natgillin/translations-raw huggingface dataset:
Dette kan resultere i tab af virologisk respons og resistensudvikling.
Rifampicin is a strong CYP3A4 inducer and has been shown to cause profound decreases in concentrations of other protease inhibitors which can result in virological failure and resistance development.
Under forsøg på at imødegå den nedsatte eksponering, hvor dosis af andre proteasehæmmere i kombination med ritonavir blev øget, blev der set en høj frekvens af leverreaktioner.
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.
4. 3).
The combination of rifampicin with APTIVUS with concomitant low-dose ritonavir is contraindicated (see section 4.3).
APTIVUS givet sammen med lavdosis ritonavir øger plasmakoncentrationerne af rifabutin med op til 3 gange og dets aktive metabolit med op til 20 gange.
APTIVUS, co-administered with low dose ritonavir, increases plasma concentrations of rifabutin by up to 3 fold, and its active metabolite by up to 20 fold.
Rifabutin øger Cmin for tipranavir med 16%.
Rifabutin increases the Cmin of tipranavir by 16%.
150 mg hver anden dag, eller tre gange om ugen).
Dosage reductions of rifabutin by at least 75% of the usual 300 mg/ day are recommended (ie 150 mg on alternate days, or three times per week).
Patienter, der får rifabutin og APTIVUS/ ritonavir, skal monitoreres tæt for at se, om der dukker bivirkninger op, der kan forbindes med rifabutin - behandlingen.
Patients receiving rifabutin with APTIVUS/ ritonavir should be closely monitored for emergence of adverse events associated with rifabutin therapy.
Perikum (Hypericum perforatum):
St John’ s wort (Hypericum perforatum):
Plasmaniveauerne for tipranavir kan blive nedsat ved samtidig brug af naturmedicin eller kosttilskud med perikum (Hypericum perforatum).
Plasma levels of tipranavir can be reduced by concomitant use of the herbal preparation St John’ s wort (Hypericum perforatum).
Dette skyldes at perikum inducerer metaboliserende enzymer.
This is due to induction of drug metabolising enzymes by St John’ s wort.
Naturmedicin indeholdende perikum bør ikke anvendes samtidig med APTIVUS.
Herbal preparations containing St John’ s wort should not be used concomitantly with APTIVUS.
Hvis en patient allerede tager perikum, skal dette middel seponeres, virusniveauerne tjekkes og om muligt også tipranavir- niveauet.
If a patient is already taking St John’ s wort, stop St John’ s wort, check viral levels and if possible tipranavir levels.
Tipranavir- niveauet kan stige, når perikum seponeres, og det kan være nødvendigt med dosisjustering af APTIVUS.
Tipranavir levels may increase on stopping St John’ s wort, and the dose of APTIVUS may need adjusting.
4. 3).
The inducing effect of St John’ s wort may persist for at least 2 weeks after cessation of treatment (see section 4.3).
CYP- isoenzym- hæmmere:
CYP isoenzyme inhibitors:
Clarithromycin:
Clarithromycin:
19% og 68% og nedsætter AUC for den 14- hydroxy- aktive metabolit med over 95%.
APTIVUS, co-administered with low dose ritonavir, increases the AUC and Cmin of clarithromycin by 19% and 68%, respectively, and decreases the AUC of the 14-hydroxy active metabolite by over 95%.
Selvom ændringerne i clarithromycin- parametre ikke anses for klinisk relevante, bør reduktionen af AUC for 14- OH- metabolitten tages med i overvejelserne ved behandling af infektioner forårsaget af Haemophilus influenzae, idet 14- OH- metabolitten den mest aktive.
Whilst the changes in clarithromycin parameters are not considered clinically relevant, the reduction in the 14-OH metabolite AUC should be considered for the treatment of infections caused by Haemophilus influenzae in which the 14-OH metabolite is most active.
Clarithromycin øger Cmin for tipranavir med mere end 100%.
Clarithromycin increases the Cmin of tipranavir by more than 100%.
Den store stigning i Cmin kan være klinisk relevant.
This large increase in Cmin may be clinically relevant.
Patienter, der tager clarithromycin i doser, der er højere end 500 mg to gange daglig, bør monitoreres omhyggeligt for tegn på toksicitet.
Patients using clarithromycin at doses higher than 500 mg twice daily should be carefully monitored for signs of toxicity.
For patienter med nedsat nyrefunktion bør følgende dosisjusteringer overvejes:
For patients with renal impairment the following dosage adjustments should be considered:
For patienter med CLCR 30- 60 ml/ min bør clarithromycin- dosis nedsættes med 50%.
For patients with CLCR 30 to 60 ml/ min the dose of clarithromycin should be reduced by 50%.
For patienter med CLCR < 30 ml/ min bør clarithromycin- dosis nedsættes med 75%.
For patients with CLCR < 30 ml/ min the dose of clarithromycin should be decreased by 75%.
Det er ikke nødvendigt med dosisjusteringer for patienter med normal nyrefunktion.
No dosage adjustments for patients with normal renal function are necessary.
10 Andre stoffer:
Other agents:
Samtidig indgift af APTIVUS med lavdosis ritonavir og aktive substanser, som i høj grad udskilles via CYP3A, og hvor forhøjede plasmakoncentrationer forbindes med alvorlige og/ eller livstruende hændelser, er kontraindiceret.
Co-administration of APTIVUS with low dose ritonavir, with active substances that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/ or life-threatening events is contraindicated.
4. 3).
These active substances include antiarrhythmics (amiodarone, bepridil, quinidine), antihistamines (astemizole, terfenadine), ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine), gastointestinal motility agents (cisapride), neuroleptics (pimozide, sertindole) and sedatives/ hypnotics (triazolam) (see section 4.3).
4. 3).
11 In addition, co-administration of APTIVUS with low dose ritonavir, with drugs that are highly dependent on CYP2D6 for clearance, such as the antiarrhythmics flecainide, propafenone and metoprolol given in heart failure, is contraindicated (see section 4.3).
4. 4).
Some anti-infectives are not recommended (halofantrine, lumefantrine) as well as miscellaneous agents (tolterodine) (see section 4.4).
Oral antikonception/ østrogener:
Oral contraceptives/ oestrogens:
APTIVUS givet sammen med lavdosis ritonavir nedsætter AUC og Cmax for ethinyl- østradiol med 50%, men ændrer ikke i væsentlig grad den farmakokinetiske adfærd af norethisteron.
APTIVUS, co-administered with low dose ritonavir, decreases the AUC and Cmax of ethinyl-oestradiol by 50%, but does not significantly alter the pharmacokinetic behaviour of norethindrone.
Samtidig indgift af disse med APTIVUS og lavdosis ritonavir anbefales ikke.
The concomitant administration with APTIVUS, co-administered with low dose ritonavir, is not recommended.
Alternative eller ekstra forholdsregler i forbindelse med antikonception skal tages, når østrogenbaseret oral antikonception anvendes sammen med APTIVUS og lavdosis ritonavir.
Alternative or additional contraceptive measures are to be used when oestrogen based oral contraceptives are co-administered with APTIVUS and low dose ritonavir.
4. 6).
Patients using oestrogens as hormone replacement therapy should be clinically monitored for signs of oestrogen deficiency (see section 4.4 and section 4.6).
Sildenafil og vardenafil:
Phosphodiesterase 5 (PDE5) inhibitors Sildenafil and vardenafil:
Der skal udvises særlig forsigtighed ved ordinering af phosphodiesterase (PDE5) - hæmmerne sildenafil eller vardenafil til patienter, der får APRIVUS sammen med lavdosis ritonavir.
Particular caution should be used when prescribing the phosphodiesterase (PDE5) inhibitors sildenafil or vardenafil in patients receiving APTIVUS co-administered with low dose ritonavir.
Samtidig indgift af APTIVUS og lavdosis ritonavir med PDE5- hæmmere forventes i væsentlig grad at øge PDE5- koncentrationerne og kan resultere i en stigning i bivirkninger, der hænger sammen med PDE5- hæmmere inkl. hypotension, synsændringer og priapisme.
Co-administration of APTIVUS and low dose ritonavir with PDE5 inhibitors is expected to substantially increase PDE5 concentrations and may result in an increase in PDE5 inhibitor-associated adverse events including hypotension, visual changes and priapism.
I et farmakokinetisk forsøg udført på raske frivillige mænd øgedes eksponeringen af enkelt - dosis tadalafil (AUC øgedes 2, 3 fold) ved samtidig administration af APTIVUS/ lavdosis ritonavir ved første dosis, mens tadalafil eksponeringen ikke øgedes i steady- state.
In a pharmacokinetic study performed in healthy male volunteers, co-administration of APTIVUS and low dose ritonavir with single dose tadalafil increased tadalafil exposure (AUC increased by 2.3 fold) at the first dose and did not change tadalafil exposure at steady-state.
Det anbefales derfor først at ordinere tadalafil efter mindst 7 dages behandling med APTIVUS/ ritonavir.
Therefore it is recommended to prescribe tadalafil after at least 7 days of APTIVUS/ ritonavir dosing.
Narkotisk analgetika (metadon/ meperidin):
Narcotic analgesics (Methadone/ Meperidine):
Samtidig brug af APTIVUS og lavdosis ritonavir med enkelt dosis metadon viste at sænke metadons farmakokinetiske parametre (AUC0- 24h ratio på 0, 47 med 90% CI [0, 44; 0, 51] og Cmax ratio på 0, 45 med 90% CI [0, 41; 0, 49]) i et studie udført med fastende, raske personer.
Co-administration of APTIVUS and low dose ritonavir with single dose methadone was demonstrated to decrease methadone pharmacokinetic parameters (AUC0-24h ratio of 0.47 with 90% CI [0.44; 0.51] and Cmax ratio of 0.45 with 90% CI [0.41; 0.49]), in a study conducted in fasted healthy subjects.
Derfor bør man i sådanne tilfælde monitorere for opiatabstinenssyndrom.
Therefore in such cases, patients should be monitored for opiate withdrawal syndrome.
APTIVUS givet sammen med lavdosis ritonavir forventes at reducere meperidin- koncentrationer og øge normeperidin- metabolitkoncentrationer.
APTIVUS, co-administered with low dose ritonavir, is expected to decrease meperidine concentrations and increase normeperidine metabolite concentrations.
Dosisøgninger og langtidsanvendelse af meperidin med APTIVUS og lavdosis ritonavir anbefales ikke pga. øgede koncentrationer af metabolitten normeperidin, som har både analgetisk aktivitet og centralnervestimulerende aktivitet (f. eks. kramper).
Dosage increase and long-term use of meperidine with APTIVUS co-administered with low dose ritonavir are not recommended due to the increased concentrations of the metabolite normeperidine which has both analgesic activity and CNS stimulant activity (eg seizures).
Immunosuppressiva (ciclosporin, tacrolimus, sirolimus):
Immunosuppressants (cyclosporin, tacrolimus, sirolimus):
Koncentrationer af ciclosporin, tacrolimus eller sirolimus kanikke forudsiges, når det gives sammen med APTIVUS og lavdosis ritonavir, som følge af den modsatrettede virkning af APTIVUX givet sammen med lavdosis ritonavir på CYP 3A og Pgp.
Concentrations of cyclosporin, tacrolimus, or sirolimus cannot be predicted when co-administered with APTIVUS co-administered with low dose ritonavir, due to conflicting effect of APTIVUS, co-administered with low dose ritonavir, on CYP 3A and Pgp.
Hyppigere monitorering af koncentrationen af disse lægemidler anbefales, indtil stabilisering af plasma koncentrationer.
More frequent concentration monitoring of these medicinal products is recommended until blood levels have been stabilised.
Warfarin og andre perorale antikoagulantia:
Warfarin and other oral anticoagulants:
Samtidig behandling med APTIVUS / ritonavir og warfarin kan ændre metaboliseringen af S- warfarin (initial hæmning og efter 10 dage blev der observeret en nettoinduktion).
Co-administration of APTIVUS with low dose ritonavir and warfarin may alter the metabolism of S-warfarin (initial inhibition and after 10 days a net induction was observed).
Derfor kan APTIVUS / ritonavir være forbundet med forandringer af INR- værdier (International Normalised Ratio) og kan påvirke antikoagulationen (den trombotiske effekt) eller øge risikoen for blødning.
Consequently, APTIVUS co-administered with low dose ritonavir, may be associated with changes in INR (International Normalised Ratio) values, and may affect anticoagulation (thrombogenic effect) or increase the risk of bleeding.
Det anbefales at udføre en tæt klinisk og biologisk monitorering (INR- målinger), når disse lægemidler gives samtidigt.
Close clinical and biological (INR measurement) monitoring is recommended when these medicinal products are combined.
11 Antacida:
Antacids:
Når APTIVUS givet sammen med lavdosis ritonavir blev givet sammen med 20 ml aluminium - og magnesium- baseret flydende antacida, blev tipranavirs AUC12t, Cmax og Cmin reduceret med 25 - 29%.
When APTIVUS, co-administered with low dose ritonavir, was co-administered with 20 ml of aluminium- and magnesium-based liquid antacid, tipranavir AUC12h, Cmax and Cmin were reduced by 25-29%.
Der skal være mindst 2 timers mellemrum mellem indtagelsen af APTIVUS/ ritonavir og antacida.
Dosing of APTIVUS, co-administered with low dose ritonavir, with antacids should be separated by at least a two hours time interval.
Protonpumpehæmmere Omeprazol:
Omeprazole:
I klinisk farmakokinetiske studier blev der ikke observeret nogen vigtig klinisk forandring af tipranavir/ ritonavir plasmakoncentrationen, når det blev givet sammen med omeprazol (40 mg daglig), hvorfor der ikke skal justeres i dosis af tipranavir/ ritonavir.
In clinical pharmacokinetic studies of tipranavir/ ritonavir in combination with omeprazole (40 mg qd), no clinically important changes in tipranavir/ ritonavir plasma concentrations were observed and thus no tipranavir/ ritonavir dose adjustment is required.
Ved steady- state på tipranavir/ ritonavir sås et fald af omeprazol AUC og Cmax med 71% henholdsvis 73%.
Tipranavir/ ritonavir at steady state resulted in decreases in omeprazole AUC and Cmax by 71% and 73%, respectively.
Et lignende fald blev set for S- enantiomeren, esomeprazol.
Similar effects were observed for the S-enantiomer, esomeprazole.
4. 4).
Therefore, the combined use of tipranavir/ ritonavir with either omeprazole or esomeprazole is not recommended (see section 4.4).
Der henvises samtidigt til produktinformationerne for omeprazol eller esomeprazol mht maksimale dosisanbefalinger.
Recommendations for maximal doses of omeprazole or esomeprazole are found in the corresponding product information.
H2- receptor antagonister:
H2-receptor antagonists:
Der foreligger ingen data med H2- receptor antagonister i kombination med tipranavir og lavdosis ritonavir.
No data are available for H2-receptor antagonists in combination with tipranavir and low dose ritonavir.
Det anses ikke for betydende for tipranavir plasma koncentrationen, at pH- værdien i maven øges grundet behandling med H2- receptor antagonister. lavdosisDer bør udvises forsigtighed, når sådanne lægemidler kombineres med tipranavir og lavdosis ritonavir.
Caution should be exercised when such drugs are combined with tipranavir and low dose ritonavir.
På baggrund at et forsøg med en cocktail at forskellige lægemidler, hvor koffein- AUC (CYP1A2 substrat) var reduceret med 43%, kan det forventes, at APTIVUS/ ritonavir vil nedsætte theophyllin- koncentrationerne.
Based on data from the cocktail study where caffeine (CYP1A2 substrate) AUC was reduced by 43%, APTIVUS/ ritonavir is expected to decrease theophylline concentrations.
Theophyllin- plasmakoncentrationen bør monitoreres de første 2 uger, når APTIVUS/ ritonavir administreres samtidig, og theophyllindosis bør øges, hvis det er nødvendigt.
Theophylline plasma concentrations should be monitored during the first two weeks of co- administration with APTIVUS/ ritonavir and the theophylline dose should be increased as needed.
Tipranavir givet sammen med lavdosis ritonavir forventes at øge desipramin - koncentrationerne.
APTIVUS, co-administered with low dose ritonavir, is expected to increase desipramine concentrations.
Dosisreduktion og monitorering af desipramin koncentrationer anbefales.
Dosage reduction and concentration monitoring of desipramine is recommended.
4. 3).
Concomitant use of APTIVUS/ ritonavir and oral midazolam is contra-indicated (see section 4.3).
Ritonavir er en potent CYP3A4- hæmmer, og vil derfor påvirke lægemidler, der metaboliseres af dette enzym.
Ritonavir is a potent inhibitor of CYP3A4 and therefore will affect drugs metabolised by this enzyme.
Koncentration af midazolam givet intravenøst som enkeltdosis blev øget 2, 8 gange (AUC0- 24h), og koncentrationen af midazolam givet peroralt blev øget 10 gange, når midazolam blev givet samtidig med APTIVUS/ ritonavir.
When co-administered with APTIVUS/ ritonavir at steady-state concentrations of intravenously administered single dose midazolam were increased 2.8 fold (AUC0-24h) and concentrations of orally administered midazolam were increased 10 fold.
Regulering af dosis bør ligeledes overvejes.
If APTIVUS/ ritonavir is administered with parenteral midazolam, close clinical monitoring for respiratory depression and/ or prolonged sedation should be instituted and dosage adjustment should be considered.
APTIVUS administreret samtidig med lavdosis ritonavir kan fordoble eksponeringen af peroralt administreret digoxin ved den første dosis, imens nettoeffekten ved steadystate nærmere vil være et mindre fald i digoxineksponeringen.
APTIVUS, co-administered with low dose ritonavir, may double the exposure of orally administered digoxin at first dose, while the net effect at steady state may rather consist in a slight decrease in digoxin exposure.
Det anbefales at monitorere koncentrationen af serumdigoxin indtil stadystate er opnået.
Monitoring of digoxin serum concentrations is recommended until steady state has been obtained.
Et farmakokinetisk studie med raske forsøgspersoner, hvor en enkelt dosis trazodon blev givet sammen med lavdosis ritonavir (200 mg 2 gange dagligt), viste øget plasmakoncentration af trazodon (AUC steg 2, 4 gange).
In a pharmacokinetic study performed in healthy volunteers, concomitant use of low dose ritonavir (200 mg twice daily) with a single dose of trazodone led to an increased plasma concentration of trazodone (AUC increased by 2.4 fold).
I dette studie så man bivirkninger som kvalme, svimmelhed hypotension og synkope ved samtidig indtagelse af trazodon og ritonavir.
Adverse events of nausea, dizziness, hypotension and syncope have been observed following co-administration of trazodone and ritonavir in this study.
Det vides dog ikke om kombinationen af tipranavir og ritonavir kan forårsage en større forøgelse af trazodoneksponering.
However, it is unknown whether the combination of tipranavir/ ritonavir might cause a larger increase in trazodone exposure.
Kombinationen bør anvendes med forsigtighed og en lavere dosis trazodon bør overvejes.
The combination should be used with caution and a lower dose of trazodone should be considered.
50% reduktion i bupropions Cmax og AUC0- 12h ved steady- state- koncentration.
APTIVUS co-administered with low-dose ritonavir at steady-state resulted in approximately a 50% decrease in bupropion Cmax and AUC0-12h.
Denne virkning kan skyldes en induktion af bupropions metabolisme.
This effect may be due to induction of bupropion metabolism.
Der var ingen relevante ændringer i TPV Cmin.
There was no relevant change in TPV Cmin.
Hvis samtidig brug af bupropion vurderes at være nødvendig, bør dette ske under tæt klinisk monitorering af bupropions virkning, uden at overskride den anbefalede dosering, til trods for den observerede induktion.
If the co- administration with bupropion is judged unavoidable, this should be done under close clinical monitoring for bupropion efficacy, without exceeding the recommended dosage, despite the observed induction.
12 Loperamid:
Loperamide:
Et farmakodynamisk interaktionsstudie med raske frivillige viste, at administration af loperamid og APTIVUS givet sammen med lavdosis ritonavir ikke forårsager klinisk relevant ændring i det respiratoriske respons på kuldioxid.
A pharmacodynamic interaction study in healthy volunteers demonstrated that administration of loperamide and APTIVUS, co-administered with low dose ritonavir does not cause any clinically relevant change in the respiratory response to carbon dioxide.
Den farmakokinetiske analyse viste, at AUC og Cmax for loperamid blev nedsat med hhv.
The pharmacokinetic
51% og 61%, og Cmin for tipranavir med 26%.
13 analysis showed that the AUC and Cmax of loperamide are reduced by 51% and 61%, respectively, and the Cmin of tipranavir by 26%.
Fluticason propionat (interaktion med ritonavir):
Fluticasone propionate (interaction with ritonavir):
86% (90% konfidensinterval 82- 89%).
In a clinical study where ritonavir 100 mg capsules bid were co-administered with 50 µg intranasal fluticasone propionate (4 times daily) for 7 days in healthy subjects, the fluticasone propionate plasma levels increased significantly, whereas the intrinsic cortisol levels decreased by approximately 86% (90% confidence interval 82-89%).
Der kan forventes større påvirkning, hvis fluticason propionat inhaleres.
Greater effects may be expected when fluticasone propionate is inhaled.
Dette kan også forekomme med andre kortikosterioder metaboliseret via P450 3A- pathway, f. eks. budesonid.
Systemic corticosteroid effects including Cushing's syndrome and adrenal suppression have been reported in patients receiving ritonavir and inhaled or intranasally administered fluticasone propionate; this could also occur with other corticosteroids metabolised via the P450 3A pathway eg budesonide.
4. 4).
Consequently, concomitant administration of tipranavir, co-administered with low dose ritonavir, and these glucocorticoids is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects (see section 4.4).
En dosisreduktion af glukokortikoidet bør overvejes med nøje monitorering af lokale og systemiske påvirkninger eller et skift til et glukokortikoid, som ikke er et substrat for CYP3A4 (f. eks. beclomethason).
A dose reduction of the glucocorticoid should be considered with close monitoring of local and systemic effects or a switch to a glucocorticoid, which is not a substrate for CYP3A4 (e. g. beclomethasone).
I tilfælde af ophør af glukokortikoider kan det desuden være nødvendig at gennemføre progressiv dosisreduktion over længere tid.
Moreover, in case of withdrawal of glucocorticoids progressive dose reduction may have to be performed over a longer period.
Effekten af høj systemisk fluticason eksponering på niveuaet af ritonavir i plasma er endnu ukendt.
The effects of high fluticasone systemic exposure on ritonavir plasma levels are as yet unknown.
Der foreligger ikke tilstrækkelige data om brugen af APTIVUS hos gravide kvinder.
There are no adequate data from the use of APTIVUS in pregnant women.
5. 3).
Studies in animals have shown reproductive toxicity (see section 5.3).
Interaktionen mellem tipranavir og orale antikonceptionsmidler er ugunstig.
APTIVUS adversely interacts with oral contraceptives.
Derfor bør der anvendes en effektiv og sikker alternativ antikonceptionsmetode i behandlingsperioden.
Therefore, an alternative, effective, safe method of contraception should be used during treatment.
I overensstemmelse med anbefalingen at HIV- smittede mødre ikke bør amme deres børn under nogen omstændigheder for at undgå risikoen for postnatal transmission af HIV, bør mødre standse amningen, hvis de får APTIVUS.
Consistent with the recommendation that HIV-infected mothers should not breast-feed their infants under any circumstances to avoid risking postnatal transmission of HIV, mothers should discontinue breast-feeding if they are receiving APTIVUS.
100 mg pr. kapsel eller 200 mg pr. dosis).
Patients should be informed that APTIVUS soft capsules contain small amounts of alcohol (7% ethanol, ie 100 mg per capsule or 200 mg per dose).
APTIVUS givet sammen med lavdosis ritonavir er blevet forbundet med rapporter om signifikant levertoksicitet.
APTIVUS co-administered with low dose ritonavir, has been associated with reports of significant liver toxicity.