natgillin/translations-raw huggingface dataset:
Dyrestudier indikerer, at baricitinib kan have en skadelig virkning på knogleudviklingen in utero ved højere doser.
Animal studies indicate that baricitinib may have an adverse effect on bone development in utero at higher dosages.
Ud af de 316 bivirkninger, der indgik i review fra post-marketing rapporter, var udslæt (n=95) den hyppigst rapporterede bivirkning.
From the 316 events included for review from post-marketing reports, rash (n=95) was the most frequently reported event.
Størstedelen af de patienter, der mistede deres status med lav sygdomsaktivitet eller remission efter dosisreduktion, kunne genvinde sygdomskontrol, efter at dosis igen var sat op til 4 mg.
The majority of patients who lost their low disease activity or remission status after dose reduction could regain disease control after the dose was returned to 4 mg.
Patienter, der fik seponeret behandlingen eller fik nødbehandling, blev herefter anset for at være ikke-responderende.
Patients who discontinued or received rescue therapy were considered as non-responders thereafter.
En risiko hos nyfødte/spædbørn kan ikke udelukkes, og Olumiant bør ikke anvendes under amning.
A risk to newborns/infants cannot be excluded and Olumiant should not be used during breast-feeding.
For Olumiant var de hyppigste alvorlige infektioner herpes zoster og cellulitis.
For Olumiant, the most common serious infections were herpes zoster, and cellulitis.
• et smertefuldt hududslæt med blærer.
• A painful skin rash with blisters.
Du og lægen skal sammen afgøre, om du skal amme eller tage Olumiant.
You and your doctor should decide if you will breast-feed or use Olumiant.
Hæmning af IL-6-induceret fosforylering af STAT3
Inhibition of IL-6 induced STAT3 phosphorylation
Patienter med hepatitis B-overflade-antistof og hepatitis B-kerne-antistof, men uden hepatitis B-overflade-antigen kunne også deltage; sådanne patienter bør monitoreres for ekspression af hepatitis B-virus (HBV)-DNA.
Patients with hepatitis B surface antibody and hepatitis B core antibody, without hepatitis B surface antigen, were also allowed to participate; such patients should be monitored for expression of hepatitis B virus (HBV) DNA.
Der blev ikke observeret nogen føtale virkninger ved eksponeringer på 2 gange eksponeringen hos mennesker baseret på AUC.
No adverse foetal effects were observed at exposures 2 times the human exposure based on AUC.
Forkortelser: QD = én gang daglig, Q2W = én gang hver anden uge, s.c. = subkutant, ACR = American College of Rheumatology, SDAI = Simplified Disease Activity Index, HAQ-DI = Health Assessment Questionnaire-Disability Index, mTSS = modified Total Sharp Score.
Abbreviations: QD = Once daily; Q2W = Once every 2 weeks; SC = Subcutaneously; ACR = American College of Rheumatology; SDAI = Simplified Disease Activity Index; HAQ-DI = Health Assessment Questionnaire-Disability Index; mTSS = modified Total Sharp Score
I alle studier rapporterede de patienter, der blev behandlet med Olumiant, forbedringer i patientrapporteret livskvalitet målt ved Short Form (36) Health Survey (SF-36) Physical Component Score og træthed målt ved Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale.
In all studies, Olumiant-treated patients reported improvements in patient-reported quality of life, as measured by the Short Form (36) Health Survey (SF-36) Physical Component Score and fatigue, as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue score (FACIT-F).
Derfor kan estimater for den glomerulære filtrationshastighed baseret på serum-kreatinin være lettere reducerede uden en reel forringelse af nyrefunktionen eller forekomst af negative renale virkninger.
Consequently, estimates of the glomerular filtration rate based on serum creatinine may be slightly reduced, without actual loss of renal function or the occurrence of renal adverse events.
Før behandling med Olumiant påbegyndes, anbefales det, at patienterne bringes a jour med al immunisering i overensstemmelse med gældende retningslinjer for immunisering.
Prior to initiating Olumiant, it is recommended that all patients be brought up to date with all immunisations in agreement with current immunisation guidelines.
Fortæl straks lægen, hvis du får symptomer på en infektion, f.eks.:
Inform your doctor immediately if you get symptoms of infection, such as:
Dette kan være et tegn på herpes zosterinfektion.
This could be a sign of a herpes zoster infection.
Baricitinib kan være en klinisk relevant hæmmer af OCT1, men der er på nuværende tidspunkt ingen kendte selektive OCT1-substrater, for hvilke klinisk signifikante interaktioner kan forudsiges.
Baricitinib may be a clinically relevant inhibitor of OCT1, however there are currently no known selective OCT1 substrates for which clinically significant interactions might be predicted.
Efter oral administration af baricitinib blev der observeret en dosisproportional stigning i den systemiske eksponering i det terapeutiske dosisinterval.
Following oral administration of baricitinib, a dose-proportional increase in systemic exposure was observed in the therapeutic dose range.
Hos hunrotter var der et nedsat antal corpora lutea og implantationssteder, et øget præ-implantationstab og/eller negative virkninger på embryoernes intrauterine overlevelse.
In female rats there were decreased numbers of corpora lutea and implantation sites, increased pre-implantation loss, and/or adverse effects on intrauterine survival of the embryos.
• hoste, der ikke vil gå over, nattesved og vægttab.
• A cough that won't go away, night sweats, and weight loss.
Patienter med dokumenteret aktiv hepatitis B- eller C-infektion blev ekskluderet fra kliniske studier.
Patients with evidence of active hepatitis B or C infection were excluded from clinical trials.
Baricitinibs potentiale til at påvirke farmakokinetikken af andre lægemidler
Potential for baricitinib to affect the pharmacokinetics of other medicinal products
Disse virkninger kan medføre, at det bliver lettere at udføre normale dagligdags aktiviteter og kan derved forbedre den helbredsrelaterede livskvalitet hos patienter med leddegigt.
These effects can help you to do normal daily activities and so improve the health-related quality of life for patients with rheumatoid arthritis.
Baricitinib modulerer disse signalveje ved delvist at hæmme den enzymatiske aktivitet af JAK1 og JAK2 og dermed reducere fosforyleringen og aktiveringen af STATs.
Baricitinib modulates these signalling pathways by partially inhibiting JAK1 and JAK2 enzymatic activity, thereby reducing the phosphorylation and activation of STATs.
I et klinisk farmakologisk studie blev ca. 75 % af den administrerede dosis udskilt i urinen, mens ca. 20 % af dosis blev udskilt i fæces.
In a clinical pharmacology study, approximately 75 % of the administered dose was eliminated in the urine, while about 20 % of the dose was eliminated in the faeces.
• Brug sikker prævention, mens du tager Olumiant (og i mindst 1 uge efter, hvis du har stoppet behandlingen).
• Use effective contraception while taking Olumiant (and for 1 week after, if you stop treatment).
Ved at nedsætte aktiviteten af dette enzym hjælper Olumiant med at mindske smerter, stivhed og hævelse i og omkring leddene samt træthed og hjælper med at bremse skader på knogler og brusk i leddene.
By reducing the activity of this enzyme, Olumiant helps to reduce pain, stiffness and swelling in your joints, tiredness, and helps to slow damage to the bone and cartilage in the joints.
Monitoreringsvejledning
Monitoring Guidance
Kombination med biologiske DMARDs eller andre Janus-kinase (JAK)-hæmmere anbefales ikke, da en risiko for additiv immunsuppression ikke kan udelukkes.
Combination with biologic DMARDs or other Janus kinase (JAK) inhibitors is not recommended, as a risk of additive immunosuppression cannot be excluded.
Olumiant virker ved at nedsætte aktiviteten af et enzym i kroppen, der kaldes ‘Janus-kinase', som er forbundet med inflammation.
Olumiant works by reducing the activity of an enzyme in the body called ‘Janus kinase', which is involved in inflammation.
Absolut neutrofiltal (ANC)
Absolute Neutrophil Count (ANC)
Patienter, der udvikler bivirkninger, skal have relevant behandling.
Patients who develop adverse reactions should receive appropriate treatment.
Du skal fortælle det til lægen, hvis du bliver gravid, da Olumiant ikke må anvendes under graviditet.
You must tell your doctor if you become pregnant as Olumiant should not be used during pregnancy.
Behandlingen bør afbrydes midlertidigt, hvis der er mistanke om lægemiddelinduceret leverskade.
Treatment should be temporarily interrupted if drug-induced liver injury is suspected
• titandioxid (E 171)
• titanium dioxide (E171)
• At Olumiant ikke må anvendes under graviditet, og at kvinder skal fortælle deres læge, hvis de bliver (eller planlægger at blive) gravide.
• That Olumiant should not be taken while pregnant and that women should inform their doctor should they become (or wish to become) pregnant
BEACON (24 uger)
BEACON (24 weeks)
Fald i parametre for røde blodceller blev observeret hos mus, rotter og hunde ved eksponeringer på ca. 6-36 gange eksponeringen hos mennesker.
Decreases in red blood cell parameters were observed in mice, rats and dogs at exposures approximately 6 to 36 times the human exposure.
Den anbefalede dosis er 2 mg én gang daglig hos patienter med kreatininclearance 30-60 ml/min.
The recommended dose is 2 mg once daily in patients with creatinine clearance between 30 and 60 mL/min.
b Sammensat term (eczema herpeticum, herpes simplex, oftalmisk herpes simplex, oral herpes).
b Combined term (eczema herpeticum, herpes simplex, ophthalmic herpes simplex, oral herpes).
Du må ikke stoppe med at tage Olumiant, medmindre lægen fortæller dig, at du skal stoppe med at tage det.
If you stop taking Olumiant Do not stop taking Olumiant unless your doctor tells you to stop taking it.
I den intracellulære signalvej fosforylerer og aktiverer JAKs signaltransduktorer og aktivatorer af transskription (STATs), hvilket aktiverer genekspression inde i cellen.
Within the intracellular signalling pathway, JAKs phosphorylate and activate signal transducers and activators of transcription (STATs), which activate gene expression within the cell.
Risiciene og fordelene ved Olumiant-behandling skal nøje overvejes forud for indledning af behandling hos patienter med aktive, kroniske eller tilbagevendende infektioner (se pkt.
The risks and benefits of treatment with Olumiant should be carefully considered prior to initiating therapy in patients with active, chronic or recurrent infections (see section 4.2).
Da der ikke var nogen indvirkning på spermatogenesen (vurderet ved histopatologi) eller sæd/sperma-endepunkter hos hanrotter, var den nedsatte samlede parringsevne sandsynligvis et resultat af virkningerne på hunrotter.
Since there were no effects on spermatogenesis (as assessed by histopathology) or semen/sperm endpoints in male rats, the decreased overall mating performance was likely the result of these female effects.
Immunsupprimerende lægemidler
Immunosuppressive medicinal products
Hvis der opstår en alvorlig allergisk eller anafylaktisk reaktion, skal behandling med baricitinib straks seponeres.
If any serious allergic or anaphylactic reaction occurs, baricitinib should be discontinued immediately.
Janus-kinaser (JAKs) er enzymer, der transducerer intracellulære signaler fra celleoverfladereceptorer for en række cytokiner og vækstfaktorer, som er involveret i hæmatopoiese, inflammation og immunfunktion.
Janus kinases (JAKs) are enzymes that transduce intracellular signals from cell surface receptors for a number of cytokines and growth factors involved in haematopoiesis, inflammation and immune function.
• feber, sår, usædvanlig træthed eller tandproblemer.
• Fever, wounds, feeling more tired than usual, or dental problems.
43,1 % (95 % CI: 34,0 %, 52,8 %) af patienterne opnåede tilfredsstillende IgG-immunresponser på tetanusvaccination.
In 43.1 % (95 % CI: 34.0 %, 52.8 %) of the patients, a satisfactory IgG immune response to tetanus vaccination was achieved.
Under hensyntagen til PRAC's vurderingsrapport om PSUR'en/PSUR'erne for baricitinib er CHMP nået frem til følgende videnskabelige konklusioner:
Taking into account the PRAC Assessment Report on the PSUR(s) for baricitinib, the scientific conclusions of CHMP are as follows:
Patienter, der var hepatitis C-antistof-positive, men negative for hepatitis C-virus-RNA, kunne deltage.
Patients, who were positive for hepatitis C antibody but negative for hepatitis C virus RNA, were allowed to participate.
Prodrugget leflunomid omdannes hurtigt til teriflunomid, der er en svag OAT3hæmmer, og som derfor kan lede til øget baricitinib-eksponering.
The prodrug leflunomide rapidly converts to teriflunomide which is a weak OAT3 inhibitor and therefore may lead to an increase in baricitinib exposure.
Radiologiske forandringer
Radiographic Changes
• Formål og anvendelse af Patientkortet.
• The purpose and use of the Patient Alert Card
JAK/STAT-signalvejen er vist at være involveret i celleadhæsion og cellepolaritet, hvilket kan påvirke den tidlige embryonale udvikling.
The JAK/STAT pathway has been shown to be involved in cell adhesion and cell polarity which can affect early embryonic development.
Hvis HBV-DNA påvises, bør en specialist i leversygdomme konsulteres for at afgøre, om det er nødvendigt at afbryde behandlingen.
If HBV DNA is detected, a liver specialist should be consulted to determine if treatment interruption is warranted.
I kontrollerede studier blev der over de første 16 uger observeret følgende forekomster for Olumiant vs. placebo:
In controlled studies, for up to 16 weeks, the following rates were observed for Olumiant vs. placebo:
• Behandlingen med Olumiant skal afbrydes i tilfælde af herpes zoster eller ved enhver anden infektion, der ikke responderer på standardbehandling, indtil symptomerne forsvinder.
• That Olumiant use should be stopped in case of herpes zoster or any other infection that doesn't respond to standard treatment until the event resolves.
Baricitinib blev påvist i mælken hos diegivende rotter.
Baricitinib was detected in the milk of lactating rats.
Efter oral administration absorberes baricitinib hurtigt med en median-tmax på ca. 1 time (interval 0,5-3,0 time) og en absolut biotilgængelighed på ca. 79 % (CV = 3,94 %).
Following oral administration, baricitinib is rapidly absorbed with a median tmax of approximately 1 hour (range 0.5 - 3.0 h) and an absolute bioavailability of approximately 79 % (CV = 3.94 %).
Behandling med baricitinib var forbundet med dosisafhængige stigninger i lipidparametre, herunder totalkolesterol, triglycerider, LDL-kolesterol og HDL-kolesterol.
Baricitinib treatment was associated with dose-dependent increases in lipid parameters including total cholesterol, triglycerides, LDL cholesterol, and HDL cholesterol.
Der blev set forbedring så tidligt som i uge 1, og i studierne RA-BEGIN og RA-BEAM blev denne opretholdt frem til uge 52.
Improvements were seen as early as Week 1 and, in studies RA-BEGIN and RA-BEAM, this was maintained for up to 52 weeks.
Hævelse i ansigtet Urticaria
Swelling of the face, Urticaria
I et studie af præ- og postnatal udvikling blev der observeret nedsat vægt hos afkommet og nedsat postnatal overlevelse ved eksponeringer på henholdsvis 4 og 21 gange eksponeringen hos mennesker.
In a pre- and postnatal development study, decreased pup weights and decreased postnatal survival were observed at exposures 4 and 21 times, respectively, the human exposure.
Du må ikke tage Olumiant, mens du ammer, da det ikke vides, om det går over i mælken.
You should not use Olumiant while breast-feeding as it is not known if this medicine passes into milk.
RA-BEACON TNF-IR patienter
RA-BEACON TNF-IR patients
Olumiant skal anvendes med forsigtighed til patienter med kendte risici for DVT/PE, såsom alder, overvægt, anamnese med DVT/PE eller patienter som gennemgår operation og immobilisering.
Olumiant should be used with caution in patients with risk factors for DVT/PE, such as older age, obesity, a medical history of DVT/PE, or patients undergoing surgery and immobilisation.
Kombination med biologiske DMARDs eller andre JAK-hæmmere er ikke blevet undersøgt.
Combination with biologic DMARDs or other JAK inhibitors has not been studied.
Olumiant 2 mg filmovertrukne tabletter EU/1/16/1170/001
Olumiant 2 mg film-coated tablets EU/1/16/1170/001
En dosis på 2 mg én gang daglig er passende til f.eks. patienter ≥ 75 år og kan være passende til patienter med kroniske eller tilbagevendende infektioner i anamnesen.
A dose of 2 mg once daily is appropriate for patients such as those aged ≥ 75 years and may be appropriate for patients with a history of chronic or recurrent infections.
Olumiant påvirker ikke eller kun i ubetydelig grad evnen til at føre motorkøretøj og betjene maskiner.
Olumiant has no or negligible influence on the ability to drive and use machines.
Hvis graviditet planlægges, skal behandling med Olumiant ophøre.
If a planned pregnancy is considered, Olumiant treatment should be stopped.
Virkningen og sikkerheden af Olumiant én gang daglig blev vurderet i 4 randomiserede, dobbeltblinde fase 3-multicenterstudier hos patienter med moderat til svær aktiv reumatoid artritis diagnosticeret i henhold til ACR/EULAR 2010-kriterierne (se tabel 3).
The efficacy and safety of Olumiant once daily was assessed in 4 Phase III randomised, double-blind, multicentre studies in patients with moderate to severe active rheumatoid arthritis diagnosed according to the ACR/EULAR 2010 criteria (see Table 3).
I tilfælde af overdosering anbefales det, at patienten monitoreres for symptomer på bivirkninger.
In case of an overdose, it is recommended that the patient be monitored for signs and symptoms of adverse reactions.
• Anvendelse af Olumiant er forbundet med hyperlipidæmi; ordinerende læge skal monitorere patientens lipidparametre og korrigere hyperlipidæmi, hvis den påvises.
• That Olumiant use is associated with hyperlipidaemia; prescribers should monitor the patient's lipid parameters and manage the hyperlipidaemia, if detected.
I analyser af de enkelte enzymer hæmmede baricitinib aktiviteten af JAK1, JAK2, tyrosinkinase 2 og JAK3 med IC50værdier på henholdsvis 5,9, 5,7, 53 og > 400 nM.
In isolated enzyme assays, baricitinib inhibited the activities of JAK1, JAK2, Tyrosine Kinase 2 and JAK3 with IC50 values of 5.9, 5.7, 53 and > 400 nM, respectively.
Oversigt over mål for nøgleresultater
Summary of key outcome measures
En ubalance i rapportering af VTE med 0% (EAIR på 0,0) for placebo vs. 0,53% (EAIR på 1,3) for baricitinib 4 mg blev rapporteret i placebokontrollerede studier.
An imbalance in reports of VTE with 0% (EAIR of 0,0) for placebo vs. 0,53% (EAIR of 1,3) for baricitinib 4-mg was noted in placebo-controlled trials.
Det skal besluttes, om amning skal ophøre eller behandling med Olumiant seponeres, idet der tages højde for fordelene ved amning for barnet i forhold til de terapeutiske fordele for moderen.
A decision must be made whether to discontinue breast-feeding or to discontinue Olumiant therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
For totalpopulationen resulterede pneumokokvaccination i tilfredsstillende IgGimmunresponser hos 68,0 % (95 % CI: 58,4 %, 76,2 %) af patienterne.
For the total population, pneumococcal vaccination resulted in a satisfactory IgG immune response in 68.0 % (95 % CI: 58.4 %, 76.2 %) of the patients.
*p ≤ 0,05, **p ≤ 0,01, ***p ≤ 0,001 vs. placebo (vs. MTX for studie RA-BEGIN).
* p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001 vs. placebo (vs. MTX for study RA-BEGIN)
Der blev observeret fald i antallet af lymfocytter, eosinofiler og basofiler såvel som lymfoid depletion i immunsystemets organer/væv hos mus, rotter og hunde.
Decreases in lymphocytes, eosinophils and basophils as well as lymphoid depletion in organs/tissues of the immune system were observed in mice, rats and dogs.
Det Europæiske Lægemiddelagentur har udsat forpligtelsen til at fremlægge resultaterne af studier med Olumiant i en eller flere undergrupper af den pædiatriske population med kronisk idiopatisk artritis (se pkt.
The European Medicines Agency has deferred the obligation to submit the results of studies with Olumiant in one or more subsets of the paediatric population in chronic idiopathic arthritis (see section 4.2 for information on paediatric use).
I klinisk farmakologiske studier var der ingen klinisk relevante effekter på eksponeringen, når baricitinib blev administreret sammen med digoxin (Pgp-substrat) eller methotrexat (substrat for flere transportører).
In clinical pharmacology studies there were no clinically meaningful effects on exposure when baricitinib was coadministered with digoxin (Pgp substrate) or methotrexate (substrate of several transporters).
I placebo-kontrollerede forsøg, hvor MTX ikke var påkrævet, fik 501 forsøgspersoner, der var randomiseret til baricitinib 2 mg eller 4 mg, MTX som basisbehandling, og 303 fik andre konventionelle DMARDs end MTX (ca. halvdelen med MTX og halvdelen uden).
In placebo-controlled trials in which MTX was not required, 501 subjects randomized to baricitinib 2 mg or 4 mg received MTX as background therapy, and 303 received conventional DMARDs other than MTX (approximately half with MTX and half without).
Farmakokinetikken af baricitinib er lineær med hensyn til tid.
The PK of baricitinib is linear with respect to time.
Foreliggende farmakodynamiske/toksikologiske data hos dyr har vist, at baricitinib udskilles i mælk (se pkt.
Available pharmacodynamic/toxicological data in animals have shown excretion of baricitinib in milk (see section 5.3).
14 filmovertrukne tabletter 28 filmovertrukne tabletter 35 filmovertrukne tabletter 56 filmovertrukne tabletter 84 filmovertrukne tabletter 98 filmovertrukne tabletter 28 x 1 filmovertrukne tabletter 84 x 1 filmovertrukne tabletter
14 film-coated tablets 28 film-coated tablets 35 film-coated tablets 56 film-coated tablets 84 film-coated tablets 98 film-coated tablets 28 x 1 film-coated tablets 84 x 1 film-coated tablets
Hver tablet indeholder 2 eller 4 milligram baricitinib.
Each tablet contains 2 or 4 milligrams of baricitinib.
Hos patienter med reumatoid artritis blev der observeret fald i serumniveauet af C-reaktivt protein (CRP) så tidligt som 1 uge efter opstart af Olumiant, og det blev opretholdt gennem hele doseringsperioden.
In patients with rheumatoid arthritis, decreases in serum C-reactive protein (CRP) were observed as early as 1 week after starting treatment with Olumiant and were maintained throughout dosing.
Effekten af Olumiant på progression af strukturel ledskade blev evalueret radiologisk i RA-BEGIN-, RA-BEAM- og RA-BUILD-studierne og bestemt ved brug af modified Total Sharp Score (mTSS) og dets komponenter, erosionsscore og score for afsmalnet ledspalte.
The effect of Olumiant on progression of structural joint damage was evaluated radiographically in studies RA-BEGIN, RA-BEAM and RA-BUILD and assessed using the modified Total Sharp Score (mTSS) and its components, the erosion score and joint space narrowing score.
• magnesiumstearat
• magnesium stearate
I et længerevarende forlængelsesstudie blev de patienter fra RA-BEAM, RA-BUILD og RA-BEACON, der opnåede vedvarende lav sygdomsaktivitet eller remission (CDAI ≤ 10) efter mindst 15 måneders behandling med Olumiant 4 mg én gang daglig, randomiseret på ny i forholdet 1:1 på dobbeltblindet vis til at fortsætte med 4 mg én gang daglig eller få reduceret dosis til 2 mg én gang daglig.
In a long-term extension study, patients from Studies RA-BEAM, RA-BUILD and RA-BEACON who achieved sustained low disease activity or remission (CDAI ≤ 10) after at least 15 months of treatment with Olumiant 4 mg once daily were re-randomized 1:1 in a double-blind manner to continue 4 mg once daily or reduce dose to 2 mg once daily.