qanastek/EMEA-V3 huggingface dataset:
Patients with a prior history of psychiatric disorders appear to be at greater risk of these serious psychiatric adverse reactions.
Pazjenti bi storja minn qabel ta ’ disturbi psikjatriċi jidhru li huma f’ riskju akbar ta ’ dawn ir - reazzjonijiet avversi psikjatriċi serji.
In particular, severe depression was more common in those with a history of depression.
B’ mod partikolari, depressjoni severa kienet aktar komuni f’ dawk bi storja ta ’ depressjoni.
There have also been post-marketing reports of severe depression, death by suicide, delusions and psychosis-like behaviour.
Il- pazjenti
Patients should be advised that if they experience symptoms such as severe depression, psychosis or suicidal ideation, they should contact their doctor immediately to assess the possibility that the symptoms may be related to the use of efavirenz, and if so, to determine whether the risk of continued therapy outweighs the benefits (see section 4.8).
5 għandhom jiġu avżati biex jekk jesperjenzaw sintomi bħal depressjoni severa, psikożi jew ideat ta ’ suwiċidju, huma għandhom jikkuntattjaw lit- tabib tagħhom minnufih biex dan jevalwa l- possibilità li s- sintomi jistgħu jkunu relatati ma ’ l- użu ta ’ efavirenz, u jekk ikun hekk, biex jistabbilixxi jekk ir - riskju ta ’ terapija li tissokta jkunx akbar mill- benefiċċji (ara sezzjoni 4. 8).
Nervous system symptoms: symptoms including, but not limited to, dizziness, insomnia, somnolence, impaired concentration and abnormal dreaming are frequently reported undesirable effects in patients receiving efavirenz 600 mg daily in clinical studies.
Sintomi tas- sistema nervuża: sintomi li jinkludu, iżda mhumiex limitati għal, sturdament, insomnja, somnolenza, konċentrazzjoni mfixkla u ħolm anormali huma effetti mhux mixtieqa rrapportati b’ mod frekwenti f’ pazjenti li ngħataw efavirenz 600 mg kuljum fi studji kliniċi.
Dizziness was also seen in clinical studies with emtricitabine and tenofovir disoproxil fumarate.
Sturdament deher ukoll fi studji kliniċi b’ emtricitabine u tenofovir disoproxil fumarate.
Headache has been reported in clinical studies with emtricitabine (see section 4.8).
L- uġigħ ta ’ ras ġie rrapportat fi studji kliniċi b’ emtricitabine (ara sezzjoni 4. 8).
Nervous system symptoms associated with efavirenz usually begin during the first one or two days of therapy and generally resolve after the first two to four weeks.
Is- sintomi tas- sistema nervuża assoċjati ma ’ efavirenz ġeneralment jibdew matul l- ewwel jum jew tnejn ta ’ terapija u ġeneralment jirrisolvu wara l- ewwel żewġ sa erba ’ ġimgħat.
Patients should be informed that if they do occur, these common symptoms are likely to improve with continued therapy and are not predictive of subsequent onset of any of the less frequent psychiatric symptoms.
Il- pazjenti għandhom jiġu infurmati li jekk iseħħu, dawn is- sintomi komuni x’ aktarx li jitjiebu b’ terapija li titkompla u mhumiex ta ’ tbassir ta ’ bidu sussegwenti ta ’ xi sintomi psikjatriċi anqas frekwenti.
5 Seizures: convulsions have been observed in patients receiving efavirenz, generally in the presence of a known medical history of seizures.
Aċċessjonijiet: ġew osservati aċċessjonijiet f’ pazjenti li kienu qed jirċievu efavirenz, ġeneralment fil - preżenza ta ’ storja medika magħrufa ta ’ aċċessjonijiet.
Patients who are receiving concomitant anticonvulsant medicinal products primarily metabolised by the liver, such as phenytoin, carbamazepine and phenobarbital, may require periodic monitoring of plasma levels.
Pazjenti li qed jirċievu prodotti mediċinali konkomitanti kontra l- aċċessjonijiet metabolizzati primarjament permezz tal- fwied, bħal ma huma phenytoin, carbamazepine u phenobarbital, jistgħu jeħtieġu sorveljanza perjodika tal- livelli fil - plażma.
In a drug interaction study, carbamazepine plasma concentrations were decreased when carbamazepine was co-administered with efavirenz (see section 4.5).
Fi studju ta ’ l- interazzjoni tal- mediċina, il- konċentrazzjonijiet fil- plażma ta ’ carbamazepine kienu mnaqqsa meta carbamazepine ngħata flimkien ma ’ efavirenz (ara sezzjoni 4. 5).
Caution must be taken in any patient with a history of seizures.
Għandha tintuża kawtela fi kwalunkwe pazjent bi storja ta ’ aċċessjonijiet.
Atripla is not recommended for patients with moderate or severe renal impairment.
Atripla mhix irrikkmandata għal pazjenti b’ indeboliment renali moderat għal sever.
Patients with moderate or severe renal impairment require a dose adjustment of emtricitabine and tenofovir disoproxil fumarate that cannot be achieved with the combination tablet (see sections 4.2 and 5.2).
Pazjenti b’ indeboliment renali moderat għal sever jeħtieġu aġġustament fid- doża ta ’ emtricitabine u tenofovir disoproxil fumarate li ma jistax jinkiseb bil- pillola kkombinata (ara sezzjonijiet 4. 2 u 5. 2).
Use of Atripla should be avoided with concurrent or recent use of a nephrotoxic medicinal product.
Għandu jiġi evitat l- użu ta ’ Atripla flimkien ma ’ jew wara użu riċenti ta ’ prodott mediċinali nefrotossiku.
If concomitant use of Atripla and nephrotoxic agents (e. g. aminoglycosides, amphotericin B, foscarnet, ganciclovir, pentamidine, vancomycin, cidofovir, interleukin-2) is unavoidable, renal function must be monitored weekly (see section 4.5).
Jekk l- użu konkomitanti ta ’ Atripla u mediċini nefrotossiċi (eż. aminoglycosides, amphotericin B, foscarnet, ganciclovir, pentamidine, vancomycin, cidofovir, interleukin- 2) ma jistax jiġi evitat, il- funzjoni renali għandha tkun sorveljata kull ġimgħa (ara sezzjoni 4. 5).
Renal failure, renal impairment, elevated creatinine, hypophosphataemia and proximal tubulopathy (including Fanconi syndrome) have been reported with the use of tenofovir disoproxil fumarate in clinical practice (see section 4.8).
Insuffiċjenza renali, indeboliment renali, livell għoli ta ’ krejatinina, ipofosfatimja u tubulopatija prossimali (inkluż is- sindromu ta ’ Fanconi) ġew irrapportati bl- użu ta ’ tenofovir disoproxil fumarate fil- prattika klinika (ara sezzjoni 4. 8).
It is recommended that creatinine clearance is calculated in all patients prior to initiating therapy with Atripla and renal function (creatinine clearance and serum phosphate) is also monitored every four weeks during the first year and then every three months.
Huwa rrikkmandat li t- tneħħija tal- krejatinina tiġi kkalkulata fil- pazjenti kollha qabel tinbeda terapija b’ Atripla u l- funzjoni renali (it- tneħħija tal- krejatinina u l- fosfat fis- serum) jiġu wkoll issorveljati kull erba ’ ġimgħat matul l- ewwel sena u mbagħad kull tliet xhur.
In patients with a history of renal dysfunction or in patients who are at risk for renal dysfunction, consideration must be given to more frequent monitoring of renal function.
F’ pazjenti bi storja ta ’ funzjoni renali ħażina jew f’ pazjenti li huma f’ riskju għal funzjoni renali ħażina, għandha tingħata konsiderazzjoni għal sorveljanza aktar frekwenti tal- funzjoni renali.
If serum phosphate is < 1.5 mg/ dl (0.48 mmol/ l) or creatinine clearance is decreased to < 50 ml/ min in any patient receiving Atripla, renal function must be re-evaluated within one week, including measurements of blood glucose, blood potassium and urine glucose concentrations (see section 4.8, proximal tubulopathy).
Jekk il- fosfat fis- serum ikun < 1. 5 mg/ dl (0. 48 mmol/ l) jew ir- rata tat- tneħħija tal- krejatinina titnaqqas għal < 50 ml/ min fi kwalunkwe pazjent li jkun qed jirċievi Atripla, il- funzjoni renali jeħtieġ li tiġi evalwata mill- ġdid fi żmien ġimgħa, fosthom kejl tal- konċentrazzjonijiet ta ’ glukows fid- demm, potassju fid- demm u glukows fl- awrina (ara sezzjoni 4. 8, tubulopatija prossimali).
Since Atripla is a combination product and the dosing interval of the individual components cannot be altered, treatment with Atripla must be interrupted in patients with confirmed creatinine clearance < 50 ml/ min or decreases in serum phosphate to < 1.0 mg/ dl (0.32 mmol/ l).
Peress li Atripla hija prodott ikkumbinat u l- intervall tad- dożaġġ tal- komponenti individwali ma jistax jinbidel, it - trattament b’ Atripla għandu jiġi interrott b’ rata tat- tneħħija tal- krejatinina < 50 ml/ min ikkonfermata jew tnaqqis fil- fosfat fis- serum għal < 1. 0 mg/ dl (0. 32 mmol/ l).
Where discontinuation of therapy with one of the components of Atripla is indicated or where dose modification is necessary, separate preparations of efavirenz, emtricitabine and tenofovir disoproxil fumarate are available.
Meta jkun indikat twaqqif tat- terapija b’ wieħed mill- komponenti ta ’ Atripla jew fejn tkun meħtieġa modifikazzjoni fid- doża, jinstabu preparazzjonijiet separati ta ’ efavirenz, emtricitabine u tenofovir disoproxil fumarate.
Skin reactions: mild-to-moderate rash has been reported with the individual components of Atripla.
Reazzjonijiet fil- ġilda: raxx ħafif għal moderat ġie rrapportat bil- komponenti individwali ta ’ Atripla.
The rash associated with the efavirenz component usually resolves with continued therapy.
Ir- raxx assoċjat mal- komponent efavirenz ġeneralment jirrisolvi b’ terapija li tkompli.
Appropriate antihistamines and/ or corticosteroids may improve tolerability and hasten the resolution of rash.
Antistamini u/ jew kortikosterojdi adattati jistgħu jtejbu t- tollerabilità u jħaffu r- risoluzzjoni tar- raxx.
Severe rash associated with blistering, moist desquamation or ulceration has been reported in less than 1% of patients treated with efavirenz (see section 4.8).
6 pazjenti ttrattati b’ efavirenz (ara sezzjoni 4. 8).
The incidence of erythema multiforme or Stevens-Johnson syndrome was approximately 0.1%.
L- inċidenza ta ’ eritema multiforme jew tas- sindromu ta ’ Stevens- Johnson kienet madwar 0. 1%.
Atripla must be discontinued in patients developing severe rash associated with blistering, desquamation, mucosal involvement or fever.
Atripla jeħtieġ li titwaqqaf f’ pazjenti li jiżviluppaw raxx sever bi nfafet, deskwamazzjoni, involviment mukożali jew deni.
Patients who discontinued treatment with other non-nucleoside reverse transcriptase inhibitors due to rash may be at higher risk of developing rash during treatment with Atripla.
Pazjenti li waqqfu t- trattament b’ inibituri non- nucleoside reverse transcriptase oħra minħabba raxx jistgħu jkunu f’ riskju akbar li jiżviluppaw raxx waqt trattament b’ Atripla.
Lipodystrophy and metabolic abnormalities: combination antiretroviral therapy has been associated with the redistribution of body fat (lipodystrophy) in HIV patients.
Lipodistrofija u anormalitajiet metaboliċi: terapija antiretrovirali kkumbinata ġiet assoċjata ma ’ distribuzzjoni mill- ġdid tax- xaħam tal- ġisem (lipodistrofija) f’ pazjenti bl- HIV.
The long-term consequences of these events are currently unknown.
Il- konsegwenzi fuq tul ta ’ żmien ta ’ dawn il- ġrajjiet attwalment mhumiex magħrufa.
Knowledge about the mechanism is incomplete.
Il- konoxxenza dwar il- mekkaniżmu mhix kompluta.
A connection between visceral lipomatosis and protease inhibitors (PI) and lipoatrophy and nucleoside reverse transcriptase inhibitors (NRTIs) has been hypothesised.
Konnessjoni bejn lipomatożi vixxerali u inibituri tal- protease (PI) u lipoatrofija u inibituri nucleoside reverse transcriptase (NRTIs) ġiet ipotizzata.
A higher risk of lipodystrophy has been associated with individual factors such as older age, and with drug-related factors such as longer duration of antiretroviral treatment and associated metabolic disturbances.
Riskju aktar għoli ta ’ lipodistrofija ġie assoċjat ma ’ fatturi individwali bħal ma huma età akbar, u ma ’ fatturi relatati mal- mediċina bħal ma huma t- tul ta ’ żmien itwal ta ’ trattament antiretrovirali u disturbi metaboliċi assoċjati.
Clinical examination should include evaluation for physical signs of fat redistribution.
Eżami kliniku għandu jinkludi evalwazzjoni għal sinjali fiżiċi ta ’ distribuzzjoni mill- ġdid tax- xaħam.
Consideration should be given to the measurement of fasting serum lipids and blood glucose.
Għandha tingħata konsiderazzjoni għat- tkejjil tal- lipidi fis- serum u l- glukows fid- demm waqt is - sawm.
Lipid disorders should be managed as clinically appropriate (see section 4.8).
Disturbi tal- lipidi għandhom jiġu mmaniġġjati kif klinikament adattat (ara sezzjoni 4. 8).
6 Effect of food: the administration of Atripla with food may increase efavirenz exposure (see section 5.2) and may lead to an increase in frequency of adverse reactions (see section 4.8).
Effetti ta ’ l- ikel: l- għoti ta ’ Atripla ma ’ l- ikel jista ’ jżid 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 Atripla be taken on an empty stomach, preferably at bedtime.
Huwa rrikkmandat li tittieħed fuq stonku vojt, preferibbilment fil- ħin ta ’ l- irqad.
Mitochondrial dysfunction: nucleoside and nucleotide analogues have been demonstrated in vitro and in vivo to cause a variable degree of mitochondrial damage.
Funzjoni mitokondrijali ħażina: analogi tan- nukleosidi u nukleotajd intwerew li jikkaġunaw grad varjabbli ta ’ ħsara mitokondrijali in vitro u in vivo.
There have been reports of mitochondrial dysfunction in HIV negative infants exposed in utero and/ or postnatally to nucleoside analogues.
Kien hemm rapporti ta ’ funzjoni mitokondrijali ħażina fi trabi negattivi għall- HIV esposti in utero u/ jew wara t- twelid għal analogi tan- nukleosidi.
The main adverse events reported are haematological disorders (anaemia, neutropenia), metabolic disorders (hyperlactataemia, hyperlipasaemia).
Il - ġrajjiet avversi ewlenin irrapportati huma disturbi ematoloġiċi (anemija, newtropenja), disturbi metaboliċi (iperlaktatimja, iperlipażimja).
These events are often transitory.
Dawn il- grajjiet huma ta ’ spiss transitorji.
Some late-onset neurological disorders have been reported (hypertonia, convulsion, abnormal behaviour).
Xi disturbi newroloġiċi li jibdew tard ġew irrapportati (ipertonija, aċċessjoni, mġiba anormali).
Whether the neurological disorders are transient or permanent is currently unknown.
Attwalment mhux magħruf jekk id- disturbi newroloġiċi humiex għaddiena jew permanenti.
Any child exposed in utero to nucleoside and nucleotide analogues, even HIV negative children, should have clinical and laboratory follow-up and should be fully investigated for possible mitochondrial dysfunction in case of relevant signs or symptoms.
Kwalunkwe tifel jew tifla esposti in utero għal analogi tan- nukleosidi u nukleotajd, anke tfal negattivi għall- HIV, għandhom ikollhom follow- up kliniku u tal- laboratorju u għandhom ikunu mistħarrġa bis- sħiħ għal funzjoni mitokondrijali ħażina possibbli f’ każ ta ’ sinjali u sintomi rilevanti.
These findings do not affect current national recommendations to use antiretroviral therapy in pregnant women to prevent vertical transmission of HIV.
Dawn is- sejbiet ma jaffettwawx rakkomandazzjonijiet nazzjonali kurrenti biex tuża terapija antiretrovirali f’ nisa tqal biex timpedixxi trasmissjoni vertikali ta ’ l- HIV.
Immune Reactivation Syndrome: in HIV infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms.
Sindromu ta ’ l- Attivazzjoni Immunitarja mill- Ġdid: f’ pazjenti infettati bl- HIV b’ defiċjenza immunitarja severa fiż- żmien tal- bidu ta ’ terapija antiretrovirali kkombinata (CART), tista ’ tqum reazzjoni infjammatorja għal patoġeni opportunisti asintomatiċi jew residwi u tikkaġuna kundizzjonijiet kliniċi serji, jew aggravament tas- sintomi.
Typically, such reactions have been observed within the first few weeks or months of initiation of CART.
Tipikament, reazzjonijiet bħal dawn ġew osservati fi żmien l- ewwel ftit ġimgħat jew xhur tal- bidu ta ’ CART.
Relevant examples are cytomegalovirus retinitis, generalised and/ or focal mycobacterial infections, and pneumonia caused by Pneumocystis jiroveci (formerly known as Pneumocystis carinii).
Eżempji rilevanti huma retinite b’ cytomegalovirus, infezzjonijiet mikobatteriċi ġeneralizzati u/ jew fokali, u pnewmonja kkaġunata minn Pneumocystis jiroveci (qabel magħrufa bħala Pneumocystis carinii).
Any inflammatory symptoms should be evaluated and treatment instituted when necessary.
Kwalunkwe sintomi infjammatorji għandhom jiġu evalwati u t- trattament mibdi meta meħtieġ.
Osteonecrosis: although the etiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV disease and/ or long term exposure to combination antiretroviral therapy (CART).
Osteonekrosi: għalkemm l- etjoloġija hija kkunsidrata li hija multifattorja (inkluż l- użu ta ’ kortikosterojdi, konsum ta ’ alkoħol, immunosoppressjoni severa, indiċi aktar għoli tal- massa tal - ġisem), każijiet ta ’ osteonekrosi ġew irrapportati partikolarment f’ pazjenti b’ mard ta ’ l- HIV avanzat u/ jew esponiment fuq tul ta ’ żmien għal terapija antiretrovirali kkumbinata (CART).
Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.
Il- pazjenti għandhom jiġu avżati biex ifittxu parir mediku jekk jesperjenzaw uġigħ fil- ġogi, ebusija fil- ġogi jew diffikultà fil- moviment.
Bone: in a 144-week controlled clinical study that compared tenofovir disoproxil fumarate with stavudine in combination with lamivudine and efavirenz in antiretroviral-naïve patients, small decreases in bone mineral density of the hip and spine were observed in both treatment groups.
Għadam: fi studju kliniku kkontrollat ta ’ 144 ġimgħa li qabbel tenofovir disoproxil fumarate ma ’ stavudine f’ kumbinazzjoni ma ’ lamivudine u efavirenz f’ pazjenti mhux konsapevoli ta ’ l - antiretrovirali, kien osservat tnaqqis żgħir fid- densità tal- minerali ta ’ l- għadam tal- ġenb u tas- sinsla fiż- żewġ gruppi ta ’ trattament.
Decreases in bone mineral density of spine and changes in bone biomarkers from baseline were significantly greater in the tenofovir disoproxil fumarate treatment group at 144 weeks.
It- tnaqqis fid- densità tal- minerali fl- għadam tas- sinsla u t- tibdil mil - linja bażi fil- bijomarkers ta ’ l- għadam kienu akbar b’ mod sinifikattiv fil- grupp ta ’ tenofovir disoproxil fumarate fil- 144 ġimgħa.
Decreases in bone mineral density of the hip were significantly greater in this group until 96 weeks.
It- tnaqqis fid- densità tal- minerali ta ’ l- għadam tal- ġenb kien akbar b’ mod
However, there was no increased risk of fractures or evidence for clinically relevant bone abnormalities over 144 weeks.
Madankollu, ma kienx hemm riskju miżjud ta ’ ksur jew evidenza għal anormalitajiet ta ’ l- għadam klinikament rilevanti fuq 144 ġimgħa.
Bone abnormalities (infrequently contributing to fractures) may be associated with proximal renal tubulopathy (see section 4.8).
Anormalitajiet ta ’ l- għadam (li b’ mod mhux frekwenti jikkontribwixxu għal ksur) jistgħu jkunu assoċjati ma ’ tubulopatija renali prossimali (ara sezzjoni 4. 8).
If bone abnormalities are suspected then appropriate consultation should be obtained.
Jekk jiġu suspettati anormalitajiet ta ’ l - għadam għandha tinkiseb konsultazzjoni adattata.
Other antiretroviral agents: no data are available on the safety and efficacy of Atripla in combination with other antiretroviral agents.
Mediċini antiretrovirali oħra: ebda dejta ma hija disponibbli fuq is- sigurtà u l- effikaċja ta ’ Atripla f’ kumbinazzjoni ma ’ mediċini antiretrovirali oħra.
Didanosine: co-administration of Atripla and didanosine is not recommended since exposure to didanosine is significantly increased following co-administration with tenofovir disoproxil fumarate (see section 4.5).
Didanosine: l- għoti ta ’ Atripla ma ’ didanosine mhux irrikkmandat peress li l- esponiment għal didanosine jiżdied b’ mod sinifikanti wara l- għoti flimkien ma ’ tenofovir disoproxil fumarate (ara sezzjoni 4. 5).
Patients with HIV-1 harbouring mutations:
Pazjenti b’ HIV- 1 b’ mutazzjonijiet moħbija:
Atripla should be avoided in patients with HIV-1 harbouring the K65R, M184V/ I or K103N mutation (see sections 4.1 and 5.1).
Atripla għandha tiġi evitata f’ pazjenti b’ HIV- 1 li jkun qed jaħbi mutazzjonijiet K65R, M184V/ I jew K103N (ara sezzjoni 4. 1 u 5. 1).
Excipients: this medicinal product contains 1 mmol (23.6 mg) of sodium per dose which should be taken into consideration by patients on a controlled sodium diet.
Sustanzi mhux attivi: dan il- prodott mediċinali fih 1 mmol (23. 6 mg) ta ’ sodju kull doża, ħaġa li għandha tiġi kkunsidrata minn pazjenti fuq dieta ta ’ sodju kkontrollata.
7 4.5 Interaction with other medicinal products and other forms of interaction
4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarijiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
No drug interaction studies have been conducted using Atripla.
Ma sarux studji dwar l- effett ta ’ mediċini jew ta ’ affarijiet oħra fuq l- effett farmaċewtiku ta ’ Atripla.
As Atripla contains efavirenz, emtricitabine and tenofovir disoproxil fumarate, any interactions that have been identified with these agents individually may occur with Atripla.
Minħabba li Atripla fiha efavirenz, emtricitabine u tenofovir disoproxil fumarate, kull interazzjoni li ġiet identifikata ma ’ dawn is- sustanzi individwalment tista ’ sseħħ b’ Atripla.
Interaction studies with these agents have only been performed in adults.
Studji dwar l- effett ta ’ mediċini jew ta ’ affarijiet oħra fuq dawn is- sustanzi saru biss fl- adulti.
As a fixed combination, Atripla should not be administered concomitantly with other medicinal products containing any of the components, efavirenz, emtricitabine or tenofovir disoproxil as fumarate.
Bħala kombinazzjoni fissa, Atripla ma għandhiex tingħata fl- istess ħin ma ’ prodotti mediċinali oħrajn li fihom xi komponenti bħalma huma efavirenz, emtricitabine jew tenofovir disoproxil bħala fumarate.
Due to similarities with emtricitabine, Atripla should not be administered concomitantly with other cytidine analogues, such as lamivudine.
Minħabba s- similaritajiet ma ’ emtricitabine, Atripla ma għandhiex tingħata fl- istess ħin ma ’ analogi ta ’ cytidine oħrajn bħal lamivudine.
Efavirenz is an inducer of CYP3A4 and an inhibitor of some CYP450 isoenzymes including CYP3A4 (see section 5.2).
Efavirenz huwa induttur ta ’ CYP3A4 u inibitur ta ’ xi isoenzimi ta ’ CYP450 inkluż CYP3A4 (ara sezzjoni 5. 2).
Other compounds that are substrates of CYP3A4 may have decreased plasma concentrations when co-administered with efavirenz.
Komposti oħrajn li huma substrati ta ’ CYP3A4 setgħu naqqsu l- konċentrazzjonijiet fil - plażma meta mogħtija fl- istess ħin ma ’ efavirenz.
Efavirenz exposure may also be altered when given with medicinal products or food (for example, grapefruit juice) which affect CYP3A4 activity.
L- esponiment għal efavirenz jista ’ jinbidel ukoll meta tingħata ma ’ prodotti mediċinali jew ikel (eżempju, meraq tal- grejpfrut) li jaffettwaw l- attività ta ’ CYP3A4.
In vitro and clinical pharmacokinetic interaction studies have shown the potential for CYP450- mediated interactions involving emtricitabine and tenofovir disoproxil fumarate with other medicinal products is low.
Studji ta ’ l- interazzjonijiet farmakokinetiċi in vitro u kliniċi wrew li l- potenzjal għal interazzjonijiet medjati minn CYP450 li jinvolvu emtricitabine u tenofovir disoproxil fumarate ma ’ prodotti mediċinali oħrajn huwa wieħed baxx.
Contraindications of concomitant use Atripla 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 ’ użu konkomitanti Atripla ma għandhiex tingħata fl- istess ħin ma ’ terfenadine, astemizole, cisapride, midazolam, triazolam, pimozide, bepridil, jew ergot alkaloids (eżempju, ergotamine, dihydroergotamine, ergonovine, u methylergonovine), minħabba li l- inibizzjoni tal- metaboliżmu tagħhom tista ’ twassal għal episodji ta ’ perikli serji għas- saħħa (ara sezzjoni 4. 3).
Voriconazole: co-administration of standard doses of efavirenz and voriconazole is contraindicated.
Voriconazole: l- għoti fl- istess ħin ta ’ dożi standard ta ’ efavirenz u voriconazole huwa kontra- indikat.
Since Atripla is a fixed-dose combination product, the dose of efavirenz cannot be altered; therefore, voriconazole and Atripla must not be co-administered (see section 4.3 and Table 1).
Billi Atripla huwa prodott ta ’ kombinazzjoni ta ’ doża fissa, id- doża ta ’ efavirenz ma tistax tinbidel; għaldaqstant, voriconazole u Atripla ma għandhomx jingħataw flimkien (ara sezzjoni 4. 3 u t - Tabella 1).
John’ s wort (Hypericum perforatum): co-administration of Atripla and St.
John’ s wort (Hypericum perforatum): l- għoti fl- istess ħin ta ’ Atripla u St.
John’ s wort or herbal preparations containing St.
John’ s wort jew preparazzjonijiet tal- ħxejjex li fihom St.
John’ s wort is contraindicated (see section 4.3).
John’ s wort huwa kontra- indikat (ara sezzjoni 4. 3).
Concomitant use not recommended Atazanavir/ ritonavir: insufficient data are available to make a dosing recommendation for atazanavir/ ritonavir in combination with Atripla.
8 L- użu konkomitanti m’ huwiex rakkomandat Atazanavir/ ritonavir: m’ hemmx biżżejjed tagħrif biex issir rakkomandazzjoni tad- doża għal atazanavir/ ritonavir f’ kombinazzjoni ma ’ Atripla.
Therefore co-administration of atazanavir/ ritonavir and Atripla is not recommended (see Table 1).
Għaldaqstant, l- għoti fl- istess ħin ta ’ atazanavir/ ritonavir u Atripla m’ huwiex rakkomandat (ara Tabella 1).
Didanosine: co-administration of Atripla and didanosine is not recommended (see section 4.4 and Table 1).
Didanosine: l- għoti fl- istess ħin ta ’ Atripla u didanosine m’ huwiex rakkomandat (ara sezzjoni 4. 4 u Tabella 1).
Renally eliminated medicinal products: since emtricitabine and tenofovir are primarily eliminated by the kidneys, co-administration of Atripla with medicinal products that reduce renal function or compete for active tubular secretion (e. g. cidofovir) may increase serum concentrations of emtricitabine, tenofovir and/ or the co-administered medicinal products.
Prodotti mediċinali eliminati mill- kliewi: minħabba li emtricitabine u tenofovir huma eliminati b’ mod ewlieni mill- kliewi, l- għoti fl- istess ħin ta ’ Atripla ma ’ prodotti mediċinali li jnaqqsu l- funzjoni renali jew li jikkompetu għal sekrezzjoni tubulari attiva (eż. cidofovir) jistgħu iżidu l- konċentrazzjonijiet fis - serum ta ’ emtricitabine, tenofovir u/ jew il- prodotti mediċinali amministrati fl- istess ħin.
Use of Atripla should be avoided with concurrent or recent use of a nephrotoxic medicinal product.
L- użu ta ’ Atripla għandu jiġi evitat ma ’ l- użu fl- istess ħin jew riċenti ta ’ prodott mediċinali nefrotossiku.
Some examples include, but are not limited to, aminoglycosides, amphotericin B, foscarnet, ganciclovir, pentamidine, vancomycin, cidofovir or interleukin-2 (see section 4.4).
Xi eżempji jinkludu, iżda m’ humiex limitati għal, aminoglycosides, amphotericin B, foscarnet, ganciclovir, pentamidine, vancomycin, cidofovir jew interleukin- 2 (ara sezzjoni 4. 4).
Other interactions Interactions between the components of Atripla and protease inhibitors, antiretroviral agents other than protease inhibitors and other non-antiretroviral medicinal products are listed in Table 1 below (increase is indicated as “↑”, decrease as “↓”, no change as “↔”, twice daily as “ b. i. d.”, once daily as “ q. d.” and once every 8 hours as “ q8h”).
Interazzjonijiet oħrajn Interazzjonijiet bejn il- komponenti ta ’ Atripla u l- inibituri tal- protease, aġenti antiretrovirali għajr inibituri tal- protease u prodotti mediċinali oħra mhux antiretrovirali huma elenkati fit- Tabella 1 taħt (żieda hija indikata b ’ “ ↑ ”, tnaqqis b ’ “ ↓ ”, ebda bidla b ’ “ ↔ ”, darbtejn kuljum b ’ “ b. i. d. ”, darba kuljum b ’ “ q. d. ” u darba kull 8 sigħat b ’ “ q8h ”).
If available, 90% confidence intervals are shown in parentheses.
Jekk disponibbli, intervalli ta ’ kunfidenza ta ’ 90% huma murija f’ parentesi.
Interactions between the individual components of Atripla and other medicinal products
Interazzjonijiet bejn il- komponenti individwali ta ’ Atripla u prodotti mediċinali oħra
Medicinal product by therapeutic
Prodott mediċinali skond l- oqsma
Recommendation
Rakkomandazzjoni dwar
areas
terapewtiċi
Mean percent change in AUC, Cmax, Cmin
Bidla perċentwali medja fl- AUC, Cmax,
concerning
l- għoti flimkien ma ’
(dose in mg)
(doża f’ milligrammi)
with 90%
Cmin b’ intervalli ta ’ kunfidenza ta ’ 90%
confidence intervals if available (mechanism)
jekk disponibbli
co-administration with Atripla (efavirenz 600 mg, emtricitabine 200 mg, tenofovir disoproxil fumarate 300 mg)
emtricitabine 200 mg, tenofovir disoproxil fumarate 300 mg)
ANTI-INFECTIVES Antiretrovirals Protease inhibitors Amprenavir/ Efavirenz (1,200 b. i. d. / 600 q. d.)
Amprenavir/ Efavirenz (1, 200 b. i. d. / 600 q. d.)
AUC: ~↓ 40% Cmax: ~↓ 40% Cmin: ~↓ 40% (CYP3A4 induction, the effect of efavirenz is compensated by the pharmacokinetic booster effect of ritonavir) For co-administration of efavirenz with low-dose ritonavir in combination with a protease inhibitor, see section on ritonavir below.
Cmax: ~↓ 40% Cmin: ~↓ 40% (Induzzjoni ta ’ CYP3A4, l- effett ta ’ efavirenz huwa kkumpensat mill- effett farmakokinetiku booster ta ’ ritonavir) Għall- għoti ta ’ efavirenz ma ’ doża baxxa ta ’ ritonavir flimkien ma ’ inibitur tal - protease, ara s- sezzjoni dwar ritonavir hawn isfel.
Co-administration of amprenavir/ ritonavir and Atripla is not recommended.
Atripla m’ huwiex rakkomandat.
Atazanavir/ Ritonavir/ Tenofovir disoproxil fumarate (300 q. d. / 100 q. d. / 300 q. d.)
9 Atazanavir/ Ritonavir/ Tenofovir disoproxil fumarate (300 q. d. / 100 q. d. / 300 q. d.)
AUC: ↓ 25% (↓ 42 to ↓ 3) Cmax: ↓ 28% (↓ 50 to ↑ 5) Cmin: ↓ 26% (↓ 46 to ↑ 10) Co-administration of atazanavir/ ritonavir with tenofovir resulted in increased exposure to tenofovir.
AUC: ↓ 25% (↓ 42 għal ↓ 3) Cmax: ↓ 28% (↓ 50 għal ↑ 5)
Higher tenofovir concentrations could potentiate tenofovir- associated adverse events, including renal disorders.
L- għoti fl- istess ħin ta ’ atazanavir/ ritonavir u Atripla mhuwiex
Co-administration of atazanavir/ ritonavir and Atripla is not recommended.
Cmin: ↓ 26% (↓ 46 għal ↑ 10) L- għoti fl- istess ħin ta ’ atazanavir/ ritonavir ma ’ tenofovir irriżulta f’ esponiment akbar għal tenofovir.
Co-administration of efavirenz with atazanavir in combination with low-dose ritonavir resulted in substantial decreases in atazanavir exposure due to CYP3A4 induction, necessitating dosage adjustment of atazanavir (refer to the Summary of Product Characteristics for the medicinal product containing atazanavir).
L- għoti fl- istess ħin ta ’ efavirenz ma ’ atazanavir flimkien ma ’ doża baxxa ta ’ ritonavir irriżulta fi tnaqqis sostanzjali fl - esponiment għal atazanavir minħabba induzzjoni ta ’ CYP3A4, li kienet teħtieġ aġġustament fid- doża ta ’ atazanavir (irreferi għas- Sommarju tal- Karatteristiċi tal- Prodott għall- prodott mediċinali li fih atazanavir).
Co-administration of efavirenz and atazanavir in combination with ritonavir may lead to increases in efavirenz exposure which may worsen the tolerability profile of efavirenz.
L- għoti fl- istess ħin ta ’ efavirenz u atazanavir flimkien ma ’ ritonavir jista ’ jwassal għal żidiet fl - esponiment għal efavirenz li jista ’ jħażżen il- profil tat- tollerabilità ta ’ efavirenz.
AUC: ↔ Cmax: ↔ Cmin: ↔
AUC: ↔
Insufficient data are available to make a dosing recommendation for indinavir when dosed with
M’ hemmx biżżejjed informazzjoni disponibbli
Indinavir/ Efavirenz (1,000 q8h/ 600 q. d.)
Indinavir/ Efavirenz
Indinavir:
Cmax: ↔ Cmin: ↔ Indinavir:
Morning AUC: ↓ 33%* (↓ 26 to ↓ 39) Afternoon AUC: ↓ 37%* (↓ 26 to ↓ 46) Evening AUC: ↓ 46%* (↓ 37 to ↓ 54) Morning Cmax: ↔ * Afternoon Cmax: ↔ * Evening Cmax: ↓ 29%* (↓ 11 to ↓ 43) Morning Cmin: ↓ 39%* (↓ 24 to ↓ 51) Afternoon Cmin: ↓ 52%* (↓ 47 to ↓ 57) Evening Cmin: ↓ 57%* (↓ 50 to ↓ 63) * when compared to indinavir 800 q8h alone (CYP3A4 induction) For co-administration of efavirenz with low-dose ritonavir in combination with a protease inhibitor, see section on ritonavir below.
AUC wara nofsinhar: ↓ 37% * (↓ 26 għal ↓ 46) AUC fil- għaxija: ↓ 46% * (↓ 37 għal ↓ 54) Cmax fil- għodu: ↔ * Cmax wara nofsinhar: ↔ * Cmax fil- għaxija: ↓ 29% * (↓ 11 għal ↓ 43) Cmin fil- għodu: ↓ 39% * (↓ 24 għal ↓ 51) Cmin wara nofsinhar: ↓ 52% * (↓ 47 għal ↓ 57) Cmin fil- għaxija ↓ 57% * (↓ 50 għal ↓ 63) * meta mqabbel ma ’ indinavir 800 q8h waħdu (Induzzjoni ta ’ CYP3A4) Għall- għoti ta ’ efavirenz ma ’ doża baxxa ta ’ ritonavir flimkien ma ’ inibitur tal - protease, ara s- sezzjoni dwar ritonavir hawn isfel.
While the clinical significance of decreased indinavir concentrations has not been established, the magnitude of the observed pharmacokinetic interaction should be taken into consideration when choosing a regimen containing both efavirenz, a component of Atripla, and indinavir.
Filwaqt li s- sinifikat kliniku ta ’ konċentrazzjonijiet imnaqqsa ta ’ indinavir ma ġietx stabbilit, id- daqs ta ’ l- interazzjoni farmakokinetika osservata għandu jiġi kkunsidrat meta jintgħażel reġim li jkun fih efavirenz, komponent ta ’ Atripla u indinavir.
Lopinavir/ Ritonavir/ Tenofovir disoproxil fumarate (400 b. i. d. / 100 b. i. d. / 300 q. d.)
10 Lopinavir/ Ritonavir/ Tenofovir disoproxil fumarate (400 b. i. d. / 100 b. i. d. / 300 q. d.)
AUC: ↔ Cmax: ↔ Cmin: ↔ Tenofovir:
AUC: ↔ Cmax: ↔
Insufficient data are available to make a dosing recommendation for lopinavir/ ritonavir when dosed with Atripla.
M’ hemmx biżżejjed informazzjoni disponibbli biex issir
Co-administration of lopinavir/ ritonavir with efavirenz resulted in a substantial decrease in lopinavir exposure, necessitating dosage adjustment of lopinavir/ ritonavir.
L- għoti fl- istess ħin ta ’ lopinavir/ ritonavir ma ’ efavirenz irriżulta fi tnaqqis sostanzjali fl- esponiment għal lopinavir, li kienet teħtieġ aġġustament fid- doża ta ’ lopinavir/ ritonavir.
When used in combination with efavirenz and two NRTIs, 533/ 133 mg lopinavir/ ritonavir (soft capsules) twice daily yielded similar lopinavir plasma concentrations as compared to lopinavir/ ritonavir (soft capsules) 400/ 100 mg twice daily without efavirenz (historical data).
Meta użati flimkien ma ’ efavirenz u żewġ NRTIs, 533/ 133 mg lopinavir/ ritonavir (kapsuli rotob) darbtejn kuljum taw konċentrazzjonijiet simili ta ’ lopinavir fil- plażma meta mqabbel ma ’ lopinavir/ ritonavir (kapsuli rotob) 400/ 100 mg darbtejn kuljum mingħajr efavirenz (dejta storika).
Refer to the Summary of Product Characteristics for lopinavir/ ritonavir tablets for pharmacokinetic data when this formulation was administered with efavirenz.
Irreferi għas - Sommarju tal- Karatteristiċi tal- Prodott dwar pilloli lopinavir/ ritonavir għal tagħrif farmakokinetiku meta din il- formulazzjoni ġiet mogħtija ma ’ efavirenz.
For co-administration of efavirenz with low-dose ritonavir in combination with a protease inhibitor, see section on ritonavir below.
Għall- għoti fl - istess ħin ta ’ efavirenz ma ’ doża baxxa ta ’ ritonavir flimkien ma ’ inibitur tal- protease, ara s- sezzjoni dwar ritonavir hawn isfel.
Ritonavir/ Efavirenz (500 b. i. d. / 600 q. d.)
(500 b. i. d. / 600 q. d.)
Morning AUC: ↑ 18% (↑ 6 to ↑ 33) Evening AUC: ↔ Morning Cmax: ↑ 24% (↑ 12 to ↑ 38) Evening Cmax: ↔ Morning Cmin: ↑ 42% (↑ 9 to ↑ 86) Evening Cmin: ↑ 24% (↑ 3 to ↑ 50) Efavirenz:
AUC fil- għaxija: ↔ Cmax fil- għodu: ↑ 24% (↑ 12 għal ↑ 38) Cmax fil- għaxija: ↔ Cmin fil- għodu: ↑ 42% (↑ 9 għal ↑ 86) Cmin fil- għaxija: ↑ 24% (↑ 3 għal ↑ 50) Efavirenz:
AUC: ↑ 21% (↑ 10 to ↑ 34) Cmax: ↑ 14% (↑ 4 to ↑ 26) Cmin: ↑ 25% (↑ 7 to ↑ 46) (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) (inibizzjoni ta ’ metaboliżmu ossidattiv medjat minn CYP) Meta efavirenz ingħata ma ’ ritonavir 500 mg jew 600 mg darbtejn kuljum, il - kombinazzjoni ma kinetx ittollerata tajjeb (per eżempju, kien hemm sturdament, dardir, parasteżija u livelli għolja ta ’ enzimi fil- fwied).
Sufficient data on the tolerability of efavirenz with low-dose ritonavir (100 mg, once or twice daily) are not available.
M’ hemmx biżżejjed informazzjoni disponibbli dwar it - tollerabilità ta ’ efavirenz ma ’ doża baxxa ta ’ ritonavir (100 mg, darba jew darbtejn kuljum).
Co-administration of ritonavir at doses of 600 mg and Atripla is not recommended.
ritonavir f’ dożi ta ’ 600 mg u Atripla mhuwiex rakkomandat.
When using Atripla in a regimen including low-dose ritonavir, the possibility of an increase in the incidence of efavirenz-associated adverse events should be considered, due to possible pharmacodynamic interaction.
Meta Atripla tintuża f’ reġim li jinkludi doża baxxa ta ’ ritonavir, il - possibilità ta ’ żieda fl - inċidenza ta ’ episodji avversi assoċjati ma ’ efavirenz għandha tiġi kkunsidrata, minħabba l - possibilità ta ’ interazzjoni farmakodinamika.
Saquinavir/ Efavirenz (1,200 soft capsule formulation q8h/ 600 q. d.)
11 Saquinavir/ Efavirenz (1, 200 formulazzjoni ta ’ kapsuli rotob q8h/ 600 q. d.)
AUC: ↓ 62% (↓ 45 to ↓ 74) Cmax: ↓ 50% (↓ 28 to ↓ 66) Cmin: ↓ 56% (↓ 16 to ↓ 77) (decrease in saquinavir concentrations:
AUC: ↓ 62% (↓ 45 għal ↓ 74) Cmax: ↓ 50% (↓ 28 għal ↓ 66)
CYP3A4 induction) Efavirenz:
Cmin: ↓ 56% (↓ 16 għal ↓ 77) (tnaqqis fil- konċentrazzjonijiet ta ’ saquinavir: induzzjoni ta ’ CYP3A4) Efavirenz:
AUC: ↓ 12% (↓ 4 to ↓ 19) Cmax: ↓ 13% (↓ 5 to ↓ 20) Cmin: ↓ 14% (↓ 2 to ↓ 24)
AUC: ↓ 12% (↓ 4 għal ↓ 19) Cmax: ↓ 13% (↓ 5 għal ↓ 20) Cmin: ↓ 14% (↓ 2 għal ↓ 24)
Use of Atripla in combination with saquinavir as the sole protease inhibitor is not recommended.
inibitur tal- protease mhuwiex rakkomandat.
11 Saquinavir/ Tenofovir disoproxil fumarate (1,000 q. d. / 300 q. d.)
Saquinavir/ Tenofovir disoproxil fumarate (1, 000 q. d. / 300 q. d.)
AUC: ↔ Cmax: ↔ Co-administration of tenofovir disoproxil fumarate with ritonavir boosted saquinavir also resulted in no pharmacokinetic interaction.
AUC: ↔ Cmax: ↔ L- għoti fl- istess ħin ta ’ tenofovir disoproxil fumarate ma ’ saquinavir miżjud b’ ritonavir ukoll ma rriżulta f’ ebda interazzjoni farmakokinetika.
Saquinavir/ Ritonavir/ Efavirenz NRTIs and NNRTIs
Saquinavir/ Ritonavir/ Efavirenz NRTIs u NNRTIs
No data are available on the potential interactions of efavirenz with the combination of saquinavir and ritonavir.
M’ hemmx informazzjoni disponibbli dwar l- interazzjonijiet potenzjali ta ’ efavirenz flimkien ma ’ saquinavir u ritonavir.
For co-administration of efavirenz with low-dose ritonavir in combination with a protease inhibitor, see section on ritonavir above.
Għall - għoti fl- istess ħin ta ’ efavirenz ma ’ doża baxxa ta ’ ritonavir flimkien ma ’ inibitur tal- protease, ara s- sezzjoni dwar ritonavir fuq.
Insufficient data are available to make a dosing recommendation for saquinavir/ ritonavir when dosed with Atripla.
M’ hemmx biżżejjed informazzjoni disponibbli biex issir rakkomandazzjoni tad - doża għal saquinavir/ ritonavir meta jingħata ma ’ Atripla.
Co-administration of saquinavir/ ritonavir and Atripla is not recommended.
L - għoti fl- istess ħin ta ’ saquinavir/ ritonavir u Atripla mhuwiex rakkomandat.
Specific interaction studies have not been performed with efavirenz and NRTIs other than lamivudine (see section 4.4), zidovudine and tenofovir disoproxil fumarate.
Ma sarux studji speċifiċi ta ’ l- interazzjoni b’ efavirenz u NRTIs oħra għajr lamivudine (ara sezzjoni 4. 4), zidovudine u tenofovir disoproxil fumarate.
Clinically significant interactions would not be expected since the NRTIs are metabolised via a different route than efavirenz and would be unlikely to compete for the same metabolic enzymes and elimination pathways.
M’ għandhomx ikunu mistennija interazzjonijiet kliniċi sinifikanti billi l- NRTIs jiġu metabolizzati permezz ta ’ rotta differenti minn efavirenz u mhumiex probabbli li jikkompetu għall - istess enzimi metaboliċi u mogħdijiet ta ’ tneħħija.
The potential for pharmacokinetic or pharmacodynamic interactions is unknown.
Mhux magħruf il- potenzjal għal interazzjonijiet farmakokinetiċi jew farmakodinamiċi.
Since use of two NNRTIs proved not beneficial in terms of efficacy and safety, co-administration of Atripla and another NNRTI is not recommended.
Billi l- użu ta ’ żewġ NNRTIs rriżulta mhux ta ’ benefiċċju f’ termini ta ’ effikaċja u sigurtà, l- għoti fl- istess ħin ta ’ Atripla u NNRTI ieħor mhuwiex rakkomandat.
Didanosine/ Tenofovir disoproxil fumarate
12 Didanosine/ Tenofovir disoproxil fumarate
Co-administration of tenofovir disoproxil fumarate and didanosine results in a 40-60% increase in systemic exposure to didanosine that may increase the risk for didanosine-related adverse events.
L- għoti fl- istess ħin ta ’ tenofovir disoproxil fumarate u didanosine jirriżulta f’ żieda ta ’ 40- 60% fl- esponiment sistemiku għal didanosine li jista ’ jżid ir- riskju ta ’ episodji avversi relatati ma ’ didanosine.
Rare cases of pancreatitis and lactic acidosis, sometimes fatal, have been reported.
Kienu rrappurtati każijiet rari ta ’ pankreatite u aċidożi lattika, kultant fatali.
Co-administration of tenofovir disoproxil fumarate and didanosine at a dose of 400 mg daily has been associated with a significant decrease in CD4 cell count, possibly due to an intracellular interaction increasing phosphorylated (i. e. active) didanosine.
L- għoti fl - istess ħin ta ’ tenofovir disoproxil fumarate u didanosine f’ doża ta ’ 400 mg kuljum ġie assoċjat ma ’ tnaqqis sinifikanti fl- għadd ta ’ ċelloli CD4, possibbilment minħabba interazzjoni intraċellulari li żiedet id - didanosine fosforilat (jiġifieri attiv).
A decreased dosage of 250 mg didanosine co-administered with tenofovir disoproxil fumarate therapy has been associated with reports of high rates of virologic failure within several tested combinations.
Doża mnaqqsa ta ’ 250 mg didanosine mogħtija fl- istess ħin ma ’ terapija b’ tenofovir disoproxil fumarate ġiet assoċjata ma ’ rapporti ta ’ rati għolja ta ’ falliment viroloġiku f’ diversi kombinazzjonijiet ittestjati.
Co-administration of Atripla and didanosine is not recommended (see section 4.4).
L- għoti fl- istess ħin ta ’ Atripla u didanosine mhuwiex rakkomandat (ara sezzjoni 4. 4).
Didanosine/ Efavirenz Didanosine/ Emtricitabine
Didanosine/ Efavirenz Didanosine/ Emtricitabine Antibijotiċi
Interaction not studied.
L- interazzjoni ma ġietx studjata L- interazzjoni ma ġietx studjata
12 Antibiotics Clarithromycin/ Efavirenz (500 b. i. d. / 400 q. d.)
Clarithromycin/ Efavirenz (500 b. i. d. / 400 q. d.)
AUC: ↓ 39% (↓ 30 to ↓ 46) Cmax: ↓ 26% (↓ 15 to ↓ 35) Clarithromycin 14-hydroxymetabolite:
Cmax: ↓ 26% (↓ 15 għal ↓ 35) Clarithromycin 14- hydroxymetabolite:
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.
livelli ta ’ clarithromycin fil- plażma mhuwiex magħruf.
Alternatives to clarithromycin (e. g. azithromycin) may be considered.
Jistgħu jiġu kkunsidrati alternattivi għal clarithromycin (eż. azithromycin).
Other macrolide antibiotics, such as erythromycin, have not been studied in combination with Atripla.
Antibijotiċi makrolidi oħra, bħal erythromycin, ma ġewx studjati f’ kombinazzjoni ma ’ Atripla.
Clarithromycin/ Emtricitabine Clarithromycin/ Tenofovir disoproxil fumarate Antimycobacterials
Clarithromycin/ Emtricitabine Clarithromycin/ Tenofovir disoproxil fumarate Antimikobatteriċi
AUC: ↓ 38% (↓ 28 to ↓ 47) Cmax: ↓ 32% (↓ 15 to ↓ 46) Cmin: ↓ 45% (↓ 31 to ↓ 56) Efavirenz:
Cmax: ↓ 32% (↓ 15 għal ↓ 46) Cmin: ↓ 45% (↓ 31 għal ↓ 56) Efavirenz:
AUC: ↔ Cmax: ↔ Cmin: ↓ 12% (↓ 24 to ↑ 1) (CYP3A4 induction) Interaction not studied.
AUC: ↔ Cmax: ↔ Cmin: ↓ 12% (↓ 24 għal ↑ 1) (Induzzjoni ta ’ CYP3A4) L- interazzjoni ma ġietx studjata.
The daily dose of rifabutin should be increased by 50% when given with Atripla.
b’ 50% meta jingħata ma ’ Atripla.
Consider doubling the rifabutin dose in regimens where rifabutin is given 2 or 3 times a week in combination with Atripla.
Wieħed għandu jikkunsidra li jirdoppja d - doża ta ’ rifabutin f’ reġimi fejn rifabutin jingħata 2 jew 3 darbiet fil- ġimgħa flimkien ma ’ Atripla.
AUC: ↓ 26% (↓ 15 to ↓ 36) Cmax: ↓ 20% (↓ 11 to ↓ 28) Cmin: ↓ 32% (↓ 15 to ↓ 46) (CYP3A4 and CYP2B6 induction)
Cmax: ↓ 20% (↓ 11 għal ↓ 28) Cmin: ↓ 32% (↓ 15 għal ↓ 46) (Induzzjoni ta ’ CYP3A4 u CYP2B6)
An additional 200 mg/ day (800 mg total) of efavirenz is recommended when rifampicin is co-administered with
200 mg/ ġurnata (800 mg total) ta ’ efavirenz meta
Rifampicin/ Tenofovir disoproxil fumarate (600 q. d. / 300 q. d.)
13 Rifampicin/ Tenofovir disoproxil fumarate (600 q. d. / 300 q. d.)
AUC: ↔ Cmax: ↔ Tenofovir:
AUC: ↔ Cmax: ↔
No dose adjustment of rifampicin is recommended when given with Atripla.
fid- doża ta ’ rifampicin meta jingħata ma ’ Atripla.
Rifampicin/ Emtricitabine Antifungals
Rifampicin/ Emtricitabine Antifungali
AUC: ↓ 39% (↓ 21 to ↓ 53) Cmax: ↓ 37% (↓ 20 to ↓ 51) Cmin: ↓ 44% (↓ 27 to ↓ 58) (decrease in itraconazole concentrations:
AUC: ↓ 39% (↓ 21 għal ↓ 53)
CYP3A4 induction) Hydroxyitraconazole:
Cmax: ↓ 37% (↓ 20 għal ↓ 51) Cmin: ↓ 44% (↓ 27 għal ↓ 58) (tnaqqis fil- konċentrazzjonijiet ta ’ itraconazole: induzzjoni ta ’ CYP3A4) Hydroxyitraconazole:
No dose recommendations can be made for the use of Atripla in combination with itraconazole.
għall- użu ta ’ Atripla flimkien ma ’ itraconazole.
An alternative antifungal treatment should be considered.
Għandu jiġi kkunsidrat trattament antifungali alternattiv.
Itraconazole/ Emtricitabine Itraconazole/ Tenofovir disoproxil fumarate
Itraconazole/ Emtricitabine Itraconazole/ Tenofovir disoproxil fumarate
AUC: ↓ 77% Cmax: ↓ 61% Efavirenz:
Cmax: ↓ 61% Efavirenz:
AUC: ↑ 44% Cmax: ↑ 38% (competitive inhibition of oxidative metabolism) Co-administration of standard doses of efavirenz and voriconazole is contraindicated (see section 4.3).
AUC: ↑ 44% Cmax: ↑ 38% (inibizzjoni kompetittiva ta ’ metaboliżmu ossidattiv) L- għoti fl- istess ħin ta ’ dożi standard ta ’ efavirenz u voriconazole huwa kontra - indikat (ara sezzjoni 4. 3).
Since Atripla is a fixed- dose combination product, the dose of efavirenz cannot be altered; therefore, voriconazole and Atripla must not be co-administered.
id- doża ta ’ efavirenz ma tistax tiġi mibdula; għalhekk, voriconazole u Atripla ma għandhomx jingħataw flimkien.
Voriconazole/ Emtricitabine Voriconazole/ Tenofovir disoproxil fumarate ANTICONVULSANTS
Voriconazole/ Emtricitabine Voriconazole/ Tenofovir disoproxil fumarate ANTIKONVULSIVI
Carbamazepine/ Efavirenz (400 q. d. / 600 q. d.)
Carbamazepine/ Efavirenz (400 q. d. / 600 q. d.)
AUC: ↓ 27% (↓ 20 to ↓ 33) Cmax: ↓ 20% (↓ 15 to ↓ 24) Cmin: ↓ 35% (↓ 24 to ↓ 44) Efavirenz:
AUC: ↓ 27% (↓ 20 għal ↓ 33)
AUC: ↓ 36% (↓ 32 to ↓ 40) Cmax: ↓ 21% (↓ 15 to ↓ 26) Cmin: ↓ 47% (↓ 41 to ↓ 53) (decrease in carbamazepine concentrations:
Cmax: ↓ 20% (↓ 15 għal ↓ 24) Cmin: ↓ 35% (↓ 24 għal ↓ 44) Efavirenz:
CYP3A4 and CYP2B6 induction) Co-administration of higher doses of either efavirenz or carbamazepine has not been studied.
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 CYP2B6) L- għoti flimkien ta ’ dożi ogħla jew ta ’ efavirenz jew ta ’ carbamazepine ma ġiex studjat.
No dose recommendation can be made for the use of Atripla with carbamazepine.
doża għall- użu ta ’ Atripla ma ’ carbamazepine.
Carbamazepine plasma levels should be monitored periodically.
Il- livelli ta ’ carbamazepine fil- plażma għandhom jiġu mmonitorjati perjodikament.
Carbamazepine/ Emtricitabine Carbamazepine/ Tenofovir disoproxil fumarate
Carbamazepine/ Emtricitabine Carbamazepine/ Tenofovir disoproxil fumarate