qanastek/EMEA-V3 huggingface dataset:
Adverse reactions reported with the individual components of Trizivir
Rapporti ta 'reazzjonijiet avversi ma' komponenti individwali ta ’ Trizivir (Reazzjonijiet avversi li jkunu seħħew mill- inqas f' 5% tal- pazjenti jidhru b' tipi grassi)
Uncommon: neutropenia, anaemia (both occasionally severe), thrombocytopenia Very rare: pure red cell aplasia
Mhux komuni: newtropenja, anemija (it- tnejn kultant qawwijin) tromboċitopenja Rari ħafna: aplasia ta ’ ċelluli ħomor puri
Common: anaemia, neutropenia and leucopenia Uncommon: thrombocytopenia and pancytopenia with marrow hypoplasia Rare: pure red cell aplasia Very rare: aplastic anaemia
Komuni: anemija, newtropenija u lewkopenija Mhux komuni: tromboċitopenija u panċitopenija b’ hypoplasia tal- mudullun.
Metabolism and nutrition disorders
Rari: aplasia ta 'ċelluli ħomor puri Rari ħafna: anemija aplastika.
Rare: anorexia, lactic acidosis in the absence of hypoxaemia
Disturbi fis- sistema immuni Komuni: sensittivita ’ eċċessiva
Very rare: peripheral neuropathy (paraesthesiae)
Disturbi fil- metaboliżmu u n- nutrizzjoni Komuni: anoressija Disturbi psikjatrċi Disturbi fis- sistema nervuża
Common: dizziness Rare: insomnia, paraesthesia, somnolence, loss of mental acuity, convulsions
Rari: anoressija, aċidożi lattika fl- assenza ta ’ nuqqas ta ’ ossiġnu Rari: ansjeta ’, depressjoni
Rare: cardiomyopathy
Komuni: ugigħ ta ’ ras
Respiratory, thoracic and mediastinal disorders
Komuni: ugigħ ta ’ ras, insomnja.
12
Rari ħafna: newropatija periferali( paresteżija) 12
Common: cough, nasal symptoms
Komuni ħafna: uġigħ ta ’ ras.
Uncommon: dyspnoea Rare: cough
Komuni: sturdament Rari: insomnja, paresteżija, ħafna ngħas,,
Gastrointestinal disorders
nuqqas ta ’ akutezza mentali, konvulżjonijiet.
Common: nausea, vomiting, Common: nausea, vomiting,
Komuni: sogħla, sintomi fl- imnieħer
Nausea
Mhux komuni: qtigħ ta ’ nifs Rari: sogħla
diarrhoea Rare: pancreatitis
Komuni: tqallih, rimettar, dijarea Rari: pankrejatite
abdominal pain, diarrhoea Rare: rises in serum amylase, pancreatitis
Komuni: tqallih, rimettar, uġigħ ta ’ żaqq, dijarea Rari: żieda fl- amylase tas - serum u pankrejatite
Common: vomiting, abdominal pain, and diarrhoea Uncommon: flatulence Rare: oral mucosa pigmentation, taste disturbance dyspepsia, pancreatitis
Komuni ħafna: tqallih Komuni: rimettar, uġigħ ta ’ żaqq, dijarea Mhux komuni: uġigħ mill - gass fl- istonku Rari: pigmentazzjoni tal - mukoża tal- ħalq, disturbi fit- togħma, pankrejatite.
Uncommon: transient rises in liver enzymes (AST, ALT) Rare: hepatitis
Mhux komuni: żieda fl - enzimi tal- fwied u l - bilirubina
Common: raised blood levels of liver enzymes and bilirubin Rare: liver disorders such as severe hepatomegaly with steatosis,
Komuni: żieda fil- livelli ta ’ enżimi tal- fwied u bilirubina Rari: disturbi fil- fwied bħal- epatomegalija bi steatożi
Common: rash (without systemic symptoms) Very rare: erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Komuni: raxx, (mingħajr sintomi sistemiċi) Rari ħafna: eritema multiformi, sindromu ta ’ Stevens- Johnson u nekroliżi tossika epidermali
Common: rash, alopecia
Komuni: raxx, alopeċja
Uncommon: rash and pruritus Rare: nail and skin pigmentation, urticaria and sweating
Mhux komuni: raxx u prurite Rari: pigmentazzjoni tad - dwiefer u l- ġilda, urtikarja u għaraq
Common: arthralgia, muscle disorders Rare: rhabdomyolysis
Komuni: artralġja, disturbi fil- muskoli Rari: rabdomijolożi
Rare: urinary frequency
Komuni: mijalġja Mhux komuni: mijopatija
Reproductive system and breast disorders
Disturbi fil- kliewi u fis- sistema urinarja Rari: awrinar ta ’ spiss Disturbi fis- sistema riproduttiva u fis- sider Rari: ġinekomastja Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata Komuni: deni, letarġija, għeja
Common: fever, lethargy, fatigue
Komuni: għeja, ma tħossokx f’ siktek, deni
Common: fatigue, malaise, fever
Komuni: ma tħossokx f’ siktek, Mhux komuni: deni, uġigħ ma ’ kullimkien u astenja.
Common: malaise Uncommon: fever, generalised pain and asthenia Rare: chills, chest pain, and influenza-like syndrome
Rari: ksieħ, uġigħ fis- sider u sindromu jixbaħ l - influwenza.
Adverse reactions associated with
Reazzjonijiet avversi assoċjati ma 'abacavir:
13 Many of the adverse reactions listed above occur commonly (nausea, vomiting, diarrhoea, fever, lethargy, rash) in patients with abacavir hypersensitivity.
Ħafna mir- reazzjonijiet avversi elenkati hawn fuq (tqallih, rimettar, dijarea, deni, ngħas, raxx) huma komuni f' pazjenti b' sensittivita 'eċċessiva għal abacavir.
Therefore, patients with any of these symptoms should be carefully evaluated for the presence of this hypersensitivity reaction.
Għalhekk, pazjenti b' dawn is- sintomi għandhom jiġu analizzati sew għall- preżenza ta 'xi reazzjoni ta' sensittivita 'eċċessiva.
If Trizivir has been discontinued in patients due to experiencing any one of these symptoms and a decision is made to restart a medicinal product containing abacavir, this must be done in a setting where medical assistance is readily available (see Section 4.4).
Jekk Trizivir ikun twaqqaf f' xi pazjenti minħabba xi sintomi minn dawn u tittieħed deċiżjoni biex jerġgħu jibdew jieħdu xi prodott mediċinali li jkun fih abacavir, dan għandu jsir f' sitwazzjoni fejn ikun hemm
Very rarely cases of erythema multiforme, Stevens Johnson syndrome or toxic epidermal necrolysis have been reported where abacavir hypersensitivity could not be ruled out.
Każi rari ħafna ta 'eritema multiformi, tas- sindromu ta ’ Stevens- Johnson jew ta' nekroliżi tossika tal- ġilda li dwarhom is- sensittivita 'eċċessiva għal abacavir ma tistax tiġi eliminata.
In such cases medicinal products containing abacavir should be permanently discontinued.
F' każi bħal dawn prodotti mediċinali li jkun fihom abacavir għandhom jitwaqqfu darba għal dejjem.
Haematological adverse reactions with zidovudine
Reazzjonijiet avversi fid- demm b’ zidovudine
Anaemia, neutropenia and leucopenia occurred more frequently at higher dosages (1200-1500 mg/ day) and in patients with advanced HIV disease (especially when there is poor bone marrow reserve prior to treatment) and particularly in patients with CD4 cell counts less than 100/ mm3.
Anemija, newtropenja u lewkopenja seħħew aktar spiss f' dożaġġi għolja (1200- 1500 mg kuljum) u f' pazjenti bil- disturbia ta ’ HIV avvanzata (speċjalment meta jkun hemm riżerva batuta ta 'mudullun fl - għadam qabel tibda l- kura) u partikolarment f' pazjenti b' għadd ta' ċelluli CD4 inqas minn 100/ mm3.
Dosage reduction or cessation of therapy may become necessary (see section 4.4).
Tnaqqis fid- dożaġġ jew twaqqif tat- terapija jistgħu jkunu meħtieġa (ara sezzjoni 4. 4).
The anaemia may necessitate transfusions.
L- anemija tista 'toħloq il- ħtieġa ta' trasfużjonijiet.
The incidence of neutropenia was also increased in those patients whose neutrophil counts, haemoglobin levels and serum vitamin B12 levels were low at the start of zidovudine therapy.
L- inċidenza ta 'newtropenja żdiedet ukoll f' dawk il- pazjenti li l- għadd tan- newtrofil, il- livelli ta' emoglobina u l- livelli ta 'vitamina B12 fis- serum tagħhom kienu baxxi meta bdew it- terapija b ’ zidovudine.
Lactic acidosis
Aċidożi lattika
Treatment with nucleoside analogues has been associated with cases of lactic acidosis, sometimes fatal, usually associated with severe hepatomegaly and hepatic steatosis, (see section 4.4).
Il- kura b' nukleosidi analogi ġiet assoċjata ma 'każi ta' aċidożi lattika, xi drabi fatali, xi drabi assoċjata ma 'epatomegalija u steatożi tal- fwied (ara sezzjoni 4. 4).
Lipodystrophy/ metabolic abnormalities
Lipodistrofija/ anormalitajiet metaboliċi
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).
It- terapija antiretrovirali kombinata ġiet assoċjata ma 'tqassim mill- ġdid ta' xaħam fil- ġisem (lipodistrofija), f' pazjenti bl- HIV inklużi t- tnaqqis ta 'xaħam taħt il- ġilda periferali u taħt il- wiċċ, żieda ta' xaħam fiż- żaqq u fil- vixxri, ipertrofija fis- sider u tiġmigħ ta 'xaħam dorsoċervikali (buffalo hump).
Combination antiretroviral therapy has been associated with metabolic abnormalities such as hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperglycaemia and hyperlactataemia (see section 4.4).
It- terapija antiretrovirali kkombinata ġiet assoċjata ma 'anormalitajiet metaboliċi bħal ipertrigliċeridemija, hypercholesterolaemia, reżistenza għall- insulina, ipergliċemija u hyperlactataemia (ara t- taqsima 4. 4).
Immune Reactivation Syndrome
Sindromu ta ’ Rijattivazzjoni Immunitarja:
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 instab li huwa partikolarment aktar komuni f’ pazjenti b’ fatturi ta ’ riskju magħrufa, b’ HIVavvanzat jew użu ta ’ terapija antiretrovirali kombinata (CART) fit- tul.
The frequency of this is unknown (see section 4.4).
Il- frekwenza ta ’ din m’ hijiex magħrufa (ara sezzjoni 4. 4).
There is no experience of overdose with Trizivir.
Għad ma teżistix xi esperjenza ta 'doża eċċessiva ta' Trizivir.
No specific symptoms or signs have been identified following acute overdose with zidovudine or lamivudine apart from those listed as undesirable effects.
L- ebda sintomi jew sinjali speċifiċi ma ġew identifikati wara xi doża eċċessiva akuta ta 'zidovudine jew lamivudine barra minn dawk elenkati bħala effetti mhux mixtieqa.
No fatalities occurred, and all patients recovered.
Ma kienx hemm fatalitajiet, u l- pazjenti kollha għaddilhom.
Single doses up to 1200 mg and daily doses up to 1800 mg of abacavir have been administered to patients in clinical studies.
Dożi waħdanin ta 'mhux aktar minn 1200 mg u dożi ta' kuljum ta 'mhux aktar minn 1800 mg ta' abacavir ġew mogħtija lil pazjenti fi studji kliniċi.
No unexpected adverse reactions were reported.
Ma kienx hemm rapporti ta 'reazzjonijiet avversi.
The effects of higher doses are not known.
L- effetti ta 'dożi aktar għolja mhumiex magħrufa.
14 If overdose occurs the patient should be monitored for evidence of toxicity (see section 4.8), and standard supportive treatment applied as necessary.
Fil- każ ta 'doża eċċessiva il- pazjent għandu jkun monitorjat għal tossiċita' (ara sezzjoni 4. 8), u għandu jingħata l- għajnuna permezz tat- trattament normali li jkun hemm bżonn.
Since lamivudine is dialysable, continuous haemodialysis could be used in the treatment of overdose, although this has not been studied.
Billi lamivudine jista 'jiġi dijaliżżat, dijalisi kontinwa tad- demm tista' tiġi użata fit- kura ta 'doża eċċessiva, għalkemm din ma ġietx studjata.
Haemodialysis and peritoneal dialysis appear to have a limited effect on elimination of zidovudine, but enhance the elimination of the glucuronide metabolite.
14 ta ’ zidovudine, biss iżidu t- tneħħija ta ’ glucuronide metabolite.
It is not known whether abacavir can be removed by peritoneal dialysis or haemodialysis.
Mhux magħruf jekk abacavir jistax jitneħħa b’ dijalisi tal- peritoneum jew b’ dijalisi tad- demm.
Antivirals for treatment of HIV infections, combinations.
Mediċini kontra l- vajrus għall- kura ta ’ infezzjonijiet b’ HIV.
ATC Code:
Kodiċi ATC Code:
J05AR04.
J05AR04
Mechanism of action: Abacavir, lamivudine and zidovudine are all NRTIs, and are potent selective inhibitors of HIV-1 and HIV-2. All three medicinal products are metabolised sequentially by intracellular kinases to the respective 5′ -triphosphate (TP).
Mekkaniżmu ta 'azzjoni: Abacavir, lamivudine u zidovudine huma kollha NRTIs, u huma inibituri selettivi ta' l- HIV- 1 u l- HIV- 2. Dawn it- tliet prodotti mediċinali huma kollha metabolizzati b' kinases intraċellulari għat- trifosfat (TP) 5 '- rispettiv tagħhom.
Lamivudine-TP, carbovir-TP (the active triphosphate form of abacavir) and zidovudine-TP are substrates for and competitive inhibitors of HIV reverse transcriptase (RT).
Lamivudine- TP, carbovir- TP (il- forma attiva tat - triphosphate ta 'abacavir) u zidovudine- TP huma substrati għal, u inibituri kompetittivi ta', HIV reverse transcriptase (RT).
However, their main antiviral activity is through incorporation of the monophosphate form into the viral DNA chain, resulting in chain termination.
Madankollu, l- attivita 'antivirali ewlenija tagħhom hi permezz ta' l - inkorporazzjoni tal- forma monofosfat fil- katina virali tad- DNA, li tirriżulta fit- tmiem tal- katina.
Abacavir, lamivudine and zidovudine triphosphates show significantly less affinity for host cell DNA polymerases.
Abacavir, lamivudine u zidovudine triphosphates juru ferm inqas affinita 'ma ’ polymerases tad- DNA taċ- ċelluli li jkunu qegħdin fihom.
Lamivudine has been shown to be highly synergistic with zidovudine, inhibiting the replication of HIV in cell culture.
Ġie ppruvat li lamivudine hu sinerġistiku ħafna ma ’ zidovudine, billi jimpedixxi r- replikazzjoni ta 'l - HIV f' kultura ta' ċelluli.
Abacavir shows synergy in vitro in combination with nevirapine and zidovudine.
Abacavir juri sinerġija in vitro flimkien ma ’ nevirapine u zidovudine.
It has been shown to be additive in combination with didanosine,, stavudine and lamivudine.
Ġie wkoll ippruvat li jkun addittiv meta jkun flimkien ma 'didanosine, stavudine u lamivudine.
In vitro resistance:
Reżistenza in vitro:
HIV-1 resistance to lamivudine involves the development of a M184I or, more commonly, M184V amino acid change close to the active site of the viral RT.
Ir- reżistenza ta ’ l- HIV- 1 għal lamivudine tiġri minħabba l- iżvilupp ta ’ bidla fl - amino acid ta ’ M184I jew iżjed spiss ta ’ M184V viċin is- sit attiv ta ’ RT tal- virus.
Abacavir-resistant isolates of HIV-1 have been selected in vitro and are associated with specific genotypic changes in the RT codon region (codons M184V, K65R, L74V and Y115F).
Iżolati ta 'l- HIV reżistenti għal abacavir ġew magħżula in vitro u ġew assoċjati ma bidliet genotipiċi speċifiċi f’ RT codon region (codons M 184V, K65R, L74V, u Y115F).
Viral resistance to abacavir develops relatively slowly in vitro, requiring multiple mutations for a clinically relevant increase in EC50 over wild-type virus.
Reżistenza anti- virali għal abacavir tiżviluppa relattivament bil- mod in vitro, u tkun teħtieġ mutazzjonijiet multipli biex tilħaq żieda klinikament relevanti fl- EC50 fuq il- virus tip selvaġġ.
In vivo resistance (Therapy naïve patients):
Resistenza in vivo (pazjenti li qatt ma ngħatalhom kura):
Most patients experiencing virological failure with a regimen containing abacavir in a pivotal clinical trial with Combivir (fixed dose combination of lamivudine and zidovudine) showed either no NRTI-related changes from baseline (15%) or only M184V or M184I selection (78%).
Ħafna mill- pazjenti li esperjenzaw falliment viroloġiku, fi studju kliniku prinċipali b’ Combivir (kumbinazzjoni ta ’ doża fissa ta ’ lamivudine u zidovudine), b’ sistema ta ’ kura li fiha abacavir jew ma wrew l- ebda bidla relatata ma ’ NRTI mill- livell bażiku (15%) jew inkella selezzjoni ta ’ M184V jew M184I biss (78%).
The overall selection frequency for M184V or M184I was high (85%), and selection of L74V, K65R and Y115F was not observed (see Table).
Il- frekwenza ta ’ selezzjoni totali għal M184V jew M184I kienet għolja (85%) u ma kienetx osservata selezzjoni ta ’ L74V, K65R u Y115F (ara t- Tabella).
Thymidine analogue mutations (TAMs) which are selected by zidovudine (ZDV) were also found (8%).
Instabu wkoll mutazzjonijiet analogi ta ’ thymidine (TAMs) li huma magħżula minn zidovudine (8%).
Number of Virological Failures
ta ’ Suġġetti
Number of On-Therapy Genotypes
Numru ta ’ fallimenti viroloġiċi
40 (100%)
40 (100%) Numru ta ’ Ġenotipi fuq Kura
TAMs might be selected when thymidine analogs are associated with abacavir.
15 TAMs jistgħu ikunu magħżula meta analogi ta ’ thymidine ikollhom x’ jaqsmu ma ’ abacavir.
In addition, the selection of L74V and K65R was reduced when co-administered with ZDV (K65R: without ZDV:
Barra minn hekk, tnaqqset is- selezzjoni ta ’ L74V u K65R meta ingħataw flimkien ma ZDV (K65R: mingħajr ZDV:
13/ 127, 10%; with ZDV:
13/ 127, 10%: ma ’ ZDV:
1/ 86, 1%; L74V: without ZDV:
1/ 86, 1%; L74V: mingħajr ZDV:
51/ 127, 40%; with ZDV:
51/ 127, 40% ma ’ ZDV:
In vivo resistance (Therapy experienced patients):
Resistenza in vivo (pazjenti b’ esperjenza ta ’ kura):
The M184V or M184I variants arise in HIV-1 infected patients treated with lamivudine-containing antiretroviral therapy and confers high-level resistance to lamivudine.
Il- varjanti ta ’ M184V jew M184I issibhom f’ pazjenti nfettati bl- HIV- 1 li jingħataw trattament antiretrovirali li fih lamivudine u jagħmlu reżistenza ta ’ livell għoli għal lamivudine.
In vitro data tend to suggest that the continuation of lamivudine in anti- retroviral regimen despite the development of M184V might provide residual anti-retroviral activity (likely through impaired viral fitness).
Data in vitro għandha t- tendenza li turi li l- kontinwazzjoni ta 'lamivudine f’ sistema ta ’ kura antiretrovirali minkejja li l- iżvilupp ta ’ M184V jista ’ jipprovdi attivita ’ antiretrovirali residwa (li tista ’ tiġri minħabba li l- virus ma jibqax jiffunzjona sewwa).
The clinical relevance of these findings is not established.
Ir - rilevanza klinika ta ’ dawn is- sejbiet m’ hijiex stabbilita.
Indeed, the available clinical data are very limited and preclude any reliable conclusion in the field.
Ċertament, id- data klinika disponibbli hija limitata ħafna u ma tħallix li ssir konklużżjoni ta ’ min joqgħod fuqha fil- qasam.
In any case, initiation of susceptible NRTIs should always be preferred to maintenance of lamivudine therapy.
F’ kull ċirkostanza, huwa dejjem preferibbli li jinbdew NRTI suxxettibli għal terapija regolari b' lamivudine.
Therefore, maintaining lamivudine therapy despite emergence of M184V mutation should only be considered in cases where no other active NRTIs are available.
Għaldaqstant, għandha tiġi kkunsidrata terapija regolari b’ lamivudine minkejja li titfaċċa mutazzjoni ta ’ M184V biss fejn l- ebda NRTI attivi oħra ma ’ jkunu disponibbli.
Similarly, the presence of TAMs gives rise to resistance to ZDV.
B’ mod simili, il- presenza tat- TAMs tikawża reżistenza ghal ZDV.
Clinically significant reduction of susceptibility to abacavir has been demonstrated in clinical isolates of patients with uncontrolled viral replication, who have been pre-treated with and are resistant to other nucleoside inhibitors.
Tnaqqis sustanzjali klinikament fis- suxxettibilita ’ ta ’ abacavir deher f’ iżolati kliniċi ta ’ pazjenti, b’ replikazzjoni mingħajr kontroll tal- virus, li kienu ttrattati minn qabel bi u huma resistenti għal nucleoside inhibitors oħra.
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 abacavir ġie miżjud 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 predikattiv 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 ’ resistenza b’ NRTI, kellhom x’ jaqsmu ma ’ reazzjoni mnaqqsa fir- 4 Ġimgħa (p=0. 015) jew 4 jew aktar mutazzjonijiet fil- linja medjana 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, V751, F77L u F116Y, jagħmlu reżistenza kbira għal abacavir.
16 Week 4
4 Ġimgħa Mutazzjoni tal - (n = 166) linja bażi ta ’ Bidla Medjana
< 400 copies/ mL vRNA
< 400 copies/ mL vRNA
None
Xejn M184V waħdu Kull mutazzjoni
-0.96
- 0. 96 - 0. 74
Any one NRTI
ta ’ NRTI waħda Kull żewg mutazzjonijiet
associated mutations Any three NRTI-
assoċjati ma ’ NRTI Kull tlett mutazzjonijiet
associated mutations Four or more NRTI-
assoċjati ma ’ NRTI 4 jew aktar mutazzjonijiet
Phenotypic resistance and cross-resistance:
Reżistenza fenotipika u cross- resistance:
Phenotypic resistance to abacavir requires M184V with at least one other abacavir-selected mutation, or M184V with multiple TAMs.
16 b’ almenu mutazzjoni waħda oħra magħżula għal abacavir, jew M184V b’ ħafna TAMs.
Phenotypic cross- resistance to other NRTIs with M184V or M184I mutation alone is limited.
Cross - resistance fenotipika għal NRTI oħra bil- mutazzjoni M184V jew M184IM waħedha hija limitata.
Zidovudine, didanosine, stavudine and tenofovir maintain their antiretroviral activities against such HIV-1 variants.
Zidovudine, didanosine, stavudine u tenofovir iżżommu l- attivita ’ antiretrovirali tagħhom kontra dawn it- tipi differenti ta ’ HIV- 1.
The presence of M184V with K65R does give rise to cross-resistance between abacavir, tenofovir, didanosine and lamivudine, and M184V with L74V gives rise to cross-resistance between abacavir, didanosine and lamivudine.
Il- preżenza ta ’ M184V ma ’ K65R tagħmel cross- resistance ma ’ abacavir, tenofovir, didanosine u lamivudine.
The presence of M184V with Y115F gives rise to cross-resistance between abacavir and lamivudine.
Il- preżenza ta ’ M184V ma ’ Y115F tagħmel cross- resistance bejn abacavir u lamivudine.
Appropriate use of abacavir can be guided using currently recommended resistance algorithms.
L- użu addattat ta ’ abacavir jista ’ jkun iggwidat bl- użu ta ’ algoriżmi ta ’ reżistenza rakkomandata u kurrenti.
PIs or NNRTIs is unlikely.
Cross- resistance bejn abacavir, lamivudine jew zidovudine u antiretrovirali minn klassijiet oħra e. ż PIs jew NNRTIs, mhix probabbli.
Clinical experience
Esperjenza klinika:
One randomised, double blind, placebo controlled clinical study has compared the combination of abacavir, lamivudine and zidovudine to the combination of indinavir, lamivudine and zidovudine in treatment naive patients.
Studju kliniku kontrollat ta 'plaċebo wieħed meħud bl- addoċċ, fejn la t- tabib u l- anqas il- pazjent ma jkun jaf x’ qiegħed jingħata, qabbel taħlita ta' abacavir, lamivudine u zidovudine ma 'taħlita ta' indinavir, lamivudine u zidovudine f' pazjenti inġenwi għall- kura.
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 l- proporzjon għoli ta 'twaqqif qabel iż- żmien (42% tal- pazjenti ma komplewx il- kura bl- addoċċ wara t- tmienja w erbgħin ġimgħa), ma tistax tintlaħaq konklużjoni definittiva dwar l- ekwivalenza bejn ir- regoli ta' dieta fit - tmienja w erbgħin 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).
Għalkemm effett antivirali simili ġie osservat bejn regoli dwar l- għoti ta 'abacavir u indinavir f' termini ta' proporzjon ta 'pazjenti b' piż virali li ma tinħassx (≤400 kopji/ ml; analiżi ta' intenzjoni ta 'kura (ITT), 47% vs 49%; analiżi ta' kura mogħtija (AT), 86% vs 94% għal tagħqid ta 'abacavir u indinavir rispettivament), ir- riżultati kienu f- favur it- taħlita indinavir, partikolarment fis- sub- sett ta' pazjenti b' piż virali għolja (> 100, 000 kopji/ ml fil- linja bażi; ITT, 46% vs 55%; AT, 84% vs 93% għal abacavir u indinavir rispettivament).
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 ta ’ plaċebo wieħed meħud bl- addoċċ, fejn la tabib u lanqas il- pazjent ma jkun jaf x’ qiegħed jingħata, li sar f’ 1147 adult infettat bl- HIV- 1 li qatt ma ħadu terapija antiretrovirali, fejn tqabblu 3 reġimenti: zidovudine (ZDV), lamivudine (3TC), abacavir (ABC), efavirenz (EFV) versu ZDV/ 3TC/ EFV versu 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 ġew segwiti għall- perijodu medjan ta ’ 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 kklassifikati bħala falliment viroloġiku (HIV RNA > 200 kopji kull ml.
At week 48 the proportion of subjects with HIV RNA < 50 copies/ ml were 63%, 80% and 86% for the ZDV/ 3TC/ ABC, ZDV/ 3TC/ EFV and ZDV/ 3TC/ ABC/ EFV arms, respectively.
Fit- 48 ġimgħa il- proporzjon ta ’ suġġetti b’ HIV RNA < 50 kopja kull ml kienu 63%, 80% u 86% għall- fergħat ZDV/ 3TC/ ABC, ZDV/ 3TC/ EFV U ZDV/ 3TC/ ABC/ EFV rispettivament.
The study Data Safety Monitoring Board stopped the ZDV/ 3TC/ ABC arm at this time based on the higher proportion of patients with virologic failure.
Il- Bord ta ’ Data fuq Osservazzjoni ta ’ Sigurta ’ għall- istudju waqqaf il- fergħa ZDV/ 3TC/ ABC f’ dan iż- zmien fuq bażi ta ’ proporzjon aktar għoli ta ’ pazjenti b’ falliment viroloġiku.
The remaining arms were continued in a blinded fashion.
Il- fergħat l- oħra komplew bl- addoċċ.
There was no significant
Wara li ġew segwiti għall- perijodu medjan ta ’ 144 ġimgħa, 25% tas- suġġetti fuq il- fergħa ZDV/ 3TCABC/ EFV u 26% fuq il- fergħa ZDV/ 3TC/ EFV ġew ikklassifikati li kellhom falliment viroloġiku.
17 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- effiċjenza.
Virologic failure (HIV 32 weeks RNA > 200 copies/ ml) 144 weeks Virologic success (48 weeks HIV RNA < 50 copies/ ml)
32 ġimgħa 144 ġimgħa
In an ongoing clinical study over 16 weeks in treatment-naive patients, the combination of abacavir, lamivudine and zidovudine showed a similar antiviral effect to the combination with nelfinavir, lamivudine and zidovudine.
Fi studju kliniku kontinwu ta '16- il ġimgħa f' pazjenti inġenwi għall- kura, it- taħlita abacavir, lamivudine u zidovudine weriet effett antivirali simili għat- taħlita b’ nelfinavir, lamivudine u
In antiretroviral-naïve patients the triple combination of abacavir, lamivudine and zidovudine was superior in terms of durability of viral load response over 48 weeks to lamivudine and zidovudine.
F' pazjenti li ma jafux li qed jingħataw kura antiretrovirali it- taħlita bi tlieta ta 'abacavir, lamivudine u zidovudine kienet superjuri f' termini ta' tul ta 'żmien għal reazzjoni antivirali f' tul ta' 120 ġimgħa għal lamivudine u zidovudine.
In a similar patient population durability of antiviral response over 120 weeks was demonstrated in approximately 70% of subjects.
F' popolazzjoni simili ta 'pazjenti iż- żmien ta' reazzjoni antivirali f' tul ta '120 ġimgħa ħarġet f' madwar 70% tas- suġġetti.
In antiretroviral-naive patients treated with a combination of abacavir, lamivudine, zidovudine and efavirenz in a small, ongoing, open label pilot study, the proportion of patients with undetectable viral load (< 400 copies/ ml) was approximately 90% with 80% having < 50 copies/ ml after 24 weeks of treatment.
F' pazjenti li ma jafux li qed jingħataw kura antiretrovirali b' kura ta 'tagħqida ta' abacavir, lamivudine, zidovudine u efavirenz waqt studju pilota żgħir li għadu sejjer b' tikketta miftuħa, il- proporzjon ta 'pazjenti b' piż virali li ma tinħassx (< 400 kopji/ ml) kien madwar 90% bi 80% li kellhom < 50 kopji/ ml wara kura ta' 24 ġimgħa.
In patients with a low baseline viral load (< 5,000 copies/ ml) and moderate exposure to antiretroviral therapy, addition of abacavir to previous treatment including lamivudine and zidovudine, produced a moderate impact on viral load at 48 weeks.
F' pazjenti bi piż virali fil- linja bażi baxx (< 5, 000 kopji/ ml) u esponiment moderat għat- terapija antiretrovirali, iż- żieda ta 'abacavir mal- kura ta' qabel li kienet tinkludi lamivudine u zidovudine, ipproduċiet impatt moderat fuq il- piż virali wara 48 ġimgħa.
Currently there are no data on the use of Trizivir in heavily pre-treated patients, patients failing on other therapies or patients with advanced disease (CD4 cells < 50 cells/ mm3).
S' issa għad m' hawnx data dwar l- użu ta Trizivir f' pazjenti li qabel kienu għaddew minn kura qawwija, pazjenti li fuqhom terapiji oħra ma ħadmux jew pazjenti b' mard avvanzat (ċelluli CD4 < 50 ċelluli/ mm3).
The degree of benefit of this nucleoside combination in heavily pre-treated patients will depend on the nature and duration of prior therapy that may have selected for HIV-1 variants with cross-resistance to abacavir, lamivudine or zidovudine.
Il- grad ta 'benefiċċju ta' din it- taħlita f' pazjenti li kienu għaddew minn kura qawwija minn qabel jiddependi min- natura u t- tul tat- terapija preċedenti li setgħat għażlet varjanti għal HIV- 1 b' reżistenza msallba għal abacavir, lamivudine jew zidovudine.
To date there are insufficient data on the efficacy and safety of Trizivir given concomitantly with NNRTIs or PIs.
Sa llum m' hawnx data biżżejjed dwar l- effikaċja u s- sigurta 'ta ’ Trizivir meta jingħata flimkien ma' NNRTIs jew PIs.
Absorption
Assorbiment:
Abacavir, lamivudine and zidovudine are rapidly and well absorbed from the gastro-intestinal tract following oral administration.
Abacavir, lamivudine u zidovudine jiġu assorbiti malajr u tajjeb mill- apparat gastro- intestinali wara li jittieħdu mill- ħalq.
The absolute bioavailability of oral abacavir, lamivudine and zidovudine in adults is about 83%, 80 - 85% and 60 - 70% respectively.
Il- biodisponibbilta 'assoluta ta' abacavir, lamivudine u zidovudine mill- ħalq f' adulti hi madwar 83%, 80- 85% u 60- 70% rispettivament.
In a pharmacokinetic study in HIV-1 infected patients, the steady state pharmacokinetic parameters of abacavir, lamivudine and zidovudine were similar when either Trizivir alone or the combination tablet lamivudine/ zidovudine and abacavir in combination were administered, and also similar to the values obtained in the bioequivalence study of Trizivir in healthy volunteers.
Fi studju farmakokinetiku ta 'pazjenti infettati bl- HIV- 1, il- parametri farmakokinetiċi fi stat stabbli ta' abacavir, lamivudine u zidovudine kienu l- istess meta jew Trizivir waħdu jew il- pillola bit- taħlita lamivudine/ zidovudine u abacavir ingħataw flimkien, u anki l- istess bħall- valuri miksuba fi studju bioekwivalenti ta ’ Trizivir fuq voluntieri f' saħħithom.
A bioequivalence study compared Trizivir with abacavir 300 mg, lamivudine 150 mg and zidovudine 300 mg taken together.
Studju ta 'bioekwivalenza qabbel Trizivir ma' 300 mg abacavir, 150 mg lamivudine u 300 mg zidovudine meħuda flimkien.
The effect of food on the rate and extent of absorption was also studied.
L- effett ta 'l- ikel fuq ir- rata u s- somma ta' assorbiment ġie studjat ukoll.
Trizivir was shown to be bioequivalent to abacavir 300 mg, lamivudine 150 mg and zidovudine 300 mg given as separate tablets for AUC0-∞ and Cmax.
Trizivir irriżulta li kien bioekwivalenti għal 300 mg abacavir, 150 mg lamivudine u 300 mg zidovudine mogħtija bħala pilloli separati għall- AUC00 u Cmax.
Food decreased the rate of absorption of Trizivir (slight decrease Cmax (mean 18 - 32%) and increase tmax (approximately 1 hour), but not the
L- ikel naqqas ir- rata ta 'assorbiment ta ’ Trivizir (tnaqqis żgħir Cmax (medja 18- 32) u żieda tmax (madwar siegħa), iżda mhux it- totalita' ta 'l - assorbiment (AUC00).
These changes are not considered clinically relevant and no food restrictions are recommended for administration of Trizivir.
Dawn il- bidliet mhumiex meqjusa klinikament rilevanti u l- ebda restrizzjonijiet ta 'ikel m' huma rakkomandati għal meta jingħata Trivizir.
At a therapeutic dosage (one Trizivir tablet twice daily) in patients, the mean (CV) steady-state Cmax of abacavir, lamivudine and zidovudine in plasma are 3.49 µg/ ml (45%), 1.33 µg/ ml (33%) and 1.56 µg/ ml (83%), respectively.
F’ dożi terapewtiċi (pillola waħda ta ’ Trizivir darbtejn kuljum) fil- pazjenti, il- medja ta ’ Cmax fi stat stabbli ta ’ abacavir, lamivudine u zidovudine fil- plażma huma 3. 49µg/ ml (45%), 1. 33µg/ ml (33%), u 1. 56µg/ ml (83%) rispettivament.
Corresponding values for Cmin could not be established for abacavir and are 0.14 µg/ ml (70%) for lamivudine and 0.01 µg/ ml (64%) for zidovudine.
L- istess valuri għall- Cmin ma setgħux ikunu stabbiliti għal abacavir u huma 0. 14µg/ ml (70%) għal lamivudine u 0. 01µg/ ml (64%) għal zidovudine.
The mean (CV) AUCs for abacavir, lamivudine and zidovudine over a dosing interval of 12 hours are 6.39 µg. h/ ml (31%), 5.73 µg. h/ ml (31%) and 1.50 µg. h/ ml (47%), respectively.
Il- medja (CV) ta ’ AUC għal abacavir, lamivudine u zidovudine fuq intervall ta ’ 12- il siegħa huma 6. 39µg. h/ ml (31%), 5. 73 µg. h/ ml (31%) u 1. 5µg. h/ ml (47%), rispettivament.
A modest increase in Cmax (28%) was observed for zidovudine when administered with lamivudine, however overall exposure (AUC) was not significantly altered.
Zidovudine m' għandux effett fuq il -
Zidovudine has no effect on the pharmacokinetics of lamivudine.
18 farmakokinetiċi ta ’ lamivudine.
An effect of abacavir is observed on zidovudine (Cmax reduced with 20%) and on lamivudine (Cmax reduced with 35%).
Effett ta 'abacavir ġie osservat fuq zidovudine (Cmax imnaqqas bi 20%) u fuq lamivudine (Cmax imnaqqas b' 35%).
Intravenous studies with abacavir, lamivudine and zidovudine showed that the mean apparent volume of distribution is 0.8, 1.3 and 1.6 l/ kg respectively.
Studji ta 'ġol- vina b ’ abacavir, lamivudine u zidovudine urew li il- volum medju li jidher ta' distribuzzjoni hu 0. 8, 1. 3 u 1. 6 l/ kg rispettivament.
Lamivudine exhibits linear pharmacokinetics over the therapeutic dose range and displays limited binding to the major plasma protein albumin (< 36% serum albumin in vitro).
Lamivudine juri farmakokinetiċi lineari fuq il - medda ta 'dożi terapewtiċi u tagħqid limitat ma' l- albumin maġġuri ta 'proteini fil- plażma (< 36% albumin fis- serum in vitro).
Zidovudine plasma protein binding is 34% to 38%.
It- tagħqid ta 'proteina tal- plażma f’ zidovudine hu 34% sa 38%.
Plasma protein binding studies in vitro indicate that abacavir binds only low to moderately (~ 49%) to human plasma proteins at therapeutic concentrations.
Studji dwar tagħqid ta 'proteina ta' plażma in vitro jindikaw li abacavir jingħaqad ftit jew moderatament (~ 49%) ma 'proteini ta' plażma umana f' konċentrazzjonijiet terapewtiċi.
This indicates a low likelihood for interactions with other medicinal products through plasma protein binding displacement.
Dan jindika probabbilta 'żgħira ta' interazzjonijiet ma 'prodotti mediċinali oħra bl- ispostament ta' tagħqid ta 'proteini mal- plażma.
Interactions involving binding site displacement are not anticipated with Trizivir.
Interazzjonijiet li jinvolvu spostament fis- sit mhumiex antiċipati b’ Trizivir.
Data show that abacavir, lamivudine and zidovudine penetrate the central nervous system (CNS) and reach the cerebrospinal fluid (CSF).
Data juru li abacavir, lamivudine u zidovudine jippenetraw is- sistema nervuża ċentrali (CNS) u jaslu sal- fluwidu ċerebrospinali.
The mean ratios of CSF/ serum lamivudine and zidovudine concentrations 2 - 4 hours after oral administration were approximately 0.12 and 0.5 respectively.
Il- proporzjonijiet medji ta 'konċentrazzjonijiet ta' CSF/ serum ta ’ lamivudine u zidovudine 2- 4 siegħat wara li jittieħdu mill- ħalq kienu madwar 0. 12 u 0. 5 rispettivament.
The true extent of CNS penetration of lamivudine and its relationship with any clinical efficacy is unknown.
Kemm verament kien hemm penetrazzjoni ta 'lamivudine fis- CNS u r- relazzjoni ta' dan ma 'xi effikaċja klinika mhux magħruf.
Studies with abacavir demonstrate a CSF to plasma AUC ratio of between 30 to 44%.
Studji fuq abacavir juru proporzjon ta 'CSF ma' AUC ta 'plażma ta' bejn it- 30 sa 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 aktar mill- IC50 ta' abacavir ta '0. 08 µg/ ml jew 0. 26 µM meta abacavir jingħata f' dożi ta' 600 mg darbtejn kuljum.
Metabolism of lamivudine is a minor route of elimination.
Il- metaboliżmu ta ’ lamivudine hu rotta żgħira ta 'tneħħija.
Lamivudine is predominately cleared by renal excretion of unchanged lamivudine.
Lamivudine jitneħħa prinċipalment bi tnixxija mill- kliewi ta 'lamivudine mhux mibdul.
The likelihood of metabolic drug interactions with lamivudine is low due to the small extent of hepatic metabolism (5 - 10%) and low plasma binding.
Il- probabbilta 'ta' interazzjonijiet ma ’ lamivudine hi żgħira minħabba l- ammont limitat ta 'metaboliżmu tal- fwied (5- 10%) u tagħqid ftit ta' plażma.
The 5’ -glucuronide of zidovudine is the major metabolite in both plasma and urine, accounting for approximately 50 - 80% of the administered dose eliminated by renal excretion.
Il- 5 '- glucuronide ta ’ zidovudine huwa l- metabolit prinċipali kemm fil- plażma u kemm fl- awrina, li waħdu jkopri madwar 50- 80% tad- doża li tkun ittieħdet u tneħħiet bi tnixxija mill- kliewi.
3’ -amino-3’ - deoxythymidine (AMT) has been identified as a metabolite of zidovudine following intravenous dosing.
3 '- amino- 3' - deoxythymidine (AMT) ġie identifikat bħala metabolit ta ’ zidovudine wara dożi fil- vina.
Abacavir is primarily metabolised by the liver with approximately 2% of the administered dose being renally excreted, as unchanged compound.
Abacavir hu prinċipalmet metabolizzat mill- fwied bejn wieħed u ieħor b' 2% tad- doża mogħtija toħroġ mill- kliewi, bħala taħlita mhux mibdul.
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 dose excreted in the urine.
Il- passaġġi ewlenin ta 'metaboliżmu fil- bniedem huma b' alkoħol dehydrogenase u bi glukurinidazzjoni biex jipproduċu il- 5' - aċidu carboxylic u l- 5 '- glukuronid li jkopru madwar 66% tad- doża mneħħija fl- awrina.
Elimination
Tneħħija:
The observed lamivudine half-life of elimination is 5 to 7 hours.
Il- ħin li ġie osservat biex il- livell ta 'tneħħija ta ’ lamivudine jinżel bin- nofs hu minn 5 sa 7 siegħat.
The mean systemic clearance of lamivudine is approximately 0.32 l/ h/ kg, with predominantly renal clearance (> 70%) via the organic
Il - medja ta 'tneħħija sistemika ta ’ lamivudine hi ta' madwar 0. 32 l/ h/ kg waqt li l- aktar tneħħija tkun mill - kliewi (> 70%) permezz tas- sistema ta 'trasport katjonika.
Studies in patients with renal impairment show lamivudine elimination is affected by renal dysfunction.
Studji f' pazjenti bi ħsara fil- fwied juru li t - tneħħija ta ’ lamivudine tiġi affettwata minn funzjonament ħażin tal- kliewi.
Dose reduction is required for patients with creatinine clearance ≤ 50 ml/ min (see section 4.2).
Tnaqqis tad- doża jkun meħtieġ f' pazjenti bi tneħħija ta 'kreatinina≤ 50 ml/ min (ara t- taqsima 4. 2)
From studies with intravenous zidovudine, the mean terminal plasma half-life was 1.1 hours and the mean systemic clearance was 1.6 l/ h/ kg.
Fi studji dwar l- għoti ta ’ ziduvidine fil- vina, il- ħin biex il- livelli medji ta 'plażma terminali niżlu bin - nofs kien ta' 1. 1 siegħat u l- medja ta 'tneħħija sistemika kienet 1. 6 l/ h/ kg.
Renal clearance of zidovudine is estimated to be 0.34 l/ h/ kg, indicating glomerular filtration and active tubular secretion by the kidneys.
It- tneħħija stmata ta ’ zidovudine mill- kliewi hi 0. 34 l/ h/ kg, li tindika filtrazzjoni glomerulari u tiġmigħ tubulari attiv fil - kliewi.
Zidovudine concentrations are increased in patients with advanced renal failure.
Il- konċentrazzjonijiet ta 'zidovudine jiżdiedu f' pazjenti indeboliment serju tal- kliewi.
The mean half-life of abacavir is about 1.5 hours.
Il- ħin medju biex il- livelli ta 'abacavir jinżlu bin- nofs hu ta' madwar 1. 5 siegħat.
Following multiple oral doses of abacavir 300 mg twice a day there is no significant accumulation of abacavir.
Wara dożi multipli ta '300 mg ta' abacavir mill- ħalq darbtejn kuljum ma kienx hemm tiġmigħ notevoli ta 'abacavir.
Elimination of abacavir is via hepatic metabolism with subsequent excretion of metabolites primarily in the urine.
It - tneħħija ta 'abacavir issir permezz ta' metaboliżmu tal- fwied bi tnixxijiet sussegwenti ta 'metaboliti primarjament fl- awrina.
The metabolites and unchanged abacavir account for about 83% of the administered abacavir dose in the urine the remainder is eliminated in the faeces.
Il- metaboliti u abacavir mhux mibdul ikopru madwar 83% tad- doża mogħtija
Hepatically impaired:
Bi ħsara fil- fwied:
There are no data available on the use of Trizivir in hepatically impaired patients.
M' hawnx data disponibbli dwar l- użu taTrizivir f' pazjenti bi ħsara fil- fwied.
Limited data in patients with cirrhosis suggest that accumulation of zidovudine may occur in patients with hepatic impairment because of decreased glucuronidation.
Data limitati ta 'pazjenti b' ċirrosi jindikaw li tiġmigħ ta' zidovudine jista 'jseħħ f' pazjenti bi ħsara fil- fwied minħabba tnaqqis ta' glukuronidazzjoni.
Data obtained in patients with moderate to severe hepatic impairment show that lamivudine pharmacokinetics are not significantly affected by hepatic dysfunction.
Data miksuba minn pazjenti bi ħsara moderata jew serja fil - fwied juru li l- farmakokinetiċi ta 'lamivudine ma tantx jintlaqtu minn funzjonament ħażin tal- fwied.
Abacavir is metabolised primarily by the liver.
Abacavir jiġi metabolizzat l- aktar mill- fwied.
The pharmacokinetics of abacavir have been studied in patients with mild hepatic impairment (Child-Pugh score 5-6) receiving a single 600 mg dose.
Il- farmakokinetiċi ta 'abacavir ġew studjati f' pazjenti bi ħsara ħafifa tal- fwied (Child- Pugh punteġġ 5- 6) li jieħdu doża waħda ta' 600 mg.
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 darbiet (1. 32; 2. 70) fl- AUC ta' abacavir, u ta '1. 58 darbiet (1. 22; 2. 04) fl- inżul għal nofs fil- livell ta' eliminazzjoni.
No recommendation on dosage reduction is possible in patients with mild hepatic impairment due to substantial variability of abacavir exposure in this patient population.
Ma tistax issir rakkomandazzjoni għal tnaqqis ta 'dożaġġi f' pazjenti bi ħsara ħafifa tal- fwied minħabba varjabilita' sostanzjali ta 'esponiment għal abacavir f' din il- popolazzjoni ta' pazjenti.
The pharmacokinetics of abacavir have not been studied in patients with moderate or severe hepatic impairment.
Il- farmakokinetiċi ta 'abacavir ma ġewx studjati f' pazjenti bi ħsara moderata jew serja fil- fwied.
Plasma concentrations of abacavir are expected to be variable and substantially increased in these patients (see section 4.3).
Konċentrazzjonijiet ta 'plażma ta' abacavir huma mistennija li jkunu varjabbli u miżjuda sostanzjalment f' dawn il- pazjenti (ara t- taqsima 4. 3).
Renally impaired:
Bi ħsara fil- kliewi:
The observed lamivudine half-life of elimination is 5 to 7 hours.
Il- ħin osservat biex il- livell ta ’ lamivudine jinżel bin- nofs hu ta 'bejn 5 u 7 siegħat.
The mean systemic clearance of lamivudine is approximately 0.32 l/ h/ kg, with predominantly renal clearance (> 70%) via the organic cationic transport system.
Il- medja ta 'tneħħija sistemika ta ’ lamivudine hi ta' madwar 0. 32 l/ h/ kg, bi tneħħija l- aktar mill- kliewi (> 70%) permezz tas- sistema katjonika organika ta 'trasport.
Studies in patients with renal impairment show lamivudine elimination is affected by renal dysfunction.
Studji fuq pazjenti bi ħsara fil- fwied juru li t- tneħħija ta ’ lamivudine hi affettwata minn funzjonament ħażin tal- kliewi.
From studies with intravenous zidovudine, the mean terminal plasma half-life was 1.1 hours and the mean systemic clearance was 1.6 l/ h/ kg.
Minn studji dwar l- għoti ta ’ zidovudine mill- vina, irriżulta li l- ħin medju biex il- livell ta 'plażma terminali jinżel bin- nofs kien ta 1. 1 siegħat u t- tneħħija medja sistemika kien ta' 1. 6 l/ h/ kg.
Renal clearance of zidovudine is estimated to be 0.34 l/ h/ kg, indicating glomerular filtration and active tubular secretion by the kidneys.
Tneħħija ta 'zidovudine mill- kliewi ġiet stmata li kienet 0. 34 l/ h/ kg, li tindika filtrazzjoni glomerulari u tiġmigħ tubulari attiv mill- kliewi.
Zidovudine concentrations are increased in patients with advanced renal failure.
Il- konċentrazzjonijiet ta 'zidovudine jiżdiedu f' pazjenti b' indeboliment avanzat tal- kliewi.
Abacavir is primarily metabolised by the liver with approximately 2% of abacavir excreted unchanged in the urine.
Abacavir jiġi metabolizzat primarjament mill- fwied b' madwar 2% ta 'abacavir joħroġ mhux mibdul fl - awrina.
The pharmacokinetics of abacavir in patients with end-stage renal disease is similar to patients with normal renal function, and, therefore, no dose reduction is required in patients with renal impairment.
Il- farmakokinetiċi ta 'abacavir f' pazjenti b' disturbi tal- kliewi fl- aħħar stadju tiegħu huma l - istess bħal dawk f' pazjenti b' funzjonament normali tal- kliewi, u għalhekk ma jkunx hemm bżonn ta' tnaqqis ta 'doża f' pazjenti bi ħsara fil- kliewi.
As dosage adjustments of lamivudine and zidovudine may be necessary it is recommended that separate preparations of abacavir, lamivudine and zidovudine be administered to patients with reduced renal function (creatinine clearance ≤ 50 ml/ min).
Billi jista 'jkun hemm ħtieġa għal aġġustament tad- dożaġġ hu rakkomandat li preparazzjinijiet separati ta' abacavir, lamivudine u zidovudine jingħataw lil pazjenti b' funzjonament tal- kliewi imnaqqas (tneħħija ta 'kreatinina≤ 50 ml/ min).
Trizivir is contraindicated in patients with end-stage renal disease (see section 4.3).
(ara t- taqsima 4. 3).
No pharmacokinetic data are available in patients over 65 years of age.
Għad m' hawnx data farmakokinetika dwar pazjenti ta '' l fuq minn 65 sena.
20 There are no data available on treatment with the combination of abacavir, lamivudine and zidovudine in animals.
Għad m' hawnx data disponibbli dwar il- kura ta 'abacavir, lamivudine u zidovudine flimkien fl - annimali.
The clinically relevant toxicological effects of these three medicinal products are anaemia, neutropenia and leucopenia.
L- effetti tossikoloġiċi klinikament rilevanti ta 'dawn it- tliet prodotti mediċinali huma l - anemija, in- newtropenja u l- lewkopenja.
Mutagenicity and carcinogenicity
Mutaġeniċita 'u karċinoġeniċita'