qanastek/EMEA-V3 huggingface dataset:
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).
Avolja l- etjoloġija hija kkunsidrata bħala affettwata minn ħafna fatturi (inklużi użu ta ’ kortikosterojdi, użu ta ’ alkoħol, suppressjoni immunitarja serja ħafna, indiċi tal- piż tal- ġisem għoli) każijiet ta ’ osteonekrożi ġew irrappurtati partikolarment f’ pazjenti fi stat avvanzat ta ’ HIV u/ jew esposizzjoni twila għal terapija antiretrovirali (CART).
Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.
Pazjenti għandhom jiġu avżati li jfittxu parir mediku jekk jesperjenzaw uġiegħ jew ebusija fil- ġogi, jew diffikulta fil- movimenti.
PR interval prolongation
Titwil ta ’ l- intervall PR
Lopinavir/ ritonavir has been shown to cause modest asymptomatic prolongation of the PR interval in some healthy adult subjects.
Ġie ppruvat li f’ xi suġġetti adulti li huma f’ saħħithom lopinavir/ ritonavir jikkawża titwil mhux kbir li ma jurix sintomi ta ’ l- intervall PR.
Rare reports of 2nd or 3rd degree atroventricular block in patients with underlying structural heart disease and pre-existing conduction system abnormalities or in patients receiving drugs known to prolong the PR interval (such as verapamil or atazanavir) have been reported in patients receiving lopinavir/ ritonavir.
F’ pazjenti li jirċievu lopinavir/ ritonavir ġew irrappurtati każi rari ta ’ imblukkar atrioventrikulari tat- tieni jew tat- tielet grad f’ pazjenti b’ mard eżistenti fl- istruttura tal- qalb u li kellhom abnormalitajiet eżistenti fis- sistema tat- trasmissjoni ta ’ l- impulsi fin- nervituri jew f’ pazjenti li kienu qegħdin jingħataw mediċini magħrufa li jtawlu l- intervall PR (bħal verapamil jew atazanavir).
Kaletra should be used with caution in such patients (see section 5.1).
F’ pazjenti bħal dawn, Kaletra għandu jintuża b’ kawtela (ara sezzjoni 5. 1).
Interactions with medicinal products
5 Interazzjonijiet ma ’ prodotti mediċinali
Kaletra contains lopinavir and ritonavir, both of which are inhibitors of the P450 isoform CYP3A.
Kaletra fiha lopinavir u ritonavir, it- tnejn li huma inibituri ta ’ l- iżoforma P450 CYP3A.
Kaletra is likely to increase plasma concentrations of medicinal products that are primarily metabolised by CYP3A.
Kaletra x’ aktarx li jżid il- konċentrazzjoni fil- plażma ta ’ prodotti mediċinali li primarjament huma metabolizzati minn CYP3A.
These increases of plasma concentrations of co-administered medicinal products could increase or prolong their therapeutic effect and adverse events (see sections 4.3 and 4.5).
Dawn iż- żidiet ta ’ konċentrazzjonjiet fil- plażma ta ’ prodotti mediċinali ko- somministrati jistgħu jżidu jew jipprolungaw l- effett terapewtiku u l- eventi avversi (ara sezzjoni 4. 3).
The HMG-CoA reductase inhibitors simvastatin and lovastatin are highly dependent on CYP3A for metabolism, thus concomitant use of Kaletra with simvastatin or lovastatin is not recommended due to an increased risk of myopathy including rhabdomyolysis.
L- inibituri HMG- CoA reductase simvastatin u lovastatin jiddependu ħafna fuq CYP3A għal metaboliżmu, allura teħid flimkien ta ’ Kaletra ma ’ simavastatin jew lovastatin mhuwiex rakkomandat minħabba żieda fir- riskju ta ’ mijopatija li jinkludi rabdomilożi.
Caution must also be exercised and reduced doses should be considered if Kaletra is used concurrently with rosuvastatin or with atorvastatin, which is metabolised to a lesser extent by CYP3A4.
Kawtiela għandha tintwera u dożi ridotti għandhom jiġu kkunsidrati jekk Kaletra jintuża flimkien ma ’ rosuvastatin jew ma ’ atorvastatin, li huma metabolizzati minn CYP3A b’ mod anqas estensiv.
If treatment with a HMG-CoA reductase inhibitor is indicated, pravastatin or fluvastatin is recommended (see section 4.5).
Jekk it- trattament b’ inibitur HMG- CoA reductase huwa indikat, pravastatin jew fluvastatin huma rakkomandati (ara sezzjoni 4. 5).
Particular caution must be used when prescribing Kaletra and medicinal products known to induce QT interval prolongation such as: chlorpheniramine, quinidine, erythromycin, clarithromycin.
Kawtiela partikolari għandha tintwera meta Kaletra qed jiġi preskritt ma ’ prodotti mediċinali oħra li huma magħrufa li jinduċu titwil fl- intervalli QT bħal chlorpheniramine, quinidine, erythromycin, clarithromycin.
Indeed, Kaletra could increase concentrations of the co-administered medicinal products and this may result in
Tassew, Kaletra jista iżid il- konċentrazzjonjiiet ta ’ prodotti mediċinali ko- amministrati u dan jista ’ jirriżulta f’ żieda fl- avvenimenti avversi kardijaċi assoċjati.
Cardiac events have been reported with Kaletra in preclinical studies; therefore, the potential cardiac effects of Kaletra cannot be currently ruled out (see sections 4.8 and 5.3).
Avvenimenti kardijaċi ġew irrappurtati fi studji ta 'qabel l- użu kliniku, allura, l- effeti kardijaċi potenzjali ta ’ Kaletra ma jistgħuwx jkunu esklużi (ara sezzjoni 4. 8 u 5. 3).
Co-administration of Kaletra with rifampicin is not recommended.
L- għoti ta ’ Kaletra flimkien ma ’ rifampicin m’ huwiex rakkommandat.
Rifampicin in combination with Kaletra causes large decreases in lopinavir concentrations which may in turn significantly decrease the lopinavir therapeutic effect.
Rifampicin użat flimkien ma ’ Kaletra jikkawża tnaqqis kbir fil- konċentrazzjoni ta ’ lopinavir li sussegwentement jista ’ inaqqas l- effett terapewtiku ta ’ lopinavir b’ mod sinifikattiv.
Adequate exposure to lopinavir/ ritonavir may be achieved when a higher dose of Kaletra is used but this is associated with a higher risk of liver and gastrointestinal toxicity.
Esponiment adegwat għal lopinavir/ ritonavir jista ’ jintlaħaq meta tiġi użata doża ogħla ta ’ Kaletra, iżda dan huwa assoċjat ma ’ riskju ogħla ta ’ tossiċità fil- fwied u gastrointestinali.
Therefore, this co-administration should be avoided unless judged strictly necessary (see section 4.5).
Għalhekk, dan l- għoti flimkien għandu jiġi evitat sakemm ma jkunx strettament neċessarju (ara sezzjoni 4. 5).
Other
Oħrajn
Kaletra is not recommended for use in children less than 2 years of age because of limited efficacy and safety data.
Kaletra mhux irrikmandat għal użu fi tfal li għandhom inqas minn sentejn minħabba data limitata ta ’ sigurtà u effikaċja.
Kaletra is not a cure for HIV infection or AIDS.
Kaletra mhijiex kura għall- infezzjoni ta ’ l- HIV jew AIDS.
It does not reduce the risk of passing HIV to others through sexual contact or contamination with blood.
Ma tnaqqasx ir- riskju li tgħaddi l- HIV lil ħaddieħor minn kuntatt sesswali jew kontaminazzjoni tad- demm.
Appropriate precautions should be taken.
Prekawzjonijiet apposta għandhom jittieħdu.
People taking Kaletra may still develop infections or other illnesses associated with HIV disease and AIDS.
Nies li qed jieħdu Kaletra jistgħu xorta jiżvillupaw infezzjonjijiet jew mard assoċjat mall - marda ta ’ l- HIV u AIDS.
There are limited data on salvage therapy on patients who have failed with Kaletra.
Hemm data limitata fuq terapija ta ’ salvataġġ f’ pazjenti li fallew it- terapija ta ’ Kaletra.
There are ongoing studies to further establish the usefulness of potential salvage therapy regimens (e. g. amprenavir or saquinavir).
Hemm studji kurrenti biex iżjed jistabbilixu l- użu ta ’ terapija ta ’ salvataġġ potenzjali (eż. amprenavir jew saquinavir).
There are currently limited data on the use of Kaletra in protease inhibitor-experienced patients.
Preżentament hemm data limitata fuq l- użu ta ’ Kaletra f’ pazjenti b’ esperjenza ta ’ inibituri tal- protease.
Kaletra soft capsules contain sunset yellow [E110] as an excipient, which can cause allergic-type reaction.
Kaletra kapsuli rotob fihom sunset yellow [E110] bħala eċċipjent li jista jikkawża reazzjoni ta ’ tip allerġiku.
Allergy is more common in those people who are allergic to aspirin.
L- allerġija hija iżjed komuni f’ dawk in- nies li huma allerġiċi għall- aspirina.
Concomitant use of Kaletra and fluticasone or other glucocorticoids that are metabolised by CYP3A4 is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects, including Cushing’ s syndrome and adrenal suppression (see section 4.5).
Użu flimkien ta ’ Kaletra u fluticasone jew glukokortikosterojdi li huma metabolizzati minn CYP3A4 mhux irrikmandat sakemm il- benefiċċju potenzjali tat- trattament jaqbeż ir- riskju ta ’ effetti sistemiċi ta kortikosterojdi, inklużi sindromi ta ’ Cushing u suppressjoni adrenali (ara sezzjoni 4. 5).
4.5 Interaction with other medicinal products and other forms of interaction
6 4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l - effett farmaċewtiku tal- prodott
Co-administration of Kaletra and medicinal products primarily metabolised by CYP3A may result in increased plasma concentrations of the other medicinal product, which could increase or prolong its therapeutic and adverse reactions.
Kaletra fih lopinavir u ritonavir, it- tnejn li huma inibituri ta ’ l- iżoforma ta ’ P450, CYP3A, in vitro. Ko - amministrazzjoni ta ’ Kaletra u prodotti mediċinali primarjament metaboliżati minn CYP3A jistgħu jirriżultaw f’ żieda fill- konċentrazzjonijiet tal- plażma tal- prodotti mediċinali l- oħra, li tista żżid jew ittawwal l- effett terapewtiku jew ir- reazzjonijiet avversi.
Kaletra does not inhibit CYP2D6, CYP2C9, CYP2C19, CYP2E1, CYP2B6 or CYP1A2 at clinically relevant concentrations (see section 4.3).
Kaletra ma jinibix CYP2D6, CYP2C9, CYP2C19, CYP2E1, CYP2B6 jew CYP1A2 f’ konċentrazzjonjiet kliniċi relevanti (ara sezzjoni 4. 3).
Kaletra has been shown in vivo to induce its own metabolism and to increase the biotransformation of some medicinal products metabolised by cytochrome P450 enzymes and by glucuronidation.
Kaletra ġie muri in vivo li jinduċi l- metaboliżmu tiegħu nnifsu u li jżid il- biotrassformazzjoni ta ’ xi prodotti mediċinali metabolizzati minn enżimi taċ- ċitokromju P450 u bil- glukorinidazzjoni.
This may result in lowered plasma concentrations and potential decrease of efficacy of co-administered medicinal products.
Dan jista ’ jirriżulta fi tnaqqis tal- konċentrazzjoni fil- plażma u tnaqqis potenzjali fl- effikaċja ta ’ prodotti mediċinali ko- amministrati.
Medicinal products that are contraindicated specifically due to the expected magnitude of interaction and potential for serious adverse events are listed in section 4.3.
Prodotti mediċinali li huma kontra- indikati specifikament minħabba l- ammont ta ’ l- interazzjonijiet u l - potenzjal għall- avvenimenti avversi serji ħafna huma imniżżla f’ sezzjoni 4. 3.
Antiretroviral agents
Aġenti antiretrovirali
Nucleoside/ Nucleotide reverse transcriptase inhibitors (NRTIs):
Inibituri Nucleoside/ Nucleotide reverse transcriptase (NRTIs):
Stavudine and Lamivudine: no change in the pharmacokinetics of lopinavir was observed when Kaletra was given alone or in combination with stavudine and lamivudine in clinical studies.
Stavudine and Lamivudine: l- ebda tibdil fil- farmakokinetika ta ’ lopinavir ma kien osservat meta Kaletra kien mogħti waħdu jew ikkombinat ma stavudine u lamivudine fi studji kliniċi.
Didanosine: it is recommended that didanosine be administered on an empty stomach; therefore, didanosine is to be given one hour before or two hours after Kaletra (given with food).
Didanosine: huwa rakkomandat illi didanosine jiġi somministrat fuq stonku vojt; allura, didanosine għandu jingħata siegħa qabel jew sagħtejn wara Kaletra (mogħti ma l- ikel).
The gastroresistant formulation of didanosine should be administered at least two hours after a meal.
Il- formulazzjoni gastroreżistenti ta ’ didanosine għandi tiġi somministrata mill- inqas sagħtejn wara l- ikel.
6 Zidovudine and Abacavir:
Zidovudine u Abacavir:
Kaletra induces glucuronidation, therefore Kaletra has the potential to reduce zidovudine and abacavir plasma concentrations.
Kaletra jinduċi glukoronidazzjoni, allura Kaletra għandu l- potenzjal inaqqas il - konċentrazzjoni fil- plażma ta ’ zidovudine u abacavir.
The clinical significance of this potential interaction is unknown.
Is- sinifikat kliniku ta ’ din l- interazzjoni mhux magħruf.
Tenofovir: when tenofovir disoproxil fumarate was co-administered with Kaletra, tenofovir concentrations were increased by approximately 30% with no changes noted in lopinavir or ritonavir concentrations.
Tenofovir: meta tenofovir disoproxil funarate kien ko- somministrat ma Kaletra, il- konċentrazzjonijiet ta ’ tenofovir żdiedu approssimament bi 30%, u ebda bidla ma ġiet innutata fil- konċentrazzjonijiet ta ’ lopinavir jew ritonavir.
Higher tenofovir concentrations could potentiate tenofovir associated adverse events, including renal disorders.
Konċentrazjonijiet ogħla ta ’ tenofovir jistgħu jsaħħu avvenimenti avversi assoċjati ma tenofovir, inklużi problemi fil- kliewi.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs):
Inibuturi Non- nucleoside reverse transcriptase (NNRTIs):
Nevirapine: no change in the pharmacokinetics of lopinavir was apparent in healthy volunteers during nevirapine and Kaletra co-administration.
Nevirapine: l- ebda tibdil fill- farmakokinetika ta ’ lopinavir ma kien apparenti fil- volontiera b’ saħħithom waqt il- ko- amministrazjoni ta ’ nevirapine u Kaletra.
Results from a study in HIV-positive paediatric patients revealed a decrease in lopinavir concentrations during nevirapine co-administration.
Ir- riżultati mill- istudju f’ pazjenti pedjatriċi bl - HIV- positive żvela tnaqqis fill- konċentrazzjoni ta ’ lopinavir waqt il- ko- amministrazzjoni ta ’ nevirapine.
The effect of nevirapine in HIV-positive adults is expected to be similar to that in paediatric patients and lopinavir concentrations may be decreased.
L- effett ta ’ nevirapine f’ adulti bl- HIV- positive huwa mistenni li jkun simili għal dawk f’ pazjenti pedjatriċi u il- konċentrazzjonijiet ta ’ lopinavir jistgħu jitnaqqsu.
The clinical significance of the pharmacokinetic interaction is unknown.
Is- sinifikat kliniku ta ’ din l - interazzjoni farmakokinetika mhix magħrufa.
No formal recommendation could be drawn on dosage adjustment when Kaletra is used in combination with nevirapine.
L- ebda rakkomandazzjoni formali ma setgħet taffettwa l - aġġustament tad- dużaġġ meta Kaletra jintuża f’ kombinazjoni ma nevirapine.
However, based on clinical experience, Kaletra dose increase to 533/ 133 mg (4 capsules) twice daily may be considered when co-administered with nevirapine, particularly for patients in whom reduced lopinavir susceptibility is likely.
Iżda, ibbażat fuq esperjenza klinika, żieda fid- doża ta ’ Kaletra għal 533/ 133 mg (4 kapsuli) darbtejn kuljum tista tiġi kkunsidrata meta ko- amministrati ma nevirapine, partikolarment għall- pazjenti li fihom hija mistennija suxettibilita mnaqqsa għal lopinavir.
Efavirenz: when used in combination with efavirenz and two nucleoside reverse transcriptase inhibitors in multiple protease inhibitor-experienced patients, increasing the dose of Kaletra 33.3% from 400/ 100 mg (3 capsules) twice daily to 533/ 133 mg (4 capsules) twice daily yielded similar lopinavir plasma concentrations as compared to historical data of Kaletra 400/ 100 mg (3 capsules) twice daily.
Efavirenz: meta wżat flimkien ma efavirenz u 2 inibituri ta ’ nucleoside reverse transcriptase f’ pazjenti b’ esperjenza ta ’ numru ta ’ inibituri tal- protease, żieda fid- doża ta ’ Kaletra bi 33. 3% minn 400/ 100 mg (3 kapsuli) darbtejn kuljum għal 533/ 133 mg (4kapsuli) darbtejn kuljum wassal għal konċentrazzjonijiet
Dosage increase of Kaletra from 400/ 100 mg (3 capsules) twice daily to 533/ 133 mg (4 capsules) twice daily should be considered when co-administered with efavirenz.
Żieda fid- doża ta ’ Kaletra minn 400/ 100 mg (3 kapsuli) darbtejn kuljum għal 533/ 133 mg (4 kapsuli) darbtejn kuljum trid tkun meqjusa meta jkun hemm ko- amministrazzjoni ma efavirenz.
Caution is warranted since this dosage adjustment might be insufficient in some patients.
Hemm bżonn ta ’ kawtiela f’ dawn il każijiet għaliex il- bidla fid- doża tista ma tkunx biżżejjed f’ uħud mill- pazjenti.
Co-administration with other HIV protease inhibitors (PIs):
Ko- amministrazzjoni ma ’ inibituri oħra ta ’ HIV- protease (PIs):
Kaletra (400/ 100 mg twice daily) has been studied in combination with reduced doses of amprenavir, indinavir, nelfinavir and saquinavir in steady-state controlled healthy volunteer studies relative to clinical doses of each HIV protease inhibitor in the absence of ritonavir.
Kaletra (400/ 100 mg darbtejn kuljum) ġie studjat ikkombinat ma dożi mnaqqsa ta ’ amprenavir, indinavir, nelfinavir u saquinavir fi studji ta ’ voluntiera f’ saħħithom ikkontrollati fi steady- state relattivament ma dożi kliniċi ta ’ kull inibitur ta ’ l- HIV- protease fl- assenza ta ’ ritonavir.
Comparisons to published pharmacokinetic data with ritonavir-enhanced amprenavir and saquinavir regimens are also described.
Tqabbil ma data farmakokinetika ppubblikata dwar reġimi ta ’ dużaġġ ta ’ amprenavir u saquinavir miżjuda b’ ritonavir ġew ukoll spjegata.
Additionally, the effect of additional ritonavir on the pharmacokinetics of lopinavir are discussed.
L- effett ta ’ ritonavir miżjud mal- farmakokinetika ta ’ lopinavir ġew ukoll diskussi.
Note that the historical comparisons to ritonavir-enhanced protease inhibitor regimens should be interpreted with caution (see details of combinations below).
Kawtiela għandha tkun murija meta reġimi ta ’ dużaġġ ta ’ inibituri tal- protease miżjuda ma ritonavir ġew imqabbla fil- passat (ara dettalji ta ’ reġimi differenti hawn taħt).
Appropriate doses of HIV-protease inhibitors in combination with Kaletra with respect to safety and efficacy have not been established.
Dożi xierqa għas- sigurta ’ u effikaċja ta ’ inibituri ta ’ l- HIV protease flimkien ma Kaltera għadhom ma ġewx stabbiliti.
Therefore, the concomitant administration of Kaletra with PIs requires close monitoring.
Għalekk, ko - amministrazzjoni ta ’ Kaletra ma PIs għandha bżonn tkun mħarsa.
On the other hand, the AUC of lopinavir decreases by 38%.
Amprenavir: l- użu konkomittanti ta ’ Kaletra ma ’ amprenavir 750 mg darbtejn kuljum, irriżulta f’ żieda f’ amprenavir AUC bi 70% u tas- Cmin b’ 4. 6- il darba, relativment ma amprenavir 1200 mg darbtejn kuljum mogħti waħdu. Mill- banda l- oħra, AUC ta ’ lopinavir jonqos bi 38%.
A dose increase of Kaletra may be necessary but may further affect concentrations of amprenavir.
Żieda fid- doża ta ’ Kaletra tista tkun neċessarja iżda tista tkompli taffetwa il- konċentrazzjonijiet ta ’ amprenavir.
Combined with Kaletra, amprenavir concentrations were lower (approximately 30%) relative to boosted amprenavir (amprenavir 600 mg/ ritonavir 100 mg) twice daily alone.
Meta ikkombinat ma ’ Kaletra, il- konċentrazzjonijiet ta’ amprenavir kienu inqas (xi 30%) relativament ma amprenavir li ġie imħeġġeġ (amprenavir 600 mg/ ritonavir 100 mg) darbtejn kuljum mogħti waħdu.
Fosamprenavir: co-administration of standard doses of lopinavir/ ritonavir with fosamprenavir results in a significant reduction in amprenavir concentrations.
Fosamprenavir: l- għoti ta ’ dożi standard ta ’ lopinavir/ ritonavir flimkien ma ’ fosamprenavir iwassal għal tnaqqis sinifikanti fil- konċentrazzjonijiet ta ’ amprenavir.
Co-administration of increased doses of fosamprenavir 1400 mg twice daily with lopinavir/ ritonavir 533/ 133 mg twice daily to protease inhibitor-experienced patients resulted in a higher incidence of gastrointestinal adverse events and elevations in triglycerides with the combination regimen without increases in virological efficacy,
Meta mqabbla ma ’ dożi standard ta ’ fosamprenavir/ ritonavir, l- għoti ta ’ dożi miżjuda ta ’ fosamprenavir ta ’ 1400 mg darbtejn kuljum flimkien ma ’ 533/ 133 mg lopinavir/ ritonavir darbtejn kuljum lil pazjenti li ġieli ngħataw inibituri protejaż, irriżulta f’ inċidenza ogħla ta ’ effetti avversi gastrointestinali u f’ żiediet fit- trigliċeridi meta ngħataw flimkien minghajr ebda żieda fl- effikaċja viroloġika.
Therefore, concomitant administration of these medicinal products is not recommended.
Għalhekk l- għoti flimkien ta ’ dawn il - prodotti mediċinali m’ huwiex irrakkomandat.
Indinavir: indinavir 600 mg twice daily in combination with Kaletra produces similar indinavir AUC, higher Cmin (by 3.5-fold) and lower Cmax relative to indinavir 800 mg three times daily alone.
Indinavir: indinavir 600 mg darbtejn kuljum ikkombinat ma Kaletra jipproduċi AUC simili ta ’ indinavir, Cmin ogħla (bi 3. 5- il darba) u Cmax iktar baxx relativament ma indinavir 800 mg tlett darbiet kuljum mogħti waħdu.
Furthermore, concentrations of lopinavir do not appear to be affected when both medicinal products, Kaletra and indinivir, are combined, based on historical comparison with Kaletra alone.
Barra minn hekk, il- konċentrazzjonijiet ta ’ lopinavir ma jidhrux li huma affetwati meta ż- żewġ prodotti mediċinali, Kaletra u indinivir, huma kkombinati, ibbażat fuq paragun storiku ta ’ Kaletra mogħti waħdu.
Nelfinavir: administration of nelfinavir 1000 mg twice daily in combination with Kaletra produces a similar nelfinavir Cmax and AUC and higher Cmin relative to nelfinavir 1250 mg twice daily alone.
Nelfinavir: l- amministrazzjoni ta ’ nelfinavir 1000 mg darbtejn kuljum ikkombinat ma Kaletra tipproduċi Cmax u AUC simili ta ’ nelfinavir u Cmin ogħla relativament ma nelfinavir 1250 mg darbtejn kuljum mogħti waħdu.
Additionally, concentrations of the active M8 metabolite of nelfinavir were increased.
Addizjonalment, il- konċentrazzjonjiet tal- metabolit attiv M8 ta ’ nelfinavir żdiedu.
On the other hand, lopinavir AUC was decreased by 27% during nelfinavir co-administration with Kaletra.
Mill- banda l- oħra, lopinavir AUC naqas bi 27% waqt il- ko- amministrazzjoni ta ’ nelfinavir ma Kaletra.
A dose increase of Kaletra may be necessary but may further affect concentrations of nelfinavir and its active metabolite.
Żieda fid- doża ta ’ Kaletra għanda mnejn tkun neċessarja iżda tista tkompli taffetwa l- konċentrazjoni ta ’ nelfinavir u l- metabolit attiv tiegħu.
Higher doses of Kaletra have not been studied.
Dożi ogħla ta ’ Kaletra ma ġewx studjati.
Saquinavir: saquinavir 800 mg twice daily co-administered with Kaletra produces an increase of saquinavir AUC by 9.6-fold relative to saquinavir 1200 mg three times daily given alone.
Saquinavir: saquinavir 800 mg darbtejn kuljum ko- amministrat ma Kaletra jipproduċi żieda f’ AUC ta ’ saquinavir b’ 9. 6- il darba relativament ma saquinavir 1200 mg tlett darbiet kuljum mogħti waħdu.
Saquinavir 800 mg twice daily co-administered with Kaletra resulted in an increase of saquinavir AUC by approximately 30% relative to saquinavir/ ritonavir 1000/ 100 mg twice daily, and produces similar exposure to those reported after saquinavir/ ritonavir 400/ 400 mg twice daily.
8 Saquinavir 800 mg darbtejn kuljum ko- amministrat ma Kaletra irriżulta f’ żieda ta ’ AUC ta ’ saquinavir b ’ xi 30% relativament ma saquinavir/ ritonavir 1000/ 100 mg darbtejn kuljum, u jipproduċi esposizzjoni simili għal dawk rappurtati wara saquinavir/ ritonavir 400/ 400 mg darbtejn kuljum.
When saquinavir 1200 mg twice daily was combined with Kaletra, no further increase of concentrations was noted.
Meta saquinavir 1200 mg darbtejn kuljum kien ikkombinat ma Kaletra, l- ebda żieda oħra fil - konċentrazjonijiet ma kienet innutata.
Furthermore, concentrations of lopinavir do not appear to be affected when both medicinal products, Kaletra and saquinavir, are combined, based on historical comparison with Kaletra alone.
Iżjed u iżjed il- konċentrazzjoni ta ’ lopinavir ma jidhirx li huma affetwati meta ż- żewġ prodotti mediċinali, Kaletra u saquinavir, huma kkombinati, ibbażat fuq paragun storiku ta ’ Kaletra mogħti waħdu.
Kaletra co-administered with an additional 100 mg ritonavir twice daily resulted in an increase of lopinavir AUC and Cmin of 33% and 64%, respectively, as compared to Kaletra alone.
Kaletra ko- amministrat ma 100 mg addizjonali ta ’ ritonavir darbtejn kuljum irriżulta f’ żieda ta ’ AUC u Cmin ta ’ lopinavir ta ’ 33% u 64% rispettivament, meta mqabbel ma Kaletra waħdu.
Other medicinal products:
Prodotti mediċinali oħrajn:
Acid reducing agents (omeprazole, ranitidine): in a study performed in healthy volunteers, no clinically relevant interaction has been observed when Kaletra tablets 400/ 100 mg twice daily was co-administered with omeprazole or with ranitidine.
Aġenti li jnaqqsu l- aċidu (omeprazole, ranitidine): fi studju magħmul fuq voluntiera b’ saħħithom, ma ġiet osservata l- ebda interazzjoni li hi klinikament relevanti meta l- pilloli Kaletra 400/ 100 mg darbtejn kuljum ittieħdu flimkien ma ’ omeprazole jew ma ’ ranitidine.
Kaletra can be co-administered with acid reducing agents with no dose adjustment.
Kaletra jista ’ jittieħed flimkien ma ’ aġenti li jnaqqsu l- aċidu mingħajr ma jsir aġġustament tad- doża.
Antiarrhythmics (bepridil, systemic lidocaine and quinidine): concentrations may be increased when co-administered with Kaletra.
Antiarritmiċi (bepridil, lidocaine sistemiku u quinidine): il- konċentrazzjonijiet jistgħu jiżdiedu meta dawn jiġu ko- amministrati ma Kaletra.
Caution is warranted and therapeutic concentration monitoring is recommended when available.
Għandha tintwera kawtiela u l- monitoraġġ tal- konċentrazzjoni terapewtika hija rakkomandata meta din hija disponibli.
Anticancer agents (eg vincristine, vinblastine): these agents may have their serum concentrations increased when co-administered with lopinavir/ ritonavir resulting in the potential for increased adverse events usually associated with these anticancer agents.
Aġenti għal kontra l- kanċer (eż vincristine, vinblastine): meta jingħataw ma ’ lopinavir/ ritonavir, dawn l - aġenti jista ’ ikollhom żieda fil- konċentrazzjoni fis- serum li twassal għal potenzjal ta ’ żieda fl- effetti avversi li soltu huma assoċjati ma ’ dawn l- aġenti għal kontra l- kanċer.
Anticoagulants: warfarin concentrations may be affected when co-administered with Kaletra.
Antikoagulanti: il - konċentrazzjonijiet ta ’ warfarin jistgħu jiġu affetwati meta ko- amministrati ma Kaletra.
It is recommended that INR (international normalised ratio) be monitored.
Huwa rakkomandat illi l- INR (international normalised ratio) ikun monitorat.
Anticonvulsants (phenobarbital, phenytoin, carbamazepine): will induce CYP3A4 and may decrease lopinavir concentrations.
Antikonvulsivi (phenobarbital, phenytoin, carbamazepine): se jinduċu CYP3A4 u jistgħu jnaqqsu il - konċentrazzjonijiet ta ’ lopinavir.
In addition, co-administration of phenytoin and lopinavir/ ritonavir resulted in moderate decreases in steady-state phenytoin concentrations.
Barra minn hekk, l- għoti flimkien ta ’ phenytoin u lopinavir/ ritonavir wassal għal tnaqqis moderat fil - konċentrazzjoni fissa ta ’ phenytoin.
Phenytoin levels should be monitored when co-administering with lopinavir/ ritonavir.
Meta phenytoin jingħata flimkien ma ’ lopinavir/ ritonavir, il- livelli ta ’ phenytoin għandhom jiġu monitorjati.
8 Bupropion: in healthy volunteers, the AUC and Cmax of bupropion and of its active metabolite, hydroxybupropion, were decreased by about 50% when co-administered with lopinavir/ ritonavir capsules 400/ 100 mg twice daily at steady-state.
Bupropion: f’ voluntiera f’ saħħithom, l- AUC u C max ta ’ bupropion u tal- metabolit attiv tiegħu, hydroxybupropion, naqsu b’ madwar 50% meta ngħataw flimkien ma ’ kapsuli lopinavir/ ritonavir ta ’ 400/ 100 mg darbtejn kuljum fi stat fiss.
This effect may be due to induction of bupropion metabolism.
Dan l- effett jista ’ jkun ikkawżat mill- induzzjoni tal - metaboliżmu ta ’ bupropion.
Therefore, if the co-administration of lopinavir/ ritonavir with bupropion is judged unavoidable, this should be done under close clinical monitoring for bupropion efficacy, without exceeding the recommended dosage, despite the observed induction.
Għalhekk, jekk l- għoti ta ’ lopinavir/ ritonavir flimkien ma ’ bupropion ma jistax jiġi evitat, dan għandu jsir taħt monitoraġġ kliniku mill- qrib għall- effikaċja ta ’ bupropion, u mingħajr ma jinqabeż id- dożaġġ irrakkomandat, u dan minkejja l- induzzjoni li ġiet osservata.
Trazodone: in a pharmacokinetic study performed in healthy volunteers, concomitant use of low dose ritonavir (200 mg twice daily) with a single dose of trazodone led to an increase in plasma concentrations of trazodone (AUC increased by 2.4 fold).
Trazodone: fi studju farmarkokinetiku li sar b’ voluntiera f’ saħħithom, użu konkomittanti ta ’ doża baxxa ta ’ ritonavir (200 mg darbtejn kuljum) ma doża waħda ta ’ trazodone wassal għal żieda fil - konċentrazzjoni ta ’ trazodone fil- plażma (AUC żied bi 2. 4- il darba).
Adverse events of nausea, dizziness, hypotension and syncope were observed following co-administration of trazodone and ritonavir in this study.
Avvenimenti avversi ta ’ nawsja, sturdament, pressjoni baxxa u sinkope kienu osservati wara ko- amministrazzjoni ta ’ trazodone u ritonavir f’ dan l- istudju.
However, it is unknown whether the combination of lopinavir/ ritonavir cause a similar increase in trazodone exposure.
Minkejja dan, mhuwiex mgħaruf jekk it- taħlit ta ’ lopinavir ma ritonavir jikkawża żieda simili ta ’ esposizzjoni għal trazodone.
The combination should be used with caution and a lower dose of trazodone should be considered.
Din it- taħlita għandha tintuża b’ mod kawtiel, u doża iżjed baxxa ta ’ trazodone għandha tiġi kkunsidrata.
Digoxin: plasma concentrations of digoxin may be increased when co-administered with Kaletra.
9 Digoxin: konċentrazzjonijiet ta ’ digoxin fil- plażma jistgħu jogħlew meta ikun amministrat ma Kaletra.
Caution is warranted and therapeutic drug monitoring of digoxin concentrations, if available, is recommended in case of co-administration of Kaletra and digoxin.
Kawtiela u monitoraġġ tal- konċentrazzjonijiet ta ’ digoxin, jekk dan ikun disponibbli, huma rrikmadati meta ikun hemm ko- amministrazzjoni ta ’ Kaletra u Digoxin.
Particular caution should be used when prescribing Kaletra in patients taking digoxin as the acute inhibitory effect of ritonavir on Pgp is expected to significantly increase digoxin levels.
Għanda tintwera kawtiela partikulari meta Kaletra ikun preskritt għal pazjenti li qiegħdin jieħdu digoxin għaliex l- effett intens ta ’ inibizzjoni tar - ritonavir fuq Pgp huwa mistenna li jżid b’ mod sinifikattiv il- konċentrazzjoni ta ’ digoxin.
The increased digoxin level may lessen over time as Pgp induction develops.
Il- livell ogħla ta ’ digoxin jista jonqos biż- żmien malli l- induzzjoni ta ’ Pgp tiżviluppa.
Initiation of digoxin in patients already taking Kaletra is expected to result in lower increase of digoxin concentrations.
Introduzzjoni ta ’ digoxin f’ pazjenti li diġa qiegħdin jieħdu Kaletra huwa mistenni li jirriżulta f’ inqa żieda ta ’ konċentrazzjonijniet ta ’ digoxin
Dihydropyridine calcium channel blockers:
Imblukkaturi tal- kalċju Dihydropyridine:
(e. g. felodipine, nifedipine, nicardipine): may have their serum concentrations increased by Kaletra.
(eż. felodipine, nifedipine, nicardipine): jista jkollom il - konċentrazzjonijiet miżjuda b’ Kaletra.
Lipid lowering agents:
Aġenti li jnaqqsu l- lipidi:
HMG-CoA reductase inhibitors which are highly dependent on CYP3A4 metabolism, such as lovastatin and simvastatin, are expected to have markedly increased plasma concentrations when co-administered with Kaletra.
Inibituri HMG- CoA reductase li jiddependu ħafna fuq metaboliżmu ta ’ CYP3A4, bħal lovastatin u simvastatin, huma mistennija li jkollom żieda fil- konċentrazzjonijiet fil - plażma markata meta ikunu ko- amministrati ma Kaletra.
Since increased concentrations of HMG-CoA reductase inhibitors may cause myopathy, including rhabdomyolysis, the combination of these medicinal products with Kaletra is not recommended.
Minħabba żieda fil- konċentrazzjonijiet ta ’ inibituri HMG- CoA reductase jistgħu jikkawżaw mijopatija, inkluż rabdomilożi, il- kombinazzjoni ta ’ dawn il- prodotti mediċinali ma Kaletra mhuwiex rakkomandat.
Atorvastatin is less dependent on CYP3A for metabolism.
Atorvastatin jiddependi inqas fuq CYP3A għal metaboliżmu.
When atorvastatin was given concurrently with Kaletra, a mean 4.7-fold and 5.9-fold increase in atorvastatin Cmax and AUC, respectively, was observed.
Meta atorvastatin kien mogħti flimkien ma Kaletra, medja ta ’ 4. 7- il darba u 5. 9- il darba żieda fis - Cmax u AUC ta ’ atorvastatin, rispettivament, kienu osservati.
When used with Kaletra, the lowest possible dose of atorvastatin should be administered.
Meta użat ma Kaletra, l- inqas doża possibli ta ’ atorvastatin għandha tkun somministrata.
Rosuvastatin is not dependent on CYP3A.
Rosuvastatin ma huwiex dipendenti fuq CYP3A.
However, when given concurrently with Kaletra a mean 5-fold and 2-fold increase in rosuvastatin Cmax and AUC, respectively, was observed.
Madanakollu, meta dan ingħata flimkien ma ’ Kaletra, ġiet osservata żieda fis - Cmax u AUC ta ’ rosuvastatin ta ’ medja ta ’ 5 darbiet aktar u darbtejn aktar, rispettivament.
Caution should be exercised when Kaletra is co-administered with rosuvastatin.
Għandha tiġi eżerċitata kawtela meta Kaletra jingħata flimkien ma ’ rosuvastatin.
Results from an interaction study with Kaletra and pravastatin reveal no clinically significant interaction.
Riżultati minn studju t’ interazzjoni ma ’ Kaletra u pravastatin żvelaw l- ebda interazzjoni klinikament sinifikanti.
The metabolism of pravastatin and fluvastatin is not dependent on CYP3A4, and interactions are not expected with Kaletra.
Il- metaboliżmu ta ’ pravastatin u fluvastatin ma jiddependix fuq CYP3A4, u interazzjonijiet mhumiex mistennija ma Kaletra.
If treatment with a HMG-CoA reductase inhibitor is indicated, pravastatin or fluvastatin is recommended.
Jekk it- trattament ma ’ inibituri HMG- CoA reductase huwa indikat, pravastatin jew fluvastatin huma rakkomandati.
Dexamethasone: may induce CYP3A4 and may decrease lopinavir concentrations.
Dexamethasone: jista jinduċi CYP3A4 u jista inaqqas il- konċentrazzjoni ta ’ lopinavir.
Phosphodiesterase inhibitors: phosphodiesterase inhibitors which are dependent on CYP3A4 metabolism, such as tadalafil and sildenafil, are expected to result in an approximately 2-fold and 11-fold increase in AUC respectively, when co-administered with ritonavir containing regimens including Kaletra and may result in an increase in PDE5 inhibitor associated adverse reactions including hypotension, synope, visual changes and prolonged erection.
Dan jista jirriżulta f’ żieda ta ’ inibitur PDE5 li huwa assoċjat ma avvenimenti avversi bħal pressjoni baxxa, sinope, bdil viżwali, u erezzjoni prolongata.
Particular caution must be used when prescribing sildenafil or tadalafil in patients receiving Kaletra with increased monitoring for adverse events.
Kawietla partikulari għandha tingħata meta sildenafil jew tadalafil jiġu preskritti f’ pazjenti li qiegħdin jieħdu Kaletra biex ikun hemm monituraġġ għal avvenimenti avversi.
Co-administration of vardenafil with rtionavir containing regimens including Kaletra is expected to result in 49-fold increase in vardenafil AUC.
Ko- aministrazzjoni ta ’ vardenafil ma reġimi ta ’ dużaġġ b’ ritonavir, inkluż Kaletra, huwa mistenni li jirriżulta f’ żieda ta ’ 49- il darba ta ’ AUC ta ’ vardenafil.
The use of vardenafil with Kaletra is contraindicated (see section 4.3).
L - użu ta ’ vardenafil ma Kaletra huwa kontra- indikat (ara sezzjoni 4. 3).
More frequent therapeutic concentration monitoring is recommended until plasma levels of these products have been stabilised.
Cyclosporin, sirolimus (rapamycin) u tacrolimus: konċentrazzjonijiet jistgħu jiżdiedu meta ko - somministrati ma Kaletra. Monitoraġġ iżjed frekwenti tal- konċentrazzjoni terapewtika hija rakkomandata sakemm jistabbilixu ruħhom il- livelli fil- plażma ta ’ dawn il- prodotti.
9 Ketoconazole and itraconazole: may have serum concentrations increased by Kaletra.
Ketoconazole u itraconazole: jista jkollom il- konċentrazzjoni fis- serum miżjuda minn Kaletra.
High doses of ketoconazole and itraconazole (> 200 mg/ day) are not recommended.
Dożi għolja ta ’ ketoconazole u itraconazole (> 200 mg/ ġurnata) mhumiex rakkomandati.
Voriconazole: due to the potential for reduced voriconazole concentrations, co-administration of voriconazole and low dose ritonavir (100 mg twice daily) as contained in Kaletra should be avoided unless an assessment of the benefit/ risk to patient justifies the use of voriconazole.
Voriconazole: minħabba il- potenzjal għal konċentrazzjonijiet inqas ta ’ voriconazole, ko - amministrazzjoni tiegħu ma doża baxxa ta ’ ritonavir (100 mg darbtejn kuljum), l- istess bħal Kaletra, trid tkun evitata sakemm isir valutazzjoni tar- riskji u l- benefiċċji għall- pazjent biex jiġġustifika l- użu ta ’ voriconazole.
Clarithromycin: moderate increases in clarithromycin AUC are expected when co-administered with Kaletra.
10 Clarithromycin: żidiet moderati fi clarithromycin AUC huma mistennija meta ko- somministrati ma Kaletra.
For patients with renal or hepatic impairment dose reduction of clarithromycin should be considered (see section 4.4).
Għal pazjenti b’ indeboliment tal - kliewi jew tal- fwied tnaqqis fid- doża ta’ clarithromycin għandu jiġi kkunsidrat (ara sezzjoni 4. 4).
Buprenorphine: buprenorphine (dosed at 16 mg daily) co-administered with lopinavir/ ritonavir (dosed at 400/ 100 mg twice daily) showed no clinically significant interaction.
Buprenorphine: buprenorphine (mgħoti f’ doża ta ’ 16 mg kuljum) ko- somministrat ma ’ lopinavir/ ritonavir (mgħoti f’ doża ta ’ 400/ 100 mg darbtejn kuljum) ma rriżulta fl- ebda interazzjoni li hi klinikament sinifikanti.
Kaletra can be co-administered with buprenorphine with no dose adjustment.
Kaletra jista ’ jiġi ko- somministrat ma ’ buprenorphine mingħajr bżonn ta ’ aġġustament fid- doża.
Methadone:
Methadone:
Kaletra was demonstrated to lower plasma concentrations of methadone.
Ġie muri li Kaletra inaqqas il- konċentrazzjoni fil- plażma ta ’ methadone.
Monitoring plasma concentrations of methadone is recommended.
Monitoraġġ tal - konċentrazzjoni fil- plażma ta ’ methadone huwa rakkomandat.
Contraceptives: levels of ethinyl oestradiol were decreased when oestrogen-based oral contraceptives were co-administered with Kaletra.
Kontraċettivi: livelli ta ’ ethinyl oestradiol naqsu meta kontraċettivi orali ġew ko- amministrati ma ’ Kaletra.
In case of co-administration of Kaletra with contraceptives containing ethinyl oestradiol (whatever the contraceptive formulation e. g. oral or patch), alternative methods of contraception are to be used.
Orali jew Garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda), metodi alternativi ta ’ kontraċezzjoni għandhom jintużaw.
Rifabutin: when rifabutin and Kaletra were co-administered for 10 days, rifabutin (parent substance and active 25-O-desacetyl metabolite) Cmax and AUC were increased by 3.5- and 5.7-fold, respectively.
Rifabutin: meta rifabutin u Kaletra kienu ko- amministrati għal 10 tijiem, rifabutin (is- sustanza oriġinali u metabolit attiv 25- O- desacetyl) Cmax u AUC żdiedu bi 3. 5 - u 5. 7- il darba, rispettivament.
On the basis of these data, a rifabutin dose reduction of 75% (i. e.
Fuq il- bażi ta ’ din id- data, tnaqqis fid- doża ta ’ rifabutin ta ’ 75% (i. e.
150 mg every other day or 3 times per week) is recommended when administered with Kaletra.
150 mg ġurnata iva u ġurnata 3 darbiet fil - ġimgħa) huwa irrikmandat meta somministrat ma Kaletra.
Further reduction may be necessary.
Riduzzjoni ulterjuri għandha mnejn tkun neċċesarja.
Rifampicin: co-administration of Kaletra with rifampicin is not recommended.
Rifampicin: l- għoti ta ’ Kaletra flimkien ma ’ rifampicin m’ huwiex rakkommandat.
Rifampicin administered with Kaletra causes large decreases in lopinavir concentrations which may in turn significantly decrease the lopinavir therapeutic effect.
Rifampicin mgħoti flimkien ma ’ Kaletra jikkawża tnaqqis kbir fil- konċentrazzjoni ta ’ lopinavir, u dan jista ’ min- naħa tiegħu inaqqas b’ mod sinifikanti l- effett terapewtiku ta ’ lopinavir.
A dose adjustment of Kaletra 400 mg/ 400 mg twice daily has allowed compensating for the CYP 3A4 inducer effect of rifampicin.
Aġġustament fid- doża ta ’ Kaletra 400 mg/ 400 mg darbtejn kuljum wasslet biex ikun hemm kumpens għall- effett ta ’ rifampicin li jinduċi CYP 3A4.
However, such a dose adjustment might be associated with ALT/ AST elevations and with increase in gastrointestinal disorders.
Madanakollu, dan l- aġġustament tad- doża jista ’ jkun assoċjat ma ’ żiediet fl- ALT/ AST u ma ’ żieda fid- disturbi gastrointestinali.
Therefore, this co-administration should be avoided unless judged strictly necessary.
Għalhekk, dan l- għoti flimkien għandu jiġi evitat sakemm ma jkunx strettament neċessarju.
If this co-administration is judged unavoidable, increased dose of Kaletra at 400 mg/ 400 mg twice daily may be administered with rifampicin under close safety and therapeutic drug monitoring.
Jekk jiġi deċiż li dan l- għoti flimkien ma jistax jiġi evitat, doża miżjuda ta ’ Kaletra 400 mg/ 400 mg darbtejn kuljum tista ’ tingħata flimkien ma ’ rifampicin taħt monitoraġġ mill - qrib għas- sigurtà u mediċina terapewtika.
The Kaletra dose should be titrated upward only after rifampicin has been initiated(see section 4.4).
Id- doża ta ’ Kaletra għandha tiġi miżjuda ftit ftit biss wara li jkun inbeda jingħata rifampicin (ara sezzjoni 4. 4).
St John’ s wort: serum levels of lopinavir and ritonavir can be reduced by concomitant use of the herbal preparation St John’ s wort (Hypericum perforatum).
St John’ s wort: livelli fis- serum ta ’ lopinavir u ritonavir jistgħu jitnaqqsu bl- użu konkomitanti ta ’ preparazzjoni ta ’ ħxejjex St John’ s wort (Hypericum perforatum).
This is due to the induction of drug metabolising enzymes by St John’ s wort.
Dan huwa minħabba li St. John’ s wort jinduċi enżimi li jimmetaboliżaw il- mediċini.
Herbal preparations containing St John’ s wort should therefore not be combined with lopinavir and ritonavir.
Preparazzjonjiet tal- ħxejjex li fihom St John’ s wort m’ għandhomx jiġu kkombinati ma lopinavir u ritonavir.
If a patient is already taking St John’ s wort, stop St John’ s wort and if possible check viral levels.
Jekk pazjent ġja qed jieħu St John’ s wort, waqqaf St John’ s wort u jekk huwa possibli ikkonferma l- livelli virali.
Lopinavir and ritonavir levels may increase on stopping St John’ s wort.
Il- livelli ta ’ Lopinavir u ritonavir jistgħu jiżdiedu mat- twaqqif ta ’ St John’ s wort.
The dose of Kaletra may need adjusting.
Id- doża ta ’ Kaletra għandha mnejn għandha tiġi aġġustata.
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 induċenti jista ’ jibqa jippersisti għall 2 ġimgħat wara ’ t- twaqqif mit- trattament bi St John’ s wort (ara sezzjoni 4. 3).
Midazolam: midazolam is extensively metabolised by CYP3A4.
Midazolam: midazolam huwa fil- biċċa l- kbira tiegħu metabolizzat b’ CYP3A4.
Co-administration with Kaletra may cause a large increase in the concentration of this benzodiazepine.
L- għoti tiegħu flimkien ma ’ Kaletra jista ’ jikkaġuna żieda kbira fil- konċentrazzjoni ta ’ dan il- benzodiazepine.
A phenotyping cocktail study in 14 healthy volunteers showed an increase of AUC by about 13 fold with oral midazolam and an increase by about 4 fold with parenteral midazolam.
Studju li sar fuq 14 - il voluntier b’ saħħithom b’ taħlita ta ’ fenotip wera żieda ta ’ madwar 13 - il darba aktar ta ’ AUC meta ingħata medazolam mill- ħalq u żieda ta ’ madwar 4 darbiet aktar meta ingħata midazolam parenterali.
Therefore, Kaletra should not be co-administered with orally administered midazolam (see section 4.3), whereas caution should be used with co-administration of Kaletra and parenteral midazolam.
Għalhekk, Kaletra m’ għandux jingħata ma ’ midazolam mittieħed mill- ħalq (ara sezzjoni 4. 3), u wieħed irid joqgħod attent meta jkun hemm it- teħid flimkien ta ’ Kaletra u midazolam parenterali.
If Kaletra 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.
Għandu jiġi kkunsirat
Dosage adjustment for midazolam should be considered especially if more than a single dose of midazolam is administered.
11 aġġustament fid- doża ta ’ midazolam, speċjalment jekk tkun ingħatat aktar minn doża waħda ta ’ midazolam.
10 Fluticasone propionate (interaction with ritonavir): in a clinical study where ritonavir 100 mg capsules twice daily were co − administered with 50 μ g intranasal fluticasone propionate (4 times daily) for seven days in healthy subjects, the fluticasone propionate plasma levels increased significantly, whereas the intrinsic cortisol levels decreased by approximately 86% (90% confidence interval 82 − 89%).
Fluticasone propionate (interazzjoni ma ritonavir): fi studju kliniku 100 mg kapsuli darbtejn kuljum ta ’ ritonavir ġew ko- amministrati ma 50ug fluticasone propionate fl- imnieħer (4 darbiet kuljum) għal 7 - ijiem f’ suġġetti f’ saħħithom, il- livelli fil- plażma ta ’ fluticasone propionate għolew sinifikament, filwaqt li il- livelli intrinsiċi tal- korisol tbaxxew b’ approssimament 86% (90% intervall ta ’ fiducja ta ’ 82- 89%).
Greater effects may be expected when fluticasone propionate is inhaled.
Effetti ikbar jistgġu ikunu mistennija fluticasone propionate ikun inalat.
Systemic corticosteroid effects including Cushing's syndrome and adrenal suppression have been reported in patients receiving ritonavir and inhaled or intranasally administered fluticasone propionate; this could also occur with other corticosteroids metabolised via the P450 3A pathway eg budesonide.
Budesonide.
Consequently, concomitant administration of Kaletra and these glucocorticoids is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects (see section 4.4).
Konsekwentement, amministrazzjoni ta ’ Kaletra u dawn il- glikokortikojdi flimkiem m’ hijiex irrikmandata sakemm il- benefiċċju potenzjali tat - trattament jegħleb it- riskju ta ’ effetti sistemiċi ta’ kortikosterojdi (ara sezzjoni 4. 4).
A dose reduction of the glucocorticoid should be considered with close monitoring of local and systemic effects or a switch to a glucocorticoid, which is not a substrate for CYP3A4 (eg beclomethasone).
Beclomethasone).
Moreover, in case of withdrawal of glucocorticoids progressive dose reduction may have to be performed over a longer period.
Barra minn hekk f’ każi ta ’ sintomi ta ’ rtirar mill- glukokortikosterojdi, tnaqqis progressiv tad- doża fuq żmien twil jista ’ jkun bżonnjuż.
The effects of high fluticasone systemic exposure on ritonavir plasma levels is yet unknown.
L- effetti ta ’ esposizzjoni sistemika għolja għal fluticasone fuq livelli ta ’ ritonavir fil- plażma għadhom mhux magħrufa.
Based on known metabolic profiles, clinically significant interactions are not expected between Kaletra and fluvastatin, dapsone, trimethoprim/ sulfamethoxazole, azithromycin or fluconazole.
Ibbażżat fuq profili metaboliċi magħrufa, mhumiex mistennija interazzjonijiet klinikament sinifikanti bejn Kaletra u fluvastatin, dapsone, trimethoprim/ sulfamethoxazole, azithromycin jew fluconazole.
There are no data from the use of Kaletra in pregnant women.
M’ hemm l- ebda data mill- użu ta ’ Kaletra f’ nisa tqal.
Studies in animals have shown reproductive toxicity (see section 5.3).
Studji fl- animali urew tossiċita riproduttiva (ara sezzjoni 5. 3).
Kaletra should not be used during pregnancy unless clearly necessary.
Kaletra m’ għandux jintuża waqt it - tqala sakemm m’ hemmx bżonn ċar ta ’ dan.
Studies in rats revealed that lopinavir is excreted in the milk.
Studji fil- firien urew li lopinavir huwa mneħħi fil- ħalib tas- sider.
It is not known whether this medicinal product is excreted in human milk.
Mhuwiex magħruf jekk dan il- prodott mediċinali huwiex mneħħi fil- ħalib tas- sider uman.
HIV infected women must not breast-feed their infants under any circumstances to avoid transmission of HIV.
Nisa infettati bl- HIV m’ għandhomx irreddgħu t - trabi tagħhom taħt l- ebda ċirkustanza sabiex jevvitaw it- trażmissjoni ta ’ l- HIV.
Patients should be informed that nausea has been reported during treatment with Kaletra (see section 4.8).
Il- pazjenti għandhom jiġu infurmati li ġew irrappurtati każi ta ’ nawseja waqt il- kura b’ Kaletra (ara sezzjoni 4. 8).