qanastek/EMEA-V3 huggingface dataset:
43 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 STOCRIN 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).
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.
47 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.
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 kienu cross- resistant għal efavirenz u kellhom is- sostituzzjoni K103N.
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 bejnefavirenz u NRTIs huwa baxx minħabba li hemm siti differenti ta ’ rbit fuq il- bersall u l- mekkaniżmu ta ’ l- azzjoni.
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.
48 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.
Responder rates (NC = Fa) Plasma HIV-RNA
Rati tar- rispons (NC = F **) Plażma HIV- RNA
Mean change from baseline-CD4 cell count
Bidla medja mill - linja bażika ta ’ l - għadd taċ - ċelluli CD4 ċelluli / mm3
(55 (41
(55
%, 69%) 48%%, 55%)
%, 69%) 48%
(11.8) 177 (11.3)
(11. 8) 177
Mean change from
Bidla medja mill- linja bażi ta ’ l- għadd taċ - ċelluli CD4
< 500 copies/ ml
< 500 kopja/ ml
46 5.2 Pharmacokinetic properties
5. 2 Tagħrif farmakokinetiku
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.
Distribuzzjoni: efavirenz jintabat ħafna (bejn wieħed u ieħor 99. 5 – 99. 75%) mal- proteini tal- plażma umana, speċjalment albumin.
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.
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.
50 magħrufa; madankollu, il- potenzjal għal frekwenza u severità akbar ta ’ l- episodji avversi assoċjati ma ’ efavirenz ma jistax jiġi eskluż.
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- inqas 52 siegħa wara dożi waħedhom u minn 40 sa 55 siegħa wara dożi multipli.
47 Gender, race, elderly:
Ġendru, razza, anzjani:
Biliary fibrosis has been observed in rats.
Fil- firen ġiet osservata fibrosi biljarja.
Capsule core Sodium laurilsulfate Lactose monohydrate Magnesium stearate Sodium starch glycolate
51 Il- qalba tal- kapsula Sodium laurilsulfate Lactose monohydrate Magnesium stearate Sodium starch glycolate.
Capsule shell Gelatine Sodium laurilsulfate Titanium dioxide (E171) Silicon dioxide (E551)
Ġelatina Sodium laurilsulfate Titanium dioxide (E171) Silicon dioxide (E551)
Printing ink Cochineal carminic acid (E120) Iindigo carmine (E132) Titanium dioxide (E171)
Linka ta ’ l- istampar Cochineal carminic acid (E120) Indigo carmine (E132) Titanium dioxide (E171)
48 6.3 Shelf life
6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
EU/ 1/ 99/ 111/ 002 - bottle
EU/ 1/ 99/ 111/ 002 - flixkun
STOCRIN 200 mg hard capsules
STOCRIN 200 mg kapsuli ibsin
Each hard capsule contains 200 mg of efavirenz.
Kull kapsula fiha 200 mg ta ’ efavirenz
Excipient: each hard capsule contains 114 mg of lactose monohydrate.
Sustanza mhux attiva: kull kapsula iebsa fiha 114 mg ta ’ lactose monohydrate.
Dark yellow, printed with “ 3809”.
Sofor skuri, stampati bi ” 3809 ”.
Although cross-resistance of efavirenz with PIs has not been documented, there are at present insufficient data on the efficacy of subsequent use of PI based combination therapy after failure of regimens containing STOCRIN.
Ghalkemm il- reżistenza msallba ta ’ efavirenz ma ’ PIs ma ġietx dokumentata, fil- preżent m’ hemmx biżżejjed tagħrif dwar l- effikaċja ta ’ l- użu tal- kura kombinata bbażata fuq PI wara li jkunu fallew il- kuri li fihom STOCRIN.
50 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).
54 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).
Hypersensitivity to the active substance or to any of the excipients.
Sensittivita` eċċessiva klinikament sinifikanti għas- sustanza attiva jew għal xi waħda mis- sustanzi mhux attivi.
As with all other non-nucleoside reverse transcriptase inhibitors (NNRTIs), resistant virus emerges rapidly when efavirenz is administered as monotherapy.
Bħal ma ’ non- nucleoside reverse transcriptase inhibitors (NNRTIs), meta efavirenz jiġi
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).
L- għażla ta ’ aġent( i) antiretrovirali li jintużaw flimkien ma ’ efavirenz għandha tqis il- potenzjali ta ’ reżistenza msallba virali (ara sezzjoni 5. 1).
51 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.
Severe rash associated with blistering, moist desquamation or ulceration has been reported in less than 1% of patients treated with efavirenz.
Ġie rrapurtat raxx qawwi marbut ma ’ nfafet, tqaxxir umdu tal- ġilda u ulċeri f’ inqas minn 1% mill- pazjenti kkurati b’ efavirenz.
The incidence of erythema multiforme or Stevens-Johnson syndrome was approximately 0.1%.
L- inċidenza ta ’ eritema multiforme jew is - sindromu ta ’ Stevens- Johnson kien ta ’ bejn wieħed u ieħor 1%.
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 (are sezzjoni 4. 8).
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.
56 mediċinali antikonvulżivi li jiġu metabolizzati primarjament fil- fwied, bħal phenytoin, carbamazepine u phenobarbital, jista ’ jkun hemm bżonn li l- livelli tagħhom fil- plażma jkun monitorjat.
52 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).
The safety and efficacy of efavirenz has not been established in patients with significant underlying liver disorders.
Is- sigurta ’ u l- effikaċja ta ’ efavirenz ma ġewx stabbiliti f’ pazjenti b’ mard ieħor sinifikanti fil- fwied.
In case of concomitant antiviral therapy for hepatitis B or C, please refer also to the relevant product information for these medicinal products.
57 ħin għall- epatite B u C, jekk jogħġbok irreferi wkoll għall- informazzjoni relevanti dwar il- prodott għal dawn il- prodotti mediċinali.
53 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.
John's wort due to induction of drug metabolising enzymes and/ or transport proteins by St.
Il- livelli tal- plasma ta ’ efavirenz jistgħu jitnaqqsu permezz ta ’ użu konkomittanti ta ’ St.
John’ s wort may persist for at least 2 weeks after cessation of treatment (see section 4.3).
John’ s wort jistgħu jibqgħu preżenti għal mill- inqas ġimagħtejn wara l- waqfien tat- trattament (see section 4. 3).
56 Medicinal product by therapeutic
60 Prodott mediċinali skond l- oqsma terapewtiċi (doża)
57 Medicinal product by therapeutic
61 Prodott mediċinali skond l- oqsma terapewtiċi (doża) NRTIs u NNRTIs
60 Medicinal product by therapeutic
Inibituri Selettivi tat- Teħid mill- ġdid Sertraline/ Efavirenz
61 Medicinal product by therapeutic
Verapamil, Felodipine, Nifedipine u Ma ġietx studjata l- interazzjoni.
Recommendation concerning
66 Prodott mediċinali skond l- oqsma
AUC: ↓ 58% (↓ 39 to ↓ 68) Cmax: ↓ 51% (↓ 32 to ↓ 58) Total HMG Co-A reductase inhibitors:
Cmax: ↓ 51% (↓ 32 għal ↓ 58) Inibituri attivi totali HMG Co- A reductase:
AUC: ↓ 60% (↓ 54 to ↓ 74) Cmax: ↓ 70% (↓ 58 to ↓ 85) (CYP3A4 induction) Co-administration of efavirenz with atorvastatin, pravastatin, or simvastatin did not affect efavirenz AUC or Cmax values.
AUC: ↓ 60% (↓ 52 għal ↓ 68) Cmax: ↓ 62% (↓ 55 għal ↓ 78) (induzzjoni ta ’ CYP3A4) L- għoti fl- istess ħin ta ’ efavirenz ma ’ atorvastatin, pravastatin, jew simvastatin ma affettwax il- valuri AUC jew Cmax ta ’ efavirenz.
Rosuvastatin/ Efavirenz
67 Prodott mediċinali skond l- oqsma terapewtiċi (doża)
63 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.
It is recommended that HIV infected women do not breast feed their infants under any circumstances in order to avoid transmission of HIV.
Huma rakkomandat li nisa nfettati bl - HIV bl- ebda mod m’ għandhom ireddgħu lit- trabi tagħhom biex jevitaw it- trażmissjoni ta ’ l- HIV.
The most notable adverse reactions associated with efavirenz are rash and nervous system symptoms.
Ir- reazzjonijiet avversi marbuta ma ’ efavirenz li kienu l- iktar prominenti kienu raxx u sintomi tas- sistema nervuża.
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).
L- għoti ta ’ STOCRIN ma ’ l- ikel jista ’ jkabbar l- esponiment għal efavirenz u jista ’ jwassal għal żieda fil - 69 frekwenza tar- reazzjonijiet avversi (ara sezzjoni 4. 4).
64 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.
65 Nervous system disorders common
Disturbi fis- sistema nervuża komuni
Hepatobiliary disorders uncommon
71 Disturbi fil- fwied u fil- marrara mhux komuni
Psychiatric disorders common
Disturbi psikjatriċi komuni
Immune Reactivation Syndrome: in HIV infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise (see section 4.4).
immunitarja qawwija meta bdew jieħdu t- terapija antiretrovirali kombinata (CART), jista ’ jkun hemm reazzjoni infjammatorja għal reazzjonijiet asintomatiċi jew residwali opportunistiċi (ara sezzjoni 4. 4)
66 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).
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
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.
67 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.
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
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.
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
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.
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.
%, 73%) 54%%, 61%)
(60%, 73%) 54%
70 5.2 Pharmacokinetic properties
5. 2 Tagħrif farmakokinetiku
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.
76 magħrufa; madankollu, il- potenzjal għal frekwenza u severità akbar ta ’ l- episodji avversi assoċjati ma ’ efavirenz ma jistax jiġi eskluż.
71 Gender, race, elderly:
Ġendru, razza, anzjani:
Capsule shell Gelatine Sodium laurilsulfate Yellow iron oxide (E172) Silicon dioxide (E551)
Ġelatina Sodium laurilsulfate Iron oxide isfar (E172) Silicon dioxide (E551)
72 6.3 Shelf life
6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
For bottles:
Għall- fliexken:
2 years.
3 snin Għall- folji: sentejn.
Each carton contains 1 bottle of 90 hard capsules.
Kull kartuna fiha flixkun wieħed ta ’ 90 kapsula iebsa.
Packs of 42 x 1 hard capsules in aluminium perforated unit dose blisters.
Pakki bil- folji ta ’ l- aluminjum bi 42 kapsula iebsa.
EU/ 1/ 99/ 111/ 003 - bottle EU/ 1/ 99/ 111/ 004 - blister
EU/ 1/ 99/ 111/ 003 - flixkun EU/ 1/ 99/ 111/ 004 - folja
STOCRIN 30 mg/ ml oral solution
STOCRIN 30 ml soluzzjoni orali
Each ml contains 30 mg of efavirenz.
Kull ml fiha 30 mg ta ’ efavirenz
Colourless to slightly yellow clear liquid.
Bla kulur sa jagħti fl- isfar.
STOCRIN 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
STOCRIN oral solution may be taken with or without food (see section 5.2).
STOCRIN soluzzjoni orali jista ’ jittieħed ma ’ l- ikel jew mingħajr ikel (ara sezzjoni 5. 2).
In order to improve the tolerability of nervous system undesirable effects, bedtime dosing is recommended during the first two to four weeks of therapy and in patients who continue to experience these symptoms (see section 4.8).
(ara sezzjoni 4. 8).
Adults: the recommended dosage of STOCRIN 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 ’ STOCRIN 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 STOCRIN 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 ’ STOCRIN soluzzjoni orali flimkien ma ’ PI u/ jew NRTIs għal pazjenti bejn it- 3 u s- 17- il sena hija deskritta f’ Tabella 1.
STOCRIN 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 ’ STOCRIN għandhom jinghataw biss lit- tfal li żgur jistgħu jibilgħu l- kapsuli ibsin jew pinnoli b’ rita.
74 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).
80 STOCRIN mhux rakkomandat għal tfal 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).
Body Weight kg
Piż tal- ġisem Kg
STOCRIN oral solution (30 mg/ ml) Dose (ml)
STOCRIN soluzzjoni orali (30 mg/ ml) Doża (ml)
Children
Children 3 - < 5 snin
3 - < 5 years
Adulti 5 snin
Adults and children aged 5 years or more
u tfal ta ’ u fuqhom
13 to < 15 15 to < 20 20 to < 25
13 sa < 15 15 sa < 20 20 sa < 25
25 to < 32.5 32.5 to < 40 ≥ 40
25 sa < 32. 5 32. 5 sa < 40 ≥ 40
STOCRIN oral solution is less bioavailable than the hard capsule on a mg per mg basis.
STOCRIN soluzzjoni orali hija inqas biodisponibbli mill- kapsula iebsa fuq bażi ta ’ tqabbil ta ’ mg ma ’ mg.
The dose recommendations in Table 1 have been adjusted to take into account the difference in bioavailability (see section 5.2).
Ir- rakkomandazzjonijiet ta ’ doża f’ Tabella 1 inbidlu biex iqisu d- differenza fil- biodisponibbilita` (ara taqsima 5. 2).
Renalimpairment: 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).
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).
81 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).
75 4.4 Special warnings and precautions for use
4. 4 Twissijiet speċjali u prekawzjonijiet għall- użu
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.
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 la darba s- sintomi ta ’ l- intoleranza jgħaddu.
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 ’
76 Seizures: convulsions have been observed in patients receiving efavirenz, generally in the presence of known medical history of seizures.
Ġew osservati konvulżjonijiet f’ pazjenti li kienu qed jieħdu efavirenz, ġeneralment meta diġà kien hemm storja medika ta ’ aċċessjonijiet.
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.
Għal pazjenti li qed jirċievu fl- istess ħin prodotti mediċinali antikonvulżivi li jiġu metabolizzati primarjament fil- fwied, bħal phenytoin, carbamazepine u phenobarbital, jista ’ jkun hemm bżonn li l- livelli tagħhom fil- plażma jkun monitorjat.
In a drug interaction study, carbamazepine plasma concentrations were decreased when carbamazepine was co-administered with efavirenz (see section 4.5).
Fi studja dwar l- interazzjoni tad- drogi, il- konċentrazzjonijiet ta ’ carbamazepine fil- plażma tnaqqsu meta carbamazepine ingħata flimkien ma ’ efavirenz (ara sezzjoni 4. 5).
Immune Reactivation Syndrome: in HIV infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms.
Sindromutar- Rijattivazzjoni Immunitarja: f’ pazjenti infettati bl- HIV b’ defiċjenza immunitarja qawwija meta jibdew jieħdu terapija kombinata antiretrovirali (CART), jista ’ jkun hemm reazzjoni infjammatorja għal patoġeni asintomatiċi jew residwi opportunistiċi u tista ’ tikkawża kondizzjonijiet kliniċi serji, jew sintomi li jiħraxu.
Relevant examples are cytomegalovirus retinitis, generalised and/ or focal mycobacterial infections, and pneumonia caused by Pneumocystis jiroveci (formerly known as Pneumocystis carinii).
Eżempji relevanti huma retinite tas- sitomegalovirus, infezzjonijiet mikobatteriċi ġenerallizzati u/ jew fokali, u pulmonite kkważata minn Pneumocystis jiroveci (li qabel kien magħruf bħala Pneumocystis carinii).
Lipodystrophy and metabolic abnormalities: combination antiretroviral therapy has been associated with the redistribution of body fat (lipodystrophy) in HIV patients.
Lipodistrofija u anormalitajiet metaboliċi: it- terapija antiretrovirali kombinata Giet assoċjata mar - ridistribuzzjoni tax- xaħam tal- ġisem (lipodistrofija) f’ pazjenti bl- HIV.
The long-term consequences of these events are currently unknown.
Il- konsegwenzi fit- tul ta ’ dawn eventi mhux magħrufa.
Knowledge about the mechanism is incomplete.
L- għarfien dwar il- mekkaniżmu mhux komplut.
A connection between visceral lipomatosis and PIs and lipoatrophy and NRTIs has been hypothesised.
Ġiet ipotizzata konnessjoni bejn lipomatosis vixxerali u PIs, u l- liportofija u NRTIs.
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 antiretrovirali u disturbi metaboliċi assoċjati magħha.
Clinical examination should include evaluation for physical signs of fat redistribution.
L- eżami kliniku għandu jinkudi evalwazzjoni għal sinjali fiżiċi ta ’ ridistribuzzjoni tax- xaħam.
Consideration should be given to the measurement of fasting serum lipids and blood glucose.
Għandu jitqies jekk għandhomx jitkejlu l- lipidi tas - serum waqt sawm u taz- zokkor fid- demm.
If there is evidence of worsening liver disease or persistent elevations of serum transaminases to greater than 5 times the upper limit of the normal range, the benefit of continued therapy with efavirenz needs to be weighed against the potential risks of significant liver toxicity.
Jekk hemm xhieda ta ’ mard tal- fwied li jeħżien jew ta ’ livelli persistentement għolja ta ’ serum transaminases għal iktar minn 5 darbiet il- livell ta ’ fuq tal- medda normali, il- benefiċċju tat -
77 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).
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.
Evidence exists indicating that efavirenz may have altered pharmacokinetics in very young children.
Hemm evidenza li tindika li efavirenz setgħet biddlet il- karatterisitiċi farmakokinetiċi ta ’ tfal żgħar ħafna.
For this reason, efavirenz oral solution should not be given to children less than 3 years of age.
Għal din ir- raġuni, efavirenz soluzzjoni orali m’ għandhiex tingħata lil tfal ta ’ inqas minn 3 snin.
Table 2:
84 Tabella 2:
If the co-administration of atazanavir with an NNRTI is required, an increase in
Jekk l- għoti fl- istess ħin ta ’ atazanavir ma ’ NNRTI ikun meħtieġ, żieda fid- doża kemm ta ’ atazanavir kif ukoll ta ’ ritonavir għal 400 mg u 200 mg, rispettivament, f’ kombinazzjoni ma ’ efavirenz tista ’ tiġi kkunsidrata b’ monitoraġġ kliniku mill- qrib.
This decrease in atazanavir Cmin might negatively
Dan it- tnaqqis f’ atazanavir Cmin jista ’ jkollu impatt negattiv fuq l- effikaċja ta ’ atazanavir. ** abbażi ta ’ tqabbil storiku
the dose of both atazanavir and ritonavir to 400 mg and 200 mg, respectively, in combination with efavirenz could be considered with close clinical monitoring.
żieda fid- doża kemm ta ’ atazanavir kif ukoll ta ’ ritonavir għal 400 mg u 200 mg, rispettivament, f’ kombinazzjoni ma ’ efavirenz tista ’ tiġi kkunsidrata b’ monitoraġġ kliniku mill- qrib
impact the efficacy of atazanavir. ** based on historical comparison
Is- sinifikat kliniku tal- bidliet għadu
Darunavir/ ritonavir/ Efavirenz (300 mg twice daily*/ 100 mg twice daily/ 600 mg once daily)
(300 mg darbtejn kuljum * / 100 mg
Similar findings are expected with the approved darunavir/ ritonavir
Tisjib simili
600/ 100 mg twice daily dose.
Din il -
(CYP3A4 induction)
AUC: ↓ 31% (↓ 8 għal ↓ 47) Cmin: ↓ 40% Tnaqqis simili fl- espożizzjonijiet għal indinavir ġew osservati meta indinavir 1. 000 mg q8h ingħata
Efavirenz:
flimkien ma ’ efavirenz 600 mg kuljum Efavirenz:
No dosage adjustment is necessary for efavirenz when given with indinavir or indinavir/ ritonavir.
M’ hemmx bżonn ta ’ aġġustament fid- doża għal efavirenz meta jingħata ma ’ indinavir jew indinavir/ ritonavir.
79 Medicinal product by therapeutic
Indinavir/ Ritonavir/ Efavirenz (800 mg darbtejn kuljum/ 100 mg
areas (dose)
Indinavir:
Mean percent change in AUC, Cmax, Cmin with confidence intervals if availablea (mechanism)
AUC: ↓ 25% (↓ 16 għal ↓ 32) b
co-administration with efavirenz
Ara wkoll ir- ringiela dwar ritonavir
(800 mg twice daily/ 100 mg twice daily/ 600 mg once daily)
darbtejn kuljum/ 600 mg darba kuljum)
AUC: ↓ 25% (↓ 16 to ↓ 32) b Cmax: ↓ 17% (↓ 6 to ↓ 26)b Cmin: ↓ 50% (↓ 40 to ↓ 59)b Efavirenz:
Cmax: ↓ 17% (↓ 6 għal ↓ 26) b Cmin: ↓ 50% (↓ 40 għal ↓ 59) b Efavirenz:
With efavirenz, an increase of the lopinavir/ ritonavir soft capsule or oral solution doses by 33% should be considered (4 capsules/ ~6.5 ml
Ma ’ efavirenz, għandha tiġi kkunsidrata żieda ta ’ 33% fid- dożi ta ’ lopinavir/ ritonavir kapsula ratba jew soluzzjoni orali
twice daily instead of 3 capsules/ 5 ml twice daily).
(4 kapsuli/ ~6. 5 ml darbtejn kuljum minflok 3 kapsuli/ 5 ml darbtejn kuljum).
Caution is warranted since this dosage adjustment might be
Hija meħtieġa kawtela billi dan l- aġġustament fid- doża jista ’ ma jkunx suffiċjenti f’ xi pazjenti.
80 Medicinal product by therapeutic
86 Prodott mediċinali skond l- oqsma terapewtiċi (doża)
Raltegravir/ Efavirenz (400 mg single dose/ -)
Inibitur ta ’ trasferiment ta ’ faxxa ta ’ integrase Raltegravir/ Efavirenz (400 mg doża waħda / -)
81 Medicinal product by therapeutic
87 Prodott mediċinali skond l- oqsma terapewtiċi (doża) NRTIs u NNRTIs
NRTIs and NNRTIs NRTIs/ Efavirenz
NRTIs/ Efavirenz
Specific interaction studies have not been performed with efavirenz and NRTIs other than lamivudine, zidovudine, and tenofovir disoproxil fumarate.
Ma sarux studji speċifiċi ta ’ l - interazzjoni b’ efavirenz u NRTIs oħra apparti minn lamivudine, zidovudine, u tenofovir disoproxil fumarate.
Clinically significant interactions are not expected since the NRTIs are metabolised via a different route than efavirenz and would be unlikely to compete for the same metabolic enzymes and elimination pathways.
Mhumiex mistennija interazzjonijiet klinikament sinifikanti billi n- NRTIs huma metabolizzati permezz ta ’ rotta differenti minn efavirenz u mhumiex probabbli li jikkompetu għall- istess enzimi metaboliċi u passaġġi tat- tneħħija.
82 Medicinal product by therapeutic
kuljum)
Effects on drug levels
AUC: ↔ Cmax: ↔ Cmin: ↓ 12% (↓ 24 għal ↑ 1) (induzzjoni ta ’ CYP3A4)
Recommendation concerning
jingħata ma ’ efavirenz.
areas (dose)
88 Prodott mediċinali skond l- oqsma terapewtiċi (doża)
Rifampicin/ Efavirenz (600 mg once daily/ 600 mg once daily) Antifungals
Rifampicin/ Efavirenz (600 mg darba kuljum/ 600 mg darba kuljum) Antifungali
83 Medicinal product by therapeutic
89 Prodott mediċinali skond l- oqsma terapewtiċi (doża)
When efavirenz is co-administered with voriconazole, the voriconazole maintenance dose must be increased to 400 mg twice daily and the efavirenz dose must be reduced by 50%, i. e., to 300 mg once daily.
Meta efavirenz jingħata fl- istess ħin ma ’ voriconazole, id- doża ta ’ manteniment ta ’ voriconazole għandha tiżdied għal 400 mg darbtejn kuljum u d- doża ta ’ efavirenz għandha titnaqqas b’ 50%, jiġifieri għal 300 mg darba kuljum.
Ketoconazole and other imidazole antifungals ACID REDUCING AGENTS
Ketoconazole u antifungali imidazole oħra SUSTANZI LI JNAQQSU L- AĊIDU
Lorazepam/ Efavirenz (2 mg single dose/ 600 mg once daily)
Lorazepam/ Efavirenz (2 mg doża waħda/ 600 mg darba kuljum)
84 Medicinal product by therapeutic
90 Prodott mediċinali skond l- oqsma terapewtiċi (doża) ANTIKONVULSIVI
ANTICONVULSANTS Carbamazepine/ Efavirenz (400 mg once daily/ 600 mg once daily)
Carbamazepine/ Efavirenz (400 mg darba kuljum/ 600 mg darba kuljum)
Vigabatrin/ Efavirenz Gabapentin/ Efavirenz ANTIDEPRESSANTS
Vigabatrin/ Efavirenz Gabapentin/ Efavirenz ANTIDIPRESSANTI
Selective Serotonin Reuptake Inhibitors (SSRIs) Sertraline/ Efavirenz (50 mg once daily/ 600 mg once daily)
(50 mg darba kuljum/ 600 mg darba
Sertraline:
AUC: ↓ 39% (↓ 27 għal ↓ 50)
AUC: ↓ 39% (↓ 27 to ↓ 50) Cmax: ↓ 29% (↓ 15 to ↓ 40) Cmin: ↓ 46% (↓ 31 to ↓ 58) Efavirenz:
Cmax: ↓ 29% (↓ 15 għal ↓ 40) Cmin: ↓ 46% (↓ 31 għal ↓ 58) Efavirenz:
Sertraline dose increases should be guided by clinical response.
rispons kliniku.
85 Medicinal product by therapeutic
91 Prodott mediċinali skond l- oqsma terapewtiċi (doża)
Mean percent change in AUC, Cmax, Cmin with confidence intervals if availablea (mechanism)
Effetti fuq il- livelli tal- mediċina Bidla perċentwali medja fl -
Paroxetine/ Efavirenz (20 mg once daily/ 600 mg once daily)
AUC, Cmax, Cmin bl- intervalli ta ’ kunfidenza jekk disponibblia (mekkaniżmu) Paroxetine/ Efavirenz (20 mg darba kuljum/ 600 mg darba kuljum)
Fluoxetine/ Efavirenz ANTIHISTAMINES
Fluoxetine/ Efavirenz ANTISTAMINI
Since fluoxetine shares a similar metabolic profile with paroxetine, i. e. a strong CYP2D6 inhibitory effect, a similar lack of interaction would be expected for fluoxetine.
Billi fluoxetine għandu profil metaboliku simili għal paroxetine, jiġifieri effett inibitorju qawwi fuq CYP2D6, huwa mistenni nuqqas simili ta ’ interazzjoni għal fluoxetine.
Cetirizine/ Efavirenz (10 mg single dose/ 600 mg once daily) CARDIOVASCULAR AGENTS Calcium Channel Blockers
Cetirizine/ Efavirenz (10 mg doża waħda/ 600 mg darba kuljum) SUSTANZI KARDJOVASKULARI Imblokkaturi tal- Kanali tal- Kalċju
AUC: ↔ Cmax: ↓ 24% (↓ 18 to ↓ 30) These changes are not considered clinically significant.
AUC: ↔ Cmax: ↓ 24% (↓ 18 għal ↓ 30) Dawn il- bidliet mhumiex meqjusa bħala klinikament sinifikanti.
Diltiazem/ Efavirenz (240 mg once daily/ 600 mg once daily)
Diltiazem/ Efavirenz
AUC: ↓ 69% (↓ 55 to ↓ 79) Cmax: ↓ 60% (↓ 50 to ↓ 68) Cmin: ↓ 63% (↓ 44 to ↓ 75) Desacetyl diltiazem:
(240 mg darba kuljum/ 600 mg darba AUC: ↓ 69% (↓ 55 għal ↓ 79) kuljum) Cmax: ↓ 60% (↓ 50 għal ↓ 68) Cmin: ↓ 63% (↓ 44 għal ↓ 75) Desacetyl diltiazem:
Interaction not studied.
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.
Nicardipine Meta efavirenz jingħata fl- istess ħin ma ’ imblokkatur tal- kanali tal - kalċju li jkun substrat ta ’ l- enzima CYP3A4, hemm potenzjal għal tnaqqis fil- konċentrazzjonijiet ta ’ l- imblokkatur tal- kanali tal- kalċju fil- plażma.
Dose adjustments of calcium channel blockers should be guided by clinical response (refer to the Summary of Product Characteristics for 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).
86 Medicinal product by therapeutic
92 Prodott mediċinali skond l- oqsma
Effects on drug levels
Effetti fuq il- livelli tal- mediċina
Recommendation concerning
Rakkomandazzjoni rigward l -
areas (dose)
terapewtiċi (doża)
Mean percent change in AUC, Cmax, Cmin with confidence intervals if availablea (mechanism)
Bidla perċentwali medja fl - AUC, Cmax, Cmin bl- intervalli ta ’ kunfidenza jekk disponibblia (mekkaniżmu)
co-administration with efavirenz
għoti fl- istess ħin ma ’ efavirenz
LIPID LOWERING MEDICINAL PRODUCTS HMG Co-A Reductase Inhibitors Atorvastatin/ Efavirenz (10 mg once daily/ 600 mg once daily)
PRODOTTI MEDIĊINALI LI JBAXXU L- LIPIDI Inibituri HMG Co- A Reductase Atorvastatin/ Efavirenz
Rosuvastatin/ Efavirenz HORMONAL CONTRACEPTIVES
Rosuvastatin/ Efavirenz
Interaction not studied.
L- interazzjoni ma ġietx studjata.
Rosuvastatin is largely excreted unchanged via the faeces, therefore interaction with efavirenz is not expected.
Ħafna minn Rosuvastatin huwa eliminat mhux mibdul permezz tal- eskreta, għalhekk mhijiex mistennija interazzjoni ma ’ efavirenz.
No dosage adjustment is necessary for either medicinal product.
Ma hemm bżonn ta ’ ebda aġġustament fid- doża la għal prodott mediċinali wieħed u lanqas għall- ieħor.
Ethinyloestradiol/ Efavirenz (50 µg single dose/ 400 mg once daily)
KONTRAĊETTIVI ORMONALI Ethinyloestradiol/ Efavirenz (50 µg doża waħda/ 400 mg darba kuljum) IMMUNOSUPPRESSANTI
IMMUNOSUPPRESSANTS Immunosuppressants metabolized by CYP3A4 (e. g., cyclosporine, tacrolimus, sirolimus)/ Efavirenz OPIOIDS
Immunosuppressanti metabolizzati minn CYP3A4 (eż., cyclosporine, tacrolimus, sirolimus) / Efavirenz OPOIDI
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.
88 Lactation: studies in rats have demonstrated that efavirenz is excreted in milk reaching concentrations much higher than those in maternal plasma.
Treddigħ: studji fil- firien urew li l- efavirenz joħroġ fil- ħalib u jilħaq konċentrazzjonijiet ħafna ogħla minn dawk fil- plażma ta ’ l- omm.
The most notableadverse reactions associated with efavirenz are rash and nervous system symptoms (see section 4.4).
Ir- reazzjonijiet avversi marbuta ma ’ efavirenz li kienu l- iktar prominenti kienu raxx u sintomi tas- sistema nervuża (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 180 weeks), efavirenz + indinavir (n = 415, median duration 102 weeks), or indinavir + zidovudine + lamivudine (n = 401, median duration 76 weeks).
95 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).
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.
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.
Fi studju kliniku, il- prevalenza kull xahar tas - 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.
In a study of uninfected volunteers, a representative nervous system symptom had a median time to onset of 1 hour post-dose and a median duration of 3 hours.
96 jitfaċċa medja ta ’ siegħa wara d- doża u kien idum medja ta ’ 3 sigħat.
Nervous system disorders common
Disturbi fis- sistema nervuża komuni
90 Ear and labyrinth disorders uncommon
Disturbi fil- widnejn u fis- sistema labirintika
Vertigo
mhux komuni
common
Disturbi gastro- intestinali komuni
Skin and subcutaneous tissue disorders
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda komuni ħafna
Rash
raxx
Pruritus
ħakk
General disorders and administration site conditions common
Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata
Fatigue
għeja
Reproductive system and breast disorders
97 Disturbi fis- sistema riproduttiva u fis- sider mhux komuni
Gynaecomastia
Disturbi psikjatriċi
Combination antiretroviral therapy has been associated with redistribution of body fat (lipodystrophy) in HIV patients including the loss of peripheral and facial subcutaneous fat, increased intra-abdominal and visceral fat, breast hypertrophy and dorsocervical fat accumulation (buffalo hump).
Lipodistrofija u anormalitajiet metaboliċi: it- terapija antiretrovirali kombinata ġiet assoċjata mar - ridistribuzzjoni tax- xaħam tal- ġisem (lipodistrofija) f’ pazjenti bl- HIV inkluż it- telf tax- xaħam periferali u ta ’ taħt il- ġilda tal- wiċċ, żieda fix- xaħam fiż- żaqq u fil- vixxri, ipertrofija tas- sider u akkumulu tax- xaħam fuq ix- xewka tad- dahar (ħotba ta ’ buflu).
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
Enzimi tal- fwied:
Similar elevations were seen in patients treated with control regimens (5% after long-term treatment).
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.
98 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.
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.
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.
92 4.9 Overdose
4. 9 Doża eċċessiva
Efavirenz is a NNRTI of HIV-1.
Kif jaħdem: efavirenz huwa NNRTI ta ’ l- HIV- 1.
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.
99 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.
Two of three delavirdine-resistant clinical isolates examined were cross-resistant to efavirenz and contained the K103N substitution.
Tnejn minn tliet iżolati kliniċi reżistenti għal delavirdine li ġew eżaminati kienu cross- resistant għal efavirenz u kellhom is- sostituzzjoni K103N.
93 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.
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.
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.
100 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.
(11.8) 177 (11.3) 153
(11. 3) 153
NC = F, noncompleter = failure. b C. I., confidence interval. c 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.
94 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.
Table 4:
101 Tabella 4:
In uninfected adult volunteers, the Cmax and AUC of a 240 mg dose of STOCRIN oral solution were 78% and 97%, respectively, of the values measured when STOCRIN was given as a 200 mg hard capsule.
F’ voluntiera adulti mhux infettati, Cmax u AUC ta ’ doża ta ’ 240 mg ta ’ STOCRIN soluzzjoni orali kienu 78% u 97%, rispettivament, tal- valuri mkejla meta STOCRIN ngħata bħala kapsula iebsa tal - 200 mg.