qanastek/EMEA-V3 huggingface dataset:
Metabolite 25-O-desacetylrifabutin AUC ↑ 1.24 (0.84-1.84) Metabolite 25-O-desacetylrifabutin Cmin ↑ 1.22 (0.86-1.74) Metabolite 25-O-desacetylrifabutin Cmax ↑ 1.29 (0.98-1.68) A clinically not relevant increase in the apparent clearance of nevirapine (by 9%) compared to historical data was reported.
Metabolit 25- O- desacetylrifabutin AUC ↑ 1. 24 (0. 84- 1. 84) Metabolit 25- O- desacetylrifabutin Cmin ↑ 1. 22 (0. 86- 1. 74) Metabolit 25- O- desacetylrifabutin Cmax ↑ 1. 29 (0. 98- 1. 68) Ġie rrappurtat li kien hemm żjeda mhix klinikament rilevanti fit - tneħħija apparenti ta ’ nevirapine (b’ 9%) meta mqabbel ma ’ dejta storika
adjustments.
flimkien mingħajr l- ebda aġġustamenti fid- doża.
However, due to the high intersubject variability some patients may experience large increases in rifabutin exposure and may be at higher risk for rifabutin toxicity.
Madankollu, minħabba l - varjabilità għolja bejn suġġett u ieħor, xi pazjenti jistgħu jħossu żidiet kbar fl- espożizzjoni għal rifabutin u jistgħu jkunu f’ riskju ogħla għal tossiċità minn rifabutin.
Therefore, caution should be used in concomitant administration.
Għalhekk għandha tintuża l- kawtela meta dan jingħata ma ’ mediċina oħra.
Rifampicin AUC ↔ 1.11 (0.96-1.28) Rifampicin Cmin ND Rifampicin Cmax ↔ 1.06 (0.91-1.22)
Rifampicin Cmin ND Rifampicin Cmax ↔ 1. 06 (0. 91- 1. 22)
It is not recommended to co- administer rifampicin and VIRAMUNE (see section 4.4).
jingħata flimkien ma ’ VIRAMUNE (ara sezzjoni 4. 4).
Physicians needing to treat patients
Tobba li jeħtieġu jittrattaw pazjenti ko- infettati bit -
Nevirapine AUC ↓ 0.42 Nevirapine Cmin ↓ 0.32 Nevirapine Cmax ↓ 0.50 compared to historical controls.
Nevirapine AUC ↓ 0. 42 Nevirapine Cmin ↓ 0. 32 Nevirapine Cmax ↓ 0. 50 meta mqabbel ma ’ kontrolli storiċi.
co-infected with tuberculosis and using a VIRAMUNE containing regimen may consider co- administration of rifabutin instead.
tuberkolożi u li qed jużaw kors maħsub li fih VIRAMUNE jistgħu jikkunsidraw li jagħtu rifabutin fl - istess ħin minfloku.
Antifungals
VIRAMUNE.
Fluconazole 200 mg QD
Itraconazole AUC ↓ 0. 39
Fluconazole AUC ↔ 0.94 (0.88- 1.01) Fluconazole Cmin ↔ 0.93 (0.86-1.01) Fluconazole Cmax ↔ 0.92 (0.85-0.99) Nevirapine: exposure: ↑ 100% compared with historical data where nevirapine was administered alone.
Itraconazole Cmin ↓ 0. 13
Because of the risk of increased exposure to VIRAMUNE, caution should be exercised if the medicinal products are given concomitantly and patients should be monitored closely.
Aġġustament biex tingħata doża ogħla
Itraconazole AUC ↓ 0.39 Itraconazole Cmin ↓ 0.13 Itraconazole Cmax ↓ 0.62 Nevirapine: there was no significant difference in Nevirapine pharmacokinetic parameters.
Itraconazole Cmax ↓ 0. 62 Nevirapine: ma kienx hemm
A dose increase for itraconazole should be considered when these two agents are administered concomitantly.
ta ’ itraconazole għandu jiġi kkunsidrat meta ż- żewġ sustanzi jingħataw flimkien.
Ketoconazole AUC ↓ 0.28 (0.20- 0.40) Ketoconazole Cmin ND Ketoconazole Cmax ↓ 0.56 (0.42- 0.73)
0. 40) Ketoconazole Cmin ND Ketoconazole Cmax ↓ 0. 56 (0. 42- 0. 73)
It is not recommended to co- administer ketoconazole and VIRAMUNE.
VIRAMUNE jingħataw flimkien.
Nevirapine: plasma levels: ↑ 1.15- 1.28 compared to historical controls.
Livelli ta ’ nevirapine fil- plażma: ↑ 1. 15- 1. 28 meta mqabbla ma ’ kontrolli storiċi.
ANTACIDS Cimetidine
ANTAĊIDI Cimetidine
Cimetidine: no significant effect on cimetidine PK parameters is seen.
Cimetidine: ma deher l- ebda effett sinifikanti fil- parametri PK ta ’ cimetidine.
Cimetidine and VIRAMUNE can be co-administered without dose adjustments.
Cimetidine u VIRAMUNE jistgħu jingħataw flimkien mingħajr aġġustamenti fid- doża..
Nevirapine Cmin ↑ 1.07 ANTITHROMBOTICS Warfarin
Nevirapine Cmin ↑ 1. 07 ANTITROMBOTIĊI Warfarin
The interaction between Nevirapine and the antithrombotic agent warfarin is complex, with the potential for both increases and decreases in coagulation time when used concomitantly.
L- interazzjoni bejn Nevirapine u l - aġent antitrombotiku warfarin hi kumplessa, bil- potenzjal kemm ta ’ żidiet kif ukoll ta ’ tnaqqis fil- ħin tal - koagulazzjoni meta jintużaw flimkien.
Close monitoring of anticoagulation levels is warranted.
Monitoraġġ mill- qrib tal- livelli ta ’ antikoagulazzjoni hu meħtieġ.
12 CONTRACEPTIVES Depo- medroxyprogesterone acetate (DMPA) 150 mg every 3
medroxyprogesterone
Viramune co-administration did not alter the ovulation suppression effects of DMPA.
bidilx l- effetti tat- trażżin tal -
DMPA and VIRAMUNE can be co-administered without dose
acetate (DMPA) 150 mg kull 3 xhur
months
Nevirapine AUC ↑ 1. 20 Nevirapine Cmax ↑ 1. 20
Nevirapine AUC ↑ 1.20 Nevirapine Cmax ↑ 1.20
DMPA u VIRAMUNE jistgħu jittieħdu fkimkien mingħajr aġġustamenti fid- doża.
adjustments.
EE AUC ↓ 0. 80 (0. 67 - 0. 97)
Ethinyl estradiol (EE) 0.035 mg
Ethinyl estradiol (EE)
EE AUC ↓ 0.80 (0.67 - 0.97) EE Cmin ND EE Cmax ↔ 0.94 (0.79 - 1.12)
EE Cmin ND EE Cmax ↔ 0. 94 (0. 79 - 1. 12)
Oral hormonal contraceptives should not be used as the sole method of contraception in women taking VIRAMUNE (see section 4.4).
mill- ħalq m’ għandhomx jintużaw bħala l- metodu ewlieni ta ’ kontraċezzjoni f’ nisa li qed jieħdu
Norethindrone (NET) 1.0 mg QD
13 NET AUC ↓ 0. 81 (0. 70 - 0. 93) Norethindrone (NET)
NET AUC ↓ 0.81 (0.70 - 0.93) NET Cmin ND NET Cmax ↓ 0.84 (0.73 - 0.97)
NET Cmin ND NET Cmax ↓ 0. 84 (0. 73 - 0. 97)
Appropriate doses for hormonal contraceptives (oral or other forms of application) other than DMPA in combination with VIRAMUNE have not been established with respect to safety and efficacy.
xierqa għal kontraċettivi ormonali (li jittieħdu mill- ħalq jew forom oħra ta ’ applikazzjoni) li mhumiex DMPA li jittieħdu flimkien ma ’ VIRAMUNE ma kinux stabbiliti fir- rigward tas - sigurtà u l- effikaċja.
DRUG ABUSE Methadone Individual Patient Dosing
Methadone Cmin ND Methadone Cmax ↓ 0. 58 (0. 50 - 0. 67)
Methadone AUC ↓ 0.40 (0.31 - 0.51) Methadone-maintained patients Methadone Cmin ND beginning VIRAMUNE therapy Methadone Cmax ↓ 0.58 (0.50 - 0.67) should be monitored for evidence of withdrawal and methadone dose should be adjusted accordingly.
jibdew it- terapija b’ VIRAMUNE għandhom jiġu mmonitorjati għal evidenza ta ’ tiżmim, u d- doża tal - methadone għandha tiġi aġġustata kif suppost.
HERBAL PRODUCTS
PRODOTTI MINN ĦXEJJEX
John's Wort
John' s Wort
Serum levels of Nevirapine can be reduced by concomitant use of the herbal preparation St.
Il- livelli ta ’ nevirapine fis- serum jistgħu jitnaqqsu bl- użu fl- istess ħin tal- preparazzjoni ta ’ St.
John's Wort (Hypericum perforatum).
John' s Wort (Hypericum perforatum).
This is due to induction of drug metabolism enzymes and/ or transport proteins by St.
Dan minħabba l- induzzjoni minn enżimi tal- metaboliżmu tal- mediċina u/ jew proteini tat- transport minn St.
John’ s Wort.
John’ s Wort.
Herbal preparations containing St.
Taħlitiet bi ħxejjex li fihom St.
John‘ s Wort and VIRAMUNE must not be co-administered (see section 4.3).
John’ s Wort u VIRAMUNE m’ għandhomx jingħataw flimkien (ara sezzjoni 4. 3).
If a patient is already taking St.
Jekk pazjent diġà jkun qed jieħu St.
John‘ s Wort check nevirapine and if possible viral levels and stop St John‘ s Wort.
John’ s Wort, iċċekkja l- livell ta ’ nevirapine u jekk possibbli l- livelli virali u waqqaf St John’ s Wort.
Nevirapine levels may increase on stopping St John‘ s Wort.
Il - livelli ta ’ nevirapine jistgħu jiżdiedu malli St John’ s Wort jitwaqqaf.
The dose of VIRAMUNE may need adjusting.
Id - doża ta ’ VIRAMUNE jista ’ jkollha tiġi aġġustata.
The inducing effect may persist for at least 2 weeks after cessation of treatment with St.
L- effett induttiv jista ’ jippersisti għal mill- inqas ġimagħtejn wara l- waqfien tal- kura b’ St.
John‘ s Wort.
John’ s Wort.
Other information:
Tagħrif ieħor:
Nevirapine metabolites:
Metaboliti ta ’ nevirapine:
Studies using human liver microsomes indicated that the formation of nevirapine hydroxylated metabolites was not affected by the presence of dapsone, rifabutin, rifampicin, and trimethoprim/ sulfamethoxazole.
Studju fuq mikrożomi tal- fwied tal- bniedem indika li l- produzzjoni ta ’ metaboliti hydroxylated ta ’ nevirapine ma kienux affettwati bil- preżenza ta ’ dapsone, rifabutin, rifampicin, u trimethoprim/ sulfamethoxazole.
Ketoconazole and erythromycin significantly inhibited the formation of nevirapine hydroxylated metabolites.
Ketoconazole u erythromycin impedixxew b’ mod sinifikanti l- produzzjoni ta ’ metaboliti hydroxylated ta ’ nevirapine.
13 4.6 Pregnancy and lactation
4. 6 Tqala u treddigħ
Currently available data on pregnant women indicate no malformative or foeto/ neonatal toxicity.
Bħalissa, it- tagħrif disponibbli għal nisa tqal jindika li m’ hemm l- ebda malformazzjoni jew tossiċità tal- fetu/ tat- tarbija għadha titwieled.
To date no other relevant epidemiological data are available.
Sal- lum, l- ebda tagħrif epidemjoloġiku ieħor mhu disponibbli.
No observable teratogenicity was detected in reproductive studies performed in pregnant rats and rabbits (see section 5.3).
Ma ġewx osservati effetti teratoġeniċi waqt studji li saru fuq firien u fniek tqal (ara sezzjoni 5. 3).
There are no adequate and well-controlled studies in pregnant women.
M’ hemm l- ebda studju ta ’ min joqgħod fuqu u b’ kontrolli tajbin fuq nisa tqal.
Caution should be exercised when prescribing VIRAMUNE to pregnant women (see section 4.4).
VIRAMUNE għandu jiġi preskritt b’ kawtela lin- nisa tqal (ara sezzjoni 4. 4).
As hepatotoxicity is more frequent in women with CD4 cell counts above 250 cells/ mm3, these conditions should be taken in consideration on therapeutic decision (see section 4.4).
Peress li l- epatotossiċità hija aktar frekwenti f’ nisa li għandhom l- għadd taċ- ċelluli CD4 ogħla minn 250 ċellula/ mm3, dawn il- kundizzjonijiet għandhom jiġu kkunsidrati f’ deċiżjoni terapewtika (ara sezzjoni 4. 4)
Women of childbearing potential should not use oral contraceptives as the sole method for birth control, since nevirapine might lower the plasma concentrations of these medications (see sections 4.4 & 4.5).
Nisa li jista ’ jkollhom it- tfal m’ għandhomx jużaw kontraċettivi orali bħala l- uniku mezz ta ’ kontroll tat- tqala peress li nevirapine jista ’ jnaqqas l- konċentrazzjonijiet ta ’ dawn il- mediċini fil- plażma (ara sezzjonijiet 4. 4 u 4. 5).
Nevirapine readily crosses the placenta and is found in breast milk.
Nevirapine faċilment jaqsam is- sekonda u jinsab fil- ħalib tas- sider.
It is recommended that HIV-infected mothers do not breast-feed their infants to avoid risking postnatal transmission of HIV and that mothers should discontinue breast-feeding if they are receiving VIRAMUNE.
14 Huwa rakkomandat li ommijiet infettati b' HIV ma jreddgħux lill- uliedhom biex jevitaw ir- riskju li jgħaddu l- HIV wara t- twelid u li l- ommijiet għandhom jieqfu jreddgħu jekk ikunu qed jieħdu VIRAMUNE.
No studies on the effects on the ability to drive and use machines have been performed.
Ma sarux studji speċifiċi dwar l- effetti fuq il- ħila biex issuq jew tħaddem magni
The most frequently reported adverse reactions related to VIRAMUNE therapy, across all clinical trials, were rash, allergic reactions, hepatitis, abnormal liver function tests, nausea, vomiting, diarrhoea, abdominal pain, fatigue, fever, headache and myalgia.
L- aktar reazzjonijiet avversi rapportati ta ’ spiss waqt il- provi kliniċi kollha li saru bit- terapija ta 'VIRAMUNE, kienu: raxx, reazzjonijiet allerġiċi, epatite, testijiet abnormali tal- funzjonament tal - fwied, tqallih, remettar, dijarea, uġigħ addominali, għeja, deni, uġigħ ta ’ ras, u uġigħ fil- muskoli.
The postmarketing experience has shown that the most serious adverse reactions are Stevens-Johnson syndrome and toxic epidermal necrolysis and serious hepatitis/ hepatic failure and hypersensitivity reactions, characterised by rash with constitutional symptoms such as fever, arthralgia, myalgia and lymphadenopathy, plus visceral involvement, such as hepatitis, eosinophilia, granulocytopenia, and renal dysfunction.
L- esperjenza ta ’ wara li l- prodott tqiegħed fis- suq uriet li l- aktar effetti mhux mixtieqa serji huma: is - sindromu ta ’ Stevens- Johnson, nekroliżi tossika epidermali, epatite serja / insuffiċjenza tal- fwied, reazzjonijiet ta ’ sensittività eċċessiva li huma kkaratterizzati b’ raxx u sintomi avversi fil- ġisem bħad - deni, artalaġja, uġigħ fil- muskoli, u limfodenopatija, kif ukoll problemi vixxerali bħal epatite, eosinofilja, granuloċitopenija u disfunzjoni renali.
The first 18 weeks of treatment is a critical period which requires close monitoring (see section 4.4).
L- ewwel 18- il ġimgħa ta 'trattament huwa perijodu kritiku li jeħtieġ monitoraġġ mill- qrib (ara sezzjoni 4. 4).
The following adverse reactions which may be causally related to the administration of VIRAMUNE have been reported.
Dawn li ġejjin huma reazzjonijiet avversi li setgħu seħħew minħabba t- teħid ta 'VIRAMUNE.
The frequencies estimated are based on pooled clinical trial data for events considered related to VIRAMUNE treatment.
Il - frekwenzi msemmija huma stmati fuq riżultati miġbura kollettivament minn provi kliniċi li għandhom x’ jaqsmu ma 'trattament b’ VIRAMUNE.
Frequency is defined using the following convention: very common (≥ 1/ 10); common (≥ 1/ 100 to < 1/ 10); uncommon (≥ 1/ 1,000 to < 1/ 100); rare (≥ 1/ 10,000 to < 1/ 1,000); very rare (< 1/ 10,000), not known (cannot be estimated from the available data).
Il- frekwenza hija mfissra permezz tal- konvenzjoni li ġejja: 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), mhux magħruf (ma jistax jiġi stmat mit- tagħrif disponibbli).
liver function tests abnormal
testijiet abnormali tal- funzjoni tal- fwied
Blood and lymphatic system disorders Common Uncommon
Disturbi tad- demm u tas- sistema limfatika Komuni Mhux komuni
granulocytopenia* anaemia
granuloċitopenija anemija
* In study 1100.1090, from which the majority of related adverse events (n=28) were received, patients on placebo had a higher incidence of events of granulocytopenia (3.3%) than patients on nevirapine (2.5%).
* Fl- istudju 1100. 1090 li minnu waslu l- maġġoranza ta ’ każijiet avversi relatati (n=28), pazjenti fuq plaċebo kellhom inċidenza ogħla ta ’ każijiet ta ’ granuloċitopenija (3. 3%) milli pazjenti fuq nevirapine (2. 5%).
14 Nervous system disorders Common
Disturbi fis- sistema nervuża Komuni
Gastrointestinal Common
Disturbi gastro- intestinali Komuni
disorders vomiting, diarrhoea, abdominal pain, nausea
rimettar, dijarea, uġigħ addominali, dardir
Skin and subcutaneous tissue disorders Very common Uncommon oedema, urticaria
Disturbi tal- ġilda u tat- tessuti ta ’ taħt il- ġilda Komuni ħafna Mhux komuni
rash (13.6%) Stevens Johnson Syndrome/ toxic epidermal necrolysis (0.1%), angioneurotic
raxx (13. 6%) sindromu ta 'Stevens Johnson / nekrolisi epidermali tossika (0. 1%), edema anġjonewtrotika, urtikarja
Musculoskeletal and connective tissue disorders Common Uncommon
Disturbi muskolo- skeletriċi u tat- tessut konnettiv Komuni Mhux komuni
myalgia arthralgia
uġigħ tal- muskoli artralġja
General disorders and administration site conditions Common
15 Disturbi ġenerali u kundizzjonijiet ta 'mnejn jingħata Komuni
fever, fatigue
deni, għeja
Immune system disorders Common Not known
Disturbi fis- sistema immuni Komuni Mhux magħrufa
hypersensitivity drug rash with eosinophilia and systemic symptoms, anaphylaxis
sensittività eċċessiva raxx tal- mediċina b’ eosinofilja, u sintomi sistematiċi anafilassi
Hepatobiliary disorders Common Uncommon Rare
Disturbi fil- fwied u fil- marrara Komuni Mhux komuni Rari
hepatitis (1.4%) jaundice hepatitis fulminant
epatite (1. 4%) suffejra epatite fulminanti
Combination antiretroviral therapy has been associated with redistribution of body fat (lipodystrophy) in HIV infected patients including the loss of peripheral and facial subcutaneous fat, increased intra- abdominal and visceral fat, breast hypertrophy and dorsocervical fat accumulation (buffalo hump).
Dan jinkludi telf ta ’ xaħam periferiku u minn taħt il- ġilda tal- wiċċ, żjieda fix- xaħam intra- addominali u vixxerali, u akkumulazzjoni ta ’ xaħam dorsoċervikali (ħotba tal- buflu).
Combination antiretroviral therapy has been associated with metabolic abnormalities such as hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperglycaemia and hyperlactataemia (see section 4.4).
Terapija antiretrovirali konġunta ġiet assoċjata ma 'abnormalitajiet metaboliċi bħal: ipertrigliċeridemja, iperkolesterolemja, reżistenza għall- insulina, u iperlactatemja (ara sezzjoni 4. 4).
The following events have also been reported when VIRAMUNE has been used in combination with other anti-retroviral agents: pancreatitis, peripheral neuropathy and thrombocytopaenia.
Il- każijiet li ġejjin ġew rapportati wkoll meta VIRAMUNE intuża: flimkien ma 'sustanzi anti - retrovirali oħra: pankreatite, newropatija periferika u tromboċitopenija.
These events are commonly associated with other antiretroviral agents and may be expected to occur when VIRAMUNE is used in combination with other agents; however it is unlikely that these events are due to VIRAMUNE treatment.
Dawn il- każijiet huma komunament assoċjati ma ’ mediċini anti- retrovirali oħrajn u jista 'jkun li jseħħu meta VIRAMUNE jiġi użat flimkien ma' mediċini oħra; madankollu huwa x' aktarx improbabbli li dawn il- każijiet iseħħu minħabba trattament b' VIRAMUNE.
Hepatic-renal failure syndromes have been reported rarely.
Sindromi ta 'falliment epatiku u renali ġew rapportati rarament b’ terapija ta ’ kombinazzjoni.
In HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise (see section 4.4).
F' pazjenti infettati b' HIV li għandhom defiċjenza immunitarja serja fiż- żmien li tinbeda t- terapija antiretrovirali kombinata (CART), jista 'jkun hemm reazzjoni infjammatorja għal infezzjonijiet asintomatiċi jew opportunistiċi 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).
Każijiet ta 'osteonekrosi ġew irrapportati, partikolarment f' pazjenti li ġeneralment għandhom predispożizzjonijiet magħrufa, mard ta' l- HIV avvanzat jew huma esposti fuq tul taż- żmien għal terapija antiretrovirali kombinata (CART).
Skin and subcutaneous tissues
Il- ġilda u t- tessuti ta ’ taħt il- ġilda
The most common clinical toxicity of VIRAMUNE is rash, with VIRAMUNE attributable rash occurring in 13.6% of patients in combination regimens in controlled studies.
L- aktar tossiċità klinika komuni ta ’ VIRAMUNE hija raxx.
Rashes are usually mild to moderate, maculopapular erythematous cutaneous eruptions, with or
Skond studji b’ kontrolli, ir- raxx jaqbad lil 13. 6% ta 'pazjenti li jużaw VIRAMUNE ma ’ mediċini oħrajn.
15 without pruritus, located on the trunk, face and extremities.
Ir- raxxijiet huma normalment minn ħfief sa moderati, li jikkonsistu minn infafet kutaneji eritematiċi makulopapulari bi jew bla prurite, u li ssibhom fit- tronk, il- wiċċ, jew fl- estremitajiet tal- ġisem.
Allergic reactions (anaphylaxis, angioedema and urticaria) have been reported.
Ġew rapportati reazzjonijiet allerġiċi (anafilassi, anġjoedema u urtikarja).
Rashes occur alone or in the context of hypersensitivity reactions, characterised by rash with constitutional symptoms such as fever, arthralgia, myalgia and lympadenopathy, plus visceral involvement, such as hepatitis, eosinophilia, granulocytopenia, and renal dysfunction.
Ir- raxxijiet jiżviluppaw waħedhom, jew ma ’ reazzjoni ipersensittiva fejn ikun hemm diversi sintomi mal- ġisem kollu bħal deni, artralġja, uġigħ ta 'muskoli, u limfadenopatija, kif ukoll problemi vixxerali, bħal epatite, eosinofilja, granuloċitopenija u problemi fil- kliewi.
Severe and life-threatening skin reactions have occurred in patients treated with VIRAMUNE, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
Kien hemm pazjenti li ġew trattati b’ VIRAMUNE u kellhom reazzjonijiet tal- ġilda qawwija jew li jistgħu jkunu ta 'periklu għal ħajja, inklużi s- sindromu Stevens- Johnson (SJS) u nekroliżi epidermali tossika (TEN).
Fatal cases of SJS, TEN and hypersensitivity reactions have been reported.
Ġew rapportati wkoll każijiet fatali ta ’ SJS, TEN u reazzjonijiet ipersensittivi.
The majority of severe rashes occurred within the first 6 weeks of treatment and some required hospitalisation, with one patient requiring surgical intervention (see section 4.4).
Fil - biċċa l- kbira, ir- raxxijiet qawwija ġraw wara l- ewwel 6 ġimgħat ta 'trattament b' xi wħud mill- pazjenti kellhom bżonn jinżammu l- isptar waqt li pazjent wieħed kellu bżonn kirurġija (ara sezzjoni 4. 4).
Hepato-biliary
16 Il- fwied u s- sistema bilarja tal- marrara
The most frequently observed laboratory test abnormalities are elevations in liver function tests (LFTs), including ALAT, ASAT, GGT, total bilirubin and alkaline phosphatase.
L- aktar abnormalitajiet komuni li jirriżultaw minn testijiet tal- laboratorju huma żjidiet fil- fatturi mkejla permezz ta ’ testijiet tal- funzjoni tal- fwied (LFTs), li jinkludu ALAT, ASAT, GGT, bilirubin totali u alkaline phosphatase.
Asymptomatic elevations of GGT levels are the most frequent.
Iż- żjieda fil - GGT mingħajr sintomi oħrajn, hija l- aktar komuni.
Cases of jaundice have been reported.
Ġew irrapportati każijiet ta ’ suffejra.
Cases of hepatitis (severe and life-threatening hepatoxicity, including fatal fulminant hepatitis) have been reported in patients treated with VIRAMUNE.
Kien hemm każijiet ta ’ pazjenti li użaw VIRAMUNE u qabadhom epatite (qawwija u ta 'periklu għal ħajja minħabba tossiċità għal fwied; kif ukoll epatite fulminanti fatali).
The best predictor of a serious hepatic event was elevated baseline liver function tests.
L- aħjar previżjoni ta ’ problema serja tal- fwied kienet meta jkun hemm il- linja ta 'riferiment bażi elevata fir- riżultati ta' testijiet tal- funzjoni tal- fwied.
Paediatric population
Popolazzjoni ta ’ tfal
Based on clinical trial experience of 361 paediatric patients the majority of which received combination treatment with ZDV or/ and ddI, the most frequently reported adverse events related to VIRAMUNE were similar to those observed in adults.
Minn esperjenza minn prova klinika msejsa fuq 361 pazjent tifel u tifla li l- maġġoranza tagħhom irċevew kura ta ’ kombinazzjoni b’ ZDV u/ jew ddI, l- aktar reazzjonijiet avversi komuni għal VIRAMUNE kienu bħal dawk osservati fl- adulti.
Granulocytopenia was more frequently observed in children.
Granuloċitopenija kienet osservata aktar frekwentament fit- tfal.
In an open-label clinical trial (ACTG 180) granulocytopenia assessed as drug- related occurred in 5/ 37 (13.5%) of patients.
Fi prova klinika open- label (ACTG 180) granuloċitopenija assessjata bħala relatata mal- mediċina seħħet f’ 5/ 37 (13. 5%) pazjent.
In ACTG 245, a double-blind placebo controlled study, the frequency of serious drug-related granulocytopenia was 5/ 305 (1.6%).
F’ ACTG 245, studju double- blind li sar bi plaċebo bħala kontroll, il- frekwenza ta ’ granuloċitopenija relatata mal- mediċina kienet ta ’ 5/ 305 (1. 6%).
Isolated cases of Stevens- Johnson syndrome or Stevens-Johnson/ toxic epidermal necrolysis transition syndrome have been reported in this population.
F’ din il- popolazzjoni ġew irrapportati każijiet iżolati ta 'sindromu ta' Stevens- Johnson jew sindromu ta ’ transazzjoni Stevens- Johnson / nekroliżi epidermali tossika.
There is no known antidote for VIRAMUNE overdosage.
M’ hemm l- ebda antidotu magħruf għal doża eċċessiva ta ’ VIRAMUNE.
Cases of VIRAMUNE overdose at doses ranging from 800 to 6000 mg per day for up to 15 days have been reported.
Kien hemm każijiet irrapportati ta ’ pazjenti li ħadu doża eċċessiva ta ’ VIRAMUNE minn 800 sa 6000 mg kuljum għal 15 - il jum.
Patients have experienced oedema, erythema nodosum, fatigue, fever, headache, insomnia, nausea, pulmonary infiltrates, rash, vertigo, vomiting, increase in transaminases and weight decrease.
Il- pazjenti qabadhom edema, eritema nodosum, għejja, deni, uġigħ ta ’ ras, nuqqas ta ’ rqad, dardir, infiltrament ġol- pulmuni, raxx, mejt, rimettar, żjieda fl- enzimi transaminases, u tnaqqis fil- piż korporali.
All of these effects subsided following discontinuation of VIRAMUNE.
Dawn l - effetti kollha telqu meta VIRAMUNE twaqqaf.
Mechanism of Action Nevirapine is a NNRTI of HIV-1.
Kif taħdem il- mediċina Nevirapine huwa NNRTI ta 'HIV- 1.
Nevirapine binds directly to reverse transcriptase and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic site.
Nevirapine jeħel direttament ma ’ reverse transcriptase u jimblokka l- azzjoni ta ’ enzimi DNA polymerase li jiddependu kemm fuq RNA kif ukoll DNA bi tkissir ta 'l- istruttura taż- żona katalitika ta' l- enzima.
The activity of nevirapine does not compete with template or nucleoside triphosphates.
L- anqas jikkompeti man- nucleoside triphosphatase.
HIV-2 reverse transcriptase and eukaryotic DNA polymerases (such as human DNA polymerases α, β, γ, or δ) are not inhibited by nevirapine.
DNA polymerases α, β, γ, jew δ tal- bniedem).
16 In vitro HIV susceptibility:
Suxxetabilità għal HIV in vitro
The in vitro antiviral activity of nevirapine has been measured in a variety of cell lines including peripheral blood mononuclear cells, monocyte derived macrophages, and lymphoblastoid cell lines.
L- attività antivirali ta ’ nevirapine in vitro ġiet imkejla f’ diversi razez ta ’ ċelloli li jinkludu ċelloli mononukleari ta ’ demm periferiku, monoċiti derivati minn makrofaġi, u razez ta ’ ċelloli limfoblastojdi.
In recent studies using human cord blood lymphocytes and human embryonic kidney 293 cells, EC50 values (50% inhibitory concentration) ranged from 14-302 nM against laboratory and clinical isolates of HIV-1.
Fi studji riċenti, li użaw limfoċiti minn demm tas- sekonda u ċelloli 293 embrijoniċi tal - kliewi umani, il- valuri EC50 (konċentrazzjoni ta ’ impediment ta ’ 50%) kienu fuq medda ta ’ 14- 302 nM meta mqabbla ma ’ kampjuni ta ’ HIV- 1 mil- laboratorju u kliniċi.
Nevirapine exhibited antiviral activity in vitro against group M HIV-1 isolates from clades A, B, C, D, F, G, and H, and circulating recombinant forms (CRF), CRF01_AE, CRF02_AG and CRF12_BF (median EC50 value of 63 nM).
Nevirapine wera attività antivirali in vitro fuq kampjuni HIV minn grupp M minn clades A, B, C, D, F, G, u H u l- għamliet rikombinanti
Nevirapine had no antiviral activity in vitro against isolates from group O HIV-1 and HIV-2.
Nevirapine ma kellux attività antivirali in vitro kontra kampjuni minn grupp O HIV- 1 u HIV- 2.
Nevirapine in combination with efavirenz exhibited a strong antagonistic anti-HIV-1 activity in vitro (see section 4.5) and was additive to antagonistic with the protease inhibitor ritonavir or the fusion inhibitor enfuvirtide. Nevirapine exhibited additive to synergistic anti-HIV-1 activity in combination with the protease inhibitors amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, saquinavir and tipranavir, and the NRTIs abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir and zidovudine.
Nevirapine wera attività addittiva sa sinerġistika kontra l- HIV- 1 flimkien ma ’ l- inibituri ta ’ protease, amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, saquinavir u tipranavir, u l- NRTIs abacavir, didanosine emtricitabine, lamivudine, stavudine, tenofovir u zidovudine.
The anti-HIV-1 activity of nevirapine was antagonized by the anti-HBV drug adefovir and by the anti-HCV drug ribavirin in vitro.
L- attività kontra HIV- 1 ta ’ nevirapine kienet antagonizzata bil- mediċina kontra l- HBV adefovir u bil- mediċina kontra l- HCV ribavirin in vitro.
Resistance HIV isolates with reduced susceptibility (100 to 250-fold) to nevirapine emerge in vitro.
Reżistenza Iżolati ta 'HIV b' suxxetibilità mnaqqsa (100 sa 250 darba) għal nevirapine seħħew in vitro.
Phenotypic and genotypic changes occur in HIV isolates from patients treated with VIRAMUNE or VIRAMUNE + zidovudine over one to 12 weeks.
Bidliet fenotipiċi u ġenotipiċi jseħħu f’ kampjuni ta ’ HIV meħuda minn pazjenti trattati minn ġimgħa sa 12- il ġimgħa b’ VIRAMUNE jew VIRAMUNE u zidovudine.
By week 8 of VIRAMUNE monotherapy, 100% of the patients tested had HIV isolates with a > 100-fold decrease in susceptibility to nevirapine, regardless of dose.
Meta tintlaħaq it- tmin ġimgħa waqt terapija b’ VIRAMUNE biss, instab li fil- pazjenti kollha ttestjati kien hemm kampjuni ta ’ HIV li kellhom > 100 darba anqas suxxettibbiltà għal nevirapine, minkejja d- doża.
VIRAMUNE + zidovudine combination therapy did not alter the emergence rate of nevirapine- resistant virus.
F' terapija kombinata ta 'VIRAMUNE u zidovudine użati flimkien ma kienx hemm bdil fir- rata ta ’ zvilupp ta ’ tipi reżistenti ta ’ vajrus.
Genotypic and phenotypic resistance was examined for patients receiving VIRAMUNE in triple and double therapy drug combination therapy, and in the non-VIRAMUNE comparative group from the INCAS study.
Ir- reżistenza ġenotipika u fenotipika ġiet studjata f’ pazjenti li ħadu VIRAMUNE flimkien ma ’ aktar minn droga waħda (terapiji tripliċi jew kkombinati), filwaqt li l- grupp komparattiv ma ngħatax VIRAMUNE, kien meħud minn studju INCAS.
Antiretroviral naive subjects with CD4 cells counts of 200-600/ mm3 were treated with either VIRAMUNE + zidovudine (n = 46), zidovudine + didanosine (n = 51) or VIRAMUNE + zidovudine + didanosine (n = 51) and followed for 52 weeks or longer on therapy.
It- terapija kienet għal 52 ġimgħa jew itwal.
Virologic evaluations were performed at baseline, six months and 12 months.
Valorizzazzjonijiet viroloġiċi saru fuq referenza bażi ta ’ sitt xhur u 12- il xahar.
The phenotypic resistance test performed required a minimum of 1000 copies/ ml HIV RNA in order to be able to amplify the virus.
It - test għal reżistenza fenotipika mwettaq kien jitlob mill- anqas 1000 kopja / ml HIV RNA biex il- vajrus seta ’ jiġi kkupjat.
Of the three study groups, 16, 19 and 28 patients respectively had evaluable baseline isolates and subsequently remained in the study for at least 24 weeks.
Mit- tliet gruppi li ġew studjati, kien hemm 16, 19 u 28 pazjent minn kull grupp li minnhom ittieħdu kampjuni li kellhom il- linja ta ’ referenza bażi li kienet tista ’ tiġi valorizzata.
At baseline, there were five cases of phenotypic resistance to nevirapine; the IC50 values were 5 to 6.5-fold increased in three and > 100 fold in two.
Fil - linja ta 'riferenza bażi kien hemm ħames każijiet ta ’ reżistenza fenotipika għal nevirapine; il- valuri IC50 kienu minn 5 sa 6. 5 darbiet aktar fi tliet pazjenti u > 100 darba fit- tnejn l- oħra.
At 24 weeks, all available isolates recoverable from patients receiving nevirapine were resistant to this agent, while 18/ 21 (86%) patients carried such isolates at 30-60 weeks.
Wara 24 ġimgħa, kull kampjun virali elevat minn fuq pazjenti li kienu fuq nevirapine, wera reżistenza għal din id- droga, filwaqt li 18 minn 21 (86%) pazjenti ġarrew dan l- vajrus għal 30- 60 ġimgħa.
In 16 subjects viral suppression was below the limits of detection (< 20 copies/ ml = 14, < 400 copies/ ml = 2).
F’ 16- il suġġett, it- trażżin tal- vajrus kien anqas mill - limiti ta 'intraċċar (< 20 kopji/ ml = 14, < 400 kopji/ ml = 2).
Assuming that suppression below < 20 copies/ ml implies nevirapine susceptibility of the virus, 45% (17/ 38) of patients had virus measured or imputed to be susceptible to nevirapine.
Fuq preżunzjoni li t- trażżin < 20 kopji/ ml, jista ’ jiġi implikat li hemm suxxettibbiltà tal- vajrus għal nevirapine, 45% (17/ 38) tal- pazjenti ġew ittestjati li kellhom il- vajrus suxxettibbli għal jew attribwit lil nevirapine.
All 11 subjects receiving VIRAMUNE + zidovudine who were tested for phenotypic resistance were resistant to nevirapine by six months.
Il- 11- il pażjent kollha li ngħataw VIRAMUNE u zidovudine, analizzati għal reżistenza fenotipika, irriżultaw li kienu reżistenti għal nevirapine b’ sitt xhur.
Over the entire period of observation, one case of didanosine resistance was seen.
Matul dan l- perijodu kollu ġie osservat każ wieħed biss ta ’ reżistenza għal didanosine.
Zidovudine resistance emerged as more frequent after 30 – 60 weeks, especially in patients receiving double combination therapy.
Reżistenza għal zidovudine tfaċċat aktar frekwenti wara 30- 60 ġimgħa, b' mod speċjali fuq pazjenti li qed jirċievu terapija kombinata doppja.
Based on the increase in IC50, zidovudine resistance appeared lower in the VIRAMUNE + zidovudine + didanosine group than the other treatment groups.
Imsejjes fuq iż- żjieda f' IC50, ir- reżistenza għal zidovudine dehret aktar baxxa fil- grupp ta ’ VIRAMUNE + zidovudine + didanosine, milli fil- gruppi l - oħra.
With respect to nevirapine resistance, all isolates that were sequenced carried at least one mutation associated with resistance, the most common single changes being K103N and Y181C.
Ir- riżultati ta 'sequencing tal- kampjuni kollha wrew li mill- anqas kien hemm mutazzjoni waħda assoċjata mar- reżistenza ta' nevirapine., L- aktar bidliet komuni f’ aċidu amminiku wieħed kienu K103N u Y181C.
Combinations of mutations were found in nine of the 12 patients observed.
'Dis ’ minn12- il pazjent osservat kellhom aktar minn mutazzjoni waħda.
These data from INCAS illustrate that the use of highly active drug therapies is associated with a delay in the development of antiretroviral drug resistance.
Din l - informazzjoni minn INCAS tiċċara kif terapiji b’ drogi li għandhom attività għolja huma assoċjati ma 'dewmin fl- iżvilupp ta ’ reżistenza kontra sustanzi anti- retrovirali.
The clinical relevance of phenotypic and genotypic changes associated with VIRAMUNE therapy has not been established.
L- implikazzjoni klinika ta 'bidliet fenotipiċi u ġenotipiċi li huma assoċjati ma ’ terapija b’ VIRAMUNE ma ġietx stabbilita.
17 In addition to the data presented above, there exists a risk of rapid emergence of resistance to NNRTIs in case of virological failure.
Mat- tagħrif ta ’ hawn fuq, irrid jiżdied li hemm riskju li titfaċċa f’ daqqa reżistenza għal NNRTIs, f’ każ ta ’ insuffiċjenza viroloġika.
Cross-resistance Rapid emergence of HIV strains which are cross-resistant to NNRTIs has been observed in vitro.
18 Reżistenza inkroċjata Fil- laboratorju ġew osservati tipi ta ’ HIV li tfaċċaw malajr u għandhom reżistenza inkroċjata ma 'NNRTI in vitro.
Data on cross-resistance between the NNRTI nevirapine and NRTIs are very limited.
Dejta fuq reazzjonijiet ta 'reżistenza inkroċjata bejn NNRTI ta' nevirapine u NRTIs oħrajn hija ristretta ħafna.
In four patients, zidovudine-resistant isolates tested in vitro retained susceptibility to nevirapine and in six patients, nevirapine-resistant isolates were susceptible to zidovudine and didanosine.
F’ kampjuni minn sitt pazjenti li kellhom reżistenza virali għal nevirapine baqgħu suxxettibbli għal zidovudine u didanosine.
Cross-resistance between nevirapine and HIV PIs is unlikely because the enzyme targets involved are different.
Reżistenza inkroċjata bejn nevirapine u HIV PIs mhux mistennija, għaliex l- enzimi bersalli involuti, huma differenti.
Cross-resistance among the currently registered NNRTIs is broad.
Hemm reżistenza inkroċjata wiesgħa madwar NNRTIs li huma attwalment reġistrati.
Some genotypic resistance data indicate that in most patients failing NNRTI, viral strains express cross-resistance to the other NNRTIs.
Xi informazzjoni miksuba fuq reżistenza ġenotipika tindika li f' ħafna pazjenti fejn dawn mhux qed jaħdmu, razez virali jesprimu reżistenza inkroċjata f’ NNRTIs oħrajn.
The currently available data do not support sequential use of NNRTIs.
L- informazzjoni attwalment disponibbli ma tappogax l- użu ta 'NNRTIs f’ sekwenza.
Pharmacodynamic Effects VIRAMUNE has been evaluated in both treatment naive and treatment experienced patients.
Effetti Farmakodinamiċi VIRAMUNE ġie valorizzat kemm fuq pazjenti inkonsapevoli mit- trattament kif ukoll fuq pazjenti b’ esperjenza ta 'trattament.
Results from a trial (ACTG 241) evaluated triple therapy with VIRAMUNE, zidovudine and didanosine compared to zidovudine + didanosine, in 398 HIV-1 infected patients (mean baseline 153 CD4+ cells/ mm3; plasma HIV1 RNA 4.59 log10 copies/ ml), who had received at least 6 months of NRTI therapy prior to enrolment (median 115 weeks).
Riżultati minn prova (ACTG 241) vvalorizza terapija bi tliet drogi b’ VIRAMUNE, zidovudine u didanosine, mqabbla ma ’ waħda b’ zidovudine u didanosine, f’ 398 pazjenti infettati b’ HIV- 1 (valur medju ta 'referenza bażi 153 CD4+ ċelluli/ mm3; plażma HIV1 RNA 4. 59 log10 kopji/ ml), u li ngħataw 6 xhur terapija b’ NRTI, qabel bdew il- prova (valur medjan ta’ 115- il ġimgħa).
These heavily experienced patients demonstrated a significant improvement of the triple therapy group over the double therapy group for one year in both viral RNA and CD4+ cell counts.
Il- pazjenti li kellhom esperjenza u kienu fuq it- terapija bit- tliet drogi marru aħjar b’ mod sinifikanti għal sena, fil- livelli ta ’ RNA virali kif ukoll taċ- ċelluli CD4+, meta mqabbla ma ’ dawk li ħadu t- terapija b 'żewġ drogi.
A durable response for at least one year was documented in a trial (INCAS) for the triple therapy arm with VIRAMUNE, zidovudine and didanosine compared to zidovudine + didanosine or VIRAMUNE + zidovudine in 151 HIV-1 infected, treatment naive patients with CD4+ cell counts of 200- 600 cells/ mm3 (mean 376 cells/ mm3) and a mean baseline plasma HIV-1 RNA concentration of 4.41 log10 copies/ ml (25,704 copies/ ml).
Dawn kellhom l- għadd ta ’ ċelluli CD4+ ta ’ 200- 600 ċelluli/ mm3 (medja 376 ċelluli/ mm3) u konċentrazzjoni ta ’ referenza bażi medja ta ’ HIV- 1 RNA fil- plażma ta ’ 4. 41 log10 kopji/ ml (25, 704 kopji/ ml).
Treatment doses were VIRAMUNE, 200 mg daily for two weeks, followed by 200 mg twice daily, or placebo; zidovudine, 200 mg three times daily; didanosine, 125 or 200 mg twice daily (depending on the weight).
Id- dożi waqt it- trattament kienu 200 mg ta ’ VIRAMUNE kuljum għal ġimagħtejn, u wara 200 mg darbtejn kuljum, jew plaċebo; 200 mg zidovudine tliet darbiet kuljum, u 125 jew 200 mg (skond il- piż) didanosine darbtejn kuljum.
Perinatal Transmission
Trasmissjoni fiż- Żmien tat- Twelid
Two studies evaluated the efficacy of VIRAMUNE to prevent vertical transmission of HIV-1 infection.
Żewġ studji evalwaw l- effikaċja ta ’ VIRAMUNE biex jiġi evitat it- tixrid vertikali ta ’ l- infezzjoni b’ HIV- 1.
Mothers received only study antiretroviral therapy during these trials.
Waqt dawn il- provi l- ommijiet ingħataw biss terapija antiretrovirali li kienet parti minn dan l- istudju.
In the HIVNET 012 study in Kampala (Uganda) mother-infant pairs were randomised to receive oral VIRAMUNE (mother:
Fl- istudju HIVNET 012, f’ Kampala (Uganda), il- parijiet ta 'ommijiet u trabi ġew mqassma bl- addoċċ biex jirċievu VIRAMUNE mill- ħalq (omm:
200 mg at the onset of labour; infant:
200 mg kif jibda l- ħlas; tarbija:
2 mg/ kg within 72 hours of birth), or an ultra-short oral zidovudine regimen (mother:
2 mg/ kg fi żmien 72 sigħat tat- twelid), jew inkella kors b' doża żgħira ħafna orali ta ’ zidovudine (omm:
600 mg at the onset of labour and 300 mg every 3 hours until delivery; infant:
600 mg kif jibda l- ħlas u 300 mg kull 3 sigħat sa meta twelled; tarbija:
4 mg/ kg twice daily for 7 days).
4 mg/ kg darbtejn kuljum għal sebat ijiem).
The cumulative HIV-1 infant infection rate at 14-16 weeks was 13.1% (n = 310) in the VIRAMUNE group, versus 25.1% (n = 308 in the ultra-short zidovudine group (p = 0.00063).
Ir- rata akkumulattiva ta ’ l- infezzjoni b' HIV- 1 fit- trabi fi żmien 14– 16- il ġimgħa kienet ta ’ 13. 1% (n = 310) fil- grupp ta ’ VIRAMUNE, u ta ’ 25. 1% (n = 308) fil- grupp li ngħata doża qasira ħafna orali ta ’ zidovudine (p = 0. 00063).
In the SAINT study conducted in South Africa, mother-infant pairs were randomised to receive oral VIRAMUNE (mother:
Fl- istudju SAINT, li sar fl- Afrika t’ Isfel, pari ta 'omm- trabi ġew magħżula bl- addoċċ biex jingħataw VIRAMUNE mill- ħalq (omm:
200 mg during labor and 200 mg 24 to 48 hours postdelivery; infant:
200 mg waqt il- ħlas, 200 mg 24 sa 48 siegħa wara t- twelid; tarbija:
6 mg 24 to 48 hours postdelivery); or a short oral zidovudine plus lamivudine regimen (mother: zidovudine 600 mg, then 300 mg every 3 hours during labour, followed by 300 mg b. i. d. for 7 days postdelivery plus lamivudine 150 mg b. i. d. during labour and for 7 days postdelivery; infant: zidovudine 12 mg b. i. d. plus lamivudine 6 mg b. i. d. for 7 days [if infant weight < 2 kg, zidovudine 4 mg/ kg b. i. d. plus lamivudine 2 mg/ kg b. i. d. for 7 days]).
Ma
There was no significant difference in HIV-1 transmission rates through 6 to 8 weeks between the VIRAMUNE group (5.7%, n = 652) and the zidovudine plus lamivudine group (3.6%, n = 649).
19 kienx hemm differenzi sinifikanti fir- rata ta ’ kemm ixxerdet l- infezzjoni HIV- 1, fi żmien 6 sa 8 ġimgħat, bejn il- grupp ta ’ VIRAMUNE (5. 7%, n = 652) u l- grupp ta ’ zidovudine flimkien ma ’ lamivudine (3. 6%, n = 649).
There was greater risk of HIV-1 transmission to babies whose mothers received their VIRAMUNE or their zidovudine plus lamivudine doses less than 2 hours before delivery.
Kien hemm riskju akbar li HIV- 1 li tittieħed mit- trabi, meta l- ommijiet ingħataw dożi ta ’ VIRAMUNE, jew ta ’ zidovudine flimkien ma ’ lamivudine, anqas minn sagħtejn qabel t- twelid.
In the SAINT study 68% of nevirapine-exposed mothers had resistant strains at
Fl- istudju SAINT, 68% ta ’ l- ommijiet li ġew esposti għal nevirapine, kellhom reżistenza għal razez għal madwar 4 ġimgħat wara t- twelid.
The clinical relevance of these data in European populations has not been established.
Ir- rilevanza klinika ta ’ din l- informazzjoni f’ popolazzjonijiet Ewropej ma ġietx stabbilita.
Furthermore, in the case VIRAMUNE is used as single dose to prevent vertical transmission of HIV-1 infection, the risk of hepatotoxicity in mother and child cannot be excluded.
Barra minn hekk, ma tista 'tiġi eskluża l- ebda tossiċità fil- fwied ta ’ l- omm u t- tarbija meta VIRAMUNE jintuża bħala doża waħda biex jimpedixxi t- tixrid vertikali ta ’ l- infezzjoni bl- HIV- 1.
A blinded randomized clinical trial in women already taking antiretroviral therapy throughout pregnancy (PACTG 316) demonstrated no further reduction of vertical HIV-1 transmission when the mother and the child received a single VIRAMUNE dose during labour and after birth respectively.
Prova klinika fl- għama li saret bl- addoċċ fuq nisa li kienu diġà fuq terapija anti- retrovirali waqt it- tqala kollha (PACTG 316), uriet li ma kienx hemm tnaqqis fit- tixrid vertikali ta 'HIV- 1, meta l- omm u t- tarbija ngħataw doża waħda ta ’ VIRAMUNE waqt il- ħlas u wara t- twelid rispettivament.
HIV-1 transmission rates were similarly low in both treatment groups (1.3% in the VIRAMUNE group, 1.4% in the placebo group).
Ir- rati tat- tixrid ta ’ HIV- 1 kienu baxxi fiż- żewġ gruppi li ġew ittrattati (1. 3% fil- grupp ta ’ VIRAMUNE, 1. 4% fil- grupp tal- plaċebo).
The vertical transmission decreased neither in women with HIV-1 RNA below the limit of quantification nor in women with HIV-1 RNA above the limit of quantification prior to partus.
Ma kienx hemm tnaqqis fit- tixrid vertikali, kemm fin- nisa b’ livell anqas milli jista ’ jitkejjel ta ’ HIV- 1 RNA, kif ukoll f’ nisa li l- livelli ta ’ HIV- 1 RNA kienu aktar milli jista jiġi mkejjel qabel il- partus.
Of the 95 women who received intrapartum VIRAMUNE, 15% developed nevirapine resistance mutations at 6 weeks post partus.
Minn dawk il- 95 mara li ngħataw VIRAMUNE waqt l- intrapartum, 15% żviluppaw mutazzjonijiet reżistenti f’ 6 ġimgħat wara l- partus.
VIRAMUNE tablets and oral suspension have been shown to be comparably bioavailable and interchangeable at doses up to 200 mg.
Intwera li kemm il- pilloli kif ukoll s- suspensjonijiet orali ta ’ VIRAMUNE għandhom bijodisponibilità komparabbli u jistgħu jittieħdu flok xulxin sa dożi ta '200 mg.
Nevirapine is readily absorbed (> 90%) after oral administration in healthy volunteers and in adults with HIV-1 infection.
Nevirapine ġie assorbit mill- ewwel (> 90%) wara li ngħata mill- ħalq f’ voluntieri b’ saħħithom u adulti infettati b' HIV- 1.
Absolute bioavailability in 12 healthy adults following single-dose administration was 93 ± 9% (mean SD) for a 50 mg tablet and 91 ± 8% for an oral solution.
Il- bijodisponibilità assoluta fi 12- il adult b’ saħħithom, wara li ngħataw doża waħda kienet ta ’ 93 ± 9% (SD medja) għal pillola ta ’ 50 mg u ta ’ 91 ± 8% għal soluzzjoni orali.
Peak plasma nevirapine concentrations of 2 ± 0.4 µg/ ml (7.5 µM) were attained by 4 hours following a single 200 mg dose.
L- ogħla konċentrazzjoni fil- plażma ta ’ nevirapine kienet ta ’ 2 ± 0. 4 µg/ ml (7. 5 µM) u ntlaħqu f’ 4 sigħat wara li ngħatat doża waħda ta ’ 200 mg.
Following multiple doses, nevirapine peak concentrations appear to increase linearly in the dose range of 200 to 400 mg/ day.
Wara dożi multipli, l- ogħla konċentrazzjoniet ta ’ nevirapine jidhru li jiżdiedu b’ mod lineari meta doża tkun minn 200 sa 400 mg/ kuljum.
Data reported in the literature from 20 HIV infected patients suggest a steady state Cmax of 5.74 µg/ ml (5.00-7.44) and Cmin of 3.73 µg/ ml (3.20-5.08) with an AUC of 109.0 h*µg/ ml (96.0-143.5) in patients taking 200 mg of nevirapine bid.
Skond dejta pubblikata fuq 20 pazjent infettati b' HIV, l- valur Cmax ta ’ nevirapine waqt ekwilibriju kien ta ’ 5. 74 µg/ ml (5. 00- 7. 44) u ta ’ Cmin kien ta ’ 3. 73 µg/ ml (3. 20- 5. 08), b’ AUC ta ’ 109. 0 h* µg/ ml (96. 0- 143. 5), meta ngħataw ammont ta ’ 200 mg nevirapine.
Other published data support these conclusions.
Informazzjoni oħra pubblikata taqbel ma ’ dawn il- konklużjonijiet.
Long-term efficacy appears to be most likely in patients whose nevirapine trough levels exceed 3.5 µg/ ml.
Effikaċja fit- tul tidher l- aktar f’ pazjenti li l- anqas livelli ta ’ nevirapine huma aktar minn 3. 5 µg/ ml.
Nevirapine is lipophilic and is essentially nonionized at physiologic pH.
Nevirapine huwa lipofiliku u f’ kundizzjonijiet ta ’ pH fiżjoloġiku ma jiġiex ijonizzat.
Following intravenous administration to healthy adults, the volume of distribution (Vdss) of nevirapine was 1.21 ± 0.09 l/ kg, suggesting that nevirapine is widely distributed in humans.
Wara injezzjoni ġol- vina f’ adulti b’ saħħithom, il- volum ta 'distribuzzjoni (Vdss) ta ’ nevirapine kien ta ’ 1. 21 ± 0. 09 l/ kg.
Nevirapine readily crosses the placenta and is found in breast milk.
Dan ifisser li nevirapine huwa mifrux sew fil- bniedem.
Nevirapine is about 60% bound to plasma proteins in the plasma concentration range of 1-10 µg/ ml.
Madwar 60% tan- nevirapine jeħel mal - proteini tal- plażma b’ konċentrazzjoni fil- plażma minn 1 - 10 µg/ ml.
Nevirapine concentrations in human cerebrospinal fluid (n = 6) were 45% (± 5%) of the concentrations in plasma; this ratio is approximately equal to the fraction not bound to plasma protein.
Il- konċentrazzjoni ta ’ nevirapine fil- fluwidu ċerebrospinali tal- bniedem (n = 6) kien 45% (±5%) tal- konċentrazzjonijiet fil- plażma; dan l- ammont huwa kważi l- istess ta ’ l- ammont tal- frazzjoni li mhux mwaħħal ma 'proteini tal- plażma.
In vivo studies in humans and in vitro studies with human liver microsomes have shown that nevirapine is extensively biotransformed via cytochrome P450 (oxidative) metabolism to several hydroxylated metabolites.
Studji fil- bniedem in vitro kif ukoll fil- laboratorju fuq mikrożomi tal- fwied tal- bniedem urew li nevirapine jiġi mibdul f’ diversi metaboliti idrossilatati, permezz tas- sistema P450.
In vitro studies with human liver microsomes suggest that oxidative metabolism of nevirapine is mediated primarily by cytochrome P450 isozymes from the CYP3A family, although other isozymes may have a secondary role.
Għalkemm jista ’ jkun li isoenzimi oħrajn għandhom rwol sekondarju.
In a mass balance/ excretion study in eight healthy male volunteers dosed to steady state with nevirapine 200 mg given twice daily followed by a single 50 mg dose of 14C-nevirapine, approximately 91.4 ± 10.5% of the radiolabelled dose was recovered, with urine (81.3 ± 11.1%) representing the primary route of excretion compared to faeces (10.1 ± 1.5%).
Madwar 91. 4 ± 10. 5% tad- doża radjutikkettata kienet irkuprata.