natgillin/translations-raw huggingface dataset:
3 b) Vaccinationer Der findes begrænset data, der beskriver virkningen af vaccination.
b) Vaccinations Limited data are available on the effects of vaccination.
Neo- vaccinationer, der gives under behandling med Raptiva, kan medføre lavere antistofniveauer end dem, man ser hos ikke behandlede personer men den kliniske signifikans af dette er ukendt..
Neo-vaccinations given during treatment with Raptiva may induce antibody levels lower than those observed in non-treated subjects, but the clinical
(Se afsnit 4. 5)
(see section 4.5).
c) Maligniteter og lymfoproliferative sygdomme Det vides endnu ikke, om Raptiva kan øge risikoen for lymfoproliferative sygdomme eller andre maligniteter hos psoriasis- patienter.
c) Malignancies and lymphoproliferative disorders It is not yet known whether or not Raptiva can increase the risk of lymphoproliferative disorders or other malignancies in psoriasis patients.
Behandling med Raptiva bør af brydes, hvis der udvikles malignitet, mens patienten er i behandling (se afsnit 4. 3 og 4. 8).
Raptiva should be discontinued if a malignancy develops while the patient is on treatment (see sections 4.3 and 4.8).
(se afsnit 4. 5).
Therefore, combination therapies with these products are not recommended (see section 4.5).
Immun- medieret hæmolytisk anæmi I post- marketing studier har der været rapporteret isolerede tilfælde af alvorlig hæmolytisk anæmi under behandlingen med Raptiva.
Immune-mediated haemolytic anaemia In post-marketing surveillance, isolated cases of severe haemolytic anaemia have been reported during treatment with Raptiva.
Trombocytopeni Trombocytopeni kan opstå under behandling med Raptiva og kan vise sig ved kliniske tegn som fx ekkymose, spontan suggilation eller blødning fra mucokutant væv.
Thrombocytopenia Thrombocytopenia may occur during Raptiva treatment and may be associated with clinical signs such as echymoses, spontaneous bruising or bleeding from muco-cutaneous tissues.
Hvis sådanne tegn opstår, bør behandling med efalizumab afbrydes med det samme, trombocyttallet måles, og den rette symptombehandling straks påbegyndes (se afsnit 4. 8).
If these manifestations occur, efalizumab should be stopped immediately, a platelet count should be performed and appropriate symptomatic treatment should be instituted immediately (see section 4.8).
Det anbefales, at sådanne målinger sker oftere i begyndelsen af behandlingen (fx hver måned) og derefter bliver mindre hyppige under den fortsatte behandling (fx hver 3. måned).
It is recommended that assessments be more frequent when initiating therapy (e. g., monthly) and may decrease in frequency with continued treatment (e. g., every 3 months).
Inflammatorisk polyradikuloneuropati Der er observeret tilfælde af inflammatorisk polyradikuloneuropati hos patienter i behandling med Raptiva.
Inflammatory polyradiculoneuropathy Cases of inflammatory polyradiculoneuropathy have been observed in post-marketing surveillance in patients receiving Raptiva (see section 4.8).
Hypersensitivitet og allergiske reaktioner Som ethvert andet rekombinant produkt er Raptiva et potentielt allergen.
Hypersensitivity and allergic reactions As with any recombinant product, Raptiva is potentially immunogenic.
I tilfælde af alvorlig hypersensitivitet eller allergisk reaktion bør anvendelsen af Raptiva derfor straks afbrydes og den rette behandling påbegyndes (se afsnit 4. 3 og 4. 8).
Consequently, if any serious hypersensitivity or allergic reaction occurs, Raptiva should be discontinued immediately and appropriate therapy initiated (see sections 4.3 and 4.8).
Arthritis I forbindelse med behandling med Raptiva, og efter ophør af Raptiva- behandling er der observeret tilfælde af arthritis.
Arthritis Cases of arthritis have been observed during treatment or after discontinuation of Raptiva.
Psoriasis I forbindelses med behandling med Raptiva er der observeret tilfælde af forværring af psoriasis, herunder andre typer som pustuløs, erythrodermisk og guttat psoriasis (se afsnit 4. 8).
Psoriasis During treatment with Raptiva, cases of exacerbation of psoriasis, including pustular, erythrodermic, and guttate subtypes, have been observed (see section 4.8).
Behandlingsstop Efter behandlingsstop med Raptiva bør patienten holdes under observation.
Discontinuation Management of patients discontinuing Raptiva includes close observation.
Gentaget behandlingen med Raptiva kan give mindre eller
Re-treatment may be associated with lower or inadequate response to Raptiva than in the earlier treatment periods.
4 utilstrækkelig effekt i forhold til tidligere behandlingsperioder.
Therapy may be continued only in those patients who respond adequately to treatment.
Særlige patientpopulationer Der er ikke observeret forskelligheder i sikkerhed eller effekt mellem ældre (≥ 65 år) patienter og yngre patienter.
4 Special patient populations No differences in safety or efficacy were observed between elderly (≥ 65 years) patients and younger patients.
Der er ikke udført undersøgelser med Raptiva hos patienter med nedsat nyre - eller leverfunktion, og Raptiva bør derfor anvendes med forsigtighed til sådanne patienter.
Raptiva has not been studied in patients with renal or hepatic impairment and should therefore be used with caution in such patients.
Se afsnit 4. 8 vedrørende påvirkning på leverfunktionen.
See section 4.8 regarding the effects on the hepatic function.
Antistofresponset mod et eksperimentelt neoantigen (ØX174) blev reduceret under Raptiva behandlingen, men begyndte at blive normaliseret 6 uger efter seponering af Raptiva behandlingen og udviste ingen tegn på tolerance udvikling.
Antibody response to an experimental neo-antigen (∅ X174) was reduced during Raptiva therapy, but began to normalize 6 weeks after discontinuation of Raptiva therapy and did not demonstrate tolerance induction.
(Se afsnit 4. 4).
(See section 4.4).
På grund af efalizumabs virkningsmekanisme kan dets effekt på immunsystemet forstærkes af almindeligt anvendte systematiske immunsuppressive midler til behandling af psoriasis (se afsnit 4. 4).
Given the mechanism of action of efalizumab, its effects on the immune system may be potentiated by systemic immunosuppressives commonly used for the treatment of psoriasis (see section 4.4).
Graviditet Det er almindeligt kendt, at immunoglobuliner kan krydse placentabarrieren.
Pregnancy In general, immunoglobulins are known to cross the placental barrier.
Dyreforsøg indikerer en reversibel hæmning af immunfunktionen hos afkommet (se afsnit 5. 3).
Animal studies indicate an impairment of the immune function of the offspring (see section 5.3).
Gravide kvinder bør ikke behandles med Raptiva Kvinder i den fødedygtige alder skal anvende effektiv antikonception under behandlingen.
Women of childbearing potential have to use appropriate contraception during treatment.
Amning Udskillelse af efalizumab i human mælk er ikke undersøgt, dog forventes det, at immunoglobuliner udskilles i human mælk.
Lactation Excretion of efalizumab in human milk has not been investigated, however immunoglobulins are expected to be excreted in human milk.
På baggrund af efalizumabs farmakologiske virkningsmekanisme forventes brugen af Raptiva ikke at påvirke patientens evne til at føre motorkøretøj eller betjene maskiner.
Based on the pharmacological mechanism of action of efalizumab, the use of Raptiva is not expected to affect patient’ s ability to drive and use machines.
I større placebokontrollerede kliniske undersøgelser blev sådanne reaktioner observeret hos ca.
The most frequent symptomatic adverse drug reactions (ADRs) observed during Raptiva therapy were mild to moderate dose-related acute flu-like symptoms including headache, fever, chills, nausea and 5 myalgia.
41% af de patienter, der var i behandling med Raptiva, og hos 24% af de patienter, der fik placebo i en behandlingsperiode på 12 uger.
In large placebo-controlled clinical studies, these reactions were observed in approximately 41% of Raptiva-treated patients and 24% in placebo-treated patients over 12 weeks of treatment.
Der blev observeret antistoffer mod efalizumab i kun 6% af patienterne.
Antibodies to efalizumab were detected in only 6% of patients.
Organklasser
System Organ Class
Ikke
Very
Enkelt
Common
(MedDRA)
Uncommon
alminde
Rare
sjælden
Very rare
stående
Not known
(> 1/ 100, lig < 1/ 1. 000) (< 1/ 10. 000)
Infections and infestations
< 1/ 10)
(> 1/ 100 < 1/ 10)
(> 1/ 1. 000, < 1/ 100)
(> 1/ 1,000, < 1/ 100)
ninger
(> 1/ 10,000, < 1/ 1,000)
Infektiøse og parasitære sygdomme
(< 1/ 10,000)
Aseptisk meningitis *, alvorlige infektioner * JC virusinfektio n som resulterer i Progressiv Multifocal Leukoenceph alopati (PML).
Aseptic meningitis*, Severe infections*, JC virus infection resulting in progressive multifocal leukoencephalopathy*
Sygdomme i blod - og lymfesystem Forstyrrelser i immunsystemet
Blood and the lymphatic system disorders
Leuko - cytose og lymfo - cytose
Leuko- cytosis and lympho- cytosis
Overføl - somheds reaktioner
Immune mediated haemolytic anaemia*
Trombo - cytopeni
Immune system disorders
Immun medieret hæmolytisk anæmi *
Hyper- sensitivity reactions
Nervesystemet Sygdomme i åndedræts - organer, brysthule og mediastinum
Nervous system disorders Respiratory, thoracic and mediastinal disorders
Facial - parese (Bells parese)
Facial palsy (Bell’ s palsy)
Inflam - matorisk polyradikulo - neuropati * Interstitiel pneumoni *
Inflammatory polyradiculo- neuropathy* Interstitial pneumonitis*
Urticaria
Urticaria
Erytem multiform *
Erythema multiforme*
6 Sygdomme i bevægeap - paratet og bindevæv
Musculoskeletal and connective tissue disorders
Arthralgi Arthritis / Psoriatisk arthritis (forvær - ring / opblussen)
Arthralgia Arthritis / Psoriatic arthritis (exacerbation/ flare)
Influenza - lignende symptomer såsom feber, hovedpine, kulde - rystelser, kvalme og muskel - smerter
Flu-like symptoms including fever, headaches, chills, nausea and myalgia
Rygsmer - ter, Asteni
Back pain, Asthenia
Reaktioner på injektions - sted
Injection site reactions
* Tilfælde set under post- marketing studier.
* Events identified during postmarketing surveillance
Sikkerhedsprofilen hos målgruppen, der er defineret i afsnit 4. 1, er lig den sikkerhedsprofil hos den samlede population, der er behandlet under den kliniske udvikling af Raptiva, der vises ovenfor.
The safety profile in the target population as defined in section 4.1 is similar to the safety profile in the overall population treated during clinical development of Raptiva as presented above.
Yderligere oplysninger
Additional Information
En analyse baseret på langtidsbrug hos en gruppe af 339 patienter (forsøg ACD 2243g) med moderat til svær psoriasis, der modtog Raptiva 1mg/ kg/ uge, hvori 166 patienter blev behandlet i mere end 2 år og op til 3 år, viste ikke nogen nævneværdig forskelle i hyppigheden af utilsigtede hændelser sammenlignet med 12 ugers behandling af Raptiva.
Analysis following long-term use in a cohort of 339 patients with moderate to severe psoriasis receiving Raptiva 1 mg/ kg/ week, of which 166 patients have been treated for more than 2 years and up to 3 years, did not show any noteworthy differences in frequency of adverse events as compared to 12 weeks of exposure to Raptiva.
I store placebo- kontrollerede og i langtids kliniske forsøg, udviklede mellem 40 og 50% af patienterne vedvarende asymptomatisk lymfocytose, mens de var i behandling med Raptiva.
Leucocytosis and lymphocytosis: in large placebo-controlled and in long-term clinical studies, between 40 and 50% of patients developed sustained asymptomatic lymphocytosis during Raptiva therapy.
Alle værdier var på mellem 2, 5 gange og 3, 5 gange ULN (øvre normalgrænse).
All values were between 2.5 fold and 3.5 fold the ULN (Upper Limit of Normal).
I den centrale sikkerhedsdatabase, der omfattende 3291 patienter, der blev behandlet med Raptiva på tidspunktet for udstedelsen af markedsføringstilladelsen, findes der ni tilfælde (0, 3%) af trombocytopeni med mindre end 52. 000 celler pr. μl rapporteret.
In the combined safety database of 3291 Raptiva-treated patients at the time of approval, there were nine occurrences (0.3%) of thrombocytopenia with less than 52,000 cells per μ l reported.
I den samme population blev 2 tilfælde af hurtigt indsættende alvorlig trombocytopeni (0, 6%) observeret (Se afsnit 4. 4).
In the same population two cases of severe thrombocytopenia (0.6%) of rapid onset were observed (See section 4.4).
7 Psoriasis:
Psoriasis:
Under de første 12 uger i placebokontrollerede undersøgelser var andelen af psoriatiske bivirkninger 3, 2% hos patienter, som blev behandlet med Raptiva, og 1, 4% hos patienter, som fik placebo.
In the first 12 weeks of placebo-controlled studies, the rate of psoriasis adverse events was 3.2% in the Raptiva-treated patients and 1.4% in the placebo-treated patients.
Blandt 3291 patienter i den centrale sikkerhedsdatabase fik 39 patienter erythrodermisk eller pustuløs psoriasis (1, 2%).
Among 3291 patients in the combined safety database, 39 patients presented an erythrodermic or pustular psoriasis (1.2%).
I de tilfælde, hvor bivirkningerne optrådte under behandlingen, forekom de fleste bivirkninger (16/ 22) hos patienter, der ikke respondere på behandlingen med Raptiva.
In the cases occurring during treatment, most of these events (16/ 22) occurred in patients presenting no response to Raptiva.
Under de første 12 uger i placebokontrollerede undersøgelser blev der observeret arthritis og eksacerbation eller opblussen af arthritis hos 1, 8% af de patienter, som blev behandlet med Raptiva, og patienter, som fik placebo.
In the first 12 weeks of placebo-controlled studies, arthritis and exacerbation or flare of arthritis were observed in 1.8% of Raptiva-treated patients and placebo-treated patients.
I disse undersøgelser var forekomsten af andre typer arthritis- relaterede bivirkninger den samme hos Raptiva - og placebo- grupperne.
In these studies, the incidence of other types of arthritis-related adverse events were similar between the Raptiva and placebo groups.
Influenza- lignende symptomer:
Flu-like symptoms:
20% flere influenza- lignende symptomer i Raptiva- gruppen end i placebogruppen, herunder hovedpine, kulderystelser, feber, kvalme og muskelsmerter.
In large placebo-controlled clinical studies, approximately 20% of patients in excess of placebo reported flu-like symptoms including headaches, chills, fever, nausea and myalgia.
Procentdelen af patienter, der rapporterede influenza- lignende symptomer, var størst ved den første injektion og faldt derefter med over 50% ved den anden injektion.
The percentage of patients reporting flu-like symptoms was greatest with the first injection and decreased by more than 50% with the second injection.
Hovedpine var det hyppigste af de influenza- lignende symptomer.
Headache was the most frequent of the flu-like symptoms.
Ingen af bivirkningerne var alvorlige, og mindre end 5% blev betragtet som svære.
None of those events was serious and less than 5% were considered severe.
Totalt var det mindre end 1% af patienterne, som afbrød behandlingen pga. akutte influenza- lignende symptomer.
Overall less than 1% of patients discontinued therapy because of acute flu-like symptoms.
I store placebokontrollerede kliniske undersøgelser var den procentdel af patienter, som oplevede en bivirkning, der mindede om hypersensitivitet, herunder urticaria, udslæt og allergiske reaktioner, lidt højere i Raptiva- gruppen (8%) end i placebogruppen (7%).
In large placebo-controlled clinical studies, the percentage of patients experiencing an adverse event suggestive of hypersensitivity, including urticaria, rash and allergic reactions was slightly higher in the Raptiva group (8%) than in the placebo group (7%).
Over lang tid (forsøg ACD2243g) øgedes antallet af hypersensivitetsrelaterede bivirkninger ikke (9, 8% i de første 12 uger og minder end 6, 65 i forsøgets resterende 12 ugers periode.
Over long term treatment, the frequency of hypersensitivity-related adverse events did not increase.
Forhøjelse af alkalisk fosfatase:
7 Elevation of alkaline phosphatase:
4, 5% af patienterne vedvarende forhøjet alkalisk fosfatase under Raptiva- behandlingen sammenlignet med 1% hos placebopatienterne.
In large placebo-controlled clinical studies approximately 4.5% of patients developed sustained elevation of alkaline phosphatase throughout Raptiva therapy compared to 1% in placebo patients.
Alle værdier var mellem 1, 5 gange og 3 gange den øvre normalgrænse (ULN) og lå efter afbrudt behandling igen på udgangsværdien.
All values were between 1.5 fold and 3 fold the ULN, and returned to baseline levels after therapy discontinuation.
5, 7% af patienterne udviklede forhøjet ALT under Raptiva- behandlingen sammenlignet med 3, 5% i placebogruppen.
About 5.7% of patients developed elevation in ALT during Raptiva therapy compared to 3.5% in placebo.
Alle tilfælde var asymptomatiske, og værdier over 2, 5 gange den øvre normalgrænse var ikke hyppigere i Raptiva- gruppen end i placebo- gruppen.
All occurrences were asymptomatic and values above 2.5 fold ULN were not more frequent in the Raptiva group than in the placebo group.
Andre behandlingsformer, der ændrer T- lymfocytfunktionerne, er blevet associeret med forhøjet risiko for alvorlige infektioner.
Other therapies that alter T-lymphocyte function have been associated with increased risk of developing serious infections.
27, 3% mod 24, 0% for patienter, der fik placebo.
In placebo controlled clinical trials, infection rates in Raptiva-treated patients was approximately 27.3% versus 24.0% in placebo-treated patients.
25, 7% mod 22, 3% for patienter, der blev behandlet med placebo.
In the target population studied in study IMP24011, the infection rate in Raptiva-treated patients was approximately 25.7% versus 22.3% in placebo-treated patients.
100 patientår for patienter, der fik placebo.
As regards serious infections, the overall incidence in both controlled and uncontrolled studies of up to 12 weeks was 2.8 per 100 patient-years for Raptiva-treated patients compared with 1.4 per 100 patient-years for placebo-treated patients.
100 patientår( Se afsnit 4. 4).
Over long term treatment, the incidence of serious infection was 1.8 per 100 patient years (see section 4.).
8 JC virusinfektion, som resulterer i Progressiv Multifocal Leukoencephalopati (PML) er rapporteret fra et post- marketing forsøg i en psoriasispatient, som var i behandling med Raptiva (se afsnit 4. 4).
JC virus infection resulting in PML has been reported in post-marketing surveillance in a patient with psoriasis receiving Raptiva (see section 4.4).
I placebokontrollerede kliniske forsøg svarede den samlede forekomst af malignitet (hvoraf størstedelen var non- melanom hudkræft) for patienter behandlet med Raptiva til den for patienter, som fik placebo.
In placebo controlled clinical trials, the overall incidences of malignancy (the majority of which were non-melanoma skin cancers) were similar in Raptiva-treated patients and in placebo-treated patients.
Endvidere var forekomsten af specifikke tumorer blandt Raptiva- patienter på linje med den, der blev observeret i kontrolleret psoriasispopulationer..
In addition, the incidences of specific tumours in Raptiva patients were in line with those observed in control psoriasis populations.
Der var ikke tegn på øget risiko for særlig malignitet over tid bort set fra non- melanom hudcancer (0, 3 vs.
There was no evidence of an increased risk of any particular malignancy over time with the exception of non-melanoma skin cancer (0.3 vs.
100 patientår, henholdsvis korttids - og langtidsbehandling) (Se afsnit 4. 4).
0.9 per 100 patient-years, short term and long term treatment, respectively) (See section 4.4).
Isolerede tilfælde er blevet observeret i post- marketing undersøgelser (se afsnit 4. 4)
(See section 4.4).
I et klinisk forsøg, hvor forsøgspersoner blev udsat for højere doser efalizumab (op til 10 mg/ kg intravenøst), oplevede en forsøgsperson, som modtog en intravenøs dosis på 3 mg/ kg, hypertension, kulderystelser og feber på dagen for doseringen af studiemedicinen, hvilket krævede hospitalsindlæggelse.
In a clinical study, where subjects were exposed to higher doses of efalizumab (up to 10 mg/ kg intravenous), one subject receiving 3 mg/ kg intravenous dose experienced hypertension, chills, and fever on the day of study drug dosing, which required hospitalization.
En anden forsøgsperson, som fik en dosis på 10 mg/ kg intravenøst, oplevede efter administrationen af efalizumab svære opkastninger ligeledes krævede hospitalsindlæggelse.
Another subject who received 10 mg/ kg intravenous dose experienced severe vomiting following administration of efalizumab, which also required hospitalization.
Doser op til 4 mg/ kg/ uge subkutant i 10 uger er blevet administreret uden toksisk effekt.
Doses up to 4 mg/ kg/ week subcutaneously for 10 weeks have been administered without any toxic effect.
Der kendes ingen modgift mod Raptiva, og der findes ingen særlig behandling mod Raptiva - overdosering udover at standse behandlingen og observere patienten.
There is no known antidote to Raptiva or any specific treatment for Raptiva overdose other than withholding treatment and patient observation.
Farmakoterapeutisk gruppe: selektive immunhæmmende stoffer, ATC- kode:
Pharmacotherapeutic group: selective immunosuppressive agents, ATC code:
Virkningsmekanisme Efalizumab er et rekombinant humaniseret monoklonalt antistof, der binder sig specifikt til CD11a - underenheden af LFA- 1 (lymfocyt- funktionsassocieret antigen- 1), et leukocyt- celleoverfladeprotein.
Mechanism of action Efalizumab is a recombinant humanized monoclonal antibody that binds specifically to the CD11a subunit of LFA-1 (lymphocyte function-associated antigen-1), a leukocyte cell surface protein.
Ved hjælp af denne mekanisme hæmmer efalizumab binding mellem LFA- 1 og ICAM- 1, der påvirker T- lymfocytters adhæsion til andre celletyper.
By this mechanism, efalizumab inhibits the binding of LFA-1 to ICAM-1, which interferes with T lymphocytes adhesion to other cell types.
LFA- 1 findes i aktiverede T- lymfocytter, og ICAM- 1 er opreguleret på endoteliale celler og keratinocytter i psoriasis- plaque.
LFA-1 is present on activated T lymphocytes, and ICAM-1 is up-regulated on endothelial cells and keratinocytes in psoriasis plaques.
Ved at forhindre binding af LFA- 1 og ICAM kan efalizumab lindre tegn og symptomer på psoriasis ved at hæmme flere stadier i den immunologiske kaskade.
By preventing LFA-1/ ICAM binding, efalizumab may alleviate signs and symptoms of psoriasis by inhibiting several stages in the immunologic cascade.
15- 30% af udgangsværdien før første dosis og mættede CD11a til < 5% af udgangsværdien af tilgængelige CD11a- bindingssteder.
Pharmacodynamic effects In studies using an initial dose of 0.7 mg/ kg followed by 11 weekly doses of 1.0 mg/ kg, efalizumab maximally reduced expression of CD11a on circulating T lymphocytes to approximately 15-30% of pre-dose baseline values and saturated CD11a to < 5% of baseline available CD11a binding sites.
Inden for 5 til 8 uger efter den 12. og sidste dosis efalizumab administreret med 1, 0 mg/ kg/ uge vendte CD11a- niveauerne tilbage til ±25% af udgangsværdierne.
Within 5 to 8 weeks following the 12th and final dose of efalizumab administered at 1.0 mg/ kg/ wk, CD11a levels returned to within a range of ±25% of baseline values.
9 En anden farmakodynamisk markør, forenelig med efalizumabs virkningsmekanisme, var en stigning i det absolutte cirkulerende leukocyttal observeret i løbet af behandlingen med efalizumab.
Another pharmacodynamic marker, consistent with the mechanism of action of efalizumab, was the increase in the absolute counts of circulating leukocytes observed during efalizumab treatment.
I kliniske forsøg skete der ca. en fordobling af lymfocyttallenes middelværdier i forhold til udgangsværdierne hos forsøgspersoner, der fik Raptiva 1, 0 mg/ kg/ uge.
In clinical trials, mean lymphocyte counts approximately doubled relative to baseline in subjects receiving 1.0 mg/ kg/ wk of Raptiva.