qanastek/EMEA-V3 huggingface dataset:
{MM/ YYYY}
Pazjenti li jkollhom dawn is- sinjali jew sintomi għandhom ikunu evalwati u t- terapija b’ Kaletra għandha tkun sospiża jekk issir dijanjosi tal - pankreatite (ara sezzjoni 4. 8).
NAME OF THE MEDICINAL PRODUCT
Ipergliċemija
Kaletra 100 mg/ 25 mg film-coated tablets
F’ xi uħud minn dawn, l- ipergliċemija kienet serja ħafna, u f’ xi każi assoċjata ukoll mal- ketoaċidożi.
QUALITATIVE AND QUANTITATIVE COMPOSITION
Ridistribuzzjoni tax- xaħam u disturbi fil- metaboliżmu
Each film-coated tablet contains 100 mg of lopinavir co-formulated with 25 mg of ritonavir as a pharmacokinetic enhancer.
It- tagħrif dwar il- mekkaniżmu mhuwiex komplut.
For a full list of excipients, see section 6.1.
76 Sindromu ta ’ Riattivazzjoni ta ’ l- Immunità
PHARMACEUTICAL FORM
Is- sintomi ta ’ infjammazzjoni għandhom jiġu evalwati, u fejn ikun hemm bżonn tinbeda l- kura.
Film-coated tablet
Ostjonekrożi
Pale yellow debossed with [Abbott logo] and “ KC”.
Il- pazjenti għandhom jiġu avżati biex jitolbu parir mediku jekk jesperjenzaw weġgħat fil- ġogi u uġigħ, ebusija tal- ġogi jew difikultà fil - movimenti.
CLINICAL PARTICULARS
Titwil ta ’ l- intervall PR
4.1 Therapeutic indications
F’ pazjenti bħal dawn, Kaletra għandu jintuża b’ kawtela (ara sezzjoni 5. 1).
Kaletra is indicated for the treatment of HIV-1 infected children above the age of 2 years and adults, in combination with other antiretroviral agents.
Effetti fuq prodotti mediċinali oħra
Most experience with Kaletra is derived from the use of the product in antiretroviral therapy naïve patients.
Kaletra fih lopinavir u ritonavir, it- tnejn li huma impedituri ta ’ l- iżoforma ta ’ P450, CYP3A.
Data in heavily pretreated protease inhibitor experienced patients are limited.
Kaletra x’ aktarx li jżid il- konċentrazzjoni fil- plażma ta ’ prodotti mediċinali li huma primarjament metabolizzati minn CYP3A.
There are limited data on salvage therapy on patients who have failed therapy with Kaletra.
Dawn iż- żidiet ta ’ konċentrazzjoni fil- plażma ta ’ prodotti mediċinali li jittieħdu flimkien ma ’ Kaletra jistgħu jżidu jew itawlu l- effett terapewtiku u l- effetti avversi tagħhom (ara sezzjoni 4. 3 u 4. 5).
The choice of Kaletra to treat protease inhibitor experienced HIV-1 infected patients should be based on individual viral resistance testing and treatment history of patients (see sections 4.4 and 5.1).
Jekk tkun indikata kura b’ impeditur HMG- CoA reductase, pravastatin jew fluvastatin huma rrakkomandati (ara sezzjoni 4. 5).
4.2 Posology and method of administration
Fl - istudji ta ’ qabel l- użu kliniku, ġew irrappurtati effetti kardijaċi meta ngħata Kaletra; għalhekk, l- effetti kardijaċi potenzjali ta ’ Kaletra ma jistgħux jiġu esklużi għalissa (ara sezzjoni 4. 8 u 5. 3).
Kaletra should be prescribed by physicians who are experienced in the treatment of HIV infection.
77 L- għoti ta ’ Kaletra flimkien ma ’ rifamficin mhuwiex irrakkomandat.
Kaletra tablets should be swallowed whole and not chewed, broken or crushed.
Kaletra mhuwiex kura għall- infezzjoni ta ’ l- HIV jew għall- AIDS.
Adult and adolescent use: the recommended dosage of Kaletra tablets is two 200/ 50 mg tablets twice daily taken with or without food.
Ma jnaqqasx ir- riskju li wieħed jgħaddi l- HIV lil ħaddieħor minn kuntatt sesswali jew kontaminazzjoni tad- demm.
Oral solution is available to patients who have difficulty swallowing.
Għandhom jittieħdu l- prekawzjonijiet adegwati.
Refer to the Summary of Product Characteristics for Kaletra oral solution for dosing instructions.
Nies li qegħdin jieħdu Kaletra xorta jistgħu jiżviluppaw infezzjonijiet jew mard ieħor assoċjat mal- marda ta ’ l- HIV u l- AIDS.
Paediatric use (2 years of age and above): the adult dose of Kaletra tablets (400/ 100 mg twice daily) may be used in children 40 kg or greater or with a Body Surface Area (BSA)* greater than 1.4 m2.
L- użu flimkien ta ’ Kaletra u fluticasone jew glukokortikojdi li huma metabolizzati minn CYP3A4, mhux irrakkomandat sakemm il- benefiċċju potenzjali tal- kura ma jkunx ogħla mir- riskju ta ’ l- effetti sistemiċi tal- kortikosterojdi, inklużi s- sindromu Cushing (Cushing’ s syndrome) u s- soppressjoni adrenali (ara sezzjoni 4. 5).
For children weighing less than 40 kg or with a BSA between 0.5 and 1.4 m2 and able to swallow tablets, refer to the dosing guideline tables below.
Kaletra fih lopinavir u ritonavir, it- tnejn li huma impedituri ta ’ l- iżoforma ta ’ P450, CYP3A in vitro.
For children unable to swallow tablets, please refer to the Kaletra oral solution Summary of Product Characteristics.
F’ konċentrazzjoni klinika rilevanti, Kaletra ma jimpedixxix CYP2D6, CYP2C9, CYP2C19, CYP2E1, CYP2B6 jew CYP1A2 (ara sezzjoni 4. 3).
Before prescribing Kaletra 100/ 25 mg tablets, infants and young children should be assessed for the ability to swallow intact tablets.
Ġie ppruvat li Kaletra in vivo, jinduċi l- metaboliżmu tiegħu nnifsu u jżid il- biotrassformazzjoni ta ’ xi prodotti mediċinali metabolizzati mill- enżimi taċ- ċitokromju P450 u mill- glukorinidazzjoni.
If a child is unable to reliably swallow a Kaletra tablet, Kaletra oral solution formulation should be prescribed.
Dan jista ’ jirriżulta fi tnaqqis tal- konċentrazzjoni fil- plażma u tnaqqis potenzjali ta ’ l- effikaċja tal- prodotti mediċinali li jittieħdu ma ’ Kaletra.
64 The following table contains dosing guidelines for Kaletra 100/ 25 mg tablets based on BSA.
Prodotti mediċinali li huma kontra- indikati speċifikament minħabba l- ammont ta ’ interazzjonijiet mistennija, u minħabba l- potenzjal tagħhom li jikkawżaw effetti avversi serji, huma mniżżla f’ sezzjoni 4. 3.
Paediatric Dosing Guidelines
L- istudji kollha li saru fuq l- interazzjoni, sakemm ma jkunx indikat mod ieħor, saru kollha bl- użu tal - kapsuli Kaletra, u dan jagħti, bejn wieħed u ieħor, esponiment ta ’ lopinavir li hu 20% aktar baxx milli jagħtu l- pilloli ta ’ 200/ 50 mg.
Body Surface Area (m2)
Aġenti antiretrovirali Impedituri Nukleòside/ Nukleòtide reverse transcriptase (NRTIs):
Recommended number of
Stavudine and Lamivudine: l- ebda tibdil fil- farmakokinetika ta ’ lopinavir ma kien osservat fi studji kliniċi meta Kaletra kien mogħti waħdu jew flimkien ma ’ stavudine u lamivudine.
100/ 25 mg tablets twice-daily
Didanosine: huwa rrakkomandat illi didanosine jingħata fuq stonku vojt; għaldaqstant, didanosine jista ’ jingħata mal- pilloli Kaletra mingħajr ikel.
≥ 0.5 to < 0.9 ≥ 0.9 to < 1.4
Zidovudine u Abacavir:
2 tablets (200/ 50 mg) 3 tablets (300/ 75 mg)
Is- sinifikat kliniku ta ’ din l - interazzjoni potenzjali għadu mhux magħruf.
≥ 1.4
Konċentrazjonijiet ogħla ta ’ tenofovir jistgħu jsaħħu l- effetti avversi assoċjati ma ’ tenofovir, inklużi disturbi renali.
4 tablets (400/ 100 mg)
Impedituri reverse transcriptase mhux nukleòside (NNRTIs):
If more convenient for patients, the Kaletra 200/ 50 mg tablets may also be considered alone or in combination with the Kaletra 100/ 25 mg tablet to achieve the recommended dose.
Għalhekk, id- dożaġġ tal- pilloli Kaletra għandu jiżdied għal 500/ 125 mg darbtejn kuljum meta jinghata flimkien ma ’ 600 mg efavirenz darba kuljum.
* Body surface area can be calculated with the following equation:
F’ dawn il- każijiet, japplikaw l- istess rakkomandazzjonijiet ta ’ monitoraġġ.
BSA (m2) = √ (Height (cm) X Weight (kg) / 3600)
L- għoti flimkien ma ’ impedituri oħra ta ’ l- HIV protejaż (PIs):
Children less than 2 years of age:
Barraminnhekk, l- effett ta ’ ritonavir miżjud, fuq il- farmakokinetika ta ’ lopinavir ġie diskuss ukoll.
Kaletra is not recommended for use in children below 2 years of age due to insufficient data on safety and efficacy (see section 5.1).
Wieħed għandu joqgħod attent meta jqabbel reġimi ta ’ dożaġġ ta ’ impedituri protejaż miżjuda ma ’ ritonavir kif imqabbla fil- passat (ara d- dettalji tat- taħlit li sar hawn taħt).
Efavirenz or nevirapine
Għalhekk, l- għoti flimkien ta ’ Kaletra mal- PIs jesiġi monitoraġġ mill- qrib.
The following table contains dosing guidelines for Kaletra 100/ 25 mg tablets based on BSA when used in combination with efavirenz or nevirapine in children.
Amprenavir: ara r- rakkomandazzjonijiet deskritti għat- teħid flimkien tal- pilloli Kaletra u efavirenz.
Paediatric Dosing Guidelines with concomitant efavirenz or nevirapine
Għalhekk l- għoti flimkien ta ’ dawn il - prodotti mediċinali m’ huwiex irrakkomandat..
Body Surface Area (m2)
Barraminnhekk, il- konċentrazzjonijiet ta ’ lopinavir ma jidhrux li huma affetwati meta ż- żewġ prodotti mediċinali, Kaletra u indinavir, jingħataw flimkien, kif ibbażat fuq paragun storiku ta ’ Kaletra mogħti waħdu.
100/ 25 mg tablets twice-daily
Nelfinavir: ara r- rakkomandazzjonijiet applikabbli għat- teħid tal- pilloli Kaletra flimkien ma ’ efavirenz.
≥ 0.5 to < 0.8 ≥ 0.8 to < 1.2
79 Saquinavir:
2 tablets (200/ 50 mg) 3 tablets (300/ 75 mg)
Meta saquinavir 1200 mg darbtejn kuljum ingħata flimkien ma ’ Kaletra, l- ebda żieda oħra fil - konċentrazzjonijiet ma kienet innutata.
≥ 1.2 to < 1.4 ≥ 1.4
Ritonavir:
4 tablets (400/ 100 mg) 5 tablets (500/ 125 mg)
Prodotti mediċinali oħrajn:
If more convenient for patients, the Kaletra 200/ 50 mg tablets may also be considered alone or in combination with the Kaletra 100/ 25 mg tablet to achieve the recommended dose.
Aġenti li jnaqqsu l- aċidu (omeprazole, ranitidine): fi studju magħmul fuq voluntiera b’ saħħithom, ma ġiet osservata l- ebda interazzjoni li hi klinikament rilevanti meta l- pilloli Kaletra 400/ 100 mg darbtejn kuljum ingħataw flimkien ma ’ omeprazole jew ma ’ ranitidine.
Hepatic impairment:
Mediċini li jaħdmu fuq ir- rittmu tat- tħabbit tal- qalb:
In HIV-infected patients with mild to moderate hepatic impairment, an increase of approximately 30% in lopinavir exposure has been observed but is not expected to be of clinical relevance (see section 5.2).
(bepridil, lidocaine sistemiku u quinidine): il - konċentrazzjonijiet jistgħu jiżdiedu meta dawn jingħataw flimkien ma ’ Kaletra.
Kaletra should not be given to these patients (see section 4.3).
Għandha tiġi eżerċitata kawtiela, u l- monitoraġġ tal- konċentrazzjoni terapewtika hija rrakkomandata, meta din hija disponibli.
Caution is warranted when Kaletra is used in patients with severe renal impairment (see section 4.4).
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 ssoltu huma assoċjati ma ’ dawn l- aġenti għal kontra l- kanċer.
4.3 Contraindications
Mediċini għal kontra l- koagulazzjoni tad- demm: il- konċentrazzjonijiet ta ’ warfarin jistgħu jiġu affetwati meta dawn il- mediċini jingħataw flimkien ma’ Kaletra.
Hypersensitivity to the active substances or to any of the excipients.
Huwa rakkomandat illi l- INR (international normalised ratio) jiġi monitorjat.
Patients with severe hepatic insufficiency.
Mediċini għal kontra l- konvulżjoni (phenobarbital, phenytoin, carbamazepine): jinduċu CYP3A4 u jistgħu jnaqqsu l- konċentrazzjonijiet ta ’ lopinavir.
Kaletra contains lopinavir and ritonavir, both of which are inhibitors of the P450 isoform CYP3A.
Barraminnhekk, l- għoti flimkien ta ’ phenytoin u lopinavir/ ritonavir wassal għal tnaqqis moderat fil - konċentrazzjoni fissa ta ’ phenytoin.
Kaletra should not be co-administered with medicinal products that are highly dependent on CYP3A
Meta phenytoin jingħata flimkien ma ’ lopinavir/ ritonavir, il- livelli ta ’ phenytoin għandhom jiġu monitorjati.
65 for clearance and for which elevated plasma concentrations are associated with serious and/ or life threatening events.
Dan l- effett jista ’ jkun ikkawżat mill- induzzjoni tal - metaboliżmu ta ’ bupropion.
These medicinal products include astemizole, terfenadine, oral midazolam (for caution on parenterally administered midazolam, see section 4.5), triazolam, cisapride, pimozide, amiodarone, ergot alkaloids (e. g. ergotamine, dihydroergotamine, ergonovine and methylergonovine) and vardenafil.
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.
Herbal preparations containing St John’ s wort (Hypericum perforatum) must not be used while taking lopinavir and ritonavir due to the risk of decreased plasma concentrations and reduced clinical effects of lopinavir and ritonavir (see section 4.5).
Trazodone: fi studju farmarkokinetiku li sar fuq voluntiera f’ saħħithom, l- użu flimkien ta ’ doża baxxa ta ’ ritonavir (200 mg darbtejn kuljum) ma ’ doża waħda ta ’ trazodone, wassal għal żieda fil - konċentrazzjoni fil- plażma ta ’ trazodone (żieda fl- AUC bi 2. 4 darbiet).
4.4 Special warnings and precautions for use
F’ dan l- istudju, effetti avversi ta ’ nawseja, sturdament, pressjoni baxxa u sinkope kienu osservati wara li ngħataw trazodone u
Patients with coexisting conditions
80 ritonavir flimkien.
Hepatic impairment: the safety and efficacy of Kaletra has not been established in patients with significant underlying liver disorders.
Digoxin: il- konċentrazzjoni ta ’ digoxin fil- plażma tista ’ tiżdied meta dan ikun mogħti flimkien ma ’ Kaletra.
Kaletra is contraindicated in patients with severe liver impairment (see section 4.3).
Għandha tiġi eżerċitata kawtiela, u fejn disponibbli huwa rrakkomandat li jsir monitoraġġ għall- mediċina terapewtika tal- konċentrazzjoni ta ’ digoxin, meta Kaletra u digoxin jingħataw flimkien.
Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse reactions.
Għandha tintwera kawtiela partikolari meta Kaletra jingħata mit- tabib lil pazjenti li qegħdin jieħdu digoxin, għaliex l- effett intens ta ’ impediment ta ’ ritonavir fuq Pgp huwa mistenni li jżid b’ mod sinifikanti l- livelli ta ’ digoxin.
In case of concomitant antiviral therapy for hepatitis B or C, please refer to the relevant product information for these medicinal products.
Iż- żieda fil- livell ta ’ digoxin tista ’ tonqos biż- żmien malli l- induzzjoni ta ’ Pgp tiżviluppa.
If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment should be considered.
L- introduzzjoni ta ’ digoxin f’ pazjenti li diġa qegħdin jieħdu Kaletra hi mistennija li tirriżulta f’ żieda iżgħar fil- konċentrazzjoni ta ’ digoxin.
Renal impairment: since the renal clearance of lopinavir and ritonavir is negligible, increased plasma concentrations are not expected in patients with renal impairment.
Imblukkaturi Dihydropyridine tal- passaġġi tal- kalċju:
Because lopinavir and ritonavir are highly protein bound, it is unlikely that they will be significantly removed by haemodialysis or peritoneal dialysis.
(eż. felodipine, nifedipine, nicardipine): jista ’ jkollom il- konċentrazzjonijiet fis- serum miżjuda b’ Kaletra.
Haemophilia: there have been reports of increased bleeding, including spontaneous skin haematomas and haemarthrosis in patients with haemophilia type A and B treated with protease inhibitors.
Aġenti li jnaqqsu l- lipidi: impedituri HMG- CoA reductase li jiddependu ħafna fuq il- metaboliżmu ta ’ CYP3A4, bħal lovastatin u simvastatin, huma mistennija li jkollom żieda kbira fil- konċentrazzjoni fil - plażma meta dawn jingħataw flimkien ma ’ Kaletra.
In some patients additional factor VIII was given.
Atorvastatin jiddependi inqas fuq CYP3A għal metaboliżmu.
In more than half of the reported cases, treatment with protease inhibitors was continued or reintroduced if treatment had been discontinued.
Meta atorvastatin ingħata flimkien ma ’ Kaletra, kienet osservata żieda medja ta ’ 4. 7 darbiet u 5. 9 darbiet fis- Cmax u fl- AUC ta ’ atorvastatin, rispettivament.
A causal relationship had been evoked, although the mechanism of action had not been elucidated.
Meta użat ma ’ Kaletra, għandha tingħata l- inqas doża possibli ta ’ atorvastatin.
Haemophiliac patients should therefore be made aware of the possibility of increased bleeding.
Rosuvastatin mhuwiex dipendenti fuq CYP3A.
Treatment with Kaletra has resulted in increases, sometimes marked, in the concentration of total cholesterol and triglycerides.
Madanakollu, meta dan ingħata flimkien ma ’ Kaletra, ġiet osservata żieda fis- Cmax u fl- AUC ta ’ rosuvastatin ta ’ medja ta ’ 5 darbiet aktar u darbtejn aktar, rispettivament.
Triglyceride and cholesterol testing is to be performed prior to initiating Kaletra therapy and at periodic intervals during therapy.
Għandha tiġi eżerċitata kawtiela meta Kaletra jingħata flimkien ma ’ rosuvastatin.
Particular caution should be paid to patients with high values at baseline and with history of lipid disorders.
Riżultati minn studju ta ’ interazzjoni b’ Kaletra u pravastatin ma żvelaw l- ebda interazzjoni li hi klinikament sinifikanti.
Lipid disorders are to be managed as clinically appropriate (see also section 4.5 for additional information on potential interactions with HMG-CoA reductase inhibitors).
Jekk tiġi indikata kura b’ impedituri HMG- CoA reductase, pravastatin jew fluvastatin huma rrakkomandati.
Pancreatitis
L- użu ta ’ vardenafil ma ’ Kaletra huwa kontra- indikat (ara sezzjoni 4. 3).
Cases of pancreatitis have been reported in patients receiving Kaletra, including those who developed hypertriglyceridaemia.
Cyclosporin, sirolimus (rapamycin) u tacrolimus: il- konċentrazzjoni tista ’ tiżdied meta dawn jingħataw flimkien ma ’ Kaletra.
In most of these cases patients have had a prior history of pancreatitis and/ or concurrent therapy with other medicinal products associated with pancreatitis.
Huwa rrakkomandat monitoraġġ iżjed frekwenti tal- konċentrazzjoni terapewtika sakemm jiffissaw ruħhom il- livelli fil- plażma ta ’ dawn il- prodotti.
Marked triglyceride elevation is a risk factor for development of pancreatitis.
Ketoconazole u itraconazole: dawn jista ’ jkollom żieda fil- konċentrazzjoni fis- serum ikkawżata minn Kaletra.
Patients with advanced HIV disease may be at risk of elevated triglycerides and pancreatitis
Dożi għolja ta ’ ketoconazole u itraconazole (> 200 mg/ ġurnata) mhumiex irrakkomandati.
Pancreatitis should be considered if clinical symptoms (nausea, vomiting, abdominal pain) or abnormalities in laboratory values (such as increased serum lipase or amylase values) suggestive of
Voriconazole: minħabba il- potenzjal ta ’ tnaqqis fil- konċentrazzjoni ta ’ voriconazole, l- għoti ta ’ voriconazole flimkien ma ’ doża baxxa ta ’ ritonavir (100 mg darbtejn kuljum) kif fih Kaletra għandu jiġi evitat sakemm ma ssirx stima tal- benefiċju/ riskju għall- pazjenti li tiġġustifika l- użu ta ’ voriconazole.
66 pancreatitis should occur.
81 Clarithromycin: żidiet moderati fl- AUC ta ’ clarithromycin huma mistennija meta dan jingħata flimkien ma ’ Kaletra.
Patients who exhibit these signs or symptoms should be evaluated and Kaletra therapy should be suspended if a diagnosis of pancreatitis is made (see section 4.8).
Għal pazjenti b’ indeboliment renali jew tal- fwied, għandu jiġi kkunsidrat tnaqqis fid- doża ta’ clarithromycin (ara sezzzjoni 4. 4).
Hyperglycaemia
Kaletra jista ’ jingħata flimkien ma ’ buprenorphine mingħajr bżonn ta ’ aġġustament fid- doża.
New onset diabetes mellitus, hyperglycaemia or exacerbation of existing diabetes mellitus has been reported in patients receiving protease inhibitors.
Ġie ppruvat li Kaletra jnaqqas il- konċentrazzjoni fil- plażma ta ’ methadone.
In some of these the hyperglycaemia was severe and in some cases also associated with ketoacidosis.
Il- monitoraġġ tal- konċentrazzjoni fil- plażma ta ’ methadone huwa rrakkomandat.
Many patients had confounding medical conditions some of which required therapy with agents that have been associated with the development of diabetes mellitus or hyperglycaemia.
Kontraċettivi: il- livelli ta ’ ethinyl oestradiol naqqsu meta kontraċettivi li huma bbażati fuq l- estroġenu ngħataw flimkien ma ’ Kaletra.
Fat redistribution and metabolic disorders
Għandha mnejn tkun neċċesarja riduzzjoni ulterjuri.
Combination antiretroviral therapy has been associated with redistribution of body fat (lipodystrophy) in HIV patients.
Madanakollu, dan l- aġġustament tad- doża jista ’ jkun assoċjat ma ’ żiediet fl- ALT/ AST u ma ’ żieda fid- disturbi gastrointestinali.
The long-term consequences of these events are currently unknown.
Għalhekk, dan l- għoti flimkien għandu jiġi evitat sakemm ma jkunx strettament neċessarju.
Knowledge about the mechanism is incomplete.
Id- doża ta ’ Kaletra għandha tiġi miżjuda ftit ftit, biss wara li jkun inbeda jingħata rifampicin (ara sezzjoni 4. 4).
A connection between visceral lipomatosis and protease inhibitors (PIs) and lipoatrophy and nucleoside reverse transcriptase inhibitors (NRTIs) has been hypothesised.
Fexfiex tar- Raba ’ (St John’ s wort): il- livelli fis- serum ta ’ lopinavir u ritonavir jistgħu jonqsu bl- użu konkomitanti tal- preparazzjoni tal- ħxejjex tal- fexfiex tar- raba ’ (Hypericum perforatum).
A higher risk of lipodystrophy has been associated with individual factors such as older age, and with drug related factors such as longer duration of antiretroviral treatment and associated metabolic disturbances.
Preparazzjonjiet tal- ħxejjex li fihom il- fexfiex tar- raba ’ m’ għandhomx jiġu mħallta ma ’ lopinavir u ritonavir.
Clinical examination should include evaluation for physical signs of fat redistribution.
Il- livelli ta ’ lopinavir u ritonavir jistgħu jiżdiedu mat- twaqqif tal- fexfiex tar- raba ’.
Consideration should be given to measurement of fasting serum lipids and blood glucose.
Jista ’ jkun li d- doża ta ’ Kaletra jkollha bżonn tiġi aġġustata.
Lipid disorders should be managed as clinically appropriate (see section 4.8).
L- effett li jinduċi jista ’ jibqa ’ jippersisti għal mill- inqas ġimagħtejn wara li titwaqqaf il- kura bil- fexfiex tar- raba ’ (ara sezzjoni 4. 3).
Immune Reactivation Syndrome
Midazolam: midazolam huwa fil- biċċa l- kbira tiegħu metabolizzat b’ CYP3A4.
In HIV-infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymtomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms.
82 Fluticasone propionate (interazzjoni ma ’ ritonavir): fi studju kliniku fejn kapsuli ta ’ ritonavir ta ’ 100 mg darbtejn kuljum ingħataw flimkien ma ’ 50 μg fluticasone propionate mogħti mill- imnieħer (4 darbiet kuljum) għal sebat (7) ijiem f’ suġġetti b’ saħħithom, il- livelli fil- plażma ta ’ fluticasone propionate għolew b’ mod sinifikanti, filwaqt li l- livelli intrinsiċi tal- kortisol tbaxxew b’ bejn wieħed u ieħor 86% (90% intervall ta ’ fiduċja 82 - 89%).
Typically, such reactions have been observed within the first few weeks or months of initiation of CART.
Effetti akbar jistgħu jkunu mistennija meta fluticasone propionate jinġibed mill- ħalq.
Relevant examples are cytomegalovirus retinitis, generalised and/ or focal mycobacterial infections, and Pneumocystis carinii pneumonia.
Barraminnhekk, f’ każi ta ’ twaqqif tal- glukokortikojdi, jista ’ jkun meħtieġ tnaqqis progressiv tad- doża fuq żmien twil.
Any inflammatory symptoms should be evaluated and treatment instituted when necessary.
L- effetti ta ’ esponiment sistemiku għoli għal fluticasone fuq il- livelli fil- plażma ta ’ ritonavir għadhom mhux magħrufa.
Osteonecrosis
4. 6 Tqala u Treddigħ
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).
Mhuwiex magħruf jekk dan il- prodott mediċinali joħroġx mal- ħalib tas- sider tal- bniedem.
Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.
Nisa infettati bl- HIV m’ għandhom ireddgħu lit- trabi tagħhom taħt l- ebda ċirkustanza biex jevitaw li jgħaddulhom l- HIV.
PR interval prolongation
4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
Lopinavir/ ritonavir has been shown to cause modest asymptomatic prolongation of the PR interval in some healthy adult subjects.
Ma sarux studji dwar l- effetti fuq il- ħila biex issuq jew tħaddem magni.
Kaletra should be used with caution in such patients (see section 5.1).
Il- pazjenti għandhom jiġu infurmati li ġew irrappurtati każi ta ’ nawseja waqt il- kura b’ Kaletra (ara sezzjoni 4. 8).
Interactions with medicinal products
4. 8 Effetti mhux mixtieqa
Kaletra contains lopinavir and ritonavir, both of which are inhibitors of the P450 isoform CYP3A.
F’ uħud mill- istudji, Kaletra kien użat flimkien ma ’ efavirenz jew nevirapine.
Kaletra is likely to increase plasma concentrations of medicinal products that are primarily metabolised by CYP3A.
L- iżjed reazzjoni avversa assoċjata mat- terapija b’ Kaletra kienet id- dijarea, u kienet ġeneralment ta ’ severità minn ħafifa għal moderata.
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).
It- twaqqif tat- terapija minħabba reazzjonijiet avversi kien ta ’ 4. 5% (f’ pazjenti li qatt ma ħadu din it- terapija qabel) u 9% (pazjenti b’ esperjenza) fuq perjodu ta ’ 48 ġimgħa.
67 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.
Huwa importanti li wieħed jinnota li ġew irrappurtati każi ta ’ pankreatite f’ pazjenti li kienu qegħdin jirċievu Kaletra, inklużi dawk li żviluppaw l- ipertrigliċeridemija.
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.
Barraminnhekk, ġew rrapurtati waqt t- terapija b’ Kaletra, każi rari ta ’ żidiet fl- intervall PR (ara sezzjoni 4. 4: sezzjoni pankreatite u sezzjoni żiediet fil- lipidi).
If treatment with a HMG-CoA reductase inhibitor is indicated, pravastatin or fluvastatin is recommended (see section 4.5).
83 Żieda fis- CPK, majalġja, mijożite u rarament, rabdomijoliżi kienu rrapurtati bl- impedituri protejaż, partikolarment meta użati flimkien ma ’ impedituri nukleòside reverse transcriptase.
Particular caution must be used when prescribing Kaletra and medicinal products known to induce QT interval prolongation such as: chlorpheniramine, quinidine, erythromycin, clarithromycin.
F’ pazjenti bl- HIV, it- terapija antiretrovirali kombinata ġiet assoċjata mar- ridistribuzzjonji tax- xaħam tal- ġisem (lipodistrofija), li jinkludi t- telf ta ’ xaħam periferali u xaħam ta ’ taħt il- ġilda tal- wiċċ, żieda fix- xaħam fiż- żaqq u dak tal- vixxri, ipertrofija tas- sider u akkumulazzjoni tax- xaħam dorso- ċervikali (buffalo hump).
Indeed, Kaletra could increase concentrations of the co-administered medicinal products and this may result in an increase of their associated cardiac adverse events.
It- terapija antiretrovirali kombinata ġiet assoċjata ma ’ problemi metaboliċi mhux normali bħall - ipertrigliċeridemija, kolesterol żejjed fid- demm, reżistenza għall- insulina, ipergliċemija u iperlaktatemija (ara sezzjoni 4. 4).
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).
F’ pazjenti infettati bl- HIV li jkollhom defiċjenza immunitarja serja ħafna fiż- żmien meta tinbeda t - terapija antiretrovirali kombinata (CART), tista ’ tiżviluppa reazzjoni infjammatorja għal infezzjonijiet li ma jikkawżawx sintomi jew infezzjonijiet opportunistiċi residwali (ara sezzjoni 4. 4).
Co-administration of Kaletra with rifampicin is not recommended.
Ġew irrappurtati r- reazzjonijiet avversi li ġejjin, ta ’ intensità minn moderata għal severa, b’ rabta possibbli jew probabbli ma ’ Kaletra.
Rifampicin in combination with Kaletra causes large decreases in lopinavir concentrations which may in turn significantly decrease the lopinavir therapeutic effect.
Ir- reazzjonjiet avversi huma murija skond il- klassi tas- sistema ta ’ l- organi.
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.
F’ kull sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa għandhom jitniżżlu skond is- serjetà tagħhom.
Therefore, this co-administration should be avoided unless judged strictly necessary (see section 4.5).
L- effetti li huma l- aktar serji għandhom jitniżżlu l- ewwel, segwiti minn dawk anqas serji: komuni ħafna > 1/ 10, komuni > 1/ 100, < 1/ 10, mhux komuni > 1/ 1000, < 1/ 100.
Other
84 Effetti mhux mixtieqa fi studji kliniċi f’ pazjenti adulti
Kaletra is not a cure for HIV infection or AIDS.
Infezzjonijiet u infestazzjonijiet
Appropriate precautions should be taken.
Mhux komuni Mhux komuni
People taking Kaletra may still develop infections or other illnesses associated with HIV disease and AIDS.
Infjammazzjoni tal- widna tan- nofs, bronkite, sinożite, furunkulosi, infezzjoni tal- batterji, infezzjoni virali
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).
Neoplażmi beninni, malinni u dawk mhux speċifikati (inklużi ċesti u polipi)
4.5 Interaction with other medicinal products and other forms of interaction
Disturbi tad- demm u tas- sistema limfatika
Kaletra contains lopinavir and ritonavir, both of which are inhibitors of the P450 isoform CYP3A in vitro.
Anemija, lewkopenja u mard fil- limfa
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.
Mhux komuni
Kaletra does not inhibit CYP2D6, CYP2C9, CYP2C19, CYP2E1, CYP2B6 or CYP1A2 at clinically relevant concentrations (see section 4.3).
Ipogonadiżmu maskili, sindromu Cushing (Cushing syndrome), ipotirojdiżmu
This may result in lowered plasma concentrations and potential decrease of efficacy of co-administered medicinal products.
Disturbi fil- metaboliżmu u n - nutrizzjoni
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.
Avitaminosi, deidratazzjoni, nefħa minn akkumulazzjoni ta ’ ilma fil- ġisem, żieda fl - aptit, aċidożi laktika, obesità, anoressija, dijabete mellitus, ipergliċemija, nuqqas ta ’ kolesterol fid- demm
All interaction studies, when otherwise not stated, were performed using Kaletra capsules, which gives an approximately 20% lower exposure of lopinavir than the 200/ 50 mg tablets.
Ħolm mhux normali, aġitazzjoni, ansjetà, konfużjoni, depressjoni, diżkinesija, nuqqas ta ’ stabbilità emozzjonali, tnaqqis fil- libido, nervożità, taħseb b’ mod mhux normali
Antiretroviral agents
Disturbi fis- sistema nervuża
Nucleoside/ Nucleotide reverse transcriptase inhibitors (NRTIs):
Uġigħ ta ’ ras, parasteżija
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.
Sturdament, amnesija, atassja, enċefalopatija, paraliżi tal- wiċċ, ipertonija, newropatija, nevrite periferali, ngħas, tregħid, telf tas- sens tat- togħma, tibdil fit- togħma, migranja, sindromu estrapiramidali
68 Didanosine: it is recommended that didanosine be administered on an empty stomach; therefore, didanosine may be co-administered with Kaletra tablets without food.
Viżjoni mhux normali, disturbi fl- għajnejn
Zidovudine and Abacavir:
Żanżin tal- widnejn
Kaletra induces glucuronidation; therefore Kaletra has the potential to reduce zidovudine and abacavir plasma concentrations.
Palpitazzjonijiet, akkumulazzjoni ta ’ ilma fil - pulmun, infart mijokardjali1
The clinical significance of this potential interaction is unknown.
Disturbi vaskulari
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.
Pressjoni għolja b’ mod anormali, thrombophlebitis, vaskulite, vini varikużi, thrombophlebitis fonda, disturbi vaskulari
Higher tenofovir concentrations could potentiate tenofovir associated adverse events, including renal disorders.
Disturbi respiratorji, toraċiċi u medjastinali
Non-nucleoside reverse transcriptase inhibitors (NNRTIs):
Dispnea, rinite, żieda fis- sogħla
In a study performed in healthy volunteers to explore the interaction between Kaletra tablets (400/ 100 mg twice daily) and efavirenz (600 mg once daily), efavirenz has been shown to decrease the lopinavir concentrations by 30 - 40%.
Nawseja, rimettar, uġigħ addominali, skart tal- ġisem mhux normali, dispepsja, gass fl - istonku, disturbi gastro- intestinali
When Kaletra tablet dosages were increased to 500/ 125 mg twice daily during co-administration of efavirenz 600 mg once daily in healthy volunteers, lopinavir pharmacokinetic parameters were similar to those obtained with Kaletra tablets 400/ 100 mg twice daily administered alone.
Nefħa fiż- żaqq, stitikezza, nixfa fil- ħalq, disfaġja, enterokolite, kolite fl- intestini, tifwiq, esofaġite, inkontinenza ta ’ l- iskart tal - ġisem, gastrite, gastro- enterite, kolite bil- ħruġ ta ’ ħafna demm, tiġriħ tal- ħalq, pankreatite2, sialadenitis, stomatite, stomatite bl- ulċeri, periodontitis
Therefore, the Kaletra tablets dosage should be increased to 500/ 125 mg twice daily when co-administered with efavirenz 600 mg once daily.
Cholecystitis, epatite, epatomegalija, depożitu ta ’ xaħam fil- fwied, sensittività tal- fwied
The same recommendations for monitoring apply in these cases of co-administration.
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
Co-administration with other HIV protease inhibitors (PIs):
Raxx, lipodistrofija, akne
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.
Alopeċja, ġilda xotta, ekżema, dermatite fejn il- ġilda taqa ’ qxur qxur, raxx makulari bl - infafet, disturbi fid- dwiefer, ħakk, saborrea, telf ta ’ kulur tal- ġilda, ulċera fil- ġilda, nefħa fil- wiċċ ikkawżata minn akkumulazzjoni ta ’ ilma, ħruġ ta ’ għaraq, marki forma ta ’ linji fil- ġilda
Comparisons to published pharmacokinetic data with ritonavir-enhanced amprenavir and saquinavir regimens are also described.
Disturbi muskolu- skeltrali u tal - connective tissue
Additionally, the effect of additional ritonavir on the pharmacokinetics of lopinavir are discussed.
Artralġja, artrożi, majalġja, uġigħ fid- dahar, disturbi fil- ġogi
Note that the historical comparisons to ritonavir-enhanced protease inhibitor regimens should be interpreted with caution (see details of combinations below).
Ħaġra fil- kliewi, urina mhux normali, albuminerija, hypercalcinuria, nefrite, hyperuricemia
Appropriate doses of HIV-protease inhibitors in combination with Kaletra with respect to safety and efficacy have not been established.
Disturbi fis- sistema riproduttiva u fis- sider
Therefore, the concomitant administration of Kaletra with PIs requires close monitoring.
Ħruġ mhux normali tas- semen mill- ġisem, amenorrea, tkabbir tas- sider, ginekomastija, impotenza, menorrhagia
Amprenavir: see recommendations described for Kaletra tablets co-administration with efavirenz.
Disturbi ġenerali u kundizzjonijiet ta 'mnejn
Fosamprenavir: co-administration of standard doses of lopinavir/ ritonavir with fosamprenavir results in a significant reduction in amprenavir concentrations.
Uġiegħ fis- sider, uġiegħ fis- sider taħt l - isternu, dehxiet, deni, sindromu ta ’ l - influenza, tħossok m’ intix f’ sikktek, nefħa periferali, interazzjoni ma ’ mediċini oħra Żieda fit- trigliċeridi, żieda fil- kolesterol totali,
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, when compared with standard doses of fosamprenavir/ ritonavir.
Żieda fil- glukosju, żieda fl- amylase, żieda fl - Komuni SGOT/ AST, żieda fl- SGPT/ ALT, riżultati tat - (Grad 3 jew 4) testijiet tal- funzjoni tal- fwied mhux normali
Therefore, concomitant administration of these medicinal products is not recommended.
Tnaqqis fit- tolleranza għall- glukosju, żieda 1
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.
fil- piż, tnaqqis fil- piż, żieda fil- bilirubin, tibdil fil- livelli ta ’ l- ormoni, riżultati tat - testijiet tal- laboratorju mhux normali
Nelfinavir: see recommendations described for Kaletra tablets co-administration with efavirenz.
Ara sezzjoni 4. 4: pankreatite u lipidi
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.
Pazjenti Pedjatriċi Fil- każ ta ’ tfal ta ’ sentejn u ikbar, in- natura tal- profil ta ’ sigurtà huwa simili għal dak fl- adulti.
69 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.
Effetti mhux mixtieqa fi studji kliniċi f’ pazjenti pedjatriċi Infezzjonijiet u infestazzjonijiet Komuni
When saquinavir 1200 mg twice daily was combined with Kaletra, no further increase of concentrations was noted.
Stitikezza, rimettar, pankreatite *
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.
Żieda fil- ħin parzjali attivat tat - tromboplastina, tnaqqis fl- emoglobina, tnaqqis fid- diski żgħar numerużi fid- demm, żieda fis- sodju, żieda fil- potassju, żieda fil - kalċju, żieda fil- bilirubin, żieda fl - SGPT/ ALT, żieda fl- SGOT/ AST, żieda fil - kolosterol totali, żieda fl- amylase, żieda fl - aċidu uriku, tnaqqis fis- sodju, tnaqqis fil - potassju, tnaqqis fil- kalċju, tnaqqis fin - newtrofili
Ritonavir:
* ara sezzjoni 4. 4: pankreatite u lipidi
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.
L- epatite, u rarament is- suffejra, kienu rrapurtati f’ pazjenti li kienu qegħdin jirċievu t- terapija b’ Kaletra fil- preżenza jew fl- assenza ta ’ fatturi ta ’ riskju għall- epatite li jistgħu jiġu identifikati.
Other medicinal products:
Ġew irrappurtati s- sindromu Stevens- Johnsos u eritema tat- tip multiforme.
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.
Ġew irrappurtati każijiet ta ’ nekrosi ta ’ l- għadam, partikolarment f’ pazjenti b’ fatturi ta ’ riskju li huma ġeneralment magħrufa, bil- marda ta ’ l- HIV fi stadju avanzat jew li kellhom esponiment fuq tul ta ’ żmien għat- terapija antiretrovirali kombinata (CART).
Kaletra can be co-administered with acid reducing agents with no dose adjustment.
Il- frekwenza ta ’ dan mhijiex magħrufa (ara sezzjoni 4. 4).
Antiarrhythmics:
4. 9 Doża eċċessiva
(bepridil, systemic lidocaine and quinidine): concentrations may be increased when co-administered with Kaletra.
Sal- lum, hemm esperjenza limitata fil- bniedem f’ każ ta ’ doża qawwija u eċċessiva ta ’ Kaletra.
Caution is warranted and therapeutic concentration monitoring is recommended when available.
Is- sinjali kliniċi avversi osservati fil- klieb inkludew tibżiq, rimettar u dijarea/ skart tal- ġisem mhux normali.
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.
Il- kura għal doża eċċessiva ta ’ Kaletra għandha tikkonsisti f’ miżuri ġenerali ta ’ sapport, li jinkludu monitoraġġ ta ’ sinjali vitali u osservazzjoni ta ’ l- istat kliniku tal- pazjent.
Anticoagulants: warfarin concentrations may be affected when co-administered with Kaletra.
Il- mekkaniżmu ta ’ l- azzjoni: lopinavir jipprovdi l- attività antivirali ta ’ Kaletra.
It is recommended that INR (international normalised ratio) be monitored.
Lopinavir huwa impeditur tal- protejaż ta ’ HIV- 1 u HIV- 2.
Anticonvulsants (phenobarbital, phenytoin, carbamazepine): will induce CYP3A4 and may decrease lopinavir concentrations.
L- intervall QTcF ġie evalwat fi studju tat- tip crossover li sar b’ ordni addoċċ li kien ikkontrollat mill- plaċebo u attiv (moxifloxacin 400mg darba kuljum) li sar fuq 39 pazjent f’ saħħtu, fejn f’ Ġurnata 3, ġie mkejjel 10 darbiet fi 12- il siegħa.
In addition, co-administration of phenytoin and lopinavir/ ritonavir resulted in moderate decreases in steady-state phenytoin concentrations.
Id- differenzi medji massimi (95% upper confidence bound) fil- QTcF mill- plaċebo kienu ta ’ 3. 6 (6. 3) u 13. 1 (15. 8) fil- każ fejn ingħatat doża ta ’ 400/ 100 mg LPV/ r darbtejn kuljum u 800/ 200 mg LPV/ r aktar milli jingħata fit- terapija darbtejn kuljum, rispettivament.
Phenytoin levels should be monitored when co-administering with lopinavir/ ritonavir.
It- titwil ikkawżat ta ’ l- intervall QRS minn 6 ms għal 9. 5 ms b’ doża għolja ta ’ lopinavir/ ritonavir (800/ 200 mg darbtejn kuljum) jikkontribwixxi għat- titwil fil QT.
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.
Titwil mhux kbir ta ’ l- intervall PR ġie nnutat ukoll fl- istess studju f’ Ġurnata 3, f’ suġġetti li kienu qegħdin jirċievu lopinavir/ ritonavir.
This effect may be due to induction of bupropion metabolism.
Fl- intervall ta ’ 12- il siegħa ta ’ wara li ngħatat id- doża, it- tibdil medju mil- linja bażi fl- intervall PR varja minn 11. 6 ms sa 24. 4 ms.
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.
L- intervall PR massimu kien ta ’ 286 msec u ma ġie osservat l- ebda imblukkar tal- qalb tat- tieni jew tat- tielet grad (ara sezzjoni 4. 4).
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).
Attività antivirali in vitro: l- attività antivirali in vitro ta ’ lopinavir kontra razez ta ’ l- HIV tal- laboratorju u kliniċi, kienet evalwata f’ linji ta ’ ċelloli limfoblastiċi u limfoċiti tad- demm periferali infettati b’ mod akut, rispettivament.
Adverse events of nausea, dizziness, hypotension and syncope were observed following co-administration of trazodone and ritonavir in this study.
Fl- assenza tas- serum uman, l- IC50 medja ta ’ lopinavir kontra ħames razez differenti tal- laboratorju ta ’ HIV- 1 kienet ta ’ 19 nM.
However, it is unknown whether the combination of lopinavir/ ritonavir causes a similar increase in trazodone exposure.
Fl- assenza u fil- preżenza ta ’ 50% ta ’ serum uman, l- IC50 medja ta ’ lopinavir kontra HIV- 1IIIB f’ ċelluli MT4 kienet ta ’ 17 nM u 102 nM, rispettivament.
The combination should be used with caution and a lower dose of trazodone should be considered.
Fl - assenza ta ’ serum uman, l- IC50 medja ta ’ lopinavir kienet ta ’ 6. 5 nM kontra ħafna iżolati kliniċi ta ’ HIV - 1.
Digoxin: plasma concentrations of digoxin may be increased when co-administered with Kaletra.
Selezzjoni ta ’ reżistenza in vitro:
Caution is warranted and therapeutic drug monitoring of digoxin concentrations, if available, is recommended in case of co-administration of Kaletra and digoxin.
L- iżolati ta ’ HIV- 1 b’ suxxettibilità mnaqqsa għal lopinavir, ġew magħżula in vitro.
Particular caution should be used when prescribing Kaletra in patients taking digoxin as the acute inhibitory effect of ritonavir on Pgp is
HIV- 1 ġie mgħoddi in vitro ma ’ lopinavir waħdu u ma ’ lopinavir flimkien ma ’ ritonavir fi proporzjonijiet ta ’ konċentrazzjoni, li jirrappreżentaw il- medda tal- proporzjonijiet ta ’ konċentrazzjoni fil- plażma osservati waqt it- terapija b’ Kaletra.
The increased digoxin level may lessen over time as Pgp induction develops.
88 jissuġġerixxu li l- preżenza ta ’ ritonavir, f’ dawn il- proporzjonijiet ta ’ konċentrazzjoni, ma tinfluwenzax bil- kbir is- selezzjoni ta ’ virus reżistenti għal lopinavir.
Initiation of digoxin in patients already taking Kaletra is expected to result in lower increase of digoxin concentrations.
Fuq kollox, il- karatterizzazzjoni in vitro ta ’ cross- resistance fenotipika bejn lopinavir u impedituri protejaż oħrajn tissuġġerixxi li s - suxxettibilità imnaqqsa għal lopinavir ikkorrelatat mill- qrib mas- suxxettibilità imnaqqsa għal ritonavir u indinavir, iżda ma kkorrelatatx mill- qrib mas- suxxettibilità imnaqqsa għal amprenavir, saquinavir, u nelfinavir.
Dihydropyridine calcium channel blockers:
Analiżi ta ’ reżistenza f’ pazjenti li qatt ma esponew ruħhom qabel għal ARV:
(e. g. felodipine, nifedipine, nicardipine): may have their serum concentrations increased by Kaletra.
Ir- reżistenza għal nelfinavir, definita bħala l- preżenza tal- mutazzjoni ta ’ D30N jew L90M fil- protejaż, kienet osservata f ’ 41/ 96 (43%) suġġett.
Lipid lowering agents:
Analiżi tar- reżistenza f’ pazjenti b’ esperjenza ta ’ PI:
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.
Ġew ukoll osservati mutazzjonijiet L33F, I50V u V32I kkombinati ma ’ I47V/ A.
Since increased concentrations of HMG-CoA reductase inhibitors may cause myopathy, including rhabdomyolysis, the combination of these medicinal products with Kaletra is not recommended.
Id- 19 - il iżolat urew żieda ta ’ 4. 3 drabi aktar f’ IC50 meta mqabbla ma ’ iżolati tal- linja bażi (minn 6. 2 sa 43 darba aktar, imqabbla ma ’ virus tat- tip mhux kkultivat).
Atorvastatin is less dependent on CYP3A for metabolism.
Ġenotipiċi kkorelatati flimkien ta ’ suxxettibilità fenotipika mnaqqsa għal lopinavir fil- virusis magħżula minn impedituri protejaż oħra.
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.
F’ dan il- kwadru, il- mutazzjonijiet fil- protejaż ta ’ l- HIV li ġejjin, kienu assoċjati ma ’ tnaqqis fis- suxxettibilità in vitro għal lopinavir:
When used with Kaletra, the lowest possible dose of atorvastatin should be administered.
L10F/ I/ R/ V, K20M/ R, L24I, M46I/ L, F53L, I54L/ T/ V, L63P, A71I/ L/ T/ V, V82A/ F/ T, I84V u L90M.
Rosuvastatin is not dependent on CYP3A.
L- EC50 medjan ta ’ lopinavir kontra iżolati b’ 0
However, when given concurrently with Kaletra a mean 5-fold and 2-fold increase in rosuvastatin Cmax and AUC, respectively, was observed.
- 3, 4 - 5, 6 - 7 u 8 - 10 mutazzjonijiet fil- pożizzjonijiet ta ’ l- aċidu amminiku kif indikat hawn fuq, kien
Caution should be exercised when Kaletra is co-administered with rosuvastatin.
0. 8, 2. 7 13. 5 u 44. 0 darba ogħla mill- EC50 kontra l- HIV tat- tip mhux ikkultivat, rispettivament.