qanastek/EMEA-V3 huggingface dataset:
9 Fluticasone propionate (interaction with ritonavir): 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%).
Fluticasone propionate (effett ma ’ ritonavir): fi studju kliniku fejn kapsuli ta ’ ritonavir 100mg darbtejn kuljum ingħataw ma ’ fluticasone propionate 50μg erba ’ darbiet kuljum fl- imnieħer għal 7 ijiem f’ suġġetti b’ saħħithom, il- livelli ta ’ fluticasone propionate fil- plażma żdiedu b’ mod sinifikanti, filwaqt li l- livelli intrinsiċi ta ’ cortisol naqqsu bejn wieħed u ieħor bi 86% (90% confidence interval 82- 89%).
Greater effects may be expected when fluticasone propionate is inhaled.
Wieħed jistenna effetti akbar meta l- fluticasone propionate jinġibed ġol- pulmun.
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 e. g. budesonide.
Effetti sistemiċi tal- kortikosterojdi bħas- sindromu ta ’ Cushing u trażżin tal- glandola adrenali ġew irrapurtati f’ pazjenti li kienu fuq ritonavir u fluticasone propionate li inġibed ġol- pulmun jew ittieħed mill - imnieħer; dan jista ’ jiġri wkoll b’ kortikosterojdi oħra li jiġu mmetaboliżżati mir- rotta P450 3A eż. budesonide.
Consequently, concomitant administration of Agenerase 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).
Għal din ir- raġuni, m’ huwiex rakkommandat li Telzir ma ’ ritonavir jingħata ma ’ dawn il - glukokortikojdi sakemm il- benefiċċji ta ’ dan it- trattament jkun akbar mir- riskju ta ’ l- effetti sistemiċi tal- kortikosterojdi (ara sezzjoni 4. 4).
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).
Għandha tiġi kkunsidrata tnaqqis fid- doża tal- glukokortikojde waqt li tingħata prekawzjoni mill- viċin għal xi effetti lokali jew sistemiċi, jew li taqleb ghal glukokortikojde ieħor li mhux substrat ta ’ CYP3A4 (eż. beclomethasone).
Moreover, in case of withdrawal of glucocorticoids progressive dose reduction may have to be performed over a longer period.
Fil- każ li jitwaqqfu l - glukokortikojdi, hemm mnejn ikun hemm bzonn tnaqqis fid- doża bil- mod fuq perjodu itwal ta ’ żmien.
The effects of high fluticasone systemic exposure on ritonavir plasma levels is yet unknown.
L- effetti ta ’ dożi għolja ta ’ fluticasone fid- demm fuq il- livelli ta ’ ritonavir fil- plazma għadhom m’ humiex magħrufa.
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 Agenerase.
Mediċini li jinibixxu HMG- CoA reductase: dawk il- mediċini li jinibixxu HMG- CoA reductase u li l - parti kbira tagħhom tiġi metabolizzata permezz ta ’ CYP3A4, bħal lovastatin u simvastatin, huma mistennija li jkollhom żieda sostanzjali fil- konċentrazzjoni tagħhom fil- plażma meta jingħataw flimkien ma ’ Agenerase.
Since increased concentrations of HMG-CoA reductase inhibitors may cause myopathy, including rhabdomyolysis, the combination of these medicinal products with Agenerase is not recommended.
Minħabba li żieda fil- koncentrazzjoni fil- plażma ta ’ dawn il- mediċini tistà twassal għal mijopatija, inkluż rhabdomyolysis, huwa rakkomandat li dawn il- mediċini ma ’ jintużawx flimkien ma ’ Agenerase.
Atorvastatin is less dependent on CYP3A4 for metabolism.
Atorvastatin jiddependi inqas fuq CYP3A4 sabiex ikun metabolizzat.
When used with Agenerase, the lowest possible dose of atorvastatin should be administered.
Meta jingħata flimkien ma ’ Agenerase għandha tintuża l- aktar doża baxxa possibbli.
The metabolism of pravastatin and fluvastatin is not dependent on CYP3A4, and interactions are not expected with protease inhibitors.
Il- metaboliżmu ta ’ pravastatin u fluvastatin ma jiddependix fuq CYP3A4 u għalhekk wieħed ma jistenniex li jkun hemm problemi meta jintużaw ma ’ inibituri protease.
If treatment with a HMG-CoA reductase inhibitor is indicated, pravastatin or fluvastatin is recommended.
B’ hekk meta jkun hemm bżonn ta ’ terapija permezz ta ’ dawn il- mediċini li jinibixxu HMG- CoA reductase, wieħed għandu juża jew pravastatin jew fluvastatin.
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 amprenavir (see section 4.4).
10 konċentrazzjonijiet ta ’ cyclosporin, rapamycin u tacrolimus fil- plażma jistgħu jiżdiedu meta jingħataw flimkien ma ’ ampenavir (ara sezzjoni 4. 4).
Midazolam: midazolam is extensively metabolized by CYP3A4.
Midazolam jiġi mmetaboliżżat b’ mod estensiv minn CYP3A4.
Coadministration with Agenerase with or without ritonavir may cause a large increase in the concentration of this benzodiazepine.
L- użu flimkien ma ’ Agenerase bi jew mingħajr ritonavir jista ’ jwassal għal żieda kbira fil- livell ta ’ dan il- benzodiazipine.
No drug interaction study has been performed for the co-administration of Agenerase with benzodiazepines.
Ma sar l- ebda studju dwar interazzjoni ta ’ mediċina għal għoti flimkien ta ’ Agenerase ma ’ benzodiazipines.
Based on data for other CYP3A4 inhibitors, plasma concentrations of midazolam are expected to be significantly higher when midazolam is given orally.
Skond informazzjoni minn inibituri oħra ta ’ CYP3A4, konċentrazzjonijiet ta ’ midazolam fil- plażma huma mistennija li jkunu ħafna aktar ogħla meta midazolam jingħata mill- ħalq.
Therefore Agenerase should not be co-administered with orally administered midazolam (see section 4.3), whereas caution should be used with co-administration of Agenerase and parenteral midazolam.
Għal dan il- għan Agenerase m’ għandux jingħata flimkien ma ’ midazolam meta dan jingħata mill- ħalq (ara sezzjoni 4. 3), u għandu jkun hemm kawtela meta Agenerase u midazolam mill- vina jingħataw flimkien.
Data from concomitant use of parenteral midazolam with other protease inhibitors suggest a possible 3-4 fold increase in midazolam plasma levels.
Informazzjoni mill- użu flimkien ta ’ midazolam mill- vina u inibituri oħra ta ’ protease juru possibilita ’ ta ’ żieda ta ’ 3- 4 darbiet aktar fil- livelli ta ’ midazolam fil- plażma.
If Agenerase with or without 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.
Jekk Agenerase bi jew mingħajr ritonavir jingħata flimkien ma ’ midazolam fil- vina, dan għandu jsir taħt kura intensiva jew x’ imkien ieħor simili li jiżgura li jkun hemm osservazzjoni klinika mill- viċin u mmaniġġar mediku kif għandu jkun f' każ ta ’ dipressjoni respiratorja u/ jew sedazzjoni fit- tul.
Dosage adjustment for midazolam should be considered, especially if more than a single dose of midazolam is administered.
Għandu jiġi kkunsidrat aġġustament fid- doża ta’ midazolam, speċjalment tingħata aktar minn doża waħda.
Methadone and opiate derivatives: co-administration of methadone with amprenavir resulted in a decrease in the Cmax and AUC of the active methadone enantiomer (R-enantiomer) of 25% and 13% respectively, whilst the Cmax, AUC and Cmin of the inactive methadone enantiomer (S-enantiomer) were decreased by 48%, 40% and 23% respectively.
Methadone u derivati opiate: meta ġie mogħti methadone flimkien ma ’ amprenavir kien hemm nuqqas fis- Cmax u AUC ta ’ l- active methadone enantiomer (R- enantiomer) ta ’ 25% u 13% rispettivament, filwaqt li Cmax, AUC u Cmin ta ’ l- inactive methadone enantiomer (S- enantiomer) naqsu b’ 48%, b’ 40% u bi 23% rispettivament.
When methadone is co-administered with amprenavir, patients should be monitored for opiate abstinence syndrome, in particular if low-dose ritonavir is also given.
Meta methadone jingħata flimkien ma’ amprenavir, il- pazjenti għandhom jiġu osservati għas- sindromu ta ’ astinenza mill opiate, speċjalment jekk tkun ingħatat doża baxxa ta ’ ritonavir.
As compared to a non-matched historical control group, co-administration of methadone and amprenavir resulted in a 30%, 27% and 25% decrease in serum amprenavir AUC, Cmax and Cmin respectively.
F’ paragun ma ’ grupp ta ’ kontroll storiku mhux imqabbel, kien hemm tnaqqis ta ’ 30%, 27% u 25% fl - AUC, Cmax u Cmin ta ’ amprenavir fis- serum, meta dan ġie mogħti flimkien ma ’ methadone.
No recommendations can currently be made regarding adjustment of amprenavir dose when amprenavir is co-administered with methadone due to the inherent low reliability of non- matched historical controls.
Bħalissa ma tistà tingħata l- ebda rakkomandazzjoni dwar tibdil fid- doża ta ’ amprenavir, meta dan jiġi mogħti flimkien ma ’ methadone, minħabba l- fatt li gruppi ta ’ kontrolli storiċi mhux mqabbla m’ humiex ta ’ min joqgħod fuqhom.
10 Oral anticoagulants: a reinforced monitoring of the International Normalised Ratio is recommended in case of administration of Agenerase with warfarin or other oral anticoagulants, due to a possible decrease or increase of their antithrombotic effect (see section 4.4).
Anti- koagulanti orali: monitoraġġ rinfurzat tal- Proporzjon Internazzjonali Normalizzat hu rakkomandat f’ każi ta ’ l- għoti ta ’ Agenerase ma ’ warfarin jew xi anti- koagulanti oħra, minħabba l - possibiltà ta ’ xi tnaqqis jew żieda ta ’ l- effett anti- trombotiku tagħhom (ara sezzjoni 4. 4).
Steroids: oestrogens and progestogens may interact with amprenavir.
Sterojdi: oestrogens u progestogens jistgħu ma jkunux jaqblu ma ’ amprenavir.
However, the information currently available is not sufficient for determining the nature of the interaction.
Iżda it- tagħrif miġbur s’ issa m’ hux biżżejjed biex wieħed jiddetermina kif dan jistà jseħħ.
Co-administration of 0.035 mg ethinyl estradiol plus 1.0 mg norethindrone resulted in a decrease of the amprenavir AUC and Cmin of 22% and 20% respectively, Cmax being unchanged.
Meta 0. 035 mg ethinyl estradiol u 1. 0 mg norethindrone ġew mogħtija ma ’ amprenavir, kien hemm nuqqas fl- AUC u Cmin ta ’ amprenavir ta ’ 22% u 20% rispettivament, filwaqt li Cmax baqà l- istess.
The Cmin of ethinyl estradiol was increased by 32%, whilst the AUC and Cmin of norethindrone were increased by 18% and 45% respectively.
Cmin ta ’ ethinyl estradiol żdied b’ 32%, filwaqt li l- AUC u Cmin ta ’ norethindrone żdiedu b’ 18% u 45% rispettivament.
Alternative methods of contraception are recommended for women of childbearing potential.
Wieħed għandu juża forom oħra ta ’ kontraċezzjoni f’ nisa li għad jistà jkollhom it- tfal.
When ritonavir is co-administered, the effect on hormonal contraceptive concentrations cannot be predicted, therefore, alternative methods of contraception are also recommended.
Meta jingħata wkoll ritonavir, l- effett li jistà jkollu fuq il- konċentrazzjoni ta ’ dawn il- kontraċettivi ma jistax jiġi mbassar u għalhekk huwa għaqli li tintuża forma oħra ta ’ kontracezzjoni.
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 Agenerase (see section 4.4).
Antidepressanti triċikliċi: monitoraġġ tajjeb ta ’ l- effetti terapewtiċi u l- effetti avversi ta ’ antidepressanti triċikliċi hu rakkomandat meta dawn (per eżempju desipramine u nortriptyline) jingħataw flimkien ma ’ Agenerase (ara sezzjoni 4. 4).
Other substances: plasma concentrations of other substances may be increased by amprenavir.
Sustanzi oħra: amprenavir jista jgħolli l- konċentrazzjoni fil- plażma ta ’ sustanzi oħra.
These include substances such as: clozapine, cimetidine, dapsone and loratadine.
Dawn is- sustanzi jinkludu: clozapine, carbamazepine, cimetidine, dapsone, itraconazole u loratadine.
Some substances (e. g. lidocaine (by systemic route) and halofantrine) given with Agenerase may cause serious adverse reactions.
Xi sustanzi (eż lidocaine (mill- vina) u halofantrine) meta jingħataw ma ’ Agenerase jista ’ jikkawżaw reazzjonijiet avversi serji.
Concomitant use is not recommended (see section 4.4).
L- użu flimkien m’ huwiex rakkomandat (ara sezzjoni 4. 4).
Pregnancy: there are no adequate data from the use of amprenavir in pregnant women.
Tqala: ma hemmx informazzjoni biżżejjed fuq l- użu ta ’ amprenavir f’ nisa tqal.
Studies in animals have shown reproductive toxicity (see section 5.3).
(ara sezzjoni 5. 3).
The potential risk for humans is unknown.
M’ huwiex magħruf ir- riskju potenzjali fil- bniedem.
This medicinal product should be used during pregnancy only after careful weighing of the potential benefits compared to the potential risk to the foetus.
11 Din il- mediċina għandha tintuża biss fit- tqala wara li jiġu meqjusa bir- reqqa l- vantaġġi u r- riskji li jistà jkun hemm għall- fetu.
Lactation: amprenavir-related material was found in rat milk, but it is not known whether amprenavir is excreted in human milk.
Treddigħ: sustanzi relatati ma ’ amprenavir ġew misjuba fil- ħalib tal- ġrieden, iżda mhux magħruf jekk amprenavir joħroġx fil- ħalib tal- omm.
A reproduction study in pregnant rats dosed from the time of uterine implantation through lactation showed reduced body weight gains in the offspring during the nursing period.
Studju dwar ir- riproduzzjoni fi ġrieden tqal, li ġew mogħtija amprenavir mill- waqt ta ’ xħin il- bajda fertilizzata weħlet mal- ħajt tal- ġuf sa żmien it- treddigħ, wera li kien hemm tnaqqis fiż- żieda fil- piż tal- frieħ.
The systemic exposure to the dams associated with this finding was similar to exposure in humans, following administration of the recommended dose.
Id- doża fid- demm tal- ommijiet ġrieden f’ dan l- istudju kienet ekwivalenti għal dik li tintlaħaq fil- bniedem wara li tingħata doża normali.
The subsequent development of the offspring, including fertility and reproductive performance, was not affected by the maternal administration of amprenavir.
L- iżvilupp tal- frieħ, inkluż il- fertilità u l- ħila riproduttiva, ma ġiex affetwat mill- użu ta ’ amprenavir fl- omm.
It is therefore recommended that mothers being treated with Agenerase do not breast-feed their infants.
Għalhekk huwa rakkomandat li dawk l- ommijiet li qegħdin jieħdu Agenerase ma jreddgħux lit- trabi tagħhom.
Additionally, it is recommended that HIV infected women do not breast feed their infants in order to avoid transmission of HIV.
Aktar minn hekk ommijiet infettati bl- HIV m’ għandhomx ireddgħu lit- trabi tagħhom sabiex ma jinxteridx il- vajrus tal- HIV.
No studies on the effects on ability to drive and use machines have been performed (see section 4.8).
Ma sarux studji dwar l- effetti fuq il- ħila biex issuq jew tħaddem magni (ara sezzjoni 4. 8).
The safety of Agenerase has been studied in adults and children at least 4 years of age, in controlled clinical trials, in combination with various other antiretroviral agents.
Saru studji kliniċi dwar is- sigurtà ta ’ Agenerase, flimkien ma ’ mediċini antiretrovirali oħra, fl- adulti u fit- tfal li għandhom ta ’ l- inqas 4 snin.
Adverse events considered associated with the use of Agenerase are gastro-intestinal symptoms, rash and oral/ peri-oral paraesthesia.
Effetti mhux mixtieqa li dehru ġejjin mill- użu ta ’ Agenerase kienu sintomi gastro- intestinali, raxx u parasteżija madwar jew ġewwa l- ħalq.
Most undesirable effects associated with Agenerase therapy were mild to moderate in severity, early in onset, and rarely treatment limiting.
Ħafna mill- effetti mhux mixtieqa assoċjati ma ’ l- użu ta ’ Agenerase kienu ħfief jew moderati u żviluppaw kmieni waqt l- użu, għalkemm rari kienu ta ’ tfixkil għat- terapija.
For many of these events, it is unclear whether they are related to Agenerase, to concomitant treatment used in the management of HIV disease or to the disease process.
Il- kawża ta ’ ħafna minn dawn l- effetti ma kienitx ċara jekk kienux ġejjin minħabba Agenerase jew minħabba terapija oħra li kienet qed tingħata fl- istess ħin għall- kontrol tal- HIV jew inkella minħabba l- marda nnifisha.
11 In children, the nature of the safety profile is similar to that seen in adults.
Il- profil tas- sigurtà fit- tfal jixbaħ lil dik fil- kbar.
Adverse reactions are listed below by MedDRA body system organ class and by frequency.
Dawn l- effetti mhux mixtieqa huma mniżżlin fil- lista t’ hawn taħt skond il- MedDRA body system organ class u skond kemm kienu frekwenti.
The frequency categories used are:
Il- kategoriji ta ’ kemm huma frekwenti dawn l- effetti huma kif ġej:
Very common Common Uncommon Rare
Komuni ħafna Komuni Mhux komuni Rari
≥ 1 in 10 ≥ 1 in 100 and < 1 in 10 ≥ 1 in 1,000 and < 1 in 100 ≥ 1 in 10,000 and < 1 in 1,000
≥ 1/ 10) ≥ 1/ 100, < 1/ 10 ≥ 1/ 1000, < 1/ 100 ≥ 1/ 10000, < 1/ 1000
Frequency categories for the events below have been based on clinical trials and postmarketing data.
Dawn il- kategoriji huma msejsa fuq informazzjoni li nġabret waqt studji kliniċi u minn informazzjoni miġbura wara li l- prodott ġie mpoġġi fuq is- suq.
Most of the adverse events below come from two clinical trials (PROAB3001, PROAB3006) involving PI naïve subjects receiving Agenerase 1200mg twice daily.
Ħafna mill- informazzjoni dwar l- effetti mhux mixtieqa li jissemmew hawn taħt inġabret waqt żewġ studji kliniċi (PROAB3001, PROAB3006) li fihom ħadu sehem pazjenti li qatt ma kienu ngħataw kura permezz tal- inibituri protease u li kienu qegħdin jirċievu 1200 mg Agenerase darbtejn kuljum.
Events (grade 2-4) reported by study investigators as attributable to study medication and occurring in > 1% of patients, are included as well as grade 3-4 treatment emergent laboratory abnormalities.
Hemm inkluż wkoll dawk l- effetti klassifikati bħala grade 3- 4 fl- anormalitajiet tal- laboratorju li tfaċċaw waqt it- trattament.
Note that the background rates in comparator groups were not taken into account.
Wieħed għandu jżomm f’ moħħu li r- rati ta ’ l- isfond ta ’ gruppi li ntużaw bħala paragun ma ġewx meqjusa.
Metabolism and nutrition disorders
Distrubi fil- metaboliżmu u n- nutrizzjoni
Elevated triglycerides, elevated amylase, abnormal fat redistribution, anorexia Hyperglycaemia, hypercholesterolaemia
ipergliċemija, livelli għoljin
Elevated triglycerides, elevated amylase and hyperglycaemia (grade 3-4) were reported primarily in patients with abnormal values at baseline.
Il- livelli għolja ta ’ trigliċeridi u amylase u l- ipergliċemija (grade 3- 4) kienu l- aktar komuni f’ pazjenti li kellhom livelli mhux normali fil- linja bażika.
Elevations in cholesterol were of grade 3-4 intensity.
Żidiet fil- kolesterol kienu ta ’ intensità ta ’ grad 3- 4.
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).
Dan it- taqsim jinkludi telf ta ’ xaħam mill- periferija u ta ’ xaħam ta ’ taħt il- ġilda, żieda ta’ xaħam intra- addominali u fil- vixxri, ipertrofija tas - sider u żieda ta ’ xaħam dorso- ċervikali (buffalo hump).
Symptoms of abnormal fat redistribution were infrequent in PROAB3001 with amprenavir.
Is- sintomi tal- lipodistrofija ma kienux daqshekk komuni fl- istudju PROAB3001 li fih kien qed jingħata amprenavir.
Only one case (a buffalo hump) was reported in 113 (< 1%) antiretroviral naive subjects treated with amprenavir in combination with lamivudine/ zidovudine for a median duration of 36 weeks.
Kien hemm każ wieħed biss (buffalo hump) irraportat f’ 113- il pazjent li qatt ma kienu ngħataw kura permezz ta ’ mediċini antiretrovirali u li kienu qed jingħataw amprenavir flimkien ma ’ lamivudine/ zidovudine għal medja ta ’ madwar 36 ġimgħa.
In study PROAB3006, seven cases (3%) were reported in 245 NRTI-experienced subjects treated with amprenavir and in 27 (11%) of 241 subjects treated with indinavir, in combination with various NRTIs for a median duration of 56 weeks (p < 0.001).
Fl- istudju PROAB3006 kien hemm sebà każi (3%), minn total ta ’ 245 pazjent li kienu diġà ngħataw kura permezz tal- inibituri protease u li kienu qed jirċievu amprenavir, u 27 (11%) minn 241 pazjent li kienu qed jirċievu indinavir flimkien ma ’ diversi mediċini oħra tat- tip NRTIs għal medja ta ’ 56 ġimgħa (p < 0. 001).
Combination antiretroviral therapy has been associated with metabolic abnormalities such as hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperglycaemia and hyperlactataemia (see section 4.4).
L- użu fl- istess ħin ta ’ aktar minn mediċina waħda antiretrovirali ġie assoċjat ma ’ anormalitàjiet fil - metaboliżmu bħal ma huma livelli għoljin ta ’ trigliċeridi u kolesterol, reżistenza għall- insulina, ipergliċemija u iperlaktemja (ara 4. 4).
Mood disorders, depressive disorders
Tibdil tal- burdata, mard dipressiv
Very Common:
Komuni ħafna:
Headache Oral/ perioral paraesthesia, tremors, sleep disorders
Uġigħ ta ’ ras parasteżija madwar jew ġewwa l- ħalq, rogħda, problemi ta ’ l- irqad
Diarrhoea, nausea, flatulence, vomiting Abdominal pain, abdominal discomfort, dyspeptic symptoms, loose stools
Dijarea, dardir, uġigħ ta ’ gass fl- istonku, rimettar Uġigħ jew skumdità addominali, sintomi ta ’ diġestjoni ħażina, ippurgar maħlul
12 Hepatobiliary disorders
Disturbi fil- fwied u fil- marrara
Elevated transaminases Hyperbilirubinaemia
livelli għoljin ta ’ transaminases livelli għoljin ta ’ bilirubina fid- demm
Elevated transaminases and hyperbilirubinaemia (grade 3-4) were reported primarily in patients with abnormal values at baseline.
Livelli għoljin ta ’ transeminejżis u livelli għoljin ta ’ bilirubina fid- demm (grad 3- 4) kienu rrapurtati l - aktar f’ pazjenti li kellhom livelli mhux normali fil- linja bażika.
Almost all subjects with abnormal liver function tests were co-infected with Hepatitis B or C virus.
Kważi il- pazjenti kollha li kellhom it - testijiet tal- fwied mhux normali kienu nfettati wkoll bil- vajrus ta ’ l- epatite B jew Ċ.
Skin and subcutaneous tissue disorders
Disturbi fil- ġilda u t- tessuti ta ’ taħt il- ġilda
Rare:
Mhux komuni Rari:
Rash Angioedema Stevens Johnson syndrome
Raxx Anġjoedema Is- sindromu ta ’ Stevens Johnson
Rashes were usually mild to moderate, erythematous or maculopapular cutaneous eruptions, with or without pruritus, occurring during the second week of therapy and resolving spontaneously within two weeks, without discontinuation of treatment with amprenavir.
Dawn il- każijiet tfaċċaw fit- tieni ġimgħa tat- terapija iżda spiċċaw waħidhom fi żmien ġimagħtejn mingħajr ma kien hemm bżonn li jitwaqqaf amprenavir.
A higher incidence of rash was reported in patients treated with amprenavir in combination with efavirenz.
Il - każijiet ta ’ raxx kienu aktar frekwenti f’ dawk il- pazjenti li kienu qed jirċievu l- amprenavir flimkien
Severe or life-threatening skin reactions have also occurred in patients treated with amprenavir (see section 4.4).
F’ xi pazjenti li kienu jirċievu amprenavir, tfaċċaw effetti mhux mixtieqa tal- ġilda li kienu serji, jew li kienu ta ’ periklu għal ħajjithom.
Musculoskeletal and connective tissue disorders
Disturbi muskolu- skeletriċi u tal- connective tissue
Increased CPK, myalgia, myositis, and rarely rhabdomyolysis have been reported with protease inhibitors, particularly in combination with nucleoside analogues.
Waqt l- użu ta ’ inibituri protease, speċjalment fejn kienu qed jingħataw ukoll analogi tan- nuklejosajd, kien hemm żieda fis- CPK, uġigħ fil- muskoli, myositis u rhabdomyolysis, għalkemm din ta ’ l- aħħar kienet rari.
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).
Każijet ta ’ nekrożi fl- għadam ġew irrappurtati partikolarment f’ pazjenti b’ fatturi ta ’ riskju magħrufa, b’ HIV avvanzat u/ jew esponiment għal terapija antiretrovirali kombinata (CART) fit- tul.
The frequency of this is unknown (see section 4.4).
(ara sezzjoni 4. 4)
Fatigue
Għeja kbira
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).
F’ pazjenti nfettati b’ HIV b’ defiċjenza serja ta ’ l- immunita ’ fiż- żmien tal- bidu ta ’ terapija antiretrovirali (CART), jista ’ jkun hemm reazzjoni nfjammatorja għal infezzjonijiet mingħajr sintomi jew opportunistiċi residwi (ara sezzjoni 4. 4).
In PI experienced patients receiving Agenerase capsules 600 mg twice daily and low dose ritonavir, 100 mg twice daily, the nature and frequency of adverse events (grade 2-4) and Grade 3/ 4 laboratory abnormalities were similar to those observed with Agenerase alone, with the exception of elevated triglyceride levels, and elevated CPK levels which were very common in patients receiving Agenerase and low dose ritonavir.
F’ pazjenti li kienu diġà ngħataw kura permezz tal- inibituri protease u li kienu qed jirċievu kapsuli ta ’ Agenerase 600 mg darbtejn kuljum, flimkien ma ’ doża baxxa ta ’ ritonavir, 100 mg darbtejn kuljum, it - tip u l- frekwenza ta ’ l- effetti mhux mixtieqa (grade 2- 4) u ta ’ Grade 3/ 4 anormalitajiet tal- laboratorju kienu jixxiebħu ma ’ dawk li tfaċċaw b’ Agenerase waħdu, minbarra iż- żieda fil- livell tat- trigliċeridi u tas- CPK li kienu ferm komuni fil- pazjenti li kienu qegħdin jirċievu Agenerase u doża baxxa ta ’ ritonavir.
There are limited reports of overdose with Agenerase.
It- tagħrif miġbur fuq l- effett ta ’ doża eċċessiva ta ’ Agenerase huwa limitat.
If overdose occurs, the patient should be monitored for evidence of toxicity (see section 4.8) and standard supportive treatment provided as necessary.
F’ każ bħal dan il- pazjent għandu jiġi osservat għal effetti tossiċi (ara 4. 8) u għandha tingħata kull għajnuna jew trattament meħtieġ.
Since amprenavir is highly protein bound, dialysis is unlikely to be helpful in reducing blood levels of amprenavir.
Minħabba li amprenavir huwa l- parti kbira minnu mwaħħal mal- proteini tad- demm, l- użu tad- dijalisi sabiex jitbaxxa l- livell ta ’ amprenavir fid- demm ftit għandu użu.
13 Pharmacotherapeutic group; protease inhibitor; ATC Code:
Inibitur protease; Kodiċi ATC:
Mechanism of Action
Mekkaniżmu ta ’ Azzjoni Amprenavir huwa inibitur kompetitiv ta ’ - HIV 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 jintrabat mas- sit attiv tal- protease ta ’ HIV- 1 u b’ hekk ma jħallix l- ipproċessar tal- prekursuri virali tal- polyprotein gag u gag- pol, li tirriżulta fil- formazzjoni ta ’ partiċelli mhux infettivi immaturi tal- vajrus.
The in vitro antiviral activity observed with fosamprenavir is due to the presence of trace amounts of amprenavir.
L- attivita ’ antivirali in vitro osservata b’ fosamprenavir hija minħabba l- preżenza ta ’ traċċi ta ’ amprenavir.
Antiviral activity in vitro
Attività antivirali in vitro
The in vitro antiviral activity of amprenavir was evaluated against HIV-1 IIIB in both acutely and chronically infected lymphoblastic cell lines (MT-4, CEM-CCRF, H9) and in peripheral blood lymphocytes.
L- attività antivirali in vitro ta ’ amprenavir ġiet valutata ma ’ l- HIV- 1 IIIB f’ razzez ta ’ ċelluli limfoblastiċi infettati b’ mod akut u b’ mod kroniku (MT- 4, CEM- CCRF, H9) u f’ limfoċiti periferali tad- demm.
The 50% inhibitory concentration (IC50) of amprenavir ranged from 0.012 to 0.08 µM in acutely infected cells and was 0.41 µM in chronically infected cells (1 µM = 0.50 µg/ ml).
Il- 50% konċentrazzjoni inibitorja (IC50) ta ’ amprenavir infirxet minn 0. 012 sa 0. 08 µM f’ ċelluli infettati b’ mod akut u kienet 0. 41 µM f’ ċelluli infettati b’ mod kroniku (1 µM=0. 50µg/ ml).
The relationship between in vitro anti-HIV-1 activity of amprenavir and the inhibition of HIV-1 replication in humans has not been defined.
Ir - relazzjoni bejn l- attività in vitro anti- HIV- 1 ta ’ amprenavir u l- impediment tar- replikazzjoni ta ’ HIV- 1 fil- bniedem għada ma ġietx definita.
Resistance
14 Reżistenza
HIV-1 isolates with decreased susceptibility to amprenavir have been selected during in vitro serial passage experiments.
Iżolati ta ’ HIV- 1 b’ suxxettibiltà mnaqqsa għal amprenavir ġew magħżula f’ esperimenti serial passage in vitro.
Reduced susceptibility to amprenavir was associated with virus that had developed I50V or I84V or V32I+I47V or I54M mutations.
Suxxettibiltà mnaqqsa għal amprenavir ġiet assoċjata ma ’ virus li kien żviluppa mutazzjonijiet ta ’ I50V jew I84V jew V32I+I47V jew I54M.
a) ART-naïve or PI-naïve patients
a) Pazjenti li m’ għandhomx esperjenza ART jew PI,
Agenerase is not approved in ART-naive or PI-naive patients).
Agenerase mhuwiex approvat f’ pazjenti mingħajr esperjenza ART jew PI
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.
Analysis of the virological failure samples across these regimens defined four main resistance pathways:
Analiżi ta ’ kampjuni ta ’ fallimenti virologiċi f’ dawn is- sistemi ta ’ kura iddefinixxew erba ’ passaġġi ta ’ reżistenza prinċipali:
V32I+I47V, I50V, I54L/ M and I84V.
V32I+I47V, I50V, I54L/ M and I84V.
Additional mutations observed which may contribute to resistance were:
Mutazzjonijiet oħra osservati li jistgħu jwasslu għal reżistenza kienu:
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 193L.
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 ’ ART ingħataw kura b’ dożi approvati bħalissa ta ’ fosamprenavir/ ritonavir, bħal sistemi oħra ta ’ kura PI imsaħħin b’ ritonavir, il- mutazzjonijiet deskritti kienu osservati rarament.
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 ngħataw fosamprenavir 700mg/ ritonavir 100mg darbtejn kuljum f’ ESS100732 esperjenzaw falliment viroloġiku sa Ġimgħa 48 b’ 14- il iżolat ġenotipat.
Three of 14 isolates had protease resistance mutations.
Tlieta mill- 14- il iżolat kellhom mutazzjonijiet ta ’ reżistenza ta ’ protease.
One resistance mutation was observed in each of 3 isolates:
Kienet osservata mutazzjoni ta ’ reżistenza waħda f’ kull waħda mit- tliet 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
14 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 600mg/ ritonavir 100mg darbtejn kuljum f’ sub- studju A u B bi 80 u 37 pazjent rispettivament), ħarġu dawn il- mutazzjonijiet 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:
(n=105), ħarġu dawn il- mutazzjonijiet f’ pazjenti b’ esperjenza ta ’ 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 ingħataw fosamprenavir/ ritonavir u minn 22 iżolat ta ’ falliment viroloġiku ġenotipat, disgħa pazjenti nstabu li kellhom mutazzjonijiet ta ’ protease minħabba t- trattament.
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 trattati b’ fosamprenavir / ritonavir.
Analyses based on genotypic resistance testing.
15 Analiżi bbażata fuq testijiet ta ’ reżistenza ġenotipika
Genotypic interpretation systems may be used to estimate the activity of amprenavir / ritonavir or fosamprenavir / ritonavir in subjects with PI-resistant isolates.
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.
The current (July 2006) ANRS AC-11 algorithm for fosamprenavir / ritonavir defines resistance as the presence of the mutations V32I+I47A/ V, or I50V, or at least four mutations among:
L- algoritmu kurrenti (Lulju 2006) ANRS AC- 11 għal fosamprenavir/ ritonavir jiddefinixxi reżistenza bħala l - preżenza tal- mutazzjonijiet V32I+I47A/ V, jew I50V, jew almenu erba ’ mutazzjonijiet minn:
L10F/ I/ V, L33F, M36I, I54A/ L/ M/ S/ T/ V, I62V, V82A/ C/ F/ G, I84V and L90M and is associated with increased phenotypic resistance to fosamprenavir with ritonavir as well as reduced likelihood of virological response (resistance).
L10F/ I/ V, L33F, M36I, I54A/ L/ M/ S/ T/ V, I62V, V82A/ C/ F/ G, I84V u L90M u hija assoċċjata ma ’ żieda fir- reżistenza fenotipika għal fosamprenavir ma ’ ritonavir kif ukoll bħala ċans anqas ta ’ rispons viroloġiku (reżistenza).
Conclusions regarding the relevance of particular mutations or mutational patterns are subject to change with additional data, and it is recommended to always consult current interpretation systems for analysing resistance test results.
Konklużżjonijiet dwar ir- rilevanza ta ’ mutazzjonijiet partikolari jew ta’ disinni ta ’ mutazzjonijiet jistgħu jiżdiedu b’ aktar data, u hu rrakkomandat li dejjem tikkonsulta sistemi ta ’ interpretazzjoni kurrenti biex tanaliżża riżultati fuq testijiet ta ’ reżistenza.
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 validata 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.
Resistance testing diagnostic companies have developed clinical phenotypic cut-offs for FPV/ RTV that can be used to interpret resistance test results.
Kumpaniji dijanjostiċi li jittestjaw ir- reżistenza żviluppaw cut- offs kliniċi fenotipiċi għal FPV/ RTV li jistgħu jintużaw biex jinterpretaw riżultati ta ’ testijiet ta ’ reżistenza.
Cross-Resistance
Cross resistance
HIV-1 isolates with a decreased susceptibility to amprenavir have been selected during in vitro serial passage experiments.
Ġew magħżula iżolati ta ’ HIV b’ suxxetibilità mnaqqsa għal amprenavir waqt esperimenti serial passage in vitro.
Reduced susceptibility to amprenavir was associated with virus that had developed I50V or I84V or V32I+I47V or I54M mutations.
Suxxettibilità mnaqqsa għal amprenavir kienet assoċċjata ma ’ virus li kien żviluppa mutazzjonijiet I50V jew I84V jew V321+I47V jew I54M.
Each of these four genetic patterns associated with reduced susceptibility to amprenavir produces some cross-resistance to ritonavir but susceptibility to indinavir, nelfinavir and saquinavir is generally retained.
Kull wieħed min dawn l- erba ’ disinni ġenetiċi assoċċjati ma ’ suxxetibilità mnaqqsa għal amprenavir tipproduċi cross- resistance għal ritonavir imma s- suxxetibilità għal indinavir, nelfinavir u saquinavir ġeneralment tibqa.
There are currently data on cross-resistance between amprenavir and other protease inhibitors for all 4 fosamprenavir resistance pathways, either alone or in combination with other mutations.
Bħalissa hemm data fuq cross- resistance bejn amprenavir u impedituri protease oħra għall- erba ’ passaġġi ta ’ reżistenza ta 'fosamprenavir, waħedhom jew f’ kumbinazzjoni ma ’ mutazzjonijiet oħra.
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)..
Fuq bażi ta ’ data minn ħamsa u għoxrin pazjent mingħajr esperjenza antiretrovirali li fallew fuq sistema ta ’ kura b’ fosamprenavir (fejn wieħed minnhom wera reżistenza tal- 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).
Conversely amprenavir retains activity against some isolates with resistance to other PIs and this retained activity would depend on the number and type of protease resistance mutations present in the isolates
Għall- kuntrarju amprenavir jibqa ’ attiv kontra xi iżolati b’ reżistenza għal PI oħra u din l- attività miżmuma tiddependi fuq in- numru u t- tipi ta ’ mutazzjonijiet ta ’ reżistenza għal protease li hemm fl- iżolati.
The number of key PI-resistance mutations increases markedly the longer a failing PI-containing regimen is continued.
In- numru ta ’ tibdil importanti li jwasslu għal reżistenza kontra l- inibituri protease jiżdied b’ mod sinifikattiv aktar ma ddum tintuża kura bl- inibituri protease li ma tkunx qed tirnexxi.
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.
Għalhekk huwa rakkomandat li kull kura li tidher li tkun qed tfalli għandha titwaqqaf sabiex titnaqqas iż- żieda ta ’ aktar tibdil, li jistgħu jkunu ta ’ detriment għal kull kura li tistà tingħata wara.
15 Cross resistance between amprenavir and reverse transcriptase inhibitors is unlikely to occur because the enzyme targets are different.
Mhux mistenni li jkun hemm reżistenza misluba bejn amprenavir u inibituri tar- rivers transkriptejż minħabba li l- enzimi involuti huma differenti.
Agenerase is not recommended for use as monotherapy, due to the rapid emergence of resistant virus.
Agenerase m’ huwiex rakkomandat għall- użu waħdu, minħabba l- emerġenza rapida ta ’ vajrus reżistenti.
Clinical experience:
Esperjenza Klinika:
PI-experienced adults, boosted Agenerase capsules
Adulti b’ esperjenza PI, kapsuli ta ’ Agenerase aktar qawwija
The evidence of efficacy of Agenerase in combination with ritonavir 100 mg twice daily is based on study PRO30017, a randomized, open-label study, in which PI-experienced adults experiencing virological failure (viral load ≥ 1000 copies/ ml) received either Agenerase (600 mg twice daily) in combination with ritonavir (100 mg twice daily) and nucleoside analogues (NRTI) or a standard of care (SOC) PI, predominantly boosted with low-dose RTV.
L- evidenza ta ’ effikaċja ta ’ Agenerase flimkien ma 'ritonavir 100mg darbtejn kuljum hija ibbażata fuq studju PRO30017, studju randomised open- label fejn pazjenti b’ esperjenza PI li esperjenzaw falliment viroloġiku (viral load ≥1000 kopja/ ml) irċevew jew Agenerase (600mg darbtejn kuljum) flimkien ma ’ ritonavir (100mg darbtejn kuljum) jew inkella analogi tan- nukleosidi (NRTI) jew PI standard ta ’ kura (SOC), l- aktar magħmul aktar qawwi b’ doża baxxa ta ’ RTV.
One hundred and sixty-three (163) patients with virus sensitive to Agenerase, at least one other PI, and at least one NRTI were included in PRO30017 substudy A.
16 Mija u tlieta u sittin (163) pazjent b’ virus sensittiv għal Agenerase, almenu PI ieħor, u almenu NRTI ieħor kienu inklużi fl- istudju sekondarju ta ’ PRO30017.
The primary analysis assessed the non- inferiority of APV/ r to the SOC PI group with respect to time-weighted average change from baseline (AAUCMB) in plasma viral load (HIV-1 RNA) at week 16 using a non-inferiority margin of 0.4 log10 copies/ ml.
L- analiżi primarja assessjat in- nuqqas ta ’ inferjorità ta ’ APV/ r għall- grupp SOC PI meta mqabbla ma ’ bidla mill- linja bażi mwieżna skond il- ħin (AAUCMB) f’ viral load fil- plażma (HIV- 1 RNA) f’ ġimgħa 16 meta jintuża marġni ta ’ nuqqas ta ’ nferjorità ta ’ 0. 4 log10 kopji/ ml.
16 Results at week 16
Riżultati f’ ġimgħa 16
Treatment
Differenza fil -
Baseline characteristics
Karatteristiċi tal- linja bażi
difference
kura
Median HIV-1 RNA (log10 copies/ ml) (range)
Medja ta ’ HIV- 1 RNA (kopji log10 / ml) (sensiela)
Median CD4 (cells/ ml) (range)
Medja ta ’ CD4 (cells/ ml) (sensiela)
Prior number of PIs taken [n (%)]
Numri ta ’ PI meħuda qabel [n (%)]
1 2 ≥ 3 Median number of PI
1 2 ≥3 Numru medja ta ’
primary mutations 1 Prior number of NRTIs
mutazzjonijiet primarji1 PI Numru ta ’ NRTI
1.0 (range 0-2)
1. 0 (range 0- 2)
taken [n (%)] ≥ 4 Outcomes a
meħuda qabel [n (%)] ≥4 Outcomes a
Mean plasma HIV-1
0. 043b
− 1.315
Medja fil- plażma ta ’
− 1.343
− 1. 315
0.043b
− 1. 343
RNA AAUCMB (log10 copies/ ml)
(−0. 250, 0. 335) c HIV- 1 RNA AAUCMB (kopji log10/ ml) HIV- 1 RNA anqas
Intent To Treat (Exposed) Population:
(−21, 9) c minn 400 kopja/ ml (%) fil- plażma a Intent To Treat Populazzjoni (Esposta):
Observed analysis b Mean stratified difference c 95% confidence interval 1 Primary mutations were as defined by the IAS USA at the time of the original analysis, 2002 D30N, M46I/ L, G48V, I50V, V82A/ F/ T/ S, I84V, L90M.
Analiżi osservata b Differenza medja stratifikata c 95% confidence interval 1 Il- mutazzjonijiet primarji kienu definiti mill- IAS USA fiż- żmien ta ’ l- analiżi oriġinali, 2002 D30N, M46I/ L, G48V, I50V, V82A/ F/ T/ S, I84V, L90M.
Heavily pre-treated children, unboosted Agenerase
Tfal trattati ħafna minn qabel, Agenerase mhux aktar qawwi
The evidence of efficacy of unboosted Agenerase was based on two uncontrolled clinical studies involving 288 HIV infected children aged between 2 and 18 years, 152 of whom were PI experienced.
L- evidenza ta ’ effikaċja ta ’ Agenerase mhux aktar qawwi kienet ibbażata fuq żewġ studji kliniċi mhux ikkontrollati b’ 288 tifel u tifla ta ’ bejn is- 2 u t- 18 il- sena infettati bl- HIV, li 152 minnhom kellhom esperjenza PI.
The studies evaluated Agenerase oral solution and capsules at doses of 15 mg/ kg three times daily, 20 mg/ kg three times daily, 20 mg/ kg twice daily and 22.5 mg/ kg twice daily although the majority received 20 mg/ kg twice daily.
L- istudji evalwaw is- soluzzjoni orali u kapsuli ta 'Agenerase f’ dożi ta ’ 15mg/ kg tliet darbiet kuljum, 20mg/ kg tliet darbiet kuljum, 20mg/ kg darbtejn kuljum u 22. 5mg/ kg darbtejn kuljum għalkemm il- maġġoranza ngħataw 20mg/ kg darbtejn kuljum.
Those of at least 13 years of age and weighing at least 50 kg received 1200 mg Agenerase twice daily.
Dawk li kellhom almenu 13- il sena u li kienu jiżnu almenu 50kg irċevew 1200mg Agenerase darbtejn kuljum.
Concomitant low dose ritonavir was not administered and the majority of the PI experienced subjects had prior exposure to at least one (78%) or two (42%) of the NRTIs co-administered with Agenerase.
F’ ġimgħa 48,
At Week 48, approximately 25% of those enrolled had plasma HIV-1 RNA < 10,000 copies/ ml and 9% < 400 copies/ ml with a median change from baseline in CD4+ cells of 26 cells/ mm3 (n=74).
17 bejn wieħed u ieħor 25% ta ’ dawk irreġistrati kellhom HIV- 1 RNA fil- plażma ta ’ < 10, 000 kopji/ ml u 9% kellhom < 400 kopji/ ml b’ bidla medja mill- linja bażi ta ’ ċelluli CD4+ ta ’ 26 ċellula/ mm3 (n=74).
Based on these data, careful consideration should be given to the expected benefit of unboosted Agenerase when optimising therapy for PI experienced children.
Fuq bażi ta ’ din l- informazzjoni, għandha tingħata konsiderazzjoni bir- reqqa lill- benefiċċju mistenni ta ’ Agenerase mhux qawwi meta tkun qed tintgħażel l- aħjar kura għal tfal b’ esperjenza PI.
There is no data on the efficacy of boosted Agenerase in children.
M’ hemmx informazzjoni fuq l- effikaċja ta ’ Agenerase aktar qawwi fit- tfal.
17 5.2 Pharmacokinetic properties
5. 2 Tagħrif farmakokinetiku
Absorption: after oral administration, amprenavir is rapidly and well absorbed.
Assorbiment: wara li jingħata mill- ħalq, amprenavir jiġi assorbit malajr u tajjeb ħafna.
The absolute bioavailability is unknown due to the lack of an acceptable intravenous formulation for use in man.
Il - bijodisponibiltà mhux magħrufa minħabba li ma teżistix preparazzjoni mediċinali li hija tajba sabiex tintuża għal ġol- vini.
Approximately 90% of an orally administered radiolabelled amprenavir dose was recovered in the urine and the faeces, primarily as amprenavir metabolites.
Madwar 90% ta ’ doża ta ’ amprenavir immarkat b’ mod radjoloġiku ġiet misjuba fl- awrina u fl- iskart tal- ġisem primarjament bħala metaboliti ta ’ amprenavir.
Following oral administration, the mean time (tmax) to maximal serum concentrations of amprenavir is between 1-2 hours for the capsule and 0.5 to 1 hour for the oral solution.
Wara li jingħata mill - ħalq, il- ħin intermedju (tmax) sakemm tintlaħaq l- għola konċentrazzjoni ta ’ amprenavir fis- serum huwa ta ’ madwar siegħa sa sagħtejn għall- kapsuli u ta ’ madwar nofs siegħa sa siegħa fil- każ tas- soluzzjoni orali.
A second peak is observed after 10 to 12 hours and may represent either delayed absorption or enterohepatic recirculation.
Livell għoli ieħor jintlaħaq wara madwar għaxra sa tnax- il siegħa u dan jista jiġri minħabba dewmien fl- assorbiment jew minħabba ċirkolazzjoni enteroepatika.
At therapeutic dosages (1200 mg twice daily), the mean maximum steady state concentration (Cmax, ss) of amprenavir capsules is 5.36 µg/ ml (0.92-9.81) and the minimum steady state concentration (Cmin, ss) is 0.28 µg/ ml (0.12-0.51).
Meta jingħataw dożi terapewtiċi (1200 mg darbtejn kuljum), il- valur intermedju tal- konċentrazzjoni fi stat stabbli massima (Cmax, ss) tal- kapsuli huwa ta ’ 5. 36 µg/ ml (0. 92- 9. 81) filwaqt li dak tal - konċentrazzjoni fi stat stabbli minima (Cmin, ss) huwa ta ’ 0. 28 µg/ ml (0. 12- 0. 51).