natgillin/translations-raw huggingface dataset:
Tarceva er indiceret til behandling af patienter med lokalt fremskreden eller metastatisk ikke- småcellet lungecancer efter behandlingssvigt af mindst et tidligere kemoterapiregime.
Tarceva is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen.
5. 1).
No survival benefit or other clinically relevant effects of the treatment have been demonstrated in patients with EGFR- negative tumours (see section 5.1).
Pancreas- cancer:
Pancreatic cancer:
Tarceva i kombination med gemcitabin er indiceret til behandling af patienter med metastatisk pancreas- cancer.
Tarceva in combination with gemcitabine is indicated for the treatment of patients with metastatic pancreatic cancer.
4. 2 og 5. 1).
When prescribing Tarceva, factors associated with prolonged survival should be taken into account (see section 4.2 and 5.1).
Tarceva skal administreres under opsyn af en læge med erfaring i anvendelsen af antineoplastiske lægemidler.
Tarceva treatment should be supervised by a physician experienced in the use of anticancer therapies.
Ikke- småcellet lungecancer (NSCLC):
Non-small cell lung cancer:
Den anbefalede daglige dosis af Tarceva er 100 mg, som tages mindst én time før eller to timer efter indtagelse af føde, i kombination med gemcitabin (se produktresuméet for gemcitabin for pancreas - cancer indikationen).
The recommended daily dose of Tarceva is 100 mg taken at least one hour before or two hours after the ingestion of food, in combination with gemcitabine (see the summary of product characteristics of gemcitabine for the pancreatic cancer indication).
5. 1).
In patients who do not develop rash within the first 4 – 8 weeks of treatment, further Tarceva treatment should be re-assessed (see section 5.1).
2 Hvis dosisjustering er nødvendig, skal dosis reduceres med 50 mg ad gangen (se pkt.
2 When dose adjustment is necessary, reduce in 50 mg steps (see section 4.4).
4. 5).
Concomitant use of CYP3A4 substrates and modulators may require dose adjustment (see section 4.5).
Dette bør udvises, selvom eksponeringen af erlotinib hos patienter med moderat nedsat leverfunktion (Child - Pugh score 7- 9) var lignende den, der blev set hos patienter med sufficient leverfunktion.
Although erlotinib exposure was similar in patients with moderately impaired hepatic function (Child-Pugh score 7-9) compared with patients with adequate hepatic function, caution should be used when administering Tarceva to patients with hepatic impairment.
Sikkerheden og virkningen af erlotinib er ikke undersøgt hos patienter med svært nedsat leverfunktion.
The safety and efficacy of erlotinib has not been studied in patients with severe hepatic impairment.
5. 2).
Use of Tarceva in patients with severe hepatic impairment is not recommended (see section 5.2).
Sikkerheden og virkningen af erlotinib er ikke undersøgt hos patienter med nedsat nyrefunktion (koncentrationen af serumkreatinin > 1, 5 gang den øvre referencegrænse).
The safety and efficacy of erlotinib has not been studied in patients with renal impairment (serum creatinine concentration > 1.5 times the upper normal limit).
5. 2).
Based on pharmacokinetic data no dose adjustments appear necessary in patients with mild or moderate renal impairment (see section 5.2).
Sikkerheden og virkningen af erlotinib er ikke undersøgt hos patienter under 18 år.
The safety and efficacy of erlotinib has not been studied in patients under the age of 18 years.
Rygere:
Smokers:
Det er vist, at erlotinib- eksponeringen reduceres med 50- 60% ved cigaretrygning.
Cigarette smoking has been shown to reduce erlotinib exposure by 50-60%.
Hos NSCLC- patienter, som er rygere, var den maksimale tolererede dosis af Tarceva 300 mg.
The maximum tolerated dose of Tarceva in NSCLC patients who currently smoke cigarettes was 300 mg.
4. 5 og 5. 2).
Efficacy and long term safety of a dose higher than the recommended starting doses have not been established in patients who continue to smoke cigarettes (see sections 4.5 and 5.2).
Rygere skal derfor rådes til at stoppe med at ryge, da plasmakoncentrationerne af erlotinib er reduceret hos rygere sammenlignet med ikke- rygere.
Therefore, current smokers should be advised to stop smoking, as plasma concentrations of erlotinib in smokers as compared to non-smokers are reduced.
Svær overfølsomhed over for erlotinib eller over for et eller flere af hjælpestofferne.
Severe hypersensitivity to erlotinib or to any of the excipients.
Potente induktorer af CYP3A4 kan nedsætte virkningen af erlotinib, mens potente hæmmere af CYP3A4 kan medføre øget toksicitet.
Potent inducers of CYP3A4 may reduce the efficacy of erlotinib whereas potent inhibitors of CYP3A4 may lead to increased toxicity.
4. 5).
Concomitant treatment with these types of agents should be avoided (see section 4.5).
Rygere skal rådes til at stoppe med at ryge, da plasmakoncentrationerne af erlotinib hos rygere er væsentligt reduceret sammenlignet med ikke- rygere.
Current smokers should be advised to stop smoking, as plasma concentrations of erlotinib in smokers as compared to non-smokers are reduced.
Graden af reduktion er sandsynligvis klinisk signifikant (se pkt. 4. 5).
The degree of reduction is likely to be clinically significant (see section 4.5).
I usædvanlige tilfælde er der rapporteret om interstitiel lungesygdom (ILD) - lignende hændelser, inklusive dødsfald, hos patienter, som modtog Tarceva som behandling af ikke- småcellet lungecancer (NSCLC), pancreas- cancer eller andre fremskredne solide tumorer.
Cases of interstitial lung disease (ILD)-like events, including fatalities, have been reported uncommonly in patients receiving Tarceva for treatment of non-small cell lung cancer (NSCLC), pancreatic cancer or other advanced solid tumours.
I det pivotale studie BR. 21 ved NSCLC var hyppigheden af ILD- lignende hændelser (0, 8%) den samme i både placebo - og Tarceva- gruppen.
In the pivotal study BR.21 in NSCLC, the incidence of ILD (0.8%) was the same in both the placebo and Tarceva groups.
I pancreas- cancerstudiet (kombination med gemcitabin) var incidensen af ILD - lignende hændelser 2, 5% i gruppen med Tarceva plus gemcitabin versus 0, 4% i gruppen behandlet med placebo plus gemcitabin.
In the pancreatic cancer study in combination with gemcitabine, the incidence of ILD-like events was 2.5% in the Tarceva plus gemcitabine group versus 0.4% in the placebo plus gemcitabine treated group.
0, 6% sammenlignet med 0, 2% hos patienter i placebo- behandling.
The overall incidence in Tarceva-treated patients from all studies (including uncontrolled studies and studies with concurrent chemotherapy) is approximately 0.6% compared to 0.2% in patients on placebo.
De rapporterede diagnoser hos patienter med mistanke om ILD- lignende hændelser omfattede pneumonitis, strålepneumonitis, allergisk pneumonitis, interstitiel pneumoni, interstitiel lungesygdom, obliterativ bronkiolitis, pulmonal fibrose, Acute Respiratory Distress Syndrome (ARDS), alveolitis og lungeinfiltrater.
Reported diagnoses in patients suspected of having ILD-like events included pneumonitis, radiation pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, pulmonary fibrosis, Acute Respiratory Distress Syndrome (ARDS), alveolitis, and lung infiltration.
Konfunderende eller medvirkende faktorer som f. eks. samtidig eller tidligere kemoterapi, tidligere stråleterapi, præ- eksisterende parenkymatisk lungesygdom, metastatisk lungesygdom eller lungeinfektioner var hyppige.
Confounding or contributing factors such as concomitant or prior chemotherapy, prior radiotherapy, pre-existing parenchymal lung disease, metastatic lung disease, or pulmonary infections were frequent.
3 Afhængig af den diagnostiske evaluering skal behandling med Tarceva stoppes hos patienter, som udvikler akutte nye og/ eller progredierende, uforklarlige lungesymptomer, som f. eks. dyspnø, hoste og feber.
3 In patients who develop acute onset of new and/ or progressive unexplained pulmonary symptoms such as dyspnoea, cough and fever, Tarceva therapy should be interrupted pending diagnostic evaluation.
Patienter, der bliver behandlet samtidig med erlotinib og gemcitabin, bør kontrolleres omhyggeligt for risikoen for udvikling af ILD- lignende toksicitet.
Patients treated concurrently with erlotinib and gemcitabine should be monitored carefully for the possibility to develop ILD-like toxicity.
4. 8).
If ILD is diagnosed, Tarceva should be discontinued and appropriate treatment initiated as necessary (see section 4.8).
50% af patienterne, der modtager Tarceva, og moderat eller svær diarré bør behandles med f. eks. loperamid.
Diarrhoea has occurred in approximately 50% of patients on Tarceva and moderate or severe diarrhoea should be treated with e. g. loperamide.
Reduktion af dosis med 25 mg ad gangen er ikke undersøgt.
Dose reductions by 25 mg steps have not been investigated.
4. 8).
In the event of severe or persistent diarrhoea, nausea, anorexia, or vomiting associated with dehydration, Tarceva therapy should be interrupted and appropriate measures should be taken to treat the dehydration (see section 4.8).
Nogle tilfælde var sekundære til svær dehydrering på grund af diarré, opkastning og/ eller appetitløshed mens andre tilfælde opstod i forbindelse med konkomitant kemoterapi.
Some cases were secondary to severe dehydration due to diarrhoea, vomiting and/ or anorexia, while others were confounded by concomitant chemotherapy.
I sværere og mere vedvarende tilfælde af diarré, eller tilfælde, der fører til dehydrering, specielt hos grupper af patienter med forværrede risikofaktorer (samtidig medicinering, symptomer eller sygdomme eller andre prædisponerede tilstande herunder høj alder) skal behandlingen med Tarceva afbrydes.
In more severe or persistent cases of diarrhoea, or cases leading to dehydration, particularly in groups of patients with aggravating risk factors (concomitant medications, symptoms or diseases or other predisposing conditions including advanced age), Tarceva therapy should be interrupted and appropriate measures should be taken to intensively rehydrate the patients intravenously.
Passende foranstaltninger bør initieres for intensivt at rehydrere patienterne intravenøst.
In addition, renal function and serum electrolytes including potassium should be monitored in patients at risk of dehydration.
Konfunderende faktorer har indbefattet tidligere leversygdom eller samtidig administration af hepatoxiske lægemidler.
Confounding factors have included pre-existing liver disease or concomitant hepatotoxic medications.
4. 8).
Tarceva dosing should be interrupted if changes in liver function are severe (see section 4.8).
Tabletterne indeholder lactose og må ikke gives til patienter med arvelig galactoseintolerans, en særlig form for hereditær lactasemangel (Lapp Lactase deficiency) eller glucose- galactosemalabsorption.
The tablets contain lactose and should not be administered to patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
Erlotinibs opløselighed reduceres ved en pH over 5.
Erlotinib is characterised by a decrease in solubility at pH above 5.
Lægemidler, der ændrer pH i den øvre del af mave- tarmkanalen, som eksempelvis protonpumpehæmmere, H2- antagonister og antacida, kan ændre erlotinibs opløselighed og derved dets biotilgængelighed.
Drugs that alter the pH of the upper GI tract, like proton pump inhibitors, H2 antagonists and antacids, may alter the solubility of erlotinib and hence its bioavailability.
Når Tarceva administreres samtidig med disse stoffer, vil en øget dosis af Tarceva sandsynligvis ikke kompensere for eksponeringstabet.
Increasing the dose of Tarceva when coadministered with such agents is not likely to compensate for the loss of exposure.
Virkningen af samtidig administration af erlotinib med H2- antagonister kendes ikke; men det er sandsynligt, at biotilgængeligheden vil være mindsket.
The effects of concomitant administration of erlotinib with H2 antagonists and antacids are unknown; however, reduced bioavailability is likely.
4. 5).
Therefore, concomitant administration of these combinations should be avoided (see section 4.5).
Når erlotinib blev administreret samtidig med ciprofloxacin, som er en moderat CYP1A2- hæmmer, blev erlotinibeksponeringen [AUC] øget signifikant med 39%, mens der ikke blev observeret signifikant ændring i Cmax.
When erlotinib was co-administered with ciprofloxacin, a moderate CYP1A2 inhibitor, the erlotinib exposure [AUC] increased significantly by 39%, while no statistically significant change in Cmax was found.
Ligeledes blev den aktive metabolits eksponering øget med 60% og 48% for henholdsvis AUC og Cmax.
Similarly, the exposure to the active metabolite increased by about 60% and 48% for AUC and Cmax, respectively.
Der skal udvises forsigtighed, når ciprofloxacin eller potente CYP1A2- hæmmere (f. eks. fluvoxamin) kombineres med erlotinib.
Caution should be exercised when ciprofloxacin or potent CYP1A2 inhibitors (e. g. fluvoxamine) are combined with erlotinib.
Hvis der observeres uønskede hændelser, der er relateret til erlotinib, kan erlotinibdosis reduceres.
If adverse events related to erlotinib are observed, the dose of erlotinib may be reduced.
4 Forbehandling eller samtidig administration af Tarceva ændrede ikke clearance af de prototypiske CYP3A4- substrater, midazolam og erythromycin, men nedsatte tilsyneladende den orale biotilgængelighed af midazolam med op til 24%.
Pretreatment or coadministration of Tarceva did not alter the clearance of the prototypical CYP3A4 substrates, midazolam and erythromycin, but did appear to decrease the oral bioavailability of midazolam by up to 24%.
I et andet klinisk studie blev det vist, at erlotinib ikke påvirkede farmakokinetikken af det samtidigt administrerede CYP3A4/ 2C8- substrat paclitaxel.
In another clinical study, erlotinib was shown not to affect pharmacokinetics
Signifikante interaktioner ved clearance af andre CYP3A4- substrater er derfor usandsynlig.
Significant interactions with the clearance of other CYP3A4 substrates are therefore unlikely.
Patienter med lavt ekspressionsniveau af UGT1A1 eller med genetiske glukoronidiseringssygdomme (f. eks.
Patients with low expression levels of UGT1A1 or genetic glucuronidation disorders (e. g.
Gilberts sygdom) kan have forhøjede serumkoncentrationer af bilirubin og skal behandles med forsigtighed.
Gilbert’ s disease) may exhibit increased serum concentrations of bilirubin and must be treated with caution.
Potente hæmmere af CYP3A4- aktivtet nedsætter metaboliseringen af erlotinib og øger plasmakoncentrationerne af erlotinib.
Potent inhibitors of CYP3A4 activity decrease erlotinib metabolism and increase erlotinib plasma concentrations.
I et klinisk studie medførte samtidig anvendelse af erlotinib og ketoconazol (200 mg oralt to gange daglig i 5 dage), en potent CYP3A4- hæmmer, en øgning af erlotinib- eksponeringen (86% af AUC og 69% af Cmax).
In a clinical study, the concomitant use of erlotinib with ketoconazole (200 mg orally twice daily for 5 days), a potent CYP3A4 inhibitor, resulted in an increase of erlotinib exposure (86% of AUC and 69% of Cmax).
Der skal derfor iagttages forsigtighed, når erlotinib kombineres med en potent CYP3A4- hæmmer, f. eks. med antimykotika af azol- gruppen (dvs. ketoconazol, itraconazol og voriconazol), proteasehæmmere, erytromycin eller claritromycin.
Therefore, caution should be used when erlotinib is combined with a potent CYP3A4 inhibitor, e. g. azole antifungals (i. e. ketoconazole, itraconazole, voriconazole), protease inhibitors, erythromycin or clarithromycin.
Potente induktorer af CYP3A4 aktivitet øger metaboliseringen af erlotinib og nedsætter plasmakoncentrationen af erlotinib signifikant.
Potent inducers of CYP3A4 activity increase erlotinib metabolism and significantly decrease erlotinib plasma concentrations.
I et klinisk studie medførte samtidig anvendelse af erlotinib og rifampicin (600 mg oralt én gang daglig i 7 dage), en potent CYP3A4 induktor, en reduktion på 69% af den mediane erlotinib AUC.
In a clinical study, the concomitant use of erlotinib and rifampicin (600 mg orally once daily for 7 days), a potent CYP3A4 inducer, resulted in a 69% decrease in the median erlotinib AUC.
Samtidig administration af rifampicin med en enkelt 450 mg Tarceva- dosis medførte en middel erlotinib- eksponering (AUC) på 57, 5% af den eksponering, der blev opnået efter en enkelt 150 mg Tarceva- dosis uden behandling med rifampicin.
Co-administration of rifampicin with a single 450 mg dose of Tarceva resulted in a mean erlotinib exposure (AUC) of 57.5% of that after a single 150 mg Tarceva dose in the absence of rifampicin treatment.
For patienter, som behøver samtidig behandling med Tarceva og en potent CYP3A4- induktor, som f. eks. rifampicin, bør det overvejes at hæve dosis til 300 mg, med tæt monitorering af patienterne (herunder nyre - og leverfunktionen samt serumelektrolytter).
For patients who require concomitant treatment with Tarceva and a potent CYP3A4 inducer such as rifampicin an increase in dose to 300 mg should be considered while their safety (including renal and liver functions and serum electrolytes) is closely monitored, and if well tolerated for more than 2 weeks, further increase to 450 mg could be considered with close safety monitoring.
Hvis det bliver tolereret godt i mere end 2 uger, kan det overvejes at hæve dosis yderligere til 450 mg under fortsat tæt kontrol.
Reduced exposure may also occur with other inducers e. g. phenytoin, carbamazepine, barbiturates or St.
Nedsat eksponering kan også forekomme med andre induktorer f. eks. phenytoin, carbamazepin, barbiturater eller prikbladet perikon (hypericum perforatum).
Johns Wort (hypericum perforatum).
Om muligt bør der overvejes andre behandlinger uden kraftig CYP3A4 inducerende aktivitet.
Alternate treatments lacking potent CYP3A4 inducing activity should be considered when possible.
4. 8) og nogle med samtidig administration af NSAIDs.
International Normalized Ratio (INR) elevations, and bleeding events including gastrointestinal bleeding have been reported in clinical studies, some associated with concomitant warfarin administration (see section 4.8) and some with concomitant NSAID administration.
Patienter, som tager warfarin eller andre coumarinderivater af antikoagulantia, skal kontrolleres regelmæssigt for ændringer i protrombintid eller INR.
Patients taking warfarin or other coumarin-derivative anticoagulants should be monitored regularly for changes in prothrombin time or INR.
Resultaterne fra et farmakokinetisk interaktionsstudie indikerede efter 24 timer en signifikant reduktion af AUCinf, Cmax samt plasmakoncentration på henholdsvis 2, 8; 1, 5 og 9 gange efter administration af Tarceva hos rygere sammenlignet med ikke- rygere (se pkt.
Results of a pharmacokinetic interaction study indicated a significant 2.8-, 1.5- and 9-fold reduced AUCinf, Cmax and plasma concentration at 24 hours, respectively, after administration of Tarceva in smokers as compared to non-smokers (see section 5.2).
Den kliniske effekt af denne nedsatte eksponering er ikke formelt blevet vurderet, men den er sandsynligvis klinisk signifikant.
The clinical effect of the decreased exposure has not been formally assessed but it is likely to be clinically significant.
Erlotinib er substrat for P- glycoprotein lægemiddeltransportøren.
Erlotinib is a substrate for the P-glycoprotein active substance transporter.
Samtidig administration af P - glycoproteinhæmmere, f. eks. cyclosporin og verapamil kan medføre ændret distribution og/ eller
Concomitant administration of inhibitors of Pgp, e. g. cyclosporine and verapamil, may lead to altered distribution and/ or altered elimination of erlotinib.
Konsekvenserne af denne interaktion for f. eks.
The consequences of this interaction for e. g.
CNS- toksicitet kendes ikke.
CNS toxicity has not been established.
Lægemidler, der ændrer pH i den øvre del af mave- tarmkanalen, kan ændre erlotinibs opløselighed og derved dets biotilgængelighed.
Co-administration of
Samtidig administration af erlotinib med omeprazol, som er en syrepumpehæmmer, nedsætter erlotinib - eksponering [AUC] og maksimumkoncentrationen [Cmax] med henholdsvis 46% og 61%.
5 erlotinib with omeprazole, a proton pump inhibitor (PPI), decreased the erlotinib exposure [AUC] and maximum concentration [Cmax] by 46% and 61%, respectively.
Samtidig administration af Tarceva med 300 mg ranitidin, en H2- receptor- antagonist, nedsatte erlotinibeksponeringen [AUC] og maksimumkoncentrationerne [Cmax] med henholdsvis 33% og 54%.
Concomitant administration of Tarceva with 300 mg ranitidine, an H2-receptor antagonist, decreased erlotinib exposure [AUC] and maximum concentrations [Cmax] by 33% and 54%, respectively.
Når Tarceva administreres samtidig med disse stoffer, vil en øget dosis af Tarceva sandsynligvis ikke kompensere for eksponeringstabet.
Increasing the dose of Tarceva when co-administered with such agents is not likely to compensate for this loss of exposure.
Hvis Tarceva derimod blev administreret forskudt enten 2 timer før eller 10 timer efter 150 mg ranitidin 2 gange daglig, blev erlotinibeksponeringen [AUC] og maksimumkoncentrationerne (Cmax) kun reduceret med henholdsvis 15% og 17%.
However, when Tarceva was dosed in a staggered manner 2 hours before or 10 hours after ranitidine 150 mg b. i. d., erlotinib exposure [AUC] and maximum concentrations [Cmax] decreased only by 15% and 17%, respectively.
Virkningen af antacida på absorptionen af erlotinib er ikke undersøgt, men absorptionen kan nedsættes, hvilket medfører lavere plasmakoncentrationer.
The effect of antacids on the absorption of erlotinib have not been investigated but absorption may be impaired, leading to lower plasma levels.
Hvis det overvejes at give ranitidin, bør det administreres forskudt; dvs.
If the use of ranitidine is considered, it should be used in a staggered manner; i. e.
I et fase 1b- studie var der ingen signifikant virkning af gemcitabin på erlotinibs farmakokinetik og heller ingen signifikant virkning af erlotinib på gemcitabins farmakokinetik.
In a Phase Ib study, there were no significant effects of gemcitabine on the pharmacokinetics of erlotinib nor were there significant effects of erlotinib on the pharmacokinetics of gemcitabine.
I et klinisk studie førte samtidig anvendelse af erlotinib med carboplatin og paclitaxel til en øget total platinum AUC0- 48 på 10, 6%.
In a clinical study, the concomitant use of erlotinib with carboplatin and paclitaxel led to an increase of total platinum AUC0-48 of 10.6%.
I klinisk praksis kan der være andre co- faktorer, der medfører en øget eksponering for carboplatin, så som nyreinsufficiens.
In clinical practice, there may be other co-factors leading to an increased exposure to carboplatin like renal impairment.
Der foreligger ingen studier om anvendelsen af erlotinib hos gravide kvinder.
There are no studies in pregnant women using erlotinib.
5. 3).
Studies in animals have shown some reproductive toxicity (see section 5.3).
Kvinder i den fødedygtige alder skal rådes til at undgå graviditet, mens de tager Tarceva.
Women of childbearing potential must be advised to avoid pregnancy while on Tarceva.
Der skal anvendes effektiv antikonception under behandlingen og i mindst 2 uger efter behandlingens afslutning.
Adequate contraceptive methods should be used during therapy, and for at least 2 weeks after completing therapy.
Det vides ikke, om erlotinib udskilles i modermælk.
It is not known whether erlotinib is excreted in human milk.
På grund af den potentielle fare for fostret, skal mødre rådes til ikke at amme, mens de tager Tarceva.
Because of the potential harm to the infant, mothers should be advised against breastfeeding while receiving Tarceva.
Erlotinib er dog ikke forbundet med påvirkning af mentale funktioner.
No studies on the effects on the ability to drive and use machines have been performed; however erlotinib is not associated with impairment of mental ability.
Ikke- småcellet lungecancer (enkeltstof administration af Tarceva i studie BR. 21):
Non-small cell lung cancer (Tarceva administered as single agent in study BR.21):