natgillin/translations-raw huggingface dataset:
6. 6, bør den endelige koncentration ikke overstige 10 mg/ ml.
When prepared according to the instructions given in section 6.6, the final panitumumab concentration should not exceed 10 mg/ ml.
Panitumumab er et humant monoklonalt IgG2- antistof, der er produceret i en pattedyrscelle (CHO) vha. rekombinant DNA- teknologi.
Panitumumab is a human monoclonal IgG2 antibody produced in a mammalian cell line (CHO) by recombinant DNA technology.
Hver ml koncentrat indeholder 0, 150 mmol natrium, som er 3, 45 mg natrium.
Each ml of concentrate contains 0.150 mmol sodium, which is 3.45 mg sodium.
Farveløs opløsning, der kan indeholde synlige amorfe panitumumab- partikler.
Colourless solution that may contain visible amorphous panitumumab particles.
Vectibix er indiceret som monoterapi til patienter med EGFR- eksprimerende, metastatisk colorectalt carcinom, hvis tumorer indeholder ikke- muteret (vildtypen) KRAS, når kemoterapi- regimener, der indeholder fluoropyrimidin, oxaliplatin og irinotecan, har fejlet.
Vectibix is indicated as monotherapy for the treatment of patients with EGFR expressing metastatic colorectal carcinoma with non-mutated (wild-type) KRAS after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.
Behandling med Vectibix bør overvåges af en læge, der er erfaren i anvendelsen af anticancerterapi.
Vectibix treatment should be supervised by a physician experienced in the use of anti-cancer therapy.
Detektering af ikke- muteret KRAS- eksprimering skal foretages af et laboratorium med erfaring, som anvender en valideret testmetode.
Detection of non-mutated KRAS expression should be performed by an experienced laboratory using a validated test method.
Den anbefalede dosis af Vectibix er 6 mg/ kg af legemsvægten indgivet én gang hver anden uge.
The recommended dose of Vectibix is 6 mg/ kg of bodyweight given once every two weeks.
6. 6 vedrørende klargøringsanvisninger).
Prior to infusion, Vectibix should be diluted in 0.9% sodium chloride injection to a final concentration not to exceed 10 mg/ ml (for preparation instructions see section 6.6).
Vectibix skal indgives som en intravenøs (IV) infusion via en infusionspumpe med et indbygget lavt proteinbindende 0, 2 eller 0, 22 μm integreret filter gennem en perifer slange eller et indlagt kateter.
Vectibix must be administered as an intravenous (IV) infusion via an infusion pump, using a low protein binding 0.2 or 0.22 micrometer in-line filter, through a peripheral line or indwelling catheter.
60 minutter.
The recommended infusion time is approximately 60 minutes.
6. 6 vedrørende håndteringsanvisninger).
Doses higher than 1000 mg should be infused over approximately 90 minutes (for handling instructions, see section 6.6).
Infusionsslangen bør skylles med en natriumchloridopløsning før og efter indgivelse af Vectibix for at undgå at blande med andre medicinske produkter eller IV- opløsninger.
The infusion line should be flushed with sodium chloride solution before and after Vectibix administration to avoid mixing with other medicinal products or IV solutions.
Vectibix må ikke indgives som en intravenøs stød - eller bolusdosis.
Do not administer as an IV push or bolus.
2 Særlige populationer
2 Special populations
Vectibix 'sikkerhed og effekt er ikke undersøgt hos patienter med nyre - eller leversvækkelse.
The safety and efficacy of Vectibix have not been studied in patients with renal or hepatic impairment.
Dosisjustering er ikke påkrævet hos ældre.
Dose adjustment is not required in the elderly.
I kliniske undersøgelser blev der ikke observeret nogen generelle forskelle i sikkerhed og effekt på patienter i alderen ≥ 65 år og yngre patienter.
In clinical studies no overall differences in safety or efficacy were observed between patients aged ≥ 65 years and younger patients.
Der er ingen erfaring med behandling af børn, og Vectibix bør ikke anvendes til patienter, der er yngre end 18 år.
There is no experience in children and Vectibix should not be used in those patients less than 18 years of age.
4. 4).
Patients with interstitial pneumonitis or pulmonary fibrosis (see Section 4.4).
Størstedelen er milde til moderate af beskaffenhed.
Dermatologic related reactions, a pharmacologic effect observed with epidermal growth factor receptor (EGFR) inhibitors, are experienced with nearly all patients (approximately 90%) treated with Vectibix (see section 4.8), the majority are mild to moderate in nature.
Hvis en patient udvikler dermatologiske reaktioner, der er af klasse 3 (NCI- CTC/ CTCAE) eller højere, eller som betragtes som utålelige, skal indgivelse af Vectibix midlertidigt tilbageholdes, indtil reaktionerne er forbedret (≤ klasse 2).
If a patient develops dermatologic reactions that are grade 3 (NCI-CTC/ CTCAE) or higher, or that are considered intolerable, temporarily withhold Vectibix administration until the reactions have improved (≤ grade 2).
Når de er forbedret til ≤ klasse 2, skal indgivelse af Vectibix genindsættes ved 50% af den oprindelige dosis.
Once improved to ≤ grade 2, reinstate Vectibix administration at 50% of the original dose.
Hvis reaktionerne ikke genopstår, skal dosis af Vectibix optrappes med intervaller på 25%, indtil den anbefalede dosis er nået.
If reactions do not recur, escalate the dose of Vectibix by 25% increments until the recommended dose is reached.
Hvis reaktionerne ikke forsvinder (til ≤ klasse 2) efter at have tilbageholdt 1 eller 2 doser af Vectibix, eller hvis reaktionerne genopstår eller bliver utålelige ved 50% af den oprindelige dosis, skal anvendelsen af Vectibix ophøre permanent.
If reactions do not resolve (to ≤ grade 2) after withholding 1 or 2 doses of Vectibix, or if reactions recur or become intolerable at 50% of the original dose, the use of Vectibix should be permanently discontinued.
Der blev i kliniske forsøg, efter udviklingen af alvorlige dermatologiske reaktioner (herunder stomatitis), rapporteret infektiøse komplikationer, herunder sepsis, i sjældne tilfælde med døden til følge, samt lokale abscesser, hvor incisioner og drænage var påkrævet.
In clinical studies, subsequent to the development of severe dermatological reactions (including stomatitis), infectious complications including sepsis, in rare cases leading to death, and local abscesses requiring incisions and drainage were reported.
Patienter, der har alvorlige dermatologiske reaktioner, eller som udvikler reaktioner, der forværres, mens de får Vectibix, bør monitoreres med henblik på udvikling af inflammatoriske eller infektiøse følgevirkninger, og en behørig behandling bør straks påbegyndes.
Patients who have severe dermatologic reactions or who develop worsening reactions whilst receiving Vectibix should be monitored for the development of inflammatory or infectious sequelae, and appropriate treatment promptly initiated.
Det anbefales, at patienterne anvender solbeskyttelsescreme og hat og begrænser soleksponering, mens de får Vectibix og oplever udslæt/ dermatologiske toksicitet, da sollys kan forværre eventuelle hudreaktioner, der kan opstå.
It is recommended that patients wear sunscreen and hats and limit sun exposure whilst receiving Vectibix and experiencing rash/ dermatological toxicities, as sunlight can exacerbate any skin reactions that may occur.
Pulmonære komplikationer
Pulmonary complications
Patienter med tidligere eller tegn på interstitiel pneumonitis eller pulmonær fibrose blev ekskluderet fra kliniske forsøg.
Patients with a history of, or evidence of, interstitial pneumonitis or pulmonary fibrosis were excluded from clinical studies.
Da interstitiel lungesygdom (ILD) er blevet observeret med EGFR- hæmmere i tilfælde af akut fremkomst eller forværring af pulmonære symptomer, bør behandlingen med Vectibix afbrydes, og der bør foretages en omgående undersøgelse af disse symptomer.
As Interstitial Lung Disease (ILD) has been observed with EGFR inhibitors, in the event of acute onset or worsening pulmonary symptoms, Vectibix treatment should be interrupted and a prompt investigation of these symptoms should occur.
Hvis pneumonitis eller lungeinfiltrater diagnosticeres, bør Vectibix seponeres, og patienten bør behandles behørigt.
If pneumonitis or lung infiltrates are diagnosed, Vectibix should be discontinued and the patient should be treated appropriately.
Der er observeret tiltagende fald i serum- magnesiumniveauerne, hvilket har ført til svær (grad 4) hypomagnesiæmi hos nogle patienter.
Progressively decreasing serum magnesium levels leading to severe (grade 4) hypomagnesaemia have been observed in some patients.
3 Andre elektrolytforstyrrelser, herunder hypokaliæmi er også observeret.
3 Other electrolyte disturbances, including hypokalaemia, have also been observed.
Retablering af disse elektrolytter anbefales også efter behov.
Repletion of these electrolytes is also recommended, as appropriate.
Dette medicinske produkt indeholder 0, 150 mmol natrium (som er 3, 45 mg natrium) pr. ml koncentrat.
This medicinal product contains 0.150 mmol sodium (which is 3.45 mg sodium) per ml of concentrate.
Vectibix kombineret med IFL
Vectibix in combination with IFL
4. 5).
Patients receiving Vectibix in combination with the IFL regimen [bolus 5-fluorouracil (500 mg/ m2), leucovorin (20 mg/ m2) and irinotecan (125 mg/ m2)] experienced a high incidence of severe diarrhoea (see section 4.8), therefore administration of Vectibix in combination with IFL should be avoided (see section 4.5).
Vectibix kombineret med bevacizumab og andre kemoterapeutiske regimener
Vectibix in combination with bevacizumab and chemotherapy regimens
I et randomiseret, open- label multicenterforsøg med 1053 patienter evaluerede man effekten af bevacizumab og kemoterapeutiske regimener, der indeholdt oxaliplatin eller irinotecan med og uden Vectibix i førstevalgsbehandlingen af metastatisk colorectal cancer.
A randomized, open-label, multicentre study of 1,053 patients evaluated the efficacy of bevacizumab and oxaliplatin- or irinotecan-containing chemotherapeutic regimens with and without Vectibix in the first-line treatment of metastatic colorectal cancer.
I en interimanalyse baseret på 947 randomiserede patienter blev der observeret forkortet progressionsfri overlevelsestid og forøget antal dødsfald hos patienter, der fik Vectibix sammen med bevacizumab og kemoterapi.
In an interim analysis based on 947 randomized patients, shortened progression free survival time and increased deaths were observed in the patients receiving Vectibix in combination with bevacizumab and chemotherapy.
Der blev desuden observeret en større hyppighed af pulmonær embolisme, infektioner (hovedsagelig af dermatologisk oprindelse), diaré og dehydrering i behandlingsarmene, der anvendte Vectibix sammen med bevacizumab og kemoterapi.
A greater frequency of pulmonary embolism, infections (predominantly of dermatologic origin), diarrhoea, and dehydration was also observed in the treatment arms using Vectibix in combination with bevacizumab and chemotherapy.
5. 1).
Therefore administration of Vectibix in combination with bevacizumab containing chemotherapy combinations should be avoided (see section 4.5 and section 5.1).
Samtidig anvendelse af Vectibix og IFL eller kemoterapeutiske kombinationer, der indeholder bevacizumab, bør ikke anvendes (se pkt.
Concomitant use of Vectibix and IFL or bevacizumab and chemotherapy combinations is not recommended (see sections 4.4 and 4.8).
4. 4).
Increased deaths were observed when panitumumab was administered in combination with bevacizumab and chemotherapy combinations (see section 4.4).
Kvinder i den fødedygtige alder skal anvende effektive antikonceptionsmidler under behandlingen med Vectibix og i 6 måneder efter den sidste dosis.
In women of childbearing potential, appropriate contraceptive measures must be used during treatment with Vectibix, and for 6 months following the last dose.
Det vides ikke, om panitumumab udskilles i human modermælk.
It is unknown whether panitumumab is excreted in human breast milk.
Da humant IgG udskilles i human modermælk, er der også mulighed for, at panitumumab bliver udskilt.
Because human IgG is secreted into human milk, panitumumab might also be secreted.
Muligheden for absorption og skade på den nyfødte efter indtagelse er ukendt.
The potential for absorption and harm to the
Bør ikke anvendes til ammende kvinder under behandlingen med Vectibix og i 3 måneder efter den sidste dosis.
It is recommended that women do not breast feed during treatment with Vectibix and for 3 months after the last dose.
4 Fertilitet
Fertility
5. 3).
Animal studies have shown reversible effects on the menstrual cycle and reduced female fertility in monkeys (see Section 5.3).
Hvis patienterne oplever behandlingsrelaterede symptomer, der påvirker deres syn og/ eller evne til at koncentrere sig eller reagere, frarådes det, at de fører motorkøretøj eller anvender maskiner, før virkningen har fortaget sig.
If patients experience treatment-related symptoms affecting their vision and/ or ability to concentrate and react, it is recommended that they do not drive or use machines until the effect subsides.
90% af patienterne.
Based on an analysis of all patients receiving Vectibix monotherapy (n = 920), the most commonly reported adverse reactions are skin reactions occurring in approximately 90% of patients.
10% alvorlige (klasse 3 eller højere, NCI- CTC).
These reactions are related to the pharmacologic effects of Vectibix, and the majority are mild to moderate in nature with approximately 10% severe (grade 3 or higher, NCI-CTC).
Medmindre andet er angivet, beskriver dataene bivirkninger, der er blevet rapporteret i kliniske forsøg med patienter med metastatisk colorectalt carcinom, som fik panitumumab som et enkelt middel:
Except where indicated, the data describe adverse reactions reported from clinical studies in patients with metastatic colorectal carcinoma who received panitumumab as a single agent:
MedDRA organsystem Hud og subkutane væv
MedDRA Organ System Skin and subcutaneous tissue disorders
Hyppighed Meget almindelig (≥ 1/ 10)
Frequency Very common (≥ 1/ 10)
Bivirkning Udslæt Erytem Hudeksfoliation Pruritus Tør hud Hudfissurer Paronychia
Undesirable Effect Rash Erythaema Skin exfoliation Pruritus Dry skin Skin fissures Paronychia
Mave- tarmkanalen Almene symptomer og reaktioner på administrationsstedet
Gastrointestinal disorders General disorders and administrative site conditions
Diaré Træthed
Diarrhoea Fatigue
Almene symptomer og reaktioner på administrationsstedet Metabolisme og ernæring
General disorders and administrative site conditions Metabolism and nutrition disorders
Infusionsreaktioner (pyreksi, kulderystelser) Hypomagnesæmi Hypocalcæmi Hypokaliæmi Dehydrering
Infusion reactions (pyrexia, chills) Hypomagnesaemia Hypocalcaemia Hypokalaemia Dehydration
Kvalme Opkastninger
Nausea Vomiting
Luftveje, thorax og mediastinum
Respiratory, thoracic and mediastinal disorders Nervous system disorders Eye disorders
Hovedpine Conjunktivitis Vækst af øjenvipper Forøget tåresekretion Okulær hyperæmi Tørhed i øjne Øjenpruritus
Dyspnoea Cough Headache Conjunctivitis Growth of eyelashes Increased lacrimation Ocular hyperaemia Dry eye Eye pruritus
5 MedDRA organsystem Hud og subkutane væv
5 MedDRA Organ System Skin and subcutaneous tissue disorders
Bivirkning Stomatitis Slimhindeinflammation Onykolyse Hypertrikose Alopeci Tørhed i næse Tørhed i mund
Undesirable Effect Stomatitis Mucosal inflammation Onycholysis Hypertrichosis Alopecia Nasal dryness Dry mouth
Sikkerhedsprofilen for panitumumab hos patienter, hvis tumor udtrykker KRAS- vildtypen (n = 123), stemte generelt overens med den overordnede analyse af mCRC- monoterapi, der er beskrevet i ovenstående.
The safety profile of panitumumab in patients whose tumour express KRAS wild-type (n = 123) was generally consistent with overall mCRC monotherapy set described above.
De eneste forskelle var, at kvalme, opkastning, dyspnø og hoste blev indberettet som meget almindelige (≥ 1/ 10) i behandlingsarmen med KRAS- vildtypen, hvorimod disse lægemiddelbivirkninger blev indberettet som almindelige (≥ 1/ 100 til < 1/ 10) i den overordnede population på mCRC- monoterapi.
The only differences were that nausea, vomiting, dyspnoea and cough were reported as very common (≥ 1/ 10) in the KRAS wild-type arm whereas these adverse drug reactions were reported as common (≥ 1/ 100 to < 1/ 10) in the overall mCRC monotherapy population.
For 2% af patienterne med KRAS- vildtypen blev diaré indberettet som alvorlig.
Two percent of patients with KRAS wild-type had diarrhoea reported as severe.
I kliniske forsøg blev der rapporteret mulige infusionsreaktioner (opstår inden for 24 timer efter den første dosis), som kan omfatte symptomer/ tegn såsom kulderystelser, feber eller dyspnø hos 2% af patienterne, der blev behandlet med Vectibix, af hvilke < 1% var alvorlige (klasse 3).
In clinical trials potential infusion reactions (occurring within 24 hours of the first dose) which may include symptoms/ signs such as chills, fever, or dyspnoea, were reported in 2% of Vectibix treated patients, of which < 1% were severe (grade 3).
Ingen patienter havde livstruende (klasse 4) eller fatale (klasse 5) infusionsreaktioner på Vectibix.
No patients had life-threatening (grade 4) or fatal (grade 5) infusion reactions to Vectibix.
De fleste af symptomerne på mulige infusionsreaktioner, der var milde i styrke, fortog sig uden behandling, var isolerede forekomster og krævede ikke nogen ændring i eller afbrydelse af behandlingen med Vectibix.
Most of the symptoms of potential infusion reactions were mild in intensity, resolved without treatment, were isolated occurrences and did not require alteration or interruption of Vectibix administration.
Efter udviklingen af alvorlige hud - og subkutane reaktioner blev der rapporteret infektiøse komplikationer, herunder sepsis, i sjældne tilfælde med døden til følge, samt lokale abscesser, hvor incisioner og drænage var påkrævet.
Subsequent to the development of severe skin and subcutaneous reactions, infectious complications including sepsis, in rare cases leading to death, and local abscesses requiring incisions and drainage were reported.
Inflammation af paronychion blev forbundet med hævelse af tæernes og fingrenes laterale negleleje.
Paronychial inflammation was associated with swelling of the lateral nail folds of the toes and fingers.
Doser på op til 9 mg/ kg er blevet afprøvet i kliniske forsøg.
Doses up to 9 mg/ kg have been tested in clinical trials.
Der er indberetninger om overdosering ved doser på op til cirka det dobbelte af den anbefalede terapeutiske dosis.
There have been reports of overdose at doses up to approximately twice the recommended therapeutic dose.
De bivirkninger, der blev observeret, var hudtoksicitet, diaré, dehydrering og træthed, og de stemte overens med sikkerhedsprofilen ved den anbefalede dosis.
Adverse events observed included skin toxicity, diarrhoea, dehydration and fatigue and were consistent with the safety profile at the recommended dose.
Farmakoterapeutisk klassifikation: antineoplastiske midler, monoklonale antistoffer, ATC- kode:
Antineoplastic agents, monoclonal antibodies, ATC code:
L01XC08 6 Virkningsmekanisme
L01XC08
EGFR er et transmembrant glycoprotein, der er medlem af en underfamilie af type I- receptor tyrosinkinaser, herunder EGFR (HER1/ c- ErbB- 1), HER2, HER3 og HER4.
EGFR is a transmembrane glycoprotein that is a member of a subfamily of type I receptor tyrosine kinases including EGFR (HER1/ c-ErbB-1), HER2, HER3, and HER4.
EGFR fremmer cellevækst i normale epitheliale væv, herunder hud - og hårfollikler, og udtrykkes på en række tumorceller.
EGFR promotes cell growth in normal epithelial tissues, including the skin and hair follicle, and is expressed on a variety of tumour cells.
Panitumumab binder til EGFR' s ligandbindende domæne og hæmmer receptor- autofosforylering, der induceres af alle kendte EGFR- ligander.
Panitumumab binds to the ligand binding domain of EGFR and inhibits receptor autophosphorylation induced by all known EGFR ligands.
KRAS- genet (Kirsten rat sarcoma 2 viral oncogene homolog) koder et lille GTP- bindende protein, der er involveret i signaltransduktionen.
The KRAS (Kirsten rat sarcoma 2 viral oncogene homologue) gene encodes a small, GTP-binding protein involved in signal transduction.
En lang række stimuli, herunder den fra EGFR, aktiverer KRAS, som til gengæld stimulerer andre intracellulære proteiner til at fremme celleproliferationen, celleoverlevelsen og angiogenesen.
A variety of stimuli, including that from the EGFR activates KRAS which in turn stimulates other intracellular proteins to promote cell proliferation, cell survival and angiogenesis.
Aktiverende mutationer i KRAS- genet opstår hyppigt i flere forskellige humane tumorer og har været impliceret i både onkogenese og tumorprogression.
Activating mutations in the KRAS gene occur frequently in a variety human tumours and have been implicated in both oncogenesis and tumour progression.
In vitro analyser og in vivo dyreforsøg har vist, at panitumumab hæmmer væksten og overlevelsen af tumorceller, der udtrykker EGFR.
In vitro assays and in vivo animal studies have shown that panitumumab inhibits the growth and survival of tumour cells expressing EGFR.
Der blev ikke observeret nogen anti- tumor- virkninger af panitumumab i humane tumorxenografter, der manglede EGFR- ekpression.
No anti-tumour effects of panitumumab were observed in human tumour xenografts lacking EGFR expression.
Tilføjelsen af panitumumab til stråling, kemoterapi og/ eller andre målrettede terapeutiske midler resulterede i dyreforsøg i en stigning i anti- tumor- virkninger sammenlignet med stråling, kemoterapi eller målrettede terapeutiske midler alene.
The addition of panitumumab to radiation, chemotherapy and/ or other targeted therapeutic agents, in animal studies resulted in an increase in anti-tumour effects compared to radiation, chemotherapy or targeted therapeutic agents alone.
Resultaterne af disse analyser indikerede, at den generelle forekomst af en anti- panitumumab- antistofrespons efter dosering var lav.
Data on the development of anti-panitumumab antibodies has been evaluated using two different immunoassays (an ELISA which detects high-affinity antibodies, and a Biosensor Immunoassay which detects both high and low-affinity antibodies), results from these assays indicated that the overall incidence of a post-dose anti-panitumumab antibody response was low.
Antistoffer før dosering blev påvist hos 5 af 636 patienter (< 1%) og 16/ 635 patienter (2, 5%), der var testet vha. henholdsvis ELISA og biosensor- immunoanalysen.
Pre-dose antibodies were detected in 5 of 636 patients (< 1%) and 16/ 635 patients (2.5%) tested by the ELISA and Biosensor Immunoassay respectively.
Postdosis neutraliserende antistoffer blev påvist hos 1 af 447 patienter (0, 2%) og 7 af 447 patienter (1, 6%) testet vha. henholdsvis ELISA og biosensor- immunoanalysen.
Post-dose neutralising antibodies were detected in 1 of 447 patients (0.2%) and 7 of 447 patients (1.6%) tested by the ELISA and Biosensor Immunoassay respectively.
Sammenlignet med patienter, der ikke udviklede antistoffer, er der ikke blevet observeret nogen forbindelse mellem forekomsten af anti- panitumumab- antistoffer og farmakokinetik, effekt og sikkerhed.
Compared with patients who did not develop antibodies, no relationship between the presence of anti-panitumumab antibodies and pharmacokinetics, efficacy and safety has been observed.
Den observerede forekomst af antistofpositivitet i en analyse kan være påvirket af adskillige faktorer, herunder prøvehåndtering, samtidig medicin og underliggende sygdom; sammenligning af forekomsten af antistoffer med andre produkter kan derfor være misvisende.
The observed incidence of antibody positivity in an assay may be influenced by several factors including sample handling, concomitant medications and underlying disease, therefore, comparison of the incidence of antibodies to other products may be misleading.