy (275 patients with relapsed SCLC and 407 with relapsed non-SCLC).
It- tagħrif ta ’ sigurtà ppreżentat huwa bbażat fuq tagħrif integrat minn 682 pazjent b’ kanċer tal- pulmun li reġa ’ tfaċċa li ħadu 2536 kors ta ’ topotecan mill- ħalq bħala monoterapija (275 pazjent b’ SCLC li reġa ’ tfaċċa u 407 b’ non- SCLC li reġa ’ tfaċċa).
30 Haematological Neutropenia:
Ematoloġiċi Newtropenja:
Severe neutropenia (Grade 4 - neutrophil count < 0.5 x 109/ l) occurred in 32% of patients in 13% of courses.
Newtropenja serja (Grad 4 - numru ta ’ newtrofili < 0. 5 x 109/ l) seħħet f’ 32% tal- pazjenti f' 13% ta 'korsijiet.
Median time to onset of severe neutropenia was Day 12 with a median duration of 7 days.
Iż- żmien medju għal bidu tan- newtropenja qawwija kien Jum 12 u ħadet medja ta ’ 7 ijiem.
In 34% of courses with severe neutropenia, the duration was > 7 days.
F’ 34% tal- korsijiet b’ newtropenja qawwija, din damet > 7 ijiem.
In course 1 the incidence was 20%, by courses 4 the incidence was 8%.
Fl- ewwel kors l- inċidenza kienet ta ’ 20%, sal- kors 4 l- inċidenza kienet ta ’ 8%.
Infection, sepsis and febrile neutropenia occurred in 17%, 2%, and 4% of patients, respectively.
32 deni f’ 17%, 2% u 4% tal- pazjenti rispettivament.
Death due to sepsis occurred in 1% of patients.
1% tal- pazjenti mietu minħabba sepsis.
Pancytopenia has been reported.
Ġiet irrappurtata panċitopenja.
Growth factors were administered to 19% of patients in 8% of courses.
19% tal- pazjenti ngħataw growth factors f’ 8% tal- korsijiet.
Severe thrombocytopenia (Grade 4 - platelets less than 10 x 109/ l) occurred in 6% of patients in 2% of courses.
Tromboċitopenja serja (Grad 4 - plejtlits inqas minn 10 x 109/ l) seħħet f’ 6% tal - pazjenti f’ 2% tal- korsijiet.
Median time to onset of severe thrombocytopenia was Day 15 with a median duration of 2.5 days.
Iż- żmien medju għal bidu ta ’ tromboċitopenja qawwija kien Jum 15 u ħadet medja ta ’ 2. 5 ġranet.
In 18% of courses with severe thrombocytopenia the duration was > 7 days.
F’ 18% tal- korsijiet b’ tromboċitopenja qawwija, din damet > 7 ijiem.
Moderate thrombocytopenia (Grade 3 - platelets between 10.0 and 50.0 x 109/ l) occurred in 29% of patients in 14% of courses.
Kien hemm tromboċitopenja moderata (Grad 3 – plejtlits bejn 10. 0 u 50. 0 x 109/ l) f’ 29% tal- pazjenti f’ 14% tal - korsijiet.
Platelet transfusions were given to 10% of patients in 4% of courses.
10% tal- pazjenti f’ 4% tal- korsijiet ingħataw trasfużjoni ta ’ plejtlits.
Reports of significant sequelae associated with thrombocytopenia including fatalities due to tumour bleeds have been infrequent.
Rapporti ta ’ konsegwenzi sinifikanti assoċjati ma ’ tromboċitopenja, inkluż il- mewt minħabba fsada mit- tumur, ma kienux frekwenti.
Moderate to severe anaemia (Grade 3 and 4 – Hb ≤ 8.0 g/ dl) occurred in 25% of patients (12% of courses).
Anemija moderata sa qawwija (Grad 3 u 4 - Hb ≤ 8. 0 g/ dl) seħħet f’ 25% tal- pazjenti (12% tal- korsijiet).
Median time to onset of moderate to severe anaemia was Day 12 with a median duration of 7 days.
Iż- żmien medju għal bidu ta ’ anemija moderata sa qawwija kien Jum 12 u ħadet medja ta ’ 7 ijiem.
In 46% of courses with moderate to severe anaemia, the duration was > 7 days.
F’ 46% tal- korsijiet b’ anemija moderata sa qawwija, din damet > 7 ijiem.
Red blood cell transfusions were given in 30% of patients (13% of courses).
Trasfużjonijiet ta ’ ċelluli ħomor ingħataw lil 30% tal- pazjenti (13% tal- korsijiet).
Erythropoietin was administered to 10% of patients in 8% of courses.
Erythropoietin ingħata lil 10% tal - pazjenti f’ 8% tal- korsijiet.
Non-haematological The most frequently reported non-haematological effects were nausea (37%), diarrhoea (29%), fatigue (26%), vomiting (24%), alopecia (21%) and anorexia (18%).
Mhux ematoloġiċi Effetti mhux ematoloġiċi li ġew irrappurtati l- aktar frekwenti kienu dardir (37%), dijareja (29%), għeja (26%), rimettar (24%), alopeċja (21%) u anoreksja (18%).
All cases were irrespective of associated causality.
Mhux bil- fors kien hemm assoċjazzjoni ta ’ kawżalità f’ dawn il- każijiet kollha.
For severe cases (CTC grade 3/ 4) reported as related / possibly related to topotecan administration the incidence was diarrhoea 5% (see section 4.4), fatigue 4%, vomiting 3%, nausea 3% and anorexia 2%.
L- inċidenza għal dawk il- każijiet severi (CTC grad 3/ 4) li ġew irrappurtati bħala relatati / possibbilment relatati kienet ta ’ 5% għad- dijareja (ara sezzjoni 4. 4), għeja 4%, rimettar 3%, dardir 3% u anoreksja 2%.
The overall incidence of drug-related diarrhoea was 22%, including 4% with Grade 3 and 0.4% with Grade 4.
L- inċidenza totali tad- dijareja kkawżata mit- trattament kienet ta ’ 22%, inkluż 4% b’ Grad 3 u 0. 4% b’ Grad 4.
Drug-related diarrhoea was more frequent in patients ≥ 65 years of age (28%) compared to those less than 65 years of age (19%).
Dijareja minħabba t- trattament kienet aktar frekwenti f’ pazjenti ≥ 65 sena (28%) meta mqabbla ma ’ dawk ta ’ taħt il- 65 sena (19%).
Complete alopecia related/ possibly related to topotecan administration was observed in 9% of patients and partial alopecia related/ possibly related to topotecan administration in 11% of patients.
Alopeċja kompleta relatata / possibbilment relatata mal- għoti ta ’ topotecan ġiet osservata f’ 9% tal - pazjenti u alopeċja parzjali relatata / possibbilment relatata mal- għoti ta ’ topotecan f’ 11% tal- pazjenti.
Therapeutic interventions associated with non-haematological effects included anti-emetic agents, given to 47% of patients in 38% of courses and anti-diarrhoeal agents, given to 15% of patients in 6% of courses.
L- intervent terapewtiku assoċjat ma ’ effetti mhux ematoloġiċi kien jinkludi mediċini kontra r- rimettar, li ngħataw lil 47% tal- pazjenti f' 38% tal- korsijiet u mediċini kontra d- dijareja, li ngħataw lil 15% tal - pazjenti f' 6% tal- korsijiet.
A 5-HT3 antagonist was administered to 30% of patients in 24% of courses.
30% tal- pazjenti rċievew antagonist 5- HT3 f’ 24% tal- korsijiet.
Loperamide was administered to 13% of patients in 5% of courses.
Loperamide ngħata lil 13% tal- pazjenti f’ 5% tal- korsijiet.
The median time to onset of grade 2 or worse diarrhoea was 9 days.
Iż- żmien medju għal- bidu ta ’ dijareja ta ’ grad 2 jew agħar kien ta ’ 9 ijiem.
31 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 - enżima u lid - DNA maqsum bl- istrand li huwa l- proċess intermedjarju tal- mekaniżmu katalitiku.
Relapsed SCLC A phase III trial (study 478) 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:
33 SCLC li reġa ’ feġġ 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 intravenous 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).
18.3, 31.6] compared to 13.9 weeks [95% C. I.
11. 1, 18. 6] għall- pazjenti li rċievew BSC waħdu.
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) 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.
(N = 54) (N
Topotecan Topotecan mill- ħalq ġol- vina (N = 52) (N = 54)
= 153)
Topotecan mill- ħalq (N = 153)
Median survival (weeks)
Sopravivenza medja (ġimgħat)
25.1
32. 3 25. 1
33.0
33. 0
35.0
35. 0
(26.3, 40.9)
(26. 3, 40. 9)
(21.1, 33.0)
(21. 1, 33. 0)
Hazard ratio (95% CI)
Proporzjon ta ’ periklu (95% CI)
0.88 (0.59, 1.31)
0. 88 (0. 59, 1. 31)
0.88 (0.7, 1.11)
0. 88 (0. 7, 1. 11)
Response rate (%)
Rata ta ’ rispons (%)
14.8
14. 8
18.3
18. 3
21.9
21. 9
(11.6, 34.5)
(11. 6, 34. 5)
(5.3, 24.3)
(5. 3, 24. 3)
32 Paediatrics Safety and effectiveness of oral topotecan in paediatric patients have not been established.
Pedjatrija Is- sigurtà u l- effikaċja ta ’ topotecan mill- ħalq f’ pazjenti pedjatriċi ma ġewx stabbiliti.
The pharmacokinetics of topotecan after oral administration have been evaluated in cancer patients following doses of 1.2 to 3.1 mg/ m2/ day and 4 mg/ m2/ day administered daily for 5 days.
Il- farmakokinetika ta ’ topotecan wara li ngħata mil- ħalq ġiet evalwata f’ pazjenti bill- kanċer wara dożi ta ’ 1. 2 sa 3. 1 mg / m2/ ġurnata u 4 mg / m2/ ġurnata li ngħataw kuljum għal 5 ijiem.
The bioavailability of oral topotecan (total and lactone) in humans is approximately 40%.
Il- bioavailability fil- bnedmin ta ’ topotecan mill- ħalq (total u lactone) hija bejn wieħed u ieħor 40%.
Plasma concentrations of total topotecan (i. e. lactone and carboxylate forms) and topotecan lactone (active moiety) peak at approximately 2.0 hours and 1.5 hours, respectively, and decline bi-exponentially with mean terminal half-life of approximately 3.0 to 6.0 hour.
Il - konċentrazzjoni ta ’ topotecan totali fil- plażma (jiġifieri fil- forom lactone u carboxylate) u dik ta ’ topotecan lactone (l- parti attiva) jilħqu l- ogħla livell tagħhom wara bejn wieħed u ieħor sagħtejjn u
Total exposure (AUC) increases approximately proportionally with dose.
L- esponiment totali (AUC) jiżdied bejn wieħed u ieħor proporzjonalment skond id- doża.
A major route of clearance of topotecan is by hydrolysis of the lactone ring to form the ring-opened carboxylate.
It- tneħħija ta ’ topotecan isseħħ l- aktar permezz ta ’ l- idroliżi tal- lactone ring biex jifforma r- ring - opened carboxylate.
Other than hydrolysis, topotecan is cleared predominantly renally, with a minor component metabolized to the N-desmethyl metabolite (SB-209780) identified in plasma, urine and faeces.
Barra l- idroliżi, topotecan jitneħħa l- iżjed mill- kliewi u parti żgħira titneħħa permeżż tas- sustanza iffurmata mill- metaboliżmu N- desmethyl (SB- 209780) li ġiet identifikata fl - awrina, fil- plasma u fil- ħmieġ.
Overall recovery of topotecan-related material following five daily doses of topotecan was 41 to 76% (mean 57%) of the administered oral dose.
Il- ġbir totali ta ’ materjali li għandhom x’ jaqsmu ma ’ topotecan wara l - ħames dożi ta ’ topotecan li ngħataw darba kuljum kien ta ’ 41 sa 76% (medja ta ’ 57%) tad- doża amministrata mill- ħalq.
Approximately 20% was excreted as total topotecan and 2% was excreted as N-desmethyl topotecan in the urine.
Bejn wieħed u ieħor 20% tneħħa bħala topotecan totali u 2% tneħħa bħala N - desmethyl topotecan fl- awrina.
Faecal elimination of total topotecan accounted for 33% while faecal elimination of N-desmethyl topotecan was 1.5%.
Eliminazzjoni mal- ħmieġ ta ’ topotecan totali kienet ta ’ 33% filwaqt li eliminazzjoni mal- ħmieġ ta ’ N- desmethyl topotecan kienet ta ’ 1. 5%.
Overall, the N-desmethyl metabolite contributed a mean of less than 6% (range 4-8%) of the total topotecan related material accounted for in the urine and faeces.
Globalment is- sustanza mill - metaboliżmu N- desmethyl ikkontribbwixxiet għal medja ta ’ anqas minn 6% (bejn 4- 8%) tat- total tal - materjali li għandhom x’ jaqsmu ma ’ topotecan li nstabu fl- awrina u fil- ħmieġ.
O-glucuronides of both topotecan and N- desmethyl topotecan have been identified in the urine.
L - O- glucuronide ta ’ topotecan u l - O- glucuronide ta ’ N- desmethyl topotecan ġew identifikati fl- awrina.
The mean metabolite: parent plasma AUC ratio was less than 10% for both total topotecan and topotecan lactone.
Il- medja tal - proporzjon tas- sustanza tal- metaboliżmu: l- AUC tas- sustanza oriġinali fil- plażma kienet anqas minn 10% kemm għal topotecan totali kif ukoll għal topotecan lactone.
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 cytosolic umani dihydropyrimidine jew xanthine oxidase.
Following coadministration of the ABCB1 (P-gp) and ABCG2 (BCRP) inhibitor, elacridar (GF120918) at 100 to 1,000 mg with oral topotecan, the AUC0- ∞ of topotecan lactone and total topotecan increased approximately 2.5-fold (see section 4.5 for guidance).
Wara li topotecan mill- ħalq ingħata flimkien ma ’ elacridar (GF120918), inibitur ta ’ ABCB1 (P- gp) u ABCG2 (BCRP), b’ doża ta ’ 100 sa 1, 000 mg, l- AUC0- ∞ ta ’ topotecan lactone u topotecan totali żdiedet għal bejn wieħed u ieħor 2. 5 darba (ara sezzjoni 4. 5 għal gwida).
Administration of oral cyclosporine A (15 mg/ kg), an inhibitor of transporters ABCB1 (P-gp) and ABCC1 (MRP-1) as well as the metabolising enzyme CYP3A4, within 4 hours of oral topotecan increased the dose normalised AUC0-24h of topotecan lactone and total topotecan approximately 2.0- and 2.5-fold, respectively (see section 4.5).
Meta cyclosporine A (15 mg/ kg), inibitur tal- ġarriera ABCB1 (P- gp) u ABCC1 (MRP- 1) kif ukoll inibitur tal- enżema tal- metaboliżmu CYP3A4, jingħata mill- ħalq fi żmien 4 sigħat wara topotecan mill- ħalq, l- AUC0- 24h, normalizzat skond id- doża, ta 'topotecan lactone u topotecan totali żdiedet għal bejn wieħed u ieħor 2. 0 u 2. 5- darba, rispettivament (ara sezzjoni 4. 5).
The extent of exposure was similar following a high fat meal and fasted state while tmax was delayed from 1.5 to 3 hours (topotecan lactone) and from 3 to 4 hours (total topotecan).
Wara ikla b’ ħafna xaħam u fuq stonku vojt, il- livell ta ’ esponiment kien jixxiebaħ, waqt li kien hemm dewmien f’ tmax minn 1. 5 sa 3 sigħat (topotecan lactone) u minn 3 sa 4 sigħat (topotecan totali)
The pharmacokinetics of oral topotecan has not been studied in patients with renal or hepatic impairment (see section 4.2 and 4.4).
Il- farmakokinetika ta ’ topotecan mill- ħalq ma ġietx studjata f’ pazjenti b’ indeboliment tal- kliewi jew tal- fwied (ara sezzjonijiet 4. 2 u 4. 4)
A cross-study analysis in 217 patients with advanced solid tumours indicated that gender did not affect the pharmacokinetics of HYCAMTIN capsules to a clinically relevant extent.
F’ analiżi ta ’ studji f’ 217 pazjent b’ tumuri solidi fi stat avvanzat, intwera li ma kienx hemm differenza klinikament rilevanti fil- farmakokinetika tal- kapsuli HYCAMTIN bejn pazjenti nisa w rġiel.
There are insufficient data to determine an effect of race on pharmacokinetics of oral topotecan.
M’ hemmx biżżejjed tagħrif biex wieħed ikun jaf jekk ir- razza għandiex effett fuq il- farmakokinetika ta ’ topotecan mill- ħalq.
Topotecan was also 33 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.
35 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.
Capsule contents:
Il- kontenut tal- kapsula:
Hydrogenated vegetable oil Glyceryl monostearate
Hydrogenated vegetable oil, Glyceryl monostearate
Gelatin Titanium dioxide (E171)
Ġelatina, Titanium dioxide (E171),
Sealing band:
Il- faxxa tas- siġill: