qanastek/EMEA-V3 huggingface dataset:
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.
The clinical relevance of these findings has not been established.
Ir- relevanza klinika ta ’ dawn is- sejbiet ma ġietx stabbilita.
See Tables 1 and 2 for more information.
Ara Tabelli 1 u 2 għal aktar informazzjoni.
The safety of this combination has not been established.
Is- sigurtà ta ’ din it- taħlita ma kinetx stabbilita.
Saquinavir soft gelatin capsule:
6 Kapsula ratba tal- ġelatina ta ’ saquinavir:
No dose adjustment is necessary for either medicinal product when nelfinavir is administered in combination with amprenavir.
L- ebda aġġustament fid- doża m’ huwa meħtieġ għall- ebda wieħed minn dawn il- prodotti mediċinali meta nelfinavir jingħata flimkien ma ’ amprenavir.
6 Non-nucleoside Analogue Reverse Transcriptase Inhibitors (NNRTIs):
Inibituri tan- Non- nucleoside Analogue Reverse Transcriptase (NNRTIs):
A dose adjustment is not needed when efavirenz is administered with VIRACEPT.
L- ebda aġġustament fid- doża m’ huwa meħtieġ meta efavirenz jingħata flimkien ma ’ VIRACEPT.
The safety of this drug combination has not been established and this combination is not recommended.
Is- sigurtà ta ’ din it- taħlita mediċinali ma kinetx stabbilita, u din it- taħlita mediċinali mhijiex irrakkomandata.
A dose adjustment is not needed when nevirapine is administered with VIRACEPT.
L- ebda aġġustament fid- doża m’ huwa meħtieġ meta nevirapine jingħata flimkien ma ’ VIRACEPT.
Metabolic enzyme inducers: rifampicin decreases nelfinavir plasma AUC by 82% and its concomitant use with nelfinavir is contraindicated (see section 4.3).
Rifampicin inaqqas l- AUC tal- plażma ta ’ nelfinavir bi 82% u l- użu tiegħu flimkien ma ’ nelfinavir huwa kontra- indikat (ara sezzjoni 4. 3).
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.
If therapy with such medicinal products is warranted, physicians should consider using alternatives when a patient is taking VIRACEPT.
Jekk terapija b’ dawn il- mediċini hija meħtieġa, it- tobba għandhom jikkunsidraw li jużaw alternattivi meta l- pazjent ikun qed jieħu VIRACEPT.
Dosage reduction of rifabutin to 150 mg once a day is necessary when nelfinavir 750 mg TID or 1250 mg BID and rifabutin are co-administered.
Tnaqqis fid- dożaġġ ta ’ rifabutin għal 150 mg darba kuljum huwa meħtieġ meta 750 mg ta ’ nelfinavir TID jew 1250 mg BID u rifabutin jingħataw flimkien.
Co-administration of nelfinavir 1250 mg BID with phenytoin 300 mg once a day did not change the concentration of nelfinavir.
L- għoti flimkien ta ’ 1250 mg ta ’ nelfinavir BID ma ’ 300 mg ta ’ phenytoin darba kuljum ma biddilx il- konċentrazzjoni ta ’ nelfinavir.
However, AUC values of phenytoin and free phenytoin were reduced by 29% and 28% by co-administration of nelfinavir, respectively.
Madankollu, il- valuri ta ’ l- AUC ta ’ phenytoin u ta ’ phenytoin liberu kienu mnaqqsa b’ 29% u bi 28% bl- għoti flimkien ta ’ nelfinavir, rispettivament.
No dose adjustment for nelfinavir is recommended.
L - ebda aġġustament fid- doża ta ’ nelfinavir mhuwa rakkomandat.
Phenytoin concentrations should be monitored during co-administration with nelfinavir.
Il- konċentrazzjonijiet ta ’ phenytoin għandhom ikunu osservati waqt l- għoti flimkien ma ’ nelfinavir.
Plasma levels of nelfinavir can be reduced by concomitant use of the herbal preparation St.
Il- livelli tal- plażma ta ’ nelfinavir jistgħu jitnaqqsu bl- użu flimkien ta ’ preparazzjoni ta ’ St.
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.
John’ s Wort.
John’ s wort must not be used concomitantly with VIRACEPT.
John’ s Wort m’ għandhomx jintużaw flimkien ma ’ VIRACEPT.
If a patient is already taking St.
Jekk il- pazjent ikun digà qed jieħu 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.
Nelfinavir levels may increase on stopping St.
Il- livelli ta ’ nelfinavir jistgħu jiżdiedu malli jitwaqqaf St.
John’ s wort, and the dose of VIRACEPT may need adjusting.
John’ s Wort, u d- doża ta ’ nelfinavir tista ’ teħtieġ li tkun aġġustata.
The inducing effect of St.
L- effett ta ’ l - induzzjoni ta ’ St.
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).
Metabolic enzyme inhibitors: co-administration of nelfinavir and a strong inhibitor of CYP3A, ketoconazole, resulted in a 35% increase in nelfinavir plasma AUC.
Inibituri ta ’ l- enzimi metaboliċi: l- għoti flimkien ta ’ nelfinavir u l- inibitur qawwi ta ’ CYP3A4, ketoconazole, irriżulta f’ żjieda ta ’ 35% fl- AUC tal- plażma ta ’ nelfinavir.
This change is not considered clinically significant and no dose adjustment is needed when ketoconazole and VIRACEPT are co-administered.
Din il- bidla mhijiex ikkunsidrata li hi klinikament sinifikattiva u l- ebda aġġustament fid- doża mhuwa meħtieġ meta l - ketoconazole u VIRACEPT jingħataw flimkien.
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).
L- għoti ta ’ nelfinavir flimkien ma ’ inibituri ta ’ CYP2C19 (e. ż., fluconazole, fluoxetine, paroxetine, lansoprazole, imipramine, amitriptyline u diazepam) hija mistennija li tista ’ tnaqqas il- konverżjoni ta ’ nelfinavir għal metabolit attiv prinċipali M8 (tert- butyl hydroxy nelfinavir) b’ żjieda fl- istess ħin tal - livelli fil- plażma ta ’ nelfinavir (ara sezzjoni 5. 2).
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.
Tagħrif limitat minn provi kliniċi minn pazjenti li qed jirċievu wieħed jew aktar minn dawn il- prodotti mediċinali ma ’ nelfinavir indika li mhux mistenni effett sinifikanti fuq is- sigurtà u l- effikaċja.
However, such an effect cannot be ruled out.
Madankollu, effett bħal dan ma jistax jiġi eskluż.
Omeprazole:
7 Omeprazole:
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 voluntier b’ saħħithom għal 4 ijiem irriżulta fi tnaqqis fl- AUC medju ta ’ nelfinavir b’ 36%, Cmax medju b’ 37% u Cmin medju b’ 39%.
Reductions were observed in the mean M8 AUC by 92%, mean Cmax by 89%, and mean Cmin by 75%.
It- tnaqqis kien osservat fl- AUC medju ta ’ M8 b’ 92%, Cmax medju b’ 89% u Cmin medju b’ 75%.
Therefore omeprazole should not be co-administered with VIRACEPT (see section 4.3)
Għalhekk, omeprazole m’ għandux jingħata flimkien ma ’ VIRACEPT (ara sezzjoni 4. 3).
7 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).
HMG-CoA reductase inhibitors which are highly dependent on CYP3A4 metabolism, such as lovastatin and simvastatin, are expected to have markedly increased plasma concentrations when co-administered with VIRACEPT.
L- inibituri ta ’ l- HMG- CoA reductase, li huma dipendenti ħafna fuq il- metaboliżmu ta ’ CYP3A4, bħal lovastatin u simvastatin, huma mistennija li jkollhom żjieda ċara fil- konċentrazzjonijiet tal- plażma meta mogħtija flimkien ma ’ VIRACEPT.
Since increased concentrations of HMG-CoA reductase inhibitors may cause myopathy, including rhabdomyolysis, the combination of these medicinal products with VIRACEPT is not recommended.
Billi ż- żjieda fil - konċentrazzjonijiet ta ’ l- inibituri ta ’ HMG- CoA reductase jistgħu jikkawżaw mijopatija, inkluża r - rabdomijolosi, it- taħlit ta ’ dawn il- prodotti mediċinali ma ’ VIRACEPT mhuwiex rakkomandat.
Atorvastatin is less dependent on CYP3A4 for metabolism.
Atorvastatin huwa inqas dipendenti fuq CYP3A4 għall- metaboliżmu.
When used with VIRACEPT, the lowest possible dose of atorvastatin should be administered.
Meta użat ma ’ VIRACEPT, l - inqas doża possibbli ta ’ atorvastatin għandha tingħata.
The metabolism of pravastatin and fluvastatin is not dependent on CYP3A4, and interactions are not expected with PIs.
Il- metaboliżmu ta ’ pravastatin u ta ’ fluvastatin mhuwiex dipendenti fuq CYP3A4, u l- azzjonijiet reċiproċi mhumiex mistennija ma ’ PIs.
If treatment with a HMG-CoA reductase inhibitor is indicated, pravastatin or fluvastatin is recommended.
Jekk it - trattament b’ inibitur ta ’ HMG- CoA reductase huwa indikat, pravastatin jew fluvastatin huma rakkomandati.
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.
None of the subjects experienced withdrawal symptoms in this study; however, due to the pharmacokinetic changes, it should be expected that some patients who received this drug combination may experience withdrawal symptoms and require an upward adjustment of the methadone dose.
Ħadd mis- suġġetti ma kellu sintomi ta ’ rtirar f’ dan l- istudju; madankollu, minħabba t- tibdiliet farmakokinetiċi, wieħed għandu jistenna li xi pazjenti li ħadu din it- taħlita mediċinali jista ’ jkollhom sintomi ta ’ rtirar u jistgħu jeħtieġu żjieda fid- doża ta ’ methadone.
Other potential interactions (see also section 4.3):
Interazzjonijiet potenzjali oħra (ara wkoll sezzjoni 4. 3):
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.
Because similar interactions are likely with astemizole and cisapride, VIRACEPT must not be administered concurrently with these drugs.
Billi interazzjonijiet bħal dawn huma probabbli ma ’ astemizole u ma ’ cisapride, VIRACEPT m’ għandux jingħata flimkien ma ’ dawn il- mediċini.
Midazolam is extensively metabolised by CYP3A4.
Midazolam huwa metabolizzat estensivament b’ CYP3A4.
Co-administration with VIRACEPT may cause a large increase in the concentration of this benzodiazepine.
L- għoti flimkien ma ’ VIRACEPT tista ’ tikkawża żjieda qawwija fil- konċentrazzjoni ta ’ dan il- benzodiazepine.
No drug interaction study has been performed for the co-administration of VIRACEPT with benzodiazepines.
Ma sar ebda studju fuq l- interazzjoni tal- mediċina dwar għoti fl- istess ħin ta ’ VIRACEPT ma ’ benzodiazepines.
Based on data for other CYP3A4 inhibitors, plasma concentrations of midazolam are expected to be significantly higher when midazolam is given orally.
Fuq il- bażi ta ’ tagħrif għal inibituri CYP3A4 oħra, il- konċentrazzjonijiet fil- plasma ta ’ midazolam huma mistennija li jkunu ferm ogħla meta midazolam jingħata mill- ħalq.
Therefore VIRACEPT should not be co-administered with orally administered midazolam (see section 4.3), whereas caution should be used with co-administration of VIRACEPT and parenteral midazolam.
Għalhekk, VIRACEPT ma għandux jingħata flimkien ma ’ midazolam li jingħata mill- ħalq (ara sezzjoni 4. 3), filwaqt li għandha tingħata attenzjoni meta VIRACEPT jingħata fl- istess ħin ma ’ midazolam mogħti ġol- vini.
Data from concomitant use of parenteral midazolam with other protease inhibitors suggest a possible 3-4 fold increase in midazolam plasma levels.
Tagħrif minn użu fl- istess ħin ta ’ midazolam mogħti ġol- vini ma ’ inibituri oħra tal- protease jissuġġerixxi l - possibiltà ta ’ żjieda ta ’ 3- 4 darbiet fil- livelli tal- plasma ta ’ midazolam.
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.
Dosage adjustment for midazolam should be considered, especially if more than a single dose of midazolam is administered.
Għandu jiġi kkunsidrat aġġustament fid- dożaġġ għal midazolam speċjalment jekk tingħata aktar minn doża waħda ta ’ midazolam.
Similarly, concomitant administration of nelfinavir with any of amiodarone, quinidine, pimozide and ergot derivatives is contraindicated.
Bl- istess mod, l- għotja ta ’ melfinavir flimkien ma ’ xi wieħed minn amiodarone, quinidine, pimozide u derivattivi ta ’ ergot hija kontra- indikata.
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 μ g 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 estradiol u fi tnaqqis ta ’ 18% fl- AUC tal- plażma ta ’ norethindrone.
Alternative contraceptive measures should be considered.
Miżuri kontraċettivi alternattivi għandhom ikunu kkunsidrati.
8 Table 1:
8 Tabella 1:
Drug Interactions:
Interazzjonijiet tal- Mediċina:
Changes in Pharmacokinetic Parameters for Co-administered Drug in the Presence of Nelfinavir Co-administered Drug, Dose
Bidliet fil- Parametri Farmakokinetiċi għall- Mediċina Mogħtija fl- Istess Waqt fil- Preżenza ta ’ Nelfinavir
Nelfinavir Dose
Doża ta ’
% Change of Co-administered Drug Pharmacokinetic Parameters AUC Cmax Cmin
% ta ’ Bidla fil- Parametri Farmakokinetiċi tal- Mediċina
Comment Other Protease Inhibitors (PIs) Ritonavir 500 mg 750 mg TID single dose X 6 doses
Inibituri ta ’ Protease Oħra (PIs) Doża waħda ta ’ ritonavir 500 mg
Indinavir 800 mg 750 mg TID single dose X 7 days
750 mg TID
C
L- aktar C
trough at 8 The safety of hrs combination ↑ 500% indinavir + nelfinavir has not been established.
baxxa wara 8 taħlita ta ’ sigħat indinavir + ↑ 500% nelfinavir ma ġietx stabbilita.
Saquinavir soft gelatin capsule 1200 mg single dose
Doża waħda ta ’ saquinavir 1200 mg kapsuli rotob tal- ġelatina
750 mg TID X 4 days
750 mg TID X 4 ijiem
↑ 189%
↑ 189% L- ebda aġġustament fid- doża m’ huwa meħtieġ għall - ebda prodott
Efavirenz 600 mg 750 mg TID QD
Inibituri Analogi Mhux Nucleoside ta ’ Reverse Transcriptase (NNRTIs) Efavirenz 600 mg 750 mg TID QD
No dose adjustment needed
M’ hemmx bżonn ta ’ aġġustament fid- doża
Delavirdine 400 mg TID Nevirapine
Delavirdine 400 mg TID Nevirapine Indutturi ta ’ l- enżima
750 mg TID
750 mg TID metabolika
Safety of combination not established; combination not recommended.
Sigurtà tat- taħlita mhijiex stabbilita; taħlita mhijiex rakkomandata.
See text
Ara t- test
Metabolic enzyme inducers Rifabutin 300 mg 750 mg TID QD
Rifabutin 300 mg 750 mg TID QD
Dosage reduction of rifabutin to 150 mg QD is necessary when nelfinavir 750 mt TID or
Tnaqqis fid- dożaġġ ta ’ rifabutin għal 150 mg QD huwa neċessarju meta nelfinavir 750 mg TID jew 1250 mg BID u rifabutin jingħataw
Rifabutin 150 mg 750 mg TID QD*** HMG-CoA reductatse inhibitors∞
Rifabutin 150 mg 750 mg TID QD *** Inibituri ta ’ HMG- CoA reductatse∞
1250 mg BID and rifabutin are co- administered.
flimkien.
Simvastatin 20 mg 1250 mg BID QD∞
Simvastatin 1250 mg BID 20 mg QD∞
See text on HMG-CoA reductase inhibitors.
Ara t- test dwar l- inibituri ta ’ HMG- CoA reductase.
Combination of simvastatin and nelfinavir is
Taħlita ta ’ simvastatin u nelfinavir mhijiex rakkomandata.
Atorvastatin 1250 mg BID 10 mg QD∞
Atorvastatin 1250 mg BID 10 mg QD∞
When used with nelfinaivr, the lowest possible dose of atorvastatin would be administered.
nelfinavir, għandha tingħata l- inqas doża possibbli ta ’ atorvastatin.
If treatment with HMG-CoA reductase inhibitors is indicated in combination with nelfinavir, pravastatin or fluvastatin is recommended.
Jekk kura b’ inibituri ta ’ HMG- CoA reductase hija indikata f’ taħlita ma ’ nelfinavir, pravastatin jew fluvastatin huwa rakkomandat.
↑ Indicates increase, ↓ indicates decrease, ↔ indicates minimal change (< 10%).
↑ Tindika żjieda, ↓ tindika tnaqqis, ↔ tindika bidla minima (< 10%).
Changes in Pharmacokinetic Parameters for Nelfinavir in the Presence of the Co-administered Drug
Bidliet fil- Parametri Farmakokinetiċi għal Nelfinavir fil - Preżenza tal- Mediċina Mogħtija fl- Istess Waqt
Co-
Mediċina
Nelfinavir
Doża ta ’
% Change of Nelfinavir Pharmacokinetic Parameters
% ta ’ Bidla fil- Parametri Farmakokinetiċi ta ’ Nelfinavir
administered Drug, Dose
Mogħtija fl - Istess Waqt, Doża
Other/ Comment
Oħra/ Kummenti
Other Protease Inhibitor (PIs) Ritonavir
Inibituri ta ’ Protease Oħra (PIs) Ritonavir
Single dose
Doża waħda
Elimination half live
Half- life ta ’ l- eliminazzjoni
500 mg BID X 3 750 mg doses
500 mg BID X 3 ta ’ 750 mg dożi
administration)
għodu)
See Sec.
Ara Sez.
5.2 regarding the formation and further metabolism of M8.
5. 2 dwar il- formazzjoni u aktar
administration)
għaxija)
The clinical relevance of these findings has not been established.
Ir- rilevanza klinika ta ’ dawn is- sejbiet ma ġietx stabbilita.
750 mg single dose
Doża waħda ta ’ 750 mg
Elimination half live ↑ 22% The safety of the combination has not been established
Half- life ta ’ l- eliminazzjoni ↑ 22%
No dosage adjustment for needed for either product
L- ebda aġġustament fid- doża m’ huwa meħtieġ għall- ebda prodott
Non-nucleoside Analogue Reverse Transcriptase Inhibitors (NNRTIs) Efavirenz 600 mg QD
Inibituri Analogi Mhux Nucleoside ta ’ Reverse Transcriptase (NNRTIs) Efavirenz 600 mg QD
No dosage adjustment needed
M’ hemmx bżonn ta ’ aġġustament fid- doża
Safety of combination not established; combination not recommended.
Is- sigurtà ta ’ din it- taħlita ma ġietx stabbilita; taħlita mhijiex rakkomandata.
See text
Ara l- kliem
Metabolic enzyme inducers Rifabutin 300 mg QD
Indutturi ta ’ l- enżima metabolika Rifabutin 300 mg QD
Dosage reduction of rifabutin to 150 mg QD is necessary when nelfinavir 750 mt TID or
Tnaqqis fid- doża ta ’ rifabutin għal 150 mg QD hija meħtieġa meta nelfinavir 750 mg TID jew 1250 mg BID u rifabutin jingħataw fl- istess
1250 mg BID and rifabutin are co-administered.
waqt.
↑ Indicates increase, ↓ indicates decrease, ↔ indicates minimal change (< 10%)
↑ Tindika żjieda, ↓ tindika tnaqqis, ↔ tindika bidla minima (< 10%).
No treatment-related adverse reactions were seen in animal reproductive toxicity studies in rats at doses providing systemic exposure comparable to that observed with the clinical dose.
L- ebda reazzjonijiet mhux mixtieqa konnessi mat- trattament ma kienu osservati fi studji fuq it - tossiċità riproduttiva fl- annimali li saru fuq il- firien, f’ dożi li kienu jipprovdu espożizzjoni sistematika komparabbli ma ’ dik osservata mad- doża klinika.
Clinical experience in pregnant women is limited.
Esperjenza klinika f’ nisa tqal hija limitata.
VIRACEPT should be given during pregnancy only if the expected benefit justifies the possible risk to the foetus.
VIRACEPT għandu jingħata waqt it- tqala biss jekk il- benefiċċju mistenni jiġġustifika ir- riskju possibli għall- fetu.
It is recommended that HIV-infected women must not breast-feed their infants under any circumstances in order to avoid transmission of HIV.
Huwa rakkomandat li nisa infettati b’ HIV ma jreddgħux lit- trabi tagħhom fl- ebda ċirkustanza sabiex jevitaw it- trasmissjoni ta ’ HIV.
Studies in lactating rats showed that nelfinavir is excreted in breast milk.
Studji f’ firien li kienu jreddgħu wrew li nelfinavir huwa mneħħi mill - ħalib tas- sider.
There is no data available on nelfinavir excretion into human breast milk.
M’ hemmx informazzjoni disponibbli fuq it- tneħħija ta ’ nelfinavir fil- ħalib tas- sider uman.
Mothers must be instructed to discontinue breast-feeding if they are receiving VIRACEPT.
L- ommijiet għandhom ikunu istruwiti biex jinterrompu t- treddigħ jekk ikunu qed jirċievu VIRACEPT.
10 4.7 Effects on ability to drive and use machines
10 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 magni.
The safety of the VIRACEPT 250 mg tablet was studied in controlled clinical trials with over 1300 patients.
Is- sigurtà tal- pillola VIRACEPT 250mg kienet studjata fi provi kliniċi kkontrollati b’ aktar minn 1300 pazjent.
The majority of patients in these studies received either 750 mg TID either alone or in combination with nucleoside analogues or 1250 mg BID in combination with nucleoside analogues.
Il- maġġoranza tal- pazjenti f’ dawn l- istudji rċevew 750 mg TID waħdu jew flimkien ma ’ analogi ta ’ nucleoside jew 1250 mg BID flimkien ma ’ analogi ta ’ nucleoside.
The following adverse events with an at least possible relationship to nelfinavir (i.e. adverse reactions) were reported most frequently: diarrhoea, nausea, and rash.
L- avvenimenti avversi li ġejjin li huma mill- inqas possibbilment konnessi ma ’ nelfinavir (i. e. reazzjonijiet avversi) kienu rrapportati l- aktar frekwenti: dijarea, tqalligħ, u raxx.
Adverse reactions from clinical trials with nelfinavir
Reazzjonijiet avversi minn provi kliniċi b’ nelfinavir
Adverse reactions in clinical studies are summarised in Table 3.
Reazzjonijiet avversi fi studji kliniċi huma miġbura fil- qosor f’ Tabella 3.
The list also includes marked laboratory abnormalities that have been observed with nelfinavir (at 48 weeks).
Il- lista tinkludi wkoll anormalitajiet sinifikanti tal- laboratorju li kienu osservati b’ nelfinavir (fit- 48 ġimgħa).
Incidences of Adverse Reactions and marked laboratory abnormalities from the phase II and phase III studies.
Inċidenza ta ’ Reazzjonijiet Avversi u anormalitajiet sinifikanti tal- laboratorju minn studji ta ’ fażi II u ta ’ fażi III.
(Very common (≥ 10%); common (≥ 1% and < 10%) Body System Frequency of Reaction
(Komuni ħafna (≥ 10%); komuni (≥ 1% u < 10%)) Reazzjonijiet Avversi Sistema tal- ġisem Frekwenza tar- Reazzjoni Disturbi gastro- intestinali
Diarrhoea Nausea, flatulence,
Dijarea Tqalligħ, gass fl- istonku,
Skin and subcutaneous tissue disorders Common Investigations
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Komuni Investigazzjonijiet
Increased alanine aminotransferase, increased aspartate aminotransferase, neutropenia, blood creatinine phosphokinase increased, neutrophil count decreased
Żjieda fl- alanine aminotransferase, żjieda fl- aspartate aminotransferase, newtropenja, żjieda fil- creatinine phosphokinase tad- demm, tnaqqis fl - għadd ta ’ newtrofili
Children and neonates:
Tfal u trabi:
A total of approximately 400 patients received nelfinavir in paediatric treatment trials (Studies 524, 556, PACTG 377/725, and PENTA-7) for up to 96 weeks.
Total ta ’ madwar 400 pazjent irċevew nelfinavir fi provi ta ’ kura pedjatrika (Studji 524, 556, PACTG 377/ 725, u PENTA- 7) għal mhux aktar minn 96 ġimgħa.
The adverse reaction profile seen during paediatric clinical trials was similar to that for adults.
Il- profil ta ’ reazzjonijiet avversi osservat waqt il- provi kliniċi pedjatriċi kien simili għal dak ta ’ l- adulti.
Diarrhoea was the most commonly reported adverse event in children.
Dijarea kienet l- avveniment avvers irrapportat bl- aktar mod komuni fit- tfal.
Neutropenia/leukopenia was the most frequently observed laboratory abnormality.
Newtropenja/ lewkopenja kienet l- aktar anormalità tal - laboratorju osservata b’ mod komuni.
During these trials less than 13% of patients in total discontinued treatment due to adverse events.
Waqt dawn il- provi inqas minn total ta ’ 13% tal- pazjenti waqqfu l- kura minħabba avvenimenti avversi.
Post-marketing experience with nelfinavir Serious and non-serious adverse reactions from post-marketing spontaneous reports (where nelfinavir was taken as the sole protease inhibitor or in combination with other antiretroviral therapy), not mentioned previously in section 4.8, for which a causal relationship to nelfinavir cannot be excluded, are summarised below.
Esperjenza ta ’ wara t- tqegħid fis- suq b’ nelfinavir Reazzjonijiet avversi serji u mhux serji minn rapporti spontanji ta ’ wara t- tqegħid fis- suq (fejn nelfinavir ittieħed bħala l- uniku inibitur ta ’ protease jew flimkien ma ’ terapija antiretrovirali oħra), mhux imsemmija qabel f’ sezzjoni 4. 8, li għalihom relazzjoni kawżali għal nelfinavir ma tistax tiġi eskluża, huma miġbura hawn isfel.
As these data come from the spontaneous reporting system, the frequency of the adverse reactions is not confirmed.
Minħabba li dan it- tagħrif ġej mis- sistema ta ’ rappurtaġġ spontanju, il- frekwenza tar- reazzjonijiet avversi mhijiex ikkonfermata.
Uncommon (≥ 0.1% - ≤ 1%): hypersensitivity including bronchospasm, pyrexia, pruritus, facial oedema and rash (maculopapular or bullous).
Mhux komuni (≥ 0. 1% - ≤ 1%): sensittività eċċessiva inkluż bronkospażmu, deni, ħakk, edima fil - wiċċ u raxx (makulari bl- infafet jew bulloża).
Metabolism and nutrition disorders:
11 Disturbi fil- metaboliżmu u n- nutrizzjoni:
Rare (≥ 0.01% - ≤ 0.1%): new onset diabetes mellitus, or exacerbation of existing diabetes mellitus.
Rari (≥ 0. 01% - ≤ 0. 1%): dehra għall- ewwel darba ta ’ dijabete mellitus, jew dijabete mellitus preżenti minn qabel tmur għall- agħar.
11 Uncommon - rare (≥ 0.01% - ≤ 1%):
Mhux komuni - rari (≥ 0. 01% - ≤ 1%):
Combination antiretroviral therapy has been associated with redistribution of body fat (lipodystrophy) in HIV patients including the loss of peripheral and facial subcutaneous fat, increased intra-abdominal and visceral fat, breast hypertrophy and dorsocervical fat accumulation (buffalo hump).
Terapija antiretrovirali kombinata kienet assoċjata ma ’ distribuzzjoni mill- ġdid tax- xaħam tal- ġsiem (lipodistrofija) f’ pazjenti bl- HIV inkluż it- telf ta ’ xaħam taħt il- ġilda periferiku jew fil- wiċċ, żjieda fix- xaħam intra- addominali u fil- vixxri, ipertrofija tas- sider u akkumulazzjoni ta ’ xaħam dorsoċervikali (buffalo hump).
Rare (≥ 0.01% - ≤ 0.1%): increased spontaneous bleeding in patients with haemophilia.
Rari (≥ 0. 01% - ≤ 0. 1%): żjieda ta ’ fsad spontanja f’ pazjenti b’ emofilja.
Rare (≥ 0.01% - ≤ 0.1%): abdominal distension, Uncommon (≥ 0.1% - ≤ 1%): vomiting, pancreatitis/blood amylase increased.
Rari (≥ 0. 01% - ≤ 0. 1%): nefħa addominali, Mhux komuni (≥ 0. 1% - ≤ 1%): rimettar, pankrejatite/ żjieda fl- amylase fid- demm.
Rare (≥ 0.01% - ≤ 0.1%): hepatitis, abnormal liver enzymes and jaundice when nelfinavir is used in combination with other antiretroviral agents.
Rari (≥ 0. 01% - ≤ 0. 1%): epatite, enżimi tal- fwied mhux normali u suffejra meta nelfinavir jiġi wżat flimkien ma ’ sustanzi antiretrovirali oħra.
Very rare (≤ 0.01%), including isolated reports:
Rari ħafna (≤ 0. 01%), inkluż rapporti iżolati:
Rare (≥ 0.01% - ≤ 0.1%):
Rari (≥ 0. 01% - ≤ 0. 1%):
Blood creatine phosphokinase increased, myalgia, myositis and rhabdomyolysis have been reported with PIs, particularly in combination with nucleoside analogues.
Żjieda tal- creatine phosphokinase fid- demm, mijalġja, mijosite u rabdomijolisi ġeww irrapportati b’ PIs, speċjalment f’ taħlita ma ’ analogi ta ’ nucleoside.
Additional adverse reactions have been reported in the post-marketing experience and are listed below.
Reazzjonijiet avversi oħra ġew irrapportati fl- esperjenza ta ’ wara t- tqegħid fis- suq u huma mniżżla taħt.
As these data come from the spontaneous reporting system, the frequency of the adverse reactions is unknown: hypertriglyceridemia, anaemia, blood lactic acid increased, and pneumonia.
Minħabba li dan it- tagħrif ġej mis- sistema ta ’ rappurtar spontanju, l- frekwenza tar- reazzjonijiet avversi mhux magħrufa: ipertrigliċeridimja, anemija, żjieda tal- lactic acid fid- demm, u pnewmonja.
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 ’ osteonekrożi ġew irrapportati, speċjalment f’ pazjenti b’ fatturi ta ’ riskju magħrufa b’ mod ġenerali, marda ta ’ l- HIV avvanzata jew esponiment fit- tul għall- terapija anitretrovirali kombinata (CART).
The frequency of this is unknown (see section 4.4).
Il- frekwenza ta ’ dan mhijiex magħrufa (ara sezzjoni 4. 4).
Combination antiretroviral therapy has been associated with metabolic abnormalities such as hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperglycaemia and hyperlactaemia.
Terapija antiretrovirali kombinata ġiet assoċjata ma ’ anormalitajiet metaboliċi bħal ipertrigliċeridimja, iperkolesterolimja, reżistenza għall- insulina, ipergliċemija u iperlaktimja.
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.
F’ pazjenti infetti bl- HIV b’ defiċjenza immuni severa fiż- żmien tal- bidu tat- terapija antiretrovirali kombinata (CART), tista ’ sseħħ reazzjoni infjammatorja għall- infezzjonijiet opportunistiċi bla sintomi jew li kien hemm.
Human experience of acute overdose with VIRACEPT is limited.
Esperjenza fil- bniedem ta ’ doża eċċessiva akuta b’ VIRACEPT hija limitata.
There is no specific antidote for overdose with nelfinavir.
M’ hemm l- ebda antidot speċifiku għal doża eċċessiva ta ’ nelfinavir.
If indicated, elimination of unabsorbed nelfinavir should be achieved by emesis or gastric lavage.
Jekk indikat, l- eliminazzjoni ta ’ nelfinavir mhux assorbit għandha ssir b’ emesi jew b’ ħasil ta ’ l- istonku.
Administration of activated charcoal may also be used to aid removal of unabsorbed nelfinavir.
Faħam tal- kannoll attivat jista ’ jingħata wkoll biex jgħin fit- tneħħija ta ’ nelfinavir mhux assorbit.
Since nelfinavir is highly protein bound, dialysis is unlikely to significantly remove it from blood.
Billi nelfinavir huwa magħqud ħafna mal- protejina, id - dijalisi x’ aktarx li ma tneħħihx b’ mod sinifikattiv mid- demm.
Overdoses of nelfinavir could theoretically be associated with prolongation of the QT-interval of the ECG (see also section 5.3).
Dożi eċċessivi ta ’ nelfinavir jistgħu teoretikament ikunu assoċjati mat- titwil ta ’ l- intervall tal- QT ta ’ l - ECG (ara wkoll sezzjoni 5. 3).
Monitoring of overdosed patients is warranted.
Is- sorveljanza ta ’ pazjenti li ħadu dożi eċċessivi hija meħtieġa.
5.1 Pharmacodynamic properties
12 5. 1 Tagħrif farmakodinamiku
Pharmacotherapeutic group:direct acting antivirals, ATC code:
Kategorija farmakoterapewtika: antivirali li jaħdmu b’ mod dirett, Kodiċi ATC:
12 Mechanism of action:
Mekkaniżmu ta ’ l- azzjoni:
HIV protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors to the individual proteins found in infectious HIV.
Il- protease ta ’ l- HIV hija enzima meħtieġa għall- qtugħ protejolitiku tal - prekursuri tal- poliproteini virali (proteolytic cleavage of the viral polyprotein precursors) għall - proteini individwali li jinsabu f’ HIV infettiva.
The cleavage of these viral polyproteins is essential for the maturation of infectious virus.
Il- qtugħ ta ’ dawn il- poliproteini virali huwa essenzjali għall- maturazzjoni tal- vajrus infettiv.
Nelfinavir reversibly binds to the active site of HIV protease and prevents cleavage of the polyproteins resulting in the formation of immature non-infectious viral particles.
Nelfinavir jingħaqad b’ mod reversibbli mal- partijiet attivi tal - protease ta ’ l- HIV u jevita l- qtugħ tal- molekuli tal- poliproteini, u jirriżulta fil- formazzjoni ta ’ partiċelli virali immaturi u mhux infettivi.
Antiviral activity in vitro: the antiviral activity of nelfinavir in vitro has been demonstrated in both HIV acute and chronic infections in lymphoblastoid cell lines, peripheral blood lymphocytes and monocytes/macrophages.
L- attività antivirali in vitro ta ’ nelfinavir kienet murija f’ infezzjonijiet ta ’ l - HIV, kemm akuti u kemm kroniċi, fil- linji taċ- ċelluli limfoblastojdi, limfoċiti periferali tad- demm u monoċiti/ makrofaġi.
Nelfinavir was found to be active against a broad range of laboratory strains and clinical isolates of HIV-1 and the HIV-2 strain ROD.
Nelfinavir instab li kien attiv kontra firxa wiesgħa ta ’ strains tal- laboratorju u iżolati kliniċi ta ’ l- istrain ROD ta ’ l- HIV- 1 u l- HIV- 2.
The EC95 (95% effective concentration) of nelfinavir ranged from 7 to 111 nM (mean of 58 nM).
L- EC95 (95% konċentrazzjoni effettiva) ta ’ nelfinavir varjat minn 7 sa 111 nM (medja ta ’ 58 nM).
Nelfinavir demonstrated additive to synergistic effects against HIV in combination with reverse transcriptase inhibitors zidovudine (ZDV), lamivudine (3TC), didanosine (ddI), zalcitabine (ddC) and stavudine (d4T) without enhanced cytotoxicity.
Nelfinavir wera effetti minn addittivi sa sinerġetiċi kontra l- HIV flimkien ma ’ l- inibituri ta ’ reverse transcriptase ta ’ zidovudine (ZDV), lamivudine (3TC), didanosine (ddI), zalcitabine (ddC), u stavudine (d4T) mingħajr żjieda fiċ - ċitotossiċità.
Drug Resistance:
Reżistenza għall- Mediċina:
HIV isolates with reduced susceptibility to nelfinavir have been selected in vitro.
Iżolati ta ’ HIV b’ suxxettibbilità mnaqqsa għal nelfinavir kienu magħżula in vitro.
HIV isolates from selected patients treated with nelfinavir alone or in combination with reverse transcriptase inhibitors were monitored for phenotypic (n=19) and genotypic (n=195, 157 of which were assessable) changes in clinical trials over a period of 2 to 82 weeks.
Iżolati ta ’ HIV minn pazjenti magħżula ttrattati b’ nelfinavir waħdu jew flimkien ma ’ l - inibituri ta ’ reverse transcriptase kienu osservati għal tibdil fenotipiku (n=19) u ġenotipiku (n=195, li minnhom 157 setgħu jkunu assessjati) fi provi kliniċi fuq perjodu ta ’ 2 sa 82 ġimgħa.
One or more viral protease mutations at amino acid positions 30, 35, 36, 46, 71, 77 and 88 were detected in > 10% of patients with assessable isolates.
Bidla waħda jew iżjed bidliet fi protease virali fil- pożizzjonijiet ta ’ l- aċidu amminiku 30, 35, 36, 46, 71, 77 u 88 kienu osservati f ’ > 10% tal- pazjenti b’ iżolati li setgħu jkunu assessjati.
Of 19 patients for whom both phenotypic and genotypic analyses were performed on clinical isolates, 9 patients isolates showed reduced susceptibility (5- to 93-fold) to nelfinavir in vitro.
Minn 19- il pazjent li għalihom analiżi fenotipiċi u ġenotipiċi kienu magħmula f’ iżolati kliniċi, 9 pazjenti wrew suxxettibbilità mnaqqsa (minn 5 sa 93 darba) għal nelfinavir in vitro.
Isolates from all 9 patients possessed one or more mutations in the viral protease gene.
Iżolati mid- 9 pazjenti kollha kellhom bidla waħda jew iżjed bidliet fil- ġene ta ’ protease virali.
Amino acid position 30 appeared to be the most frequent mutation site.
Il- pożizzjoni 30 ta ’ l- aċidu amminiku tidher li kienet l- aktar parti li fiha seħħ it- tibdil.
The overall incidence of the D30N mutation in the viral protease of assessable isolates (n=157) from patients receiving nelfinavir monotherapy or nelfinavir in combination with zidovudine and lamivudine or stavudine was 54.8%.
L- inċidenza totali tat- tibdil ta ’ D30N f’ protease virali ta ’ iżolati li setgħu jkunu assessjati (n=157) minn pazjenti li kienu qed jirċievu l- monoterapija ta ’ nelfinavir jew nelfinavir flimkien ma ’ zidovudine, lamivudine jew stavudine kienet ta ’ 54. 8%.
The overall incidence of other mutations associated with primary PI resistance was 9.6% for the L90M substitution where as substitutions at 48, 82 and 84 were not observed.
L- inċidenza totali ta ’ tibdil ieħor assoċjat ma ’ reżistenza primarja ta ’ PI kienet ta ’ 9. 6% għas- sostituzzjoni L90M filwaqt li s- sostituzzjonijiet fi 48, 82 u 84 ma kinux osservati.
Cross resistance:
Reżistenza inkroċjata (cross resistance):
HIV isolates obtained from 5 patients during nelfinavir therapy showed a 5- to 93-fold decrease in nelfinavir susceptibility in vitro when compared to matched baseline isolates but did not demonstrate a concordant decrease in susceptibility to indinavir, ritonavir, saquinavir or amprenavir in vitro.
Iżolati ta ’ HIV miksuba minn 5 pazjenti waqt it- terapija b’ nelfinavir urew suxxettibbilità mnaqqsa (minn 5 sa 93 darba) għal nelfinavir in vitro meta mqabbla ma ’ iżolati tal- linja bażi li taqbel iżda ma wrewx tnaqqis li jaqbel fis- suxxettibbilità għal indinavir, għal ritonavir, għal saquinavir jew għal amprenavir in vitro.
Conversely, following ritonavir therapy, 6 of 7 clinical isolates with decreased ritonavir susceptibility (8- to 113-fold) in vitro compared to baseline also exhibited decreased susceptibility to nelfinavir in vitro (5- to 40 fold).
Bil- maqlub, wara terapija b’ ritonavir, 6 minn 7 iżolati kliniċi b‘ suxxettibbilità mnaqqsa għal ritonavir (minn 8 sa 113 darba) in vitro meta mqabbla ma ’ iżolati tal- linja bażi li taqbel, urew ukoll suxxettibbilità mnaqqsa għal nelfinavir in vitro (minn 5 sa 40 darba).
An HIV isolate obtained from a patient receiving saquinavir therapy showed decreased susceptibility to saquinavir (7- fold) but did not demonstrate a concordant decrease in susceptibility to nelfinavir.
Iżolat ta ’ HIV miksub minn pazjent li kien qed jirċievi t- terapjija ta ’ saquinavir wera suxxettibbilità mnaqqsa għal saquinavir (7 darbiet) iżda ma weriex tnaqqis li jaqbel fis - suxxettibbilità għal nelfinavir.
Cross-resistance between nelfinavir and reverse transcriptase inhibitors is unlikely because different enzyme targets are involved.
Ir- reżistenza inkroċjata bejn nelfinavir u l- inibituri ta ’ reverse transcriptase mhijiex probabbli minħabba li hemm targits ta ’ l- enzimi differenti involuti.
Clinical isolates (n=5) with decreased susceptibility to zidovudine, lamivudine, or nevirapine remain fully susceptible to nelfinavir in vitro.
Iżolati kliniċi (n=5) b’ suxxettibbilità mnaqqsa għal zidovudine, għal lamivudine, jew għal nevirapine jibqgħu kompletament suxxettibbli għal nelfinavir in vitro.
Clinical pharmacodynamic data: treatment with nelfinavir alone or in combination with other antiretroviral agents has been documented to reduce viral load and increase CD4 cell counts in HIV-1 seropositive patients.
It- trattament b’ nelfinavir waħdu jew flimkien ma ’ mediċini antitretrovirali oħra kien muri li jnaqqas it- tagħbija virali u jżid l- għadd taċ- ċelluli CD4 f’ pazjenti seropożittivi għal HIV- 1.
Decreases in HIV RNA observed with nelfinavir monotherapy were less pronounced and of shorter duration.
Tnaqqis f’ RNA ta ’ HIV osservati bil- monoterapija ta ’ nelfinavir kienu inqas intensi u damu inqas.
The effects of nelfinavir (alone or combined with other antiretroviral agents) on biological markers of disease activity, CD4 cell count and viral RNA, were evaluated in several studies involving HIV-1 infected patients.
L- effetti ta ’ nelfinavir (waħdu jew flimkien ma ’ mediċini antitretrovirali oħra) fuq il- markaturi bijoloġiċi ta ’ l- attività tal- marda, l- għadd taċ- ċelluli CD4 u l- RNA virali, kienu evalwati f’ diversi studji li kienu jinvolvu pazjenti infettati bl- HIV- 1.
The efficacy of the BID regimen has been evaluated versus the TID regimen with VIRACEPT 250 mg tablets primarily in patients naïve to PIs.
13 L- effikaċja tal- kors BID kien evalwat kontra l- kors TID b’ pilloli VIRACEPT 250 mg primarjament f’ pazjenti ġodda għal PIs.
A randomised open-label study compared the HIV RNA suppression of nelfinavir 1250 mg BID versus nelfinavir 750 mg TID in PI naïve patients also receiving stavudine (30-40 mg BID) and lamivudine (150 mg BID).
Studju fejn l- investigatur u s- suġġett kienu jafu xi trattament kien qed jingħata, magħżul bl- addoċċ, ipparaguna s- sopressjoni ta ’ RNA ta ’ HIV ta ’ 1250 mg ta ’ nelfinavir BID kontra 750 mg ta ’ nelfinavir TID f’ pazjenti mhux affettwati minn PIs li kienu qed jirċievu wkoll stavudine (30- 40 mg BID) u lamivudine (150 mg BID).
13 Proportion of patients with HIV RNA below LOQ (sensitive and ultrasensitive assays) at Week 48 Assay
Proporzjon ta ’ pazjenti b’ RNA ta ’ - HIV taħt LOQ (analiżi sensittiva u ultrasensittiva) f’ Ġimgħa 48
Analysis Observed data
Analiżi Analiżi
Sensitive
Sensittiva
LOCF ITT (NC = F) Observed data
Informazzjoni osservata
145/200 (73%) 135/200 (68%) 114/164 (70%)
LOCF ITT (NC = F) Informazzjoni osservata
161/206 (78%) 146/206 (71%) 125/169 (74%)
145/ 200 (73%) 135/ 200 (68%) 114/ 164 (70%)
(-14, +3) (-12, +6) (-14, +5)
161/ 206 (78%) 146/ 206 (71%) 125/ 169 (74%)
Ultrasensitive LOCF= Last observation
(- 14, +3) (- 12, +6) (- 14, +5)
ITT = Intention to Treat NC = F: non-completers = failures
LOCF= L- aħħar osservazzjoni carried forward ITT =Intenzjoni li jrid isir it- trattament NC = F: dawl li ma komplewx = falliment
The BID regimen produced statistically significantly higher peak nelfinavir plasma levels versus the TID regimen.
Il- kors BID ipproduċa livelli massimi tal- plażma ta ’ nelfinavir statistikament sinifikanti meta mqabbel mal- kors TID.
Small, non-statistically significant differences were observed in other pharmacokinetic parameters with no trend favouring one regimen over the other.
Differenzi żgħar u mhux statistikament sinifikanti kienu osservati f’ parametri farmakokinetiċi oħra u ma kien hemm l- ebda tendenza li tiffavorixxi kors wieħed fuq l- ieħor.
Although study 542 showed no statistically significant differences between the two regimens in efficacy in a predominantly antiretroviral naïve patient population, the significance of these findings for antiretroviral experienced patients is unknown.
Għalkemm studju 542 ma wera l- ebda differenzi statistikament sinifikanti bejn iż- żewġ korsijiet fl - effikaċja l- aktar f’ popolazzjoni mhux affettwata mill- antiretrovirali, l- importanza ta ’ dawn ir- riżultati f’ pazjenti b’ esperjenza antiretrovirali mhijiex magħrufa.
In a study of 297 HIV-1 seropositive patients receiving zidovudine and lamivudine plus nelfinavir (2 different doses) or zidovudine and lamivudine alone, the mean baseline CD4 cell count was 288 cells/mm3 and the mean baseline plasma HIV RNA was 5.21 log10 copies/ml (160,394 copies/ml).
(160, 394 kopji/ ml).
The mean decrease in plasma HIV RNA using a PCR assay (< 400 copies/ml) at 24 weeks was 2.33 log10 in patients receiving combination therapy with nelfinavir 750 mg TID, compared to 1.34 log10 in patients receiving zidovudine and lamivudine alone.
It- tnaqqis medjan fil- plażma ta ’ l - RNA ta ’ l- HIV bl- użu ta ’ analiżi tat- tip PCR (< 400 kopji/ ml) fl- 24 ġimgħa kien ta ’ 2. 33 log10 f’ pazjenti li kienu qed jirċievu t- terapija mħallta ma ’ 750 mg ta ’ nelfinavir TID, meta mqabbel ma ’ 1. 34 log10 f’ pazjenti li kienu qed jirċievu zidovudine u lamivudine waħdu.
At 24 weeks, the percentage of patients whose plasma HIV RNA levels had decreased to below the limit of detection of the assay (< 400 copies/ml) were 81% and 8% for the groups treated with nelfinavir 750 mg TID plus zidovudine and lamivudine or zidovudine and lamivudine, respectively.
Fl- 24 ġimgħa, il- perċentaġġ ta ’ pazjenti li l- livelli tal- plażma ta ’ l- RNA ta ’ l- HIV tagħhom kienu naqsu għal taħt il- limitu li jista ’ jkun osservat (< 400 kopji/ ml) kien ta ’ 81% u 8% għall- gruppi ttrattati b’ 750 mg ta ’ nelfinavir TID flimkien ma ’ zidovudine u lamivudine, jew ma ’ zidovudine u lamivudine waħidhom, rispettivament.
Mean CD4 cell counts at 24 weeks were increased by 150 and 95 cells/mm3 for the groups treated with nelfinavir 750 mg TID plus zidovudine and lamivudine or zidovudine and lamivudine, respectively.
L- għadd medju taċ- ċelluli CD4 fl- 24 ġimgħa kien miżjud b’ 150 u b’ 95 ċelluli / mm3 għall- gruppi ttrattati b’ 750 mg ta ’ nelfinavir TID flimkien ma ’ zidovudine u lamivudine, jew ma ’ zidovudine u lamivudine waħidhom, rispettivament.
At 48 weeks, approximately 75% of the patients treated with nelfinavir 750 mg TID plus zidovudine and lamivudine remained below the level of detection of the assay (< 400 copies/ml); mean increase in CD4 cell counts was 198 cells/mm3 at 48 weeks in this group.
Fit- 48 ġimgħa, madwar 75% tal- pazjenti ttrattati b’ 750 mg ta ’ nelfinavir TID flimkien ma ’ zidovudine u lamivudine, baqgħu taħt il- limitu li jista ’ jkun osservat f’ testijiet (< 400 kopji/ ml); iż- żjieda medja fl- għadd taċ- ċelluli CD4 kienet ta ’ 198 ċelluli/ mm3 wara 48 ġimgħa f’ dan il- grupp.
No important differences in safety or tolerability were observed between the BID and TID dosing groups, with the same proportion of patients in each arm experiencing adverse events of any intensity, irrespective of relationship to trial medication.
L- ebda differenzi importanti fis- sigurtà jew fit- tollerabiltà ma kienu osservati bejn il- gruppi bid - dożaġġ BID u TID, bl- istess proporzjon ta ’ pazjenti f’ kull parti tat- trattament li sofrew okkorrenzi avversi ta ’ kwalunkwe intensità, irrispettivament mill- konnessjoni tal- medikazzjoni tal- prova.
Plasma levels of certain HIV-1 protease inhibitors, which are metabolised predominantly by CYP3A4, can be increased by the co-administration of low-dose ritonavir, which is an inhibitor of this metabolism.
Livelli fil- plażma ta ’ ċertu tipi ta ’ inibituri ta ’ HIV- 1 protease, li huma mmetabolizzati primarjament minn CYP3A4, jistgħu jiżdiedu bl- għotja flimkien ta ’ doża baxxa ta ’ ritonavir, li huwa inibitur ta ’ dan il- metaboliżmu.