FrancophonIA/ELRC3.0 huggingface dataset:
English: An O-glucuronidation metabolite of topotecan and N-desmethyl topotecan has been identified in the urine.
Danish: En O-glucuroniseret metabolit af topotecan og N-desmethyl topotecan er identificeret i urin.
English: In combining topotecan with other chemotherapy agents, reduction of the doses of each medicinal product may be required to improve tolerability.
Danish: Når topotecan gives sammen med andre kemoterapeutika, kan det være nødvendigt, at reducere dosis af de enkelte lægemidler for at forbedre stoffernes tolerabiliteten.
English: 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.
Danish: 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.
English: 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).
Danish: I en populationsundersøgelse havde et antal faktorer, såsom alder, vægt og ascites ingen signifikant virkning på clearance af total topotecan (aktiv og inaktiv form).
English: If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless reconstitution/dilution has taken place in controlled and validated aseptic conditions.
Danish: Hvis det ikke anvendes omgående, er ansvaret for i-brug-tid og opbevaringsbetingelser forud for anvendelse brugers og vil normalt ikke være længere end 24 timer ved 2° C til 8° C, medmindre rekonstituering/fortynding er foretaget under kontrollerede og validerede aseptiske forhold.
English: Following intravenous administration of topotecan at doses of 0.5 to 1.5 mg/m 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.
Danish: Efter intravenøs administration af topotecandoser på 0,5 til 1,5 mg/m2, som 30 minutters infusion dagligt i 5 dage, demonstrerede topotecan en høj plasmaclearance på 62 l/time (SD 22), hvilket svarer til ca. 2/3 af blodgennemstrømning gennem leveren.
English: Very rare side effects (may affect up to 1 in 10,000 people) - Mild pain and inflammation at the site of injection due to accidental administration of the medicinal product into the surrounding tissue (extravasation) e.g. by leakage.
Danish: Meget sjældne bivirkninger (kan ske hos 1 ud af 10.000personer): - Lette smerter og betændelse på injektionsstedet pga. fejlagtigindgivelse af lægemidlet i det omkringliggende væv (ekstravasation), f.eks. på grund af udsivning.
English: Your dose of Topotecan Actavis will depend on: - the disease being treated, - your body surface area (m - the results of blood tests carried out before and during treatment, - how well you tolerate treatment.
Danish: Din dosis af Topotecan Actavis afhænger af: din kropsoverflade (overfladeareal målt i kvardratmeter) resultaterne af blodprøverne, der er tages inden og under behandlingen
English: Very common side effects (may affect more than 1 in 10 people) - Feeling generally weak and tired, which can be symptoms of a decrease in the number of red blood cells (anaemia).
Danish: Meget almindelige bivirkninger (kan ske hos flere end 1 ud af 10 personer): - Generel følelse af slaphed og træthed, som kan være symptomer på fald i antallet af røde blodceller (anæmi).
English: Haematological toxicity is dose-related and full blood count including platelets should be monitored regularly (see section 4.2).
Danish: Den hæmatologiske toksicitet er dosisafhængig, og det samlede blodbillede, herunder trombocytter, bør monitoreres jævnligt (se pkt.
English: Patient self-reports of symptoms using an unblinded assessment showed a consistent trend for symptom benefit for oral topotecan + BSC.
Danish: Patienternes egen rapportering af symptomer vha. ublindede vurderinger viste en klar tendens mod symptomforbedring med peroral topotecan + BSC.
English: Yellow lyophilisate.
Danish: Gult pulver.
English: PARTICULARS TO APPEAR ON THE OUTER PACKAGING Outer Carton
Danish: MÆRKNING, DER SKAL ANFØRES PÅ DEN YDRE EMBALLAGE Ydre æske
English: Severe (grade 3 or 4) fatigue and asthenia incidence was 3 and 3 % respectively.
Danish: Hyppigheden af alvorlig (grad 3 eller 4) træthed og asteni var 3 og 3 %, respektivt.
English: Oral topotecan plus BSC group had a statistically significant improvement in overall survival compared with the BSC alone group (Log-rank p = 0.0104).
Danish: Oral topotecan plus BSC-gruppen oplevede en statisistiks signifikant forbedring i samlet overlevelse sammenlignet med gruppen med BSC alene (log-rank p = 0,0104).
English: 5.2 mg/m in children (n = 8), adolescents (n = 3), and young adults (n = 3) with leukaemia.
Danish: (n = 8), unge (n = 3) og yngre voksne (n = 3) med leukæmi.
English: The prescribing information for cisplatin should be consulted for a full list of adverse events associated cisplatin use.
Danish: Den eksisterende information for cisplatin bør konsulteres for information om den komplette liste over bivirkninger associeret til brugen af cisplatin.
English: For intravenous use as infusion, after reconstitution and dilution.
Danish: Til intravenøst brug som infusion, efter rekonstituering og fortynding.
English: The mean metabolite:parent AUC ratio was less than 10 % for both total topotecan and topotecan lactone.
Danish: Det gennemsnitlige forhold mellem hovedmetabolitten og lægemiddelstoffets AUC var mindre end 10 % for såvel topotecan som topotecanlacton.
English: Insufficient data are available to make a recommendation for patients with a creatinine clearance <20 ml/min.
Danish: Der findes ikke tilstrækkeligt datamateriale til at anbefale behandling af patienter med en kreatininclearance på < 20 ml/min.
English: Hypersensitivity reactions including rash, urticaria, angioedema and anaphylactic reactions have been reported rarely.
Danish: I sjældne tilfælde er der rapporteret overfølsomhedsreaktioner heriblandt hududslæt, urticaria, angioødem og anafylaktiske reaktioner.
English: Storage after reconstitution and dilution
Danish: Opbevaring efter rekonstituering og fortynding
English: Infections and infestations Very common:
Danish: Infektioner og parasitære sygdomme Meget almindelig: infektion
English: anaphylactic reaction angioedema urticaria
Danish: anafylaktisk reaction angioødem urticaria
English: 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 %.
Danish: Responsraten for topotecan i det kombinerede program for småcellet lungecancer (n = 480) for patienter med recidiverende sygdom efter førstelinjebehandling var 20,2 %.
English: Τηλ: +30 210 5401500
Danish: Specifar ABEE Τηλ: +30 210 5401500
English: Volume for 50 microgram/ml solution
Danish: Volumen for 50 migrogram/ml opløsning
English: The recommended monotherapy dose of topotecan in patients with small cell lung carcinoma and a creatinine clearance between 20 and 39 ml/min is 0.75 mg/m2/day for five consecutive days.
Danish: Den rekommenderede topotecandosis ved monoterapi hos patienter med småcellet lungecancer og en kreatininclearance mellen 20 og 39 ml/min er 0,75 mg/m2/dag i fem sammenhængende dage.
English: Precautions to be taken before handling or administering the medicinal product Reconstitution and dilution of the medicinal product must be performed by trained personnel.
Danish: Sikkerhedsforanstaltninger, der skal tages før håndtering og administration af lægemidlet Rekonstitution og fortynding af lægemidlet må kun foretages af oplært personale.
English: Topotecan monotherapy is indicated for the treatment of 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).
Danish: Topotecan-monoterapi er indiceret til behandling af patienter med recidiverende småcellet lungecancer (SCLC) for hvem gentagelse af førstelinjebehandling ikke anses for hensigtsmæssig (se pkt.
English: Very rare:
Danish: Almindelig: Meget sjælden:
English: Each vial contains 2.07 mg (0.09 mmol) sodium.
Danish: Hver hætteglas indeholder 2,07 mg natrium (0,09 mmol).
English: Pregnant staff should not handle the cytotoxic preparation.
Danish: Gravide kvinder blandt personalet bør ikke arbejde med cytotoksiske præparation.
English: The incidence of adverse reactions listed above have the potential to occur with a higher frequency in patients who have a poor performance status (see section 4.4).
Danish: Bivirkningsfrekvenserne overfor kan forekomme med større hyppighed hos patienter, som har en dårlig performancestatus (se pkt.
English: In case of skin contact, thoroughly wash the affected area with large amount of water.
Danish: Ved kontakt med huden, vaskes det berørte område grundigt med rigelige mængder vand.
English: In the event of contact with the eyes, irrigate with large amounts of water.
Danish: Hvis det kommer i kontakt med øjnene, skylles der med rigelige mængder af vand.
English: OTHER SPECIAL WARNING(S), IF NECESSARY Cytotoxic, special handling instructions (see package leaflet).
Danish: Cytotoksisk, særlig instruktion (se indlægsseddel).
English: How Topotecan Actavis is prepared
Danish: Hvordan Topotecan Actavis er tilberedt
English: 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.
Danish: Som for andre cytostatika kan topotecan forårsage fosterskader, hvorfor kvinder i den fertile alder bør tilrådes at undgå graviditet, hvis de er i behandling med topotecan.
English: The unadjusted hazard ratio for oral topotecan plus BSC group relative to BSC alone group was 0.64 (95 % CI: 0.45, 0.90).
Danish: 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).
English: Each vial contains 0.52 mg (0.0225 mmol) sodium.
Danish: Hvert hætteglas indeholder 0,52 mg natrium (0,0225 mmol).
English: Hafnarfjörður
Danish: Hafnarfjordur
English: Topotecan does not inhibit human P450 enzymes (see section 5.2).
Danish: Topotecan hæmmer ikke humane CYP-enzymer (se pkt.
English: This should be taken into account, when prescribing topotecan e.g. in case patients at increased risk of tumour bleeds are considered for therapy.
Danish: Dette skal der tages hensyn til, når Topotecan ordineres f.eks. til patienter med øget risiko for tumorblødning.
English: Rarely, it can lead to more severe bleeding (haemorrhage).
Danish: I sjældne tilfælde kan det resultere i mere alvorlig blødning.
English: Adequate care and precautions should be taken in the disposal of items (syringes, needles etc) used to reconstitute and/or dilute cytotoxic medicinal products.
Danish: Tilstrækkelig beskyttelse og forsigtighed skal udvises ved håndtering af alle genstande (hætteglas, nåle etc.) som bruges ved rekonstituering og fortynding af cytotoksiske lægemidler.
English: 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).
Danish: På baggrund af den toksiske grænseværdi for myelosuppression blev den maximalt tolererede dosis (MTD) fastsat til 2,0 mg/m2/dag med G-CSF og 1,4 mg/m2/dag uden GCSF i et farmakokinetisk studie af børn med refraktære solide tumorer (se pkt.
English: Topotecan Actavis is for intravenous infusion after reconstitution and dilution.
Danish: Topotecan Actavis er til til intravenøs infusion efter rekonstituion og fortynding.
English: Reconstitution and dilution of the medicinal product must be performed by trained personnel.
Danish: Rekonstitution og fortynding af lægemidlet må kun foretages af oplært personale.
English: Any unused product or waste material should be disposed of in accordance with local requirements.
Danish: Eventuelt ubrugt lægemiddel eller affaldsmateriale skal håndteres i henhold til lokale retningslinier.
English: 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).
Danish: 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).
English: 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/m given as a
Danish: I et ikke blindet studie af børn (n = 108; aldersgruppe: børn op til 16 år) med recidiverende eller progredierende solide tumorer, blev topotecan administreret med en startdosis på 2,0 mg/m2 som intravenøs infusion over 30 minutter i 5 dage.
English: What you need to know before you use Topotecan Actavis
Danish: Det skal du vide, før du får Topotecan Actavis
English: Initial dose The recommended dose of topotecan is 0.75 mg/m2/day administered as 30 minute intravenous infusion daily on days 1, 2 and 3.
Danish: Første dosis Den anbefalede dosis af topotecan er 0,75 mg/m2 legemsoverflade/dag administreret som intravenøs infusion over 30 minutter på dag 1, 2 og 3.
English: The clear concentrate is pale yellow in colour and provides 1 mg per ml of topotecan, as Topotecan Actavis 1 mg contains a 10 % overage of fill.
Danish: Det klare koncentrat, hvis farve er lys gul, giver 1 mg/ml topotecan, da Topotecan Actavis 1 mg indeholder et overskud på 10 %.
English: Combination therapy (Cervical carcinoma)
Danish: Kombinationsterapi (cervixcancer):
English: Precautions should be taken to avoid the medicinal product accidentally coming into contact with the eyes.
Danish: Der skal udvises forsigtighed for at undgå at medikamentet ved et uheld kommer i kontakt med øjnene.
English: For storage conditions of the reconstituted and diluted medicinal product, see section 6.3.
Danish: For information om opbevaringsforhold for det rekonstituerede og fortyndede lægemiddel, se pkt.
English: This medicinal product contains less than 1 mmol sodium (23 mg) per vial, i.e. essentially ‘sodiumfree'.
Danish: Dette lægemiddel indeholder mindre end 1 mmol natrium (23 mg) pr. hætteglas, d.v.s. det er hovedsagligt ”natriumfri”.
English: In an intravenous population study, the coadministration of granisetron, ondansetron, morphine or corticosteroids did not appear to have a significant effect on the pharmacokinetics of total topotecan (active and inactive form).
Danish: I en intravenøs populationsundersøgelse synes samtidig administration af granisetron, ondansetron, morphin eller kortikosteroider ikke at have nogen, signifikant indvirkning på farmakokinetikken af totaltopotecan (aktiv og inaktiv form).
English: Topotecan monotherapy and topotecan in combination with cisplatin are commonly associated with clinically relevant thrombocytopenia.
Danish: Topotecan monoterapi og topotecan i kombination med cisplatin, er i almindelighed associeret med klinisk relevant trombocytopeni.
English: The observed signs and symptoms for overdose were consistent with the known undesirable events associated with topotecan (see section 4.8).
Danish: De observerede tegn og symptomer på overdosering var i overensstemmelse med de kendte bivirkninger forbundet med topotecan (se pkt.
English: The cellular sequela of inhibition of topoisomerase-I by topotecan is the induction of protein-associated DNA single-strand breaks.
Danish: Den cellulære følge af den af topotecan forårsagede hæmning af topoisomerase-1 er fremkaldelse af proteinassocierede enkelstrengsbrud på DNA.
English: Patients with impaired kidney function Your doctor might need to reduce your dose based on your kidney function.
Danish: Pantienter med nedsat nyrefunktion Afhængigt af din nyrefunktion vil læge eventuelt nedsætte din dosis.
English: 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.
Danish: 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.
English: - Feeling sick (nausea), vomiting; diarrhoea; stomach pain; constipation.
Danish: - Utilpashed (kvalme), opkastning, diaré, mavesmerter, forstoppelse.
English: Median (95 % C.I.)
Danish: Median (95 % CI)
English: Reykjavíkurvegi 76-78
Danish: Reykjavikurvegi 76-78 Hafnarfjordur Island
English: 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.
Danish: Ved administration af topotecan (0,75 mg/m2 legemsoverflade/dag i 5 sammenhængende dage) og cisplatin (60 mg/m2 legemsoverflade/dag på dag 1) til 13 patienter med ovariecancer, blev en svag stigning set i AUC (12 %, n = 9) og Cmax (23 %, n = 11) på dag 5.
English: You must not breast-feed while on treatment with Topotecan Actavis.
Danish: Du må ikke amme under behandlingen med Topotecan Actavis.
English: The concentrates tested were stored at 25 ± 2°C for 12 hours and 24 hours respectively after reconstitution, and then diluted.
Danish: De testede opløsninger blev opbevaret i henholdsvis 12 timer og 24 timer ved 25 ± 2° C efter rekonstitution og derefter fortyndet.
English: 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.
Danish: 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 %).
English: MARKETING AUTHORISATION NUMBER(S) EU/1/09/536/001
Danish: MARKEDSFØRINGSTILLADELSESNUMMER (NUMRE) EU/1/09/536/001
English: Skin and subcutaneous tissue disorders Very common:
Danish: Hud og subkutane væv Meget almindelig: alopeci Almindelig:
English: MARKETING AUTHORISATION NUMBER(S) EU/1/09/536/002
Danish: MARKEDSFØRINGSTILLADELSESNUMMER (NUMRE) EU/1/09/536/002
English: Actavis Deutschland GmbH & Co. KG Telefon: +49 (0)89 558909 0
Danish: KG Telefon: +49 (0)89 558909 0
English: As with all cytotoxic chemotherapy, effective contraceptive methods must be advised when either partner is treated with topotecan.
Danish: Som for andre cytostatika tilrådes effektive præventionsmetoder s, når den ene partner er i behandling med topotecan.
English: A small number of hepatically impaired patients (serum bilirubin between 1.5 and 10 mg/dl) were given intravenous topotecan at 1.5 mg/m for five days every three weeks.
Danish: Et lille antal patienter med nedsat leverfunktion (serumbilirubin mellem 1,5 og 10 mg/dl) fik 1,5 mg/m2 intravenøst i fem dage hver tredje uge.
English: anorexia (which may be severe) Respiratory, thoracic and mediastinal disorders Rare:
Danish: Meget almindelig: appetitmangel ( kan være alvorlig) Luftveje, thorax og mediastinum Sjælden:
English: Mannitol (E421) Tartaric acid (E334) Sodium hydroxide Hydrochloric acid (E507)
Danish: Mannitol (E421) Vinsyre (E334) Natriumhydroxid Saltsyre (E507)
English: Topotecan Actavis 1 mg vials must be reconstituted with 1.1 ml water for injections.
Danish: Topotecan Actavis 1 mg hætteglas skal opløses med 1,1 ml vand til injektionsvæsker.
English: febrile neutropenia neutropenia (see Gastrointestinal disorders below) thrombocytopenia anaemia leukopenia
Danish: Meget almindelig: febril neutropeni neutropeni (se mave-tarm-kanalen nedenfor) trombocytopeni anæmi leukopeni
English: 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.
Danish: For de patienter (n = 102) med recidiv efter 180 dage, var medianoverlevelse i gruppen, der fik topotecan + cisplatin 9,9 mdr.
English: METHOD OF ADMINISTRATION Read the package leaflet before use.
Danish: Læs pakningens indlægsseddel inden brug.
English: Actavis treatment is combined with medicines containing cisplatin.
Danish: I sådanne tilfælde er behandling med Topotecan Actavis kombineret med medicin, der indeholder cisplatin.
English: Initial dose The recommended dose of topotecan is 1.5 mg/m body surface area/day administered by intravenous infusion over 30 minutes daily for five consecutive days with a three week interval between the start of each course.
Danish: Første dosis Den anbefalede dosis af topotecan er 1,5 mg/m2 legemsoverflade/dag administreret som intravenøs infusion over 30 minutter hver dag fem dage i træk, med et interval på tre uger mellem påbegyndelse af behandling.
English: - Infections (very common; may affect more than 1 in 10 people), with signs such as: - fever - serious decline of your general condition - local symptoms, such as sore throat or burning sensation when urinating - severe stomach pain, fever and possibly diarrhoea (rarely with blood) can be signs of bowel inflammation (neutropenic colitis) Topotecan Actavis may reduce your ability to fight infections.
Danish: - alvorlig forværring af din generelle tilstand - lokale symptomer såsom halssmerter eller en brændende følelse, når du tisser - stærke mavesmerter, feber og muligvis diare (i sjældne tilfælde blodig) kan være tegn på tyktarmsbetændelse (neutropenisk colitis).
English: Type I colourless glass vial (8 ml), with grey bromobutylic stopper and aluminium seal with plastic flip-off cap containing 4 mg topotecan.
Danish: Type I farveløst hætteglas (8 ml), med grå brombutylprop og aluminiumsforsegling med plastik flipoff låg indeholdende 4 mg topotecan.
English: Topotecan is supplied as a powder for concentrate for solution for infusion.
Danish: Topotecan leveres som pulver til koncentrat til opløsning før infusion.
English: DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorisation: 24 July 2009
Danish: DATO FOR FØRSTE MAKEDSFØRINGSTILLADELSE/FORNYELSE AF
English: 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.
Danish: Bivirkningsprofilen fra kliniske studier af topotecan, givet i kombination med cisplatin mod cervixcancer, er i overensstemmelse med hvad der er set ved monoterapi med topotecan.
English: Topotecan Actavis is available in cartons containing 1 vial and 5 vials.
Danish: Topotecan Actavis fås i pakninger med 1 hætteglas og 5 hætteglas.
English: Chemical and physical stability of the concentrate has been demonstrated for 24 hours at 25 ± 2°C, in normal light conditions and 24 hours at 2°C to 8°C, protected from light.
Danish: Den fysiske og kemiske stabilitet af koncentratet er påvist i 24 timer ved 25 ± 2° C, under normale lysforhold og i 24 timer ved 2° C til 8° C beskyttet mod lys.
English: Packs:
Danish: Pakninger:
English: For cervical cancer, it will be used together with another anticancer medicines containing cisplatin.
Danish: Ved behandling af livmoderhalskræft gives Topotecan Actavis sammen med et andet lægemiddel mod cancer, der indeholder cisplatin.
English: After reconstitution, 1 ml concentrate contains 1 mg topotecan.
Danish: Efter rekonstituering: 1 ml koncentrat indeholder 1 mg topotecan.
English: Type I colourless glass vial (5 ml) with grey bromobutylic stopper and aluminium seal with plastic flip-off cap containing 1 mg topotecan.
Danish: Type I farveløst hætteglas (5 ml) med grå brombutylprop og aluminiumsforsegling med plastik flip-off låg indeholdende 1 mg topotecan.