natgillin/translations-raw huggingface dataset:
Fund i uterus/ovarier og nedsat hæmatopoiese syntes at være forbigående, mens virkninger på knogleparametre og leverpigmentering var vedblivende.
Findings in uterus/ovaries and decreased haematopoiesis appeared to be transient, while effects on bone parameters and liver pigmentation were sustained.
• Inflammation ved hårrødderne, acne, blistere (på dele af kroppen udover hænder og fødder)
• Inflammation at the root of your hair, acne, blisters (on parts of your body other than the hands or feet)
Cabozantinib blev metaboliseret in vivo.
Cabozantinib was metabolized in vivo.
65 quai Georges Gorse 92100 Boulogne-Billancourt Frankrig
65 quai Georges Gorse 92100 Boulogne-Billancourt France
COMETRIQ er et lægemiddel, der anvendes til behandling af medullær thyroideacancer, en sjælden type thyroideacancer, der ikke kan fjernes ved operation eller som har spredt sig til andre dele af kroppen.
COMETRIQ is a medicine used to treat medullary thyroid cancer, a rare type of thyroid cancer, that cannot be removed by surgery or that has spread to other parts of the body.
På grund af den potentielle skade for spædbarnet, bør mødre stoppe med at amme under behandling med cabozantinib og i mindst 4 måneder efter fuldførelsen af behandlingen.
Because of the potential harm to the infant, mothers should discontinue breast-feeding during treatment with cabozantinib, and for at least 4 months after completing therapy.
Ikke-GI fistler bør udelukkes i tilfælde med indtræden af mucositis efter behandlingens start.
Non-GI fistula should be ruled out as appropriate in cases of onset of mucositis after start of therapy.
Blisterkort indeholdende enten:
Blister cards containing either:
Beslutningen om at genoptage behandling med cabozantinib efter operation bør baseres på klinisk bedømmelse af tilstrækkelig sårheling.
The decision to resume cabozantinib therapy after surgery should be based on clinical judgment of adequate wound healing.
Dette er en betinget markedsføringstilladelse, og i henhold til artikel 14, stk. 7, i forordning (EF) nr. 726/2004 skal indehaveren af markedsføringstilladelsen inden for den fastsatte tidsramme gennemføre følgende foranstaltninger:
E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES FOR THE CONDITIONAL MARKETING AUTHORISATION This being a conditional marketing authorisation and pursuant to Article 14(7) of Regulation (EC) No 726/2004, the MAH shall complete, within the stated timeframe, the following measures: Description
Der bør udvises forsigtighed hos patienter, der får midler forbundet med ONJ, såsom bisfosfonater.
Caution should be used in patients receiving agents associated with ONJ, such as bisphosphonates.
Der er vigtigt for dig, at du udøver god mundpleje under behandling med COMETRIQ.
It is important for you to practice good mouth care during treatment with COMETRIQ.
Cabozantinib er et CYP3A4-substrat.
Cabozantinib is a CYP3A4 substrate.
Der er kun lille erfaring med cabozantinib hos ikke-kaukasiske patienter.
There is little experience with cabozantinib in non-White patients.
Der er en mulighed for, at din frugtbarhed kunne blive påvirket af behandlingen med COMETRIQ.
There is a possibility your fertility could be affected by treatment with COMETRIQ.
Alvorlige GI perforationer og fistler, af og til med dødelig udgang, og intra-abdominale abscesser er blevet observeret med cabozantinib.
Serious GI perforations and fistulas, sometimes fatal, and intra-abdominal abscesses have been observed with cabozantinib.
Figur 1: Kaplan Meier kurve for progressionfri overlevelse
Figure 1: Kaplan Meier curve of progression free survival
Vævsprøver fra tumor vil indledningsvis gennemgå histologisk evaluering, manuel tumor opformering og DNA-isolation.
Tumor tissue samples initially will undergo histological evaluation, manual tumor enrichment, and DNA isolation.
RPLS er ikke almindelig (påvirker færre end 1 ud af 100 mennesker).
RPLS is uncommon (it affects less than 1 in 100 people).
Hver 28-dages pakning indeholder medicin nok til 28 dage.
Each 28 day pack contains enough medicine for 28 days.
• Hypotension (fald i blodtryk)
• Hypotension (decrease in blood pressure)
Af de 215 forsøgspersoner med tilstrækkelige data til bestemmelse af mutationsstatus blev 78,6 % (n=169) klassificeret som RET-mutationspositive (hvoraf 126 var positive for M918T-mutationen), og 21,4 % (n=46) blev klassificeret som RET-mutationsnegative.
Of the 215 subjects with sufficient data to determine mutational status, 78.6% (n=169) were classified as RET mutation positive (126 of which were positive for the M918T mutation), and 21.4% (n=46) were classified as RET mutation negative.
Median varigheden af objektivt respons var 14,6 måneder (95 % CI: 11,1-17,5) for forsøgspersoner i cabozantinib-armen.
The median duration of objective responses was 14.6 months (95% CI: 11.1, 17.5) for subjects in the cabozantinib arm.
In vitro data viser, at cabozantinib er substrat for MRP2.
In vitro data demonstrate that cabozantinib is a substrate of MRP2.
COMETRIQ kan sinke eller stoppe væksten af medullær thyroideacancer.
COMETRIQ may slow or stop the growth of medullary thyroid cancer.
Et neutraliserende antistof over for CYP2C9 viste en minimal effekt på dannelse af cabozantinib metabolit (dvs. en <20 % reduktion).
A neutralizing antibody to CYP2C9 showed a minimal effect on cabozantinib metabolite formation (ie, a <20% reduction).
En værdi for thyroideastimulerende hormon (TSH) over normalen efter den første dosis blev observeret hos 57 % af patienterne på cabozantinib versus 19 % af patienterne på placebo (uanset baseline værdier).
A thyroid stimulating hormone (TSH) value above normal after first dose was observed in 57% of patients on cabozantinib versus 19% of patients on placebo (regardless of baseline values).
Når PPES er alvorlig, bør seponering af behandling med cabozantinib overvejes.
When PPES is severe, interruption of treatment with cabozantinib should be considered.
Bivirkninger såsom træthed og svaghed er blevet forbundet med cabozantinib.
Adverse reactions such as fatigue and weakness have been associated with cabozantinib.
Disse kan være tegn på en tilstand, der kaldes reversibel posterior leukoencefalopati syndrom (RPLS).
These may be signs of a condition called reversible posterior leukoencephalopathy syndrome (RPLS).
Dine kapsler findes også som en 28-dages pakning, der indeholder kapsler nok til at vare 28 dage, i 4 blisterkort med kapsler til 7 dage på hvert kort.
Your capsules are also available as a 28 day pack, which contains enough capsules to last for 28 days, in 4 blister cards with seven days of capsules on each card.
Fortæl det til lægen, hvis du eller din partner er gravid eller planlægger at blive gravid, mens du tager COMETRIQ.
Tell your doctor if you or your partner become pregnant or plan to become pregnant while you are being treated with COMETRIQ.
Valg af et alternativt samtidigt administreret lægemiddel uden eller med minimalt potentiale til at inducere eller hæmme CYP3A4 bør overvejes.
Selection of an alternative concomitant medicinal product with no or minimal potential to induce or inhibit CYP3A4 should be considered.
Samlet responsratea (95 % CI)
Overall Response Ratea (95% CI)
• En rift i eller abnorm forbindelse af væv i dit fordøjelsessystem; symptomer kan omfatte kraftig eller vedblivende mavepine
• A tear or abnormal connection of the tissue in your digestive system; symptoms can include severe or persistent stomach ache
Inden indledning af behandling med cabozantinib bør denne risiko overvejes nøje for patienter med risikofaktorer såsom hypertension eller tidligere aneurisme.
Before initiating cabozantinib, this risk should be carefully considered in patients with risk factors such as hypertension or history of aneurysm.
Farmakoterapeutisk klassifikation: antineoplastisk middel, proteinkinase-hæmmer, ATC-kode: L01XE26
Pharmacotherapeutic group: antineoplastic agent, protein kinase inhibitor, ATC code: L01XE26.
Cabozantinib var ikke karcinogent i rasH2-musemodellen ved en eksponering, der var anelse højere end den tilsigtede terapeutiske eksponering hos mennesker.
Cabozantinib was not carcinogenic in the rasH2 mouse model at a slightly higher exposure than the intended human therapeutic exposure.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS), også kendt som Posterior Reversible Encephalopathy Syndrome (PRES) er blevet observeret med cabozantinib.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS), also known as Posterior Reversible Encephalopathy Syndrome (PRES) has been observed with cabozantinib.
Cabozantinib blev evalueret for dets hæmmende aktivitet mod en række kinaser og blev identificeret som en hæmmer af MET (hepatocyt vækstfaktor receptorprotein) og VEGF (vaskulær endothelial vækstfaktor) receptorer.
Cabozantinib was evaluated for its inhibitory activity against a variety of kinases and was identified as an inhibitor of MET (hepatocyte growth factor receptor protein) and VEGF (vascular endothelial growth factor) receptors.
Et dosissammenlignende studie (XL-184-401) (140 mg vs 60 mg) hos 112 patienter med nedarvet eller sporadisk medullær thyroideacancer.
A dose-comparison study (XL-184-401) (140 mg vs 60 mg) in 112 patients with hereditary or sporadic medullary thyroid cancer.
Fertilitetsstudier hos rotter har vist reduceret fertilitet hos hanner og hunner.
Fertility studies in rats have shown reduced male and female fertility.
Cabozantinib har ikke udvist mutagent eller klastogent potentiale i et standardbatteri af analyser til bestemmelse af genotoksicitet.
Cabozantinib has shown no mutagenic or clastogenic potential in a standard battery of genotoxicity assays.
Virkning med cabozantinib blev observeret hos patienter med medullær thyroideacancer med vildttype eller mutant RET.
Efficacy with cabozantinib was observed in medullary thyroid cancer patients with wild-type or mutant RET.
Reduktioner af dosis og seponering forekom hos henholdsvis 79 % og 72 % af patienter behandlet med cabozantinib i det pivotale kliniske studie.
Dose reductions and dose interruptions occurred in 79% and 72%, respectively, of cabozantinib-treated patients in the pivotal clinical trial.
• Absces (ansamling af pus, med hævelse og inflammation) i abdomen eller underlivsområdet eller i dine tænder/gummer
• Abscess (collection of pus, with swelling and inflammation) in the abdomen or pelvis area or in your teeth/gums
Galdesyrebindende midler såsom colestyramin og colesevelam kan interagere med cabozantinib og kan påvirke absorptionen (eller reabsorptionen) resulterende i potentielt nedsat eksponering (se pkt.
Bile salt-sequestering agents such as cholestyramine and cholestagel may interact with cabozantinib and may impact absorption (or reabsorption) resulting in potentially decreased exposure (see section 5.2).
Median for samlet overlevelse
Median Overall Survival
Det Europæiske Lægemiddelagentur har udskudt forpligtelsen at indsende resultaterne af studier med cabozantinib i en eller flere undergrupper af den pædiatriske population ved behandlingen af maligne, faste tumorer (se pkt.
The European Medicines Agency has deferred the obligation to submit the results of studies with cabozantinib in one or more subsets of the paediatric population in the treatment of malignant solid tumours (see section 4.2 for information on paediatric use).
• Nedsat hørelse
• Impaired hearing
Efter oral administration af cabozantinib opnås cabozantinib-peak-plasmakoncentrationer 2 til 5 timer efter dosering.
Following oral administration of cabozantinib, peak cabozantinib plasma concentrations are reached at 2 to 5 hours post-dose.
Cabozantinib (S)-malat
Cabozantinib (S)-malate
Derudover hæmmer cabozantinib andre tyrosinkinaser inklusive RET, GAS6receptoren (AXL), stamcellefaktor receptoren (KIT) og Fms-lignende tyrosinkinase-3 (FLT3).
In addition, cabozantinib inhibits other tyrosine kinases including RET, the GAS6 receptor (AXL), the stem cell factor receptor (KIT), and Fms-like tyrosine kinase-3 (FLT3).
• Smerter i armene, hænderne, benene eller fødderne
• Pain in the arms, hands, legs or feet
Alle tre undergrupper viste øget PFS i cabozantinib-armen sammenlignet med placebo-armen (HR'er på henholdsvis 0,23, 0,53, og 0,30 for RET-mutationspositive, -negative og ukendte undergrupper).
All three subgroups showed increased PFS in the cabozantinib arm compared to the placebo arm (HRs of 0.23, 0.53, and 0.30 for RET mutation positive, negative, and unknown subgroups, respectively).
Patienterne bør instrueres i ikke at spise noget i mindst 2 timer før og til og med 1 time efter at have taget COMETRIQ.
Patients should be instructed to not eat anything for at least 2 hours before through 1 hour after taking COMETRIQ.
Cabozantinib er et substrat for CYP3A4-metabolisme in vitro, som et neutraliserende antistof til CYP3A4-hæmmet dannelse af metabolit XL184 N-oxid med >80 % i en NADPH-katalyseret human lever mikrosomal (HLM) inkubation; som en kontrast havde neutraliserende antistoffer over for CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2D6 og CYP2E1 ingen effekt på dannelse af cabozantinib metabolit.
Cabozantinib is a substrate for CYP3A4 metabolism in vitro, as a neutralizing antibody to CYP3A4 inhibited formation of metabolite XL184 N-oxide by >80% in a NADPH-catalyzed human liver microsomal (HLM) incubation; in contrast, neutralizing antibodies to CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2D6 and CYP2E1 had no effect on cabozantinib metabolite formation.
En øgning fra baseline i korrigeret QT-interval efter Fridericia (QTcF) på 10 - 15 ms på dag 29 (men ikke på dag 1) efter indledning af behandling med cabozantinib (ved en dosis på 140 mg qd) blev observeret i et kontrolleret klinisk studie med cancerpatienter.
An increase from baseline in corrected QT interval by Fridericia (QTcF) of 10 - 15 ms on Day 29 (but not on Day 1) following initiation of cabozantinib treatment (at a dose of 140 mg qd) was observed in a controlled clinical study in cancer patients.
Ved brug af cabozantinib bør man overveje periodisk monitorering med EKG'er under behandlingen og elektrolytter (serum calcium, kalium og magnesium).
When using cabozantinib, periodic monitoring with on-treatment ECGs and electrolytes (serum calcium, potassium, and magnesium) should be considered.
Tæt monitorering af patienterne anbefales derfor under de første 8 ugers behandling (se pkt.
Close monitoring of patients is therefore recommended during the first eight weeks of therapy (see section 4.2).
Protein i urinen bør monitoreres regelmæssigt under behandling med cabozantinib.
Urine protein should be monitored regularly during cabozantinib treatment.
• Protein eller blod i urinen, galdesten, smertefuld vandladning
• Protein or blood in the urine, gallstones, painful urination
Patienter, der har bevis for involvering af trachea eller bronkierne af tumor eller en anamnese med hæmoptyse forud for indledning af behandlingen, bør evalueres omhyggeligt inden indledning af behandling med cabozantinib.
Patients who have evidence of involvement of the trachea or bronchi by tumour or a history of haemoptysis prior to treatment initiation should be carefully evaluated before initiating cabozantinib therapy.
Monitorér for bivirkninger og justér dosis eller anvend dosisafbrydelse efter behov (se pkt.
Monitor for adverse events and adjust dose or use dosing interruption as needed (see section 4.2).
Et multi-center, randomiseret dobbelt-blindet studie sammenlignende cabozantinib (N = 219) med placebo (N = 111) blev gennemført hos patienter med inoperable, lokalt fremskreden eller metastatisk MTC og dokumenteret radiografisk sygdomsprogression inden for 14 måneder forud for indtræden i studie.
A multi-center, randomized double-blind study comparing cabozantinib (N = 219) with placebo (N = 111) was conducted in patients with unresectable locally advanced or metastatic MTC and documented radiographic disease progression within 14 months prior to study entry.
ORR var henholdsvis 27,9 % og 0 % for forsøgspersoner i cabozantinib-armen og placebo-armen (p<0,0001; Tabel 2).
The ORR was 27.9% and 0% for subjects in the cabozantinib arm and placebo arm, respectively (p<0.0001; Table 2).
• Svaghed eller nedsat følelse eller prikken i lemmerne
• Weakness or reduced sensation or tingling in the limbs
I tilfælde af vedvarende hypertension på trods af anti-hypertensiver, bør dosis af cabozantinib reduceres.
In the case of persistent hypertension despite use of anti-hypertensives, the cabozantinib dose should be reduced.
Undgå at blive gravid under behandlingen med COMETRIQ.
Avoid becoming pregnant while being treated with COMETRIQ.
RET-mutation negative patienter uden bevis for RAS mutation (n=33) udviste en nedsat PFS-fordel på cabozantinib (HR på 0,87) og en lavere responsrate på 18 % sammenlignet med andre mutationsundergrupper.
RET mutation negative patients with no evidence of RAS mutation (n=33) showed a decreased PFS benefit on cabozantinib (HR of 0.87) and a lower response rate of 18% compared to other mutational subgroups.
• Lysnen af huden, hud i flager, usædvanlig bleg hud
• Lightening of skin, flakey skin, unusual pale skin
Opbevares i den originale emballage til beskyttelse mod fugt.
Store in the original package in order to protect from moisture.
Gentagen daglig dosering af cabozantinib på 140 mg i 19 dage resulterede i circa en 4- til 5-dobbelt middel cabozantinib akkumulation (baseret på AUC) sammenlignet med administration af en enkelt dosis; steady state opnås på cirka dag 15.
Repeat daily dosing of cabozantinib at 140 mg for 19 days resulted in an approximately a 4- to 5-fold mean cabozantinib accumulation (based on AUC) compared to a single dose administration; steady state is achieved by approximately Day 15.
• En tilstand, der kaldes posterior reversibel encefalopati syndrom (PRES) eller reversibel posterior leukoencefalopati syndrom (RPLS), der har symptomer såsom krampeanfald,
• A condition called posterior reversible encephalopathy syndrome (PRES) or reversible posterior leukoencephalopathy syndrome (RPLS), which has symptoms such as seizures, headaches,
Cabozantinib bør anvendes med forsigtighed til patienter med en anamnese for forlængelse af QTinterval, patienter, der tager anti-arytmetika, eller patienter med præ-eksisterende hjertelidelse, bradykardi eller elektrolytforstyrrelser.
Cabozantinib should be used with caution in patients with a history of QT interval prolongation, patients who are taking antiarrhythmics, or patients with relevant pre-existing cardiac disease, bradycardia, or electrolyte disturbances.
En oral undersøgelse børe foretages forud for start med cabozantinib og periodisk under behandlingen med cabozantinib.
An oral examination should be performed prior to initiation of cabozantinib and periodically during cabozantinib therapy.
Tabel 1: Bivirkninger rapporteret med cabozantinib
Table 1: Adverse reactions reported with cabozantinib
• Sår, der har svært ved at hele op
• Wounds that have difficulties healing
• Blodpropper i arterierne
• Blood clots in the arteries
Cabozantinib bør seponeres hos patienter, som udvikler et akut myokardieinfarkt eller nogen anden klinisk signifikant arteriel thromboembolisk komplikation.
Cabozantinib should be discontinued in patients who develop an acute myocardial infarction or any other clinically significant arterial thromboembolic complication.
Psykiske forstyrrelser angst, depression, konfus tilstand abnorme drømme, delirium
Psychiatric disorders anxiety, depression, confusional state abnormal dreams, delirium
Cabozantinib bør seponeres, hvis hypertension er svær og vedvarende på trods af anti-hypertensiv terapi og dosisreduktion af cabozantinib.
Cabozantinib should be discontinued if hypertension is severe and persistent despite anti-hypertensive therapy and dose reduction of cabozantinib.
Patienterne bør derfor overvåges nøje under de første otte ugers behandling (se pkt.
Patients should therefore be closely monitored during the first eight weeks of therapy (see section 4.4).
4,0 måneder
4.0 months
Hjerte atrieflimmer angina pectoris, supraventrikulær takykardi myokardieinfarkt
Cardiac disorders atrial fibrillation angina pectoris, supraventricular tachycardia myocardial infarction
20 mg og 80 mg
20 mg and 80 mg
Cabozantinib er et lille molekyle, der hæmmer multiple receptortyrosinkinaser (RTK'er) impliceret i tumorvækst og angiogenese, patologisk knogle genmodellering og metastatisk progression af cancer.
Cabozantinib is a small molecule that inhibits multiple receptor tyrosine kinases (RTKs) implicated in tumour growth and angiogenesis, pathologic bone remodeling, and metastatic progression of cancer.
Hvert blisterkort indeholder tilstrækkelig medicin til 7 dage.
Each blister card contains enough medicine for 7 days.
Samtidige administreret lægemidler
Concomitant medicinal products
Ligeledes kan visse andre lægemidler påvirke den måde, som COMETRIQ fungerer.
Also, some medicines can affect the way COMETRIQ works.
Kliniske data i medullær thyroideacancer
Clinical data in medullary thyroid cancer
4.5 Interaktion med andre lægemidler og andre former for interaktion Virkningen af andre lægemidler på cabozantinib
4.5 Interaction with other medicinal products and other forms of interaction
Hos kaniner producerede cabozantinib ændringer i føtalt bløddelsvæv (reduceret størrelse på milten, lille eller manglende intermediær lunge-del) og øget føtal incidens af totale misdannelser.
In rabbits, cabozantinib produced foetal soft tissue changes (reduced spleen size, small or missing intermediate lung lobe) and increased foetal incidence of total malformations.
Cabozantinib bør seponeres hos patienter, der oplever en GI perforation eller en GI eller ikke-GI fistel.
Cabozantinib should be discontinued in patients who experience a GI perforation or a GI or non-GI fistula.
Kontrol af formodede lægemiddelbivirkninger kan betyde midlertidig seponering og/eller dosisreduktion ved behandlingen med COMETRIQ.
Management of suspected adverse drug reactions may require temporary interruption and/or dose reduction of COMETRIQ therapy.
COMETRIQ indeholder
What COMETRIQ contains
Hvis du har glemt at tage COMETRIQ
If you forget to take COMETRIQ
Ikke almindelig (≥1/1.000 til
Uncommon (1/1,000 to
Behandling med cabozantinib bør om muligt stoppes mindst 28 dage forud for planlagt operation.
Cabozantinib treatment should be stopped at least 28 days prior to scheduled surgery, if possible.
I tilfælde af mistanke om overdosering bør cabozantinib seponeres og understøttende behandling skal indledes.
In the event of suspected overdose, cabozantinib should be withheld and supportive care instituted.
Kvinder i den fertile alder/antikonception hos mænd og kvinder Kvinder i den fertile alder skal tilrådes at undgå graviditet, mens de får cabozantinib.
Women of childbearing potential/Contraception in males and females Women of childbearing potential must be advised to avoid pregnancy while on cabozantinib.
Thromboemboliske bivirkninger
Thromboembolic events
Cabozantinib kan derfor have potentialet til at øge plasmakoncentrationerne af co-administrerede substrater af P-gp.
Therefore, cabozantinib may have the potential to increase plasma concentrations of co-administered substrates of P-gp.
Du bør ikke spise noget i mindst 2 timer før, du tager COMETRIQ og i 1 time efter at have taget lægemidlet.
You should not eat anything for at least 2 hours before taking COMETRIQ and for 1 hour after taking the medicine.
I tilfælde af hypertensiv krise, bør cabozantinib seponeres.
In case of hypertensive crisis, cabozantinib should be discontinued.
Det skal du vide, før du begynder at tage COMETRIQ 3.
What you need to know before you take COMETRIQ 3.
I det 2-årige karcinogenicitetsstudie med rotter bestod de cabozantinib-relaterede neoplastiske fund af en øget forekomst af benignt fæokromocytom, alene eller i kombination med malignt fæokromocytom/komplekst malignt fæokromocytom i binyremarven hos begge køn ved eksponering et stykke under den tilsigtede eksponering hos mennesker.
In the 2-year rat carcinogenicity study, cabozantinib-related neoplastic findings consisted of an increased incidence of benign pheochromocytoma, alone or in combination with malignant pheochromocytoma/complex malignant pheochromocytoma of the adrenal medulla in both sexes at exposures well below the intended exposure in humans.