natgillin/translations-raw huggingface dataset:
Du kan finde yderligere oplysninger om dette lægemiddel på Det Europæiske Lægemiddelagenturs hjemmeside: http://www.ema.europa.eu/.
Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu.
Hvis patienten glemmer en dosis Zydelig inden for 6 timer fra det tidspunkt den normalt tages, skal patienten tage den glemte dosis snarest muligt og genoptage det normale doseringsskema.
If the patient misses a dose of Zydelig within 6 hours of the time it is usually taken, the patient should take the missed dose as soon as possible and resume the normal dosing schedule.
Stevens-Johnsons syndrom og toksisk epidermal nekrolyse Tilfælde af Stevens-Johnsons syndrom (SJS) og toksisk epidermal nekrolyse (TEN) med dødelig udgang er blevet rapporteret, når idelalisib blev administreret samtidigt med andre lægemidler forbundet med disse syndromer.
Stevens-Johnson syndrome and toxic epidermal necrolysis Cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with fatal outcomes have been reported when idelalisib was administered concomitantly with other medicinal products associated with these syndromes.
I et embryoføtalt udviklingsstudie med rotter blev der observeret øget post-implantationstab, misdannelser (ingen kaudal vertebra og i nogle tilfælde også ingen sakral vertebra), variationer i skelettet og lavere legemsvægt af fosteret.
In an embryo-foetal development study in rats, increased post-implantation loss, malformations (absence of caudal vertebrae and in some cases also of sacral vertebrae), skeletal variations and lower foetal body weights were observed.
Ud af de 125 patienter, der indgik, var 80 (64 %) mænd, og medianalderen var 64 år (interval: 33 til 87 år), og 110 (89 %) var hvide.
Of the 125 subjects enrolled, 80 (64%) were male, the median age was 64 years (range: 33 to 87), and 110 (89%) were white.
Den primære metabolit, GS-563117, kan øge fototoksicitet, når cellerne samtidigt eksponeres over for UVA-lys.
The major metabolite, GS-563117, may enhance phototoxicity when cells are simultaneously exposed to UVA light.
Vablerne kan også omfatte slimhinden i munden, kønsdelene og/eller øjnene.
Blistering can also involve the lining of the mouth, genitals, and/or eyes.
Forventet virkning af idelalisib på lægemiddelniveauer
Expected effect of idelalisib on drug levels
Varigheden af profylakse efter behandling skal baseres på en klinisk vurdering, eventuelt under hensyntagen til patientens risikofaktorer såsom samtidig kortikosteroidbehandling og forlænget neutropeni (se pkt.
The duration of post-treatment prophylaxis should be based on clinical judgment and may take into account a patient's risk factors such as concomitant corticosteroid treatment and prolonged neutropenia (see section 4.8).
• som førstevalgsbehandling hos patienter med 17p-deletion eller TP53-mutation, som ikke er egnede til at få andre behandlinger (se pkt.
• as first line treatment in the presence of 17p deletion or TP53 mutation in patients who are not eligible for any other therapies (see section 4.4).
En dosisrelateret forøgelse af pankreatiske øcelletumorer blev observeret med lav hyppighed hos hanrotter ved eksponeringer op til 0,4 gange sammenlignet med den menneskelige eksponering ved den anbefalede dosis; lignende fund blev ikke konstateret hos hunrotter ved 0,62 gange eksponeringsmargin.
A dose-related increase in pancreatic islet cell tumors was observed at low incidence in male rats at exposures up to 0.4-fold compared to the human exposure at the recommended dose; a similar finding was not observed in female rats at 0.62-fold exposure margin.
Hos patienter, der får alvorlige lungehændelser, bør idelalisib afbrydes, og patienten vurderes for en forklarende ætiologi.
In patients presenting with serious lung events, idelalisib should be interrupted and the patient assessed for an explanatory aetiology.
Start af isoleret lymfocytose forekommer typisk i de første 2 uger af behandling med idelalisib og er ofte forbundet med reduceret lymfadenopati.
The onset of isolated lymphocytosis typically occurs during the first 2 weeks of idelalisib therapy and is often associated with reduction of lymphadenopathy.
Potentielle interaktioner mellem idelalisib ved administration sammen med lægemidler, der er CYP3A-substrater er opstillet i tabel 1 (en stigning er indikeret ved ”↑”).
Potential interactions between idelalisib and co-administered medicinal products that are CYP3A substrates are listed in Table 1 (increase is indicated as “↑”).
Hud og subkutane væv Udslæt***
Skin and subcutaneous tissue disorders Rash***
Da en reduktion af plasmakoncentrationen af idelalisib kan føre til nedsat virkning, bør det undgås at administrere Zydelig sammen med moderate eller stærke CYP3A-inducere (se pkt.
Since a reduction in idelalisib plasma concentrations may result in decreased efficacy, co-administration of Zydelig with moderate or strong CYP3A inducers should be avoided (see section 4.5).
^ Analysen af samlet overlevelse (OS, overall survival) inkluderer data fra patienter, der fik placebo + R i studie 312-0116 og efterfølgende fik idelalisib i et forlængelsesstudie, baseret på intent-to-treat-analyse.
^ Overall survival (OS) analysis includes data from subjects who received placebo + R on study 312-0116 and subsequently received idelalisib in an extension study, based on intent-to-treat analysis.
Efter start af idelalisib er der blevet observeret en midlertidig stigning i antallet af lymfocytter (dvs. ≥ 50 % stigning fra baseline og over det absolutte lymfocyttal på 5.000/mikroliter).
Upon initiation of idelalisib, a temporary increase in lymphocyte counts (i.e., ≥ 50% increase from baseline and above absolute lymphocyte count of 5,000/mcL) has been observed.
Ketoconazol, itraconazol, posaconazol, voriconazol
Ketoconazole, itraconazole, posaconazole, voriconazole
Pakningsstørrelser og yderligere oplysninger Zydelig indeholder:
Contents of the pack and other information What Zydelig contains
• pimozid, et lægemiddel, der anvendes til at behandle unormale tanker og følelser
• pimozide, a medicine used to treat abnormal thoughts or feelings
Regelmæssig klinisk og laboratoriemæssig monitorering for CMV-infektion anbefales hos patienter med positiv CMV-serologi ved påbegyndelse af idelalisib eller med anden evidens for CMV-infektion i anamnesen.
Regular clinical and laboratory monitoring for CMV infection is recommended in patients with positive CMV serology at the start of treatment with idelalisib or with other evidence of a history of CMV infection.
Kronisk hepatitis
Chronic hepatitis
Analyserne af PFS, samlet responsrate (ORR, overall response rate) og lymfeknude responsrate (LNR, lymph node response rate) var baseret på evaluering af en uafhængig bedømmelseskomité (IRC, independent review committee).
The analyses of PFS, overall response rate (ORR) and lymph node response rate (LNR) were based on evaluation by an independent review committee (IRC).
Hyppighederne er defineret som: meget almindelig (≥ 1/10), almindelig (≥ 1/100 til < 1/10), ikke almindelig (≥ 1/1.000 til < 1/100), sjælden (≥ 1/10.000 til
(≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to
Ved formodning om SJS eller TEN, bør idelalisib straks seponeres, og patienten bør behandles i overensstemmelse hermed.
If SJS or TEN is suspected, idelalisib should be immediately interrupted and the patient treated accordingly.
Tyrosinkinasehæmmere, såsom dasatinib og nilotinib, også vincristin og vinblastin
Tyrosine kinase inhibitors such as dasatinib and nilotinib, also vincristine and vinblastine
Behandlingen med Zydelig skal pauseres i tilfælde af en grad 3 eller 4 aminotransferaseforhøjelse (alaninaminotransferase [ALAT]/aspartataminotransferase [ASAT] > 5 x øvre normalgrænse [ULN]).
Treatment with Zydelig must be withheld in the event of a Grade 3 or 4 aminotransferase elevation (alanine aminotransferase [ALT]/aspartate aminotransferase [AST] > 5 x upper limit of normal [ULN]).
Du skal også anvende en barrieremetode til prævention, såsom kondomer eller spiral, mens du tager Zydelig, og i 1 måned efter din sidste behandling.
You must also use a barrier method of contraception such as condoms or the “coil” while taking Zydelig and for 1 month after your last treatment.
• hvis du er stakåndet eller har vejrtrækningsbesvær
• if you have shortness of breath or difficulty breathing
Zydelig kan forårsage lungebetændelse.
Zydelig can cause lung inflammation.
Behandlingen med Zydelig skal pauseres hos patienter, så længe patientens absolutte neutrofiltal (ANC) er under 500 pr. mm3.
Treatment with Zydelig should be withheld in patients while absolute neutrophil count (ANC) is below 500 per mm3.
Derfor har idelalisib potentialet til at påvirke andre lægemidler, der metaboliseres af CYP3A, som kan føre til øgede serumkoncentrationer af det andet produkt (se pkt.
Thus, idelalisib has the potential to interact with medicinal products that are metabolised by CYP3A, which may lead to increased serum concentrations of the other product (see section 4.5).
Populationsfarmakokinetiske analyser indikerede, at køn og race ikke havde nogen klinisk relevant virkning på eksponeringerne over for idelalisib eller GS-563117.
Population pharmacokinetic analyses indicated that gender and race had no clinically relevant effect on the exposures to idelalisib or GS-563117.
Der er utilstrækkelige data til at give dosisanbefalinger for patienter med svært nedsat leverfunktion.
There is insufficient data to make dose recommendations for patients with severe hepatic impairment.
Idelalisib og GS-563117 er substrater af P-gp og BCRP.
Idelalisib and GS-563117 are substrates of P-gp and BCRP.
• som har fået mindst en tidligere behandling (se pkt.
• who have received at least one prior therapy (see section 4.4), or
Reaktion
Reaction
Der rådes til forsigtighed, hvis Zydelig anvendes sammen med lægemidler med et snævert terapeutisk indeks, der er substrater for disse enzymer (warfarin, phenytoin, S-mephenytoin).
Caution is advised if Zydelig is used together with narrow therapeutic index drugs that are substrates of these enzymes (warfarin, phenytoin, S-mephenytoin).
En indledende dosisjustering af idelalisib anses ikke for at være nødvendig ved administration sammen med CYP3A/P-gp-hæmmere, men det anbefales at intensivere overvågning for bivirkninger.
No initial dose adjustment of idelalisib is considered necessary when administered with CYP3A/P-gp inhibitors, but an intensified monitoring of adverse reactions is recommended.
Makrolid-antibiotika
Macrolide antibiotics
↑ serumkoncentrationer Nøje overvågning af bivirkninger (f.eks. respirationsdepression, sedation) anbefales.
↑ serum concentrations Careful monitoring of adverse reactions (e.g., respiratory depression, sedation) is recommended.
Forhøjelser i serumtransaminase korrelerede med levernekrose hos hunde, men blev ikke observeret hos rotter.
Serum transaminase elevations correlated with hepatic necrosis in dogs, but were not observed in rats.
Der rådes til forsigtighed, hvis Zydelig anvendes sammen med lægemidler med et snævert terapeutisk indeks, der er substrater for CYP2C8 (paclitaxel).
Caution is advised if Zydelig is used together with narrow therapeutic index drugs that are substrates of CYP2C8 (paclitaxel).
Højdensitets-polyethylen (HDPE)-tabletbeholder med et børnesikret lukke af polypropylen, der indeholder 60 filmovertrukne tabletter og en vatspiral af polyester.
High density polyethylene (HDPE) bottle, capped with a polypropylene child-resistant closure, containing 60 film-coated tablets and a polyester coil.
• Zydelig kan få p-piller og implanterede hormonelle præventionsmidler til at være mindre effektive.
• Zydelig may make the contraceptive “pill” and implanted hormonal contraceptives work less well.
Desuden fik 86 patienter fra dette studie, som blev randomiseret til placebo + rituximab, efterfølgende idelalisib som enkeltstof i et forlængelsesstudie (studie 312-0117).
In addition, 86 subjects from this study who were randomised to receive placebo + rituximab went on to receive idelalisib as a single agent in an extension study (study 312-0117).
Behandlingen med Zydelig skal pauseres i tilfælde af grad 3 eller 4 diarré/colitis.
Treatment with Zydelig must be withheld in the event of Grade 3 or 4 diarrhoea/colitis.
Der er desuden blevet rapporteret hepatocellulær leverskade, herunder leversvigt.
There have also been reports of hepatocellular injury including hepatic failure.
Blod og lymfesystem Neutropeni
Blood and lymphatic system disorders Neutropenia
Der er set tilfælde af PJP efter seponering af idelalisib.
There have been cases of PJP after stopping idelalisib treatment.
Amlodipin, diltiazem, felodipin, nifedipin, nicardipin
Amlodipine, diltiazem, felodipine, nifedipine, nicardipine
• clarithromycin, telithromycin, lægemidler, der anvendes til at behandle bakterieinfektioner
• clarithromycin, telithromycin, medicines used to treat bacterial infections
Der er blevet observeret forhøjelser af ALAT og ASAT af grad 3 og 4 (> 5 x ULN) i kliniske studier med idelalisib.
Elevations in ALT and AST of Grade 3 and 4 (> 5 x ULN) have been observed in clinical studies of idelalisib.
For patienter i placebo + R-gruppen inkluderer oversigten data op til den første idelalisib-dosis i et forlængelsesstudie.
For subjects in the placebo + R group, the summary includes data up to the first dosing of idelalisib in an extension study.
Der blev ikke observeret nedsat leverfunktion eller kroniske transaminaseforhøjelser hos rotter eller hunde i studier, der varede 13 uger eller længere.
No hepatic impairment or chronic transaminase elevations were observed in rats or dogs in studies of 13 weeks and longer duration.
Patienterne blev randomiseret i forholdet 1:1 til 8 cyklusser rituximab (første cyklus med 375 mg/m2 kropsoverfladeareal (BSA, body surface area), efterfølgende cyklusser med 500 mg/m2 BSA) i kombination med enten oralt placebo to gange dagligt eller med idelalisib 150 mg to gange dagligt indtil sygdomsprogression eller uacceptabel toksicitet.
Subjects were randomised 1:1 to receive 8 cycles of rituximab (first cycle at 375 mg/m2 body surface area [BSA], subsequent cycles at 500 mg/m2 BSA) in combination with either an oral placebo twice daily or with idelalisib 150 mg taken twice daily until disease progression or unacceptable toxicity.
Alle patienter skal have deres blodtal monitoreret mindst hver 14. dag i de første 6 måneder af behandlingen med idelalisib og mindst én gang ugentligt hos patienter med et ANC på under 1.000 pr. mm3 (se pkt.
Blood counts should be monitored in all patients at least every 2 weeks for the first 6 months of treatment with idelalisib, and at least weekly in patients while ANC is less than 1,000 per mm3 (see section 4.2).
Idelalisibs sikkerhed og virkning blev vurderet i et klinisk multicenterstudie med en enkelt arm (studie 101-09), som blev udført hos 125 patienter med indolent B-celle non-Hodgkin lymfom (iNHL, herunder: FL, n = 72; SLL, n = 28; lymfoplasmacytisk lymfom/Waldenströms makroglobulinæmi [LPL/WM], n = 10; og marginalzonelymfom [MZL], n = 15).
The safety and efficacy of idelalisib were assessed in a single-arm, multicentre clinical study (study 101-09) conducted in 125 subjects with indolent B-cell non-Hodgkin lymphoma (iNHL, including: FL, n = 72; SLL, n = 28; lymphoplasmacytic lymphoma/Waldenström macroglobulinaemia [LPL/WM], n = 10; and marginal zone lymphoma [MZL], n = 15).
Samtidig behandling med idelalisib og CYP3A-substrater med alvorlige og/eller livstruende bivirkninger (f.eks. alfuzosin, amiodaron, cisaprid, pimozid, quinidin, ergotamin, dihydroergotamin, quetiapin, lovastatin, simvastatin, sildenafil, midazolam, triazolam) bør undgås, og der bør om muligt anvendes andre lægemidler, som er mindre følsomme over for CYP3A4-hæmning.
Concomitant treatment of idelalisib with CYP3A substrates with serious and/or life-threatening adverse reactions (e.g., alfuzosin, amiodarone, cisapride, pimozide, quinidine, ergotamine, dihydroergotamine, quetiapine, lovastatin, simvastatin, sildenafil, midazolam, triazolam) should be avoided and alternative medicinal products that are less sensitive to CYP3A4 inhibition should be used if possible.
Virkning af idelalisib på andre lægemidlers farmakokinetik
Effect of idelalisib on the pharmacokinetics of other medicinal products
Idelalisib AUC (ubundet), efter der tages hensyn til forskelle i proteinbinding, var ~80 % (1,8 gange) højere ved moderat og ~152 % (2,5 gange) højere ved svært nedsat leverfunktion, sammenlignet med matchede kontroller.
The idelalisib AUC (unbound), after accounting for differences in protein binding, was ~80% (1.8-fold) higher in moderate and ~152% (2.5-fold) higher in severe impairment compared to matched controls.
Idelalisib var ikke kræftfremkaldende ved eksponeringer på op til 1,4/7,9 gange (begge køn) hos mus sammenlignet med eksponeringen hos patienter med hæmatologiske maligniteter, der fik den anbefalede dosis på 150 mg to gange dagligt.
Idelalisib was not carcinogenic at exposures up to 1.4/7.9-fold (male/female) in mice compared to the exposure in patients with haematologic malignancies administered the recommended dose of 150 mg twice daily.
Patienterne fik idelalisib 150 mg to gange dagligt, og rituximab 375 mg/m2 BSA ugentligt for 8 doser.
Subjects received idelalisib 150 mg twice daily and rituximab 375 mg/m2 BSA weekly for 8 doses.
ANC 1.000 til < 1.500/mm3
ANC 1,000 to < 1,500/mm3
En generelt højere forekomst af infektioner (herunder infektioner af grad 3 og 4) blev observeret i idelalisib-armene sammenlignet med kontrolarmene i de kliniske studier med idelalisib.
Higher frequencies of infections overall, including Grade 3 and 4 infections, were observed in the idelalisib arms compared to the control arms of idelalisib clinical studies.
↑ serumkoncentrationer Niveauerne af antikonvulsiva bør monitoreres.
↑ serum concentrations Anticonvulsant drug levels should be monitored.
Oralt budesonid
Oral budesonide
ANC 500 til < 1.000/mm3
ANC 500 to < 1,000/mm3
Efter en enkelt 150 mg oral dosis af [14C]-mærket idelalisib, blev hhv. ca. 78 % og 15 % udskilt i fæces og urin.
Following a single 150 mg oral dose of [14C]-labelled idelalisib, approximately 78% and 15% was excreted in faeces and urine, respectively.
Brug af anden medicin sammen med Zydelig
Other medicines and Zydelig
• sildenafil, tadalafil, lægemidler, der anvendes til at behandle impotens og pulmonal hypertension, en lungesygdom, der gør det vanskeligt at trække vejret
• sildenafil, tadalafil, medicines used to treat impotence and pulmonary hypertension, a lung disease that makes breathing difficult
Der er en potentiel risiko for, at idelalisib, via den primære metabolit, GS-563117, kan forårsage fotosensitivitet hos behandlede patienter.
There is a potential risk that idelalisib, via its major metabolite, GS-563117, may cause photosensitivity in treated patients.
Klinisk overvågning anbefales.
Clinical monitoring is recommended.
Fortæl det til lægen, hvis du har allergi over for sunset yellow FCF (E110).
Tell your doctor if you have an allergy to sunset yellow FCF (E110).
• hvis du har rødme og vabler på huden
• if you have redness and blistering of the skin
Buspiron, clorazepat, diazepam, estazolam, flurazepam, zolpidem
Buspirone, clorazepate, diazepam, estazolam, flurazepam, zolpidem
Indeholder sunset yellow FCF (E110), se indlægssedlen for yderligere information.
Contains sunset yellow FCF (E110), see leaflet for further information.
Substrater for inducerbare enzymer (f.eks. CYP2C9, CYP2C19, CYP2B6 og UGT) Idelalisib inducerede adskillige enzymer in vitro, og en risiko for nedsat eksponering og dermed reduceret virkning over for substrater af inducerbare enzymer, såsom CYP2C9, CYP2C19, CYP2B6 og UGT kan ikke udelukkes.
Substrates of inducible enzymes (e.g., CYP2C9, CYP2C19, CYP2B6 and UGT) In vitro, idelalisib was an inducer of several enzymes, and a risk for decreased exposure and thereby decreased efficacy of substrates of inducible enzymes such as CYP2C9, CYP2C19, CYP2B6 and UGT cannot be excluded.
Ikke muteret IGHV
Unmutated IGHV
MIDLER MOD CANCER
ANTI-CANCER AGENTS
Pneumonitis og organiserende pneumoni
Pneumonitis and organising pneumonia
Idelalisib bør ikke administreres sammen med midazolam (oral) eller triazolam.
Idelalisib should not be co-administered with midazolam (oral) or triazolam.
Et studie af idelalisibs farmakokinetik og sikkerhed blev udført hos raske personer og hos patienter med moderat (Child-Pugh klasse B) eller svært (Child-Pugh klasse C) nedsat leverfunktion.
A study of pharmacokinetics and safety of idelalisib was performed in healthy subjects and subjects with moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment.
Det skal du vide, før du begynder at tage Zydelig Tag ikke Zydelig
What you need to know before you take Zydelig Do not take Zydelig
Zydelig indeholder sunset yellow FCF (E110)
Zydelig contains sunset yellow FCF (E110)
Fuldt optrukken linje: idelalisib + R (N = 110), stiplet linje: placebo + R (N = 110) R: rituximab; N: antal patienter i gruppen
Solid line: idelalisib + R (N = 110), dashed line: placebo + R (N = 110) R: rituximab; N: number of subjects per group
Ældre Specifik dosisjustering er ikke nødvendig hos ældre patienter (i alderen ≥ 65 år) (se pkt.
Elderly No specific dose adjustment is required for elderly patients (aged ≥ 65 years) (see section 5.2).
Af disse havde 5,7 %, som fik idelalisib + et anti-CD20 monoklonalt antistof (rituximab eller ofatumumab), og 1,5 %, der kun fik et anti-CD20 monoklonalt antistof (rituximab eller ofatumumab), udslæt af grad 3, og ingen patienter havde en grad 4-bivirkning.
Of these, 5.7% who received idelalisib + an anti-CD20 monoclonal antibody (rituximab or ofatumumab) and 1.5% who received an anti-CD20 monoclonal antibody only (rituximab or ofatumumab) had rash of Grade 3, and no subjects had an adverse reaction of Grade 4.
↑ serumkoncentrationer Nøje dosistitrering af det antidepressive middel og overvågning af det antidepressive respons anbefales.
↑ serum concentrations Careful dose titration of the antidepressant and monitoring for antidepressant response is recommended.
Der blev ikke inkluderet nogen patienter med svært nedsat leverfunktion i kliniske studier af idelalisib.
No patients with severe hepatic impairment were included in clinical studies of idelalisib.
Bepridil, disopyramid, lidocain
Bepridil, disopyramide, lidocaine
Når idelalisib administreres sammen med andre lægemidler, henvises til produktresuméerne (SPC'er) for de andre præparater for anbefalinger angående administration sammen med CYP3A4-hæmmere.
When idelalisib is co-administered with other medicinal products, the Summary of Product Characteristics (SmPC) for the other product must be consulted for the recommendations regarding co-administration with CYP3A4 inhibitors.
Gentagen dosistoksicitet
Repeated dose toxicity
Kaplan-Meier-kurven for PFS ses i figur 2.
The Kaplan-Meier curve for PFS is provided in Figure 2.
Kaplan-Meier-kurven for PFS ses i figur 1.
The Kaplan-Meier curve for PFS is provided in Figure 1.
Hvis en patient glemmer en dosis i mere end 6 timer, skal patienten ikke tage den glemte dosis, og blot genoptage det normale doseringsskema.
If a patient misses a dose by more than 6 hours, the patient should not take the missed dose and simply resume the usual dosing schedule.
Den anbefalede dosis er 150 mg, der tages gennem munden, to gange dagligt.
The recommended dose is 150 mg by mouth twice a day.
↑ serumkoncentrationer Monitorering af international normaliseret ratio (INR) anbefales ved administration sammen med og efter ophør af idelalisib-behandling.
↑ serum concentrations It is recommended that the international normalised ratio (INR) be monitored upon co-administration and following ceasing treatment with idelalisib.