qanastek/EMEA-V3 huggingface dataset:
9 Medicinal product by therapeutic
9 Prodott mediċinali skond l- oqsma terapewtiċi (doża) NRTIs u NNRTIs
Effects on drug levels
Effetti fuq il- livelli tal- mediċina Bidla perċentwali medja fl - AUC, Cmax, Cmin bl- intervalli ta ’ kunfidenza jekk disponibblia (mekkaniżmu)
Recommendation concerning
Rakkomandazzjoni rigward l - għoti fl- istess ħin ma ’ efavirenz
percent change in AUC,
NRTIs/ Efavirenz
co-administration with
Ma sarux studji speċifiċi ta ’ l - interazzjoni b’ efavirenz u NRTIs oħra apparti minn lamivudine, zidovudine, u tenofovir disoproxil fumarate.
Cmax, Cmin with confidence intervals if availablea (mechanism)
M’ hemm bżonn ta ’ aġġustament fid- doża għall- ebda wieħed minn dawn il- prodotti mediċinali.
NNRTIs/ Efavirenz Antibiotics
NNRTIs/ Efavirenz Antibijotiċi
Since use of two NNRTIs proved not beneficial in terms of efficacy and safety, co-administration of efavirenz 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.
Azithromycin/ Efavirenz (600 mg single dose/ 400 mg once daily)
Azithromycin/ Efavirenz (600 mg doża waħda/ 400 mg darba kuljum)
No clinically significant pharmacokinetic interaction.
Ebda interazzjoni farmakokinetika klinikament sinifikanti.
Clarithromycin/ Efavirenz (500 mg q12h/ 400 mg once daily)
Clarithromycin/ Efavirenz (500 mg q12h/ 400 mg darba kuljum)
AUC: ↓ 39% (↓ 30 to ↓ 46) Cmax: ↓ 26% (↓ 15 to ↓ 35) Clarithromycin 14-hydroxymetabolite:
AUC: ↓ 39% (↓ 30 għal ↓ 46) Cmax: ↓ 26% (↓ 15 għal ↓ 35) Clarithromycin 14- hydroxymetabolite:
AUC: ↑ 34% (↑ 18 to ↑ 53) Cmax: ↑ 49% (↑ 32 to ↑ 69) Efavirenz:
AUC: ↑ 34% (↑ 18 għal ↑ 53) Cmax: ↑ 49% (↑ 32 għal ↑ 69) Efavirenz:
AUC: ↔ Cmax: ↑ 11% (↑ 3 to ↑ 19) (CYP3A4 induction) Rash developed in 46% of uninfected volunteers receiving efavirenz and clarithromycin.
AUC: ↔ Cmax: ↑ 11% (↑ 3 għal ↑ 19) (induzzjoni ta ’ CYP3A4) Żviluppa raxx f’ 46% tal- voluntiera mhux infettati li rċevew efavirenz u clarithromycin.
The clinical significance of these changes in clarithromycin plasma levels is not known.
Mhux magħruf is- sinifikat kliniku ta ’ dawn il- bidliet fil- livelli ta ’ clarithromycin fil- plażma.
Alternatives to clarithromycin (e. g. azithromycin) may be considered.
Jistgħu jiġu kkunsidrati alternattivi għall - clarithromycin (eż. azithromycin).
No dosage adjustment is necessary for efavirenz.
M’ hemmx bżonn ta ’ aġġustament fid- doża għal efavirenz.
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
AUC: ↓ 38% (↓ 28 to ↓ 47) Cmax: ↓ 32% (↓ 15 to ↓ 46) Cmin: ↓ 45% (↓ 31 to ↓ 56) Efavirenz:
Id- doża ta ’ kuljum ta ’ rifabutin
AUC: ↔ Cmax: ↔ Cmin: ↓ 12% (↓ 24 to ↑ 1) (CYP3A4 induction)
AUC: ↓ 38% (↓ 28 għal ↓ 47)
The daily dose of rifabutin should be increased by 50% when administered with efavirenz.
għandha tiżdied b’ 50% meta
Consider doubling the rifabutin dose in regimens where rifabutin is given 2 or 3 times a week in combination with efavirenz.
Wieħed għandu jikkunsidra li jirdoppja d - doża ta ’ rifabutin fi trattamenti fejn rifabutin jingħata 2 jew 3 darbiet fil- ġimgħa f’ kombinazzjoni ma ’ efavirenz.
Rifampicin/ Efavirenz (600 mg once daily/ 600 mg once daily)
Rifampicin/ Efavirenz (600 mg darba kuljum/ 600 mg darba kuljum) Antifungali
AUC: ↓ 26% (↓ 15 to ↓ 36) Cmax: ↓ 20% (↓ 11 to ↓ 28) Cmin: ↓ 32% (↓ 15 to ↓ 46) (CYP3A4 and CYP2B6 induction)
AUC: ↓ 26% (↓ 15 għal ↓ 36) Cmax: ↓ 20% (↓ 11 għal ↓ 28) Cmin: ↓ 32% (↓ 15 għal ↓ 46) (induzzjoni ta ’ CYP3A4 u ta ’ CYP2B6)
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.
The clinical effect of this dose adjustment has not been adequately evaluated.
L- effett kliniku ta ’ dan l- aġġustament fid - doża ma ġiex evalwat adegwatament.
Individual tolerability and virological response should be considered when making the dose adjustment (see section 5.2).
Għandu jiġi kkunsidrat ir- rispons individwali tat- tollerabilità u viroloġiku meta wieħed jagħmel l- aġġustament fid - doża (ara sezzjoni 5. 2).
No dosage adjustment is necessary for rifampicin.
M’ hemmx bżonn ta ’ aġġustament fid- doża għal rifampicin.
Itraconazole/ Efavirenz (200 mg q12h/ 600 mg once daily)
Itraconazole/ Efavirenz (200 mg q12h/ 600 mg darba kuljum)
CYP3A4 induction) Hydroxyitraconazole:
AUC: ↓ 39% (↓ 21 għal ↓ 53) Cmax: ↓ 37% (↓ 20 għal ↓ 51) Cmin: ↓ 44% (↓ 27 għal ↓ 58) (tnaqqis fil- konċentrazzjonijiet ta ’ itraconazole: induzzjoni ta ’ CYP3A4) Hydroxyitraconazole:
AUC: ↓ 37% (↓ 14 to ↓ 55) Cmax: ↓ 35% (↓ 12 to ↓ 52) Cmin: ↓ 43% (↓ 18 to ↓ 60) Efavirenz:
AUC: ↓ 37% (↓ 14 għal ↓ 55) Cmax: ↓ 35% (↓ 12 għal ↓ 52) Cmin: ↓ 43% (↓ 18 għal ↓ 60) Efavirenz:
No clinically significant pharmacokinetic change.
Ebda bidla farmakokinetika klinikament sinifikanti.
Since no dose recommendation for itraconazole can be made, alternative antifungal treatment should be considered.
Billi ma tista ’ ssir ebda rakkomandazzjoni ta ’ doża għal itraconazole, għandu jiġi kkunsidrat trattament antifungali alternattiv.
Posaconazole/ Efavirenz --/ 400 mg once daily
Posaconazole/ Efavirenz -- / 400 mg darba kuljum
AUC: ↓ 50% Cmax: ↓ 45% (UDP-G induction)
AUC: ↓ 50% Cmax: ↓ 45% (induzzjoni ta ’ UDP- G)
Concomitant use of posaconazole and efavirenz should be avoided unless the benefit to the patient outweighs the risk.
Użu fl- istess ħin ta ’ posaconazole u efavirenz għandu jiġi evitat sakemm il- benefiċċju għall- pazjent ma jisboqx ir- riskju.
Voriconazole/ Efavirenz (200 mg twice daily/ 400 mg once daily)
Voriconazole/ Efavirenz (200 mg darbtejn kuljum/ 400 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
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)
(400 mg darbtejn kuljum/ 300 mg
AUC: ↓ 7% (↓ 23 to ↑ 13) * Cmax: ↑ 23% (↓ 1 to ↑ 53) * Efavirenz:
b’ voriconazole, għandha terġa ’
AUC: ↑ 17% (↑ 6 to ↑ 29) ** Cmax: ↔ ** *compared to 200 mg twice daily alone ** compared to 600 mg once daily alone (competitive inhibition of oxidative metabolism)
AUC: ↑ 17% (↑ 6 għal ↑ 29) ** Cmax: ↔ ** * meta mqabbel ma ’ 200 mg darbtejn kuljum waħdu ** meta mqabbel ma ’ 600 mg darba kuljum waħdu (inibizzjoni kompetittiva tal - metaboliżmu kompetittiv)
reduced by 50%, i. e., to 300 mg once daily.
tiddaħħal id- doża inizjali ta ’ efavirenz.
When treatment with voriconazole is stopped, the initial dosage of efavirenz should be restored.
L- għoti flimkien ta ’ dożi standard ta ’ efavirenz u voriconazole huwa kontra- indikat.
Fluconazole/ Efavirenz (200 mg once daily/ 400 mg once daily)
Fluconazole/ Efavirenz (200 mg darba kuljum/ 400 mg darba kuljum)
No clinically significant pharmacokinetic interaction
Ebda interazzjoni farmakokinetika klinikament sinifikanti
Ketoconazole and other imidazole antifungals
Ketoconazole u antifungali imidazole oħra SUSTANZI LI JNAQQSU L- AĊIDU
Interaction not studied
Ma ġietx studjata l- interazzjoni
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
Neither aluminium/ magnesium hydroxide antacids nor famotidine altered the absorption of efavirenz.
La l- antaċidi ta ’ l - aluminju/ idrossidu tal- manjesju u lanqas il- famotidine ma bidlu l - assorbiment ta ’ efavirenz.
Co-administration of efavirenz with medicinal products that alter gastric pH would not be expected to affect efavirenz absorption.
L- għoti fl- istess ħin ta ’ efavirenz ma ’ prodotti mediċinali li jbiddlu l - pH gastriku mhuwiex mistenni li jaffettwa l- assorbiment ta ’ efavirenz.
Lorazepam/ Efavirenz (2 mg single dose/ 600 mg once daily) ANTICONVULSANTS
Lorazepam/ Efavirenz (2 mg doża waħda/ 600 mg darba kuljum)
AUC: ↑ 7% (↑ 1 to ↑ 14) Cmax: ↑ 16% (↑ 2 to ↑ 32) These changes are not considered clinically significant.
AUC: ↑ 7% (↑ 1 għal ↑ 14) Cmax: ↑ 16% (↑ 2 għal ↑ 32) Dawn il- bidliet mhumiex meqjusa bħala klinikament sinifikanti.
Carbamazepine/ Efavirenz (400 mg once daily/ 600 mg once daily)
Carbamazepine/ Efavirenz (400 mg darba kuljum/ 600 mg darba kuljum)
Carbamazepine:
Carbamazepine:
AUC: ↓ 27% (↓ 20 to ↓ 33) Cmax: ↓ 20% (↓ 15 to ↓ 24) Cmin: ↓ 35% (↓ 24 to ↓ 44) Efavirenz:
AUC: ↓ 27% (↓ 20 għal ↓ 33) Cmax: ↓ 20% (↓ 15 għal ↓ 24) Cmin: ↓ 35% (↓ 24 sa ↓ 44) Efavirenz:
CYP3A4 and CYP2B6 induction) The steady-state AUC, Cmax and Cmin of the active carbamazepine epoxide metabolite remained unchanged.
AUC: ↓ 36% (↓ 32 għal ↓ 40) Cmax: ↓ 21% (↓ 15 għal ↓ 26) Cmin: ↓ 47% (↓ 41 għal ↓ 53) (tnaqqis fil- konċentrazzjonijiet ta ’ carbamazepine: induzzjoni ta ’ CYP3A4; tnaqqis fil - konċentrazzjonijiet ta ’ efavirenz: induzzjoni ta ’ CYP3A4 u ta ’ CYP2B6) L- AUC stabbli, il- Cmax u l- Cmin tal - metabolit epossidu attiv ta ’ carbamazepine baqa ’ mhux mibdul.
Co-administration of higher doses of either efavirenz or carbamazepine has not been studied.
L- għoti flimkien ta ’ dożi akbar ta ’ efavirenz jew carbamazepine ma ġiex studjat.
No dosage recommendation can be made.
Ma tista ’ ssir ebda rakkomandazzjoni dwar doża.
An alternative anticonvulsant should be considered.
Għandu jiġi kkunsidrat antikonvulsiv alternattiv.
Carbamazepine plasma levels should be monitored periodically.
Il- livelli ta ’ carbamazepine fil- plażma għandhom jiġu mmonitorjati b’ mod perjodiku.
Phenytoin, Phenobarbital, and other anticonvulsants that are substrates of CYP450 isoenzymes
Phenytoin, Phenobarbital, u antikonvulsivi oħra li huma substrati ta ’ isoenzimi CYP450
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.
Valproic acid/ Efavirenz (250 mg twice daily/ 600 mg once daily)
Aċidu valprojku/ Efavirenz (250 mg darbtejn kuljum/ 600 mg darba kuljum)
No clinically significant effect on efavirenz pharmacokinetics.
Ebda effett klinikament sinifikanti fuq il- farmakokinetiċi ta ’ efavirenz.
Limited data suggest there is no clinically significant effect on valproic acid pharmacokinetics.
Dejta limitata tissuġġerixxi li ma hemm ebda effett klinikament sinifikanti fuq il- farmakokinetiċi tal- aċidu valprojku.
No dosage adjustment is necessary for efavirenz.
Ma hemm bżonn ta ’ ebda aġġustament fid- doża għal efavirenz.
Patients should be monitored for seizure control.
Il- pazjenti għandhom jiġu mmonitorjati għall- kontroll ta ’ puplesija.
Vigabatrin/ Efavirenz Gabapentin/ Efavirenz
Vigabatrin/ Efavirenz Gabapentin/ Efavirenz ANTIDIPRESSANTI
Clinically significant interactions are not expected since vigabatrin and gabapentin are exclusively eliminated unchanged in the urine and are unlikely to compete for the same metabolic enzymes and elimination pathways as efavirenz.
Mhumiex mistennija interazzjonijiet klinikament sinifikanti billi vigabatrin u gabapentin jitneħħew esklussivament mhux mibdula fl - awrina u mhumiex probabbli li jikkompetu għall- istess enzimi metaboliċi u passaġġi ta ’ eliminazzjoni bħal efavirenz.
No dosage adjustment is necessary for any of these medicinal products.
M’ hemm bżonn ta ’ aġġustament fid- doża għall- ebda wieħed minn dawn il- prodotti mediċinali.
12 Medicinal product by therapeutic
Inibituri Selettivi tat- Teħid mill- ġdid Sertraline/ Efavirenz
Effects on drug levels
ta ’ Serotonin (SSRIs)
Recommendation concerning
Iż- żidiet fid- doża ta ’ sertraline
areas (dose)
(50 mg darba kuljum/ 600 mg darba
Mean percent change in AUC, Cmax, Cmin with confidence intervals if availablea (mechanism)
AUC: ↓ 39% (↓ 27 għal ↓ 50)
co-administration with efavirenz
għandhom ikunu ggwidati mir -
Sertraline:
kuljum)
(50 mg once daily/ 600 mg once daily) 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:
AUC: ↔ Cmax: ↑ 11% (↑ 6 to ↑ 16) Cmin: ↔ (CYP3A4 induction)
AUC: ↔ Cmax: ↑ 11% (↑ 6 għal ↑ 16) Cmin: ↔ (induzzjoni ta ’ CYP3A4)
be guided by clinical response.
rispons kliniku.
Paroxetine/ Efavirenz No clinically significant (20 mg once daily/ 600 mg once daily) pharmacokinetic interaction
AUC, Cmax, Cmin bl- intervalli ta ’ kunfidenza jekk disponibblia (mekkaniżmu) Paroxetine/ Efavirenz (20 mg darba kuljum/ 600 mg darba kuljum)
Fluoxetine/ Efavirenz Interaction not studied.
Ma ġietx studjata l- interazzjoni.
ANTIHISTAMINES
Billi fluoxetine għandu profil metaboliku simili għal paroxetine, jiġifieri effett inibitorju qawwi fuq CYP2D6, huwa mistenni nuqqas simili ta ’ interazzjoni għal fluoxetine.
Cetirizine/ Efavirenz Cetirizine:
Cetirizine:
(10 mg single dose/ 600 mg once AUC: ↔ daily) 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.
No clinically significant pharmacokinetic interaction.
Ebda interazzjoni farmakokinetika klinikament sinifikanti
(240 mg once daily/ 600 mg once AUC: ↓ 69% (↓ 55 to ↓ 79) daily) 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:
AUC: ↓ 75% (↓ 59 to ↓ 84) Cmax: ↓ 64% (↓ 57 to ↓ 69) Cmin: ↓ 62% (↓ 44 to ↓ 75) N-monodesmethyl diltiazem:
AUC: ↓ 75% (↓ 59 għal ↓ 84) Cmax: ↓ 64% (↓ 57 għal ↓ 69) Cmin: ↓ 62% (↓ 44 għal ↓ 75) N- monodesmethyl diltiazem:
AUC: ↓ 37% (↓ 17 to ↓ 52) Cmax: ↓ 28% (↓ 7 to ↓ 44) Cmin: ↓ 37% (↓ 17 to ↓ 52) Efavirenz:
AUC: ↓ 37% (↓ 17 għal ↓ 52) Cmax: ↓ 28% (↓ 7 għal ↓ 44) Cmin: ↓ 37% (↓ 17 għal ↓ 52) Efavirenz:
AUC: ↑ 11% (↑ 5 to ↑ 18) Cmax: ↑ 16% (↑ 6 to ↑ 26) Cmin: ↑ 13% (↑ 1 to ↑ 26) (CYP3A4 induction) The increase in efavirenz pharmacokinetic parameters is not considered clinically significant.
AUC: ↑ 11% (↑ 5 għal ↑ 18) Cmax: ↑ 16% (↑ 6 għal ↑ 26) Cmin: ↑ 13% (↑ 1 għal ↑ 26) (induzzjoni ta ’ CYP3A4) Iż- żieda fil- parametri farmakokinetiċi ta ’ efavirenz mhijiex meqjusa bħala klinikament sinifikanti.
Dose adjustments of diltiazem should be guided by clinical response (refer to the Summary of Product Characteristics for diltiazem).
diltiazem għandhom ikunu ggwidati mir- rispons kliniku (irreferi għas- Sommarju tal - Karatteristiċi tal- Prodott għal diltiazem).
13 Medicinal product by therapeutic
Verapamil, Felodipine, Nifedipine u Ma ġietx studjata l- interazzjoni.
Effects on drug levels
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).
Recommendation concerning
14 Prodott mediċinali skond l- oqsma
percent change in AUC,
Effetti fuq il- livelli tal- mediċina
co-administration with
Rakkomandazzjoni rigward l -
(dose)
terapewtiċi (doża)
Cmax, Cmin with confidence intervals if availablea (mechanism)
Bidla perċentwali medja fl - AUC, Cmax, Cmin bl- intervalli ta ’ kunfidenza jekk disponibblia (mekkaniżmu)
efavirenz
għoti fl- istess ħin ma ’ efavirenz
Verapamil, Felodipine, Nifedipine and Nicardipine LIPID LOWERING MEDICINAL PRODUCTS HMG Co-A Reductase Inhibitors
PRODOTTI MEDIĊINALI LI JBAXXU L- LIPIDI Inibituri HMG Co- A Reductase Atorvastatin/ Efavirenz
Interaction not studied.
Atorvastatin:
Dose adjustments of calcium channel blockers should be guided by clinical response (refer to the Summary of Product Characteristics for the calcium channel blocker).
Il- livelli tal- kolesterol għandhom
Atorvastatin/ Efavirenz (10 mg once daily/ 600 mg once daily)
(10 mg darba kuljum/ 600 mg darba
Atorvastatin:
AUC: ↓ 43% (↓ 34 għal ↓ 50)
AUC: ↓ 43% (↓ 34 to ↓ 50) Cmax: ↓ 12% (↓ 1 to ↓ 26) 2-hydroxy atorvastatin:
Cmax: ↓ 12% (↓ 1 għal ↓ 26) 2- hydroxy atorvastatin:
AUC: ↓ 35% (↓ 13 to ↓ 40) Cmax: ↓ 13% (↓ 0 to ↓ 23) 4-hydroxy atorvastatin:
AUC: ↓ 35% (↓ 13 għal ↓ 40) Cmax: ↓ 13% (↓ 0 għal ↓ 23) 4- hydroxy atorvastatin:
AUC: ↓ 4% (↓ 0 to ↓ 31) Cmax: ↓ 47% (↓ 9 to ↓ 51) Total active HMG Co-A reductase inhibitors:
AUC: ↓ 4% (↓ 0 għal ↓ 31) Cmax: ↓ 47% (↓ 9 għal ↓ 51) Inibituri attivi totali HMG Co- A reductase:
AUC: ↓ 34% (↓ 21 to ↓ 41) Cmax: ↓ 20% (↓ 2 to ↓ 26)
AUC: ↓ 34% (↓ 21 għal ↓ 41) Cmax: ↓ 20% (↓ 2 għal ↓ 26)
Dosage adjustments of atorvastatin may be required (refer to the Summary of Product Characteristics for the 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)
(40 mg darba kuljum/ 600 mg darba kuljum)
AUC: ↓ 40% (↓ 26 to ↓ 57) Cmax: ↓ 18% (↓ 59 to ↑ 12)
AUC: ↓ 40% (↓ 26 għal ↓ 57) Cmax: ↓ 18% (↓ 59 għal ↑ 12)
Cholesterol levels should be periodically monitored.
Il- livelli tal- kolesterol għandhom jiġu mmonitorjati b’ mod perjodiku.
Dosage adjustments 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).
Simvastatin/ Efavirenz (40 mg once daily/ 600 mg once daily)
Simvastatin/ Efavirenz (40 mg darba kuljum/ 600 mg darba kuljum)
AUC: ↓ 69% (↓ 62 to ↓ 73) Cmax: ↓ 76% (↓ 63 to ↓ 79) Simvastatin acid:
AUC: ↓ 69% (↓ 62 għal ↓ 73) Cmax: ↓ 76% (↓ 63 għal ↓ 79) Aċidu ta ’ simvastatin:
AUC: ↓ 58% (↓ 39 to ↓ 68) Cmax: ↓ 51% (↓ 32 to ↓ 58) Total active HMG Co-A reductase inhibitors:
Cmax: ↓ 51% (↓ 32 għal ↓ 58) Inibituri attivi totali HMG Co- A reductase:
AUC: ↓ 60% (↓ 52 to ↓ 68) Cmax: ↓ 62% (↓ 55 to ↓ 78) (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.
Dosage adjustments 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).
Rosuvastatin/ Efavirenz
15 Prodott mediċinali skond l- oqsma terapewtiċi (doża)
Rosuvastatin is largely excreted unchanged via the faeces, therefore interaction with efavirenz is not expected.
Effetti fuq il- livelli tal- mediċina Bidla perċentwali medja fl - AUC, Cmax, Cmin bl- intervalli ta ’ kunfidenza jekk disponibblia (mekkaniżmu)
No dosage adjustment is necessary for either medicinal product.
Rakkomandazzjoni rigward l - għoti fl- istess ħin ma ’ efavirenz
Effects on drug levels
Rosuvastatin/ Efavirenz
Recommendation concerning
L- interazzjoni ma ġietx studjata.
Mean percent change in AUC, Cmax, Cmin with confidence intervals if availablea (mechanism)
Ħafna minn Rosuvastatin huwa eliminat mhux mibdul permezz tal- eskreta, għalhekk mhijiex mistennija interazzjoni ma ’ efavirenz.
co-administration with efavirenz
Ma hemm bżonn ta ’ ebda aġġustament fid- doża la għal prodott mediċinali wieħed u lanqas għall- ieħor.
HORMONAL CONTRACEPTIVES Ethinyloestradiol/ Efavirenz (50 µg single dose/ 400 mg once daily) IMMUNOSUPPRESSANTS
KONTRAĊETTIVI ORMONALI Ethinyloestradiol/ Efavirenz (50 µg doża waħda/ 400 mg darba kuljum) IMMUNOSUPPRESSANTI
AUC: ↑ 37% (↑ 25 to ↑ 51) Cmax: ↔ Efavirenz:
AUC: ↑ 37% (↑ 25 għal ↑ 51) Cmax: ↔ Efavirenz:
AUC: ↔ Cmax: ↔ (mechanism unknown) The clinical significance of the effect on ethinyloestradiol AUC is not known.
AUC: ↔ Cmax: ↔ (mhux magħruf il- mekkaniżmu) Mhux magħruf is- sinifikat kliniku ta ’ l- effett fuq l- AUC ta ’ ethinyloestradiol.
Only the ethinyloestradiol component of oral contraceptives has been studied.
Ġie studjat biss il- komponent ta ’ ethinyloestradiol tal- kontraċettivi orali.
The potential interaction of efavirenz with oral contraceptives has not been fully characterised.
L- interazzjoni potenzjali ta ’ efavirenz mal- kontraċettivi orali ma ġietx ikkaratterizzata b’ mod sħiħ.
A reliable method of barrier contraception must be used in addition to oral contraceptives (see section 4.6).
Għandu jintuża metodu affidabbli ta ’ kontraċezzjoni barriera flimkien mal- kontraċettivi orali (ara sezzjoni 4. 6).
Immunosuppressants metabolized by CYP3A4 (e. g., cyclosporine, tacrolimus, sirolimus)/ Efavirenz OPIOIDS
Immunosuppressanti metabolizzati minn CYP3A4 (eż., cyclosporine, tacrolimus, sirolimus) / Efavirenz OPOIDI
Interaction not studied.
Tista ’ tkun mistennija interazzjoni mhux studjata.
Decreased exposure of the immunosuppressant may be expected (CYP3A4 induction).
Espożizzjoni mnaqqsa tal- immunosuppressant (CYP3A4 induction).
These immunosuppressants are not anticipated to affect exposure of efavirenz.
Dawn l - immunosuppressanti mhumiex mistennija li jkollhom effett fuq l - espożizzjoni ta ’ efavirenz.
Dose adjustments of the immunosuppressant may be required.
Jista ’ jkun hemm bżonn ta ’ aġġustamenti fid- doża tal - immunosuppressant.
Close monitoring of immunosuppressant concentrations for at least 2 weeks (until stable concentrations are reached) is recommended when starting or stopping treatment with efavirenz.
Huwa meħtieġ monitoraġġ mill- qrib tal - konċentrazzjonijiet tal - immunosuppressant għal mill- inqas ġimagħtejn (sakemm jintlaħqu konċentrazzjonijiet stabbli) meta jkun hemm bidu jew waqfien ta ’ trattament b’ efavirenz.
Methadone/ Efavirenz (stable maintenance, 35-100 mg once daily/ 600 mg once daily)
Methadone/ Efavirenz (manteniment stabbli, 35- 100 mg darba kuljum/ 600 mg darba kuljum)
AUC: ↓ 52% (↓ 33 to ↓ 66) Cmax: ↓ 45% (↓ 25 to ↓ 59) (CYP3A4 induction) In a study of HIV infected intravenous drug users, co-administration of efavirenz with methadone resulted in decreased plasma levels of methadone and signs of opiate withdrawal.
AUC: ↓ 52% (↓ 33 għal ↓ 66) Cmax: ↓ 45% (↓ 25 għal ↓ 59) (induzzjoni ta ’ CYP3A4) Fi studju fuq utenti infettati bl - HIV li kienu jieħdu d- droga mill - vina, l- għoti flimkien ta ’ efavirenz u l- methadone rriżulta f’ livelli aktar baxxi ta ’ methadone fil - plażma u sinjali ta ’ opiate withdrawal.
The methadone dose was increased by a mean of 22% to alleviate withdrawal symptoms.
Id- doża tal- methadone ġiet miżjuda b’ medja ta ’ 20% biex jittaffew is- sintomi ta ’ l- irtirar.
Patients should be monitored for signs of withdrawal and their methadone dose increased as required to alleviate withdrawal symptoms.
Il- pazjenti għandhom jiġu mmonitorjati għal sinjali ta ’ l- irtirar u d- doża tagħhom tal- methadone tiġi miżjuda kif meħtieġ biex jittaffew is- sintomi ta ’ l- irtirar.
Buprenorphine/ naloxone/ Efavirenz
AUC, Cmax, Cmin bl- intervalli ta ’ kunfidenza jekk disponibblia (mekkaniżmu) Buprenorphine/ naloxone/ Efavirenz
Buprenorphine:
Buprenorphine:
AUC: ↓ 50% Norbuprenorphine:
AUC: ↓ 50% Norbuprenorphine:
Despite the decrease in buprenorphine exposure, no patients exhibited withdrawal symptoms.
Minkejja t- tnaqqis fl- espożizzjoni ta ’ buprenorphine, ebda pazjent ma wera sintomi talli ma ħax buprenorphine.
Dose adjustment of buprenorphine or efavirenz may not be necessary when co-administered.
Jista ’ ma jkunx hemm bżonn ta ’ aġġustament fid - doża ta ’ buprenorphine meta mogħti flimkien ma ’ sustanza oħra.
a 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%.
Efavirenz should not be used during pregnancy unless there are no other appropriate treatment options.
Efavirenz m’ għandux jintuża waqt it- tqala sakemm ma jkun hemm ebda għażliet oħra xierqa ta ’ kura.
15 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.
Barrier contraception should always be used in combination with other methods of contraception (for example, oral or other hormonal contraceptives).
Għandha dejjem tintuża kontraċezzjoni tat- tip barriera flimkien ma ’ metodi oħrajn ta ’ kontraċezzjoni (ngħidu aħna, kontraċettivi orali jew ormonali oħrajn).
Because of the long half-life of efavirenz, use of adequate contraceptive measures for 12 weeks after discontinuation of efavirenz is recommended.
Minħabba l- half- life twila ta ’ efavirenz, huwa rakkomandat l - użu ta ’ miżuri adegwati ta ’ kontraċezzjoni għal 12- il ġimgħa wara t- twaqqif ta ’ efavirenz.
Women of childbearing potential should undergo pregnancy testing before initiation of efavirenz.
Nisa li jista ’ jkollhom it- tfal għandhom jittestjaw jekk humiex tqal qabel ma jibdew jieħdu efavirenz.
Pregnancy: there are limited amount of data from the use of efavirenz in pregnant women.
Tqala: jeżisti ammont limitat ta ’ dejta mill- użu ta ’ efavirenz f’ nisa tqal.
In postmarketing experience through an antiretroviral pregnancy registry, more than 200 pregnancies with first-trimester exposure to efavirenz as part of a combination antiretroviral regimen have been reported with no specific malformation pattern.
Fl- esperjenza ta ’ wara li l - prodott tpoġġa fuq is- suq, permezz ta ’ reġistru antiretrovirali tat- tqala, kien hemm iktar minn 200 tqala li ġew esposti għal efavirenz bħala parti minn kura antiretrovirali kombinata waqt l- ewwel trimestru tat- tqala, u li fihom ma ġie rrapurtat l- ebda mudell speċifiku ta ’ malformazzjoni.
Retrospectively in this registry, a small number of cases of neural tube defects, including meningomyelocele, have been reported but causality has not been established.
B’ mod retrospettiv f’ dan ir- reġistru, ġew irrapurtati numru żgħir ta ’ każijiet iżolati ta ’ difetti fit- tubi newrali, inkluż meninġomajloċeli, imma ma ġiex stabbilit li dan kien marbut mal- kura.
Studies in animals have shown reproductive toxicity including marked teratogenic effects (see section 5.3).
Studji fuq l- annimali urew li hemm tossiċita` fir- riproduzzjoni inkluż effetti qawwija teratoġeniċi (ara sezzjoni 5. 3).
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.
It is not known whether efavirenz is excreted in human milk.
Mhux magħruf jekk efavirenz joħroġx fil- ħalib uman.
Since animal data suggest that the substance may be passed into breast milk, it is recommended that mothers taking efavirenz do not breast feed their infants.
Billi t- tagħrif mill- istudji fuq l- annimali jissuġġerixxi li s- sustanza tista ’ tgħaddi fil- ħalib, huwa rakkomandat li l - ommijiet li qed jieħdu efavirenz ma jreddgħux lit- trabi tagħhom.
It is recommended that HIV infected women do not breast feed their infants under any circumstances in order to avoid transmission of HIV.
Huwa rakkomandat li nisa nfettati bl - HIV bl- ebda mod m’ għandhom ireddgħu lit- trabi tagħhom biex jevitaw it- trażmissjoni ta ’ l- HIV.
Efavirenz may cause dizziness, impaired concentration, and/ or somnolence.
Efavirenz jista ’ jikkawża sturdament, tnaqqis fil- konċentrazzjoni, u/ jew ngħas.
Patients should be instructed that if they experience these symptoms they should avoid potentially hazardous tasks such as driving or operating machinery.
Il- pazjenti għandhom jingħataw istruzzjonijiet li jekk ikollhom dawn is- sintomi għandhom jevitaw attivita` li tista ’ tkun perikoluża bħal sewqan u t - tħaddim ta ’ makkinarju.
Efavirenz has been studied in over 9,000 patients.
Efavirenz ġie studjat f’ iktar minn 9, 000 pazjent.
In a subset of 1,008 adult patients who received 600 mg efavirenz daily in combination with PIs and/ or NRTIs in controlled clinical studies, the most frequently reported adverse reactions of at least moderate severity reported in at least 5% of patients were rash (11.6%), dizziness (8.5%), nausea (8.0%), headache (5.7%) and fatigue (5.5%).
Fi grupp ta ’ 1, 008 minn dawn li ngħataw 600 mg ta ’ efavirenz kuljum flimkien ma ’ PIs u/ jew NRTIs fi studji kliniċi kkontrollati, l- iktar reazzjonijiet avversi ta ’ severita` moderata jew agħar f’ minimu ta ’ 5% li kienu rrapurati kienu raxx (11. 6%), sturdament (8. 5%), dardir (8. 0%), uġigħ ta ’ ras (5. 7%) u għeja (5. 5%).
The administration of STOCRIN with food may increase efavirenz exposure and may lead to an increase in the frequency of adverse reactions (see section 4.4).
Ir- reazzjonijiet avversi marbuta ma ’ efavirenz li kienu l- iktar prominenti kienu raxx u sintomi tas- sistema nervuża L- għoti ta ’ STOCRIN ma ’ l- ikel jista ’ jkabbar l- esponiment għal efavirenz u jista ’ jwassal għal żieda fil - 17 frekwenza tar- reazzjonijiet avversi (ara sezzjoni 4. 4).
The long-term safety profile of efavirenz-containing regimens was evaluated in a controlled trial (006) in which patients received efavirenz + zidovudine + lamivudine (n = 412, median duration 180 weeks), efavirenz + indinavir (n = 415, median duration 102 weeks), or indinavir + zidovudine + lamivudine (n = 401, median duration 76 weeks).
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).
Long-term use of efavirenz in this study was not associated with any new safety concerns.
Użu fit- tul ta ’ efavirenz f’ dan l- istudju ma kienx assoċjat ma ’ tħassib ġdid dwar is- sigurtà.
Rash: in clinical studies, 26% of patients treated with 600 mg of efavirenz experienced skin rash compared with 17% of patients treated in control groups.
Raxx: fi studji kliniċi, 26% tal- pazjenti kkurati b’ 600 mg ta ’ efavirenz kellhom raxx fil- ġilda mqabbla ma ’ 17% ta ’ pazjenti kkurati fil- gruppi ta ’ kontroll.
Skin rash was considered treatment related in 18% of patients treated with efavirenz.
Ir- raxx fil- ġilda tqies li kien marbut mal- kura fi 18% tal- pazjenti kkurati b’ efavirenz.
Severe rash occurred in less than 1% of patients treated with efavirenz, and 1.7% discontinued therapy because of rash.
Inqas minn 1% tal- pazjenti kkurati b’ efavirenz kollhom raxx sever u 1. 7% ma komplewx il- kura minħabba r- raxx.
The incidence of erythema multiforme or Stevens-Johnson syndrome was approximately 0.1%.
L- inċidenza ta ’ eritema multiforme jew is - sindromu ta ’ Stevens- Jahnson kienet bejn wieħed u ieħor ta ’ 0. 1%.
Rashes are usually mild-to-moderate maculopapular skin eruptions that occur within the first two weeks of initiating therapy with efavirenz.
Ir- raxxijiet is- soltu huma eruzzjoniiet makulopapulari minn ħfief sa moderati li jseħħu fl- ewwel ġimgħatejn mill- bidu tal- kura b’ efavirenz.
In most patients rash resolves with continuing therapy with efavirenz within one month.
Fil- biċċa l- kbira tal- pazjenti r- raxx jgħaddi mat- tkomplija tat- terapija b’ efavirenz bi żmien xahar.
Efavirenz can be reinitiated in patients interrupting therapy because of rash.
Efavirenz jista ’ jerġa ’ jinbeda f’ pazjenti li jinterrompu t - terapija minħabba r- raxx.
Use of appropriate antihistamines and/ or corticosteroids is recommended when efavirenz is restarted.
Huwa rakkomandat l- użu ta ’ anti- istaminiċi u/ jew kortikosterojdi meta jerġa ’ jinbeda l- efavirenz.
16 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.
Nineteen patients who discontinued nevirapine because of rash have been treated with efavirenz.
Dsatax- il pazjent li ma komplewx jieħdu nevirapine minħabba r- raxx kienu kkurati b’ efavirenz.
Nine of these patients developed mild-to-moderate rash while receiving therapy with efavirenz, and two discontinued because of rash.
Disgħa minn dawn il- pazjenti żviluppaw raxx waqt li kienu qed jiġu kkurati b’ efavirenz, u tnejn ma komplewx minħabba r- raxx.
Psychiatric symptoms: serious psychiatric adverse reactions have been reported in patients treated with efavirenz.
Ġew irrapurati reazzjonijiet psikjatriċi avversi serji f’ pazjenti kkurati b’ efavirenz.
In controlled trials of 1,008 patients treated with regimens containing efavirenz for an 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:
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:
- severe depression - suicidal ideation - non-fatal suicide attempts - aggressive behaviour - paranoid reactions - manic reactions
- depressjoni severa - ideat suwiċidali - attentati mhux fatali ta ’ suwiċidju - mġieba aggressive - reazzjonijiet paranojdi - reazzjonijiet manijaċi
1.6% 0.6% 0.4% 0.4% 0.4% 0.1%
b’ Efavirenz 1. 6% 0. 6% 0. 4% 0. 4% 0. 4% 0. 1%
0.6% 0.3% 0% 0.3% 0.3% 0%
ta ’ kontroll 0. 6% 0. 3% 0% 0. 3% 0. 3% 0%
Patients with a history of psychiatric disorders appear to be at greater risk of these serious psychiatric adverse reactions with frequencies of each of the above events 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.
There have also been post-marketing reports of death by suicide, delusions and psychosis-like behaviour.
Kien hemm ukoll rapporti wara li l- prodott tpoġġa fuq is- suq ta ’ mewt minħabba suwiċidju, delużjonijiet u mġieba li qisha psikotika.
Nervous system symptoms: in clinical controlled trials, frequently reported adverse reactions in patients receiving 600 mg efavirenz with other antiretroviral agents included, but were not limited to: dizziness, insomnia, somnolence, impaired concentration and abnormal dreaming.
Sintomi tas- sistema nervuża: fi provi kliniċi kkontrollati, ir- reazzjonijiet avversi li ġew irrappurtati b’ mod frekwenti f’ pazjenti li kienu qed jingħataw 600 mg ta ’ efavirenz ma ’ aġenti antiretrovirali oħra kienu jinkludu, imma ma kinux limitati għal: sturdament, nuqqas ta ’ rqad, ngħas, nuqqas ta ’ konċentrazzjoni u ħolm mhux normali.
Nervous system symptoms of moderate-to-severe intensity were experienced by 19.4% of patients compared to 9.0% of patients receiving control regimens.
19. 4% mill- pazjenti kellhom sintomi tas- sistema nervuża li kienu minn moderati sa severi, imqabbla ma ’ 9. 0% mill- pazjenti li kienu taħt kura kkontrollata.
These symptoms were severe in 2.0% of patients receiving efavirenz 600 mg daily and in 1.3% of patients receiving control regimens.
Dawn is- sintomi kienu severi għal 2. 0% mill- pazjenti li kienu qed jirċievu 600 mg ta ’ efavirenz kuljum u f’ 1. 3% tal- pazjenti li kienu qed jirċievu kura kkontrollata.
In clinical studies 2.1% of patients treated with 600 mg of efavirenz discontinued therapy because of nervous system symptoms.
Fi studji kliniċi 2. 1% tal- pazjenti kkurati b’ 600 mg ta ’ efavirenz ma komplewx il- kura minħabba is- sintomi tas- sistema nervuża.
Nervous system symptoms usually begin during the first one or two days of therapy and generally resolve after the first 2 - 4 weeks.
Is- sintomi tas- sistema nervuża s- soltu jibdew waqt l- ewwel jew it- tieni ġurnata tat- terapija u ġeneralment jgħaddu wara l- ewwel 2 – 4 ġimgħat.
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 ’
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.
Fi studju ta ’ voluntiera mhux infettati, sintomu rappreżentattiv tas- sistema nervuża kien jitfaċċa medja ta ’ siegħa wara d- doża u kien idum medja ta ’ 3 sigħat.
Nervous system symptoms may occur more frequently when efavirenz is taken concomitantly with meals possibly due to increased efavirenz plasma levels (see section 5.2).
Is- sintomi tas- sistema nervuża jistgħu iseħħu b’ mod iktar frekwenti meta efavirenz tittieħed flimkien ma ’ l- ikel, possibilment minħabba livelli ogħla ta ’ efavirenz fil- plażma (ara sezzjoni 5. 2).
Dosing at bedtime seems to improve the tolerability of these symptoms and can be recommended during the first weeks of therapy and in patients who continue to experience these symptoms (see section 4.2).
Meta d- doża tittieħed qabel l- irqad jidher li s- sintomi huma iktar tollerabbli; dan jista ’ jkun rakkomondat waqt l- ewwel ġimgħat tat - terapija u f’ pazjenti li jkomplu jesperjenzaw dawn is- sintomi (ara sezzjoni 4. 2).
Dose reduction or splitting the daily dose has not been shown to provide benefit.
It- tnaqqis tad- doża jew it- tqassim tad- doża ta ’ kuljum ma werietx li hija ta ’ benefiċċju.
Analysis of long-term data from study 006 (median follow-up 180 weeks, 102 weeks, and 76 weeks for patients treated with efavirenz + zidovudine + lamivudine, efavirenz + indinavir, and indinavir + zidovudine + lamivudine, respectively) showed that, beyond 24 weeks of therapy, the incidences of new-onset nervous system symptoms among efavirenz-treated patients were generally similar to those in the control arm.
L- analiżi ta ’ tagħrif fit- tul minn studju 006 (medja ta ’ follow- up ta ’ 180 ġimgħa, 102 ġimgħa, u 76 ġimgħa għal pazjenti kkurati b’ efavirenz + zidovudine + lamivudine, efavirenz + indinavir, u indinavir + zidovudine + lamivudine, rispettivament) uriet li, wara l- 24 ġimgħa ta ’ terapija, l- inċidenza ta ’ sintomi ġodda marbuta mas- sistema nervuża fost pazjenti kkurati b’ efavirenz kienet ġeneralment simili għall- grupp ta ’ l- istudju ta ’ kontroll.
Adverse reactions of moderate or greater severity with at least possible relationship to treatment regimen (based on investigator attribution) reported in clinical trials of efavirenz at the recommended dose in combination therapy (n = 1,008) are listed below.
Reazzjonijiet avversi ta ’ severità moderata jew akbar b’ għallinqas relazzjoni possibbli għar- reġimen tat- trattament (abbażi tal- attribuzzjoni tal- investigatur) irrapportati fi provi kliniċi ta ’ efavirenz fid - doża rakkomandata f’ terapija ta ’ kombinazzjoni (n = 1, 008) huma elenkati taħt.
Frequency is defined using the following convention: very common (≥ 1/ 10); common (≥ 1/ 100 to < 1/ 10); uncommon (≥ 1/ 1,000 to < 1/ 100); rare (≥ 1/ 10,000 to < 1/ 1,000); very rare (< 1/ 10,000) including isolated reports.
Il- frekwenza hija definite permezz tal- konvenzjoni li ġejja: komuni ħafna (≥ 1/ 10); komuni (≥ 1/ 100 sa < 1/ 10); mhux komuni (≥ 1/ 1, 000 sa < 1/ 100); rari (≥ 1/ 10, 000 sa < 1/ 1, 000); rari ħafna (< 1/ 10, 000) inkluż rapporti iżolati.
17 Nervous system disorders common
Disturbi fis- sistema nervuża komuni
disturbance in attention, dizziness, headache, somnolence
disturbi fl- attenzjoni, sturdament, uġiġħ ta ’ ras, ngħas
agitation, amnesia, ataxia, coordination abnormal, convulsions, thinking abnormal
aġitazzjoni, amneżija, ataksja, ko- ordinament anormali, konvulżjonijiet, ħsieb anormali
Eye disorders uncommon
Disturbi fl- għajnejn mhux komuni
vision blurred
viżta mċajpra
Gastrointestinal disorders common
Disturbi gastro- intestinali komuni
abdominal pain, diarrhoea, nausea, vomiting
uġigħ fiż- żaqq, dijarea, dardir, rimettar
pancreatitis acute
pankreite akuta
Skin and subcutaneous tissue disorders very common
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda komuni ħafna
pruritus
ħakk
erythema multiforme, Stevens-Johnson syndrome
eritema multiforme, sindromu ta ’ Stevens - Johnson
Hepatobiliary disorders uncommon
Disturbi fil- fwied u fil- marrara mhux komuni
hepatitis acute
epatite akuta
Reproductive system and breast disorders
19 Disturbi fis- sistema riproduttiva u fis- sider mhux komuni
uncommon
ginekomastja
gynaecomastia
Disturbi psikjatriċi
abnormal dreams, anxiety, depression, insomnia
ħolm anormali, ansjetà, depressjoni, nuqqas ta ’ rqad
affect lability, aggression, confusional state, euphoric mood, hallucination, mania, paranoia, suicide attempt, suicide ideation
bidla kontinwa fil- burdata, aggressjoni, stat konfużjonali, burdata ewforika, alluċinazzjoni, manija, paranoja, attentat ta ’ suwiċidju, ideat dwar suwiċidju
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).
Sindromu tar- Rijattivazzjoni Immunitarja: f’ pazjenti infettati bl- HIV li kellhom defiċjenza 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)
Lipodystrophy and metabolic abnormalities: 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).
18 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).
Osteonecrosis: cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to combination antiretroviral therapy (CART).
Ostjonekrożi: ġew irrappurtati każijiet ta ’ ostjonekrożi, b’ mod speċjali f’ pazjenti li għandhom fatturi ta ’ riskju li huma ġeneralment rikonoxxuti, mard avvanzat ta ’ l- HIV jew esponiment fit- tul ta ’ terapija antiretrovirali kombinata (CART).
The frequency of this is unknown (see section 4.4).
Il- frekwenza ta ’ dan mhix magħrufa (ara sezzjoni 4. 4).
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).
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).
Isolated elevations of GGT in patients receiving efavirenz may reflect enzyme induction.
Fi studju fit- tul (006).
In the long-term study (006), 1% of patients in each treatment arm discontinued because of liver or biliary system disorders.
1% tal- pazjenti fiż- żewġ partijiet ta ’ l- istudju ma komplewx il- kura minħabba mard tal- fwied jew tas- sistema biljari.
In the long-term data set from study 006, 137 patients treated with efavirenz-containing regimens (median duration of therapy, 68 weeks) and 84 treated with a control regimen (median duration, 56 weeks) were seropositive at screening for hepatitis B (surface antigen positive) and/ or C (hepatitis C antibody positive).
Fis- sett ta ’ tagħrif fit- tul minn studju numru 006, 137 pazjent li kien taħt kuri li kien fihom efavirenz (tul medju tal- kura ta ’ 68 ġimgħa) u 84 li kienu taħt kura ta ’ kontroll (tul medju ta ’ 56 ġimgħa) kienu seropożittivi meta ġew ittestjati għall- epatite B (pożitivi għall- antiġen tal- wiċċ) u/ jew C (pożittiv għall- antikorpi ta ’ l- epatite C).
Among these co-infected patients, elevations in AST to greater than five times ULN developed in 13% of patients in the efavirenz arms and 7% of those in the control arm, and elevations in ALT to greater than five times ULN developed in 20% of patients in the efavirenz arms and 7% of the patients in the control arm.
Fost dawn il- pazjenti infettati bit- tnejn, il- livelli elevati f’ AST għolew għal iktar minn ħames darbiet l- ULN fi 13% tal- pazjenti fil- partijiet ta ’ l- istudju li kienu qed jieħdu efavirenz, u f’ 7% tal- pazjenti fil- parti ta ’ kontroll ta ’ l- istudju.
Among co-infected patients, 3% of those treated with efavirenz-containing regimens and 2% in the control arm discontinued from the study because of liver or biliary system disorders.
Fost il- pazjenti infettati bit- tnejn, 3% minn dawk li kienu taħt kuri li kien fihom efavirenz u 2% fil- parti ta ’ kontroll ta ’ l- istudju ma komplewx l- istudju minħabba mard fil- fwied jew fis- sistema biljari.
Reasons for discontinuation among co-infected recipients of efavirenz included abnormalities in hepatic enzymes; there were no discontinuations reported in this study for cholestatic hepatitis, hepatic failure, or fatty liver (see section 4.4).
Fost ir- raġunijiet għan- nuqqas ta ’ tkomplija ta ’ min kien qed jirċievi efavirenz kien hemm anormalitajiet fl- enżimi epatiċi; ma ġewx irrappurtati twaqqif f’ dan l- istudju minħabba l- epatite kolestatika, insuffiċjenza epatika, jew fwied xaħmi (ara sezzjoni 4. 4).