qanastek/EMEA-V3 huggingface dataset:
In order to improve the tolerability of nervous system undesirable effects, bedtime dosing is recommended (see section 4.8).
Biex titjieb it- tollerabilita` tas- sistema nervuża għall- effetti mhux mixtieqa, huwa rakkomandat li d - dożi jittieħdu qabel l- irqad (ara sezzjoni 4. 8).
Adults: the recommended dosage of SUSTIVA in combination with nucleoside analogue reverse transcriptase inhibitors (NRTIs) with or without a PI (see section 4.5) is 600 mg orally, once daily.
Adulti: id- doża rakkomandata ta ’ SUSTIVA flimkien ma ’ nucleoside analogue reverse transcriptase inhibitors (NRTIs) flimkien ma ’ PIs jew mingħajrhom (ara sezzjoni 4. 5) hija ta ’ 600 mg kuljum, darba kuljum.
Paediatric patients (3 to 17 years): the recommended dose of SUSTIVA in combination with a PI and/ or NRTIs for patients between 3 and 17 years of age is described in Table 1.
Pazjenti pedjatriċi (minn 3 sa 17- il sena): id- doża rakkomandata ta ’ SUSTIVA flimkien ma ’ PI u/ jew NRTIs għal pazjenti bejn it- 3 u s- 17- il sena hija deskritta f’ Tabella 1.
SUSTIVA hard capsules must only be administered to children who are able to reliably swallow hard capsules.
Il- kapsuli ibsin ta ’ SUSTIVA għandhom jinghataw biss lit- tfal li żgur jistgħu jibilgħu l- kapsuli ibsin.
2 SUSTIVA is not recommended for use in children below the age of 3 years or weighing less than 13 kg due to a lack of data on safety and efficacy in that age group (see sections 5.1 and 5.2).
2 għal pazjenti 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).
Alternative method of administration: for children at least 3 years old and weighing at least 13 kg and adults who cannot reliably swallow hard capsules, SUSTIVA oral solution is the preferred formulation.
Metodu alternattiv tal- għoti: għal tfal li għandhom mill- inqas 3 snin u li jiżnu għallinqas 13- il kg u adulti li ma jistgħux jibilgħu l- kapsuli iebsin b’ mod affidabbli, is- soluzzjoni orali SUSTIVA hija l - formulazzjoni ppreferuta.
Administration of the capsule contents with a small amount (1-2 teaspoons) of food may be considered for patients who cannot tolerate the oral solution.
1- 2 kuċċarini) ta ’ ikel jista ’ jiġi kkunsidrat għal pazjenti li ma jistgħux jittolleraw is- soluzzjoni orali.
In a palatability study in healthy adults of efavirenz mixed with applesauce, grape jelly, yogurt, or infant formula, grape jelly received the highest rating of good overall taste.
Fi studju tal - palatabilità f’ adulti b’ saħħithom ta ’ efavirenz imħallat mal- meraq tat- tuffieħ, jelly ta ’ l- għeneb, jogurt jew ħalib tat- trabi, il- jelly ta ’ l- għeneb irċieva l- ogħla punteġġ ta ’ l- aktar togħma tajba in ġenerali.
Patients and caregivers must be instructed to open the capsule carefully to avoid spillage or dispersion of the capsule contents into the air.
Il - pazjenti u dawk li jieħdu ħsieb it- tfal għandhom jiġu avżati biex jiftħu l- kapsula b’ attenzjoni biex jevitaw tifrigħ jew tixrid tal- kontenut tal- kapsula fl- arja.
It is recommended to hold the capsule vertically with the cap facing up and to pull the cap away from the body of the capsule, and to mix the capsule contents with food in a small container.
Huwa rrakkomandat li l- kapsula tinżamm f’ pożizzjoni wieqfa bil- kappa tħares ’ il fuq u li l- kappa tinġibed ’ il bogħod mill- bqija tal- kapsula, u li l- kontenut tal- kapsula jitħallat ma ’ l- ikel f’ reċipjent żgħir.
The mixture should be administered as soon as possible, but no more than 30 minutes after mixing.
It- taħlita għandha tingħata kemm jista ’ jkun malajr, iżda mhux aktar tard minn 30 minuta wara li ssir it- taħlita.
After administration of the efavirenz-food mixture, an additional small amount (approximately 2 teaspoons) of food must be added to the empty mixing container, stirred to disperse any remaining residue of the medicinal product, and administered to the patient.
Wara l- għoti tat- taħlita efavirenz - ikel, ammont żgħir addizzjonali (madwar 2 kuċċarini) ta ’ ikel għandu jiżdied fir- reċipjent tat- taħlit il - vojt, jiġi mħawwad sabiex idub kwalunkwe residwu tal- mediċina, u din għandha tingħata lill- pazjent.
No additional food should be consumed for up to 2 hours after administration of efavirenz.
Ebda ikel addizzjonali ma għandu jiġi kkunsmat sa sagħtejn wara l- għoti ta ’ efavirenz.
There are limited safety and tolerability data for administration of the capsule contents in paediatric patients.
Hemm tagħrif limitat dwar is- sigurtà u t- tollerabbiltà għall- għoti tal- kontenut tal- kapsuli f’ pazjenti pedjatriċi.
Table 1 Paediatric dose to be administered once daily*
Tabella 1 Doża għat- tfal li għandha tingħata darba kuljum *
SUSTIVA Dose (mg) 200 250 300 350 400 600
SUSTIVA Doża (mg) 200 250 300 350 400 600
*For information on the bioavailability of the capsule contents mixed with food vehicles, see section 5.2.
* Għal informazzjoni dwar il- bijodisponibbiltà tal- kontenut tal- kapsuli mħallat ma ’ sustanzi li fihom l- ikel, ara sezzjoni 5. 2.
If SUSTIVA is coadministered with voriconazole, the voriconazole maintenance dose must be increased to 400 mg every 12 hours and the SUSTIVA dose must be reduced by 50%, i. e., to 300 mg once daily.
Aġġustament fid- dożaġġ: jekk SUSTIVA jingħata flimkien ma ’ voriconazole, id- doża ta ’ manteniment ta ’ voriconazole għandha tiżdied sa 400 mg kull 12- il siegħa u d- doża ta ’ SUSTIVA għandha titnaqqas b’ 50%, jiġifieri għal 300 mg darba kuljum.
If SUSTIVA is coadministered with rifampicin, an increase in the dose of SUSTIVA to 800 mg/ day may be considered (see section 4.5).
Jekk SUSTIVA jingħata flimkien ma ’ rifampicin, tista ’ tiġi kkunsidrata żieda fid- doża ta ’ SUSTIVA għal 800 mg/ kuljum (ara sezzjoni 4. 5).
Efavirenz must not be used in patients with severe hepatic impairment (Child Pugh Grade C) (see section 5.2).
3 Efavirenz m’ għandux jintuża minn pazjenti b’ indeboliment sever tal- fwied (Grad Child Pugh C) (ara sezzjoni 5. 2).
3 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, sedazzjoni fit- tul jew depressjoni respiratorja] (ara sezzjoni 4. 5).
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.
When prescribing medicinal products concomitantly with SUSTIVA, physicians should refer to the corresponding Summary of Product Characteristics.
Meta jiġu preskritti prodotti mediċinali flimkien ma ’ SUSTIVA, it- tobba għandhom jirreferu għall - Karatteristiċi tal- Prodott fil- Qosor korrispondenti.
In particular, severe depression was more common in those with a history of depression.
B’ mod partikulari, depressjoni qawwija iktar komuni fost dawk li
4 immediately to assess the possibility that the symptoms may be related to the use of efavirenz, and if so, to determine whether the risks of continued therapy outweigh the benefits (see section 4.8).
Kien hemm ukoll rapporti wara li prodott beda jinbiegħ ta ’ depressjoni qawwija, mewt b’ suwiċidju, delużjonijiet u mġieba li tixbah dik psikotika.
Seizures: convulsions have been observed in patients receiving efavirenz, generally in the presence of known medical history of seizures.
Aċċessjonijiet: ġew osservati konvulżjonijiet fpazjenti li kienu qed jieħdu efavirenz, ġeneralment meta diġà kien hemm storja medika ta aċċessjonijiet.
Effect of food: the administration of SUSTIVA with food may increase efavirenz exposure (see section 5.2) and may lead to an increase in the frequency of adverse reactions (see section 4.8).
Effett ta ’ l- ikel: l- għoti ta SUSTIVA ma l- ikel jista jkabbar l- esponiment għal efavirenz (ara sezzjoni 5. 2) u jista jwassal għal żieda fil- frekwenza tar- reazzjonijiet avversi (ara sezzjoni 4. 8).
It is recommended that SUSTIVA be taken on an empty stomach, preferably at bedtime.
Huwa rakkomandat li SUSTIVA jittieħed fuq stonku vojt, preferibbilment qabel l- irqad.
The long-term consequences of these events are currently unknown.
Bħalissa l- konsekwenzi fit- tul ta ’ dawn l- reazzjonijiet mhumiex magħrufin.
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.
Il- pazjenti
Patients should be monitored carefully for dose-related adverse reactions, especially nervous system symptoms.
5 għandhom jiġu mmonitorjati sew għal reazzjonijiet avversi marbuta mal- mediċina, speċjalment għal sintomi tas- sistema nervuża.
Efavirenz is contraindicated in patients with severe hepatic impairment (see
Efavirenz m’ għandux jingħata lil pazjenti b’ indeboliment sever tal- fwied (ara sezzjoni 4. 3).
Patients with pre- existing liver dysfunction including chronic active hepatitis have an increased frequency of liver function abnormalities during combination antiretroviral therapy and should be monitored according to standard practice.
Pazjenti li l- fwied tagħhom ma kienx jaħdem tajjeb minn qabel inkluż b’ epatite attiva kronika għandhom frekwenza ikbar ta ’ anormalitajiet fil- funzjoni tal- fwied waqt it- terapija antiretrovirali kombinata u għandhom jiġi mmonitorjati skond il - prattika normali.
Lactose: patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Lactose: pazjenti bi problemi ereditarji rari ta ’ intolleranza ta ’ galactose, defiċjenza ta ’ Lapp lactase jew assorbiment ħażin ta ’ glucose- galactose m’ għandhomx jieħdu dan il- prodott mediċinali.
Contraindications of concomitant use Efavirenz must not be administered concurrently with terfenadine, astemizole, cisapride, midazolam, triazolam, pimozide, bepridil, or ergot alkaloids (for example, ergotamine, dihydroergotamine, ergonovine, and methylergonovine), since inhibition of their metabolism may lead to serious, life-threatening events (see section 4.3).
Kontra- indikazzjonijiet ta ’ l- użu simultanju Efavirenz m’ għandux jingħata flimkien ma ’ terfenadine, astemizole, cisapride, midazolam, triazolam, pimozide, bepridil, jew ergot alkaloids (ngħidu aħna, ergotamine, dihydroergotamine, ergonovine, u methylergonovine) billi l- inibizzjoni tal- metaboliżmu tagħhom jista ’ jwassal għal avvenimenti serji u ta ’ riskju għall- ħajja (ara sezzjoni 4. 3).
John’ s wort due to induction of drug metabolising enzymes and/ or transport proteins by St.
John' s wort minħabba l- induzzjoni ta ’ enzimi li jimmetabolizzaw il- mediċini u/ jew jittrasportaw il- proteini permezz ta ’ St.
John’ s wort.
John' s wort.
Efavirenz levels may increase on stopping St.
John’ s wort
John’ s wort and the dose of efavirenz may need adjusting.
6 u d- doża ta ’ efavirenz jista ’ jkollha bżonn ta ’ aġġustament.
(see section 4.3).
John’ s wort jistgħu jibqgħu preżenti għal mill- inqas ġimagħtejn wara l- waqfien tat- trattament (ara sezzjoni 4. 3).
therapeutic areas (dose)
Prodott mediċinali skond l- oqsma terapewtiċi (doża) ANTI- INFETTIVI Antiretrovirali Inibituri protease (PI)
If the co- administration of atazanavir with an NNRTI is required, an increase in the dose of both
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.
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
Darunavir/ ritonavir/ Efavirenz (300 mg twice daily*/ 100 mg twice daily/ 600 mg once daily)
Darunavir/ ritonavir/ Efavirenz (300 mg darbtejn kuljum * / 100 mg darbtejn kuljum/ 600 mg darba kuljum)
AUC: ↓ 13% Cmin: ↓ 31% (CYP3A4 induction)
AUC: ↓ 13% Cmin: ↓ 31% (induzzjoni ta ’ CYP3A4) Efavirenz:
The clinical significance of the changes has not been established.
Is- sinifikat kliniku tal- bidliet għadu ma ġiex stabbilit.
Similar findings are expected with the approved
Din il -
*lower than recommended dose
* inqas mid- doża rakkomandata
AUC: ↑ 21% Cmin: ↑ 17% (CYP3A4 inhibition)
AUC: ↑21% Cmin: ↑17% (inibizzjoni ta ’ CYP3A4)
darunavir/ ritonavir 600/ 100 mg twice daily dose.
kombinazzjoni għandha tintuża b’ kawtela.
This combination should be used with caution.
Ara r- ringiela ta ’ ritonavir taħt.
Fosamprenavir/ ritonavir/ Efavirenz (700 mg twice daily/ 100 mg twice daily/ 600 mg once daily)
Fosamprenavir/ Ritonavir/ Efavirenz (700 mg darbtejn kuljum/ 100 mg darbtejn kuljum/ 600 mg darba kuljum)
No clinically significant pharmacokinetic interaction
Ebda interazzjoni farmakokinetika klinikament sinifikanti.
No dosage adjustment is necessary for any of these medicinal products.
Ebda aġġustament fid- doża għall - ebda wieħed minn dawn il- prodotti mediċinali.
Interaction not studied.
L- interazzjoni ma ġietx studjata
Not recommended as the exposure to both PIs is expected to be significantly decreased.
Mhux rakkomandat minħabba li l - espożizzjoni għaż- żewġ PIs hija mistennija li tkun ferm inqas.
therapeutic areas (dose)
Indinavir/ Efavirenz (1, 000 mg q8h/ 600 mg darba kuljum)
Mean percent change in AUC, Cmax, Cmin with confidence intervals if availablea (mechanism)
Ebda interazzjoni farmakokinetika klinikament sinifikanti
co-administration with efavirenz
M’ hemmx bżonn ta ’ aġġustament fid- doża għal efavirenz meta jingħata ma ’ indinavir jew indinavir/ ritonavir.
AUC: ↓ 25% (↓ 16 to ↓ 32)b Cmax: ↓ 17% (↓ 6 to ↓ 26)b Cmin: ↓ 50% (↓ 40 to ↓ 59)b Efavirenz:
AUC: ↓ 25% (↓ 16 għal ↓ 32) b
No clinically significant pharmacokinetic interaction The geometric mean Cmin for indinavir (0.33 mg/ l) when given with ritonavir
Ara wkoll ir- ringiela dwar ritonavir
No dosage adjustment is necessary for efavirenz when given with indinavir or indinavir/ ritonavir.
darbtejn kuljum/ 600 mg darba kuljum)
and efavirenz was higher than the mean historical Cmin (0.15 mg/ l) when indinavir was given alone at 800 mg q8h.
Ebda interazzjoni farmakokinetika klinikament sinifikanti Il- Cmin ġeometrika medja għal indinavir (0. 33 mg/ l) meta ngħata ma ’ ritonavir u efavirenz kienet ogħla mill- Cmin storika medja (0. 15 mg/ l) meta indinavir ingħata waħdu f’ doża ta ’ 800 mg q8h.
With efavirenz, an increase of the lopinavir/ ritonavir soft capsule or oral solution doses
Ma ’ efavirenz, għandha tiġi kkunsidrata żieda ta ’ 33% fid- dożi ta ’ lopinavir/ ritonavir kapsula ratba jew soluzzjoni orali
since this dosage adjustment might be insufficient in some patients.
Hija meħtieġa kawtela billi dan l- aġġustament fid- doża jista ’ ma jkunx suffiċjenti f’ xi pazjenti.
The dosage of lopinavir/ ritonavir tablets should be increased to 500/ 125 mg twice daily when co-administered with efavirenz 600 mg once daily.
Id- dożaġġ ta ’ pilloli ta ’ lopinavir/ ritonavir għandu jiżdied għal 500/ 125 mg darbtejn kuljum meta mogħti flimkien ma ’ efavirenz 600 mg kuljum.
8
8 Prodott mediċinali skond l- oqsma terapewtiċi (doża)
Morning AUC: ↑ 18% (↑ 6 to ↑ 33) Evening AUC: ↔ Morning Cmax: ↑ 24% (↑ 12 to ↑ 38) Evening Cmax: ↔ Morning Cmin: ↑ 42% (↑ 9 to ↑ 86) b Evening Cmin: ↑ 24% (↑ 3 to ↑ 50) b Efavirenz:
AUC filgħodu: ↑ 18% (↑ 6 għal ↑ 33) AUC filgħaxija: ↔ Cmax filgħodu: ↑ 24% (↑ 12 għal ↑ 38) Cmax filgħaxija: ↔ Cmin filgħodu: ↑ 42% (↑ 9 għal ↑ 86) b Cmin filgħaxija ↑ 24% (↑ 3 għal ↑ 50) b Efavirenz:
AUC: ↑ 21% (↑ 10 to ↑ 34) Cmax: ↑ 14% (↑ 4 to ↑ 26) Cmin: ↑ 25% (↑ 7 to ↑ 46) b (inhibition of CYP-mediated oxidative metabolism) When efavirenz was given with ritonavir 500 mg or 600 mg twice daily, the combination was not well tolerated (for example, dizziness, nausea, paraesthesia and elevated liver enzymes occurred).
AUC: ↑ 21% (↑ 10 għal ↑ 34) Cmax: ↑ 14% (↑ 4 għal ↑ 26) Cmin: ↑ 25% (↑ 7 għal ↑ 46) b (inibizzjoni ta ’ metaboliżmu ossidattiv medjat minn CYP) Meta efavirenz ingħata ma ’ ritonavir 500 mg jew 600 mg darbtejn kuljum, it- taħlita ma kinetx ittollerata sewwa (per eżempju, kien hemm sturdament, dardir, parasteżija u żieda fl - enzimi tal- fwied).
9
9 Prodott mediċinali skond l- oqsma terapewtiċi (doża) NRTIs u NNRTIs
therapeutic areas (dose)
NRTIs/ Efavirenz
Mean percent change in AUC, Cmax, Cmin with confidence intervals if availablea (mechanism)
Ma sarux studji speċifiċi ta ’ l - interazzjoni b’ efavirenz u NRTIs oħra apparti minn lamivudine, zidovudine, u tenofovir disoproxil fumarate.
co-administration with efavirenz
M’ hemm bżonn ta ’ aġġustament fid- doża għall- ebda wieħed minn dawn il- prodotti mediċinali.
and another NNRTI is not recommended.
Billi l- użu ta ’ żewġ NNRTIs ma rriżultax benefiku f’ termini ta ’ l - effikaċja u s- sigurtà, l- għoti flimkien ta ’ efavirenz u NNRTI ieħor mhuwiex rakkomandat.
Antibiotics Azithromycin/ Efavirenz (600 mg single dose/ 400 mg once daily)
Azithromycin/ Efavirenz (600 mg doża waħda/ 400 mg darba kuljum)
Other macrolide antibiotics (e. g. ,erythromycin)/ Efavirenz Antimycobacterials
Antibijotiċi makrolidi oħrajn (e. ż., erythromycin) / Efavirenz Antimikobatteriċi
Rifabutin/ Efavirenz (300 mg once daily/ 600 mg once daily)
Rifabutin/ Efavirenz (300 mg darba kuljum/ 600 mg darba kuljum)
AUC: ↓ 38% (↓ 28 to ↓ 47) Cmax: ↓ 32% (↓ 15 to ↓ 46) Cmin: ↓ 45% (↓ 31 to ↓ 56) Efavirenz:
AUC: ↓ 38% (↓ 28 għal ↓ 47) Cmax: ↓ 32% (↓ 15 għal ↓ 46) Cmin: ↓ 45% (↓ 31 għal ↓ 56) Efavirenz:
AUC: ↔ Cmax: ↔ Cmin: ↓ 12% (↓ 24 to ↑ 1) (CYP3A4 induction)
AUC: ↔ Cmax: ↔ Cmin: ↓ 12% (↓ 24 għal ↑ 1) (induzzjoni ta ’ CYP3A4)
The daily dose of rifabutin should be increased by 50% when administered with efavirenz.
Id- doża ta ’ kuljum ta ’ rifabutin għandha tiżdied b’ 50% meta jingħata ma ’ efavirenz.
When taken with rifampicin, increasing efavirenz daily dose to 800 mg may provide exposure similar to a daily dose of 600 mg when taken without rifampicin.
Meta meħud ma ’ rifampicin, iż - żieda fid- doża ta ’ kuljum ta ’ efavirenz għal 800 mg tista ’ tipprovdi esponiment simili għal doża ta ’ 600 mg, meta jittieħed mingħajr rifampicin.
Antifungals Itraconazole/ Efavirenz (200 mg q12h/ 600 mg once daily)
Itraconazole/ Efavirenz (200 mg q12h/ 600 mg darba kuljum)
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
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.
Voriconazole/ Efavirenz (400 mg twice daily/ 300 mg once daily)
Voriconazole/ Efavirenz (400 mg darbtejn kuljum/ 300 mg darba kuljum)
AUC: ↓ 7% (↓ 23 to ↑ 13) * Cmax: ↑ 23% (↓ 1 to ↑ 53) * Efavirenz:
AUC: ↓ 7% (↓ 23 għal ↑ 13) * Cmax: ↑ 23% (↓ 1 għal ↑ 53) * Efavirenz:
When treatment with voriconazole is stopped, the initial dosage of efavirenz should be restored.
Meta jitwaqqaf it- trattament b’ voriconazole, għandha terġa ’ tiddaħħal id- doża inizjali ta ’ efavirenz.
ACID REDUCING AGENTS Aluminium hydroxide-magnesium hydroxide-simethicone antacid/ Efavirenz (30 ml single dose/ 400 mg single dose) Famotidine/ Efavirenz (40 mg single dose/ 400 mg single dose) ANTIANXIETY AGENTS
Aluminium hydroxide- magnesium hydroxide- simethicone antacid/ Efavirenz (30 mL doża waħda/ 400 mg doża waħda) Famotidine/ Efavirenz (40 ng doża waħda/ 400 mg doża waħda) SUSTANZI KONTRA L- ANSJETÀ
There is a potential for reduction or increase in the plasma concentrations of phenytoin, phenobarbital and other anticonvulsants that are substrates of CYP450 isoenzymes when co- administered with efavirenz.
Hemm potenzjal għal tnaqqis jew żieda fil- konċentrazzjonijiet fil - plażma ta ’ phenytoin, phenobarbital u antikonvulsivi oħra li huma substrati ta ’ isoenzimi CYP450 meta jingħataw fl- istess ħin ma ’ efavirenz.
When efavirenz is co- administered with an anticonvulsant that is a substrate of CYP450 isoenzymes, periodic monitoring of anticonvulsant levels should be conducted.
Meta efavirenz jingħata fl- istess ħin ma ’ antikonvulsiv li jkun substrat ta ’ isoenzimi CYP450, għandu jsir monitoraġġ perjodiku tal- livelli ta ’ l- antikonvulsiv.
Recommendation concerning
Inibituri Selettivi tat- Teħid mill- ġdid
therapeutic areas (dose)
ta ’ Serotonin (SSRIs)
ANTIDEPRESSANTS Selective Serotonin Reuptake Inhibitors (SSRIs) Sertraline/ Efavirenz (50 mg once daily/ 600 mg once daily)
Sertraline/ Efavirenz (50 mg darba kuljum/ 600 mg darba kuljum)
AUC: ↓ 39% (↓ 27 to ↓ 50) Cmax: ↓ 29% (↓ 15 to ↓ 40) Cmin: ↓ 46% (↓ 31 to ↓ 58) Efavirenz:
AUC: ↓ 39% (↓ 27 għal ↓ 50) Cmax: ↓ 29% (↓ 15 għal ↓ 40) Cmin: ↓ 46% (↓ 31 għal ↓ 58) Efavirenz:
Sertraline dose increases should be guided by clinical response.
Iż- żidiet fid- doża ta ’ sertraline għandhom ikunu ggwidati mir - rispons kliniku.
Verapamil, Felodipine, Nifedipine and Nicardipine
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
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
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).
Medicinal product by
14 Prodott mediċinali skond l- oqsma
therapeutic areas (dose)
terapewtiċi (doża)
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 (10 mg darba kuljum/ 600 mg darba kuljum)
AUC: ↓ 43% (↓ 34 to ↓ 50) Cmax: ↓ 12% (↓ 1 to ↓ 26) 2-hydroxy atorvastatin:
AUC: ↓ 43% (↓ 34 għal ↓ 50) Cmax: ↓ 12% (↓ 1 għal ↓ 26) 2- hydroxy atorvastatin:
Dosage adjustment of atorvastatin may be required (refer to the Summary of Product Characteristics for atorvastatin).
Jistgħu jkunu meħtieġa aġġustamenti fid- doża ta ’ atorvastatini (irreferi għas - Sommarju tal- Karatteristiċi tal - Prodott għall- atorvastatin).
Pravastatin/ Efavirenz (40 mg once daily/ 600 mg once daily)
Pravastatin/ Efavirenz
Dosage adjustment of pravastatin may be required (refer to the Summary of Product Characteristics for pravastatin).
Jistgħu jkunu meħtieġa aġġustamenti fid- doża ta ’ pravastatin (irreferi għas- Sommarju tal- Karatteristiċi tal- Prodott).
Dosage adjustment of simvastatin may be required (refer to the Summary of Product Characteristics for simvastatin).
Jistgħu jkunu meħtieġa aġġustamenti fid- doża ta ’ simvastatin (irreferi għas - Sommarju tal- Karatteristiċi tal - Prodott għal simvastatin).
Immunosuppressants metabolized by CYP3A4 (eg, cyclosporine, tacrolimus, sirolimus)/ Efavirenz OPIOIDS
Immunosuppressanti metabolizzati minn CYP3A4 (eż., cyclosporine, tacrolimus, sirolimus) / Efavirenz OPOIDI
Buprenorphine/ naloxone/ Efavirenz a
AUC, Cmax, Cmin bl- intervalli ta ’ kunfidenza jekk disponibblia (mekkaniżmu) Buprenorphine/ naloxone/ Efavirenz
90% confidence intervals unless otherwise noted. b 95% confidence intervals.
a intervalli ta ’ kunfidenza ta ’ 90% sakemm mhux indikat mod ieħor. b intervalli ta ’ kunfidenza ta ’ 95%.
15 Pregnancy: there are limited amount of data from the use of efavirenz in pregnant women.
Tqala: jeżisti ammont limitat ta ’ dejta mill- użu ta ’ efavirenz f’ nisa tqal.
The administration of SUSTIVA with food may increase efavirenz exposure and may lead to an increase in the frequency of adverse reactions (see section 4.4).
Ir- reazzjonijiet avversi marbuta ma ’ efavirenz li kienu l- iktar prominenti kienu raxx u sintomi tas- sistema nervuża L- għoti ta ’ SUSTIVA ma ’ l- ikel jista ’ jkabbar l- esponiment għal efavirenz u jista ’ jwassal għal żieda fil - 17 frekwenza tar- reazzjonijiet avversi (ara sezzjoni 4. 4).
In controlled trials of 1,008 patients treated with regimens containing efavirenz for an
Fi provi kkontrollati b’ 1, 008 pazjent li ħadu kuri li kien fihom efavirenz għal medja ta ’ 1. 6 snin u 635 pazjent li ħadu kuri ta ’ kontroll għal medja ta ’ 1. 3 snin, il- frekwenza ta ’ eventi psikjatriċi serji kienet kif muri hawn taħt:
16 average of 1.6 years and 635 patients treated with control regimens for an average of 1.3 years, the frequency of specific serious psychiatric events are detailed hereafter:
- depressjoni severa - ideat suwiċidali - attentati mhux fatali ta ’ suwiċidju - mġieba aggressiva - reazzjonijiet paranojdi - reazzjonijiet manijaċi
Patients with a history of psychiatric disorders appear to be at greater risk of these serious psychiatric adverse reactions with frequencies ranging from 0.3% for manic reactions to 2.0% for both severe depression and suicidal ideation.
Pazjenti bi storja medika ta ’ mard psikjatriku jidher li għandhom riskju ikbar ta ’ dawn ir- reazzjonijiet psikjatriċi avversi serji bi frekwenzi għal kull wieħed mill- eventi ta ’ hawn fuq li jvarjaw minn 0. 3% rigward reazzjonijiet manijakali għal 2. 0% rigward depressjoni severa u ideat suwiċidali.
Gastrointestinal disorders
Disturbi gastro- intestinali komuni
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 - ipertrigliċeridemija, iperkolesterolemija, reżistenza għall- insulina, ipergliċemija u iperlaktatemija (ara sezzjoni 4. 4).
18 Laboratory test abnormalities:
Anormalitajiet f’ testijiet tal- laboratorju:
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).
Enzimi tal- fwied: 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).
Elevations of gamma-glutamyltransferase (GGT) to greater than five times ULN were observed in 4% of all patients treated with 600 mg of efavirenz and 1.5-2% of patients treated with control regimens (7% of efavirenz-treated patients and 3% of control-treated patients after long-term treatment).
Ġew osservati elevazzjonijiet simili f’ pazjenti kkurati b’ gamma- glutamyltransferase (GGT) għal iktar minn ħames darbiet ULN f’ 4% mill- pazjenti kollha kkurati b’ 600 mg ta ’ efavirenz u 1. 5 – 2% tal- pazjenti f’ kuri ta ’ kontroll (7% ta ’ tal- pazjenti kkurati b’ efavirenz u 3% ta ’ pazjenti f’ kuri ta ’ kontroll wara kura fit- tul).
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).
Paediatric patients: undesirable effects in children were generally similar to those of adult patients.
Pazjenti pedjatriċ: l- effetti mhux mixtieqa fit- tfal kienu ġeneralment simili għal dawk tal- pazjenti adulti.
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
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.
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.
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 kellhom reżistenza msallba għal efavirenz u kellhom is- sostituzzjoni K103N.
Five of these NNRTI-resistant isolates were found to have K103N or a valine-to-
Tlettax- il iżolat li qabel kienu karatterizzati bħala reżistenti għal efavirenz kienu reżistenti wkoll għal nevirapine u delavirdine.
20 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.
Pharmacodynamic effects:
Effetti farmakodinamiċi
400 copies/ ml (95% C. I. b)
400 kopja/ ml (95% C. I. b)
EFV +
Tul tal- Kurad EFV + ZDV + 3TC EFV + IDV 206
(60%, 73%)
48 ġimgħa 67% (60%, 73%) 54% (47%, 61%)
(55%, 69%)
48 ġimgħa 62% (55%, 69%) 48% (41%, 55%)
(11.8)
48 ġimgħa 187 (11. 8) 177 (11. 3)
EFV + IDV
IDV +
54% (47%, 61%)
45%
48% (41%, 55%)
40%
177 (11.3)
153
a
a b c
IDV + ZDV + 3TC
ZDV + 3TC NC = F, mhux komplut = falliment.
45% (38%, 52%)
(38%, 52%)
40% (34%, 47%)
(34%, 47%)
153 (12.3)
(12. 3)
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.
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),
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.
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.
Mean change from baseline-CD4 cell count
Bidla medja mill - linja bażi ta ’ l- għadd taċ - ċelluli CD4
Study Number/ Treatment Regimensb
Celluli/ m (S. E. M. d)
(95% C. I.)
% (95% C. I.)
cells/ mm3 (S. E. M. d)
m3
22 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).
Bioavailability of hard capsule contents mixed with food vehicles: in healthy adult subjects, the efavirenz AUC when administered as the contents of three 200 mg hard capsules mixed with 2 teaspoons of certain food vehicles (applesauce, grape jelly, yogurt or infant formula) met bioequivalency criteria for the AUC of the intact capsule formulation administered under fasted conditions.
Il- bijodisponibbiltà tal- kontenut tal- kapsuli iebsin ma ’ sustanzi li fihom l- ikel: f’ suġġetti adulti b’ saħħithom, l- AUC ta ’ efavirenz meta mogħti bħala l- kontent ta ’ tliet kapsuli iebsin ta ’ 200 mg imħalltin ma ’ 2 kuċċarini ta ’ ċerti sustanzi li fihom l- ikel (meraq tat- tuffieħ, jelly tal- għeneb, jogurt jew ħalib tat- trabi) issodisfa l- kriterji ta ’ bijoekwivalenza għall- AUC tal- formula tal- kapsula intatta mogħtija taħt kundizzjonijiet ta ’ sawm.
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.
24 responsabbli għall- metaboliżmu ta ’ efavirenz u li hu impedixxa iżozimi P450 2C9, 2C19, and 3A4.
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- reazzjonijiet avversi assoċjati ma ’ efavirenz ma jistax jiġi eskluż.
Malformations were observed in 3 of 20 foetuses/ newborns from efavirenz-treated cynomolgus monkeys given doses resulting in plasma efavirenz
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.
Capsule core Sodium laurilsulfate Lactose monohydrate Magnesium stearate Sodium starch glycolate
Il- qalba tal- kapsula Sodium laurilsulfate Lactose monohydrate Magnesium stearate Sodium starch glycolate
24 6.5 Nature and content of container
6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
Bristol-Myers Squibb Pharma EEIG Uxbridge Business Park, Sanderson Road Uxbridge UB8 1DH United Kingdom
Bristol- Myers Squibb Pharma EEIG Uxbridge Business Park, Sanderson Road Uxbridge UB8 1DH Ir- Renju Unit
EU/ 1/ 99/ 110/ 001 - bottle
EU/ 1/ 99/ 110/ 001 - flixkun
28 May 1999 Date of latest renewal:
28 ta ’ Mejju 1999 Data ta ’ l- aħħar tiġdid:
28 May 2004
28 ta ’ Mejju 2004
SUSTIVA 100 mg hard capsules
SUSTIVA 100 mg kapsuli ibsin
White, printed with "SUSTIVA" on the body and "100 mg" on the cap.
Bajda, b ’ ” SUSTIVA ” stampata fuqha u "100 mg ” fuq il- kappa.
26 SUSTIVA is not recommended for use in children below the age of 3 years or weighing less than 13 kg due to a lack of data on safety and efficacy in that age group (see sections 5.1 and 5.2).
28 għal pazjenti 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).
After administration of the efavirenz-food mixture, an additional small amount (approximately 2 teaspoons) of food must be added to the empty mixing container, stirred to disperse any remaining residue of the medicinal product, and administered to the patient.
Wara l- għoti tat- taħlita efavirenz - ikel, ammont żgħir addizzjonali (madwar 2 kuċċarini) ta ’ ikel għandu jiżdied fir- reċipjent tat- taħlit il - vojt, jiġi mħawwad sabiex idub kwalunkwe residwu tal- mediċina, u din għanda tingħata lill- pazjent.
Efavirenz must not be used in patients with severe hepatic impairment (Child Pugh Grade C) (see section 5.2).
29 Efavirenz m’ għandux jintuża minn pazjenti b’ indeboliment sever tal- fwied (Grad Child Pugh C) (ara sezzjoni 5. 2).
27 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).
There have also been post-marketing reports of severe depression, death by suicide, delusions and psychosis-like behaviour.
30 għandhom storja medika ta ’ depressjoni.
Patients should be advised that if they experience symptoms such as severe depression, psychosis or suicidal ideation, they should contact their doctor
Kien hemm ukoll rapporti wara li prodott beda jinbiegħ ta ’ depressjoni qawwija, mewt b’ suwiċidju, delużjonijiet u mġieba li tixbah dik psikotika.
28 immediately to assess the possibility that the symptoms may be related to the use of efavirenz, and if so, to determine whether the risks of continued therapy outweigh the benefits (see section 4.8).
Il- pazjenti għandhom jiġu mgħarrfa li jekk ikollhom sintomi bħal depressjoni qawwija, psikożi jew ħsibijiet dwar is- suwiċidju, għandhom jikkuntattjaw mal- ewwel lit- tabib tagħhom biex titqies il- possibilta` li dawn is- sintomi huma marbuta ma ’ l- użu ta ’ efavirenz, u jekk iva, biex jiġi determinat jekk ir- riskju li titkompla t- terapija jegħlbux il- benefiċċji (ara sezzjoni 4. 8).
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.
Mard 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
John’ s wort, check viral levels and if possible efavirenz levels.
32 possibbli l- livelli ta ’ efavirenz.
therapeutic areas (dose)
34 Prodott mediċinali skond l- oqsma terapewtiċi (doża)
NNRTIs/ Efavirenz
NNRTIs/ Efavirenz Antibijotiċi
Since use of two NNRTIs proved not beneficial in terms of efficacy and safety, co-administration of efavirenz
Billi l- użu ta ’ żewġ NNRTIs ma rriżultax benefiku f’ termini ta ’ l - effikaċja u s- sigurtà, l- għoti flimkien ta ’ efavirenz u NNRTI ieħor mhuwiex rakkomandat.
therapeutic areas (dose)
Azithromycin/ Efavirenz (600 mg doża waħda/ 400 mg darba kuljum)
Medicinal product by
40 Prodott mediċinali skond l- oqsma
39 Pregnancy: there are limited amount of data from the use of efavirenz in pregnant women.
Tqala: jeżisti ammont limitat ta ’ dejta mill- użu ta ’ efavirenz f’ nisa tqal.
The administration of SUSTIVA with food may increase efavirenz exposure and may lead to an increase in the frequency of adverse reactions (see section 4.4).
Ir- reazzjonijiet avversi marbuta ma ’ efavirenz li kienu l- iktar prominenti kienu raxx u sintomi tas- sistema nervuża L- għoti ta ’ SUSTIVA ma ’ l- ikel jista ’ jkabbar l- esponiment għal efavirenz u jista ’ jwassal għal żieda fil - 43 frekwenza tar- reazzjonijiet avversi (ara sezzjoni 4. 4).
40 average of 1.6 years and 635 patients treated with control regimens for an average of 1.3 years, the frequency of specific serious psychiatric events are detailed hereafter:
- depressjoni severa - ideat suwiċidali - attentati mhux fatali ta ’ suwiċidju - mġieba aggressiva - reazzjonijiet paranojdi - reazzjonijiet manijaċi
42 Laboratory test abnormalities:
Anormalitajiet f’ testijiet tal- laboratorju:
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 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.
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 SUSTIVA 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).
44 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.
46 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).
These metabolites are essentially inactive against HIV-1.
Dawn il- metaboliti essenzjalment mhumiex attivi kontra
Carcinogenicity studies in male mice, male and female rats were negative.
51 Studji dwar ir- riskju ta ’ kanċer fi ġrieden irġiel, u f’ firien irġiel u nisa huma negattivi.
Capsule shell Gelatine Sodium laurilsulfate Titanium dioxide (E171) Silicon dioxide (E551)
Il- qoxra tal- kapsula Ġelatina Sodium laurilsulfate Titanium dioxide (E171) Silicon dioxide (E551)
48 6.5 Nature and content of container
6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
EU/ 1/ 99/ 110/ 002 - bottle
EU/ 1/ 99/ 110/ 002 - flixkun
SUSTIVA 200 mg hard capsules
SUSTIVA 200 mg kapsuli ibsin
Excipient: each hard capsule contains 114.0 mg of lactose monohydrate.
Sustanza mhux attiva: kull kapsula iebsa fiha 114 mg ta ’ lactose monohydrate.
Dark yellow, printed with "SUSTIVA" on the body and "200 mg" on the cap.
Lewn isfar skur, b ’ ” SUSTIVA ” stampata fuqha u "200 mg ” fuq il- kappa
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 SUSTIVA.
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 SUSTIVA.
Adults: the recommended dosage of SUSTIVA in combination with nucleoside analogue reverse transcriptase inhibitors (NRTIs) with or without a PI (see section 4.5) is 600 mg orally, once daily.
Id- doża rakkomandata ta ’ SUSTIVA flimkien ma ’ nucleoside analogue reverse transcriptase inhibitors (NRTIs) flimkien ma ’ PIs jew mingħajrhom (ara sezzjoni 4. 5) hija ta ’ 600 mg kuljum, darba kuljum.
50 SUSTIVA is not recommended for use in children below the age of 3 years or weighing less than 13 kg due to a lack of data on safety and efficacy in that age group (see sections 5.1 and 5.2).
54 għal pazjenti 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).
Efavirenz must not be used in patients with severe hepatic impairment (Child Pugh Grade C) (see section 5.2).
55 Efavirenz m’ għandux jintuża minn pazjenti b’ indeboliment sever tal- fwied (Grad Child Pugh C) (ara sezzjoni 5. 2).
51 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).
There have also been post-marketing reports of severe depression, death by suicide, delusions and psychosis-like behaviour.
56 għandhom storja medika ta ’ depressjoni.
52 immediately to assess the possibility that the symptoms may be related to the use of efavirenz, and if so, to determine whether the risks of continued therapy outweigh the benefits (see section 4.8).
Il- pazjenti għandhom jiġu mgħarrfa li jekk ikollhom sintomi bħal depressjoni qawwija, psikożi jew ħsibijiet dwar is- suwiċidju, għandhom jikkuntattjaw mal- ewwel lit- tabib tagħhom biex titqies il- possibilta` li dawn is- sintomi huma marbuta ma ’ l- użu ta ’ efavirenz, u jekk iva, biex jiġi determinat jekk ir- riskju li titkompla t- terapija jegħlbux il- benefiċċji (ara sezzjoni 4. 8).
Paediatric patients: efavirenz has not been evaluated in children below 3 years of age or who weigh less than 13 kg.
Pazjenti pedjatriċ: efavirenz ma ġiex evalwat fi tfal taħt it- 3 snin jew li jiżnu inqas minn 13 kg.
John’ s wort, check viral levels and if possible efavirenz levels.
58 possibbli l- livelli ta ’ efavirenz.
therapeutic areas (dose)
60 Prodott mediċinali skond l- oqsma terapewtiċi (doża)
Medicinal product by
66 Prodott mediċinali skond l- oqsma
63 Pregnancy: there are limited amount of data from the use of efavirenz in pregnant women.
Tqala: jeżisti ammont limitat ta ’ dejta mill- użu ta ’ efavirenz f’ nisa tqal.
The administration of SUSTIVA with food may increase efavirenz exposure and may lead to an increase in the frequency of adverse reactions (see section 4.4).
Ir- reazzjonijiet avversi marbuta ma ’ efavirenz li kienu l- iktar prominenti kienu raxx u sintomi tas- sistema nervuża L- għoti ta ’ 69 SUSTIVA ma ’ l- ikel jista ’ jkabbar l- esponiment għal efavirenz u jista ’ jwassal għal żieda fil - frekwenza tar- reazzjonijiet avversi (ara sezzjoni 4. 4).
64 average of 1.6 years and 635 patients treated with control regimens for an average of 1.3 years, the frequency of specific serious psychiatric events are detailed hereafter:
- depressjoni severa - ideat suwiċidali - attentati mhux fatali ta ’ suwiċidju - mġieba aggressiva - reazzjonijiet paranojdi - reazzjonijiet manijaċi
In one clinical study, the monthly prevalence of nervous system symptoms of at least moderate severity between weeks 4 and 48, ranged from 5% - 9% in patients treated with regimens containing efavirenz and 3% - 5% in patients treated with the control regimen.
70 sa 9% f’ pazjenti li kellhom kura li kien fiha efavirenz u minn 3% sa 5% f’ pazjenti li kellhom kura ta ’ kontroll.
66 Laboratory test abnormalities:
Anormalitajiet f’ testijiet tal- laboratorju: