natgillin/translations-raw huggingface dataset:
Det Europæiske Lægemiddelagentur har dispenseret fra kravet om at fremlægge resultaterne af studier med Odomzo i alle undergrupper af den pædiatriske population ved basalcellecarcinom (se pkt.
The European Medicines Agency has waived the obligation to submit the results of studies with Odomzo in all subsets of the paediatric population in basal cell carcinoma (see section 4.2 for information on paediatric use).
Tag ikke Odomzo, hvis du er gravid, har mistanke om, at du er gravid, eller planlægger at blive gravid under din behandling eller i de første 20 måneder efter, at din behandling er afsluttet.
Do not take Odomzo if you are pregnant, think you may be pregnant, or are planning to become pregnant during your treatment or during the 20 months after your treatment has finished.
Stoffer, der er BCRP-substrater med snævre terapeutiske områder (fx methotrexat, mitoxantron, irinotecan, topotecan), skal undgås.
Substances that are BCRP substrates with narrow therapeutic range (e.g. methotrexate, mitoxantrone, irinotecan, topotecan) should be avoided.
Det er påvist, at sonidegib er føtotoksisk hos kaniner, idet meget lave eksponeringer medførte abort og/eller fuldstændig resorption af fostre samt teratogene virkninger i form af alvorlige misdannelser.
Sonidegib was shown to be foetotoxic in rabbits, as evidenced by abortion and/or complete resorption of foetuses and teratogenic resulting in severe malformations at very low exposure.
De teratogene virkninger omfattede misdannelser af rygsøjle, distale lemmer og digiti, svære kraniofaciale misdannelser og andre svære midtlinjedefekter.
Teratogenic effects included vertebral, distal limb and digit malformations, severe craniofacial malformations and other severe midline defects.
• uro i maven eller fordøjelsesbesvær
• upset stomach or indigestion
• At returnere ubrugte kapsler ved behandlingens afslutning (bortskaffelse vil afhænge af lokale retningslinjer)
• To return unused capsules at the end of the treatment (disposal will depend on local requirements)
AUClast var 35 % lavere ved let nedsat leverfunktion, 14 % højere ved moderat nedsat leverfunktion og 23 % lavere ved svært nedsat leverfunktion.
AUClast was 35% lower in mild hepatic impairment, 14% higher in moderate hepatic impairment and 23% lower in severe hepatic impairment.
79 ud af de 230 randomiserede patienter fik tildelt Odomzo 200 mg. Af disse 79 var 66 (83,5 %) laBCCpatienter (37 [46,8 %] med aggressiv histologi og 29 [36,7 %] med ikke-aggressiv histologi) og 13 (16,5 %) var mBCC-patienter.
Of the 230 patients randomised, 79 patients were assigned to Odomzo 200 mg. Of these 79 patients, 66 (83.5%) were laBCC patients (37 [46.8%] with aggressive histology and 29 [36.7%] with non-aggressive histology) and 13 (16.5%) were mBCC patients.
Andre bivirkninger Hvis en eller flere af disse bivirkninger bliver alvorlige, skal du fortælle det til lægen eller apotekspersonalet.
Other possible side effects If any of these side effects become severe, tell your doctor or pharmacist.
• Odomzo udgør en teratogen risiko for det ufødte barn, hvis han har ubeskyttet samleje med en gravid kvinde.
• Odomzo exposes a teratogenic risk to the unborn child if he engages in unprotected sexual activity with a pregnant woman.
MARKEDSFØRINGSTILLADELSESNUMMER (-NUMRE) EU/1/15/1030/001
MARKETING AUTHORISATION NUMBER(S) EU/1/15/1030/001
(bugspytkirtelfunktion), alaninaminotransferase (ALAT) og/eller aspartataminotransferase (ASAT)
(pancreas function), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) (liver function)
Sonidegib metaboliseres primært af CYP3A4, og samtidig administration af stærke hæmmere eller inducere af CYP3A4 kan øge eller nedsætte koncentrationen af sonidegib væsentligt.
Sonidegib undergoes metabolism primarily by CYP3A4, and concomitant administration of strong inhibitors or inducers of CYP3A4 can increase or decrease sonidegib concentrations significantly.
Fortæl det straks til lægen, hvis din partner bliver gravid, mens du tager Odomzo og i 6 måneder efter, din behandling er afsluttet.
Tell your doctor straight away if your partner becomes pregnant while you are taking Odomzo and for 6 months after your treatment has finished.
• alvorlig hudkløe med rødt udslæt eller knopper.
• severe itching of the skin, with a red rash or raised bumps.
Forhøjet blodglukose
Blood glucose increased
Du skal også bruge en barrieremetode, som fx:
You must also use one barrier method, such as:
Hver kapsel indeholder 200 mg sonidegib.
Each capsule contains 200 mg sonidegib.
Hvis du holder op med at tage Odomzo Du må ikke holde op med at tage Odomzo uden først at tale med din læge.
Do not stop taking Odomzo without talking to your doctor first.
Dyreforsøg har påvist teratogenicitet og føtotoksicitet (se pkt.
Studies in animals have shown teratogenicity and foetotoxicity (see section 5.3).
Klinisk relevante laboratorieabnormaliteter
Clinically relevant laboratory abnormalities
Hvis der måles klinisk betydende forhøjet CK, skal nyrefunktionen vurderes (se pkt.
If clinically notable elevation of CK is detected, renal function should be assessed (see section 4.2).
Baseret på virkningsmekanismen har sonidegib i dyreforsøg vist sig at være teratogent og føtotoksisk.
Based on the mechanism of action, in animal studies, sonidegib has been shown to be teratogenic and foetotoxic.
Odomzo bruges til at behandle voksne med en type hudkræft, der hedder basalcellecarcinom.
Odomzo is used to treat adults with a type of skin cancer called basal cell carcinoma.
Fertile kvinder skal have deres graviditetsstatus klarlagt inden for 7 dage før initiering af behandling med Odomzo og månedligt under behandlingen ved hjælp af en test, der udføres af sundhedspersonale.
The pregnancy status of women of child-bearing potential must be established within 7 days prior to the initiation of Odomzo treatment and monthly during treatment by means of a test performed by a healthcare professional.
Hvis du har taget for meget Odomzo, eller hvis en anden ved et uheld tager din medicin, skal du straks kontakte en læge eller tage på hospitalet.
If you take more Odomzo than you should, or if someone else accidentally takes your medicine, talk to a doctor or go to a hospital straight away.
Når dosisafbrydelse er nødvendigt, skal det overvejes at genoptage Odomzo-behandlingen ved den samme dosis efter forbedring af bivirkningen til ≤ grad 1.
When dose interruption is required, consider resuming Odomzo at the same dose after resolution of the adverse reaction to ≤ grade 1.
Inden for hver enkelt frekvenskategori er bivirkningerne opstillet efter faldende alvorlighedsgrad.
Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness.
Kutant pladecellecarcinom (cuSCC)
Cutaneous squamous cell carcinoma (cuSCC)
Figur 1 viser den bedste ændring i mållæsionens størrelse hos hver enkelt patient med laBCC ved en dosis på 200 mg ifølge central vurdering.
Figures 1 shows the best change in target lesion size for each patient with laBCC at the dose of 200 mg per central review.
Der forekom ét dødsfald under behandlingen eller inden for 30 dage efter den sidst indtagne dosis hos patienter med enten BCC eller lokalt fremskredet BCC, som tog Odomzo 200 mg.
One death occurred while on treatment or within 30 days of the last dose taken in either metastatic BCC or locally advanced BCC patients taking Odomzo 200 mg.
• problemer med at trække vejret eller synke
• difficulty breathing or swallowing
Samtidig behandling med CYP-induktorer (fx rifampicin, carbamazepin eller phenytoin) bør undgås, da risiko for nedsat plasmakoncentration og nedsat effekt af sonidegib ikke kan udelukkes (se også pkt.
Concomitant treatment with strong CYP inducers (e.g. rifampicin, carbamazepine or phenytoin) should be avoided, as a risk for decreased plasma concentrations and decreased efficacy of sonidegib cannot be excluded (see also section 4.5).
De sekundære endepunkter omfattede responsvarighed, tid til tumorrespons og progressionsfri overlevelse (PFS) ifølge mRECIST hos patienter med laBCC og RECIST 1.1 hos patienter med mBCC bestemt ved central vurdering.
The secondary endpoints included duration of response, time to tumour response and progression free survival (PFS) according to mRECIST in patients with laBCC and RECIST 1.1 in patients with mBCC as determined by central review.
• hvis du kan blive gravid, men ikke kan eller ikke vil tage de nødvendige forholdsregler mod graviditet,
• if you are able to become pregnant but are unable or unwilling to follow the necessary pregnancy prevention measures that are listed in the Odomzo Pregnancy Prevention Programme.
Der var nedsat fertilitet ved lave eksponeringer hos hunrotter.
There was reduced fertility at low exposure in female rats.
Meget almindelig * 5 ud af 79 patienter, der fik Odomzo 200 mg var fertile kvinder.
Very common * Of the 79 patients receiving Odomzo 200 mg, 5 were women of childbearing age.
hvornår du skal tage din medicin.
This will help you to remember when to take your medicine.
Hvis den samme bivirkning optræder efter skiftet til dosering hver anden dag og ikke bedres, skal seponering af behandlingen med Odomzo overvejes.
If the same adverse drug reaction occurs following the switch to alternate daily dosing and does not improve, consider discontinuing treatment with Odomzo.
Inden lancering skal indehaveren af markedsføringstilladelsen komme til enighed med den nationale lægemiddelmyndighed i hvert medlemsland om:
Prior to launch in each Member State the Marketing Authorisation Holder (MAH) shall agree the following with the National Competent Authority:
• Du skal anvende to præventionsmetoder; en yderst effektiv metode og en barrieremetode (se eksemplerne herunder), så længe du tager Odomzo.
• you must use 2 methods of contraception, one highly effective method and one barrier method (see the examples below) while you are taking Odomzo,
Tag ikke Odomzo:
Do not take Odomzo:
Hud og subkutane væv Alopeci
Skin and subcutaneous tissue disorders Alopecia
Den mediane varighed af eksponering for sonidegib under studie X2104 var 97 dage (område 34 til 511 dage) for voksne patienter og 55 dage (område 2 til 289 dage) for pædiatriske patienter.
The median duration of exposure to sonidegib during Study X2104 was 97 days (range 34 to 511 days) for adult patients and 55 days (range 2 to 289 days) for paediatric patients.
Sonidegibs binding til Smo vil hæmme Hh-signalering og dermed blokere transduktion.
Sonidegib binding to Smo will inhibit Hh signalling and consequently block signal transduction.
Atypisk Hh-signalering er blevet koblet til flere cancertypers patogenese, herunder basalcellecarcinom (BCC).
Aberrant Hh signalling has been linked to the pathogenesis of several types of cancer, including basal cell carcinoma (BCC).
Blodprøverne bruges til at kontrollere dine musklers sundhedstilstand ved at måle indholdet af enzymet kreatinkinase i dit blod.
These tests will check the health of your muscles by measuring the levels of an enzyme in your blood called creatine phosphokinase.
Studie CLDE225X2104 var et fase I/II-studie af sonidegib hos pædiatriske patienter med recidiverende eller refraktær medulloblastoma eller andre tumorer, som er potentielt afhængige af hedgehog-signaleringsvej (Hh) og voksne patienter med recidiverende eller refraktær medulloblastoma.
Study CLDE225X2104 was a Phase I/II study of sonidegib in paediatric patients with recurrent or refractory medulloblastoma or other tumours potentially dependent on the Hedgehog (Hh) signalling pathway and adult patients with recurrent or refractory medulloblastoma.
Studie CLDE225C2301 var et fase II, multicenter, ikke-blindet, enarmet studie af effektiviteten og sikkerheden aforal sonidegib hos patienter med Hh-aktiveret recidiveret medulloblastoma.
Study CLDE225C2301 was a Phase II, multi-centre, open-label, single-arm study of the efficacy and safety of oral sonidegib in patients with Hh-activated relapsed medulloblastoma.
Patienterne skal monitoreres nøje for muskelrelaterede symptomer, hvis Odomzo anvendes i kombination med visse lægemidler, der kan øge den potentielle risiko for at udvikle muskeltoksicitet (fx CYP3A4hæmmere, chloroquin, hydroxychloroquin, fibrinsyrederivativer, penicillamin, zidovudin, niacin og HMGCoA-reduktasehæmmere) (se pkt.
Patients should be closely monitored for muscle-related symptoms if Odomzo is used in combination with certain medicinal products that may increase the potential risk of developing muscle toxicity (e.g. CYP3A4 inhibitors, chloroquine, hydroxychloroquine, fibric acid derivatives, penicillamine, zidovudine, niacin and HMG-CoA reductase inhibitors) (see section 4.5).
Ingen af de patienter, der tog HMG-CoA-reduktasehæmmere, oplevede forhøjet CK i grad 3/4, i modsætning til 6 patienter (9,0 %), der ikke tog HMG-CoA-reduktasehæmmere.
No patient taking HMG-CoA reductase inhibitors experienced grade 3/4 CK elevations, as opposed to 6 (9.0%) patients not taking HMG-CoA reductase inhibitors.
En af de patienter, der fik Odomzo 200 mg, oplevede muskelsymptomer og CK-stigninger over 10x ULN og havde behov for intravenøs væske sammenlignet med 6 patienter, der fik Odomzo 800 mg.
One patient receiving Odomzo 200 mg experienced muscle symptoms and CK elevations above 10x ULN and required intravenous fluids, compared to 6 patients receiving Odomzo 800 mg.
Grad 3/4 stigninger i blod-CK blev indberettet hos 8 % af de patienter, der tog Odomzo 200 mg.
Grade 3/4 increase in blood CK was reported in 8% of patients taking Odomzo 200 mg.
Hos de fleste patienter bedredes muskelsymptomerne og CK-stigningerne med relevant behandling.
For most patients, muscle symptoms and CK elevations resolved with appropriate management.
• medicin, som hedder nefazodon mod depression
• a medicine called nefazodone used to treat depression
• Hvis symptomerne vender tilbage, afbrydes behandlingen indtil bedring til baseline.
• If symptoms re-occur, interrupt treatment until resolution to baseline.
Derudover er den tilsvarende frekvenskategori for hver bivirkning baseret på følgende konvention (CIOMS III): meget almindelig (≥1/10); almindelig (≥1/100 til <1/10); ikke almindelig (≥1/1.000 til <1/100); sjælden (≥1/10.000 til <1/1.000); meget sjælden (<1/10.000); ikke kendt (kan ikke estimeres ud fra forhåndenværende data).
In addition, the corresponding frequency category for each adverse drug reaction is based on the following convention (CIOMS III): very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000
Partielt respons Stabil sygdom Sygdomsprogression Ukendt Tid til tumorrespons (måneder) Median 95 % CI Responsvarighed Antal hændelser* Antal censureret Median (måneder) 95 % CI
Partial response Disease stabilisation Disease progression Unknown Time to tumour response (months) Median 95% CI Duration of response No. of events* No. censored Median (months) 95% CI
Hvis du glemmer at tage en dosis af Odomzo, skal du tage den, så snart du kommer i tanke om det.
If you forget to take Odomzo If you forget to take a dose of Odomzo, take it as soon you realise.
EVENTUELLE ANDRE SÆRLIGE ADVARSLER Risiko for alvorlige fostermisdannelser.
OTHER SPECIAL WARNING(S), IF NECESSARY Risk of severe birth defects.
Myopati [muskeltræthed og muskelsvækkelse]
Myopathy [muscular fatigue and muscular weakness]
Kvinder, der tager Odomzo, må ikke være eller blive gravide under behandlingen og i 20 måneder efter endt behandling.
Women taking Odomzo must not be pregnant or become pregnant during treatment and for 20 months after ending treatment.
De skal anvende to anbefalede præventionsmetoder, herunder en yderst effektiv metode og en barrieremetode, under behandlingen med Odomzo og i 20 måneder efter den sidste dosis.
They must use two methods of recommended contraception, including one highly effective method and a barrier method, during Odomzo therapy and for 20 months after the final dose.
Tabel 1 Anbefalede dosisjusteringer og håndtering ved symptomatisk forhøjet CK og muskelrelaterede bivirkninger
Table 1 Recommended dose modifications and management for symptomatic CK elevations and muscle-related adverse events
Farmakokinetiske populationsanalyser viste, at alder (testet interval 20-93 år, middelværdi 61 år), kropsvægt (testet interval 42-181 kg, middelværdi 77 kg), køn eller kreatininclearance (testet interval 27,3-290 ml/min, middelværdi 92,9 ml/min) ikke har nogen klinisk relevant påvirkning af den systemiske eksponering for sonidegib.
Population pharmacokinetic analyses showed that there are no clinically relevant effects of age (range tested from 20-93 years, mean 61 years), body weight (range tested 42-181 kg, mean 77 kg), gender, or creatinine clearance (range tested 27.3-290 ml/min, mean 92.9 ml/min) on the systemic exposure of sonidegib.
Tabel 1 opsummerer anbefalingerne for dosisafbrydelse og/eller dosisreduktion af Odomzo-behandling ved håndtering af symptomatisk forhøjet CK og muskelrelaterede bivirkninger (såsom myalgi, myopati og/eller spasmer).
Table 1 summarises recommendations for dose interruption and/or dose reduction of Odomzo therapy in the management of symptomatic CK elevations and muscle-related adverse events (such as myalgia, myopathy, and/or spasm).
Da sonidegib ikke udskilles via nyrerne, forventes ingen ændring af den systemiske eksponering hos patienter med nedsat nyrefunktion.
Since sonidegib is not renally excreted, no change in systemic exposure is anticipated in patients with renal impairment.
Ved eksponering et godt stykke over den kliniske eksponering var nyren et yderligere målorgan.
At exposures well above the clinical exposure, an additional target organ was the kidney.
• diarré eller halsbrand
• diarrhoea or heartburn
Det vides ikke, om der kan være en sammenhæng mellem SCC og behandling med Odomzo.
It is not known whether SCC can be related to treatment with Odomzo.
Abnorm hårvækst
Abnormal hair growth
Samtidig administration af sonidegib og stærke CYP3A-inducere nedsætter plasmakoncentrationen af sonidegib.
Co-administration of sonidegib with strong CYP3A inducers decreases sonidegib plasma concentration.
Når der er opnået bedring, genoptages behandlingen ved samme dosisniveau, og CK måles månedligt derefter.
Upon resolution, resume treatment at the same dose level and measure CK monthly thereafter.
• et naturlægemiddel, som hedder perikon (kaldes også Hypericum perforatum) mod depression.
• a herbal medicine called St. John's wort (also known as Hypericum perforatum) used to treat depression.
Grad 1 [Forhøjet CK >ULN - 2,5 x ULN]
Grade 1 [CK elevation >ULN - 2.5 x ULN]
Den indberettede sonidegib-relaterede toksicitet hos pædiatriske patienter var lig med de indberettede resultaterhos voksne med undtagelse af en reduceret hyppighed af muskeltoksicitet (f.eks. CKstigninger observeret hos 16,7 % af pædiatriske patienter sammenlignet med 50 % af voksne i studie X2104) og observationen af post-natal udviklingsmæssig virkning især med forlænget eksponering (indberettet som tilfælde af epifyseskive i forbindelse med phalanxlidelse, knæ subchondral kondensering af epifyseskiveområdet, physeal distal lårbenslidelse, chondropati og krakeleret tand).
The sonidegib-related toxicity reported in paediatric patients was similar to the results reported in adults, with the exceptions of a reduced incidence of muscle toxicity (e.g. CK elevations observed in 16.7% of paediatric patients compared with 50% of adults in study X2104) and the observation of post-natal development effect particularly with prolonged exposure (reported as cases of epiphyseal plate of phalanx disorder, knee subchondral condensation of area of growth plate, physeal distal femur disorder, chondropathy, and chipped tooth).
I fase II-hovedforsøget tog 12 (15,2 %) af de patienter, der blev behandlet med Odomzo 200 mg, samtidig HMG-CoA-reduktasehæmmere (9 tog pravastatin, 3 tog non-pravastatin-HMG-CoA-reduktasehæmmere, herunder rosuvastatin og simvastatin).
In the phase II pivotal trial, 12 (15.2%) patients treated with Odomzo 200 mg took concomitant HMG-CoA reductase inhibitors (9 took pravastatin, 3 took non-pravastatin HMG-CoA reductase inhibitors including rosuvastatin and simvastatin).
Du skal bruge én yderst effektiv metode, som fx:
You must use one highly effective method, such as:
INFORMATION I BRAILLESKRIFT Odomzo 200 mg
INFORMATION IN BRAILLE Odomzo 200 mg
De mest almindelige bivirkninger, som forekom hos ≥10 % af de patienter, der blev behandlet med Odomzo 200 mg, var muskelspasmer, alopeci, dysgeusi, træthed, kvalme, muskel-, led- og knoglesmerter, diarré, nedsat vægt, nedsat appetit, myalgi, mavesmerter, hovedpine, smerter, opkastning og pruritus.
The most common adverse drug reactions occurring in ≥10% of patients treated with Odomzo 200 mg were muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhoea, weight decreased, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting and pruritus.
• At patienten skal informere lægen om en hvilken som helst bivirkning
• That the patient should tell the healthcare professional about any adverse event
Det vides ikke, om Odomzo bliver udskilt i brystmælk og dermed kan skade barnet.
It is not known whether Odomzo can pass into your breast milk and cause harm to your baby.
Stærke CYP3A-hæmmere inkluderer, men er ikke begrænset til, ritonavir, saquinavir, telithromycin, ketoconazol, itraconazol, voriconazol, posaconazol og nefazodon.
Strong CYP3A inhibitors include, but are not limited to, ritonavir, saquinavir, telithromycin, ketoconazole, itraconazole, voriconazole, posaconazole and nefazodone.
Den optimale behandlingsvarighed kan variere for hver enkelt patient.
Benefit of continued treatment should be regularly assessed, with the optimal duration of therapy varying for each individual patient.
Bivirkningerne for den anbefalede dosis fra fase II-hovedforsøget (tabel 2) er opstillet efter MedDRAsystemorganklasse version 18.
Adverse drug reactions for the recommended dose from the phase II pivotal clinical study (Table 2) are listed by Medical Dictionary for Regulatory Activities (MedDRA) version 18 system organ class.
• udebleven menstruation
• absence of menstrual periods
Hvis noget af ovenstående gælder for dig, eller hvis du er i tvivl, skal du tale med lægen eller apotekspersonalet, før du tager Odomzo.
If any of the above apply to you or you are not sure, talk to your doctor or pharmacist before taking Odomzo.
KVALITATIV OG KVANTITATIV SAMMENSÆTNING Hver hård kapsel indeholder 200 mg sonidegib (som fosfat).
QUALITATIVE AND QUANTITATIVE COMPOSITION Each hard capsule contains 200 mg sonidegib (as phosphate).
• Informere patienter om, at de ikke må donere blod under behandling med Odomzo og i mindst
• Inform patients that they should not donate blood during treatment with Odomzo and for at least
En fertil kvinde defineres i Odomzo-programmet for svangerskabsforebyggelse som en kønsmoden kvinde, der
A woman of childbearing potential is defined in the Odomzo Pregnancy Prevention Programme as a sexually mature female who
Den mediane varighed af eksponering for sonidegib under studie C2301 var 2,8 måneder (område 0,4 til 33,2 måneder) for voksne patienter og 3,5 måneder (område 1,3 til 5,7 måneder) for pædiatriske patienter.
The median duration of exposure to sonidegib during Study C2301 was 2.8 months (range 0.4 to 33.2 months) for adult patients and 3.5 months (range 1.3 to 5.7 months) for paediatric patients.
Fortæl det især til lægen eller apotekspersonalet, hvis du tager en eller flere af følgende:
In particular tell your doctor or pharmacist if you are taking any of the following:
Gastro-øsofageal reflukssygdom
Gastro-oesophageal reflux disorder
Fortæl det straks til lægen eller apotekspersonalet, hvis du får ondt i musklerne, eller hvis du får uforklarlige muskelkramper eller muskelsvækkelse under behandling med Odomzo.
Tell your doctor or pharmacist immediately if your muscles hurt or you have unexplained muscle cramps or weakness during treatment with Odomzo.
Figur 1 Bedste ændring fra baseline af mållæsioner hos laBCC-patienter ifølge vurdering ved central vurdering efter FAS
Figure 1 Best change from baseline in the target lesions of laBCC patients per central review assessment by FAS
Generel toksicitet
General toxicology