qanastek/EMEA-V3 huggingface dataset:
In vitro and clinical pharmacokinetic interaction studies have shown the potential for CYP450 mediated interactions involving emtricitabine and tenofovir disoproxil fumarate with other medicinal products is low.
Studji in vitro u kliniċi dwar interazzjonijiet farmakokinetiċi wrew li l- potenzjal għall- interazzjonijiet medjati minn CYP450 li jinvolvu emtricitabine u tenofovir disoproxil fumarate ma ’ prodotti mediċinali oħrajn hija baxxa.
Interactions relevant to emtricitabine:
Interazzjonijiet rilevanti għal emtricitabine:
There are no clinically significant interactions when emtricitabine is co-administered with indinavir, zidovudine, stavudine or famciclovir.
M’ hemmx interazzjonijiet kliniċi sinifikanti meta emtricitabine jingħata flimkien ma ’ indinavir, zidovudine, stavudine, jew famciclovir.
Co-administration of Truvada with medicinal products that are eliminated by active tubular secretion may lead to an increase in serum concentrations of either emtricitabine or a co-administered medicinal product due to competition for this elimination pathway.
L- għoti ta ’ Truvada flimkien ma ’ prodotti mediċinali li huma eliminati permezz ta ’ sekrezzjoni tubulari attiva tista ’ twassal għal żieda ta ’ konċentrazzjonijiet fis- serum ta ’ emtricitabine jew tal- prodott mediċinali li jkun qed jingħata miegħu minħabba kompetizzjoni għal din ir- rotta ta ’ l- eliminazzjoni.
There is no clinical experience with the co-administration of emtricitabine and cytidine analogues.
M’ hemm l- ebda esperjenza klinika dwar l- għoti ta ’ emtricitabine flimkien ma analogi ta ’ cytidine.
Consequently, Truvada should not be administered in combination with lamivudine or zalcitabine for the treatment of HIV infection (see section 4.4).
Konsegwentement Truvada m’ għandhiex tingħata flimkien ma ’ lamivudine jew zalcitabine għat - trattament ta ’ infezzjoni bl- HIV (ara sezzjoni 4. 4).
Interactions relevant to tenofovir:
Interazzjonijiet rilevanti għal tenofovir:
Co-administration of lamivudine, indinavir, efavirenz, nelfinavir or saquinavir (ritonavir boosted) with tenofovir disoproxil fumarate did not result in any clinically relevant interaction.
L- għoti ta ’ lamivudine, indinavir, efavirenz, nelfinavir u saquinavir (ibboostjat ma ’ ritonavir) flimkien ma ’ tenofovir disoproxil fumarate ma rriżulta f’ ebda interazzjoni klinikament rilevanti.
When tenofovir disoproxil fumarate was administered with lopinavir/ ritonavir, no changes were observed in the pharmacokinetics of lopinavir and ritonavir.
Meta tenofovir disoproxil fumarate ngħata flimkien ma ’ lopinavir/ ritonavir, l- ebda tibdil ma kien osservat fil- farmakokinetiċi ta ’ lopinavir u ritonavir.
Tenofovir AUC was increased by approximately 30% when tenofovir disoproxil fumarate was administered with lopinavir/ ritonavir.
L- AUC ta ’ tenofovir żdiedet b’ madwar 30% meta tenofovir disoproxil fumarate ngħata ma ’ lopinavir/ ritonavir.
Higher tenofovir concentrations could potentiate tenofovir associated adverse events, including renal disorders.
Konċentrazzjonijiet ogħla ta ’ tenofovir jistgħu jqawwu l- effetti avversi marbuta ma ’ tenofovir, inklużi disturbi fil- kliewi.
When didanosine gastro-resistant capsules were administered 2 hours prior to or concurrently with tenofovir disoproxil fumarate, the AUC for didanosine was on average increased by 48% and 60% respectively.
7 Meta l- kapsuli gastro- reżistenti ta ’ didanosine ngħataw sagħtejn qabel jew flimkien ma ’ tenofovir disoproxil fumarate, l- AUC għal didanosine bħala medja żdiedet bi 48% u 60% rispettivament.
The mean increase in the AUC of didanosine was 44% when the buffered tablets were administered 1 hour prior to tenofovir.
Iż - żieda medja fl- AUC ta ’ didanosine kienet ta ’ 44% meta l- pilloli bafferjati ngħataw siegħa qabel tenofovir.
In both cases the pharmacokinetic parameters for tenofovir administered with a light meal were unchanged.
Fiż- żewġ każijiet, il- parametri farmakokinetiċi ta ’ tenofovir li ngħata ma ’ ikla ħafifa ma nbidlux.
The co-administration of tenofovir disoproxil fumarate and didanosine is not recommended (see section 4.4).
Mhux rakkomandat li tenofovir disoproxil fumarate jingħata flimkien ma ’ didanosine (ara sezzjoni 4. 4).
When tenofovir disoproxil fumarate was administered with atazanavir, a decrease in concentrations of atazanavir was observed (decrease of 25% and 40% of AUC and Cmin respectively compared to atazanavir 400 mg).
Meta tenofovir disoproxil fumarate ngħata ma ’ atazanavir, tnaqqis fil- konċentrazzjonijiet ta ’ atazanavir kien osservat (tnaqqis ta ’ 25% u 40% fl- AUC u Cmin rispettivament meta mqabbla ma ’ atazanavir 400 mg).
When ritonavir was added to atazanavir, the negative impact of tenofovir on atazanavir Cmin was significantly reduced, whereas the decrease of AUC was of the same magnitude (decrease of 25% and 26% of AUC and Cmin respectively compared to atazanavir/ ritonavir 300/ 100 mg).
Meta ritonavir kien miżjud ma ’ atazanavir, l- impatt negattiv ta ’ tenofovir fuq Cmin ta ’ atazanavir kien imnaqqas b’ mod sinifikanti, filwaqt li t- tnaqqis ta ’ l- AUC kien ta ’ l- istess livell (tnaqqis ta ’ 25% u 26% ta ’ l- AUC u Cmin rispettivament meta mqabbla ma ’ atazanavir/ ritonavir 300/ 100 mg).
The co-administration of atazanavir/ ritonavir with tenofovir resulted in increased exposure to tenofovir.
L- għoti ta ’ atazanavir/ ritonavir flimkien ma ’ tenofovir irriżulta f’ żieda ta ’ l- esponiment għal tenofovir.
Tenofovir is excreted renally, both by filtration and active secretion via the human organic anion transporter 1 (hOAT1).
Tenofovir jitneħħa mill- ġisem permezz tal- kliewi, kemm permezz tal- filtrazzjoni kif ukoll permezz tas- sekrezzjoni attiva permezz ta ’ trasportatur enajoniku organiku uman 1 (hOAT1).
Co-administration of tenofovir disoproxil fumarate with other medicinal
L- għoti ta ’ tenofovir disoproxil fumarate flimkien ma ’ prodotti mediċinali oħra li huma ukoll imnixxija attivament permezz tat- trasportatur enajoniku (eż. cidofovir) jista ’ jirriżulta f’ żieda fil - konċentrazzjonijiet ta ’ tenofovir jew tal- prodott mediċinali li jkunu qed jingħataw miegħu.
Tenofovir disoproxil fumarate has not been evaluated in patients receiving nephrotoxic medicinal products (e. g. aminoglycosides, amphotericin B, foscarnet, ganciclovir, pentamidine, vancomycin, cidofovir or interleukin-2).
Tenofovir disoproxil fumarate ma ġiex evalwat f’ pazjenti li kienu qed jirċievu prodotti mediċinali nefrotossiċi (eż. aminoglycosides, amphotericin B, foscarnet, ganciclovir, pentamidine, vancomycin, cidofovir jew interleukin 2).
Use of tenofovir disoproxil fumarate should be avoided with concurrent or recent use of a nephrotoxic medicinal product.
Għandu jiġi evitat l- użu ta ’ tenofovir disoproxil fumarate flimkien ma ’ jew fi żmien qasir minn meta jkun ittieħed prodott mediċinali nefrotossiku.
If concomitant use of Truvada and nephrotoxic agents is unavoidable, renal function should be monitored weekly (see section 4.4).
Jekk l- użu ta ’ Truvada flimkien ma ’ sustanzi nefrotossiċi ma jistax jkun evitat, il- funzjoni renali għandha tkun immonitorjata ta ’ kull ġimgħa (ara sezzjoni 4. 4).
Co-administration of tenofovir disoproxil fumarate and methadone, ribavirin, rifampicin, adefovir dipivoxil or the hormonal contraceptive norgestimate/ ethinyl oestradiol did not result in any pharmacokinetic interaction.
L- għoti ta ’ tenofovir disoproxil fumarate flimkien ma ’ methadone, ribavirin, rifampicin, adefovir dipivoxil jew il- kontraċettiv ormonali norgestimate/ ethinyl oestradiol ma rriżultax f’ xi interazzjoni farmakokinetika.
Interactions relevant to Truvada:
Interazzjonijiet rilevanti għal Truvada:
Co-administration of tacrolimus with the combination product emtricitabine/ tenofovir disoproxil fumarate did not result in any clinically significant interactions.
L- għoti ta ’ tacrolimus flimkien ma ’ taħlita tal- prodott emtricitabine/ tenofovir disoproxil fumarate ma rriżultax f’ interazzjonijiet kliniċi sinifikanti.
For emtricitabine and tenofovir disoproxil fumarate, insufficient data on exposed pregnancies are available.
Għal emtricitabine u tenofovir disoproxil fumarate m’ hemmx biżżejjed tagħrif dwar l- użu waqt it- tqala.
Animal studies do not indicate direct or indirect harmful effects of emtricitabine or tenofovir disoproxil fumarate with respect to pregnancy, embryonal/ foetal development, parturition or postnatal development (see section 5.3).
Studji fuq il- bhejjem dwar emtricitabine jew tenofovir disoproxil fumarate ma jurux effetti ħżiena diretti jew indiretti fuq it- tqala, fuq l- iżvilupp ta ’ l- embriju/ fetu, ħlas jew żvilupp wara t- twelid (ara sezzjoni 5. 3).
However, Truvada should not be used during pregnancy unless no other alternative is available.
Madankollu, Truvada m’ għandux jintuża waqt it- tqala ħlief jekk l- ebda alternattiva oħra ma tkun disponibbli.
The use of Truvada must be accompanied by the use of effective contraception.
L- użu ta ’ Truvada jrid ikun akkompanjat ma ’ l- użu ta ’ kontraċettiv effettiv.
It is not known whether emtricitabine or tenofovir are excreted in human milk.
Mhux magħruf jekk emtricitabine jew tenofovir joħoroġux fil- ħalib tas- sider uman.
It is recommended that HIV infected women do not breast-feed their infants under any circumstances in order to avoid transmission of HIV to the infant.
Huwa rakkomandat li nisa infettati bl- HIV ma jreddgħux lit- trabi tagħhom taħt l- ebda ċirkustanza sabiex jevitaw li jgħaddu HIV lit- tarbija.
However, patients should be informed that dizziness has been reported during treatment with both emtricitabine and tenofovir disoproxil fumarate.
Madankollu, il- pazjenti għandhom jiġu infurmati li l- isturdament kien irrappurtat waqt it- trattament kemm b’ emtricitabine u anke b’ tenofovir disoproxil fumarate.
In an open-label randomised clinical study in antiretroviral-naïve patients (GS-01-934; see section 5.1), patients received emtricitabine, tenofovir disoproxil fumarate and efavirenz for 144 weeks (administered as the combination formulation Truvada, plus efavirenz from week 96).
Fi studju kliniku open- label u randomised f’ pazjenti li qatt ma ’ kienu ngħataw mediċini antiretrovirali qabel (GS- 01- 934; ara sezzjoni 5. 1), il- pazjenti rċievew emtricitabine, tenofovir disoproxil fumarate u efavirenz għal 144 ġimgħa (mogħtija bħala l- formulazzjoni kkombinata ta ’ Truvada, u efavirenz minn ġimgħa 96).
The safety profile of emtricitabine and tenofovir disoproxil fumarate was consistent with the previous experience with these agents when each was administered with other antiretroviral agents.
Il- profil tas- sigurtà ta ’ emtricitabine u tenofovir disoproxil fumarate kien konsistenti ma ’ l- esperjenza fil- passat tal- komponenti individwali mogħtija ma ’ sustanzi antiretrovirali oħra.
The most frequently reported adverse reactions considered possibly or probably related to emtricitabine and/ or tenofovir disoproxil fumarate were nausea (12%) and diarrhoea (7%).
L- iktar reazzjonijiet avversi li kienu rrappurtati b’ mod frekwenti u li kienu kkunsidrati bħala possibbilment jew probabbilment relatati ma ’ emtricitabine u/ jew tenofovir disoproxil fumarate, kienu t- tqalligħ (12%) u d- dijarea (7%).
The adverse reactions considered at least possibly related to treatment with the components of Truvada from clinical trial and post-marketing experience are listed below by body system organ class and absolute frequency.
Ir- reazzjonijiet avversi kkunsidrati li kienu mill- inqas possibbilment relatati mat- trattament bil - komponenti ta ’ Truvada, li dehru fi prova klinika u mill- esperjenza miksuba wara li l- prodott tpoġġa fuq is- suq, huma elenkati hawn taħt skond il- klassi ta ’ sistema ta ’ l- organi fil- ġisem u skond il - frekwenza assoluta.
Frequencies are defined as very common (≥ 1/ 10), common (≥ 1/ 100, < 1/ 10),
L- effetti li huma l- aktar serji għandhom jitniżżlu l- ewwel, segwiti minn dawk anqas serji.
8 uncommon (≥ 1/ 1,000, < 1/ 100), rare (≥ 1/ 10,000, < 1/ 1,000) or very rare (< 1/ 10,000) including isolated reports, or not known (identified through post-marketing safety surveillance and the frequency cannot be estimated from the available data).
Il- frekwenzi huma deskritti bħala komuni ħafna (≥ 1/ 10), komuni (≥ 1/ 100, < 1/ 10), mhux komuni (≥ 1/ 1, 000, < 1/ 100), rari (≥ 1/ 10, 000, < 1/ 1, 000) jew rari ħafna (< 1/ 10, 000) inklużi rapporti iżolati, jew mhux magħrufa (identifikati permezz ta ’ sorveljanza tas- sigurtà ta ’ wara l- bejgħ, u l - frekwenza ma tistax tiġi stmata mill- informazzjoni disponibbli).
Common: allergic reaction
Komuni: reazzjoni allergika
Very common: hypophosphataemia Common: hyperglycaemia, hypertriglyceridaemia Rare: lactic acidosis Not known: hypokalaemia
Komuni ħafna: ipofosfatimja Komuni: ipergliċemija, ipertrigliċeridimija Rari: aċidożi lattika Mhux magħrufa: ipokalimja
Very common: headache, dizziness
Komuni ħafna: uġigħ ta ’ ras, sturdament
Very rare: dyspnoea
Rari ħafna: qtugħ ta ’ nifs
Very common: diarrhoea, vomiting, nausea Common: elevated serum lipase, elevated amylase including elevated pancreatic amylase, abdominal pain, dyspepsia, flatulence Rare: pancreatitis
Komuni ħafna: dijarea, rimettar, tqalligħ Komuni: livell għoli tal- lipase fis- serum, amylase għoli li jinkludi amylase pankreatika għolja, uġigħ addominali, dispepsja, gass fl- istonku
Common: increased transaminases, hyperbilirubinaemia Very rare: hepatitis Not known: hepatic steatosis
Komuni: żieda fit- transaminases, iperbilirubinimja Rari ħafna: epatite Mhux magħrufa: stejatożi epatika
Common: urticaria, vesiculobullous rash, pustular rash, maculopapular rash, pruritus, rash and skin discolouration (increased pigmentation)
Komuni: urtikarja, raxx vesikulobullożu, raxx bil- ponot, raxx makulari bl- imfafet, ħakk, raxx u tibdil fil- kulur tal- ġilda (żieda tal- pigmentazzjoni)
Very common: elevated creatine kinase Not known: rhabdomyolysis, osteomalacia (manifested as bone pain and infrequently contributing to fractures), muscular weakness, myopathy
Komuni ħafna: creatine kinase għolja Mhux magħrufa: rabdomijolosi, osteomalaċja (li tidher bħala wġigħ fl- għadam u b’ mod mhux frekwenti tikkontribwixxi għal ksur), dgħjufija fil- muskoli, mijopatija
Rare: renal failure (acute and chronic), proximal renal tubulopathy including Fanconi syndrome, increased creatinine, proteinuria Very rare: acute tubular necrosis Not known: nephritis (including acute interstitial nephritis), nephrogenic diabetes insipidus.
Rari: kollass tal- kliewi (akuta u kronika), tubulopatija renali prossimali inkluż is- sindromu ta ’ Fanconi, żieda fil- krejatinina, proteinurja Rari ħafna: nekrożi tubulari akuta Mhux magħrufa: nefrite (li tinkludi nefrite interstinali akuta), dijabete insipidus nefroġenika
Common: pain, asthenia
Komuni: uġigħ, astenja
9 The following adverse reactions, listed under the body system headings above, may occur as a consequence of proximal renal tubulopathy: rhabdomyolysis, osteomalacia (manifested as bone pain and infrequently contributing to fractures), hypokalaemia, muscular weakness, myopathy and hypophosphataemia.
Ir- reazzjonijiet avversi li ġejjin, elenkati taħt l- intestaturi tas- sistema tal- ġisem hawn fuq, jistgħu jseħħu bħala konsegwenza ta ’ tubulopatija renali prossimali: rabdomijolosi, osteomalaċja (li tidher bħala wġigħ fl- għadam u b’ mod mhux frekwenti tikkontribwixxi għal ksur), ipokalimja, dgħjufija fil - muskoli, mijopatija u ipofosfatimja.
These events are not considered to be causally associated with tenofovir disoproxil fumarate therapy in the absence of proximal renal tubulopathy.
Dawn l- avvenimenti mhumiex ikkunsidrati li huma assoċjati b’ mod kawżali mat- trattament b’ tenofovir disoproxil fumarate fl- assenza ta ’ tubulopatija renali prossimali.
In addition anaemia was common and skin discolouration (increased pigmentation) was very common when emtricitabine was administered to paediatric patients.
Flimkien ma ’ dan, l- anemija kienet komuni u t- tibdil fil- kulur tal- ġilda (żieda fil- pigmentazzjoni) kien komuni ħafna meta emtricitabine ngħata f’ pazjenti pedjatriċi.
HIV/ HBV or HCV co-infected patients:
Pazjenti infettati kemm bl- HIV/ HBV jew bl- HCV:
Only a limited number of patients were co-infected with HBV (n=13) or HCV (n=26) in study GS-01-934.
Numru limitat biss ta ’ pazjenti kienu infettati wkoll bl- HBV (n=13) jew bl- HCV (n=26) fi studju GS- 01- 934.
The adverse reaction profile of emtricitabine and tenofovir disoproxil fumarate in patients co-infected with HIV/ HBV or HIV/ HCV was similar to that observed in patients infected with HIV without co-infection.
Il- profil tar- reazzjoni avversa ta ’ emtricitabine u tenofovir disoproxil fumarate f’ pazjenti infettati kemm bl- HIV/ HBV jew bl- HIV/ HCV kien jixbah lil dak osservat f’ pazjenti infettati bl- HIV biss.
However, as would be expected in this patient population, elevations in AST and ALT occurred more frequently than in the general HIV infected population.
Madankollu, bħalma jkun mistenni f’ dan il - grupp ta ’ pazjenti, żieda fl- AST u l- ALT seħħet iżjed ta ’ spiss milli fil- popolazzjoni ġenerali infettatata bl- HIV.
Combination antiretroviral therapy has been associated with metabolic abnormalities such as hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperglycaemia and hyperlactataemia (see section 4.4).
It- terapija antiretrovirali kombinata ġiet assoċjata ma ’ anormalitajiet metaboliċi bħalma huma l - ipergliċeridimja, l- iperkolesterolimja, reżistenza għall- insulina, ipergliċemija u l- iperlaktejtimja (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).
Kienu rrappurtati każijiet ta ’ osteonekrożi, partikularment f’ pazjenti li jkollhom fatturi ta ’ riskju li huma magħrufa b’ mod ġenerali, mard ta ’ l- HIV li jkun fi stadju avvanzat jew esponiment fit- tul għal
If overdose occurs the patient must be monitored for evidence of toxicity (see section 4.8), and standard supportive treatment applied as necessary.
Jekk iseħħ każ ta ’ doża eċċessiva, il- pazjent għandu jiġi mmonitorjat għal sinjali ta ’ tossiċità (ara sezzjoni 4. 8), u t- trattament ta ’ appoġġ regolari għandu jingħata kif meħtieġ.
Up to 30% of the emtricitabine dose and approximately 10% of the tenofovir dose can be removed by haemodialysis.
Sa 30% tad- doża ta ’ emtricitabine u madwar 10% tad- doża ta ’ tenofovir tista titneħħa permezz ta ’ dijaliżi tad- demm.
It is not known whether emtricitabine or tenofovir can be removed by peritoneal dialysis.
Mhux magħruf jekk emtricitabine jew tenofovir jistgħux jitneħħew permezz ta ’ dijaliżi peritoneali.
Mechanism of action and pharmacodynamic effects:
Mekkaniżmu ta ’ l- azzjoni u effetti farmakodinamiċi:
Emtricitabine is a nucleoside analogue of cytidine.
Emtricitabine huwa analogu tan- nukleosidi ta ’ cytidine.
Tenofovir disoproxil fumarate is converted in vivo to tenofovir, a nucleoside monophosphate (nucleotide) analogue of adenosine monophosphate.
Tenofovir disoproxil fumarate jinbdel in vivo għal tenofovir, li huwa analogu ta ’ nucleoside monophosphate (nucleotide) analogu ta ’ adenosine monophosphate.
Both emtricitabine and tenofovir have activity that is specific to human immunodeficiency virus (HIV-1 and HIV-2) and hepatitis B virus.
Kemm emtricitabine kif ukoll tenofovir għandhom attività li hi speċifika għall- virus ta ’ l- immunodefiċjenza uman (HIV- 1 u HIV- 2) u l- virus ta ’ l- epatite B.
10 Emtricitabine and tenofovir are phosphorylated by cellular enzymes to form emtricitabine triphosphate and tenofovir diphosphate, respectively.
Emtricitabine u tenofovir jiġu fosforilati permezz ta ’ enzimi ċellulari biex jifformaw emtricitabine triphosphate u tenofovir diphosphate, rispettivament.
In vitro studies have shown that both emtricitabine and tenofovir can be fully phosphorylated when combined together in cells.
Studji in vitro wrew li kemm emtricitabine u tenofovir jistgħu jkunu fosforilati b’ mod sħiħ meta kkombinati flimkien fiċ- ċelluli.
Emtricitabine triphosphate and tenofovir diphosphate competitively inhibit HIV-1 reverse transcriptase, resulting in DNA chain termination.
Emtricitabine triphosphate u tenofovir diphosphate jinibixxu kompetittivament ir- reverse transcriptase ta ’ l- HIV- 1 li jirriżulta fit- terminazzjoni tal- katina tad- DNA.
Both emtricitabine triphosphate and tenofovir diphosphate are weak inhibitors of mammalian DNA polymerases and there was no evidence of toxicity to mitochondria in vitro and in vivo.
Kemm emtricitabine triphosphate u tenofovir diphosphate huma impedituri dgħajfa tal- polimerases tad- DNA mammifera u ma kienx hemm evidenza ta ’ tossiċità lill- mitokondrija in vitro jew in vivo.
Synergistic antiviral activity was observed with the combination of emtricitabine and tenofovir in vitro.
Attività antivirali sinerġistika dehret bil- kumbinazzjoni ta ’ emtricitabine u tenofovir in vitro.
Additive to synergistic effects were observed in combination studies with protease inhibitors, and with nucleoside and non-nucleoside analogue inhibitors of HIV reverse transcriptase.
Żidiet ma ’ l- effetti sinerġistiċi dehru fi studji kombinati ta ’ emtricitabine flimkien ma ’ impedituri tal- protease, u ma ’ impedituri tal- analogi tan- nukleosidi u mhux nukleosidi tar- reverse transcriptase ta ’ l- HIV.
Resistance has been seen in vitro and in some HIV-1 infected patients due to the development of the M184V/ I mutation with emtricitabine or the K65R mutation with tenofovir.
Ir- reżistenza ntweriet in vitro u f’ xi pazjenti infettati bl- HIV- 1 minħabba l- iżvilupp tal - mutazzjoni M184V/ I b’ emtricitabine jew il- mutazzjoni K65R b’ tenofovir.
No other pathways of resistance to emtricitabine or tenofovir have been identified.
Ma kienu identifikati l- ebda passaġġi ta ’ reżistenza oħra għal emtricitabine jew tenofovir.
Emtricitabine-resistant viruses with the M184V/ I mutation were cross-resistant to lamivudine, but retained sensitivity to didanosine, stavudine, tenofovir, zalcitabine and zidovudine.
Il- viri reżistenti għal emtricitabine bil - mutazzjoni M184V/ I kienu cross- resistant għal lamivudine, iżda żammew is- sensittività għal didanosine, stavudine, tenofovir, zalcitabine u zidovudine.
The K65R mutation can also be selected by abacavir, didanosine or zalcitabine and results in reduced susceptibility to these agents plus lamivudine, emtricitabine and tenofovir.
Il- mutazzjoni K65R tista ’ ukoll tintgħażel minn abacavir, didanosine jew zalcitabine u tikkawża tnaqqis fis- sensittività għal dawn il- mediċini flimkien ma ’ lamivudine, emtricitabine u tenofovir.
Tenofovir disoproxil fumarate should be avoided in patients with HIV-1 harbouring the K65R mutation.
Tenofovir disoproxil fumarate għandu jkun evitat f’ pazjenti bl- HIV- 1 bil- mutazzjoni K65R.
Patients with HIV-1 expressing three or more thymidine analogue associated mutations (TAMs) that included either the M41L or L210W reverse transcriptase mutation showed reduced susceptibility to tenofovir disoproxil fumarate.
Pazjenti li l- marda tal- HIV tagħhom kellha 3 mutazzjonijiet assoċjati ma ’ l- analogi ta ’ thymidine (TAMs) jew aktar li kienu jinkludu l- mutazzjoni M41L jew L210W reverse transcriptase wrew tnaqqis fis- sensittività għal tenofovir disoproxil fumarate.
In vivo resistance (antiretroviral-naïve patients):
Reżistenza in vivo (pazjenti li qatt ma ’ kienu ngħataw mediċini antiretrovirali qabel):
In an open-label randomised clinical study (GS-01-934) in antiretroviral-naïve patients, genotyping was performed on plasma HIV-1 isolates from all patients with confirmed HIV RNA > 400 copies/ ml at weeks 48, 96 or 144 or at the time of early study drug discontinuation.
11 kellhom RNA tal- HIV ta ’ > 400 kopja/ ml f’ ġimgħat 48, 96 jew 144, jew fiż- żmien tat- twaqqif bikri tal- mediċina.
• The M184V/ I mutation developed in 2/ 19 (10.5%) isolates analysed from patients in the emtricitabine/ tenofovir disoproxil fumarate/ efavirenz group and in 10/ 29 (34.5%) isolates analysed from the lamivudine/ zidovudine/ efavirenz group (p-value < 0.05, Fisher’ s Exact test comparing the emtricitabine+tenofovir disoproxil fumarate group to the lamivudine/ zidovudine group among all subjects). • No virus analysed contained the K65R mutation. • Genotypic resistance to efavirenz, predominantly the K103N mutation, developed in virus from 13/ 19 (68%) patients in the emtricitabine/ tenofovir disoproxil fumarate/ efavirenz group and in virus from 21/ 29 (72%) patients in the comparative group.
• Il- mutazzjoni M184V/ I żviluppat fi 2/ 19 (10. 5%) iżolati analizzati minn pazjenti fil- grupp ta ’ emtricitabine/ tenofovir disoproxil fumarate/ efavirenz u f’ 10/ 29 (34. 5%) iżolati analizzati fil - grupp ta ’ lamivudine/ zidovudine/ efavirenz (valur p ta ’ < 0. 05, it- Test ta ’ Fisher Exact li qabbel il- grupp ta’ emtricitabine+tenofovir disoproxil fumarate mal - grupp ta ’ lamivudine/ zidovudine fost l- individwi kollha). • L- ebda virus li kien analizzat ma kien fih il- mutazzjoni K65R. • Ir- reżistenza ġenotipika għal efavirenz, l- aktar il- mutazzjoni K103N, żviluppat f’ virus f’ 13/ 19 (68%) tal- pazjenti fil- grupp ta ’ emtricitabine/ tenofovir disoproxil fumarate/ efavirenz u f’ virus f’ 21/ 29 (72%) tal- pazjenti fil- grupp komparattiv.
In an open-label randomised clinical study (GS-01-934), antiretroviral-naïve HIV-1 infected patients received either a once daily regimen of emtricitabine, tenofovir disoproxil fumarate and efavirenz (n=255) or a fixed combination of lamivudine and zidovudine (Combivir) administered twice daily and efavirenz once daily (n=254).
Fi studju kliniku open- label u randomised (GS- 01- 934), pazjenti infettati bl- HIV- 1 li qatt ma ’ kienu ngħataw mediċini antiretrovirali qabel irċievew jew kors ta ’ darba kuljum ta ’ emtricitabine, tenofovir disoproxil fumarate u efavirenz (n=255), jew kumbinazzjoni fissa ta ’ lamivudine u zidovudine (Combivir), mogħti darbtejn kuljum, u efavirenz mogħti darba kuljum (n=254).
Patients in the emtricitabine and tenofovir disoproxil fumarate group were given Truvada and efavirenz from week 96 to week 144.
Il- pazjenti fil- grupp ta ’ emtricitabine u tenofovir disoproxil fumarate ingħataw Truvada u efavirenz minn ġimgħa 96 sa ġimgħa 144.
At baseline the randomised groups had similar median plasma HIV-1 RNA (5.02 and 5.00 log10 copies/ ml) and CD4 counts (233 and 241 cells/ mm3).
Fil- linja bażi, il- gruppi randomised kellhom medjan simili ta ’ l- RNA tal- HIV- 1 tal- plażma (5. 02 u 5. 00 log10 kopja/ ml) u ta ’ l - għadd tas- CD4 (233 u 241 ċelluli/ mm3).
The primary efficacy endpoint for this study was the achievement and maintenance of confirmed HIV-1 RNA concentrations < 400 copies/ ml over 48 weeks.
Ir- riżultat aħħari ta ’ l- effikaċja primarja għal dan l- istudju kien li ġew ottenuti u miżmuma it- twettiq u l- manutenzjoni ta ’ konċentrazzjonijiet ikkonfermati tal- RNA tal- HIV- 1 ta ’ < 400 kopja/ ml fuq perjodu ta ’ 48 ġimgħa.
Secondary efficacy analyses over 144 weeks included the proportion of patients with HIV-1 RNA concentrations < 400 or < 50 copies/ ml, and change from baseline in CD4 cell count.
L- analiżi ta ’ l- effikaċja sekondarja fuq perjodu ta ’ 144 ġimgħa kienet tinkludi l- proporzjon ta ’ pazjenti b’ konċentrazzjonijiet tal- RNA tal- HIV- 1 ta ’ < 400 jew < 50 kopja/ ml, u l- bidla mil- linja bażi fl- għadd taċ- ċelluli tas- CD4.
The 48-week primary endpoint data showed that the combination of emtricitabine, tenofovir disoproxil fumarate and efavirenz provided superior antiviral efficacy as compared with the fixed combination of lamivudine and zidovudine (Combivir) with efavirenz as shown in Table 1.
Informazzjoni dwar ir- riżultat aħħari primarju wara 48 ġimgħa wera li l- kumbinazzjoni ta ’ emtricitabine, tenofovir disoproxil fumarate u efavirenz, ipprovdiet effikaċja antivirali superjuri meta mqabbla mal- kumbinazzjoni fissa ta ’ lamivudine u zidovudine (Combivir) flimkien ma ’ efavirenz kif muri f’ Tabella 1.
The 144 week secondary endpoint data are also presented in Table 1.
L- informazzjoni mir- riżultat aħħari sekondarju wara 144 ġimgħa hi ppreżentata wkoll f’ Tabella 1.
48- and 144-week efficacy data from study GS-01-934 in which emtricitabine, tenofovir disoproxil fumarate and efavirenz were administered to antiretroviral-naïve patients with HIV-1 infection
Informazzjoni dwar l- effikaċja wara 48 u 144 ġimgħa minn studju GS- 01- 934 li fih emtricitabine, tenofovir disoproxil fumarate u efavirenz, ingħataw lil pazjenti li qatt ma ’ kienu ngħataw mediċini antiretrovirali qabel li kellhom infezzjoni bl- HIV- 1.
Treatment for 48 weeks
għal 48 ġimgħa
Treatment for 144 weeks
għal 144 ġimgħa
tenofovir disoproxil fumarate+efavirenz
tenofovir disoproxil zidovudine+efavirenz fumarate+efavirenz
tenofovir disoproxil fumarate+efavirenz*
tenofovir disoproxil fumarate+efavirenz *
zidovudine+efaviren z
zidovudine+efavirenz
HIV-1 RNA < 400 copies/ ml (TLOVR)
RNA tal- HIV- 1 < 400 kopja/ ml (TLOVR)
p-value
Valur p
0.002**
0. 002 **
0.004**
0. 004 **
% difference (95%CI)
% differenza (95% CI)
(4% to 19%)
(4% sa 19%)
(4% to 22%)
(4% sa 22%)
HIV-1 RNA < 50 copies/ ml (TLOVR)
RNA tal- HIV- 1 < 50 kopja/ ml (TLOVR)
0.021**
0. 021 **
0.082**
0. 082 **
(2% to 17%)
(2% sa 17%)
Mean change from baseline in CD4 cell count (cells/ mm3)
Bidla medja mil - linja bażi fl- għadd taċ- ċelluli CD4 (ċelluli/ mm3)
p-value Difference (95%CI)
Differenza (95% CI)
0.002a 32 (9 to 55)
32 (9 sa 55)
0.089a 41 (4 to 79)
41 (4 sa 79)
* Patients receiving emtricitabine, tenofovir disoproxil fumarate and efavirenz were given Truvada plus efavirenz from week 96 to 144. ** The p-value based on the Cochran-Mantel-Haenszel Test stratified for baseline CD4 cell count TLOVR=Time to Loss of Virologic Response a:
* Il- pazjenti li jkunu qed jirċievu emtricitabine, tenofovir disoproxil fumarate u efavirenz ngħataw Truvada flimkien ma ’ efavirenz minn ġimgħa 96 sa 144. ** Il- valur p ibbażat fuq it- Test ta ’ Cochran- Mantel- Haenszel stratifikat għal- linja bażi ta ’ l- għadd taċ- ċelluli CD4 TLOVR=Ħin ta ’ nuqqas ta ’ respons viroloġiku a:
Van Elteren Test
Test ta ’ Van Elteren
In a separate randomised clinical study (M02-418), one hundred and ninety antiretroviral-naïve adults were also treated once daily with emtricitabine and tenofovir disoproxil fumarate in combination with lopinavir/ ritonavir given once or twice daily.
Fi studju kliniku separat randomised (M02- 418), mija u disgħin pazjent adult li qatt ma ’ kienu ħadu terapija antiretrovirali, kienu wkoll ittrattati darba kuljum b’ emtricitabine u tenofovir disoproxil fumarate flimkien ma ’ lopinavir/ ritonavir mogħti darba jew darbtejn kuljum.
At 48 weeks, 70% and 64% of patients demonstrated HIV-1 RNA < 50 copies/ ml with the once and twice daily regimens of lopinavir/ ritonavir, respectively.
Fil- ġimgħa 48, 70% u 64% tal- pazjenti wrew RNA ta ’ l- HIV- 1 < 50 kopja/ ml bil- korsijiet fejn ingħataw lopinavir/ ritonavir darba u darbtejn kuljum rispettivament.
The mean changes in CD4 cell count from baseline were +185 cells/ mm3 and +196 cells/ mm3 with the once and twice daily regimens of lopinavir/ ritonavir, respectively.
It- tibdil medju fl- għadd taċ- ċelluli CD4 mil- linja bażi kien ta ’ +185 ċelluli/ mm3 u +196 ċelluli/ mm3 bil- korsijiet fejn ingħataw lopinavir/ ritonavir darba u darbtejn kuljum rispettivament.
Limited clinical experience in patients co-infected with HIV and HBV suggests that treatment with emtricitabine or tenofovir disoproxil fumarate in antiretroviral combination therapy to control HIV infection also results in a reduction in HBV DNA (3 log10 reduction or 4 to 5 log10 reduction, respectively) (see section 4.4).
Esperjenza klinika limitata f’ pazjenti infettati kemm bl- HIV kif ukoll bl- HBV tissuġġerixxi li t - trattament b’ emtricitabine jew tenofovir disoproxil fumarate f’ terapija kombinata antiretrovirali biex tikkontrolla l- infezzjoni bl- HIV tirriżulta wkoll fi tnaqqis fin- DNA ta ’ l- HBV (tnaqqis ta ’ 3 log10 jew tnaqqis ta ’ 4 sa 5 log10, rispettivament) (ara sezzjoni 4. 4).
The bioequivalence of one Truvada film-coated tablet with one emtricitabine 200 mg hard capsule and one tenofovir disoproxil fumarate 245 mg film-coated tablet was established following single dose administration to fasting healthy subjects.
Il- bijoekwivalenza ta ’ pillola waħda miksija b’ rita ta ’ Truvada flimkien ma ’ kapsula iebsa ta ’ 200 mg emtricitabine u pillola waħda miksija b’ rita ta ’ 245 mg tenofovir disoproxil fumarate kienet stabbilita wara li ngħatat doża waħda lill- individwi f’ saħħithom fl- istat sajjem.
Following oral administration of Truvada to healthy subjects, emtricitabine and tenofovir disoproxil fumarate are rapidly absorbed and tenofovir disoproxil fumarate is converted to tenofovir.
Wara l- għoti mill- ħalq ta ’ Truvada lill- individwi f’ saħħithom, emtricitabine u tenofovir disoproxil fumarate jiġu assorbiti malajr u tenofovir disoproxil fumarate jinbidel għal tenofovir.
Maximum emtricitabine and tenofovir concentrations are observed in serum within 0.5 to 3.0 h of dosing in the fasted state.
Konċentrazzjonijiet massimi ta ’ emtricitabine u tenofovir jidhru fis- serum fi żmien 0. 5 sa 3. 0 sigħat minn mindu tkun ingħatat id - doża fl- istat sajjem.
Administration of Truvada with food resulted in a delay of approximately three quarters of an hour in reaching maximum tenofovir concentrations and increases in tenofovir AUC and Cmax of approximately 35% and 15%, respectively, when administered with a high fat or light meal, compared to administration in the fasted state.
L- għoti ta ’ Truvada ma ’ l- ikel irriżulta f’ ittardjar ta ’ madwar tliet kwarti ta ’ siegħa biex jintlaħqu konċentrazzjonijiet massimi ta ’ tenofovir u żidiet fl- AUC u Cmax ta ’ tenofovir ta ’ madwar 35% u 15%, rispettivament, meta mgħotija ma ’ ikla li fiha ammont għoli ta ’ xaħam jew ikla ħafifa, meta mqabbla ma ’ l- għoti fl- istat sajjem.
12 Distribution:
13 Distribuzzjoni:
Following intravenous administration the volume of distribution of emtricitabine and tenofovir was approximately 1.4 l/ kg and 800 ml/ kg, respectively.
Wara l- għoti minn ġol- vina, il- volum ta ’ distribuzzjoni ta ’ emtricitabine u tenofovir kien ta ’ madwar 1. 4 l/ kg u 800 ml/ kg, rispettivament.
After oral administration of emtricitabine or tenofovir disoproxil fumarate, emtricitabine and tenofovir are widely distributed throughout the body.
Wara l- għoti mill- ħalq ta ’ emtricitabine jew tenofovir disoproxil fumarate, emtricitabine u tenofovir jitqassmu jiġu distribwiti sew madwar il - ġisem.
In vitro binding of emtricitabine to human plasma proteins was < 4% and independent of concentration over the range of 0.02 to 200 µg/ ml.
It- twaħħil in vitro ta ’ emtricitabine ma ’ proteini tal- plażma umana kienet ta ’ < 4% u indipendenti mill- konċentrazzjoni fil- medda ta ’ 0. 02- 200 μg/ ml.
In vitro protein binding of tenofovir to plasma or serum protein was less than 0.7 and 7.2%, respectively, over the tenofovir concentration range 0.01 to 25 µg/ ml.
Ir- rabta in vitro ta ’ tenofovir ma ’ proteini tal- plażma jew proteini fis- serum kienet anqas minn 0. 7 u 7. 2%, rispettivament, ogħla mill - medda tal- konċentrazzjoni ta ’ tenofovir 0. 01 sa 25 μg/ ml.
In vitro studies have determined that neither tenofovir disoproxil fumarate nor tenofovir are substrates for the CYP450 enzymes.
Studji in vitro wrew li la tenofovir disoproxil fumarate u lanqas tenofovir ma huma sottostrati għall- enzimi CYP450.
Neither emtricitabine nor tenofovir inhibited in vitro drug metabolism mediated by any of the major human CYP450 isoforms involved in drug biotransformation.
La emtricitabine u lanqas tenofovir ma inibixxew in vitro l - metaboliżmu tal- mediċina medjat minn xi wieħed mill- iżoformi umani maġġuri ta ’ CYP450 involuti fil- bijotrasformazzjoni tal- mediċina.
Also, emtricitabine did not inhibit uridine-5'-diphosphoglucuronyl transferase, the enzyme responsible for glucuronidation.
Emtricitabine, ukoll, ma impedixxix lill- enzima uridine- 5 ’ diphosphoglucuronyl transferase, li hija responsabbli għall- glukoronidazzjoni.
Emtricitabine is primarily excreted by the kidneys with complete recovery of the dose achieved in urine (approximately 86%) and faeces (approximately 14%).
Emtricitabine jiġi eliminat prinċipalment mill- kliewi bl- irkupru komplet tad- doża fl - awrina (madwar 86%) u fl- ippurgar (madwar 14%).
The systemic clearance of emtricitabine averaged 307 ml/ min.
It- tneħħija sistemika ta ’ emtricitabine kienet medja ta ’ 307 ml/ min.
Tenofovir is primarily excreted by the kidney by both filtration and an active tubular transport system with approximately 70-80% of the dose excreted unchanged in urine following intravenous administration.
Tenofovir jitneħħa mill- ġisem prinċipalment mill- kliewi kemm permezz tal- filtrazzjoni kif ukoll permezz ta ’ sistema attiva ta ’ trasport tubulari b’ madwar 70- 80% tad- doża titneħħa mingħajr tibdil fl - awrina wara l- għoti minn ġol- vina.
The apparent clearance of tenofovir averaged approximately 307 ml/ min.
It- tneħħija apparenti ta ’ tenofovir kellha medja ta ’ madwar 307 ml/ min.
Renal clearance has been estimated to be approximately 210 ml/ min, which is in excess of the glomerular filtration rate.
It- tneħħija mill- kliewi ġiet stmata li hi madwar 210 ml/ min), li huwa iżjed mir- rata tal - filtrazzjoni glomerulari.
This indicates that active tubular secretion is an important part of the elimination of tenofovir.
Dan jindika li s- sekrezzjoni tubulari attiva hija parti importanti mill - eliminazzjoni ta ’ tenofovir.
Following oral administration, the elimination half-life of tenofovir is approximately 12 to 18 hours.
Wara li jittieħed mill- ħalq il- half life ta ’ l- eliminazzjoni ta ’ tenofovir hi ta ’ madwar 12 sa 18- il siegħa.
Emtricitabine and tenofovir pharmacokinetics are similar in male and female patients.
Il- farmakokinetiċi ta ’ emtricitabine u tenofovir huma simili f’ pazjenti rġiel u nisa.
Pharmacokinetic studies have not been performed with tenofovir in children and adolescents (under 18 years).
Studji farmakokinetiċi ma ’ sarux b’ tenofovir fuq it- tfal u l- adolexxenti (taħt it- 18- il sena).
Pharmacokinetic studies have not been performed with emtricitabine or tenofovir in the elderly (over 65 years).
Studji farmakokinetiċi ma ’ sarux b’ emtricitabine jew tenofovir fuq l- anzjani (’ il fuq minn 65 sena).
Limited pharmacokinetic data are available for emtricitabine and tenofovir after co-administration of separate preparations or as Truvada in patients with renal impairment.
Hemm dejta farmakokinetika limitata disponibbli għal emtricitabine u tenofovir wara l- għoti flimkien ta ’ preparazzjonijiet separati jew bħala Truvada f’ pazjenti b’ indeboliment renali.
Pharmacokinetic parameters were mainly determined following administration of single doses of emtricitabine 200 mg or tenofovir disoproxil 245 mg to non-HIV infected patients with varying degrees of renal impairment.
Il- parametri farmakokinetiċi kienu deċiżi primarjament wara l- għoti ta ’ dożi waħedhom ta ’ 200 mg emtricitabine jew 245 mg tenofovir disoproxil lil pazjenti mhux infettati b’ HIV b’ livelli differenti ta ’ indeboliment renali.
The degree of renal impairment was defined according to baseline creatinine clearance (CrCl) (normal renal function when CrCl > 80 ml/ min; mild impairment with CrCl = 50-79 ml/ min; moderate impairment with CrCl = 30-49 ml/ min and severe impairment with CrCl = 10-29 ml/ min).
Il- grad ta ’ indeboliment renali kien definit skond il- linja bażi tat- tneħħija tal - krejatinina (CrCl) (funzjoni renali normali meta CrCl > 80 ml/ min; indeboliment ħafif b’ CrCl = 50- 79 ml/ min; indeboliment moderat b’ CrCl = 30- 49 ml/ min u indeboliment sever b’ CrCl = 10- 29 ml/ min).
The mean (%CV) emtricitabine drug exposure increased from 12 (25%) µg• h/ ml in subjects with normal renal function, to 20 (6%) µg• h/ ml, 25 (23%) µg• h/ ml and 34 (6%) µg• h/ ml, in patients with mild, moderate and severe renal impairment, respectively.
L- esponiment medju tal- mediċina ta ’ emtricitabine (% CV) żdied minn 12 (25%) µg• h/ ml f’ individwi b’ funzjoni renali normali, għal 20 (6%) µg• h/ ml, 25 (23%) µg• h/ ml u 34 (6%) µg• h/ ml, f’ pazjenti b’ indeboliment ħafif, moderat u sever rispettivament.
The mean (%CV) tenofovir drug exposure increased from 2,185 (12%) ng• h/ ml in patients with normal renal function, to 3,064 (30%) ng• h/ ml, 6,009 (42%) ng• h/ ml and 15,985 (45%) ng• h/ ml, in patients with mild, moderate and severe renal impairment, respectively.
L- esponiment medju tal- mediċina ta ’ tenofovir (% CV) żdiedet minn 2, 185 (12%) ng• h/ ml f’ pazjenti b’ funzjoni renali normali, għal 3, 064 (30%) ng• h/ ml, 6, 009 (42%) ng• h/ ml u 15, 985 (45%) ng• h/ ml f’ pazjenti b’ indeboliment renali ħafif, moderat u sever, rispettivament.
The increased dose interval for Truvada in patients with moderate renal impairment is expected to result in higher peak plasma concentrations and lower Cmin levels as compared to patients with normal renal function.
Iż- żieda fl- intervall tad- dożaġġ ta ’ Truvada f’ pazjenti b’ indeboliment renali moderata huma mistennija li tirriżulta f’ livelli ogħla tal- konċentrazzjonijiet massimi fil- plażma u livelli aktar baxxi ta ’ Cmin meta
The clinical implications of this are unknown.
14 mqabbla ma ’ pazjenti b’ funzjoni renali normali.
13 In patients with end-stage renal disease (ESRD) requiring haemodialysis, between dialysis drug exposures substantially increased over 72 hours to 53 (19%) µg• h/ ml of emtricitabine, and over 48 hours to 42,857 (29%) ng• h/ ml of tenofovir.
F’ pazjenti b’ mard renali fl- aħħar stadju (ESRD) li jeħtieġu d- dijaliżi tad- demm, bejn dijaliżi u oħra, l - esponimenti tal- mediċina tad- dijaliżi, żdiedu sostanzjalment fi żmien 72 siegħa għal 53 (19%) µg• h/ ml ta ’ emtricitabine, u matul 48 siegħa għal 42, 857 (29%) ng• h/ ml ta ’ tenofovir.
It is recommended that the dosing interval for Truvada is modified in patients with creatinine clearance between 30 and 49 ml/ min.
Huwa rrakkomandat li l- intervall tad- dożaġġ ta ’ Truvada jinbidel f’ pazjenti li għandhom rata ta ’ tneħħija tal- krejatinina ta ’ bejn 30 u 49 ml/ min.
Truvada is not suitable for patients with CrCl < 30 ml/ min or for those on haemodialysis (see section 4.2).
Truvada mhijiex adattata għal pazjenti b’ CrCl < 30 ml/ min jew għal dawk fuq id- dijaliżi tad- demm (ara sezzjoni 4. 2).
A small clinical study was conducted to evaluate the safety, antiviral activity and pharmacokinetics of tenofovir disoproxil fumarate in combination with emtricitabine in HIV infected patients with renal impairment.
Sar studju kliniku żgħir biex jevalwa s- sigurtà, l- attività antivirali u l- farmakokinetika ta ’ tenofovir disoproxil fumarate flimkien ma ’ emtricitabine f’ pazjenti infettati bl- HIV li kellhom indeboliment renali.
A subgroup of patients with baseline creatinine clearance between 50 and 60 ml/ min, receiving once daily dosing, had a 2-4-fold increase in tenofovir exposure and worsening renal function.
Sotto- grupp ta ’ pazjenti bi tneħħija tal- krejatinina fil- linja bażi bejn 50 u 60 ml/ min, li rċivew dożaġġ ta ’ darba kuljum, kellhom esponiment ogħla ta ’ 2- 4 darbiet aktar għal tenofovir u l- funzjoni renali marret għall- agħar.
The pharmacokinetics of Truvada have not been studied in patients with hepatic impairment.
Il- farmakokinetiċi ta ’ Truvada ma ġewx studjati f’ pazjenti b’ indeboliment epatiku.
However, it is unlikely that a dose adjustment would be required for Truvada in patients with hepatic impairment.
Madankollu, x’ aktarx li aġġustament fid- doża mhux ser ikun meħtieġ għal Truvada f’ pazjenti b’ indeboliment epatiku.
A single 245 mg dose of tenofovir disoproxil was administered to non-HIV infected patients with varying degrees of hepatic impairment defined according to Child-Pugh-Turcotte (CPT) classification.
Doża waħda ta ’ 245 mg ta ’ tenofovir disoproxil ngħatat lill- pazjenti li ma kienux infettati b’ HIV li kellhom indeboliment epatiku fi stadji differenti skond il- klassifikazzjoni ta ’ Child Pugh Turcotte (CPT).
Tenofovir pharmacokinetics were not substantially altered in subjects with hepatic impairment suggesting that no dose adjustment is required in these subjects.
Il- farmakokinetiċi ta ’ tenofovir ma nbidlux sostanzjalment f’ individwi b’ indeboliment epatiku, li jissuġġerixxi li l- ebda aġġustament fid- doża mhuwa meħtieġ f’ dawn l- individwi.
The mean (%CV) tenofovir Cmax and AUC0-∞ values were 223 (34.8%) ng/ ml and 2,050 (50.8%) ng• h/ ml, respectively, in normal subjects compared with 289 (46.0%) ng/ ml and 2,310 (43.5%) ng• h/ ml in subjects with moderate hepatic impairment, and 305 (24.8%) ng/ ml and 2,740 (44.0%) ng• h/ ml in subjects with severe hepatic impairment.
Il- medja (% CV) tal- valuri ta ’ Cmax ta ’ tenofovir u l- valuri ta ’ l- AUC0- ∞ kienu ta ’ 223 (34. 8%) ng/ ml u 2, 050 (50. 8%) ng• h/ ml rispettivament, f’ individwi normali, meta pparagunata ma ’ 289 (46. 0%) ng/ ml u 2, 310 (43. 5%) ng• h/ ml f’ individwi b’ indeboliment epatiku moderat, u 305 (24. 8%) ng/ ml u 2, 740 (44. 0%) ng• h/ ml f’ individwi b’ indeboliment epatiku sever.
Non-clinical data on emtricitabine reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity.
Informazzjoni li mhiex klinika dwar emtricitabine, magħmula fuq studji konvenzjonali ta ’ sigurtà farmakoloġika, effett tossiku minn dożi ripetuti u l- effett tossiku fuq il- ġeni, ma ’ turi l- ebda periklu speċjali għall- bnedmin.
Emtricitabine did not show any carcinogenic potential in long-term oral carcinogenicity studies in mice and rats.
Emtricitabine ma ’ wera l- ebda riskju ta ’ kanċer fi studji orali, fit- tul dwar il - karċinoġeniċità fil- ġrieden u fil- firien.
Preclinical studies of tenofovir disoproxil fumarate conducted in rats, dogs and monkeys revealed target organ effects in gastrointestinal tract, kidney, bone and a decrease in serum phosphate concentration.
Studji ta ’ qabel l- użu kliniku ta ’ tenofovir disoproxil fumarate li saru fil- firien, fil- klieb u fix- xadini wrew effetti fuq l- organi milquta fil- passaġġ gastro- intestinali, fil- kliewi, fil- għadam u tnaqqis fil - konċentrazzjoni ta ’ phosphate fis- serum.
Bone toxicity was diagnosed as osteomalacia (monkeys) and reduced bone mineral density (rats and dogs).
It- tossiċità fl- għadam kienet dijanjostikata bħala osteomalaċja (fix- xadini) u tnaqqis fid- densità minerali ta ’ l għadam (fil- firien u l- klieb).
Findings in the rat and monkey studies indicated that there was a substance-related decrease in intestinal absorption of phosphate with potential secondary reduction in bone mineral density.
Sejbiet fl - istudji fuq il- firien u x- xadini indikaw li kien hemm tnaqqis konness mas- sustanza fl- assorbiment intestinali ta ’ phosphate b’ potenzjali ta ’ tnaqqis sekondarju fid- densità minerali ta ’ l- għadam.
The mechanisms of these toxicities are not completely understood.
Il - mekkaniżmi ta ’ dawn it- tossiċitajiet m’ humiex mifhuma kompletament.
Conventional reproductive/ developmental toxicity studies with emtricitabine and tenofovir disoproxil fumarate reveal no special hazard for humans.
Studji konvenzjonali dwar it- tossiċità fis- sistema riproduttiva/ ta ’ l- iżvilupp b’ emtricitabine u tenofovir disoproxil fumarate ma żvelaw l- ebda periklu speċjali għall- bnedmin.
Tenofovir disoproxil fumarate was positive in two out of three in vitro genotoxicity studies but negative in the in vivo micronucleus assay.
Tenofovir disoproxil fumarate kien pożittiv fi tnejn minn kull tliet studji ġenotossiċi in vitro iżda kien negattiv fl- analiżi mikronuklejari in vivo.
Tenofovir disoproxil fumarate did not show any carcinogenic potential in a long-term oral carcinogenicity study in rats.
Tenofovir disoproxil fumarate ma wera l- ebda riskju ta ’ kanċer fi studju dwar il- karċinoġeniċità fuq il - firien bl- użu orali fit- tul.
A long-term oral carcinogenicity study in mice showed a low incidence of duodenal tumours, considered likely related to high local concentrations in the gastrointestinal tract at a dose of 600 mg/ kg/ day.
15 tumuri tad- duwodenu, li kienu kkunsidrati li x’ aktarx kienu relatati mal- konċentrazzjonijiet għolja fil - passaġġ gastro- intestinal f’ doża ta ’ 600 mg/ kg kuljum.
While the mechanism of tumour formation is uncertain, the findings are unlikely to be of relevance to humans.
Għalkemm il- mekkaniżmu tal- formazzjoni tat - tumuri mhuwiex ċar, dawn is- sejbiet m’ humiex mistennija li jkunu rilevanti għall- bniedem.