qanastek/EMEA-V3 huggingface dataset:
Treatment paradigms for several protease inhibitors, which are subject to this interaction, require the co-administration of low-dose ritonavir (‘boosting’) in order to enhance plasma levels and optimise antiviral efficacy.
Paradigma ta ’ kura għal bosta inibituri ta ’ protease, li huma soġġetti għal din l - interazzjoni, jinħtieġu l- għotja flimkien ma ’ doża baxxa ta ’ ritonavir (‘ biex isaħħaħ ’) sabiex iżid il - livelli fil- plażma u jtejjeb l- effikaċja antivirali.
Plasma levels of nelfinavir, which is metabolised predominantly by CYP2C19 and only partially by CYP3A4, are not greatly increased by co-administration with ritonavir, and therefore co-administration of nelfinavir with low-dose ritonavir does not appear to be beneficial.
Livelli fil- plażma ta ’ nelfinavir, li jiġi mmetabolizzat primarjament minn CYP2C19 u parzjalment biss minn CYP3A4, mhumiex miżjuda ħafna bl- għotja flimkien ma ’ ritonavir, u għalhekk l- għotja flimkien ta ’ nelfinavir ma ’ doża baxxa ta ’ ritonavir ma tidhirx li hija ta ’ benefiċċju.
Two studies have compared the safety and efficacy of nelfinavir (unboosted) with ritonavir- boosted protease inhibitors, each in combination with other antiretroviral agents.
14 imsaħħaħ) ma ’ inibituri ta ’ protease msaħħa b’ ritonavir, kull wieħed f’ taħlita ma ’ sustanzi antiretrovirali oħra.
Study M98-863 is a randomised, double blind trial of 653 antiretroviral-naïve patients investigating lopinavir/ritonavir (400/100 mg BID n=326) compared to nelfinavir (750 mg TID n=327), each in combination with lamivudine (150 mg twice daily) and stavudine (40 mg twice daily).
Studju M98- 863 huwa prova randomised, double blind b’ 653 pazjent ġodda għal terapija antiretrovirali li nvestiga lopinavir/ ritonavir (400/ 100 mg BID n=326) mqabbel ma ’ nelfinavir (750 mg TID n=327), kull wieħed f’ taħlita ma ’ lamivudine (150 mg darbtejn kuljum) u stavudine (40 mg darbtejn kuljum).
Median baseline HIV-1 RNA was 4.98 log10 copies/ml and 5.01 log10 copies/ml in the nelfinavir and lopinavir/ritonavir treatment groups respectively.
Medjan tal- RNA ta ’ HIV- 1 RNA fil- linja bażi kien ta ’ 4. 98 log10 kopji/ ml u 5. 01 log10 kopji/ ml fil- gruppi ta ’ kura b’ nelfinavir u lopinavir/ ritonavir rispettivament.
Median baseline CD4+ cell count was 232 cells/mm3 in both groups.
Medjan ta ’ l- għadd ta ’ ċelluli CD4+ fil- linja bażi kien ta ’ 232 ċellula/ mm3 fiż- żewġ gruppi.
At week 48, 63% nelfinavir and 75% lopinavir/ritonavir patients had HIV-1 RNA < 400 copies/ml, whereas 52% nelfinavir and 67% lopinavir/ritonavir patients had HIV-1 RNA < 50 copies/ml (intent-to-treat, missing = failure).
Fit- 48 ġimgħa, 63% tal - pazjenti b’ nelfinavir u 75% tal- pazjenti b’ lopinavir/ ritonavir kellhom RNA ta ’ HIV- 1 < 400 kopja/ ml, filwaqt li 52% tal- pazjenti b’ nelfinavir u 67% tal- pazjenti b’ lopinavir/ ritonavir kellhom RNA ta ’ HIV- 1 < 50 kopja/ ml (ħsieb biex tikkura, assenti = falliment).
The mean increase from baseline in CD4+ cell count at week 48 was 195 cells/mm3 and 207 cells/mm3 in the nelfinavir and lopinavir/ritonavir groups
Iż- żjieda medja mill- linja bażi ta ’ l - għadd taċ- ċelluli CD4+ fit- 48 ġimgħa kienet ta ’ 195 ċellula/ mm3 u 207 ċellula/ mm3 fil- gruppi b’ nelfinavir u b’ lopinavir/ ritonavir rispettivament.
Through 48 weeks of therapy, a statistically significantly higher proportion of patients in the lopinavir/ritonavir arm had HIV-1 RNA < 50 copies/ml compared to the nelfinavir arm.
Matul it- 48 ġimgħa ta ’ terapija, proporzjoni statistikament sinifikanti għola ta ’ pazjenti fil- grupp b’ lopinavir/ ritonavir kellhom RNA ta ’ HIV- 1 ta ’ < 50 kopja/ ml meta mqabbel mal- grupp b’ nelfinavir.
Study APV30002 is a randomised, open-label trial of 649 antiretroviral treatment naïve patients with advanced HIV-disease, investigating fosamprenavir/ritonavir (1400 mg/200 mg QD n=322) compared to nelfinavir (1250 mg BID n=327), each in combination with lamivudine (150 mg twice daily) and abacavir (300 mg twice daily).
Studju APV30002 huwa prova randomised, open- label b’ 649 pazjent ġodda għal terapja antiretrovirali b’ marda ta ’ l- HIV avvanzata, li nvestiga fosamprenavir/ ritonavir (1400 mg/ 200 mg QD n=322) mqabbel ma ’ nelfinavir (1250 mg BID n=327), kull wieħed f’ taħlita ma ’ lamivudine (150 mg darbtejn kuljum) u abacavir (300 mg darbtejn kuljum).
Median baseline HIV-1 RNA was 4.8 log10 copies/ml in both treatment groups.
Medjan tal- RNA ta ’ HIV- 1 fil- linja bażi kien ta ’ 4. 8 log10 kopja/ ml fiż- żewġ gruppi ta ’ kura.
Median baseline CD4+ cell counts were 177 and 166 x106 cells/l for the nelfinavir and fosamprenavir/ritonavir groups respectively.
Medjan ta ’ l- għadd taċ- ċelluli CD4+ fil- linja bażi kien ta ’ 177 u 166 x106 cellula/ l għall- gruppi b’ nelfinavir u b’ fosamprenavir/ ritonavir rispettivament.
At week 48, non-inferiority was shown with 68% of patients in the group treated with nelfinavir and 69% patients treated with fosamprenavir/ritonavir having plasma HIV-1 RNA < 400 copies/ml whereas 53% in the nelfinavir and 55% in the fosamprenavir/ritonavir patients had HIV-1 RNA < 50 copies/ml (intent-to-treat, rebound/discontinuation = failure).
Fit- 48 ġimgħa, nuqqas ta ’ inferjorità intweriet b’ 68% tal- pazjenti fil- grupp ikkurat b’ nelfinavir u 69% tal - pazjenti kkurati b’ fosamprenavir/ ritonavir li kellhom RNA ta ’ HIV- 1 fil- plażma ta ’ < 400 kopja/ ml filwaqt li 53% tal- pazjenti b’ nelfinavir u 55% tal- pazjenti b’ fosamprenavir/ ritonavir kellhom RNA ta ’ HIV- 1 ta ’ < 50 kopja/ ml (ħsieb biex tikkura, rkadar/ twaqqif = falliment).
The median increase from baseline in CD4+ cell count over 48 weeks was 207 cells/mm3 and 203 cells/mm3 in the nelfinavir and fosamprenavir/ritonavir groups respectively.
Iż- żjieda medja mill- linja bażi fl- għadd ta ’ ċelluli CD4+ matul lt- 48 ġimgħa kien ta ’ 207 cellula/ mm3 u 203 ċellula/ mm3 fil - gruppi b’ nelfinavir u b’ fosamprenavir/ ritonavir rispettivament.
The virological failure was greater in the nelfinavir group (17%) than in the fosamprenavir/ritonavir group (7%).
Il- falliment viroloġiku kien akbar fil - grupp b’ nelfinavir (17%) milli fil- grupp b’ fosamprenavir/ ritonavir (7%).
Treatment emergent NRTI resistance was significantly less frequent with fosamprenavir/ritonavir compared to nelfinavir (13% versus 57%; p < 0.001).
Reżistenza għal NRTI li dehret mal- kura kienet sinifikatament inqas b’ fosamprenavir/ ritonavir meta mqabbel ma ’ nelfinavir (13% kontra 57%; p < 0. 001).
The pharmacokinetic properties of nelfinavir have been evaluated in healthy volunteers and HIV-infected patients.
Il- proprjetajiet farmakokinetiċi ta ’ nelfinavir kienu evalwati f’ voluntiera f’ saħħithom u f’ pazjenti infettati bl- HIV.
No substantial differences have been observed between healthy volunteers and HIV-infected patients.
L- ebda differenzi sostanzjali ma kienu osservati bejn voluntiera f’ saħħithom u pazjenti infettati bl- HIV.
Absorption: after single or multiple oral doses of 500 to 750 mg (two to three 250 mg tablets) with food, peak nelfinavir plasma concentrations were typically achieved in 2 to 4 hours.
Wara doża waħda jew dożi multipli ta ’ 500 jew 750 mg (minn tnejn sa tliet pilloli tal - 250 mg) ma ’ l- ikel, livelli massimi tal- konċentrazzjonijiet tal- plażma ta ’ nelfinavir intlaħqu tipikament f’ 2 sa 4 sigħat.
After multiple dosing with 750 mg every 8 hours for 28 days (steady-state), peak plasma concentrations (Cmax) averaged 3-4 µg/ml and plasma concentrations prior to the next dose (trough) were 1-3 µg/ml.
Wara dożi multipli b’ 750 mg kull 8 sigħat għal 28 jum (fi stat stabbli), konċentrazzjonijiet massimi tal- plażma (Cmax) kellhom medja ta ’ 3- 4 µg/ ml u konċentrazzjonijiet fil- plażma qabel id- doża li jkun imiss (il- punt ta ’ l- aktar konċentrazzjoni baxxa) kienu ta ’ 1- 3 µg/ ml.
A greater than dose-proportional increase in nelfinavir plasma concentrations was observed after single doses; however, this was not observed after multiple dosing.
Żjieda akbar miż- żjieda tal - proporzjon tad- doża fil- konċentrazzjonijiet fil- plażma ta ’ nelfinavir kienu osservati wara dożi waħidhom; madankollu, dan ma kienx osservat wara dożaġġ multiplu.
A pharmacokinetic study in HIV-positive patients compared multiple doses of 1250 mg twice daily (BID) with multiple doses of 750 mg three times daily (TID) for 28 days.
Studju farmakokinetiku f’ pazjenti pożittivi għal HIV ipparaguna dożi multipli ta ’ 1250 mg mogħtija darbtejn kuljum (BID) ma ’ dożi multipli ta ’ 750 mg mogħtija tliet kuljum (TID) għal 28 jum.
Patients receiving VIR ACEPT BID (n=10) achieved nelfinavir Cmax of 4.0 ± 0.8 µg/ml and morning and evening trough concentrations of 2.2 ± 1.3 µg/ml and 0.7 ± 0.4 µg/ml, respectively.
Pazjenti li kienu qed jirċievu VIRACEPT BID (n=10) laħqu s- Cmax ta ’ nelfinavir ta ’ 4. 0 ± 0. 8 µg/ ml u konċentrazzjonijiet baxxi ta ’ filgħodu u ta ’ filgħaxija ta ’ 2. 2 ±1. 3 µg/ ml u ta ’ 0. 7 ± 0. 4 µg/ ml, rispettivament.
Patients receiving VIRACEPT TID (n=11) achieved nelfinavir peak plasma concentrations (Cmax) of 3.0 ± 1.6 µg/ml and morning and evening trough concentrations of 1.4 ± 0.6 µg/ml and 1.0 ± 0.5 µg/ml, respectively.
Pazjenti li kienu qed jirċievu VIRACEPT TID (n=11) laħqu s- Cmax ta ’ nelfinavir ta ’ 3. 0 ± 1. 6 µg/ ml u konċentrazzjonijiet baxxi ta ’ filgħodu u ta ’ filgħaxija ta ’ 1. 4 ± 0. 6 µg/ ml u ta ’ 1. 0 ± 0. 5 µg/ ml, rispettivament.
The difference between morning and afternoon or evening trough concentrations for the TID and BID regimens was also observed in healthy volunteers who were dosed at precise 8- or 12-hour intervals.
15 nofsinhar jew ta ’ filgħaxija għall- korsijiet BID u TID kienet osservata wkoll f’ voluntiera f’ saħħithom li ngħataw id- dożaġġ f’ intervalli preċiżi ta ’ 8 jew 12- il siegħa.
The pharmacokinetics of nelfinavir are similar during BID and TID administration.
Il- farmakokinetika ta ’ nelfinavir huma simili waqt l- għoti BID u l- għoti TID.
In patients, the nelfinavir AUC0-24 with 1250 mg BID administration was 52.8 ± 15.7 µg⋅h/ml (n=10) and with 750 mg TID administration was 43.6 ± 17.8 µg⋅h/ml (n=11).
Fil- pazjenti, l- AUC0- 24 tan- nelfinavir bl- għoti BID ta ’ 1250 mg kien ta ’ 52. 8 ± 15. 7 µg⋅h/ ml (n=10) u bl- għoti ta ’ 750 mg TID kien ta ’ 43. 6 ± 17. 8 µg⋅h/ ml (n=11).
Trough drug exposures remain at least twenty fold greater than the mean IC95 throughout the dosing interval for both regimens.
Espożizzjonijiet ta ’ l- aktar konċentrazzjoni baxxa tal- mediċina jibqgħu mill- anqas 20 darba akbar mill- IC95 medju f’ kull parti ta ’ l- intervall tad- dożaġġ għaż- żewġ korsijiet.
The clinical relevance of relating in vitro measures to drug potency and clinical outcome has not been established.
Ir- rilevanza klinika li tagħmel konnessjoni bejn il- miżuri in vitro u l- potenza tal- mediċina u r- riżultat kliniku ma kinetx stabbilita.
A greater than dose-proportional increase in nelfinavir plasma concentrations was observed after single doses; however, this was not observed after multiple dosing.
Żjieda akbar milli proporzjonali għad- doża fil- konċentrazzjonijiet fil- plażma ta ’ nelfinavir kienet osservata wara dożi singoli; iżda din ma kienetx osservata wara dożi multipli.
The absolute bioavailability of VIRACEPT has not been determined.
Il- biodisponibilità assoluta ta ’ VIRACEPT ma ġietx determinata.
Effect of food on gastrointestinal absorption: maximum plasma concentrations and area under the plasma concentration-time curve were consistently 2 to 3-fold higher under fed conditions compared to fasting.
L- effett ta ’ l- ikel fuq l- assorbiment gastro- intestinali: il- massimu tal- konċentrazzjonijiet fil- plażma u l - erja taħt il- kurva tal- konċentrazzjoni- żmien tal- plażma kienu konsistentement minn darbtejn sa tliet darbiet ogħla f’ kondizzjonijiet meta wieħed ikun kiel meta pparagunati ma ’ meta wieħed ikun sajjem.
The increased plasma concentrations with food were independent of fat content of the meals.
Il- konċentrazzjonijiet tal- plażma ogħla ma ’ l- ikel kienu indipendenti mill- kontenut tax- xaħam ta ’ l - ikel.
The effect of meal content on nelfinavir exposure was investigated in a study using the 250 mg film-coated tablets formulation.
L- effett tal- kontenut ta ’ l- ikla fuq l- esponiment ta ’ nelfinavir kien studjat fi studju bl- użu ta ’ formulazzjoni ta ’ pilloli miksija b’ rita ta ’ 250 mg.
Steady state nelfinavir AUC and Cmax were respectively 15% and 20% higher when doses followed a 800 kcal/50% fat meal compared to those following a light meal
L- AUC u Cmax ta ’ nelfinavir fi stat stabbli kienu 15% u 20% rispettivament għola meta d- dożi ngħataw wara ikla ta ’ 800 kcal/ 50% xaħam meta mqabbla ma ’ dawk wara ikla ħafifa (350 kcal/ 33% xaħam), biex b’ hekk jissuġġerixxu li l- kontenut ta ’ ikla għandu inqas effett fuq l- espożizzjonijiet ta ’ nelfinavir waqt dożi multipli milli tista ’ tistenna bbażat fuq tagħrif minn studji b’ doża waħda.
Distribution: in both animals and humans, the estimated volumes of distribution (2-7 l/kg) exceeded total body water, suggesting extensive penetration of nelfinavir into tissues.
Distribuzzjoni: kemm fl- annimali u kemm fil- bniedem, il- volumi stmati ta ’ distribuzzjoni (2- 7 l/ kg) qabżu t- total ta ’ l- ilma tal- ġisem, li jissuġġerixxu penetrazzjoni estensiva ta ’ nelfinavir fit- tessuti.
Although no studies have been conducted in humans, studies with a single 50 mg/kg dose of 14C-nelfinavir in rats showed that concentrations in the brain were lower than in other tissues, but exceeded the in vitro EC95 for antiviral activity.
Għalkemm l- ebda studji ma saru fil- bniedem, studji b’ doża waħda ta ’ 50 mg/ kg ta ’ 14C- nelfinavir fil - firien urew li konċentrazzjonijiet fil- moħħ kienu inqas milli f’ tessuti oħra, iżda qabżu l- EC95 in vitro għall- attività antivirali.
Nelfinavir in serum is extensively protein-bound (≥ 98%).
Nelfinavir fis- serum huwa magħqud ħafna mal- proteina (≥ 98%).
Metabolism: unchanged nelfinavir comprised 82-86% of the total plasma radioactivity after a single oral 750 mg dose of 14C-nelfinavir.
Nelfinavir mhux mibdul inkluda 82- 86% tat- total tar- radjuattività tal- plażma wara doża waħda mill- ħalq ta ’ 14C- nelfinavir.
In vitro, multiple cytochrome P-450 isoforms including CYP3A, CYP2C19/C9 and CYP2D6 are responsible for metabolism of nelfinavir.
In vitro, isoformi multipli taċ- ċitokromju P- 450 inkluż CYP3A, CYP2C19/ C9 u CYP2D6 huma responsabbli għall- metaboliżmu ta ’ nelfinavir.
One major and several minor oxidative metabolites were found in plasma.
Metabolit li jossida prinċipali u diversi metaboliti li jossidaw minuri oħra instabu fil- plażma.
The major oxidative metabolite, M8 (tert-butyl hydroxy nelfinavir), has in vitro antiviral activity equal to the parent drug and its formation is catalysed by the polymorphic cytochrome CYP2C19.
Il- metabolit prinċipali li jossida, M8 (tert- butyl hydroxy nelfinavir), għandu attività antivirali in vitro ekwivalenti għall- mediċina prinċipali u l- formazzjoni tiegħu hija kkatalizzata miċ- ċitokromju polimorfiku CYP2C19.
The further degradation of M8 appears to be catalysed by CYP3A4.
Aktar degradazzjoni ta ’ M8 tidher li hija kkatalizzata minn CYP3A4.
In subjects with normal CYP2C19 activity, plasma levels of this metabolite are approximately 25% of the total plasma nelfinavir-related concentration.
F’ soġġetti b’ attività normali ta ’ CYP2C19, livelli tal- plażma ta ’ dan il- metabolit huma ta ’ madwar 25% tat- total tal- plażma tal- konċentrazzjoni konnessa ma ’ nelfinavir.
It is expected that in CYP2C19 poor metabolisers or in patients receiving concomitantly strong CYP2C19 inhibitors (see section 4.5), nelfinavir plasma levels would be elevated whereas levels of tert-butyl hydroxy nelfinavir would be negligible or non-measurable.
Huwa mistenni li f’ metabolizzaturi fqar ta ’ CYP2C19 jew f’ pazjenti li qed jirċievu fl- istess ħin inibituri qawwija ta ’ CYP2C19 (ara sezzjoni 4. 5), livelli fil- plażma ta ’ nelfinavir jogħlew filwaqt li l - livelli ta ’ tert- butyl hydroxy nelfinavir jkunu negliġibli jew ma jitkejlux.
Limited clinical data suggest that patients with very low or non-measurable plasma concentrations of the metabolite and elevated concentrations of nelfinavir do not show a reduced virological response or a different safety profile when compared with the whole study population.
Tagħrif kliniku limitat jissuġġerixxi li pazjenti b’ konċentrazzjonijiet fil- plażma tal- metabolit baxxi ħafna jew li ma jitkejlux u b’ konċentrazzjonijiet elevati ta ’ nelfinavir ma jurux respons viroloġiku mnaqqas jew profil ta ’ siġurtà differenti meta mqabbel mal- popolazzjoni kollha ta ’ l- istudju.
Elimination: oral clearance estimates after single doses (24-33 l/h) and multiple doses (26-61 l/h) indicate that nelfinavir exhibits medium to high hepatic bioavailability.
Stimi ta ’ l- eliminazzjoni mill- ħalq wara dożi waħidhom (24- 33 l/ h) u dożi multipli (26 - 61 l/ h) jindikaw li nelfinavir juri bijo- disponibilità tal- fwied medja sa għolja.
The terminal half-life in plasma was typically 3.5 to 5 hours.
Iż- żmien biex l- ammont terminali fil- plażma jonqos bin- nofs kienet tipikament minn 3. 5 sa 5 siegħat.
The majority (87%) of an oral 750 mg dose containing 14 C-nelfinavir was recovered in the faeces; total faecal radioactivity consisted of nelfinavir (22%) and numerous oxidative metabolites (78%).
Il- maġġoranza (87%) ta ’ doża ta ’ 750 mg mill- ħalq li kien fiha l- 14C- nelfinavir kienet irkuprata fl- ippurgar; ir- radjuattività totali tal- ippurgar kienet tikkonsisti f’ nelfinavir (22%) u f’ metaboliti numerużi li jossidaw (78%).
Only 1-2% of the dose was recovered in urine, of which unchanged nelfinavir was the major component.
1- 2% biss tad- doża kienet irkuprata fl- awrina, li minnha nelfinavir mhux mibdul kien il- komponent ewlieni.
Pharmacokinetics in special clinical situations:
Farmakokinetiċi f’ sitwazzjonijiet kliniċi speċjali:
Pharmacokinetics in children and the elderly: in children between the ages of 2 and 13 years, the clearance of orally administered nelfinavir is approximately 2 to 3 times higher than in adults, with large intersubject variability.
Farmakokinetiċi fit- tfal u fl- anzjani: fi tfal ta ’ bejn is- sentejn u t- 13- il sena, l- eliminazzjoni ta ’ nelfinavir mogħti mill- ħalq hija ta ’ madwar darbtejn u 3 darbiet ogħla milli fl- adulti, b’ varjabilità
Administration of VIRACEPT oral powder or tablets with food at a dose of approximately 25-30 mg/kg TID achieves steady-state plasma concentrations similar to adult patients receiving 750 mg TID.
L- għoti tat- trab ta ’ VIRACEPT li jittieħed mill- ħalq jew ta ’ pilloli ma ’ l- ikel f’ doża ta ’ madwar 25- 30 mg/ kg TID laħqet konċentrazzjonijiet tal- plażma f’ kondizzjoni ta ’ stat stabbli simili għall- pazjenti adulti li kienu qed jirċievu 750 mg TID.
In an open prospective study, the pharmacokinetics of BID and TID VIRACEPT regimens in 18 HIV infected children aged 2-14 years were investigated.
Fi studju prospettiv miftuħ il- farmakokinetiċi tal- korsijiet ta ’ VIRACEPT BID u TID fi 18- il tifel u tifla infettati bl- HIV li kellhom bejn is- sentejn u l- 14- il sena kienu investigati.
Children weighing less than 25 kg received 30-37 mg/kg nelfinavir TID or 45-55 mg/kg nelfinavir BID.
Tfal li kienu jiżnu inqas minn 25 kg irċivew 30- 37 mg/ kg ta ’ nelfinavir TID jew 45- 55 mg/ kg ta ’ nelfinavir BID.
Children over 25 kg received 750 mg TID or 1250 mg BID.
Tfal li kienu jiżnu iktar minn 25 kg irċivew 750 mg TID jew 1250 mg BID.
The Cmin, Cmax and AUC0-24 were all significantly higher with the BID regimen compared with the TID regimen.
Is- Cmin, is- Cmax u l- AUC0- 24 kienu kollha ogħla b’ mod sinifikattiv fil- kors BID meta pparagunati mal- kors TID.
In addition, in twice daily application, 14 out of 18 (78%) and 11 out of 18 (61%) reached Cmin values of 1-3 µg/ml and Cmax values of 3-4 µg/ml, whereas in TID application only 4 out of 18 (22%) and 7 out of 18 (39%) reached these values.
Ma ’ dan, meta mogħti darbtejn kuljum, 14 minn 18 (78%) u 11 minn 18 (61%) laħqu valuri tas- Cmin ta ’ 1- 3 µg/ ml u valuri tas- Cmax ta ’ 3- 4 µg/ ml, filwaqt li fl- għoti TID, 4 biss minn 18 (22%) u 7 minn 18 (39%) laħqu dawn il- valuri.
There are no data available in the elderly.
M’ hemmx informazzjoni disponibbli fuq l- anzjani.
Pharmacokinetics in patients with liver impairment:
Farmakokinetiċi f' pazjenti b’ mard tal- fwied:
Pharmacokinetics of nelfinavir after a single dose of 750 mg was studied in patients with liver impairment and healthy volunteers.
Il- farmakokinetiċi ta’ nelfinavir wara doża waħda ta ’ 750 mg kienu studjati f’ pazjenti b’ mard tal- fwied u f’ voluntiera f’ saħħithom.
A 49 %-69% increase was observed in AUC of nelfinavir in the hepatically impaired groups with impairment (Child-Turcotte Classes A to C) compared to the healthy group.
Żjieda ta ’ 49% - 69% kienet osservata fl- AUC ta ’ nelfinavir fi gruppi b’ mard tal- fwied (Child- Turcotte Klassijiet A sa C) meta pparagunati mal- grupp b’ saħħtu.
Specific dose recommendations for nelfinavir cannot be made based on the results of this study.
Rakkommandazzjonijiet speċifiċi dwar id- doża għal nelfinavir ma jistgħux ikunu bbażati fuq ir - riżultati ta ’ dan l- istudju.
16 5.3 Preclinical safety data
5. 3 Tagħrif ta ’ qabel l- użu kliniku dwar is- sigurtà tal- mediċina
During in vitro studies, cloned human cardiac potassium channels (hERG) were inhibited by high concentrations of nelfinavir and its active metabolite M8. hERG potassium channels were inhibited by 20% at nelfinavir and M8 concentrations that are about four- to five-fold and seventy-fold, respectively, above the average free therapeutic levels in humans.
Waqt studji in vitro, kanali tal- potassju kardijaċi umani kklonati (hERG) kienu inibiti b’ 20% f’ konċentrazzjonijiet għolja ta ’ nelfinavir u ta ’ l- M8 li huwa l- metabolit attiv li huma madwar erba ’ sa ħames darbiet u sebgħin darba, rispettivament, ’ il fuq mill- medja tal- livelli liberi terapewtiċi fil - bniedem.
By contrast, no effects suggesting prolongation of the QT-interval of the ECG were observed at similar doses in dogs or in isolated cardiac tissue.
B’ kuntrast ma ’ dan, l- ebda effetti li jissuġġerixxu t- titwil ta ’ l- intervall tal- QT ta ’ l- ECG ma kienu osservati f’ dożi simili fil- klieb jew f’ tessut iżolat kardijaku.
The clinical relevance of these in vitro data is unknown.
Ir- rilevanza klinika ta ’ din l - informazzjoni in vitro mhijiex magħrufa.
However, based on data from products known to prolong the QT-interval, a block of hERG potassium channels of > 20% may be clinically relevant.
Madankollu, ibbażat fuq informazzjoni minn prodotti li huma magħrufa li jtawwlu l- intervall tal- QT, imblokk ta ’ l- hERG ta ’ > 20% jista ’ jkun klinikament rilevanti.
Therefore the potential for QT prolongation should be considered in cases of overdose (see section 4.9).
Għalhekk, il- potenzjal tat- titwil tal- QT għandu jkun ikkunsidrat f’ każi ta ’ doża eċċessiva (ara sezzjoni 4. 9).
Acute and chronic toxicity: oral acute and chronic toxicity studies were conducted in the mouse (500 mg/kg/day), rat (up to 1,000 mg/kg/day) and monkey (up to 800 mg/kg/day).
Studji dwar it- tossiċità akuta u kronika fil- ħalq saru fil- ġrieden (500 mg/ kg/ kuljum), fil- firien (sa 1, 000 mg/ kg/ kuljum) u fix- xadini (sa 800 mg/ kg/ kuljum).
There were increased liver weights and dose-related thyroid follicular cell hypertrophy in rats.
Kien hemm żjieda fil- piżijiet tal- fwied u ipertrofija taċ- ċelluli tat- tirojde follikulari konnessa mad- doża fil - firien.
Weight loss and general physical decline was observed in monkeys together with general evidence of gastrointestinal toxicity.
Tnaqqis fil- piż u kondizzjoni ġenerali fiżika li tmur għall- agħar kienu osservati fix- xadini flimkien ma ’ evidenza ta ’ tossiċità gastro- intestinali.
Mutagenicity: in vitro and in vivo studies with and without metabolic activation have shown that nelfinavir has no mutagenic or genotoxic activity.
Studji in vitro u in vivo bi u mingħajr l- attivazzjoni metabolika wrew li nelfinavir m’ għandu l- ebda attività mutaġenika jew ġenotossika.
Carcinogenicity:
Karċinoġeneċità:
Two year oral carcinogenicity studies with nelfinavir mesilate were conducted in mice and rats.
Saru studji dwar il- karċenoġeniċità mill- ħalq li damu sentejn fil- firien u ġrieden.
In mice, administration of up to 1000 mg/kg/day did not result in any evidence for an oncogenic effect.
Fil - ġrieden l- għotja mill- ħalq sa 1000 mg/ kg/ kuljum ma wasslet għal l- ebda evidenza ta ’ effett onkoġeniku.
In rats administration of 1000 mg/kg/day resulted in increased incidences of thyroid follicular cell adenoma and carcinoma, relative to those for controls.
Fil- firien l- għotja ta ’ 1000 mg/ kg/ kuljum irriżulta fi żjieda f’ inċidenzi ta ’ adenoma taċ - ċelluli tat- tirojde follikulari u karċinoma, meta mqabbla ma dawk tal- kontrolli.
Systemic exposures were 3 to 4 times those for humans given therapeutic doses.
Espożizzjonijiet sistematiċi kienu minn 3 sa 4 darbiet iktar minn dawk ta ’ nies li ngħataw dożi terapewtiċi.
Administration of 300 mg/kg/day resulted in an increased incidence of thyroid follicular cell adenoma.
L- għoti ta ’ 1000 mg/ kg/ kuljum irriżulta f’ żjieda fl- inċidenza ta ’ adenoma taċ- ċelluli follikulari fit- tirojde.
Chronic nelfinavir treatment of rats has been demonstrated to produce effects consistent with enzyme induction, which predisposed rats, but not humans, to thyroid neoplasms.
It - trattament kroniku b’ nelfinavir tal- firien kien muri li jipproduċi effetti konsistenti ma ’ l- induzzjoni ta ’ enzimi, li ppredispona l- firien, imma mhux il- bnedmin, għan- neoplażmi tat- tirojde.
The weight of evidence indicates that nelfinavir is unlikely to be a carcinogen in humans.
Il- piż ta ’ l - evidenza jindika li n- nelfinavir aktarx li ma jkunx karċinoġeniku fil- bniedem.
The oral powder contains:
17 It- trab orali fih:
- dibasic potassium phosphate
- dibasic potassium phosphate
- hydroxypropyl methylcellulose
- hydroxypropyl methylcellulose
- sucrose palmitate
- sucrose palmitate
- natural and artificial flavour
- benna naturali u artifiċjali.
This medicinal product must not be mixed with acidic substances due to taste (see section 4.2).
Dan il- prodott mediċinali m’ għandux jitħallat ma ’ sustanzi aċidużi minħabba t- togħma (ara sezzjoni 4. 2).
17 6.5 Nature and contents of container
6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fiħ
VIRACEPT 50 mg/g oral powder is provided in HDPE plastic bottles fitted with polypropylene child resistant closures with a polyethylene liner.
VIRACEPT 50 mg/ g trab orali huwa pprovdut fi fliexken tal- plastik HDPE li għandhom tapp tal - polypropylene reżistenti għat- tfal li fih inforra tal- polyethylene.
Each bottle contains 144 grams of oral powder and is supplied with a 1 gram (white) and a 5 gram (blue) polypropylene scoop.
Kull flixkun fih 144 gramma ta ’ trab orali u huwa pprovdut ma ’ kuċċarina tal- polypropylene ta ’ gramma (bajda) u ta ’ 5 grammi (kaħla).
There are two scoops provided in the box, a white 1 gram scoop and a blue 5 gram scoop.
Hemm żewġ kuċċarini pprovduti fil- kaxxa, kuċċarina bajda ta ’ ġramma waħda u kuċċarina blu ta ’ 5 grammi.
Measure out a level scoop of powder by using the handle of the second scoop to scrape off the extra powder.
Kejjel kuċċarina minsuħa ta ’ trab billi tuża l- manku tat- tieni kuċċarina biex tneħħi t- trab żejjed.
2. mix powder with water, milk, formula, soy milk, dietary supplements or pudding 3. do not mix powder with acidic food or juice 4. powder mixed in the media as described under 2 is recommended to be used within 6 hours
2. ħallat it- trab ma ’ ilma, ħalib, trab tal- ħalib, ħalib tas- sojja, supplimenti tad- dieta jew pudina 3. tħallatx it- trab ma ’ ikel jew meraq aċiduż 4. huwa rakkomandat li trab imħallat kif deskritt taħt 2 għandu jintuża fi żmien 6 sigħat
Date of first authorisation:
18 Data ta ’ l- ewwel awtorizzazzjoni:
22 January 1998 Date of latest renewal:
22 ta ’ Jannar 1998 Data ta ’ l- aħħar tiġdid:
23 January 2008
23 ta ’ Jannar 2008
VIRACEPT 250 mg film-coated tablets.
VIRACEPT 250 mg pilloli miksija b’ rita.
Each film-coated tablet contains nelfinavir mesilate corresponding to 250 mg of nelfinavir.
Kull pillola miksija b’ rita fiha nelfinavir mesilate li jikkorrispondi għal 250 mg ta ’ nelfinavir.
Blue, oblong biconvex film-coated tablets.
Pilloli blu, oblung, ibbuzzati fuq iż- żewġ naħat, miksija b’ rita.
VIRACEPT is indicated in antiretroviral combination treatment of human immunodeficiency virus (HIV-1) infected adults, adolescents and children of 3 years of age and older.
Il- VIRACEPT huwa indikat fit- terapija mħallta antiretrovirali għat- trattament ta ’ adulti, adoloxxenti u tfal li għandhom aktar minn 3 snin, infettati bil- vajrus ta ’ l- immunodefiċjenza uman (HIV- 1).
In protease inhibitor (PI) experienced patients the choice of nelfinavir should be based on individual viral resistance testing and treatment history.
F’ pazjenti b’ esperjenza ta ’ l- inibitur tal- protease (PI), l- għażla tan- nelfinavir għandha tkun ibbażata fuq testijiet tar- reżistenza virali u fuq l- istorja tat- trattament tal- pazjent.
See section 5.1.
Ara s- Sezzjoni 5. 1.
VIRACEPT is administered orally and should always be ingested with food (see section 5.2).
VIRACEPT huwa mogħti mill- ħalq u għandu dejjem jittieħed ma ’ l- ikel (ara sezzjoni 5. 2).
Patients older than 13 years: the recommended dosage of VIRACEPT film-coated tablets is 1250 mg (five 250 mg tablets) twice a day (BID) or 750 mg (three 250 mg tablets) three times a day (TID) by mouth.
Id- doża rakkomandata tal- pilloli miksija b’ rita ta ’ VIRACEPT hija ta ’ 1250 mg (ħames pilloli ta ’ 250 mg) mogħtija darbtejn kuljum (BID) jew 750 mg (tliet pilloli ta ’ 250 mg) mogħtija tliet darbiet kuljum (TID) mill- ħalq.
The efficacy of the BID (twice daily) regimen has been evaluated versus the TID (three times daily) regimen primarily in patients naïve to PIs (see section 5.1).
L- effikaċja tal- kors BID (darbtejn kuljum) kienet evalwata kontra l- kors TID (tliet darbiet kuljum), primarjament f’ pazjenti li ma ħadux PIs (ara Sezzjoni 5. 1).
Patients aged 3 to 13 years: for children, the recommended starting dose is 50-55 mg/kg BID or, if using a TID regimen, 25 – 30 mg/kg body weight per dose.
Pazjenti b’ età minn 3 snin sa 13- il sena: għat- tfal, id- doża rakkomandata tal- bidu hija ta ’ 50- 55 mg/ kg BID jew jekk qed tuża l- kors TID, 25 – 30 mg/ kg ta ’ piż tal- ġisem kull doża.
For children unable to take tablets, VIRACEPT oral powder may be administered (see Summary of Product Characteristics for VIRACEPT oral powder).
Għat- tfal li ma jistgħux jieħdu l- pilloli, it- trab ta ’ VIRACEPT tal- ħalq jista ’ jingħata (ara s- Sommarju tal- Karatteristiċi tal - Prodott għal VIRACEPT trab orali).
The recommended dose of VIRACEPT film-coated tablets to be administered BID to children aged 3 to 13 years is as follows:
Id- doża rakkomandata tal- pilloli miksija b’ rita ta ’ VIRACEPT biex jingħataw BID lil tfal b’ età minn 3 snin sa 13- il sena huwa kif ġej:
Body
Piż tal- Ġisem
Number of VIRACEPT 250 mg film-coated tablets per dose*
Numru ta ’ pilloli miksija b’ rita ta ’ VIRACEPT 250 mg
18
(kg) 18 sa < 22 ≥ 22
4 5
kull doża * 4 5
19 The recommended dose of VIRACEPT film-coated tablets to be administered TID to children aged 3 to 13 years is as follows:
20 Id- doża rakkomandata tal- pilloli miksija b’ rita ta’ VIRACEPT biex jingħataw TID lil tfal b’ età minn 3 snin sa 13- il sena huwa kif ġej:
Number of VIRACEPT 250 mg film-coated tablets per dose*
Numru ta ’ pilloli miksija b’ rita ta’ VIRACEPT 250 mg
18
(kg) 18 to < 23 ≥ 23
2 3
kull doża * 2 3
*see Summary of Product Characteristics for VIRACEPT oral powder for patients with less than 18 kg body weight.
* ara s- Sommarju tal- Karatteristiċi tal- Prodott għal VIRACEPT trab orali għall- pazjenti li għandhom piż tal- ġisem ta ’ inqas minn 18 kg.
There are not sufficient data from patients with liver impairment and therefore specific dose recommendations cannot be made (see section 5.2).
M’ hemmx informazzjoni biżżejjed fuq pazjenti b’ mard tal- kliewi u għalhekk rakkommandazzjonijiet speċifiċi dwar id- dożaġġ ma jistgħux jingħataw (ara sezzjoni 5. 2).
Co-administration with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 [e.g., terfenadine, astemizole, cisapride, amiodarone, quinidine, pimozide, triazolam, orally administered midazolam (for caution on parenterally administered midazolam, see section 4.5), ergot derivatives; see section 4.5].
L- għotja flimkien ma ’ prodotti mediċinali oħra li għandhom indiċi terapewtiku żgħir u li huma sottostrati ta ’ CYP3A4 [eż. terfenadine, astemizole, cisapride, amiodarone, quinidine, pimozide, triazolam, midazolam li jingħata mill- ħalq (għal attenzjoni dwar midazolam mogħti b’ mod parenterali, ara sezzjoni 4. 5), derivattivi ta ’ ergot; ara sezzjoni 4. 5].
John’s wort (Hypericum perforatum) must not be used while taking nelfinavir due to the risk of decreased plasma concentrations and reduced clinical effects of nelfinavir (see section 4.5).
John’ s wort [Hypericum perforatum] m’ għandhomx jintużaw meta nelfinavir ikun qed jittieħed minħabba r- riskju ta ’ konċentrazzjonijiet tal- plażma mnaqqsa u effetti kliniċi mnaqqsa ta’ nelfinavir (ara sezzjoni 4. 5).
Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterium infections, and Pneumocystis carinii pneumonia.
Eżempji rilevanti huma retinite kkawżata minn cytomegalovirus, infezzjonijiet ġeneralizzati u/ jew lokalizzati b’ mycobacterium, u pnewmonja kkawżata minn Pneumocystis carinii.
Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse events.
F’ każ tat- terapija antivirali
In case of concomitant antiviral therapy for hepatitis B or C, please refer also to the relevant product information for these medicinal products.
21 mogħtija flimkien għall- epatite B jew C, jekk jogħġbok irreferi wkoll għall- informazzjoni rilevanti tal - prodott għal dawn il- prodotti mediċinali.
Patients with pre-existing liver dysfunction including chronic active hepatitis have an increased frequency of liver function abnormalities during combination antiretroviral therapy and should be
Pazjenti b’ marda tal- fwied li kienet teżisti minn qabel li tinkludi epatite attiva kronika għandhom frekwenza miżjuda ta ’ anormalitajiet fil- funzjoni tal- fwied waqt it- terapija mħallta antiretrovirali u għandhom ikunu osservati skond il- prattika normali.
In the absence of such studies, caution should be exercised, as increases in nelfinavir levels and/or increases in liver enzymes may occur.
Fin- nuqqas ta ’ dawn l- istudji, għandha tittieħed attenzjoni, peress li jista ’ jkun hemm żjieda fil- livelli ta ’ nelfinavir u/ jew żjieda fl- enżimi tal- fwied.
Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV-disease and/or long-term exposure to combination antiretroviral therapy (CART).
Għalkemm l- etjoloġija hija kkunsidrata li ġejja minn ħafna fatturi (inkluż l- użu ta ’ kortikosterojdi, konsum ta ’ alkoħol, immunosoppressjoni severa, indiċi tal- massa tal- ġisem għola), każijiet ta ’ osteonekrożi ġew irrappurtati partikolarment f’ pazjenti b’ marda ta ’ l- HIV avvanzata u/ jew esponiment fit- tul għal terapija antiretrovirali kombinata (CART).
Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.
Il- pazjenti għandhom jiġu avżati biex iffitxu parir mediku jekk ikollhom esperjenza ta ’ weġgħat u uġigħ fil- ġogi, għebusija fil- ġogi jew dffikultà fil- moviment.
Caution is advised whenever VIRACEPT is co- administered with medicinal products which are inducers or inhibitors and/or substrates of CYP3A4; such combinations may require dose adjustment (see also sections 4.3, 4.5 and 4.8).
Taħlita ma ’ prodotti mediċinali oħra: attenzjoni hija meħtieġa kull meta VIRACEPT jingħata flimkien ma ’ prodotti mediċinali li huma sustanzi li jinduċu u/ jew jinibixxu sottostrati ta ’ CYP3A4; meta dawn jingħataw flimkien jeħtieġ ssir aġġustament tad- doża (ara wkoll sezzjonijiet 4. 3, 4. 5 u 4. 8).
The HMG (hydroxyl-3-methyl-glutaryl)-CoA reductase inhibitors simvastatin and lovastatin are highly dependent on CYP3A4 for metabolism, thus concomitant use of VIRACEPT with simvastatin or lovastatin is not recommended due to an increased risk of myopathy including rhabdomyolysis.
L- inibituri ta ’ HMG (hydroxy- 3- methyl- glutaryl) - CoA reductase, simvastatin u lovastatin, huma dipendenti ħafna fuq is- CYP3A4 għall- metaboliżmu, għaldaqstant l- użu flimkien ta ’ VIRACEPT ma ’ simvastatin jew ma ’ lovastatin mhuwiex rakkomandat minħabba r- riskju miżjud ta ’ mijopatija li jinkludi r- rabdomijolosi.
If treatment with a HMG-CoA reductase inhibitor is indicated, pravastatin or fluvastatin is recommended (see section 4.5).
Jekk it- trattament b’ inibituri ta ’ HMG- CoA reductase huwa indikat, pravastatin jew fluvastatin huma rakkomandati (ara sezzjoni 4. 5).
Co-administration of a PI with sildenafil is expected to substantially increase sildenafil concentration and may result in an increase in sildenafil associated adverse events, including hypotension, visual changes, and priapism.
L- għoti flimkien ta ’ PI ma ’ sildenafil huwa mistenni li jżid sostanzjalment il - konċentrazzjonijiet ta’ sildenafil u jista ’ jirriżulta fi żjieda ta ’ effetti mhux mixtieqa assoċjati ma ’ sildenafil, li jinkludu pressjoni baxxa ħafna, tibdil fil- viżta u priapiżmu.
Potent inducers of CYP3A (e.g., phenobarbital and carbamazepine) may reduce nelfinavir plasma concentrations.
Sustanzi li jinduċu potenti ta ’ CYP3A4 (eż. phenobarbital u carbamazepine) jistgħu wkoll inaqqsu l - konċentrazzjonijiet tal- plażma ta ’ nelfinavir.
Co-administration of the combination oral contraceptive containing norethindrone and 17 α-ethinylestradiol with VIRACEPT resulted in a decrease in AUC of the contraceptive drug; therefore alternative contraceptive measure should also be considered (see section 4.5).
L- għoti flimkien ta ’ kontraċettivi orali li fihom norethindrone u 17 α- ethinyl estradiol flimkien ma ’ VIRACEPT irriżulta fi tnaqqis ta ’ l- AUC tal- mediċina kontraċettiva; għalhekk, miżuri kontraċettivi alternattivi għandhom ikunu kkunsidrati (ara sezzjoni 4. 5).
Diabetes mellitus and hyperglycaemia:
22 Dijabete mellitus u ipergliċemija:
New onset diabetes mellitus, hyperglycaemia or exacerbation of existing diabetes mellitus has been reported in patients receiving PIs.
Dijabete mellitus fil- bidu, ipergliċemija jew taħrix ta ’ dijabete mellitus eżistenti kien irrappurtat f’ pazjenti li qed jirċievu l- PIs.
21 Patients with haemophilia:
Pazjenti bl- emofilja:
Combination antiretroviral therapy has been associated with the redistribution of body fat (lipodystrophy) in HIV patients.
It- terapija mħallta antiretrovirali kienet assoċjata mat- tqassim mill- ġdid ta ’ xaħam tal - ġisem (lipodistrofija) f’ pazjenti infettati b’ HIV.
A connection between visceral lipomatosis and PIs and lipoatrophy and nucleoside analogue reverse transcriptase inhibitors (NRTIs) has been hypothesised.
Konnessjoni bejn il - lipomatosi tal- vixxri u PIs u l- lipoatrofija u l- Inibituri ta ’ Nucleoside Analogue Reverse Transcriptase (NRTIs) kienet ipotizzata.
A higher risk of lipodystrophy has been associated with individual factors such as older age, and with drug related factors such as longer duration of antiretroviral treatment and associated metabolic disturbances.
Riskju ogħla ta ’ lipodistrofija kien assoċjat ma ’ fatturi individwali bħal età avanzata u fatturi konnessi mal- mediċina bħal dewma aktar fit- tul tat- trattament antiretrovirali u disturbi metaboliċi assoċjati.
Clinical examination should include evaluation for physical signs of fat redistribution.
L- eżami kliniku għandu jinkludi evalwazzjoni għal sinjali fiżiċi ta ’ tqassim mill- ġdid tax- xaħam.
Please refer to Table 1 and Table 2 for interactions of nelfinavir with selected compounds, Table 1 for impact on the pharmacokinetics of the co-administered compound, Table 2 for the impact of other drugs on pharmacokinetics of nelfinavir.
Jekk jogħġbok irreferi għal Tabella u Tabella 2 għall- interazzjonijiet ta ’ nelfinavir ma ’ sustanzi magħżula, Tabella 1 għall- effett fuq il- farmakokinetika tas- sustanza mogħtija fl- istess waqt, Tabella 2 għall- effett ta ’ mediċini oħra fuq il- farmakokinetika ta ’ nelfinavir.
There were no significant differences between low doses of ritonavir (either 100 or 200 mg BID) for effects on AUCs of nelfinavir and M8.
Ma kien hemm l- ebda differenza sinifikanti bejn dożi baxxi ta ’ ritonavir (100 jew 200 mg BID) għall- effetti fuq l- AUCs ta ’ nelfinavir u M8.
Indinavir:
23 Indinavir:
Saquinavir soft gelatin capsule:
Kapsula ratba tal- ġelatina ta ’ saquinavir:
22 Non-nucleoside Analogue Reverse Transcriptase Inhibitors (NNRTIs):
Inibituri tan- Non- nucleoside Analogue Reverse Transcriptase (NNRTIs):
Other potent inducers of CYP3A (e.g., phenobarbital, carbamazepine) may also reduce nelfinavir plasma concentrations.
Sustanzi oħra potenti li jinduċu CYP3A4 (eż. phenobarbital, carbamazepine) jistgħu wkoll inaqqsu l- konċentrazzjonijiet tal - plażma ta ’ nelfinavir.
John’s wort (Hypericum perforatum):
John’ s wort (Hypericum perforatum):
This is due to induction of drug metabolising enzymes and/or transport proteins by St.
Dan hu minħabba l- induzzjoni ta ’ enzimi metabolanti fil- mediċina u/ jew fit- transport tal- proteini minn St.
John’s wort, stop St.
John’ s Wort, waqqaf St.
John’s wort, check viral levels and if possible nelfinavir levels.
John’ s Wort, iċċekkja l - livelli virali u jekk possibbli l- livelli ta ’ nelfinavir.
John’s wort, and the dose of VIRACEPT may need adjusting.
John’ s Wort, u d- doża ta ’ nelfinavir tista ’ teħtieġ li tkun aġġustata.
John’s wort may persist for at least 2 weeks after cessation of treatment (see section 4.3).
John’ s Wort jista ’ jippersisti għal mill- inqas ġimgħatejn wara l- waqfien tat - trattament (ara sezzjoni 4. 3).
Based on the metabolic profiles, a clinically relevant drug interaction would not be expected with other specific inhibitors of CYP3A (e.g., fluconazole, itraconazole, clarithromycin, erythromycin); however, the possibility cannot be excluded.
Ibbażat fuq il- profili metaboliċi, interazzjoni rilevanti klinika ma tkunx mistennija ma ’ inibituri speċifiċi oħra ta’ CYP3A4 (eż. fluconazole, itraconazole, clarithromycin, erythromycin); madankollu, l- possibbiltà ma tistax tkun eskluża.
Co-administration of nelfinavir with inhibitors of CYP2C19 (e.g., fluconazole, fluoxetine, paroxetine, lansoprazole, imipramine, amitriptyline and diazepam) may be expected to reduce the conversion of nelfinavir to its major active metabolite M8 (tert-butyl hydroxy nelfinavir) with a concomitant increase in plasma nelfinavir levels (see section 5.2).
Tagħrif limitat minn provi kliniċi minn pazjenti li
Limited clinical trial data from patients receiving one or more of these medicinal products with nelfinavir indicated that a clinically significant effect on safety and efficacy is not expected.
24 qed jirċievu wieħed jew aktar minn dawn il- prodotti mediċinali ma ’ nelfinavir indika li mhux mistenni effett sinifikanti fuq is- sigurtà u l- effikaċja.
Omeprazole:
Omerprazole:
Co-administration of omeprazole (20 mg twice daily) and Viracept (1250 mg twice daily) to 19 healthy volunteers for 4 days resulted in reduced mean nelfinavir AUC by 36%, mean Cmax by 37%, and mean Cmin by 39%.
L- għoti flimkien ta ’ omeprazole (20 mg darbtejn kuljum) u Viracept (1250 mg darbtejn kuljum) lil 19- il voluntiera b’ saħħithom għal 4 t’ ijiem irriżulta fi tnaqqis fl- AUC medju ta ’ nelfinavir b’ 36%, Cmax medju b’ 37% u Cmin medju b’ 39%.
23 The absorption of nelfinavir may be reduced in conditions where gastric pH is increased, therefore concomitant use of VIRACEPT with Proton Pump Inhibitors is not recommended (see section 4.4), except for omeprazole which is contra-indicated (see section 4.3).
L- assorbiment ta ’ nelfinavir jista ’ jonqos f’ sitwazzjonijiet fejn il- pH ta ’ l- istonku tiżdied, għalhekk l - użu ta ’ VIRACEPT flimkien ma ’ Inibituri tal- Pompi tal- Protoni mhux rakkomandat (ara sezzjoni 4. 4), ħlief għal omeprazole li huwa kontra- indikat (ara sezzjoni 4. 3).
Co-administration of nelfinavir 1250 mg BID with methadone 80 +/- 21 mg once a day in HIV negative methadone maintenance patients resulted in a 47% decrease in methadone AUC.
L- għoti flimkien ta ’ 1250 mg ta ’ nelfinavir BID ma ’ 80 + / - 21 mg ta ’ methadone darba kuljum lill- pazjenti li kienu negattivi għall- HIV bil- manteniment ta ’ methadone, irriżulta fi tnaqqis ta ’ 47% fl- AUC ta ’ methadone.
Nelfinavir increases terfenadine plasma concentrations; therefore, VIRACEPT must not be administered concurrently with terfenadine because of the potential for serious and/or life-threatening cardiac arrhythmias.
Nelfinavir iżid il- konċentrazzjonijiet tal - plażma ta ’ terfenadine; għalhekk, VIRACEPT m’ għandux jingħata flimkien ma ’ terfenadine minħabba l- potenzjal għal arritmiji kardijaċi serji u/ jew ta ’ periklu għall- ħajja.
If VIRACEPT is co-administered with parenteral midazolam, it should be done in an intensive care unit (ICU) or similar setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation.
Jekk VIRACEPT jingħata flimkien ma ’ midazolam ġol- vini, dan għandu jsir f’ taqsima ta ’ kura intensiva (ICU) jew post simili li jassigura sorveljanza klinika mill- qrib u kontroll mediku xieraq f’ każ ta ’ depressjoni respiratorja u/ jew sedazzjoni mtawwla.
For other compounds that are substrates for CYP3A (e.g., calcium channel blockers including bepridil, immunosuppressants including tacrolimus and ciclosporin, and sildenafil) plasma concentrations may be elevated when co-administered with VIRACEPT; therefore, patients should be monitored for toxicities associated with such medicinal products.
Għal sustanzi oħra li huma sottostrati għal CYP3A (e. ż. blokkaturi tal- kanali tal- kalċju inkluż bepridil, immunosoppressanti li jinkludu tacrolimus u ciclosporin u sildenafil) konċentrazzjonijiet tal- plażma jistgħu jkunu għoljin meta mogħtija flimkien ma ’ VIRACEPT; għalhekk il- pazjenti għandhom ikunu osservati għat- tossiċitajiet assoċjati ma ’ prodotti mediċinali bħal dawn.
Oral contraceptives: administration of nelfinavir 750 mg TID and a combination oral contraceptive which included 0.4 mg of norethindrone and 35 μg of 17 α-ethinylestradiol for 7 days resulted in a 47% decrease in ethinylestradiol and an 18% decrease in norethindrone plasma AUC.
L- għoti ta ’ 750 mg ta ’ nelfinavir TID u kontraċettivi orali li kienu jinkludu 0. 4 mg ta ’ norethindrone u 35 μg ta ’ 17 α- ethinyl estradiol għal 7 ijiem irriżulta fi tnaqqis ta ’ 47% f’ ethinyl
Alternative contraceptive measures should be considered.
25 estradiol u fi tnaqqis ta ’ 18% fl- AUC tal- plażma ta ’ norethindrone.
Comment Other Protease Inhibitors (PIs) Ritonavir 500 mg 750 mg TID single dose X 6 doses
750 mg TID X 6 dożi
either product Non-nucleoside Analogue Reverse Transcriptase Inhibitors (NNRTIs) Efavirenz 600 mg 750 mg TID QD
Inibituri Analogi Mhux Nucleoside ta ’ Reverse Transcriptase (NNRTIs) Efavirenz 600 mg 750 mg TID QD
See text on HMG-CoA reductase inhibitors.
Ara l- kliem dwar l- inibituri ta ’ HMG- CoA reductase.
Atorvastatin 1250 mg BID 10 mt QD∞
Atorvastatin 1250 mg BID 10 mg QD∞
25 Table 2:
26 Tabella 2:
No dosage adjustment needed for either product
L- ebda aġġustament fid- doża m’ huwa meħtieġ għall- ebda prodott
26 4.7 Effects on ability to drive and use machines
27 4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
VIRACEPT has no or negligible influence on the ability to drive and use machines.
VIRACEPT m’ għandu l- ebda jew ftit li xejn għandu effett fuq il- ħila biex issuq u tħaddem l- magni.