natgillin/translations-raw huggingface dataset:
Baseret på den farmakokinetiske populationsanalyse påvirker let til moderat nedsat nyrefunktion ikke eksponeringen af cobimetinib.
Mild to moderate renal impairment does not influence cobimetinib exposure based on the population pharmacokinetic analysis.
Ældre
Increased ALT
Afhængig af sværhedsgraden af rabdomyolyse, kan dosisreducering eller afbrydelse af behandling kræves (se pkt.
Depending on the severity of rhabdomyolysis, dose reduction or treatment discontinuation may be required (see section 4.2).
Fald i LVEF i forhold til baseline kan håndteres med behandlingsafbrydelse, dosisreduktion eller seponering (se pkt.
Decrease in LVEF from baseline can be managed using treatment interruption, dose reduction or with treatment discontinuation (see section 4.2).
ANGIVELSE AF AKTIVT STOF/AKTIVE STOFFER Hver filmovertrukken tablet indeholder cobimetinibhemifumarat svarende til 20 mg cobimetinib.
STATEMENT OF ACTIVE SUBSTANCE(S) Each film-coated tablet contains cobimetinib hemifumarate equivalent to 20 mg cobimetinib
Cotellics farmakokinetik er ikke undersøgt hos pædiatriske patienter.
No studies have been conducted to investigate the pharmacokinetics of cobimetinib in paediatric patients.
Forekomsten af lysfølsomhedsreaktioner var højere i Cotellic-plus-vemurafenib-armen end i placeboplus-vemurafenib-armen (47% versus 35%).
Photosensitivity has been observed with a higher frequency in the Cotellic plus vemurafenib arm vs placebo plus vemurafenib arm (47% vs 35%).
Cortellic-behandling skal seponeres permanent hvis ikke rabdomyolyse eller symptomatiske stigninger i kreatinkinase forbedres indenfor 4 uger.
If rhabdomyolysis or symptomatic CPK elevations do not improve within 4 weeks, Cotellic treatment should be permanently discontinued.
Der skal monitoreres for abnorme leverværdier inden påbegyndelse af behandlingen samt månedligt under behandlingen eller oftere, hvis klinisk indiceret (se pkt.
Liver value abnormalities should be monitored by liver laboratory tests before initiation of combination treatment and monthly during treatment, or more frequently as clinically indicated (see section 4.2).
Lægen bør individuelt diskutere, om fordelene ved behandlingen opvejer risiciene med patienter med arvelig galactoseintolerans, en særlig form for arvelig lactasemangel (Lapp Lactase deficiency) eller glucose/galactose-malabsorption.
Patients with rare hereditary problems of galactose intolerance, congenital lactase deficiency or glucose-galactose malabsorption should consult with their physician and discuss whether the benefits outweigh the risks on an individual basis.
4% af patienterne i Cotellic-plus-vemurafenib-armen oplevede bivirkninger af grad ≥ 3 versus 0% i placeboplus-vemurafenib-armen.
The majority of events were Grades 1 or 2, with Grade ≥3 events occurring in 4% of patients in the Cotellic plus vemurafenib arm vs 0% in the placebo plus vemurafenib arm.
Asymptomatiske stigninger i kreatinkinase
Asymptomatic CPK elevations
Hvis blødninger opstår, skal de behandles som klinisk indiceret (se pkt.
If haemorrhage occurs, treat as clinically indicated (see section 4.2 and 4.4).
Serum kreatinkinase- og kreatininniveauer bør monitoreres inden behandlingen startes for at etablere en værdi for baseline.
Serum CPK and creatinine levels should be measured before initiation of treatment, to establish baseline values, and then monitored monthly during treatment, or as clinically indicated.
Vejledning i dosisændringer ved blødning
Dose modification advice for haemorrhage
Dette protein har stor betydning for kontrollen af kræftcellernes vækst.
These measures will help to protect the environment.
Analyse stratificeret i forhold til geografisk region og metastase-klassifikation (sygdomsstadie) c Ved hjælp af Clopper-Pearsons metode d
Using Clopper-Pearson method d Using Hauck-Anderson method e
Hvis kreatinkinase forbedres til grad ≤ 3 inden for 4 uger, kan Cotellic-behandling genoptages ved en dosis reduceret med 20 mg, hvis det er klinisk indiceret.
If CPK improves to Grade ≤3 within 4 weeks, Cotellic could be restarted, if clinically indicated, at a dose reduced by 20 mg and the patient should be closely monitored.
Grad 4: Behandling med Cotellic og vemurafenib afbrydes.
Cotellic treatment and vemurafenib treatment should be interrupted.
Genoptagelse af Cotellic-behandling skal baseres på klinisk vurdering.
Clinical judgment should be applied when considering restarting Cotellic treatment.
Forhøjet ASAT
Increased AST
Der blev indberettet færre tilfælde af hyperkeratose i Cotellic-plusvemurafenib-armen end i placebo-plus-vemurafenib-armen (alle grader: 11% versus 30%).
Hyperkeratosis has been reported with a lower frequency in the Cotellic plus vemurafenib vs placebo plus vemurafenib arm (all Grade: 11% vs 30%).
I Cotellic-plus-vemurafenib-armen var median tiden 6.1 måned før første blødning.
The median time to first onset was 6.1 months in the Cotellic plus vemurafenib arm.
Serøs retinopati
Renal impairment
495 tidligere ubehandlede patienter med ikke-operabelt, lokalt fremskredent eller metastatisk melanom blev, efter BRAF-V600-mutation var verificeret ved hjælp af cobas® 4800 BRAF-V600-mutationstest,
Following confirmation of a BRAF V600 mutation, using the cobas® 4800 BRAF V600 mutation test,
Vaskulære sygdomme Hypertension, blødning* Luftveje, thorax og mediastinum
Respiratory, thoracic and mediastinal disorders
Der er indberettet fald i LVEF i forhold til baseline hos patienter behandlet med Cotellic (se pkt.
Decrease in LVEF from baseline has been reported in patients receiving Cotellic (see section 4.4).
Se produktresuméet for vemurafenib.
Please refer to the vemurafenib SmPC.
Hauck-Anderson metode er anvendt e p-værdi for den samlede overlevelse (0,0050) krydsede den tidligere specificerede grænse (p værdi <0,0499)
The OS p-value (0.0050) crossed the pre-specified boundary (p value <0.0499) f The data cut-off date for this updated PFS analysis and the secondary endpoints of ORR, BOR and DoR is 16 January 2015.
Der blev indberettet færre tilfælde af keratoakantom i Cotellic-plus-vemurafenib-armen end i placebo-plus-vemurafenib-armen (alle grader: 2% versus 9%).
Keratoacanthoma has been reported with a lower frequency in the Cotellic plus vemurafenib arm vs placebo plus vemurafenib arm (all Grade: 2% vs 9%).
Muskelproblemer (ikke almindelige: kan optræde hos op til 1 ud af 100 patienter) Cotellic kan forårsage muskelbeskadigelse (rabdomyolyse).
Muscle problems (uncommon: may affect up to 1 in 100 people) Cotellic can result in the breakdown of muscle (rhabdomyolysis), symptoms may include: · muscle aches · muscle spasms and weakness · dark- or red-coloured urine.
Potente CYP3A-hæmmere inkluderer, men er ikke begrænset til, ritonavir, cobicistat, telaprevir, lopinavir, itraconazol, voriconazol, clarithromycin, telithromycin,
cobicistat, telaprevir, lopinavir, itraconazole, voriconazole, clarithromycin, telithromycin, posaconazole, nefazodone and grapefruit juice.
Hvis det er klinisk indiceret, kan vemurafenib-dosering fortsættes, mens Cotellic-behandlingen afbrydes.
Vemurafenib dosing can be continued when Cotellic treatment is interrupted, if clinically indicated.
Rabdomyolyse***
Rhabdomyolysis***
Baseret på farmakokinetiske populationsanalyser er dosisjustering ikke nødvendig til patienter med let til moderat nedsat nyrefunktion (se pkt.
No dose adjustment is recommended in patients with mild or moderate renal impairment based on population pharmacokinetic analysis (see section 5.2).
Primært endepunktaf
Primary Endpoint a, f
Hvis du har taget for meget Cotellic
If you take more Cotellic than you should
4.4 Særlige advarsler og forsigtighedsregler vedrørende brugen Før anvendelse af Cotellic i kombination med vemurafenib skal det bekræftes ved en valideret test, at patienten tumorstatus er BRAF-V600-mutationspositiv.
Before taking Cotellic in combination with vemurafenib, patients must have BRAF V600 mutationpositive tumour status confirmed by a validated test.
Er du i tvivl, så spørg lægen eller apotekspersonalet.
· If you have any further questions, ask your doctor, pharmacist or nurse.
Der blev indberettet færre tilfælde af kutant pladecellekarcinom i Cotellic-plus-vemurafenib-armen end i placebo-plus-vemurafenib-armen (alle grader: 3% versus 13%).
Cutaneous squamous cell carcinoma has been reported with a lower frequency in the Cotellic plus vemurafenib arm vs placebo plus vemurafenib arm (all Grade: 3% vs 13%).
(eller og < 10% absolut fald fra baseline)
(or 40-49% and < 10% absolute decrease from baseline)
Kontakt lægen, inden du tager denne medicin, hvis lægen har fortalt dig, at du ikke tåler visse former for sukker.
If you have been told by your doctor that you have an intolerance to some sugars, talk to your doctor before taking this medicine.
Cotellic-behandling skal seponeres permanent hvis ikke stigninger i kreatinkinase forbedres til grad ≤ 3 inden for 4 uger efter dosis afbrydelse.
If CPK elevations do not improve to Grade ≤3 within 4 weeks following dose interruption, Cotellic treatment should be permanently discontinued.
Mediantiden til debut af de første grad ≥ 3 bivirkninger var 0,6 måned i Cotellic-plus-vemurafenib-armen versus 0,8 måned i placebo-plusvemurafenib-armen.
The safety of Cotellic in combination with vemurafenib has been evaluated in 247 patients with advanced BRAF V600 mutated melanoma in Study GO28141.The median time to onset for the first Grade ≥3 adverse events was 0.6 months in the Cotellic plus vemurafenib arm vs 0.8 months in the placebo plus vemurafenib arm.
Sekundære nøgle-endepunkteraf
Tablet core
I kliniske studier er der rapporteret synsforstyrrelser hos patienter behandlet med cobimetinib (se pkt.
Visual disturbances have been reported in some patients treated with cobimetinib during clinical trials (see sections 4.4 and 4.8).
INFORMATION I BRAILLESKRIFT cotellic
INFORMATION IN BRAILLE
Baseret på farmakokinetiske populationsanalyser er dosisjustering ikke nødvendig hos patienter med let til moderat nedsat nyrefunktion.
Dose adjustment is not recommended for mild to moderate renal impairment based on the results of the population pharmacokinetic analysis.
Hvis det er klinisk indiceret, kan behandlingen med vemurafenib fortsætte, mens behandlingen med Cotellic ændres.
Vemurafenib treatment can be continued when Cotellic treatment is modified, if clinically indicated.
Der er rapporteret rabdomyolyse hos patienter, der får Cotellic (se pkt.
Rhabdomyolysis has been reported in patients receiving Cotellic (see section 4.8).
Hud og subkutane væv Lysoverfølsomhedb, udslæt, makulopapuløst udslæt, akneiform dermatitis, hyperkeratose**
Photosensitivityb, Rash, Rash maculo-papular, Dermatitis acneiform, Hyperkeratosis**
f
c
Der er ikke gennemført farmakokinetiske studier med patienter med nedsat nyrefunktion.
No pharmacokinetic trial in subjects with renal impairment has been conducted.
LVEF
LVEF value
Det er vigtigt, at du bliver ved med at tage Cotellic lige så længe, lægen har ordineret det. Spørg lægen, apotekspersonalet eller sundhedspersonalet, hvis der er noget, du er i tvivl om.
It is important to keep taking Cotellic for as long as your doctor prescribes it.
De harmoniserede områder omfatter følgende:
The areas harmonised include:
Den 12. september 2013 EMA/319080/2013 Rev.1 EMEA/H/A-30/1301
EMA/319080/2013 Rev.1 EMEA/H/A-30/1301
Europa-Kommissionen traf en afgørelse den 12. september 2013.
The European Commission issued a decision on 12 September 2013.
Targocid blev godkendt i EU via nationale procedurer.
Targocid is authorised in the EU via national procedures.
Hvad er Targocid?
What is Targocid?
Den virksomhed, der markedsfører disse lægemidler, er Sanofi-Aventis.
The company that markets these medicines is Sanofi-Aventis.
Lægemidlets koncentration i blodet bør måles for at sikre, at der er opnået et effektivt niveau.
The amount of the medicine in the blood should be measured to ensure that effective levels have been reached.
Hvorfor blev Targocid vurderet igen?
Why was Targocid reviewed?
Den 30. maj 2013 afsluttede Det Europæiske Lægemiddelagentur en gennemgang af Targocid.
On 30 May 2013, the European Medicines Agency completed a review of Targocid.
Targocid fås desuden i EU under andre handelsnavne: Targosid, Teicomid.
Targocid is also available in the EU under other trade names: Targosid, Teicomid.
Udvalget anbefalede ikke anvendelse af Targocid til forebyggelse af infektioner.
The Committee did not recommend the use of Targocid to prevent infections.
Udvalget fastlagde desuden dosisområder for voksne og børn (fra fødslen) for de forskellige infektioner.
The Committee also agreed on specific dose ranges for adults and children (from birth) for the various infections.
Targocid er et antibiotikum, der indeholder det aktive stof teicoplanin.
Targocid is an antibiotic that contains the active substance teicoplanin.
Targocid bør anvendes til behandling af alvorlige infektioner, hvor sædvanlig antibiotisk behandling ikke er hensigtsmæssig.
Targocid should be used to treat severe infections where standard antibiotic treatment is not suitable.
CHMP harmoniserede desuden andre afsnit af produktresuméet, herunder afsnit 4.3 (kontraindikationer), 4.5 (interaktion med andre lægemidler), 4.6 (anvendelse under graviditet og amning), 4.8 (bivirkninger), 5.1 (farmakodynamiske egenskaber), 5.2 (farmakokinetiske egenskaber) og 5.3 (prækliniske sikkerhedsdata).
The Committee also harmonised other sections of the SmPC, including sections 4.3 (contraindications), 4.5 (interactions with other medicines), 4.6 (use in pregnancy and breast feeding), 4.8 (undesirable effects), 5.1 (pharmacodynamic properties), 5.2 (pharmacokinetic properties) and 5.3 (preclinical safety data).
Det aktive stof, teicoplanin, tilhører en gruppe antibiotika, der kaldes glykopeptider.
The active substance, teicoplanin, is one of a group of antibiotics known as glycopeptides.
CHMP vedtog, at Targocid bør anvendes ved injektion eller infusion til behandling af følgende infektioner hos voksne og børn:
The CHMP agreed that Targocid should be used by injection or infusion to treat the following infections in adults and children:
Langvarig brug kan medføre vækst af bakterier, som det ikke virker mod.
Prolonged use may encourage the growth of bacteria against which it is not active.
Den 17. november 2011 indbragte Europa-Kommissionen sagen for CHMP med henblik på at harmonisere markedsføringstilladelserne for Targocid i EU.
On 17 November 2011, the European Commission referred the matter to the CHMP in order to harmonise the marketing authorisations for Targocid in the EU.
Dette har ført til afvigelser mellem medlemsstaterne i den måde, lægemidlet kan anvendes på, således som det fremgår af forskellene i produktresuméer, etikettering og indlægssedler i de lande, hvor lægemidlet markedsføres.
This has led to divergences across Member States in the way the medicine can be used, as seen in the differences in the summaries of product characteristics (SmPCs), labelling and package leaflets in the countries where the medicine is marketed.
Udvalget anmodede den virksomhed, der markedsfører lægemidlet, om at indsende en risikostyringsplan for sikker anvendelse af Targocid, herunder en undersøgelse til overvågning af sikkerheden af den øgede anbefalede startdosis (12 mg/kg kropsvægt to gange dagligt).
The Committee asked the company that markets the medicine to submit a risk management plan for the safe use of Targocid, including a study to monitor the safety of the increased initial dose recommendations (12 mg per kg body-weight twice daily).
• bakteriæmi (bakterieinfektion i blodet) forårsaget af en af ovennævnte tilstande.
• bacteraemia (bacterial infection in the blood) resulting from any of the above.
Dette omfattede start- og vedligeholdelsesdoser samt doser til patienter med nedsat nyrefunktion.
This includes initial doses as well as doses for maintenance treatment and doses to be used in patients with reduced kidney function.
Det virker ved at binde sig til bakteriernes overflade.
It works by attaching to the surface of bacteria.
Da Targocid kun er effektivt mod visse bakteriearter, bør det om nødvendigt anvendes i kombination med andre antibiotika og i henhold til officielle anbefalinger for anvendelse af antibiotika.
Since Targocid is only effective against certain kinds of bacteria, it should be used in combination with other antibiotics if necessary, and in line with official recommendations on antibiotic use.
Agenturets Udvalg for Lægemidler til Mennesker (CHMP) konkluderede, at der er behov for harmonisering af produktinformationen for Targocid i Den Europæiske Union (EU).
The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that there is a need to harmonise the prescribing information for Targocid in the European Union (EU).
• endokarditis (infektion af hjertets indervæg - oftest hjerteklapperne)
• endocarditis (infection of the inner lining of the heart - most commonly the valves of the heart);
Det er kun effektivt mod bestemte typer bakterier (grampositive bakterier) og bør om nødvendigt anvendes i kombination med andre antibiotika.
It is only effective against certain types of bacteria (called Gram-positive bacteria) and should be used in combination with other antibiotics if necessary.
Det anvendes til injektion eller infusion (med drop) til behandling af alvorlige bakterielle infektioner.
It is used by injection or infusion (drip) to treat serious bacterial infections.
Særlig omhyggelig overvågning kræves, hvis patienten får højere startdosis (12 mg/kg kropsvægt to gange dagligt).
Patients should be particularly carefully monitored if given higher initial doses (12 mg per kg body-weight twice daily).
For visse typer infektioner fastlagde CHMP en højere begyndelsesdosis på 12 mg/kg kropsvægt to gange dagligt (som anvendes i enkelte medlemsstater i EU).
For certain types of infections, a higher initial dose of 12 mg per kg body-weight twice daily (used in a few member states of the EU), was agreed by the CHMP.
Andre mulige effekter, der kan gøre det nødvendigt at stoppe eller ændre behandlingen, er infusionsrelaterede reaktioner (såkaldt “red man syndrome” alvorligt hududslæt, trombocytopeni (lavt indhold i blodet af blodplader, som er vigtige for blodets evne til at størkne), nyrebeskadigelse og påvirkning af hørelsen.
Other possible effects for which treatment may need to be stopped or altered include infusion-related reactions called ‘red man syndrome', severe skin rashes, thrombocytopenia (low blood-levels of cells called platelets that are important for clotting), kidney damage, and effects on hearing.
Under behandlingen anbefales regelmæssig kontrol af blodet og nyrefunktionen samt overvågning af eventuel påvirkning af hørelsen.
Regular blood and kidney function tests and monitoring of any effects on hearing are recommended during treatment.
• lungebetændelse, der er hospitals- eller samfundserhvervet (erhvervet på eller uden for hospitalet).
• hospital- or community-acquired pneumonia (infection of the lung caught in or outside hospital);
Hertil hører, at Targocid kan forårsage alvorlige livstruende allergiske reaktioner (hypersensitivitetsreaktioner), som kræver øjeblikkeligt ophør af behandling og akut behandling med lægemidlet; ved allergi over for et andet antibiotikum, vancomycin.
These include the fact that Targocid may cause serious life-threatening hypersensitivity (allergic) reactions which require immediate cessation of the medicine and emergency treatment; care is needed in patients who are allergic to another antibiotic, vancomycin, as they may be at greater risk.
• komplicerede infektioner i hud og underliggende væv
• complicated infections of the skin and soft-tissues;
Koordinationsgruppen Vedrørende Gensidig Anerkendelse og Decentraliserede Godkendelsesprocedurer - human (CMD(h)) fandt harmonisering for Targocid nødvendig.
Targocid was identified as needing harmonisation by the Co-ordination Group for Mutual Recognition and Decentralised Procedures - Human (CMDh).
Udvalget fandt desuden, at Targocid kunne gives gennem munden til behandling af diarré og inflammation af tarmen (colitis) forårsaget af infektion med bakterien Clostridum difficile.
The Committee also agreed that Targocid could be taken by mouth to treat diarrhoea and colitis (inflammation of the bowel) associated with infection by bacteria called Clostridium difficile.
Det kan desuden gives gennem munden til behandling af diarré og inflammation af tarmen (colitis) forårsaget af bakterien Clostridum difficile.
It can also be given by mouth to treat diarrhoea and colitis (inflammation of the bowel) caused by infection with a bacterium called Clostridum difficile.
• infektioner i knogler og led
• bone and joint infections;
• peritonitis (inflammation af peritoneum, dvs. den membran, der beklæder bughulen indvendigt)
• peritonitis (inflammation of the peritoneum, the membrane lining the abdominal cavity) in patients undergoing ‘continuous ambulatory peritoneal dialysis';
4.4 Særlige advarsler og forsigtighedsregler vedrørende brugen CHMP vedtog at harmonisere advarsler og forsigtighedsregler for lægemidlet.
The CHMP agreed to harmonise the warnings and precautions for the medicine.
• komplicerede urinvejsinfektioner
• complicated urinary tract infections (infections of the structures that carry urine);
EMA nummer
EMA Number
Proceduren blev derfor henvist til CHMP i oktober 2008.
The procedure was therefore referred to the CHMP in October 2008.
Det har været markedsført siden 1979 til intramuskulær anvendelse.
It has been marketed since 1979, for intramuscular use.
Sammendrag af rapporten fra BPWP og CHMP's holdning:
Summary of the report from the BPWP and CHMP position:
Ansøgeren forelagde endvidere eksponeringsdata, hvoraf det fremgik, at der i alt var givet ca. 143.589 injektioner til patienter.
The Applicant also provided exposure data, stating that a total of about 143,589 injections were given to patients.
Hvilke ikkekliniske undersøgelser skal der i bekræftende fald foretages?
And if yes, what kind of non-clinical studies shall be performed?
SAMLET RESUMÉ AF DEN FAGLIGE VURDERING AF UMAN BIG
OVERALL SUMMARY OF THE SCIENTIFIC EVALUATION OF UMAN BIG
CHMP er derfor af den mening, at benefit/risk-forholdet for produktet kan betragtes som positivt, og at produktet kan godkendes.
Therefore, the CHMP is of the opinion that the benefit/risk balance of the product can be considered to be positive and that the product is approvable.
Der blev nået niveauer af antistoffer på ≥100IE/ml.
Levels of antibodies of ≥100IU/ml were achieved.
Der er også set et begrænset antal tilfælde af kvalme, opkastning, hypotension, takykardi og allergiske eller anafylaktiske reaktioner.
Limited cases of nausea, vomiting, hypotension, tachycardia, allergic or anaphylactic reactions have also been reported.
Selv om referencemedlemsstaten konkluderede, at indsigelserne var blevet afklaret, var den berørte medlemsstat, der havde gjort indsigelser, stadig af den opfattelse, at der var påvist en potentiel alvorlig risiko for folkesundheden ved dette specifikke produkt for så vidt angår sikkerhed og effekt.
Although the Reference Member State concluded that the objections raised had been resolved, the Objecting Concerned Member State was still of the opinion that a potential serious risk to public health was identified for this particular product, with regards to safety and efficacy.
Specifikke neutraliserende antistoffer imod hepatitis B-virus forekommer ved en koncentration på ikke mindre end 180 IE/ml.
Specific neutralizing antibodies against the Hepatitis B virus are present at a concentration of not less than 180 IU/ml.