natgillin/translations-raw huggingface dataset:
Kombination med anastrozol, letrozol og tamoxifen Der er blevet udført et klinisk studie til vurdering af kombinationen af olaparib og anastrozol, letrozol eller tamoxifen.
Combination with anastrozole, letrozole and tamoxifen A clinical study has been performed to assess the combination of olaparib with anastrozole, letrozole or tamoxifen.
Data, der viser klinisk validering af tumor BRCA1/2-test i brystcancer, er ikke tilgængelige på nuværende tidspunkt.
Data demonstrating clinical validation of tumour BRCA1/2 tests in breast cancer are not currently available.
Der er begrænsede data for patienter med somatiske BRCA-muterede tumorer; 10 patienter i olaparib-armen og 10 patienter i placebo-armen blev defineret som at have somatisk BRCA1/2-mutation.
There are limited data in patients with somatic BRCA mutated tumours; 10 patients in the olaparib arm and 10 patients in the placebo arm were defined as having somatic BRCA1/2 mutation.
Det anbefales også at undlade at indtage grapefrugtjuice under behandling med Lynparza, da det er en CYP3A-inhibitor.
It is also not recommended to consume grapefruit juice while on Lynparza therapy as it is a CYP3A inhibitor.
gBRCA1/2-muteret HER2-negativ metastatisk brystcancer OlympiAD (Studie D0819C00003)
gBRCA1/2-mutated HER2-negative metastatic breast cancer OlympiAD (Study D0819C00003)
• træthed eller svaghed
• feeling tired or weak
Ikke almindelig Stigning i blodkreatinin
Uncommon Increase in blood creatinine
• anden medicin mod kræft
• any other anticancer medicines
Lynparzas sikkerhed og virkning hos børn og unge er ikke klarlagt.
The safety and efficacy of Lynparza in children and adolescents has not been established.
Ikke almindelig Hypersensitivitet a, dermatitis
Uncommon Hypersensitivity a, Dermatitis
Derfor anbefales det, at patienterne tager Lynparza mindst 1 time efter fødevarer og ikke bør spise i fortrinsvis op til 2 timer derefter (se pkt.
Therefore, it is recommended that patients take Lynparza at least one hour after food, and refrain from eating preferably for up to 2 hours afterwards (see section 4.2).
Skift ikke til Lynparza tabletter, medmindre din læge fortæller dig det
Do not switch to Lynparza tablets unless your doctor tells you
De sekundære endepunkter TFST og PFS2 viste en vedvarende og statistisk signifikant forbedring for olaparib sammenlignet med placebo (Tabel 4).
The secondary endpoints TFST and PFS2 demonstrated a persistent and statistically significant improvement for olaparib compared with placebo (Table 4).
Op til 20, 37 og 20 metabolitter blev detekteret i henholdsvis plasma, urin og fæces, hvoraf størstedelen af dem repræsenterede < 1 % af det doserede materiale.
Up to 20, 37 and 20 metabolites were detected in plasma, urine and faeces respectively, the majority of them representing <1% of the dosed material.
Bivirkningerne er opstillet efter MedDRA-systemorganklasse (SOC) og derefter efter den foretrukne MedDRA-term i Tabel 1.
Adverse drug reactions are listed by MedDRA System Organ Class (SOC) and then by MedDRA preferred term in Table 1.
Der blev ikke observeret nogen signifikant interaktion med anastrozol eller letrozol, hvorimod tamoxifen reducerede eksponeringen for olaparib med 27 %.
No significant interaction was observed with anastrozole or letrozole, whereas tamoxifen decreased exposure to olaparib by 27%.
De begrænsede data for disse somatisk tumor-BRCA (sBRCA)-muterede patienter viser, at færre patienter på olaparib rapporterede progressionshændelser eller dødsfald sammenlignet med placebo (Tabel 3).
The limited data for these somatic tumour BRCA (sBRCA) mutated patients show that fewer patients on olaparib reported progression events or death events compared with placebo (Table 3).
Via central germline-test blev der identificeret risikogivende eller formodet risikogivende mutationer hos henholdsvis 95,3 % (365/383) og 4,7 % (18/383) af patienterne.
By central germline testing, deleterious or suspected deleterious mutations were identified in 95.3% (365/383) and 4.7% (18/383) of patients, respectively.
Det er ukendt, om olaparib eller dets metabolitter udskilles i human mælk.
It is unknown whether olaparib or its metabolites are excreted in human milk.
I cancertyper, der mangler de funktionelle komponenter af HRR såsom BRCA1 eller 2, kan DNADSB'er ikke repareres nøjagtigt eller effektivt.
In cancers that lack functional components of HRR such as BRCA1 or 2, DNA DSBs cannot be repaired accurately or effectively.
Andelen af patienter, som progredierede inden for 6 måneder efter den sidste dosis af platinbaseret kemoterapi, var 3,5 % for olaparib og 8,4 % for placebo.
The proportion of patients who progressed within 6 months of the last dose of platinum-based chemotherapy was 3.5% for olaparib and 8.4% for placebo.
• dabigatran - anvendes til at fortynde blodet
• dabigatran - used to thin the blood
PARP'er er nødvendige for effektiv reparation af enkeltstrengsbrud på DNA, og et vigtigt aspekt af PARP-induceret reparation kræver, at PARP, efter kromatinmodificering, automodificerer sig selv og skiller sig fra DNA'et for at lette adgang for baseexcisionsreparationsenzymer (BER).
PARPs are required for the efficient repair of DNA single strand breaks and an important aspect of PARP-induced repair requires that after chromatin modification, PARP auto-modifies itself and dissociates from the DNA to facilitate access for base excision repair (BER) enzymes.
Retrospektiv test af patienter med tilgængelige tumorprøver blev udført under anvendelse af en central test og genererede vellykkede resultater hos 341 patienter, hvoraf 95 % havde en egnet mutation (kendt [n=47] eller sandsynligvis patogen [n=277]) og 2 gBRCAwt-patienterne blev bekræftet kun at have sBRCAm.
Retrospective testing of patients with available tumour samples was performed using central testing and generated successful results in 341 patients, of which 95% had an eligible mutation (known [n=47] or likely pathogenic [n=277]) and 2 gBRCAwt patients were confirmed to have sBRCAm only.
På grund af indvirkningen af fødevarer på absorptionen af olaparib bør patienterne tage Lynparza mindst 1 time efter indtagelse af fødevarer og undlade at spise i op til 2 timer derefter.
Due to the effect of food on olaparib absorption, patients should take Lynparza at least one hour after food, and refrain from eating preferably for up to 2 hours afterwards.
Patienterne blev stratificeret efter respons på platinbaseret førstelinjekemoterapi; komplet respons (CR) eller delvist respons (PR).
Patients were stratified by response to first-line platinum chemotherapy; complete response (CR) or partial response (PR).
Alle patienterne havde potentielle bidragende faktorer for udvikling af MDS/AML, idet de tidligere havde fået platinholdig kemoterapi.
All patients had potential contributing factors for the development of MDS/AML, having received previous chemotherapy with platinum agents.
Din læge har udskrevet Lynparza filmovertrukne tabletter til dig.
Your doctor has prescribed Lynparza film-coated tablets for you.
• proteaseinhibitorer boostet med ritonavir eller cobicistat, boceprevir, telaprevir, nevirapin,
• protease inhibitors boosted with ritonavir or cobicistat, boceprevir, telaprevir, nevirapine,
Rapporterne om pneumonitis havde intet konsistent klinisk mønster og blev påvirket af en række prædisponerende faktorer (cancer og/eller metastaser i lungerne, underliggende pulmonær sygdom, tidligere rygning og/eller tidligere kemoterapi og strålebehandling).
Reports of pneumonitis had no consistent clinical pattern and were confounded by a number of pre-disposing factors (cancer and/or metastases in lungs, underlying pulmonary disease, smoking history, and/or previous chemotherapy and radiotherapy).
Lynparza kan påvirke din evne til at føre motorkøretøj og betjene maskiner.
Lynparza may influence your ability to drive and use machines.
• hvis du er allergisk over for olaparib eller et af de øvrige indholdsstoffer i dette lægemiddel
• if you are allergic to olaparib or any of the other ingredients of this medicine (listed in section 6)
Olaparib er en type kræftmedicin, der kaldes en PARP-inhibitor (poly [adenosindifosfatribose]polymerase inhibitor).
Olaparib is a type of cancer medicine called a PARP inhibitor (poly [adenosine diphosphate-ribose] polymerase inhibitor).
CYP3A4/5 er de isozymer, der hovedsageligt er ansvarlige for den metaboliske clearance af olaparib.
CYP3A4/5 are the isozymes predominantly responsible for the metabolic clearance of olaparib.
Hvis du har glemt at tage Lynparza
If you forget to take Lynparza
• rifampicin, rifapentin, rifabutin - anvendes mod bakterieinfektioner, herunder tuberkulose (TB)
• rifampicin, rifapentine, rifabutin - used for bacterial infections, including tuberculosis (TB)
Hvis blodparametrene forbliver klinisk unormale efter 4 ugers afbrydelse af behandling med Lynparza, anbefales analyse af knoglemarv og/eller cytogenetisk analyse af blodet.
If the blood parameters remain clinically abnormal after 4 weeks of Lynparza dose interruption, bone marrow analysis and/or blood cytogenetic analysis are recommended.
Når der blev givet doser oralt til rotter, inducerede olaparib mikronuclei i knoglemarven.
When dosed orally to rats, olaparib induced micronuclei in bone marrow.
Påvirkning fra andre lægemidler på olaparib
Effect of other medicinal products on olaparib
Det kan heller ikke udelukkes, at olaparib potentielt kan inducere CYP2C9, CYP2C19 og P-gp.
The potential for olaparib to induce CYP2C9, CYP2C19 and P-gp can also not be excluded.
Nogle af patienterne havde en historik med cancer eller knoglemarvsdysplasi.
Some of the patients had a history of previous cancer or of bone marrow dysplasia.
Kvalme medførte dosisafbrydelse og dosisreduktion hos henholdsvis 14 % og 4 % af de olaparibbehandlede patienter.
Nausea events led to dose interruption and dose reductions in 14% and 4%, respectively, of olaparib-treated patients.
Patienterne blev randomiseret til studiet gennemsnitligt 40 dage efter at have fuldført deres sidste platinkemoterapi.
Patients were randomised into the study a median of 40 days after completing their final platinum chemotherapy.
Der blev også udført eksplorative analyser af tiden til første efterfølgende behandling eller død (TFST) og tiden til anden efterfølgende behandling eller død (TSST- en tilnærmelse af PFS2).
Exploratory analyses of time to first subsequent therapy or death (TFST) and time to second subsequent therapy or death (TSST- an approximation of PFS2) were also performed.
Der er ingen data for patienter med svært nedsat leverfunktion (Child-Pugh klassifikation C).
There are no data in patients with severe hepatic impairment (Child-Pugh classification C).
Dosisafbrydelserne og -reduktionerne forekom hyppigst i de første 3 måneder af behandlingen.
Dose interruptions and reductions occurred most frequently in the first 3 months of treatment.
Den mest almindelige histologiske type var serøs (> 90 %), endometrioid histologi blev rapporteret hos 6 % af patienterne.
The most common histological type was serous (> 90%), endometrioid histology was reported in 6% of the patients.
Patienterne skulle have fået behandling med et antracyklin, medmindre det var kontraindiceret, og et taxan i enten (neo)adjuverende eller metastatisk regi.
Patients must have received treatment with an anthracycline unless contraindicated and a taxane in either a (neo)adjuvant or metastatic setting.
Patienterne blev stratificeret baseret på: modtagelse af tidligere kemoterapibehandlinger for metastatisk brystcancer (ja/nej), hormonreceptor (HR) positiv versus tripel negativ (TNBC), tidligere platinbehandling mod brystcancer (ja/nej).
Patients were stratified based on: receipt of prior chemotherapy regimens for metastatic breast cancer (yes/no), hormone receptor (HR) positive vs triple negative (TNBC), prior platinum treatment for breast cancer (yes/no).
Af de patienter, der blev behandlet med Lynparza, som deltog i studiet med tegn på sygdom (mål- eller ikke-mål-læsioner ved baseline), oplevede 15,0 % fuldt respons sammenlignet med 9,1 % af patienterne på placebo.
Of patients treated with Lynparza, who entered the study with evidence of disease (target or non-target lesions at baseline), 15.0% experienced complete response compared with 9.1% of patients on placebo.
Det anbefales, at behandlingen fortsættes indtil progression af den underliggende sygdom eller uacceptabel toksicitet.
It is recommended that treatment be continued until progression of the underlying disease or unacceptable toxicity.
Opkastning, diarré, kvalme, dyspepsi, øvre abdominalsmerter
Vomiting, Diarrhoea, Nausea, Dyspepsia, Upper abdominal pain
Alle patienterne havde modtaget platinbaseret førstelinjebehandling.
All patients had received first-line platinum-based therapy.
Patienter med HR+ (ER og/eller PgR-positive) tumorer skulle have modtaget og have haft sygdomsprogression efter mindst en endokrin behandling (adjuverende eller metastatisk) eller skulle have sygdom, som den behandlende læge mente var uegnet til endokrin behandling.
Patients with HR+ (ER and/or PgR positive) tumours must have received and progressed on at least one endocrine therapy (adjuvant or metastatic) or had disease that the treating physician believed to be inappropriate for endocrine therapy.
Der blev også observeret en fordel hos patienter med BRCA1/2-vildtype/varianter af usikker betydning (BRCA1/2 wt/VUS), selvom dette var af mindre størrelsesorden.
A benefit was also observed in patients with BRCA1/2 wild-type/variants of uncertain significance (BRCA1/2 wt/VUS), although of a lesser magnitude.
Olaparib hæmmede UGT1A1 in vitro, men PBPK-simulationer tyder på, at dette ikke er af klinisk betydning.
Olaparib inhibited UGT1A1 in vitro, however, PBPK simulations suggest this is not of clinical importance.
gBRCA1/2-mutationsstatus skal fastslås af et erfarent laboratorium ved hjælp af en valideret testmetode.
gBRCA1/2 mutation status should be determined by an experienced laboratory using a validated test method.
Patienter med hormonreceptor (HR)-positiv brystcancer bør også have haft progression på eller efter tidligere endokrin behandling eller anses for værende uegnede til endokrin behandling.
Patients with hormone receptor (HR)-positive breast cancer should also have progressed on or after prior endocrine therapy, or be considered unsuitable for endocrine therapy.
Din læge har udskrevet Lynparza kapsler til dig.
Your doctor has prescribed Lynparza capsules for you.
• Det vides ikke, om Lynparza går over i modermælken.
• It is not known whether Lynparza passes into breast milk.
Der er ikke noget krav om BRCA1/2-test før anvendelse af Lynparza til vedligeholdelsesbehandling af recidiverende EOC, FTC eller PPC til patienter, som udviser helt eller delvist respons på platinbaseret behandling.
There is no requirement for BRCA1/2 testing prior to using Lynparza for the maintenance treatment of relapsed EOC, FTC or PPC who are in a complete or partial response to platinum-based therapy.
Studier med humane knoglemarvsceller viste også, at direkte eksponering for olaparib kan medføre toksicitet overfor knoglemarvsceller i ex vivo-analyser.
Studies using human bone marrow cells also showed that direct exposure to olaparib can result in toxicity to bone marrow cells in ex vivo assays.
Behandlingen fortsatte indtil radiologisk progression af den underliggende sygdom, uacceptabel toksicitet eller i op til 2 år.
Treatment was continued until radiological progression of the underlying disease, unacceptable toxicity or for up to 2 years.
• lavt antal hvide blodlegemer (lymfopeni), som kan nedsætte din evne til at bekæmpe infektioner, og som kan være forbundet med feber
• low white blood cell count (lymphopenia) which may decrease your ability to fight infection and may be associated with fever
I et fertilitetsstudie med hunrotter fik rotterne doser indtil implantation, og selvom der blev observeret forlænget østral periode hos nogle dyr, sås der ingen påvirkning af parringsaktivitet og drægtighedsrate.
In a female fertility study where rats were dosed until implantation, although extended oestrus was observed in some animals, mating performance and pregnancy rate was not affected.
Dosisafbrydelserne forekom hyppigst i de første 3 måneder, og dosisreduktionerne i de første 3-6 måneder af behandlingen.
Dose interruptions occurred most frequently in the first 3 months and dose reductions in the first 3-6 months of treatment.
Den mest almindelige histologiske type var serøs (96 %), og endometrioid histologi blev rapporteret hos 2 % af patienterne.
The most common histological type was serous (96%), endometrioid histology was reported in 2% of the patients.
• Lægen vil fortælle dig, hvor mange tabletter Lynparza, du skal tage.
• Your doctor will tell you how many tablets of Lynparza to take.
Patienter, som tager Lynparza, kan opleve træthed, asteni eller svimmelhed.
Patients who take Lynparza may experience fatigue, asthenia or dizziness.
Anæmi og anden hæmatologisk toksicitet var generelt af lav grad (CTCAE grad 1 eller 2), men der var rapporter om CTCAE grad 3 og højere forekomster.
Anaemia and other haematological toxicities were generally low grade (CTCAE grade 1 or 2), however, there were reports of CTCAE grade 3 and higher events.
En piperazin-3-ol-del med åben ring og to monooxygenerede metabolitter (hver ~10 %) var de største cirkulerende dele, hvor den ene monooxygenerede metabolit også var den største metabolit i ekskretet (henholdsvis 6 % og 5 % af radioaktiviteten i urinen og fæces).
A ring-opened piperazin-3-ol moiety, and two mono-oxygenated metabolites (each ~10%) were the major circulating components, with one of the mono-oxygenated metabolites also being the major metabolite in the excreta (6% and 5% of the urinary and faecal radioactivity, respectively).
Deltagelse krævede ikke bevis for BRCA1/2-mutation (BRCA-mutationsstatus blev for nogle patienter bestemt retrospektivt).
Enrolment did not require evidence of BRCA1/2 mutation (BRCA mutation status for some patients was determined retrospectively).
• telithromycin, clarithromycin, erythromycin - anvendes til bakterieinfektioner
• telithromycin, clarithromycin, erythromycin - used for bacterial infections
Antal tidligere kemoterapilinjer mod metastatisk brystcancer (%)
Missing Number of prior lines of chemotherapy for metastatic breast cancer (%)
35 % af patienterne havde interval debulking kirurgi, og af disse rapporterede 82 % ingen makroskopisk residualsygdom.
Interval debulking surgery was performed in 35% of the patients and of these 82% had no macroscopic residual disease reported.
Brug af Lynparza sammen med drikke
Lynparza with drink
Som efterfølgende behandling, modtog 0,5 % og 8 % af patienterne en PARP-inhibitor i henholdsvis behandlings- og komparator-armene; henholdsvis 29 % og 42 % af patienterne fik efterfølgende platinbehandling.
As subsequent therapy, 0.5% and 8% of patients received a PARP inhibitor in the treatment and comparator arms, respectively; 29% and 42% of patients, respectively, received subsequent platinum therapy.
Der er blevet vist induktion af CYP1A2, CYP2B6 og CYP3A4 in vitro, hvor CYP2B6 er den, der mest sandsynligt induceres i klinisk relevant omfang.
Induction of CYP1A2, 2B6 and 3A4 has been shown in vitro with CYP2B6 being most likely to be induced to a clinically relevant extent.
• Doserne i Lynparza kapsler og tabletter er ikke de samme.
• The doses of Lynparza capsules and tablets are not the same.
Kemoterapi (N = 97) Olaparib 300 mg to gange dagligt (N = 205)
Chemotherapy (N = 97) Olaparib 300 mg twice daily (N = 205)
Meget almindelig Hoste a, dyspnø
Very common Cough a, Dyspnoea
63 % af patienterne havde primær debulking kirurgi, og af disse havde størstedelen (75 %) ingen makroskopisk residualsygdom.
Sixty-three percent (63%) of the patients had upfront debulking surgery and of these the majority (75%) had no macroscopic residual disease.
Der blev ikke observeret nogen statistisk signifikante forskelle mellem olaparib og placebo blandt patientrapporterede symptomer eller helbredsrelateret livskvalitet som målt ved forbedrings- og forværringsrater i FACT/NCCN Ovarian Symptom Index (FOSI), Trial Outcome Index (TOI) og Functional Analysis of Cancer Therapy-Ovarian total score (FACT-O total).
No statistically significant differences were observed between olaparib and placebo in patient reported symptoms or HRQoL as measured by improvement and worsening rates in the FACT/NCCN Ovarian Symptom Index (FOSI), Trial Outcome Index (TOI) and Functional Analysis of Cancer TherapyOvarian total score (FACT-O total).
Lynparza kan, baseret på dets virkningsmekanisme (PARP-hæmning), forårsage føtal skade, når det administreres til en gravid kvinde.
Based on its mechanism of action (PARP inhibition), Lynparza could cause foetal harm when administered to a pregnant woman.
Antal patienter i risikogruppen Olaparib 300 mg tablet to gange dagligt
Number of patients at risk Olaparib 300 mg twice daily tablet
93 % af patienterne blev randomiseret inden for 8 uger af deres sidste dosis platinbaserede kemoterapi.
Ninety three percent (93%) of patients were randomised within 8 weeks of their last dose of platinum-based chemotherapy.
• Kapselindhold: lauroylmacrogol-32-glycerider.
• Capsule content: lauroyl macrogol-32 glycerides.
Patienterne skal tidligere have været i behandling med et antracyklin og et taxan til (neo)adjuverende eller metastatisk regi, medmindre patienterne ikke var egnede til disse behandlinger (se pkt.
Patients should have previously been treated with an anthracycline and a taxane in the (neo)adjuvant or metastatic setting unless patients were not suitable for these treatments (see section 5.1).
Der var 389 patienter med germline BRCA1/2m og 2 med somatisk BRCA1/2m i SOLO1.
There were 389 patients who were germline BRCA1/2m and 2 who were somatic BRCA1/2m in SOLO1.
Gentagen behandling med olaparib var ikke tilladt efter progression på olaparib.
Retreatment with olaparib was not permitted following progression on olaparib.
Der var ingen påvist sygdom ved indtræden i studiet (CR), defineret af investigator som intet radiologisk bevis på sygdom og cancerantigen 125 (CA-125) inden for det normale interval, hos 73 % og 77 % af patienterne i henholdsvis olaparib- og placeboarmene.
There was no evidence of disease at study entry (CR), defined by the investigator as no radiological evidence of disease and cancer antigen 125 (CA-125) within normal range, in 73% and 77% of patients in the olaparib and placebo arms, respectively.
Derfor kan Lynparza tages uden hensyntagen til fødevarer (se pkt.
Consequently, Lynparza may be taken without regard to food (see section 4.2).
OS-analyse hos patienter uden forudgående kemoterapi for metastatisk brystcancer indikerede fordele for disse patienter med en HR på 0,45 (95 % CI 0,27-0,77), mens for yderligere behandlingslinjer overskred HR 1.
OS analysis in patients with no prior chemotherapy for metastatic breast cancer indicated benefit in these patients with a HR of 0.45 (95% CI 0.27-0.77), while for further lines of therapy HR exceeded 1.
56 filmovertrukne tabletter (7 blisterkort).
56 film-coated tablets (7 blisters).
• allergiske reaktioner (fx nældefeber, vejrtrækningsbesvær eller synkebesvær, svimmelhed, som alle er tegn og symptomer på overfølsomhedsreaktioner).
• allergic reactions (e.g. hives, difficulty breathing or swallowing, dizziness which are signs and symptoms of hypersensitivity reactions).
Det anbefales at udføre passende klinisk monitorering af patienter, der får CYP3A-substrater med en snæver terapeutisk margin samtidig med olaparib.
Appropriate clinical monitoring is recommended for patients receiving CYP3A substrates with a narrow therapeutic margin concomitantly with olaparib.
I normale celler er homolog rekombinationsreparation (HRR), som kræver funktionelle BRCA1- og -2-gener, effektiv til at reparere disse DNA-DSB'er.
In normal cells, homologous recombination repair (HRR), which requires functional BRCA1 and 2 genes, is effective at repairing these DNA DSBs.
Der findes ingen dyrestudier om udskillelse af olaparib i modermælk.
There are no animal studies on the excretion of olaparib in breast milk.
Hos rotter blev der også bemærket minimale degenerative virkninger på mave-tarm-kanalen.
In rats, minimal degenerative effects on gastrointestinal tract were also noted.