natgillin/translations-raw huggingface dataset:
Samtidig administration kan resultere i kompetitiv hæmning af metabolismen af disse lægemidler og skabe grundlag for alvorlige og/ eller livstruende bivirkninger såsom hjertearytmier (f. eks. amiodaron, bepridil, quinidin, terfenadin, astemizol, cisaprid, pimozid), respiratorisk depression og/ eller forlænget sedation (f. eks. oral triazolam og oral midazolam (se afsnit 4. 5 mht parenteral midazolam)), perifere vasospasmer eller iskæmi og iskæmi i andre væv, herunder iskæmi i hjernen henholdsvis hjertet (f. eks. ergotaminderivater).
Co-administration may result in competitive inhibition of the metabolism of these medicinal products and create the potential for serious and/ or life-threatening adverse events such as cardiac arrhythmia (e. g. amiodarone, bepridil, quinidine, terfenadine, astemizole, cisapride, pimozide), respiratory depression and / or prolonged sedation (e. g. oral triazolam and oral midazolam (for caution on parenterally administered midazolam, see section 4.5)) or peripheral vasospasm or ischaemia and ischaemia of other tissues, including cerebral or myocardial ischaemia (e. g. ergot derivatives).
Samtidig behandling med Agenerase og lavdosis ritonavir i kombination med rifampicin er kontraindiceret (se afsnit 4. 5).
(see section 4.5).
Samtidig administration af Agenerase og ritonavir må ikke kombineres med lægemidler med smalt terapeutisk vindue, som er afhængige af CYP2D6 metabolisme, f. eks. flecainid og propafenon (se afsnit 4. 5).
Agenerase with ritonavir must not be co-administered with medicinal products with narrow therapeutic windows that are highly dependent on CYP2D6 metabolism, e. g. flecainide and propafenone (see section 4.5).
Naturprodukter indeholdende prikbladet perikum (Hypericum perforatum) må ikke anvendes samtidig med amprenavir på grund af risikoen for fald i plasmakoncentrationerne og reduceret klinisk effekt af amprenavir (se afsnit 4. 5).
Herbal preparations containing St John’ s wort (Hypericum perforatum) must not be used while taking amprenavir due to the risk of decreased plasma concentrations and reduced clinical effects of amprenavir (see section 4.5).
3 4. 4 Særlige advarsler og forsigtighedsregler vedrørende brugen
3 4.4 Special warnings and precautions for use
De kan fortsat udvikle opportunistiske infektioner eller andre komplikationer af HIV - infektionen.
Patients should be advised that Agenerase, or any other current antiretroviral therapy does not cure HIV and that they may still develop opportunistic infections and other complications of HIV infection.
Resistente virus fremkommer hurtigt, når amprenavir gives som monoterapi (se afsnit 5. 1).
When amprenavir is administered as monotherapy, resistant viruses rapidly emerge (see section 5.1).
Agenerase kapsler bør normalt administreres sammen med en lav dosis af ritonavir og i kombination med andre antiretrovirale midler (se afsnit 4. 2).
Agenerase capsules should normally be given in combination with low dose ritonavir and in combination with other antiretroviral agents (see section 4.2).
Leversygdom
Liver Disease:
Sikkerheden og effekten af amprenavir er ikke klarlagt hos patienter med underliggende leversygdomme.
The safety and efficacy of amprenavir has not been established in patients with significant underlying liver disorders.
Brugen af Agenerase kapsler i kombination med ritonavir er kontraindiceret hos patienter med svært nedsat leverfunktion (se afsnit 4. 3).
Agenerase capsules are contraindicated in patients with severe hepatic impairment when used in combination with ritonavir (see section 4.3).
Samtidig brug af Agenerase med ritonavir og fluticason eller andre glukokortikoider, som metaboliseres af CYP3A4, anbefales ikke, med mindre de potentielle fordele ved behandlingen opvejer risikoen for systemiske bivirkninger forårsaget af kortikosteroider, herunder Cushings syndrom og binyrebarksuppression (se afsnit 4. 5).
Concomitant use of Agenerase with ritonavir and fluticasone or other glucocorticoids that are metabolised by CYP3A4 is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects, including Cushing’ s syndrome and adrenal suppression (see section 4.5).
HMG- CoA reduktase hæmmerne lovastatin og simvastatin metaboliseres i udstrakt grad af CYP3A4.
The HMG-CoA reductase inhibitors lovastatin and simvastatin are highly dependent on CYP3A4 for metabolism, thus concomitant use of Agenerase with simvastatin or lovastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis.
Derfor kan samtidigt brug af Agenerase og simvastatin eller lovastatin ikke anbefales på grund af øget risiko for udvikling af myopati herunder rhabdomyolyse.
Caution must also be exercised if Agenerase is used concurrently with atorvastatin, which is metabolized to a lesser extent by CYP3A4.
Selvom atorvastatin metaboliseres i mindre grad af CYP3A4, bør der også her udvises forsigtighed ved samtidig anvendelse af Agenerase, og dosisnedsættelse af atorvastatin bør overvejes.
In this situation, a reduced dose of atorvastatin should be considered.
Hvis behandling med en HMG- CoA reduktasehæmmer er indiceret, anbefales pravastatin eller fluvastatin (se afsnit 4. 5).
If treatment with a HMG-CoA reductase inhibitor is indicated, pravastatin or fluvastatin are recommended (see section 4.5).
Dette burde minimere risikoen for potentielle sikkerhedsproblemer ved samtidig anvendelse.
For some medicinal products that can cause serious or life-threatening undesirable effects, such as carbamazepine, phenobarbital, phenytoin, tricyclic antidepressants and warfarin (monitor International Normalised Ratio), concentration monitoring is available; this should minimise the risk of potential safety problems with concomitant use.
Samtidig brug af Agenerase og halofantrin eller lidocain (systemisk) er ikke anbefalet (se afsnit 4. 5).
The use of Agenerase concomitantly with halofantrine or lidocaine (systemic) is not recommended (see section 4.5).
Effekten af Agenerase kan være nedsat på grund af fald i plasmakoncentrationer af amprenavir hos patienter, der samtidig bruger disse lægemidler (se afsnit 4. 5).
Agenerase may be less effective due to decreased amprenavir plasma concentrations in patients taking these medicinal products concomitantly (see section 4.5).
Terapeutiske koncentrationsmålinger anbefales for immunosuppresive lægemidler (cyclosporin, tacrolimus, rapamycin), når disse administreres samtidig med Agenerase (se afsnit 4. 5).
Therapeutic concentration monitoring is recommended for immunosuppressant medicinal products (cyclosporine, tacrolimus, rapamycin) when co-administered with Agenerase (see section 4.5).
Forsigtighed er tilrådet ved samtidig brug af Agenerase og PDE5 hæmmere (f. eks. sildenafil og vardenafil) (se afsnit 4. 5).
Caution is advised when Agenerase is used concomitantly with PDE5 inhibitors (e. g. sildenafil and vardenafil) (see section 4.5).
4 Forsigtighed er tilrådet ved samtidig brug af Agenerase og delavirdin (se afsnit 4. 5).
4 Caution is advised when Agenerase is used concomitantly with delavirdine (see section 4.5).
En nedsættelse af rifabutin dosis med mindst 50% er anbefalet ved samtidig brug af Agenerase.
A reduction of rifabutin dosage of at least 50% is recommended when administered with Agenerase.
Gives ritonavir samtidig er yderligere dosisnedsættelse muligvis nødvendigt (se afsnit 4. 5).
When ritonavir is co-administered further dose reduction may be necessary (see section 4.5).
Derfor anbefales alternativ sikker svangerskabsforebyggelse til kvinder i den fertile alder (se afsnit 4. 5).
Therefore, alternative reliable methods of contraception are recommended for women of childbearing potential (see section 4.5).
Agenerase kapsler indeholder vitamin E (36 IU/ 50 mg kapsel), derfor anbefales ekstra vitamin E - tilskud ikke.
Agenerase capsules contain vitamin E (36 IU/ 50 mg capsule), therefore additional vitamin E supplementation is not recommended.
Udslæt/ hudreaktioner
Rash / cutaneous reactions
Egnede antihistaminer (f. eks. cetirizindihydrochlorid) kan reducere kløe og fremskynde heling af udslættet.
Appropriate antihistamines (e. g. cetirizine dihydrochloride) may reduce pruritus and hasten the resolution of rash.
Agenerase skal seponeres permanent, hvis udslættet er ledsaget af systemiske eller allergiske symptomer, eller hvis slimhinderne er involveret (se afsnit 4. 8).
Agenerase should be permanently discontinued when rash is accompanied with systemic symptoms or allergic symptoms or mucosal involvement (see section 4.8).
Klinisk undersøgelse bør inkludereevaluering af fysiske tegn på omfordeling af fedt.
Clinical examination should include evaluation for physical signs of fat redistribution.
Måling af fastende serumlipider og blodglucose bør overvejes.
Consideration should be given to the measurement of fasting serum lipids and blood glucose.
Lipide dysfunktioner bør behandles i henhold til klinisk praksis (se afsnit 4. 8).
Lipid disorders should be managed as clinically appropriate (see section 4.8).
Hæmofilipatienter
5 Haemophiliac patients
Hos nogle patienter blev
There have been reports of increased bleeding, including spontaneous skin haematomas and haemarthroses, in haemophiliac patients type A and B treated with protease inhibitors.
5 der givet ekstra faktor VIII.
In some patients, additional factor VIII was given.
Hos HIV- inficerede patienter med svær immuninsufficiens kan der ved påbegyndelse af antiretroviral kombinationsbehandling (CART) opstå en inflammatorisk reaktion på asymptomatiske eller residuale opportunistiske patogener, som kan forårsage alvorlige kliniske tilstande eller forværring af symptomer.
In HIV-infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms.
Relevante eksempler er cytomegalovirus retinitis, generaliserede og/ eller fokale mycobakterielle infektioner og pneumocystis carinii pneumoni.
Relevant examples are cytomegalovirus retinitis, generalised and/ or focal mycobacterium infections, and Pneumocystis carinii pneumonia.
Ætiologien anses dog for at være multifaktoriel (omfattende anvendelse af kortikosteroider, alkoholforbrug, svær immunosuppression, højere Body Mass Index (BMI)).
Although the etiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV-disease and/ or long-term exposure to combination antiretroviral therapy (CART).
Associerede kontraindikationer (se afsnit 4. 3)
Associations contraindicated (see section 4.3)
CYP3A4 substrater med smalt terapeutisk indeks Agenerase må ikke administreres samtidig med lægemidler med smalt terapeutisk vindue indeholdende aktive stoffer, der er substrater for cytochrome P4503A4 (CYP3A4).
CYP3A4 substrates with narrow therapeutic index Agenerase must not be administered concurrently with medicinal products with narrow therapeutic windows containing active substances that are substrates of cytochrome P450 3A4 (CYP3A4).
Herved øges deres plasmaniveau, hvilket kan medføre alvorlige og / eller livstruende bivirkninger såsom hjertearytmi (f. eks. amiodaron, astemizol, bepridil, cisaprid, pimozid, quinidin, terfanadin) eller periferale vasospasmer eller iskæmi (f. eks. ergotamin, dihydroergotamin).
Co-administration may result in competitive inhibition of the metabolism of these active substances thus increasing their plasma level and leading to serious and / or life-threatening adverse reactions such as cardiac arrhythmia (e. g. amiodarone, astemizole, bepridil, cisapride, pimozide, quinidine, terfenadine) or peripheral vasospasm or ischaemia (e. g. ergotamine, dihydroergotamine).
CYP2D6 substrater med smalt terapeutisk index Kombinationsbehandling med Agenerase og ritonavir må ikke administreres samtidig med lægemidler indeholdende aktive substanser, der i høj grad er afhængige af CYP2D6 metabolismen, og for hvilke en forøget plasmakoncentration er forbundet med alvorlige og/ eller livstruende bivirkninger.
CYP2D6 substrates with narrow therapeutic index Agenerase with ritonavir must not be co-administered with medicinal products containing active substances that are highly dependent on CYP2D6 metabolism and for which elevated plasma concentrations are associated with serious and / or life-threatening adverse reactions.
Disse aktive stoffer inkluderer flecainid og propafenon.
Rifampicin
Rifampicin Rifampicin er en potent CYP3A4 inducer og har vist sig at forårsage en reduktion i amprenavir AUC med 82%, hvilket kan føre til manglende virologisk effekt og resistensudvikling.
6 Rifampicin is a strong CYP3A4 inducer and has been shown to cause an 82% decrease in amprenavir AUC, which can result in virological failure and resistance development.
Forsøg på at modvirke denne reduktion i amprenavir AUC, ved at øge dosis af andre proteasehæmmere sammen
During attempts to overcome the decreased exposure by increasing the dose of other protease inhibitors with ritonavir, a high frequency of liver reactions was seen.
Rifampicin i kombination med Agenerase og lavdosis ritonavir er kontraindiceret (se afsnit 4. 3).
The combination of rifampicin and Agenerase with concomitant low-dose ritonavir is contraindicated (see section 4.3).
Prikbladet Perikum (Hypericum perforatum) Serumkoncentrationer af amprenavir kan reduceres ved samtidig anvendelse af naturlægemidler indeholdende prikbladet perikum (Hypericum perforatum).
St John’ s wort (Hypericum perforatum) Serum levels of amprenavir can be reduced by concomitant use of the herbal preparation St John’ s wort (Hypericum perforatum).
Virkningen skyldes, at prikbladet perikum inducerer de medikamentelle metaboliseringsenzymer.
This is due to induction of drug metabolising enzymes by St John’ s wort.
Naturlægemidler indeholdende prikbladet perikum bør derfor ikke gives samtidig med Agenerase.
Herbal preparations containing St John’ s wort should therefore not be combined with Agenerase.
Hvis en patient allerede indtager prikbladet perikum bør amprenavirniveau og om muligt virusniveau kontrolleres og behandlingen med prikbladet perikum afbrydes.
If a patient is already taking St John’ s wort, check amprenavir and if possible viral levels and stop St John’ s wort.
Niveauet af amprenavir kan stige ved afbrydelse af behandlingen med prikbladet perikum.
The dose of amprenavir may need adjusting.
Den induktive effekt kan vedblive i op til 2 uger efter ophør af behandlingen med prikbladet perikum.
The inducing effect may persist for at least 2 weeks after cessation of treatment with St John’ s wort.
• Proteasehæmmere (PI)
• Protease inhibitors (PIs):
AUC, Cmin og Cmax for indinavir var nedsat med henholdsvis 38%, 27% og 22%, når det blev givet med amprenavir.
Indinavir: the AUC, Cmin and Cmax of indinavir were decreased by 38%, 27%, and 22%, respectively, when given with amprenavir.
AUC, Cmin og Cmax for amprenavir var øget med henholdsvis 33%, 25% og 18%.
The AUC, Cmin and Cmax of amprenavir were increased by 33%, 25%, and 18%, respectively.
AUC, Cmin og Cmax for saquinavir var henholdsvis nedsat med 19% og 48% og øget med 21%, når det blev givet med amprenavir.
Saquinavir: the AUC, Cmin and Cmax of saquinavir were decreased by 19% and 48% and increased by 21%, respectively, when given with amprenavir.
AUC, Cmin og Cmax for amprenavir var nedsat med henholdsvis 32%, 14% og 37%.
The AUC, Cmin and Cmax of amprenavir were decreased by 32%, 14%, and 37%, respectively.
AUC, Cmin og Cmax for nelfinavir var øget med henholdsvis 15%, 14% og 12%, når det blev givet med amprenavir.
Nelfinavir: the AUC, Cmin and Cmax of nelfinavir were increased by 15%, 14%, and 12%, respectively, when given with amprenavir.
Cmax for amprenavir var nedsat med 14%, mens AUC og Cmin var øget med henholdsvis 9% og 189%.
The Cmax of amprenavir was decreased by 14% whilst the AUC and Cmin were increased by 9% and 189%, respectively.
AUC og Cmin for amprenavir blev forøget med henholdsvis 64% og 508% og Cmax blev nedsat med 30%, når ritonavir (100 mg 2 gange daglig) blev administreret sammen med amprenavir kapsler (600 mg 2 gange daglig), sammenlignet med værdier opnået efter administration af amprenavir kapsler i doseringen 1200 mg 2 gange daglig.
Ritonavir: the AUC and Cmin of amprenavir were increased by 64% and 508% respectively and the Cmax decreased by 30% when ritonavir (100 mg twice daily) was co-administered with amprenavir capsule (600 mg twice daily) compared to values achieved after 1200 mg twice daily doses of amprenavir capsules.
I en åben ikke- fastende farmakokinetisk undersøgelse mindskedes AUC, Cmax og Cmin for lopinavir med henholdsvis 38%, 28% og 52%, når amprenavir (750 mg 2 gange daglig) blev givet i kombination med Kaletra (400 mg lopinavir + 100 mg ritonavir 2 gange daglig).
Lopinavir / ritonavir (Kaletra): in an open-label, non-fasting pharmacokinetic study, the AUC, Cmax and Cmin of lopinavir were decreased by 38%, 28% and 52% respectively when amprenavir (750 mg twice daily) was given in combination with Kaletra (400 mg lopinavir + 100 mg ritonavir twice daily).
I den samme undersøgelse øgedes AUC, Cmax og Cmin for amprenavir med henholdsvis 72%, 12% og 483% sammenlignet med værdier efter standard doser af amprenavir (1200 mg 2 gange daglig).
In the same study, the AUC, Cmax, and Cmin of amprenavir were increased 72%, 12%, and 483%, respectively, when compared to values after standard doses of amprenavir (1200 mg twice daily).
40- 50% lavere end da amprenavir (600 mg 2 gange daglig) blev givet i kombination med ritonavir (100 mg 2 gange daglig).
The amprenavir plasma Cmin values achieved with the combination of amprenavir (600 mg twice daily) in combination with Kaletra (400 mg lopinavir + 100 mg ritonavir twice daily) are approximately 40- 50% lower than when amprenavir (600 mg twice daily) is given in combination with ritonavir 100 mg twice daily.
Ved at give yderligere ritonavir til amprenavir plus Kaletra regimet øges lopinavir Cmin værdierne, men ikke amprenavir Cmin værdierne.
No dose recommendation can be given for the co-
Der kan ikke gives anbefalinger vedrørende dosering ved samtidig administration af amprenavir og Kaletra, men hyppig monitorering anbefales, da sikkerhed og effekt af denne kombination er uafklaret.
7 administration of amprenavir and Kaletra, but close monitoring is advised because the safety and efficacy of this combination is unknown.
7 • Nukleosidanalog revers transkriptasehæmmere (NRTI)
• Nucleoside analogue reverse transcriptase inhibitors (NRTIs):
AUC og Cmax for zidovudin var øget med henholdsvis 31% og 40%, når det blev givet med amprenavir.
Zidovudine: the AUC and Cmax of zidovudine were increased by 31% and 40%, respectively, when given with amprenavir.
AUC og Cmax for henholdsvis lamivudin og amprenavir var begge uændrede, når disse lægemidler blev givet samtidigt.
Lamivudine: the AUC and Cmax of lamivudine and amprenavir, respectively, were both unaltered when these two medicinal products were given concomitantly.
AUC, Cmin og Cmax for abacavir var uændrede, når det blev givet med amprenavir.
Abacavir: the AUC, Cmin and Cmax of abacavir were unaltered when given with amprenavir.
AUC, Cmin og Cmax for amprenavir var øget med henholdsvis 29%, 27% og 47%.
The AUC, Cmin and Cmax of amprenavir were increased by 29%, 27%, and 47%, respectively.
• Non- nukleosid revers transkriptasehæmmere (NNRTI)
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs):
40% hos voksne.
Efavirenz: efavirenz has been seen to decrease the Cmax, AUC and Cmin, ss of amprenavir by approximately 40% in adults.
Påvirkningen af nevirapin på andre proteasehæmmere og de få data, som er tilgængelige, tyder på at nevirapin kan nedsætte serumkoncentrationerne af amprenavir.
The effect of nevirapine on other protease inhibitors and the limited evidence available suggest that nevirapine may decrease the serum concentrations of amprenavir.
Ved samtidig indgift af delavirdin og amprenavir blev AUC, Cmax og Cmin for delavirdin mindsket med henholdsvis 61%, 47% og 88%, mens AUC, Cmax og Cmin for amprenavir blev øget med henholdsvis 130%, 40% og 125%.
The AUC, Cmax and Cmin of amprenavir were increased by 130%, 40% and 125% respectively.
Antibiotika/ svampemidler
8 Antibiotics/ antifungals
Samtidig administration af amprenavir og rifabutin resulterede i en øgning på 193% for rifabutin AUC og en øgning i rifabutin- relaterede bivirkninger.
Rifabutin: co-administration of amprenavir with rifabutin resulted in a 193% increase in rifabutin AUC and an increase of rifabutin-related adverse events.
Øgningen i plasmakoncentrationen af rifabutin stammer sandsynligvis fra amprenavirs hæmning af CYP3A4- medieret metabolisme af rifabutin.
The increase in rifabutin plasma concentration is likely to result from inhibition of rifabutin CYP3A4 mediated metabolism by amprenavir.
AUC og Cmin for clarithromycin var uændrede og Cmax nedsat med 10%, når det blev givet med amprenavir.
Clarithromycin: the AUC and Cmin of clarithromycin were unaltered and the Cmax decreased by 10% when given with amprenavir.
AUC, Cmin og Cmax for amprenavir var øget med henholdsvis 18%, 39% og 15%.
The AUC, Cmin and Cmax of amprenavir were increased by 18%, 39% and 15%, respectively.
Ved samtidig administration kan plasmakoncentrationerne for begge lægemidler dog eventuelt øges.
Erythromycin: no pharmacokinetic study has been performed with Agenerase in combination with erythromycin, however, plasma levels of both medicinal products may be increased when co-administered.
AUC og Cmax for ketoconazol var øget med henholdsvis 44% og 19%, når stoffet blev givet sammen med amprenavir alene.
Ketoconazole / Itraconazole: the AUC and Cmax of ketoconazole were increased by 44% and 19%, respectively when given with amprenavir alone.
AUC og Cmax for amprenavir var henholdsvis øget med 31% og nedsat med 16%.
The AUC and Cmax of amprenavir were increased by 31% and decreased by 16%, respectively.
AUC( 0- τ) blev forøget til værdier 2, 69 gange større end dem observeret ved administration af ketoconazol 200 mg én gang daglig uden samtidig administration af fosamprenavir med ritonavir.
Co- administration of fosamprenavir 700 mg with ritonavir 100 mg twice daily and ketoconazole 200 mg once daily increased plasma ketoconazole Cmax by 25% and increased AUC(0-τ) to values 2.69-fold those observed on administration of ketoconazole 200 mg once daily without concurrent fosamprenavir with ritonavir.
Høje doser af ketoconazol og af itraconazol (> 200 mg/ dag) frarådes i de tilfælde, hvor de to stoffer anvendes samtidig med Agenerase i kombination med ritonavir.
When used with Agenerase with ritonavir, high doses (> 200 mg/ day) of ketoconazole or itraconazole are not recommended.
På baggrund af data fra andre proteasehæmmere, tilrådes det, at antacida ikke tages på samme tid som Agenerase, da absorptionen kan forringes.
Antacids: on the basis of the data for other protease inhibitors, it is advisable not to take antacids at the same time as Agenerase, since its absorption may be impaired.
Samtidig administration af krampestillende aktive substanser, kendt som enzymatiske induktorer (phenytoin, carbamazepin, phenobarbital), og amprenavir kan føre til nedsat plasmakoncentration af amprenavir.
Anticonvulsant active substances: concomitant administration of anticonvulsant active substances known as enzymatic inductors (phenytoin, phenobarbital, carbamazepine) with amprenavir may lead to a decrease in the plasma concentrations of amprenavir.
Disse kombinationer skal bruges med forsigtighed og terapeutisk monitorering af koncentrationer er anbefalet (se afsnit 4. 4).
These combinations should be used with caution and therapeutic concentration monitoring is recommended (see section 4.4).