qanastek/EMEA-V3 huggingface dataset:
PIs) unlikely.
Il- metaboliżmu ta ’ lamivudine u zidovudine ma jinkludix CYP3A, u għalhekk mhux probabbli li jkun hemm interazzjonijiet ma 'prodotti mediċinali li jiġu mmetaboliżżati b’ din is- sistema (eż PI).
Interactions relevant to lamivudine
Interazzjonijiet li għandhom x' jaqsmu ma ’ lamivudine
The possibility of interactions with other medicinal products administered concurrently with Combivir should be considered, particularly when the main route of elimination is active renal secretion, especially via the cationic transport system e. g. trimethoprim.
Il- possibbilta 'ta' nuqqas ta 'interazzjonijiet ma' prodotti mediċinali oħra li jingħataw fl- istess ħin għandha tiġi kkunsidrata, partikolarment meta r- rotta ewlenija tat- tneħħija tkun is- sekrezzjoni attiva mill- kliewi permezz tas- sistema tat- trasport organika u katajonika p. e. trimethoprim.
Nucleoside analogues (e. g. zidovudine, didanosine and zalcitabine) and other medicinal products (e. g. ranitidine, cimetidine) are eliminated only in part by this mechanism and were shown not to interact with lamivudine.
Analogi nuklejosidi (e. g. zidovudine, didanosine u zalcitabine) u prodotti mediċinali oħra (p. e. ranitidine, cimetidine) jitneħħew parzjalment biss b' dan il- mekkaniżmu u mingħajr interazzjonijiet ma ’ lamivudine.
Administration of trimethoprim/ sulfamethoxazole 160 mg/ 800 mg results in a 40% increase in lamivudine exposure, because of the trimethoprim component; the sulfamethoxazole component does not interact.
L- għoti ta ’ 160 mg/ 800 mg trimethoprim/ sulphamethoxazole jirriżulta f' żieda ta '40% fl- esponiment ta ’ lamivudine, minħabba li fih trimethoprim; Ma kienx hemm interazzjonijiet mas - sulphamethoxazole.
However, unless the patient has renal impairment, no dosage adjustment of lamivudine is necessary (see section 4.2).
Madankollu, sakemm il- pazjent ma jkollux indeboliment tal- kliewi, ma jkunx hemm bżonn ta 'bdil fid- dożaġġ ta ’ lamivudine (ara taqsima 4. 2).
Lamivudine has no effect on the pharmacokinetics of trimethoprim or sulfamethoxazole.
Lamivudine m' għandu l- ebda effett fuq il- farmakokinetika ta ’ trimethoprim jew ta ’ sulphamethoxazole.
When concomitant administration with co-trimoxazole is warranted, patients should be monitored clinically.
Meta tinħass il- ħtieġa li jingħata flimkien ma ’ co- trimaxozole, il- pazjenti għandhom ikunu mmonitorjati klinikament.
Co-administration of Combivir with high doses of co-trimoxazole for the treatment of Pneumocystis jiroveci pneumonia (formerly known as Pneumocystis carinii pneumonia [PCP]) and toxoplasmosis should be avoided.
L- għoti ta ’ Combivir flimkien ma 'dożi qawwija ta co- trimoxazole għall- kura tal- pulmonite Pneumocystis jiroveci (li qabel kienet magħrufa bħala pulmonite b’ Pneumocystis carinii [PCP]) u toxoplażmożi għandu jiġi evitat.
Co-administration of lamivudine with intravenous ganciclovir or foscarnet is not recommended.
L- għoti ta ’ lamivudine flimkien ma 'ganċiklovir jew foskarnet minn ġol- vini mhux irrakkomandat sakemm jinkiseb aktar tagħrif.
Interactions relevant to zidovudine
Interazzjonijiet li għandhom x' jaqsmu ma ’ zidovudine
Limited data suggest that co-administration of zidovudine and rifampicin decreases the AUC of zidovudine by 48% ± 34%.
Informazzjoni limitata tindika li l- għoti ta ’ zidovudine u rifampicin flimkien inaqqas l- AUC ta ’ zidovudine b' 48% ± 34%.
However the clinical significance of this is unknown.
Madankollu is- sinifikat kliniku ta 'dan mhux magħruf.
Dose modifications of zidovudine in this situation have not been formally evaluated.
Għadhom ma ġewx evalwati formalment tibdil fid- doża ta ’ zidovudine f’ din is- sitwazzjoni.
Limited data suggest that probenecid increases the mean half-life and area under the plasma concentration curve of zidovudine by decreasing glucuronidation.
Informazzjoni limitata tindika li probecenid iżid il- half- life u l- AUC ta ’ zidovudine fil- plażma billi jnaqqas il- glukuronidazzjoni.
Renal excretion of the glucuronide (and possibly zidovudine itself) is reduced in the presence of probenecid.
It- tneħħija tal- glukuronid mill- kliewi (u possibilment it- tneħħija ta’ zidovudine stess) tonqos meta jkun hemm probenecid.
Patients receiving both medicinal products should be closely monitored for haematological toxicity.
Pazjenti li qegħdin jirċievu iż- żewġ prodotti mediċinali għandu jiġu osservati mill- qrib għal tossiċità ematoloġika.
Phenytoin blood levels have been reported to be low in some patients receiving zidovudine, while in one patient a high level was noted.
Instab li livelli ta 'phenytoin fid- demm kienu baxxi f' xi pazjenti li kienu qed jieħdu zidovudine, waqt li f’ pazjent wieħed instab livell għoli.
These observations suggest that phenytoin concentrations should be carefully monitored in patients receiving Combivir and phenytoin.
Dawn l- osservazzjonijiet jindikaw li l- konċentrazzjonijiet ta 'phenytoin għandhom jiġu mmonitorjati bir- reqqa f' pazjenti li jkunu qed jieħdu Combivir u phenytoin.
In a pharmacokinetic study co-administration of zidovudine and atovaquone tablets showed a decrease in zidovudine clearance after oral dosing leading to a 35% ± 23% increase in plasma zidovudine AUC.
Fi studju farmakokinetiku meta zidovudine ingħata ma ’ pilloli ta ’ atovaquone kien hemm nuqqas fit - tneħħija ta 'zidovudine mill- kliewi wara doża li ttieħdet mill- ħalq li rriżulta fi żieda ta 35% ± 23% fl - AUC ta' zidovudine fil- plażma.
Given the limited data available the clinical significance of this is unknown.
Mhuwiex magħruf il- mod ta ’ interazzjoni u billi konċentrazzjonijiet ta ’ atovaquone aktar għoljin jistgħu jintlaħqu bis- sospensjoni ta ’ atavaquone, huwa possibli li bdil akbar fl- AUC għal zidovudine jistgħu jkunu indotti meta atovaquone tingħata bħala sospensjoni. Skond l- informazzjoni limitata eżistenti l- importanza klinika ta 'dan mhux magħruf.
Valproic acid, fluconazole or methadone when co-administered with zidovudine have been shown to increase the AUC of zidovudine, with a corresponding decrease in its clearance.
6 Meta valproic acid, fluconazole jew methadone jittieħdu flimkien ma ’ zidovudine instab li jżidu l - AUC ta ’ zidovudine, bi tnaqqis korrispondenti fit- tneħħija tiegħu.
As only limited data are available the clinical significance is not known.
Peress li l- informazzjoni eżistenti hija limitata l- importanza klinika ta 'dan mhux magħruf.
If zidovudine is used concurrently with either valproic acid, fluconazole or methadone, patients should be monitored closely for potential toxicity of zidovudine.
Jekk zidovudine jintuża flimkien ma ’ jew valproic acid jew fluconazole jew methadone, il- pazjenti għandhom jiġu osservati mill- qrib għal possibilità ta ’ tossiċità b’ zidovudine.
Zidovudine and stavudine in combination are antagonistic in vitro, therefore the concomitant use of stavudine with Combivir should be avoided (see section 4.4).
Zidovudine u stavudine flimkien huma antagonistiċi in vitro, għalhekk wieħed għandu jevita li jieħu ribavirina jew stavudine flimkien ma ’ Combivir.
Exacerbation of anaemia due to ribavirin has been reported when zidovudine is part of the regimen used to treat HIV although the exact mechanism remains to be elucidated.
Ġie irrapurtat li anemija marret għall- agħar minħabba ribavirin meta zidovudine kien parti mis - sistema ta ’ kura użat biex jittratta HIV għalkemm il- mekkaniżmu eżatt għadu mhux magħruf.
The concomitant use of ribavirin with zidovudine is not recommended due to an increased risk of anaemia (see section 4.4).
Mhuwiex rakkomandat li ribavirin u zidovudine jittieħdu flimkien minħabba riskju akbar ta ’ anemija (ara sezzjoni 4. 4).
6 Consideration should be given to replacing zidovudine in a combination ART regimen if this is already established.
Għandu jiġi kkunsidrat li jinbidel zidovudine f’ sistema ta ’ kura ART kombinata jekk din tkun digà stabbilita.
This would be particularly important in patients with a known history of zidovudine induced anaemia.
Din tkun partikolarment importanti f’ pazjenti li kellhom anemija b’ zidovudine fil- passat.
Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products (e. g. systemic pentamidine, dapsone, pyrimethamine, co-trimoxazole, amphotericin, flucytosine, ganciclovir, interferon, vincristine, vinblastine and doxorubicin) may also increase the risk of adverse reactions to zidovudine.
It- teħid fl- istess ħin, speċjalment f' terapija akuta, ta 'prodotti mediċinali li jistgħu ikunu nefrotossiċi jew majelosuppressivi (e. g. pentamidine, dapsone, pyrimethamine, co- trimaxozole, amphotericin, flucytosine, ganciclovir, interferon, vincristine, vinblastine u doxorubicin) jistgħu ukoll iżidu r- riskju ta' reazzjonijiet avversi għal zidovudine.
If concomitant therapy with Combivir and any of these medicinal products is necessary then extra care should be taken in monitoring renal function and haematological parameters and, if required, the dosage of one or more agents should be reduced.
Jekk ikun hemm bżonn ta ’ xi wieħed minn dawn il- prodotti flimkien ma ’ Combivir trid tingħata attenzjoni speċjali tal- funzjoni tal- kliewi u l- parametri ematoloġiċi u, jekk hemm bżonn, id- dożaġġ ta 'xi prodott jew prodotti għandu jitnaqqas.
Since some patients receiving Combivir may continue to experience opportunistic infections, concomitant use of prophylactic antimicrobial therapy may have to be considered.
Billi xi pazjenti li jkunu qed jieħdu Combivir jista ’ jkollhom infezzjonijiet opportunistiċi, irid jiġi kkunsidrat l- użu tat- terapija profilattika għal kontra l- mikrobi.
Limited data from clinical trials do not indicate a significantly increased risk of adverse reactions to zidovudine with co- trimoxazole (see interaction information above relating to lamivudine and co-trimoxazole), aerosolised pentamidine, pyrimethamine and acyclovir at doses used in prophylaxis.
Data limitata minn studji kliniċi ma turix żieda sostanzjali f’ reazzjonijiet mhux mixtieqa għal zidovudine ma ’ co- trimoxazole (ara hawn fuq għal informazzjoni fuq interazzjoni relatata ma lamivudine u co- trimoxazole), pentamidine bħala aerosol, pyrimethamine u acyclovir f’ dożi użati għal profilassi.
Clarithromycin tablets reduce the absorption of zidovudine.
Il- pilloli ta ’ clarithromycin inaqqsu l- assorbiment ta ’ zidovudine.
This can be avoided by separating the administration of Combivir and clarithromycin by at least two hours.
Dan jista ’ jkun evitat billi tissepara it- tehid ta ’ Combivir u clarithromycin almenu b’ sagħtejn.
The safety of lamivudine in human pregnancy has not been established.
Is- sigurta` ta ’ lamivudine fit- tqala fil- bniedem ma ġietx stabbilita.
No data are available for the treatment with a combination of lamivudine and zidovudine in humans or animals (see also section 5.3).
Ma hemmx informazzjoni disponibbli dwar il- kura b’ lamivudine u b’ zidovudine flimkien fil- bniedem jew fl- annimali (ara wkoll taqsima 5. 3).
The use in pregnant women of zidovudine alone, with subsequent treatment of the newborn infants, has been shown to reduce the rate of maternal-foetal transmission of HIV.
L- użu ta ’ zidovudine waħdu f' nisa tqal, flimkien mal- kura ta 'trabi wara t- twelid, wera li jnaqqas ir- rata tat- trasmissjoni ta' l- HIV mill- omm għall- fetu.
However, no such data are available for lamivudine.
Madanakollu, m' hemmx informazzjoni disponibbli dwar dan b’ lamivudine.
In humans, consistent with passive transmission of lamivudine across the placenta, lamivudine concentrations in infant serum at birth were similar to those in maternal and cord serum at delivery.
Fil- bniedem, konsistenti ma 'trasmissjoni passiva ta ’ lamivudine li jgħaddi għall- plaċenta, il - konċentrazzjonijiet ta ’ lamivudine fis- serum ta' trabi fit- twelid kienu l- istess bħal dawk fis- serum ta 'l - omm u tal- kurdun waqt it- twelid.
Zidovudine was measured in plasma and gave similar results to those observed for lamivudine (see section 5.2).
Zidovudine tkejjel fil- plażma u ta riżultati simili għal dawk li dehru b’ lamivudine (ara taqsima 5. 2).
As the active ingredients of Combivir may inhibit cellular DNA replication, any use, especially during the first trimester of pregnancy, presents a potential risk to the foetus.
Billi s- sustanzi attivi ta ’ Combivir jistgħu jimpedixxu r- replikazzjoni tad- DNA fiċ- ċelluli, kwalunkwe użu, speċjalment fl- ewwel tliet xhur tat- tqala, jista ’ jkun ta 'riskju għall- fetu.
Consequently the administration of Combivir during pregnancy should only be considered if expected benefits outweigh any possible risks.
Għalhekk l- għoti ta ’ Combivir waqt it- tqala għandu jitqies biss jekk wieħed iħoss li l- benefiċċji tiegħu huma akbar mir - riskji possibbli.
Pregnant women considering using Combivir during pregnancy should be made aware of the findings from animal carcinogenicity and mutagenicity studies (see section 5.3).
Nisa tqal li jkunu qed jikkunsidraw jieħdux Combivir għandhom ikunu jafu b' dawn is- sejbiet minn studji fuq il- karċinoġeniċità u l- mutaġeniċità fl- annimali (ara taqsima 5. 3).
In men zidovudine has not been shown to affect sperm count, morphology or motility.
Fl- irġiel zidovudine ma ntweriex li għandu xi effett fuq in- numru, il- morfoloġija u l- motilita 'ta' l - isperma.
Lactation:
7 Treddigħ:
Both lamivudine and zidovudine are excreted in breast milk at similar concentrations to those found in serum.
Kemm lamivudine, kif ukoll zidovudine joħorġu fil- ħalib tas- sider fil- bniedem f' konċentrazzjonijiet simili għal dawk li jinsabu fis- serum.
It is recommended that mothers taking Combivir do not breast-feed their infants.
Hu rrakkomandat li l- ommijiet m' għandhomx ireddgħu lit- tarbija waqt li jkunu fuq Combivir.
It is recommended that HIV infected women do not breast-feed their infants under any circumstances in order to avoid transmission of HIV.
Hu rrakkomandat li nisa nfettati bl - HIV taħt l- ebda ċirkostanza m' għandhom ireddgħu lit- trabi tagħhom, biex ma jgħaddulhomx l- HIV.
Adverse reactions have been reported during therapy for HIV disease with lamivudine and zidovudine separately or in combination.
Ġew rappurtati reazzjonijiet avversi waqt terapija għall- marda tal- HIV b’ lamivudine u b’ zidovudine separatament jew flimkien.
7 lamivudine, zidovudine, the wide range of medicinal products used in the management of HIV disease, or as a result of the underlying disease process.
F' ħafna minn dawn ma ħariġx ċar jekk hemmx xi konnessjoni ma ’ lamivudine, ma ’ zidovudine, mal- firxa kbira ta 'prodotti mediċinali użati għal kura tal- marda HIV, jew bħala riżultat tal- proċess tal- marda li kien hemm minn qabel.
As Combivir contains lamivudine and zidovudine, the type and severity of adverse reactions associated with each of the compounds may be expected.
Billi Combivir fih lamivudine u zidovudine, wieħed jista ’ jistenna t- tip u s- severita 'tar- reazzjonijiet avversi assoċjati ma' kull waħda mis- sustanzi.
There is no evidence of added toxicity following concurrent administration of the two compounds.
M' hemmx evidenza ta 'tossiċita' żejda wara li ż- żewġ sustanzi jingħataw flimkien.
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, kultant fatali, li normalment ikunu assoċjati ma' epatomegalija severa u steatożi tal- fwied, ġew rappurtati bl- użu ta 'analogi nuklejosidi (ara taqsima 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 antiretrovirali kombinata ġiet assoċjata ma 'tibdil fid- distribuzzjoni mill- ġdid tax- xaħam fil - ġisem (lipodistrofija) f' pazjenti bl- HIV inklużi tnaqqis fix- xaħam periferali u ta' taħt il- ġilda tal- wiċċ, żieda fix- xaħam intra- addominali u tal- vixxri, ipertrofija 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 kkombinata ġiet assoċjata ma 'anormalitajiet metaboliċi bħal ipergliċeridimja, iperkoleserolimja, reżistenza għall- insulina, ipergliċemija u iperlaktejtimja (ara taqsima 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 nfettati bl- HIV, b’ defiċjenza severa fl- immunita’ fiż- żmien li tkun inbdiet it- terapija antiretrovirali kkombinata (TARK), jista ’ jkun hemm reazzjoni ta ’ infjammazzjoni 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).
Każi ta ’ ostejonekrożi nstabu li huma partikolarment aktar komuni f’ pazjenti b’ fatturi ta ’ riskju magħrufa, b’ HIV avvanzat u/ jew użu ta ’ terapija antiretrovirali kkombinata (TARK) fit- tul.
The frequency of this is unknown (see section 4.4).
Mhux magħruf kemm huma komuni dawn il- każi (ara sezzjoni 4. 4).
The adverse reactions considered at least possibly related to the treatment are listed below by body system, organ class and absolute frequency.
Ir- reazzjonijiet avversi meqjusa li huma għallinqas possibilment relatati mal- kura huma elenkati hawn taħt skond is- sistema klinika, il- klassi tal- organi u l- frekwenza assoluta.
Frequencies are defined as very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10), uncommon (≥ 1/ 1000 to < 1/ 100), rare (≥ 1/ 10,000 to < 1/ 1000), very rare (< 1/ 10,000).
Il- frekwenzi huma definiti bħala komuni ħafna (> 1/ 10), komuni (> 1/ 100 sa < 1/ 10), mhux komuni (> 1/ 1, 000 sa < 1/ 100), rari (> 1/ 10, 000 sa < 1/ 1, 000), rari ħafna (< 1/ 10, 000).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
F’ kull grupp ta ’ frekwenza, l- effetti mhux mixtieqa huma ppreżentati bl- aktar serji l- ewwel.
Blood and lymphatic systems disorders Uncommon:
Disturbi tad- demm u tas- sistema limfatika Mhux komuni:
Neutropenia and anaemia (both occasionally severe), thrombocytopenia Very rare:
Newtropenja u anemija (it- tnejn li huma kultant serji), tromboċitopenja Rari ħafna:
Pure red cell aplasia
Aplasija pura taċ- ċelluli l- ħomor
Nervous system disorders Common:
Disturbi fis- sistema nervuża Komuni:
Headache, insomnia Very rare:
Uġigħ ta 'ras, insomnja Rari ħafna:
Peripheral neuropathy (or paraesthesiae)
Newropatija periferali (jew parastesija).
Respiratory, thoracic and mediastinal disorders Common:
Disturbi respiratorji, toraċiċi u medjastinali Komuni:
Cough, nasal symptoms
Sogħla, sintomi fl- imnieħer
Gastrointestinal disorders Common:
8 Disturbi gastro- intestinali Komuni:
Nausea, vomiting, abdominal pain or cramps, diarrhoea Rare:
Dardir, remettar, uġigħ addominali jew spażmi, dijarrea Rari:
Pancreatitis, rises in serum amylase
Żidiet fl- amylase tas- serum.
Transient rises in liver enzymes (AST, ALT) Rare:
Rari:
Skin and subcutaneous tissue disorders Common:
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Komuni:
Rash, alopecia
Raxx, alopeċja
Musculoskeletal and connective tissue disorders
Disturbi muskolu- skeletrali u tal- connective tissue Komuni:
Arthralgia, muscle disorders Rare:
Artralġja, disturbi fil- muskoli Rari:
Rhabdomyolysis
Rabdomajoliżi
General disorders and administration site conditions Common:
Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata Komuni:
Fatigue, malaise, fever
Għeja, telqa, deni.
The adverse reactions profile appears similar for adults and adolescents.
Il- profil tar- reazzjonijiet avversi jidher li hu simili fil- kbar u fl- adolexxenti.
The most serious adverse reactions include anaemia (which may require transfusions), neutropenia and leucopenia.
Ir- reazzjonijiet avversi li huma l- aktar serji jinkludu anemija (li tista ’ teħtieġ trasfużjonijiet tad- demm), newtropenja u lewkopenja.
These 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 (see section 4.4).
Dawn kienu aktar spissi f' dożaġġi għolja (1200- 1500 mg/ kuljum) u f' pazjenti bil- marda ta 'l- HIV avanzata (speċjalment jekk ir- riserva tal- mudullun qabel ma tinbeda l- kura tkun batuta), u partikularment f' pazjenti bl- għadd taċ- ċelluli CD4 inqas minn 100/ mm3.
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' pazjenti li l- għadd ta' newtrofili, il- livelli ta 'l- emoglobina u l- livelli tal- vitamina B 12 fis- serum kienu baxxi fil- bidu tat- terapija b’ zidovudine.
The adverse reactions considered at least possibly related to the treatment are listed below by body system, organ class and absolute frequency.
Ir- reazzjonijiet avversi meqjusa li huma għallinqas possibilment relatati mal- kura huma elenkati hawn taħt skond is- sistema tal- ġisem, il- klassi ta 'l- organi u l- frekwenza assoluta.
Frequencies are defined as very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10), uncommon (≥ 1/ 1000 to < 1/ 100), rare (≥ 1/ 10,000 to < 1/ 1000), very rare (< 1/ 10,000).
Il- frekwenzi huma definiti bħala komuni ħafna (> 1/ 10), komuni (> 1/ 100 sa < 1/ 10), mhux komuni (> 1/ 1, 000 sa 1/ 100), rari (> 1/ 10, 000 sa < 1/ 1, 000), rari ħafna (< 1/ 10, 000).
Blood and lymphatic system disorders Common:
Disturbi tad- demm u tas- sistema limfatika Komuni:
Pure red cell aplasia Very rare:
Anemija, newtropenja u lewkopenja, Mhux komuni: Tromboċitopenja u panċitopenja (b' ipoplasija tal- mudullun) Rari: Aplasija ta 'ċelluli ħomor puri Rari ħafna:
Aplastic anaemia
Anemija aplastika
Metabolism and nutrition disorders Rare:
Disturbi fil- metaboliżmu u n- nutrizzjoni Rari:
Lactic acidosis in the absence of hypoxaemia, anorexia
Aċidożi lattika meta ma jkunx hemm ipoximja, anoreksja
Psychiatric disorders Rare:
Disturbi psikjatriċi Rari:
Anxiety and depression
Ansjeta 'u depressjoni
Nervous system disorders Very common:
Disturbi fis- sistema nervuża Komun ħafnai:
Headache Common:
Uġigħ ta 'ras Komuni:
Dizziness Rare:
Sturdamenti Rari:
Insomnia, paraesthesiae, somnolence, loss of mental acuity, convulsions
Insomnja, parastesja, ngħas żejjed, nuqqas ta 'akutezza mentali, aċċessjonijiet
Cardiac disorders Rare: Cardiomyopathy
Kardjomijopatija.
Dyspnoea Rare:
9 Disturbi respiratorji, toraċiċi u medjastinali Mhux komuni: dispneja Rari:
Cough
Sogħla
Gastrointestinal disorders Very common:
Disturbi gastro- intestinali Komuni ħafna:
Nausea Common:
Dardir Komuni:
Vomiting, abdominal pain and diarrhoea Uncommon:
Mhux komuni:
Flatulence Rare:
Gass fl- istonku Rari:
Oral mucosa pigmentation, taste perversion and dyspepsia.
Pigmentazzjoni tal- mukosa tal- ħalq, bidliet strambi fit- togħma, u dispepsja.
Pancreatitis
Pankreatite
Hepatobiliary disorders Common:
Disturbi fil- fwied u fil- marrara Komuni:
Raised blood levels of liver enzymes and bilirubin Rare:
Żieda fil- livelli ta 'l- enzimi tal- fwied u l- bilirubin fid- demm.
Liver disorders such as severe hepatomegaly with steatosis
Mard tal- fwied bħal epatomegalija severa bi steatożi
9 Skin and subcutaneous tissue disorders Uncommon:
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Mhux komuni:
Rash and pruritus Rare:
Raxx u ħakk Rari:
Nail and skin pigmentation, urticaria and sweating
Pigmentazzjoni tad- dwiefer u l- ġilda, urtikarja u għaraq.
Musculoskeletal and connective tissue disorders Common:
Disturbi muskulo- skeletali u tal- connective tissue Komuni:
Myalgia Uncommon:
Mijalġja Mhux komuni:
Myopathy
Mijopatija
Renal and urinary disorders Rare:
Disturbi fil- kliewi u fis- sistema urinarja Rari:
Urinary frequency
Bżonn li tagħmel l- awrina spiss
Reproductive system and breast disorders Rare:
Disturbi fis- sistema riproduttiva u fis- sider Rari:
General disorders and administration site conditions Common:
Disturbi ġenerali u kondizzjonijiet ta’ mnejn jingħata Komuni:
Malaise Uncommon:
Ma tħossokx f' siktek Mhux komuni:
Fever, generalised pain and asthenia Rare: Chills, chest pain and influenza-like syndrome
Deni, uġigħ u telqa ġenerali Rari: Tkexkix ta ’ bard, uġigħ fis- sider, sindromu jixbah l- influwenza.
The available data from both placebo-controlled and open-label studies indicate that the incidence of nausea and other frequently reported clinical adverse events consistently decreases over time during the first few weeks of therapy with zidovudine.
L- informazzjoni disponibbli li ħarġet minn studji kkontrollati bi plaċebo u oħrajn tat- tip open- label jindikaw li l- inċidenza ta 'dardir u effetti ħżiena oħra li ġew irrappurtati ta' spiss naqsu konsistentement fl- ewwel ġimgħat ta 'terapija b’ zidovudine.
There is limited experience of overdosage with Combivir.
L- esperjenza ta 'każi ta' teħid eċċessiv ta 'Combivir hija limitata.
No specific symptoms or signs have been identified following acute overdose with zidovudine or lamivudine apart from those listed as undesirable effects.
Ma ġew identifikati l- ebda sintomi jew sinjali speċifiċi f’ każijiet serji ta 'dożi eċċessivi ta' zidovudine jew lamivudine ħlief dawk elenkati bħala effetti mhux mixtieqa.
No fatalities occurred, and all patients recovered.
Ma miet ħadd, u l- pazjenti kollha irkupraw.
If overdosage 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 jiġi mmonitorjat għal xi sinjali ta' tossiċita '(ara taqsima 4. 8), u għandu jingħata l- għajnuna permezz tal- kura standard li jkun hemm bżonn.
Since lamivudine is dialysable, continuous haemodialysis could be used in the treatment of overdosage, although this has not been studied.
Billi lamivudine jista ’ jissaffa bid- dijalisi kontinwa,, tad- demm, din tista 'tintuża fil- 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.
Id- dijalisi tad- demm u tal- peritoneum jidhru li ftit għandhom effett duq it - tneħħija ta 'zidovudine, imma jżidu t- tneħħija tal- metabolit glucuronide.
For more details physicians should refer to the individual prescribing information for lamivudine and zidovudine.
Għal aktar tagħrif it- tobba għandhom jirreferu għal informazzjoni dwar kif għandhom jiġu preskritti dawn il- prodotti mediċinali individwalment.
Antivirals for treatment of HIV infections, combinations, ATC Code:
Antivirali għal kura ta ’ infezzjonijiet b’ HIV, kombinazzjonijiet, Kodiċi ATC:
J05AR01
J05 AR01
Lamivudine and zidovudine are nucleoside analogues which have activity against HIV.
Lamivudine u Zidovudine huma analogi nuklejosidi li għandhom attivita 'kontra l- virus ta' l- HIV.
Additionally, lamivudine has activity against hepatitis B virus (HBV).
Barra minn hekk, lamivudine għandu attivita 'kontra l- virus ta' l- epatite B (HBV).
Both medicinal products are metabolised intracellularly to their active moieties, lamivudine 5’ -triphosphate (TP) and zidovudine 5’ -TP respectively.
Iż- żewġ prodotti mediċinali jiġu metabolizzati fiċ- ċelluli, għas- sustanza attiva, lamivudine 5 '- trifosfat (TP) u zidovudine 5' - TP rispettivament.
Their main modes of action are as chain terminators of viral reverse transcription.
Il- metodi prinċipali ta 'azzjoni tagħhom huma li jwaqqfu l- katina tar - reverse transcription tal- virus.
Lamivudine-TP and zidovudine-TP have selective inhibitory activity against HIV-1 and HIV-2 replication in vitro; lamivudine is also active against zidovudine-resistant clinical isolates of HIV.
Lamivudine – TP u Zidovudine – TP għandhom attivita 'inibitorja selettiva kontra r- replikazzjoni in vitro ta' l- HIV- 1 u l- HIV- 2; lamivudine hu wkoll attiv kontra iżolati kliniċi ta 'l- HIV li huma reżistenti għal zidovudine.
Lamivudine in combination with zidovudine exhibits synergistic anti-HIV activity against clinical isolates in cell culture.
Lamivudine flimkien ma ’ zidovudine juri attivita 'anti- HIV sinerġistika kontra iżolati kliniċi f' razza ta' ċelluli.
HIV-1 resistance to lamivudine involves the development of a M184V amino acid change close to the active site of the viral reverse transcriptase (RT).
Ir- reżistenza ta ’ HIV- 1 għal lamivudine tinvolvi l- iżvilupp ta 'bidla fl- aċidu amino M184V qrib is- sit attiv tar- reverse transcriptase tal- virus (RT).
This variant arises both in vitro and in HIV-1 infected patients treated with lamivudine-containing antiretroviral therapy.
Dan il- varjant joħroġ kemm in vitro kif ukoll f' pazjenti infettati bl- HIV- 1 li jkunu fuq terapija antiretrovirali li tinkludi lamivudine.
In
Mutanti ta 'l- M184V juru suxxettibilta' mnaqqsa ħafna għal lamivudine u juru tnaqqis tal- ħila replikattiva virali in vitro.
10 vitro studies indicate that zidovudine-resistant virus isolates can become zidovudine sensitive when they simultaneously acquire resistance to lamivudine.
Studji in vitro jindikaw li iżolati tal- virus reżistenti għal zidovudine jistgħu isiru sensittivi għal zidovudine meta fl- istess ħin jiżviluppaw reżistenza għal lamivudine.
The clinical relevance of such findings remains, however, not well defined.
Madankollu, ir- relevanza klinika ta 'dawn is- sejbiet tibqa' mhux definita.
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 mhix 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 tistax tikkonkludi li ta ’ min joqgħod fuqha f’ dawn iċ- ċirkustanzi.
In any case, initiation of susceptible NRTI’ s 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.
Cross-resistance conferred by the M184V RT is limited within the nucleoside inhibitor class of antiretroviral agents.
Ir- reżistenza inkroċjata li jagħti l- M184V RT hi limitata fil- grupp tal- inibitur nukleosidi ta 'prodotti antiretrovirali.
Zidovudine and stavudine maintain their antiretroviral activities against lamivudine-resistant HIV-1.
Zidovudine u stavudine iżommu l- attivitajiet antiretrovirali tagħhom kontra l- HIV- 1 li jkunu reżistenti għal lamivudine.
Abacavir maintains its antiretroviral activities against lamivudine- resistant HIV-1 harbouring only the M184V mutation.
Abacavir iżomm l- attivitajiet antiretrovirali tiegħu kontra l- HIV- 1 li jkun jirreżisti għal lamivudine waqt li jżomm biss il- mutazzjoni M184V.
The M184V RT mutant shows a < 4-fold decrease in susceptibility to didanosine and zalcitabine; the clinical significance of these findings is unknown.
Il- mutant M184V juri tnaqqis ta '< 4 darbiet fis- suxxettibilta' tiegħu għal didanosine u għal zalcitabine; l- importanza klinika ta 'dawn is- sejbiet mhix magħrufa.
In vitro susceptibility testing has not been standardised and results may vary according to methodological factors.
It- testjar tas- suxxettibilta 'in vitro ma ġiex standardizzat u r - riżultati jistgħu ivarjaw skond kif isiru t- testijiet.
Lamivudine demonstrates low cytotoxicity to peripheral blood lymphocytes, to established lymphocyte and monocyte-macrophage cell lines, and to a variety of bone marrow progenitor cells in vitro.
Lamivudine juri ċitotossiċita 'baxxa għal- limfoċiti periferali tad- demm, għal- linji ta' ċelluli stabbiliti ta 'limfoċiti u monoċiti- makrofagi, u għal varjeta' ta 'ċelluli proġenituri tal- mudullun in vitro.
Resistance to thymidine analogues (of which zidovudine is one) is well characterised and is conferred by the stepwise accumulation of up to six specific mutations in the HIV reverse transcriptase at codons 41, 67, 70, 210, 215 and 219.
Ir - reżistenza għal analogi ta ’ thymidine (li zidovudine hu wieħed minnhom) hi karatterizzata sew u tiġi konferita bl- akkumulazzjoni pass pass ta 'sitt mutazzjonijiet speċifiċi fir- reverse transcriptase tal- HIV fil- codons 41, 67, 70, 210, 215 u 219.
Viruses acquire phenotypic resistance to thymidine analogues through the combination of mutations at codons 41 and 215 or by the accumulation of at least four of the six mutations.
Dan il- virus jibni reżistenza fenotipika għall- analogi ta ’ thymidine permezz ta 'mutazzjonijiet f' codons 41 u 215 jew bl- akkumulazzjoni mill- inqas ta' erba 'minn sitt mutazzjonijiet.
These thymidine analogue mutations alone do not cause high-level cross-resistance to any of the other nucleosides, allowing for the subsequent use of any of the other approved reverse transcriptase inhibitors.
Dawn il- mutazzjonijiet ta ’ l- analogi ta 'thymidine waħedhom ma jikkawżawx cross resistance ta' livell għoli għal xi wieħed min- nuklejosidi l- oħra, u għalhekk jippermettu l- użu aktar tard ta 'xi wħud mill- inibituri oħra tar- reverse transcriptase approvati.
Two patterns of multi-drug resistance mutations, the first characterised by mutations in the HIV reverse transcriptase at codons 62, 75, 77, 116 and 151 and the second involving a T69S mutation plus a 6-base pair insert at the same position, result in phenotypic resistance to AZT as well as to the other approved NRTIs.
Żewġ tipi ta 'formazzjonijiet ta' mutazzjonijiet reżistenti għal diversi prodotti mediċinali, ta 'l- ewwel karatterizzati b' mutazzjonijiet fir- reverse transcriptase tal- HIV f’ codons 62, 75, 77, 116 u 151 u tat- tieni li jinvolvu mutazzjoni T69S u l- introduzzjoni ta ’ 6- base pair fl- istess pożizzjoni jirriżultaw f’ reżistenza fenotipika għal AZT u għal l- NRTIs approvati l- oħra.
Either of these two patterns of multinucleoside resistance mutations severely limits future therapeutic options.
Kull wieħed minn dawn iż- żewġ tipi ta 'formazzjonijiet ta' mutazzjonijiet ta 'reżistenza multinukleosidi jillimitaw serjament l- għażliet terapewtiċi fil- futur.
Clinical Experience
11 Esperjenza klinika
In clinical trials, lamivudine in combination with zidovudine has been shown to reduce HIV-1 viral load and increase CD4 cell count.
Waqt provi kliniċi, lamivudine mgħoti flimkien ma ’ zidovudine wera li jnaqqas mill- ammont ta 'viri tal- HIV- 1 u jżid fl- għadd taċ- ċelluli CD4.
Clinical end-point data indicate that lamivudine in combination with zidovudine, results in a significant reduction in the risk of disease progression and mortality.
L- informazzjoni klinika ta 'l- aħħar stadju tindika li lamivudine mogħti flimkien ma ’ zidovudine jirriżulta fi tnaqqis konsiderevoli tar- riskju li l- marda tmur għall- agħar jew li tirriżulta f' mewt.
Lamivudine and zidovudine have been widely used as components of antiretroviral combination therapy with other antiretroviral agents of the same class (NRTIs) or different classes (PIs, non- nucleoside reverse transcriptase inhibitors).
Lamivudine u Zidovudine intużaw ħafna bħala komponenti ta 'terapija kkombinata antiretrovirali ma' prodotti oħra antiretrovirali ta 'l- istess klassi (NRTI) jew ta' klassijiet differenti (PIs, inibituri tar - reverse transcriptase li mhumiex nuklejosidi)
Multiple drug antiretroviral therapy containing lamivudine has been shown to be effective in antiretrovirally-naive patients as well as in patients presenting with viruses containing the M184V mutations.
It- terapija anti- retrovirali b’ aktar minn mediċina waħda li tinkludi lamivudine irriżulta li kienet effettiva f' pazjenti naïve anti- retroviralment kif ukoll f' pazjenti bil- virus bil- mutazzjonijiet M184V.
Evidence from clinical studies shows that lamivudine plus zidovudine delays the emergence of zidovudine resistant isolates in individuals with no prior antiretroviral therapy.
Evidenza minn studji kliniċi turi li meta lamivudine u zinovudine jittieħdu flimkien, idumu aktar biex jitfaċċaw iżolati reżistenti għal zidovudine f' dawk li qabel ma kinux ħadu terapija antiretrovirali.
Subjects receiving lamivudine and zidovudine with or without additional concomitant antiretroviral therapies and who already present with the M184V mutant virus also experience a delay in the onset of mutations that confer resistance to zidovudine and stavudine (Thymidine Analogue Mutations; TAMs).
Pazjenti li jkunu ħadu lamivudine u zidovudine, weħedhom jew flimkien ma ’ terapiji antiretrovirali addizzjonali fl- istess ħin, u li diġa 'jkollhom virus mutant M184 idumu aktar biex ikollhom mutazzjonijiet li jikkonferixxu reżistenza għal zidovudine u għal stavudine (Mutazzjonijiet Analogi ta ’ Thymidine; TAM)
11 The relationship between in vitro susceptibility of HIV to lamivudine and zidovudine and clinical response to lamivudine/ zidovudine containing therapy remains under investigation.
Ir- relazzjoni bejn is- suxxettibilta 'in vitro ta' l- HIV għal lamivudine u z- zidovudine u r- reazzjoni klinika għat- terapija b’ lamivudine/ zidovudine għadha qed tiġi nvestigata.
Lamivudine at a dose of 100 mg once daily has also been shown to be effective for the treatment of adult patients with chronic HBV infection (for details of clinical studies, see the prescribing information for Zeffix).
Lamivudine f' doża ta '100 mg kuljum intwera wkoll li hu effettiv fil- kura ta' pazjenti adulti li jbatu minn infezzjoni kronika ta 'l- HBV (għad- dettalji ta' l- istudji kliniċi, ara t- tagħrif għall- preskrizzjoni ta ’ Zeffix).
However, for the treatment of HIV infection only a 300 mg daily dose of lamivudine (in combination with other antiretroviral agents) has been shown to be efficacious.
Madankollu, għall- kura ta 'l- infezzjoni HIV doża ta' 300 mg kuljum ta 'lavimudine biss (flimkien ma' prodotti oħra antiretrovirali) irriżulta li kienet effikaċi.
Lamivudine has not been specifically investigated in HIV patients co-infected with HBV.
Lamivudine ma ġiex investigat speċifikament f' pazjenti bl- HIV ko- infettati bl- HBV.
Lamivudine and zidovudine are well absorbed from the gastrointestinal tract.
Lamivudine u Zidovudine jiġu assorbiti tajjeb mis- sistema gastrointestinali.
The bioavailability of oral lamivudine in adults is normally between 80– 85% and for zidovudine 60– 70%.
Il - biodisponibilita ’ ta ’ lamivudine li jittieħed mill- ħalq fl- adulti hi normalment bejn it- 80- 85% u għal zidovudine 60- 70%.
A bioequivalence study compared Combivir with lamivudine 150 mg and zidovudine 300 mg tablets taken together.
Studju dwar bioekwivalenza qabbel lil Combivir ma 'pilloli ta' 150 mg lamivudine u ta '300mg zidovudine meħudin flimkien.
The effect of food on the rate and extent of absorption was also studied.
L- effett ta 'l- ikel fuq ir- rata u l- ammont ta' assorbiment kien studjat ukoll.
Combivir was shown to be bioequivalent to lamivudine 150 mg and zidovudine 300 mg given as separate tablets, when administered to fasting subjects.
Combivir irriżulta li kien bioekwivalenti għal 150 mg lamivudine u 300 mg zidovudine bħala pilloli separati, meta mogħtija lil pazjenti sajma.
Following single dose Combivir administration in healthy volunteers, mean (CV) lamivudine and zidovudine Cmax values were 1.6 µg/ ml (32%) and 2.0 µg/ ml (40%), respectively and the corresponding values for AUC were 6.1 µg h/ ml (20%) and 2.4 µg h/ ml (29%) respectively.
Wara li voluntieri f' saħħithom ingħataw doża waħda ta 'Combivir, il- valuri C max medji (CV) ta ’ lamivudine u ta ’ zidovudine kienu 1. 6 µg/ ml (32%) u 2. 0 µg/ ml (40%), rispettivament u l- valuri korrispondenti għall- AUC kienu 6. 1 µg. h/ ml (20%) u 2. 4 µg. h/ ml (29%) rispettivament.
The median (range) lamivudine and zidovudine tmax values were 0.75 (0.50-2.00) hours and 0.50 (0.25- 2.00) hours respectively.
Il- valuri T max medjani (firxa) ta ’ lamivudine u ta ’ zidovudine kienu 0. 75 (0. 50 – 2. 00) sigħat u 0. 50 (0. 25– 2. 00) sigħat rispettivament.
The extent of lamivudine and zidovudine absorption (AUC∞) and estimates of half-life following administration of Combivir with food were similar when compared to fasting subjects, although the rates of absorption (Cmax, tmax) were slowed.
L- ammont ta 'assorbiment ta' lamivudine u ta ’ zidovudine (AUC ) u stimi tal - half- life wara t- teħid ta ’ Combivir ma 'l- ikel kienu l- istess meta mqabbla ma' pazjenti sajma, għalkemm ir- rati ta 'assorbiment (C max, t max) kienu inqas.
Based on these data Combivir may be administered with or without food.
Fuq il- bażi ta 'din l- informazzjoni Combivir jista ’ jingħata kemm ma' l- ikel, kif ukoll fuq stonku vojt.
Administration of crushed tablets with a small amount of semi-solid food or liquid would not be expected to have an impact on the pharmaceutical quality, and would therefore not be expected to alter the clinical effect.
It- teħid ta ’ pilloli mfarrka b’ ammont żgħir ta ’ ikel semi- solidu jew likwidu ma jkunx mistenni li jkollu effett fuq il- kwalita ’ farmaċewtika, u għalhekk ma jkunx mistenni li jbiddel l- effett kliniku.
This conclusion is based on the physiochemical and pharmacokinetic data assuming that the patient crushes and transfers 100% of the tablet and ingests immediately.
Din il - konklużjoni hija bbażata fuq id- data fiżikokimika u farmakokinetika meta wieħed jassumi li l- pazjent ifarrak u jittrassferixxi 100% tal- pillola u jeħodha mill- ewwel.
Distribution:
12 Distribuzzjoni:
Intravenous studies with lamivudine and zidovudine showed that the mean apparent volume of distribution is 1.3 and 1.6 l/ kg respectively.
Studji dwar lamivudine u zidovudine injettati ġol- vini urew li l- volum medju evidenti ta 'distribuzzjoni hu 1. 3 u 1. 6 l/ kg rispettivament.
Zidovudine plasma protein binding is 34% to 38%.
Lamivudine juri farmakokinetika lineari fuq il- firxa ta 'dożi terapewtiċi u juri irbit limitat mal- albumin, il- proteina l- aktar komuni tal- plażma (< 36% albumin fis- serum in vitro). lL- għaqda ta' zidovudine mal- proteini tal- plażma hi bejn 34% u 38%.
Interactions involving binding site displacement are not anticipated with Combivir.
Interazzjonijiet li jinvolvu spostament tas- sit tat- tagħqid mhumiex mistennija b’ Combivir.
Data show that lamivudine and zidovudine penetrate the central nervous system (CNS) and reach the cerebrospinal fluid (CSF).
Informazzjoni limitata turi li lamivudine u zidovudine jidħlu fis- sistema nervuża ċentrali (CNS) u jilħqu l- fluwidu ċerebro- spinali (CSF).
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- medja tal- proporzjon tas- CSF/ konċentrazzjoni ta ’ lamivudine u ta ’ zidovudine fis- serum 2- 4 sigħat wara li jittieħdu mill- ħalq kienet ta '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 kienet il- penetrazzjoni ta ’ lamivudine fis- CNS u r- relazzjoni ta 'dan ma' xi effikaċja klinika mhux magħruf.
Metabolism of lamivudine is a minor route of elimination.
Il- metaboliżmu ta ’ lamivudine hu mezz żgħir ta 'tneħħija mill- ġisem.
Lamivudine is predominately cleared unchanged by renal excretion.
Lamivudine jitneħħa mill- ġisem prinċipalment bħala sekrezzjoni mill- kliewi mingħajr ma ’ jinbidel.
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 metaboliċi ta ’ lamivudine mal- prodotti mediċinali hi żgħira minħabba l- ammont limitat ta 'metaboliżmu fil- fwied (5- 10%) u ta ’ irbit fil- 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.
5 '- glukuronid ta ’ zidovudine huwa l- metabolit prinċipali kemm fil- plażma kif ukoll fl- awrina, li waħdu jkopri madwar 50- 80% tad- doża li tkun ittieħdet u tneħħiet 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 injezzjoni fil- vina.
Elimination:
Tneħħija mill- ġisem:
The observed lamivudine half-life of elimination is 5 to 7 hours.
Il- half- life ta 'lamivudine li ġiet osservata hija bejn 5 u 7 sigħat.
The mean systemic clearance of lamivudine is approximately 0.32 l/ h/ kg, with predominantly renal clearance (> 70%) via
Il- medja ta 'tneħħija sistemika ta ’ lamivudine hi ta' madwar 0. 32 l/ siegħa/ kg, l- aktar tneħħija tkun mill- kliewi (> 70%) permezz tas- sistema ta 'trasport organiku katijoniku.
Studies in patients with renal impairment show lamivudine elimination is affected by renal dysfunction.
Studji li saru f' pazjenti b’ indeboliment tal - kliewi juru li t- tneħħija ta ’ lamivudine mill- ġisem tiġi affettwata jekk il- kliewi ma jkunux qed jaħdmu sew.
Dose reduction is required for patients with creatinine clearance ≤ 50 ml/ min (see section 4.2).
Hemm bżonn li titnaqqas id- doża f' pazjenti li t- tneħħija tal- krejatinina tagħhom tkun ≤50 ml/ min (ara 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 minn ġol- vina, il- half- life terminali tal- plażma kienet ta ’ 1. 1 sigħat u l- medja ta 'tneħħija sistemika kienet 1. 6 l/ siegħa/ 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 ta ’ zidovudine mill- kliewi hi stmata li tkun 0. 34 l/ h/ kg, li tindika filtrazzjoni glomerulari u sekrezzjoni tubulari attiva mill- kliewi.
Zidovudine concentrations are increased in patients with advanced renal failure.
Il- konċentrazzjonijiet ta 'zidovudine jiżdiedu f' pazjenti b' indeboliment serju tal- kliewi.
Pharmacokinetics in children:
Farmakokinetika fit- tfal:
In children over the age of 5-6 months, the pharmacokinetic profile of zidovudine is similar to that in adults.
Fi tfal ta ’ aktar minn 5- 6 xhur, il- profil farmakokinetiku ta ’ zidovudine huwa bħal dak fl- adulti.
Zidovudine is well absorbed from the gut and at all dose levels studied in adults and children, the bioavailability was between 60-74% with a mean of 65%.
Zidovudine jiġi assorbit tajjeb mill- musrana u fil- livelli kollha ta ’ dożi studjati fit - tfal u fl- adulti, il- biodisponibilità kienet ta ’ bejn 60- 74% b’ medja ta ’ 65%.
Cssmax levels were 4.45 μ M (1.19 μ g/ ml) following a dose of 120 mg zidovudine (in solution)/ m2 body surface area and 7.7 μ M (2.06 μ g/ ml) at 180 mg/ m2 body surface area.
Livelli ta ’ C ssmax kienu ta ’ 4. 45μM (1. 19μg/ ml) wara doża ta ’ 120mg ta 'zidovudine (f’ soluzzjoni) / m2 ta ’ surface area tal- ġisem u 7. 7μM (2. 06μg/ ml) f’ surface area tal- ġisem ta ’ 180mg/ m².
Dosages of 180 mg/ m2 four times daily in children produced similar systemic exposure (24 hour AUC 40.0 h μ M or 10.7 h μ g/ ml) as doses of 200 mg six times daily in adults (40.7 h μ M or 10.9 h μ g/ ml).
Dożi ta ’ 180mg/ m2 erba ’ darbiet kuljum fit- tfal irriżultat f’ espożizzjoni simili fid- demm (AUC fuq 24 siegħa ta ’ 40. 0hrμM jew 10. 7hr μg/ ml) daqs dożi ta ’ 200mg sitt darbiet kuljum f’ adulti (40. 7 hr μM jew 10. 9 hr μg/ ml).