qanastek/EMEA-V3 huggingface dataset:
Amylase: in the clinical trial subset of 1,008 patients, asymptomatic increases in serum amylase levels greater than 1.5 times the upper limit of normal were seen in 10% of patients treated with efavirenz and 6% of patients treated with control regimens.
72 Amylase: fis- sottogrupp ta ’ 1, 008 pazjenti fil- prova klinika, ġew osservati żidiet asintomatiċi fil- livelli ta ’ serum amylase iktar minn 1. 5 darbiet il- livell ta ’ fuq tan- normal f’ 10% tal- pazjenti kkurati b’ efavirenz u f’ 6% tal- pazjenti f’ kuri ta ’ kontroll.
Antiviral activity: the free concentration of efavirenz required for 90 to 95% inhibition of wild type or zidovudine-resistant laboratory and clinical isolates in vitro ranged from 0.46 to 6.8 nM in lymphoblastoid cell lines, peripheral blood mononuclear cells (PBMCs) and macrophage/ monocyte cultures.
73 Attivita` antivirali: il- konċentrazzjoni ħielsa ta ’ efavirenz li kien hemm bżonn għall- inibizzjoni ta ’ bejn id- 90 u l- 95% ta ’ iżolati wild type jew iżolati tal- laboratorju reżistenti għal zidovudine u iżolati kliniċi in vitro kienet minn 0. 46 sa 6. 8 nM f’ razez ta ’ ċelluli limfoblastojdi, ċelluli periferali mononukleari tad- demm (PBMCs) u kolturi makrofaġi monoċistiċi.
68 isoleucine substitution at position 108 (V108I) in RT.
Ħamsa minn dawn l- iżolati reżistenti għal NNTRIs instabu li kellhom K103N jew sostizzjoni minn- valine- għal- isoleucine fil- pożizzjoni 108 (V108I) fl- RT.
Study 006, a randomized, open-label trial, compared efavirenz + zidovudine + lamivudine or efavirenz + indinavir with indinavir + zidovudine + lamivudine in 1,266 patients who were required to be efavirenz-, lamivudine-, NNRTI-, and PI-naive at study entry.
Studju 006, prova randomized bil- mediċina meħuda magħrufa, qabbel efavirenz + zidovudine + lamivudine jew efavirenz + indinavir ma ’ indinavir + zidovudine + lamivudine f’ 1, 266 pazjent li ma
70 Effect of food: the bioavailability of a single 600 mg dose of efavirenz hard capsules in uninfected volunteers was increased 22% and 17%, respectively, when given with a meal of high fat or normal composition, relative to the bioavailability of a 600 mg dose given under fasted conditions (see section 4.4).
L- effett ta ’ l- ikel: il- biodisponibbilita` ta ’ doża waħda ta ’ kapsuli ibsin ta ’ 600 mg ta ’ efavirenz f’ voluntiera mhux infettati żdiedet minn 22% għal 17% rispettivament, meta mogħti ma ’ ikla b’ livell għoli ta ’ xaħam jew kompożizzjoni normali, meta mqabbel mal- biodisponibbilita` ta ’ doża ta ’ 600 mg mogħtija f’ kondizzjonijiet ta ’ sawm (ara sezzjoni 4. 4).
Biotransformation: studies in humans and in vitro studies using human liver microsomes have demonstrated that efavirenz is principally metabolised by the cytochrome P450 system to hydroxylated metabolites with subsequent glucuronidation of these hydroxylated metabolites.
Bijotrasformazzjoni: studji fil- bnedmin u studji in vitro bil- mikrosomi tal- fwied uman urew li efavirenz l- iktar li jkun metabolizzat bis- sistema cytochrome P450 f’ metaboliti idrossilati li wara
Carcinogenicity studies in male mice, male and female rats were negative.
77 Studji dwar ir- riskju ta ’ kanċer fi ġrieden irġiel, u f’ firien irġiel u nisa huma negattivi.
Capsule shell Gelatine Sodium laurilsulfate Yellow iron oxide (E172) Silicon dioxide (E551)
Il- qoxra tal- kapsula Ġelatina Sodium laurilsulfate Iron oxide isfar (E172) Silicon dioxide (E551)
72 6.5 Nature and content of container
6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
Packs of 42 x 1 hard capsules in aluminium/ PVC perforated unit dose blisters.
Pakki bil- folji ta ’ l- aluminjum bi 42 kapsula iebsa.
EU/ 1/ 99/ 110/ 003 - bottle EU/ 1/ 99/ 110/ 004 - blister
EU/ 1/ 99/ 110/ 003 - flixkun EU/ 1/ 99/ 110/ 004 - folja
SUSTIVA 30 mg/ ml oral solution
SUSTIVA 30 mg/ ml soluzzjoni orali
Each ml contains 30 mg of efavirenz
Kull ml fiha 30 mg ta ’ efavirenz
Colourless to slightly yellow clear liquid.
Likwidu ċar li jvarja bejn bla kulur għal isfar ċar.
SUSTIVA oral solution is indicated in antiviral combination treatment of human immunodeficiency virus-1 (HIV-1) infected adults, adolescents and children 3 years of age and older, who are unable to swallow the hard capsules or the film-coated tablets.
4. 1 Indikazzjonijiet terapewtiċi
SUSTIVA oral solution may be taken with or without food (see section 5.2).
SUSTIVA soluzzjoni orali jista ’ jittieħed ma ’ l- ikel jew mingħajr ikel (ara sezzjoni 5. 2).
Adults: the recommended dosage of SUSTIVA in combination with nucleoside analogue reverse transcriptase inhibitors (NRTIs) with or without a PI (see section 4.5) is 24 ml orally, once daily.
Id- doża rakkomandata ta ’ SUSTIVA flimkien ma ’ nucleoside analogue reverse transcriptase inhibitors (NRTIs) flimkien ma ’ PIs jew mingħajrhom (ara sezzjoni 4. 5) hija ta ’ 24 ml mill- ħalq, darba kuljum.
Paediatric patients (3 to 17 years): the recommended dose of SUSTIVA oral solution in combination with a PI and/ or NRTIs for patients between 3 and 17 years of age is described in Table 1.
Pazjenti pedjatriċi (minn 3 sa 17- il sena): id- doża rakkomandata ta ’ SUSTIVA soluzzjoni orali flimkien ma ’ PI u/ jew NRTIs għal pazjenti bejn it- 3 u s- 17- il sena hija deskritta f’ Tabella 1.
SUSTIVA hard capsules or film-coated tablets must only be administered to children who are able to reliably swallow capsules or tablets.
Il- kapsuli ibsin jew pinnoli miksijin b’ rota ta ’ SUSTIVA għandhom jinghataw biss lit- tfal li żgur jistgħu jibilgħu l- kapsuli ibsin jew pinnoli b’ rita.
SUSTIVA is not recommended for use in children below the age of 3 years or weighing less than 13 kg due to a lack of data on safety and efficacy in that age group (see sections 5.1 and 5.2).
SUSTIVA mhux rakkomandat għal pazjenti taħt l- eta` tat- 3 snin jew li jiżnu inqas minn 13- il kg minħabba n- nuqqas ta ’ tagħrif dwar is- sigurtà u l- effikaċja f’ dan il- grupp (ara sezzjonijiet 5. 1 u 5. 2).
74 Table 1 Paediatric dose of SUSTIVA oral solution to be administered once daily
80 Tabella 1 Doża pedjatrika ta ’ soluzzjoni orali ta ’ SUSTIVA li għandha tingħata darba kuljum
Body Weight kg
Piż tal- ġisem kg
SUSTIVA oral solution (30 mg/ ml) Dose (ml)
SUSTIVA soluzzjoni orali (30 mg/ ml) Doża (ml)
Adults and children aged 5 years or more
Adulti 5 snin
SUSTIVA oral solution is less bioavailable than the hard capsule on a mg per mg basis.
SUSTIVA soluzzjoni orali hija inqas biodisponibbli mill- kapsula iebsa fuq bażi ta ’ tqabbil ta ’ mg ma ’ mg.
Alternative method of administration:
Metodu alternattiv tal- għoti: is- soluzzjoni orali SUSTIVA hija l- formulazzjoni ppreferuta għal pazjenti li ma jistgħux jibilgħu l- kapsuli iebsin b’ mod affidabbli.
SUSTIVA oral solution is the preferred formulation for patients who cannot reliably swallow capsules or tablets.
Għoti tal- kontenut tal- kapsuli ma ’ ammont żgħir ta ’ ikel (eż.
Administration of the capsule contents with a small amount (1-2 teaspoons) of food may be considered for patients who cannot tolerate the oral solution (see Table 2 and the Summary of Product Characteristics for SUSTIVA hard capsules).
1- 2 kuċċarini) ta ’ ikel jista ’ jiġi kkunsidrat għal pazjenti li ma jistgħux jittolleraw is- soluzzjoni orali.
In a palatability study in healthy adults of efavirenz mixed with applesauce, grape jelly, yogurt, or infant formula, grape jelly received the highest rating of good overall taste.
Fi studju tal- palatabilità f’ adulti b’ saħħithom ta ’ efavirenz imħallat mal - meraq tat- tuffieħ, jelly ta ’ l- għeneb, jogurt jew ħalib tat- trabi, il- jelly ta ’ l- għeneb irċieva l- ogħla punteġġ ta ’ l- aktar togħma tajba in ġenerali.
Patients and caregivers must be instructed to open the capsule carefully to avoid spillage or dispersion of the capsule contents into the air.
Il- pazjenti u dawk li jieħdu ħsieb it- tfal għandhom jiġu avżati biex jiftħu l- kapsula b’ attenzjoni biex jevitaw tifrigħ jew tixrid tal- kontenut tal- kapsula fl- arja.
After administration of the efavirenz-food mixture, an additional small amount (approximately 2 teaspoons) of food must be added to the empty mixing container, stirred to disperse any remaining residue of the medicinal product, and administered to the patient.
Wara l- għoti tat- taħlita efavirenz- ikel, ammont żgħir addizzjonali (madwar 2 kuċċarini) ta ’ ikel għandu jiżdied fir- reċipjent tat- taħlit il- vojt, jiġi mħawwad sabiex idub kwalunkwe residwu tal- mediċina, u din għanda tingħata lill- pazjent.
Table 2 Paediatric dose of SUSTIVA hard capsules to be administered once daily*
Tabella 2 Doża pedjatrika ta ’ SUSTIVA li għandha tingħata darba kuljum *
Body Weight kg 13 to < 15 15 to < 20 20 to < 25 25 to < 32.5 32.5 to < 40 ≥ 40
Piż tal- Ġisem kg 13 sa < 15 15 sa < 20 20 sa < 25 25 sa < 32. 5 32. 5 sa < 40 ≥ 40
If SUSTIVA is coadministered with rifampicin, an increase in the dose of SUSTIVA to 800 mg/ day may be considered (see section 4.5).
81 Jekk SUSTIVA jingħata flimkien ma ’ rifampicin, tista ’ tiġi kkunsidrata żieda fid- doża ta ’ SUSTIVA għal 800 mg/ kuljum (ara sezzjoni 4. 5).
75 Renal impairment: the pharmacokinetics of efavirenz have not been studied in patients with renal insufficiency; however, less than 1% of an efavirenz dose is excreted unchanged in the urine, so the impact of renal impairment on efavirenz elimination should be minimal (see section 4.4).
(ara sezzjoni 4. 4).
Rash: mild-to-moderate rash has been reported in clinical studies with efavirenz and usually resolves with continued therapy.
82 Raxx: ġie rraportat raxx minn ħafif sa moderat fi studju kliniċi b’ efavirenz, u s- soltu jgħaddi mat - tkomplija tat- terapija.
76 interrupting therapy with other antiretroviral agents to avoid development of resistant virus (see section 4.8).
Jekk titwaqqaf it- terapija b’ efavirenz, għandha titqies il- possibilita` li tiġi interrotta t- terapija b’ aġenti antiretrovirali oħra biex ma jiżviluppax virus reżistenti (ara sezzjoni 4. 8).
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 ġie assoċjat ma ’ fatturi individwali bħal eta` ikbar, u ma ’ fatturi marbuta mal- mediċina bħalm’ hu tul tal- kura
Osteonecrosis: although the etiology 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
Ostjonekrożi: għalkemm l- etjoloġija titqies li għandha għadd ta ’ fatturi (inklużi użu ta ’ kortikosterojdi, konsum ta ’ l- alkoħol, immunosoppressjoni qawwija, indiċi ogħla tal- massa tal- ġisem), ġew irrappurtati każijiet ta ’ ostjonekrożi speċjalment f’ pazjenti b’ mard avvanzat ta ’ l- HIV u/ jew esponiment fit- tul għat- terapija antiretrovirali kombinata (CART).
Efavirenz exposure may also be altered when given with medicinal products or food (for example, grapefruit juice) which affect CYP3A4 activity.
84 tinbidel meta jingħata ma ’ prodotti mediċinali jew ikel (ngħidu aħna, meraq tal- grejpfrut) li jista ’ jaffettwa l- attivita` ta ’ CYP3A4.
John’ s wort, check
John’ s wort, waqqaf St.
78 viral levels and if possible efavirenz levels.
John’ s wort, iċċekkja l- livelli virali u jekk possibbli l- livelli ta ’ efavirenz.
Other interactions Interactions between efavirenz and protease inhibitors, antiretroviral agents other than protease inhibitors and other non-antiretroviral medicinal products are listed in Table 3 below (increase is indicated as “↑”, decrease as “↓”, no change as “↔”, and once every 8 or 12 hours as “ q8h” or “ q12h”).
Interazzjonijiet oħra L- interazzjonijiet bejn efavirenz u l- inibituri protease, sustanzi antiretrovirali li mhumiex inibituri protease u prodotti mediċinali oħra li mhumiex anti- retrovirali huma elenkati f’ Tabella 2 hawn isfel (żieda hija indikata bħala “ ↑ ”, tnaqqis bħala “ ↓ ”, ebda bidla bħala “ ↔ ”, u darba kull 8 jew 12- il siegħa bħala “ q8h ” jew “ q12h ”).
Table 3:
Tabella 2:
(400 mg once daily/ 100 mg once daily/ 600 mg once daily, all administered with food)
Atazanavir/ ritonavir/ Efavirenz (400 mg darba kuljum/ 100 mg darba kuljum/ 600 mg darba kuljum, kollha mogħtija mal- ikel)
with atazanavir/ ritonavir is not recommended.
L- għoti fl- istess ħin ta ’ efavirenz ma ’ atazanavir/ ritonavir mhuwiex rakkomandat.
Medicinal product by
Indinavir/ Efavirenz (800 mg q8h/ 200 mg darba kuljum)
Recommendation concerning
Filwaqt li ma ġiex stabbilit is - sinifikat kliniku ta ’ konċentrazzjonijiet imnaqqsa ta ’ indinavir, għandu jiġi kkunsidrat id- daqs ta ’ l- interazzjoni farmakokinetika osservata meta
Indinavir/ Efavirenz (800 mg q8h/ 200 mg once daily)
Indinavir/ Ritonavir/ Efavirenz (800 mg darbtejn kuljum/ 100 mg
(CYP3A4 induction) Efavirenz:
AUC: ↓ 25% (↓ 16 għal ↓ 32) b
No dosage adjustment is
Ara wkoll ir- ringiela dwar ritonavir
No clinically significant pharmacokinetic interaction The geometric mean Cmin for indinavir (0.33 mg/ l) when given with
Ebda interazzjoni farmakokinetika klinikament sinifikanti Il- Cmin ġeometrika medja għal indinavir (0. 33 mg/ l) meta ngħata ma ’ ritonavir u efavirenz kienet ogħla mill- Cmin storika medja (0. 15 mg/ l) meta indinavir ingħata waħdu f’ doża ta ’ 800 mg q8h.
necessary for efavirenz when given with indinavir or indinavir/ ritonavir.
F’ pazjenti infettati bl- HIV- 1 (n = 6), il- farmakokinetiċi ta ’ indinavir u efavirenz kienu ġeneralment komparabbli ma ’ din id- dejta dwar voluntiera mhux infettati.
ritonavir and efavirenz was higher than the mean historical Cmin (0.15 mg/ l) when indinavir was given alone at 800 mg q8h.
86 Prodott mediċinali skond l- oqsma terapewtiċi (doża)
In HIV-1 infected patients (n = 6), the pharmacokinetics of indinavir and efavirenz were generally comparable to these uninfected volunteer data.
Effetti fuq il- livelli tal- mediċina Bidla perċentwali medja fl - AUC, Cmax, Cmin bl- intervalli ta ’ kunfidenza jekk disponibblia (mekkaniżmu)
See also ritonavir row below.
Rakkomandazzjoni rigward l - għoti fl- istess ħin ma ’ efavirenz
Lopinavir concentrations: similar to lopinavir/ ritonavir 400/ 100 mg twice daily without efavirenz
Hija meħtieġa kawtela billi dan l- aġġustament fid- doża jista ’ ma jkunx suffiċjenti f’ xi pazjenti.
since this dosage adjustment might be insufficient in some patients The dosage of lopinavir/ ritonavir tablets should be increased to 500/ 125 mg twice daily when co-administered with efavirenz 600 mg once daily. See also ritonavir row below.
Ara wkoll ir- ringiela dwar ritonavir hawn isfel.
Raltegravir/ Efavirenz (400 mg single dose/ -) NRTIs and NNRTIs
Inibitur ta ’ trasferiment ta ’ faxxa ta ’ integrase Raltegravir/ Efavirenz (400 mg doża waħda / -) NRTIs u NNRTIs
Other macrolide antibiotics (e. g. ,erythromycin)/ Efavirenz Antimycobacterials
Antibijotiċi makrolidi oħrajn (e. ż., erythromycin) / Efavirenz
Aluminium hydroxide-magnesium hydroxide-simethicone antacid/ Efavirenz (30 ml single dose/ 400 mg single dose) Famotidine/ Efavirenz (40 mg single dose/ 400 mg single dose) ANTIANXIETY AGENTS
Aluminium hydroxide- magnesium hydroxide- simethicone antacid/ Efavirenz (30 mL doża waħda/ 400 mg doża waħda) Famotidine/ Efavirenz (40 ng doża waħda/ 400 mg doża waħda) SUSTANZI KONTRA L- ANSJETÀ
therapeutic areas (dose)
90 Prodott mediċinali skond l- oqsma terapewtiċi (doża) ANTIKONVULSIVI
Selective Serotonin Reuptake Inhibitors (SSRIs) Sertraline/ Efavirenz (50 mg once daily/ 600 mg once daily)
Sertraline/ Efavirenz (50 mg darba kuljum/ 600 mg darba kuljum)
Paroxetine/ Efavirenz (20 mg once daily/ 600 mg once daily)
91 Prodott mediċinali skond l- oqsma terapewtiċi (doża)
Effects on drug levels
Effetti fuq il- livelli tal- mediċina Bidla perċentwali medja fl -
therapeutic areas (dose)
AUC, Cmax, Cmin bl- intervalli ta ’ kunfidenza jekk disponibblia (mekkaniżmu) Paroxetine/ Efavirenz (20 mg darba kuljum/ 600 mg darba kuljum)
Medicinal product by
92 Prodott mediċinali skond l- oqsma
Dosage adjustment of atorvastatin may be required (refer to the Summary of Product Characteristics for atorvastatin.
Jistgħu jkunu meħtieġa aġġustamenti fid- doża ta ’ atorvastatini (irreferi għas - Sommarju tal- Karatteristiċi tal - Prodott għall- atorvastatin).
Rosuvastatin/ Efavirenz
93 Prodott mediċinali skond l- oqsma terapewtiċi (doża)
Ethinyloestradiol/ Efavirenz (50 µg single dose/ 400 mg once daily) IMMUNOSUPPRESSANTS
KONTRAĊETTIVI ORMONALI Ethinyloestradiol/ Efavirenz (50 µg doża waħda/ 400 mg darba kuljum) IMMUNOSUPPRESSANTI
87 Pregnancy: there are limited amount of data from the use of efavirenz in pregnant women.
Tqala: jeżisti ammont limitat ta ’ dejta mill- użu ta ’ efavirenz f’ nisa tqal.
In a subset of 1,008 adult patients who received 600 mg efavirenz daily in combination with PIs and/ or NRTIs in controlled clinical studies, the most frequently reported adverse reactions of at least moderate severity reported in at least 5% of patients were rash (11.6%), dizziness (8.5%), nausea (8.0%), headache (5.7%) and fatigue (5.5%).
Ir- reazzjonijiet avversi
The most notable adverse reactions associated with efavirenz are rash and nervous system symptoms (see section 4.4).
95 marbuta ma ’ efavirenz li kienu l- iktar prominenti kienu raxx u sintomi tas- sistema nervuża (ara sezzjoni 4. 4).
88 average of 1.6 years and 635 patients treated with control regimens for an average of 1.3 years, the frequency of specific serious psychiatric events are detailed hereafter:
- depressjoni severa - ideat suwiċidali - attentati mhux fatali ta ’ suwiċidju - mġieba aggressiva - reazzjonijiet paranojdi - reazzjonijiet manijaċi
In one clinical study, the monthly prevalence of nervous system symptoms of at least moderate severity between weeks 4 and 48, ranged from 5% - 9% in patients treated with regimens containing efavirenz and 3% - 5% in patients treated with the control regimen.
96 sa 9% f’ pazjenti li kellhom kura li kien fiha efavirenz u minn 3% sa 5% f’ pazjenti li kellhom kura ta ’ kontroll.
89 Eye disorders uncommon
Disturbi fl- għajnejn mhux komuni
Hepatobiliary disorders uncommon
97 Disturbi fil- fwied u fil- marrara mhux komuni
90 Laboratory test abnormalities:
Anormalitajiet f’ testijiet tal- laboratorju:
Among co-infected patients, 3% of those treated with efavirenz -containing regimens and 2% in the control arm discontinued from the study because of liver or biliary system disorders.
Fost il- pazjenti infettati bit- tnejn, 3% minn dawk li kienu taħt kuri li kien fihom efavirenz u 2% fil- parti ta ’ kontroll ta ’ l- istudju ma komplewx l- istudju minħabba mard fil- fwied jew fis- sistema biljari.
Amylase: in the clinical trial subset of 1,008 patients, asymptomatic increases in serum amylase levels greater than 1.5 times the upper limit of normal were seen in 10% of patients treated with efavirenz and 6% of patients treated with control regimens.
98 Amylase: fis- sottogrupp ta ’ 1, 008 pazjenti fil- prova klinika, ġew osservati żidiet asintomatiċi fil- livelli ta ’ serum amylase iktar minn 1. 5 darbiet il- livell ta ’ fuq tan- normal f’ 10% tal- pazjenti kkurati b’ efavirenz u f’ 6% tal- pazjenti f’ kuri ta ’ kontroll.
Diarrhoea occurred in six of nineteen (32%) children, aged 3 - 8 years, who took efavirenz oral solution in combination with nelfinavir (20 - 30 mg/ kg given three times a day) and one or more NRTIs.
Dijarrea seħħet f’ sitta minn dsattax (32%) tfal, eta ’ 3 – 8 snin, li ħadu soluzzjoni orali ta ’ efavirenz ikkombinat ma ’ nelfinavir (20 - 30 mg/ kg mogħti tlett darbiet kuljum) u wieħed jew aktar NRTIs.
Antiviral activity: the free concentration of efavirenz required for 90 to 95% inhibition of wild type or zidovudine-resistant laboratory and clinical isolates in vitro ranged from 0.46 to 6.8 nM in lymphoblastoid cell lines, peripheral blood mononuclear cells (PBMCs) and macrophage/ monocyte cultures.
99 Attivita` antivirali: il- konċentrazzjoni ħielsa ta ’ efavirenz li kien hemm bżonn għall- inibizzjoni ta ’ bejn id- 90 u l- 95% ta ’ iżolati wild type jew iżolati tal- laboratorju reżistenti għal zidovudine u iżolati kliniċi in vitro kienet minn 0. 46 sa 6. 8 nM f’ razez ta ’ ċelluli limfoblastojdi, ċelluli periferali mononukleari tad- demm (PBMCs) u kolturi makrofaġi monoċistiċi.
Thirteen
L- iżolati virali li ttieħdu mill- PBMCs tal- pazjenti li kienu fl- istudji kliniċi ta ’ efavirenz li kienu juru evidenza ta ’ falliment fil- kura (tkattir mill- ġdid tan- numru tal- virus) kienu eżaminati għas - suxxettibilita` għal NNRTIs.
92 isolates previously characterised as efavirenz-resistant were also resistant to nevirapine and delavirdine.
Tlettax- il iżolat li qabel kienu karatterizzati bħala reżistenti għal efavirenz kienu reżistenti wkoll għal nevirapine u delavirdine.
Study 006, a randomized, open-label trial, compared efavirenz + zidovudine + lamivudine or efavirenz + indinavir with indinavir + zidovudine + lamivudine in 1,266 patients who were required to be efavirenz-, lamivudine-, NNRTI-, and PI-naive at study entry.
100 Studju 006, prova randomized bil- mediċina meħuda magħrufa, qabbel efavirenz + zidovudine + lamivudine jew efavirenz + indinavir ma ’ indinavir + zidovudine + lamivudine f’ 1, 266 pazjent li ma setgħux kienu ħadu efavirenz, lamivudine, NNRTI, jew PI meta daħlu fl- istudju.
Efficacy results for study 006 on a subset of 614 patients who had been enrolled for at least 48 weeks are found in Table 4.
Ir- riżultati ta ’ l- effikaċja għal studju 006 għal sottogrupp ta ’ 614- il pazjent li kienu fl- istduju mill- inqas għal 48 ġimgħa jinstabu f’ Tabella 4.
93 Long-term results at 168 weeks of study 006 (160 patients completed study on treatment with EFV+IDV, 196 patients with EFV+ZDV+3TC and 127 patients with IDV+ZDV+3TC, respectively), suggest durability of response in terms of proportions of patients with HIV RNA < 400 copies/ ml, HIV RNA < 50 copies/ ml and in terms of mean change from baseline CD4 cell count.
Riżultati fit- tul mal- 168 ġimgħa ta ’ l- istudju 006 (160 pazjent spiċċaw l- istudju bil- kura b’ EFV +IDV, 196 pazjent b’ EFV + ZDV + 3TC u 127 pazjent b’ IDV + ZDV + 3TC, rispettivament), jissuġġerixxu li r- rispons ma jisfaxxax fix- xejn, fis- sens tal- proporzjoni ta ’ pazenti b’ HIV RNA < 400 kopji/ ml, HIV RNA < 50 kopji/ ml u fis- sens tal- bidla medja mil- linja bażi CD4 ta ’ l- għadd taċ- ċelluli.
Efficacy results for studies ACTG 364 and 020 are found in Table 5.
Studji dwar l- effikaċja għall- istudji ACTG 364 u 020 jinstabu f’ Tabella 5.
In 35 patients receiving efavirenz 600 mg once daily, steady
F’ 35 pazjent li kienu qed jirċievu 600 mg ta ’ efavirenz darba kuljum, Cmax fiss kien 12. 9 ± 3. 7 μM (29%) [medja ± S. D.
In uninfected adult volunteers, the Cmax and AUC of a 240 mg dose of SUSTIVA oral solution were 78% and 97%, respectively, of the values measured when SUSTIVA was given as a 200 mg hard capsule.
F’ voluntiera adulti mhux infettati, Cmax u AUC ta ’ doża ta ’ 240 mg ta ’ SUSTIVA soluzzjoni orali kienu 78% u 97%, rispettivament, tal- valuri mkejla meta SUSTIVA ngħata bħala kapsula iebsa tal- 200 mg.
Effect of food: the AUC and Cmax of a single 240 mg dose of efavirenz oral solution in uninfected adult volunteers was increased by 30% and 43%, respectively, when given with a high-fat meal, relative to fasted conditions.
AUC u Cmax ta ’ doża waħda ta ’ 240 mg ta ’ efavirenz soluzzjoni orali f’ voluntiera mhux infettati żdiedet bi 30% u 43% rispettivament, meta mogħti ma ’ ikla b’ livell għoli ta ’ xaħam, meta mqabbel ma ’ kondizzjonijiet ta ’ sawm.
Bioavailability of hard capsule contents mixed with food vehicles:
Il- bijodisponibbiltà tal- kontenut tal- kapsuli iebsin ma ’ sustanzi li fihom l- ikel:
In healthy adult subjects, the efavirenz AUC when administered as the contents of three 200 mg hard capsules mixed with 2 teaspoons of certain food vehicles (applesauce, grape jelly, yogurt or infant formula) met bioequivalency criteria for the AUC of the intact capsule formulation administered under fasted conditions.
F’ suġġetti adulti b’ saħħithom, l- AUC ta ’ efavirenz meta mogħti bħala l- kontent ta ’ tliet kapsuli iebsin ta ’ 200 mg imħalltin ma ’ 2 kuċċarini ta ’ ċerti sustanzi li fihom l- ikel (meraq tat- tuffieħ, jelly tal- għeneb, jogurt jew ħalib tat- trabi) issodisfa l- kriterji ta ’ bijoekwivalenza għall- AUC tal- formula tal- kapsula intatta mogħtija taħt kundizzjonijiet ta ’ sawm.
In HIV-1 infected patients (n = 9) who received efavirenz 200 to 600 mg once daily for at least one month, cerebrospinal fluid concentrations ranged from 0.26 to 1.19% (mean 0.69%) of the corresponding plasma concentration.
Dan il- proporzjon
This proportion is approximately 3-fold higher than the non-protein-bound (free) fraction of efavirenz in plasma.
102 huwa bejn wieħed u ieħor 3 darbiet ogħla mill- frazzjoni mhux marbuta mal- proteina (ħielsa) ta ’ efavirenz fil- plażma.
Therefore, the
Fi grupp ta ’ sitta minn dawn it- tfal li kellhom bejn 3 u 5 snin u li kienu qed jieħdu l- kura b’ mod regolari, il- medja ta ’ AUC kienet ta ’ 147 μM· h, li kien 23% inqas milli mistenni.
95 dosage recommendation provided in Table 1 incorporates a higher dose of efavirenz oral solution for these younger children.
Għalhekk, ir- rakkomandazzjoni tad- doża pprovduta f’ Tabella 1 tinkorpora doża ogħla ta ’ efevirenz soluzzjoni orali għal dan it- tfal li huma iżgħar.
Biliary hyperplasia was observed in cynomolgus monkeys given efavirenz for ≥ 1 year at a dose resulting in mean AUC values approximately 2-fold greater than those in humans given the recommended dose.
103 Ġiet osservata iperplażja biljarja f’ xadini cynomolgus li kienu mogħtija efavirenz għal ≥ sena b’ doża li wasslet għal valuri medji ta ’ AUC bejn wieħed u ieħor darbtejn ikbar minn dawk tal- bnedmin li ngħataw id- doza rakkomandata.
Medium chain triglycerides Benzoic acid (E210) Strawberry/ mint flavour
Medium chain triglycerides Benzoic acid (E210) Togħma ta ’ frawli/ menta.
96 6.5 Nature and content of container
6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
EU/ 1/ 99/ 110/ 005 - bottle
EU/ 1/ 99/ 110/ 005 - flixkun
SUSTIVA 600 mg film-coated tablets
SUSTIVA 600 mg pilloli miksija b’ rita
Dark yellow, capsule-shaped, printed with “ SUSTIVA” on both sides.
Pillola safra skura, b ’ ” SUSTIVA ” stampata fuq iż- żewġ naħat.
The increased efavirenz concentrations observed following administration of SUSTIVA with food may lead to an increase in frequency of adverse reactions (see sections 4.4 and 5.2).
(ara sezzjonijiet 4. 4 u 5. 2).
Adults and adolescents over 40 kg: the recommended dosage of SUSTIVA in combination with nucleoside analogue reverse transcriptase inhibitors (NRTIs) with or without a PI (see section 4.5) is 600 mg orally, once daily.
Adulti u adoloxxenti ’ l fuq minn 40 kg: id- doża rakkomandata ta ’ SUSTIVA flimkien ma ’ nucleoside analogue reverse transcriptase inhibitors (NRTIs) flimkien ma ’ PIs jew mingħajrhom (ara sezzjoni 4. 5) hija ta ’ 600 mg kuljum, darba kuljum.
Efavirenz film-coated tablets are not suitable for children weighing less than 40 kg.
Il- pilloli miksija efavirenz mhumiex tajbin għal tfal li jiżnu inqas minn 40 kg.
Efavirenz hard capsules are available for these patients.
Dawn il- pazjenti jistgħu jieħdu Efavirenz kapsuli ibsin.
If SUSTIVA is coadministered with voriconazole, the voriconazole maintenance dose must be increased to 400 mg every 12 hours and the SUSTIVA dose must be reduced by 50%, i. e., to 300 mg once daily.
106 Aġġustament fid- dożaġġ: jekk SUSTIVA jingħata flimkien ma ’ voriconazole, id- doża ta ’ manteniment ta ’ voriconazole għandha tiżdied sa 400 mg kull 12- il siegħa u d- doża ta ’ SUSTIVA għandha titnaqqas b’ 50%, jiġifieri għal 300 mg darba kuljum.
John's wort (Hypericum perforatum) must not be used while taking efavirenz due to the risk of decreased plasma concentrations and reduced clinical effects of efavirenz (see section 4.5).
Waqt li qed jintuża efavirenz m’ għandhomx jintużaw preparazzjonijiet ta ’ ħxejjex li fihom il- fexfiex tar- raba ’ (Hypericum perforatum) minħabba li joktor ir- riskju ta ’ konċentrazzjonijiet imnaqqsa fil - plażma u ta ’ effetti kliniċi mnaqqsa ta ’ efavirenz (ara sezzjoni 4. 5).
The antiretroviral medicinal products should be restarted at the same time upon resolution of the intolerance symptoms.
Il- prodotti mediċinali antiretrovirali għandhom jerġgħu jibdew jittieħdu fl- istess ħin
99 Rash: mild-to-moderate rash has been reported in clinical studies with efavirenz and usually resolves with continued therapy.
Ġie rraportat raxx minn ħafif sa moderat fi studju kliniċi b’ efavirenz, u s- soltu jgħaddi mat - tkomplija tat- terapija.
Psychiatric symptoms: psychiatric adverse reactions have been reported in patients treated with efavirenz.
Sintomi Psikjatriċi: f’ pazjenti kkurati b’ efavirenz ġew irrapurtati reazzjonijiet avversi psikjatriċi.
Nervous system symptoms: symptoms including, but not limited to, dizziness, insomnia, somnolence, impaired concentration and abnormal dreaming are frequently reported undesirable effects in patients receiving efavirenz 600 mg daily in clinical studies (see section 4.8).
Sintomi fis- sistema nervuża: f’ pazjenti li kienu qed jieħdu 600 mg ta ’ efavirenz kuljum fi studji kliniċi ġew irrapurati b’ mod frekwenti sintomi li jinkludu, imma mhux limitati għal, sturdament, nuqqas ta ’ rqad, ngħas, diffikulta` ta ’ konċentrazzjoni u ħolm mhux normali (are sezzjoni 4. 8).
Effect of food: the administration of SUSTIVA with food may increase efavirenz exposure (see section 5.2) and may lead to an increase in the frequency of adverse reactions (see section 4.8).
Effett ta ’ l- ikel: l - għoti ta ’ SUSTIVA ma ’ l- ikel jista ’ jkabbar l- esponiment għal efavirenz (ara sezzjoni 5. 2) u jista ’ jwassal għal żieda fil- frekwenza ta ’ effetti mhux mixtieqa.
Relevant examples are cytomegalovirus retinitis, generalised and/ or focal mycobacterial infections, and pneumonia caused by Pneumocystis jiroveci (formerly known as Pneumocystis carinii).
108 jiroveci (li qabel kien magħruf bħala Pneumocystis carinii).
A connection
M’ hemmx għarfien sħiħ ta ’ dan il- mekkaniżmu.
100 between visceral lipomatosis and PIs and lipoatrophy and NRTIs has been hypothesised.
Ġiet ipotiżżata konnessjoni bejn lipomatożi vixxerali u PIs u lipoatrofija u NRTIs.
Elderly patients: insufficient numbers of elderly patients have been evaluated in clinical studies to determine whether they respond differently than younger patients.
Pazjenti anzjani ma kienx hemm biżżejjed pazjenti anzjani li ġew evalwati fi studji kliniċi biex jiġi determinat jekk jirrispondux b’ mod differenti minn pazjenti iżgħar.
Paediatric patients: efavirenz has not been evaluated in children below 3 years of age or who weigh less than 13 kg.
Pazjenti pedjatriċi:: efavirenz ma ġiex evalwat fi tfal taħt it- 3 snin jew li jiżnu inqas minn 13 kg.
Lactose: patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
109 Lactose: pazjenti bi problemi ereditarji rari ta ’ intolleranza ta ’ galactose, defiċjenza ta ’ Lapp lactase jew assorbiment ħażin ta ’ glucose- galactose m’ għandhomx jieħdu dan il- prodott mediċinali.
101 concentrations when co-administered with efavirenz.
Komposti oħra li huma substrati ta ’ CYP3A4 jista ’ jkollhom konċentrazzjonijiet imnaqqsa tal- plażma meta jingħataw flimkien ma ’ efavirenz.
Other interactions Interactions between efavirenz and protease inhibitors, antiretroviral agents other than protease inhibitors and other non-antiretroviral medicinal products are listed in Table 1 below (increase is indicated as “↑”, decrease as “↓”, no change as “↔”, and once every 8 or 12 hours as “ q8h” or “ q12h”).
Interazzjonijiet oħra L- interazzjonijiet bejn efavirenz u l- inibituri protease, sustanzi antiretrovirali li mhumiex inibituri protease u prodotti mediċinali oħra li mhumiex anti- retrovirali huma elenkati f’ Tabella 2 hawn isfel (żieda hija indikata bħala “ ↑ ”, tnaqqis bħala “ ↓ ”, ebda bidla bħala “ ↔ ”, u darba kull 8 jew 12- il siegħa bħala “ q8h ” jew “ q12h ”).
Table 1:
Tabella 2:
AUC: ↓ 31% (↓ 8 to ↓ 47) Cmin: ↓ 40% A similar reduction in indinavir exposures was observed when indinavir 1000 mg q8h was given with efavirenz 600 mg daily.
AUC: ↓ 31% (↓ 8 għal ↓ 47) Cmin: ↓ 40% Tnaqqis simili fl- espożizzjonijiet għal indinavir ġew osservati meta indinavir 1. 000 mg q8h ingħata
(CYP3A4 induction) Efavirenz:
flimkien ma ’ efavirenz 600 mg kuljum Efavirenz:
No clinically significant
Ebda interazzjoni farmakokinetika klinikament sinifikanti
While the clinical significance of decreased indinavir concentrations has not been established, the magnitude of the observed pharmacokinetic interaction should be taken into consideration when choosing a regimen containing both efavirenz and indinavir.
M’ hemmx bżonn ta ’ aġġustament fid- doża għal efavirenz meta jingħata ma ’ indinavir jew
pharmacokinetic interaction
111 Prodott mediċinali skond l- oqsma terapewtiċi (doża)
No dosage adjustment is
Rakkomandazzjoni rigward l - għoti fl- istess ħin ma ’ efavirenz
AUC: ↓ 25% (↓ 16 to ↓ 32) b Cmax: ↓ 17% (↓ 6 to ↓ 26)b Cmin: ↓ 50% (↓ 40 to ↓ 59)b Efavirenz:
AUC: ↓ 25% (↓ 16 għal ↓ 32) b
necessary for efavirenz when given with indinavir or indinavir/ ritonavir.
indinavir/ ritonavir.
ritonavir and efavirenz was higher than the mean historical Cmin (0.15 mg/ l) when indinavir was given alone at 800 mg q8h.
(800 mg darbtejn kuljum/ 100 mg
See also ritonavir row below.
Cmax: ↓ 17% (↓ 6 għal ↓ 26) b
Recommendation concerning
Ara wkoll ir- ringiela dwar ritonavir
therapeutic areas (dose)
darbtejn kuljum/ 600 mg darba kuljum)
Mean percent change in AUC, Cmax, Cmin with confidence intervals if availablea (mechanism)
Cmin: ↓ 50% (↓ 40 għal ↓ 59) b Efavirenz:
co-administration with efavirenz
hawn isfel.
by 33% should be considered (4 capsules/ ~6.5 ml twice daily instead of 3 capsules/ 5 ml twice
(4 kapsuli/ ~6. 5 ml darbtejn kuljum minflok 3 kapsuli/ 5 ml darbtejn kuljum).
Caution is warranted since this dosage adjustment
Hija meħtieġa kawtela billi dan l- aġġustament fid- doża jista ’ ma jkunx suffiċjenti f’ xi pazjenti.
Other macrolide antibiotics (e. g. ,erythromycin)/ Efavirenz
Antibijotiċi makrolidi oħrajn (e. ż., erythromycin) / Efavirenz Antimikobatteriċi
therapeutic areas (dose)
Rifabutin/ Efavirenz (300 mg darba kuljum/ 600 mg darba kuljum)
therapeutic areas (dose)
115 Prodott mediċinali skond l- oqsma terapewtiċi (doża)
Cetirizine/ Efavirenz (10 mg single dose/ 600 mg once daily)
Cetirizine/ Efavirenz (10 mg doża waħda/ 600 mg darba kuljum) SUSTANZI KARDJOVASKULARI Imblokkaturi tal- Kanali tal- Kalċju
Medicinal product by
Diltiazem/ Efavirenz
Effects on drug levels
Diltiazem:
co-administration with efavirenz
L- aġġustamenti fid- doża ta ’
Verapamil, Felodipine, Nifedipine and Nicardipine LIPID LOWERING MEDICINAL PRODUCTS HMG Co-A Reductase Inhibitors
Verapamil, Felodipine, Nifedipine u Ma ġietx studjata l- interazzjoni.
When efavirenz is co-administered with a calcium channel blocker that is a substrate of the CYP3A4 enzyme, there is a potential for reduction in the plasma concentrations of the calcium channel blocker.
L- aġġustamenti fid- doża ta ’ l - imblokkaturi tal- kanali tal- kalċju għandhom ikunu ggwidati mir - rispons kliniku (irreferi għas - Sommarju tal- Karatteristiċi tal - Prodott għall- imblokkatur tal - kanali tal- kalċju).
Dose adjustments of calcium channel blockers should be guided by clinical response (refer to the Summary of Product Characteristics for the calcium channel blocker).
Bidla perċentwali medja fl - AUC, Cmax, Cmin bl- intervalli ta ’ kunfidenza jekk disponibblia (mekkaniżmu)
Atorvastatin/ Efavirenz (10 mg once daily/ 600 mg once daily)
PRODOTTI MEDIĊINALI LI JBAXXU L- LIPIDI Inibituri HMG Co- A Reductase Atorvastatin/ Efavirenz (10 mg darba kuljum/ 600 mg darba kuljum)
therapeutic areas (dose)
Simvastatin/ Efavirenz (40 mg darba kuljum/ 600 mg darba kuljum)
therapeutic areas (dose)
120 Prodott mediċinali skond l- oqsma terapewtiċi (doża)
The administration of SUSTIVA with food may increase efavirenz exposure and may lead to an increase in the frequency of adverse reactions (see section 4.4).
Ir- reazzjonijiet avversi 121 marbuta ma ’ efavirenz li kienu l- iktar prominenti kienu raxx u sintomi tas- sistema nervuża L- għoti ta ’ SUSTIVA ma ’ l- ikel jista ’ jkabbar l- esponiment għal efavirenz u jista ’ jwassal għal żieda fil - frekwenza tar- reazzjonijiet avversi (ara sezzjoni 4. 4).
The long-term safety profile of efavirenz-containing regimens was evaluated in a controlled trial (006) in which patients received efavirenz + zidovudine + lamivudine (n = 412, median duration
Il- profil ta ’ sigurtà fit- tul ta ’ kuri li fihom efavirenz ġie evalwat fi prova kkontrollata (006) li fiha pazjenti ngħataw efavirenz + zidovudine + lamivudine (n = 412, tul medju ta ’ 180 ġimgħa), efavirenz + indinavir (n = 415, tul medju ta ’ 102 ġimgħa), jew indinavir + zidovudine + lamivudine (n = 401, tul medju ta ’ 76 ġimgħa).
In one clinical study, the monthly prevalence of nervous system symptoms of at least moderate severity between weeks 4 and 48, ranged from 5% - 9% in patients treated with regimens containing efavirenz and 3% - 5% in patients treated with the control regimen.
122 sintomi tas- sistema nervuża ta ’ severita` mill- inqas moderata bejn ir- 4 u t- 48 ġimgħa, kienet minn 5% sa 9% f’ pazjenti li kellhom kura li kien fiha efavirenz u minn 3% sa 5% f’ pazjenti li kellhom kura ta ’ kontroll.
Dosing at bedtime seems to improve the tolerability of these symptoms and can be recommended during the first weeks of therapy and in patients who continue to experience
Meta d- doża tittieħed qabel l- irqad jidher li s- sintomi huma iktar tollerabbli; dan jista ’ jkun rakkomondat waqt l- ewwel ġimgħat tat - terapija u f’ pazjenti li jkomplu jesperjenzaw dawn is- sintomi (ara sezzjoni 4. 2).
Hepatobiliary disorders uncommon
123 Disturbi fil- fwied u fil- marrara mhux komuni
113 Psychiatric disorders common
Disturbi psikjatriċi komuni
Amylase: in the clinical trial subset of 1,008 patients, asymptomatic increases in serum amylase levels greater than 1.5 times the upper limit of normal were seen in 10% of patients treated with efavirenz and 6% of patients treated with control regimens.
124 Amylase: fis- sottogrupp ta ’ 1, 008 pazjenti fil- prova klinika, ġew osservati żidiet asintomatiċi fil- livelli ta ’ serum amylase iktar minn 1. 5 darbiet il- livell ta ’ fuq tan- normal f’ 10% tal- pazjenti kkurati b’ efavirenz u f’ 6% tal- pazjenti f’ kuri ta ’ kontroll.
114 Lipids: increases in total cholesterol of 10 - 20% have been observed in some uninfected volunteers receiving efavirenz.
Lipidi: ġew osservati żidiet fil- kolesterol totali ta ’ 10- 20% f’ voluntiera mhux infettati li kienu qed jieħdu efavirenz.
Paediatric patients: undesirable effects in children were generally similar to those of adult patients.
Adoloxxenti u tfal: l- effetti mhux mixtieqa fit- tfal kienu ġeneralment simili għal dawk tal- pazjenti adulti.
Antiviral activity: the free concentration of efavirenz required for 90 to 95% inhibition of wild type or zidovudine-resistant laboratory and clinical isolates in vitro ranged from 0.46 to 6.8 nM in lymphoblastoid cell lines, peripheral blood mononuclear cells (PBMCs) and macrophage/ monocyte cultures.
125 Attivita` antivirali: il- konċentrazzjoni ħielsa ta ’ efavirenz li kien hemm bżonn għall- inibizzjoni ta ’ bejn id- 90 u l- 95% ta ’ iżolati wild type jew iżolati tal- laboratorju reżistenti għal zidovudine u iżolati kliniċi in vitro kienet minn 0. 46 sa 6. 8 nM f’ razez ta ’ ċelluli limfoblastojdi, ċelluli periferali mononukleari tad- demm (PBMCs) u kolturi makrofaġi monoċistiċi.
115 Resistance: the potency of efavirenz in cell culture against viral variants with amino acid substitutions at positions 48, 108, 179, 181 or 236 in RT or variants with amino acid substitutions in the protease was similar to that observed against wild type viral strains.
Reżistenza: il- qawwa ta ’ efavirenz fil- kulturi taċ- ċelluli kontra varjanti virali bis- sostituzzjonijiet ta ’ amino acid fil- pożizzjonijiet 48, 108, 179, 181 or 236 fl- RT jew varjanti bis- sostituzzjonijiet ta ’ amino acid fi protease kien simili għal dak osservat kontra razez virali wild type.
Five of these NNRTI-resistant isolates were found to have K103N or a valine-to- isoleucine substitution at position 108 (V108I) in RT.
Ħamsa minn dawn l- iżolati reżistenti għal NNTRIs instabu li kellhom K103N jew sostizzjoni minn- valine- għal- isoleucine fil- pożizzjoni 108 (V108I) fl- RT.
Efficacy results for study 006 on a subset of 614 patients who had been enrolled for at least 48 weeks are found in Table 2.
Ir- riżultati ta ’ 2- effikaċja għal studju 006 għal sottogrupp ta ’ 614- il pazjent li kienu fl- istduju mill- inqas għal 48 ġimgħa jinstabu f’ Tabella 1.
In the analysis of responder rates (the non-completer equals failure analysis [NC = F]), patients who terminated the study early for any reason, or who had a missing HIV-RNA measurement that was
Fl- analiżi tar- rati tar- rispons (l - analiżi li fiha n- nuqqas ta ’ tkomplija titqies bħala falliment [NC = F]), pazjenti li temmew l- istudju kmieni kienet x’ kienet ir- raġuni, jew li kellhom kejl ta ’ HIV- RNA nieqes li qablu jew warajh sar kejl li kien ogħla mill- livell ta ’ kwantifikazzjoni ta ’ l- assay kienu kkonsidrati li kellhom HIV- RNA ‘ il fuq minn 50 jew ‘ il fuq minn 400 kopja/ ml fil- punti ta ’ żmien neqsin.
Long-term results at 168 weeks of study 006 (160 patients completed study on treatment with EFV+IDV, 196 patients with EFV+ZDV+3TC and 127 patients with IDV+ZDV+3TC, respectively), suggest durability of response in terms of proportions of patients with HIV RNA < 400 copies/ ml, HIV RNA < 50 copies/ ml and in terms of mean change from baseline CD4 cell count.
Riżultati fit- tul mal- 168 ġimgħa ta ’ l- istudju 006 (160 pazjent spiċċaw l- istudju bil- kura b’ EFV +IDV, 196 pazjent b’ EFV + ZDV + 3TC u 127 pazjent b’ IDV + ZDV + 3TC, rispettivament), jissuġġerixxu li r- rispons ta ’ jisfaxxax fix- xejn, fis- sens tal- proporzjoni ta ’ pazenti b’ HIV RNA < 400 kopji/ ml, HIV RNA < 50 kopji/ ml u fis- sens tal- bidla medja mil- linja bażi CD4 ta ’ l- għadd taċ- ċelluli.
Efficacy results for studies ACTG 364 and 020 are found in Table 3.
Studji dwar l- effikaċja għall- istudji ACTG 364 u 020 jinstabu f’ Tabelli 3.
117 Table 3:
Tabella 3:
58-102%), respectively, when given with a high fat meal, relative to when given under fasted conditions (see section 4.4).
22 – 33%) u 79% (90% CI: 58 – 102%), rispettivament, meta ngħataw ikla b’ ħafna xaħam meta mqabble ma ’ meta kienu f’ kondizzjonijiet ta ’ sawm (ara sezzjoni 4. 4).
In HIV-1 infected patients (n = 9) who received efavirenz 200 to 600 mg once daily for at least one month, cerebrospinal fluid concentrations ranged from 0.26 to 1.19% (mean
F’ pazjenti nfettati bl- HIV- 1 (n = 9) li rċevew efavirenz 200 sa 600 mg darba kuljum għall- inqas għal xahar, il- konċentrazzjonijiet tal- fluwidu ċerebrospinali kienu jvarjaw minn 0. 26 sa 1. 19% (medja 0. 69%) tal- konċentrazzjoni korrospondenti tal- plażma.
The clinical implications of such an association are unknown; however, the potential for an increased frequency and severity of efavirenz-associated adverse events cannot be excluded.
128 magħrufa; madankollu, il- potenzjal għal frekwenza u severità akbar ta ’ l- reazzjonijiet avversi assoċjati ma ’ efavirenz ma jistax jiġi eskluż.
119 Carcinogenicity studies showed an increased incidence of hepatic and pulmonary tumours in female mice, but not in male mice.
Studji dwar ir- riskju ta ’ kanċer urew inċidenza ikbar ta ’ tumuri fil- fwied u fil- pulmun fi ġrieden nisa, imma mhux fi ġrieden irġiel.
Printing ink Hypromellose (E464) Propylene glycol Cochineal carminic acid (E120) Indigo carmine (E132) Titanium dioxide (E171)
Linka għall- istampar Hypromellose (E464) Propylene glycol Cochineal carminic acid (E120) Indigo carmine (E132) Titanium dioxide (E171)
Packs of 30 x 1 or 90 (3 x 30 x 1) film-coated tablets in aluminium/ PVC perforated unit dose blisters.
Kull kartuna fiha flixkun wieħed ta ’ 30 pillola miksija Pakketti ta ’ 30 x 1 jew 90 (3 x 30 x 1) pillola miksija b’ rita f’ folji ta ’ l - aluminju/ PVC mtaqqba għal dożi singoli.
EU/ 1/ 99/ 110/ 008 - bottle EU/ 1/ 99/ 110/ 009 - blister EU/ 1/ 99/ 110/ 010 - blister
EU/ 1/ 99/ 110/ 008 - flixkun EU/ 1/ 99/ 110/ 009 - folja EU/ 1/ 99/ 110/ 010 - folja
121 ANNEX II
131 ANNESS II
122 A.
132 A.
Bristol-Myers Squibb Champ “ Lachaud” La Goualle 19250 Meymac France
Bristol- Myers Squibb Champ “ Lachaud ” La Goualle 19250 Meymac Franza
The MAH must ensure that the system of pharmacovigilance, as described in version 3.0 presented in Module 1.8.1 of the Marketing Authorisation Application, is in place and functioning before and whilst the product is on the market.
Id- detentur ta ’ l- awtorizzazzjoni għat- tqegħid fis- suq għandu jiżgura li s- sistema ta ’ farmakoviġilanza, kif deskritta fil- verżjoni 3. 0 ippreżentata fil- Modulu 1. 8. 1. ta ’ l- Applikazzjoni għall- Awtorizzazzjoni għat- Tqegħid fis- Suq, tkun fis- seħħ u li din tkun qegħda taħdem qabel u waqt li l- prodott ikun fis- suq.
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan as agreed in version 1.0 of the Risk Management Plan (RMP) presented in Module 1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP agreed by the CHMP.
Id- Detentur tal- Awtorizzazzjoni għat- Tqegħid fis- Suq jimpenja ruħu li jwettaq l- istudji u l- attivitajiet ta ’ farmakoviġilanza addizzjonali mogħtija fid- dettall fil- Pjan ta ’ Farmakoviġilanza, kif miftiehem fil - verżjoni 1. 0 tal- Pjan tal- Ġestjoni tar- Riskju (RMP) ippreżentat fis- Sezzjoni 1. 8. 2. tal- Applikazzjoni għall- Awtorizzazzjoni għat- Tqegħid fis- Suq u kull aġġornament sussegwenti tal- RMP miftiehem mill - CHMP.
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the updated RMP should be submitted at the same time as the next Periodic Safety Update Report (PSUR).
B’ mod konformi mal- Linja gwida tal- CHMP dwar Sistemi ta ’ Ġestjoni tar- Riskji għal prodotti mediċinali għall- użu mill- bniedem, l- RMP aġġornat għandu jiġi ippreżentat fl- istess żmien tar -
In addition, an updated RMP should be submitted When new information is received that may impact on the current Safety Specification, Pharmacovigilance Plan or risk minimisation activities
Barra minn hekk, għandu jiġi ppreżentat RMP aġġornat:
123 Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being reached, At the request of the EMEA.
• Meta tasal informazzjoni ġdida li jista ’ jkollha impatt fuq l- Ispeċifikazzjoni tas- Sigurtà attwali, fuq il- Pjan tal- Farmakoviġilanza jew fuq l- attivitajiet ta ’ minimizzazzjoni tar- riskji • Fi żmien 60 jum minn meta tintlaħaq mira importanti (farmakoviġilanza jew minimizzazzjoni tar- riskji) • Fuq talba ta ’ l- EMEA
124 ANNEX III
134 ANNESS III
125 A.
135 A.
126 PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE PACKAGING
136 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA U L- PAKKETT LI JMISS MAL- PRODOTT
SUSTIVA 50 mg hard capsules efavirenz
SUSTIVA 50 mg kapsuli ibsin efavirenz
Each hard capsule contains: efavirenz 50 mg.
Kull kapsula iebsa fiha: efavirenz 50 mg
See package leaflet for further information.
Għal aktar informazzjoni ara l- fuljettt ta ’ tagħrif..
128 PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE PACKAGING
138 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA U L- PAKKETT LI JMISS MAL- PRODOTT
SUSTIVA 100 mg hard capsules efavirenz
SUSTIVA 100 mg kapsuli ibsin efavirenz
Each hard capsule contains: efavirenz 100 mg.
Kull kapsula iebsa fiha: efavirenz 100 mg
130 PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE PACKAGING
140 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA U L- PAKKETT LI JMISS MAL- PRODOTT
SUSTIVA 200 mg hard capsules efavirenz
SUSTIVA 200 mg kapsuli ibsin efavirenz
EU/ 1/ 99/ 110/ 003: bottle EU/ 1/ 99/ 110/ 004: blister
EU/ 1/ 99/ 110/ 003 - flixkun EU/ 1/ 99/ 110/ 004 - folja
132 MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS
142 TAGĦRIF MINIMU LI GĦANDU JIDHER FUQ L- ISTRIXXI JEW FUQ IL- FOLJI
133 PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE PACKAGING
143 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA U L- PAKKETT LI JMISS MAL- PRODOTT
SUSTIVA 30 mg/ ml oral solution efavirenz
SUSTIVA 30 mg/ ml soluzzjoni orali efavirenz
134 11.
144 11.
135 PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE PACKAGING
145 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA U L- PAKKETT LI JMISS MAL- PRODOTT