qanastek/EMEA-V3 huggingface dataset:
In more than a half of the reported cases, treatment with PIs was continued or re-introduced if treatment had been discontinued.
F’ iktar minn nofs il - każijiet irrapurtati, il- kura bil- PIs tkompliet jew reġgħet iddaħħlet jekk il- kura kienet twaqqfet.
A causal relationship has been evoked, although the mechanism of action has not been elucidated.
Tqajmet il- possiblita` ta ’ relazzjoni kawża- effett, għalkemm il- mekkaniżmu ta ’ l- azzjoni ma ġietx iċċarata.
Haemophiliac patients should therefore be made aware of the possibility of increased bleeding.
Pazjenti emofiliċi għandhom isiru konxji tal- possibilita` ta ’ żieda fid- dmija.
Patients with mild– to– moderate hepatic insufficiency due to cirrhosis will require a dosage reduction of indinavir due to decreased metabolism of indinavir (see section 4.2).
Ma
Patients with severe hepatic impairment have not been studied.
5 ġewx studjati pazjenti li għandhom mard qawwi fil- fwied.
In the absence of such studies, caution should be exercised as increased levels of indinavir may occur.
Fin- nuqqas ta ’ studji bħal dawn, trid tintuża l- kawtela billi jistgħu jogħlew il- livelli ta ’ indinavir.
5 Safety in patients with impaired renal function has not been studied; however, less than 20% of indinavir is excreted in the urine as unchanged drug or metabolites (see section 4.2).
Ma ġietx studjata s- sigurta` f’ pazjenti b’ mard fil- kliewi, madankollu, inqas minn 20% ta ’ indinavir jitneħħa ma ’ l- urina bħala mediċina mhux mibdula jew bħala metaboliti (ara sezzjoni 4. 2).
Although the etiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV-disease and/ or long-term exposure to combination antiretroviral therapy (CART).
Għalkemm l- etjoloġija titqies li hi multifattorjali (inkluż l- użu ta ’ kortikosterojdi, il- konsum ta ’ l - alkolħol immunosoppressjoni severa, indiċi ogħla tal- massa tal- ġisem), ġew irrapurtati każijiet ta ’ ostejonekrożi speċjalment f’ pazjenti b’ mard avvanzat ta ’ l- HIV u/ jew espożizzjoni fit- tul għat- terapija antiretrovirali kombinata (CART).
Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.
Il- pazjenti għandhom jingħataw il- parir li jfittxu parir mediku jekk ikollhom uġigħ fil- ġogi u uġigħ, ġogi ibsin u diffikultà fil- muviment.
Lactose This medicinal product contains 299.2 mg of lactose in each 800-mg dose (maximum single dose).
Lactose Il- prodott mediċinali fih 299. 2 mg ta ’ lactose f’ kull doża ta ’ 800- mg (doża singola massima).
This quantity is not likely to induce symptoms of lactose intolerance (milk intolerance).
Din il - kwantità aktarx li ma twassalx għal sintomi ta ’ intolleranza ta ’ lactose (intolleranza tal- ħalib).
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose- galactose malabsorption should not take this medicine.
Pazjenti bi problemi rari ereditarji ta ’ intolleranza ta ’ galactose, defiċjenza ta ’ Lapp lactase jew assorbiment hażin ta ’ glucose- galactose m’ għandhomx jieħdu din il- mediċina.
Interaction studies have only been performed in adults.
L- istudji ta ’ interazzjoni saru biss fuq adulti.
The relevance of the results from these studies in paediatric patients is unknown.
Mhix magħrufa r- relevanza tar- riżultati minn dawn l - istudji għal pazjenti tfal.
The metabolism of indinavir is mediated by the cytochrome P450 enzyme CYP3A4.
Il- metaboliżmu ta ’ indinavir jsir permezz ta ’ l- enzima CYP3A4 cytochrome P450.
Therefore, other substances that either share this metabolic pathway or modify CYP3A4 activity may influence the pharmacokinetics of indinavir.
Għalhekk, sustanzi oħra li jew jużaw l- istess triq metabolika jew jimmodifikaw l- attivita` ta ’ CYP3A4 jistgħu jinfluwenzaw il- karatteristiċi farmakokinetiċi ta ’ indinavir.
Similarly, indinavir might also modify the pharmacokinetics of other substances that share this metabolic pathway.
Bl- istess mod, indinavir jista ’ wkoll jimmodifika l- karatteristiċi farmakokinetiċi ta ’ sustanzi oħra li jużaw l- istess passaġġ metaboliku.
Boosted indinavir (indinavir with ritonavir) may have additive pharmacokinetic effects on substances that share the CYP3A4 pathway as both ritonavir and indinavir inhibit the cytochrome P450 enzyme CYP3A4.
Indinavir imsaħħaħ (indinavir ma ’ ritonavir) jista ’ jkollu effetti farmakokinetiċi addittivi fuq sustanzi li jaqsmu l- istess mogħdija ta ’ CYP3A4 minħabba li kemm ritonavir kif ukoll indinavir jinibixxu l - enzim ta ’ cytochrome P450, CYP3A4.
CRIXIVAN with or without ritonavir should not be administered concurrently with amiodarone, terfenadine, cisapride, astemizole, alprazolam, triazolam, midazolam administered orally (for caution on parenterally administered midazolam, see Table 1 and 2 below), pimozide, ergot derivatives, simvastatin or lovastatin.
CRIXIVAN bi jew mingħajr ritonavir ma għandux jingħata fl- istess ħin ma ’ amiodarone, terfenadine, cisapride, astemizole, alprazolam, triazolam, midazolam mogħti mill- ħalq (għal twissija fuq midazolam mogħti b’ mod parneterali, ara t- Tabella 1 u 2 taħt), pimozide, derivattivi ergot, simvastatin jew lovastatin.
In addition, indinavir with ritonavir should not be administered with alfuzosin, meperidine, piroxicam, propoxyphene, bepridil, encainide, flecanide, propafenone, quinidine, fusidic acid, clozapine, clorazepate, diazepam, estazolam and flurazepam.
Barra minn hekk, indinavir ma ’ ritonavir ma għandux jingħata ma ’ alfuzosin, meperidine, piroxicam, propoxyphene, bepridil, encainide, flecanide, propafenone, quinidine, fusidic acid, clozapine, clorazepate, diazepam, estazolam u flurazepam.
Concurrent use of indinavir with rifampicin or herbal preparations containing St John’ s wort (hypericum perforatum) is contraindicated.
Użu fl- istess ħin ta ’ indinavir ma ’ rifampicin jew ma ’ preparazzjonijiet erbali li fihom St John’ s wort (hypericum perforatum) huwa kontra- indikat.
Drugs listed above are not repeated in Table 1 and 2 unless specific interaction data is available.
Mediċini elenkati fuq mhumiex ripetuti fit- Tabella 1 u 2 sakemm ma tkunx disponibbli data speċifika.
Refer also to sections 4.2 and 4.3.
Irreferi wkoll għas- sezzjonijiet 4. 2 u 4. 3.
Table 1.
6 Tabella 1.
Interactions and dose recommendations with other medical products – UNBOOSTED INDINAVIR
Interazzjonijiet u rakkomandazzjonijiet tad- doża ma ’ prodotti mediċinali oħrajn – INDINAVIR MHUX IMSAĦĦAĦ
Interactions between indinavir and other medicinal products are listed in the tables below (increase is indicated as “↑”, decrease as “↓”, no change (≤ +/ - 20%) as “↔”, single dose as “ SD”, once daily as “ QD”, twice daily as “ BID”, three times daily as “ TID”, and four times as "QID").
Interazzjonijiet bejn indinavir u prodotti mediċinali oħrajn huma elenkati fit- tabelli taħt (żieda hija indikata bħala “ ↑ ”, tnaqqis huwa indikat bħala “ ↓ ”, ebda bidla (≤ + / - 20%) bħala “ ↔ ”, doża waħda bħala “ SD ”, darba kuljum bħala “ QD ”, darbtejn kuljum bħala “ BID ”, tliet darbiet kuljum bħala “ TID ” u erba ’ darbiet bħala "QID").
6 Medicinal products by therapeutic areas ANTI-INFECTIVES Antiretrovirals NRTIs
Prodotti medinċinali skond l- oqsma terapewtiċi ANTI- INFETTIVI Antiretrovirali NRTIs
Interaction
Interazzjoni
Recommendations concerning co- administration
Rakkomandazzjonijiet dwar l- għoti fl - istess ħin
Didanosine Formulation with buffer
Didanosine Formulazzjoni b’ buffer
No formal interaction study has been performed.
Ma twettaq ebda studju ta ’ interazzjoni formali.
A normal (acidic) gastric pH may be necessary for optimum absorption of indinavir whereas acid rapidly degrades didanosine which is formulated with buffering agents to increase pH.
Jista ’ jkun hemm bżonn ta ’ pH gastriku normali (aċidiku) għal assorbiment ottimu ta ’ indinavir filwaqt li l- aċidu jiddegrada rapidament didanosine li hija fformulata b’ sustanzi ta ’ buffer sabiex iżidu l- pH.
Antiretroviral activity was unaltered when didanosine was administered 3 hours after treatment with indinavir.
L- attività antiretrovirali ma kinitx mibdula meta didanosine ngħata 3 sigħat wara t- trattament b’ indinavir.
Indinavir and didanosine formulations containing buffer should be administered at least one hour apart on an empty stomach.
Formolazzjonijiet ta ’ indinavir u didanosine li fihom buffer għandhom jingħataw għallinqas siegħa ’ l bogħod minn xulxin fuq stonku vojt.
Didanosine enteric-coated 400 mg SD (Indinavir 800 mg SD)
Didanosine b’ kisja enterika 400 mg
(Relative to Indinavir 800 mg SD alone) Didanosine:
(Għal Indinavir 800 mg SD
Can be administered without any restrictions with respect to time of administration or food.
fir- rigward tal- ħin ta ’ l- għoti jew ta ’ l -
Stavudine 40 mg BID (Indinavir 800 mg TID)
Stavudine 40 mg BID (Indinavir 800 mg TID)
Indinavir AUC:
AUC Indinavir:
Indinavir Cmin :↔ (Relative to Indinavir 800 mg TID alone)
Cmin Indinavir: ↔ (Għal Indinavir 800 mg TID waħdu)
Indinavir and NRTIs can be co-administered without dose adjustment.
Indinavir u NRTIs jistgħu jingħataw flimkien mingħajr aġġustament fid - doża.
Stavudine AUC: ↑ 21% Staudine Cmin: not evaluated Zidovudine 200 mg TID (Indinavir 1000 mg TID)
AUC Stavudine: ↑ 21% Cmin Staudine: mhux evalwat Zidovudine 200 mg TID (Indinavir 1000 mg TID)
Indinavir Cmin:
Cmin Indinavir:
(Relative to Indinavir 1000 mg TID alone)
(Għal Indinavir 1000 mg TID waħdu)
Zidovudine AUC:
AUC Zidovudine:
Zidovudine Cmin: ↑ 51%
Cmin Zidovudine: ↑ 51%
Zidovudine/ Lamivudine 200/ 150 mg TID (Indinavir 800 mg TID)
Zidovudine/ Lamivudine 200/ 150 mg TID (Indinavir 800 mg TID)
(Relative to Indinavir 800 mg TID alone)
(Għal Indinavir 800 mg TID waħdu)
Zidovudine AUC: ↑ 39% Zidovudine Cmin:
AUC Zidovudine: ↑ 39% Cmin Zidovudine:
Lamivudine AUC:
AUC Lamivudine:
Lamivudine Cmin:
Cmin Lamivudine:
NNRTIs Delavirdine 400 mg TID (Indinavir 600 mg TID)
Delavirdine 400 mg TID (Indinavir 600 mg TID)
Indinavir AUC: ↑ 53% Indinavir Cmin ↑ 298% (Relative to Indinavir 800 mg TID alone)
AUC Indinavir: ↑ 53% Cmin Indinavir ↑ 298% (Għal Indinavir 800 mg TID waħdu)
Dose reduction of CRIXIVAN to 400-600 mg every 8 hours should be considered.
Għandu jitqies tnaqqis fid- doża ta ’ CRIXIVAN għal 400- 600 mg kull 8 sigħat.
Delavirdine 400 mg TID Indinavir 400 mg TID
Delavirdine 400 mg TID
Indinavir AUC: ↔ Indinavir Cmin: ↑ 118% (Relative to Indinavir 800 mg TID alone)
AUC Indinavir: ↔ Cmin Indinavir: ↑ 118% (Għal Indinavir 800 mg TID waħdu)
57% (Relative to Indinavir 800 mg TID alone) An increased dose (1000mg TID) of indinavir does not compensate for the inducing effect of efavirenz.
57% (Għal Indinavir 800 mg TID waħdu) Doża miżjuda (1000mg TID) ta ’ indinavir ma tikkumpensax għall- effett ta ’ induzzjoni ta ’
No specific dose recommendation can be given.
doża ma tista ’ tingħata.
31% Indinavir Cmin:
31% Cmin Indinavir:
Efavirenz AUC:
AUC Efavirenz:
Nevirapine 200 mg BID (Indinavir 800 mg TID) PIs
Nevirapine 200 mg BID (Indinavir 800 mg TID) PIs
28% Nevirapine:
28% Nevirapine:
(CYP3A induction)
(Induzzjoni CYP3An)
A dose increase of indinavir to 1000 mg every 8 hours should be considered if given with nevirapine.
Żieda fid- doża ta ’ indinavir għal 1000 mg kull 8 sigħat għandha tkun ikkunsidrata jekk mogħti ma ’ nevirapine.
Amprenavir AUC: ↑ 90% Indinavir: ↔
AUC Amprenavir: ↑ 90% Indinavir: ↔
The appropriate doses for this combination, with respect to efficacy and safety, have not been established.
Id- dożi xierqa għal din il - kombinazzjoni, fir- rigward ta ’ l - effikaċja u s- sigurtà, għadhom ma ġewx stabbiliti.
Indinavir AUC24hr:
AUC Indinavir24hr:
178% Indinavir Cmin:
178% Cmin Indinavir:
11-fold; (Relative to Indinavir 800 mg TID alone*) Ritonavir AUC:
11- il darba; (Għal Indinavir 800 mg TID waħdu *) AUC Ritonavir:
72% Ritonavir Cmin:
72% Cmin Ritonavir:
Preliminary clinical data suggest that CRIXIVAN 400 mg in
Data klinika preliminari tissuġġerixxi li CRIXIVAN 400 mg f’ kombinazzjoni ma ’ ritonavir 100 mg, it- tnejn li huma
24-fold; (Relative to Indinavir 800 mg TID alone*) Ritonavir AUC:
24 darba; (Għal Indinavir 800 mg TID waħdu *) AUC Ritonavir:
371%
371% AUC Indinavir24hr:
Ritonavir 400 mg BID (Indinavir 800 mg BID)
220% Cmin Indinavir: ↑ 24- il darba (Għal Indinavir 800 mg TID waħdu *) AUC Ritonavir24hr:
220% Indinavir Cmin :↑ 24-fold (Relative to Indinavir 800 mg TID alone*) Ritonavir AUC24hr:
jista ’ jkun reġimen ta ’ dosaġġ alternattiv (ara sezzjoni 5. 2).
indinavir/ 100 mg ritonavir twice daily results in increased risk of adverse events.
Doża msaħħa ta ’ 800 mg indinavir/ 100 mg ritonavir darbtejn kuljum tirriżulta f’ riskju miżjud ta ’ episodji avversi.
68% Indinavir Cmin: ↑ 10-fold (Relative to Indinavir 800 mg TID alone*) Ritonavir AUC24hr:
68% Cmin Indinavir: ↑ 10- il darba (Għal Indinavir 800 mg TID waħdu *) AUC Ritonavir24hr:
Indinavir AUC and Cmin: ↔ (Relative to Indinavir 800 mg TID alone*) () * historical controls
AUC Indinavir and Cmin: ↔ (Għal Indinavir 800 mg TID waħdu *) () * kontrolli storiċi
Saquinavir 600 mg SD (hard gel capsule formulation) (Indinavir 800 mg TID)
9 Prodotti medinċinali skond l- oqsma terapewtiċi Saquinavir 600 mg SD
Saquinavir AUC:
Interazzjoni AUC Saquinavir:
190% (Relative to saquinavir 600 mg SD (hard gel formulation) alone)
190% (Għal saquinavir 600 mg SD (formulazzjoni b’ ġell iebes waħdu)
The appropriate doses for this combination, with respect to efficacy and safety, have not been established.
kombinazzjoni, fir- rigward ta ’ l - effikaċja u s- sigurtà, għadhom ma ġewx stabbiliti.
Saquinavir 800 mg SD (soft gel capsule formulation) (Indinavir 800 mg TID)
Saquinavir 800 mg SD (formulazzjoni ta ’ kapsula b’ ġell artab) (Indinavir 800 mg TID)
Saquinavir AUC:
AUC Saquinavir:
620% Saquinavir Cmin:
620% Cmin Saquinavir:
450% (Relative to saquinavir 800 mg SD (soft gel formulation) alone)
450% (Għal saquinavir 800 mg SD (formulazzjoni b’ ġell artab waħdu)
450% (Relative to saquinavir 1200 mg (soft gel formulation) alone)
450% (formulazzjoni ta ’ kapsula b’ ġell (Għal saquinavir 1200 mg artab) (formulazzjoni b’ ġell artab) (Indinavir 800 mg TID) waħdu)
The design of the study does not allow for definitive evaluation of the effect of saquinavir on indinavir, but suggests there is less than a two– fold increase in indinavir AUC8h during co– administration with saquinavir
Id- disinn ta ’ l- istudju ma jippermettix evalwazzjoni definittiva ta ’ l- effett ta ’ saquinavir fuq indinavir, iżda jissuġġerixxi li hemm inqas minn darbtejn iż- żieda fl - AUC Indinavir8h matul għoti fl- istess ħin ma ’ saquinavir
Antibiotics Sulphamethoxazole/ Trimethoprim 800 mg/ 160 mg BID (Indinavir 400 mg QID) Antifungals
Antibijotiċi Sulphamethoxazole / Trimethoprim 800 mg/ 160 mg BID (Indinavir 400 mg QID) Antifungali
Indinavir AUC and Cmin:
AUC u Cmin Indinavir:
(Relative to Indinavir 400 mg QID alone) Sulphamethoxazole AUC and Cmin:
(Għal Indinavir 400 mg QID waħdu) AUC u Cmin Sulphamethoxazole:
Indinavir and sulphamethoxazole/ trimethoprim can be co- administered without dose adjustment.
Indinavir and sulphamethoxazole / trimethoprim jistgħu jingħataw flimkien mingħajr aġġustament fid - doża.
Fluconazole 400 mg QD (Indinavir 1000 mg TID)
Fluconazole 400 mg QD (Indinavir 1000 mg TID)
Indinavir AUC: ↓ 24% Indinavir Cmin:
AUC Indinavir: ↓ 24% Cmin Indinavir:
Indinavir and fluconazole can be co-administered without dose adjustment.
Indinavir and fluconazole jistgħu jingħataw flimkien mingħajr aġġustament fid- doża.
Itraconazole 200 mg BID (Indinavir 600 mg TID)
Itraconazole 200 mg BID (Indinavir 600 mg TID)
Indinavir Cmin: ↑ 49% (Relative to Indinavir 800 mg TID alone)
Cmin Indinavir: ↑ 49% (Għal Indinavir 800 mg TID waħdu)
Dose reduction of CRIXIVAN to 600 mg every 8 hours is recommended with administering itraconazole concurrently.
Tnaqqis fid- doża ta ’ CRIXIVAN għal 600 mg kull 8 sigħat huwa rakkomandat b’ għoti ta ’ itraconazole fl- istess ħin.
Ketoconazole 400 mg QD (Indinavir 600 mg TID)
Ketoconazole 400 mg QD (Indinavir 600 mg TID)
Indinavir AUC: ↓ 20% Indinavir Cmin: ↑ 29% (Relative to Indinavir 800 mg TID alone)
AUC Indinavir: ↓ 20% Cmin Indinavir: ↑ 29% (Fir- rigward ta ’ Indinavir 800
Dose reduction of CRIXIVAN to 600 mg every 8 hours should be
Għandu jitqies tnaqqis fid- doża ta ’ CRIXIVAN għal 600 mg kull 8 sigħat.
Ketoconazole 400 mg QD (Indinavir 400 mg TID)
Ketoconazole 400 mg QD (Indinavir 400 mg TID)
Indinavir AUC ↓ 56% Indinavir Cmin ↓ 27% (Relative to Indinavir 800 mg TID alone)
mg TID waħdu) AUC Indinavir ↓ 56% CmiIndinavir n ↓ 27% (Fir- rigward ta ’ Indinavir 800 mg TID waħdu)
considered.
Interazzjoni
Anti-Mycobacterial Isoniazid 300 mg QD (Indinavir 800 mg TID)
Isoniazid 300 mg QD (Indinavir 800 mg TID)
Indinavir AUC and Cmin: ↔ (Relative to Indinavir 800 mg TID alone) Isoniazid AUC and Cmin:
AUC u Cmin Indinavir: ↔ (Għal Indinavir 800 mg TID waħdu) AUC u Cmin Isoniazid:
Indinavir and isoniazid can be co-administered without dose adjustment.
Indinavir u isoniazid jistgħu jingħataw flimkien mingħajr aġġustament fid - doża.
Indinavir AUC ↓ 34% Indinavir Cmin: ↓ 39% (Relative to Indinavir 800 mg TID alone)
AUC Indinavir ↓ 34% Indinavir Cmin: ↓ 39% (Għal Indinavir 800 mg TID waħdu)
Dose reduction of rifabutin and dose increase of Crixivan has not been confirmed in clinical
Tnaqqis fid- doża ta ’ rifabutin u żieda fid- doża ta ’ Crixivan ma ġewx ikkonfermati fi studji kliniċi.
Therefore co- administration is not recommended.
Għalhekk l- amministrazzjoni fl - istess ħin mhijiex rakkomandata.
Indinavir AUC: ↓ 32% Indinavir Cmin: ↓ 40% (Relative to Indinavir 800 mg TID alone)
AUC Rifabutin: ↑ 173% Cmin Rifabutin: ↑ 244% (Għal rifabutin 300 mg QD waħdu) AUC Indinavir: ↓ 32% Cmin Indinavir: ↓ 40% (Għal Indinavir 800 mg TID waħdu)
treating HIV infection should be sought.
Jekk ikun meħtieġ trattament b’ rifabutin, wieħed għandu jfittex sustanzi alternattivi għat- trattament ta ’ infezzjoni ta ’ l- HIV.
Rifabutin AUC*: ↑ 54% Rifabutin Cmin*: ↑ 99% (*Relative to rifabutin 300 mg QD alone.
AUC Rifabutin *: ↑ 54% Cmin Rifabutin *: ↑ 99% (* Għal rifabutin 300 mg QD waħdu.
No data has been obtained comparing rifabutin 150 mg QD in combination with indinavir 800 mg TID with a reference dose of 150 mg rifabutin alone)
Ma nkisbet ebda data bit- tqabbil ta ’ rifabutin 150 mg QD f’ kombinazzjoni ma ’ indinavir 800 mg TID b’ doża ta ’ referenza ta ’ 150 mg rifabutin waħdu)
Rifampicin 600 mg QD (Indinavir 800 mg TID) ANALGESICS
Rifampicin 600 mg QD (Indinavir 800 mg TID) ANALĠESIĊI
92% (Relative to Indinavir 800 mg TID alone) This effect is due to an induction of CYP3A4 by rifampicin.
92% (Għal Indinavir 800 mg TID waħdu) Dan l- effett huwa dovut għal induzzjoni ta ’ CYP3A4 minn rifampicin.
The use of rifampicin with indinavir is contraindicated.
L- użu ta ’ rifampicin ma ’ indinavir mhuwiex rakkomandat.
Methadone 20-60 mg QD (Indinavir 800 mg TID) ANTIARRHYTHMICS
Methadone 20- 60 mg QD (Indinavir 800 mg TID) ANTIARRITMIĊI
Indinavir AUC: ↔ (Relative to Indinavir 800 mg TID historical controls) Methadone AUC and Cmin:
AUC Indinavir: ↔ (Għal kontrolli storiċi Indinavir 800 mg TID) AUC u Cmin Methadone:
Indinavir and methadone can be co-administered without dose adjustment.
Indinavir u methadone jistgħu jingħataw flimkien mingħajr aġġustament fid- doża.
Quinidine 200 mg SD (Indinavir 400 mg SD) ANTIASTHMATIC
Quinidine 200 mg SD (Indinavir 400 mg SD)
Indinavir AUC and Cmin: ↔ (Relative to Indinavir 400 mg SD) Quinidine concentration expected (CYP3A4 inhibition by indinavir)
AUC u Cmin Indinavir: ↔ (Għal Indinavir 400 mg SD) fil- konċentrazzjoni ta ’ Quinidine mistennija (inibizzjoni ta ’ CYP3A4 minn indinavir)
Caution is warranted and therapeutic concentration monitoring is recommended for quinidine when coadministered with CRIXIVAN.
Hija meħtieġa kawtela u huwa rrakkomandat monitoraġġ tal - konċentrazzjoni terapewtika għal quinidine meta mogħti fl- istess ħin ma ’ CRIXIVAN.
The use of indinavir/ ritonavir with quinidine is contraindicated.
L- użu ta ’ indinavir/ ritonavir ma ’ quinidine mhuwiex rakkomandat.
Theophylline 250 mg SD (Indinavir 800 mg TID) ANTICOAGULANT
Theophylline 250 mg SD (Indinavir 800 mg TID)
Theophylline AUC and Cmin: ↔
AUC u Cmin Theophylline: ↔
Indinavir and theophylline can be co-administered without dose adjustment.
Indinavir u theophylline jistgħu jingħataw flimkien mingħajr aġġustament fid- doża.
Warfarin ANTICONVULSANTS
Warfarin ANTIKONVULŻANTI
Not studied, combined administration may result in increased warfarin levels.
Mhux studjat, għoti kombinat jista ’ jirriżulta f’ livelli ta ’ warfarin miżjudin.
Dose adjustment of warfarin may be required.
Jista ’ jkun meħtieġ aġġustament fid - doża ta 'warfarin.
Carbamazepine, phenobarbital phenytoin
Carbamazepine, phenobarbital phenytoin ANTIDEPRESSANTI
Indinavir inhibits CYP3A4 and as a result is expected to increase the plasma concentrations of these anticonvulsants.
Indinavir jinibixxi CYP3A4 u b’ riżultat ta ’ dan huwa mistenni li jżid il- konċentrazzjonijiet tal - plażma ta ’ dawn l - antikonvulżanti.
Concomitant use of medicinal products that are inducers of CYP3A4, such as carbamazepine, phenobarbital and phenytoin may reduce indinavir plasma concentrations.
Użu fl- istess ħin ta ’ prodotti mediċinali li huma indutturi ta ’ CYP3A4, bħal carbamazepine, phenobarbital u phenytoin jistgħu jnaqqsu l - konċentrazzjonijiet tal- plażma ta ’ indinavir.
Careful monitoring of therapeutic and adverse effects is recommended when these medicines are concomitantly administered with indinavir.
Huwa rrakkomandat monitoraġġ attent ta ’ l- effetti terapewtiċi u avversi meta dawn il- mediċini jingħataw fl- istess ħin ma ’ indinavir.
Venlafaxine 50 mg TID (Indinavir 800 mg SD) CALCIUM CHANNEL BLOCKERS
Venlafaxine 50 mg TID (Indinavir 800 mg SD) IMBLOKKATURI TAL- KANAL TAL- KALĊJU
28% (Relative to Indinavir 800 mg SD alone) Venlafaxine and active metabolite O- desmethyl-venlafaxine: ↔
28% (Għal Indinavir 800 mg SD waħdu) Venlafaxine l- metabolit attiv O - desmethyl- venlafaxine: ↔
The clinical significance of this finding is unknown.
Is- sinjifikat kliniku ta ’ dan it- tisjib mhuwiex magħruf.
Dihydropyridine: e. g., felodipine, nifedipine, nicardipine HERBAL MEDICATIONS
Dihydropyridine: eż., felodipine, nifedipine, nicardipine
dihydropyridine calcium channel blocker concentration Calcium channel blockers are metabolized by CYP3A4 which is inhibited by indinavir.
konċentrazzjoni ta ’ imblokkatur tal- kanal tal- kalċju ta ’ dihydropyridine
Caution is warranted and clinical monitoring of patients is recommended.
Hija meħtieġa l- kawtela u huwa rrakkomandat il- monitoraġġ kliniku tal- pazjenti.
John’ s wort (Hypericum perforatum) 300 mg TID (Indinavir 800 mg TID)
John’ s wort (Hypericum perforatum) 300 mg TID (Indinavir 800 mg TID)
54% Indinavir Cmin: ↓ 81% (Relative to Indinavir 800 mg TID alone) Reduction in indinavir concentrations due to induction of drug metabolising and/ or transport proteins by St.
54% Cmin Indinavir: ↓ 81% (Għal Indinavir 800 mg TID waħdu) Tnaqqis fil- konċentrazzjonijiet ta ’ indinavir minħabba induzzjoni ta ’ proteini metabolizzaturi u/ jew ta ’ trasport tal- mediċina minn St.
Herbal preparations containing St.
Preparazzjonijiet erbali li fihom St.
John’ s wort are contraindicated with Crixivan.
John’ s wort mhumiex rakkomandati ma ’ Crixivan.
If a patient is already taking St.
Jekk pazjent diġà qiegħed jieħu St.
John’ s wort, stop St.
John’ s wort, waqqaf St.
John’ s wort, check viral levels and if possible indinavir levels.
John’ s wort, ikkontrolla l- livelli virali u jekk jista ’ jkun il- livelli ta ’ indinavir levels.
Indinavir levels may increase on stopping St.
Il- livelli ta ’ indinavir jistgħu jiżdiedu malli jitwaqqaf St.
John’ s wort, and the dose of CRIXIVAN may need adjusting.
John’ s wort, u d- doża ta ’ CRIXIVAN jista ’ jkollha bżonn ta ’ aġġustament.
The inducing effect may persist up to 2 weeks after cessation of treatment with St.
L- effett ta ’ induzzjoni jista ’ jibqa ’ sejjer għal mhux aktar minn ġimagħtejn wara l- waqfien tat - trattament b’ St.
Cimetidine 600 mg BID (Indinavir 400 mg SD)
ANTAGONISTA HISTAMINE H2 Cimetidine 600 mg BID (Indinavir 400 mg SD)
(Relative to Indinavir 400 mg SD alone)
(Għal Indinavir 400 mg SD waħdu)
Indinavir and cimetidine can be co-administered without dose adjustment.
Indinavir u cimetidine jistgħu jingħataw flimkien mingħajr aġġustament fid- doża.
Indinavir inhibits CYP3A4 and as a result is expected to markedly increase the plasma concentrations of these HMG-CoA reductase inhibitors, which are highly dependent on CYP3A4 metabolism.
Indinavir jinibixxi CYP3A4 u għalhekk huwa mistenni li jżid sostanzjalment il - konċentrazzjonijiet tal- plażma ta ’ dawn l- inibituri reductase ta ’ HMG- CoA, li huma dipendenti ferm fuq il- metaboliżmu ta ’ CYP3A4.
Combination contraindicated due to an increased risk of myopathy including rhabdomyolysis.
Il- kombinazzjoni hija kontra- indikata minħabba żieda fir- riskju ta ’ mijopatija inkluż rabdomijoliżi
Interaction not studied.
Interazzjoni mhux studjata.
Interaction study with Lopinavir/ ritonavir + rosuvastatin:
Studju ta ’ interazzjoni b ’ Lopinavir/ ritonavir + rosuvastatin:
Rosuvastatin AUC ↑ 2.08 -fold Rosuvastatin Cmax ↑ 4.66 -fold (Mechanism unknown)
AUC Rosuvastatin ↑ 2. 08 - il darba Cmax Rosuvastatin ↑ 4. 66 - il darba (Mekkaniżmu mhux magħruf)
Combination not recommended
Il- kombinazzjoni mhijiex rakkomandata
atorvastatin concentration Atorvastatin is less dependent on CYP3A4 for metabolism than lovastatin or simvastatin
konċentrazzjoni atorvastatin Atorvastatin huwa inqas dipendenti fuq CYP3A4 għal metaboliżmu minn lovastatin jew simvastatin
Use the lowest possible dose of atorvastatin with careful monitoring.
Uża l- iżgħar doża possibbli ta ’ atorvastatin b’ monitoraġġ attent.
Caution is advised.
Hija rrakkomandata l- kawtela.
Pravastatin, fluvastatin
Pravastatin, fluvastatin IMMUNOSUPPRESSIVI
Interaction not studied Metabolism of pravastatin and fluvastatin is not dependent on CYP3A4.
Interazzjoni mhux studjata Il- metaboliżmu ta ’ pravastatin u fluvastatin mhuwiex dipendenti fuq CYP3A4.
Interaction via effects on transport proteins cannot be excluded.
Interazzjoni permezz ta ’ effetti fu il- proteini tat- trasport ma tistax tkun eskluża.
Interaction unknown.
Interazzjoni mhux magħrufa.
If no alternative treatment is available, use with careful monitoring.
Jekk ebda kura alternattiva ma tkun disponibbli, uża b’ monitoraġġ attent.
Cyclosporine A ORAL CONTRACEPTIVES
Cyclosporine A KONTRAĊETTIVI ORALI
Cyclosporine A (CsA) levels markedly increase in patients on PIs, including indinavir.
Livelli ta ’ Cyclosporine A (CsA) jiżdiedu sostanzjalment f’ pazjenti fuq PIs, inkluż indinavir.
CsA levels require progressive dose adjustment using therapeutic drug monitoring.
Il- livelli CsA jeħtieġu aġġustament progressiv fid- doża permezz ta ’ monitoraġġ terapewtiku tal- mediċina.
Norethindrone/ ethinyl estradiol 1/ 35 1 mcg QD (Indinavir 800 mg TID) PDE5 INHIBITOR
Norethindrone/ ethinyl estradiol 1/ 35 1 mcg QD (Indinavir 800 mg TID) INIBITUR PDE5
Norethindrone AUC: ↑ 26% Norethindrone Cmin: ↑ 44%
AUC Norethindrone: ↑ 26% Cmin Norethindrone: ↑ 44%
Indinavir and norethindrone/ ethinyl estradiol 1/ 35 can be co- administered without dose adjustment.
Indinavir u norethindrone/ ethinyl estradiol 1/ 35 jistgħu jingħataw flimkien mingħajr aġġustament fid - doża.
11% Sildenafil AUC 340%
11% AUC Sildenafil 340%
Sildenafil dose should not exceed a maximum of 25 mg in a 48-hour period in
Doża ta ’ Sildenafil ma għandhiex taqbeż massimu ta ’ 25 mg f’ perjodu ta ’ 48 siegħa f’ pazjenti li jirċievu kura
Coadministration of CRIXIVAN with sildenafil is likely to result in an increase of sildenafil by competitive inhibition of metabolism.
L- għoti fl- istess ħin ta ’ CRIXIVAN u sildenafil x’ aktarx li jirriżulta f’ żieda ta ’ sildenafil b’ inibizzjoni kompetittiva tal- metaboliżmu.
patients receiving concomitant indinavir therapy.
b’ indinavir fl- istess ħin.
Vardenafil AUC: ↑ 16-fold Coadministration of CRIXIVAN with vardenafil is likely to result in an increase of vardenafil by competitive inhibition of metabolism.
AUC Vardenafil: ↑ 16- il darba L- għoti fl- istess ħin ta ’ CRIXIVAN ma ’ vardenafil x’ aktarx li jirriżulta f’ żieda ta ’ vardenafil b’ inibizzjoni kompetittiva tal- metaboliżmu.
Vardenafil dose should not exceed a maximum of 2.5 mg in a 24-hour period in patients receiving concomitant indinavir therapy.
Doża ta ’ Vardenafil ma għandhiex taqbeż massimu ta ’ 2. 5 mg f’ perjodu ta ’ 24 siegħa f’ pazjenti li jirċievu terapija ta ’ indinavir fl- istess ħin.
Interaction not studied
Interazzjoni mhux studjata
Tadalafil dose should not exceed a maximum of 10
Doża ta ’ Tadalafil ma għandhiex taqbeż massimu ta ’ 10 mg f’ perjodu
SEDATIVES/ HYPNOTICS
SEDATTIVI/ IPNOTIĊI
Coadministration of CRIXIVAN with tadalafil is likely to result in an increase of tadalafil by competitive inhibition of metabolism.
L- għoti fl- istess ħin ta ’ CRIXIVAN ma ’ tadalafil x’ aktarx li jirriżulta f’ żieda ta ’ tadalafil b’ inibizzjoni kompetittiva tal- metaboliżmu.
mg in a 72 hour period in patients receiving concomitant indinavir therapy.
ta ’ 72 siegħa f’ pazjenti li jirċievu terapija ta ’ indinavir fl- istess ħin.
Midazolam (parenteral)
Midazolam (parenterali)
Not studied, combined administrations are expected to significantly increase concentrations of midazolam, particularly when midazolam is given orally.
Ma ġietx studjata, għoti kkombinat huwa mistenni li jżid b’ mod sinjifikanti l - konċentrazzjonijiet ta ’ midazolam, b’ mod partikolari meta midazolam jingħata mill - ħalq.
CRIXIVAN and oral midazolam should not be coadministered (see section 4.3).
CRIXIVAN u midazolam li jittieħed mill- ħalq ma għandhomx jingħataw flimkien (ara sezzjoni 4. 3).
Caution should be used with coadministration
Jekk CRIXIVAN jingħata fl - istess ħin ma ’ midazolam parenterali, dan għandu jsir f’ taqsima ta ’ kura
Midazolam is extensively metabolized by CYP3A4.
Midazolam huwa metabolizzat b’ mod estensiv minn CYP3A4.
If CRIXIVAN is coadministered with parenteral midazolam, it should be done in an intensive care unit with close clinical monitoring in case of respiratory depression and/ or prolonged sedation.
intensiva b’ monitoraġġ kliniku mill - qrib fil- każ ta ’ depressjoni respiratorja u/ jew sedazzjoni mtawwla.
Dosage adjustment for midazolam should be considered, especially if more than a single dose of midazolam is administered.
Għandu jkun ikkunsidrat aġġustament fid- doża għal midazolam, b’ mod pseċjali jekk tingħata aktar minn doża waħda ta ’ midazolam.
Interaction not studied ↑ dexamethasone exposure expected (CYP3A inhibition). ↓ indinavir plasma concentrations may be expected (CYP3A induction).
Interazzjoni mhux studjata ↑ mistennija espożizzjoni għal dexamethasone (inibizzjoni CYP3A). ↓ jistgħu jkunu mistennija konċentrazzjonijiet tal- plażma ta ’ indinavir (induzzjoni CYP3An).
Careful monitoring of therapeutic and adverse effects is recommended when dexamethasone is concomitantly administered with indinavir.
Huwa rrakkomandat monitoraġġ attent ta ’ l- effetti terapewtiċi u avversi meta dexamethasone jingħata fl- istess ħin ma ’ indinavir.
Interactions and dose recommendations with other medical products – INDINAVIR BOOSTED WITH RITONAVIR.
Interazzjonijiet u rakkomandazzjonijiet dwar id- doża ma ’ prodotti mediċinali oħrajn – INDINAVIR IMSAĦĦAĦ MA ’ RITONAVIR.
No specific interaction studies have been performed with the boosted dose 400 mg indinavir with 100 mg ritonavir.
Ma sar ebda studju speċifiku dwar l- interazzjoni bid- doża msaħħa ta ’ 400 mg indinavir b’ 100 mg ritonavir.
Interactions between indinavir/ ritonavir and other medicinal products are listed in the tables below (increase is indicated as “↑”, decrease as “↓”, no change (≤ +/ - 20%) as “↔”, single dose as “ SD”, once daily as “ QD”, twice daily as “ BID”, three times daily as “ TID”, and four times as "QID").
Interazzjonijiet bejn indinavir/ ritonavir u prodotti mediċinali oħrajn huma elenkati fit- tabelli taħt (żieda hija indikata bħala “ ↑ ”, tnaqqis bħala “ ↓ ”, ebda bidla (≤ + / - 20%) bħala “ ↔ ”, doża waħda bħala “ SD ”, darba kuljum bħala “ QD ”, darbtejn kuljum bħala “ BID ”, tliet darbiet kuljum bħala “ TID ” u erba ’ darbiet bħala "QID").
Medicinal products by therapeutic areas ANTI-INFECTIVES Antiretrovirals
Prodotti mediċinali skond il - qasam terapewtiku ANTI- INFETTIVI Antiretrovirali
Recommendations concerning co-administration
Rakkomandazzjonijiet dwar l - għoti fl- istess ħin
Amprenavir 1200 mg BID AUC ↑ 90% with 800 mg TID indinavir alone (see Table 1).
AUC Amprenavir BID 1200 mg ↑90% b’ 800 mg TID indinavir waħdu (ara Tabella 1).
Amprenavir 600 mg BID AUC ↑ 64% with 100 mg BID ritonavir alone (relative to amprenavir 1200 mg BID alone).
AUC Amprenavir BID 600 mg ↑ 64% b’ 100 mg BID ritonavir waħdu (Għal amprenavir 1200 mg BID waħdu).
Ritonavir increases the serum levels of amprenavir as a result of CYP3A4 inhibition.
Ritonavir iżid il- livelli tas- serum ta ’ amprenavir bħala konsegwenza ta ’ l- inibizzjoni ta ’ CYP3A4.
There are no interaction data available on the coadministration of indinavir/ ritonavir and amprenavir.
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The appropriate doses for this combination, with respect to efficacy and safety, have not been established.
Id- dożi xierqa għal din il - kombinazzjoni, fir- rigward ta ’ l- effikaċja u s- sigurtà, għadhom ma ġewx stabbiliti.
Ritonavir 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.
Is- soluzzjoni orali Ritonavir ma għandhiex tingħata fl - istess ħin mas- soluzzjoni orali amprenavir lil tfal minħabba r - riskju ta ’ tossiċità minn sustanzi attivi fiż- żewġ formulazzjonijiet.
25% Indinavir Cmin ↓ 50% (Relative to Indinavir/ ritonavir 800/ 100 BID alone)
25% Indinavir Cmin ↓ 50% (Għal Indinavir/ ritonavir 800/ 100 BID waħdu)
Dose increases of indinavir/ ritonavir when given in combinatin with efavirenz have not been studied.
Żidiet fid- doża ta ’ indinavir/ ritonavir meta mogħti f’ kombinazzjoni ma ’ efavirenz ma ġewx studjati.
Ritonavir AUC ↓ 36% Ritonavir Cmin:
AUC Ritonavir ↓ 36% Cmin Ritonavir:
Efavirenz AUC and Cmin: ↔
AUC u Cmin Efavirenz: ↔
Anti-Mycobacterial Rifabutin
Anti- Mijkobatterjali Rifabutin
Interaction with indinavir/ ritonavir not studied Decreased indinavir concentrations and increased rifabutin concentrations are expected.
L- interazzjoni indinavir/ ritonavir ma ġietx studjata Huma mistennija konċentrazzjonijiet imnaqqsa ta ’ indinavir u konċentrazzjonijiet miżjuda ta ’ rifabutin.
No dose recommendations for indinavir/ ritonavir with rifabutin could be given, therefore the combination is not recommended.
Ebda rakkomandazzjoni tad - doża għal indinavir/ ritonavir b ’ rifabutin ma tista ’ tingħata, għalhekk il- kombinazzjoni mhijiex rakkomandata.
If rifabutin treatment is required, alternative agents for treating HIV infection should be sought.
Jekk il - kura b’ rifabutin hija meħtieġa, wieħed għandu jirrikorri għal sustanzi alternattivi għat - trattament ta ’ infezzjoni tal - HIV.
Rifampicin Other Anti-infectives
Rifampicin Anti- infettivi oħrajn
Rifampicin is a strong CYP3A4 inducer and has been shown to cause a 92% decrease in indinavir AUC which can result in virological failure and resistance development.
Rifampicin huwa induttur b’ saħħtu ta ’ CYP3A4 u ntwera li jikkawża tnaqqis ta ’ 92% fl- AUC ta ’ indinavir li tista ’ tirriżulta fi ħsara viroloġika u f’ reżistenza għall- iżvilupp.
During attempts to overcome the decreased exposure by increasing the dose of other protease inhibitors with ritonavir, a high frequency of liver reactions was seen.
Matul tentattivi biex tingħeleb l- espożizzjoni mnaqqsa billi tiżdied id- doża ta ’ inibituri protease oħrajn b’ ritonavir, intweriet frekwenza għolja ta ’ reazzjonijiet tal- fwied.
The combination of rifampicin and CRIXIVAN with concomitant low-dose ritonavir is contraindicated (see section 4.3).
Il- kombinazzjoni ta ’ rifampicin u CRIXIVAN ma ’ doża baxxa ta ’ ritonavir li tingħata fl- istess ħin hija kontraindikata (ara sezzjoni 4. 3).
Interaction with indinavir/ ritonavir not studied Ritonavir induces glucuronidation and as a result is expected to decrease the plasma concentrations of atovaquone.
Ritonavir jinduċi glukuronidazzjoni u b’ konsegwenza t’ hekk huwa mistenni li jnaqqas il- konċentrazzjonijiet tal- plażma ta ’ atovaquone.
Careful monitoring of therapeutic and adverse effects is recommended when atovaquone is concomitantly administered with indinavir/ ritonavir.
Huwa rrakkomandat monitoraġġ attent ta ’ l- effetti terapewtiċi u avversi meta atovaquone jingħata fl- istess ħin ma ’ indinavir/ ritonavir.
Erythromycin, Itraconazole
Erythromycin, Itraconazole
Interaction with indinavir/ ritonavir not studied Indinavir and ritonavir inhibit CYP3A4 and as a result are expected to increase the plasma concentrations of erythromycin and itraconazole.
Indinavir u ritonavir jinibixxu CYP3A4 u b’ konsegwenza t’ hekk huma mistennija li jżidu l- konċentrazzjonijiet tal - plażma ta ’ erythromycin and itraconazole.
Careful monitoring of therapeutic and adverse effects is recommended when erythromycin or itraconazole are concomitantly administered with indinavir/ ritonavir.
Huwa rrakkomandat monitoraġġ attent ta ’ l- effetti terapewtiċi u avversi meta erythromycin jew itraconazole jingħataw fl- istess ħin ma ’ indinavir/ ritonavir.
Ketoconazole ANALGESICS
Ketoconazole ANALĠESIĊI
Interaction with indinavir/ ritonavir not studied Indinavir and ritonavir inhibit CYP3A4 and as a result are expected to increase the plasma concentrations of ketoconazole.
Indinavir u ritonavir jinibixxu CYP3A4 u b’ konsegwenza t’ hekk huma mistennija li jżidu l- konċentrazzjonijiet tal- plażma ta ’ ketoconazole.
Co- administration of ritonavir and ketoconazole caused an increased incidence of gastrointestinal and hepatic adverse events.
L- għoti fl- istess ħin ta ’ ritonavir u ketoconazole ikkawża żieda fl- inċidenza ta ’ episodji avversi gastrointestinali u epatiċi.
Careful monitoring of therapeutic and adverse effects is recommended when ketoconazole is concomitantly administered with indinavir/ ritonavir.
Huwa rrakkomandat monitoraġġ attent ta ’ l- effetti terapewtiċi u avversi meta ketoconazole jingħata fl- istess ħin ma ’ indinavir/ ritonavir.
A dose reduction of ketoconazole should be considered when co- administered with indinavir/ ritonavir.
Għandu jitqies tnaqqis fid - doża ta ’ ketoconazole meta mogħti flimkien ma ’ indinavir/ ritonavir.
Interaction with indinavir/ ritonavir not studied Indinavir and ritonavir inhibit CYP3A4 and as a result are expected to increase the plasma concentrations of fentanyl.
15
Careful monitoring of therapeutic and adverse effects is recommended when fentanyl is concomitantly administered with indinavir/ ritonavir.
Huwa rrakkomandat monitoraġġ attent ta ’ l- effetti terapewtiċi u avversi meta fentanyl jingħata fl- istess ħin ma ’ indinavir/ ritonavir.
Methadone
Methadone
Interaction with indinavir/ ritonavir not studied
L- interazzjoni indinavir/ ritonavir ma ġietx studjata
Increased methadone dose may be necessary when
Doża miżjuda ta ’ methadone tista ’ tkun meħtieġa meta mogħtija fl- istess ħin ma ’
There is no significant effect of unboosted indinavir on methadone AUC (see Table 1 above).
Ma hemm ebda effett sinjifikanti ta ’ indinavir mhux imsaħħaħ fuq l- AUC tal- methadone (ara t- Tabella 1 fuq).
Dose adjustment should be considered based on the
Aġġustament fid- doża għandu jkun ikkunsidrat abbażi tar - rispons kliniku tal- pazjent għal
Decreases in methadone AUC has been observed with other ritonavir-boosted protease inhibitors.
Ġie osservat tnaqqis fl- AUC tal- methadone b’ inibituri tal- protease b ’ ritonavir imsaħħaħ oħrajn.
Ritonavir may induce glucuronidation of methadone.
Ritonavir jista ’ jwassal għal glukuronizzazzjoni tal- methadone.
patient’ s clinical response to methadone therapy.
terapija b’ methadone.
Morphine
Morfina ANTIARRITTMIĊI
Interaction with indinavir/ ritonavir not studied Morphine levels may be decreased due to induction of glucuronidation by coadministered ritonavir.
L- interazzjoni indinavir/ ritonavir ma ġietx studjata.
Careful monitoring of therapeutic and adverse effects is recommended when morphine is concomitantly administered with indinavir/ ritonavir.
Il- livelli tal- morfina jistgħu jitnaqqsu minħabba induzzjoni ta ’ glukuronidazzjoni minn ritonavir mogħti fl- istess ħin.
14 Medicinal products by therapeutic areas ANTIARRTHYMICS
Huwa rrakkomandat monitoraġġ attent ta ’ l- effetti terapewtiċi u avversi meta l - morfina tingħata fl- istess ħin ma ’ indinavir/ ritonavir.
Digoxin 0.4 mg SD Ritonavir 200 mg BID ANTICOAGULANT
Digoxin 0. 4 mg SD Ritonavir 200 mg BID ANTIKOAGULANTI
Interaction with indinavir/ ritonavir not studied Digoxin AUC:
AUC Digoxin:
Ritonavir may increase digoxin levels due to modification of P-glycoprotein mediated digoxin efflux.
Ritonavir jista ’ jżid il- livelli ta ’ digoxin minħabba modifikazzjoni ta ’ efflussi ta ’ digoxin medjati b’ P - glycoprotein.
Careful monitoring of digoxin levels is recommended when digoxin is concomitantly administered with indinavir/ ritonavir.
Huwa rrakkomandat monitoraġġ attent meta digoxin jingħata fl - istess ħin ma ’ indinavir/ ritonavir.
Warfarin Ritonavir 400 mg BID ANTICONVULSANTS
Warfarin Ritonavir 400 mg BID ANTIKONVULŻANTI
Interaction with indinavir/ ritonavir not studied R-warfarin levels may be decreased leading to reduced anticoagulation due to induction of CYP1A2 and CYP2C9 by ritonavir.
L- interazzjoni indinavir/ ritonavir ma ġietx studjata Il- livelli ta ’ R- warfarin jistgħu jitnaqqsu u jwasslu għal antikoagulazzjoni mnaqqsa minħabba induzzjoni ta ’ CYP1A2 u CYP2C9 ma ’ ritonavir.
Anticoagulation parameters should be monitored when warfarin is coadministered with indinavir/ ritonavir.
Il- parametri ta ’ antikoagulazzjoni għandhom jiġu mmonitorjati meta warfarin jingħata fl- istess ħin ma ’ indinavir/ ritonavir.
Interaction with indinavir/ ritonavir not studied Indinavir and ritonavir inhibit CYP3A4 and as a result are expected to increase the plasma concentrations of carbamazepine.
Indinavir u ritonavir jinibixxu CYP3A4 u b’ konsegwenza t’ hekk huma mistennija li jżidu l- konċentrazzjonijiet tal - plażma ta ’ carbamazepine.
Careful monitoring of therapeutic and adverse effects is recommended when carbamazepine is concomitantly administered with indinavir/ ritonavir.
Huwa rrakkomandat monitoraġġ attent ta ’ l- effetti terapewtiċi u avversi meta carbamazepine jingħata fl - istess ħin ma ’ indinavir/ ritonavir.
Divalproex, lamotrigine, phenytoin ANTIDEPRESSANTS
Divalproex, lamotrigine, phenytoin ANTIDEPRESSJONI
Interaction with indinavir/ ritonavir not studied Ritonavir induces oxidation by CYP2C9 and glucuronidation and as a result is expected to decrease the plasma concentrations of anticonvulsants.
Ritonavir jinduċi l- ossidazzjoni minn CYP2C9 u glukuronidazzjoni u b’ konsegwenza huwa mistenni li jnaqqas il - konċentrazzjoni tal- plażma ta ’ antikonvulsanti.
Careful monitoring of serum levels or therapeutic effects is recommended when these medicines are concomitantly administered with indinavir/ ritonavir.
Huwa rrakkomandat monitoraġġ b’ attenzjoni tal - livelli ta ’ serum jew ta ’ l - effetti terapewtiċi meta dawn il- mediċini jingħataw fl- istess ħin ma ’ indinavir/ ritonavir.
Phenytoin may decrease serum levels of ritonavir.
Phenytoin jista ’ jnaqqas il - livelli fis- serum ta ’ ritonavir.
Trazodone 50 mg SD Ritonavir 200 mg BID ANTIHISTAMINES
Trazodone 50 mg SD Ritonavir 200 mg BID
Interaction with indinavir/ ritonavir not studied Trazodone AUC:
AUC Trazodone:
2.4-fold An increase in the incidence in trazodone- related adverse events was noted when coadministered with ritonavir.
2. 4- il darba Ġiet innotata żieda fl- inċidenza f’ episodji avversi relatati ma ’ trazodone meta mogħti flimkien ma ’ ritonavir.
The combination of trazodone with indinavir/ ritonavir should be used with caution, initiating trazodone at the lowest dosage and monitoring for clinical response and tolerability.
Il- kombinazzjoni ta ’ trazodone ma ’ indinavir/ ritonavir għandha tintuża b’ kawtela, filwaqt li trazodone jinbeda fl - iżgħar doża u filwaqt li jsir monitoraġġ għar- rispons kliniku u t- tollerabilità.
Interaction with indinavir/ ritonavir not studied Ritonavir may modify P-glycoprotein mediated fexofenadine efflux when coadministered resulting in increased concentrations of fexofenadine.
Ritonavir jista ’ jimmodifika efflussi ta ’ fexofenadine medjati b’ P- glycoprotein meta mogħti fl- istess ħin u dan iwassal f’ konċentrazzjonijiet miżjuda ta ’ fexofenadine.
Careful monitoring of therapeutic and adverse effects is recommended when fexofenadine is concomitantly administered with indinavir/ ritonavir.
Huwa rrakkomandat monitoraġġ attent ta ’ l- effetti terapewtiċi u avversi meta fexofenadine jingħata fl- istess ħin ma ’ indinavir/ ritonavir.
Loratidine CALCIUM CHANNEL BLOCKERS
Loratidine IMBLOKKATURI TAL- KANALI TAL - KALĊJU
Interaction with indinavir/ ritonavir not studied Indinavir and ritonavir inhibit CYP3A4 and as a result are expected to increase the plasma concentrations of loratidine.
Indinavir u ritonavir jinibixxu CYP3A4 u b’ konsegwenza t’ hekk huma mistennija li jżidu l- konċentrazzjonijiet tal - plażma ta ’ loratidine.
Careful monitoring of therapeutic and adverse effects is recommended when loratidine is concomitantly administered with indinavir/ ritonavir.
Huwa rrakkomandat monitoraġġ attent ta ’ l- effetti terapewtiċi u avversi meta loratidine jingħata fl- istess ħin ma ’ indinavir/ ritonavir.
Dilitazem AUC0-24hr:
AUC0- 24hr Dilitazem:
43% Indinavir/ ritonavir AUCs: ↔
43% AUC Indinavir / Ritonavir: ↔
Dose modification of calcium channel blockers should be considered when co-
modifikazzjoni fid- doża ta ’ imblokkaturi tal- kanali tal - kalċju meta mogħti fl- istess
Amlodipine 5 mg QD (Indinavir/ ritonavir 800/ 100 BID)
Amlodipine 5 mg QD (Indinavir/ ritonavir 800/ 100 BID) INIBITURI REDUCTASE HMG- CoA IMMUNOSUPPRESSIVI
Amlodipine AUC0-24hr:
AUC0- 24hr Amlodipine:
80% Indinavir/ ritonavir AUCs: ↔
80% AUC Indinavir / Ritonavir: ↔
administered with indinavir/ ritonavir as it may result in an increased response.
ħin ma ’ indinavir/ ritonavir minħabba li tista ’ tirriżulta f’ rispons miżjud.
15 Medicinal products by Interaction therapeutic areas HMG-CoA REDUCTASE INHIBITORS IMMUNOSUPPRESSIVES
L- istess rakkomandazzjonijiet bħal ta ’ indinavir mingħajr tisħiħ ta ’ ritonavir (ara Tabella 1).
Recommendations concerning co-administration Same recommendations as for indinavir without ritonavir boosting (see Table 1).
Cyclosporine A (Indinavir/ ritonavir 800/ 100 BID)
Cyclosporine A Following initiation of indinavir/ ritonavir (Indinavir/ ritonavir 800/ 100 800/ 100 BID or lopinavir/ ritonavir 400/ 100 BID) BID, dose reduction of cyclosporine A to 5- 20% of prior dose was needed to maintain cyclosporine A levels within therapeutic range in one study.
Wara l- bidu ta ’ indinavir/ ritonavir 800/ 100 BID jew lopinavir/ ritonavir 400/ 100 BID, tnaqqis fid- doża ta ’ cyclosporine A għal 5 - 20% ta ’ doża preċedenti kienet meħtieġa sabiex il- livelli ta ’ cyclosporine A jinżammu fi ħdan il- medda terapewtika fi studju wieħed.
Cyclosporine A dose adjustments should be made according to measured cyclosporine A trough blood levels.
Għandhom isiru aġġustamenti fid- doża ta ’ Cyclosporine A skond l- inqas livelli tad- demm cyclosporine A imkejla.
PDE5 INHIBITOR
Tacrolimus INIBITUR PDE5
Careful monitoring of therapeutic and adverse effects is recommended when tacrolimus is concomitantly administered with indinavir/ ritonavir.
Huwa rrakkomandat monitoraġġ attent ta ’ l- effetti terapewtiċi u avversi meta tacrolimus jingħata fl- istess ħin ma ’ indinavir/ ritonavir.
For sildenafil and tadalafil, same recommendations as for indinavir without ritonavir boosting (see Table 1).
Għal sildenafil u tadalafil, l - istess rakkomandazzjonijiet bħal ta ’ indinavir mingħajr tisħiħ ta ’ ritonavir (ara Tabella 1).
SEDATIVES/ HYPNOTICS
Vardenafil SEDATTIVI/ IPNOTIĊI
Vardenafil dose should not exceed a maximum of 2.5 mg in a 72-hour period when given with a boosted protease inhibitor.
Id- doża ta ’ Vardenafil ma għandhiex taqbeż massimu ta ’ 2. 5 mg f’ perjodu ta ’ 72 siegħa meta mogħtija b’ inibitur tal - protease imsaħħaħ.
Buspirone Interaction with indinavir/ ritonavir not studied Indinavir and ritonavir inhibit CYP3A4 and as a result are expected to increase the plasma concentrations of buspirone.
Indinavir u ritonavir jinibixxu CYP3A4 u b’ konsegwenza t’ hekk huma mistennija li jżidu l- konċentrazzjonijiet tal - plażma ta ’ buspirone.