natgillin/translations-raw huggingface dataset:
4. 4).
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).
Hud og subkutane væv Meget almindelig: alopecia.
Skin and subcutaneous tissue disorders Very common: alopecia.
Metabolisme og ernæring Meget almindelig: anoreksi (muligvis alvorlig).
Metabolism and nutrition disorders Very common: anorexia (which may be severe).
Infektioner og parasitære sygdomme Meget almindelig: infektion Almindelig: sepsis
Infections and infestations Very common: infection Common: sepsis
Almene symptomer og reaktioner på administrationsstedet Meget almindelig: pyreksi, asteni, træthed Almindelig: utilpashed Meget sjælden: extravasation * * Extravasation er meget sjældent rapporteret.
Very rare: extravasation*. *Extravasation has been reported very rarely.
Immunsystemet Almindelig: overfølsomhedsreaktion inkl. udslæt Sjælden: anafylaktisk reaktion, angioødem, urticaria.
Immune system disorders Common: hypersensitivity reaction including rash Rare: anaphylactic reaction, angioedema, urticaria.
Lever - og galdeveje Almindelig: hyperbilirubinæmi.
Hepato-biliary disorders Common: hyperbilirubinaemia.
4. 4).
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).
Frekvenserne forbundet med hæmatologiske og ikke- hæmatologiske bivirkninger anført nedenfor viser de bivirkningsrapporter, som anses for at være relateret eller muligvis relateret til behandling med topotecan.
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.
Hæmatologiske Neutropeni:
6 Haematological Neutropenia:
Alvorlig (neutrofiltal < 0, 5 x 109/ l) under behandlingsperiode 1 blev observeret hos 55% af patienterne og med en varighed ≥ 7 dage hos 20% og totalt set hos 77% af patienterne (39% af behandlingerne).
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).
Sammen med alvorlig neutropeni forekom der feber eller infektion hos 16% af patienterne under kur 1 og totalt set hos 23% af patienterne (6% af behandlingerne).
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).
Mediantiden til indtræden af alvorlig neutropeni var 9 dage, og medianvarigheden 7 dage.
Median time to onset of severe neutropenia was 9 days and the median duration was 7 days.
Alvorlig neutropeni varede længere end 7 dage i 11% af alle behandlingerne.
Severe neutropenia lasted beyond 7 days in 11% of courses overall.
Blandt alle patienterne, der blev behandlet i de kliniske forsøg (herunder både dem med alvorlig neutropeni og dem, der ikke udviklede alvorlig neutropeni), udviklede 11% (4% af behandlingerne) feber, og 26% (9% af behandlingerne) udviklede infektion.
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.
4. 4).
In addition, 5% of all patients treated (1% of courses) developed sepsis (see section 4.4).
Alvorlig (trombocyttal under 25 x 109/ l) hos 25% af patienterne (8% af behandlingerne), moderat (trombocyttal mellem 25, 0 og 50, 0 x 109/ l) hos 25% af patienterne (15% af behandlingerne).
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).
Mediantiden før indtræden af alvorlig trombocytopeni var dag 15, og medianvarigheden var 5 dage.
Median time to onset of severe thrombocytopenia was Day 15 and the median duration was 5 days.
Der blev givet trombocyttransfusioner i 4% af behandlingerne.
Platelet transfusions were given in 4% of courses.
Moderat til alvorlig (Hb ≤ 8, 0 g/ dl) hos 37% af patienterne (14% af behandlingerne).
Moderate to severe (Hb ≤ 8.0 g/ dl) in 37% of patients (14% of courses).
Der blev givet transfusioner af røde blodlegemer til 52% af patienterne (21% af behandlingerne).
Red cell transfusions were given in 52% of patients (21% of courses).
Non- hæmatologiske I kliniske undersøgelser af 445 patienter med ovariecancer, var de oftest rapporterede non - hæmatologiske bivirkninger gastrointestinale, såsom kvalme (52%), opkastning (32%) og diare (18%), konstipation (9%) og mucositis (15%).
Non-haematological Frequently reported non-haematological effects were gastrointestinal such as nausea (52%), vomiting (32%), and diarrhoea (18%), constipation (9%) and mucositis (15%).
Hyppigheden af alvorlig (grad 3 eller 4) kvalme, opkastning, diare og mucositis var henholdsvis 4, 3, 2 og 1%.
Severe (grade 3 or 4) nausea, vomiting, diarrhoea and mucositis incidence was 4, 3, 2 and 1% respectively.
Milde abdominalsmerter blev også rapporteret blandt 4% patienterne.
Mild abdominal pain was also reported amongst 4% of patients.
25% og asteni hos 16% af patienterne, mens de blev behandlet med topotecan.
Fatigue was observed in approximately 25% and asthenia in 16% of patients whilst receiving topotecan.
Hyppigheden af alvorlig (grad 3 eller 4) træthed og asteni var 3 og 3%, respektivt.
Severe (grade 3 or 4) fatigue and asthenia incidence was 3 and 3% respectively.
Total eller udtalt alopecia blev observeret hos 30% af patienterne, og partiel alopecia hos 15% af patienterne.
Total or pronounced alopecia was observed in 30% of patients and partial alopecia in 15% of patients.
Andre alvorlige hændelser observeret hos ≥ 1% af patienterne, som var registreret som relateret til eller muligt relateret til behandling med topotecan omfattede anorexia (12%), utilpashed (3%) og hyperbilirubinæmi (1%).
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%).
I kliniske undersøgelser er hududslæt rapporteret hos 4% af patienterne og pruritus hos 1, 5% af patienterne.
In clinical trials, rash was reported in 4% of patients and pruritus in 1.5% of patients.
Andre antineoplastiske stoffer:
Other antineoplastic agents:
Anti- tumor aktiviteten af topotecan involverer hæmning af topoisomerase- 1, et enzym tæt involveret i DNA replikation, da den eliminerer det torsionale belastning, der opstår foran den bevægelige replikationsgaffel.
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.
Topotecan hæmmer topoisomerase- 1 ved at stabilisere det kovalente kompleks af enzym og strengkløvet DNA, som er et intermediært produkt af den katalytiske mekanisme.
Topotecan inhibits topoisomerase-I by stabilising the covalent complex of enzyme and strand-cleaved DNA which is an intermediate of the catalytic mechanism.
Den cellulære følge af den af topotecan forårsagede hæmning af topoisomerase- 1 er fremkaldelse af proteinassocierede enkelstrengsbrud på DNA.
The cellular sequela of inhibition of topoisomerase-I by topotecan is the induction of protein-associated DNA single-strand breaks.
I en sammenlignende undersøgelse med topotecan og paclitaxel hos patienter tidligere behandlet for ovariecancer med platinbaseret kemoterapi (n = 112 og n = 114, respektivt), var responsraten (95% CI) 20, 5% (13%, 28%) versus 14% (8%, 20%) og mediantiden til progression var 19 uger versus 15 uger (risiko ratio 0, 7 [0, 6; 1, 0] for topotecan og paclitaxel respektivt.
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.
Median total overlevelse var 62 uger for topotecan versus 53 uger for paclitaxel (risiko ratio 0, 9 [0, 6; 1, 3]).
Median overall survival was 62 weeks for topotecan versus 53 weeks for paclitaxel (hazard ratio 0.9 [0.6, 1.3]).
Responsraten i hele ovariecancerprogrammet (n = 392, alle tidligere behandlet med cisplatin eller cisplatin og paclitaxel) var 16%.
The response rate in the whole ovarian carcinoma programme (n = 392, all previously treated with cisplatin or cisplatin and paclitaxel) was 16%.
I kliniske undersøgelser var den mediane tid indtil respons 7, 6 – 11, 6 uger.
The median time to response in clinical trials was 7.6- 11.6 weeks.
Hos patienter, der var refraktære eller som fik tilbagefald inden for 3 måneder efter cisplatinbehandling (n = 186), var responsraten 10%.
In patients refractory to, or relapsing within 3 months after cisplatin therapy (n = 186), the response rate was 10%.
(se afsnit 4. 8)
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).
Ialt 87 fuldstændige og partielle responser blev observeret, heraf 13, som optrådte mellem 5. og 6. serie, og 3, som optrådte derefter.
Altogether, 87 complete and partial responses were observed, with 13 of these occurring during cycles 5 and 6 and 3 occurring thereafter.
Af de patienter, som modtog flere end 6 serier af kemoterapi, fuldførte 91% undersøgelsen som planlagt eller blev behandlet, indtil sygdommen progredierede, og heraf blev kun 3% ekskluderet på grund af bivirkninger.
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.
I en fase III undersøgelse blev oral topotecan plus Best Supportive Care [BSC] [n = 71] sammenlignet med BSC alene [n = 70] hos patienter, som havde tilbagefald efter førstebehandling [mediantid til progression [TTP] fra førstebehandling:
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:
84 dage for oral topotecan + BSC, 90 dage for BSC] og for hvem gentagelse af behandling med i. v kemoterapi ikke var hensigtsmæssig.
84 days for oral topotecan + BSC, 90 days for BSC] and for whom retreatment with i. v chemotherapy was not considered appropriate.
Oral topotecan plus BSC- gruppen oplevede en statistisk signifikant forbedring i samlet overlevelse sammenlignet med gruppen med BSC alene (log- rank p = 0, 0104).
Oral topotecan plus BSC group had a statistically significant improvement in overall survival compared with the BSC alone group (Log- rank p=0.0104).
Det ikke- justerede risikoforhold for oral topotecan plus BSC- gruppen i forhold til gruppen med BSC alene var 0, 64 (95% CI; 0, 45; 0, 90).
0.45, 0.90).
Medianoverlevelsen for patienter behandlet med topotecan + BSC var 25, 9 uger [95% C. I.
The median survival for patients treated with topotecan + BSC was 25.9 weeks [95% C. I.
18, 3; 31, 6] sammenlignet med 13, 9 uger [95% C. I.
18.3, 31.6] compared to 13.9 weeks [95% C. I.
11, 1; 18, 6] for patienter, der modtog BSC alene [p = 0, 0104].
11.1, 18.6] for patients receiving BSC alone [p=0.0104].
Et fase II- forsøg (forsøg 065) og et fase III- forsøg (forsøg 396) blev gennemført til vurdering af effekten af oral topotecan versus intravenøs topotecan til patienter, der havde oplevet tilbagefald ≥ 90 dage efter afslutningen af et tidligere behandlingsforløb med kemoterapi (se tabel 1).
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).
I patienternes egne rapporteringer vha. en ublindet vurdering på en symptomskala i begge forsøg, var oral og iv topotecan forbundet med samme symptomlindring hos patienter med recidiverende, sensitiv SCLC.
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.
Oversigt over overlevelse, responsrate og tiden indtil progression hos SCLC- patienter, der er behandlet med oral Hycamtin eller intravenøs Hycamtin
Summary of survival, response rate, and time to progression in SCLC patients treated with oral HYCAMTIN or intravenous HYCAMTIN
Oral topotecan
Oral topotecan
Intravenøs Oral topotecan
Intravenous Oral topotecan topotecan
(N = 52)
(N = 52)
(N = 54) (N
(N = 54) (N = 153)
(N = 151)
(N = 151)
Risikoforhold (95% CI)
Median survival (weeks) (95% CI) Hazard ratio (95% CI) Response rate (%) (95% CI)
Responsrate (%)
35.0 (31.0, 37.1) 1.11) 21.9 (15.3, 28.5)
(95% CI)
Difference in response rate (95% CI)
Risikoforhold (95% CI) antal behandlede patienter
Hazard ratio (95% CI) total number of patients treated.
CI = konfidensinterval
CI = Confidence interval.
I en anden randomiseret fase III undersøgelse som sammenlignede IV topetecan med cyclophosphamid, Adriamycin (doxorubicin) og vincristin (CAV) hos patienter med recidiverende, sensitiv SCLC, var den samlede responsrate 24, 3% for topotecan sammenlignet med 18, 3% for CAV gruppen.
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.
Mediantid til progression var ens i de to grupper (13, 3 uger henholdsvis 12, 3 uger).
Median time to progression was similar in the two groups (13.3 weeks and 12.3 weeks respectively).
Medianoverlevelsen for de to grupper var 25, 0 henholdsvis 24, 7 uger.
Median survivals for the two groups were 25.0 and 24.7 weeks respectively.
Risiko ratio for overlevelse af IV topotecan relativt til CAV var 1, 04 (95% CI 0, 78; 1, 40).
The hazard ratio for survival of IV topotecan relative to CAV was 1.04 (95% CI 0.78 – 1.40).
Responsraten for topotecan i det kombinerede program for småcellet lungecancer [n = 480] for patienter med recidiverende sygdom efter førstebehandling var 20, 2%.
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%.
Medianoverlevelsen var 30, 3 uger (95% CI:
The median survival was 30.3 weeks (95% CI:
I en population af patienter med refraktær SCLC (dem som ikke responderer på førstebehandling) var responsraten 4, 0%.
In a population of patients with refractory SCLC (those not responding to first line therapy), the response rate to topotecan was 4.0%.
I et randomiseret, sammenlignende fase III- studie, udført af Gynaecological Oncology Group (GOG 0179), blev topotecan + cisplatin (n = 147) sammenlignet med cisplatin alene (n = 146) for behandling af histologisk bekræftet, persisterende, recidiverende eller stadium IVB- cervixcancer, hvor kurativ intenderet behandling med kirurgi og/ eller stråleterapi ikke var vurderet hensigtsmæssig.
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.
Behandling med topotecan + cisplatin resulterede i en statistisk signifikant forlængelse af den samlede overlevelse i forhold til cisplatin- monoterapi efter justering for interimanalyser (Log- rank p = 0, 033).
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).
9 Resultater Studie GOG- 0179 ITT- population
ITT population
cisplatin
Cisplatin
50 mg/ m2 d.
50mg/ m2 d.
1 q 21 d.
1 q21 d.
mg/ m2 d.
50mg/ m2 d.
1 + topotecan
1 + Topotecan 0.75mg/ m2 dx3 q21
Overlevelse (mdr.)
Survival (months) Median (95% C. I.)
(n = 146)
(n= 146) 6.5 (5.8, 8.8)
Median (95% C. I.)
Hazard ratio (95% C. I.) Log rank p-value
9, 4 (7, 9; 11, 9)
(0.59-0.98) 0.033
Patienter uden forudgåede cisplatin kemo/ stråleterapi
Patients without Prior Cisplatin Chemoradiotherapy
topotecan/ cisplatin
Topotecan/ Cisplatin
Median (95% C. I.)
Median (95% C. I.)
Risikoforhold (95% C. I.)
Hazard ratio (95% C. I.)
Patienter med forudgående cisplatin kemo/ stråleterapi
Patients with Prior Cisplatin Chemoradiotherapy
Median (95% C. I) Risikoforhold (95% C. I.)
Median (95% C. I) Hazard ratio (95% C. I.)
For patienter (n = 39) med recidiv inden for 180 dage efter kemo/ stråleterapi med cisplatin, var medianoverlevelsen i den gruppe, der fik topotecan + cisplatin 4, 6 mdr.
In patients (n=39) with recurrence within 180 days after chemoradiotherapy with cisplatin, the median survival in the topotecan plus cisplatin arm was 4.6 months (95% C. I.:
2, 6; 6, 1) versus 4, 5 mdr.
2.6, 6.1) versus 4.5 months (95%C. I.:
2, 9; 9, 6) for gruppen, der fik cisplatin alene og med et risikoforhold på 1, 15 (0, 59; 2, 23).
2.9, 9.6) for the cisplatin arm with an hazard ratio of 1.15 (0.59, 2.23).
For de patienter (n = 102) med recidiv efter 180 dage, var medianoverlevelse i gruppen, der fik topotecan + cisplatin 9, 9 mdr.
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.:
7; 12, 6) versus 6, 3 mdr.
7, 12.6) versus 6.3 months (95%C. I.:
4, 9; 9, 5) for gruppen, der fik cisplatin alene og med et risikoforhold på 0, 75 (0, 49; 1, 16).
4.9, 9.5) for the cisplatin arm with an hazard ratio of 0.75 (0.49, 1.16).
Administration af topotecan til børn er undersøgt, men der er kun begrænset data om effekt og sikkerhed tilgængelig.
Topotecan was also evaluated in the paediatric population; however, only limited data on efficacy and safety are available.
Behandlingen blev gentaget hver 3. uge i op til et år afhængig af terapirespons.
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.
Ewing’ s sarkom/ primitiv neuroektoderm tumor, neuroblastoma, osteoblastoma og rhabdomyosarcoma.
Tumour types included were Ewing's Sarcoma/ primitive neuroectodermal tumour, neuroblastoma, osteoblastoma, and rhabdomyosarcoma.
65 patienter (60%) fik transfusion af pakket blod og 50 patienter (46%) fik transfusion af trombocytter henholdsvis over 139 og 159 behandlingsserier (henholdsvis 30, 5% og 34, 9%).
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.
5. 2)
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).
2/ 3 af blodgennemstrømning gennem leveren.
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.
Topotecan havde ligeledes et højt distributionsvolumen på omkring 132 l (SD 57), samt en relativ kort halveringstid på 2- 3 timer.
Topotecan also had a high volume of distribution, about 132 l, (SD 57) and a relatively short half-life of 2-3 hours.
10 Sammenligning af farmakokinetiske parametre viste ingen farmakokinetiske ændringer i løbet af de 5 doseringsdage.
Comparison of pharmacokinetic parameters did not suggest any change in pharmacokinetics over the 5 days of dosing.
Der ses ringe eller ingen akkumulering af topotecan efter gentagen daglig dosering, og der er ingen tegn på ændring i PK efter multiple doser.
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.
Prækliniske forsøg tyder på, at topotecans plasmaproteinbinding er lav (35%), og fordelingen mellem blodceller og plasma er omtrent homogen.
Preclinical studies indicate plasma protein binding of topotecan is low (35%) and distribution between blood cells and plasma was fairly homogeneous.
Metabolisme udgør < 10% af topotecans eliminering.
Metabolism accounts for < 10% of the elimination of topotecan.
En N- desmethyl metabolit, som i en cellebaseret assay har vist sig at have samme eller mindre aktivitet end lægemiddelstoffet, er fundet i urin, plasma og fæces.
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.
Det gennemsnitlige forhold mellem hovedmetabolitten og lægemiddelstoffets AUC var mindre end 10% for såvel topotecan som topotecanlacton.
The mean metabolite: parent AUC ratio was less than 10% for both total topotecan and topotecan lactone.
En O- glucuroniseret metabolit af topotecan og N- desmethyl topotecan er identificeret i urin.
An O-glucuronidation metabolite of topotecan and N-desmethyl topotecan has been identified in the urine.
Overordnet genvinding af lægemiddelstofrelateret materiale efter fem daglige doser af topotecan var 71 til 76% af den administrerede IV dosis.
Overall recovery of medicinal product-related material following five daily doses of topotecan was 71 to 76% of the administered IV dose.
Omtrent 51% blev udskilt som uomdannet topotecan og 3% blev udskilt som N- desmethyl topotecan i urinen.
Approximately 51% was excreted as total topotecan and 3% was excreted as N-desmethyl topotecan in the urine.
Fæcal eliminering af uomdannet topotecan udgjorde 18% mens fæcal eliminering af N- desmethyl topotecan var 1, 7%.
Faecal elimination of total topotecan accounted for 18% while faecal elimination of N-desmethyl topotecan was 1.7%.
Samlet set, bidrog N - desmethyl metabolitten i gennemsnit mindre end 7% (interval 4 - 9%) til det lægemiddelstofrelateret materiale i urin og fæces, som der kunne gøres rede for.
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.
Topotecan- O- glucuronid og N- desmethyl topotecan – O- glucuronid i urinen var mindre end 2, 0%.
The topotecan-O-glucuronide and N-desmethyl topotecan-O-glucuronide in the urine were less than 2.0%.
In vitro data på humane levermikrosomer indikerer dannelsen af små mængder af N- demethyleret topotecan.
In vitro data using human liver microsomes indicate the formation of small amounts of N- demethylated topotecan.
In vitro hæmmede topotecan hverken de menneskelige P450- enzymer CYP1A2, CYP2A6, CYP2C8/ 9, CYP2C19, CYP2D6, CYP2E, CYP3A og CYP4A eller de menneskelige cytosoliske enzymer dihydropyrimidin eller xanthin oxidase.
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.
4. 5)
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).
67% sammenlignet med en kontrolgruppe af patienter.
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.