qanastek/EMEA-V3 huggingface dataset:
Almost all hypersensitivity reactions will have fever and/ or rash as part of the syndrome.
Kważi r- reazzjonijiet kollha ta ’ sensittività eċċessiva jkollhom deni u/ jew raxx bħala parti mis- sindromu.
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 jkunu 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 majlożi, artralġja).
The symptoms related to this hypersensitivity reaction worsen with continued therapy and can be life- threatening.
Is- sintomi relatati ma ’ din ir- reazzjoni ta` sensittività eċċessiva jaggravaw b`terapija kontinwa u jistgħu jkunu ta` periklu għall- ħajja.
These symptoms usually resolve upon discontinuation of Ziagen.
Dawn is- sintomi normalment ma jibqgħux jidhru meta jitwaqqaf Ziagen.
Patients should be monitored closely, especially during the first two months of treatment with Ziagen, with consultation every two weeks.
Il- pazjenti għandhom ikunu monitorati mill- viċin, b`mod speċjali matul l- ewwel xaharejn tal- kura b`Ziagen, u għandhom imorru għand it- tabib għall- konsulta kull ġimgħatejn.
Patients who are diagnosed with a hypersensitivity reaction whilst on therapy MUST discontinue Ziagen immediately.
Pazjenti li jkollhom dijanjożi ta` reazzjoni ta` sensittività eċċessiva waqt it- terapija GĦANDHOM jieqfu jieħdu Ziagen immedjatament.
Ziagen, or any other medicinal product containing abacavir (i. e.
Ziagen, jew xi prodott mediċinali ieħor li fih abacavir (i. e.
Kivexa, Trizivir), MUST NEVER be restarted in patients who have stopped therapy due to a hypersensitivity reaction.
Kivexa, Trizivir), M`GĦANDU QATT jerġa jibda jingħata lill- pazjenti li jkunu waqqfu t- terapija minħabba sensittività eċċessiva.
Restarting abacavir following a hypersensitivity reaction results in a prompt return of symptoms within hours.
Jekk abcavir jerġa jibda jingħata wara li jkun hemm reazzjonijiet ta` sensittività eċċessiva, l- istess sintomi jerġgħu joħorġu fi żmien ta` ftit sigħat.
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).
4 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).
Għandha tingħata attenzjoni speċjali lill- pazjenti li jibdew kura b` Ziagen flimkien ma kura bi prodotti mediċinali oħra li huma magħrufa li jikkawżaw tossiċità fil- ġilda.
This is because it is currently difficult to differentiate between rashes induced
(bħal inibituri non- nuklejosajd tar - reverse transcriptasereverse transcriptase - NNRTIs).
4 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.
• Management after an interruption of Ziagen therapy
• Maniġġar wara interruzjoni fit- terapija b’ Ziagen
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 hemm il- ħsieb li terġa tingħata t- terapija, għandu jiġi stabbilit għall- liema raġuni kienet twaqqfet it- terapija sabiex ikun aċċertat jekk il- pazjent kellux xi sintomi ta ’ sensittività eċċessiva.
If a hypersensitivity reaction cannot be ruled out, Ziagen or any other medicinal product containing abacavir (i. e.
Jekk ir- reazzjoni ta` sensittività eċċessiva ma tistax tiġi stabbilita, Ziagen jew xi prodott mediċinali ieħor li fih abacavir (i. e.
Kivexa, Trizivir) must not be restarted.
Kivexa, Trizivir) m`għandux jerġa jingħata.
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.
Attakki ta` sensittività eċċessiva qawwija u f’ daqqa, li jinkludu reazzjonijiet ta` perikli għall - ħajja dehru 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.
The most common isolated symptom of a hypersensitivity reaction was a skin rash.
L- aktar sintomu iżolat ta` reazzjoni ta` sensittività eċċessiva kien raxx tal- ġilda.
In both cases, if a decision is made to restart Ziagen this must be done in a setting where medical assistance is readily available.
Fiż- żewġ każijiet, jekk tittieħed deċiżjoni sabiex jerġa jibda jingħata Ziagen, dan għandu jingħata biss fejn ikun hemm assistenza medika lesta.
- patients must be made aware of the possibility of a hypersensitivity reaction to abacavir that
- il- pazjent għandu jkun jaf bil- possibiltà ta` reazzjonijiet ta ’ sensittività eċċessiva għal abacavir li
may result in a life-threatening reaction or death.
jistgħu jwasslu għal reazzjonijiet ta ’ periklu għall- ħajja kif ukoll għall- mewt.
- patients developing signs or symptoms possibly linked with a hypersensitivity reaction
- pazjenti li jkollhom sinjali jew sintomi li huma possibilment relatati ma ’ reazzjonijiet ta`
MUST CONTACT their doctor IMMEDIATELY.
sensittività eċċessiva GĦANDHOM JINFURMAW lit- tabib tagħhom MINNUFIH.
- patients who are hypersensitive to abacavir should be reminded that they must never take
- pazjenti li għandhom sensittività eċċessiva għal abacavir għandhom jiġu mfakkra li
Ziagen or any other medicinal product containing abacavir (i. e.
m`għandhom qatt jieħdu Ziagen jew xi prodott mediċinali ieħor li fih abacavir (i. e.
- in order to avoid restarting Ziagen, patients who have experienced a hypersensitivity reaction
- sabiex tiġi evitata li jerġa jingħata Ziagen, pazjenti li kellhom xi reazzjoni ta` sensittività
should be asked to return the remaining Ziagen tablets or oral solution to the pharmacy.
eċċessiva għandhom jiġu mitluba sabiex jirritornaw il- pilloli Ziagen jew is- soluzzjoni li tittiehed mill- ħalq li jkun għad baqalhom lura lill- ispiżjar.
- patients who have stopped Ziagen for any reason, and particularly due to possible adverse
- pazjenti li għal xi raġuni waqfu jieħdu Ziagen, u partikolarment jekk waqfu minħabba l -
reactions or illness, must be advised to contact their doctor before restarting.
possibiltà ta` reazzjonijiet avversi jew mard, għandhom jingħataw parir biex jinfurmaw lit- tabib qabel ma jerġgħu jibdewh.
- patients should be advised of the importance of taking Ziagen regularly.
- il- pazjenti għandhom ikunu infurmati bl- importanza li jieħdu b’ mod regolari Ziagen.
- each patient should be reminded to read the Package Leaflet included in the Ziagen pack.
- għandha tinġibed l- attenzzjoni ta ’ kull pazjenti sabiex jaqraw il- fuljett ta` tagħrif li jinstab fil -
They 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 jneħħu 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.
5 Aċidożi lattika: aċidożi lattika, ħafna drabi assoċjata ma ’ ħepatomegalija u stejatożi epatika, deheret bl- użu ta` analogi tan- nuklejosajd.
Early symptoms (symptomatic hyperlactatemia) include benign digestive symptoms (nausea, vomiting and abdominal pain), non-specific malaise, loss of appetite, weight loss, respiratory symptoms (rapid and/ or deep breathing) or neurological symptoms (including motor weakness).
Sintomi fil- bidu (iperlaktejtimja sintomatika) jinkludu sintomi diġestivi beninji li mhumiex perikolużi (dardir, rimettar kif ukoll uġigħ addominali), ħass ħażin mhux speċifiku, nuqqas ta ’ aptit, telf fil- piż, sintomi respiratorji (nifs mgħaġġel u/ jew fil- fond) jew sintomi newroloġiċi (li jinkludu indeboliment fil- movimenti).
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, indeboliment fil- fwied, jew indeboliment tal- kliewi.
Lactic acidosis generally occurred after a few or several months of treatment.
Aċidożi lattika ġeneralment toħroġ wara ftit jew numru ta ’ xhur tal- kura.
5 Treatment with nucleoside analogues should be discontinued in the setting of symptomatic hyperlactatemia and metabolic/ lactic acidosis, progressive hepatomegaly, or rapidly elevating aminotransferase levels.
Trattament b`analogi tan- nuklejosajd għandu jitwaqqaf meta jkun hemm iperlaktejtimja sintomatika u aċidożi lattika metabolika, epatomegalija progressiva, jew meta l- livell ta ’ aminotransferase 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 meta jingħataw l- 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).
Patients co-infected with hepatitis C and treated with alpha interferon and ribavirin may constitute a special risk.
Jista jkun hemm ukoll riskju speċjali f’ pazjenti li għandhom ukoll epatite C u qed jingħataw kura b`alpha interferon u ribavirin.
Patients at increased risk should be followed closely.
Pazjenti li huma aktar f`riskju għandha tingħatalhom attenzjoni mill- viċin.
There have been reports of mitochondrial dysfunction in HIV-negative infants exposed in utero and/ or post-natally to nucleoside analogues.
Kien hemm rapporti ta ’ disfunzjoni tal- mitokondrija fi trabi li huma negattivi għall- HIV li kienu esposti in utero u/ jew wara t- twelid għall - analogi tan- nukleosidi.
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, iperlajpejżimja).
Some late-onset neurological disorders have been reported (hypertonia, convulsion, abnormal behaviour).
Xi mard newroloġiku li deher iktar tard ġie rrapurtat (ipertonja, aċċessjoni, imġieba mhux normali).
Any child exposed in utero to nucleoside and nucleotide analogues, even HIV-negative children, should have clinical and laboratory follow-up and should be fully investigated for possible mitochondrial dysfunction in case of relevant signs or symptoms.
Kull tarbija esposta in utero għall- analogi tan- nukleosidi u tan- nukleotidi, anke trabi li huma negattivi għall- HIV, għandhom jiġu segwiti klinikament u f’ testijiet tal- laboratorju u jridu jiġu investigati kompletament għall- possibilita ’ ta ’ disfunzjoni tal- mitokondrija f’ każ ta ’ sinjali jew sintomi rilevanti.
The long-term consequences of these events are currently unknown.
L- effett fit- tul ta` dawn l- effetti għadhom mhux magħrufa.
A connection between visceral lipomatosis and protease inhibitors (PIs) and lipoatrophy and nucleoside reverse transcriptase inhibitors (NRTIs) has been hypothesised.
Konnessjoni bejn lipomatożi vixerali u inibituri protejejż (PIs) u lipoatrofija u inibituri tan- nuklejosajd tar- reverse transcriptase (NRTIs) ġiet ipotizzata.
A higher risk of lipodystrophy has been associated with individual factors such as older age, and with drug related factors such as longer duration of antiretroviral treatment and associated metabolic disturbances.
Riskju akbar ta` lipodistrofija kien assoċjat ma ’ fatturi individwali bħal xjuħija, kif ukoll ma ’ fatturi relatati mal- mediċina, bħal żmien itwal ta` kura b`antiretrovirali kif ukoll disturbi metaboliċi assoċjati.
Clinical examination should include evaluation for physical signs of fat redistribution.
Eżamijiet kliniċi għandhom jinkludu evalwazzjoni ta` sinjali fiżiċi tar - ridistribuzzjoni tax- xaħam.
Consideration should be given to the measurement of fasting serum lipids and blood glucose.
Għandu jkun ikkunsidrat il- kejl tax- xaħam fid- demm u tal- glucose fid - demm ta ’ meta l- pazjent ikun sajjem.
Lipid disorders should be managed as clinically appropriate (see section 4.8).
Problemi ta` xaħam fid- demm għandhom ikunu kurati kif jixraq klinikament (ara sezzjoni 4. 8).
Pancreatitis: pancreatitis has been reported, but a causal relationship to Ziagen treatment is uncertain.
Pankrejatite: kien hemm pankrejatite, iżda għadu mhux magħruf jekk dan l- effett huwiex relatat mal - kura b`Ziagen.
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).
There have been reports of a high rate of virological failure and of emergence of resistance at an early stage when abacavir was combined with tenofovir disoproxil fumarate and lamivudine as a once daily regimen.
Kien hemm rapporti ta ’ rata għolja ta ’ falliment viroloġiku u żvilupp ta’ resistenza fi stadju tal- bidu meta abacavir ingħata f’ kumbinazzjoni ma ’ tenofovir disoproxil fumarate u lamivudine darba kuljum.
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).
6 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).
Liver disease: the safety and efficacy of Ziagen has not been established in patients with significant underlying liver disorders.
Mard tal- fwied: is- sigurtà u l- effikaċja ta` Ziagen għadhom ma ġewx stabbiliti f` pazjenti li għandhom mard fil- fwied sinifikanti.
Ziagen is contraindicated in patients with severe hepatic impairment (see section 4.3).
Ziagen ma jistax jingħata lill- pazjenti b`indeboliment sever tal- fwied (ara sezzjoni 4. 3).
Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an increased risk of severe and potentially fatal hepatic adverse events.
Pazjenti b' epatite B kronika jew b' epatite C li jingħataw kura flimkien ma` terapija antiretrovirali għandhom riskju akbar li jsofru minn effetti epatiċi avversi severa u possibilment fatali.
In case of concomitant antiviral therapy for hepatitis B or C, please refer also to the relevant product information for these medicinal products.
F`każ ta` terapija simultanja b`mediċini antivirali għall- epatite B jew C, jekk jogħġbok irreferi wkoll għat- tagħrif rilevanti ta ’ dawn il- prodotti mediċinali.
Patients with pre-existing liver dysfunction, including chronic active hepatitis, have an increased frequency of liver function abnormalities during combination antiretroviral therapy, and should be monitored according to standard practice.
Pazjenti b' disfunzjoni tal- fwied pri- eżistenti, li tinkludi epatite kronika u attiva, għandhom numru akbar ta ’ abnormalitajiet fil- funzjoni tal- fwied meta jingħataw ukoll terapija antiretrovirali, u għandhom jiġu monitorjati skond il- prattika stàndard.
If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered.
F' każ li l- mard tal- fwied qiegħed imur għall - agħar f`dawn il- pazjenti, għandha tiġi kunsidrata waqfien tal- kura għal ċertu żmien jew għal kollox.
6 A pharmacokinetic study has been performed in patients with mild hepatic impairment.
Sar studju farmakokinetiku f`pazjenti b’ indeboliment epatiku ħafif.
However, a definitive recommendation on dose reduction is not possible due to substantial variability of drug exposure in this patient population (see section 5.2).
Madankollu, rakkomandazzjoni definittiva għal tnaqqis fid- doża mhux possibli minħabba varjabilità sostanzjali fl- esponiment għall - mediċina f`dan il- grupp ta ’ pazjenti (ara sezzjoni 5. 2).
The clinical safety data available with abacavir in hepatically impaired patients is very limited.
It- tagħrif kliniku ta ’ sigurtà li hemm dwar l- użu ta’ abacavir f`pazjenti li jsofru b' indeboliment epatiku huwa limitat ħafna.
Due to the potential increases in exposure (AUC) in some patients, close monitoring is required.
Minħabba li jista jkun hemm żieda fl- esponiment (AUC) f`xi pazjenti, dawn għandhom jinżammu taħt osservazzjoni.
No data are available in patients with moderate or severe hepatic impairment.
Ma teżisti l - ebda informazzjoni fuq pazjenti li jsofru minn epatite moderata jew severa.
Plasma concentrations of abacavir are expected to substantially increase in these patients.
Il- livell ta ’ abacavir fil - plażma huwa mistenni li jiżdied sostanzjalment f`dawn il- pazjenti.
Therefore, the use of abacavir in patients with moderate hepatic impairment is not recommended unless judged necessary and requires close monitoring of these patients.
Għalhekk l- użu ta ’ abacavir mhux rakkomandat f`pazjenti b`mard tal- fwied moderat sakemm ma tkunx meqjusa neċċessarja u f’ dan il - każ ikun hemm bżonn li jinżammu taħt osservazzjoni.
For patients with severe hepatic impairment, Ziagen is contraindicated (see section 4.3).
F' pazjenti li jsofru minn epatite severa, l- użu ta ’ Ziagen huwa kontra- indikat (ara sezzjoni 4. 3).
Renal disease:
Mard renali:
Ziagen should not be administered to patients with end-stage renal disease (see section 5.2).
(ara sezzjoni 5. 2).
In HIV-infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms.
Sindromu ta ’ Rijattivazzjoni Immunitarja: f’ pazjenti infettati bl- HIV, b’ defiċjenza immunitarja severa fiż- żmien li tkun inbdiet it- terapija antiretrovirali kombinata (TARK), jista ’ jkun hemm reazzjoni nfjammatorja għall- mikrobi opportunistiċi asintomatiċi jew residwali li jwasslu għall- kundizzjonijiet kliniċi serji jew li sintomi jmorru għall- agħar.
Relevant examples are cytomegalovirus retinitis, generalised and/ or focal mycobacterium infections, and Pneumocystis carinii pneumonia.
Eżempji rilevanti jinkludu retinite ċitomegalovirus, infezzjonijiet mikobatterjali lokali jew mifruxa, u pulmonite b’ Pneumocvstis carinii.
Opportunistic infections: patients receiving Ziagen or any other antiretroviral therapy may still develop opportunistic infections and other complications of HIV infection.
Infezzjonijiet opportunistiċi: pazjenti li qed jingħataw Ziagen jew xi terapija antiretrovirali oħra, xorta jistgħu joħorġulhom infezzjonijiet opportunistiċi u kumplikazzjonijiet oħra ta ’ l- infezzjoni ta` l- HIV.
Therefore patients should remain under close clinical observation by physicians experienced in the treatment of these associated HIV diseases.
Għalhekk il- pazjenti għandhom ikunu taħt osservazzjoni klinika minn tobba li għandhom esperjenza fuq il- kura ta ’ dawn li huma assoċjati mal- mard ta` l- HIV.
Transmission: patients should be advised that current antiretroviral therapy, including Ziagen, have not been proven to prevent the risk of transmission of HIV to others through sexual contact or blood contamination.
Tixrid ta’ l- HIV: il- pazjenti għandhom ikunu avżati li t- terapija antiretrovirali li hawn sa llum, incluż Ziagen, għadhom ma ġewx pruvati li jneħħu r- riskju tat- tixrid ta` l- HIV lill- ħaddieħor waqt kuntatt sesswali jew kontaminazzjoni tad- demm.
Appropriate precautions should continue to be taken.
Għandhom jibqgħu jittieħdu l- prekawzzjonijiet adattati.
Based on the results of in vitro experiments and the known major metabolic pathways of abacavir, the potential for P450 mediated interactions with other medicinal products involving abacavir is low.
Fuq il- bażi ta ’ riżultati ta ’ esperimenti in vitro u r- reazzjonijiet metaboliċi prinċipali magħrufa ta ’ abacavir, il- possibiltà ta` interazzjonijiet permezz ta ’ P450 ma 'prodotti mediċinali li fihom abacavir
P450 does not play a major role in the metabolism of abacavir, and abacavir does not inhibit metabolism mediated by CYP 3A4.
Il- P450 ma jieħux sehem importanti fil- metaboliżmu ta ’ abacavir, u abacavir ma ’ jfixkilx il- metaboliżmu li jseħħ permezz ta ’ CYP3A4.
Abacavir has also been shown in vitro not to inhibit CYP 3A4, CYP2C9 or CYP2D6 enzymes at clinically relevant concentrations.
Abacavir wera wkoll in vitro li ma jfixkilx l- enżimi CYP3A4, CYP2C9 jew CYP2D6 f`konċentrazzjonijiet klinikament rilevanti.
Induction of hepatic metabolism has not been observed in clinical studies.
Minn studji kliniċi ma deherx li kienx hemm metaboliżmu epatiku.
Therefore, there is little potential for interactions with antiretroviral PIs and other medicinal products metabolised by major P450 enzymes.
Għalhekk mhux probabli li jseħħu interazzjonijiet ma 'PIs antiretrovirali u prodotti mediċinali oħra metabolizzati bl- enżimi ewlenien ta ’ P450.
Clinical studies have shown that there are no clinically significant interactions between abacavir, zidovudine, and lamivudine.
Studji kliniċi wrew li m`hemm l- ebda interazzjonijiet klinikament sinifikanti bejn abacavir, zidovudine, u lamivudine.
Potent enzymatic inducers such as rifampicin, phenobarbital and phenytoin may via their action on UDP-glucuronyltransferases slightly decrease the plasma concentrations of abacavir.
Inducers enżimatiċi qawwija bħall rifampicin, phenobarbital u phenytoin jistgħu mill- azzjoni tagħhom fuq UDP- glukuronajltransferejżis, inaqqsu bi ftit il- konċentrazzjonijiet fil- plażma ta` abacavir.
Ethanol: the metabolism of abacavir is altered by concomitant ethanol resulting in an increase in AUC of abacavir of about 41%.
Ethanol: il- metaboliżmu ta ’ abacavir jinibidel jekk jittieħed ma ’ l- ethanol u dan jirriżulta f' żieda fl - AUC ta ’ abacavir ta` madwar 41%.
These findings are not considered clinically significant.
Dawn ir- riżultati m`humiex kunsidrati klinikalment sinifikanti.
Abacavir has no effect on the metabolism of ethanol.
Abacavir m`għandu l- ebda effett fuq il- metaboliżmu ta` l- ethanol.
7 Methadone: in a pharmacokinetic study, coadministration of 600 mg abacavir twice daily with methadone showed a 35% reduction in abacavir Cmax and a one hour delay in tmax but the AUC was unchanged.
Methadone: waqt studji farmakokinetiċi, meta 600 mg ta` abacavir darbtejn kuljum ingħata ma 'methadone kien hemm tnaqqis ta ’ 35% fis- Cmax ta ’ abacavir u t- tmax żdiedet b' siegħa, iżda l`AUC ma nbidilx.
The changes in abacavir pharmacokinetics are not considered clinically relevant.
Il- bidliet farmakokinetiċi ta ’ abacavir mhumiex kunsidrati klinikalment rilevanti.
In this study abacavir increased the mean methadone systemic clearance by 22%.
F`dan l - istudju abacavir żied il- medja tal- clearance ta` methadone mis- sistema b '22%.
The induction of drug metabolising enzymes cannot therefore be excluded.
L- induction ta ’ enżimi risponsabbli mill- metaboliżmu tal- mediċini għalhekk ma tistax tiġi eskluża.
Patients being treated with methadone and abacavir should be monitored for evidence of withdrawal symptoms indicating under dosing, as occasionally methadone re-titration may be required.
Pazjenti li qed jingħataw kura b`methadone u abacavir għandhom jiġu eżaminati għal- sintomi ta ’ twaqqif mil- kura li jindikaw dożi baxxi, minħabba li f`kulltant jista jkun meħtieġ re- titration ta ’ methadone.
Retinoids: retinoid compounds are eliminated via alcohol dehydrogenase.
Retinojdi: is- sustanzi retinojdi jiġu eliminati permezz ta ’ l- alcohol dehydrogenase.
Interaction with abacavir is possible but has not been studied.
Interazzjoni b`abacavir hija possibbli iżda għadha ma ġietx studjata.
Ziagen is not recommended during pregnancy.
Ziagen mhux rakkomandat waqt it- tqala.
The safe use of abacavir in human pregnancy has not been established.
Għadu ma ġiex stabbilit jekk abacavir jistax ikun ta ’ ħsara għall- bniedem meta jittieħed waqt it- tqala.
Placental transfer of abacavir and/ or its related metabolites has been shown to occur in animals.
Deher li abacavir u/ jew il- metaboli relatati għaddew mill - plaċenta ta ’ l- annimali.
Toxicity to the developing embryo and foetus occurred in rats, but not in rabbits (see section 5.3).
Effetti tossiċi fuq l- embriju u fuq il- fetu waqt l- iżvilupp tagħhom dehru fil - firien, iżda mhux fil- fniek (ara sezzjoni 5. 3).
The teratogenic potential of abacavir could not be established from studies in animals.
Il- potenzjal teratoġeniku ta ’ abacavir ma setgħax jiġi stabbilit minn studji li saru fl- annimali.
Abacavir and its metabolites are secreted into the milk of lactating rats.
Abacavir u l- metaboli tiegħu joħorġu fil- ħalib tas- sider tal- firien li qed ireddgħu.
It is expected that these will also be secreted into human milk, although this has not been confirmed.
Huwa mistenni li dawn joħorġu ukoll fil- ħalib uman, għalkemm dan għadu ma ġiex konfermat.
There are no data available on the safety of abacavir when administered to babies less than three months old.
M' hemmx tagħrif fuq is - sigurtà ta ’ abacavir meta jingħata lit- trabi li għandhom anqas minn tlett xhur.
It is therefore recommended that mothers do not breast-feed their babies while receiving treatment with abacavir.
Għalhekk huwa rakkomandat li l- ommijiet ma jreddgħux waqt li qed jingħataw kura b` abacavir.
Additionally, it is recommended that HIV infected women do not breast-feed their infants under any circumstances in order to avoid transmission of HIV.
Minbarra hekk, huwa rrakkomandat li nisa infettati bl- HIV ma jreddgħux lit- trabi tagħhom taħt l- ebda ċirkostanza sabiex ma tinxteridtx il- marda ta` l- HIV.
Hypersensitivity (see also section 4.4):
Sensittività eċċessiva (ara wkoll sezzjoni 4. 4):
In clinical studies with abacavir 600 mg once daily the reported rate of hypersensitivity remained within the range recorded for abacavir 300 mg twice daily.
Minn studji kliniċi li saru, nstab li bejn wieħed u ieħor ir- rata ta` 45% tas- suġġetti li jirċievu abacavir ikollhom reazzjoni ta` sensittività eċċessiva; Fi studji kliniċi b’ abacavir 600mg darba kuljum, ir- rata ta ’ sensittività eċċessiva rrappurtata baqgħat fl- istess limitu rreġistrat għal abacavir 300mg darbtejn kuljum.
Some of these hypersensitivity reactions were life-threatening and resulted in fatal outcome despite taking precautions.
Xi wħud minn dawn ir- reazzjonijiet ta ’ sensittività eċċessiva kienu ta` periklu għall- ħajja u kienu fatali minkejja li kienu ttieħdu l- prekawzjonijiet.
This reaction is characterised by the appearance of symptoms indicating multi-organ/ body-system involvement.
Din ir- reazzjoni tingħaraf mid- dehra ta ’ sintomi li jindikaw involviment ta ’ ħafna organi/ sistemi tal- ġisem.
Almost all patients developing hypersensitivity reactions will have fever and/ or rash (usually maculopapular or urticarial) as part of the syndrome, however reactions have occurred without rash or fever.
Kważi l- pazjenti kollha li jkollhom reazzjonijiet ta` sensittività eċċessiva jkollhom deni u/ jew raxx (normalment makulopapulari jew bl- urtikarja) bħala parti mis- sindromu, għalkemm ġieli dehru reazzjonijiet mingħajr raxx jew deni.
The signs and symptoms of this hypersensitivity reaction are listed below.
Is- sinjali u sintomi ta` dawn ir- reazzjonijiet ta` sensittività eċċessiva huma mniżżlin hawn taħt.
These have been identified either from clinical studies or post marketing surveillance.
Dawn ġew identifikati minn studji kliniċi jew minn stħarriġ li sar wara l- bejgħ tal- prodott.
Those reported in at least 10% of patients with a hypersensitivity reaction are in bold text.
Dawk li ġew rappurtati minn ta`l- anqas f 10% tal- pazjenti b`reazzjoni ta` sensittività eċċessiva huma miktubin b`kitba ħoxna.
Skin Rash (usually maculopapular or urticarial)
Raxx (normalment makulopapulari jew urtikarja) Ġilda
Nausea, vomiting, diarrhoea, abdominal pain, mouth ulceration
Nawsja, rimettar, dijarrea, uġigħ addominali, ulċera fil- ħalq Sistema gastro- intestinali
Dyspnoea, cough, sore throat, adult respiratory distress syndrome, respiratory failure
Dispneja, sogħla, uġigħ tal- griżmejn, sindromu ta ’ tbatija Sistema respiratorja respiratorja fl- adulti, insuffiċjenza respiratorja
Fever, lethargy, malaise, oedema, lymphadenopathy,
Deni, letarġija, ħass ħażin, edima, limfadenopatija, pressjoni Imħalltin baxxa ħafna, konġunktivite, anafilassi
8 hypotension, conjunctivitis, anaphylaxis
Uġigħ ta` ras, parasteżija Newroloġika/ Psikjatrija
Neurological/ Psychiatry
Limfopenja Ħematoloġiċi
Elevated liver function tests, hepatitis, hepatic failure
Riżultati għoljin tat- testijiet ghall- funzjoni tal- fwied, epatite, Fwied/ pankrejas indeboliment tal- fwied
Myalgia, rarely myolysis, arthralgia, elevated creatine phosphokinase
Mijalġja, rarament majolajiżi, artralġja, livelli elevati ta ’ Muskolo- skeletriku krejatinina fosfokajnejż
Elevated creatinine, renal failure
Livelli għoljin tal- krejatinina, indeboliment renali Uroloġija
Rash (81% vs 67% respectively) and gastrointestinal manifestations (70% vs 54% respectively) were more frequently reported in children compared to adults.
Raxx (81% vs 67% rispettivament) u manifestazzjonijiet gastrointestinali (70% vs 54% rispettivament) dehru aktar spiss fit- tfal meta mqabbla ma 'l- adulti.
Some patients with hypersensitivity reactions were initially thought to have gastroenteritis, respiratory disease (pneumonia, bronchitis, pharyngitis) or a flu-like illness.
F’ xi wħud mill- pazjenti b`reazzjonijiet ta` sensittività eċċessiva għall- ewwel kien hemm il- ħsieb li kellhom gastroenterite, mard respiratorju (pulmonite, bronkite, farinġite) jew mard simili għal dak ta`l- influwenza.
This delay in diagnosis of hypersensitivity has resulted in Ziagen being continued or re-introduced, leading to more severe hypersensitivity reactions or death.
Minħabba li d- dijanjożi ta` sensittività eċċessiva ma saritx mill- ewwel, Ziagen tkompla jew reġa 'ingħata u dan wassal għal reazzjonijiet ta ’ sensittività eċċessiva severi jew fatali.
Therefore, the diagnosis of hypersensitivity reaction should be carefully considered for patients presenting with symptoms of these diseases.
Għalhekk, id- dijanjożi ta` sensittività eċċessiva għandha issir bir- reqqa f`pazjenti li għandhom xi sintomi ta` dawn il- mard.
Symptoms usually appeared within the first six weeks (median time to onset 11 days) of initiation of treatment with abacavir, although these reactions may occur at any time during therapy.
Is- sintomi normalment ħargu fl- ewwel sitt ġimgħat (medja tal- ħin biex jibdew 11- il ġurnata) mill - bidu tal- kura b`abacavir, għalkemm dawn ir- reazzjonijiet jistgħu joħorġu f`kull żmien matul it -
Close medical supervision is necessary during the first two months, with consultations every two weeks.
Il- pazjenti għandhom jingħataw attenzjoni mil- qrib, b`mod speċjali matul l- ewwel xaharejn tal- kura b`Ziagen, b’ konsulti kull ġimgħatejn.
It is likely that intermittent therapy may increase the risk of developing sensitisation and therefore occurrence of clinically significant hypersensitivity reactions.
Aktarx li t- terapija intermittenti tista żżid ir- riskju li jiżviluppaw sensibilizzazzjoni u għalhekk okkorrenza ta ’ reazzjonijet ta` sensittività eċċessiva klinikament sinifikanti.
Consequently, patients should be advised of the importance of taking Ziagen regularly.
Għaldaqstant, il - pazjenti għandhom jiġu mgħarrfa kemm huwa importanti li jieħdu Ziagen b`mod regolari.
Restarting Ziagen following a hypersensitivity reaction results in a prompt return of symptoms within hours.
Meta jerġa jibda jingħata Ziagen wara li kien hemm reazzjonijiet ta` sensittività eċċessiva jista jirriżulta li l- istess reazzjonijiet jerġgħu joħorġu fi ftit sigħat.
Patients who develop this hypersensitivity reaction must discontinue Ziagen and must never be rechallenged with Ziagen, or any other medicinal product containing abacavir (i. e.
Pazjenti li jkollhom reazzjoni ta`sensittività eċċessiva għandhom jieqfu jieħdu Ziagen immedjatament u m`għandhom qatt jerġgħu jippruvaw jieħdu Ziagen jew xi prodott mediċinali ieħor li fih abacavir (i. e.
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 id- dijanjożi issir mill- ewwel u tnaqqas ir- riskju ta` reazzjoni ta` sensittività eċċessiva ta` periklu għall- ħajja, Ziagen għandu jitwaqqaf hekk kif ikun hemm suspett ta ’ sensittività eċċessiva anki meta jkun hemm possibiltà ta` dijanjożi oħra (mard respiratorju, mard simili għal dak ta` l - influwenza, gastroenterie jew reazzjonijiet għal mediċini oħra).
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.
Kien hemm reazzjonijiet ta ’ sensittività eċċessiva li bdew malajr, li kienu jinkludu reazzjonijiet ta` periklu għall- ħajja wara li reġa ngħata Ziagen lill- pazjenti li kellhom biss wieħed mis- sintomi ewlenin magħrufa ta` sensittività eċċessiva (raxx tal- ġilda, deni, sintomi gastrointestinali, sintomi respiratorji jew kostituzzjonali 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 reaction.
Minn barra hekk, f`okkażżjonijiet rari ħafna reazzjonijiet ta` sensittività eċċessiva ġew rappurtati f`pazjenti li reġgħu bdew it- terapija, u li ma kellhom l- ebda sintomi preċedenti ta ’ xi reazzjoni ta` sensittività eċċessiva.
In both cases, if a decision is made to restart Ziagen this must be done in a setting where medical assistance is readily available.
Fiż- żewġ każijiet jekk tittieħed deċiżjoni sabiex jerġa jibda jingħata Ziagen, dan għandu jingħata fejn hemm assistenza medika lesta.
Each patient must be warned about this hypersensitivity reaction to abacavir.
Kull pazjent għandu jiġi mwissi fuq ir- reazzjonijiet ta` sensittività eċċessiva għal abacavir.
For many of the other adverse reactions reported, it is unclear whether they are related to Ziagen, to the wide range of medicinal products used in the management of HIV infection or as a result of the disease process.
Għal ħafna mir- reazzjonijiet avversi li ġew rappurtati, għadu mhux magħruf jekk kienux relatati ma 'Ziagen, jew ma ’ xi wieħed mill- għażla vasta ta` prodotti mediċinali li jiġu wżati fit- kura ta ’ l - infezzjonijiet ta` l- HIV, jew jekk kienux riżultat tal- proċess tal- marda.
9 Many of those listed below occur commonly (nausea, vomiting, diarrhoea, fever, lethargy, rash) in patients with abacavir hypersensitivity.
Ħafna minn dawn li huma mniżżla hawn taħt huma komuni (nawżeja, rimettar, dijarrea, deni, letarġija raxx) f` pazjenti b`sensittività eċċessiva għal abacavir.
Therefore, patients with any of these symptoms should be carefully evaluated for the presence of this hypersensitivity reaction.
Għalhekk, pazjenti li jkollhom wieħed minn dawn is- sintomi għandhom jiġu studjati sewwa għal xi reazzjonijiet ta` sensittività eċċessiva li jista jkun hemm.
If Ziagen 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 Ziagen kien twaqqaf f’ xi pazjenti minħabba li kien instab li kellhom xi wieħed minn dawn is- sintomi u reġgħet ttieħdet id- deċiżjoni sabiex jerġa jibda jingħata prodott medicinali li fih abacavir, dan għandu jingħata f`sitwazzjonijiet fejn ikun hemm assistenza medika lesta (ara sezzjoni 4. 4.).
Very rarely cases of erythema multiforme, Stevens Johnson syndrome or toxic epidermal necrolysis have been reported where abacavir hypersensitivity could not be ruled out.
Rari ħafna każijiet ta ’ erythema multiforme, sindromu ta ’ Stevens Johnson jew nekroliżi tossika epidermali dehru meta reazzjoni ta ’ sensittività eċċessiva għal abacavir ma setghatx tiġi eskluża.
Many of the adverse reactions have not been treatment limiting.
Ħafna mill- effetti avversi ma jfixklux il- kura.
The following convention has been used for their classification: very common (> 1/ 10), common (> 1/ 100 ,< 1/10), uncommon (> 1/ 1,000 ,< 1/100), rare (> 1/ 10,000, < 1/ 1,000) very rare (< 1/ 10,000).
Kienu klassifikati b' dawn il- kriterji: - komuni ħafna (> 1/ 10), komuni (> 1/ 100, < 1/ 10), mhux komuni (> 1/ 1, 000, < 1/ 100), rari (> 1/ 10, 000, < 1/ 1, 000) rari ħafna (< 1/ 10, 000).
Metabolism and nutrition disorders Common: anorexia
Mard tal- metaboliżmu u nutrizzjoni Komuni: anoressja
Nervous system disorders Common: headache
Mard tas- sistema nervuża Komuni: uġigħ ta` ras
Gastrointestinal disorders Common: nausea, vomiting, diarrhoea Rare: pancreatitis
10 Mard gastro- intestinali Komuni: nawżeja, rimettar, dijarrea Rari: deheret pankrejatite.
Skin and subcutaneous tissue disorders Common: rash (without systemic symptoms) Very rare: erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis
Mard tal- ġilda u tessuti ta ’ taħt il- ġilda Komuni: raxx (mingħajr sintomi sistemiċi) Rari ħafna: erythema multiforme, sindromu ta ’ Stevens- Johnson u nekroliżi tossika epidermali
General disorders and administration site conditions Common: fever, lethargy, fatigue
Mard ġenerali u kondizzjonijiet ta ’ mnejn jingħata Komuni: deni, letarġija, għejja.
Cases of lactic acidosis, sometimes fatal, usually associated with severe hepatomegaly and hepatic steatosis, have been reported with the use of nucleoside analogues (see section 4.4).
Każijiet ta` aċidożi lattika, ġieli fatali, normalment assoċjati ma 'epatomegalija severa u stejatożi epatika, ġew rappurtati waqt l- użu ta` analogi tan- nuklejosajd (ara sezzjoni 4. 4).
Combination antiretroviral therapy has been associated with redistribution of body fat (lipodystrophy) in HIV patients including the loss of peripheral and facial subcutaneous fat, increased intra-abdominal and visceral fat, breast hypertrophy and dorsocervical fat accumulation (buffalo hump).
Terapija kombinata ma` terapija antiretrovirali ikawżat ridistribuzzjoni tax- xaħam fil- ġisem (lipodistrofija) f`pazjenti bl- HIV li jinkludi t- telf ta ’ xaħam ta ’ taħt il- ġilda f’ żoni periferali u fil- wiċċ, żieda fix- xaħam intra- addominali u vixxerali, tkabbir tas- sider u akkumulazzjoni 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).
Terapija antiretrovirali kombinata ikawżat abnormalitajiet metaboliċi bħal ipertrajgliserajdimja, iperkolesterolimja, reżistenza għall- insulina, u iperlaktejtimja (ara sezzjoni 4. 4).
In HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART) an inflammatory reaction to asymptomatic or residual opportunistic infections may arise (see section 4.4).
F’ pazjenti infettati bl- HIV, b’ defiċjenza immunitarja severa fiż- żmien li tkun inbdiet it- terapija antiretrovirali kombinata (TARK), jista ’ jkun hemm reazzjoni nfjammatorja għall- mikrobi opportunistiċi asintomatiċi jew residwali (ara sezzjoni 4. 4)
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 ’ ostejonekrożi nstabu li huwa partikolarment aktar komuni f’ pazjenti b’ fatturi ta ’ riskju magħrufa, b’ HIV avvanzat u/ jew użu ta ’ terapija antiretrovirali kombinata (TARK) fit- tul.
The frequency of this is unknown (see section 4.4).
Il - frekwenza ta ’ din m’ hijiex magħrufa (ara sezzjoni 4. 4).
Laboratory abnormalities In controlled clinical studies laboratory abnormalities related to Ziagen treatment were uncommon, with no differences in incidence observed between Ziagen treated patients and the control arms.
Abnormalitajiet tal- laboratorju Fi studji kliniċi kontrollati l- abnormalitajiet tal- laboratorju relatati mal- kura ta` Ziagen ma kienux komuni, u ma ġiet osservata l- ebda differenza fl- inċidenza ta ’ l- abnormalitajiet bejn pazjenti fuq Ziagen u dawk fil- grupp ta ’ kontroll.
10 4.9 Overdose
4. 9 Doża eċċessiva
Single doses up to 1200 mg and daily doses up to 1800 mg of Ziagen have been administered to patients in clinical studies.
F' studji kliniċi ngħataw dożi waħdiet ta` 1200 mg sa 1800 mg kuljum ta` Ziagen lill- pazjenti.
No unexpected adverse reactions were reported.
Ma deher l- ebda effett avvers mhux mistenni.
The effects of higher doses are not known.
L- effetti ta` dożi aktar għolja għadhom mhux magħrufa.
If overdose occurs the patient should be monitored for evidence of toxicity (see section 4.8), and standard supportive treatment applied as necessary.
Hekk ikun hemm każ ta` doża eċċessiva l- pazjent għandu jibqa taħt osservzzjoni għall- evidenza ta` tossiċità (ara sezzjoni 4. 8), u kura ta ’ support bażika għandha tingħata kif ikun hemm bżonn.
It is not known whether abacavir can be removed by peritoneal dialysis or haemodialysis.
Għadu mhux magħruf jekk abacavir jistax jitneħħa b`dijaliżi peritonali jew b' imodijaliżi.
Pharmacotherapeutic group: nucleoside reverse transcriptase inhibitors, ATC Code:
Kategorija farmakoterapewtika - Inibituri tan- nuklejosajd reverse transcriptase, Kodiċi ATC:
Abacavir is a NRTI.
Mod ta ’ kif jaħdem: Abacavir huwa NRTI.
It is a potent selective inhibitor of HIV-1 and HIV-2.
Huwa sustanza selettiva antivirali qawwija kontra L- HIV- 1 u HIV- 2.
Abacavir is metabolised intracellularly to the active moiety, carbovir 5’ - triphosphate (TP).
Abacavir jiġi mmetaboliżżat fiċ- ċelloli għal sustanza attiva, carbovir 5 ’ - triphosphate (TP).
In vitro studies have demonstrated that its mechanism of action in relation to HIV is inhibition of the HIV reverse transcriptase enzyme, an event which results in chain termination and interruption of the viral replication cycle.
Studji in vitro wrew li jaħdem fuq l- HIV billi jimpedixxi l- enżima HIV reverse transcriptase, li jwassal għal egħluq tat- tarf tal- katina u l- interruzzjoni taċ- ċiklu ta ’ replikazzjoni tal- vajrus.
Abacavir shows synergy in vitro in combination with nevirapine and zidovudine.
Abacavir juri effett sinerġetiku in vitro meta jingħata ma` nevirapine u zidovudine.
It has been shown to be additive in combination with didanosine, lamivudine and stavudine.
Intwera li jkun hemm effett addittiv meta jingħata ma` didanosine, lamivudine u stavudine.
Abacavir-resistant isolates of HIV-1 have been selected in vitro and are associated with specific genotypic changes in the reverse transcriptase (RT) codon region (codons M184V, K65R, L74V and Y115F).
11 Reżistenza in vitro: Iżolati ta` l- HIV- 1 reżistenti għal abacavir ġew magħżula in vitro u huma assoċjati ma 'tibdiliet ġenotipiċi speċifiċi tar- reverse transcriptase (RT) codon region (codons M184V, 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 virali għal abacavir tiżviluppa relattivament bil- mod in vitro, li jirrikjedu bosta mutazzjonijiet sabiex tintlaħaq żieda klinikament rilevanti fl- EC50 fuq dak tal- vajrus li jinsab fin - natura.
In vivo resistance (Therapy naïve patients) Isolates from most patients experiencing virological failure with a regimen containing abacavir in pivotal clinical trials showed either no NRTI-related changes from baseline (45%) or only M184V or M184I selection (45%).
Iżolati minn ħafna pazjenti li jkunu għaddejin minn falliment viroloġiku b’ sistema ta ’ kura li jkun fiha abacavir, ma urew l- ebda bdil mill- livell bażiku fejn għandu x’ jaqsam NRTI (45%) jew M184V biss jew għażla ta ’ M184I (45%) fi studji kliniċi prinċipali.
The overall selection frequency for M184V or M184I was high (54%), and less common was the selection of L74V (5%), K65R (1%) and Y115F (1%).
Il- frekwenza ta ’ selezzjoni totali għal M184V jew M184I kienet għolja (54%), u s - selezzjoni ta ’ L74V (5%), K65R (1%) u Y115F (1%) kienet anqas komuni.
Therapy
Totali
PI (or PI/ ritonavir)
PI (jew PI/ ritonavir)
Subjects
Suġġetti
Number of Virological Failures Number of
Fallimenti Viroloġiċi Numru ta ’
On-Therapy Genotypes
51 (100%) 2 Genotipi fuq Terapija
Number of subjects with ≥ 1 Thymidine Analogue Mutations (TAMs).
Numru ta ’ suġġetti b’ ≥1 Mutazzjonijiet ta ’ l- Analogi ta ’ Thymidine (MAT).
11 TAMs might be selected when thymidine analogs are associated with abacavir.
MAT jistgħu ikunu magħżula meta analogi ta ’ thymidine ikollhom x’ jaqsmu ma ’ abacavir.
In a meta-analysis of six clinical trials, TAMs were not selected by regimens containing abacavir without zidovudine (0/ 127), but were selected by regimens containing abacavir and the thymidine analogue zidovudine (22/ 86, 26%).
F’ meta - analiżi ta’ sitt studji kliniċi, l- MAT ma kienux magħżula minn sistemi ta ’ kura li fihom abacavir mingħajr zidovudine (0/ 127), imma kienu magħżula minn sistemi ta ’ kura li fihom abacavir u l - analogu ta ’ thymidine zidovudine (22/ 86, 26%).
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 klinikament sustanzjali fis- suxxettibilita ’ ta ’ abacavir deher f’ iżolati kliniċi ta ’ pazjenti, b’ replikazzjoni mingħajr kontroll tal- virus, li kienu ttrattati minn qabel bi u huma reżistenti għall- inibituri ta ’ nukleosidi oħra.