natgillin/translations-raw huggingface dataset:
Soliris (eculizumab) er indiceret til behandling af paroksystisk nokturn hæmoglobinuri (PNH).
Soliris (eculizumab) is indicated for the treatment of patients with paroxysmal nocturnal haemoglobinuria (PNH).
Den kliniske fordel ved Soliris til behandling af PNH er kun dokumenteret for patienter, der tidligere har fået foretaget transfusion.
Evidence of clinical benefit of Soliris in the treatment of patients with PNH is limited to patients with history of transfusions.
For at mindske risikoen for infektion med Neisseria meningitidis skal alle patienter vaccineres mindst 2 uger, før de får Soliris, og skal revaccineres efter de gældende retningslinjer for vaccination (se pkt.
To reduce the risk of meningococcal infection (Neisseria meningitidis), all patients must be vaccinated at least 2 weeks prior to receiving Soliris and must be re-vaccinated according to current medical guidelines for vaccination use (see section 4.4).
Soliris bør gives af sundhedspersoner under opsyn af en læge med erfaring i behandling af patienter med hæmatologiske sygdomme.
Soliris should be administered by a healthcare professional and under the supervision of a physician experienced in the management of patients with haematological disorders.
Dosisregimet består af en 5- ugers startfase efterfulgt af en vedligeholdelsesfase.
The dosing regimen consists of a 5-week initial phase followed by a maintenance phase:
Startfasen:
Initial phase:
600 mg eculizumab, givet som en intravenøs infusion af 25- 45 minutters varighed hver uge de første fire uger, efterfulgt af 900 mg eculizumab i startfasens femte uge.
600 mg of eculizumab via a 25 - 45 minute intravenous infusion every week for the first 4 weeks, followed by 900 mg of eculizumab for the fifth week of the initial phase.
Vedligeholdelsesfasen:
Maintenance phase:
5. 1).
900 mg of Soliris administered via a 25 - 45 minute intravenous infusion every 14 ± 2 days (see Section 5.1).
6. 6.
Instructions for preparation of the diluted solutions are described in section 6.6.
2 Soliris må ikke gives som en intravenøs bolusinjektion.
2 Do not administer as an intravenous push or bolus injection.
Den fortyndede opløsning af Soliris gives ved intravenøs infusion i løbet af 25- 45 minutter enten ved naturligt tilløb, med en pumpe af sprøjtetypen eller med en infusionspumpe.
The diluted solution of Soliris should be administered by intravenous infusion over 25 – 45 minutes via gravity feed, a syringe-type pump, or an infusion pump.
Patienterne bør overvåges i en time efter infusionen.
Patients should be monitored for one hour following infusion.
Hvis infusionshastigheden nedsættes, må den samlede infusionsvarighed ikke overstige to timer.
If the infusion is slowed, the total infusion time may not exceed two hours.
5. 2).
There is no experience in children (see section 5.2) Elderly:
Sikkerheden og virkningen af Soliris er ikke undersøgt hos patienter med nedsat nyrefunktion.
The safety and efficacy of Soliris have not been studied in patients with renal impairment.
Overfølsomhed over for eculizumab, murine proteiner eller et eller flere af hjælpestofferne.
Hypersensitivity to eculizumab, murine proteins or to any of the excipients.
Påbegynd ikke behandling med Soliris hos patienter:
Do not initiate Soliris therapy in patients:
• med Neisseria meningitidis- infektion, der ikke er færdigbehandlet, • som på nuværende tidspunkt ikke er vaccineret mod Neisseria meningitidis, eller • som har en kendt eller formodet arvelig komplementdefekt.
• with unresolved Neisseria meningitidis infection. • who are not currently vaccinated against Neisseria meningitidis. • who have known or suspected hereditary complement deficiencies.
Meningokokinfektion:
Meningococcal Infection:
Sådanne patienter kan tænkes at være udsat for infektion med usædvanlige serogrupper (specielt Y, W135 og X), men infektion med meningokokker af enhver serogruppe kan forekomme.
These patients might be at risk of disease by uncommon serogroups (particularly Y, W135 and X), although meningococcal disease due to any serogroup may occur.
For at mindske infektionsrisikoen skal alle patienter vaccineres mindst 2 uger, før de får Soliris, og skal revaccineres efter de gældende retningslinjer for vaccination.
To reduce the risk of infection, all patients must be vaccinated at least 2 weeks prior to receiving Soliris and must be re-vaccinated according to current medical guidelines for vaccination use.
Det kan stærkt anbefales at anvende tetravalente vacciner mod serogruppe A, C, Y og W- 135, fortrinsvis konjugerede.
Tetravalent vaccines against serotypes A, C, Y and W135 are strongly recommended, preferably conjugated ones.
De to vedrørte vaccinerede PNH- patienter, det tredje en uvaccineret patient med idiopatisk membranøs glomerulonefropati.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.There have been 3 reported cases of meningococcal infection in Soliris treated patients: two in vaccinated PNH patients and one in an unvaccinated patient with idiopathic membranous glomerulonephropathy.
Ved mistanke om infektion bør patienten straks vurderes og antibiotikabehandling om nødvendigt indledes.
All patients should be monitored for early signs of meningococcal infection, evaluated immediately if infection is suspected, and treated with antibiotics if necessary.
Patienterne bør informeres om sådanne tegn og symptomer og om, at de straks skal søge lægehjælp (se beskrivelsen i indlægssedlen).
Patients should be informed of these signs and symptoms and steps taken to seek medical care immediately (see Patient Information Leaflet for a description).
Andre systemiske infektioner:
Other Systemic Infections:
Øget infektionshyppighed og - sværhed, især med kapselbærende
The overall severity and frequency of infections in Soliris treated patients was similar to placebo treated patients in clinical studies, although an increase in the number and severity of infections, particularly due to encapsulated bacteria, cannot
3 bakterier, kan dog ikke udelukkes.
3 be excluded.
Oplysninger fra indlægssedlen bør formidles til patienterne, så de er særligt opmærksomme på muligheden for alvorlige infektioner og tegn og symptomer herpå.
Patients should be provided with information from the Patient Information Leaflet to increase their awareness of potential serious infections and the signs and symptoms of them.
Infusionsreaktioner:
Infusion Reactions:
Der sås dog ingen forskel fra placebo i forekomsten af forstyrrelser i immunsystemet inden for 48 timer efter administration af Soliris i de PNH- undersøgelser og andre undersøgelser, hvor Soliris blev anvendt.
As with all therapeutic proteins, administration of Soliris may result in infusion reactions or immunogenicity that could cause allergic or hypersensitivity reactions (including anaphylaxis), though immune system disorders within 48 hours of Soliris administration did not differ from placebo treatment in PNH and non-PNH studies conducted with Soliris.
I de kliniske undersøgelser forekom der ingen infusionsreaktioner blandt PNH- patienterne, der gjorde det nødvendigt at seponere Soliris.
In clinical trials, no PNH patients experienced an infusion reaction which required discontinuation of Soliris.
Ved svære infusionsreaktioner skal administrationen af Soliris afbrydes og passende medicinsk behandling gives.
Soliris administration should be interrupted in all patients experiencing severe infusion reactions and appropriate medical therapy administered.
Blandt Soliris- behandlede patienter i samtlige undersøgelser, herunder PNH - undersøgelser, er der konstateret antistofdannelse med lav titer i nogle få tilfælde med en hyppighed (3, 4%) svarende til placebobehandlede patienters (4, 8%).
Infrequent, low titre antibody responses have been detected in Soliris treated patients across all PNH and non-PNH studies with a frequency (3.4%) similar to that of placebo (4.8%).
Der er ikke beskrevet dannelse af neutraliserende antistoffer efter behandling med Soliris, og der er ikke iagttaget sammenhæng mellem antistofdannelse og klinisk respons eller bivirkninger.
No patients have been reported to develop neutralizing antibodies following therapy with Soliris, and there has been no observed correlation of antibody development to clinical response or adverse events.
Vaccination:
Immunization:
Før iværksættelse af Soliris- behandling anbefales det, at PNH- patienter vaccineres i henhold til de gældende retningslinjer for vaccination.
Prior to initiating Soliris therapy, it is recommended that PNH patients should receive immunizations according to current immunization guidelines.
For at mindske infektionsrisikoen skal alle patienter vaccineres mod meningokokker mindst to uger, før de får Soliris.
Additionally, all patients must be vaccinated against meningococcus at least 2 weeks prior to receiving Soliris.
Det anbefales at anvende en tetravalent, konjugeret vaccine, hvis en sådan forefindes (se meningokoksygdom).
If available, tetravalent, conjugated vaccines are recommended (see meningococcal disease).
Antikoagulationsbehandling: antikoagulationsbehandling.
Treatment with Soliris should not alter anticoagulant management.
Løbende kontrol af laboratorieprøver:
Laboratory Monitoring:
PNH- patienter bør overvåges for tegn og symptomer på intravaskulær hæmolyse, herunder indholdet i serum af laktatdehydrogenase (LDH).
PNH patients should be monitored for signs and symptoms of intravascular haemolysis, including serum lactate dehydrogenase (LDH) levels.
Der kan være have behov for dosisjustering inden for det anbefalede 14+ / - 2- dages doseringsskema i vedligeholdelsesfasen (op til hver 12. dag).
PNH patients receiving Soliris therapy should be similarly monitored for intravascular haemolysis by measuring LDH levels, and may require dose adjustment within the recommended 14±2 day dosing schedule during the maintenance phase (up to every 12 days).
Seponering af behandlingen:
Treatment Discontinuation:
Patienter, der får Soliris seponeret, bør overvåges for tegn og symptomer på alvorlig intravaskulær hæmolyse.
Patients who discontinue treatment with Soliris should be monitored for signs and symptoms of serious intravascular haemolysis.
Alvorlig hæmolyse er kendetegnet ved serum- LDH- værdier, der er højere end før behandlingen og er ledsaget af et eller flere af følgende tegn: et absolut fald på mere end 25% i PNH- klonstørrelse (uden at fortynding pga. transfusion medregnes) i løbet én uge eller mindre, et hæmoglobinindhold, der er < 5 g/ dl eller er faldet > 4 g/ dl i løbet af én uge eller mindre, angina, ændret mentaltilstand, 50% stigning i serumkreatinin, eller trombose.
Serious haemolysis is identified by serum LDH levels greater than the pre-treatment level, along with any of the following: greater than 25% absolute decrease in PNH clone size (in the absence of dilution due to transfusion) in one week or less; a haemoglobin level of < 5 gm/dL or a decrease of > 4 gm/dL in one week or less; angina; change in mental status; a 50% increase in serum creatinine level; or thrombosis.
Patienter, der får Soliris seponeret, skal overvåges i mindst 8 uger for tegn og symptomer på alvorlig intravaskulær hæmolyse og andre reaktioner.
Monitor any patient who discontinues Soliris for at least 8 weeks to detect serious haemolysis and other reactions.
Opstår der alvorlig hæmolyse efter seponering af Soliris, bør følgende procedurer/ behandlinger overvejes: blodtransfusion (pakkede erytrocytter), udskiftningstransfusion hvis PNH- erytrocytter udgør > 50% af den samlede mængde erytrocytter ifølge flowcytometri, antikoagulationsbehandling, kortikosteroider, genoptagelse af Soliris- behandlingen.
If serious haemolysis occurs after Soliris discontinuation, consider the following procedures/treatments: blood transfusion (packed RBCs), or exchange transfusion if the PNH RBCs are > 50% of the total RBCs by flow cytometry; anticoagulation; corticosteroids; or reinstitution of Soliris.
I de kliniske undersøgelser vedrørende PNH fik 16 patienter seponeret Soliris- behandlingsregimet.
In PNH clinical studies, 16 patients discontinued the Soliris treatment regimen.
Produktet indeholder 5, 00 mmol natrium pr. dosis (1 hætteglas).
This medicinal product contains 5.00 mmol sodium per dose (1 vial).
4 Der foreligger ikke kliniske data om eksponering for Soliris under graviditet.
For Soliris, no clinical data on exposed pregnancies are available.
5. 3).
Animal reproduction studies have not been conducted with eculizumab (see section 5.3).
Eculizumab kan derfor tænkes at medføre terminal komplementhæmning i det føtale kredsløb.
4 Human IgG are known to cross human placental barrier, and thus eculizumab may potentially cause terminal complement inhibition in the foetal circulation.
Til gravide bør Soliris derfor kun anvendes, hvis der er klart behov for det.
Therefore, Soliris should be given to a pregnant woman only if clearly needed.
Kvinder i den fødedygtige alder skal bruge sikker antikonception under behandlingen og indtil fem måneder efter behandlingen.
Woman of childbearing potential have to use adequate contraception methods during treatment and up to 5 months after treatment.
Det vides ikke, om eculizumab udskilles i modermælk.
It is not known whether eculizumab is secreted into human milk.
Da mange lægemidler og immunglobuliner udskilles i modermælk, og da der er mulighed for alvorlige uønskede reaktioner hos diende spædbørn, bør amning undlades under behandlingen og indtil fem måneder efter behandlingen.
Since many medicinal products and immunoglobulins are secreted into human milk, and because of the potential for serious adverse reactions in nursing infants, lactation should be discontinued during treatment and up to 5 months after treatment.
Heraf er størstedelen indgået i den forlængede undersøgelse E05- 001.
4.8 Undesirable effects Eculizumab for the treatment of PNH was studied in three clinical studies that included 195 eculizumab-treated patients and most of these patients have been enrolled in the E05-001 extension study.
Der var én hovedundersøgelse, hvori eculizumab- behandlingsarmen blev sammenlignet med en placeboarm.
There was one pivotal trial comparing the eculizumab-treatment arm to a placebo-treatment arm.
De hyppigst indberettede bivirkninger er hovedpine, rhinofaryngitis, kvalme pyreksi, myalgi, træthed og herpes simplex, som hver forekommer hos flere end 5 ud af hver 100 patienter.
The most commonly reported adverse reactions are headache, nasopharyngitis, nausea, pyrexia, myalgia, fatigue, and herpes simplex, each occurring in 5 or more out of 100 patients.
De bivirkninger af eculizumab, der blev rapporteret med en hyppighed svarende til meget almindelige (≥1/ 10) eller almindelige (> 5/ 100 og < 10/ 100) hos i alt 140 patienter i C04- 001 og C04- 002, er opført i tabel 1, fordelt på organklasse og foretrukket betegnelse.
Adverse events reported at a very common (≥1/10) or common (> 5/100 and < 10/100) frequency with eculizumab in a total of 140 patients in C04-001 and C04-002 are listed by system organ class and preferred term in Table 1.
Bivirkningerne var hovedsagelig lette til moderate.
Adverse events were mostly mild to moderate in severity.
Usædvanlige eller sjældne bivirkninger kan ikke vurderes som følge af det begrænsede antal eksponerede patienter (195 PNH- patienter).
Uncommon or rare events cannot be estimated due to limited patient exposure (195 PNH patients).
Inden for hver frekvensgruppe er bivirkningerne opstillet i rækkefølge efter, hvor alvorlige de er.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Indberettede bivirkninger i undersøgelse C04- 001 og C04- 002 Hændelse
Adverse Events Reported in Studies C04-001 and C04-002 Adverse Event
Systemorganklasse
Preferred Term
Almindelig (5/ 100- 1/ 10)
System Organ Class Infections and infestations
Infektioner og parasitære sygdomme Urinvejsinfektion Rhinofaryngitis Øvre luftvejsinfektion
Very Common (> 1/10) Urinary tract infection Nasopharyngitis Upper Respiratory Tract Infection
Virusinfektion Gastroenteritis
Common (5/100 – 1/10) Respiratory Tract Infection Herpes Simplex Sinusitis Viral Infection Gastroenteritis
Psykiske forstyrrelser Nervesystemet
Psychiatric disorders Nervous System Disorders
5 Luftveje, thorax og mediastinum
Respiratory, Thoracic and Mediastinal Disorders
Epistakse Faryngolaryngeale smerter Hoste
Epistaxis Pharyngolaryngeal pain Cough
Mave- tarmkanalen
5 Gastrointestinal Disorders
Diarré Nausea
Diarrhoea Nausea
Opkastning Abdominalsmerter Øvre abdominalsmerter Konstipation
Vomiting Abdominal Pain Abdominal Pain Upper Constipation
Udslæt Pruritis
Rash Pruritis
Sygdomme i bevægeapparatet og bindevævssygdomme
Musculoskeletal and Connective Tissue Disorders
Rygsmerter Artralgi
Back Pain Arthralgia
Myalgi Smerter i ekstremiteter Muskelkrampe
Myalgia Pain in extremity Muscle cramp
Influenzalignende sygdom Træthed
Influenza-Like Illness Fatigue
I undersøgelse C04- 001 var hovedpine den hyppigst iagttagne bivirkning af eculizumab.
In the C04-001 study, headache was the most common adverse event observed with eculizumab.
Hovedpinen var i alle tilfælde let til moderat, bortset fra 1 patient på eculizumab og 1 patient på placebo.
Headaches were observed in 44.2% (19/43 patients) of patients treated with eculizumab and 27.3% (12/44 patients) in placebo-treated patients and were mild/moderate in all but 1 eculizumab treated and 1 placebo-treated patients.
I de fleste tilfælde var hovedpinen let og varede ikke ud over startfasen af Soliris- behandlingen.
Most headaches were mild and did not persist after the initial administration phase of Soliris.
Desuden forekom følgende bivirkninger mindst 5% hyppigere med Soliris end med placebo: rhinofaryngitis (25, 0%), kvalme (17, 1%), pyreksi (14. 3%), myalgi (7, 9%), træthed (7, 9%) og herpes simplex (5, 7%).
In addition, the following adverse events were increased in frequency by 5% or more with Soliris as compared to placebo: nasopharyngitis (25.0%), nausea (17.1%), pyrexia (14.3%), myalgia (7.9%), fatigue (7.9%), and herpes simplex (5.7%).
Intet tydede på, at infektionshyppigheden i samtlige PNH - undersøgelser under ét var forhøjet i forhold til placebo, heller ikke alvorlige infektioner, svære infektioner eller multiple infektioner.
There was no evidence of an increased incidence of infection across PNH studies with eculizumab as compared to placebo, including serious infections, severe infections or multiple infections.
4. 4).
The most serious adverse event was meningococcal septicaemia in two vaccinated PNH patients (see section 4.4).
Antistoffer med lav titer blev konstateret hos 2% af de Soliris- behandlede PNH- patienter.
Low titres of antibodies were detected in 2% patients with PNH treated with Soliris.
Sikkerhedsdata fra andre kliniske undersøgelser Der blev uddraget støttende sikkerhedsdata fra 11 kliniske undersøgelser med 716 patienter, som var blevet eksponeret for eculizumab og tilhørte seks andre sygdomspopulationer end PNH.
Safety Data From Other Clinical Studies Supportive safety data were obtained in 11 clinical studies that included 716 patients exposed to eculizumab in six disease populations other than PNH.
Af øvrige bivirkninger blev følgende rapporteret med mindst 2% større hyppighed for Soliris end for placebo i alle placebokontrollerede dobbeltblindundersøgelser under ét hos patienter med andre diagnoser end PNH (N=526 patienter behandlet med Soliris; N=221 patienter behandlet med placebo): øvre luftvejsinfektioner, udslæt og traumer.
With regard to other AEs and considering all double-blind, placebo-controlled studies in patients diagnosed with diseases other than PNH (N=526 patients with Soliris; N=221 patients with placebo), AEs reported with Soliris at a frequency of 2% or greater than the frequency reported with placebo were: upper respiratory tract infection, rash, and injury.
Immunmodulerende midler, ATC- kode:
Immunomodulators, ATC code:
Soliris er et rekombinant, humaniseret, monoklonalt IgG2/ 4κ- antistof, der bindes til humant komplementprotein C5 og hæmmer den terminale komplementaktivering.
Soliris is a recombinant humanised monoclonal IgG2/4k antibody that binds to the human C5 complement protein and inhibits the activation of terminal complement.
Soliris- antistoffet indeholder dels humane konstante områder, dels murine antigen- bindende områder der er indsat i det variable område af den humane struktur af lette og tunge kæder.
The Soliris antibody contains human constant regions and murine complementarity-determining regions grafted onto the human
Soliris- antistoffet indeholder dels humane konstante områder, dels murine komplementaritetsbestemmende områder, der er indsat i de variable områder af den humane ramme med lette og tunge kæder.
6 framework light- and heavy-chain variable regions.
148 kDa.
Soliris is composed of two 448 amino acid heavy chains and two 214 amino acid light chains and has a molecular weight of approximately 148kDa.
Soliris produceres i et ekspressionssystem for murint myelom (NS0 cellelinje) og renses ved affinitets - og ionbytningskromatografi.
Soliris is produced in a murine myeloma (NS0 cell line) expression system and purified by affinity and ion exchange chromatography.
Virkningsmekanisme Eculizumab, det aktive indholdsstof i Soliris, er en terminal komplementhæmmer, der specifikt bindes til komplementproteinet C5 med høj affinitet og derved blokerer dettes spaltning til C5a og C5b, så dannelsen af det terminale komplementkompleks C5b- 9 forhindres.
Mechanism of Action Eculizumab, the active ingredient in Soliris, is a terminal complement inhibitor that specifically binds to the complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a and C5b and preventing the generation of the terminal complement complex C5b-9.
Soliris genopretter derved PNH - patienternes terminale regulering af komplement i blodet og hæmmer den komplementmedierede intravaskulære hæmolyse hos disse patienter.
Soliris therefore restores terminal complement regulation in the blood of PNH patients and inhibits terminal complement mediated intravascular haemolysis in PNH patients.
Administration af Soliris resulterer i hurtig og vedholdende reduktion i den terminale komplementaktivitet.
Administration of Soliris results in a rapid and sustained reduction in terminal complement activity.
35 µg/ ml er tilstrækkelig til at bevirke stort set fuldstændig hæmning af den terminale komplementmedierede intravaskulære hæmolyse hos de fleste PNH- patienter.
Administration of Soliris haemolytic activity.
Administration af Soliris resulterer i hurtig og vedholdende reduktion af den komplementmedierede hæmolytiske aktivitet.
resulted in a rapid and sustained reduction in complement-mediated
PNH- patienter blev desuden behandlet med Soliris i en 52 ugers undersøgelse med én enkelt arm (C04- 002) og i en langvarig forlængelsesundersøgelse (E05- 001).
The safety and efficacy of Soliris in PNH patients with haemolysis were assessed in a randomized, double-blind, placebo-controlled 26 week study (C04-001); PNH patients were also treated with Soliris in a single arm 52 week study (C04-002); and in a long term extension study (E05-001).
I alle undersøgelserne blev Soliris givet i en dosis på 600 mg af testpræparatet hver 7 ± 2 dage i 4 uger, efterfulgt af 900 mg 7 ± 2 dage senere, derefter 900 mg hver 14 ± 2 dage i hele undersøgelsens varighed.
In all studies, the dose of Soliris was 600 mg study drug every 7 ± 2 days for 4 weeks, followed by 900 mg 7 ± 2 days later, then 900 mg every 14 ± 2 days for the study duration.
Soliris blev indgivet som en intravenøs infusion af 25- 45 minutters varighed.
Soliris was administered as an intravenous infusion over 25 – 45 minutes.
I undersøgelse C04- 001 (TRIUMPH) blev PNH- patienter, der havde fået mindst fire transfusioner de foregående 12 måneder, og som havde et flowcytometrisk verificeret indhold af PNH- celler på mindst 10% og et trombocyttal på mindst 100 000/ µl, randomiseret til enten Soliris (n = 43) eller placebo (n = 44).
In study C04-001 (TRIUMPH) PNH patients with at least 4 transfusions in the prior 12 months, flow cytometric confirmation of at least 10% PNH cells and platelet counts of at least 100,000/microliter were randomized to either Soliris (n = 43) or placebo (n = 44).