qanastek/EMEA-V3 huggingface dataset:
However, the twice- daily dose was slightly more effective in patients who were at risk of a reduced response to HIV treatment, due to high viral load, low levels of immunity or few available treatment options.
Madankollu, id- doża ta ’ darbtejn kuljum kienet kemmxejn iktar effettiva f’ pazjenti li kellhom riskju ikbar ta ’ tnaqqis fir - rispons għat- trattament ta ’ l- HIV, minħabba tagħbija virali għolja, livelli ta ’ immunità baxxi jew ftit għażliet ta ’ trattament disponibbli.
What is the risk associated with CELSENTRI?
X’ inhu r- riskju assoċċat ma ’ CELSENTRI?
The most common side effect with CELSENTRI (seen in more than 1 patient in 10) is nausea (feeling sick).
L- iktar effett sekondarju komuni b’ CELSENTRI (li deher f’ iktar minn pazjent wieħed minn kull 10) huwa d- dardir.
For the full list of all side effects reported with CELSENTRI, see the Package Leaflet.
Għal- lista sħiħa ta ’ l- effetti sekondarji kollha rrappurtati b’ CELSENTRI, ara l- Fuljett ta ’ Tagħrif.
CELSENTRI should not be used in patients who may be hypersensitive (allergic) to maraviroc, peanut, soya or any of the other ingredients.
CELSENTRI m’ għandux jintuża f’ pazjenti li jistgħu jkunu allerġiċi għal maraviroc, għall- karawett, għas- soja jew għal xi sustanza oħra tiegħu.
As with other anti-HIV medicines, patients taking CELSENTRI may be at risk of immune reactivation syndrome (symptoms of infection caused by the recovering immune system) or osteonecrosis (death of bone tissue).
Bħal fil- każ ta ’ mediċini oħra ta ’ kontra l- HIV, il- pazjenti li jieħdu CELSENTRI jista ’ jkollhom riskju ikbar tas- sindromu tar- riattivazzjoni immunitarja (sintomi ta ’ infezzjoni kkawżati minn sistema immunitarja li tkun qed tirkupra) jew minn ostjonekrożi (mewt tat- tessut tal- għadam).
Patients who have problems with their liver (including hepatitis B or C infection) may be at an elevated risk of liver damage when taking CELSENTRI.
Il- pazjenti li jkollhom problemi bil- fwied (inkluż infezzjoni ta ’ l- epatite B jew Ċ) jista ’ jkollhom riskju ogħla ta ’ ħsara fil- fwied meta jieħdu CELSENTRI.
Why has CELSENTRI been approved?
Għaliex ġie approvat CELSENTRI?
The Committee for Medicinal Products for Human Use (CHMP) decided that CELSENTRI’ s benefits are greater than its risks, in combination with other antiretroviral medicinal products, for treatment- experienced adult patients infected with only CCR5-tropic HIV-1 detectable.
Il- Kumitat għall- Prodotti Mediċinali għall- Użu mill- Bniedem (CHMP) iddeċieda li CELSENTRI għandu iktar benefiċċji milli riskji meta wżat f’ kombinazzjoni ma ’ prodotti mediċinali antiretrovirali oħra, għal pazjenti adulti li jkunu rċevew trattament għal infezzjoni ta ’ l- HIV- 1 CCR5- tropic li tista ’ tiġi rivelata.
The Committee recommended that CELSENTRI be given marketing authorisation.
Il- Kumitat irrakkomanda li CELSENTRI jingħata l- awtorizzazzjoni għat- tqegħid fis- suq.
Other information about CELSENTRI:
Tagħrif ieħor dwar CELSENTRI:
The European Commission granted a marketing authorisation valid throughout the European Union for CELSENTRI to Pfizer Limited on 18 September 2007.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fis- suq valida madwar l- Unjoni Ewropea kollha għal CELSENTRI lil Pfizer Limited fit- 18 ta ’ Settembru 2007.
The full EPAR for CELSENTRI can be found here.
L- EPAR sħiħ għal CELSENTRI jista ’ jinstab hawnhekk.
This summary was last updated in 08-2007.
Dan is- sommarju ġie aġġornat l- aħħar f’ 08- 2007.
Route of EU number
EU
administration
jingħata
Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet
Pillola miksija b’ rita Pillola miksija b’ rita Pillola miksija b’ rita Pillola miksija b’ rita Pillola miksija b’ rita Pillola miksija b’ rita Pillola miksija b’ rita Pillola miksija b’ rita Pillola miksija b’ rita Pillola miksija b’ rita
Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use
Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali
Bottle (HDPE/ alu) Blister (PVC/ alu) Blister (PVC/ alu) Blister (PVC/ alu) Blister (PVC/ alu) Bottle (HDPE/ alu) Blister (PVC/ alu) Blister (PVC/ alu) Blister (PVC/ alu) Blister (PVC/ alu)
Flixkun (HDPE/ alu) Folja (PVC/ alu) Folja (PVC/ alu) Folja (PVC/ alu) Folja (PVC/ alu) Flixkun (HDPE/ alu) Folja (PVC/ alu) Folja (PVC/ alu) Folja (PVC/ alu) Folja (PVC/ alu)
180 tablets 30 tablets 60 tablets 90 tablets 180 (2x90) tablets 180 tablets 30 tablets 60 tablets 90 tablets 180 (2x90) tablets
180 pilloli 30 pilloli 60 pilloli 90 pilloli 180 (2x90) pilloli 180 pilloli 30 pilloli 60 pilloli 90 pilloli 180 (2x90) pilloli
CELSENTRI 150 mg film-coated tablets.
CELSENTRI 150 mg pilloli miksijin b’ rita.
Each film-coated tablet contains 150 mg of maraviroc.
Kull pillola miksija b’ rita fiha 150 mg ta ’ maraviroc.
Excipients Each 150 mg film-coated tablet contains 0.84 mg of soya lecithin.
Sustanzi mhux attivi Kull pillola miksija b’ rita ta ’ 150 mg fiha 0. 84 mg ta ’ leċitina tas- soja.
Film-coated tablet.
Pillola miksija b’ rita.
Blue, biconvex, oval film-coated tablets debossed with “ Pfizer” on one side and “ MVC 150” on the other.
Pilloli blu ġejjin għat- tond miż- żewġ naħat ta ’ forma ovali miksijin b’ rita bi “ Pfizer ” imnaqqax fuq naħa u “ MVC 150 ” fuq in- naħa l- oħra.
CELSENTRI, in combination with other antiretroviral medicinal products, is indicated for treatment- experienced adult patients infected with only CCR5-tropic HIV-1 detectable (see section 4.2).
CELSENTRI, flimkien ma ’ prodotti mediċinali oħra antiretrovirali, huwa indikat għal pazjenti adulti b’ esperjenza ta ’ kura infettati bl- HIV- 1 CCR5- tropiku tat- tip detectable biss (ara sezzjoni 4. 2).
This indication is based on safety and efficacy data from two double-blind, placebo-controlled trials in treatment-experienced patients (see section 5.1).
Din l- indikazzjoni hija bbażata fuq tagħrif dwar is- sigurtà u l- effikaċja minn żewġ provi double- blind ikkontrollati bil- plaċebo f’ pazjenti esperjenzati bil- kura (ara sezzjoni 5. 1).
Therapy should be initiated by a physician experienced in the management of HIV infection.
It- terapija għandha tinbeda minn tabib esperjenzat fil- ġestjoni ta ’ infezzjoni tal- HIV.
Before taking CELSENTRI it has to be confirmed that only CCR5-tropic HIV-1 is detectable (i. e.
Qabel ma jittieħed CELSENTRI, għandu jkun ikkonfermat jekk HIV- 1 CCR5- tropiku jista jiġi misjub (i. e.
CXCR4 or dual/ mixed tropic virus not detected) using an adequately validated and sensitive detection method on a newly drawn blood sample.
CXCR4 jew viruses tropiċi doppji/ mħallta li ma jinstabux) b’ metodu adegwatament sensittiv u validat ta ’ kxif minn fuq kampjun ta ’ demm meħud frisk.
The Monogram Trofile assay was used in the clinical studies of CELSENTRI (see sections 4.4 and 5.1).
Il- metodu assay Monogram Trofile intuża fl - istudji kliniċi ta ’ CELSENTRI( ara sezzjonijiet 4. 4 u 5. 1).
Other phenotypic and genotypic assays are currently being evaluated.
Assays oħrajn tat- tip fenotipiku u ġenotipiku qed jiġu attwalment evalwati.
The viral tropism cannot be safely predicted by treatment history and assessment of stored samples.
It- tropiżmu virali ma jistax jiġi mbassar b’ sigurta ’ bl- istorja tat - trattament u mill- assessjar ta ’ kampjuni merfugħa.
There are currently no data regarding the reuse of CELSENTRI in patients that currently have only CCR5-tropic HIV-1 detectable, but have a history of failure on CELSENTRI (or other CCR5 antagonists) with a CXCR4 or dual/ mixed tropic virus.
Ma hemm l- ebda tgħarif fuq l- użu ieħor ta ’ CELSENTRI f’ pazjenti, li għandhom biss HIV- 1 CCR5 - tropiku li jista ’ jiġi misjub, iżda li għandhom storja ta ’ falliment fuq CELSENTRI (jew antagonisti oħra ta ’ CCR5) b ’ CXCR4 jew virus tropiku doppju/ imħallat.
There are no data regarding the switch from a medicinal product of a different antiretroviral class to CELSENTRI in virologically suppressed patients.
Ma hemm l- ebda tgħarif fuq il- bidla minn mediċina oħra ta ’ klassi antiretrovali oħra għall CELSENTRI f’ pazjenti mgħakksin viroloġikament.
Alternative treatment options should be considered.
Trattament ieħor għandu jigi kkunsidrat.
Adults: the recommended dose of CELSENTRI is 150 mg, 300 mg or 600 mg twice daily depending on interactions with co-administered antiretroviral therapy and other medicinal products (see Table 2 in Section 4.5).
Adulti: id- doża rakkomandata ta ’ CELSENTRI hi 150 mg, 300 mg jew 600 mg darbtejn kuljum jiddependi mill- interazzjonijiet ma ’ terapija antiretrovirali mogħtija fl- istess ħin ma ’ prodotti mediċinali oħra (ara Tabella 2 f’ sezzjoni 4. 5).
CELSENTRI can be taken with or without food.
CELSENTRI jista ’ jittieħed ma ’ l- ikel jew waħdu.
CELSENTRI is not recommended for use in children due to lack of data on safety, efficacy and pharmacokinetics (see section 5.2).
CELSENTRI m’ huwiex rakkomandat sabiex jintuża fuq it- tfal billi m’ hemmx tagħrif dwar is - sigurtà, l- effikaċja u l- farmakokinetika (ara sezzjoni 5. 2).
2 Elderly: there is limited experience in patients > 65 years of age (see section 5.2), therefore CELSENTRI should be used with caution in this population.
2 Anzjani: hemm esperjenza limitata f’ pazjenti ta ’ > 65 sena (ara sezzjoni 5. 2), għaldaqstant CELSENTRI għandu jintuża b’ kawtela f’ din il- popolazzjoni.
Renal impairment: dosage adjustment is only recommended in patients with renal impairment who are receiving potent CYP3A4 inhibitors such as: • protease inhibitors (except tipranavir/ ritonavir) • ketoconazole, itraconazole, clarithromycin, telithromycin.
Indeboliment tal- kliewi: aġġustament tad- doża hu rakkomandat biss f’ pazjenti li għandhom indeboliment tal- kliewi li qed jirċievu inibituri CYP3A4 qawwijin bħal: • inibituri tal- protease (għajr tipranavir/ ritonavir), • ketoconazole, itraconazole, clarithromycin, telithromycin)
CELSENTRI should be used with caution in patients with renal impairment (CLcr < 80ml/ min) who are taking potent CYP3A4 inhibitors (see sections 4.4 and 5.2).
CELSENTRI għandu jintuża b’ kawtela f’ pazjenti b’ indeboliment tal- kliewi (CLcr < 80ml/ min) li qegħdin jieħdu inibituri CYP3A4 qawwijin (ara sezzjonijiet 4. 4 u 5. 2).
Table 1 below provides dose interval adjustment guidelines based on simulations of increasing renal impairment in patients being coadministered potent CYP3A4 inhibitors.
Tabella 1 t’ hawn taħt tagħti linji gwida ta ’ aġġustament ta ’ l- intervall ta ’ bejn doża u oħra fuq il- bażi ta ’ simulazzjonijiet ta ’ żieda fl- indeboliment tal- kliewi f’ pazjenti mogħtija inibituri CYP3A4 qawwijin fl- istess ħin.
The safety and efficacy of these dose interval adjustments have not been clinically evaluated.
Is- sigurtà u l - effikaċja ta ’ dawn l- aġġustamenti fl- intervall ta ’ bejn doża u oħra għadhom ma ġewx evalwati klinikament.
Therefore, clinical response to treatment should be closely monitored in these patients.
Għalhekk, ir- rispons kliniku għat- trattament għandu jiġi mmonitorjat mill- qrib f’ dawn il - pazjenti.
Dose interval adjustments based on simulations of increasing renal impairment (for dose recommendations, see Section 4.5 Table 2) Recommended CELSENTRI dose interval
Aġġustamenti fl- intervall ta ’ bejn doża u oħra fuq il- bażi ta ’ simulazzjonijiet ta ’ żieda fl- indeboliment tal- kliewi (għal aġġustament tad- doża ara sezzjoni 4. 5 Tabella 2) Intervall ta ’ bejn doża u oħra ta ’
Creatinine clearance (CLcr) (ml/ min)
Creatinine clearance (CLcr) (ml/ min)
50- 80 ml/ min
CELSENTRI
< 50 – 30 ml/ min
50 - 80
< 30 ml/ min
ml/ min < 50 – 30 ml/ min < 30 ml/ min
Without potent CYP3A4 inhibitors or co- administered with tipranavir/ ritonavir If coadministered with potent CYP3A4
Jekk mogħti mingħajr inibituri CYP3A4 qawwijin jew fl- istess ħin ma tipranavir/ ritonavir
No dose interval adjustment required
tal- ħin bejn kull doża huwa neċessarju
inhibitors, e. g. lopinavir/ ritonavir, darunavir/ ritonavir, atazanavir/ ritonavir, ketoconazole (see also section 4.5)
Lopinavir/ ritonavir, darunavir/ ritonavir, atazanavir / ritonavir, ketoconazole, (ara wkoll sezzjoni 4. 5)
Every 24 hours
Kull 24 siegħa
If coadministered with saquinavir/ ritonavir Every 24 hours
Kull 24 siegħa
Every 48 hours
Kull 48 siegħa
Every 72 hours
Kull 72 siegħa
Hepatic impairment: limited data are available in patients with hepatic impairment, therefore CELSENTRI should be used with caution in this population (see sections 4.4 and 5.2).
Tagħrif disponibbli f’ pazjenti b’ indeboliment tal- fwied huwa limitat (ara sezzjoni 4. 4 u 5. 2), għaldaqstant CELSENTRI għandu jintuża b’ kawtela f’ din il- popolazzjoni.
Hypersensitivity to the active substance or to peanut or soya or to any of the excipients.
Sensittività eċċessiva għas- sustanza attiva jew għall- karawett jew għas- soja jew għal xi sustanzi mhux attivi.
CELSENTRI should be taken as part of an antiretroviral combination regimen.
CELSENTRI għandu jittieħed bħala parti minn reġim ta ’ kombinazzjoni antiretrovirali.
CELSENTRI should optimally be combined with other antiretrovirals to which the patient's virus is sensitive (see section 5.1).
Bħal kull antiretrovirali ieħor, CELSENTRI l- aħjar li jiġi mgħaqqad ma ’ antiretrovirali oħra li l- virus tal- pazjent ikun sensittiv għalihom (ara sezzjoni 5. 1).
CELSENTRI should only be used when only CCR5-tropic HIV-1 is detectable (i. e.
CELSENTRI għandu jintuża biss meta jinstab HIV- 1 CCR5- tropiku (i. e.
CXCR4 or dual/ mixed tropic virus not detected) as determined by an adequately validated and sensitive detection method (see sections 4.1, 4.2 and 5.1).
CXCR4 jew viruses tropiċi doppji/ mħallta li ma jinstabux) kif stabbilit b’ metodu adegwatament sensittiv u validat ta ’ kxif (ara sezzjonijiet 4. 1, 4. 2 u 5. 1).
The Monogram Trofile assay was used in the clinical studies of CELSENTRI.
Il- metodu assay Monogram Trofile intuża fl- istudji kliniċi ta ’ CELSENTRI( ara sezzjonijiet 4. 4 u 5. 1).
The viral tropism cannot be predicted by treatment history or assessment of stored samples.
It- tropiżmu virali ma jistax jiġi mbassar b’ sigurta ’ bl- istorja tat- trattament u mill - assessjar ta ’ kampjuni merfugħa.
Changes in viral tropism occur over time in HIV-1 infected patients.
Bdil fit- tropiżmu virali jiġri kull tant żmien f’ pazjenti infettati bl- HIV- 1.
Therefore there is a need to start therapy shortly after a tropism test.
Għalekk hemm il- bżonn li tinbeda it- terapija ftit wara li jsir it- test ta ’ tropiżmu.
Background resistance to other classes of antiretrovirals have been shown to be similar in previously undetected CXCR4-tropic virus of the minor viral population, as that found in CCR5-tropic virus.
Reżistenza ġenerali għal klassijiet antiretrovirali oħra kienet simili ta ’ CXCR4- tropic virus fil - populazzjoni virali minuri, li ma kienx ġie mikxuf qabel, kif ukoll bħa; CCR5- tropic virus.
Dose adjustment: physicians should ensure that appropriate dose adjustment of CELSENTRI is made when CELSENTRI is co-administered with CYP3A4 inhibitors and/ or inducers since maraviroc concentrations and its therapeutic effects may be affected (see sections 4.2 and 4.5).
3 Aġġustament tad- doża: it- tobba għandhom jiżguraw li jsir aġġustament adegwat fid- doża ta ’ CELSENTRI meta CELSENTRI jingħata ma ’ inibituri u/ jew indutturi ta ’ CYP3A4 billi l - konċentrazzjonijiet ta ’ maraviroc u l- effetti terapewtiċi tiegħu jistgħu jiġu affettwati (ara sezzjoni 4. 2 u 4. 5).
Please also refer to the respective Summary of Product Characteristics of the other antiretroviral medicinal products used in the combination.
Jekk jogħġbok irreferi għas- Sommarju rispettiv tal- Karatteristiċi tal- Prodott ta ’ prodotti mediċinali antiretrovirali oħra użati fil- kombinazzjoni.
3 Information for patients: patients should be advised that antiretroviral therapies including CELSENTRI have not been shown to prevent the risk of transmission of HIV to others through sexual contact or contamination with blood.
Tagħrif għall- pazjenti: il- pazjenti għandhom jiġu informati li t- terapiji antiretrovirali fosthom CELSENTRI ma ġewx murija li jevitaw ir- riskju ta ’ trasmissjoni ta ’ l- HIV lil ħaddieħor permezz ta ’ kuntatt sesswali jew kontaminazzjoni bid- demm.
They should continue to use appropriate precautions.
Huma għandhom ikomplu jużaw prekawzjonijiet xierqa.
Patients should also be informed that CELSENTRI is not a cure for HIV-1 infection.
Il- pazjenti għandhom jiġu informati wkoll li CELSENTRI mhux kura għal infezzjoni ta ’ l - HIV- 1.
Postural hypotension: when CELSENTRI was administered in studies with healthy volunteers at doses higher than the recommended dose, cases of symptomatic postural hypotension were seen at a greater frequency than with placebo.
Pressjoni baxxa relatata mal- pożizzjoni tal- ġisem: meta CELSENTRI ngħata fi studji fuq voluntiera b’ saħħithom f’ dożi ogħla mid- doża rakkomandata, każijiet ta ’ pressjoni baxxa sintomatika relatata mal- pożizzjoni tal- ġisem dehru bi frekwenza akbar minn bil- plaċebo.
However, when CELSENTRI was given at the recommended dose in HIV infected patients in Phase 3 studies, postural hypotension was seen at a similar rate compared to placebo (approximately 0.5%).
Madankollu, meta CELSENTRI ngħata bid- doża rakkomandata f’ pazjenti infettati bl- HIV fi studji ta ’ Fażi 3, pressjoni baxxa relatata mal- pożizzjoni tal- ġisem dehret b’ rata simili meta mqabbla mal- plaċebo (madwar 0. 5%).
Caution should be used when administering CELSENTRI in patients with a history of postural hypotension or on concomitant medicinal products known to lower blood pressure.
Wieħed għandu juża kawtela meta CELSENTRI jingħata lil pazjenti bi storja ta ’ pressjoni baxxa marbuta mal - pożizzjoni tal- ġisem jew li jkunu qegħdin jieħdu prodotti mediċinali konkomittanti magħrufa li jbaxxu l- pressjoni tad- demm.
Potential effect on immunity:
Effett potenzjali fuq l- immunita ’:
CCR5 antagonists could potentially impair the immune response to certain infections.
Antagonisti ta’ CCR5 jista ’ potenzjalment ifixkel ir- reazzjoni ta ’ immunita ’ fuq ċretu infezzjonijiet.
This should be taken into consideration when treating infections such as active tuberculosis and invasive fungal infections.
Dan għandu jiġi kkunsidrat meta jigu ttrattati infezzjonijiet bħal - tuberkulożi attiva u infezzjonijiet fungali invażivi.
The incidence of AIDS-defining infections was similar between CELSENTRI and placebo arms in the pivotal studies.
Il- frekwenza ta ’ infezzjonijiet relatati ma l- AIDS kienet l- istess bejn CELSENTRI u placebo fi studji pivotali.
Cardiovascular safety: limited data exist with the use of CELSENTRI in patients with severe cardiovascular disease, therefore special caution should be exercised when treating these patients with CELSENTRI.
Sigurtà kardjovaskulari: jeżisti tagħrif limitat fuq l- użu ta ’ CELSENTRI f’ pazjenti b’ mard kardjovaskulari serju għalekk attenzjoni speċjali għandha tkun murija meta dawn il- pazjenti ikunu itrattati b’ CELSENTRI.
Immune reconstitution 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.
Sindrome tar- rikostituzzjoni immuni: f’ pazjenti infettati bl- HIV li jkollhom defiċjenza immunitarja severa fiż- żmien li tinbeda terapija antiretrovirali kkombinata (CART), tista ’ tiżviluppa reazzjoni infjammatorja għal patoġeni opportunistiċi bla sintomi jew residwi u tikkawża kondizzjonijiet kliniċi serji, jew aggravament tas- sintomi.
Typically, such reactions have been observed within the first few weeks or months of initiation of CART.
Ġeneralment, reazzjonijiet bħal dawn ġew osservati fl- ewwel ftit ġimgħat jew xhur mill- 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 cytomegalovirus retinitis, infezzjonijiet mikobatteriċi ġeneralizzati u/ jew fokali, u pnewmonja ikkawżata minn Pneumocystis jiroveci (preċedentament magħrufa bħala Pneumocystis carinii).
Any inflammatory symptoms should be evaluated and treatment initiated when necessary.
Kwalunkwe sintomu infjammatorju għandu jiġi valutat u tinbeda kura meta tkun meħtieġa.
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).
Għalkemm l- etjoloġija hija meqjusa li għandha aktar minn fattur wieħed (inkluż użu kortikosterojde, il- konsum ta ’ l- alkoħol, immunosuppressjoni qawwija, indiċi tal- piż tal- ġisem ogħla), ġew irrapportati każijiet ta ’ osteonekrożi f’ pazjenti bil- marda HIV fi stat avvanzat u/ jew espożizzjoni fuq perjodu ta ’ żmien twil għat- terapija ta ’ kombinazzjoni antiretrovirali (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 jingħataw il- parir li jfittxu parir mediku jekk jesperjenzaw uġigħ fil- ġogi, ebusija fil- ġogi jew diffikultà fil- movimenti.
Hepatic safety: the safety and efficacy of CELSENTRI have not been specifically studied in patients with significant underlying liver disorders.
Sigurta ’ tal- fwied: is- sigurtà u l- effikaċja ta ’ CELSENTRI ma ġewx studjati speċifikament f’ pazjenti li għandhom disturbi primarji sinifikanti fil- fwied.
A case of possible CELSENTRI-induced hepatotoxicity with allergic features has been reported in a study in healthy volunteers.
Każ ta ’ possibilita ’ ta ’ tossiċita ’ fil- fwied imġiegħla minn CELSENTRI, b’ fatturi allerġiċi kienet irrappurtata fi studju ta ’ voluntiera b’ saħħithom.
In addition, an increase in hepatic adverse reactions with CELSENTRI was observed during studies of treatment-experienced subjects with HIV infection, although there was no overall increase in ACTG Grade 3/ 4 liver function test abnormalities (see section 4.8).
Barra minn hekk, ġiet osservata żieda fir reazzjonijiet aversi b’ CELSENTRI waqt studji fuq suġġetti b’ infezzjoni HIV, b’ esperjenza bit- trattament, għalkemm ma kien hemm l- ebda żieda ġenerali f’ riżulati mhux normali tal- funzjoni tal- fwied ACTG Grad ¾ (ara sezzjoni 4. 8).
Patients with pre-existing liver dysfunction, including chronic active hepatitis, can have an increased frequency of liver function abnormalities during combination antiretroviral therapy and should be monitored according to standard practice.
Pazjenti bi fwied li ma jaħdimx normali, inklużi dawk b’ epatite kronika attiva, setgħu kellhom frekwenza ogħla ta ’ riżultati mhux normali ta ’ testijiet tal- funzjoni tal- fwied waqt terapija antiretrovirali ikkombinata.
Discontinuation of CELSENTRI should be considered in any patient with signs or symptoms of acute hepatitis, in particular if drug-related hypersensitivity is suspected or with increased liver transaminases combined with rash or other systemic symptoms of potential hypersensitivity (e. g. pruritic rash, eosinophila or elevated IgE).
Dan għandu jkun mmonitorjat b’ attenzjoni skond il- pratika standard.
In case of concomitant antiviral therapy for hepatitis B and/ or C, please refer also to the relevant product information for these medicinal products.
4 Twaqqif tat- trattament b’ CELSENTRI għandu jkun ikkunsidrat f’ kwalinkwe pazjent b’ sinjali jew sintomi ta ’ epatite akuta, partikolarment jekk tkun issuspettata ipersensitivita ’ relatata ma ’ xi prodott, jew ma żieda ta ’ transaminases tal- fwied flimkien ma ’ raxx jew sintomi sistemiċi oħra (eż. raxx, prurite, esinofila jew IgE elevat).
4 There is limited experience in patients with reduced hepatic function, therefore CELSENTRI should be used with caution in this population (see sections 4.2 and 5.2).
Hemm esperjenza limitata f’ pazjenti li għandhom funzjoni tal- fwied imnaqqsa, għalhekk CELSENTRI għandu jintuża b’ kawtela f’ din il- popolazzjoni (ara sezzjoni 4. 2 u 5. 2).
Renal impairment: the safety and efficacy of CELSENTRI have not been specifically studied in patients with renal impairment, therefore CELSENTRI should be used with caution in this population.
Indeboliment tal- kliewi: is- sigurtà u l- effikaċja ta ’ CELSENTRI ma ġewx studjati b’ mod speċifiku f’ pazjenti b’ indeboliment tal- kliewi, għalhekk CELSENTRI għandu jintuża b’ kawtela f’ din il - popolazzjoni.
In the absence of metabolic inhibitors, renal clearance accounts for less than 25% of total clearance of maraviroc and hence renal impairment is not expected to significantly alter maraviroc exposures.
Fin- nuqqas ta ’ inibituri metaboliċi, it- tneħħija mill- kliewi jammonta għal inqas minn 25% tat- tneħħija totali ta ’ marivoc u għalhekk l- indeboliment tal- fwied, m’ huwiex mistenni li jibdel b’ mod sinjifikanti l- espożizzjonijiet ta ’ maraviroc.
In the presence of metabolic inhibitors, renal clearance may account for up to 70% of total clearance of maraviroc, hence renal impairment may result in increased maraviroc exposures in this case.
Fil- preżenza ta ’ inibituri metaboliċi, it- tneħħija mill- kliewi tista ’ tammonta għal 70% tat- tneħħija totali ta ’ maraviroc u għalhekk l- indeboliment tal - fwied jista ’ jirriżulta f’ espożizzjonijiet ikbar ta ’ maraviroc f’ dan il- każ.
Therefore, CELSENTRI should be used with caution in patients with renal impairment (CLcr < 80 ml/ min) who are also taking potent CYP3A4 inhibitors.
Għalhekk, CELSENTRI għandu jintuża b’ kawtela f’ pazjenti b’ indeboliment renali (CLcr < 80ml/ min) li qegħdin jieħdu wkoll inibituri CYP3A4 qawwijin.
Table 1 provides dose interval adjustment guidelines based on simulations of increasing renal impairment in patients being coadministered potent CYP3A4 inhibitors.
Tabella 1 tipprovdi linji gwida għal aġġustament fl- intervall ta ’ bejn doża u oħra fuq il- bażi ta ’ simulazzjonijiet ta ’ żieda fl- indeboliment tal- kliewi f’ pazjenti mogħtija inibituri CYP3A4 qawwijin fl- istess ħin.
The safety and efficacy of these dose interval adjustments have not been clinically evaluated.
Is- sigurtà u l- effikaċja ta ’ dawn l- aġġustamenti fl- intervall ta ’ bejn doża u oħra għadhom ma ġewx evalwati klinikament.
Therefore, clinical response to treatment should be closely monitored in these patients (see sections 4.2 and 5.2).
Għalhekk, ir- rispons kliniku għat- trattament u l - funzjoni renali għandhom jiġu mmonitorjati mill- qrib f’ dawn il- pazjenti (ara sezzjoni 4. 2 u 5. 2).
Soya lecithin:
Soya lecithin:
CELSENTRI contains soya lecithin.
CELSENTRI fih Soya lecithin.
If a patient is hypersensitive to peanut or soya, CELSENTRI should not be used.
Jekk pazjent huwa allerġiku għal karawett jew soya, CELSENTRI ma għandux jintuza.
Maraviroc is a substrate of cytochrome P450 CYP3A4.
Maraviroc hu sottostrat taċ- ċitokromu P450 CYP3A4.
Co-administration of CELSENTRI with medicinal products that induce CYP3A4 may decrease maraviroc concentrations and reduce its therapeutic effects.
L- amministrazzjoni ta ’ CELSENTRI ma ’ prodotti mediċinali li jinduċu CYP3A4 tista ’ tnaqqas il- konċentrazzjonijiet ta ’ maraviroc u tnaqqas l - effetti terapewtiċi tiegħu.
Co-administration of CELSENTRI with medicinal products that inhibit CYP3A4 may increase maraviroc plasma concentrations.
L- amministrazzjoni ta ’ CELSENTRI ma ’ prodotti mediċinali li jimpedixxu CYP3A4 tista ’ żżid il- konċentrazzjonijiet ta ’ maraviroc fil- plasma.
Dose adjustment of CELSENTRI is recommended when CELSENTRI is co-administered with CYP3A4 inhibitors and/ or inducers.
Huwa rakkomandat aġġustament fid- doża ta ’ CELSENTRI meta CELSENTRI jiġi amministrat ma ’ inibituri u/ jew indutturi ta ’ CYP3A4.
Further details for concomitantly administered medicinal products are provided below (see Table 2).
Aktar dettalji dwar prodotti mediċinali amministrati fl- istess ħin huma pproduti hawn isfel (ara Tabella 2).
Studies in human liver microsomes and recombinant enzyme systems have shown that maraviroc does not inhibit any of the major P450 enzymes at clinically relevant concentrations (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4).
L- istudji dwar il- mikrosomi tal- fwied uman u s- sistemi ta ’ l- enzimi rikombinanti wrew li maraviroc ma jinibixxi l- ebda waħda mill- enzimi P450 prinċipali f’ konċentrazzjonijiet kliniċi rilevanti (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 u CYP3A4).
Maraviroc had no clinically relevant effect on the pharmacokinetics of midazolam, the oral contraceptives ethinylestradiol and levonorgestrel, or urinary 6β -hydroxycortisol/ cortisol ratio, suggesting no inhibition or induction of CYP3A4 in vivo.
Maraviroc ma kellux effett kliniku rilevanti fuq il- farmakokinetiċi ta ’ midazolam, il- kontraċettivi orali ethinylestradiol u levonorgestrel, jew il- proporzjon 6β- hydroxycortisol/ cortisol ta ’ l- awrina, li ma jissuġġerixxi l- ebda inibizzjoni jew induzzjoni ta ’ CYP3A4 in vivo.
At higher exposure of maraviroc a potential inhibition of CYP2D6 cannot be excluded.
F’ espożizzjoni ogħla ta ’ maraviroc, inibizzjoni potenzjali ta ’ CYP2D6 ma tistax tiġi eskluża.
Based on the in vitro and clinical data, the potential for maraviroc to affect the pharmacokinetics of coadministered medicinal products is low.
Fuq il- bażi tat- tagħrif in vitro u kliniku, il- potenzjal li maraviroc jaffettwa l- farmakokinetiċi ta ’ prodotti mediċinali amministrati miegħu (p. e. methadone, cyclosporine) hu baxx.
Renal clearance accounts for approximately 23% of total clearance of maraviroc when maraviroc is administered without CYP3A4 inhibitors.
Il- clearance mill- kliewi tirrappreżenta madwar 23% tal- clearance totali ta ’ maraviroc meta maraviroc jingħata mingħajr inibituri CYP3A4.
As both passive and active processes are involved, there is the potential for competition for elimination with other renally eliminated active substances.
Billi huma involuti kemm proċessi attivi kif ukoll passivi, jeżisti l- potenzjal ta ’ kompetizzjoni għat- tneħħija ma ’ sustanzi attivi oħra li jitneħħew mill- kliewi.
However, co-administration of CELSENTRI with tenofovir (substrate for renal elimination) and Cotrimoxazole (contains trimethoprim, a renal cation transport inhibitor), showed no effect on the pharmacokinetics of maraviroc.
Madankollu, l- amministrazzjoni ta ’ CELSENTRI ma ’ tenofovir (sottostrat ta ’ l- eliminazzjoni mill - kliewi) u Co- trimoxazole (fih trimethoprim, inibitur tat- trasport renali ta ’ katjoni), ma wriet l- ebda effett fuq il- farmakokinetiċi ta ’ maraviroc.
In addition, co-administration of CELSENTRI with lamivudine/ zidovudine showed no effect of maraviroc on lamivudine (primarily renally cleared) or zidovudine (non-P450 metabolism and renal clearance) pharmacokinetics.
Barra minn hekk, l- amministrazzjoni ta ’ CELSENTRI ma ’ lamivudine/ zidovudine ma wriet ebda effett ta ’ maraviroc fuq il- farmakokinetiċi ta ’ lamivudine (imneħħi prinċipalment mill- kliewi) jew ta ’ zidovudine (metaboliżmu mhux P450 u tneħħija mill - kliewi).
In vitro results indicate that maraviroc could inhibit P- glycoprotein in the gut and may thus affect bioavailability of certain drugs.
Riżultati in vitro jindikaw li maraviroc jista jinibixxi P- glycoprotein fl- imsaren u għalhekk jista jaffetwa il - bijodisponibilità ta ’ ċertu mediċini.
Table 2.
5 Tabella 2.
Interactions and dose recommendations with other medical products Medicinal product by therapeutic areas (dose of CELSENTRI used in study) ANTI-INFECTIVES Antiretrovirals NRTIs
Effetti ma ’ prodotti mediċinali oħra u rakkomandazzjonijiet dwar id- doża Prodott mediċinali skond il- klassi terapewtika (doża ta ’ CELSENTRI użata fl - istudju) KONTRA L - INFEZZJONIJIET Antiretrovirali NRTIs
Effects on drug levels Geometric mean ratio (range) if not stated otherwise
Effetti fuq livelli ta ’ Prodotti Mediċinali Proporzjon Ġeometriku medju (intervall) jekk mhux indikat mod ieħor
Recommendations concerning co- administration
Rakommandazzjonijiet dwar l - amministrazzjoni ma ’ mediċini oħra
5 Lamivudine 150 mg BID (maraviroc 300 mg BID)
Lamivudine 150 mg BID (maraviroc 300 mg BID)
Lamivudine AUC12: ↔ 1.13 (0.82, 2.09) Lamivudine Cmax: ↔ 1.16 (0.46, 2.55) Maraviroc concentrations not measured, no effect is expected.
Lamivudine Cmax: ↔ 1. 16 (0. 46, 300 mg darbtejn kulljum u NRTIs
No significant interaction seen/ expected.
2. 55) Il- konċetrazzjonijiet ta ’ Maraviroc ma kienux imkejjla, l - ebda effett mhu mistenni
CELSENTRI 300 mg twice daily and NRTIs can be co- administered without dose
jistgħu jiġu amministrati flimkien mingħajr ebda aġġustament fid- doża.
Tenofovir 300 mg QD (maraviroc 300 mg BID)
Tenofovir 300 mg QD (maraviroc 300 mg BID)
Maraviroc AUC12: ↔ 1.03 (0.83, 1.19) Maraviroc Cmax: ↔ 1.03 (0.68, 1.45) Tenofovir concentrations not measured, no effect is expected.
Maraviroc AUC12: ↔ 1. 03 (0. 83, 1. 19) Maraviroc Cmax: ↔ 1. 03 (0. 68, 1. 45) Il- konċetrazzjonijiet ta ’ Tenofovir ma kienux imkejjla, l - ebda effett mhu mistenni
Zidovudine 300 mg BID (maraviroc 300 mg BID) NNRTIs
Zidovudine 300 mg BID (maraviroc 300 mg BID) NNRTIs
Zidovudine AUC12: ↔ 0.98 (0.45, 1.88) Zidovudine Cmax: ↔ 0.93 (0.38, 2.70) Maraviroc concentrations not measured, no effect is expected.
Zidovudine AUC12: ↔ 0. 98 (0. 45, 1. 88) Zidovudine Cmax: ↔ 0. 93 (0. 38, 2. 70) Il- konċetrazzjonijiet ta ’ Maraviroc ma kienux imkejjla, l - ebda effett mhu mistenni
Maraviroc AUC12: ↓ 0.55 (90% CI:
Maraviroc AUC12: ↓ 0. 55 (90% Id- doża ta ’ CELSENTRI għandha CI:
0.38, 0.63) Efavirenz concentrations not measured, no effect is expected.
0. 49, 0. 62) tiżdied għal 600mg meta mogħtija Maraviroc Cmax: ↓ 0. 49 (90% ma ’ efavirenz mingħajr il- preżenza CI:
CELSENTRI dose should be increased to 600 mg twice daily when co-administered with efavirenz in the absence of a PI or other potent CYP3A4 inhibitor.
0. 38, 0. 63) ta ’ PI jew inibitur CYP3A4 qawwi Il- konċetrazzjonijiet ta ’ ieħor.
For combination with efavirenz + PI, see below.
Meta mogħtija ma ’ efavirenz Efavirenz ma kienux imkejjla, l - fil- preżenza ta ’ PI ara hawn taħt. ebda effett mhu mistenni
Nevirapine 200 mg BID (maraviroc 300 mg Single Dose) PIs
Nevirapine 200 mg BID (maraviroc 300 mg SD) PIs
Comparison to exposure in historical controls suggests that CELSENTRI 300 mg twice daily and nevirapine can be co-administered without dose adjustment.
Maraviroc AUC12: ↔ mqabbla Meta tqabbel ma espożizzjoni ma kontrolli storiċi f’ kontrolli li saru fil- passat Maraviroc Cmax: ↑ mqabbla ma CELSENTRI 300 mg darbtejn kontrolli storiċi kulljum u nevirapine jistgħu jiġu Il- konċetrazzjonijiet ta ’ mgħotija flimkien mingħajr ebda Nevirapine ma kienux imkejjla, aġġustament fid- doża. l- ebda effett mhu mistenni
CELSENTRI dose should be decreased to 150 mg twice daily when co-administered with a PI; except in combination with
Maraviroc AUC12 ↑ 3. 57 (2. 55, Id- doża ta ’ CELSENTRI għandha 4. 45) tkun imnaqqsa għal 150mg darbtejn Maraviroc Cmax: ↑ 2. 09 (1. 31, kulljum meta jkun mgħoti flimkien 4. 19) ma PI; ħlief meta jkun mgħoti Il- konċetrazzjonijiet ta ’ flimkien ma ’ tipranavir/ ritonavir jew Atazanavir ma kienux imkejjla, fosamprenavir/ ritonavir, fejn id- doża l- ebda effett mhu mistenni għandha tkun 300mg BID.
Atazanavir/ ritonavir 300 mg/ 100 mg QD (maraviroc 300 mg BID)
6 Atazanavir/ ritonavir 300 mg/ 100 mg QD (maraviroc 300 mg BID)
Maraviroc AUC12 ↑ 4.88 (3.28, 6.49) Maraviroc Cmax: ↑ 2.67 (1.52, 3.90) Atazanavir/ ritonavir concentrations not measured, no effect is expected.
Maraviroc AUC12 ↑ 4. 88 (3. 28, 6. 49) Maraviroc Cmax: ↑ 2. 67 (1. 52, 3. 90) Il- konċetrazzjonijiet ta ’ Atazanavir/ ritonavir ma kienux imkejjla, l- ebda effett mhu mistenni
Maraviroc does not significantly
Maraviroc ma jaffetwax sinfikattivament il- livelli tal- PI.
Maraviroc AUC12 ↑ 3.95 (2.32, 5.52) Maraviroc Cmax: ↑ 1.97 (1.26, 2.70) Lopinavir/ ritonavir concentrations not measured, no effect is expected.
Maraviroc AUC12 ↑ 3. 95 (2. 32, 5. 52) Maraviroc Cmax: ↑ 1. 97 (1. 26, 2. 70) Il- konċetrazzjonijiet ta ’ Lopinavir/ ritonavir ma kienux imkejjla, l- ebda effett mhu mistenni
Maraviroc AUC12 ↑ 9.77 (5.42, 20.5) Maraviroc Cmax: ↑ 4.78 (2.11, 9.88) Saquinavir/ ritonavir concentrations not measured, no effect is expected.
Maraviroc AUC12 ↑ 9. 77 (5. 42, 20. 5) Maraviroc Cmax: ↑ 4. 78 (2. 11, 9. 88) Il- konċetrazzjonijiet ta ’ Saquinavir/ ritonavir ma kienux imkejjla, l- ebda effett mhu mistenni
Darunavir/ ritonavir 600 mg/ 100 mg BID (maraviroc 150 mg BID)
Darunavir/ ritonavira) 600 mg/ 100 mg BID (maraviroc 150 mg BID)
Maraviroc AUC12 ↑ 4.05 (2.10, 21.2) Maraviroc Cmax: ↑ 2.29 (0.74, 17.8) Darunavir/ ritonavir concentrations were consistent with historical data.
Maraviroc AUC12 ↑ 4. 05 (2. 10, 21. 2) Maraviroc Cmax: ↑ 2. 29 (0. 74, 17. 8) Il- konċetrazzjonijiet ta ’ Darunavir u ritonavir kienu konsistenti mat- tgħarif li nġabar fil- passat
Limited data are available for co- administration with nelfinavir.
Hemm tgħarif limitat fuq l- użu ma ’ nelfinavir.
Nelfinavir is a potent CYP3A4 inhibitor and would be expected to increase maraviroc concentrations.
Nelfinavir hu inibitur qawwi ta ’ CYP3A4 għalhekk hu mistenni li jżid il - konċetrazzjonijiet ta ’ maraviroc.
Limited data are available for co- administration with indinavir.
Hemm tgħarif limitat fuq l- użu ma ’ indinavir.
Indinavir is a potent CYP3A4 inhibitor.
Indinavir hu inibitur qawwi ta ’ CYP3A4.
Population PK analysis in phase 3 studies suggests dose reduction of maraviroc when coadministered with indinavir gives appropriate maraviroc exposure.
Studju fuq il- popolazzjoni PK f’ fażi 3 juru li tnaqqis tad doża ta maraviroc metya jingħata ma indinavir, tagħti esposizzjoni tajba għal maraviroc.
Fosamprenavir is considered to be a moderate CYP3A4 inhibitor.
Fosamprenavir hu kkunsidrat bħala inibitur qawwi ta ’ CYP3A4.
Population PK studies suggest that a dose adjustment of maraviroc is not required.
Studju fuq il - popolazzjoni PK jindikaw li ma hemmx bżonn aġġustament fid - doża ta ’ maraviroc.
CELSENTRI 300 mg twice daily and tipranavir/ ritonavir or fosamprenavir/ ritonavir can be co- administered without dose
CELSENTRI 300 mg darbtejn kulljum u tipranavir/ ritonavir jew fosamprenavir/ ritonavir jistgħu jiġu amministrati flimkien mingħajr ebda aġġustament fid- doża.
Maraviroc AUC12 ↔ 1.02 (0.65, 1.87) Maraviroc Cmax: ↔ 0.86 (0.37, 3.20) Tipranavir/ ritonavir concentrations were consistent with historical data.
Maraviroc AUC12 ↔ 1. 02 (0. 65, 1. 87) Maraviroc Cmax: ↔ 0. 86 (0. 37, 3. 20) Il- konċentrazzjonijiet ta; Tipranavir/ ritonavir kienu konsistenti mat- tgħarif li nġabar
adjustment.
7 fil- passat
Efavirenz 600 mg QD + lopinavir/ ritonavir 400mg/ 100 mg BID (maraviroc 300 mg BID) Efavirenz 600 mg QD + saquinavir/ ritonavir 1000 mg/ 100 mg BID (maraviroc 100 mg BID) Efavirenz and atazanavir/ ritonavir or darunavir/ ritonavir Antibiotics
Efavirenz 600 mg QD + lopinavir/ ritonavir 400mg/ 100 mg BID (maraviroc 300 mg BID)
Maraviroc AUC12: ↑ 2.53 (1.71, 3.15) Maraviroc Cmax: ↑ 1.25 (0.87, 2.82) Efavirenz, lopinavir/ ritonavir concentrations not measured, no effect expected.
Maraviroc AUC12: ↑ 2. 53 (1. 71, 3. 15) Maraviroc Cmax: ↑ 1. 25 (0. 87, 2. 82)
Maraviroc AUC12: ↑ 5.00 (3.04, 6.31) Maraviroc Cmax: ↑ 2.26 (0.68, 4.09) Efavirenz, saquinavir/ ritonavir concentrations not measured, no effect expected.
Id- doża ta ’ CELSENTRI għandha tkun imnaqqsa għal 150mg darbtejn kulljum meta dan ikun mgħoti ma efavirenz fil- preżenza ta PI (barra ma fosamprenavir/ ritonavir fejn id -
Based on the extent of inhibition by atazanavir/ ritonavir or darunavir/ ritonavir in the absence of efavirenz, an increased exposure is expected.
Il- konċetrazzjonijiet ta ’ Efavirenz, lopinavir/ ritonavir ma kienux imkejjla, l- ebda effett mhu mistenni
CELSENTRI dose should be decreased to 150 mg twice daily when co-administered with efavirenz in the presence of a PI (except fosamprenavir/ ritonavir where the dose should be 300 mg twice daily).
doża għandha tkun ta ’ 300 mg darbtejn kulljum)
Sulphamethoxazole/ Trimethoprim 800 mg/ 160 mg BID (maraviroc 300 mg BID)
Sulphamethoxazole / Trimethoprim 800 mg/ 160 mg BID (maraviroc 300 mg BID)
Maraviroc AUC12: ↔ 1.11 (0.84, 1.53) Maraviroc Cmax: ↔ 1.19 (0.69, 1.73) Sulphamethoxazole/ trimethoprim concentrations not measured, no effect expected.
Maraviroc AUC12: ↔ 1. 11 (0. 84, 1. 53) Maraviroc Cmax: ↔ 1. 19 (0. 69, 1. 73) Il- konċetrazzjonijiet ta ’ Sulphamethoxazole/ trimethoprim ma kienux imkejjla, l- ebda effett mhu mistenni
CELSENTRI 300 mg twice daily and sulphamethoxazole/ trimethoprim can be co-administered without dose adjustment.
CELSENTRI 300 mg darbtejn kulljum u sulphamethoxazole / trimethoprim jistgħu jingħataw flimkien mingħajr ebda aġġustament fid- doża.
Rifampicin 600 mg QD (maraviroc 100 mg BID)
Rifampicin 600 mg QD (maraviroc 100 mg BID)
Maraviroc AUC: ↓ 0.37 (90% CI:
Maraviroc AUC: ↓ 0. 37 (90% CI:
0.33, 0.41) Maraviroc Cmax: ↓ 0.34 (90% CI:
0. 33, 0. 41) Maraviroc Cmax: ↓ 0. 34 (90% CI:
0.26, 0.43) Rifampicin concentrations not measured, no effect expected.
0. 26, 0. 43) Il- konċetrazzjonijiet ta ’ Rifampicin ma kienux imkejjla, l- ebda effett mhu mistenni
CELSENTRI dose should be increased to 600 mg twice daily when co-administered with rifampicin in the absence of a potent CYP3A4 inhibitor.
Id- doża ta ’ CELSENTRI għandha tkun miżjuda għal 600mg darbtejn kulljum meta jkun mgħoti flimkien ma rifampicin, mingħajr il- preżenza ta ’ inibitur qawwi ta ’ CYP3A4.
This dose adjustment has not been studied in HIV patients.
Il - bdil fid- doża ma ġiex studjat f’ pazjenti b’ HIV.
See also section 4.4.
Ara wkoll sezzjoni 4. 4.
Combination with two inducers has not been studied.
Il- kombinazzjoni ma ’ żewġt indutturi ma kienetx studjata.
There may be a risk of suboptimal levels with risk of loss of virologic response and resistance development.
Jista jkun hemm riskju ta ’ livelli anqas milli mixtieqa flimkien ma riskju ta ’ nuqqas ta ’ rispons viroloġiku u żviluppament ta ’ reżistenza.
Concomitant use of CELSENTRI and rifampicin + efavirenz is not recommended.
L- użu ta ’ CELSENTRI flimkien ma refampicin+efavirenz mhux rakkomandat.
Not studied.
Ma kienux studjati.
Rifabutin is considered to be a weaker inducer than rifampicin.
Rifabutin hu kkunsidrat bħala induttur anqas qawwi minn rifampicin.
When combining rifabutin with protease inhibitors that are potent inhibitors of CYP3A4 a net inhibitory effect on maraviroc is expected.
Meta jingħata rifabutin ma inibitturi Protease li huma inibituri qawwija ta ’ CYP3A4, f’ laħħar
CELSENTRI dose should be decreased to 150 mg twice daily when co-administered with rifabutin in the presence of a PI (except tipranavir/ ritonavir or fosamprenavir/ ritonavir where the dose should be 300 mg twice daily).
għandha tkun ta ’ 300 mg darbtejn kulljum).
Clarithromycin, Telithromycin Antifungals
Clarithromycin, Telithromycin Antifungali
Not studied, but both are potent CYP3A4 inhibitors and would be expected to increase maraviroc concentrations.
Ma kienux studjati, madanakollu it- tnejn huma inibituri qawwija ta ’ CYP3A4 u għalekk mistennija li jżidu il - konċentrazzjoni ta ’ maraviroc.
CELSENTRI dose should be decreased to 150 mg twice daily when co-administered with clarithromycin and telithromycin.
Id- doża ta ’ CELSENTRI għandha titnaqqas għal 150mg darbtejn kulljum meta mogħtija ma’ clarithromycin u telithromycin.
Ketoconazole 400 mg QD (maraviroc 100 mg BID)
Ketoconazole 400 mg QD (maraviroc 100 mg BID)
Maraviroc AUCtau: ↑ 5.00 (2.40, 9.62) Maraviroc Cmax: ↑ 3.38 (1.11, 7.68) Ketoconazole concentrations not measured, no effect is expected.
Maraviroc AUCtau: ↑ 5. 00 (2. 40, 9. 62) Maraviroc Cmax: ↑ 3. 38 (1. 11, 7. 68) Il- konċetrazzjonijiet ta ’ Ketoconazole ma kienux imkejjla, l- ebda effett mhu mistenni
CELSENTRI dose should be decreased to 150 mg twice daily when co-administered with ketoconazole.
Id- doża ta ’ CELSENTRI għandha titnaqqas għal 150mg darbtejn kulljum meta mogħtija ma ’ ketoconazole.
Itraconazole
Itraconazole,
Not studied.
Ma kienx studjat.
Itraconazole, is a potent CYP3A4 inhibitor and would be expected to increase the exposure of maraviroc.
Itraconazole huwa inibitur qawwi ta’ CYP3A4 u mistenni li jżid l- espożizzjoni ta ’ maraviroc.
CELSENTRI dose should be decreased to 150 mg twice daily when co-administered with itraconazole.
Id- doża ta ’ CELSENTRI għandha titnaqqas għal 150mg darbtejn kulljum meta mogħtija ma ’ itraconazole.
Fluconazole Antivirals
Fluconazole, Antivirali
Fluconazole is considered to be a moderate CYP3A4 inhibitor.
Fluconazole, huwa kkunsidrat bħala inibitur moderat ta’ CYP3A4.
Population PK studies suggest that a dose adjustment of maraviroc is not required.
Studji fuq il - popolazzjoni PK jindikaw li ma hemmx bżonn aġġustament fid - doża ta ’ maraviroc.
CELSENTRI 300 mg twice daily should be administered with caution when coadministered with fluconazole.
CELSENTRI 300 mg darbtejn kulljum għandu jkun mgħoti b’ kawtela meta dan jingħata flimkien ma fluconazole.
HCV agents
Aġenti HCV ABBUŻ TA ’ DROGA
Pegylated interferon and ribavirin have not been studied, no interaction is expected.
ma kienux studjati, l- ebda effett mhu mistenni
CELSENTRI 300 mg twice daily and pegylated interferon or
CELSENTRI 300 mg darbtejn kulljum u pegylated interferon jew ribavirin jistgħu jiġu mgħotija flimkien mingħajr ebda aġġustament tad- doża.
DRUG ABUSE Methadone
Methadone
Not studied, no interaction expected.
Ma kienx studjat, l- ebda effett mhu mistenni
CELSENTRI 300 mg twice daily and methadone can be coadministered without dose adjustment.
CELSENTRI 300 mg darbtejn kulljum u methadone jistgħu jiġu mgħotija flimkien mingħajr ebda aġġustament tad- doża.
Buprenorphine LIPID LOWERING MEDICINAL PRODUCTS
Buprenorphine AĠENTI LI JNAQQSU IL - LIPIDI FID- DEMM
CELSENTRI 300 mg twice daily and buprenorphine can be coadministered without dose adjustment.
CELSENTRI 300 mg darbtejn kulljum u buprenorphine jistgħu jiġu mgħotija flimkien mingħajr ebda aġġustament tad- doża.
Statins
Ma kienx studjat, l- ebda effett Statins KONTRAĊETTIVI ORALI
Not studied, no interaction expected.
mhu mistenni
CELSENTRI 300 mg twice daily and statins can be coadministered without dose adjustment.
CELSENTRI 300 mg darbtejn kulljum u statins jistgħu jiġu mgħotija flimkien mingħajr ebda aġġustament tad- doża.
ORAL CONTRACEPTIVES Ethinylestradiol 30 mcg QD (maraviroc 100 mg BID)
Ethinylestradiol 30 mcg QD (maraviroc 100 mg BID)
AUCt: ↔ 1.00 (0.79, 1.20) Ethinylestradiol.
AUCt: ↔ 1. 00 (0. 79, 1. 20) Ethinylestradiol.
Cmax: ↔ 0.99 (0.61, 1.32) Maraviroc concentrations not measured, no interaction expected.
Cmax: ↔ 0. 99 (0. 61, 1. 32) Il- konċetrazzjonijiet ta ’
CELSENTRI 300 mg twice daily. and ethinylestradiol can be co- administered without dose adjustment.
CELSENTRI 300 mg darbtejn kulljum u ethinylestradiol jistgħu jiġu mgħotija flimkien mingħajr ebda aġġustament tad- doża.
Levonorgestrel 150mcg QD (maraviroc 100 mg BID) SEDATIVES
Maraviroc ma kienux imkejjla, l - ebda effett mhu mistenni Levonorgestrel 150mcg QD (maraviroc 100 mg BID) SEDATIVI Benzodiazepines
AUC12: ↔ 0.99 (0.70, 1.31) Levonorgestrel.
AUC12: ↔ 0. 99 (0. 70, 1. 31) Levonorgestrel.
Cmax: ↔ 1.01 (0.66, 1.51) Maraviroc concentrations not measured, no interaction expected.
Cmax: ↔ 1. 01 (0. 66, 1. 51) Il- konċetrazzjonijiet ta ’ Maraviroc ma kienux imkejjla, l - ebda effett mhu mistenni
CELSENTRI 300 mg twice daily and levonorgestrel can be co- administered without dose adjustment.
CELSENTRI 300 mg darbtejn kulljum u levonorgestrel jistgħu jiġu mgħotija flimkien mingħajr ebda aġġustament tad- doża.
Midazolam 7.5 mg Single Dose (maraviroc 300 mg BID) HERBAL PRODUCTS
Midazolam 7. 5 mg Dose waħda (maraviroc 300 mg BID) PRODOTTI ERBALI
AUC: ↔ 1.18 (0.68, 1.77) Midazolam.
AUC: ↔ 1. 18 (0. 68, 1. 77) Midazolam.
Cmax: ↔ 1.21 (0.51, 2.97) Maraviroc concentrations not measured, no interaction expected.
Cmax: ↔ 1. 21 (0. 51, 2. 97) Il- konċetrazzjonijiet ta ’ Maraviroc ma kienux imkejjla, l - ebda effett mhu mistenni Il- konċentrazzjoni ta ’ maraviroc
CELSENTRI 300 mg twice daily and midazolam can be co- administered without dose adjustment.
CELSENTRI 300 mg darbtejn kulljum u midazolam jistgħu jiġu mgħotija flimkien mingħajr ebda aġġustament tad- doża.
Coadministration of maraviroc with St.
mistennija li tonqos sostanzjalment meta dan ikun mgħoti flimkien ma St.