natgillin/translations-raw huggingface dataset:
Syv mandlige patienter blev randomiseret (5 olaparib og 2 komparator).
Seven male patients were randomised (5 olaparib and 2 comparator).
Passende klinisk monitorering anbefales til patienter, der får denne type lægemiddel samtidig.
Appropriate clinical monitoring is recommended for patients receiving this type of medicinal product concomitantly.
gBRCAm-statussen af patienter, som blev inkluderet via lokal test, blev bekræftet retrospektivt via central test.
The gBRCAm status of patients enrolled via local testing was confirmed retrospectively by central testing.
(Se forrige afsnit ”Kvinder i den fertile alder/antikonception hos kvinder” for yderligere oplysninger om antikonception og graviditetsundersøgelser.)
(See previous paragraph: “Women of childbearing potential/contraception in females” for further information about birth control and pregnancy testing.)
Tag ikke Lynparza:
Do not take Lynparza:
Patienterne kunne tidligere have modtaget bevacizumab, undtagen i regimet umiddelbart inden randomisering.
Patients could have received prior bevacizumab, except in the regimen immediately prior to randomisation.
Metabolismen af olaparib er omfattende.
The metabolism of olaparib is extensive.
Inden for hver SOC er de foretrukne termer opstillet efter faldende hyppighed og derefter efter hvor alvorlige de er.
Within each SOC, preferred terms are arranged by decreasing frequency and then by decreasing seriousness.
Der bør især udvises forsigtighed, hvis olaparib administreres i kombination med statiner.
In particular, caution should be exercised if olaparib is administered in combination with any statin.
Lynparza tabletter kan tages uden hensyntagen til måltider.
Lynparza tablets may be taken without regard to meals.
Patienter med påvist sygdom efter 2 år, som efter den behandlende læges skøn kan få yderligere fordel af fortsat behandling, kan behandles ud over de 2 år.
Patients with evidence of disease at 2 years, who in the opinion of the treating physician can derive further benefit from continuous treatment, can be treated beyond 2 years.
Samlet sygdomsklassifikation Metastatisk
Overall disease classification Metastatic
Der er begrænset erfaring med overdosering af olaparib.
There is limited experience of overdose with olaparib.
Da det ikke kan udelukkes, at olaparib kan reducere eksponeringen af substrater for CYP2C9 via enzyminduktion, kan effektiviteten af nogle hormonelle antikonceptiva være nedsat ved samtidig administration af olaparib.
Since it cannot be excluded that olaparib may reduce exposure to substrates of CYP2C9 through enzyme induction, the efficacy of some hormonal contraceptives may be reduced if co-administered with olaparib.
Patienterne fik tumorvurdering ved baseline og hver 12. uge i 3 år og derefter hver 24. uge i forhold til randomiseringsdatoen, indtil objektiv radiologisk sygdomsprogression.
Patients had tumour assessments at baseline and every 12 weeks for 3 years, and then every 24 weeks relative to date of randomisation, until objective radiological disease progression.
PARP-inhibitorer kan ødelægge kræftceller, der ikke er gode til at reparere DNA-skader.
PARP inhibitors can destroy cancer cells that are not good at repairing DNA damage.
Andre særlige populationer Der er begrænsede sikkerhedsdata tilgængelige for ældre (alder  75 år) og ikke-kaukasiske patienter.
Other special populations Limited safety data are available in elderly (age  75 years) and non-Caucasian patients.
• fald i antallet af blodplader i blodet (trombocytopeni) - du kan få følgende symptomer:
• decrease in the number of platelets in blood (thrombocytopenia) - you may notice the following symptoms:
I toksicitetsstudier med gentagne doser af op til 6 måneders varighed med rotter og hunde var daglige orale doser af olaparib veltolererede.
In repeat-dose toxicity studies of up to 6 months duration in rats and dogs, daily oral doses of olaparib were well-tolerated.
hændelser/patienter
events/patients
Hvis du foretrækker det, kan du opbevare Lynparza kapsler udenfor køleskabet (under 30°C) i op til 3 måneder.
If preferred, you can keep Lynparza capsules out of the refrigerator (below 30°C) for up to 3 months.
Fortæl det til lægen, hvis du tager et hormonelt præventionsmiddel, da din læge kan anbefale at supplere med en ikke-hormonel beskyttelse mod graviditet.
Please tell your doctor if you are taking a hormonal contraceptive, as your doctor may recommend the addition of a non-hormonal contraceptive method.
• Du bør ikke tage Lynparza, hvis du er gravid eller måske bliver gravid.
• You should not take Lynparza if you are pregnant or might become pregnant.
Frekvens af CTCAE grad 3 og derover
Frequency of CTCAE grade 3 and above
Patienterne i olaparibgruppen fortsatte med at få behandling i længere tid end patienterne i placebogruppen.
Patients in the olaparib group continued to receive treatment longer than those in the placebo group.
Størstedelen af metabolismen skyldtes oxideringsreaktioner, hvor en række af de producerede komponenter gennemgik efterfølgende glucuronid- eller sulfatkonjugering.
The majority of the metabolism was attributable to oxidation reactions with a number of the components produced undergoing subsequent glucuronide or sulfate conjugation.
Se punkt 4 for mere information om disse bivirkninger, herunder tegn og symptomer, som du skal holde øje med (for eksempel feber eller infektion, blå mærker eller blødning).
See section 4 for more information about these side effects, including the signs and symptoms you need to look out for (for example, fever or infection, bruising or bleeding).
Kliniske undersøgelser af olaparib i kombination med andre anticancerlægemidler, herunder DNA-beskadigende lægemidler, indikerer en potensering og forlængelse af myelosuppressiv toksicitet.
Clinical studies of olaparib in combination with other anticancer medicinal products, including DNA damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.
Det er ikke nødvendigt at justere startdosis hos ældre patienter.
No adjustment in starting dose is required for elderly patients.
Karcinogenicitet Der er ikke udført karcinogenicitetsstudier med olaparib.
Carcinogenicity Carcinogenicity studies have not been conducted with olaparib.
Hvad Lynparza er, og hvordan det virker
What Lynparza is and how it works
Symptomerne på overdosering er ikke fastslået, og der findes ingen specifik behandling i tilfælde af overdosering med Lynparza.
Symptoms of overdose are not established and there is no specific treatment in the event of Lynparza overdose.
Frekvens af alle CTCAE grader
Frequency of All CTCAE grades
Der er ikke rapporteret nogen uventede bivirkninger blandt et lille antal patienter, som tog en daglig dosis på op til 900 mg olaparib tabletter over to dage.
No unexpected adverse reactions were reported in a small number of patients who took a daily dose of up to 900 mg of olaparib tablets over two days.
Du må helst ikke spise i op til 2 timer efter, du har taget Lynparza.
Do not eat preferably for up to 2 hours after taking Lynparza.
Du må ikke drikke grapefrugtjuice, mens du er i behandling med Lynparza.
Do not drink grapefruit juice while you are being treated with Lynparza.
Effektresultater er præsenteret i tabel 2 og figur 1 og 2.
Efficacy results are presented in Table 2 and Figures 1 and 2.
Det væsentligste primære målorgan for toksicitet for begge arter var knoglemarven med associerede forandringer i perifere hæmatologiske parametre.
The major primary target organ for toxicity in both species was the bone marrow, with associated changes in peripheral haematology parameters.
YDRE ÆSKE MULTIPAKNING - med blue box
OUTER CARTON MULTIPACK -including the blue box
Der er meget begrænsede data hos patienter med somatisk BRCA-mutation.
There are very limited data in patients with a somatic BRCA mutation.
En ikke fuldt funktionel HRR-mekanisme er en af de vigtigste determinanter for platinsensitivitet i ovariecancer og andre cancertyper.
Absence of fully functional HRR pathway is one of the key determinants of platinum sensitivity in ovarian and other cancers.
Tidligere behandling med antracyklin og taxan
Previous anthracycline and taxane treatment
• hvis du har lavt antal blodlegemer i en blodprøve.
• if you have low blood cell counts on testing.
Denne klastogenicitet er i overensstemmelse med den kendte farmakologi af olaparib og indikerer potentiale for genotoksicitet hos mennesker.
This clastogenicity is consistent with the known pharmacology of olaparib and indicates potential for genotoxicity in man.
Når olaparib bindes til det aktive site af DNA-associeret PARP, forhindrer det, at PARP dissocierer og indfanger det på DNA'et, hvorved der blokeres for reparation.
When olaparib is bound to the active site of DNA-associated PARP it prevents the dissociation of PARP and traps it on the DNA, thus blocking repair.
• du tager visse lægemidler, der kan påvirke Lynparza (se punkt 2).
• you are taking certain medicines that may affect Lynparza (see section 2).
Ingen tidligere behandling med en PARP-inhibitor, herunder olaparib, var tilladt.
No previous treatment with a PARP inhibitor, including olaparib, was permitted.
• en bestemt type brystkræft (BRCA-muteret, HER2-negativ), som har spredt sig ud over den oprindelige tumor.
• a certain type of breast cancer (BRCA-mutated, HER2-negative) which has spread beyond the original tumour.
Forekomsten af stigninger i middelcellevolumen fra lav eller normal ved baseline til over ULN var ca. 55 %.
The incidence of elevations in mean corpuscular volume from low or normal at baseline to above the ULN was approximately 55%.
Derfor bør det overvejes at anvende en yderligere ikke-hormonel antikonceptionsmetode under behandlingen (se pkt.
Therefore, an additional non-hormonal contraceptive method should be considered during treatment (see section 4.5).
Dette kan være lavt antal røde eller hvide blodlegemer eller lavt antal blodplader.
These may be low counts for red or white blood cells or low platelet counts.
Genetisk test skal udføres af et erfarent laboratorium ved hjælp af en valideret test.
Genetic testing should be conducted by an experienced laboratory using a validated test.
Et lille antal patienter, som blev behandlet med Lynparza, rapporterede om lungebetændelse (pneumonitis).
A small number of patients treated with Lynparza reported inflammation of the lungs (pneumonitis).
Lokalt fremskreden Ny metastatisk brystcancer (%) Hormonreceptorstatus (%) HR+
New metastatic breast cancer (%) Hormone receptor status (%) HR+
Kombinationen af olaparib og vacciner eller immunsuppressive lægemidler er ikke undersøgt.
Combination of olaparib with vaccines or immunosuppressant agents has not been studied.
Den kliniske forsøgsrapport skal indsendes senest:
The clinical study report should be submitted by:
C-olaparib blev ~86 % af den doserede radioaktivitet genfundet inden for en opsamlingsperiode på 7 dage, ~44 % via urinen og ~42 % via fæces.
C-olaparib, ~86% of the dosed radioactivity was recovered within a 7-day collection period, ~44% via the urine and ~42% via the faeces.
Skift ikke til Lynparza kapsler, medmindre din læge fortæller dig det
Do not switch to Lynparza capsules unless your doctor tells you
efavirenz - anvendes mod virusinfektioner, herunder hiv
efavirenz - used for viral infections, including HIV
Hvis du tager mere Lynparza end din normale dosis, skal du straks kontakte din læge eller det nærmeste hospital.
If you take more Lynparza than your normal dose, contact your doctor or nearest hospital straight away.
I opløsninger af rensede proteiner var olaparibfraktionen, der var bundet til albumin, ca. 56 %, som var uafhængig af olaparibkoncentrationerne.
In solutions of purified proteins, the olaparib fraction bound to albumin was approximately 56%, which was independent of olaparib concentrations.
Tests og undersøgelser Din læge vil undersøge dit blod inden og under behandlingen med Lynparza.
Tests and checks Your doctor will check your blood before and during treatment with Lynparza.
* (2-sidet)
* (2-sided)
90 % af patienterne havde kreatininværdier på CTCAE grad 0 ved baseline, og 10 % var CTCAE grad 1 ved baseline.
90% of patients had creatinine values of CTCAE grade 0 at baseline and 10% were CTCAE grade 1 at baseline.
For patienter, som forblev i komplet klinisk respons (dvs. uden radiologisk påvist sygdom), var den maksimale varighed 2 år, men patienter, hvor det var påvist, at sygdommen forblev stabil (dvs. uden påvist sygdomsprogression) kunne fortsætte med at få Lynparza ud over de 2 år.
For patients who remained in complete clinical response (i.e. no radiological evidence of disease), the maximum duration of treatment was 2 years; however, patients who had evidence of disease that remained stable (i.e. no evidence of disease progression) could continue to receive Lynparza beyond 2 years.
Påvirkning fra olaparib på andre lægemidler
Effect of olaparib on other medicinal products
Opkastning medførte afbrydelse hos 10 % af de olaparibbehandlede patienter; ingen olaparibbehandlede patienter oplevede opkastning, som medførte dosisreduktion.
Vomiting events led to interruption in 10% of olaparib-treated patients; no olaparib-treated patients experienced a vomiting event leading to dose reduction.
Incidensen af MDS/AML-tilfælde var sammenlignelig hos patienter med gBRCA1m og gBRCA2m (henholdsvis 1,7 % og 1,4 %).
The incidence of MDS/AML cases was similar among gBRCA1m and gBRCA2m patients (1.7% and 1.4%, respectively).
På tidspunktet for PFSanalysen havde 1 patient et bekræftet delvist respons med en responsvarighed på 9,7 måneder i olaparib-armen.
At the time of the PFS analysis, 1 patient had a confirmed partial response with a duration of response of 9.7 months in the olaparib arm.
Lynparza er til oral anvendelse.
Lynparza is for oral use.
Der er imidlertid ikke behov for dosisjustering på baggrund af etnicitet (se pkt.
However, no dose adjustment is required on the basis of ethnicity (see section 5.2).
Der var ingen strategi for multiple tests for subgruppeanalyserne eller for alle patienterne TFST.
There was no strategy for multiple testing in place for the sub-group analyses or for the all patients TFST.
Median opfølgningstid hos censurerede patienter var 25,3 måneder for olaparib versus 26,3 måneder for komparator.
The median follow-up time in censored patients was 25.3 months for olaparib versus 26.3 months for comparator.
En statistisk signifikant forbedring af PFS, det primære effektresultat, blev påvist for olaparibbehandlede patienter sammenlignet med patienterne i komparator-armen (se tabel 8 og figur 6).
A statistically significant improvement in PFS, the primary efficacy outcome, was demonstrated for olaparib-treated patients compared with those in the comparator arm (see Table 8 and Figure 6).
HDPE-plastikflaske med børnesikret lukning indeholdende 112 hårde kapsler.
HDPE plastic bottle with a child-resistant closure containing 112 hard capsules.
• Én dosis (8 kapsler) Lynparza synkes med vand, én gang om morgenen og én gang om aftenen.
• Take one dose (8 capsules) of Lynparza by mouth with water, once in the morning and once in the evening.
Olaparib udviste intet mutagent potentiale, men var klastogent i pattedyrsceller in vitro.
Olaparib showed no mutagenic potential, but was clastogenic in mammalian cells in vitro.
Den anbefalede Lynparza-monoterapidosis er ikke egnet til kombination med myelosuppressive anticancerlægemidler.
The recommended Lynparza monotherapy dose is not suitable for combination with myelosuppressive anticancer medicinal products.
I dyrestudier blev der ikke observeret nogen effekt på konception, men der er bivirkninger på embryoføtal overlevelse (se pkt.
In animal studies, no effect on conception was observed but there are adverse effects on embryofoetal survival (see section 5.3).
Det vides ikke, om Lynparza kan påvirke effekten af visse hormonelle præventionsmidler.
It is not known whether Lynparza may affect the effectiveness of some hormonal contraceptives.
Lynparza anvendes til behandling af:
Lynparza is used for the treatment of:
Både kvalme og opkastning blev rapporteret at være intermitterende for størstedelen af patienterne og kan håndteres ved afbrydelse af doseringen, dosisreduktion og/eller behandling med antiemetika.
Both nausea and vomiting were reported to be intermittent for the majority of patients and can be managed by dose interruption, dose reduction and/or antiemetic therapy.
Ved multipel dosering blev der observeret en AUC-akkumulationsratio på 1,8, og PK viste sig at være tidsafhængig i en lav grad.
On multiple dosing, an AUC accumulation ratio of 1.8 was observed and PK appeared to be time-dependent to a small extent.
Hos patienter med mutationer (forandringer) i visse gener, der kaldes BRCA (brystcancergen), som har risiko for at udvikle visse typer kræft, kan PARP-inhibitorer slå kræftcellerne ihjel ved at blokere et enzym, der er med til at reparere DNA.
In patients with mutations (changes) in certain genes called BRCA (breast cancer gene), who are at risk of developing some forms of cancer, PARP inhibitors are able to trigger the death of cancer cells by blocking an enzyme that helps repair DNA.
Derfor kan olaparib ved samtidig administration reducere eksponeringen for substrater for disse metaboliske enzymer og transportprotein.
Therefore, olaparib upon co-administration may reduce the exposure to substrates of these metabolic enzymes and transport protein.
• du har visse bivirkninger, mens du tager Lynparza (se punkt 4).
• you have certain side effects while you are taking Lynparza (see section 4).
Efter 2 år forblev 43 % olaparibbehandlede patienter progressionsfrie i sammenligning med kun 15 % placebobehandlede patienter.
At 2 years, 43% olaparib-treated patients remained progression free compared with only 15% placebo-treated patients.
Der blev observeret konsistente resultater i subgruppen af patienter mht. påvist sygdom ved indtræden i studiet.
Consistent results were observed in the subgroups of patients by evidence of the disease at study entry.
Lynparza bør udelukkende anvendes til patienter med svært nedsat nyrefunktion, hvis fordelene opvejer den potentielle risiko, og patienten bør overvåges omhyggeligt for nyrefunktion og bivirkninger.
Lynparza may only be used in patients with severe renal impairment if the benefit outweighs the potential risk, and the patient should be carefully monitored for renal function and adverse events.
Anæmi var den mest almindelige CTCAE grad ≥ 3 bivirkning, som blev rapporteret i kliniske studier.
Anaemia was the most common CTCAE grade ≥3 adverse reaction reported in clinical studies.
Der er påvist et eksponerings-respons-forhold mellem olaparib og fald i hæmoglobin.
An exposure-response relationship between olaparib and decreases in haemoglobin has been demonstrated.
Graviditet/antikonception
Pregnancy/contraception
Hvis du glemmer at tage Lynparza, skal du tage din næste normale dosis på det planlagte tidspunkt.
If you forget to take Lynparza, take your next normal dose at its scheduled time.
Stigning i blodkreatinin Ikke almindelig
Increase in blood creatinine Uncommon
Afhængig af den anvendte test samt international konsensus om klassifikation, er BRCA1/2-mutationerne blevet klassificeret som risikogivende/formodet risikogivende eller patogene/sandsynligvis patogene.
Depending on the test used and the international classification consensus, the BRCA1/2 mutations have been classified as deleterious/suspected deleterious or pathogenic/likely pathogenic.
Data fra et dobbeltblindet placebokontrolleret studie viste en middelstigning op til 23 % fra baseline, som forblev konsistent over tid og vendte tilbage til baseline efter seponering af behandlingen, tilsyneladende uden nogen kliniske følger.
Data from a double-blind placebo-controlled study showed median increase up to 23% from baseline remaining consistent over time and returning to baseline after treatment discontinuation, with no apparent clinical sequelae.
Pædiatrisk population Der er ikke udført nogen studier med pædiatriske patienter.
Paediatric population No studies have been conducted in paediatric patients.
Behandlingsvarigheden med olaparib til patienter, som udviklede MDS/AML, varierede fra < 6 måneder til > 2 år.
The duration of therapy with olaparib in patients who developed MDS/AML varied from < 6 months to > 2 years.
Derfor bør der udvises forsigtighed, hvis disse lægemidler administreres samtidigt med Lynparza, og patienterne bør følges nøje.
Therefore, caution should be taken if these medicinal products are co-administered with Lynparza and patients should be closely monitored.
Efter oral dosering af
Following oral dosing of
Forekomsten af bivirkningen anæmi var 22,8% (CTCAEgrad ≥ 3 7,4%).
The incidence of anaemia adverse reactions was 22.8% (CTCAE grade ≥3 7.4%).
Tabel 3 Resumé af progressionsfri overlevelse og samlet overlevelse: sBRCA-muteret population i Study 19
Table 3 Summary of progression-free survival and overall survival: sBRCA mutated population in Study 19
I fravær af BRCA1- eller BRCA2-mutationer kan HRR-stien kompromitteres via andre mekanismer, men den tilgrundliggende afvigelse og penetrans er ikke fuldt ud belyst.
In the absence of BRCA1 or BRCA2 mutations, HRR pathway may be compromised by other mechanisms, although the causative aberrancy and penetrance are not fully elucidated.
Behandlingsvarigheden med olaparib til patienter, som udviklede MDS/AML, varierede fra < 6 måneder til > 2 år; data med længere eksponeringvarighed er begrænsede.
The duration of therapy with olaparib in patients who developed MDS/AML varied from <6 months to >2 years; data with longer durations of exposure are limited.
Olaparib påvirker ikke tamoxifens farmakokinetik.
Olaparib does not affect the pharmacokinetics of tamoxifen.
Sikkerhedsprofilen er baseret på poolede data fra 1.826 patienter med solide tumorer, som blev behandlet med Lynparza-monoterapi i kliniske studier med den anbefalede dosis.
The safety profile is based on pooled data from 1,826 patients with solid tumours treated with Lynparza monotherapy in clinical trials at the recommended dose.
PFS (DCO 30. juni
PFS (DCO 30 June
Kassér Lynparza kapsler, der har været frosset.
Throw away any Lynparza capsules that have been frozen.
Lynparza leveres i HDPE-plastikflasker indeholdende 112 hårde kapsler.
Lynparza is provided in HDPE plastic bottles containing 112 hard capsules.
Der var ingen strategi for multiple tests for sub-gruppeanalyserne.
There was no strategy for multiple testing in place for the sub-group analyses.
Meget almindelig Svimmelhed, hovedpine, dysgeusi
Very common Dizziness, Headache, Dysgeusia
Pneumonitis, herunder hændelser med dødelig udgang, er rapporteret hos <1,0 % af patienterne, behandlet med Lynparza i kliniske studier.
Pneumonitis, including events with a fatal outcome, has been reported in <1.0% of patients treated with Lynparza in clinical studies.
I Study 19 blev der identificeret 20 patienter med en somatisk tumor-BRCA-mutation (en mutation i tumoren, men vildtype i germline).
In Study 19, 20 patients were identified with a somatic tumour BRCA mutation (a mutation in the tumour but wildtype in the germline).
Kvindelige patienter:
Female patients:
Meget almindelige bivirkninger, der kan ses i blodprøver:
Very common side effects that may show up in blood tests:
Studiet viste en klinisk relevant og statistisk signifikant forbedring af investigatorvurderet PFS for olaparib sammenlignet med placebo.
The study demonstrated a clinically relevant and statistically significant improvement in investigator assessed PFS for olaparib compared to placebo.
Farmakoterapeutisk klassifikation: antineoplastiske midler, andre antineoplastiske midler, ATC-kode: L01XX46
Pharmacotherapeutic group: antineoplastic agents, other antineoplastic agents, ATC code: L01XX46
I sjældne tilfælde kan dette være et tegn på mere alvorlige problemer med knoglemarven, såsom "myelodysplastisk syndrom" (MDS) eller "akut myeloid leukæmi" (AML).
Rarely, these may be a sign of more serious problems with the bone marrow such as ‘myelodysplastic syndrome' (MDS) or ‘acute myeloid leukaemia' (AML).