qanastek/EMEA-V3 huggingface dataset:
In a meta-analysis of five clinical trials where abacavir was added to intensify therapy, of 166 subjects, 123 (74%) had M184V/ I, 50 (30%) had T215Y/ F, 45 (27%) had M41L, 30 (18%) had K70R and 25 (15%) had D67N.
F’ meta- analiżi ta ’ ħames studji kliniċi fejn żdied abacavir biex iqawwi t- terapija, minn 166 suġġett, 123 (74%) kellhom M184V/ I, 50( 30%) kellhom T215Y/ F, 45 (27%) kellhom M41L, 30 (18%) kellhom K70R u 25 (15%) kellhom D67N.
Logistic regression modelling of the predictive value for genotype (adjusted for baseline plasma HIV-1 RNA [vRNA], CD4+ cell count, number and duration of prior antiretroviral therapies), showed that the presence of 3 or more NRTI resistance-associated mutations was associated with reduced response at Week 4 (p=0.015) or 4 or more mutations at median Week 24 (p≤ 0.012).
Rigressjoni fl - immudellar loġistiku tal- valur imbassar tal- ġenotip (addattat għall- livell bażiku fil- plażma ta ’ HIV- 1 RNA [vRNA], l- għadd ta ’ ċelloli CD4+, in- numru ta ’ drabi u t- tul ta ’ terapiji antiretrovirali fil- passat), wera li l- preżenza ta ’ 3 jew aktar mutazzjonijiet assoċċjati ma ’ reżistenza b’ NRTI, kellhom x’ jaqsmu ma ’ reazzjoni mnaqqsa fir- 4 Ġimgħa (p=0. 015) jew 4 jew aktar mutazzjonijiet fil- medja ta ’ 24 Ġimgħa (p≤0. 012).
In addition, the 69 insertion complex or the Q151M mutation, usually found in combination with A62V, V75I, F77L and F116Y, cause a high level of resistance to abacavir.
Barra minn hekk, il- kumpless ta ’ dħul 69 jew il- mutazzjoni Q151M, li l- biċċa l - kbira ssibhom ma ’ A62V, V75I, F77L u F116Y, dawn jagħmlu reżistenza kbira għal abacavir.
Week 4 Baseline (n = 166) Reverse
12 4 Ġimgħa Mutazzjoni tal - (n = 166) lina bażi ta ’
Transcriptase
Reverse
Median
Bidla Medja
Percent with
Persentaġġ b ’
Mutation
Transcriptase
Change vRNA
vRNA (log10
< 400 copies/ mL
< 400
(log10 c/ mL)
c/ mL)
M184V alone
M184V waħdu Kull mutazzjoni
associated mutations
assoċjati ma ’ NRTI 4 jew aktar mutazzjonijiet
Phenotypic resistance and cross-resistance:
Reżistenza finotipika u cross- resistance:
Phenotypic resistance to abacavir requires M184V with at least one other abacavir-selected mutation, or M184V with multiple TAMs.
Reżistenza finotipika għal abacavir għanda bżonn almenu mutazzjoni waħda oħra magħżula għal abacavir, jew M184V b’ ħafna MAT.
Phenotypic cross- resistance to other NRTIs with M184V or M184I mutation alone is limited.
Cross- resistance finotipika għal NRTI oħra bil- mutazzjoni M184V jew M184IM waħedha hija limitata.
Appropriate use of abacavir can be guided using currently recommended resistance algorithms.
L- użu addattat ta ’ abacavir jista ’ jkun iggwidat bl- użu ta ’ algoritmi ta ’ reżistenza kurrenti.
Cross-resistance between abacavir and antiretrovirals from other classes (e. g.
Cross- resistance bejn abacavir u antiretrovirali ta ’ tip ieħor (e. ż.
PIs or NNRTIs) is unlikely.
PIs jew NNRTIs) mhix probabli.
Clinical Experience
Esperjenza klinika
The demonstration of the benefit of Ziagen is mainly based on results of studies performed in adult treatment-naïve patients using a regimen of Ziagen 300 mg twice daily in combination with zidovudine and lamivudine.
Id- dimostrazzjoni tal- benefiċċju ta ’ Ziagen hija bbażata l- aktar fuq studji li saru f’ adulti li qatt ma ingħatalhom kura billi ntużat sistema ta ’ Ziagen 300mg darbtejn kuljum flimkien ma ’ zidovudine u lamivudine.
12 Twice daily (300 mg) administration:
Doża (300mg) darbtejn kuljum:
• Therapy naïve adults
• Adulti li qatt m`ingħatalhom kura antiretrovirali –
In adults treated with abacavir in combination with lamivudine and zidovudine the proportion of patients with undetectable viral load (< 400 copies/ ml) was approximately 70% (intention to treat analysis at 48 weeks) with corresponding rise in CD4 cells.
F’ pazjenti adulti li qed jingħataw abacavir ma ’ lamivudine u zidovudine il- proporzjon ta` pazjenti b’ viral load li ma jitkejjilx (< 400 copies/ ml) kien bejn wieħed u ieħor ta` 70% (l- analiżi intent- to- treat fi żmien 48 ġimgħa) b`żieda korrispondenti f`ċelloli CD4.
One randomised, double blind, placebo controlled clinical study in adults has compared the combination of abacavir, lamivudine and zidovudine to the combination of indinavir, lamivudine and zidovudine.
Studju kliniku fl- adulti randomised, double blind, kontrollat bil- plaċebo, qabbel l- użu ta ’ abacavir, lamivudine u zidovudine mogħtija flimkien ma ’ l- użu ta ’ indinavir, lamivudine u zidovudine mogħtija flimkien.
Due to the high proportion of premature discontinuation (42% of patients discontinued randomised treatment by week 48), no definitive conclusion can be drawn regarding the equivalence between the treatment regimens at week 48.
Minħabba numru kbir li kellhom iwaqqfu l- kura qabel il- waqt (42% tal- pazjenti bdew u ma komplewx il- kura sat- 48 ġimgħa), ma setgħax ikun hemm konklużjoni definittiva rigward l - ekwivalenza bejn dawn iż- żewġ tipi ta ’ reġimens fit- 48 ġimgħa.
Although a similar antiviral effect was observed between the abacavir and indinavir containing regimens in terms of proportion of patients with undetectable viral load (≤ 400 copies/ ml; intention to treat analysis (ITT), 47% versus 49%; as treated analysis (AT), 86% versus 94% for abacavir and indinavir combinations respectively), results favoured the indinavir combination, particularly in the subset of patients with high viral load (> 100,000 copies/ ml at baseline; ITT, 46% versus 55%; AT, 84% versus 93% for abacavir and indinavir respectively).
Ghalkemm effett antivirali simili deher bejn il- kura b’ abacavir u indinavir f`termini tan- numru ta ’ pazjenti b` viral load li ma jitkejjilx (≤400 kopji/ ml; analiżi ta ’ l- intenzjoni għal- kura (ITT), 47% kontra 49%; bħala analiżi tal- kura (AT), 86% kontra 94% għal kombinazzjonijiet ta’ abacavir u ta ’ indinavir rispettivament), ir- riżultati wrew li
In a multicentre, double-blind, controlled study (CNA30024), 654 HIV-infected, antiretroviral therapy-naïve patients were randomised to receive either abacavir 300 mg twice daily or zidovudine 300 mg twice daily, both in combination with lamivudine 150 mg twice daily and efavirenz 600 mg once daily.
Fi studju kliniku kkontrollat, double- blind, f’ aktar minn ċentru wieħed, (CAN 30024), 654 pazjent infettati bl- HIV u li qatt ma ingħatalhom kura antretrovirali, irċevew b’ mod randomised jew abacavir 300mg jew zidovudine 300mg darbtejn kuljum, kemm flimkien ma ’ lamivudine 150mg darbtejn kuljum u efavirenz 600mg darba kuljum.
The duration of double-blind treatment was at least 48 weeks.
It- trattament double- blind dam mill- anqas 48 ġimgħa.
In the intent-to-treat (ITT) population, 70% of patients in the abacavir group, compared to 69% of patients in the zidovudine group, achieved a virologic response of plasma HIV-1 RNA ≤ 50 copies/ ml by Week 48 (point estimate for treatment difference:
Fil - popolazzjoni bl- intenzjoni ta ’ kura (intent- to- treat jew ITT), 70% tal- pazjenti fil- grupp ta ’ abacavir mqabbla ma ’ 69% tal- pazjenti fil- grupp ta ’ zidovudine, laħqu livell viroloġiku ta ’ HIV- 1 RNA fil - plażma ta ’ ≤50kopji/ ml sat- 48 ġimgħa (point estimate ta ’ differenza fil- kura:
0.8, 95% CI -6.3, 7.9).
0. 8, 95% CI - 6. 3, 7. 9).
However, both analyses were compatible with a conclusion of non-inferiority between both treatment arms.
Fl- analiżi kif trattat (as treated jew AT), id- differenza bejn iż- żewġ friegħi kienet aktar ċara (88% fil - grupp ta ’ abacavir mqabbla ma ’ 95% tal- pazjenti fil- grupp ta ’ zidovudine (point estimate ta ’ differenza fil- kura: - 6. 8, 95% CI – 11. 8; - 1. 7), Iż- żewġ analiżi iżda, kienu jaqblu mal- konklużżjoni li ma kien hemm ebda inferjorita ’ bejn i ż- żewġ friegħi ta ’ kura.
ACTG5095 was a randomised (1:1:1), double-blind, placebo-controlled trial performed in 1147 antiretroviral naïve HIV-1 infected adults, comparing 3 regimens: zidovudine (ZDV), lamivudine (3TC), abacavir (ABC), efavirenz (EFV) vs ZDV/ 3TC/ EFV vs ZDV/ 3TC/ ABC.
ACTG5095 kien studju kliniku kkontrollat bil- plaċebo, randomised (1: 1: 1), double- blind, li sar f’ 1147 adult infettat bl- HIV- 1 li qatt ma ħadu terapija antiretrovirali, fejn tqabblu 3 tipi ta ’ kura: zidovudine (ZDV), lamivudine (3TC), abacavir (ABC), efavirenz (EFV) ma ’ ZDV/ 3TC/ EFV ma ’ ZDV/ 3TC/ ABC.
After a median follow-up of 32 weeks, the tritherapy with the three nucleosides ZDV/ 3TC/ ABC was shown to be virologically inferior to the two other arms regardless of baseline viral load (< or > 100 000 copies/ml) with 26% of subjects on the ZDV/3TC/ABC arm, 16% on the ZDV/3TC/EFV arm and 13% on the 4 drug arm categorised as having virological failure (HIV RNA > 200 copies/ml).
Wara li kienu segwiti għall- 32 ġimgħa, it- terapija triplika bit- tlett nukleosidi ZDV/ 3TC/ ABC instabet li kienet inferjuri viroloġikament għaż- żewġ friegħi l- oħra irrespettivament mill- piż virali tal- linja bażi (< jew > 100, 000 kopja kull ml), b’ 26% tas- suġġetti fuq il- fergħa ZDV/ 3TC/ ABC, 16% fuq il- fergħa ZDV/ 3TC/ EFV u 13% fuq il- fergħa ta ’ erbgħa mediċini li kienu kkatergoriżżati bħala falliment viroloġiku (HIV RNA > 200 kopji kull ml).
The remaining arms were continued in a blinded fashion.
Il- fergħat l- oħra komplew b’ mod blinded.
After a median follow-up of 144 weeks, 25% of subjects on the ZDV/ 3TC/ ABC/ EFV arm and 26% on the ZDV/ 3TC/ EFV arm were categorised as having virological failure.
Wara li ġew segwiti għal medja ta ’ 144 ġimgħa, 25% tas- suġġetti fuq il- fergħa ZDV/ 3TC/ ABC/ EFV u 26% fuq il - fergħa ZDV/ 3TC/ EFV ġew kategoriżżati li kellhom falliment viroloġiku.
There was no significant difference in the time to first virologic failure (p=0.73, log-rank test) between the 2 arms.
Ma kienx hemm differenza kbira fiż- żmien għall- ewwel falliment viroloġiku (p=0. 73 test log- rank) bejn iż- żewġ fergħat.
In this study, addition of ABC to ZDV/ 3TC/ EFV did not significantly improve efficacy.
F’ dan l - istudju, iż- żieda ta ’ ABC ma ’ ZDV/ 3TC/ EFV ma żieditx b’ ħafna l- effikaċja.
Virologic failure (HIV 32 weeks RNA > 200 copies/ ml) 144 weeks Virologic success (48 weeks HIV RNA < 50 copies/ ml)
Falliment virologiku (HIV RNA > 200 kopja/ ml)
13 • Therapy naïve children
14 Tfal li qatt ma ingħatalhom kura qabel
In a study comparing the unblinded NRTI combinations (with or without blinded nelfinavir) in children, a greater proportion treated with abacavir and lamivudine (71%) or abacavir and zidovudine (60%) had HIV-1 RNA ≤ 400 copies/ ml at 48 weeks, compared with those treated with lamivudine and zidovudine (47%)[ p=0.09, intention to treat analysis].
Fi studju fejn ġew mqabbla l- kombinazzjonijiet NRTI unblinded (bil jew mingħajr blinded nelfinavir) fit- tfal, numru akbar ta ’ pazjenti kurati b`abacavir u lamivudine (71%) jew abacavir u zidovudine (60%) kellhom HIV- 1 RNA ≤400kopji/ ml fit- 48 ġimgħa, meta mqabbla ma ’ dawk li rċevew kura b` lamivudine u zidovudine (47%) [p=0. 09, analiżi ta ’ l- intenzjoni għal- kura].
Similarly, greater proportions of children treated with the abacavir containing combinations had HIV-1 RNA ≤ 50 copies/ ml at 48 weeks (53%, 42% and 28% respectively, p=0.07).
Bl- istess mod, numri akbar ta` tfal mogħtija kombinazzjonijiet ta ’ terapija li kien fihom abacavir kellhom HIV- 1 RNA ≤kopji/ ml fit- 48 ġimgħa (53%, 42% u 28% rispettivament, p=0. 07).
• Therapy experienced patients
• Pazjenti esperjenzati bit- terapija
In adults moderately exposed to antiretroviral therapy the addition of abacavir to combination antiretroviral therapy provided modest benefits in reducing viral load (median change 0.44 log10 copies/ ml at 16 weeks).
F' adulti li jkollhom esponiment moderat ta ’ terapija antiretrovirali l- użu ta ’ abacavir mal - kombinazzjoni tat- terapija antiretrovirali kienet ftit aktar effettiva biex tnaqqas il- viral load (bidla medjana 0. 44 log10 kopji/ ml f’ 16- il ġimgħa).
In heavily NRTI pretreated patients the efficacy of abacavir is very low.
F' pazjenti li jingħataw minn qabel doża għolja ta ’ NRTI l- effikaċja t’ abacavir hija baxxa ħafna.
The degree of benefit as part of a new combination regimen will depend on the nature and duration of prior therapy which may have selected for HIV-1 variants with cross-resistance to abacavir.
Kemm dan jista jservi bħala parti minn reġimen kombinat ġdid jiddependi minn- natura u t- tul tat- terapija li tingħata qabel li jista jkun laqtet varjanti ta ’ l- HIV- 1 b’ cross- resistance għal abacavir.
Once daily (600 mg) administration:
Doża (600mg) darba kuljum:
• Therapy naïve adults
• Adulti li qatt ma ingħatalhom kura qabel:
The once daily regimen of abacavir is supported by a 48 weeks multi-centre, double-blind, controlled study (CNA30021) of 770 HIV-infected, therapy-naïve adults.
Studju kkontrollat, double- blind ta ’ 48 ġimgħa b’ 770 adult infettati bl- HIV li qatt ma ingħatalhom kura qabel, f’ aktar minn ċentru wieħed (CAN 30021), wera li d- doża ta ’ darba kuljum ta ’ abacavir hija effettiva.
These were primarily asymptomatic HIV infected patients (CDC stage A).
Dawn kienu primarjament pazjenti asintomatiċi nfettati bl- HIV (CDC Stadju A).
They were randomised to receive either abacavir 600 mg once daily or 300 mg twice daily, in combination with efavirenz and lamivudine given once daily.
Dawn ġew randomised u ingħataw jew abacavir 600mg darba kuljum jew 300mg darbtejn kuljum, flimkien ma ’ efavirenz u lamivudine darba kuljum.
Similar clinical success (point estimate for treatment difference -1.7, 95% CI -8.4, 4.9) was observed for both regimens.
Suċċess kliniku simili (point estimate għal differenza fil- kura – 1. 7, 95% CI- 8. 4, 4. 9) kienu osservati għaż- żewġ dożi.
From these results, it can be concluded with 95% confidence that the true difference is no greater than 8.4% in favour of the twice daily regimen.
Min dawn ir- riżultati, wieħed jista ’ jikkonkludi b’ kunfidenza ta ’ 95% li d- differenza vera ma hijiex akbar min 8. 4% lejn id- doża ta ’ darbtejn kuljum.
This potential difference is sufficiently small to draw an overall conclusion of non-inferiority of abacavir once daily over abacavir twice daily.
Din id- differenza potenzjali hija biżżejjed żgħira biex tiddeċiedi fuq kollox li abacavir darba kuljum ma huwiex inferjuri għal abacavir darbtejn kuljum.
There was a low, similar overall incidence of virologic failure (viral load > 50 copies/ ml) in both the once and twice daily treatment groups (10% and 8% respectively).
Kien hemm ukoll inċidenza baxxa ta ’ falliment viroloġiku (viral load ta ’ > 50kopja/ ml) kemm fil - gruppi li kienu qed jieħdu l- kura darba kuljum kif ukoll gruppi li kienu qed jieħdu l- kura darbtejn kuljum (10% u 8% rispettivament).
In the small sample size for genotypic analysis, there was a trend toward a higher rate of NRTI-associated mutations in the once daily versus the twice daily abacavir regimens.
F’ kampjun żgħir għal analiżi ġenotipika, kien hemm it - tendenza ta ’ rata aktar għolja ta ’ mutazzjonijiet assoċjati ma NRTI fid- doża ta ’ darba kuljum meta mqabbla mad- doża ta’ abacavir darbtejn kuljum.
No firm conclusion could be drawn due to the limited data derived from this study.
L- ebda konklużżjoni soda ma setgħet tkun deċiża minħabba n- nuqqas ta ’ informazzjoni li ħarget min dan l- istudju.
Long term data with abacavir used as a once daily regimen (beyond 48 weeks) are currently limited.
Informazzjoni fit- tul fuq abacavir użat darba kuljum (għal aktar min 48 ġimgħa) hija limitata bħalissa.
• Therapy experienced patients
• Pazjenti b’ esperjenza tat- terapija
In study CAL30001, 182 treatment-experienced patients with virologic failure were randomised and received treatment with either the fixed-dose combination of abacavir/ lamivudine (FDC) once daily or abacavir 300 mg twice daily plus lamivudine 300 mg once daily, both in combination with tenofovir and a PI or an NNRTI for 48 weeks.
Fl- istudju CAL30001, 182 pazjent b’ esperjenza tat- terapija u li kellhom indeboliment viroloġiku ġew randomised u ngħataw trattament b’ doża fissa ta ’ abacavir/ lamivudine (FDC) darba kuljum jew bi 300 mg abacavir darbtejn kuljum u 300 mg lamivudine darba kuljum, it- tnejn mgħotija flimkien ma ’ tenovir u PI jew NNRTI għal 48 ġimgħa.
Results indicate that the FDC group was non-inferior to the abacavir twice daily group, based on similar reductions in HIV-1 RNA as measured by average area under the curve minus baseline (AAUCMB, -1.65 log10 copies/ ml versus -1.83 log10 copies/ ml respectively, 95% CI -0.13, 0.38).
Ir- riżultati indikaw li l- grupp FDC ma kienux inferjuri għall- grupp li ħadu abacavir darbtejn kuljum, bażati fuq tnaqqis simili fl- HIV- 1 RNA kif imkejjel b’ żona medja taħt il- curve minus baseline (AAUCMB, - 1. 65 log10 kopji/ ml kontra - 1. 83 log10kopji/ ml rispettivament, 95% CI - 0. 13, 0. 38).
However, as there were only moderately experienced patients included in this study with an imbalance in baseline viral load between the arms, these results should be interpreted with caution.
Madankollu, billi kien hemm biss pazjenti b’ esperjenza moderata inklużi f’ dan l- istudju bi żbilanċ fil - baseline viral load bejn id- dirgħajn, dawn ir- riżultati għandhom ikun interpretati b’ ċerta kawtela.
Results indicate that the FDC group was associated with a similar virologic outcome (non-
Fl- istudju ESS30008, 260 pazjent b’ soppressjoni viroloġika fuq sistema ta ’ terapija first line bi 300 mg abacavir u 150 mg lamivudine, it- tnejn meħudin darbtejn kuljum flimkien ma ’ PI jew NNRTI, ġew randomised biex ikomplu b’ din is- sistema jew jaqilbu għal abacavir/ lamivudine FDC flimkien ma ’ PI 15 jew NNRTI għal 48 ġimgħa.
14 inferior) compared to the abacavir plus lamivudine group, based on proportions of subjects with HIV- 1 RNA < 50 copies/ ml (90% and 85% respectively, 95% CI -2.7, 13.5).
Ir- riżultati indikaw li l- grupp FDC kien assoċjat ma ’ riżultat viroloġiku simili mhux inferjuri, paragunat mall- grupp ta ’ abacavir u lamivudine, bażati fuq proporzjonijiet ta ’ individwi b ’ HIV- 1 RNA < 50 kopji/ ml (90% u 85% rispettivament, 95% CI - 2. 7, 13. 5).
Additional information:
• Aktar tagħrif
The safety and efficacy of Ziagen in a number of different multidrug combination regimens is still not completely assessed (particularly in combination with NNRTIs).
Is- sigurtà u l- effikaċja ta` Ziagen f`numru ta ’ kuri kombinati differenti għadhom s`issa ma ġewx mkejla għal kollox (l- aktar b`kombinazzjoni ma ’ NNRTIs).
Abacavir penetrates the cerebrospinal fluid (CSF) (see section 5.2), and has been shown to reduce HIV-1 RNA levels in the CSF.
Abacavir jidħol fil- fluwidu ċerebrospinali (CSF) (ara sezzjoni 5. 2), u deher li jnaqqas il- livelli ta` l - HIV- 1 RNA fis- CSF.
However, no effects on neuropsychological performance were seen when it was administered to patients with AIDS dementia complex.
Madanakollu, ma deheru l- ebda effetti fuq funzjonijiet newrofiżjoloġiċi meta ngħata lill- pazjenti bl- AIDS dementia complex.
Absorption: abacavir is rapidly and well absorbed following oral administration.
Assorbiment: abacavir jiġi assorbit malajr u tajjeb wara jittieħed mill- ħalq.
The absolute bioavailability of oral abacavir in adults is about 83%.
Il- biodisponibiltà totali ta` ta ’ abacavir orali fl- adulti huwa ta` madwar 83%.
Following oral administration, the mean time (tmax) to maximal serum concentrations of abacavir is about 1.5 hours for the tablet formulation and about 1.0 hour for the solution formulation.
Wara li jkun ingħata mill- ħalq, il- ħin medju (tmax) biex jintlaħqu konċentrazzjonijiet massimi ta’ abacavir fis- serum huwa ta` madwar 1. 5 sigħat għall - formulazzjoni tal- pilloli u madwar siegħa għas- soluzzjoni.
At therapeutic dosages a dosage of 300 mg twice daily, the mean (CV) steady state Cmax and Cmin of abacavir are approximately 3.00 μ g/ ml (30%) and 0.01 µg/ ml (99%), respectively.
F`dożi terapewtiċi (doża ta ’ 300 mg darbtejn kuljum) f`pazjenti, il- medji (CV) fissi Cmax and Cmin ta ’ abacavir fil- plażma kienu bejn wieħed u ieħor 3. 0 µg/ ml (30%), u 0. 01 µg/ ml (99%), rispettivament.
The mean (CV) AUC over a dosing interval of 12 hours was 6.02 μ g. h/ ml (29%), equivalent to a daily AUC of approximately 12.0 μ g. h/ ml.
(29%) ekwivalenti għal AUC ta ’ bejn wieħed u ieħor 12. 0μg. h/ ml kuljum.
The Cmax value for the oral solution is slightly higher than the tablet.
Il- valur Cmax għas- soluzzjoni orali hija ftit aktar għolja min dak tal- pilloli.
After a 600 mg abacavir tablet dose, the mean (CV) abacavir Cmax was approximately 4.26 μ g/ ml (28%) and the mean (CV) AUC ∞ was 11.95 μ g. h/ ml (21%).
Wara doża ta ’ pillola ta ’ 600mg ta ’ abacavir, il- medja Cmax ta ’ abacavir (CV) kien bejn wieħed u ieħor 4. 26μg/ ml (28%) u l- medja ta ’ AUC kien 11. 95μg. h/ ml (21%).
Food delayed absorption and decreased Cmax but did not affect overall plasma concentrations (AUC).
L- ikel irritarda l- assorbiment fil- ġisem u naqqas is- Cmax iżda ma effettwax il- konċentrazzjonjiet tal - plażma (AUC).
Therefore Ziagen can be taken with or without food.
Għalhekk Ziagen jista jittieħed kemm ma ’ l- ikel kif ukoll waħdu.
Administration of crushed tablets with a small amount of semi-solid food or liquid would not be expected to have an impact on the pharmaceutical quality, and would therefore not be expected to alter the clinical effect.
It- tehid ta ’ pilloli mfarrka b’ ammont żgħir ta ’ ikel semi- solidu jew likwidu ma jkunx mistenni li jħalli impatt fuq il- kwalita ’ farmaċewtika, u għalhekk ma jkunx mistenni li jbiddel l- effett kliniku.
This conclusion is based on the physiochemical and pharmacokinetic data, assuming that the patient crushes and transfers 100% of the tablet and ingests immediately.
Din il - konklużjuni hija bbażata fuq tagħrif dwar il- fiżjokimika u l- farmakokinetika meta wieħed jassumi li l - pazjent ifarrak u jittrassferixxi 100% tal- pillola u jeħodha mill- ewwel.
Distribution: following intravenous administration, the apparent volume of distribution was about 0.8 l/ kg, indicating that abacavir penetrates freely into body tissues.
Distribuzzjoni: wara li jkun ingħata fil- vina, il- volum ta` distribizzjoni apparenti kien ta` madwar 0. 8 l/ kg, li juri li abacavir jidħol liberament fit- tessuti tal- ġisem.
Studies in HIV infected patients have shown good penetration of abacavir into the cerebrospinal fluid (CSF), with a CSF to plasma AUC ratio of between 30 to 44%.
Studji li saru fuq pazjenti nfettati bl- HIV urew li abacavir jidħol sew fil- fluwidi ċerebrospinali (CSF), bil- proporzjon (AUC) ta ’ CSF għal plażma ta` bejn 30 u 44%.
The observed values of the peak concentrations are 9 fold greater than the IC50 of abacavir of 0.08 µg/ ml or 0.26 µM when abacavir is given at 600 mg twice daily.
Il- valuri osservati ta` l- ogħla konċentrazzjonijiet huma 9 darbiet akbar mill- IC50 ta ’ abacavir ta` 0. 08 µg/ ml jew 0. 26 µM meta tingħata doża ta’ abcavir ta ’ 600mg darbtejn kuljum.
Plasma protein binding studies in vitro indicate that abacavir binds only low to moderately (~49%) to human plasma proteins at therapeutic concentrations.
Studji in vitro dwar kemm jeħel mal- proteini tad- demm juru li abacavir jeħel ftit biss għal moderat (~49%) mal proteini tal- plażma umana f`konċentrazzjonijiet terapewtiċi.
This indicates a low likelihood for interactions with other medicinal products through plasma protein binding displacement.
Dan jindika possibiltà baxxa ta ’ interazzjonijiet ma ’ prodotti mediċinali oħra permezz ta ’ spostament minn mal- proteini tal- plażma.
Metabolism: abacavir is primarily metabolised by the liver with approximately 2% of the administered dose being renally excreted, as unchanged compound.
Metaboliżmu: abacavir huwa primarjament metabolizzat mill- fwied u bejn wieħed u ieħor 2% tad - doża li tingħata titneħħa mill- ġisem permezz tal- kliewi, bħala sustanza mhux mibdula.
The primary pathways of metabolism in man are by alcohol dehydrogenase and by glucuronidation to produce the 5’ -carboxylic acid and 5’ - glucuronide which account for about 66% of the administered dose.
Ir- rottot tal - metaboliżmu prinċipali fil- bnedmin huwa bl- alcohol dehydrogenase u b`glucuronidation sabiex jiproduċi l- 5 ’ - carboxylic acid u 5 ’ - glucuronide li jirrappreżentaw 66% tad- doża li tkun ittieħdet.
The metabolites are excreted in the urine.
Is - sustanzi ffurmati joħorġu mill- urina.
Elimination: the mean half-life of abacavir is about 1.5 hours.
Eliminazzjoni: il- medja tal- half- life ta ’ abacavir hija madwar 1. 5 sigħat.
Following multiple oral doses of abacavir 300 mg twice a day there is no significant accumulation of abacavir.
Wara diversi dożi ta ’ abacavir mill- ħalq ta` 300mg darbtejn kuljum ma` jkunx hemm akkumulazzjoni sinifikanti ta ’ abcavir.
Elimination of abacavir is via hepatic metabolism with subsequent excretion of metabolites primarily in the urine.
It - tneħħija mil- ġisem ta ’ abacavir issir b’ metaboliżmu fil- fwied u s- sustanzi li jiffurmaw jitneħħew
The metabolites and unchanged abacavir account for about 83% of the administered abacavir dose in the urine.
Is- sustanzi ffurmati mill- metaboliżmu u l- abacavir mhux mibdul fl- urina jilħqu it- 83% mid- doża li tingħata.
The remainder is eliminated in the faeces.
Il- bqija jitneħħa fl- ippurgar.
15 Intracellular pharmacokinetics
Farmakokinetiċi intraċellulari
In a crossover study in 27 HIV-infected patients, intracellular carbovir-TP exposures were higher for the abacavir 600 mg once daily regimen (AUC24, ss + 32%, Cmax24, ss + 99% and Ctrough + 18%) compared to the 300 mg twice daily regimen.
Fi studju crossover f’ 27 pazjent infettat bl- HIV, espożizzjoni għal carbovir- TP ġewwa ċ- ċellola kienu aktar għoljin għas- sistema ta ’ kura b’ abacavir 600mg darba kuljum (AUC24, ss + 32%, Cmax 24, ss + 99% u C trough + 18%) meta mqabbla mas- sistema ta ’ kura ta ’ 300mg darbtejn kuljum.
Overall, these data support the use of abacavir 600 mg once daily for the treatment of HIV infected patients.
Kollox ma ’ kollox dan it- tagħrif jiffavorixxi l- użu ta ’ 300 mg lamivudine u 600 mg abacavir darba kuljum għall- kura ta ’ pazjenti nfettati bl- HIV.
Additionally, the efficacy and safety of abacavir given once daily has been demonstrated in a pivotal clinical study (CNA30021- See section 5.1 Clinical experience).
Barra dan, l- effikaċja u s- sigurtà ta ’ abacavir darba kuljum intweriet fi studju kliniku ta ’ importanza kbira (CNA30021 – Ara sezzjoni 5. 1 Esperjenza klinika).
Special populations
Gruppi speċjali:
Hepatically impaired: abacavir is metabolised primarily by the liver.
Indeboliment epatiku: abacavir huwa primarjament metabolizzat mill- fwied.
The results showed that there was a mean increase of 1.89 fold [1.32; 2.70] in the abacavir AUC, and 1.58 [1.22; 2.04] fold in the elimination half-life.
Ir- riżultati wrew li kien hemm żieda medja ta` 1. 89- il darba [1. 32; 2. 70] f' l- AUC ta ’ abacavir, u ta ’ 1. 58- il darba [1. 22; 2. 04] fil- half- life ta ’ l- eliminazzjoni mill- ġisem.
No recommendation on dosage reduction is possible in patients with mild hepatic impairment due to the substantial variability of abacavir exposure.
Ma tistgħax tingħata rakkomandazzjoni għal tnaqqis fid- doża f`pazjenti li jbgħatu minn indeboliment epatiku ħafif minħabba l- varjazzjoni sostanzjali fl- esponiment għal abcavir.
Renally impaired: abacavir is primarily metabolised by the liver with approximately 2% of abacavir excreted unchanged in the urine.
Indeboliment renali: abacavir huwa primarjament metabolizzat mill- fwied u bejn wieħed u ieħor 2% ta ’ abacavir jitneħħa mingħajr ma jinbidel fl- urina.
Therefore no dosage reduction is required in patients with renal impairment.
Għalhekk m`hemmx bżonn ta` tnaqqis fid- dożaġġ f`pazjenti li jbgħatu minn indebboliment renali.
Based on limited experience Ziagen should be avoided in patients with end-stage renal disease.
Minħabba esperjenza limitata, Ziagen għandu jiġi evitat f`pazjenti fl- aħħar stadju ta ’ mard renali.
Children: according to clinical trials performed in children abacavir is rapidly and well absorbed from an oral solution administered to children.
Tfal: skond studji kliniċi li saru f’ tfal, abacavir huwa assorbit tajjeb u malajr minn soluzzjoni orali u li tingħata lit- tfal.
The overall pharmacokinetic parameters in children are comparable to adults, with greater variability in plasma concentrations.
B’ kollox il- parametri farmakokinetiċi fit- tfal huma komparabli ma ’ ta ’ l- adulti, b`varjabilità akbar f’ konċentrazzjonijiet tal- plażma.
The recommended dose for children from three months to 12 years is 8 mg/ kg twice daily.
Id- doża rakkomandata għal tfal minn tlett xhur sa 12- il sena hija 8mg/ kg darbtejn kuljum.
This will provide slightly higher mean plasma concentrations in children, ensuring that the majority will achieve therapeutic concentrations equivalent to 300 mg twice daily in adults.
Din tipprovdi medja daqxejn akbar ta` konċentrazzjonijiet fil - plażma tat- tfal, li tiżgura li f`ħafna minnhom jintlaħqu konċentrazzjonijiet terapewtiċi ekwivalenti għal 300 mg darbtejn kuljum fl- adulti.
There are insufficient safety data to recommend the use of Ziagen in infants less than three months old.
M’ hemmx biżżejjed tagħrif dwar is- sigurtà ta` Ziagen f’ trabi ta ’ anqas minn tlett xhur.
The limited data available indicate that a dose of 2 mg/ kg in neonates less than 30 days old provides similar or greater AUCs, compared to the 8 mg/ kg dose administered to older children.
It- tagħrif limitat li hemm jindika li doża ta ’ 2 mg/ kg fi trabi li għadhom kemm twieldu u li għandhom anqas minn xahar tipprovdi l- istess jew akbar AUCs, meta mqabbla ma ’ doża ta` 8 mg/ kg mogħtija lil tfal akbar.
Elderly: the pharmacokinetics of abacavir have not been studied in patients over 65 years of age.
Anzjani: il- farmakokinetika ta ’ abacavir ma ġietx studjata f`pazjenti ‘ l fuq minn 65 sena.
Abacavir was not mutagenic in bacterial tests but showed activity in vitro in the human lymphocyte chromosome aberration assay, the mouse lymphoma assay, and the in vivo micronucleus test.
Abacavir ma kienx mutaġeniku f`testijiet batteriċi li saru iżda wera attività in vitro fil- lymphocyte chromosome aberration assay umana, fil- lymphoma assay tal- ġurdien, u l- in vivo micronucleus test.
This is consistent with the known activity of other nucleoside analogues.
Dan huwa konsistenti ma ’ l- attività magħrufa t`analogi tan- nuklejosajds oħra.
These results indicate that abacavir has a weak potential to cause chromosomal damage both in vitro and in vivo at high test concentrations.
Dawn ir- riżultati jindikaw li abacavir għandu potenzjal dgħajjef li jikkawża ħsara fil- kromożomi kemm in vitro kif ukoll in vivo f`testijiet b’ konċentrazzjonijiet għolja.
Carcinogenicity studies with orally administered abacavir in mice and rats showed an increase in the incidence of malignant and non-malignant tumours.
Studji dwar il- karċinoġeniċità ta ’ abacavir orali f’ ġrieden u firien urew żieda ta ’ inċidenza ta` tumuri malinni kif ukoll mhux malinni.
Malignant tumours occurred in the preputial gland of males and the clitoral gland of females of both species, and in rats in the thyroid gland of males and the liver, urinary bladder, lymph nodes and the subcutis of females.
17 fil- glandola tat- tirojde, u fil- fwied, fil- bużżieqa ta ’ l- urina, fil- glandoli żgħar limfatiċi u fis- subkute tal- firien femminili.
The majority of these tumours occurred at the highest abacavir dose of 330 mg/ kg/ day in mice and 600 mg/ kg/ day in rats.
Il- parti l- kbira ta` dawn it- tumuri ħarġu waqt li kienet qed tingħata l- aktar doża għolja ta ’ abacavir ta` 330 mg/ kg/ kuljum fil- ġrieden u 600 mg/ kg/ kuljum fil- firien.
The systemic exposure at the no effect level in mice and rats was equivalent to 3
L- eċċezzjoni kienet fil- każ tat- tumur tal - glandola prepuzzjali li deher f`doża ta` 110 mg/ kg fil- ġrieden.
16 and 7 times the human systemic exposure during therapy.
L- esponiment tas- sistema għall- livell ta ’ bla effett fil- ġrieden u fil- firien kienet ekwivalenti għal minn 3 u 7 darbiet ta` l- esponiment sistemiku uman li jkun hemm waqt it- terapija.
While the carcinogenic potential in humans is unknown, these data suggest that a carcinogenic risk to humans is outweighed by the potential clinical benefit.
Filwaqt li l- potenzjal karċinoġeniku fil- bnedmin mhux magħruf, dan it- tagħrif tindika li r- riskju ta` karċinoġeniċità fil- bnedmin huwa anqas mill- potenzjal tal - benefiċċju kliniku.
In pre-clinical toxicology studies, abacavir treatment was shown to increase liver weights in rats and monkeys.
Studji tossikoloġiċi li saru qabel l- użu kliniku, urew li l- kura b’ abacavir kabbar il- piż tal- fwied fil - firien u x- xadini.
The clinical relevance of this is unknown.
Ir- relevanza klinika ta` dan mhiex magħrufa.
Additionally, autoinduction of abacavir metabolism or induction of the metabolism of other medicinal products hepatically metabolised has not been observed in man.
Minbarra hekk, awto- induzzjoni tal- metaboliżmu ta ’ abacavir jew l- induzzjoni tal- metaboliżmu ta` xi prodotti mediċinali oħra ma ġewx osservati fil - bniedem.
The systemic exposures were equivalent to 7 to 24 times the expected systemic exposure in humans.
L- esponimenti sistemiċi kienu ekwivalenti għal 7 sa 24 darba ta` l- esponiment sistemiku li jkun mistenni fil- bnedmin.
The clinical relevance of this finding has not been determined.
Ir- relevanza klinika ta`dan l- istħarriġ għadu ma ġiex determinat.
In reproductive toxicity studies, embryo and foetal toxicity have been observed in rats but not in rabbits.
Fi studji tossiċi dwar ir- reproduttività, kein hemm effett tossiku fuq l- embriju u l- fetu fil- firien iżda mhux fil- fniek.
These findings included decreased foetal body weight, foetal oedema, and an increase in skeletal variations/ malformations, early intra-uterine deaths and still births.
Dawn is- sejbiet kienu jinkludu tnaqqis fil- piż tal- fetu, edima tal- fetu, u żieda f’ varjazzjonijiet/ malformazzjonijiet skeletriċi, mwiet prematuri fil- ġuf u trabi li jitwieldu mejta.
A fertility study in the rat has shown that abacavir had no effect on male or female fertility.
Fi studju fuq il- fertilità tal- firien ntwera li abacavir ma kellu l- ebda effett fuq il- fertilita` ta ’ l- annimali maskili u femminili.
Microcrystalline cellulose Sodium starch glycollate Magnesium stearate Colloidal anhydrous silica
Microcrystalline cellulose Sodium starch glycollate Magnesium stearate Colloidal anhydrous silica
Triacetin Methylhydroxypropylcellulose Titanium dioxide Polysorbate 80 Iron oxide yellow
Triacetin Methylhydroxypropylcellulose Titanium dioxide Polysorbate 80 Iron oxide yellow
Do not store above 30°C
Taħżinx f`temperatura `l fuq minn 30°C
6.5 Nature and contents of container
18 6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
Polyvinyl chloride/ foil blister packs containing 60 tablets.
Il- pilloli Ziagen issibhom f’ pakketti ta ’ polyvinyl chloride/ foil li fihom 60 pillola.
8 July 1999
Data ta ’ l- ewwel awtorizzazzjoni: 8 Lulju - 1999
8 July 2004
Data ta ’ tiġdid: 8 Lulju – 2004
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu
Informazzjoni ddettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il - mediċini (EMEA) http: // www. emea. europa. eu / >
Ziagen 20 mg/ ml oral solution
Ziagen 20 mg/ ml soluzzjoni li tittieħed mill- ħalq
Oral solution containing 20 mg/ ml of abacavir (as sulfate).
Likwidu li jittieħed mill- ħalq li fih doża ta ’ 20 mg/ ml ta’ abacavir.
Sorbitol (E420)340 mg/ ml Methyl parahydroxybenzoate (E218) 1.5 mg/ ml Propyl parahydroxybenzoate (E216) 0.18 mg/ ml
Sorbitol (E420) 340mg/ ml Methyl parahydroxybenzoate (E218) 1. 5mg/ ml Propyl parahydroxybenzoate (E216) 0. 18mg/ ml
Oral solution
Likwidu li jittieħed mill- ħalq.
The oral solution is clear to slightly opalescent yellowish, aqueous solution.
Din hija soluzzjoni ċara jew kemkem imdardra fl- isfar, jiddi bħafna ilwien.
The demonstration of the benefit of Ziagen is mainly based on results of studies performed in treatment-naïve adult patients on combination therapy with a twice daily regimen (see section 5.1).
Il- benefiċċju għall- użu ta` Ziagen huwa bbażat ħafna minn riżultati li ħarġu minn studji fuq pazjenti adulti li qatt ma ħadu din it- tip ta ’ kura qabel u li bdew jieħdu terapija kombinata darbtejn kuljum (ara sezzjoni 5. 1).
Adults and adolescents: the recommended dose of Ziagen is 600 mg daily (30 ml).
Id- doża rakkomandata ta` Ziagen hija 600mg kuljum (30ml).
This may be administered as either 300 mg (15 ml) twice daily or 600 mg (30 ml) once daily (see sections 4.4 and 5.1).
Din tista ’ tingħata jew 300 mg (15ml) darbtejn kuljum jew 600mg (30ml) darba kuljum (ara sezzjoni 4. 4 u 5. 1).
Patients changing to the once daily regimen should take 300 mg (15 ml) twice a day and switch to 600 mg (30 ml) once a day the following morning.
Pazjenti li jaqilbu fuq is- sistema ta ’ darba kuljum, għandhom jieħdu 300mg darbtejn kuljum u jaqilbu fuq 600mg darba kuljum ‘ l għada filgħodu.
Where an evening once daily regimen is preferred, 300 mg (15 ml) of Ziagen should be taken on the first morning only, followed by 600 mg (30 ml) in the evening.
Meta is- sistema ta ’ darba kuljum filgħaxija tkun ippreferuta, 300mg ta ’ Ziagen għandhom jittieħdu biss fl- ewwel għodwa, imbagħad jittieħdu 600mg filgħaxija.
When changing back to a twice daily regimen, patients should complete the day's treatment and start 300 mg (15 ml) twice a day the following morning.
Meta terġa taqleb għas- sistema ta ’ darbtejn kuljum, il- pazjenti għandhom jispiċċaw it - trattament tal- ġurnata u jibdew jieħdu 300mg darbtejn kuljum minn l- għada filgħodu
Children from three months to 12 years: the recommended dose is 8 mg/ kg twice daily up to a maximum of 600 mg (30 ml) daily.
Id- doża rakkomandata hija 8 mg/ kg darbtejn kuljum għal massimu ta` 600 mg kuljum.
19 Children less than three months: the data available on the use of Ziagen in this age group are very limited (see section 5.2).
L- informazzjoni fuq l- użu ta` Ziagen f`din il- kategorija ta ’ età huma limitati ħafna (ara sezzjoni 5. 2).
Ziagen can be taken with or without food.
20 Ziagen jista jittieħed ma ’ l- ikel kif ukoll waħdu.
Ziagen is also available as a tablet formulation.
Ziagen jinstab ukoll bħala pilloli.
Ziagen is contraindicated in patients with known hypersensitivity to the active substance or to any of the excipients.
Ziagen m`għandux jingħata lill- pazjenti li jbgħatu minn sensittività eċċessiva għas- sustanza attiva jew għall xi sustanzi mhux attivi tal- pilloli Ziagen.
See BOXED INFORMATION ON HYPERSENSITIVITY REACTIONS in sections 4.4. and 4.8.
Ara L- KAXXA TA`L- INFORMAZZJONI FUQ REAZZJONIJIET TA ’ SENSITTIVITÀ EĊĊESSIVA f`sezzjonijiet 4. 4. u 4. 8.
In clinical studies approximately 5% of subjects receiving abacavir develop a hypersensitivity reaction; some of these cases were life-threatening and resulted in a fatal outcome despite taking precautions.
Fi studji kliniċi li saru nstab li bejn wieħed u ieħor ir- rata ta` 5% tal- pazjenti li rċevew abacavir żviluppaw reazzjonijiet ta ’ sensittività eċċessiva; xi wħud minn dawn il- każijiet kienu ta` periklu għall- ħajja u kienu fatali minkejja li ttieħdu prekawzjonijiet.
Skin patch testing was used as a research tool for the PREDICT-1 study but has no utility in the clinical
Gew użati testijiet fuq roqgħa tal- ġilda bħala għodda ta ’ riċerka għall- istudju PREDICT- 1,
20 management of patients and therefore should not be used in the clinical setting.
21 madankollu ma kellhom l- ebda użu fl- imaniġġjar kliniku tal- pazjenti u għalhekk m’ għandhomx jintużaw fl- isfond kliniku.
Other signs and symptoms may include respiratory signs and symptoms such as dyspnoea, sore throat, cough and abnormal chest x-ray findings (predominantly infiltrates, which can be localised), gastrointestinal symptoms, such as nausea, vomiting, diarrhoea, or abdominal pain, and may lead to misdiagnosis of hypersensitivity as respiratory disease (pneumonia, bronchitis, pharyngitis), or gastroenteritis.
Sinjali u sintomi oħra jistgħu jinkludu sinjali u sintomi respiratorji bħall- qtugħ ta ’ nifs, uġigħ tal - griżem, sogħla kif ukoll riżultati abnormli fuq x- ray tas- sider (il- parti l- kbira infiltrati, li jistgħu jiġu lokaliżżati), sintomi gastrointestinali, bħal dardir, rimettar, dijarrea, jew uġigħ addominali, u jistgħu jwasslu għal dijanjożi ħażina ta ’ sensittività eċċessiva bħal mard respiratorju (pulmonite, bronkite, farinġite), jew gastro- enterite.
Other frequently observed signs or symptoms of the hypersensitivity reaction may include lethargy or malaise and musculoskeletal symptoms (myalgia, rarely myolysis, arthralgia).
Sinjali u sintomi oħra li dehru fir- reazzjonijiet ta` sensittività eċċessiva jistgħu jinkludu letarġija jew ħass ħażin u sintomi muskolu- skeletriċi (majalġja, rarament mijoliżi, artralġja).
Hypersensitivity reaction symptoms usually appear within the first six weeks of initiation of treatment with abacavir, although these reactions may occur at any time during therapy.
Ir- reazzjonijiet ta` sensittività eċċessiva normalment joħorġu fl- ewwel sitt ġimgħat mill- bidu tal- kura b` abacavir, għalkemm dawn ir- reazzjonijiet jistgħu joħorġu f`kull żmien matul it- terapija.
Patients should be monitored closely, especially during the first two months of treatment with Ziagen, with consultation every two weeks.
Il - pazjenti għandhom ikunu taħt osservazzjoni mill- viċin, b`mod speċjali matul l- ewwel xaharejn tal - kura b`Ziagen, u għandhom jingħataw pariri kull ġimgħatejn.
Kivexa, Trizivir), MUST NEVER be restarted in patients who have stopped therapy due to a hypersensitivity reaction.
Kivexa, Trizivir), M`GĦANDU QATT jerġa jingħata lill- pazjenti li jkunu waqqfu t- terapija minħabba sensittività eċċessiva.
This recurrence is usually more severe than on initial presentation, and may include life-threatening hypotension and death.
Din ir- rikkorrenza normalment hija aktar severa mill - ewwel waħda, u tista tinkludi ipotensjoni li tkun ta ’ periklu għall- ħajja kif ukoll tista twassal għal mewt.
To avoid a delay in diagnosis and minimise the risk of a life-threatening hypersensitivity reaction, Ziagen must be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible (respiratory diseases, flu-like illness, gastroenteritis or reactions to other medications).
Sabiex tevita dewmien tad- dijanjożi u tnaqqas ir- riskju ta` reazzjoni ta` sensittività eċċessiva ta` periklu għall- ħajja, Ziagen għandu jitwaqqaf kif ikun hemm dubju ta ’ sensittività eċċessiva, ukoll meta jkun hemm possibiltà ta` dijanjożi oħra (mard respiratorju, mard simili għal dak ta` l- influwenza, gastro- enterite jew reazzjonijiet għal mediċini oħra).
Special care is needed for those patients simultaneously starting treatment with Ziagen and other medicinal products known to induce skin toxicity (such as non-nucleoside reverse transcriptase inhibitors - NNRTIs).
(bħal inibituri non- nuklejosajd reverse transcriptase - NNRTIs).
This is because it is currently difficult to differentiate between rashes induced by these products and abacavir related hypersensitivity reactions.
Dan minħabba l- fatt li fil- preżent huwa diffiċli sabiex tagħmel distinzjoni bejn raxx li ħareġ minħabba dawn il- prodotti u reazzjonijiet ta` sensittività eċċessiva relatati m`abacavir.
If therapy with Ziagen has been discontinued for any reason and restarting therapy is under consideration, the reason for discontinuation must be established to assess whether the patient had any symptoms of a hypersensitivity reaction.
Jekk it- terapija b`Ziagen kienet twaqqfet minħabba xi raġuni jew oħra u aktarx terġa tinbeda, għandu jiġi stabbilit għall- liema raġuni kienet twaqqfet it- terapija sabiex jiġi stabbilit jekk il- pazjent kellux xi sintomi ta ’ sensittività eċċessiva.
Hypersensitivity reactions with rapid onset, including life-threatening reactions have occurred after restarting Ziagen in patients who had only one of the key symptoms of hypersensitivity (skin rash, fever, gastrointestinal, respiratory or constitutional symptoms such as lethargy and malaise) prior to stopping Ziagen.
22 Attakk qawwi u mgħaġġel ta` sensittività eċċessiva, li jinkludi reazzjonijiet ta` perikli għall - ħajja deher wara li reġa ’ ingħata Ziagen f`pazjenti li kellhom biss wieħed mis- sintomi ewlenin ta` sensittività eċċessiva (sintomi ta ’ raxx tal- ġilda, deni, sintomi gastrointestinali, respiratorji jew konstituzzjonali bħal letarġija u ħass ħażin) qabel ma twaqqaf Ziagen.
Moreover, on very rare occasions hypersensitivity reactions have been reported in patients who have restarted therapy, and who had no preceding symptoms of a hypersensitivity
Fuq kollox, okkażjonijiet rari ta` reazzjonijiet ta` sensittività eċċessiva dehru f`pazjenti li reġgħu bdew it- terapija, u li ma kellhom l- ebda sintomu qabel ta` reazzjoni ta` sensittività eċċessiva.
Prescribers must ensure that patients are fully informed regarding the following information on the hypersensitivity reaction:
Min jagħti dan il- prodott għandu jkun fiż- żgur li l- pazjenti jingħataw it- tagħrif kollu meħtieġ fuq ir- reazzjonijiet ta` sensittività eċċessiva:
Kivexa, Trizivir)
Kivexa Trizivir).
reactions or illness, must be advised to contact their doctor before restarting.
possibiltà ta` reazzjonijiet mhux mixtieqa jew mard, għandu jingħatalhom parir biex jinfurmaw lit- tabib qabel ma jerġgħu jibdewh.
They
- għandha tinġibed l- attenzzjoni tal- pazjenti sabiex jaqraw il- fuljett ta` tagħrif li jinstab fil -
should be reminded of the importance of removing the Alert Card included in the pack, and keeping it with them at all times.
Għandhom ikunu mfakkra bl- importanza li jneħħ l- Alert Card li tkun inkluża fil- pakkett u jżommuha dejjem fuqhom.
Lactic acidosis: lactic acidosis, usually associated with hepatomegaly and hepatic steatosis, has been reported with the use of nucleoside analogues.
23 Aċidożi lattika: aċidożi lattika, ħafna drabi assoċjata ma ’ ħepatomegalija u stejatożi epatika, deheret bl- użu ta` analogi tan- nuklejosajd.
Lactic acidosis has a high mortality and may be associated with pancreatitis, liver failure, or renal failure.
Aċidożi lattika għandha rata għolja ta` mortalità u din tista tkun assoċjata ma ’ pankrejatite, ħsara fil - fwied, jew ħsara tal- kliewi.
Treatment with nucleoside analogues should be discontinued in the setting of symptomatic hyperlactatemia and metabolic/ lactic acidosis, progressive hepatomegaly, or rapidly elevating aminotransferase levels.
Kura b`analogi tan- nuklejosajd għandu jitwaqqaf meta jkun hemm iperlaktejtimja sintomatika u aċidożi lattika metabolika, epatomegalija progressiva, jew meta l- livell ta ’ emajnotransferejż jitla ’ malajr.
Caution should be exercised when administering nucleoside analogues to any patient (particularly obese women) with hepatomegaly, hepatitis or other known risk factors for liver disease and hepatic steatosis (including certain medicinal products and alcohol).
Għandha tingħata attenzjoni waqt l- użu ta ’ analogi tan- nuklejosajd lill- kull pazjent (b`mod speċjali lil nisa obeżi) b`epatomegalija, epatite jew xi fatturi ta ’ riskju oħra magħrufa għall- mard tal- fwied u stejatożi epatika (li jinkludi ċerti prodotti mediċinali u alkoħol).
The main adverse events reported are haematological disorders (anaemia, neutropenia), metabolic disorders (hyperlactatemia, hyperlipasemia).
L- effetti avversi l- aktar komuni li kienu rrapurtati jinkludu mard ematoloġiku (anemija, newtropenja) u mard metaboliku (iperlaktimja, iperlipejżemja).
Whether the
Xi mard newroloġiku li deher iktar tard ġie rrapurtat (ipertonja, aċċessjoni, imġieba mhux normali).
22 neurological disorders are transient or permanent is currently unknown.
Bħalissa għadu mhux mgħaruf jekk dan il- mard newroloġiku jgħaddix maż- żmien jew huwiex permanenti.
Triple nucleoside therapy: in patients with high viral load (> 100,000 copies/ ml) the choice of a triple combination with abacavir, lamivudine and zidovudine needs special consideration (see section 5.1).
Terapija triplika bin- nukleosidi: f`pazjenti b` viral load għoli (> 100, 000 copies\ ml) għandha tkun kunsidrata b’ mod speċjali l- għażla ta` kombinazzjoni tripla b`abacavir, lamivudine u zidovudine. (ara 5. 1).
Once daily administration (abacavir 600 mg): the benefit of abacavir as a once daily regimen is mainly based on a study performed in combination with efavirenz and lamivudine, in antiretroviral- naïve adult patients (see section 5.1).
24 Doża ta ’ darba kuljum (ta ’ abacavir 600mg): il- vantaġġ ta ’ abacavir f’ doża ta ’ darba kuljum huwa bbażat fuq studju li sar f’ kumbinazzjoni ma ’ efavirenz u lamiduvine, f’ pazjenti adulti naΐve għal kura antiretrovirali (ara sezzjoni 5. 1).