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.
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.
The clinical significance of asymptomatic increases in serum amylase is unknown.
Is- sinifikat kliniku taż- żidiet asintomatiċi fis- serum amylase mhux magħruf.
Lipids: increases in total cholesterol of 10 - 20% have been observed in some uninfected volunteers receiving efavirenz.
20 Lipidi: ġew osservati żidiet fil- kolesterol totali ta ’ 10- 20% f’ voluntiera mhux infettati li kienu qed jieħdu efavirenz.
In clinical trials of various efavirenz-containing regimens in treatment naive patients, total cholesterol, HDL-cholesterol, and triglycerides increased over 48 weeks of treatment (21 – 31%, 23 – 34%, and 23 – 49%, respectively).
Fi provi kliniċi ta ’ kuri differenti b’ efavirenz f’ pazjenti li ma kinux jafu x’ kura kienu qed jieħdu, il- kolesterol totali, HDL- kolesterol, u t- trigliċeridi żdiedu fuq medda ta ’ 48 ġingħa ta ’ kura (21 – 31%, 23 – 34%, u 23 – 49%, rispettivament).
The proportion of patients with a total cholesterol/ HDL-cholesterol ratio greater than 5 was unchanged.
Il- proporzjon ta ’ pazjenti bi proporzjon bejn il - kolesterol totali u HDL kolesterol iktar minn 5 ma nbidilx.
The magnitude of changes in lipid levels may be influenced by factors such as duration of therapy and other components of the antiretroviral regimen.
Id- daqs tal- bidliet fil- livelli tal- lipidi jista ’ jkun influwenzat minn fatturi bħal m’ huma t- tul tal- kura u komponenti oħra fil- kura antiretrovirali.
Cannabinoid test interaction: efavirenz does not bind to cannabinoid receptors.
Interazzjoni tat- test cannabinoid: efavirenz ma jintrabatx mar- reċetturi cannabinoid.
False positive urine cannabinoid test results have been reported in uninfected volunteers who received efavirenz.
Riżultati pożittivi foloz ta ’ l- urina cannabinoid ġew irrapuratati minn voluntiera mhux infettati li kienu jirċievu efavirenz.
False positive test results have only been observed with the CEDIA DAU Multi-Level THC assay, which is used for screening, and have not been observed with other cannabinoid assays tested including tests used for confirmation of positive results.
Riżultati pożittivi foloz ġew osservati biss bit- test DAU Multi- Level THC, li jintuża biex jintgħarblu (għall- iscreening), u ma ġewx osservati b’ testijiet oħra cannabinoid inkluż testijiet li jintużaw biex jiġu kkonfermati r- riżultati pożittivi.
Postmarketing experience with efavirenz has shown the following additional adverse reactions to occur in association with efavirenz-containing antiretroviral treatment regimens: cerebellar coordination and balance disturbances, delusion, hepatic failure, neurosis, photoallergic dermatitis, psychosis and completed suicide.
L- esperjenza b’ efavirenz wara li l- prodott tpoġġa fuq is- suq uriet li kien hemm ukoll dawn ir - reazzjonijiet avversi marbuta mal- kura antiretrovirali li fiha efavirenz: disturbi fil- koordinazzjoni ċelebrali u fil- bilanċ, delużjoni, insuffiċjenza tal- fwied, nevrożi, dermatite allerġika għad- dawl, psikożi u suwiċidju komplut.
19 Paediatric patients: undesirable effects in children were generally similar to those of adult patients.
Pazjenti pedjatriċi: l- effetti mhux mixtieqa fit- tfal kienu ġeneralment simili għal dawk tal- pazjenti adulti.
Rash was reported more frequently in children (in a clinical study including 57 children who received efavirenz during a 48-week period, rash was reported in 46%) and was more often of higher grade than in adults (severe rash was reported in 5.3% of children).
Ir- raxx kien iktar irrapurtat fit- tfal (fi studju kliniku li kien jinkludi 75 tifel u tifla li ngħataw efavirenz waqt perjodu ta ’ 48 ġimgħa, ir- raxx kien irrapurtat f’ 46%) u kien ta ’ grad ogħla iktar ta ’ spiss mill- adulti (raxx sever kien irrapurat f’ 5. 3% mit- tfal).
Prophylaxis with appropriate antihistamines prior to initiating therapy with efavirenz in children may be considered.
Fit- tfal tista ’ titqies il- prevenzjoni permezz ta ’ anti- istaminiċi xierqa qabel ma tibda t- terapija b’ efavirenz.
Although nervous system symptoms are difficult for young children to report, they appear to be less frequent in children and were generally mild.
Għalkemm huwa diffiċli għat - tfal żgħar biex jirrapurtaw is- sintomi tas- sistema nervuża, jidher li huma inqas frekwenti fit- tfal u ġeneralment ħfief.
In the study of 57 children, 3.5% of patients experienced nervous system symptoms of moderate intensity, predominantly dizziness.
Fi studju ta ’ 57 tifel u tifla, 3. 5% tal- pazjenti kellhom sintomi tas- sistema nervuża ta ’ intensita` moderata, l- iktar sturdament.
No child had severe symptoms or had to discontinue because of nervous system symptoms.
L- ebda tifel jew tifla ma kellu sintomi severi jew kellu jwaqqaf it- terapija minħabba s- sintomi tas- sistema nervuża.
Some patients accidentally taking 600 mg twice daily have reported increased nervous system symptoms.
Xi pazjenti li bi żball ħadu żewġ dożi ta ’ 600 mg irrapurtaw sintomi eħrex tas- sistema nervuża.
One patient experienced involuntary muscle contractions.
Pazjent wieħed kellu kontrazzjonijiet involvontarji tal- muskoli.
Treatment of overdose with efavirenz should consist of general supportive measures, including monitoring of vital signs and observation of the patient ’ s clinical status.
Il- kura ta ’ doża eċċessiva ta ’ efavirenz għandha tikkonsisti f’ miżuri mediċi normali, inkluż l - immonitorjar tas- sinjali vitali u l- osservazzjoni tal- qagħda klinika tal- pazjent.
Administration of activated charcoal may be used to aid removal of unabsorbed efavirenz.
L- għoti ta ’ activated charcoal jista ’ jintuża biex jgħin fit- tneħħija ta ’ efavirenz mhux assorbit.
There is no specific antidote for overdose with efavirenz.
M’ hemmx antidotu speċifiku għad- doża eċċessiva b’ evafirenz.
Since efavirenz is highly protein bound, dialysis is unlikely to remove significant quantities of it from blood.
Billi efavirenz huwa marbut ħafna mal- proteina, id- dijalisi mhux mistenni li jneħħi kwantitajiet sinifikanti minnu mid- demm.
Non-nucleoside reverse transcriptase inhibitors.
Inibituri non- nukleosidi ta ’ reverse transcriptase.
Mechanism of action: efavirenz is a NNRTI of HIV-1.
Kif jaħdem: efavirenz huwa NNRTI ta ’ l- HIV- 1.
Efavirenz is a non-competitive inhibitor of HIV-1 reverse transcriptase (RT) and does not significantly inhibit HIV-2 RT or cellular DNA polymerases (α, β, γ or δ).
Efavirenz huwa impeditur mhux kompetittiv ta ’ HIV- 1 reverse transcriptase (RT) u ma jimpedix b’ mod sinifikanti HIV- 2 RT jew polymerases (α, β, γ or δ) tad- DNA ċellulari.
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.
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.
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.
21 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.
The single substitutions which led to the highest resistance to efavirenz in cell culture correspond to a leucine-to-isoleucine change at position 100 (L100I, 17 to 22-fold resistance) and a lysine-to-asparagine at position 103 (K103N, 18 to 33-fold resistance).
Is- sostituzzjonijiet singoli li wasslu għall- ogħla reżistenza lil efavirenz fil- kulturi taċ- ċelluli jikkorrispondu għall- bidla minn - leucine- għal- isoleucine f’ pożizzjoni 100 (L100I, reżistenza minn 17 sa 22 darba iktar) u bidla minn - lysine- għal- asparagine fil- pożizzjoni 103 (K103N, reżistenza minn 18 sa 33 darba iktar).
Greater than 100-fold loss of susceptibility was observed against HIV variants expressing K103N in addition to other amino acid substitutions in RT.
Kien osservat telfien tas- suxxettibilita` għal mitt darba kontra varjanti ta ’ l- HIV li kellhom K103N apparti sostituzzjonijiet oħra ta’ amino acid f’ RT.
K103N was the most frequently observed RT substitution in viral isolates from patients who experienced a significant rebound in viral load during clinical studies of efavirenz in combination with indinavir or zidovudine + lamivudine.
K103N kienet l- iktar sostituzzjoni RT osservata fl- iżolati virali minn pazjenti li rkadew b’ mod sinifikanti fin- numru ta ’ virus waqt studji kliniċi b’ efavirenz flimkien ta ’ indinavir jew zidovudine + lamivudinee.
This mutation was observed in 90% of patients receiving efavirenz with virological failure.
Din il- mutazzjoni kienet osservata f’ 90% mill- pazjenti li kienu qed jingħataw efavirenz b’ falliment viroloġiku.
Substitutions at RT positions 98, 100, 101, 108, 138, 188, 190 or 225 were also observed, but at lower frequencies, and often only in combination with K103N.
Kienu osservati wkoll sostituzzjonjiet fil- pożizzjonijiet RT 98, 100, 101, 108, 138, 188, 190 jew 225, imma fil- frekwenzi iktar baxxi u ħafna drabi biss flimkien ma ’ K103N.
The pattern of amino acid substitutions in RT associated with resistance to efavirenz was independent of the other antiviral medications used in combination with efavirenz.
Il- mudell ta ’ sostituzzjonijiet amino acid fl- RT li kienu assoċjati mar- reżistenza lil efavirenz kien indipendenti minn medikazzjonijiet antivirali oħra li jintużaw flimkien ma ’ efavirenz.
Cross resistance: cross resistance profiles for efavirenz, nevirapine and delavirdine in cell culture demonstrated that the K103N substitution confers loss of susceptibility to all three NNRTIs.
Reżistenza msallba: il- profili ta ’ reżistenza msallba għal efavirenz, nevirapine u delavirdine fil- koltura taċ- ċelluli urew li s- sostituzzjoni K103N tagħti nuqqas ta ’ suxxettibilita` lit- tliet NNRTIs li huma.
Two of three delavirdine-resistant clinical isolates examined were cross-resistant to efavirenz and contained
Tnejn minn tliet iżolati kliniċi reżistenti għal delavirdine li ġew eżaminati kellhom reżistenza msallba għal efavirenz u kellhom is- sostituzzjoni K103N.
A third isolate which carried a substitution at position 236 of RT was not cross-resistant to efavirenz.
It- tielet iżolat li kellu sostituzzjoni fil- pożizzjoni 236 ta ’ RT ma kellux reżistenza msallba għal efavirenz.
Viral isolates recovered from PBMCs of patients enrolled in efavirenz clinical studies who showed evidence of treatment failure (viral load rebound) were assessed for susceptibility to NNRTIs.
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.
Thirteen 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.
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.
Three of the efavirenz treatment failure isolates tested remained sensitive to efavirenz in cell culture and were also sensitive to nevirapine and delavirdine.
Tlieta mill- iżolati tal- falliment tal- kura b’ efavirenz li ġew ittestjati baqgħu sensittivi għal efavirenz fil- kulturi taċ- ċelluli u kienu sensittivi wkoll għal nevirapine u delavirdine.
The potential for cross resistance between efavirenz and PIs is low because of the different enzyme targets involved.
Il- potenzjal għal reżistenza msallba bejn efavirenz u l- PIs huwa baxx minħabba l- enzimi differenti li qed jiġu mmirati.
The potential for cross-resistance between efavirenz and NRTIs is low because of the different binding sites on the target and mechanism of action.
Il- potenzjal ghal reżistenza msallba bejn efavirenz u NRTIs huwa baxx minħabba li hemm siti differenti ta ’ rbit fuq il- bersall u l- mekkaniżmu ta ’ l- azzjoni.
Efavirenz has not been studied in controlled studies in patients with advanced HIV disease, namely with CD4 counts < 50 cells/ mm3, or in PI or NNRTI experienced patients.
Efavirenz ma ġiex studjat fi studji kkontrollati f’ pazjenti b’ mard avvanzat ta ’ l- HIV, speċifikament b’ numru ta ’ CD4 < 50 ċelluli / mm3, jew f’ pazjenti li kienu ħadu PI jew NNRTI.
Clinical experience in controlled studies with combinations including didanosine or zalcitabine is limited.
L- esperjenza klinika fi studji kkontrollati b’ kombinazzjonijiet inkluż didanosine jew zalcitabine hija limitata.
Two controlled studies (006 and ACTG 364) of approximately one year duration with efavirenz in combination with NRTIs and/ or PIs, have demonstrated reduction of viral load below the limit of quantification of the assay and increased CD4 lymphocytes in antiretroviral therapy-naïve and NRTI-experienced HIV-infected patients.
Żewġ studji kkontrollati (006 u ACTG 364) li damu bejn wieħed u ieħor sena b’ efavirenz flimkien ma ’ NRTIs u/ jew PIs, urew li n- numru tal- virus naqas taħt il- livell tal- kwantifikazzjoni ta ’ l- assay u CD4 lymphoċiti f’ pazjenti nfettati bl- HIV li ma kinux ħadu terapija antiretrovirali u li kienu ħadu NRTI.
Study 020 showed similar activity in NRTI-experienced patients over 24 weeks.
Studju 020 wera l- istess tip ta ’ attivita` f’ pazjenti li kienu ħadu NRTI fuq medda ta ’ 24 ġimgħa.
In these studies the dose of efavirenz was 600 mg once daily; the dose of indinavir was 1,000 mg every 8 hours when used with efavirenz and 800 mg every 8 hours when used without efavirenz.
F’ dawn l- istudji d- doża ta ’ efavirenz kienet ta ’ 600 mg darba kuljum; id- doża ta ’ indinavir kienet ta ’ 1, 000 mg kull 8 sigħat meta użat ma ’ efavirenz u 800 mg kull 8 sigħat meta wżat mingħajr efavirenz.
The dose of nelfinavir was 750 mg given three times a day.
Id- doża ta ’ nelfinavir kienet ta ’ 750 mg tliet darbiet kuljum.
The standard doses of NRTIs given every 12 hours were used in each of these studies.
F’ kull wieħed minn dawn l- istudji ġew użati d- dożi normali ta ’ NRTIs mogħtija kull 12- il siegħa.
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 setgħux kienu ħadu efavirenz, lamivudine, NNRTI, jew PI meta daħlu fl- istudju.
The mean baseline CD4 cell count was 341 cells/ mm3 and the mean baseline HIV-RNA level was 60,250 copies/ ml.
Il- medja tal- linja bażi CD4 ta ’ l- għadd taċ- ċelluli kienet ta ’ 341 ċelloli/ mm3 u l- medja tal- linja bażi tal- livell HIV- RNA kienet ta ’ 60, 250 kopji/ ml.
Efficacy results for study 006 on a subset of 614 patients who had been enrolled for at least 48 weeks are found in Table 3.
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 3.
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 either preceded or followed by a measurement above the limit of assay quantification were considered to have HIV-RNA above 50 or above 400 copies/ ml at the missing time points.
22 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.
Efficacy results for study 006
Riżultati ta ’ l- effikaċja għall- istudju 006
Responder rates (NC = Fa) Plasma HIV-RNA
Rati tar- rispons (NC = Fa) Plażma HIV- RNA
Mean change from baseline-CD4 cell count
Bidla medja mill - linja bażi ta ’ l - għadd taċ - ċelluli CD4 ċelluli / mm3
400 copies/ ml (95% C. I. b)
400 (95
< 50 copies/ ml (95% C. I. b)
< 50 kopja/ ml (95% C. I. b)
Regimend EFV +
Tul tal- Kurad EFV +
202
N 202
67%
ġimgħa 67%
62%
48 ġimgħa 62%
187
48 ġimgħa 187
%, 73%) 54%
(60%, 73%) 54%
(11.8) 177
(11. 8) 177
153
(11. 3) 153
(12.3)
(12. 3)
S. E. M., standard error of the mean. d EFV, efavirenz; ZDV, zidovudine; 3TC, lamivudine; IDV, indinavir.
NC = F, mhux komplut = falliment. b C. I., intervall ta ’ konfidenza. c S. E. M., żball standardizzat mill- medja. d EFV, efavirenz; ZDV, zidovudine; 3TC, lamivudine; IDV, indinavir.
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 4.
Studji dwar l- effikaċja għall- istudji ACTG 364 u 020 jinstabu f’ Tabella 4.
Study ACTG 364 enrolled 196 patients who had been treated with NRTIs but not with PIs or NNRTIs.
Studju ACTG 364 kellu 196 pazjent li kienu ġew ikkurati b’ NRTIs imma mhux b’ PIs jew NNRTIs.
Study 020 enrolled 327 patients who had been treated with NRTIs but not with PIs or NNRTIs.
Studju 020 kellu 327 pazjent li kienu ġew ikkurati b’ NRTIs imma mhux b’ PIs jew NNRTIs.
Physicians were allowed to change their patient ’ s NRTI regimen upon entry into the study.
It- tobba setgħu ibiddlu l - kura NRTI tal- pazjenti tagħhom wara li daħlu fl- istudju.
Responder rates were highest in patients who switched NRTIs.
Ir- rati ta ’ rispons kienu l- ogħla f’ pazjenti li biddlu l- NRTIs.
Table 4:
23 Tabella 4:
Efficacy results for studies ACTG 364 and 020
Riżultati ta ’ l- effikaċja għall- istudji ACTG 364 u 020
Responder rates (NC = Fa)
Rati tar- rispons (NC = Fa) Plażma HIV- RNA
Mean change from
Bidla medja mill - linja bażi ta ’ l- għadd taċ - ċelluli CD4
baseline-CD4 cell count
Celluli/ m (S. E. M. d)
Study Number/ Treatment Regimensb
Numru ta ’ l- istudju / Tipi ta ’ Kurab Studju ACTG 364 48 ġimgħa
(95
% (95% C. I.)
% C. I. c)%
m3
Study ACTG 364 48 weeks
Studju ACTG 364 48 ġimgħa
< 50 copies/ ml
kopja/ ml < 50 kopja/ ml
(17.9) (21.0) (13.6)
(17. 9) (21. 0) (13. 6)
Study 020 24 weeks
Studju 020 24 ġimgħa
< 400 copies/ ml
< 400 kopja/ ml
< 50 copies/ ml
< 50 kopja/ ml
(9.1) (9.9)
(9. 1) (9. 9)
NC = F, noncompleter = failure. b EFV, efavirenz; ZDV, zidovudine; 3TC, lamivudine; IDV, indinavir; NRTI, nucleoside reverse transcriptase inhibitor; NFV, nelfinavir. c C. I., confidence interval for proportion of patients in response. d S. E. M., standard error of the mean. ---, not performed.
NC = F, mhux komplut = falliment. b EFV, efavirenz; ZDV, zidovudine; 3TC, lamivudine; IDV, indinavir; NRTI, inibitur nukleosid reverse transcriptase; NFV, nelfinavir c C. I., intervall ta ’ konfidenza għall- proporzjon ta ’ pazjent fir- rispons. d S. E. M., żball standardizzat mill- medja ---, ma sarx
Paediatric trial:
Prova fuq it- tfal:
ACTG 382 is an ongoing uncontrolled study of 57 NRTI-experienced paediatric patients (3 - 16 years) which characterises the pharmacokinetics, antiviral activity and safety of efavirenz in combination with nelfinavir (20 - 30 mg/ kg given three times a day) and one or more NRTIs.
ACTG 382 huwa studju bla miżuri ta ’ kontroll li għadu għaddej fuq 57 tifel u tifla pazjent (3 – 16- il sena) li kienu ħadu NRTI li jidentifika l- karatteristiċi farmakokinetiċi, l- attivita` antivirali u s- sigurta` ta ’ efavirenz meta tintuża flimkien ma ’ nelfinavir (20 – 30 mg/ kg tliet darbiet kuljum) u NRTI wieħed jew iktar.
The starting dose of efavirenz was the equivalent of a 600 mg dose (adjusted from calculated body size based on weight).
Id- doża tal- bidu ta ’ efavirenz kienet ekwivalenti għal doża ta ’ 600 mg (irranġat mid- daqs ikkalkulat tal- ġisem ibbażat fuq il- piż).
The response rate, based on the NC = F analysis of the percentage of patients with plasma HIV-RNA < 400 copies/ ml at 48 weeks was 60% (95%, C. I.
Ir- rata ta ’ rispons, ibbażat fuq l - analiżi NC = F tal- persentaġġ ta ’ pazjenti bi plażma HIV- RNA < 400 copji/ ml fit- 48 ġimgħa kienet 60% (95%, C. I.
47, 72), and 53% (C. I.
47, 72), u 53% (C. I.
The mean CD4 cell counts were increased by 63 ± 34.5 cells/ mm3 from baseline.
L- għadd tal- medja ta ’ ċelluli CD4 kibret bi 63 ± 34. 5 ċelluli / mm3 mil- linja bażi.
The durability of the response was similar to that seen in adult patients.
It- tul tar- rispons kien simili għal dak li ġie osservat f’ pazjenti adulti.
Absorption: peak efavirenz plasma concentrations of 1.6 - 9.1 μ M were attained by 5 hours following single oral doses of 100 mg to 1,600 mg administered to uninfected volunteers.
Assorbiment: l- ogħla konċentrazzjonijiet ta ’ efavirenz fil- plażma ta ’ 1. 6 - 9. 1 μM intlaħqu 5 sigħat wara dożi orali waħedhom ta ’ 100 mg sa 1, 600 mg mogħti lil voluntiera mhux infettati.
Dose related increases in Cmax and AUC were seen for doses up to 1,600 mg; the increases were less than proportional suggesting diminished absorption at higher doses.
Ġew osservati żidiet f’ Cmax u AUC marbuta mad- dożi għal dożi sa 1, 600 mg; iż- żidiet kienu inqas minn proporzjonali li kien jindika li kien hemm inqas assorbiment ma ’ dożi ogħla.
Time to peak plasma concentrations (3 - 5 hours) did not change following multiple dosing and steady-state plasma concentrations were reached in 6 - 7 days.
Il- ħin sakemm intlaħqu l- ogħla konċentrazzjonijiet fil- plażma (3 – 5 sigħat) ma nbidilx wara dożi multipli u konċentrazzjonijiet fissi fil- plażma ntlaħqu f’ 6 – 7 ijiem.
In HIV infected patients at steady state, mean Cmax, mean Cmin, and mean AUC were linear with 200 mg, 400 mg, and 600 mg daily doses.
F’ pazjenti nfettati bl- HIV fi stat fiss, Cmax medju, Cmin medju, and AUC medju kienu lineari b’ dożi ta ’ kuljum ta ’ 200 mg, 400 mg u 600 mg.
In 35 patients receiving efavirenz 600 mg once daily, steady state Cmax was 12.9 ± 3.7 μ M (29%) [mean ± S. D.
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.
(% C. V.)], steady state Cmin was 5.6 ± 3.2 μ M (57%), and AUC was 184 ± 73 μ M·h (40%).
(% C. V.)], Cmin fiss kien 5. 6 ± 3. 2 μM (57%), u AUC kien 184 ± 73 μM· h (40%).
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).
Distribution: efavirenz is highly bound (approximately 99.5 - 99.75%) to human plasma proteins, predominantly albumin.
24 Distribuzzjoni: efavirenz jintabat ħafna (bejn wieħed u ieħor 99. 5 – 99. 75%) mal- proteini tal- plażma umana, speċjalment albumin.
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.
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.
This proportion is approximately 3-fold higher than the non-protein-bound (free) fraction of efavirenz in plasma.
Dan il - proporzjon huwa bejn wieħed u ieħor 3 darbiet ogħla mill- frazzjoni mhux marbuta mal- proteina (ħielsa) ta ’ efavirenz fil- plażma.
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 jgħaddu minn proċess ta ’ glukuronidazzjoni.
These metabolites are essentially inactive against HIV-1.
Dawn il- metaboliti essenzjalment mhumiex attivi kontra HIV- 1.
The in vitro studies suggest that CYP3A4 and CYP2B6 are the major isozymes responsible for efavirenz metabolism and that it inhibited P450 isozymes 2C9, 2C19, and 3A4.
Studji in vitro jissuġġerixxu li CYP3A4 u CYP2B6 huma l- iżozimi li l- iktar huma responsabbli għall- metaboliżmu ta ’ efavirenz u li hu impedixxa iżozimi P450 2C9, 2C19, and 3A4.
In in vitro studies efavirenz did not inhibit CYP2E1 and inhibited CYP2D6 and CYP1A2 only at concentrations well above those achieved clinically.
Fi studji in vitro efavirenz ma impedixxiex CUP2E1 u impedixxa CYP2D6 u CYP1A2 biss f’ konċentrazzjonijiet ogħla sew minn dawk li setgħu jintlaħqu klinikament.
Efavirenz plasma exposure may be increased in patients with the homozygous G516T genetic variant of the CYP2B6 isoenzyme.
L- esponiment tal- plażma ta 'efavirenz jista ’ jkun ogħla f’ pazjenti bil- varjant ġenetiku omozigota G516T ta ’ l- isoenzima CYP2B6.
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.
L- implikazzjonijiet kliniċi ta ’ assoċjazzjoni bħal din mhumiex magħrufa; madankollu, il- potenzjal għal frekwenza u severità akbar ta ’ l- episodji avversi assoċjati ma ’ efavirenz ma jistax jiġi eskluż.
Efavirenz has been shown to induce P450 enzymes, resulting in the induction of its own metabolism.
Efavirenz wera li jinduċi enzimi P450, bir- riżultat li induċa l- metaboliżmu tiegħu stess.
In uninfected volunteers, multiple doses of 200 - 400 mg per day for 10 days resulted in a lower than predicted extent of accumulation (22 - 42% lower) and a shorter terminal half-life compared with single dose administration (see below).
F’ voluntiera mhux infettati, dożi multipli ta ’ 200 – 400 mg kuljum għal 10 ijiem irriżulta f’ akkumulu li kien iktar baxx minn dak imbassar (22 - 42% iktar baxx) u half- life terminali iqsar meta mqabbel ma ’ l- għoti ta ’ doża waħda (ara taħt).
Elimination: efavirenz has a relatively long terminal half-life of at least 52 hours after single doses and 40 – 55 hours after multiple doses.
Tneħħija: efavirenz għandu half- life terminali relattivament twil ta ’ mill- anqas 52 siegħa wara dożi waħedhom u minn 40 sa 55 siegħa wara dożi multipli.
Approximately 14 - 34% of a radiolabelled dose of efavirenz was recovered in the urine and less than 1% of the dose was excreted in urine as unchanged efavirenz.
Bejn wieħed u ieħor 14 - 34% tad- doża radjutikkettata ta ’ efavirenz instabet fl- urina u inqas minn 1% tad- doża tneħħiet fl- urina bħala efavirenz mhux mibdul.
In the single patient studied with severe hepatic impairment (Child Pugh Grade C), half life was doubled indicating a potential for a much greater degree of accumulation.
Fil- pazjent studjat li kellu indeboliment sever tal- fwied, (Grad Child Pugh C), il- half- life irduppjat, u dan jindika li hemm potenzjal għal akkumulu ħafna ikbar.
Paediatric pharmacokinetics: in 49 paediatric patients receiving the equivalent of a 600 mg dose of efavirenz (dose adjusted from calculated body size based on weight), steady state Cmax was 14.1 μ M, steady state Cmin was 5.6 μ M, and AUC was 216 μ M·h.
Karatterisitiċi farmakokinetiċi fit- tfal: f’ 49 tifel u tifla pazjent li kienu qed jirċievu l- ekwivalenti ta ’ doża ta ’ 600 mg ta ’ efavirenz (doża rranġata mid- daqs ikkalkulat tal- ġisem ibbażat fuq il- piż), Cmax fiss kien ta ’ 14. 1 μM, Cmin fiss kien ta ’ 5. 6 μM, u AUC kien ta ’ 216 μM· h.
The pharmacokinetics of efavirenz in paediatric patients were similar to adults.
Il- karatteristiċi farmakokinetiċi ta ’ efavirenz f’ pazjenti tfal kienu simili għall- adulti.
23 Gender, race, elderly:
Ġendru, razza, anzjani:
Although limited data suggest that females as well as Asian and Pacific Island patients may have higher exposure to efavirenz, they do not appear to be less tolerant of efavirenz.
Għalkemm it- tagħrif limitat jissuġġerixxi li n- nisa kif ukoll pazjenti Ażjatiċi u mill- Gżejjer tal- Paċifiku jista ’ jkunu esposti iktar għal efavirenz, ma jidhrux li huma inqas tolleranti għal efavirenz.
Pharmacokinetic studies have not been performed in the elderly.
Ma sarux studji farmakokinetiċi fuq l- anzjani.
Efavirenz was not mutagenic or clastogenic in conventional genotoxicity assays.
F’ assays konvenzjonali dwar l- effett tossiku fuq il- ġeni, efavirenz ma kienx mutaġeniku jew klastoġeniku.
Efavirenz induced foetal resorptions in rats.
Efavirenz wassal biex il- firien jirriassorbixxu l- feti tagħhom.
Malformations were observed in 3 of 20 foetuses/ newborns from efavirenz-treated cynomolgus monkeys given doses resulting in plasma efavirenz concentrations similar to those seen in humans.
Ġew osservati malformazzjonijiet fi 3 minn 20 fetu / mwieled frisk minn xadini cynomolgus ikkurati b’ efavirenz li ngħataw dożi li rriżultaw f’ konċentrazzjonijiet ta ’ efavirenz fil- plażma li kienu simili għal dawk li ġew osservati fil - bnedmin.
Anencephaly and unilateral anophthalmia with secondary enlargement of the tongue were observed in one foetus, microophthalmia was observed in another foetus, and cleft palate was observed in a third foetus.
F’ fetu wieħed kienu osservati anenċefalija u anoftalmija unilaterali bi tkabbir sekondarju ta ’ l- ilsien, f’ fetu ieħor kienet osservata mikro- oftalmija u fit- tielet fetu kienet osservata qasma fis- saqaf tal- ħalq.
No malformations were observed in foetuses from efavirenz-treated rats and rabbits.
Ma ġewx osservati malformazzjonijiet f’ feti ta ’ firien u fniek mogħtija efavirenz.
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.
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.
The biliary hyperplasia regressed upon cessation of dosing.
L- iperplażja biljarja naqset kif waqfu d- dożi.
Biliary fibrosis has been observed in rats.
Fil- firen ġiet osservata
Non-sustained convulsions were observed in some monkeys receiving efavirenz for ≥ 1 year, at doses yielding plasma AUC values 4- to 13-fold greater than those in humans given the recommended dose (see sections 4.4 and 4.8).
Kienu osservati konvulżjonijiet mhux sostnuti f’ xi xadini li kienu qed jingħataw efavirenz għal ≥ sena, b’ dożi li kienu jwasslu għal valuri ta ’ AUC fil- plażma bejn 4 u 13- il darba ikbar minn dawk fil- bnedmin li ngħataw id- doża rakkomandata (ara sezzjonijiet 4. 4 u 4. 8).
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.
The mechanism of tumour formation and the potential relevance for humans are not known.
Il- mekkaniżmu tal- formazzjoni tat- tumur u tar- relevanza potenzjali lill - bnedmin mhumiex magħrufa.
Carcinogenicity studies in male mice, male and female rats were negative.
Studji dwar ir- riskju ta ’ kanċer fi ġrieden irġiel, u f’ firien irġiel u nisa huma negattivi.
While the carcinogenic potential in humans is unknown, these data suggest that the clinical benefit of efavirenz outweighs the potential carcinogenic risk to humans.
Waqt li l - potenzjal għar- riskju tal- kanċer fil- bnedmin mhux magħruf, dan it- tagħrif jissuġġerixxi li l- benefiċċju kliniku ta ’ efavirenz jegħleb il- potenzjal ta ’ riskju ta ’ kanċer għall- bnedmin.
Capsule core Sodium laurilsulfate Lactose monohydrate Magnesium stearate Sodium starch glycolate
Il- qalba tal- kapsula Sodium laurilsulfate Lactose monohydrate Magnesium stearate Sodium starch glycolate.
Capsule shell Gelatine Sodium laurilsulfate Yellow iron oxide (E172) Titanium dioxide (E171) Silicon dioxide (E551)
Il- qoxra tal- kapsula Ġelatina Sodium laurilsulfate Iron oxide isfar (E172) Titanium dioxide (E171) Silicon dioxide (E551)
Printing ink Cochineal carminic acid (E120) Indigo carmine (E132) Titanium dioxide (E171)
Linka ta ’ l- istampar Cochineal carminic acid (E120) Indigo carmine (E132) Titanium dioxide (E171)
24 6.3 Shelf life
6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
This medicinal product does not require any special storage conditions.
Dan il- prodott mediċinali m’ għandux bżonn prekawzjonijiet speċjali għall- ħażna.
HDPE bottles with a child-resistant polypropylene closure.
Fliexken ta ’ l- HDPE b’ għatu tal- polypropylene li ma jinfetaħx mit- tfal.
Each carton contains 1 bottle of 30 hard capsules.
Kull kartuna fiha flixkun wieħed ta ’ 30 kapsula iebsa.
EU/ 1/ 99/ 111/ 001 - bottle
EU/ 1/ 99/ 111/ 001 - flixkun
Date of latest renewal:
28 ta ’ Mejju 1999 Data ta ’ l- aħħar tiġdid:
28 May 2004.
28 ta ’ Mejju 2004
STOCRIN 100 mg hard capsules
STOCRIN 100 mg kapsuli ibsin
Each hard capsule contains 100 mg of efavirenz.
Kull kapsula iebsa fiha 100 mg ta ’ efavirenz
Excipient: each hard capsule contains 57.0 mg of lactose monohydrate.
Sustanza mhux attiva: kull kapsula iebsa fiha 57. 0 mg ta ’ lactose monohydrate.
For a full list of excipients, see section 6.1.
Għall- lista sħiħa ta ’ sustanzi mhux attivi, ara Sezzjoni 6. 1.
White, printed with “ 3807”.
Bojod, stampati bi ” 3807 ”.
26 STOCRIN 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).
28 STOCRIN mhux rakkomandat għal tfal taħt l- eta` tat- 3 snin jew fi tfal 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).
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
Dosage adjustment: if STOCRIN is coadministered with voriconazole, the voriconazole maintenance dose must be increased to 400 mg every 12 hours and the STOCRIN dose must be reduced by 50%, i. e., to 300 mg once daily.
Aġġustament fid- dożaġġ: jekk STOCRIN jingħata flimkien ma ’ voriconazole, id- doża ta ’ manteniment ta ’ voriconazole għandha tiżdied sa 400 mg kull 12- il siegħa u d- doża ta ’ STOCRIN għandha titnaqqas b’ 50%, jiġifieri, għal 300 mg darba kuljum.
Efavirenz must not be administered concurrently with terfenadine, astemizole, cisapride, midazolam, triazolam, pimozide, bepridil, or ergot alkaloids (for example, ergotamine, dihydroergotamine, ergonovine, and methylergonovine) because competition for CYP3A4 by efavirenz could result in inhibition of metabolism and create the potential for serious and/ or life-threatening undesirable effects [for example, cardiac arrhythmias, prolonged sedation or respiratory depression] (see section 4.5).
[ngħidu aħna, arritmiji kardijaċi, rqad fit- tul jew tnaqqis fin- nifs] (ara sezzjoni 4. 5).
The choice of new antiretroviral agent(s) to be used in combination with efavirenz should take into consideration the potential for viral cross-resistance (see section 5.1).
29 jintużaw flimkien ma ’ efavirenz għandha tqis il- potenzjali ta ’ reżistenza msallba virali (ara sezzjoni 5. 1).
27 Co-administration of efavirenz with the fixed combination tablet containing efavirenz, emtricitabine, and tenofovir disoproxil fumarate, is not recommended.
L- għoti flimkien ta ’ efavirenz mal- pillola ta ’ kombinazzjoni fissa li fiha efavirenz, emtricitabine, u tenofovir disoproxil fumarate, mhuwiex rakkomandat.
Rash was reported in 26 of 57 children (46%) treated with efavirenz during a 48-week period and was severe in three patients.
Ġie rrapurat raxx f’ 26 minn 57 tifel u tifla (46%) li ġew ikkurati bi efavirenz waqt perjodu ta ’ 48 ġimgħa, u kien qawwi fi tliet pazjenti.
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).
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 (ara sezzjoni 4. 8).
Nervous system symptoms usually begin during the first one or two days of therapy and generally resolve after the first 2 - 4 weeks.
Is- sintomi fis - sistema nervuża s- soltu jibdew waqt l- ewwel jum jew jumejn tal- kura u ġeneralment jgħaddu wara l - ewwel ġimgħatejn sa 4 ġimgħat.
Patients who are receiving concomitant anticonvulsant medicinal products primarily metabolised by the liver, such as phenytoin, carbamazepine and phenobarbital, may require periodic monitoring of plasma levels.
30 u phenobarbital, jista ’ jkun hemm bżonn li l- livelli tagħhom fil- plażma jkun monitorat.
In a drug interaction study, carbamazepine plasma concentrations were decreased when carbamazepine was co-administered with efavirenz (see section 4.5).
Fi studju dwar l- interazzjoni tad- drogi, il- konċentrazzjonijiet ta ’ carbamazepine fil- plażma tnaqqsu meta carbamazepine ingħata flimkien ma ’ efavirenz (ara sezzjoni 4. 5).
Caution must be taken in any patient with a history of seizures.
Tris issir attenzjoni ma ’ kull pazjent li jkollu storja ta ’ aċċessjonijiet.
28 Effect of food: the administration of STOCRIN 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 ’ STOCRIN ma ’ l- ikel jista ’ jkabbar l- esponiment għal efavirenz (ara sezzjoni 5. 2) u jista ’ jwassal għal żieda fil- frekwenza tar- reazzjonijiet avversi (ara sezzjoni 4. 8).
Lipid disorders should be managed as clinically appropriate (see section 4.8).
Disturbi tal- lipidi għandhom jiġu kkurati kif jixraq klinikament (ara sezzjoni 4. 8).
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 combination antiretroviral therapy (CART).
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).
Liver disease: because of the extensive cytochrome P450-mediated metabolism of efavirenz and limited clinical experience in patients with chronic liver disease, caution must be exercised in administering efavirenz to patients with mild-to-moderate liver disease.
Indeboliment fil- fwied: minħabba l- metaboliżmu ta ’ efavirenz li hu medjat estensivament minn cytochrome P450, u minħabba l- esperjenza klinika limitata f’ pazjenti b’ mard kroniku fil- fwied, trid issir attenzjoni meta jingħata efavirenz lil pazjenti li għandhom mard tal- fwied minn ħafif sa moderat.
In case of concomitant antiviral therapy for hepatitis B or C, please refer also to the relevant product information for these medicinal products.
31 ħin għall- epatite B u C, jekk jogħġbok irreferi wkoll għall- informazzjoni relevanti dwar il- prodott għal dawn il- prodotti mediċinali.
Renal insufficiency: 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 4.2).
Indeboliment renali: il- karatteristiċi farmakokinetiċi ta ’ efavirenz ma ġewx studjati f’ pazjenti b’ Insuffiċjenza fil- kliewi; madankollu, inqas minn 1% tad- doża ta ’ efavirenz titneħħa fl- urina bla ma tinbidel, għalhekk l- impatt ta ’ l- indeboliment tal- kliewi fuq it- tneħħija ta ’ efavirenz huwa minimu (ara sezzjoni 4. 2).
29 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.
Table 2:
32 Tabella 2:
32 Medicinal product by therapeutic
34 Prodott mediċinali skond l- oqsma terapewtiċi (doża)
33 Medicinal product by therapeutic
35 Prodott mediċinali skond l- oqsma terapewtiċi (doża) NRTIs u NNRTIs
36 Medicinal product by therapeutic
Inibituri Selettivi tat- Teħid mill- ġdid Sertraline/ Efavirenz
37 Medicinal product by therapeutic
Verapamil, Felodipine, Nifedipine u Ma ġietx studjata l- interazzjoni.
Recommendation concerning
40 Prodott mediċinali skond l- oqsma
Rosuvastatin/ Efavirenz
41 Prodott mediċinali skond l- oqsma terapewtiċi (doża)
39 Women of childbearing potential: pregnancy should be avoided in women treated with efavirenz.
Nisa li jistgħu jinqabdu tqal: nisa li qed jieħdu efavirenz m’ għandhomx joħorġu tqal.
Efavirenz may cause dizziness, impaired concentration, and/ or somnolence.
Ma sarux studji dwar l- effetti fuq il- ħila biex issuq jew tħaddem magni Efavirenz jista ’ jikkawża sturdament, tnaqqis fil- konċentrazzjoni, u/ jew ngħas.
The administration of STOCRIN 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 marbuta ma ’ efavirenz li kienu l- iktar prominenti kienu raxx u sintomi tas- sistema nervuża L- għoti ta ’ STOCRIN ma ’ l- ikel jista ’ jkabbar l- esponiment għal efavirenz u jista ’ jwassal għal żieda fil - 43 frekwenza tar- reazzjonijiet avversi (ara sezzjoni 4. 4).
40 Experience with efavirenz in patients who discontinued other antiretroviral agents of the NNRTI class is limited.
L- esperjenza ta ’ efavirenz f’ pazjenti li ma komplewx jieħdu aġenti antiretrovirali oħra tal- klassi NNRTI hija limitata.
Nervous system symptoms: in clinical controlled trials, frequently reported adverse reactions in patients receiving 600 mg efavirenz with other antiretroviral agents included, but were not limited to: dizziness, insomnia, somnolence, impaired concentration and abnormal dreaming.
Sintomi tas- sistema nervuża: fi provi kliniċi kkontrollati, ir- reazzjonijiet avversi li ġew irrappurtati b’ mod frekwenti f’ pazjenti li kienu qed jingħataw 600 mg ta ’ efavirenz ma ’ aġenti antiretrovirali oħra kienu jinkludu, imma ma kinux limitati għal: sturdament, nuqqas ta ’ rqad, ngħas, nuqqas ta ’ konċentrazzjoni u ħolm anormali.
These symptoms were severe in 2.0% of patients receiving efavirenz 600 mg daily and in 1.3% of patients receiving control regimens.
Dawn is - sintomi kienu severi għal 2. 0% mill- pazjenti li kienu qed jirċievu 600 mg ta ’ efavirenz kuljum u f’ 1. 3% tal- pazjenti li kienu qed jirċievu kura kkontrollata.
Analysis of long-term data from study 006 (median follow-up 180 weeks, 102 weeks, and 76 weeks for patients treated with efavirenz + zidovudine + lamivudine, efavirenz + indinavir, and indinavir + zidovudine + lamivudine, respectively) showed that, beyond 24 weeks of therapy, the incidences of new-onset nervous system symptoms among efavirenz-treated patients were generally similar to those in the control arm.
L- analiżi ta ’ tagħrif fit- tul minn studju 006 (medja ta ’ follow up ta ’ 180 ġimgħa, 102 ġimgħa, u 76 ġimgħa għal pazjenti kkurati b’ efavirenz + zidovudine + lamivudine, efavirenz + indinavir, u indinavir + zidovudine + lamivudine, rispettivament) uriet li, wara l- 24 ġimgħa ta ’ terapija, l- inċidenza ta ’ sintomi ġodda marbuta mas- sistema nervuża fost pazjenti kkurati b’ efavirenz kienet ġeneralment simili għall- grupp ta ’ l- istudju ta ’ kontroll.
41 Nervous system disorders common
Disturbi fis- sistema nervuża komuni
Reproductive system and breast disorders
45 Disturbi fis- sistema riproduttiva u fis- sider mhux komuni
42 Combination antiretroviral therapy has been associated with metabolic abnormalities such as hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperglycaemia and hyperlactataemia (see section 4.4).
It- terapija antiretrovirali kombinata ġiet marbuta ma ’ anormalitajiet metaboliċi bħall - ipertriglajseridemija, iperkolesterolemija, reżistenza għall- insulina, ipergliċemija u iperlaktatemija (ara sezzjoni 4. 4).
Liver enzymes: elevations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) to greater than five times the upper limit of the normal range (ULN) were seen in 3% of 1,008 patients treated with 600 mg of efavirenz (5 - 8% after long-term treatment in study 006).
Fi 3% ta ’ 1, 008 pazjenti li ngħataw 600 mg ta ’ efavirenz (5- 8% wara kura fit- tul fi studju 006) l- elevazzjoniet ta ’ aspartate aminotransferase (AST) u alanine aminotransferase (ALT) għolew għal iktar minn ħames darbiet il- livell ta ’ fuq tal- medda normali (ULN).
Lipids: increases in total cholesterol of 10 - 20% have been observed in some uninfected volunteers receiving efavirenz.
46 Lipidi: ġew osservati żidiet fil- kolesterol totali ta ’ 10- 20% f’ voluntiera mhux infettati li kienu qed jieħdu efavirenz.
False positive test results have only been observed with the CEDIA DAU Multi-Level THC assay, which is used for screening, and have not been observed with other cannabinoid assays tested including tests used for confirmation of positive results.
Riżultati pożittivi foloz ġew osservati biss bit- test DAU Multi- Level THC, li jintuża biex jintgħarblu (għall- iscreening),, u ma ġewx osservati b’ testijiet oħra cannabinoid inkluż testijiet li jintużaw biex jiġu kkonfermati r- riżultati pożittivi.