qanastek/EMEA-V3 huggingface dataset:
The inhibitory effect of ritonavir (with or without other protease inhibitors) on P-gp activity may decrease over time (eg digoxin and fexofenadine-see table “ Ritonavir effects on non-antiretroviral drugs” below).
L- effett li ritonavir għandu li jimpedixxi (kemm ma ’, kif ukoll mhux ma ’ impedituri protejaż oħra) fuq l- attività P- gp jista ’ jonqos maż- żmien (eż digoxin u fexofenadine- ara t- tabella t’ hawn taħt – “ L- Effetti ta ’ ritonavir fuq mediċini li m’ humiex antiretrovirali ”).
Ritonavir may induce glucuronidation and oxidation by CYP1A2, CYP2C8, CYP2C9 and CYP2C19 thereby increasing the biotransformation of some medicinal products metabolised by these pathways, and may result in decreased systemic exposure to such medicinal products, which could decease or shorten their therapeutic effect.
Ritonavir jista ’ jikkawża glukuronidazzjoni u ossidazzjoni permezz ta ’ CYP1A2, CYP2C8, CYP2C9 u CYP2C19 u għalhekk iżid il- biotrasformazzjoni ta ’ xi prodotti mediċinali li huma metabolizzati minn dawn il- passaġġi, u jista ’ jirriżulta fi tnaqqis ta ’ l- esponiment sistemiku għal dawn il- prodotti mediċinali, li jista ’ jnaqqas l- effett terapewtiku jew iqassar il- perijodu ta ’ l- effett terapewtiku tagħhom.
Important information regarding drug interactions when ritonavir is used as a pharmacokinetic enhancer is also contained in the Summary of Product Characteristics of the co-administered protease inhibitor.
9 Informazzjoni importanti fuq interazzjonijiet bejn mediċini meta ritonavir jiġi użat biex iżid l- effett farmakokinetiku tinsab ukoll fis- Sommarju tal- Karatteristiċi tal- Prodott ta ’ l- impeditur protejaż li jingħata ma ’ ritonavir.
Drugs that affect ritonavir levels
Mediċini li jaffetwaw il- livelli ta ’ ritonavir
Serum levels of ritonavir can be reduced by concomitant use of herbal preparations containing St John’ s wort (Hypericum perforatum).
Il- livelli fis- serum ta ’ ritonavir jistgħu jiġu mnaqqsa bl- użu ta ’ preparazzjonijiet tal- ħxejjex li jkollhom fihom il- fexfiex tar- raba ’ (Hypericum perforatum) flimkien ma ’ ritonavir.
This is due to the induction of drug metabolising enzymes by St John’ s wort.
Dan huwa dovut lill - induzzjoni ta ’ enzimi li jimmetabolizzaw il- mediċina permezz tal- fexfiex tar- raba ’.
Herbal preparations containing St John’ s wort must not be used in combination with ritonavir.
Preparazzjonijiet tal- ħxejjex li għandhom fihom il- fexfiex tar- raba ’ m’ għandhomx jintużaw flimkien ma ’ ritonavir.
If a patient is already taking St John’ s wort, stop St John’ s wort and if possible check viral levels.
Jekk pazjent diġà qiegħed jieħu l- fexfiex tar- raba ’, waqqaf il- fexfiex tar- raba ’ u jekk huwa possibbli iċċekja l- livelli virali.
Ritonavir levels may increase on stopping St John’ s wort.
Il- livelli ta ’ ritonavir jistgħu jiżdiedu mat- twaqqif tal- fexfiex tar- raba ’.
The dose of ritonavir may need adjusting.
Jista ’ jkun hemm bżonn ta ’ aġġustament tad- doża ta ’ ritonavir.
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 mill - inqas ġimagħtejn wara t- twaqqif tal- kura bil- fexfiex tar- raba ’ (ara sezzjoni 4. 3).
Serum levels of ritonavir may be affected by select co-administered medicinal products (eg delavirdine, efavirenz, phenytoin and rifampicin).
Il- livelli fis- serum ta ’ ritonavir jistgħu jiġu affetwati minn prodotti mediċinali speċifiċi li jingħataw flimkien ma ’ ritonavir (eż delavirdine, efavirenz, phenytoin u rifampicin).
These interactions are noted in the drug interaction tables below.
Dawn l- interazzjonijiet huma mniżżla fit- tabella t’ hawn taħt dwar l- interazzjonijiet tal- mediċina.
9 Drugs that are affected by the use of ritonavir
Mediċini li huma affetwati bl- użu ta ’ ritonavir
Interactions between ritonavir and protease inhibitors, antiretroviral agents other than protease inhibitors and other non-antiretroviral drugs are listed in the tables below.
Interazzjonijiet bejn ritonavir u impedituri protejaż, aġenti antiretrovirali minbarra impedituri protejaż u mediċini oħra li m’ humiex antiretrovirali huma mniżżla fit- tabelli t’ hawn taħt.
Drug Interactions – Ritonavir with Protease Inhibitors
Interazzjonijiet tal- mediċini – Ritonavir ma ’ Impedituri Protejaż
Co-
Mediċina li
Dose of Co-administered
Doża tal - mediċina li
Dose of NORVIR
Doża ta ’
Drug
Il- Mediċina
administered Drug
jittieħdu ma ’ ritonavir
Drug
jittieħdu
(mg)
ma ’ ritonavir (mg)
Assessed
Studjata
↑ 5 fold
↑ b’ 5 darbiet
Ritonavir increases the serum levels of amprenavir as a result of CYP3A4 inhibition.
Bħala riżulatat ta ’ impediment minn CYP3A4, ritonavir iżid il- livelli tas- serum ta ’ amprenavir.
Clinical trials confirmed the safety and efficacy of 600 mg amprenavir twice daily with ritonavir 100 mg twice daily.
Provi kliniċi kkonfermaw is- sigurtà u l- effikaċja ta ’ 600 mg amprenavir darbtejn kuljum flimkien ma ’ 100 mg ritonavir darbtejn kuljum.
Norvir oral solution should not be co-administered with amprenavir oral solution to children due to the risk of toxicity from excipients in the two formulations.
Minħabba r- riskju ta ’ tossiċità mis- sustanzi mhux attivi fiż - żewġ formulazzjonijiet, is- soluzzjoni orali Norvir m’ għandhiex tingħata lit- tfal flimkien mas - soluzzjoni orali amprenavir.
For further information, physicians should refer to the Agenerase Summary of Product Characteristics.
Għal aktar informazzjoni, it- tobba għandhom jirreferu għas- Sommarju tal- Karatteristiċi tal- Prodott ta ’ Agenerase.
↑ 11 fold
↑ bi 11 - il darba
Atazanavir1
Atazanavir1 ↑ b’ 2 (darbtejn)
↑ 3-7 fold
↑ bi 3- 7 darbiet
Ritonavir increases the serum levels of atazanavir as a result of CYP3A4 inhibition.
Bħala riżultat ta ’ impediment minn CYP3A4, ritonavir iżid il- livelli tas- serum ta ’ atazanavir.
Clinical trials confirmed the safety and efficacy of 300 mg atazanavir once daily with ritonavir 100 mg once daily in treatment experienced patients.
Provi kliniċi kkonfermaw is- sigurtà u l- effikaċja ta ’ 300 mg atazanavir darba kuljum ma ’ 100 mg ritonavir darba kuljum fuq pazjenti illi għandhom esperjenza tat- trattament.
For further information, physicians should refer to the Reyataz Summary of Product Characteristics.
Għal aktar informazzjoni, it- tobba għandhom jirreferu għas- Sommarju tal- Karatteristiċi tal- Prodott ta ’ Reyataz.
600, single
600, doża waħda
Darunavir 600, single 100 q12h Darunavir
Darunavir 600, doża waħda 100 q12h Darunavir
↑ 14 fold
↑ b’ 14 - il
Ritonavir increases the serum levels of darunavir as a result of CYP3A inhibition.
darba Bħala riżultat ta ’ impediment minn CYP3A, ritonavir iżid il- livelli tas- serum ta ’ darunavir.
Darunavir must be given with ritonavir to ensure its therapeutic effect.
Biex jiġi żgurat l- effett terapewtiku tiegħu, darunavir għandu jingħata flimkien ma ’ ritonavir.
Ritonavir doses higher than 100 mg twice daily have not been studied with darunavir.
Ma ġewx studjati dożi ta ’ ritonavir akbar minn 100 mg darbtejn kuljum flimkien ma ’ darunavir.
For further information, refer to the Summary of Product Characteristics for Prezista.
Għal aktar informazzjoni, irreferi ghas- Sommarju tal- Karatteristiċi tal- Prodott ta ’ Prezista.
↑ 2.4 fold
↑ bi 2. 4 drabi
Ritonavir increases the serum levels of amprenavir (from fosamprenavir) as a result of CYP3A4 inhibition.
Bħala riżultat ta ’ impediment minn CYP3A4, ritonavir iżid il- livelli tas- serum ta ’ amprenavir (minn fosamprenavir).
Fosamprenavir must be given with ritonavir to ensure its therapeutic effect.
10 jingħata ma ’ ritonavir.
Clinical trials confirmed the safety and efficacy of fosamprenavir 700 mg twice daily with ritonavir 100 mg twice daily.
Provi kliniċi kkonfermaw is- sigurtà u l- effikaċja ta ’ 700 mg fosamprenavir darbtejn kuljum ma ’ 100 mg ritonavir darbtejn kuljum.
Ritonavir doses higher than 100 mg twice daily have not been studied with fosamprenavir.
Ma ġewx studjati dożi ta ’ ritonavir akbar minn 100 mg darbtejn kuljum ma ’ fosamprenavir.
For further information, physicians should refer to the Telzir Summary of Product Characteristics.
Għal aktar informazzjoni, it- tobba għandhom jirreferu għas- Sommarju tal- Karatteristiċi tal- Prodott ta ’ Telzir.
ND ND
MD MD
↑ 4 fold ↔
↑ b’ 4 darbiet
Ritonavir increases the serum levels of indinavir as a result of CYP3A4 inhibition.
Bħala riżultat ta ’ impediment minn CYP3A4, ritonavir iżid il- livelli tas- serum ta ’ indinavir.
Appropriate doses for this combination, with respect to efficacy and safety, have not been established.
Għadhom ma ġewx stabbiliti d- dożi t- tajba relatati mas- sigurtà u l- effikaċja għal din it- taħlita.
Minimal benefit of ritonavir-mediated pharmacokinetic enhancement is achieved with doses higher than 100 mg twice daily.
B’ dożi akbar minn 100 mg darbtejn kuljum, irriżulta biss benefiċju minimu medjat minn żieda farmakokinetika minn ritonavir.
In cases of co-administration of ritonavir (100 mg twice daily) and indinavir (800 mg twice daily) caution is warranted as the risk of nephrolithiasis may be increased.
F’ każi tat- teħid flimkien ta ’ ritonavir (100 mg darbtejn kuljum) u indinavir (800 mg darbtejn kuljum) għandha tiġi eżerċitata attenzjoni minħabba li r- riskju ta ’ ġebla fil- kliewi jista ’ jiżdied.
↑ 20to39%
↑ 20sa39%
ND
MD
750, single
750, doża waħda
ND ↔
MD ↔
Ritonavir increases the serum levels of nelfinavir as a result of CYP3A4 inhibition.
Bħala riżultat ta ’ impediment minn CYP3A4, ritonavir iżid il- livelli tas- serum ta ’ nelfinavir.
Saquinavir
Saquinavir4 ↑ bi 15 - il Saquinavir
Saquinavir4 Ritonavir
↑ b’ 5 darbiet
Ritonavir increases the serum levels of saquinavir as a result of CYP3A4 inhibition.
Bħala riżultat ta ’ impediment minn CYP3A4, ritonavir iżid il- livelli tas- serum ta ’ saquinavir.
Saquinavir should only be given in combination with ritonavir.
Saquinavir għandu jingħata biss flimkien ma ’ ritonavir.
Ritonavir 100 mg twice daily with saquinavir 1000 mg twice daily provides saquinavir systemic exposure over 24 hours similar to or greater than those achieved with saquinavir 1200 mg three times daily without ritonavir.
100 mg ritonavir darbtejn kuljum flimkien ma ’ 1000 mg saquinavir darbtejn kuljum jipprovdu esponiment sistemiku fuq 24 siegħa li huwa simili jew ikbar minn dak li jirrizulta b’ 1200 mg saquinavir tliet darbiet kuljum, mingħajr ritonavir.
For further information, physicians should refer to the Invirase or Fortovase Summary of Product Characteristics.
Għal aktar informazzjoni, it- tobba għandhom jirreferu għas- Sommarju tal- Karatteristiċi tal- Prodott ta ’ Invirase jew Fortovase.
↑ 11 fold
Tipranavir ↑ bi 11 - il darba
↑ 29 fold
↑ b’ 29 darba
↓ 40%
Ritonavir ↓ 40%
Ritonavir increases the serum levels of tipranavir as a result of CYP3A inhibition.
Bħala riżultat ta ’ impediment minn CYP3A, ritonavir iżid il- livelli tas- serum ta ’ tipranavir.
Tipranavir must be given with low dose ritonavir to ensure its therapeutic effect.
Biex jiġi żgurat l- effett terapewtiku tiegħu, tipranavir għandu jingħata ma ’ doża żgħira ta ’ ritonavir.
Doses of ritonavir less than 200 mg twice daily should not be used with tipranavir as they might alter the efficacy of the combination.
M’ għandhomx jintużaw ma ’ tipranavir dożi ta ’ ritonavir ta ’ inqas minn 200 mg darbtejn kuljum għax dawn jistgħu jbiddlu l- effikaċja tat- taħlita.
For further information, physicians should refer to the Aptivus Summary of Product Characteristics.
Għal aktar informazzjoni, it- tobba għandhom jirreferu għas- Sommarju tal- Karatteristiċi tal- Prodott ta ’ Aptivus.
ND:
MD:
1.
Mhux determinat 1.
Based on cross-study comparison to 400 mg atazanavir once daily alone.
Ibbażat fuq studju komparattiv li jinqeleb ma ’ 400 mg atazanavir darba kuljum waħdu.
Based on cross-study comparison to 1200 mg amprenavir twice daily alone.
Ibbażat fuq studju komparattiv li jinqeleb ma ’ 1200 mg amprenavir darbtejn kuljum waħdu.
Based on cross-study comparison to 800 mg indinavir three times daily alone.
Ibbażat fuq studju komparattiv li jinqeleb ma ’ 800 mg indanavir tlett darbiet kuljum waħdu.
Based on cross-stud y comparison to 600 mg saquinavir three times daily alone.
Ibbażat fuq studju komparattiv li jinqeleb ma ’ 600 mg sequinavir tlett darbiet kuljum waħdu.
Drug Interactions – Ritonavir with Antiretroviral Agents Other Than Protease Inhibitors Co-
Interazzjonijiet tal- mediċini – Ritonavir ma ’ Aġenti Antiretrovirali minbarra Impedituri Protejaż
Dose of Co-
Mediċina li
Dose of NORVIR (mg)
Doża ta ’
administered Drug (mg)
ma ’ ritonavir (mg)
600 q12h 2 h later
600 q12h 2
Didanosine 200 q12h 600 q12h 2 h later Didanosine
Didanosine 200 q12h 600 q12h 2 h wara Didanosine
As ritonavir is recommended to be taken with food and didanosine should be taken on an empty stomach, dosing should be separated by 2.5 h.
Peress illi huwa rrakkomandat li ritonavir jittieħed ma ’ l- ikel u didanosine għandu jittieħed fuq stonku vojt, id- dożi jridu jkunu separati b’ 2. 5 siegħat.
Dose alterations should not be necessary.
Tibdil fid- dożi m’ għandux ikun neċessarju.
Delavirdine
Delavirdine1 ↔ Delavirdine
Based on comparison to historical data, the pharmacokinetics of delavirdine did not appear to be affected by ritonavir.
Meta bbażata fuq tqabbil ma ’ informazzjoni storika, il- farmakokinetika ta ’ delavirdine ma dehrux illi huma affetwati minn ritonavir.
When used in combination with delavirdine, dose reduction of ritonavir may be considered.
Meta jiġi użat flimkien ma ’ delavirdine, għandu jiġi kkonsidrat tnaqqis fid- doża ta ’ ritonavir.
A higher frequency of adverse events (eg, dizziness, nausea, paraesthesia) and laboratory abnormalities (elevated liver enzymes) have been observed when efavirenz is co-administered with ritonavir dosed as an antiretroviral agent.
Frekwenza ogħla ta ’ effetti avversi (eż, sturdament, nawseja, parasteżija) u abnormalitajiet fir - riżultati tal- laboratorju (enzimi tal- fwied għoljin) ġew innotati meta efavirenz jingħata ma ’ ritonavir f’ doża bħala aġent antiretrovali.
100 q12h 100 q12h
100 q12h 100 q12h Maraviroc Bħala riżultat ta ’ impediment minn CYP3A, ritonavir iżid il- livelli
Maraviroc ↑161%
↑161% tas- serum ta ’ maraviroc.
Maraviroc may be given with ritonavir to increase the maraviroc exposure.
Maraviroc jista ’ jingħata flimkien ma ’ ritonavir biex iżid l- espożizzjoni ta ’ maraviroc.
For further information, refer to the Summary of Product Characteristics for Celsentri.
Għal aktar informazzjoni, irreferi għas- Sommarju tal- Karatteristiċi tal- Prodott ta ’ Celsentri.
Nevirapine 200 q12h 600 q12h Nevirapine
Nevirapine ↔ Ritonavir ↔
Co-administration of ritonavir with nevirapine does not lead to clinically relevant changes in the pharmacokinetics of either nevirapine or ritonavir.
It- teħid flimkien ta ’ ritonavir u nevirapine ma twassal għal ebda bidliet li huma klinikament relevanti, la fil- farmakokinetika ta ’ nevirapine u lanqas f’ ta ’ ritonavir.
Zidovudine ↓ 25%
Zidovudine ↓ 25% MD
Ritonavir may induce the glucuronidation of zidovudine, resulting in slightly decreased levels of zidovudine.
Ritonavir jista ’ jikkaġuna l- glukuronidazzjoni ta ’ zidovudine, li jirriżulta f’ livelli ta ’ zidovudine li jkunu ftit aktar baxxi.
Dose alterations should not be necessary.
M’ għandux ikun hemm bżonn ta ’ tibdil fid- doża.
Not determined 1.
Mhux determinat 1.
Based on parallel group comparison.
Ibbażat fuq paragun ta ’ gruppi paralleli.
Ritonavir effects on Non-antiretroviral Co-administered Drugs Co-administered Drug
L- Effetti ta ’ ritonovir fuq mediċini li ma humiex antiretrovirali, u li jittieħdu miegħu
Dose of Co- administered Drug (mg)
Mediċina li jittieħdu ma ’ ritonavir
Dose of NORVIR (mg)
Doża tal - mediċina Doża ta ’ li jittieħdu ma ’ NORVIR ritonavir (mg) (mg)
Effect on Co- administered Drug AUC
Effett fuq il - mediċina li tittieħed ma ’ ritonavir AUC
Effect on Co- administered Drug Cmax
Effett fuq il - mediċina li tittieħed ma ’ ritonavir Cmax
11
Meta dawn il- mediċini jittieħdu flimkien ma ’ dożi antiretrovirali ta ’ ritonavir, hija rrakkomandata osservazzjoni b’ attenzjoni ta ’ effetti terapewtiċi u avversi (ara sezzjoni 4. 4).
Ritonavir effects on Non-antiretroviral Co-administered Drugs Co-administered Drug
12 L- Effetti ta ’ ritonovir fuq mediċini li ma humiex antiretrovirali, u li jittieħdu miegħu
Analgesics Buprenorphine Norbuprenorphine Glucuronide metabolites
Mediċini Anaġesiċi Buprenorphine Norbuprenorphine Metabolati Glucuronide
The increases of plasma levels of buprenorphine and its active metabolite did not lead to clinically significant pharmacodynamic changes in a population of opioid tolerant patients.
Iż- żidiet fil- livelli fil- plażma ta ’ buprenorphine u l- metabolat attiv tiegħu ma kkaġunawx tibdil farmakodinamiku li hu klinikament sinifikanti f’ popolazzjoni ta ’ pazjenti li huma tolleranti għall- opioid.
Adjustment to the dose of buprenorphine or ritonavir may therefore not be necessary when the two are dosed together.
Għaldaqstant, jista ’ jkun li ma jkunx hemm bżonn ta ’ aġġustament fid- doża ta ’ buprenorphine jew ritonavir meta dawn it- tnejn ikunu dożati flimkien.
When ritonavir is used in combination with another protease inhibitor and buprenorphine, the SPC of the co-administered protease inhibitor should be reviewed for specific dosing information.
Meta ritonavir ikun użat flimkien ma ’ impeditur protejaż ieħor u ma ’ buprenorphine, l- SPC ta ’ l- impeditur protejaż li jingħata miegħu għandu jkun rivedut għal informazzjoni speċifika dwar id- dożaġġ.
Ritonavir co-administration is likely to result in increased plasma concentrations of meperidine, piroxicam, and propoxyphene and is therefore contraindicated (see section 4.3).
It- teħid ta ’ ritonavir flimkien ma ’ meperidine, piroxicam, propoxyphene x’ aktarx li jwassal għal żieda fil- konċentrazzjoni fil- plażma ta ’ meperidine, piroxicam, u propoxyphene, u għalhekk huwa kontro- indikat (ara sezzjoni 4. 3).
Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent inhibits CYP3A4 and as a result is expected to increase the plasma concentrations of fentanyl.
Ritonavir f’ doża biex iżid l- effett farmakokinetiku jew bħala aġent antiretrovirali jimpedixxi s- CYP3A4, u għalhekk huwa mistenni li jżid il - konċentrazzjoni fil- plażma ta ’ fentanyl.
Careful monitoring of therapeutic and adverse effects is recommended when fentanyl is concomitantly administered with ritonavir.
Meta fentanyl jittieħed flimkien ma ’ ritonavir, hija rikommandata osservazzjoni b’ attenzjoni ta ’ effetti terapewtiċi u avversi
5, single dose
5, doża waħda
Increased methadone dose may be necessary when concomitantly administered with ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer due to induction of glucuronidation.
Minħabba l- induzzjoni tal- glukuronidazzjoni, jista ’ jkun hemm bżonn ta ’ żieda fid- doża ta ’ methadone meta dan jittieħed flimkien ma ’ ritonavir f’ doża bħala aġenti antriretrovirali jew biex iżid l- effett farmakokinetiku.
Dose adjustment should be considered based on the patient’s clinical response to methadone therapy.
Tibdil fid- doża għandu jiġi kkonsidrat, skond ir- rispons kliniku tal- pazjent għat- terapija ta ’ methadone.
Morphine levels may be decreased due to induction of glucuronidation by co-administered ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer.
Minħabba l- induzzjoni tal- glukuronidazzjoni li ssir meta l- morfina tittieħed ma ’ ritonavir f’ doża bħala aġent antiretrovirali jew biex iżid l - effett farmakokinetiku, il- livelli tal- morfina jistgħu jonqsu.
Antiarrthymics Amiodarone, bepridil, encainide, flecanide, propafenone, quinidine
Mediċini li jaħdmu fuq ir- rittmu tat - tħabbit tal- qalb Amiodarone, bepridil, encainide, flecanide, propafenone, quinidine
Ritonavir co-administration is likely to result in increased plasma concentrations of amiodarone, bepridil, encainide, flecanide, propafenone, and quinidine and is therefore contraindicated (see section 4.3).
It- teħid ta ’ ritonavir flimkien ma ’ amiodarone, bepridil, encainide, flecanide, propafenone u quinidine x’ aktarx li jwassal għal żieda fil - konċentrazzjoni fil- plażma ta ’ amiodarone, bepridil, encainide, flecanide, propafenone u quinidine, u għalhekk huwa kontro- indikat (ara sezzjoni 4. 3).
12 Ritonavir effects on Non-antiretroviral Co-administered Drugs Co-administered Drug
13 L- Effetti ta ’ ritonovir fuq mediċini li ma humiex antiretrovirali, u li jittieħdu miegħu
This interaction may be due to modification of P-glycoprotein mediated digoxin efflux by ritonavir dosed as an antriretroviral agent or as a pharmacokinetic enhancer.
Din l- interazzjoni tista ’ tkun kkaġunata mill- modifikazzjoni ta ’ effluss ta ’ digoxin medjat b’ P - glycoprotein minn ritonavir f’ doża bħala aġent antiretrovirali jew biex iżid l- effett farmakokinetiku.
Increased digoxin levels observed in patients receiving ritonavir may lessen over time as induction develops (see section 4.4).
Maż- żmien, ma ’ l - iżvilupp ta ’ l- induzzjoni, iż- zieda fil- livelli ta ’ digoxin osservata f’ pazjenti li jieħdu ritonavir tista ’ tonqos (ara sezzjoni 4. 4).
Antiasthmatic Theophylline1
Mediċini kontra l- Ażżma Theophylline1
An increased dose of theophyline may be required when co- administered with ritonavir, due to induction of CYP1A2.
Minħabba l- induzzjoni ta ’ CYP1A2, jista ’ jkun hemm bżonn ta ’ doża akbar ta ’ theophylline meta dan jittieħed flimkien ma ’ ritronavir.
Anticancer agents Vincristine, vinblastine
Aġenti kontra l- kanċer Vincristine, vinblastine
Serum concentrations may be increased when co-administered with ritonavir resulting in the potential for increased incidence of adverse events.
Il- konċentrazzjonijiet tal- mediċina fis- serum jistgħu jiżdiedu meta dawn l- aġenti jittieħdu flimkien ma ’ ritonavir, b’ konsegwenza li jkun hemm potenzjal ta ’ żieda fl- inċidenza ta ’ effetti avversi.
Induction of CYP1A2 and CYP2C9 lead to decreased levels of R- warfarin while little pharmacokinetic effect is noted on S- warfarin when co-administered with ritonavir.
Fil- waqt illi l- effett farmakokinetiku innotat fuq S- warfarin meta dan ittieħed ma ’ ritonavir huwa żgħir, l- induzzjoni ta ’ CYP1A2 u CYP2C9 wassal għal tnaqqis fil- livelli ta ’ R- warfarin.
Decreased R-warfarin levels may lead to reduced anticoagulation, therefore it is recommended that anticoagulation parameters are monitored when warfarin is co- administered with ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer.
Livelli mnaqqsa ta ’ R - warfarin jistgħu jwasslu għal tnaqqis fil- koagulazzjoni, għalhekk huwa rrakkomandat illi meta warfarin jittieħed flimkien ma ’ ritonavir mogħti f’ doża bħala aġent antiretrovirali jew biex iżid l- effett farmakokinetiku, jiġu monitorjati il- parametri ta ’ kontra l- koagulazzjoni.
Anticonvulsants Carbamazepine
Mediċini għal kontra l- Konvulżjoni Carbamazepine
Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent inhibits CYP3A4 and as a result is expected to increase the plasma concentrations of carbamazepine.
Ritonavir f’ doża biex iżid l- effett farmakokinetiku jew bħala aġent antiretrovirali jimpedixxi CYP3A4, u għalhekk huwa mistenni li jżid il - konċentrazzjoni fil- plażma ta ’ carbamazepine.
Careful monitoring of therapeutic and adverse effects is recommended when carbamazepine is concomitantly administered with ritonavir.
Meta carbamazepine jittieħed flimkien ma ’ ritonavir, huwa rrakkomandat illi jssir osservazzjoni b’ attenzjoni ta ’ l- effetti terapewtiċi u avversi.
Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent induces oxidation by CYP2C9 and glucuronidation and as a result is expected to decrease the plasma concentrations of anticonvulsants.
Ritonavir f’ doża biex iżid l- effett farmakokinetiku jew bħala aġent antiretrovirali jikkaġuna l- ossidazzjoni permezz ta ’ CYP2C9 u glukuronidazzjoni, u għalhekk huwa mistenni li jnaqqas il- konċentrazzjoni fil- plażma ta ’ mediċini għal kontra l- konvulżjonijiet.
Careful monitoring of serum levels or therapeutic effects is recommended when these medicines are concomitantly administered with ritonavir.
Meta dawn il - mediċini jingħataw flimkien ma ’ ritonavir, huwa rrakkomandat li ssir osservazzjoni b’ attenzjoni tal- livelli tas- serum jew ta ’ l- effetti terapewtiċi.
Phenytoin may decrease serum levels of ritonavir.
Phenytoin jista ’ jnaqqas il- livelli tas- serum ta ’ ritonavir.
13 Ritonavir effects on Non-antiretroviral Co-administered Drugs Co-administered Drug
14 L- Effetti ta ’ ritonovir fuq mediċini li ma humiex antiretrovirali, u li jittieħdu miegħu
Amitriptyline, fluoxetine, imipramine, nortriptyline, paroxetine, sertraline
Mediċini għal kontra d- Dipressjoni Amitriptyline, fluoxetine, imipramine, nortriptyline, paroxetine, sertraline
Ritonavir dosed as an antiretroviral agent is likely to inhibit CYP2D6 and as a result is expected to increase concentrations of desipramine, imipramine, amitriptyline, nortriptyline, fluoxetine, paroxetine or sertraline.
X’ aktarx li ritonavir f’ doża bħala aġent antiretrovirali jimpedixxi CYP2D6 u għalhekk huwa mistenni li jżid il- konċentrazzjoni ta ’ desipramine, imipramine, amitriptyline, nortriptyline, fluoxetine, paroxetine jew sertraline.
Careful monitoring of therapeutic and adverse effects is recommended when these medicines are concomitantly administered with antiretroviral doses of ritonavir (see section 4.4).
Meta dawn il- mediċini jingħataw flimkien ma ’ dożi antiretrovirali ta ’ ritonavir, huwa rrakkomandat li ssir osservazzjoni b’ attenzjoni ta ’ l- effetti terapewtiċi u avversi (ara sezzjoni 4. 4).
100 single oral dose 500 q12h ↑ 145% ↑ 22% The AUC and Cmax of the 2-hydroxy metabolite were decreased 15 and 67%, respectively.
100 doża waħda orali 500 q12h ↑ 145% ↑ 22% L- AUC u Cmax tal- metabolat 2- hydroxy ġew imnaqqsa b ’ 15 u 67%, rispettivament.
Dosage reduction of desipramine is recommended when co-administered with ritonavir dosed as an antiretroviral agent.
Huwa rrakkomandat tnaqqis fid- doża ta ’ desipramine meta dan jittieħed ma ’ ritonavir dożat bħala aġent antiretrovirali.
50, single dose
50, doża waħda
↑ 2.4-fold
↑ bi 2. 4 drabi
An increase in the incidence in trazodone-related adverse events was noted when co-administered with ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer.
Meta trazodone ittieħed ma ’ ritonavir dożat bħala aġent antiretrovirali jew biex iżid l- effett farmakokinetiku, ġiet osservata żieda fl- inċidenza ta ’ l - effetti avversi relatati ma ’ trazodone.
If trazodone is co- administered with ritonavir, the combination should be used with caution, initiating trazodone at the lowest dosage and monitoring for clinical response and tolerability.
Jekk trazodone jingħata flimkien ma ’ ritonavir, it- taħlita għandha tintuża b’ attenzjoni, b’ trazodone jinbeda bl - inqas doża, u għandha ssir ukoll osservazzjoni tar- rispons kliniku u tat - tolleranza.
Antihistamines Astemizole, terfenadine
Mediċini għal kontra l- istamina Astemizole, terfenadine
Ritonavir co-administration is likely to result in increased plasma concentrations of astemizole and terfenadine and is therefore contraindicated (see section 4.3).
It- teħid ta ’ ritonavir flimkien ma ’ astemizole u terfenadine x’ aktarx iwassal għal żieda fil- konċentrazzjoni fil- plażma ta ’ astemizole u terfenadine, u għalhekk huwa kontro- indikat (ara sezzjoni 4. 3).
Increased fexofenadine levels may lessen over time as induction develops.
Meta dożat bħala aġent antiretrovirali jew biex iżid l- effett farmakokinetiku, ritonavir jista jbiddel l- effluss medjat b ’ P- glycoprotein ta ’ fexofenadine, u maż- żmien, ma ’ l- iżvilupp tal- induzzjoni, il- livelli miżjuda ta ’ fexofenadine jistgħu jonqsu.
Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent inhibits CYP3A and as a result is expected to increase the plasma concentrations of loratadine.
Ritonavir dożat biex iżid l- effett farmakokinetiku jew bħala aġent antiretrovirali jimpedixxi s- CYP3A u għalhekk huwa mistenni li jżid il - konċentrazzjoni fil- plażma ta ’ loratadine.
Careful monitoring of therapeutic and adverse effects is recommended when loratidine is concomitantly administered with ritonavir.
Meta loratidine jingħata flimkien ma ’ ritonavir, hija rrakkomandata li ssir b’ attenzjoni osservazzjoni ta ’ l - effetti terapewtiċi u l- effetti avversi.
Anti-infectives Fusidic Acid
Mediċini għal kontra il- mikrobi Fusidic Acid
Ritonavir co-administration is likely to result in increased plasma concentrations of both fusidic acid and ritonavir and is therefore contraindicated (see section 4.3).
L- użu ta ’ fusidic acid flimkien ma ’ ritonavir x’ aktarx iwassal għal żieda fil- konċentrazzjoni fil- plażma kemm ta ’ fusidic acid kif ukoll ta ’ ritonavir, u għalhekk huwa kontro- indikat (ara sezzjoni 4. 3).
150 daily 500 q12h, ↑ 4-fold ↑ 2.5-fold
150 kuljum 500 q12h, ↑b ’ 4 darbiet ↑ bi 2. 5 drabi
25-O-desacetyl rifabutin metabolite
Metabolat 25- O- desacetyl rifabutin
↑ 38-fold
↑ bi 38 darba
↑ 16-fold
↑ b’ 16 - il darba
14 Ritonavir effects on Non-antiretroviral Co-administered Drugs Co-administered Drug
L- Effetti ta ’ ritonovir fuq mediċini li ma humiex antiretrovirali, u li jittieħdu miegħu
Due to the large increase in rifabutin AUC, the concomitant use of rifabutin with ritonavir dosed as an antiretroviral agent is contraindicated (see section 4.3).
Minħabba ż- żieda kbira fl- AUC ta ’ rifabutin, l- użu flimkien ta ’ rifabutin ma ’ ritonavir dożat bħala aġent antiretrovirali huwa kontro- indikat (ara sezzjoni 4. 3).
The reduction of the rifabutin dose to 150 mg 3 times per week may be indicated for select PIs when co-administered with ritonavir as a pharmacokinetic enhancer.
Jista ’ jiġi indikat li d- doża ta ’ rifabutin tiġi mnaqqsa għal 150 mg 3 darbiet fil- ġimgħa f’ każ ta ’ ċerti PIs meta jiġu użati flimkien ma ’ ritonavir dożat biex iżid l- effett farmakokinetiku.
The Summary of Product Characteristics of the co-administered protease inhibitor should be consulted for specific recommendations.
Is- Sommarju tal - Karatteristiċi tal- Prodott ta ’ l- impeditur protejaż li jkun qiegħed jittieħed għandha tiġi kkonsultata.
Consideration should be given to official guidance on the appropriate treatment of tuberculosis in HIV-infected patients.
Għandha tingħata konsiderazzjoni lil gwida uffiċjali għat- trattament adegwat tat- tuberkulosi f ’ pazjenti infettati bl - HIV.
Although rifampicin may induce metabolism of ritonavir, limited data indicate that when high doses of ritonavir (600 mg twice daily) is co-administered with rifampicin, the additional inducing effect of rifampicin (next to that of ritonavir itself) is small and may have no clinical relevant effect on ritonavir levels in high-dose ritonavir therapy.
Għalkemm rifampicin jista ’ jġiegħel il- metaboliżmu ta ’ ritonavir, informazzjoni limitata tindika, li meta dożi għolja ta ’ ritonavir (600 mg darbtejn kuljum) jingħataw flimkien ma ’ rifampicin, l- effett addizzjonali li jġiegħel rifampicin (meta mqabbel ma ’ dak ta ’ ritonavir innifsu) huwa żgħir u jista ’ jkun li ma jħallix effett li huwa klinikament sinifikanti fuq il - livelli ta ’ ritonavir f’ każ ta ’ terapija fejn jingħataw dożi għoljin ta ’ ritonavir.
The effect of ritonavir on rifampicin is not known.
L- effett ta ’ ritonavir fuq rifampicin m’ huwiex magħruf.
200 q12h 400 q12h ↓ 82% ↓ 66% 200 q12h 100 q12h ↓ 39% ↓ 24% Concomitant use of ritonavir dosed as an antiretroviral agent and voriconazole is contraindicated due to reduction in voriconazole concentrations (see section 4.3).
200 q12h 400 q12h ↓ 82% ↓ 66% 200 q12h 100 q12h ↓ 39% ↓ 24% L- użu ta ’ ritonavir dożat bħala aġent antiretrovirali flimkien ma ’ voriconazole huwa kontro- indikat minħabba tnaqqis fil- konċentrazzjoni ta ’ voriconazole (ara sezzjoni 4. 3).
Co-administration of voriconazole and ritonavir dosed as a pharmacokinetic enhancer should be avoided, unless an assessment of the benefit/risk to the patient justifies the use of voriconazole.
L- użu ta ’ voriconazole flimkien ma ’ ritonavir dożat biex iżid l- effett farmakokinetiku għandu jiġi evitat, ħlief jekk l- istima tal- benefiċju/ riskju tal- pazjent tiġġustifika l- użu ta ’ voriconazole.
Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent induces glucuronidation and as a result is expected to decrease the plasma concentrations of atovaquone.
Ritonavir dożat biex iżid l- effett farmakokinetiku jew bħala aġent antiretrovirali jikkaġuna glukuronidazzjoni, u għalhekk hu mistenni li jnaqqas il- konċentrazzjoni fil- plażma ta ’ atovaquone.
Careful monitoring of serum levels or therapeutic effects is recommended when atovaquone is concomitantly administered with ritonavir.
Meta atovaquone jiġi mogħti flimkien ma ’ ritonavir, huwa rrakkomandat li ssir osservazzjoni b’ attenzjoni tal- livelli fis- serum jew ta ’ l- effetti terapewtiċi.
500 q12h, 200 q8h ↑ 77% ↑ 31%
200 q8h
14-OH clarithromycin metabolite
Metabolat 14- OH clarithromycin
↓ 99%
↓
Due to the large therapeutic window of clarithromycin no dose reduction should be necessary in patients with normal renal function.
Minħabba t- tieqa terapewtika kbira li għandu clarithromycin m’ hemm bżonn l- ebda tnaqqis fid- doża f’ pazjenti li għandhom funzjoni renali normali.
Clarithromycin doses greater than 1 g per day should not be co- administered with ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer.
Dożi ta ’ Clarithromycin akbar minn 1 g kull ġurnata m’ għandhomx jingħataw flimkien ma ’ ritonavir dożat bħala aġent antiretrovirali jew biex iżid l- effett farmakokinetiku.
For patients with renal impairment, a clarithromycin dose reduction should be considered: for patients with creatinine clearance of 30 to 60 ml/min the dose should be reduced by 50%, for patients with creatinine clearance less than 30 ml/min the dose should be reduced by 75%.
Għal pazjenti illi jbatu minn indeboliment renali għandu jiġi kkunsidrat tnaqqis fid- doża ta ’ clarithromycin: għal pazjenti li għandhom tneħħija tal- krejatina ta ’ minn 30 sa 60 ml/ min id- doża għandha tiġi mnaqqsa b’ 50%, għal pazjenti li għandhom tneħħija tal- krejatina ta ’ inqas minn 30 ml/ min id- doża għandha tiġi mnaqqsa b ’ 75%.
15 Ritonavir effects on Non-antiretroviral Co-administered Drugs Co-administered Drug
16 L- Effetti ta ’ ritonovir fuq mediċini li ma humiex antiretrovirali, u li jittieħdu miegħu
Ritonavir inhibits CYP3A-mediated metabolism of ketoconazole.
200 kuljum 500 q12h ↑ bi 3. 4 drabi ↑ 55% Ritonavir jimpedixxi l- metaboliżmu medjat b ’ CYP3A ta ’ ketoconazole.
Due to an increased incidence of gastrointestinal and hepatic adverse events, a dose reduction of ketoconazole should be considered when co- administered with ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer.
Minħabba żieda fl- inċidenza ta ’ l- effetti avversi gastrointestinali u epatiċi, għandu jiġi kkunsidrat tnaqqis fid- doża ta ’ ketoconazole meta dan jingħata flimkien ma ’ ritonavir dożat bħala aġent antiretrovirali jew biex iżid l - effett farmakokinetiku.
Sulfamethoxazole/Trimethoprim2
Sulfamethoxazole/ Trimethoprim2
800/160, single dose
800/ 160, doża waħda
Dose alteration of sulfamethoxazole/trimethoprim during concomitant ritonavir therapy should not be necessary.
M’ għandux għalfejn ikun hemm bżonn ta ’ tibdil fid- doża ta ’ sulfamethoxazole/ trimethoprim meta dan jingħata fl- istess żmien illi tkun qiegħda tingħata t- terapija b’ ritonavir.
Antipsychotics/Neuroleptics Clozapine, pimozide
Mediċini Anti- Psikotiċi / Newrolettiċi Clozapine, pimozide
Ritonavir co-administration is likely to result in increased plasma concentrations of clozapine or pimozide and is therefore contraindicated (see section 4.3).
L- għoti flimkien ma ’ ritonavir x’ aktarx iwassal għal żieda fil - konċentrazzjoni fil- plażma ta ’ clozapine jew pimozide, u għalhekk huwa kontro- indikat (ara sezzjoni 4. 3).
Ritonavir dosed as an antiretroviral agent is likely to inhibit CYP2D6 and as a result is expected to increase concentrations of haloperidol, risperidone and thioridazine.
Ritonavir dożat bħala aġent antiretrovirali x’ aktarx li jimpedixxi s - CYP2D6 u għalhekk huwa mistenni li jżid il- konċentrazzjoni ta ’ haloperidol, risperidone u thioridazine.
Careful monitoring of therapeutic and adverse effects is recommended when these medicines are concomitantly administered with antiretroviral doses of ritonavir (see section 4.3).
(ara sezzjoni 4. 3).
Calcium channel antagonists Amlodipine, diltiazem, nifedipine
Mediċini li jinblukkaw ir- riċetturi tal - kanali tal kalċju Amlodipine, diltiazem, nifedipine
Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent inhibits CYP3A4 and as a result is expected to increase the plasma concentrations of calcium channel antagonists.
Ritonavir dożat biex iżid l- effett farmakokinetiku jew bħala aġent antiretrovirali jimpedixxi s - CYP3A4, u għalhekk huwa mistenni li jżid il - konċentrazzjoni fil- plażma tal- mediċini li jimblukkaw ir- riċetturi tal- kanali tal- kalċju.
Careful monitoring of therapeutic and adverse effects is recommended when these medicines are concomitantly administered with ritonavir.
Meta dawn il- mediċini jingħataw flimkien ma ’ ritonavir dożat bħala aġent antiretrovirali, huwa rrakkomandat li ssir osservazzjoni b’ attenzjoni ta ’ l- effetti terapewtiċi u ta ’ l- effetti avversi.
Ergot Derivatives
(ara sezzjoni 4. 3).
Dihydroergotamine, ergonovine, ergotamine, methylergonovine
17 L- Effetti ta ’ ritonovir fuq mediċini li ma humiex antiretrovirali, u li jittieħdu miegħu
Ritonavir co-administration is likely to result in increased plasma concentrations of ergot derivatives and is therefore contraindicated (see section 4.3).
Mediċina li jittieħdu ma ’ ritonavir
Ritonavir co-administration is likely to result in increased plasma concentrations of cisapride and is therefore contraindicated (see section 4.3).
Doża tal - mediċina Doża ta ’ li jittieħdu ma ’ NORVIR ritonavir (mg) (mg)
16 Ritonavir effects on Non-antiretroviral Co-administered Drugs Co-administered Drug
Effett fuq il - mediċina li tittieħed ma ’ ritonavir AUC
Dose of Co- administered Drug (mg)
Effett fuq il - mediċina li tittieħed ma ’ ritonavir Cmax
Dose of NORVIR (mg)
Derivattivi ta ’ l- Ergotina Dihydroergotamine, ergonovine, ergotamine, methylergonovine
Effect on Co- administered Drug AUC
L- għotja ta ’ ritonavir flimkien ma ’ dihydroergotamine, ergonovine, ergotamine, methylergonovine aktarx li twassal għal żieda fil - konċentrazzjoni fil- plażma tad- derivattivi ta ’ l- ergotina, u għalhekk hija kontra- indikata (ara sezzjoni 4. 3).
Effect on Co- administered Drug Cmax
Mediċini li jaħdmu fuq il- passaġġ ta ’ fluwidi fis- sistema gastrointestinali
HMG Co-A Reductase Inhibitors
Cisapride
Atorvastatin, Fluvastatin, Lovastatin, Pravstatin, Rosuvastatin, Simvastatin
Impedituri HMG Co- A Reductase Atorvastatin, Fluvastatin, Lovastatin, Pravstatin, Rosuvastatin, Simvastatin
HMG-CoA reductase inhibitors which are highly dependent on CYP3A metabolism, such as lovastatin and simvastatin, are expected to have markedly increased plasma concentrations when co-administered with ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer.
L- impedituri HMG- CoA reductase li huma dipendenti ħafna fuq il - metaboliżmu b ’ CYP3A, bħal lovastatin u simvastatin huma mistennija li jkollhom żieda sostanzjali fil- konċentrazzjoni fil- plażma meta dawn jingħataw flimkien ma ’ ritonavir dożat bħala aġent antiretrovirali jew biex iżid l- effett farmakokinetiku.
Since increased concentrations of lovastatin and simvastatin may predispose patients to myopathies, including rhabdomyolysis, the combination of these medicinal products with ritonavir is contraindicated (see section 4.3).
Peressi illi żieda fil- konċentrazzjoni ta ’ lovastatin u simvastatin tista ’ tippredisponi lill- pazjenti għall- mijopatija, li jinkludi rabdomijoli, l- għotja ta ’ dawn il- prodotti mediċinali flimkien ma ’ ritonavir hija kontro- indikata (ara sezzjoni 4. 3).
Atorvastatin is less dependent on CYP3A for metabolism.
Atorvastatin huwa inqas dipendenti fuq is- CYP3A għall- metaboliżmu.
The mechanism of this interaction is not clear, but may be the result of transporter inhibition.
Il- mekkaniżmu ta ’ din l- interazzjoni m’ huwiex ċar, iżda jista jkun riżultat ta ’ inibizzjoni tat- trasportatur.
When used with ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent, the lowest possible doses of atorvastatin or rosuvastatin should be administered.
Meta użat ma ’ ritonavir dożat biex iżid l- effett farmakokinetiku jew bħala aġent antiretrovirali, għandhom jingħataw l- inqas dożi possibbli ta ’ atorvastatin jew rosuvastatin.
The metabolism of pravastatin and fluvastatin is not dependent on CYP3A, and interactions are not expected with ritonavir.
Il- metaboliżmu ta ’ pravastatin u fluvastatin ma jiddependix fuq CYP3A, u m’ humiex mistennija interazzjonijiet ma ’ ritonavir.
If treatment with an HMG-CoA reductase inhibitor is indicated, pravastatin or fluvastatin is recommended.
Pravastatin jew fluvastatin huwa rrakkomandat f’ każ illi jkun indikat trattament b’ impeditur HMG- CoA reductase.
Hormonal contraceptive Ethinyl estradiol
Ethinyl estradiol
50 µg single dose
X’ aktarx li ritonavir ibiddel il- profil ta ’ telf ta ’ demm mill- ġuf u jnaqqas l- effettività ta ’ kontraċettivi li jkun fihom estradiol (ara sezzjoni 4. 4).
500 q12h
18 L- Effetti ta ’ ritonovir fuq mediċini li ma humiex antiretrovirali, u li jittieħdu miegħu
↓ 40%
Mediċina li jittieħdu ma ’ ritonavir
↓ 32%
Doża tal - mediċina Doża ta ’ li jittieħdu ma ’ NORVIR ritonavir (mg) (mg)
Due to reductions in ethinyl estradiol concentrations, barrier or other non-hormonal methods of contraception should be considered with concomitant ritonavir use when dosed as an antiretroviral agent or as a pharmacokinetic enhancer.
Effett fuq il - mediċina li tittieħed ma ’ ritonavir AUC
Ritonavir is likely to change the uterine bleeding profile and reduce the effectiveness of estradiol-containing contraceptives (see section 4.4).
Effett fuq il - mediċina li tittieħed ma ’ ritonavir Cmax
Immunosupressants Cyclosporine, tacrolimus, everolimus
Mediċini Immuno- Suppressanti Cyclosporine, tacrolimus, everolimus
Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent inhibits CYP3A4 and as a result is expected to increase the plasma concentrations of cyclosporine, tacrolimus or everolimus.
Ritonavir dożat biex iżid l- effett farmakokinetiku jew bħala aġent antiretrovirali jimpedixxi CYP3A4 u għalhekk huwa mistenni li jżid il - konċentrazzjoni fil- plażma ta ’ cyclosporine, tacrolimus jew everolimus.
Careful monitoring of therapeutic and adverse effects is recommended when these medicines are concomitantly administered with ritonavir.
Meta dawn il- mediċini jingħataw flimkien ma ’ ritonavir, huwa rrakkomandat li ssir osservazzjoni b’ attenzjoni ta ’ l- effetti terapewtiċi u ta ’ l- effetti avversi.
Phosphodiesterase inhibitors Sildenafil
Impedituri Phosphodiesterase Sildenafil
100, single dose
100, doża waħda
↑ 11-fold
↑ b’ 11 - il darba
↑ 4-fold
↑ b’ 4 darbiet
Concomitant use of sildenafil with ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer is not recommended and in no instance should sildenafil doses exceed 25 mg in 48 hours (see also section 4.4).
L- użu flimkien ta ’ sildenafil ma ’ ritonavir dożat bħala aġent antiretrovirali jew biex iżid l- effett farmakokinetiku m’ huwiex rrakkomandat, u fl- ebda każ m’ għandhom id- dożi ta ’ sildenafil jeċċedu 25 mg fi 48 siegħa (ara ukoll sezzjoni 4. 4).
Concomitant use of sildenafil with ritonavir is contraindicated in pulmonary arterial hypertension patients.
L- użu flimkien ta ’ sildenafil ma ’ ritonavir huwa kontro- indikat f’ pazjenti li jbatu minn pressjoni għolja fl- arterji pulmonari.
20, single dose
20, doża waħda
The concomitant use of tadalafil with ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer should be with caution at reduced doses of no more than 10 mg tadalafil every 72 hours with increased monitoring for adverse events (see section 4.4).
L- użu flimkien ta ’ tadalafil ma ’ ritonavir dożat bħala aġent antiretrovirali jew biex iżid l- effett farmakokinetiku għandu jsir b’ attenzjoni u b’ dożi mnaqqsa ta ’ mhux aktar minn 10 mg tadalafil kull 72 siegħa, u għandu jkun hemm aktar osservazzjoni għall- effetti avversi (ara sezzjoni 4. 4).
dose
5, doża waħda
↑ 49-fold
↑ b’ 49 darba
↑ 13-fold
↑ bi 13 - il darba
17
L- użu flimkien ta ’ vardenafil ma ’ ritonavir dożat bħala aġent antiretrovirali jew biex iżid l- effett farmakokinetiku għandu jsir b’ attenzjoni u b’ dożi mnaqqsa ta ’ mhux aktar minn 2. 5 mg kull 72 siegħa, u għandu jkun hemm aktar osservazzjoni għall- effetti avversi (ara sezzjoni 4. 4).
Ritonavir effects on Non-antiretroviral Co-administered Drugs Co-administered Drug
19 L- Effetti ta ’ ritonovir fuq mediċini li ma humiex antiretrovirali, u li jittieħdu miegħu
Sedatives/hynoptics Clorazepate, diazepam, estazolam, flurazepam, oral and parenteral midazolam and triazolam
Mediċina Sedattiva / Ipnotika Clorazepate, diazepam, estazolam, flurazepam, L- għoti ta ’ ritonavir ma ’ clorazepate, diazepam, estazolam, flurazepam, midazolam mittieħed mill- ħalq u parenterali u midazolam u triazolam x’ aktarx li jwassal għal żieda fil- konċentrazzjoni triazolam
Ritonavir co-administration is likely to result in increased plasma concentrations of clorazepate, diazepam, estazolam and flurazepam and is therefore contraindicated (see section 4.3).
fil- plażma ta ’ clorazepate, diazepam, estazolam u flurazepam u għalhekk huwa kontro- indikat (ara sezzjoni 4. 3).
Midazolam is extensively metabolised by CYP3A4.
Midazolam huwa fil- biċċa l- kbira tiegħu metabolizzat b’ CYP3A4.
Co-administration with Norvir may cause a large increase in the concentration of this benzodiazepine.
L- għoti tiegħu flimkien ma ’ Norvir jista ’ jikkaġuna żieda kbira fil- konċentrazzjoni ta ’ dan il- benzodiazepine.
No drug interaction study has been performed for the co-administration of Norvir with benzodiazepines.
Ma sar l- ebda studju dwar l- effett ta ’ mediċina waħda fuq oħra fir- rigward tat - teħid flimkien ta ’ Norvir ma ’ benzodiazepines.
Based on data for other CYP3A4 inhibitors, plasma concentrations of midazolam are expected to be significantly higher when midazolam is given orally.
Skond informazzjoni dwar impedituri CYP3A4 oħra, il- konċentrazzjoni fil- plażma ta ’ midazolam hija mistennija li tkun ogħla b’ mod sinifikanti meta midazolam jingħata mill - ħalq.
Therefore, Norvir should not be co-administered with orally administered midazolam (see section 4.3), whereas caution should be used with co-administration of Norvir and parenteral midazolam.
Għalhekk, Norvir m’ għandux jingħata ma ’ midazolam mittieħed mill- ħalq (ara sezzjoni 4. 3), u wieħed għandu joqgħod attent meta jkun hemm it- teħid flimkien ta ’ Norvir u midazolam parenterali.
Data from concomitant use of parenteral midazolam with other protease inhibitors suggest a possible 3 – 4 fold increase in midazolam plasma levels.
Informazzjoni li ħarġet mill- użu ta ’ midazolam perenterali flimkien ma ’ impedituri protejażi oħra tissuġġerixxi żieda fil- livelli fil- plażma ta ’ midazolam li tista ’ tkun possibilment 3- 4 darbiet aktar.
If Norvir 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 Norvir jingħata flimkien ma ’ midazolam parenterali, dan għandu jseħħ f’ post għal kura intensiva (ICU) jew post simili fejn ikunu jsiru osservazzjoni klinikali mill- qrib u treġija medika adegwata f’ każ illi jkun hemm deppressjoni respiratorja u/ jew sedazzjoni twila aktar milli sippost.
Dosage adjustment for midazolam should be considered, especially if more than a single dose of midazolam is administered.
Għandu jiġi kkunsirat aġġustament fid- doża ta ’ midazolam, speċjalment jekk tkun ingħatat aktar minn doża waħda ta ’ midazolam.
0.125 single dose 200, 4 doses ↑ > 20 fold ↑ 87% Ritonavir co-administration is likely to result in increased plasma concentrations of triazolam and is therefore contraindicated (see section 4.3).
0. 125 doża waħda 200, 4 dożi ↑ > 20 darba ↑ 87% L- għoti ta ’ ritonavir ma ’ triazolam x’ aktarx li jwassal għal żieda fil - konċentrazzjoni fil- plażma ta ’ triazolam, u għalhekk huwa kontro- indikat (ara sezzjoni 4. 3).
50 oral single dose
50 doża waħda orali 500 q12h
↓ 62%
↓
↓ 59%
59%
Normeperidine metabolite
Metabolat Normeperidine