FrancophonIA/ELRC3.0 huggingface dataset:
English: Enzymes responsible for rucaparib metabolism have not been identified.
Danish: Enzymer, der er ansvarlige for rucaparib-metabolisme, er ikke blevet identificeret.
English: Rucaparib has been shown to decrease tumour growth in mouse xenograft models of human cancer with or without deficiencies in BRCA.
Danish: Rucaparib har vist sig at formindske tumorvækst i muse-xenograftmodeller af human cancer med eller uden defekter i BRCA.
English: In vitro, the IC50 of rucaparib against the human ether-à-go-go related gene (hERG) was 22.6 µM, which is approximately 13-fold higher than the Cmax in patients at the recommended dose.
Danish: In vitro var IC50 af rucaparib mod det humane ether-à-go-go relaterede gen (hERG) 22,6 µM, hvilket er cirka 13 gange højere end Cmax hos patienter ved den anbefalede dosis.
English: Patients with moderate or severe renal impairment should be carefully monitored for renal function and adverse reactions.
Danish: Patienter med moderat eller svært nedsat nyrefunktion bør følges nøje for nyrefunktion og bivirkninger.
English: Grade 1-3 elevations in AST/ALT can be managed without change to the rucaparib dose, or with treatment modification (interruption and/or dose reduction).
Danish: Klasse 1-3 forhøjelser i ASAT/ALAT kan håndteres uden ændring af rucaparib-dosis, eller ved behandlingsændring (afbrydelse og/eller dosisnedsættelse).
English: Rucaparib was not mutagenic in a bacterial reverse mutation (Ames) assay.
Danish: Rucaparib var ikke mutagent i en bakteriel revers mutation (Ames) analyse.
English: The findings in non-clinical toxicology studies performed with oral rucaparib were generally consistent with the adverse events observed in clinical studies.
Danish: Resultaterne i ikke-kliniske toksikologiforsøg udført med oral rucaparib var generelt konsistente med de bivirkninger, der blev observeret i kliniske forsøg.
English: Caution should be used when rucaparib is co-administered with UGT1A1 substrates (i.e. irinotecan) to patients with UGT1A1*28 (poor metabolizer) due to a possible increase in the exposure of SN-38 (the active metabolite of irinotecan) and associated toxicities.
Danish: Der skal udvises forsigtighed, når rucaparib administreres samtidig med UGT1A1-substrater (ex irinotecan) til patienter med UGT1A1*28 (dårlig metabolisator) på grund af en mulig øgning af eksponeringen af SN-38 (den aktive metabolit af irinotecan)og tilknyttede toksiciteter.
English: Rubraca contains the active substance rucaparib.
Danish: Rubraca indeholder det aktive stof rucaparib.
English: • Women who are able to become pregnant must use effective birth control (contraception):
Danish: - Kvinder i den fødedygtige alder skal bruge effektiv prævention:
English: Effect of other medicinal products on rucaparib
Danish: Virkning af andre lægemidler på rucaparib
English: Patients should not start Rubraca treatment until they have recovered from haematological toxicities caused by previous chemotherapy (≤ CTCAE Grade 1).
Danish: Patienter bør ikke starte Rubraca-behandling, før hæmatologisk toksicitet forårsaget af tidligere kemoterapi er restitueret (≤ CTCAE klasse 1).
English: Patients with germline (g)BRCA (n=88, 83.0%) or somatic (s)BRCA (n=18, 17.0%) mutations were included.
Danish: Patienter med kimcelle (g)BRCA (n=88, 83,0 %) eller somatiske (s)BRCA (n=18, 17,0 %) mutationer blev inkluderet.
English: In addition, rucaparib is an inhibitor of the BCRP with IC50 value suggesting potential BCRP inhibition and increased exposures of medicinal products that are BCRP substrates (e.g., rosuvastatin).
Danish: Derudover er rucaparib en hæmmer af BCRP med IC50 værdi, hvilket antyder potentiel BCRP-hæmning og øgede eksponeringer af lægemidler, som er BCRP-substrater (f.eks. rosuvastatin).
English: As such, efficacy of Rubraca in patients who have received prior treatment with a PARP inhibitor in the maintenance setting, has not been investigated and cannot be extrapolated from the available data.
Danish: Effekten af Rubraca hos patienter, der tidligere har fået behandling med en PARP-hæmmer i vedligeholdelsesforløbet, er således ikke undersøgt og kan ikke ekstrapoleres ud fra de tilgængelige data.
English: Rucaparib has been shown to have in vitro and in vivo anti-tumour activity in BRCA mutant cell lines through a mechanism known as synthetic lethality, whereby the loss of two DNA repair pathways is required for cell death.
Danish: Rucaparib har vist sig at have in vitro og in vivo anti-svulst-aktivitet i BRCA mutationscellelinjer gennem en mekanisme, der er kendt som ”synthetic lethality”, hvor tab af to DNA-reparationsveje er påkrævet for celledød.
English: No events met Hy's Law criteria for drug-induced liver injury.
Danish: Ingen bivirkninger indfriede kriterierne for Hy's lov for lægemiddelinduceret leverskade.
English: The mean age was 61 years (range: 36 to 85); most of the patients were white (80%); and all had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Danish: Gennemsnitsalderen var 61 år (interval: 36 til 85); de fleste af patienterne var hvide (80 %), og alle havde en Eastern Cooperative Oncology Group (ECOG)-præstationsstatus på 0 eller 1.
English: The most abundant metabolite was M324, an oxidative deamination product of rucaparib, accounting for 18.6% of the radioactivity in plasma.
Danish: Den mest fremherskende metabolit var M324, et oxidativt deamineringsprodukt af rucaparib, der tegnede sig for 18,6 % af radioaktiviteten i plasma.
English: Gastrointestinal toxicities
Danish: Gastrointestinale toksiciteter
English: The clinical relevance of UGT1A1 inhibition by rucaparib is not clear.
Danish: Den kliniske relevans af UGT1A1-hæmning af rucaparib er ikke klarlagt.
English: The progression-free interval to penultimate platinum therapy was 6-12 months in 39% of patients and > 12 months in 61%.
Danish: Det progressionsfrie interval til næstsidste platinbehandling var 6-12 måneder hos 39 % af patienterne og > 12 måneder hos 61 %.
English: Increased alanine aminotransferase, Increased aspartate aminotransferase
Danish: Øget alaninaminotransferase/øget aspartataminotransferase
English: Hypercholesterolaemiab, Dehydration
Danish: Hypercholesterolæmib, dehydrering
English: Tumour tissue samples for all of the patients (N=564) were tested centrally to determine HRD positive status (as defined by the presence of a deleterious tumour BRCA [tBRCA] mutation or high genomic loss of heterozygosity).
Danish: Tumorvævsprøver for alle patienterne (N = 564) blev testet centralt for at bestemme positiv status for HRD (defineret som tilstedeværelse af en skadelig tumor BRCA [tBRCA]-mutation eller højt genomisk tab af heterozygositet).
English: Vomiting and nausea were reported in 42% and 77% of patients, respectively and were generally low grade (CTCAE Grade 1 to 3).
Danish: Opkastning og/eller kvalme blev rapporteret hos hhv. 42 % og 77 % af patienterne og var generelt af lav grad (CTCAE klasse 1 til 3).
English: The clinical relevance MRP2 and MRP3 interaction in the gut is not known.
Danish: Den kliniske relevans af MRP2- og MRP3-interaktion i tarmsystemet er ikke kendt.
English: None of the patients had received prior treatment with a PARP inhibitor.
Danish: Ingen af patienterne havde fået forudgående behandling med en PARP-hæmmer.
English: a The median duration of response is determined from the patients who had an objective tumour response according to RECIST guidelines, following treatment with rucaparib.
Danish: a. Den gennemsnitlige virknings varighed bestemmes ud fra patienterne med objektivt tumorrespons ifølge RECIST-retningslinjerne efter behandling med rucaparib.
English: Adverse reactions may be managed through dose interruptions and/or dose reductions for moderate to severe reactions (i.e. CTCAE Grade 3 or 4) such as neutropenia, anaemia and thrombocytopenia.
Danish: Bivirkninger kan reguleres ved dosisafbrydelser og/eller dosisreduktioner for moderate til svære reaktioner (dvs. CTCAE klasse 3 eller 4) såsom neutropeni, anæmi og trombocytopeni.
English: Intravenous administration of rucaparib in the rat and dog induced cardiac effects at a high Cmax (5.4 to 7.3-fold higher than patients), but not at a lower Cmax (1.3 to 3.8-fold higher than patients).
Danish: Intravenøs administration af rucaparib hos rotter og hunde medførte hjertepåvirkninger ved en høj Cmax (5,4 til 7,3 gange højere end for patienter), men ikke ved en lavere Cmax (1,3 til 3,8 gange højere end for patienter).
English: During treatment with rucaparib, events of myelosuppression (anaemia, neutropenia, thrombocytopenia) may be observed and are typically first observed after 8-10 weeks of treatment with rucaparib.
Danish: Under behandling med rucaparib kan der ses hændelser med myelosuppression (anæmi, neutropeni, trombocytopeni), og de ses typisk først efter 8-10 ugers behandling med rucaparib.
English: The adverse reaction frequency is listed by MedDRA System Organ Class (SOC) at the preferred term level.
Danish: Bivirkningsfrekvenserne er medtaget på MedDRA systemorganklasse på det foretrukne termniveau.
English: The risk for a clinically relevant effect of concomitant administration of proton pump inhibitors (PPIs) is likely small (see section 5.2).
Danish: Risikoen for en klinisk relevant effekt ved samtidig administration af protonpumpehæmmere (PPI'er) er sandsynligvis lille (se pkt.
English: In vitro studies have shown that rucaparibinduced cytotoxicity involves inhibition of PARP enzymatic activity and the trapping of PARP-DNA complexes resulting in increased DNA damage, apoptosis, and cell death.
Danish: In vitro-studier har vist, at rucaparibinduceret cytotoksicitet indebærer hæmning af PARP-enzymatisk aktivitet, og ”binding” af PARPDNA komplekser, der resulterer i øgede DNA-skader, apoptose og celledød.
English: For the platinum-resistant population (N=20), ORR by investigator review was 35.0% (95% CI [15.4, 59.2], with a complete response rate of 5.0%, and a partial response rate of 30.0%.
Danish: For den platinresistente population (N = 20) var ORR ved investigators gennemgang 35,0 % (95 % CI [15,4; 59,2] med en komplet responsrate på 5,0 % og en delvis responsrate på 30,0 %.
English: Elevations in creatinine with rucaparib treatment may be due to inhibition of the renal transporters MATE1 and MATE2-K (see section 4.5).
Danish: Forhøjelser af kreatinin ved rucaparibbehandling kan skyldes hæmning af nyretransportørerne MATE1 og MATE2-K (se pkt.
English: Rucaparib accounted for 44.9% and 94.9% of radioactivity in urine and faeces, respectively; while M324 accounted for 50.0% and 5.1% of radioactivity in urine and faeces, respectively.
Danish: Rucaparib tegnede sig for 44,9 % og 94,9 % af radioaktiviteten i henholdsvis urin og fæces, mens M324 tegnede sig for 50,0 % og 5,1 % af radioaktiviteten i henholdsvis urin og fæces.
English: The ORR, by independent radiology review for the platinum-sensitive population, was 42/79, 53.2% (95% CI [41.6-64.5]).
Danish: ORR'en var ved uafhængig radiologisk gennemgang for den platinfølsomme population 42/79, 53,2 % (95 % CI [41,6-64,5]).
English: No effects on male and female fertility were observed in 3-month general toxicology studies in rats and dogs at exposures of 0.09 to 0.3 times the human AUC at the recommended dose.
Danish: Der blev ikke set nogen virkning på hanners og hunners fertilitet i 3 måneders generelle toksikologiske forsøg med rotter og hunde ved eksponeringer på 0,09 til 0,3 gange den humane AUC ved den anbefalede dosis.
English: All patients had received at least two prior platinum-based chemotherapies (range: 2 to 6) and 28% of patients had received at least three prior platinum-based chemotherapies.
Danish: Alle patienter havde fået mindst to tidligere platinbaserede kemoterapier (interval: 2 til 6), og 28 % af patienterne havde fået mindst tre tidligere platinbaserede kemoterapier.
English: If you take Rubraca because your cancer has progressed you will need to have a clinical test to identify an abnormality in the BRCA gene.
Danish: Hvis du tager Rubraca, fordi din kræft har udviklet sig, skal du have foretaget en klinisk test for at undersøge, om du har et unormalt BRCA-gen.
English: Following administration of a single oral dose of [14C]-rucaparib to patients with solid tumours, unchanged rucaparib accounted for 64.0% of the radioactivity in plasma.
Danish: Efter administration af en enkelt oral dosis [14C]-rucaparib til patienter med faste tumorer tegnede uændret rucaparib sig for 64,0 % af radioaktiviteten i plasma.
English: Tell your doctor, pharmacist or nurse if you are taking any of the following medicines:
Danish: Fortæl din læge, apotekspersonalet eller sundhedspersonalet, hvis du tager nogle af følgende lægemidler:
English: The median duration of response was 196 days (95% CI [113 - NA]).
Danish: Den gennemsnitlige responsvarighed var 196 dage (95 % CI [113 - NA]).
English: Haematological adverse reactions of all CTCAE Grades of anaemia, thrombocytopenia and neutropenia were reported in 42%, 26% and 16% of patients respectively.
Danish: Hæmatologiske bivirkninger af alle CTCAE-klasser af anæmi, trombocytopeni og neutropeni blev rapporteret hos henholdsvis 42 %, 26 % og 16 % af patienterne.
English: Plasma exposures of rucaparib, as measured by Cmax and AUC, were approximately dose proportional at evaluated doses (40 to 500 mg daily, 240 to 840 mg twice a day).
Danish: Plasmaeksponeringer af rucaparib, som målt ved Cmax og AUC, var tilnærmelsesvis dosisproportional ved evaluerede doser (40 til 500 mg dagligt, 240 til 840 mg to gange dagligt).
English: This is because it is not known if rucaparib passes into breast milk.
Danish: Det skyldes, at det ikke vides, om rucaparib går over i modermælken.
English: Photosensitivity was reported in 13% of patients as low grade skin reactions (CTCAE Grade 1 or 2), and by 2 (0.2%) patients as ≥ CTCAE Grade 3 reaction.
Danish: Lysfølsomhed blev rapporteret hos 13 % af patienterne som hudreaktioner af lav grad (CTCAE klasse 1 eller 2) og hos 2 (0,2 %) af patienterne som ≥ CTCAE klasse 3-reaktion.
English: Potential in vivo BCRP inhibition cannot be excluded.
Danish: Potentiel in vivo BCRP-hæmning kan ikke udelukkes.
English: AST/ALT elevations may need to be managed with treatment interruption and/or dose reduction as described in Table 2 (see section 4.2).
Danish: ASAT/ALAT-stigninger skal muligvis håndteres med afbrydelse af behandling og/eller dosisreduktion som beskrevet i tabel 2 (se pkt.
English: Medicinal product interactions
Danish: Lægemiddelinteraktioner
English: Patients with Renal Impairment
Danish: Patienter med nedsat nyrefunktion
English: E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES FOR THE CONDITIONAL MARKETING AUTHORISATION
Danish: E. SÆRLIG FORPLIGTELSE TIL AT AFSLUTTE FORANSTALTNINGER EFTER UDSTEDELSE AF MARKEDSFøRINGSTILLADELSE TIL LÆGEMIDLER GODKENDT UNDER BETINGEDE OMSTÆNDIGHEDER
English: In the subset of 79 platinum-sensitive patients, progression free interval after last platinum dose was ≥ 6 - 12 months for 55 (69.6%) patients and > 12 months for 24 (30.4%) patients.
Danish: I delmængde af 79 platinfølsomme patienter var det progressionsfrie interval efter sidste platindosis ≥ 6-12 måneder for 55 (69,6 %) patienter og > 12 måneder for 24 (30,4 %) patienter.
English: If you stop taking Rubraca
Danish: Hvis du holder op med at tage Rubraca
English: Caution should be used for concomitant use of strong CYP3A4 inhibitors or inducers.
Danish: Der skal udvises forsigtighed ved samtidig brug af stærke CYP3A4-hæmmere eller inducere.
English: Photosensitivity has been observed in patients treated with rucaparib.
Danish: Lysfølsomhed er set hos patienter i behandling med rucaparib.
English: Elevations in serum creatinine
Danish: Forhøjelser af serumkreatinin
English: What Rubraca is and what it is used for What Rubraca is and how it works
Danish: Virkning og anvendelse Hvad er Rubraca, og hvordan fungerer det
English: Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu
Danish: Du kan finde yderligere oplysninger om dette lægemiddel på Det Europæiske Lægemiddelagenturs hjemmeside: http://www.ema.europa
English: Decreased appetite, Dehydration
Danish: AlmindeligNedsat appetit, dehydrering
English: Abdominal pain (combined terms abdominal pain, abdominal pain lower, abdominal pain upper) was reported in 40.1% of rucaparib treated patients, but was also very common (33%) in placebo patients, most likely associated with underlying disease.
Danish: Der blev indberettet mavesmerter (sammensat term for mavesmerter, mavesmerter lokaliseret til nedre abdomen, mavesmerter lokaliseret til øvre abdomen) hos 40,1 % af de rucaparib-behandlede patienter, men mavesmerter var også meget almindelige (33 %) hos placebopatienter, hvilket sandsynligvis var forbundet med underliggende sygdom.
English: HRD Groupc
Danish: HRD-gruppec
English: b Includes laboratory findings c Includes fatigue, asthenia and lethargy
Danish: b Omfatter laboratoriefund c Omfatter træthed, asteni og letargi
English: The proportion of platinum-sensitive patients with gBRCA and sBRCA mutations was comparable to the primary efficacy population at n=66 (83.5%) and n=13 (16.5%) respectively.
Danish: Andelen af platinfølsomme patienter med gBRCA- og sBRCAmutationer var sammenlignelig med den primære effektpopulation med henholdsvis n=66 (83,5 %) og n=13 (16,5 %).
English: In the pivotal Phase 3 study (ARIEL3), the incidence of MDS/AML during therapy in patients who received rucaparib was 0.8%.
Danish: I det pivotale fase 3 forsøg (ARIEL3) var forekomsten af MDS/AML 0,8 % under behandling hos patienter, som fik rucaparib.
English: Increased blood creatinine, Hypercholesterolaemiab
Danish: Øget blodkreatinin, hypercholesterolæmib
English: Increased transaminases
Danish: Øgede transaminaser
English: Most of the primary efficacy population were platinum-sensitive (n=79, 74.5%); the remaining patients were platinum-resistant (n=20, 18.9%) or platinum-refractory (n=7, 6.6%).
Danish: Størstedelen af den primære effektpopulation var platinfølsomme (n=79, 74,5 %); de resterende patienter var platinresistente (n=20, 18,9 %) eller platinrefraktære (n=7, 6,6 %).
English: Although in vitro rucaparib metabolism mediated by CYP3A4 was slow, a significant contribution of CYP3A4 in vivo cannot be excluded.
Danish: Selvom in vitro metabolismen af rucaparib medieret af CYP3A4 var langsom, kan det ikke udelukkes, at CYP3A4 bidrager signifikant in vivo.
English: In vitro, rucaparib was shown to be a substrate of P-gp and BCRP.
Danish: In vitro blev rucaparib påvist at være et substrat af P-gp og BCRP.
English: Rubraca is used to treat a type of cancer of the ovary.
Danish: Rubraca bruges til at behandle en form for kræft i æggestokkene.
English: The tumour histology was high grade serous in 91.5% of patients, endometrioid in 2.8% and mixed histology in 4.7%.
Danish: Tumorhistologien var serøs high grade hos 91,5 % af patienterne, endometrioid hos 2,8 % og blandet histologi hos 4,7 %.
English: Rubraca can be used as maintenance therapy immediately after a course of chemotherapy that has caused the tumour to shrink.
Danish: Rubraca kan anvendes som vedligeholdelsesbehandling umiddelbart efter, at et forløb med kemoterapi har fået kræftknuden til at blive mindre.
English: Because of the potential for serious adverse reactions in breast-fed infants from rucaparib, breast-feeding is contraindicated during treatment with Rubraca and for 2 weeks after the final dose (see section 4.3).
Danish: Grundet potentialet for alvorlige uønskede hændelser hos ammede spædbørn fra rucaparib, er amning kontraindikeret under behandling med Rubraca og i 2 uger efter sidste dosis (se pkt.
English: Contents of the pack and other information What Rubraca contains
Danish: Pakningsstørrelser og yderligere oplysninger Rubraca indeholder
English: In patients with cancer, rucaparib had a steady-state volume of distribution of 113 L to 262 L following a single intravenous dose of 12 mg to 40 mg rucaparib.
Danish: Hos patienter med kræft havde rucaparib et steady state fordelingsvolumen på 113 l til 262 l efter en enkelt intravenøs dosis på 12 mg til 40 mg rucaparib.
English: The clearance ranged from 13.9 to 18.4 L/hour, following a single intravenous dose of rucaparib 12 mg to 40 mg.
Danish: Clearance varierede mellem 13,9 og 18,4 l/timen efter en enkelt intravenøs dosis rucaparib 12 mg til 40 mg.
English: If a patient vomits after taking Rubraca, the patient should not retake the dose and should take the next scheduled dose.
Danish: Hvis en patient kaster op efter at have taget Rubraca, må patienten ikke tage dosen igen og skal tage den næste planlagte dosis.
English: Concentration-QTcF prolongation analysis was conducted using data from 54 patients with a solid tumour administered continuous rucaparib at doses ranging from 40 mg once daily to 840 mg twice daily (1.4 times the approved recommended dose).
Danish: Analysen koncentration-QTcF-forlængelse blev udført ved brug af data fra 54 patienter med en solid tumor, som fik rucaparib kontinuerligt ved doser fra 40 mg en gang dagligt til 840 mg to gange dagligt (1,4 gange den godkendte anbefalede dosis).
English: If you forget to take Rubraca
Danish: Hvis du har glemt at tage Rubraca
English: There are no clinical data in patients with severe renal impairment (CLcr less than 30 mL/min), therefore rucaparib is not recommended for use in patients with severe renal impairment.
Danish: Der er ingen kliniske data for patienter med alvorligt nedsat nyrefunktion (CLCR mindre end 30 ml/min), hvorfor rucaparib ikke anbefales til brug hos patienter med alvorligt nedsat nyrefunktion.
English: In an embryo-foetal development study in rats, rucaparib was associated with post-implantation loss at exposures of approximately 0.04 times the human AUC at the recommended dose.
Danish: I et embryoføtalt forsøg med rotter var rucaparib forbundet med tab efter implantation ved eksponeringer på ca. 0,04 gange den humane AUC ved den anbefalede dosis.
English: • Rubraca is not recommended during pregnancy.
Danish: - Rubraca frarådes under graviditet.
English: Myelodysplastic syndrome/Acute myeloid leukaemia MDS/AML are serious adverse reactions that occur uncommonly (0.5%) in patients on treatment and during the 28 day safety follow up, and commonly (1.3%) for all patients including during the long term safety follow up (rate is calculated based on overall safety population of 1321 patients exposed to at least one dose of oral rucaparib in all clinical studies).
Danish: MDS/AML er alvorlige bivirkninger, der opstår med hyppigheden Ikke almindelig (0,5 %) hos patienter i behandling og i løbet af de 28 dages sikkerhedsopfølgning, og med hyppigheden Almindelig (1,3 %) hos alle patienter, herunder under den langsigtede sikkerhedsopfølgning (raten beregnes på basis af den samlede sikkerhedspopulation på 1321 patienter, som fik mindst én dosis oral rucaparib fra alle kliniske forsøg).
English: Platinum-sensitive patients had received 2 (n=47, 59.5%), 3 (n=28, 35.4%), or > 3 (n=4, 5.1%) prior lines of platinumbased chemotherapy.
Danish: Platinfølsomme patienter havde modtaget 2 (n=47, 59,5 %), 3 (n=28, 35,4 %) eller > 3 (n=4, 5,1 %) forudgående linjer med platinbaseret kemoterapi.
English: Inhibition of MRP4 by rucaparib cannot be fully ruled out at clinical exposures.
Danish: Hæmning af MRP4 af rucaparib kan ikke helt udelukkes ved kliniske eksponeringer.
English: Caution is advised when co-administering medicinal products that are CYP3A substrates with a narrow therapeutic index (e.g., alfentanil, astemizole, cisapride, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, terfenadine).
Danish: Forsigtighed tilrådes ved samtidig indgivelse af lægemidler som er CYP3Asubstrater med et snævert terapeutisk indeks (f.eks. alfentanil, astemizol, cisaprid, cyclosporin, dihydroergotamin, ergotamin, fentanyl, pimozid, quinidin, sirolimus, tacrolimus, terfenadin).