qanastek/EMEA-V3 huggingface dataset:
Compared to the historical adult population receiving fosamprenavir with ritonavir 700 mg / 100 mg twice daily, a subset of five pediatric subjects ages 6 to < 24-months receiving fosamprenavir / ritonavir 45/ 7 mg/ kg twice daily demonstrated that despite an approximate 5-fold increase in fosamprenavir and ritonavir doses on a mg/ kg basis, plasma amprenavir AUC(0-τ) was approximately 48% lower, Cmax 26% lower, and Cτ 29% lower in the paediatric subjects.
Meta mqabbla ma ’ popolazzjoni adulta li fil- passat ħadu fosamprenavir ma 'ritonavir 700mg / 100mg darbtejn kuljum, grupp sekondarju ta' ħames suġġetti pedjatriċi ta ’ bejn is- 6 u < 24 xahar li ħadu fosamprenavir / ritonavir 45/ 7 mg/ kg darbtejn kuljum urew li għalkemm kien hemm żieda ta ’ bejn wieħed u ieħor 5 darbiet fid- doża ta ’ fosamprenavir u ritonavir fuq bażi ta ’
No dosing recommendations can be made for the very young (children < 2 years of age) and Telzir with ritonavir is not recommended for this patient population (see section 4.2).
Ma jistgħux isiru rakkomandazzjonijiet fuq dożaġġ fiż- żgħar ħafna (tfal < sentejn) u Telzir ma ritonavir m’ huwiex rakkomandat għal din il - popolazzjoni ta ’ pazjenti (ara sezzjoni 4. 2).
The pharmacokinetics of fosamprenavir in combination with ritonavir has not been studied in patients over 65 years of age.
Il- farmakokinetiċi ta ’ fosamprenavir ma ’ ġewx studjati f’ pazjenti li l- età tagħhom hija minn 65 sena ’ l fuq.
Patients with renal impairment have not been specifically studied.
Ma sarux studji partikolari fuq nies li għandhom indeboliment tal- kliewi.
Less than 1% of the therapeutic dose of amprenavir is excreted unchanged in the urine.
Inqas minn 1% tad- doża terapewtika ta ’ amprenavir tispiċċa fl- awrina mingħajr ma tinbidel.
Renal clearance of ritonavir is also negligible, therefore the impact of renal impairment on amprenavir and ritonavir elimination should be minimal
Anke t- tneħħija ta ’ ritonavir mill - kliewi hi żgħira ħafna; għalhekk l- impatt ta ’ l- indeboliment tal- kliewi fuq l- eliminazzjoni ta ’ amprenavir u ritonavir għandu jkun minimu.
Fosamprenavir is converted in man to amprenavir.
Fil- bniedem fosamprenavir jiġi mibdul f’ amprenavir.
The principal route of amprenavir and ritonavir elimination is hepatic metabolism.
Ir- rotta ewlenija tat- tneħħija ta ’ amprenavir u ritonavir hi l- metaboliżmu tal- fwied.
The plasma amprenavir pharmacokinetics were evaluated in a 14 day repeat-dose study in HIV-1 infected adult subjects with mild, moderate, or severe hepatic impairment receiving fosamprenavir with ritonavir compared to matched control subjects with normal hepatic function.
Il- farmakokinetiċi ta ’ amprenavir fil- plażma ġew evalwati fi studju ta ’ 14- il ġurnata b’ doża ripetuta f’ suġġetti adulti bl- infezzjoni HIV- 1 u b’ indeboliment tal- fwied ħafif, moderat jew sever li qegħdin jirċievu fosamprenavir flimkien ma ’ ritonavir u dawn ġew mqabbla ma 'suġġetti simili b’ funzjoni tal - fwied normali bħala kontroll.
In subjects with mild hepatic impairment (Child-Pugh score of 5-6), the dosage regimen of fosamprenavir 700 mg twice daily with a reduced dosing frequency of ritonavir 100 mg once daily provided slightly higher plasma amprenavir Cmax (17%), slightly higher plasma amprenavir AUC(0-12) (22%), similar plasma total amprenavir C12 values and approximately 117% higher plasma unbound amprenavir C12 values compared to subjects with normal hepatic function receiving the standard fosamprenavir / ritonavir 700 mg / 100 mg twice daily regimen.
F’ suġġetti b’ indeboliment tal- fwied ħafif (Child- Pugh score ta ’ 5- 6), is- sistema ta ’ dożaġġ ta ’ fosamprenavir 700 mg darbtejn kuljum flimkien ma ’ ritonavir 100mg bil- frekwenza tad- doża mnaqqsa għal darba kuljum waslet għal Cmax ta 'amprenavir ġol- plażma kemm kemm ogħla (17%), għal AUC (0- 12) ta ’ amprenavir ġol- plażma kemm kemm ogħla (22%), għall- livell simili ta ’ C12 ta' amprenavir totali fil- plażma u livell ta ’ C12 ta ’ amprenavir mhux marbut fil- plażma ta ’ bejn wieħed u ieħor 117% ogħla meta mqabbla ma ’ dawk ta ’ suġġetti b’ funzjoni tal- fwied normali li qegħdin jirċievu s- sistema ta ’ dożaġġ standard ta ’ fosamprenavir / ritonavir 700 mg / 100 mg darbtejn kuljum.
In subjects with moderate hepatic impairment (Child-Pugh score of 7-9), a reduced dose of fosamprenavir 450 mg twice daily with a reduced dosing frequency of ritonavir 100 mg once daily is 20 predicted to deliver similar plasma amprenavir Cmax and AUC(0-12), but approximately 35% lower plasma total amprenavir C12 values and approximately 88% higher plasma unbound amprenavir C12 values than achieved in subjects with normal hepatic function receiving the standard fosamprenavir with ritonavir 700 mg / 100 mg twice daily regimen.
F’ suġġetti b’ indeboliment tal- fwied moderat (Child- Pugh score ta ’ 7- 9), huwa stmat li doża mnaqqsa ta ’ fosamprenavir 450 mg darbtejn kuljum flimkien ma ’ ritonavir 100mg bil- frekwenza tad- doża mnaqqsa għal darba kuljum twassal għal- livell simili ta ’ Cmax u AUC (0- 12) ta 'amprenavir ġol- plażma, imma twassal għal- livell ta ’ C12 ta ’ amprenavir totali fil- plażma ta ’ bejn wieħed u ieħor 35% iżjed baxx u livell ta ’ C12 ta ’ amprenavir mhux marbut fil- plażma ta ’ bejn wieħed u ieħor 88% ogħla min dik milqugħa f’ suġġetti b’ funzjoni tal- fwied normali li qed jirċievu s- sistema ta ’ dożaġġ standard ta ’ fosamprenavir / ritonavir 700 mg / 100 mg darbtejn kuljum.
In subjects with severe hepatic impairment (Child-Pugh score of 10-13), a reduced dose of fosamprenavir 300 mg twice daily with a reduced dosing frequency of ritonavir 100 mg once daily delivered 19% lower plasma amprenavir Cmax, 23% lower AUC(0-12), and 38% lower C12 values, but similar unbound plasma amprenavir C12 values than achieved in subjects with normal hepatic function receiving the standard fosamprenavir with ritonavir 700 mg / 100 mg twice daily regimen.
F’ suġġetti b’ indebboliment sever tal- fwied (Child- Pugh score ta ’ 10- 13), doża mnaqqsa ta ’ fosamprenavir 300mg darbtejn kuljum bi frekwenza ta ’ dożaġġ ta ’ ritonavir imnaqqsa għal 100mg darba kuljum wassal 19% ta ’ amprenavir Cmax anqas fil- plażma, 23% anqas AUC (0- 12), u 38% anqas fil- valur ta ’ C12, imma valuri simili ta ’ C12 ta ’ amprenavir fil- plażma minn dawk f’ suġġetti b’ funzjoni normali tal- fwied li ħadu sistema ta ’ kura standard b’ fosamprenavir ma ’ ritonavir 700mg / 100mg darbtejn kuljum.
Despite reducing the dosing frequency of ritonavir, subjects with severe hepatic impairment had 64% higher ritonavir Cmax, 40% higher ritonavir AUC(0-24), and 38% higher ritonavir C12 than achieved in subjects with normal hepatic function receiving the standard fosamprenavir with ritonavir 700 mg / 100 mg twice daily regimen.
Minkejja li kien tnaqqis fil- frekwenza tad- doża ta ’ ritonavir, suġġetti b’ indebboliment sever tal- fwied kellhom 64% ta ’ Cmax ta ’ ritonavir aktar għoli, 40% AUC( 0- 24) aktar għoli, u 38% ta ’ C12 ta ’ ritonavir aktar għoli minn dak li ntlaħaq f’ suġġetti b’ funzjoni normali tal- fwied li kienu fuq sistema ta ’ kura standard ta ’ fosamprenavir ma ’ ritonavir ta ’ 700mg / 100mg darbtejn kuljum.,
Fosamprenavir with ritonavir was generally well-tolerated in subjects with mild, moderate, or severe hepatic impairment, and these regimens had similar adverse event and clinical laboratory profiles as previous studies of HIV-1 infected subjects with normal hepatic function.
Il- biċċa l- kbira ta ’ suġġetti b’ indeboliment tal- fwied ħafif, moderat jew sever felħu għat- trattament b ’ fosamprenavir ma ’ ritonavir u dawn s- sistemi ta 'trattament urew profil ta ’ effetti avversi u profil
Toxicity was similar to that of amprenavir and occurred at amprenavir plasma exposure levels below human exposure after treatment with fosamprenavir in combination with ritonavir at the recommended dose.
It- tossiċità kienet simili għal ta ’ amprenavir u seħħet f’ livelli ta ’ esponiment ta ’ amprevanir fil- plażma inqas mill- esponiment tal- bniedem wara l- kura b’ fosamprenavir flimkien ma ’ ritonavir skond id- doża rakkomandata.
In repeated dose toxicity studies in adult rats and dogs, fosamprenavir produced evidence of gastrointestinal disturbances (salivation, vomiting and soft to liquid faeces), and hepatic changes (increased liver weights, raised serum liver enzyme activities and microscopic changes, including hepatocyte necrosis).
Fi studji ripetuti tat- tossiċità tad- doża f’ firien u klieb adulti, fosamprenavir wera evidenza ta ’ disturbi gastro- intestinali (żieda fil- bżieq, rimettar u purgar artab jew maħlul), u tibdil fil- fwied, (żieda fil- piż tal- fwied, attivitajiet aktar ta ’ enżimi tal- fwied fis- serum u tibdiliet mikroskopiċi, inkluża nekrosi ta ’ l - epatoċiti).
Toxicity was not aggravated when juvenile animals were treated as compared with adult animals, but the data did indicate a steeper dose response.
It- tossiċità ma aggravatx meta annimali minorenni ingħataw l- istess kura bħal annimali adulti, imma d- data uriet rispons fid- doża aktar wieqfa.
In reproductive toxicity studies with fosamprenavir in rats, male fertility was not affected, but in females gravid uterine weights, numbers of ovarian corpora lutea and uterine implantation sites were reduced.
Fi studji b’ fosamprenavir dwar tossicità riproduttiva fil- firien, il- fertilità maskili ma ġietx affettwata, imma fin- nisa kien hemm tnaqqis ta ’ piż fl- utru waqt il- gravidanza, fin- numru ta ’ corpora lutea ovarji u fis- siti ta ’ impjantazzjoni fl- utru.
In pregnant rats and rabbits there were no major effects on embryo-foetal development.
F’ firien u fniek tqal ma kienx hemm effetti sinifikanti fuq l - iżvilupp embrijo- fetali.
However, the number of abortions increased.
Iżda, in- numru ta ’ aborti żdied.
In rabbits, systemic exposure at the high dose level was only 0.3 times human exposure at the maximum clinical dose and thus the developmental toxicity of fosamprenavir has not been fully determined.
Fil- fniek, esponiment sistemiku għal dożi għolja kien biss ta ’ 0. 3- il darba ta’ l- esponiment tal- bniedem fl- ogħla dożi kliniċi u għalhekk it - tossiċità ta ’ waqt l- iżvilupp ta ’ fosamprenavir ma ġietx stabbilita għal kollox.
In rats exposed pre- and post-natally to fosamprenavir, pups showed impaired physical and functional development and reduced growth.
F’ firien li b’ xi mod ħadu fosamprenavir qabel u wara t- twelid, iż- żgħar urew nuqqas ta ’ żvilupp fiżiku u funzjonali u kibru bil- mod.
Pup survival was decreased.
Iż- żgħar li baqgħu ħajjin naqsu.
In addition, decreased number of implantation sites per litter and a prolongation of gestation were seen when pups were mated after reaching maturity.
Barra minn hekk, deher ukoll nuqqas ta ’ siti ta ’ impjantazzjoni għal kull boton u tqala aktar fit- tul meta ż- żgħar tgħammru wara li mmaturaw.
Fosamprenavir was not mutagenic or genotoxic in a standard battery of in vitro and in vivo assays.
Fosamprenavir ma nstabx li kien mutaġeniku jew ġenotossiku f’ analiżi in vitro u in vivo ta ’ standard battery.
In long-term carcinogenicity studies with fosamprenavir in mice and rats, there were increases in hepatocellular adenomas and hepatocellular carcinomas in mice at exposure levels equivalent to 0.1 to 0.3-fold those in humans given 700 mg of fosamprenavir plus 100mg ritonavir twice daily, and increases in hepatocellular adenomas and thyroid follicular cell adenomas in rats at exposure levels equivalent to 0.3 to 0.6-fold those in humans given 700 mg of fosamprenavir plus 100mg ritonavir twice daily.
Fi studji fit- tul dwar karċinoġeniċità b’ fosamprenavir fi ġrieden u firien, kien hemm żidiet f’ adenomi epatoċellulari u kanċer epatoċellulari fi ġrieden meta kienu esposti għall- livelli ekwivalenti għal 0. 1 sa 0. 3 darbiet dawk fi bnedmin li ħadu 700mg ta ’ fosamprenavir u 100mg ritonavir darbtejn kuljum, u żidiet f’ adenomi epatoċellulari u adenomi follikulari tat- tirojde fi firien meta kienu esposti għall- livelli ekwivalenti għal 0. 3 sa 0. 6 darbiet dawk fi bnedmin li ħadu 700mg ta’ fosamprenavir u 100mg ta ’ ritonavir darbtejn kuljum.
The relevance of the hepatocellular findings in the rodents for humans is uncertain; however, there is no evidence from clinical trials or marketed use to suggest that these findings are of clinical significance.
Ma hijiex ċerta ir- rilevanza tas- sejbiet epatoċellulari f’ kull animal gerriemi għall- bnedmin; madankollu m’ hemm l- ebda evidenza minn studji kliniċi jew wara li jitqiegħed fis- suq li jissuġerixxi li dawn is- sejbiet fihom xi relevanza klinika.
Repeat dose studies with fosamprenavir in rats produced effects consistent with hepatic enzyme induction, which predisposes rats to thyroid neoplasms.
Studji b’ dożi ripetuti ta ’ fosamprenavir fil- firien ipproduċew effetti konsistenti ma ’ induzzjoni ta ’ enżima tal- fwied, li jippridisponi l- firien għal neoplażmi tat- tirojde.
The thyroid tumorigenic potential is regarded to be species-specific.
Il- potenzjal tumoriġeniku tat- tirojde huwa meqjus bħala speċifiku għall- ispeċi.
The clinical relevance of these findings is unknown.
Mhijiex magħrufa ir- rilevanza klinika ta ’ dawn is- sejbiet.
In rats 21 only there was an increase in interstitial cell hyperplasia in males at exposure levels equivalent to 0.5- fold those in humans, and an increase in uterine endometrial adenocarcinoma in females at an exposure level equivalent to 1.1-fold those in humans.
Fil- firien biss kien hemm żieda fl- iperplasija fiċ- ċelloli interstitial fl- irġiel li kienu esposti għal livelli ekwivalenti għal 0. 5 darbiet dawk fil- bniedem, u żieda f’ adenokarċinoma ta ’ l- endometriju ta ’ l- utru fin- nisa meta kienu esposti għall- livelli ekwivalenti għal 1. 1 darbiet dawk fil- bniedem.
The incidence of endometrial findings was slightly increased over concurrent controls, but within background range for female rats.
L- inċidenza ta ’ sejbiet fl - endometriju kienu ftit aktar minn kontrolli fl- istess żmien, imma ġewwa l- limiti ta’ sfond fi firien nisa.
The relevance of the uterine endometrial adenocarcinomas for humans is uncertain; however there is no evidence from clinical trials or marketed use to suggest that these findings are of clinical significance.
Ir- rilevanza ta ’ l- adenokarċinoma ta ’ l- endometriju ta ’ l- utru fil- bniedem hija nċerta; madankollu m’ hemm l- ebda evidenza minn studi kliniċi jew wara li jitqiegħed fis- suq li tindika li dawn is- sejbiet huma klinikament sinifikanti.
Microcrystalline cellulose Croscarmellose sodium Povidone K30 Magnesium stearate Colloidal anhydrous silica
Microcrystalline cellulose Croscarmellose sodium Povidone K30 Magnesium stearate
Tablet film-coat:
Ir- rita li tiksi l- pillola:
Hypromellose Titanium dioxide (E171) Glycerol triacetate Iron oxide red (E172)
Hypromellose Titanium dioxide (E 171) Glycerol triacetate Iron oxide red (E 172)
This medicinal product does not require any special storage conditions.
M’ hemm l- ebda struzzjonijiet dwar ħażna speċjali.
HDPE bottles with a child resistant polypropylene closure containing 60 tablets.
Fliexken HDPE li jingħalqu b’ tapp tal- polypropylene li ma jistax jinfetaħ minn tfal u li jkun fihom 60 pillola.
Any unused product should be disposed of in accordance with local requirements..
Kull fdal tal- prodott li ma jkunx intuża jew skart li jibqa wara l- użu tal- prodott għandu jintrema kif jitolbu l- liġijiet lokali.
MARKETING AUTHORISATION HOLDER
ID- DENTATUR TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ
Glaxo Group Ltd Greenford Road Greenford
Glaxo Group Ltd Greenford Road Greenford Middlesex UB6 0NN Renju Unit
12 July 2004
12 ta ’ Lulju 2004
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu
Informazzjoni ddettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il - Medicini (EMEA) http: // www. emea. europa. eu /
Telzir 50 mg/ ml oral suspension.
Sospensjoni orali ta ’ 50 mg/ ml Telzir
Each ml of oral suspension contains 50 mg fosamprenavir as fosamprenavir calcium (equivalent to approximately 43 mg amprenavir).
Kull ml ta ’ sospensjoni orali fih 50 mg ta ’ fosamprenavir bħala fosamprenavir calcium (ekwivalenti għal 43 mg ta ’ amprenavir)
Oral suspension.
Sospensjoni orali
The suspension is white to off-white in colour.
Il- kulur tas- sospensjoni jkun bejn abjad u offwajt.
In protease inhibitor (PI) experienced patients, the choice of Telzir should be based on individual viral resistance testing and treatment history (see section 5.1).
F’ pazjenti li diġà ngħataw l- impeditur protease (PI) l- għażla ta ’ Telzir trid tkun ibbażata fuq it- testijiet tar- reżistenza għal virus ta ’ l- individwu, u l- kura li kien ingħata qabel (ara sezzjoni 5. 1).
24 Caution is advised if the recommended dose of fosamprenavir with ritonavir detailed below are exceeded (see section 4.4).
Għandha tiġi irrikkmandata l- kawtela jekk il- limiti tad- dożi ta ’ Telzir ma ’ ritonavir irrakkomandati hawn taħt jinqabżu (ara sezzjoni 4. 4).
Telzir suspension is administered orally.
24 Is- sospensjoni ta ’ Telzir tingħata mill- ħalq.
Shake the bottle vigorously for 20 seconds before first dose is removed and 5 seconds before each subsequent dose.
Ħawwad il- flixkun sew għal 20 sekondi qabel titneħħa l- ewwel doża u 5 sekondi qabel kull doża li jmiss.
Telzir is also available as 700 mg film-coated tablets.
Telzir issibu wkoll bħala pilloli ta ’ 700mg miksijin b’ rita.
In adults, the oral suspension should be taken without food and on an empty stomach.
Fl - adulti is- sospensjoni orali għandha tittieħed mingħajr ikel fuq stonku vojt.
Please refer to the table below for the dosing recommendations in adults.
Jekk jogħġbok irreferi għat- tabella hawn taħt għar- rakkomandazzjonijiet ta ’ dożaġġ fil- kbar.
Paediatric patients (from 6 years of age)
Pazjenti pedjatriċi (mill- eta ’ ta ’ 6 snin)
In paediatric patients, the oral suspension should be taken with food in order to aid palatability and assist compliance (see section 5.2).
F’ pazjenti pedjatriċi, is- sospensjoni orali għandha tittieħed ma ’ l- ikel biex tgħin fit- togħma u biex jeħduha aktar (ara sezzjoni 5. 2).
Telzir oral suspension is the recommended option for the most accurate dosing in children based on body weight.
Is- sospensjoni orali ta ’ Telzir hija l- għażla rakkomandata għal dożaġġ l- aktar preċiż fit- tfal fuq bażi ta ’ piż tal- ġisem.
Please refer to the table below for the dosing recommendations in paediatric patients.
Jekk jogħġbok irreferi għat- tabella hawn taħt għar- rakkomandazzjonijiet tad- doża f’ pazjenti pedjatriċi.
No dosing recommendations can be made for children weighing less than 25 kg.
Ma jistgħux isiru rakkomandazzjonijiet fuq id- doża għal tfal li jiżnu anqas minn 25 kg.
Telzir with ritonavir is not recommended in children below 6 years due to insufficient data on pharmacokinetics, safety and antiviral response (see section 5.2).
Telzir ma ’ ritonavir mhux irrakkomandat ghall- użu fit- tfal ta ’ taħt it- 12 il- sena u adolexxenti bejn it- 12 u s- 17 il- sena peress li m’ hemmx biżżejjed informazzjoni dwar is- sigurtà u l- effikaċja (ara sezzjoni 5. 2).
Dosing recommendations for Telzir with ritonavir
25 Rakkomandazzjonijiet għad- dożaġġ ta ’ Telzir ma ’ ritonavir
Age
Eta ’
Body weight
Piż tal - ġisem
Telzir dose (TWICE DAILY)
Doża ta ’ Telzir (DARBTEJN KULJUM)
Ritonavir dose (TWICE DAILY)
Doża ta ’ Ritonavir (DARBTEJN KULJUM)
Adult (> 18
Adult (> 18 sena)
Tablet or Oral suspension
Pillola jew Sospensjoni orali
Capsule or Solution
Kapsula jew Soluzzjoni
700 mg (1 tablet or 14 ml suspension)
700mg (pillola 1 jew 14ml ta ’ sospensjoni)
Oral suspension should be taken without food 6-17 years
Sospensjoni orali għandha tittieħed mingħajr ikel
700 mg (1 tablet or 14 ml suspension)
700mg (pillola 1 tablet jew 14ml ta ’ sospensjoni)
Oral suspension should be taken with food
Sospensjoni orali għandha tittieħed ma 'l- ikel
Oral suspension
Sospensjoni orali
18 mg/ kg (0.36 ml/ kg); maximum 700 mg or 14 ml
18mg/ kg (0. 36 ml/ kg); massimu ta ’ 700 mg jew 14 ml
Solution
Soluzzjoni
18 mg/ kg (0.36 ml/ kg)
18mg/ kg (0. 36 ml/ kg)
3 mg/ kg
3mg/ kg
No dosing recommendations
L- ebda rakkomandazzjonijiet fuq id- doża
< 6 years
< 6 snin
Not recommended
Mhux rakkomandat
Hepatic impairment
26 Indeboliment tal- fwied
7-9) the recommended dose is 450 mg fosamprenavir (i. e.
7- 9) hija ta ’ 450 mg fosamprenavir (i. e.
9 ml Telzir oral suspension) twice daily with 100 mg ritonavir once daily.
9ml ta ’ sospensjoni orali ta ’ Telzir) darbtejn kuljum ma ’ 100 mg ritonavir darba kuljum.
Even with these dose adjustments for adults with, some patients with hepatic impairment may have higher or lower than anticipated amprenavir and/ or ritonavir plasma concentrations as compared to patients with normal hepatic function, due to increased inter-patient variability (see section 5.2), therefore a close monitoring of safety and virologic response is warranted.
Ukoll b’ dawn l- aġġustamenti fid- doża f’ adulti, xi pazjenti b’ indebboliment tal- fwied jista ’ jkollhom konċentrazzjonijiet aktar għolja jew baxxi ta ’ amprenavir jew/ u ritonavir fil- plażma milli mistenni meta mqabbla ma ’ pazjenti b’ funzjoni normali tal- fwied, minħabba varjeta ’ akbar bejn pazjent u ieħor (ara sezzjoni 5. 2), għalhekk huwa indikat monitoraġġ mill- qrib tar- rispons tas- sigurta ’ u viroloġika.
In this patient population, the oral suspension should be taken without food and on an empty stomach.
F’ din il- popalazzjoni ta 'pazjenti, is- sospensjoni orali għandha tittieħed bi jew mingħajr ikel u fuq stonku vojt.
No dose recommendation can be made for children and adolescents with hepatic impairment as no studies have been conducted in these age groups.
Ma jistgħux isiru rakkomandazzjonijiet ta ’ doża għal tfal u adolexxenti b’ indebboliment tal- fwied billi ma sarux studji f’ dawn il- gruppi ta 'eta ’
Hypersensitivity to fosamprenavir, amprenavir or to any of the excipients of Telzir, or to ritonavir.
Ipersensittività għal fosamprenavir jew għal xi sustanzi mhux attivi li jinsabu f’ Telzir jew għal ritonavir.
26 Telzir must not be administered concurrently with medicinal products with narrow therapeutic windows that are substrates of cytochrome P450 3A4 (CYP3A4), e. g. amiodarone, astemizole, bepridil, cisapride, dihydroergotamine, ergotamine, pimozide, quinidine, terfenadine, oral midazolam (for caution on parenterally administered midazolam, see section 4.5), oral triazolam.
Telzir m’ għandux jingħata fl- istess ħin ma ’ prodotti mediċinali b’ therapeutic windows dojoq li huma substrati taċ- ċitokromju P450 3A4 (CYP3A4), e. g. amiodarone, astemizole, bepridil, cisapride, dihydroergotamine, ergotamine, pimozide, quinidine, terfenadine midazolam mill- ħalq (kawtela meta midazolam jingħata mill- vina ara sezzjoni 4. 5), triazolam mill- ħalq.
Telzir with ritonavir must not be co-administered with medicinal products with narrow therapeutic windows that are highly dependent on CYP2D6 metabolism e. g. flecainide and propafenone (see section 4.5).
Telzir ma’ ritonavir m’ għandhomx jingħataw fl- istess ħin ma ’ prodotti mediċinali b’ therapeutic windows dojoq li jiddependu ħafna mill- metaboliżmu ta ’ CYP2D6, e. ż. flecainide u propafenone (ara sezzjoni 4. 5).
(see section 4.5).
Il- kumbinazzjoni ta ’ rifampicin u Telzir flimkien ma ’ doża baxxa ta ’ ritonavir hija kontraindikata (ara sezzjoni 4. 5)
Patients should be advised that treatment with the Telzir, or any other current antiretroviral therapy, does not cure HIV and that they may still develop opportunistic infections and other complications of HIV infection.
Il- pazjenti għandhom jigu mgħarrfa li kura b’ Telzir, jew kull xorta ta ’ terapija antiretrovirali li teżisti bħalissa, ma jfejjaqx l- HIV u li xorta waħda jistgħu jiżviluppaw infezzjonijiet opportunistiċi u komplikazzjonijiet oħra marbuta ma ’ l- HIV.
Current antiretroviral therapies, including Telzir, have not been proven to prevent the risk of transmission of HIV to others through sexual contact or blood contamination.
Bħalissa, mhemmx provi li terapija antiretrovirali inkluż Telzir tnaqqas ir- riskju tat- tixrid tal- HIV permezz ta ’ kuntatti sesswali jew kontaminazzjoni mid - demm.
The potential for cross-sensitivity between medicinal products in the sulphonamide class and fosamprenavir is unknown.
Il- potenzjal ta ’ cross- sensitivity bejn prodotti mediċinali tal- klassi tas- sulphonamides u fosamprenavir mhux magħruf.
In the pivotal studies of Telzir, in patients receiving fosamprenavir with ritonavir there was no evidence of an increased risk of rashes in patients with a history of sulphonamide allergy versus those who did not have a sulphonamide allergy.
27 f’ pazjenti li qed jieħdu fosamprenavir ma’ ritonavir ma ma kien hemm l- ebda evidenza ta ’ riskju akbar ta ’ raxx f’ pazjenti b’ passat ta ’ allergiji għas- sulphonamides meta mqabbla ma ’ dawk li ma kellhomx allerġiji għas- sulphonamides.
The Telzir oral suspension contains propyl and methyl parahydroxybenzoate.
Is- sospensjoni orali Telzir fiha propyl u methyl parahydroxybenzoate.
These products may cause an allergic reaction in some individuals.
Dawn il- prodotti jistgħu jikkaġunaw reazzjoni allerġika f’ xi individwi.
This reaction may be delayed.
Din ir- reazzjoni tista ’ ma sseħħx mill- ewwel.
Co-administration of Telzir 700 mg twice daily with ritonavir in doses greater than 100 mg twice daily has not been clinically evaluated.
L- użu ta ’ Telzir 700mg darbtejn kuljum ma ’ ritonavir f’ dożi akbar minn 100mg darbtejn kuljum ma ġiex evalwat klinikament.
Telzir with ritonavir should be used with caution and at reduced doses in adults with mild, moderate or severe hepatic impairment (see section 4.2). Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an increased risk of severe and potentially fatal hepatic adverse events.
Pazjenti b ’ l- epatite B jew C kronika u li jingħataw terapija antiretrovirali kombinata jinsabu f’ riskju akbar li jsofru minn reazzjonijiet epatiċi severi u li jistgħu jkunu fatali.
In case of concomitant antiviral therapy for hepatitis B or C, please refer also to the relevant Summary of Product Characteristics for these medicinal products.
Fil- każ ta ’ terapija anti- retrovirali kombinata għall- epatite B jew C, wieħed għandu dejjem jikkonsulta mas- Sommarju tal- Karatteristiċi tal- Prodott ta ’ dawn il- prodotti mediċinali.
Patients with pre-existing liver dysfunction, including chronic active hepatitis, have an increased frequency of liver function abnormalities during combination antiretroviral therapy and should be monitored according to standard practice.
Pazjenti li jkollhom fwied diġà ma jaħdimx normali, inkluża l- epatite attiva u kronika, ibatu minn rata aktar frekwenti ta ’ abnormalità fil- funzjoni tal- fwied meta jirċievu terapija kombinata antiretrovirali u għalhekk għandhom jinżammu taħt osservazzjoni kif isir issoltu f’ dawn il- każijiet.
If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered.
Jekk ikun hemm evidenza li juru li l- mard tal- fwied mar għall- agħar, wieħed għandu jikkunsidra jwaqqafx it- terapija għal ftit taż- żmien jew anke għal kollox.
The use of Telzir concomitantly with halofantrine or lidocaine (systemic) is not recommended.
L- użu ta ’ Telzir fl- istess ħin ma ’ halofantrine jew lidocaine (sistemiku) mhux rakkomandat
27 The use of Telzir concomitantly with PDE5 inhibitors (e. g. sildenafil and vardenafil) is not recommended (see section 4.5).
L- użu ta ’ Telzir fl- istess ħin ma ’ impedituri PDE5 (e. g. sildenafil u vardenafil) mhux rakkomandat (ara sezzjoni 4. 5).
Concomitant use of Telzir with simvastatin or lovastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis (see section 4.5).
L- użu fl- istess ħin ta ’ Telzir ma ’ simvastatin jew lovastatin mhux rakkomandat minħabba li jiżdied ir - riskju ta ’ mijopatija, inkluż rabdomajoliżi (ara sezzjoni 4. 5).
No data are available on the co-administration of fosamprenavir and ritonavir with oestrogens and/ or progestogens when used as hormonal replacement therapies.
Ma hemm l- ebda data fuq fosamprenavir u ritonavir meta jingħataw flimkien ma ’ estrogeni jew progestogeni meta dawn jintużaw bħala terapija ta ’ sostituzzjoni ta ’ l- ormoni.
Therapeutic concentration monitoring is recommended for tricyclic antidepressants (e. g. desipramine and nortriptyline) when co-administered with Telzir (see section 4.5).
28 Monitoraġġ ta ’ konċentrazzjonijiet terapewtiċi hu rakkomandat għal meta antidepressanti triċikliċi (e. g desipramine u nortriptyline) jittieħdu flimkien ma ’ Telzir (ara sezzjoni 4. 5).
When warfarin or other oral anticoagulants are co-administered with Telzir a reinforced monitoring of INR (International normalised ratio) is recommended (see section 4.5).
Meta warfarin u antikoagulanti oħra li jittieħdu mill- ħalq jingħataw flimkien ma ’ Telzir hu rakkomandat monitoraġġ aktar strett ta ’ l- INR (Proporzjon Internazzjonali Normalizzat) (ara sezzjoni 4. 5).
Concomitant use of Telzir with ritonavir and fluticasone or other glucocorticoids that are metabolised by CYP3A4 is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects, including Cushing’ s syndrome and adrenal suppression (see section 4.5).
L- użu ta ’ Telzir flimkien ma ’ ritonavir u fluticasone jew glukokortikojdi oħra li huma mmetaboliżżati minn CYP3A4 mhuhiex rakkomandat sakemm il- benefiċċju potenzjali tal- kura ma tkunx akbar mir - riskju ta ’ effetti tal- kortikojde fiċ- cirkulazzjoni, bħas- sindromu ta ’ Cushing u trażżin tal- glandola adrenali (ara sezzjoni 4. 5)
Appropriate antihistamines (e. g. cetirizine dihydrochloride) may reduce pruritus and hasten the resolution of rash.
Anti- istamini indikati (eż. cetirizine dihydrochloride) jistgħu jnaqqsu l- ħakk u jħaffu l- proċess biex jgħaddi r- raxx.
Haemophiliac patients
Pazjenti bl- emofilja
There have been reports of increased bleeding including spontaneous skin haematomas and haemarthroses in haemophiliac patients type A and B treated with protease inhibitors (PIs).
Kien hemm xi rapporti ta ’ żieda fil- fsada inklużi ematomi spontanji u emartrożi fil- ġilda ta ’ pazjenti bl- emofilja tat- tipi A u B fuq kura ta ’ impedituri protease (PIs).
In some patients administration of factor VIII was necessary.
Xi pazjenti kellhom il- bżonn li li jingħataw fattur VIII.
In more than half of the reported cases, treatment with protease inhibitors was continued, or reintroduced if treatment had been discontinued.
F’ iżjed minn nofs il- każi rappurtati, il- kura b’ impedituri protease tkompliet, jew reġgħat inbdiet wara li kienet twaqqfet.
28 New onset of diabetes mellitus, hyperglycaemia or exacerbations of existing diabetes mellitus have been reported in patients receiving antiretroviral therapy, including protease inhibitors.
Ħruġ mill- ġdid tad- dijabete mellitus, ipergliċemija jew aggravar tad- dijabete mellitus eżistenti ġew rappurtati f’ pazjenti fuq terapija antiretrovirali, inklużi impedituri protease.
A connection between visceral lipomatosis and protease inhibitors and lipoatrophy and nucleoside reverse transcriptase inhibitors has been hypothesised.
Konnessjoni bejn il- lipomatożi vixxerali u impedituri protease u l- lipoatrofija u inibituri ta ’ nucleoside reverse transcriptase ġiet ipotizzata.
Immune Reactivation Syndrome
Immune Reactivation Syndrome
In HIV-infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms.
F’ pazjenti infettati bl- HIV b’ deffiċjenza aeveri fl- immunità fiż- żmien li tkun bdiet it- terapija antiretrovirali konġunt (TARK), jista jkun hemm reazzjoni nfjammatorja għal mikrobi asintomatiċi jew mikrobi opportunistiċi residwali li jwasslu għal kundizzjonijiet kliniċi serji, jew sintomi li jmorru għall- agħar.
Relevant examples are cytomegalovirus retinitis, generalised and/ or focal mycobacterium infections, and Pneumocystis carinii pneumonia.
29 mycobacterium mifruxa jew lokaliżżati u pnemojnja bi Pneumocystis carinii.
Any inflammatory symptoms should be evaluated and treatment instituted when necessary.
Kull sintomu ta ’ nfjammazzjoni għandu jiġi vvalutat u fejn neċessarju tinbeda l- kura.
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 il- kawża tista ’ tkun minħabba ħafna fatturi, (li jinkludu l- użu ta ’ kortikosterojdi, il- konsum ta ’ alkoħol, trażżin severi fl- immunita ’, indiċi tal- massa tal- ġisem għoli), każijet ta ’ nekrożi fl- għadam instab li huwa partikolarment aktar komuni f’ pazjenti b’ HIVavvanzat u/ jew esponiment għal terapija antiretrovirali kombinata (CART) fit- tul.
When fosamprenavir and ritonavir are co-administered, the ritonavir metabolic drug interaction profile may predominate because ritonavir is a more potent CYP3A4 inhibitor.
Meta fosamprenavir u ritonavir jingħataw flimkien, il- profil ta ’ interazzjoni metabolika tad - droga ta ’ ritonavir jista ’ jkun predominanti għaliex ritonavir hu impeditur CYP3A4 aktar potenti.
The full prescribing information for ritonavir must therefore be consulted prior to initiation of therapy with Telzir with ritonavir.
L- informazzjoni kollha ta ’ preskrizzjoni għal ritonavir għandha għalhekk tinqara sew qabel tinbeda t- terapija ta ’ Telzir ma ’ ritonavir.
Ritonavir also inhibits CYP2D6 but to a lesser extent than CYP3A4.
Ritonavir jimpedixxi wkoll CYP2D6 imma mhux daqs CYP3A4.
Additionally, both amprenavir, the active metabolite of fosamprenavir, and ritonavir are primarily metabolised in the liver by CYP3A4.
Barra hekk, kemm amprenavir, il- metabolu attiv ta ’ fosamprenavir, u kemm ritonavir huma primarjament metabolizzati fil- fwied b ‘ CYP3A4.
Therefore, any medicinal products that either share this metabolic pathway or modify CYP3A4 activity may modify the pharmacokinetics of amprenavir and ritonavir.
Għalhekk, kull prodott mediċinali li juża wkoll dan il- passaġġ metaboliku jew jibdel l- attività CYP3A4 jista ’ jibdel il- farmakokinetiċi ta ’ amprenavir u ritonavir.
Similarily, administration of fosamprenavir with ritonavir may modify the pharmacokinetics of other active substances that share this metabolic pathway.
Hekk ukoll meta fosamprenavir jingħata ma ’ ritonavir jista ’ jġib tibdil fil- farmakokinetiċi ta ’ sustanzi attivi oħra li jużaw dan il- passaġġ metaboliku.
• Associations contraindicated (see section 4.3)
• Assoċjazzjonijiet kontra- indikati (ara sezzjoni 4. 3)
CYP3A4 substrates with narrow therapeutic index
Substrati CYP3A4 b’ indiċi terapewtiku dejjaq.
29 Telzir must not be administered concurrently with medicinal products with narrow therapeutic windows containing active substances that are substrates of cytochrome P450 3A4 (CYP3A4).
Telzir m’ għandux jingħata flimkien ma ’ prodotti mediċinali b’ therapeutic windows dojoq li jkun fihom sustanzi attivi li huma substrati taċ- ċitokromju P450 3A4 (CYP3A4).
Co-administration may result in competitive inhibition of the metabolism of these active substances thus increasing their plasma levels and leading to serious and / or life-threatening adverse reactions such as cardiac arrhythmia (e. g. amiodarone, astemizole, bepridil, cisapride, pimozide, quinidine, terfenadine) or peripheral vasospasm or ischaemia (e. g. ergotamine, dihydroergotamine).
Meta jingħataw flimkien jistgħu jikkaġunaw impediment kompetittiv tal- metaboliżmu ta ’ dawn is- sustanzi attivi li jiżdidilhom il- livell fil- plażma u li jista ’ jwassal għal effetti serji u/ jew li jkunu ta ’ periklu għall- ħajja bħal arritmja kardijaka (e. g. amiodarone, astemizole, bepridil, cisapride, pimozide, quinidine, terfenadine) jew vażospażmu periferali jew iskemija (e. g ergotamine, dihydroergotamine).
This is due to induction of drug metabolising enzymes by St John’ s wort.
Dan iseħħ minħabba induzzjoni minn St John’ s wort ta ’ enżimi li jimmetabolizzaw il- mediċina.
Amprenavir and ritonavir levels may increase on stopping St John’ s wort.
L -
• Other combinations
• Taħlitiet oħra
Based on data derived from these studies and because ritonavir is not expected to have a significant impact on the pharmacokinetics of NRTIs, the co-administration of fosamprenavir and ritonavir with these medicinal products is not expected to significantly alter the exposure of the co-administered active substances.
Fuq il- bażi ta ’ tagħrif miksub minn dawn l- istudji u minħabba li ritonavir mhux mistenni li jkollu xi impatt sinifikanti fuq il- farmakokinetiċi ta ’ NRTIs, it- teħid flimkien ta ’ fosamprenavir u ritonavir ma ’ dawn il- prodotti mediċinali mhux mistenni li jbiddel b’ mod sinifikanti l - esponiment tas - sustanzi attivi li jkunu ttieħdu flimkien.
No significant interaction is expected with didanosine gastro-resistent capsule
Ebda interazzjoni sinifikanti m’ hi mistennija mill- kapsula gastro - reżistenti ta ’ didanosine.
30 Tenofovir: no recommendations can be drawn at this stage on the co-administration of fosamprenavir with ritonavir with tenofovir.
F’ dan l- istadju, għad ma ħarġux rakkomandazzjonijiet fuq doża dwar it- teħid flimkien ta ’ fosamprenavir ma ritonavir ma ’ tenofovir.
No interaction studies have been undertaken between fosamprenavir with ritonavir and the following protease inhibitors: indinavir, saquinavir, nelfinavir and atazanavir.
Ma saru ebda studji dwar interazzjoni bejn fosamprenavir b’ ritonavir u l- impedituri protease: indinavir, saquinavir, nelfinavir u atazanavir.
Clarithromycin: a reduction in the clarithromycin dose should be considered when co-administered with Telzir with ritonavir in patients with renal impairment as moderate increases in clarithromycin concentrations are expected when coadministered with Telzir with ritonavir.
Clarithromycin: tnaqqis tad- doża ta ’ clarithromycin għandu jitqies meta jingħata flimkien ma ’ Telzir b’ ritonavir f’ pazjenti b’ indeboliment tal- kliewi għaliex żidiet moderati ta ’ konċentrazzjonijiet ta ’ clarithromycin huma mistennija meta jingħata ma ’ Telzir b’ ritonavir.
Ketoconazole / Itraconazole: co-administration of fosamprenavir 700 mg with ritonavir 100 mg twice daily and ketoconazole 200 mg once daily increased plasma ketoconazole Cmax by 25% and increased AUC(0-τ) to values 2.69-fold those observed on administration of ketoconazole 200 mg once daily without concurrent fosamprenavir with ritonavir.
31 Ketoconazole/ Itraconazole: fosamprenavir 700mg flimkien ma ’ ritonavir 100mg darbtejn kuljum u ketoconazole 200mg darba kuljum, żiedu il- livelli Cmax ta ’ ketoconazole fil- plażma b’ 25% u l- AUC( 0 - τ) b’ 2. 69 il darba dawk osservati b’ ketoconazole 200mg darba kuljum mingħajr fosamprenavir ma ’ ritonavir.
Rifabutin: compared to rifabutin administered alone (300 mg once daily), plasma rifabutin AUC (0- 48) was unchanged and Cmax was decreased 14% following co-administration of reduced doses of rifabutin (150 mg every other day) with fosamprenavir 700 mg twice daily with ritonavir 100 mg twice daily.
Meta mqabbla ma ’ rifabutin (300mg darba kuljum) waħdu, l- AUC (0- 48) ta ’ rifabutin fil - plażma baqa ’ l- istess u s- Cmax naqas b’ 14% wara li dożi mnaqqsa ta ’ rifabutin (150mg darba iva u darba le) ingħataw ma ’ fosamprenavir 700mg darbtejn kuljum u ritonavir 100mg darbtejn kuljum.
However, 25-O-desacetylrifabutin AUC (0-48) and Cmax were increased 11-fold and 6- fold respectively, which could potentially lead to an increase of rifabutin related adverse events, notably uveitis.
It - 25- O- desacetylrifabutin AUC (0- 48) u s- Cmax iżda żdiedu bi 11- il darba u b’ 6 darbiet rispettivament li tista ’ potenzjalment twassal għal żieda ta ’ eventi avversi relatati ma ’ rifabutin, l- aktar uvejite.
On the basis of these data, a 75% reduction of the standard rifabutin dose (i. e. to 150 mg every other day) is recommended when administered with Telzir with ritonavir.
Fuq bażi ta ’ din l- informazzjoni, tnaqqis fid- dożaġġ normali ta ’ rifabutin ta ’ għallinqas 75% (jiġifieri ghall - 150mg darba iva u darba le) hu rakkomandat meta jingħata flimkien ma ’ Telzir u ritonavir.
Other medicinal products
Prodotti mediċinali oħra
Medicinal products that may reduce plasma amprenavir concentrations when co-administered with Telzir
Prodotti mediċinali li jistgħu inaqqsu l- konċentrazzjonijiet fil - plażma ta ’ amprenavir meta jingħataw ma ’ Telzir
Antacids, Histamine H2 receptor antagonist and Proton-Pump inhibitors: no dose adjustment for any of the respective medicinal products is considered necessary when antacids, proton-pump inhibitors or histamine H2 receptor antagonists are administered concomitantly with fosamprenavir.
Mediċini kontra l- aċidu fl- istonku, antagonist tar- riċettur ta ’ l- istamina H2 u impedituri Proton- Pump: l- ebda tibdil fid- doża għal kull prodott mediċinali rispettiv ma hu meqjus neċessarju meta mediċini kontra l- aċidu, impedituri proton- pump jew antagonisti tar- riċettur ta ’ l- istamina H2 jingħataw flimkien ma ’ fosamprenavir.
The AUC and Cmax of amprenavir were decreased by 18% and 35% respectively, whilst the Cmin (C12h) was comparable, when a single 1400 mg dose of fosamprenavir was co-administered with a single 30 ml
L- AUC u Cmax ta ’ amprenavir tnaqqsu bi 18% u 35% rispettivament, waqt li Cmin (C12h) kien komparabbli, meta doża waħda ta ’ 1400 mg fosamprenavir ingħatat flimkien ma ’ doża waħda ta ’ 30 ml ta ’ sospensjoni kontra l- aċidu (ekwivalenti għal 3. 6 grammi aluminium hydroxide u 1. 8 grammi magnesium hydroxide).
Therefore, if fosamprenavir plus ritonavir is given in combination with phenytoin, no change to the fosamprenavir plus ritonavir dosage regimen is required.
Għalhekk jekk fosamprenavir ma ’ ritonavir jingħataw flimkien ma 'phenytoin, ma jkun hemm bżonn l- ebda bidla fid- doża ta' ta 'fosamprenavir ma' ritonavir.
However, it is recommended that phenytoin plasma concentrations be monitored and phenytoin dose increased as appropriate.
Madanakollu huwa rakkommandat li jiġu osservati l- konċentrazzjonijiet ta ’ phenytoin fil- plażma u d - doża ta ’ phenytoin miżjuda jekk ikun hemm bżonn.
Erectile dysfunction medicinal products: concomitant use is not recommended.
Prodotti mediċinali għal meta l- pene ma ’ jaħdimx normali: l- użu ta ’ dawn fl- istess ħin mhux rakkomandat.
Based on data for ritonavir and other protease inhibitors, plasma concentrations of PDE5 inhibitors (e. g. sildenafil and vardenafil) are expected to substantially increase when co-administered with Telzir with ritonavir and may result in an increase in PDE5 inhibitor associated adverse reactions, including hypotension, visual changes and priapism.
Fuq il- bażi ta ’ informazzjoni dwar ritonavir u impedituri protease oħra, il - konċentrazzjonijiet ta ’ impedituri PDE5 (e. g. sildenafil u vardenafil) fil- plażma ikunu mistennija li
Fluticasone propionate (interaction with ritonavir): in a clinical study where ritonavir 100 mg capsules bid were co-administered with 50 µg intranasal fluticasone propionate (4 times daily) for 7 days in healthy subjects, the fluticasone propionate plasma levels increased significantly, whereas the intrinsic cortisol levels decreased by approximately 86% (90% confidence interval 82-89%).
Fluticasone propionate (effett ma ’ ritonavir): fi studju kliniku fejn kapsuli ta ’ ritonavir 100mg darbtejn kuljum ingħataw ma ’ fluticasone propionate 50μg erba ’ darbiet kuljum fl- imnieħer għal 7 ijiem f’ suġġetti b’ saħħithom, il- livelli intrinsiċi ta ’ fluticasone propionate fil- plażma żdiedu b’ mod sinifikanti, filwaqt li l- livelli ta ’ cortisol fil- ġisem naqqsu bejn wieħed u ieħor bi 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 sistemiċi tal- kortikosterojdi bħas- sindromu ta ’ Cushing u trażżin tal- glandola adrenali ġew irrapurtati f’ pazjenti li kienu fuq ritonavir u fluticasone propionate li nġibed mill- pulmun jew ittieħed mill- imnieħer; dan jista ’ jiġri wkoll b’ kortikosterojdi oħra li jiġu mmetaboliżżati mir- rotta P450 3A eż. budesonide.
HMG-CoA reductase inhibitors: if treatment with a HMG-CoA reductase inhibitor is indicated, pravastatin or fluvastatin is recommended because their metabolism is not dependent on CYP3A4 and interactions are not expected with protease inhibitors.
Meta tkun indikata kura b’ impeditur HMG- CoA reductase, pravastatin jew fluvastatin huma rakkomandati għaliex il- metaboliżmu tagħhom ma jiddependix minn CYP3A4 u mhumiex mistennija interazzjonijiet b’ impedituri protease.
Since increased concentrations of HMG-CoA reductase inhibitors may cause myopathy, including rhabdomyolysis, the combination of lovastatin or simvastatin with Telzir with ritonavir is not
Billi konċentrazzjonijiet ogħla ta ’ impedituri HMG- CoA reductase jistgħu jikkaġunaw mijopatija, inkluż rabdomajoliżi, it- taħlita ta ’ lovastatin jew simvastatin ma ’ Telzir b’ ritonavir mhix rakkomandata.
The Cmax, AUC and Cmin of atorvastatin were increased by 184%, 153% and 73% respectively when atorvastatin (10 mg once daily for 4 days) was given with fosamprenavir 700 mg twice daily with ritonavir 100 mg twice daily for two weeks.
Cmx, AUC u Cmin ta ’ atorvastatin żdiedu b’ 184%, 153% u 73% rispettivament meta atorvastatin (10 mg darba kuljum għal erbat ijiem) ingħata ma ’ 700 mg fosamprenavir darbtejn kuljum ma ’ 100 mg ritonavir darbtejn kuljum għal ġimgħatejn.
When used with Telzir with ritonavir, doses of atorvastatin no greater than 20 mg/ day should be administered, with careful monitoring for atorvastatin toxicity.
Meta użati ma ’ Telzir b’ ritonavir, għandhom jingħataw dożi ta ’ atorvastatin ta ’ mhux iktar minn 20 mg kuljum, b’ monitoraġġ tajjeb għal xi tossiċità ta ’ atorvastatin.
Immunosuppressants: frequent therapeutic concentration monitoring of immunosuppresant levels is recommended until levels have stabilised as plasma concentrations of cyclosporin, rapamycin and tacrolimus may be increased when co-administered with fosamprenavir with ritonavir.
Immunosuppressanti: monitoraġġ ta ’ konċentrazzjonijiet terapewtiċi ta ’ spiss ta ’ livelli ta ’ immunosuppressanti hu rakkomandat sakemm il- livelli jistabbilizzaw ruħhom għaliex konċentrazzjonijiet ta ’ cyclosporin, rapamycin u tacrolimus fil- plażma jistgħu jiżdiedu meta jingħataw flimkien ma ’ fosamprenavir b’ ritonavir.
Data from concomitant use of parenteral midazolam with other protease inhibitors suggest a possible 3-4 fold increase in midazolam plasma levels.
Informazzjoni mill- użu ta ’ midazolam mill- vina flimkien ma ’ inibituri oħra ta ’ protease juru possibilita ’ ta ’ żieda ta ’ 3- 4 darbiet aktar fil- livelli ta ’ midazolam fil- plażma.
Tricyclic antidepressants: careful monitoring of the therapeutic and adverse reactions of tricyclic antidepressants is recommended when they (for example desipramine and nortriptyline) are concomitantly administered with Telzir.
Monitoraġġ tajjeb ta ’ l- effetti terapewtiċi u l- effetti avversi ta ’ antedepressanti triċikliċi hu rakkomandat meta dawn (per eżempju desipramine u notriptyline) jingħataw flimkien ma ’ Telzir.
Medicinal products whose plasma levels may be decreased when co-administered with Telzir
Prodotti mediċinali li l- livelli tagħhom fil- plażma jistgħu jonqsu meta jingħataw ma ’ Telzir:
Methadone: co-administration of fosamprenavir 700 mg and ritonavir 100 mg twice daily with methadone once daily (≤ 200 mg) for 14 days decreased the active (R-) methadone enantiomer AUC(0- τ) and Cmax by 18% and 21% respectively.
Methadone: l- għoti ta ’ fosamprenavir 700mg u ritonavir 100mg darbtejn kuljum flimkien ma ’ methadone darba kuljum (≤200mg) għal 14- il ġurnata naqqas l- AUC( 0- τ) u Cmax ta ’ l- enantiomer attiv ta ’ (R -) methadone b’ 18% u 21% rispettivament.