natgillin/translations-raw huggingface dataset:
Dog bliver 25- O- desacetylrifabutin AUC (0- 48) og Cmax henholdsvis 11 og 6 gange højere, hvilket potentielt kan føre til stigning i rifabutin relaterede bivirkninger, især uveitis.
However, 25-O-desacetylrifabutin AUC (0-48) and Cmax were increased 11-fold and 6- fold respectively, which could potentially lead to an increase of rifabutin related adverse events, notably uveitis.
Historiske sammenligninger tyder ikke på at rifabutin reducerer amprenavir eksponeringen.
Based on historical comparison, rifabutin did not appear to reduce amprenavir exposure.
På basis af disse data anbefales en 75% reduktion af standard dosis af rifabutin (fx til 150 mg hver anden dag), når dette administreres sammen med Telzir i kombination med ritonavir.
On the basis of these data, a 75% reduction of the standard rifabutin dose (i. e. to 150 mg every other day) is recommended when administered with Telzir with ritonavir.
Yderligere dosisreduktion kan være nødvendig.
Further dose reduction may be necessary.
Andre lægemidler
8 Other medicinal products
Lægemidler der kan reducere plasmakoncentrationen for amprenavir når administreret i kombination med Telzir
Medicinal products that may reduce plasma amprenavir concentrations when co-administered with Telzir
Dosisjustering er ikke nødvendig for nogen af lægemidlerne, når antacida, protonpumpehæmmere eller histamin H2 receptorantagonister administreres samtidig med fosamprenavir.
Antacids, Histamine H2 receptor antagonist and Proton-Pump inhibitors: no dose adjustment for any of the respective medicinal products is considered necessary when antacids, proton-pump inhibitors or histamine H2 receptor antagonists are administered concomitantly with fosamprenavir.
Når en enkelt 1400 mg dosis af fosamprenavir blev administreret sammen med en enkelt 30 ml dosis af antacidsuspension (equivalent med 3, 6 gram aluminiumhydroxid og 1, 8 gram magnesiumhydroxid) blev AUC og Cmax for amprenavir nedsat med henholdsvis 18% og 35%, mens Cmin (C12h) var uændret.
The AUC and Cmax of amprenavir were decreased by 18% and 35% respectively, whilst the Cmin (C12h) was comparable, when a single 1400 mg dose of fosamprenavir was co-administered with a single 30 ml dose of antacid suspension (equivalent to 3.6 grams aluminium hydroxide and 1.8 grams magnesium hydroxide).
Serumniveauer for amprenavir kan reduceres ved samtidig brug af histamin H2 receptorantagonister (f. eks. ranitidin og cimitidin).
Serum levels of amprenavir can be reduced by concomitant use of histamine H2 receptor antagonists (for example ranitidine and cimetidine).
Samtidig administration af ranitidin (300 mg enkeltdosis) og fosam - prenavir (1400 mg enkeltdosis) nedsatte plasma AUC for amprenavir med 30% og Cmax med 51%.
Concurrent administration of ranitidine (300 mg single dose) with fosamprenavir (1400 mg single dose) decreased plasma amprenavir AUC by 30% and Cmax by 51%.
Der blev ikke observeret ændringer i Cmin for amprenavir (C12h).
There was, however, no change observed in the amprenavir Cmin (C12h).
Krampestillende lægemidler:
Anticonvulsant active substances:
Phenytoins AUC, Cmin og Cmax blev reduceret med hhv.
The AUC and Cmin of amprenavir were increased by 20% and 19% respectively, with Cmax unchanged when fosamprenavir (700 mg twice daily) plus ritonavir (100 mg twice daily) was given concomitantly with phenytoin (300 mg once daily).
22%, 20% og 29%.
The AUC, Cmax and Cmin of phenytoin were decreased by 22%, 20% and 29% respectively.
Hvis fosamprenavir plus ritonavir gives i kombination med phenytoin, er det derfor ikke nødvendigt med en dosisjustering af fosamprenavir og ritonavir.
Therefore, if fosamprenavir plus ritonavir is given in combination with phenytoin, no change to the fosamprenavir plus ritonavir dosage regimen is required.
Det anbefales dog at måle phenytoins plasmakonncentration og øge dosis af phenytoin om nødvendigt.
However, it is recommended that phenytoin plasma concentrations be monitored and phenytoin dose increased as appropriate.
Samtidig administration af andre antikonvulsiva kendt som enzymatiske inducere (fx phenobarbital, carbamazepin) er ikke blevet undersøgt, men kan medføre et fald i plasmakoncentrationen af amprenavir.
Concomitant administration of other anticonvulsant agents known to be enzymatic inducers (e. g. phenobarbital, carbamazepine) has not been studied but may lead to a decrease in the plasma concentrations of amprenavir.
Disse kombinationer bør derfor anvendes med forsigtighed.
These combinations should be used with caution.
8 Lægemidler hvis plasmaniveauer kan blive forøget når disse administreres i kombination med Telzir
Medicinal products whose plasma levels may be increased when co-administered with Telzir
Nogle stoffer (f. eks. lidokain (ved systemisk administration) og halofantrin) kan i kombination med Telzir medføre alvorlige bivirkninger.
Other medicinal products with a narrow therapeutic window: some substances (e. g. lidocaine (by systemic route) and halofantrine) given with Telzir may cause serious adverse reactions.
Samtidig behandling kan derfor ikke anbefales.
Concomitant use is not recommended.
Samtidig administration er ikke anbefalet.
Erectile dysfunction medicinal products: concomitant use is not recommended.
Dette kan resultere i en stigning i PDE5- hæmmer associerede bivirkninger, herunder hypotension, visuelle ændringer og priapismus.
Based on data for ritonavir and other protease inhibitors, plasma concentrations of PDE5 inhibitors (e. g. sildenafil and vardenafil) are expected to substantially increase when co-administered with Telzir with ritonavir and may result in an increase in PDE5 inhibitor associated adverse reactions, including hypotension, visual changes and priapism.
4. 4).
Consequently, concomitant administration of Telzir with ritonavir and these glucocorticoids is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects (see section 4.4).
I tilfælde af behandlingsophør med glukokortikoider skal nedtrapningen ske gradvist over en længere periode.
Moreover, in case of withdrawal of glucocorticoids progressive dose reduction may have to be
Hvis behandling med HMG- CoA- reduktasehæmmere er indiceret, anbefales behandling med pravastatin eller fluvastatin, fordi deres metabolisme ikke afhænger af CYP3A4 og der forventes ikke interaktioner med proteasehæmmere.
HMG-CoA reductase inhibitors: if treatment with a HMG-CoA reductase inhibitor is indicated, pravastatin or fluvastatin is recommended because their metabolism is not dependent on CYP 3A4 and interactions are not expected with protease inhibitors.
HMG- CoA- reduktasehæmmere, der primært metaboliseres af CYP3A4 (f. eks. lovastatin og simvastatin), forventes at få en markant stigning af plasmakoncentrationen ved samtidig administration med Telzir og ritonavir.
HMG-CoA reductase inhibitors which are highly dependent on CYP3A4 for metabolism, such as lovastatin and simvastatin, are expected to have markedly increased plasma concentrations when co-administered with Telzir with ritonavir.
Da en øget koncentration af HMG- CoA- reduktasehæmmere kan forårsage myopati, herunder rhabdomyolyse, kan samtidig administration af Telzir og ritonavir ikke anbefales.
Since increased concentrations of HMG-CoA reductase inhibitors may cause myopathy, including rhabdomyolysis, the combination of lovastatin or simvastatin with Telzir with ritonavir is not recommended.
Dosisjustering er ikke nødvendig for hverken Telzir eller ritonavir, når Telzir administreres sammen med atorvastatin.
No adjustment of the fosamprenavir or ritonavir dose is required when co-administered with atovarstatin.
Cmax, AUC og Cmin for atorvastatin blev forøget med henholdsvis 184%, 153% og 73%, når atorva - statin (10 mg 1 gang daglig i 4 dage) blev givet sammen med 700 mg fosamprenavir 2 gange daglig i kombination med 100 mg ritonavir 2 gange daglig i 2 uger.
The Cmax, AUC and Cmin of atorvastatin were increased by 184%, 153% and 73% respectively when atorvastatin (10 mg once daily for 4 days) was given with fosamprenavir 700 mg twice daily with ritonavir 100 mg twice daily for two weeks.
Cmax, AUC og Cmin for amprenavir var uændret.
The Cmax, AUC and Cmin of amprenavir were unchanged.
Når atorvastatin administreres sammen med Telzir og ritonavir, bør doser større end 200 mg/ dag anvendes med omhyggelig observation for tegn på toksicitet af atorvastatin.
When used with Telzir with ritonavir, doses of atorvastatin no greater than 20 mg / day should be administered, with careful monitoring for atorvastatin toxicity.
Hyppig koncentrationsmåling af immunosuppressanten anbefales indtil niveauet er stabiliseret, idet plasmakoncentrationen af cyklosporin, rapamycin og tacrolimus kan være forhøjet, når stofferne administreres sammen med fosamprenavir og ritonavir.
Immunosuppressants: frequent therapeutic concentration monitoring of immunosuppresant levels is recommended until levels have stabilised as plasma concentrations of cyclosporin, rapamycin and tacrolimus may be increased when co-administered with fosamprenavir with ritonavir.
Samtidig administration af Telzir/ ritonavir og midazolam kan medføre en stor stigning i koncentrationen af benzodiazepinet.
Coadministration with Telzir/ ritonavir may cause a large increase in the concentration of this benzodiazepine.
Der er ikke udført interaktionsanalyser af kombinationen med Telzir/ ritonavir og benzodiazepiner.
No drug interaction study has been performed for the co-administration of Telzir/ ritonavir with benzodiazepines.
4. 3), og der bør udvises forsigtighed, når Telzir/ ritonavir anvendes i kombination med parenteral midazolam.
Therefore Telzir/ ritonavir should not be co-administered with orally administered midazolam (see section 4.3), whereas caution should be used with co-administration of Telzir/ ritonavir and parenteral midazolam.
Hvis Telzir/ ritonavir gives i kombination med parenteral midazolam, skal det gøres på en intensivafdeling eller under tilsvarende forhold, som sikrer tæt klinisk monitorering og tilgængelig medicinsk behandling i tilfælde af, at der
If Telzir/ ritonavir is co-administered with parenteral midazolam, it should be done in an intensive care unit (ICU) or similar setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/ or prolonged sedation.
Effekten og bivirkninger af tricykliske antidepressiva skal omhyggelig overvåges, når disse (f. eks. desipramin og nortriptylin) anvendes samtidig med Telzir.
Tricyclic antidepressants: careful monitoring of the therapeutic and adverse reactions of tricyclic antidepressants is recommended when they (for example desipramine and nortriptyline) are concomitantly administered with Telzir.
Lægemidler hvis plasmaniveau kan nedsættes når administreret samtidig med Telzir
Medicinal products whose plasma levels may be decreased when co-administered with Telzir
Samtidig administration af 700 mg fosamprenavir og 100 mg ritonavir 2 gange daglig og metadon en gang daglig (≤ 200 mg) i 14 dage reducerede AUC( 0- τ) og Cmax for den aktive (R -) enantiomer af metadon med henholdsvis 18% og 21%.
Methadone: co-administration of fosamprenavir 700 mg and ritonavir 100 mg twice daily with methadone once daily (≤ 200 mg) for 14 days decreased the active (R-) methadone enantiomer AUC(0- τ) and Cmax by 18% and 21% respectively.
Den begrænsede indflydelse forventes ikke at være klinisk signifikant, men for en sikkerheds skyld skal patienterne observeres for abstinenser.
However, as a precaution, patients should be monitored for withdrawal syndrome.
Ifølge tidligere erfaringer forventes metadon ikke at ændre de farmakokinetiske parametre for amprenavir i plasma.
Based on historical comparisons, methadone did not appear to alter plasma amprenavir pharmacokinetic parameters.
Når warfarin eller andre orale antikoagulanter administreres samtidig med Telzir og ritonavir, anbefales en øget monitorering af den International Normaliseret Ratio på grund af et muligt fald i antikoagulanternes effekt.
Oral anticoagulants: a reinforced monitoring of the International Normalised Ratio is recommended in case of administration of Telzir with ritonavir with warfarin or other oral anticoagulants, due to a possible decrease or increase of their antithrombotic effect.
Steroider:
Steroids:
Samtidig administration af fosamprenavir 700 mg 2 gange daglig + ritonavir 100 mg 2 gange daglig med et oralt præventionsmiddel indeholdende ethinyl estradiol (EE) 0, 035 mg/ norethisteron (NE) 0, 5 mg en gang daglig nedsatte plasma EE AUC( 0- τ) og Cmax med henholdsvis 37% og 28% og nedsatte plasma NE AUC( 0- τ), Cmax og Cτ med henholdsvis 34%, 38% og 26%.
Co-administration of fosamprenavir 700 mg twice daily + ritonavir 100 mg twice daily with an oral contraceptive containing ethinyl estradiol (EE) 0.035 mg/ norethisterone (NE) 0.5 mg once
Steady state plasma farmokokinetiske (PK) parametre for amprenavir blev ikke signifikant påvirket ved samtidig administration af dette orale præventionsmiddel, men ritonavir AUC( 0- τ) og Cmax var henholdsvis 45% og 63% højere sammenlignet med baggrundsdata for kvinder doseret med fosamprenavir/ ritonavir alene.
Steady state plasma amprenavir pharmacokinetic (PK) parameters were not significantly affected by co-administration with this oral contraceptive; however, ritonavir AUC(0- τ) and Cmax were 45% and 63% higher, respectively, compared to historical data in female subjects dosed with fosamprenavir / ritonavir alone.
I tillæg til den nedsatte eksponering for hormonale præventionsmidler resulterede samtidig administration af fosamprenavir med ritonavir og dette orale præventionsmiddel i klinisk signifikante levertransaminase stigninger hos nogle raske personer.
In addition to the decreased hormonal contraceptive exposures, co-administration of fosamprenavir with ritonavir and this oral contraceptive resulted in clinically significant hepatic transaminase elevations in some healthy subjects.
4. 4).
Therefore alternative non-hormonal methods of contraception are recommended for women of childbearing potential (see section 4.4).
Samtidig administration af 20 mg paroxetin en gang daglig og 700 mg fosamprenavir i kombination med 100 mg ritonavir to gange daglig til raske frivillige i 10 dage medførte et fald i Cmax og AUC for paroxetin på henholdsvis 51% og 55%.
The Cmax and AUC of paroxetine were decreased by 51% and 55% respectively when paroxetine 20 mg once daily was given with fosamprenavir 700 mg and ritonavir 100 mg twice daily for 10 days in healthy volunteers.
Dette gøres ud fra en klinisk vurdering af det antidepressive respons.
Therefore, if paroxetine is co-administered with Telzir and ritonavir, the recommended approach is a dose titration of paroxetine based on a clinical assessment of antidepressant response.
Patienter, der allerede er i behandling med en bestemt dosis paroxetin og som påbegynder behandling med Telzir og ritonavir, bør overvåges for antidepressivt respons.
In addition, patients on stable dose of paroxetine who start treatment with Telzir and ritonavir should be monitored for antidepressant response.
Der foreligger ikke kliniske data om brugen af Telzir under graviditet.
There is no clinical experience with fosamprenavir in pregnant women.
I dyreforsøg blev der observeret tegn på toksicitet ved systemiske plasmaniveauer (AUC) for amprenavir som var lavere end den terapeutiske dosis der anvendes til patienter som behandles med Telzir (se pkt.
In animal studies at systemic plasma exposures (AUC) to amprenavir lower than therapeutic exposure in patients treated with Telzir, some developmental toxicity was observed (see section 5.3).
Idet doserne anvendt i reproduktionsstudierne var lave, er den potentielle toksicitet af Telzir er ikke fastslået.
In view of the low exposure in reproductive toxicity studies, the potential developmental toxicity of Telzir has not been fully determined.
10 Amning
Lactation
Der er fundet materiale relateret til amprenavir i rottemælk, men det vides ikke, om amprenavir udskilles i modermælk.
Amprenavir-related material was found in rat milk, but it is not known whether amprenavir is excreted in human milk.
5. 3).
Rat pups exposed pre and post-natally to amprenavir and fosamprenavir showed developmental toxicity (see section 5.3).
Det anbefales derfor, at mødre undlader at amme deres børn, mens de er i behandling med Telzir.
It is therefore recommended that mothers treated with Telzir do not breast-feed their infants.
Som en generel regel anbefales det, at HIV- inficerede kvinder ikke under nogen omstændigheder ammer deres børn for at undgå at overføre HIV.
As a general rule, it is recommended that HIV-infected women must not breast-feed under any circumstances to avoid transmission of HIV.
Der er ikke foretaget undersøgelser af virkninger på evnen til at føre motorkøretøj eller betjene maskiner for Telzir i kombination med ritonavir.
No studies on the effects of Telzir in combination with ritonavir on the ability to drive and use machines have been performed.
4. 8).
The adverse reaction profile of Telzir should be borne in mind when considering the patient’ s ability to drive or operate machinery (see section 4.8).
Sikkerheden ved fosamprenavir er undersøgt hos 755 voksne i fase II og III kontrollerede kliniske afprøvninger.
The safety of fosamprenavir has been studied in 755 adult patients in Phase II and III controlled clinical trials.
Sikkerheden af den samtidige administration af fosamprenavir og en lav dosis ritonavir blev undersøgt i to pivotale fase III forsøg:
The safety of the co-administration of fosamprenavir with low dose ritonavir was established in two pivotal Phase III trials:
I APV30002 (n = 322) med behandlingsnaive patienter, blev fosamprenavir (1400 mg) administreret 1 gang daglig sammen med ritonavir (200 mg) som del af et tripel- regime indeholdende abacavir og lamivudin.
APV30002 (n = 322) in antiretroviral naïve patients, fosamprenavir (1400 mg) given once daily in combination with ritonavir (200 mg) as part of a triple regimen including abacavir and lamivudine.
I APV30003, med patienter tidligere behandlet med proteasehæmmere, blev fosamprenavir administreret sammen med en lav dosis ritonavir enten 1 gang daglig (1400 mg / 200 mg) (n = 106) eller 2 gange daglig (700 mg / 100 mg) (n = 106) i kombination med to aktive reverse transkriptasehæmmere (RTI’ er).
APV30003 in protease inhibitor experienced patients, fosamprenavir given in combination with low dose ritonavir either once daily (1400 mg / 200 mg) (n =
Bivirkningsprofilen var ens i alle de respektive studier med voksne; behandlingsnaive patienter (APV30002) og patienter, der tidligere har været behandlet med proteasehæmmere (dosering 2 gange daglig, APV30003).
The adverse reaction profile was similar across all the respective adult studies: antiretroviral naïve (APV30002) and protease inhibitor experienced (twice daily dosing, APV30003) patient populations.
Bivirkninger vises nedenfor iht.
Adverse reactions are listed by MedDRA system organ class and absolute frequency.
MedDRA- systemorganklasser og absolut frekvens.
Frequencies are defined as:
Frekvenserne er defineret som Meget almindelig (≥1/ 10), Almindelig (≥1/ 100, < 1/ 10), Ikke almindelig (≥1/ 1. 000, < 1/ 100), Sjælden (≥1/ 10. 000, < 1/ 1. 000) og Meget sjælden (< 1/ 10. 000), herunder enkeltstående rapporter.
Very common (≥ 1/ 10), Common (≥ 1/ 100, < 1/ 10), Uncommon (≥ 1/ 1,000, < 1/ 100), Rare (≥ 1/ 10,000, < 1/ 1,000) or Very rare (< 1/ 10,000), including isolated reports.
Frekvenskategorierne for nedennævnte bivirkninger er baseret på kliniske forsøg og data efter markedsføringen.
Frequency categories for the events below have been based on clinical trials and postmarketing data.
Bivirkningerne havde som minimum moderat intensitet (grad 2 eller derover) hos mindst 1% af patienterne og blev rapporteret af investigator som relateret til lægemidlet anvendt i studiet.
Most of the adverse events below were reported from two large clinical studies in adults, where the adverse events were of at least moderate intensity (Grade 2 or more) occurring in at least 1% of patients and reported by investigators as being attributable to the medicinal products used in the studies.
11 Organklasse
Body System
Udslæt (se nedenfor under ” Udslæt/ hudreaktioner ”)
Rash (see text below “ rash/ cutaneous reactions”)
Stevens- Johnson syndrom
Stevens Johnson syndrome
5. 1 for information om doseringsanbefalinger til forskellige aldersgrupper).
The adverse event profile in children and adolescents is based on integrated safety data from two studies (APV29005 and APV20003) in which 126 HIV-1 infected subjects 2 to 18 years of age received fosamprenavir with ritonavir with background nucleoside reverse transcriptase inhibitor therapy (see section 5.1 for information on dosing regimens applied for each age group).
70% af patienterne fik behandlingen i mere end 48 uger.
70% of subjects received greater than 48 weeks of exposure.
Den overordnede bivirkningsprofil hos disse 126 børn og unge var identisk med bivirkningsprofilen observeret hos voksne.
Overall the safety profile in these 126 children and adolescents was similar to that observed in the adult population.
Lægemiddelrelaterede bivirkninger var mere almindelige i APV20003 (55%), hvor patienterne fik behandling med fosamprenavir/ ritonavir 1 gang daglig sammenlignet med APV29005 (39%), hvor patienterne fik fosamprenavir/ ritonavir 2 gange daglig.
Drug-related adverse events were more common in APV20003 (55%) where subjects received once daily fosamprenavir / ritonavir when compared to APV29005 (39%) where subjects received twice daily fosamprenavir / ritonavir.
Erytematøse eller makulopapulære kutane eruptioner med eller uden pruritus kan forekomme under behandlingen.
Rash / cutaneous reactions: erythematous or maculopapular cutaneous eruptions, with or without pruritus, may occur during therapy.
Alvorlige og livstruende hudreaktioner, herunder Stevens- Johnson syndrom, er sjældne.
12 Severe or life-threatening cases of rash, including Stevens-Johnson syndrome are rare.
4. 4).
Fosamprenavir with ritonavir therapy should be definitively stopped in case of severe rash or in case of rash of mild or moderate intensity associated with systemic or mucosal signs (see section 4.4).
Forhøjet ALAT (almindelig), ASAT (almindelig), serumlipase (almindelig) og triglycerider (meget al - mindelig).
Clinical chemistry abnormalities: clinical chemistry abnormalities (Grade 3 or 4) potentially related to treatment with fosamprenavir with ritonavir and reported in greater than or equal to 1% of adult patients, included: increased ALT (common), AST (common), serum lipase (common) and triglycerides (very common).
Der blev observeret grad 3 og 4 stigninger i total kolesterol hos mindre end 1% af de voksne patienter (< 1% APV30002; 0% APV30003).
Grade 3 or 4 elevations in total cholesterol values were observed in less than 1% of adult patients (< 1% APV30002; 0% APV 30003).
4. 4).
Lipodystrophy: combination antiretroviral therapy has been associated with redistribution of body fat (lipodystrophy) in HIV patients including the loss of peripheral and facial subcutaneous fat, increased intra-abdominal and visceral fat, breast hypertrophy and dorsocervical fat accumulation (buffalo hump) (see section 4.4).
4. 4).
Metabolic abnormalities: combination antiretroviral therapy has been associated with metabolic abnormalities such as hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperglycaemia and hyperlactataemia (see section 4.4).
4. 4).
Hyperglycaemia: new onset of diabetes mellitus, hyperglycaemia or exacerbations of existing diabetes mellitus have been reported in patients receiving antiretroviral protease inhibitors (see section 4.4).
Der er kun sjældent rapporteret om rhabdomyolyse, hvilket dog bliver mere udtalt, når proteasehæmmerne administreres sammen med nukleosidanaloger.
Rhabdomyolysis: an increase in CPK, myalgia, myositis, and rarely, rhabdomyolysis, have been reported with protease inhibitors, more specifically in association with nucleoside analogues.
4. 4).
Haemophiliac patients: there have been reports of increased spontaneous bleeding in haemophiliac patients receiving antiretroviral protease inhibitors (see section 4.4).