qanastek/EMEA-V3 huggingface dataset:
Frequency categories for the events below have been based on clinical trials and postmarketing data.
Il- kategoriji ta ’ frekwenza għal dawn l- eventi msemmija hawn taħt ġew ibbażati fuq studji kliniċi u informazzjoni wara t- tqegħid fis- suq.
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.
Ħafna mill- eventi avversi hawn taħt ġew irrapurtati minn żewġ studji kliniċi kbar fuq adulti, fejn l - effetti avversi kienu għall- inqas ta ’ intensità moderata (Grad 2 jew iżjed), li seħħew għall- inqas f’ 1% ta ’ pazjenti u li l- investigaturi rrapurtawhom li jista ’ jkunu attribwiti għal prodotti mediċinali wżati f’ dawn l- istudji. huma nklużi.
Nervous system disorders
Komuni
Headache, dizziness, oral paraesthesia
Uġigħ ta ’ ras, sturdament, Disturbi fis- sistema nervuża parasiteżija tal- ħalq
Loose stools, nausea, vomiting, abdominal pain
Ippurgar maħlul, dardir, rimettar, uġigħ addominali
Rash (see text below “ rash/ cutaneous reactions”)
Komuni Raxx (ara l- kliem hawn taħt Disturbi fil- ġilda u fit - tessuti "raxx/ reazzjonijiet tal- ġilda ”) ta ’ taħt il- ġilda
Angioedema
Mhux komuni Anġjoedema,
Stevens Johnson syndrome
Rari Sindromu Stevens Johnson
Children and adolescents:
12 Tfal u adolexxenti:
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).
Il- profil ta ’ eventi avversi fi tfal u adolexxenti hu bbażat fuq informazzjoni integrata ta ’ sigurtà minn żewġ studji (APV 29005 u APV 20003) fejn 126 il- suġġett minn 2 sa 18 il - sena infettati bl- HIV irċevew fosamprenavir ma ’ ritonavir bi sfond ta ’ terapija ta ’ inibitur nukleosajd rivers transkiptejż (ara sezzjoni 5. 1 għal informazzjoni fuq is- sistemi ta ’ kura għad- dożaġġ għal kull età).
70% of subjects received greater than 48 weeks of exposure.
70% tas- suġġetti irċevew aktar minn 48 ġimgħa ta ’ espożizzjoni.
Overall the safety profile in these 126 children and adolescents was similar to that observed in the adult population.
Kollox ma ’ kollox il- profil ta ’ sigurtà ta ’ dawn il- 126 tfal u adolexxenti kien l- istess għal dak osservat fil- popolazzjoni adulta.
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.
Eventi avversi minħabba mediċina kienu aktar komuni f’ APV20003 (55%) fejn is- suġġetti irċevew fosamprenavir/ ritonavir darba kuljum meta mqabbla ma ’ APV29005 (39%) fejn is- suġġetti irċevew fosamprenavir/ ritonavir darbtejn kuljum.
Rash / cutaneous reactions: erythematous or maculopapular cutaneous eruptions, with or without pruritus, may occur during therapy.
Ħruġ eritematuż jew makulopapulari fil- ġilda, bil - jew mingħajr ħakk fil - ġilda, jistgħu jiżviluppaw waqt it- terapija.
The rash generally will resolve spontaneously without the necessity of discontinuing treatment with the fosamprenavir with ritonavir.
Ġeneralment ir- raxx jgħaddi waħdu mingħajr il- bżonn li titwaqqaf il- kura ta’ fosamprenavir b’ ritonavir.
12 Severe or life-threatening cases of rash, including Stevens-Johnson syndrome are rare.
Każijiet ta ’ raxx severi jew li jipperikolaw il- ħajja, inkluża s- sindromu Stevens- Johnson huma rari.
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).
It - terapija b’ fosamprenavir ma ’ ritonavir trid tiġi mwaqqfa għall- kollox fil- każ ta ’ raxx severi jew fil- każ ta ’ raxx ħafif jew moderat assoċjat ma ’ sinjali sistemiċi jew mukużi (ara sezzjoni 4. 4).
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).
Anormalitajiet kliniċi ta ’ kimika: anormalitajiet kliniċi ta ’ kimika (Grad 3 jew 4) li setgħu kienu relatati ma ’ kura b’ fosamprenavir b’ ritonavir u li ġew rappurtati f’ 1% jew aktar ta ’ pazjenti adulti, kienu jinkludu: żieda ta ’ ALT (komuni), ta ’ AST (komuni), ta ’ serum lipase (komuni) u ta ’ trigliċeridi (komuni ħafna).
Grade 3 or 4 elevations in total cholesterol values were observed in less than 1% of adult patients (< 1% APV30002; 0% APV 30003).
Żidiet ta ’ Grad 3 jew 4 fil- valuri totali ta ’ kolesterol dehru f’ inqas minn 1% ta ’ pazjenti adulti (< 1% APV30002; 0% APV 30003).
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).
Lipodistrofija: it- terapija antiretrovirali kombinata ġiet assoċjata ma ’ tqassim differenti tax- xaħam tal - ġisem (lipodistrofija) f’ pazjenti bl- HIV li jinkludi t- tnaqqis ta ’ xaħam taħt il- ġilda kemm periferali u kemm fil- wiċċ, żieda fix- xaħam addominali u fil- vixxri, ipertrofija tas- sider u tiġmigħ ta ’ xaħam dorso- ċervikali (buffalo hump) (ara sezzjoni 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).
Anormalitajiet metaboliċi: it- terapija antiretrovirali kombinata ġiet assoċjata ma ’ anormalitajiet metaboliċi bħal ipertrigliċeridimja, iperkolesterolimja, reżistenza għall- insulina, ipergliċemija u iperlaktejtimja (ara sezzjoni 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).
Ħruġ mill- ġdid ta ’ dijabete mellitus, ipergliċemija jew aggravar ta ’ dijabete mellitus li diġà kienet teżisti ġew rappurtati f’ pazjenti li kienu qed jieħdu impedituri protease antiretrovirali (ara sezzjoni 4. 4)
Rhabdomyolysis: an increase in CPK, myalgia, myositis, and rarely, rhabdomyolysis, have been reported with protease inhibitors, more specifically in association with nucleoside analogues.
Rabdomajoliżi: żieda ta ’ CPK, mijalġa, mijosite, u rarament ta ’ rabdomajoliżi ġew rappurtati ma ’ impedituri protease, speċifikament aktar f’ assoċjazzjoni ma ’ analogi nuklejosidi.
Haemophiliac patients: there have been reports of increased spontaneous bleeding in haemophiliac patients receiving antiretroviral protease inhibitors (see section 4.4).
Pazjenti emofilijaċi: ġew rappurtati każi ta ’ żieda fil- fsada spontanja f’ pazjenti emofilijaċi li jkunu jieħdu impedituri protease antiretrovirali (ara sezzjoni 4. 4).
Immune Reactivation Syndrome: in HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise (see section 4.4).
Sindromu tar- Riattivazzjoni Immunitarja: f’ pazjenti infettati bl- HIV b’ defiċjenza severa fl- immunità fiż- żmien tal- bidu tat- terapija antiretrovirali kombinata (TARK), reazzjoni nfjammatorja tista ’ tinħoloq ghal infezzjonijiet mingħajr sintomi jew opportunistiċi residwi.
Osteonecrosis: cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to combination antiretroviral therapy (CART).
Ostejonekrożi: Każijet ta ’ nekrożi fl- għadam ġew irrappurtati partikolarment f’ pazjenti b’ fatturi ta ’ riskju magħrufa, b’ HIVavvanzat u/ jew esponiment għal terapija antiretrovirali kombinata (CART) fit - tul.
There is no known antidote for Telzir.
Ma hawnx antidotu magħruf għal Telzir.
It is not known whether amprenavir can be removed by peritoneal dialysis or haemodialysis.
Mhux magħruf jekk amprenavir jistax jitneħħa b’ dijaliżi peritonali jew b’ dijaliżi tad- demm.
If overdosage occurs, the patient should be monitored for evidence of toxicity (see section 4.8) and standard supportive treatment applied as necessary.
F’ każ ta doża eċċessiva, il- pazjent għandu jkun monitorat għal xi sinjali ta ’ tossiċità (ara sezzjoni 4. 8) u biex jingħata l- kura standard li hemm bżonn.
Antivirals for systemic use, protease inhibitor, ATC Code:
Antivirali għal użu sistemiku, impeditur protease, Kodiċi ATC:
Amprenavir is a competitive inhibitor of the HIV-1 protease.
L- attività antivirali in vitro osservata b’ fosamprenavir kienet minħabba il- preżenza ta ’ traċċi ta ’ amprenavir. Amprenavir huwa impeditur kompetittiv tal- HIV- 1 protease.
Amprenavir binds to the active site of HIV-1 protease and thereby prevents the processing of viral gag and gag-pol polyprotein precursors, resulting in the formation of immature non-infectious viral particles.
Amprenavir jeħel mas- sit attiv tal- protease HIV- 1 li ma jħallix il- proċessar ta ’ prekursuri virali ta ’ gag u gag- pol polyprotein u b’ hekk jiġu ffurmati partiċelli virali mhux maturi li ma jinfettawx.
13 Co-administration of ritonavir with fosamprenavir increase plasma amprenavir AUC by approximately 2-fold and plasma C τ, ss by 4- to 6-fold, compared to values obtained when fosamprenavir is administered alone.
L- għoti ta ’ ritonavir flimkien ma ’ fosamprenavir iżid l- AUC ta ’ amprenavir fil- plażma għal bejn wieħed u ieħor darbtejn u l- plażma Cτ, ss għal erba ’ sa sitt darbiet, imqabbel mal- valuri miksuba meta fosamprenavir jingħata waħdu.
Administration of fosamprenavir 700 mg twice daily with ritonavir 100 mg twice daily results in plasma amprenavir concentrations (data from study APV30003 in antiretroviral experienced patients) which results in protein adjusted median ratios of Cmin/ IC50 and Cmin/ IC95 of 21.7 (range 1.19-240) and 3.21 (range 0.26-30.0), respectively.
L- għoti ta ’ 700 mg fosamprenavir darbtejn kuljum ma ’ 100 mg ritonavir darbtejn kuljum tirriżulta f’ konċentrazzjonijiet ta ’ amprenavir fil- plażma (data mill- istudju APV30003 f’ pazjenti b’ esperjenza ta ’ kura antiretrovirali) li tirriżulta fil- medja ta ’ proporzjon aġġustata ta ’ proteina ta ’ Cmin/ IC50 u Cmin/ IC50 ta ’ 21. 7 (medda 1. 19- 240) u 3. 21 (medda 0. 26- 30. 0) rispettivament
a) ART-naïve or PI-naïve patients Various regimens have been assessed in the amprenavir/ fosamprenavir development programs with and without co-administration of ritonavir.
Ġew assessjati diversi sistemi ta ’ kura differenti fil- programmi ta ’ żvilupp amprenavir/ fosamprenavir kemm meta jingħata ma ’ ritonavir u kemm meta le.
L10V/ F/ R, I13V, K20R/ T, L33F/ V, M36I, M46I/ L, I47V/ L Q58E, I62V, L63P, V77I, I85V, and I93L.
L10V/ F/ R, II3V, K20R/ T, L33F/ V, M361, M461/ L, 147V/ L Q58E, 162V, L63P, V771, 185V, u
When ART naïve patients were treated with the currently approved doses of fosamprenavir/ ritonavir, as for other ritonavir boosted PI regimens, the mutations described were infrequently observed.
Meta pazjenti mingħajr esperjenza ta ’ kura ART ingħataw kura b’ dożi approvati bħalissa ta ’
Sixteen of 434 ART-naïve patients who received fosamprenavir 700mg/ ritonavir 100mg twice daily in ESS100732 experienced virological failure by Week 48 with 14 isolates genotyped.
Sittax mill- 434 pazjent mingħajr esperjenza ART li ingħataw fosamprenavir 700mg/ ritonavir 100mg darbtejn kuljum f’ ESS100732 esperjenzaw falliment viroloġiku sa Ġimgħa 48 b’ 14- iliżolat ġenotipat.
One resistance mutation was observed in each of 3 isolates:
14 Kienet osservata mutazzjoni ta ’ reżistenza waħda f’ kull waħda mit- tlett iżolati rispettivament:
K20K/ R, I54I/ L and I93I/ L respectively
K20K/ R, I54I/ L and I93I/ L.
Genotypic analysis of isolates from 13 of 14 paediatric patients exhibiting virological failure among the 59 PI-naïve patients enrolled, demonstrated resistance patterns similar to those observed in adults.
Analiżi ġenotipika ta ’ iżolati minn 13 minn 14- il- pazjent pedjatriku li wrew falliment viroloġiku fost il- 59 pazjent mingħajr esperjenza PI, li ħadu sehem urew mudell ta ’ reżistenza simili ta ’ dawk osservati fl- adulti.
b) PI-experienced patients
b) Pazjenti b’ esperjenza PI
In the studies of PI-experienced patients, PRO30017 (amprenavir 600 mg / ritonavir 100 mg twice daily in sub-study A and B with 80 and 37 patients respectively), the following mutations emerged in patients with virological failure:
Fl- istudji ta ’ pazjenti b’ esperjenza PI, PRO30017 (amprenavir 600 mg / ritonavir 100 mg darbtejn kuljum f’ sotto- studju A u B bi 80 u 37 pazjent rispettivament), ħarġu dawn il- mutazzjonijiet li ġejjin f’ pazjenti b’ falliment viroloġiku:
L10F/ I/ V, V11I, I13V, K20R, V32I, L33F, E34Q, M36I, M46I/ L, I47V, G48V, I50V, I54L/ M/ T/ V, Q58E, D60E, I62V, A71V, V77I, V82A/ I, I84V, I85V, L90M and I93L/ M.
L10F/ I/ V, V11I, I13V, K20R, V32I, L33F, E34Q, M36I, M46I/ L, I47V, G48V, I50V, I54L/ M/ T/ V, Q58E, D60E, I62V, A71V, V77I, V82A/ I, I84V, I85V, L90M u I93L/ M.
In the studies of PI-experienced patients, APV30003 and its extension, APV30005 (fosamprenavir 700 mg / ritonavir 100 mg twice daily: n=107), the following mutations emerged in patients experiencing virological failure through 96 weeks:
Fl- istudji ta ’ pazjenti b’ esperjenza PI, APV30003 u l- estensjoni tiegħu, APV30005 (fosamprenavir 700 mg / ritonavir 100 mg darbtejn kuljum: n=107), ħarġu dawn il- mutazzjonijiet li ġejjin f’ pazjenti li esperjenzaw falliment viroloġiku matul 96 ġimgħa:
L10F/ I, L24I, V32I, L33F, M36I, M46I/ L, I47V, I50V, I54L/ M/ S, A71I/ T/ V, G73S, V82A, I84V, and L90M.
L10F/ I, L24I, V32I, L33F, M36I, M46I/ L, I47V, I50V, I54L/ M/ S, A71I/ T/ V, G73S, V82A, I84V, u L90M.
In the paediatric studies APV20003 and APV29005, 67 PI-experienced patients were treated with fosamprenavir / ritonavir and of 22 virological failure isolates genotyped, nine patients were found with treatment-emergent protease mutations.
Fl- istudji pedjatriċi APV20003 u APV29005, 67 pazjent b’ esperjenza PI ġew ittrattati b ’ fosamprenavir / ritonavir u 22 iżolat ta ’ falliment viroloġiku ġew ġenotipati, disa ’ pazjenti nstabu b’ mutazzjonijiet ta ’ protease li ħarġu minħabba l- kura.
The mutational profiles were similar to those described for PI-experienced adults treated with fosamprenavir / ritonavir.
Il- profili ta ’ mutazzjonijiet kienu simili għal dawk deskritti għal adulti b' esperjenza PI ttrattati b' fosamprenavir/ ritonavir.
Genotypic interpretation systems may be used to estimate the activity of amprenavir / ritonavir or fosamprenavir / ritonavir in subjects with PI-resistant isolates.
Analiżi bbażata fuq testijiet ta ’ reżistenza ġenotipika Jistgħu jintużaw sistemi ta ’ interpretazzjonijiet ġenotipiċi biex tagħmel stimi ta ’ l- attività ta ’ amprenavir/ ritonavir jew fosamprenavir/ ritonavir f’ suġġetti b’ iżolati reżistenti għal PI.
Clinically validated phenotypic interpretation systems may be used in association with the genotypic data to estimate the activity of amprenavir / ritonavir or fosamprenavir / ritonavir in patients with PI- resistant isolates.
Analiżi bbażata fuq testijiet ta ’ reżistenza fenotipika Sistemi ta ’ interpretazzjoni fenotipika valida klinikament tista ’ tintuża flimkien ma ’ data ġenotipika biex tagħmel stima ta ’ l- attività ta ’ amprenavir / ritonavir jew fosamprenavir / ritonavir f’ pazjenti b’ iżolati reżistenti għal PI.
Reduced susceptibility to amprenavir was associated with virus that had developed I50V or I84V or V32I+I47Vor I54M mutations.
Suxxettibilità mnaqqsa għal amprenavir kienet assoċċjata ma ’ virus li kien żviluppa mutazzjonijiet I50V jew I84V jew V321+I47V jew I54M.
Based on data from twenty-five antiretroviral naïve patients failing a fosamprenavir containing regimen (one of whom showed Baseline resistance to lopinavir and saquinavir and another to tipranavir the resistance pathways associated with amprenavir produce limited cross-resistance to atazanavir/ ritonavir (three of 25 isolates), darunavir/ ritonavir (four of 25 isolates), indinavir/ ritonavir (one of 25 isolates), lopinavir/ ritonavir (three of 24 isolates, saquinavir (three of 24 isolates) and tipranavir/ ritonavir (four of 24 isolates).
15 b’ fosamprenavir (fejn wieħed minnhom wera reżistenza fil- Linja Bażi għal lopinavir u saquinavir u ieħor għal tipranavir), il- passaġġi ta ’ reżistenza assoċċjati ma ’ amprenavir jipproduċu cross- resistance limitata għal atazanavir/ ritonavir (tlieta minn 25 iżolat), darunavir/ ritonavir (erba ’ minn 25 iżolat), indinavir/ ritonavir (wieħed minn 25 iżolat), lopinavir/ ritonavir (tlieta minn 24 iżolat), saquinavir (tlieta minn 24 iżolat) u tipranavir/ ritonavir (erba ’ minn 24 iżolat).
The number of key PI-resistance mutations increases markedly the longer a failing PI-containing regimen is continued.
In- numru ta ’ mutazzjonijiet ċentrali ta ’ reżistenza PI jiżdiedu sostanzjalment aktar ma ddum tintuża sistema ta ’ kura li fiha PI falluta.
Early discontinuation of failing therapies is recommended in order to limit the accumulation of multiple mutations, which may be detrimental to a subsequent rescue regimen.
Ikun aħjar jekk jittwafqu sistema ta ’ kura falluti kmieni kemm jista ’ jkun biex tillimita l- akkumulazzjoni ta ’ ħafna mutazzjonijiet, li jistgħu ifixxklu sistemi ta ’ kura ta ’ salvataġġ li jiġu wara.
Cross-resistance between amprenavir and reverse transcriptase inhibitors is unlikely to occur because the enzyme targets are different.
Cross resistance bejn amprenavir u impedituri reverse transcriptase x’ aktarx ma sseħħx għaliex l - enżimi immirati huma differenti.
Telzir is not recommended for use as monotherapy, due to the rapid emergence of resistant virus.
Telzir mhux rakkomandat għal użu f' monoterapija, minħabba li jitrabba malajr il- virus reżistenti.
15 Clinical experience
Esperjenza klinika
Clinical experience with fosamprenavir boosted with ritonavir is mainly based on three open label studies.
L- esperjenza klinika b’ fosamprenavir imsaħħaħ b’ ritonavir hi bażata l- aktar fuq tliet studji open- label.
Two studies performed in antiretroviral naïve patients, one in comparison to nelfinavir (study APV30002) and one in comparison to lopinavir / ritonavir (study ESS100732), and one study in antiretroviral experienced patients, in comparison to lopinavir / ritonavir (study APV30003).
Żewġ studji mwettqa f’ pazjenti li m’ għandhomx esperjenza ta ’ terapija antiretrovirali, wieħed f’ paragun ma ’ nelfinavir (studju APV30002) u wieħed f’ paragun ma ’ lopinavir / ritonavir (studju ESS100732), u studju f’ pazjenti b’ esperjenza antiretrovirali f’ paragun ma ’ lopinavir/ ritonavir (studju APV30003).
Antiretroviral Naïve Adult Patients
Pazjenti Adulti li m’ għandhomx esperjenza ta ’ kura Antiretrovirali
In antiretroviral naïve patients in APV30002, fosamprenavir (1400 mg) given once daily in combination with low dose ritonavir (200 mg) as part of a triple regimen including abacavir (300 mg twice daily) and lamivudine (150 mg twice daily) showed similar efficacy over 48 weeks compared to nelfinavir (1250 mg) given twice daily in combination with abacavir with lamivudine (300 and 150 mg twice daily).
F’ pazjenti li m’ għandhomx esperjenza ta ’ kura antiretrovirali fl- APV30002, fosamprenavir (1400 mg) darba kuljum flimkien ma ’ doża żgħira ta ’ ritonavir (200 mg) bħala parti minn kura trippla li tinkludi abacavir (300 mg darbtejn kuljum) u lamivudine (150 mg darbtejn kuljum) wera effikaċja simili matul 48 ġimgħa paragunat ma ’ nelfinavir (1250 mg) darbtejn kuljum flimkien ma ’ abacavir ma ’ lamivudine (300 u 150 mg darbtejn kuljum).
Non-inferiority was demonstrated between fosamprenavir with ritonavir and nelfinavir based on the proportions of patients achieving plasma HIV-1 RNA levels < 400 copies/ ml at 48 weeks (primary endpoint).
Intwera li ma kienx hemm inferjorità bejn fosamprenavir ma ’ ritonavir u nelfinavir ibbażata fuq il - proporzjon ta ’ pazjenti li laħqu livelli ta ’ HIV- 1 RNA fil- plażma ta ’ < 400 kopji/ ml fil- ġimgħa 48 (endpoint primarja).
In the ITT (Rebound or Discontinuation = Failure) analysis, 69% (221 / 322) of patients receiving fosamprenavir with ritonavir achieved < 400 copies/ ml compared to 68% (221 / 327) of patients receiving nelfinavir.
Fl- analiżi ITT (Irkadar jew twaqqif = Falliment), 69% (221 / 322) ta ’ pazjenti fuq fosamprenavir ma ’ ritonavir laħqu < 400 kopji/ ml meta mqabbla ma ’ 68% (221 / 327) ta ’ pazjenti fuq nelfinavir.
The median plasma HIV-1 RNA had decreased by 3.1 log10 copies/ ml and 3.0 log10 copies/ ml at Week 48 in the fosamprenavir with ritonavir and nelfinavir arms respectively.
Il- plażma medjana HIV- 1 RNA naqset bi 3. 1 log10 kopji/ ml u 3. 0 log10 kopji/ ml f’ Ġimgħa 48 fil- gruppi kemm ta ’ fosamprenavir b’ ritonavir u kemm ta ’ nelfinavir rispettivament.
CD4 + cell counts increased in both the fosamprenavir with ritonavir and nelfinavir groups, with median increases above baseline being similar in magnitude at Week 48 (+ 203 and + 207 cells/ mm3, respectively).
L- għadd ta ’ ċelluli CD4+ żdied kemm fil- grupp fosamprenavir b’ ritonavir u kemm f’ dak nelfinavir, biż- żidiet medjani ’ l fuq mill- linja bażi jixxiebħu fid- daqs fil- Ġimgħa 48 (+ 203 u + 207 ċelluli/ mm3, rispettivament).
The data presented above demonstrates that the once daily regimen of fosamprenavir with ritonavir (1400 / 200 mg OD) in antiretroviral naïve patients showed similar efficacy compared to nelfinavir given twice daily.
It- tagħrif preżentat hawn fuq juri li f’ pazjenti li m’ għandhomx esperjenza ta ’ kura antiretrovirali, fosamprenavir ma ’ ritonavir darba kuljum (1400 / 200mg OD) wera effikaċja simili meta mqabbel ma ’ nelfinavir darbtejn kuljum.
As a conservative approach, based on enhanced amprenavir Ctrough levels, the twice daily dosing regimen of fosamprenavir with ritonavir was recommended for optimal therapeutic management of this population (see section 4.2).
Dan l- istudju minħabba id- disinn tiegħu open- label, kontra nelfinavir) ma weriex effikaċja robusta biżżejjed f’ pazjenti li m’ għandhomx esperjenza ta ’ kura antiretrovirali biex isostni s- sistema ta ’ kura fosamprenavir ma ’ ritonavir darba kuljum. Għalhekk b’ mod konservattiv, ibbażat fuq livelli għolja ta ’ amprenavir Ctrough, kura ta ’ fosamprenavir b’ ritonavir li tingħata darbtejn kuljum hija rakkomandata għall- aħjar trattament terapewtiku f’ dan il- qasam ta ’ pazjenti (ara sezzjoni 4. 2).
In a subsequent randomised open-label study (ESS100732) in antiretroviral naïve patients, fosamprenavir (700 mg) co-administered with low dose ritonavir (100 mg) in a twice daily regimen including abacavir / lamivudine (600 mg / 300 mg) fixed dose combination tablet once daily showed comparable efficacy over 48 weeks to lopinavir / ritonavir (400 mg / 100 mg) given twice daily in combination with abacavir / lamivudine (600 mg / 300 mg once daily).
16 Fi studju randomised open label (ESS100732) f’ pazjenti li m’ għandhomx esperjenza ta ’ kura antiretrovirali, fosamprenavir (700mg) flimkien ma ’ doża baxxa ta ’ ritonavir (100mg) darbtejn kuljum flimkien ma ’ pillola b’ doża fissa ta ’ abacavir/ lamivudine (600mg/ 300mg) darba kuljum wriet fuq 48 ġimgħa effikaċja komparabbli ma ’ lopinavir/ ritonavir (400mg/ 100mg) darbtejn kuljum flimkien ma ’ abacavir/ lamivudine (600mg/ 300mg darba kuljum).
Non-inferiority was demonstrated between fosamprenavir co-administered with ritonavir and lopinavir / ritonavir based on the proportions of patients achieving plasma HIV-1 RNA levels < 400 copies/ ml at 48 weeks (primary endpoint).
Intweriet nuqqas ta ’ nferjorità bejn fosamprenavir flimkien ma ’ ritonavir u lopinavir/ ritonavir, ibbażat fuq il- proporzjon ta ’ pazjenti li jilħqu livelli ta ’ HIV- 1 RNA fil- plażma ta ’ < 400 kopji / ml fit- 48 ġimgħa (endpoint primarju).
In the Time to loss of virological response (TLOVR) analysis for the ITT(E) population, the proportion of patients achieving < 400 copies/ ml was 73% (315 / 434) in the fosamprenavir with ritonavir group compared to 71% (317 / 444) of patients receiving lopinavir / ritonavir, with a 95% confidence interval of the difference of [-4,84%; 7; 05%].
Fl- analiżi ta ’ Żmien u t- telfa ta ’ effett viroloġiku TLOVR) għall - popolazzjoni ITT( E), il- proporzjon ta ’ pazjenti fil- grupp ta ’ fosamprenavir ma ’ ritonavir li laħqu < 400 kopja/ ml kienet 73% (315/ 434) meta mqabbla ma ’ 71% (317/ 444) ta ’ pazjenti li ngħataw lopinavir/ ritonavir, b’ 95% intervall ta ’ kunfidenza tad- differenza ta ’ [- 4, 84%; 7; 05%].
The median plasma HIV-1 RNA had decreased by 3.34 log10 copies/ ml and 3.33 log10 copies/ ml at Week 48 in the fosamprenavir with ritonavir and lopinavir / ritonavir arms respectively.
Il- medja fil- plażma ta ’ HIV- 1 RNA kienet naqset b’ 3. 34 log10 kopji / ml u 3. 33 log10 kopji/ ml fit- 48 ġimgħa fil- gruppi fosamprenavir ma ’ ritonavir u lopinavir/ ritonavir rispettivament.
16 Median increase in CD4 cell count was 176 cells/ mm3 in the fosamprenavir with ritonavir arm and 191 cells/ mm3 in the lopinavir / ritonavir arm respectively by Week 48.
Żieda fil- medja fil- livell ta ’ ċelloli CD4 kien ta ’ 173 ċellola/ mm³ fil- grupp ta ’ fosamprenavir ma ’ ritonavir u 191 ċellola/ mm³ fil- grupp ta ’ lopinavir/ ritonavir rispettivament sat- 48 Ġimgħa.
Antiretroviral Experienced Adult Patients
Pazjenti Adulti b’ Esperjenza Antiretrovirali
In a randomised open-label study (APV30003) in protease inhibitor experienced patients with virological failure (less than or equal to two PIs) the fosamprenavir with ritonavir combination (700 / 100 mg twice daily or 1400 / 200 mg once daily) did not demonstrate non-inferiority to lopinavir / ritonavir with regard to viral suppression as measured by the average area under the curve minus baseline (AAUCMB) for plasma HIV-1 RNA over 48 weeks (the primary end point).
Fi studju open- label randomised (APV30003) fuq pazjenti li kelhom l- impeditur protease b’ falliment viroloġiku (inqas minn jew ugwali għal żewġ PIs) fosamprenavir flimkien ma ’ ritonavir (700/ 100 mg darbtejn kuljum jew 1400/ 200 mg darba kuljum) ma wrewx nuqqas ta ’ non- inferjorità għal lopinavir / ritonavir fir- rigward ta ’ soppressjoni virali kif imkejla mill- medja ta ’ l- erja ta ’ taħt il- kurva (AAUCMB) għal HIV- 1 RNA fil- plażma matul 48 ġimgħa (l- end- point primarju).
Results were in favour of the lopinavir / ritonavir arm as detailed below.
Ir- riżultat kien favur il- grupp ta ’ lopinavir / ritonavir kif dettaljat hawn taħt.
All patients in this study had failed treatment with a previous protease inhibitor regimen (defined as plasma HIV-1 RNA that never went below 1,000 copies/ ml after at least 12 consecutive weeks of therapy, or initial suppression of HIV-1 RNA which subsequently rebounded to ≥ 1,000 copies/ ml).
Il- kura b’ impeditur protease li ngħatat qabel (definita bħala HIV- 1 fil- plażma li qatt ma niżlet taħt l - 1000 kopji/ ml wara għall- inqas 12- il ġimgħa ta ’ terapija, jew soppressjoni inizjali ta ’ l- HIV- 1 RNA li wara reġgħet marret għal ≥1, 000 kopji/ ml) ma rnexxiet fl- ebda pazjent.
However, only 65% of patients were receiving a PI based regimen at study entry.
Madankollu, 65% biss ta ’ pazjenti kienu qegħdin jirċievu kura bbażata fuq PI meta bdew dan l- istudju.
The population enrolled mainly consisted of moderately antiretroviral experienced patients.
Il- grupp ta ’ pazjenti li ħadu sehem kien jikkonsisti primarjament minn pazjenti b’ esperjenza antiretrovirali moderata.
The median durations of prior exposure to NRTIs were 257 weeks for patients receiving fosamprenavir with ritonavir twice daily (79% had ≥ 3 prior NRTIs) and 210 weeks for patients receiving lopinavir/ ritonavir (64% had ≥ 3 prior NRTIs).
It- tul medjan ta ’ esponimenti ta ’ qabel għal NRTIs kien ta ’ 257 ġimgħa għal pazjenti li kienu jieħdu fosamprenavir b’ ritonavir darbtejn kuljum (79% ħadu ≥3 NRTIs minn qabel) u ta ’ 210 ġimgħa għal pazjenti li kienu jieħdu lopinavir/ ritonavir (64% ħadu ≥3 NRTIs minn qabel).
The median durations of prior exposure to protease inhibitors were 149 weeks for patients receiving fosamprenavir with ritonavir twice daily (49% received ≥ 2 prior PIs) and 130 weeks for patients receiving lopinavir/ ritonavir (40% received ≥ 2 prior PIs).
It- tul medjan ta ’ esponimenti ta ’ qabel għal impedituri protease kien ta ’ 149 ġimgħa għal pazjenti li kienu jieħdu fosamprenavir b’ ritonavir darbtejn kuljum (49% ħadu ≥2 PIs minn qabel) u ta ’ 130 ġimgħa għal pazjenti li kienu jieħdu lopinavir/ ritonavir (40% ħadu ≥ PIs minn qabel).
The mean AAUCMBs (log10 c/ ml) in the ITT (E) population (Observed analysis) at 48 weeks are described in the table below:
Il- medja ta ’ AAUCMBs (log10 c/ ml) fil- grupp ITT (E) (Analiżi osservata) wara 48 ġimgħa huma deskritti fit- tabella t’ hawn taħt:
Plasma HIV-1 RNA Average Area Under the Curve Minus Baseline (AAUCMB) Values (log10 copies/ ml) at week 48 by Randomisation Strata in APV30003 ITT (E) Population (Observed Analysis)
17 Plasma HIV- 1 RNA Il- Medja ta ’ l- Erja ta ’ Taħt il- Kurva bil- Linja Bażi Mnaqqsa (AAUCMB) Values (log10 copies/ ml) f’ ġimgħa 48 b’ Randomisation Strata f ’ APV30003 ITT (E) Popolazzjoni (Analiżi osservata)
Observed analysis Observed analysis FPV/ RTV BID LPV/ RTV BID
Analiżi osservata Analiżi osservata FPV/ RTV BID LPV/ RTV BID
Observed analysis Mean Diff.
Analiżi osservata Diff. medja
Plasma HIV-1 RNA stratum 1000 – 10,000
Plażma HIV- 1 RNA stratum 1000 – 10, 000 kopji/ ml > 10, 000 – 100, 000 kopji/ ml
N=107 N=103 Mean (n) Mean (n)
N=107 N=103 Medja (n) Medja (n) - 1. 43 (43) - 1. 53 (41) - 1. 81 (46) - 1. 59 (45)
(97.5% CI) FPV/ RTV BID vs LPV/ RTV BID
(97. 5% CI) FPV/ RTV BID vs LPV/ RTV BID - 0. 104 (- 0. 550, 0. 342) 0. 216 (- 0. 213, 0. 664)
copies/ ml > 10,000 – 100,000
> 100, 000 kopji/ ml
-1.53 (41) -1.43 (43)
- 2. 61 (14) - 1. 38 (19)
-0.104 (-0.550, 0.342)
1. 232 (0. 512, 1. 952)
-1.59 (45) -1.81 (46)
Popolazzjoni totali
-1.38 (19) -2.61 (14)
- 1. 53 (105)
1.232 (0.512, 1.952)
- 1. 76 (103)
Total population
0. 244
0.244 (-0.047, 0.536)
(- 0. 047, 0. 536) Spjegazzjoni:
FPV/ RTV BID – Fosamprenavir with ritonavir twice daily, LPV/ RTV BID – Lopinavir / ritonavir twice daily
FPV/ RTV BID – Fosamprenavir b’ ritonavir darbtejn kuljum, LPV/ RTV BID – Lopinavir/ ritonavir darbtejn kuljum
58% versus 61% (plasma HIV-1 RNA < 400 copies/ ml) or 46% versus 50% (plasma HIV-1 RNA < 50 copies/ ml) at Week 48 (secondary efficacy endpoint) in the intent to treat (RD=F) analysis.
Meta tikkonsidra l- proporzjon ta ’ pazjenti b’ viral load li ma tistax tiġi osservata fuq kura b’ fosamprenavir ma ’ ritonavir darbtejn kuljum u dawk fuq lopinavir / ritonavir rispettivament, ir - riżultati kienu favur il- gruppi ta ’ lopinavir / ritonavir; 58% kontra 61% (plażma HIV- 1 RNA < 400 kopji/ ml) jew 46% kontra 50% (plażma HIV- 1 RNA < 50 kopji/ ml fil- Ġimgħa 48 (endpoint sekondarju ta ’ effikaċja) fl- analiżi intent to treat (RD=F).
17 In patients with high viral load at baseline (> 100,000 copies/ ml) 7/ 14 (50%) patients in the lopinavir / ritonavir group and 6/ 19 (32%) patients in the fosamprenavir with ritonavir group had plasma HIV-1 RNA < 400 copies/ ml.
F’ pazjenti b’ viral load għoli fil- linja bażi (> 100, 000 kopji/ ml) 7/ 14 (50%) ta ’ pazjenti fil- grupp ta ’ lopinavir / ritonavir u 6/ 19 (32%) ta ’ pazjenti fil- grupp ta ’ fosamprenavir b’ ritonavir kellhom plażma HIV- 1 RNA < 400 kopji/ ml.
The fosamprenavir with ritonavir twice daily regimen and the lopinavir / ritonavir twice daily regimen showed similar immunological improvements through 48 weeks of treatment as measured by median change from baseline in CD4 + cell count (fosamprenavir with ritonavir twice daily:
Il- kura b’ fosamprenavir ma ’ ritonavir darbtejn kuljum u dik ta ’ lopinavir/ ritonavir darbtejn kuljum it - tnejn urew l- istess titjib immunoloġiku matul l- 48 ġimgħa ta ’ terapija kif imkejjla b’ tibdil medjan mill - linja bażi ta ’ l- għadd ta ’ ċelluli CD4+ (fosamprenavir b’ ritonavir darbtejn kuljum:
81 cells/ mm3: lopinavir / ritonavir twice daily:
81 ċelluli/ mm3: lopinavir/ ritonavir darbtejn kuljum:
91 cells/ mm3).
91 ċelluli/ mm3).
There are insufficient data to recommend the use of fosamprenavir with ritonavir in heavily pre-treated patients.
M’ hemmx tagħrif biżżejjed biex ikun jista ’ jiġi rakkomandat l- użu ta ’ fosamprenavir b’ ritonavir f’ pazjenti li kienu diġà fuq kura qawwija fil- passat.
Children and adolescent patients above the age of six
Pazjenti tfal u adolexxenti ta ’ età il- fuq minn 6 snin
Fosamprenavir tablets and oral suspension with ritonavir in combination with NRTIs have been evaluated in protease inhibitor naïve and experienced children and adolescent patients.
Il- pilloli u s- sospensjoni orali ta ’ fosamprenavir ma ’ ritonavir flimkien ma ’ NRTI kienu evalwati f’ pazjenti tfal u adolexxenti li kienu ħadu kura u li qatt ma kienu ħadu kura ta ’ inibitur tal- protease.
The benefit in this age group has mainly been derived from the ongoing study, APV29005, an open label 48 week study evaluating the pharmacokinetic profiles, safety, and antiviral activity of fosamprenavir with ritonavir administered twice daily to HIV 1 protease inhibitor experienced and naive patients 2 to 18 years of age.
Il- benefiċċju f’ dan il- grupp ħareġ primarjament minn studju li għaddej bħalissa, APV29005, studju open label ta ’ 48 ġimgħa li jevalwa il- profili farmakokinetiċi, ta ’ sigurtà, u attività antivirali ta ’ fosamprenavir ma ’ ritonavir li ingħataw darbtejn kuljum lil pazjenti ta ’ bejn is- 2 u t- 18 il- sena bi u mingħajr esperjenza ta ’ inibitur tal- protease.
Results through 24 weeks of treatment are provided below.
Ir- riżultati fuq 24 ġimgħa ta ’ kura huma pprovduti hawn taħt.
APV29005 enrolled 25 patients aged 6 to 11 (the majority of whom were treated with fosamprenavir / ritonavir 18/ 3 mg/ kg twice daily or the adult tablet regimen), and 29 patients aged 12 to 18 (the majority of whom were treated with the adult tablet regimen).
APV29005 irreġistra 25 pazjent bejn is- 6 u l- 11 il- sena (li l- maġġoranza tagħhom ġew trattati b’ fosamprenavir/ ritonavir 18/ 3mg/ kg darbtejn kuljum jew bis- sistema ta ’ kura ta’ pilloli ta ’ l- adulti) u 29 pazjent bejn it- 12 u t- 18 il- sena (li l- maġġoranza tagħhom ġew trattati b’ sistema ta ’ kura ta ’ pilloli ta ’ l- adulti).
Overall, 27 (50%) were PI-naïve, 9 of whom were ART naïve, and 27 (50%) were PI-experienced.
Kollox ma 'kollox, 27 (50%) qatt ma ingħataw PI, li 9 minnhom kienu mingħajr esperjenza ART, u 27 (50%) li kienu ingħataw PI.
Prior NRTI exposure was extensive, with median durations of 421 and 389 weeks for the PI naïve and experienced patients respectively.
L- espożizzjoni minn qabel għal NRTI kienet estensiva, b’ medja ta ’ tul ta ’ 421 ġimgħa u 389 ġimgħa għall- pazjenti li kienu ħadu kura u li qatt ma
The median duration of prior PI exposure was 239 weeks.
It- tul medju ta ’ espożizzjoni minn qabel ta ’ PI kienet ta ’ 239 ġimgħa.
Overall, patients enrolled with a median 4.6 HIV-1 RNA log10 copies/ ml (33% of whom had > 100,000 copies/ ml at baseline) and a median% CD4+ cell of 18% (37% of whom had% CD4+ of < 15% at baseline).
Kollox ma 'kollox, pazjenti irreġistrati b’ medja ta’ 4. 6 kopji/ ml ta' HIV- 1 RNA log 10 (fejn 33% minnhom kellhom > 100, 000 kopji/ ml fil- linja ta ’ bażi) u% medja ta ’ ċelluli CD4+ ta ’ 18% (37% minnhom kellhom% CD4+ ta ‘ < 15% fil- linja bażi.
Through 24 weeks of therapy, 70% (19/ 27) of protease inhibitor naive and 56% (15/ 27) of protease inhibitor experienced patients achieved and maintained a plasma HIV 1 RNA < 400 copies/ ml (ITT(E), TLOVR).
Matul 24 gimgħa ta ’ kura, 70% (19/ 27) ta 'pazjenti mingħajr esperjenza ta ’ inibitur tal- protease u 56% (15/ 27) ta ’ pazjenti b’ esperjenza ta ’ inibitur tal- protease, waslu sa u żammew HIV- 1 RNA fil- plażma ta ’ < 400 kopja/ ml (ITT( E), TLOVR).
In the ITT(E) population (Observed analysis) at Week 24 the median% CD4+ cell counts increased by 8% in the PI-naïve subjects and 4% in the PI-experienced subjects.
Fil- popolazzjoni ITT( E) (Analiżi osservata) f’ Ġimgħa 24 il -% medja ta 'l- għadd ta ’ ċelluli CD4+ żdiedet bi 8% f’ suġġetti mingħajr esperjenza PI u 5% f’ suġġetti b’ esperjenza PI.
These data were further substantiated by the supportive study APV20003; however, a different dosage regimen than that of study APV29005 was used.
Din l- informazzjoni kienet aktar sostanzjata mill- istudju ta ’ sapport APV20003; madankollu kienet użata sistema ta ’ dożaġġ differenti minn dik ta ’ l- istudju APV29005.
After oral administration, fosamprenavir is rapidly and almost completely hydrolysed to amprenavir and inorganic phosphate prior to reaching the systemic circulation.
Wara li jingħata mill- ħalq, fosamprenavir jiġi idrolizzat malajr u kważi kompletament f’ amprenavir u fosfat inorganiku qabel ma jasal fiċ- ċirkolazzjoni sistemika.
The conversion of fosamprenavir to amprenavir appears to primarily occur in the gut epithelium.
Il- konverżjoni ta ’ fosamprenavir għal amprenavir tidher li sseħħ primarjament fl- epitilju ta ’ l- intestin.
The pharmacokinetic properties of amprenavir following co-administration of Telzir with ritonavir have been evaluated in healthy adult subjects and HIV-infected patients and no substantial differences were observed between these two groups.
Il- kwalitajiet farmakokinetiċi ta ’ amprenavir wara li jkun ingħata flimkien ma ’ Telzir b’ ritonavir ġew valutati f’ persuni adulti b’ saħħithom u f’ pazjenti bl- infezzjoni HIV u l- ebda differenzi sostanzjali ma ’ ġew osservati bejn dawn iż- żewġ gruppi.
Telzir tablet and oral suspension formulations, both given fasted, delivered equivalent plasma amprenavir AUC∞ values and the Telzir oral suspension formulation delivered a 14% higher plasma amprenavir Cmax as compared to the oral tablet formulation.
Il- formulazzjonijiet ta ’ pilloli u sospensjoni orali Telzir, meħudin waqt sawma, ipproduċew valuri ekwivalenti ta ’ AUC∞ ta ’ amprenavir fil- plażma u l- formulazzjoni ta ’ sospensjoni orali ta ’ Telzir ipproduċiet 14% aktar ta ’ Cmax ta ’ amprenavir fil- plażma meta mqabbla mal- formulazzjoni ta ’ pillola mill- ħalq.
18 After single dose administration of fosamprenavir, amprenavir peak plasma concentrations are observed approximately 2 hours after administration.
Wara li tittieħed doża waħda ta ’ fosamprenavir, l- ogħla konċentrazzjonijiet ta ’ amprenavir fil- plażma iseħħu wara xi sagħtejn li tingħata.
Fosamprenavir AUC values are, in general, less than 1% of those observed for amprenavir.
Il- valuri AUC ta ’ fosamprenavir ġeneralment huma inqas minn 1% ta ’ dawk osservati minn amprenavir.
The absolute bioavailability of fosamprenavir in humans has not been established.
Il- bijodisponibiltà assoluta ta ’ fosamprenavir fil- bniedem għad ma ġietx stabbilita.
After multiple dose oral administration of equivalent fosamprenavir and amprenavir doses, comparable amprenavir AUC values were observed; however, Cmax values were approximately 30% lower and Cmin values were approximately 28% higher with fosamprenavir.
Wara t- teħid mill- ħalq ta ’ dożi multipli ekwivalenti ta ’ fosamprenavir u amprenavir, ġew osservati valuri komparabbli ta ’ AUC ta’ amprenavir; madankollu, il- valuri Cmax kienu madwar 30% aktar baxxi u l- valuri Cmin kienu madwar 28% ogħla b’ fosamprenavir.
After multiple dose oral administration of fosamprenavir 700 mg with ritonavir 100 mg twice daily, amprenavir was rapidly absorbed with a geometric mean (95% CI) steady state peak plasma amprenavir concentration (Cmax) of 6.08 (5.38-6.86) µg/ ml occurring approximately 1.5 (0.75-5.0) hours after dosing (tmax).
Wara t- teħid mill- ħalq ta ’ dożi multipli ta ’ 700 mg fosamprenavir ma ’ 100 mg ritonavir darbtejn kuljum, amprenavir ġie assorbit malajr ma ’ l- ogħla konċentrazzjoni (Cmax) ta ’ medja ġeometrika (95% CI) fl- istat fiss ta ’ amprenavir fil- plażma ta ’ 6. 08( 5. 38- 6. 86) μg/ ml li jkun hemm madwar 1. 5 (0. 75 - 5. 0) sigħat wara t- teħid tad- doża (tmax).
The mean steady state plasma amprenavir trough concentration (Cmin) was 2.12 (1.77-2.54) µg/ ml and AUC0-tau was 39.6 (34.5– 45.3) h*µg/ ml.
Il- konċentrazzjoni medja fl- istat fiss ta ’ amprenavir fil- plażma fl- aktar livell baxx kienet 2. 12 (1. 77- 2. 54) μg/ ml u AUC0- tau kienet 39. 6 (34. 5- 45. 3) h* μg/ ml.
Administration of the fosamprenavir tablet formulation in the fed state (standardised high fat meal:
It- teħid ta ’ amprenavir fil- formolazzjoni ta ’ pillola fi stat mitmugħ (ikla standardised b' ħafna xaħam:
967 kcal, 67 grams fat, 33 grams protein, 58 grams carbohydrate) did not alter plasma amprenavir pharmacokinetics (Cmax, tmax or AUC0- ∞) compared to the administration of this formulation in the fasted state.
967 kcal, 67 gramma ta ’ xaħam, 33 gramma proteina, 58 gramma karboidrati) ma ’ bidilx il - farmakokinetiċi ta ’ amprenavir fil- plażma (Cmax, Tmax jew AUC0- ∞) meta mqabbel ma ’ t- teħid ta ’ din il- formolazzjoni fi stat sajjem.
Telzir tablets may be taken without regard to food intake.
Il- pilloli Telzir jistgħu jittieħdu bla konsiderazzjoni għall- ikel.
Co-administration of amprenavir with grapefruit juice was not associated with clinically significant changes in plasma amprenavir pharmacokinetics.
It- teħid ta ’ amprenavir ma ’ meraq tal- grejpfrut ma ġiex assoċjat ma ’ xi tibdil kliniku sostanzjali fil - farmakokinetiċi ta ’ amprenavir fil- plażma.
Distribution
19 Distribuzzjoni
The apparent volume of distribution of amprenavir following administration of Telzir is approximately 430 l (6 l/ kg assuming a 70 kg body weight), suggesting a large volume of distribution, with penetration of amprenavir freely into tissues beyond the systemic circulation.
Jidher li l- volum tad- distribuzzjoni ta ’ amprenavir wara li jittieħed Telzir, huwa ta ’ madwar 430 1( 6 1/ kg jekk tieħu piż ta ’ ġisem ta ’ 70 kg), li jissuġġerixxi li l- volum tad- distribuzzjoni huwa kbir, b’ amprenavir jippenetra liberament fit- tessuti tal- ġisem lil hinn sewwa miċ- cirkolazzjoni sistemika.
This value is decreased by approximately 40% when Telzir is co-administered with ritonavir, most likely due to an increase in amprenavir bioavailability.
Dan il- valur jonqos b’ madwar 40% meta Telzir jingħata flimkien ma ’ ritonavir, x’ aktarx minħabba żieda fil- bijodisponibiltà ta ’ amprenavir.
In in vitro studies, the protein binding of amprenavir is approximately 90%.
Fi studji in vitro, il- kwantità ta ’ amprenavir li teħel mal- proteini hija ta ’ madwar 90%.
It is bound to the alpha-1- acid glycoprotein (AAG) and albumin, but has a higher affinity for AAG.
Din tkun imwaħħla l- biċċa l- kbira ma ’ l- alpha- 1- acid glycoprotein (AAG) u ma ’ l- albumina, iżda għandha iżjed affinità għal AAG.
Concentrations of AAG have been shown to decrease during the course of antiretroviral therapy.
Ġie muri li l- konċentrazzjoni ta ’ AAG naqset waqt kura b’ mediċini antiretrovirali.
This change will decrease the total active substance concentration in the plasma, however the amount of unbound amprenavir, which is the active moiety, is likely to be unchanged.
Dan it- tibdil iġib miegħu tnaqqis fil- konċentrazzjoni totali tas- sustanza attiva fil - plażma, iżda x’ aktarx li l- kwantità ta ’ amprenavir mhux imwaħħal, li hija l- parti attiva, ma tinbidilx.
CSF penetration of amprenavir is negligible in humans.
Il- penetrazzjoni ta ’ amprenavir fis- CSF fil- bniedem hi ftit li xejn.
Amprenavir appears to penetrate into semen, though semen concentrations are lower than plasma concentrations.
Jidher li amprenavir jidħol fis - semen, għalkemm il- konċentrazzjonijiet fis- semen huma inqas mill- konċentrazzjonijiet fil- plażma.
Fosamprenavir is rapidly and almost completely hydrolysed to amprenavir and inorganic phosphate as it is absorbed through the gut epithelium, following oral administration.
Fosamprenavir jiġi idrolizzat malajr u kważi kompletament f’ amprenavir u fosfat inorganiku waqt li jkun qed jiġi assorbit mill- epitelju ta ’ l- intestin, wara li jittieħed mill- ħalq.
Amprenavir is primarily metabolised by the liver with less than 1% excreted unchanged in the urine.
Amprenavir hu primarjament metabolizzat mill- fwied b’ inqas minn 1% jitneħħa bla ma ’ jinbidel fl- awrina.
The primary route of metabolism is via the cytochrome P450 3A4 enzyme.
Ir- rotta ewlenija tal- metaboliżmu hi permezz ta ’ l- enzima ċitokromju P450 3A4.
Amprenavir metabolism is inhibited by ritonavir, via inhibition of CYP3A4, resulting in increased plasma concentrations of amprenavir.
Il- metaboliżmu ta ’ amprenavir hu impedit b’ ritonavir, permezz ta ’ l- impeditur CYP3A4, u dan jirriżulta f’ konċentrazzjonijiet ogħla ta ’ amprenavir fil- plażma.
Amprenavir in addition is also an inhibitor of the CYP3A4 enzyme, although to a lesser extent than ritonavir.
Barra minn hekk amprenavir huwa wkoll impeditur għall- enzima CYP3A4, għalkemm inqas minn ritonavir.
Therefore medicinal products that are inducers, inhibitors or substrates of CYP3A4 must be used with caution when administered concurrently with Telzir with ritonavir (see sections 4.3 and 4.5).
Għalhekk prodotti mediċinali li huma indjusers, jew huma impedituri jew substrati ta ’ CYP3A4 għandhom jintużaw b’ prekawzjoni meta jingħataw flimkien ma ’ Telzir b’ ritonavir (ara t- taqsimiet 4. 3 u 4. 5)
Following administration of Telzir, the half-life of amprenavir is 7.7 hours.
Wara li jingħata Telzir, il- half- life ta ’ amprenavir hi ta ’ 7. 7 sigħat.
When Telzir is co-administered with ritonavir, the half-life of amprenavir is increased to 15 – 23 hours.
Meta Telzir jingħata flimkien ma ’ ritonavir, il- half- life ta ’ amprenavir tiżdied għal 15 – 23- il siegħa.
19 The primary route of elimination of amprenavir is via hepatic metabolism with less than 1% excreted unchanged in the urine and no detectable amprenavir in faeces.
Ir- rotta ewlenija ta ’ mnejn jiġi eliminat amprenavir hi permezz ta ’ metaboliżmu fil- fwied u l- ammont mhux metabolizzat li jispiċċa fl- awrina huwa ta ’ inqas minn 1% u fil- purgar ma jkun hemm kważi xejn.
Metabolites account for approximately 14% of the administered amprenavir dose in the urine, and approximately 75% in the faeces.
Il- metaboliti fl- awrina jagħmlu tajjeb għal madwar 14% tad- doża ta ’ amprenavir li tkun ingħatat, u għal madwar 75% fil - purgar.
In a clinical study on pharmacokinetics of fosamprenavir in paediatric patients, eight subjects 12 to 18 years of age received the standard fosamprenavir adult tablet dose of 700 mg twice daily (with ritonavir 100 mg twice daily).
Fi studju kliniku fuq il- farmakokinetika ta ’ fosamprenavir f’ pazjenti pedjatriċi, 8 suġġetti minn 12 sa 18 il- sena irċevew id- doża standard għall- kbar ta ’ 700mg darbtejn kuljum għal pilloli ta ’ fosamprenavir (ma ’ ritonavir 100mg darbtejn kuljum).
Compared to the historical adult population receiving fosamprenavir / ritonavir 700 / 100 mg twice daily, 12 to 18 year old subjects had 20% lower plasma APV AUC(0- 24), 23% lower Cmax, and 20% lower Cmin values.
Meta mqabbla ma ’ popolazzjoni adulta li fil - passat kienet qed tieħu fosamprenavir / ritonavir 700mg / 100mg darbtejn kuljum, suġġetti ta ’ bejn it - 12 u t- 18 il- sena kellhom valuri ta ’ AUC ta ’ APV aktar baxx fil- plażma b’ 20% (0- 24), Cmax aktar baxx bi 23% u Cmin aktar baxx b’ 20%.
Children 6 to 11 years of age (n=9) receiving fosamprenavir / ritonavir 18 / 3 mg/ kg twice daily had 26% higher AUC(0-24) and similar Cmax and Cmin values when compared to the historical adult population receiving fosamprenavir / ritonavir 700 / 100 mg twice daily.
Tfal ta ’ bejn is- 6 u l- 11 il- sena (n=9) li kienu qed jieħdu fosamprenavir / ritonavir 18 / 3 mg/ kg darbtejn kuljum kellhom valuri ta ’ AUC (0- 24) aktar għolja b’ 26% u valuri simili għal Cmax u Cmin meta mqabbla ma ’ popolazzjoni adulta li fil- passat kienet qed tieħu fosamprenavir / ritonavir 700 / 100 mg darbtejn kuljum.
APV20002 is a 48 week, Phase II, open label study designed to evaluate the pharmacokinetics, safety, tolerability and antiviral activity of fosamprenavir with and without ritonavir in paediatric subjects 4 weeks to < 2 years of age.
APV20002 huwa studju open label, Fażi II ta ’ 48 ġimgħa iddisinjat biex jevalwa il- farmakokinetika, sigurtà, tolleranza u attività antivirali ta ’ fosamprenavir bi jew mingħajr ritonavir f’ suġġetti pedjatriċi minn 4 ġimgħat sa < sentejn.