natgillin/translations-raw huggingface dataset:
● Gastrointestinale perforationer (se pkt 4. 4). ● Blødninger, inklusive pulmonær blødning/ hæmoptyse, som er mere almindelig hos patienter med ikke- småcellet lungekræft (se pkt 4. 4). ● Arteriel tromboemboli (se også pkt 4. 4).
• Gastrointestinal perforations (see section 4.4). • Haemorrhage, including pulmonary haemorrhage/ haemoptysis, which is more common in non- small cell lung cancer patients (see section 4.4). • Arterial thromboembolism (see section 4.4).
De hyppigst observerede bivirkninger i alle kliniske studier hos patienter, som fik Avastin med eller uden kemoterapi, var hypertension, træthed eller asteni, diarré og abdominalsmerter.
The most frequently observed adverse drug reactions across clinical trials in patients receiving Avastin were hypertension, fatigue or asthenia, diarrhoea and abdominal pain.
Tabel 1 opsummerer de bivirkninger, som er associeret til brugen af Avastin i kombination med forskellige kemoterapiregimer til flere indikationer.
Table 1 lists adverse drug reactions associated with the use of Avastin in combination with different chemotherapy regimens in multiple indications.
Disse hændelser forekom med mindst 2% forskel i forhold til kontrolarmen (NCI- CTC grad 3- 5 reaktioner) eller med mindst 10% forskel i forhold til kontrolarmen (NCI- CTC grad 1- 5 reaktioner) og i mindst et af de større kliniske studier.
These reactions had occurred either with at least a 2% difference compared to the control arm (NCI-CTC grade 3-5 reactions) or with at least a 10% difference compared to the control arm (NCI-CTC grade 1-5 reactions), in at least one of the major clinical trials.
De bivirkninger, som er opsummeret i tabellen, er delt ind i følgende kategorier:
The adverse drug reactions listed in this table fall into the following categories:
Meget almindelig (≥ 10%) og almindelig (≥ 1% - < 10%).
Very Common (≥ 10%) and Common (≥ 1% - < 10%).
Bivirkningerne er anført under den relevante kategori i henhold til den højeste frekvens, som observeredes i de store kliniske studier.
Adverse drug reactions are added to the appropriate category in the table below according to the highest incidence seen in any of the major clinical trials.
Inden for hver frekvensgruppering er bivirkningerne anført med de mest alvorlige først.
Within each frequency grouping adverse drug reactions are presented in the order of decreasing seriousness.
De fleste bivirkninger ses almindeligvis ved behandling med kemoterapi (f. eks palmar- plantar erytrodysæstesi syndrom med capecitabin og perifer sensorisk neuropati med paclitaxel eller oxaliplatin); men en forværring som følge af behandling med Avastin kan ikke udelukkes.
Some of the adverse drug reactions are reactions commonly seen with chemotherapy, (e. g. palmar-plantar erythrodysaesthesia syndrome with capecitabine and peripheral sensory neuropathy with paclitaxel or oxaliplatin); however, an exacerbation by Avastin therapy can not be excluded.
Meget almindelige og almindelige bivirkninger
Very Common and Common Adverse Drug Reactions
NCI- CTC grad 3- 5 reaktioner (≥ 2% forskel mellem forsøgsarmene i mindst et klinisk forsøg)
NCI-CTC Grade 3-5 Reactions (≥ 2% difference between the study arms in at
Alle grader af hændelser ≥ 10% forskel mellem forsøgsarmene i mindst
All Grade Reactions (≥ 10% difference
et klinisk forsøg)
least one clinical trial)
Meget almindelig
between the study arms in at least one clinical trial)
Almindelig
Very common
Infektioner og
Very Common
Sepsis
Infections and infestations
parasitære sygdomme
Sepsis Abscess Infection
Absces
Blood and the
Infektion
Leucopenia
Blod og lymfesystem
Febrile neutropenia
Febril neutropeni
lymphatic systems disorders
Cerebrovaskulært tilfælde Synkope Somnolens Hovedpine
Cerebrovascular accident Syncope Somnolence Headache
Smagsforstyrrelser Hovedpine
Dysgeusia Headache
Forstyrrelser i øjne
Eye disorder
Kongestiv hjertesygdom Supraventrikulær
Supraventricular tachycardia
NCI- CTC grad 3- 5 reaktioner
NCI-CTC Grade 3-5 Reactions
Alle grader af hændelser
All Grade Reactions
(≥ 2% forskel mellem forsøgsarmene i mindst et
(≥ 2% difference between the study arms in at
≥ 10% forskel mellem
(≥ 10% difference
klinisk forsøg)
least one clinical trial)
forsøgsarmene i mindst et klinisk forsøg)
between the study arms in at least one clinical trial)
takykardi
Very Common
Tromboembolisme (arteriel) * Dyb venetrombose Blødning
Thromboembolism (arterial)*
Luftveje, thorax og mediastinum
Deep vein thrombosis Haemorrhage Respiratory, thoracic and mediastinal disorders
Lungeemboli Dyspnø Hypoxi Epistaxis
Pulmonary embolism Dyspnoea Hypoxia Epistaxis
Dyspnø Epistaxis Rhinitis
Dyspnoea Epistaxis Rhinitis
Tarmperforation
Diarrhoea Nausea
Ileus
Intestinal Perforation Ileus
Stomatitis
Constipation Stomatitis
Opkastning
Vomiting
Intestinal obstruktion Abdominale smerter Gastrointestinale forstyrrelser
Intestinal obstruction Abdominal pain Gastrointestinal disorder
Palmar- plantar erytrodysæstesi syndrom
Palmar-plantar
Eksfoliativ dermatitis Tør hud Pigmentforandringer
Exfoliative dermatitis
Knogler, led, muskler og bindevæv
erythrodysaesthesia syndrome
Muskelsvaghed
Musculoskeletal,
Nyrer og urinveje
Muscular weakness
Proteinuri Urinvejsinfektion
connective tissue and bone disorders
Proteinuri
Renal and urinary
Almene symptomer og
Proteinuria
Asteni
Proteinuria
Smerte
disorders
Pyreksi
Urinary Tract Infection
reaktioner på
General disorders and
Træthed
Asthenia
Letargi
Pain
Smerte
Fatigue
* Samlede data for arterielle tromboemboliske hændelser inklusive cerebrovaskulære tilfælde, myokardieinfarkt, transitoriske iskæmiske anfald og andre arterielle tromboemboliske hændelser.
* Pooled arterial thromboembolic events including cerebrovascular accident, myocardial infarction, transient ischaemic attack and other arterial thromboembolic events.
Data er er ikke justeret for forskelle i tidspunktet for behandlingen.
Data are unadjusted for the differential time on treatment.
Yderligere information om visse alvorlige bivirkninger:
Further information on selected serious adverse drug reactions:
Gastrointestinale perforationer (se pkt 4. 4.):
Gastrointestinal perforations (see section 4.4):
Avastin er blevet forbundet med alvorlige tilfælde af gastrointestinal perforation eller fistel (se også under overskriften ” Fistler ”).
Avastin has been associated with serious cases of gastrointestinal perforation or fistulae (see also under heading Fistulae).
Gastrointestinale perforationer er blevet rapporteret i kliniske studier med en hyppighed på mindre end 1% hos patienter med metastatisk brystkræft eller ikke- småcellet lungekræft og med en hyppighed på op til 2% hos patienter med metastatisk kolorektalkræft.
Gastrointestinal perforation have been reported in clinical trials with an incidence of less than 1% in patients with metastatic breast cancer or non-squamous non-small cell lung cancer, and in up to 2.0% in metastatic colorectal cancer patients.
Der blev rapporteret dødelig udgang i ca. en tredjedel af de alvorlige tilfælde af gastrointestinal blødning, hvilket svarer til mellem 0, 2% - 1% af alle Avastin- behandlede patienter.
Fatal outcome was reported in approximately a third of serious cases of gastrointestinal perforations, which represents between 0.2%-1% of all Avastin treated patients.
Hændelserne varierede i type og intensitet fra fri luft set på et almindeligt røntgenbillede af abdomen og som normaliseredes uden behandling til perforation af kolon med abdominal absces og fatalt udfald.
The presentation of these events varied in type and severity, ranging from free air seen on the plain abdominal X-ray, which resolved without treatment, to intestinal perforation with abdominal abscess and fatal outcome.
I nogle af disse tilfælde var intraabdominal inflammation allerede erkendt, enten fra mavesår, tumornekrose, divertikulitis eller kemoterapiassocieret kolitis.
In some cases underlying intra-abdominal inflammation was present, either from gastric ulcer disease, tumour necrosis, diverticulitis, or chemotherapy-associated colitis.
4. 4):
8 Fistulae (see section 4.4):
Brugen af Avastin er blevet knyttet sammen med alvorlige tilfælde af fistler, herunder også hændelser, som førte til død.
Avastin use has been associated with serious cases of fistulae including events resulting in death.
8 I kliniske forsøg er gastrointestinale fistler set hos op til 2% af patienterne med metastatisk carcinom i kolon eller rektum og er også set i mindre grad hos patienter med andre cancertyper.
In clinical trials, gastrointestinal fistulae have been reported with an incidence of up to 2% in patients with metastatic colorectal cancer, but were also reported less commonly in patients with other types of cancers.
Dette er rapporteret med en frekvens, der svarer til ikke almindelig (≥ 0, 1% op til < 1%).
Uncommon (≥ 0.1% to < 1%) reports of other types of fistulae that involve areas of the body other than the gastrointestinal tract (e. g. bronchopleural, urogenital and biliary fistulae) were observed across various indications.
Fistler er også rapporteret post- marketing.
Fistulae have also been reported in post-marketing experience.
De fleste hændelser fandt sted inden for de første 6 måneder af behandlingen.
Events were reported at various time points during treatment ranging from one week to greater than 1 year from initiation of Avastin, with most events occurring within the first 6 months of therapy.
Sårheling (se pkt 4. 4):
Wound healing (see section 4.4):
Hyppigheden varierede mellem 10% (4/ 40) og 20% (3/ 15).
The incidence varied between 10% (4/ 40) and 20% (3/ 15).
I lokalt recidiverende eller metastatisk brystkræft blev der observeret sårhelingskomplikationer af grad 3- 5 hos 1, 1% af patienterne, som fik Avastin samt paclitaxel, hvorimod det ikke sås for patienter, som kun modtog paclitaxel.
In locally recurrent and metastatic breast cancer, Grade 3-5 wound healing complications were observed in 1.1% of patients receiving Avastin + paclitaxel and in none of the patients receiving paclitaxel alone.
Hypertension (se pkt 4. 4):
Hypertension (see section 4.4):
Der er observeret en øget hyppighed (alle grader) på op til 34% af hypertension hos Avastinbehandlede patienter sammenlignet med en hyppighed på op til 14% hos de patienter, som blev behandlet med kontrolbehandlingen.
An increased incidence of hypertension (all grades) of up to 34% has been observed in Avastin-treated patients in clinical trials compared with up to 14% in those treated with comparator.
Grad 3 og 4 hypertension (behandling med orale antihypertensiva er påkrævet) blev set hos mellem 3, 0% og 17, 9% af patienterne, som fik Avastin.
Grade 3 and 4 hypertension (requiring oral anti-hypertensive medication) in patients receiving Avastin ranged from 3.0% to 17.9%.
Grad 4 hypertension (hypertensiv krise) sås hos 1, 0% af patienterne, som fik Avastin, i forhold til op til 0, 2% af patienterne, som fik kemoterapi alene.
Grade 4 hypertension (hypertensive crisis) occurred in up to 1.0% of patients treated with Avastin and chemotherapy compared to up to 0.2% of patients treated with the same chemotherapy alone.
Hypertension blev generelt adækvat behandlet med orale antihypertensiva som f. eks. angiotensinkonverteringshæmmere, diuretika og calcium- kanal- blokkere.
Hypertension was generally adequately controlled with oral anti-hypertensives such as angiotensin-converting enzyme inhibitors, diuretics and calcium-channel blockers.
Hypertensionen resulterede sjældent i afbrydelse af Avastin- behandlingen eller hospitalsindlæggelse.
It rarely resulted in discontinuation of Avastin treatment or hospitalisation.
Meget sjældne tilfælde af hypertensiv encephalopati er rapporteret, enkelte var fatale.
Very rare cases of hypertensive encephalopathy have been reported, some of which were fatal.
Risikoen for Avastin- associeret hypertension korrelerede ikke med patienternes baseline karakteristika, med den underliggende sygdom eller med anden samtidig behandling.
The risk of Avastin-associated hypertension did not correlate with the patients’ baseline characteristics, underlying disease or concomitant therapy.
Proteinuri (se pkt 4. 4) Proteinuri er blevet set hos mellem 0, 7% og 38% af patienterne, som fik Avastin i kliniske studier.
In clinical trials, proteinuria has been reported within the range of 0.7% to 38% of patients receiving Avastin.
Proteinurien varierede i sværhed fra klinisk symptomfri, forbigående, spor af protein i urinen til nefrotisk syndrom, dog med størstedelen som grad 1 proteinuri.
Proteinuria ranged in severity from clinically asymptomatic, transient, trace proteinuria to nephrotic syndrome, with the great majority as Grade 1 proteinuria.
Hos patienter behandlet for fremskreden og/ eller metastatisk renalcellecarcinom, sås dette imidlertid hos op til 7% af patienterne.
Grade 3 proteinuria was reported in < 3% of treated patients: however, in patients treated for advanced and/ or metastatic renal cell carcinoma this was up to 7%.
Grad 4 proteinuri (nefrotisk syndrom) blev set hos op mod 1, 4% af de behandlede patienter.
Grade 4 proteinuria (nephrotic syndrome) was seen in up to 1.4% of treated patients.
Den i de kliniske studier observerede proteinuri, var ikke ledsaget af renal dysfunktion og krævede sjældent permanent afbrydelse af behandlingen.
The proteinuria seen in clinical trials was not associated with renal dysfunction and rarely required permanent discontinuation of therapy.
Det anbefales at teste for proteinuri før start på Avastinbehandling.
Testing for proteinuria is recommended prior to start of Avastin therapy.
I de fleste kliniske studier førte proteinkoncentrationer i urinen på ≥ 2g/ 24 timer til stop i Avastinbehandling, indtil der sås bedring ved < 2g/ 24 timer.
In most clinical studies urine protein levels of ≥ 2g / 24 hrs led to the holding of Avastin until recovery to < 2g/ 24 hrs.
9 Blødning (se pkt 4. 4):
9 Haemorrhage (see section 4.4):
I kliniske studier inden for alle indikationer spændte hyppigheden af NCI- CTC grad 3- 5 blødninger fra 0, 4% – 5% for de Avastin- behandlede patienter, og for de patienter, der fik kemoterapi alene, var hyppigheden 2, 9%.
In clinical trials across all indications the overall incidence of NCI-CTC Grade 3-5 bleeding events ranged from 0.4% to 5% in Avastin treated patients, compared with up to 2.9% of patients in chemotherapy control group.
De blødninger, som observeredes i de kliniske studier, var fortrinsvis tumorassocierede blødninger (se nedenfor) og mindre slimhindeblødninger (f. eks epistaxis).
The haemorrhagic events that have been observed in clinical studies were predominantly tumour- associated haemorrhage (see below) and minor mucocutaneous haemorrhage (e. g. epistaxis).
Tumorassocieret blødning (se pkt.
Tumour-associated haemorrhage (see section 4.4).
4. 4) Alvorlig eller massiv pulmonær blødning/ hæmoptyse er observeret fortrinsvis i studier af patienter med ikke- småcellet lungekræft (NSCLC).
Major or massive pulmonary haemorrhage/ haemoptysis has been observed primarily in studies in patients with non-small cell lung cancer (NSCLC).
Mulige risikofaktorer inkluderer planocellulær histologi, behandling med antireumatiske/ anti- inflammatoriske lægemidler, behandling med antikoagulantia, tidligere strålebehandling, Avastinbehandling, aterosklerose i anamnesen, central placering af tumor og kavernedannelse i tumorer før eller under behandling.
Possible risk factors include squamous cell histology, treatment with antirheumatic/ anti-inflammatory drugs, treatment with anticoagulants, prior radiotherapy, Avastin therapy, previous medical history of atherosclerosis, central tumour location and cavitation of tumours prior to or during therapy.
Patienter med NSCLC med kendt planocellulær histologi eller blandet celletype med dominerende planocellulær histologi, blev ekskluderet fra de efterfølgende fase III- studier, mens patienter med ukendt tumorhistologi blev inkluderet.
Patients with NSCLC of known squamous cell histology or mixed cell type with predominant squamous cell histology were excluded from subsequent phase III studies, while patients with unknown tumour histology were included.
Hos de patienter med NSCLC, der ikke har dominerende planocellulær histologi, der blev behandlet med Avastin og kemoterapi, blev der set hændelser af alle grader med frekvenser på op til 9% sammenlignet med 5% hos de patienter, der kun blev behandlet med kemoterapi.
In patients with NSCLC excluding predominant squamous histology, all grade events were seen with a frequency of up to 9% when treated with Avastin plus chemotherapy compared with 5% in the patients treated with chemotherapy alone.
Dette skal ses i sammenligning med < 1% af de patienter, der kun fik kemoterapi.
Grade 3-5 events have been observed in up to 2.3% of patients treated with Avastin plus chemotherapy as compared with < 1% with chemotherapy alone.
Alvorlig eller massiv pulmonær blødning/ hæmoptyse kan opstå pludseligt, og op mod to tredjedele af de alvorlige pulmonære blødninger fik en fatal udgang.
Major or massive pulmonary haemorrhage/ haemoptysis can occur suddenly and up to two thirds of the serious pulmonary haemorrhages resulted in a fatal outcome.
Disse blødninger er blevet vurderet som tumorassocierede blødninger.
Gastrointestinal haemorrhages, including rectal bleeding and melaena have been reported in colorectal cancer patients, and have been assessed as tumour-associated haemorrhages.
I sjældne tilfælde blev der også iagttaget tumorassocieret blødning ved andre tumorer og anden lokalitet, inklusive et tilfælde af blødning i centralnervesystemet (CNS) hos en patient med hepatocellulært carcinom med okkulte CNS- metastaser (se pkt 4. 3) samt en anden patient, som udviklede kontinuerlig siveblødning fra et femoralt sarkom med nekroser.
Tumour-associated haemorrhage was also seen rarely in other tumour types and locations, including a case of central nervous system (CNS) bleeding in a patient with hepatoma with occult CNS metastases (see section 4.3) and another patient who developed continuous oozing of blood from a thigh sarcoma with necrosis.
I alle kliniske studier er der set slimhindeblødninger hos 20% – 40% af de Avastin- behandlede patienter.
Across all clinical trials, mucocutaneous haemorrhage has been seen in 20% - 40% of Avastin- treated patients.
Det drejede sig for det meste om NCI- CTC grad 1 næseblod, som varede mindre end 5 minutter og ophørte uden behandling, og som ikke krævede ændringer i Avastin- behandlingen.
These were most commonly NCI-CTC Grade 1 epistaxis that lasted less than 5 minutes, resolved without medical intervention and did not require any changes in the Avastin treatment regimen.
Kliniske sikkerhedsdata antyder, at forekomsten af mindre mukokutane blødninger (f. eks. epistaxis) kan være dosisafhængig.
Clinical safety data suggest that the incidence of minor mucocutaneous haemorrhage (e. g. epistaxis) may be dose-dependent.
Der har også været mindre almindelige hændelser af mindre slimhindeblødninger, lokaliseret andre steder, som f. eks. gingival eller vaginal blødning.
There have also been less common events of minor mucocutaneous haemorrhage in other locations, such as gingival bleeding or vaginal bleeding.
Tromboemboli (se pkt 4. 4):
Thromboembolism (see section 4.4):
Arteriel tromboemboli:
Arterial thromboembolism:
Disse hændelser inkluderer cerebrovaskulære hændelser, myokardieinfarkt, transitoriske iskæmiske anfald og andre arterielle tromboemboliske hændelser.
An increased incidence of arterial thromboembolic events was observed in patients treated with Avastin across indications, including cerebrovascular accidents, myocardial infarction, transient ischemic attacks, and other arterial thromboembolic events.
I kliniske studier var den samlede incidens af arterielle tromboemboliske hændelser op til 3, 8% i Avastin- armen sammenlignet med op til 1, 7% i kontrolgruppen, som fik kemoterapi alene.
In clinical trials, the overall incidence of arterial thromboembolic events ranged up to 3.8% in the Avastin containing arms compared with up to 1.7% in the chemotherapy control arms.
Fatal udgang blev rapporteret hos 0, 8% af patienterne, som fik Avastin, sammenholdt med 0, 5% hos patienter, som fik kemoterapi alene.
Fatal outcome was reported in 0.8% of patients receiving Avastin compared to 0.5% in patients receiving chemotherapy alone.
Cerebravaskulære tilfælde (inklusive transitoriske iskæmiske anfald) blev rapporteret hos op til 2, 3% af patienterne, som fik Avastin i kombination med kemoterapi i forhold til 0, 5% af patienterne, som fik kemoterapi alene.
Cerebrovascular accidents (including transient ischemic attacks) were reported in up to 2.3% of patients treated with Avastin in combination with chemotherapy compared to 0.5% of patients treated with chemotherapy alone.
Myokardieinfarkt blev rapporteret hos
Myocardial infarction was reported in 1.4% of patients
10 1, 4% af patienterne, som fik Avastin i kombination med kemoterapi, sammenlignet med 0, 7% af patienterne, som fik kemoterapi alene.
10 treated with Avastin in combination with chemotherapy compared to 0.7% of patients treated with chemotherapy alone.
I et klinisk studie, AVF2192g blev der inkluderet patienter med metastatisk kolorektalkræft, som ikke var kandidater til behandling med irinotecan.
In one clinical trial, AVF2192g, patients with metastatic colorectal cancer who were not candidates for treatment with irinotecan were included.
I dette studie blev der observeret arterielle tromboemboliske hændelser hos 11% (11/ 100) af patienterne i forhold til 5, 8% (6/ 104) i kemoterapikontrolgruppen.
In this trial arterial thromboembolic events were observed in 11% (11/ 100) of patients compared to 5.8% (6/ 104) in the chemotherapy control group.
Venøs tromboembolisme Hyppigheden af venøse tromboemboliske hændelser i kliniske studier var den samme for patienter, som fik Avastin i kombination med kemoterapi, sammenlignet med dem, som fik kemoterapi alene.
The incidence of venous thromboembolic events in clinical trials was similar in patients receiving Avastin in combination with chemotherapy compared to those receiving the control chemotherapy alone.
Venøse tromboemboliske hændelser omfatter dyb venetrombose, lungeemboli og tromboflebitis.
Venous thromboembolic events include deep venous thrombosis, pulmonary embolism and thrombophlebitis.
I kliniske studier, inden for alle indikationer, var hyppigheden af venøse tromboemboliske hændelser mellem 2, 8% til 17, 3% af de Avastinbehandlede patienter i forhold til 3, 2% - 15, 6% i kontrolgrupperne.
In clinical trials across indications, the overall incidence of venous thromboembolic events ranged from 2.8% to 17.3% of Avastin-treated patients compared with 3.2% to 15.6% in the control arms.
Venøse tromboliske hændelser af grad 3 – 5 sås hos op mod 7, 8% af patienter behandlet med kemoterapi plus bevacizumab i forhold til op mod 4, 9% hos patienter, som fik kemoterapi alene.
Grade 3-5 venous thromboembolic events have been reported in up to 7.8% of patients treated with chemotherapy plus bevacizumab compared with up to 4.9% in patients treated with chemotherapy alone.
Patienter, som tidligere har oplevet en venøs tromboembolisk hændelse, kan have en højere risiko for fornyet hændelse, hvis de får Avastin i kombination med kemoterapi, end hvis de får kemoterapi alene.
Patients who have experienced a venous thromboembolic event may be at higher risk for a recurrence if they receive Avastin in combination with chemotherapy versus chemotherapy alone.
Kongestiv hjertesygdom (CHF) I kliniske studier med Avastin blev kongestiv hjertesygdom (CHF) observeret i alle de kræftindikationer, som er undersøgt indtil videre, men forekom primært hos patienter med metastatisk brystkræft.
Congestive Heart Failure (CHF) In clinical trials with Avastin, congestive heart failure (CHF) was observed in all cancer indications studied to date, but occurred predominantly in patients with metastatic breast cancer.
I to fase III- studier (AVF2119g og E2100), der omhandlede metastatisk brystkræft, blev der observeret en højere hyppighed af CHF af grad 3 eller mere hos patienter, som fik Avastin.
In two phase III studies (AVF2119g and E2100) in patients with metastatic breast cancer an increase of CHF Grade 3 or more with Avastin was seen.