qanastek/EMEA-V3 huggingface dataset:
There was a 37% decrease in etravirine exposure in the presence of darunavir/ritonavir and no relevant change in exposure to darunavir.
Kien hemm tnaqqis ta ’ 37% fl- esponiment ta ’ etravirine fil- preżenza ta ’ darunavir/ ritonavir u ma kien hemm l- ebda bidla rilevanti fl- esponiment ta ’ darunavir.
Therefore, PREZISTA co-administered with low dose ritonavir can be co-administered with etravirine 200 mg b.i.d. without dose adjustments.
Għalhekk, PREZISTA mogħti flimkien ma ’ doża baxxa ta ’ ritonavir jista ’ jingħata flimkien ma ’ etravirine 200 mg b. i. d. mingħajr l- ebda aġġustament tad- dożi.
Darunavir/ritonavir increases the plasma concentrations of nevirapine as a result of CYP3A4 inhibition.
Darunavir/ ritonavir iżidu l- konċentrazzjonijiet ta ’ nevirapine fil- plażma minħabba impediment ta ’ CYP3A4.
Since this difference is not considered to be clinically relevant, the combination of PREZISTA co-administered with 100 mg ritonavir and nevirapine can be used without dose adjustments.
Minħabba li din id- differenza m’ hijiex meqjusa bħala klinkament rilevanti, PREZISTA flimkien ma ’ 100 mg ritonavir jistgħu jiġu amministrati ma ’ nevirapine mingħajr aġġustament tad- dożi.
Ritonavir effect on MDR-1 transport in renal tubuli has been a proposed mechanism for increased plasma concentrations of tenofovir.
L- effett ta ’ ritonavir fuq it- trasport MDR- 1 fit- tubuli renali kien il- mekkanizmu propost għaż- żieda tal- konċentrazzjonijiet ta ’ tenofovir fil- plażma.
Monitoring of renal function may be indicated when PREZISTA co-administered with 100 mg ritonavir is given in combination with tenofovir, particularly in patients with underlying systemic or renal disease, or in patients taking nephrotoxic agents.
Monitoraġġ tal- funzjoni renali jista ’ jkun indikat meta PREZISTA flimkien ma 100 mg ritonavir ikunu amministrati flimkien ma tenofovir, b’ mod partikolari f’ dawk il- pazjenti li diġà għandhom mard sistemiku jew renali jew f’ dawk il- pazjenti li qed jieħdu mediċini nefrotossiċi.
Based on the different elimination pathways of the other NRTIs zidovudine, zalcitabine, emtricitabine, stavudine, lamivudine, that are primarily renally excreted, and abacavir for which metabolism is not mediated by CYP450, no interactions are expected for these medicinal compounds and PREZISTA co-administered with 100 mg ritonavir.
Meta bbazati fuq il- passaġġi differenti ta ’ eliminazzjoni ta ’ l- NRTI l- oħra zidovudine, zalcitabine, emtricitabine, stavudine, lamivudine, li huma primarjament imneħħija permezz tal- kliewi, u abacavir li l- metaboliżmu tagħhom mhux medjat b’ CYP450, ma huma mistennija l- ebda interazzjonijiet bejn dawn il- prodotti mediċinali u PREZISTA amministrata flimkien ma ’ 100 mg ritonavir. ↔
Didanosine ↔ NA Darunavir ↔ ↔ Didanosine was administered on an empty stomach 2 hours prior to administration of darunavir/ritonavir.
Didanosine NA ↔ ↔ Darunavir Didanosine kien amministrat fuq stonku vojt sagħtejn qabel l- amministrazzjoni ta ’ darunavir/ ritonavir.
Systemic exposure to darunavir co-administered with low dose ritonavir, with or without didanosine was comparable.
L- esponiment sistemiku għal darunavir kien komparabbli meta ġie amministrat flimkien ma ’ doża baxxa ta ’ ritonavir, kemm b’ didanosine kif ukoll mingħajru.
The combination of PREZISTA co-administered with 100 mg ritonavir and didanosine can be used without dose adjustments.
L- użu flimkien ta ’ PREZISTA u 100 mg ritonavir flimkien ma ’ didanosine jista ’ jsir mingħajr aġġustamenti tad- doża. ↑ 305%
Maraviroc ↑ 305% ND Darunavir ↔ ND The maraviroc dose should be 150 mg twice daily when co-administered with PREZISTA with low dose ritonavir.
Maraviroc ND ↔ Darunavir ND Id- doża ta ’ maraviroc għandha tkun ta ’ 150 mg darbtejn kuljum meta tkun mogħtija flimkien ma ’ PREZISTA mogħti flimkien ma ’ doża baxxa ta ’ ritonvir.
Darunavir/ritonavir concentrations were consistent with historical data.
Il - konċentrazzjonijiet ta ’ darunavir/ ritonavir kienu jaqblu ma ’ data storika.
Interactions – Darunavir/ritonavir with Non-antiretroviral co-administered Medicinal Products Co-administered
Interazzjonijiet – Darunavir/ ritonavir amministrat flimkien ma ’ Prodotti Mediċinali mhux Antiretrovirali Prodott Mediċinali
Medicinal
Do
Antiarrhythmics
Flimkien Miegħu
Digoxin
Flimkien Miegħu (mg) Antiarritmiċi ↑ 60% Digoxin
0.4 mg single dose
doża waħda ta ’
600/100
Digoxin doża waħda ta ’ 600/ 100 b. i. d.
Darunavir/ritonavir increases the plasma concentrations of digoxin.
0. 4 mg Darunavir/ ritonavir iżidu l- konċentrazzjonijiet ta ’ digoxin fil- plażma.
Inhibition of Pgp may be a likely explanation.
Impediment ta ’ Pgp x’ aktarx jispjega dan.
Given that digoxin has as a narrow therapeutic index, it is recommended that the lowest possible dose of digoxin should initially be prescribed in case digoxin is given to patients on darunavir/ritonavir therapy.
Minħabba li digoxin għandu indiċi terapewtiku strett, huwa rrakkomandat li fil- bidu tat- terapija l- aktar doża baxxa possibbli ta ’ digoxin għandha tiġi preskritta f’ każ li digoxin jingħata lill- pazjenti li qed jieħdu trattament b’ darunavir/ ritonavir.
The digoxin dose should be carefully titrated to obtain the desired clinical effect while assessing the overall clinical state of the subject.
Id- doża ta ’ digoxin għandha tiġi ddożata b’ attenzjoni biex jinkiseb l- effett kliniku mixtieq filwaqt li jkun eżaminat l- istat kliniku totali tal- pazjent.
Antibiotics Clarithromycin
Antibijotiċi Clarithromycin
400/100 b.i.d.# Clarithromycin
Clarithromycin Darunavir
↔
57% ↑ 174% ↔ ↔
7 Darunavir/ritonavir increases the plasma concentrations of clarithromycin as a result of CYP3A4 inhibition and possible Pgp inhibition.
Darunavir/ ritonavir iżidu l- konċentrazzjonijiet ta ’ clarithromycin fil- plażma minħabba impediment ta ’ CYP3A4 u possibbilment impedimnet ta ’ Ppg.
Concentrations of the metabolite 14-OH-clarithromycin were not detectable.
Konċentrazzjonijiet tas - sustanza iffurmata mill- metaboliżmu 14- OH- clarithromycin ma ġewx osservati.
Caution is warranted and clinical monitoring is recommended.
Hija mistħoqqa attenzjoni u huwa rrakkomandat monitoraġġ kliniku.
For patients with renal impairment, a dose reduction of clarithromycin should be considered.
Għall- pazjenti b’ indeboliment renali għandu jiġi kkunsidrat tnaqqis fid- doża ta ’ clarithromycin.
Anticoagulant Warfarin Anticonvulsants
Antikoagulanti Warfarin Antikonvulżivi
Warfarin concentrations may be affected when co-administered with darunavir with ritonavir.
Il- konċentrazzjonijiet ta ’ warfarin jistgħu jiġu affettwati meta dan jiġi amministrat ma ’ darunavir flimkien ma ’ ritonavir.
The international normalised ratio (INR) should be monitored when warfarin is combined with PREZISTA co-administered with 100 mg ritonavir.
Il- proporzjon internazzjonali normalizzat (INR) għandu jiġi segwit meta l- warfarin jingħata ma ’ PREZISTA amministrata flimkien ma ’ 100 mg ritonavir.
Phenobarbital and phenytoin are inducers of CYP450 enzymes.
Phenobarbital u phenytoin huma indutturi ta ’ l- enzimi CYP450.
PREZISTA co-administered with 100 mg ritonavir should not be used in combination with these medicines, as co-administration may cause significant decreases in darunavir plasma concentrations.
PREZISTA amministrat flimkien ma ’ 100 mg ritonavir m’ għandux jingħata ma ’ dawn il- mediċini minħabba li l - amministrazzjoni tagħhom flimkien tista ’ tikkawża tnaqqis sinifikanti fil - konċentrazzjonijiet ta’ darunavir fil- plażma.
Carbamazepine Antifungals
Carbamazepine Antifungali
Carbamazepine ↑ 45% ↑ 54% Darunavir ↔ ↔ Exposure to darunavir, co-administered with ritonavir, was unaffected by carbamazepine.
Carbamazepine ↔ ↔ Darunavir Espożizzjoni għal darunavir, amministrat flimkien ma ’ ritonavir, ma ġiex affettwat minn carbamazepine.
Ritonavir exposure (AUC12h) was decreased by 49%.
Espożizzjoni għal ritonavir (AUC12h) ġie mnaqqas b’ 49%.
For carbamazepine, AUC12h was increased by 45%.
Għal carbamazepine, AUC12h ġie miżjud b’ 45%.
No dose adjustment for PREZISTA/rtv is recommended.
Mhux irrakkomandat aġġustament fid- doża għal PREZISTA/ rtv.
If there is a need to combine PREZISTA/rtv and carbamazepine, patients should be monitored for potential carbamazepine-related adverse events.
Jekk hemm ħtieġa li jiġu kombinati PREZISTA/ rtv u carbamazepine, pazjenti għandhom jiġu monitorati għall- potenzjal ta ’ effetti avversi relatati ma ’ carbamazepine.
Carbamazepine concentrations should be monitored and its dose should be titrated for adequate response.
Għandhom jiġu monitorati l- konċentrazzjonijiet ta ’ carbamazepine u jrid isir titrazzjoni tad- doża għal rispons adegwat.
Based upon the findings, the carbamazepine dose may need to be reduced by 25% to 50% in the presence of PREZISTA/rtv.
Fuq bażi tas- sejbiet, jista ’ jkun hemm bżonn ta ’ tnaqqis fid- doża ta ’ carbamazepine b’ 25% sa 50% fil - preżenza ta ’ PREZISTA/ rtv.
The combined use of voriconazole with darunavir co-administered with 100 mg ritonavir has not been studied.
L- użu ta ’ voriconazole flimkien ma ’ darunavir amministrat ma ’ 100 mg ritonavir ma ġiex studjat.
Voriconazole is metabolised by cytochrome P450 isoenzymes, CYP2C19, CYP2C9 and CYP3A4.
Voriconazole huwa metabolizzat pemezz ta ’ l- isoenzimi ta ’ cytochrome P450, CYP2C19, CYP2C9 u CYP3A4.
Ritonavir, which can induce some of these isoenzymes, may decrease voriconazole plasma concentrations.
Ritonavir, li jista ’ jinduċi xi wħud minn dawn l - isoenzimi, jista ’ jnaqqas il- konċentrazzjonijiet ta ’ voriconazole fil- plażma.
Voriconazole should not be co-administered with PREZISTA with 100 mg ritonavir unless an assessment of the benefit/risk ratio justifies the use of voriconazole.
Voriconazole m’ għandux jingħata ma ’ PREZISTA flimkien ma ’ 100 mg ritonavir sakemm eżami tal - proporzjon tar- riskju mqabbel mal- benefiċċju ma jiġġustifikax l- użu ta ’ voriconazole.
400/100 b.i.d.# Ketoconazole
Ketoconazole Darunavir
Ketoconazole is a potent inhibitor as well as substrate of CYP3A4.
8 Ketoconazole huwa impeditur potenti kif ukoll sustrat ta ’ CYP3A4.
When co-administration is required the daily dose of ketoconazole should not exceed 200 mg.
Meta l- amministrazzjoni tagħhom flimkien hija meħtieġa, id- doża ta ’ kuljum ta ’ ketoconazole m’ għandiex taqbeż 200 mg.
Itraconazole, like ketoconazole, is a potent inhibitor as well as substrate of CYP3A4.
Itraconazole, bħal ketoconazole, huwa impeditur potenti kif ukoll sustrat ta ’ CYP3A4.
Concomitant systemic use of itraconazole and darunavir co-administered with 100 mg ritonavir may increase plasma concentrations of darunavir.
L - użu sistemiku konkomitanti ta ’ itraconazle u darunavir amministrat flimkien ma 100 mg ritonavir jista ’ jżid il- konċentrazzjonijiet ta ’ darunavir fil- plażma.
Simultaneously, plasma concentrations of itraconazole may be increased by darunavir co-administered with 100 mg ritonavir.
Fl- istess waqt, il - konċentrazzjonijiet ta ’ itraconazole fil- plażma jistgħu jiżdiedu permezz ta ’ darunavir amministrat flimkien ma100 mg ritonavir.
When co-administration is required the daily dose of itraconazole should not exceed 200 mg.
Meta l- amministrazzjoni tagħhom flimkien hija meħtieġa id- doża ta ’ itraconazole m’ għandiex taqbeż 200 mg kuljum.
Clotrimazole
Clotrimazole
Concomitant systemic use of clotrimazole and darunavir co-administered with 100 mg ritonavir may increase plasma concentrations of darunavir.
L- użu sistemiku konkomitanti ta ’ clotrimazole u darunavir amministrat flimkien ma ’ 100 mg ritonavir jista ’ jżid il- konċentrazzjonijiet ta ’ darunavir fil- plażma.
This was confirmed using a population pharmacokinetic model.
Dan ġie kkonfermat permezz ta ’ użu ta ’ mudell farmakokinetiku tal- popolazzjoni.
The increase in the median darunavir AUC24h value for the patients taking clotrimazole from the overall median was 33%.
Iż- żieda fil - valur medjan ta ’ darunavir AUC24h mill- medjan totali, għall- pazjenti li qed jieħdu clotrimazole, kien ta ’ 33%.
Caution is warranted and clinical monitoring is recommended, when co-administration of clotrimazole is required.
Hija mistħoqqa attenzjoni u huwa rrakkomandat monitoraġġ kliniku meta jkun hemm bżonn ta ’ amministrazzjoni flimkien ma ’ clotrimazole.
Calcium channel blockers Felodipine Nifedipine Nicardipine
Mediċini blokkaturi tal- kanali tal- kalċju Felodipine Nifedipine Nicardipine
Darunavir and ritonavir inhibit CYP3A4 and as a result can be expected to increase the plasma concentrations of calcium channel antagonists, which are CYP3A4 substrates.
Darunavir u ritonavir jimpedixxu CYP3A4 u b’ riżultat ta ’ dan huma mistennija li jżidu l- konċentrazzjonijiet ta ’ antagonisti tal- kanali tal- kalċju fil- plażma li huma sustrati ta ’ CYP3A4.
Clinical monitoring of therapeutic and adverse effects is recommended when these medicines are concomitantly administered with PREZISTA with 100 mg ritonavir.
Hija mistħoqqa attenzjoni u huwa rrakkomandat monitoraġġ kliniku meta dawn il- mediċini jingħataw konkomitament ma ’ PREZISTA flimkien ma 100 mg ritonavir.
8 Lovastatin Simvastatin
Impedituri ta ’ HMG Co- A Reductase Lovastatin u simvastatin, li huma dipendenti ħafna fuq metaboliżmu ta ’ CYP3A4 huma Lovastatin Simvastatin
Lovastatin and simvastatin, which are highly dependent on CYP3A4 metabolism are expected to have markedly increased plasma concentrations when co-administered with darunavir co-administered with 100 mg ritonavir.
mistennija li jkollhom konċentrazzjonijiet għolja fil- plażma meta jiġu amministrati flimkien ma ’ darunavir mogħti ma ’ 100 mg ritonavir.
This may cause myopathy, including rhabdomyolysis.
Dan jista ’ jikkawża majopatija, inkluż rabdomajoliżi.
Concomitant use of PREZISTA co-administered with 100 mg ritonavir with lovastatin and simvastatin is therefore contraindicated (see section 4.3).
300/ 100 b. i. d. #
300/100 b.i.d.# Atorvastatin 3-4
Atorvastatin 3– 4
3-4
3– 4
times ↑
darbiet ↑ darbiet ↑
The results of this interaction trial show that atorvastatin (10 mg q.d.) in combination with darunavir/ritonavir (300/100 mg b.i.d.) provides an exposure to atorvastatin, which is only 15% lower than that obtained with (40 mg q.d.) atorvastatin alone.
Ir- riżultati ta ’ din il- prova ta ’ interazzjoni juru li atorvastatin (10 mg q. d.) flimkien ma ’ darunavir/ ritonavir (300/ 100 mg b. i. d.) jipprovdi esponiment għal atorvastatin li huwa 15% biss anqas minn dak li jinkiseb b ’ (40 mg q. d.) atorvastatin waħdu.
When administration of atorvastatin and PREZISTA co-administered with 100 mg ritonavir is desired, it is recommended to start with an atorvastatin dose of 10 mg q.d.
Meta l - amministrazzjoni ta ’ atorvastatin u PREZISTA amministrat flimkien ma ’ 100 mg ritonavir hija mixtieqa, huwa rrakkommandat li tibda b’ doża ta ’ atorvastatin ta ’ 10 mg q. d.
A gradual dose increase of atorvastatin may be tailored to the clinical response.
Żieda bil- mod il- mod fid- doża tista ’ tiġi addattata għar- rispons kliniku.
40 mg single dose
Doża waħda ta ’
Pravastatin 40 mg single dose 600/100 b.i.d.
Pravastatin Doża waħda ta ’ 600/ 100 b. i. d.
times ↑ Darunavir/ritonavir did not increase exposure to a single dose of pravastatin in most subjects but up to 5-fold in a limited subset of subjects.
drabi ↑ 40 mg Darunavir/ ritonavir ma żiedux l- esponiment għal doża waħda ta ’ pravastatin f’ ħafna mill- pazjenti iżda kien hemm żjieda sa 5 darbiet aktar fi grupp limitat ta ’ pazjenti.
When administration of pravastatin and PREZISTA co-administered with 100 mg ritonavir is required, it is recommended to start with the lowest possible dose of pravastatin and titrate it up to the desired clinical effect while monitoring for safety.
Kontraċettivi ormonali
Hormonal contraceptive Ethinylestradiol Norethindrone
Ethinylestradiol Norethindrone
Ethinylestradiol Norethindrone
Ethinylestradiol Norethindrone
Alternative or additional contraceptive measures are recommended when oestrogen-based contraceptives are co-administered with PREZISTA and 100 mg ritonavir.
Miżuri kontraċettivi alternattivi jew addizzjonali huma rrakkomandati meta kontraċettivi b’ bażi ta ’ estroġenu jingħataw flimkiem ma ’ PREZISTA u 100 mg ritonavir.
Patients using oestrogens as hormone replacement therapy should be clinically monitored for signs of oestrogen deficiency.
Immunosoppressanti
Immunosupressants Cyclosporine Tacrolimus Sirolimus
9 Cyclosporine Tacrolimus Sirolimus
Exposure to cyclosporine, tacrolimus, or sirolimus will be increased when co-administered with PREZISTA co-administered with 100 mg ritonavir.
Esponiment għal cyclosporine, tacrolimus, jew sirolimus jiżdied meta dawn jiġu amministrati flimkien ma ’ PREZISTA mogħti flimkien ma’ 100 mg ritonavir.
Therapeutic drug monitoring of the immunosuppressive agent must be done when co-administration occurs.
Monitoraġġ terapewtiku mediċinali tal- prodott immunosoppressiv għandu jsir meta jkun hemm amministrazzjoni tagħhom flimkien.
H2-receptor antagonists and proton pump inhibitors Ranitidine
Antagonisti tar- riċetturi H2 u impedituri tal- pompa tal- proton Ranitidine
Based on these results, PREZISTA co-administered with 100 mg ritonavir can be co-administered with H2-receptor antagonists without dose adjustments.
Ibbażat fuq dawn ir- riżultati, PREZISTA amministrat flimkien ma ’ 100 mg ritonavir jista ’ jingħata flimkien ma ’ antagonisti tar- riċetturi H2 mingħajr aġġustament tad- doża.
Omeprazole
Omeprazole
Based on these results, PREZISTA co-administered with 100 mg ritonavir can be co-administered with proton pump inhibitors without dose adjustments.
Opjojdi
Opiods Methadone
Methadone
55-150 q.d.
55 - 150 q. d.
↓ 15%
R- methadone
(dosed for 7 days) Based on pharmacokinetic and clinical findings, no adjustment of methadone dosage is required when initiating co-administration with PREZISTA/ritonavir.
(doża mogħtija għall- 7 ijiem) Fuq bażi ta ’ sejbiet kliniċi u farmakokinetiċi, id- doża ta ’ methadone m’ hemmx bżonn tiġi aġġustata meta dan jibda jingħata flimkien ma ’ PREZISTA/ ritonavir.
However, increased methadone dose may be necessary when concomitantly administered for a longer period of time due to induction of metabolism by ritonavir.
Madankollu, jista ’ jkun hemm bżonn doża ogħla ta ’ methadone meta l- amministrazzjoni konkomitanti tieħu fit- tul minħabba induzzjoni tal- metabolizmu minn ritonavir.
Therefore, clinical monitoring is recommended, as maintenance therapy may need to be adjusted in some patients.
Għalhekk monitoraġġ kliniku huwa rrakomandat minħabba li l- kura ta ’ manteniment jista ’ jkollha bżonn tkun aġġustata f’ xi pazjenti.
PDE-5 inhibitors Sildenafil Vardenafil Tadalafil Rifamycines
Impedituri PDE- 5 Sildenafil Vardenafil Tadalafil Rifamycines
In an interaction study a comparable systemic exposure to sildenafil was observed for a single intake of 100 mg sildenafil alone and a single intake of 25 mg sildenafil co-administered with darunavir/ritonavir (400/100 mg b.i.d.).
Fi studji ta ’ interazzjoni esponiment sistemiku komparabbli għal sildenafil kien osservat għat- teħid uniku ta ’ 100 mg sildenafil waħdu u teħid uniku ta ’ 25 mg sildenafil amministrat flimkien ma ’ darunavir/ ritonavir (400/ 100 mg b. i. d.).
Concomitant use of PDE-5 inhibitors with PREZISTA co-administered with 100 mg ritonavir should be done with caution.
L- użu konkomitanti ta ’ impedituri PDE- 5 ma ’ PREZISTA amministrat flimkien ma ’ 100 mg ritonavir għandu jsir b’ attenzjoni.
If concomitant use of PREZISTA co-administered with 100 mg ritonavir with sildenafil, vardenafil, or tadalafil is indicated, sildenafil at a single dose not exceeding 25 mg in 48 hours, vardenafil at a single dose not exceeding 2.5 mg dose in 72 hours or tadalafil at a single dose not exceeding 10 mg dose in 72 hours is recommended.
Jekk ikun indikat l- użu konkomitanti ta ’ PREZISTA amministrat flimkien ma’ 100 mg ritonavir flimkien ma ’ sildenafil, vardenafil, jew tadalafil hija rrakommandata doża waħda ta ’ sildenafil li ma ’ taqbiżx il- 25 mg f’ 48 siegħa, doża waħda ta ’ vardenafil li ma taqbiżx il- 2. 5 mg f ’ 72 siegħa jew doża waħda ta ’ tadalafil li ma ’ taqbiżx 10 mg f’ 72 siegħa.
9 Rifampicin
Rifampicin
Rifampicin is a strong CYP3A4 inducer and has been shown to cause profound decreases in concentrations of other protease inhibitors, which can result in virological failure and resistance development.
Rifampicin huwa induttur qawwi ta ’ CYP 3A4 u ntwera li jikkaġuna tnaqqis profond fil - konċentrazzjonijiet ta ’ impedituri oħra ta ’ protease li jista ’ jirriżulta f’ indeboliment viroloġiku u żvilupp ta ’ reżistenza.
The combination of rifampicin and PREZISTA with concomitant low dose ritonavir is contraindicated (see section 4.3).
Il- kombinazzjoni ta ’ rifampicin ma ’ PREZISTA flimkien ma ’ doża baxxa ta ’ ritonavir hija kontra- indikata (ara sezzjoni 4. 3).
Rifabutin* 1.6 times ↑
Rifabutin * 1. 6 ND darbiet ↑ ↑ 53% ↑ 68% Darunavir
* sum of active moieties of rifabutin (parent drug + 25-O-desacetyl metabolite) A dosage reduction of rifabutin by 75% of the usual dose of 300 mg/day [i.e. rifabutin 150 mg q.o.d.
10 * l- għadd tan- nofsijiet attivi ta ’ rifabutin (mediċina oriġinali + metabolit 25- O- desacetyl) Tnaqqis fid- doża ta ’ rifabutin b’ 75% mid- doża tas- soltu ta ’ 300 mg/ kuljum [i. e. rifabutin 150 mg q. o. d.
(once every other day)] and increased monitoring for rifabutin related adverse events is warranted in patients receiving the combination.
(ġurnata iva u oħra le)] u żieda fil- monitoraġġ għal każijiet avversi relatati ma ’ rifabutin hija meħtieġa f’ pazjenti li qed jirċievu ż- żewġ mediċini flimkien.
In case of safety issues, a further increase of the dosing interval for rifabutin and/or monitoring of rifabutin levels should be considered.
Fil- każ ta ’ kwistjonijiet ta ’ sigurtà, aktar tul fl- intervall bejn id- dożi ta ’ rifabutin u/ jew monitoraġġ għal- livelli ta ’ rifabutin għandu jiġi kkunsidrat.
Consideration should be given to official guidance on the appropriate treatment of tuberculosis in HIV infected patients.
Għandhom jiġu kkunsidrati l- gwidi uffiċjali dwar il- kura xierqa tat- tuberkulożi f’ pazjenti infettati bl- HIV.
Rifabutin is an inducer and substrate of CYP3A4.
Rifabutin huwa induttur u substrat għal CYP3A4.
An increase of systemic exposure to darunavir was observed when PREZISTA co-administered with 100 mg ritonavir was co-administered with rifabutin [150 mg q.o.d.
Żieda fl- esponiment sistemiku għal darunavir kienet osservata meta PREZISTA mogħti flimkien ma ’ 100 mg ritonavir ingħata flimkien ma ’ rifabutin [150 mg q. o. d.
(once every other day)].
(ġurnatia iva u oħra le)].
Based upon the safety profile of PREZISTA/ritonavir, this increase in darunavir exposure in the presence of rifabutin does not warrant a dose adjustment for PREZISTA/ritonavir.
Fuq bażi tal - profil ta ’ sigurtà ta ’ PREZISTA/ ritonavir, din iż- żieda fl- esponiment ta ’ darunavir fil - preżenza ta ’ rifabutin ma tinħtieġx aġġustament fid- doża ta ’ PREZISTA/ ritonavir.
The interaction trial showed a comparable daily systemic exposure for rifabutin between treatment at 300 mg q.d.
Il - pova ta ’ prodotti mediċinali li ma jaqblux mal- prodott uriet esponiment sistemiku kuljum għal rifabutin kumparabbli bejn kura bi 300 mg q. d.
(once daily) alone and 150 mg q.o.d.
(darba kuljum) waħdu u 150 mg q. o. d.
(once every other day) in combination with PREZISTA/ritonavir (600/100 mg b.i.d.) with an about 10-fold increase in the daily exposure to the active metabolite 25-O-desacetylrifabutin.
(ġurnata iva u oħra le) flimkien ma ’ PREZISTA/ ritonavir (600/ 100 mg b. i. d.) b’ madwar żieda ta ’ 10 darbiet aktar fl- esponiment ta ’ kuljum għall- metabolit attiv 25- O- desacetylrifabutin.
Furthermore, AUC of the sum of active moieties of rifabutin (parent drug + 25-O-desacetyl metabolite) was increased 1.6-fold, while Cmax remained comparable.
Barra minn hekk, l- AUC tal- għadd tan- nofsijiet attivi ta ’ rifabutin (mediċina oriġinali + il- metabolit 25- O- desacetyl) żdiedet b’ 1. 6 darbiet aktar, filwaqt li s- Cmax baqgħet kumparabbli.
Data on comparison with a 150 mg q.d.
Hemm nuqqas ta ’ dejta dwar tqabbil ma ’ doża ta ’ riferenza ta ’ 150 mg q. d.
(once daily) reference dose is lacking.
(darba kuljum).
Sedatives/Hypnotics Parenteral midazolam
Sedattivi/ Ipnotiċi Midazolam parenterali
Midazolam is extensively metabolised by CYP3A4.
Midazolam huwa mmetabolizzat b’ mod estensiv minn CYP3A4.
Co-administration with PREZISTA/ritonavir may cause a large increase in the concentration of this benzodiazepine.
L- amministrazzjoni tiegħu flimkien ma ’ PREZISTA/ ritonavir tista ’ tikkawża żieda kbira fil- konċentrazzjoni ta ’ dan il- benzodiazepine.
No drug interaction study has been performed for the co-administration of PREZISTA/ritonavir with benzodiazepines.
Ma sar l- ebda studju dwar l- amministrazzjoni ta ’ PREZISTA/ ritonavir mal- benzodiazepines.
Based on data for other CYP3A4 inhibitors, plasma concentrations of midazolam are expected to be significantly higher when midazolam is given orally.
Ibbażat fuq tagħrif ta ’ impedituri ta ’ CYP3A4 oħrajn, il- konċentrazzjonijiet ta ’ midazolam fil- plażma huma mistennija li jkunu sinifikament ogħla meta midazolam jingħata mill- ħalq.
Therefore PREZISTA/ritonavir should not be co-administered with orally administered midazolam (see section 4.3), whereas caution should be used with co-administration of PREZISTA/ritonavir and parenteral midazolam.
Għaldaqstant PREZISTA/ ritonavir m’ għandhomx jiġu amministrati flimkien ma ’ midazolam mogħti mill- ħalq (ara sezzjoni 4. 3), filwaqt li PREZISTA/ ritonavir flimkien ma ’ midazolam parenterali għandom jingħataw b’ attenzjoni.
Data from concomitant use of parenteral midazolam with other protease inhibitors suggest a possible 3-4 fold increase in midazolam plasma levels.
Tagħrif minn użu konkomitanti ta ’ midazolam parenterali ma ’ impedituri tal- protease oħra, jissuġġerixxu żieda ta ’ bejn 3 sa 4 darbiet aktar midazolam fil- plażma.
If PREZISTA/ritonavir is co-administered with parenteral midazolam, it should be done in an intensive care unit (ICU) or similar setting, which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation.
Jekk PREZISTA/ ritonavir jingħata flimkien ma ’ midazolam parenterali, dan għandu jsir f’ qasam tal- kura intensiva (ICU) jew post jixbħu li jiżgura monitoraġġ kliniku mill- qrib u immaniġġar mediku xieraq f’ każ ta ’ depressjoni respiratorja u/ jew sedazzjoni fit- tul.
Dosage adjustment for midazolam should be considered, especially if more than a single dose of midazolam is administered.
Aġġustament tad- doża għandha tiġi kkunsidrata għall- midazolam speċjalment jekk tiġi mogħtija aktar minn doża waħda ta ’ midazolam.
Selective Serotonin Reuptake Inhibitors (SSRIs) Paroxetine
Impedituri tar- Riassorbiment Selettiv tas- Serotonin (SSRIs) Paroxetine
400/100 b.i.d.# Paroxetine
Paroxetine Darunavir
↓ 37%
39% ↓ 37% ↔ ↔
Darunavir
400/ 100 b. i. d. #
↔
↓ 49% ↓ 49%
If SSRIs are co-administered with PREZISTA and ritonavir, the recommended approach is a dose titration of the SSRI based on a clinical assessment of antidepressant response.
Jekk l- SSRIs jiġu amministrati flimkien ma ’ PREZISTA u ritonavir, ir - rakkomandazzjoni hija li jsir ddożar tad- doża ta’ l- SSRI ibbażat fuq stima klinika tar - rispons antidepressiv.
In addition, patients on a stable dose of sertraline or paroxetine who start treatment with PREZISTA co-administered with 100 mg ritonavir should be monitored for antidepressant response.
Flimkien ma’ dan, pazjenti fuq doża stabbli ta ’ sertraline jew paroxetine li jibdew trattament bi PREZISTA amminstrat flimkien ma 100 mg ritonavir għandhom jiġu segwiti għar- rispons antidepressiv.
Steroids
Sterojdi
10 Fluticasone propionate Budesonide
11 Fluticasone propionate Budesonide
In a clinical study where ritonavir 100 mg capsules b.i.d were co-administered with 50 µg intranasal fluticasone propionate (4 times daily) for 7 days in healthy subjects, fluticasone propionate plasma concentrations increased significantly, whereas the intrinsic cortisol levels decreased by approximately 86% (90% confidence interval 82-89%).
Fi studju kliniku fejn kapsuli ta’ ritonavir 100 mg b. i. d kienu amministrati flimkien ma ’ 50 µg fluticasone propionate amminstrat ġol- imnieħer (4 darbiet kuljum) għall- 7 ijiem f’ pazjenti b’ saħħithom, konċentrazzjonijiet ta ’ fluticasone propionate fil- plażma żdiedu sinifikament filwaqt li l- livelli intrinsiċi tal- cortisol naqsu b’ bejn wieħed u ieħor 86% (90% confidence interval 82 - 89%).
Systemic corticosteroid effects including Cushing's syndrome and adrenal suppression have been reported in patients receiving ritonavir and inhaled or intranasally administered fluticasone propionate; this could also occur with other corticosteroids metabolised via the P450 3A pathway e.g. budesonide.
Effetti akbar għandhom jiġu mistennija meta fluticasone propionate jinġibed man- nifs. Effetti sistemiċi tal- kortikosterojdi inkluż is - sindrome ta ’ Cushing u soppressjoni adrenali ġew irrappurtati f’ pazjenti li qed jirċievu ritonavir u fluticasone propionate li jinġibed man- nifs jew jiġi amministrat minn ġol - imnieħer; dan jista ’ jiġri wkoll b’ kortikosterojdi oħra mmetabolizzati minn sensiela ta ’ reazzjonijiet ta ’ P450 3A e. ż. budesonide.
Consequently, concomitant administration of PREZISTA, co-administered with 100 mg ritonavir and these glucocorticoids, is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects.
B’ konsegwenza ta ’ dan, l- amministrazzjoni konkomitanti ta ’ PREZISTA amministrat flimkien ma ’ 100 mg ritonavir u dawn il - glukokortikojdi, m’ hijiex rakkomandata sakemm il- benefiċċju potenzjali tat- trattament ma jegħlibx ir- riski ta ’ l- effetti sistemiċi tal- kortikosterojdi.
A dose reduction of the glucocorticoid should be considered with close monitoring of local and systemic effects or a switch to a glucocorticoid, which is not a substrate for CYP3A4 (e.g. beclomethasone).
Tnaqqis fid- doża tal - glukokortikojd għandu jiġi kkunsidrat b’ monitoraġġ mill- qrib ta ’ l- effetti lokali u sistemiċi jew bidla għall- glukokortikojd li ma huwiex sustrat għal CYP3A4 (e. ż. beclomethasone).
Moreover, in case of withdrawal of glucocorticoids progressive dose reduction may have to be performed over a longer period.
Fuq kollox, f’ każ li jitwaqqaf il- glukokortikojd jista ’ jkun li jkollu jsir tnaqqis progressiv tad- doża fuq medda ta ’ żmien itwal.
The effects of high fluticasone systemic exposure on ritonavir plasma levels are as yet unknown.
L- effetti ta ’ esponiment sistemiku għoli ta ’ fluticasone fuq il- livelli ta’ ritonavir fil- plażma sa issa għadu mhux magħruf.
Dexamethasone Others
Dexamethasone Oħrajn
Systemic dexamethasone induces CYP3A4 and thereby may decrease darunavir exposure.
Dexamethasone sistemiku jinduċi CYP3A4 u permezz ta ’ hekk jista ’ jnaqqas l - esponiment ta ’ darunavir.
Therefore this combination should be used with caution.
Għalhekk dawn it- tnejn flimkien għandhom jintużaw b’ attenzjoni.
John’s wort
John’ s wort
PREZISTA co-administered with 100 mg ritonavir must not be used concomitantly with products containing St John’s wort (Hypericum perforatum) because co-administration may cause significant decreases in darunavir plasma concentrations and also in ritonavir concentrations.
John’ s wort (Hypericum perforatum) minħabba li l - amministrazzjoni tagħhom flimkien tista ’ tikkawża tnaqqis sinifikanti fil - konċentrazzjonijiet ta ’ darunavir fil- plażma u anke fil- konċentrazzjonijiet ta ’ ritonavir.
This is due to the induction of metabolising enzymes by St John’s wort.
Dan minħabba l- induzzjoni ta ’ l- enzimi metabolizzaturi permezz ta ’ St.
If a patient is already taking St John’s wort, stop St John’s wort and if possible check viral levels.
Jekk pazjent diġà qed jieħu St John’ s wort, waqqaf is- St John’ s wort u jekk possibbli iċċekkja il- livelli virali.
Darunavir exposure (and also ritonavir exposure) may increase on stopping St John’s wort.
Esponiment ta ’ darunavir (u anke esponiment ta ’ ritonavir) jista ’ jkun li jżdied mal- waqfien tas- St.
The inducing effect may persist for at least 2 weeks after cessation of treatment with St John’s wort (see section 4.3).
L- effett induttiv jista ’ jippersisti għal ta ’ l- anqas ġimgħatejn wara l- waqfien mit- trattament bis- St John’ s wort (ara sezzjoni 4. 3).
Pregnancy There are no adequate and well controlled studies with darunavir in pregnant women.
Tqala M’ hemmx studji suffiċjenti u kontrollati tajjeb b’ darunavir f’ nisa tqal.
Studies in animals do not indicate direct harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3).
Studji fuq il- bhejjem ma jurux effetti ħziena diretti jew indiretti fuq it- tqala, fuq l- iżvilupp ta ’ l- embriju/ fetu, ħlas jew żvilupp wara t - twelid (ara sezzjoni 5. 3).
PREZISTA co-administered with 100 mg ritonavir should be used during pregnancy only if the potential benefit justifies the potential risk.
PREZISTA amministrat flimkien ma ’ 100 mg ritonavir għandu jintuża fit- tqala biss jekk il- benefiċċju li jista’ jkun hemm jiġġustifika ir- riskju li jista ’ jkun hemm.
Lactation It is not known whether darunavir is excreted in human milk.
Treddigħ Ma huwiex magħruf jekk darunavir jgħaddix fil- ħalib uman.
Studies in rats have demonstrated that darunavir is excreted in milk and at high levels (1,000 mg/kg/day) resulted in toxicity.
Studji fil- firien urew li darunavir jgħaddi fil- ħalib u fl- livelli għolja (1, 000 mg/ kg/ ġurnata) wassal għal tossiċità.
Because of both the potential for HIV transmission and the potential for adverse events in nursing infants, mothers should be instructed not to breast-feed under any circumstances if they are receiving PREZISTA.
Kemm minħabba l- potenzjal ta ’ trasmissjoni ta ’ l- HIV kif ukoll il- potenzjal ta ’ ġrajjiet avversi fit- trabi li qed jieħdu l- ħalib tas- sider, l - ommijiet għandhom jiġu mwissija biex ma jreddgħux fl- ebda ċikustanza jekk ikunu qed jirċievu PREZISTA.
Fertility No human data on the effect of darunavir on fertility are available.
Fertilità L- ebda tagħrif uman m’ huwa disponibbli dwar l- effett ta ’ darunavir fuq il- fertilità.
There was no effect on mating or fertility with darunavir treatment in rats (see section 5.3).
Ma kien hemm l - ebda effett bi trattament ta ’ darunavir fuq it- tgħammir jew il- fertilità fil- firien (ara sezzjoni 5. 3).
No studies on the effects of PREZISTA in combination with ritonavir on the ability to drive and use machines have been performed.
Ma saru l- ebda studji dwar l- effetti ta ’ PREZISTA flimkien ma ’ ritonavir fuq il- ħila biex issuq u tħaddem magni.
However, dizziness has been reported in some patients during treatment with regimens containing PREZISTA co-administered with 100 mg ritonavir and should be borne in mind when considering a patient’s ability to drive or operate machinery (see section 4.8).
12 b’ kors ta ’ mediċini li kien fihom PREZISTA flimkien ma ’ 100 mg ritonavir u dan għandu jinżamm fil - moħħ meta jiġi kkunsidrat jekk pazjent għandux ħila jsuq jew iħaddem magni (ara sezzjoni 4. 8).
The adverse drug reactions are derived from Phase IIb and Phase III trials, in which a total of 1,968 treatment-experienced patients initiated therapy with the recommended dose of PREZISTA 600 mg 11 with ritonavir 100 mg twice daily.Median exposure to PREZISTA/ritonavir in this group was 37.3 weeks.
L- esponiment medjan għal - PREZISTA/ ritonavir f’ dan il- grupp kien 37. 3 ġimgħat.
Thirty percent of these patients experienced at least one adverse drug reaction of at least grade 2 severity.
Tletin fil- mija ta ’ dawn il- pazjenti esperjenzaw mill- anqas reazzjoni avversa waħda għall- mediċina ta ’ mill- anqas grad 2 fil- qawwa.
The most frequent (≥ 2%) of those were diarrhoea (3.9%), hypertriglyceridaemia (3.8%), rash (2.8%), nausea (2.6%), hypercholesterolaemia (2.5%) and headache (2.0%).
L- aktar frekwenti (≥ 2%) minn dawk kienu dijarea (3. 9%), ipertrigliċeridemija (3. 8%), raxx (2. 8%) nawsja (2. 6%), iperkolesterolimja (2. 5%) u uġigħ ta ’ ras (2. 0%).
2.6% of the patients discontinued treatment due to adverse reactions.
2. 6% tal- pazjenti waqqfu t- trattament minħabba reazzjonijiet avversi.
Adverse reactions are listed by system organ class (SOC) and frequency.
Ir- reazzjonijiet avversi huma elenkati skond is- sistema tal- klassifika ta ’ l- organi (SOC) u l- frekwenza.
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
F’ kull sezzjoni ta ’ frekwenza, ir- reazzjonijiet avversi huma mniżżla skond is- serjetà tagħhom bl- aktar serji jitniżżlu l- ewwel.
Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10) and uncommon (≥ 1/1,000 to < 1/100).
Il- frekwenzi huma definiti bħala komuni ħafna (≥ 1/ 10), komuni (≥ 1/ 100 sa < 1/ 10), u mhux komuni (≥ 1 /, 000 sa < 1/ 100).
SOC Frequency category
SOC Kategorija ta ’ frekwenza
Adverse reaction* All grades
Reazzjoni avversa * Il- gradi kollha
Adverse reaction** Grade 2-4
Reazzjoni avversa ** Gradi minn 2- 4
Infections and infestations uncommon
Infezzjonijiet u infestazzjonijiet mhux komuni
Blood and lymphatic system disorders uncommon
Disturbi tad- demm u tas- sistema limfatika mhux komuni
thrombocytopenia, neutropenia, anaemia, increased eosinophil count, leukopenia
tromboċitopenija, newtropenija, anemija, żieda fl- għadd ta ’ eosinophils, lewkopenija
thrombocytopenia, neutropenia, anaemia
tromboċitopenija, newtropenija, anemija
Immune system disorders uncommon Endocrine disorders
Disturbi fis- sistema immuni mhux komuni
immune reconstitution syndrome
sindrome tar- rikostituzzjoni immuni
uncommon
lipodistrofija, (inkluż lipoipertrofija, lipodistrofija, lipoatrofija), ipertrigliserajdimja, iperkolesterolimja, iperlipidimja
hypothyroidism, increased blood thyroid stimulating hormone
ipertrigliserajdimja, iperkolesterolimja, iperlipidimja
Metabolism and nutrition disorders common
mhux komuni
lipodystrophy (including lipohypertrophy, lipodystrophy, lipoatrophy), hypertriglyceridaemia, hypercholesterolaemia, hyperlipidaemia
dijabete mellitus, gotta, anoreksja, tnaqqis fl- aptit, tnaqqis fil- piż, żieda fil- piż, ipergliċemija, reżistenza għall - insulina, tnaqqis fil- lipoproteina ta ’
hypertriglyceridaemia, hypercholesterolaemia, hyperlipidaemia
dijabete mellitus, lipodistrofija, (inkluż lipoipertrofija, lipodistrofija, lipoatrofija), gotta, anoreksja, tnaqqis fl- aptit, tnaqqis fil- piż, żieda fil- piż,
uncommon
Disturbi psikjatriċi
diabetes mellitus, gout, anorexia, decreased appetite, decreased weight, increased weight, hyperglycaemia, insulin resistance, decreased high density lipoprotein, increased appetite, polydipsia, increased blood lactate dehydrogenase
densità għolja, żieda fl- aptit, polidipsja, żieda fil- lactate dehydrogenase fid- demm
diabetes mellitus, lipodystrophy (including lipohypertrophy, lipodystrophy, lipoatrophy), gout, anorexia, decreased appetite, decreased weight, increased weight, hyperglycaemia, insulin resistance
ipergliċemija, reżistenza għall - insulina
Psychiatric disorders common
komuni
insomnia
insomnja
depression, confusional state, disorientation, anxiety, altered mood, sleep disorder, abnormal dreams, nightmare, decreased libido, restlessness
depressjoni, stat konfużjonali, diżorjentament, ansjetà, bidla fil - burdata, disturb fl- irqad, ħolm mhux normali, ħmar il- lejl, tnaqqis fil - libido, nuqqas ta ’ kwiet
depression, confusional state, disorientation, anxiety, altered mood, insomnia, sleep disorder, abnormal dreams
depressjoni, stat konfużjonali, diżorjentament, ansjetà, bidla fil - burdata, insomnja, disturb fl- irqad, ħolm mhux normali
Nervous system disorders common
Disturbi fis- sistema nervuża
headache, peripheral neuropathy, dizziness
uġigħ ta ’ ras, newropatija periferali, sturdament
uncommon Eye disorders
mhux komuni Disturbi fl- għajnejn
syncope, convulsion, lethargy, paraesthesia, hypoaesthesia, ageusia, dysgeusia, disturbance in attention, memory impairment, somnolence, sleep phase rhythm disturbance
sinkope, konvulżjoni, letarġija, paraestesija, ipoestesija, agewżja, disgewżja, disturb fl- attenzjoni, indeboliment tal- memorja, ħeddla ta ’ rqad, disturb fir- ritmu tal- fażi tal - irqad
peripheral neuropathy, dizziness, lethargy, paraesthesia, hypoaesthesia, somnolence
newropatija periferali, sturdament, letarġija, paraestesija, ipoestesija, ħeddla ta ’ rqad
12 uncommon
mhux komuni
visual disturbance, conjunctival hyperaemia, dry eye
Disturb fil- vista, iperimija konġuntivali, għajn xotta
conjunctival hyperaemia
iperimija konġuntivali
Ear and labyrinth disorders uncommon Cardiac disorders
Disturbi fil- widnejn u fis- sistema labirintika mhux komuni Disturbi fil- qalb
un common Vascular disorders
mhux komuni Disturbi vaskulari
acute myocardial infarction, myocardial infarction, angina pectoris, prolonged electrocardiogram QT, sinus bradycardia, tachycardia, palpitations
infart miokardijaku akut, infart miokardijaku, angina pectoris, QT ta ’ l- elettrokardjogram imtawwal, bradikardija tas- sinus, takikardija, palpitazzjonijiet
acute myocardial infarction, myocardial infarction, angina pectoris, prolonged electrocardiogram QT
infart miokardijaku akut, infart miokardijaku, angina pectoris, QT ta ’ l- elettrokardjogram imtawwal
hypertension, flushing
pressjoni għolja, fwawar
hypertension
pressjoni għolja
Respiratory, thoracic and mediastinal disorders uncommon
Disturbi respiratorji, toraċiċi u medjastinali mhux komuni
dyspnoea, cough, epistaxis, rhinorrhoea, throat irritation
qtugħ ta ’ nifs, sogħla, epistassi, rinoreja, irritazzjoni fil- gerżuma
dyspnoea, cough
qtugħ ta ’ nifs, sogħla
Gastrointestinal disorders very common
Disturbi gastro- intestinali komuni ħafna
diarrhoea
dijarea
vomiting, nausea, abdominal pain, increased blood amylase, dyspepsia, abdominal distension, flatulence
rimettar, tqalligħ, uġigħ fl- addome, żieda fl- amylase fid- demm, dispepsja, nefħa fl- addome, gass
vomiting, diarrhoea, nausea, abdominal pain, increased blood amylase
rimettar, dijarea, tqalligħ, uġigħ fl - addome, żieda fl- amylase fid- demm
pancreatitis, gastritis, gastrooesophageal reflux disease, aphthous stomatitis, stomatitis, retching, haematemesis, dry mouth, abdominal discomfort, constipation, increased lipase, eructation, oral dysaesthesia, cheilitis, dry lip, coated tongue
pankreatite, gastrite, mard ta ’ rifluss gastroesofagali, stomatite bl- afte, taqligħ, rimettar tad- demm, ħalq xott, nefħa fl- addome, skonfort fl- addome, stitikezza, żieda fil- lipase, tifwieq, disastesija orali, kejlite, xufftejn xotti, ilsien miksi
pancreatitis, gastritis, gastrooesophageal reflux disease, aphthous stomatitis, retching, dry mouth, abdominal distension, abdominal discomfort, flatulence, dyspepsia, constipation, increased lipase
pankreatite, gastrite, mard ta ’ rifluss gastroesofagali, stomatite bl- afte, taqligħ, ħalq xott, nefħa fl- addome, skonfort fl- addome, gass, dispepsja, stitikezza, żieda fil- lipase
Hepatobiliary disorders common
Disturbi fil- fwied u fil- marrara komuni
increased alanine aminotransferase, increased aspartate aminotransferase
żieda fl- alanine aminotransferase, żieda fl- aspartate aminotransferase
increased alanine aminotransferase
żieda fl- alanine aminotransferase
hepatitis, cytolytic hepatitis, hepatic steatosis, hepatomegaly, increased transaminase, increased blood bilirubin, increased blood alkaline phosphatase, increased gamma-glutamyltransferase
epatika, epatomegalija, żieda fit - transaminase, żieda fil- bilirubin fid - demm, żieda fl- alkaline phosphatase fid- demm, żieda fil - gamma- glutamyltransferase
hepatitis, cytolytic hepatitis, hepatic steatosis, increased transaminase, increased aspartate aminotransferase, increased blood alkaline phosphatase, increased gamma-glutamyltransferase
epatika, żieda fit- transaminase, żieda fl- aspartate aminotransferase, żieda fl - alkaline phosphatase fid- demm, żieda fil - gamma- glutamyltransferase
Skin and subcutaneous tissue disorders common
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda komuni
rash (including macular, maculopapular, papular, erythematous and pruritic rash), pruritus
raxx (inkluż makulari, makulopapulari, papulari, raxx bil - ħmura u bil- ħakk), ħakk
rash (including macular, maculopapular, papular, erythematous and pruritic rash)
raxx (inkluż makulari, makulopapulari, papulari, raxx bil - ħmura u bil- ħakk)
uncommon
14 mhux komuni
generalised rash, allergic dermatitis, face oedema, urticaria, dermatitis, eczema, erythema, hyperhidrosis, night sweats, alopecia, acne, seborrhoeic dermatitis, skin lesion, xeroderma, dry skin, nail pigmentation
raxx mifrux, dermatite allerġika, edima fil- wiċċ, urtikarja, dermatite,
generalised rash, allergic dermatitis, urticaria, pruritus, hyperhidrosis, night sweats, alopecia
raxx mifrux, dermatite allerġika, urtikarja, ħakk, iperidrosi, għaraq bil -
Musculoskeletal and connective tissue disorders uncommon
Disturbi muskolu- skeltrali u tal- connective tissue mhux komuni
myalgia, muscle spasms, muscular weakness, musculoskeletal stiffness, arthritis, arthralgia, joint stiffness, pain in extremity, osteoporosis, increased blood creatine phosphokinase
majalġja, artralġja, uġigħ fl- idejn u s - saqajn, osteoporożi, żieda fil- creatine
myalgia, arthralgia, pain in extremity, osteoporosis, increased blood creatine phosphokinase
muskolu- skelettrali, artrite, artralġja, ebusija fil- ġogi, uġigħ fl- idejn u s - saqajn, osteoporożi, żieda fil- creatine phosphokinase fid- demm
13
phosphokinase fid- demm
Renal and urinary disorders uncommon
Disturbi fil- kliewi u fis- sistema urinarja mhux komuni
acute renal failure, renal failure, nephrolithiasis, increased blood creatinine, decreased creatinine renal clearance, proteinuria, bilirubinuria, dysuria, nocturia, pollakiuria
Insuffiċjenza renali akuta, insuffiċjenza renali, nefrolitiażi, żieda fil- kreatinina fid- demm, tnaqqis fit - tneħħija renali tal- kreatinina, proteinurja, bilirubinurja, disurja, nokturja, pollakijurja
acute renal failure, renal failure, nephrolithiasis, increased blood creatinine, decreased creatinine renal clearance, proteinuria, bilirubinuria
Insuffiċjenza renali akuta, falliment tal- kliewi, nefrolitiażi, żieda fill - kreatinina fid- demm, tnaqqis fit - tneħħija renali tal- kreatinina, proteinurja, bilirubinurja
Reproductive system and breast disorders uncommon
Disturbi fis- sistema riproduttiva u fis- sider mhux komuni
erectile dysfunction, gynaecomastia
disfunzjoni tal- erezzjoni, ġinekomastja
General disorders and administration site conditions common
Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata komuni
asthenia, fatigue
astenja, għejja
fatigue
għejja
pyrexia, chest pain, peripheral oedema, malaise, chills, abnormal feeling, feeling hot, irritability, pain, xerosis
deni, uġigħ fis- sider, edima periferali, telqa ’ mingħajr sinjali ta ’ mard, tkexkix ta ’ bard, ma tħossokx normali, tħoss is- sħana, irritabbiltà, uġigħ, kserożi
pyrexia, chest pain, asthenia, peripheral oedema, malaise
deni, uġigħ fis- sider, astenja, edima periferali, telqa ’ mingħajr sinjali ta ’ mard
* Adverse events, considered at least possibly related by the investigator to PREZISTA co-administered with low dose ritonavir, occurring in more than 1 patient.
* Każijiet avversi, ikkunsidrati bħala tal- anqas possibbilment relatati mill- investigatur ma ’ PREZISTA mogħti flimkien ma ’ doża baxxa ta ’ ritonavir, li seħħew f’ aktar minn pazjent wieħed.
** Adverse events, at least grade 2 in severity and considered at least possibly related by the investigator to PREZISTA co-administered with low dose ritonavir, occurring in more than 1 patient.
** Każijiet avversi, li huma mill- anqas Grad 2 fil - qawwa u kkunsidrati bħala tal- anqas possibbilment relatati mill- investigatur ma ’ PREZISTA mogħti flimkien ma ’ doża baxxa ta ’ ritonavir, li seħħew f’ aktar minn pazjent wieħed.
In clinical trials (n=1,968), rash (all grades, at least possibly related) occurred in 5.6% of patients treated with PREZISTA.
Fi provi kliniċi (n=1, 968), raxx (il- gradi kollha, tal- anqas possibbilment relatat) seħħ f’ 5. 6% tal - pazjenti kkurati bi PREZISTA.
Rash was mostly mild to moderate, often occurring within the first four weeks of treatment and resolving with continued dosing.
Ir- raxx kien il- biċċa l- kbira ħafif sa moderat, li spiss seħħ fl- ewwel erba ’ ġimgħat ta ’ kura u fieq meta tkomplew id- dożi.
Grade 2-4 rash was reported in 2.9% of patients.
Raxx ta ’ grad 2- 4 kien irrappurtat f’ 2. 9% tal - pazjenti.
The discontinuation rate due to rash in patients using PREZISTA co-administered with 100 mg ritonavir was 0.5%.
Ir- rata ta ’ twaqqif tal- kura minħabba raxx f’ pazjenti li kienu qed jużaw PREZISTA mogħti flimkien ma ’ 100 mg ritonavir kien ta ’ 0. 5%.