qanastek/EMEA-V3 huggingface dataset:
Fatal and non-fatal intracranial haemorrhage (ICH) have been reported in patients receiving APTIVUS, many of whom had other medical conditions or were receiving concomitant medicinal products that may have caused or contributed to these events.
Emorraġiji intrakranjali fatali u mhux fatali (ICH) ġew rapportati f' pazjenti li kienu qed jieħdu APTIVUS, li ħafna minnhom kellhom kundizzjonijiet mediċi oħra jew kienu qed jieħdu prodotti mediċinali flimkien ma 'dawn li setgħu rriżultaw jew ikkontribwew għal dawn l- effetti.
However, in some cases the role of APTIVUS cannot be excluded.
Madankollu, f' xi każijiet ir- rwol ta 'APTIVUS ma jistax jiġi eskluż.
No pattern of abnormal haematological or coagulation parameters has been observed in patients in general, or preceding the development of ICH.
B’ mod ġenerali ma ġiet osservata l- ebda skema ta 'parametri ematoloġiċi anormali jew tal- koagulazzjoni fil- pazjenti jew qabel l- iżvilupp ta' ICH.
Therefore, routine measurement of coagulation parameters is not currently indicated in the management of patients on APTIVUS.
Għalhekk, attwalment għadu mhux indikat li jrid ikun hemm kejl regolari tal- parametri tal- koagulazzjoni fil- ġestjoni ta 'pazjenti fuq APTIVUS.
An increased risk of ICH has previously been observed in patients with advanced HIV disease/ AIDS such as those treated in the APTIVUS clinical trials.
Riskju ogħla ta 'ICH kien osservat qabel f' pazjenti li għandhom marda avvanzata ta ’ l- HIV/ AIDS bħal dawk trattati fil- provi kliniċi ta' APTIVUS.
In in vitro experiments, tipranavir was observed to inhibit human platelet aggregation at levels consistent with exposures observed in patients receiving APTIVUS/ ritonavir.
F’ esperimenti in vitro, tipranavir kien osservat li jimpedixxi l- aggregazzjoni ta ’ pjastrini umani f’ livelli konsistenti ma ’ espożizzjonijiet osservati f’ pazjenti li qed jirċievu APTIVUS/ ritonavir.
In rats, co-administration with vitamin E increased the bleeding effects of tipranavir (see section 5.3 Preclinical safety data).
Fil- firien, meta ngħata flimkien ma ’ vitamina E kien hemm żieda fl- effetti ta ’ emorraġija ta ’ tipranavir (ara sezzjoni 5. 3 Tagħrif ta 'qabel l- użu kliniku dwar is- sigurtà tal- mediċina).
APTIVUS, co-administered with low dose ritonavir, should be used with caution in patients who may be at risk of increased bleeding from trauma, surgery or other medical conditions, or who are receiving medicinal products known to increase the risk of bleeding such as antiplatelet agents and anticoagulants or who are taking supplemental vitamin E.
APTIVUS, mogħti flimkien ma 'doża baxxa ta' ritonavir, għandu jintuża b' attenzjoni f' pazjenti li jinsabu f' riskju ta 'aktar fsada minħabba trawmiet, kirurġiji, jew kundizzjonijiet mediċi oħra, jew li qed jirċievu prodotti mediċinali magħrufa li jgħollu r- riskju ta' fsada bħal mediċini kontra l- plejtlets u anti- koagulanti jew li qed jieħdu vitamina supplimentali E.
Based on the limits of exposure available from observation in clinical trials, it is recommended not to co-administer to adults more than 1200 IU vitamin E per day.
Skond il- limiti ta ’ espożizzjoni disponibbli minn osservazzjoni tal- provi kliniċi, huwa rakkomandat li m’ għandux jingħata aktar minn 1200 IU ta ’ vitamina E lil adulti kuljum.
Diabetes mellitus/ hyperglycaemia:
Diabetes mellitus/ hyperglycaemia:
New onset of diabetes mellitus, hyperglycaemia or exacerbations of existing diabetes mellitus has been reported in patients receiving antiretroviral therapy, including protease inhibitors.
Kien hemm rapporti li pazjenti fuq terapiji antiretrovirali, li jinkludu wkoll impedituri ta ’ l- enżimi protease, mardu għall- ewwel darba b’ diabetes mellitus, ipergliċemja, jew inkella l- marda ta ’ diabetes mellitus tqawwitilhom meta kienu diġà morda biha.
In some of these the hyperglycaemia was severe and in some cases also associated with ketoacidosis.
F’ xi pazjenti l- ipergliċemija kienet qawwija, u xi drabi kienet assoċjata ma ’ keto- aċidożi.
Many of the patients had confounding medical conditions, some of which required therapy with agents that have been associated with the development of diabetes mellitus or hyperglycaemia.
Il- kundizzjonijiet mediċi li kienu fihom ħafna mill- pazjenti kienu mħawwda, u xi wħud kellhom bżonn terapija b’ mediċini li kienu ġew assoċjati ma ’ żvilupp ta ’ diabetes mellitus jew ipergliċemija.
Lipid elevations:
5 Żjieda fil- livelli tal- lipidi:
Treatment with APTIVUS co-administered with low dose ritonavir and other antiretroviral agents has resulted in increased plasma total triglycerides and cholesterol.
Il- kura permezz ta ’ APTIVUS li jingħata flimkien ma ’ doża baxxa ta 'ritonavir, u mediċini antiretrovirali oħrajn irriżultaw f' livelli ogħla ta ’ trigliċeridi u kolesterol fil- plażma.
Triglyceride and cholesterol testing should be performed prior to initiating tipranavir therapy and during therapy.
Għandhom isiru testijiet għal trigliċeridi u kolesterol qabel tibda t- terapija b’ tipranavir, kif ukoll matulha.
Treatment-related lipid elevations should be managed as clinically appropriate.
It- terapija għandha titmexxa b’ mod xieraq jekk ikun hemm żjieda fil- livelli tal- lipidi minħabba t- trattament.
Fat redistribution:
Tqassim mill- ġdid tax- xaħam:
Combination antiretroviral therapy has been associated with the redistribution of body fat (lipodystrophy) in HIV infected patients.
Terapiji b’ mediċini antiretrovirali differenti ġew assoċjati ma ’ tqassim mill- ġdid tax- xaħam fil- ġisem (lipodistrofija) f’ pazjenti infettati bl- HIV.
The long-term consequences of these events are currently unknown.
Għadhom mhux magħrufa l- konsegwenzi fit- tul ta ’ dan l- effett.
Knowledge about the mechanism is incomplete.
Għad m’ hemmx tagħrif biżżejjed dwar kif jaħdem dan il- mekkaniżmu.
A connection between visceral lipomatosis and protease inhibitors and lipoatrophy and nucleoside reverse transcriptase inhibitors has
Gie ipotizzat li hemm rabta bejn il- lipomatożi vixxerali u l- impedituri ta ’ l- enżimi protease, kif ukoll il- lipodistrofija u l- impedituri ta ’ l- enżima nucleoside reverse transcriptase.
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.
Riskju ogħla ta ’ lipodistrofija kien assoċjat ma ’ fatturi individwali bħal per eżempju x- xjuħija, u fatturi assoċjati ma ’ l- użu ta ’ mediċini bħal meta jintużaw trattamenti antiretrovirali fit- tul, kif ukoll disturbi li huma marbuta mal- metaboliżmu minħabba t- trattament.
Clinical examination should include evaluation for physical signs of fat redistribution.
L- eżami kliniku għandu jinkludi evalwazzjonii għal xi sinjali li juru tqassim mill- ġdid tax- xaħam fil- ġisem.
Consideration should be given to the measurement of fasting serum lipids and blood glucose.
Għandu jkun ikkunsidrat li jsiru testijiet għal- livelli tal- lipidi fis- serum u tal- glukożju fid- demm f’ sawm.
Lipid disorders should be managed as clinically appropriate (see section 4.8).
Mard li jaffettwa l- metaboliżmu tal- lipidi għandu jiġi kkurat b’ mod xieraq (ara sezzjoni 4. 8).
In HIV-infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms.
Sindromu ta ’ l- attivazzjoni mill- ġdid tas- sistema immunitarja Pazjenti infettati b’ HIV b' immunità batuta b' mod serju meta jkunu se jibdew it- terapija permezz ta ’ mediċini antiretrovirali, magħrufa bħala CART, jistgħu jiżviluppaw reazzjonijiet infjammatorji jew infezzjonijiet minn xi mikrobi opportunistiċi u patoġeniċi li jistgħu ma jurux sintomi jew is- sintomi li jkollhom jistgħu jmorru għall- agħar.
Typically, such reactions have been observed within the first few weeks or months of initiation of CART.
Ġeneralment, reazzjonijiet bħal dawn ġew osservati fl- ewwel ġimgħat jew xhur wara li tinbeda l- CART.
Relevant examples are cytomegalovirus retinitis, generalised and/ or focal mycobacterial infections and Pneumocystis pneumonia.
Eżempji rilevanti huma infezzjonijiet b' cytomegalovirus retinitis, infezzjonijiet majkobatteriċi ġenerali u/ jew iffokati u Pneumocystis pneumonia.
Any inflammatory symptoms should be evaluated and treatment instituted when necessary.
Kull sintomu ta ’ infjammazzjoni għandu jkun evalwat u għandu jinbeda trattament kif meħtieġ.
In addition, reactivation of herpes simplex and herpes zoster has been observed in clinical studies with APTIVUS, co-administered with low dose ritonavir.
Barraminhekk, ġiet osservata r- riattivazzjoni ta 'herpes simplex u herpes zoster fl- istudji kliniċi b' APTIVUS, mogħti ma' doża baxxa ta 'ritonavir.
APTIVUS contains macrogolglycerol ricinoleate which may cause stomach upset and diarrhoea.
APTIVUS fihom macrogolglycerol ricinoleate li jista 'jikkaġuna tqalligħ fl- istonku u dijarrea.
APTIVUS soft capsules contain small amounts of alcohol (7% ethanol, ie 100 mg per capsule or 200 mg per dose).
Il- kapsuli rotob ta ’ APTIVUS fihom ammont żgħir ta ’ alkoħol (7% ethanol ie 100 mg kull kapsula jew 200 mg kull doża).
Rash:
Raxx:
Mild to moderate rashes including urticarial rash, maculopapular rash, and photosensitivity have been reported in subjects receiving APTIVUS, co-administered with low dose ritonavir.
Kien hemm rapporti f' suġġetti li qed jingħataw APTIVUS, mogħti flimkien ma 'doża baxxa ta' ritonavar, ta 'raxx minn ħafif sa moderat li jinkludi raxx urtikarju, raxx mukulopapulari u fotosensittività.
At 48-weeks in Phase III trials rash of various types was observed in 15.5% males and 20.5% females receiving APTIVUS, co-administered with low dose ritonavir.
Wara 48 ġimgħa ta ’ provi ta ’ Fażi III raxx ta ’ diversi tipi kien osservat f’ 15. 5% ta ’ l- irġiel u 20. 5% tan- nisa li qed jirċievu APTIVUS, li ngħata flimkien ma ’ doża baxxa ta ’ ritonavir.
Additionally, in one interaction trial in healthy female volunteers administered a single dose of ethinyl oestradiol followed by APTIVUS co- administered with low dose ritonavir, 33% of subjects developed a rash.
Barra minn hekk, fi prova ta 'interazzjoni f' nisa voluntieri b' saħħithom li ngħataw doża waħda ta' ethinyl oestradiol segwita b' APTIVUS li ngħata flimkien ma 'doża baxxa ta' ritonavir, 33% tas - suġġetti żviluppaw raxx.
Rash accompanied by joint pain or stiffness, throat tightness, or generalized pruritus has been reported in both men and women receiving APTIVUS co-administered with low dose ritonavir.
Raxx flimkien ma 'uġigħ fil- ġogi jew ebusija, griżmejn issikkati jew prurite ġeneralizzata ġew irrapportati kemm f' nisa u rġiel li kienu qed jirċievu APTIVUS flimkien ma' doża baxxa ta 'ritonavir.
Osteonecrosis:
Osteonekrosi:
Although the etiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV-disease and/ or long-term exposure to combination antiretroviral therapy (CART).
Għalkemm l- etjoloġija hi kkonsidrata li hi multifattorjali (li tinkludi l- użu ta 'corticosteroid, il- konsum ta' alkoħol, immunosuppressjoni serja, indiċi ogħla tal- piż korporali), każijiet ta 'osteonekrosi ġew rapportati f' pazjenti li għandhom mard avvanzat ta' HIV u/ jew espożizzjoni fuq tul ta 'żmien għal terapija antiretrovirali kombinata (CART).
Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.
Il- pazjenti għandhom jingħataw parir biex ifittxu għal parir mediku jekk ikollhom uġigħ fil- ġogi, ebusija tal- ġogi jew diffikultà fiċ- ċaqliq.
Interactions:
Interazzjonijiet:
The interaction profile of APTIVUS, co-administered with low dose ritonavir, is complex.
Il- profil ta 'interazzjoni ta' APTIVUS, mogħti flimkien ma ’ doża baxxa ta 'ritonavir, hu kumpless.
For a description of the mechanisms and potential mechanisms contributing to the interaction profile of APTIVUS, see section 4.5.
Għal deskrizzjoni tal- mekkaniżmi u l- mekkaniżmi potenzjali li jinkontribwixxu għal profil ta 'interazzjonijiet ta' APTIVUS, ara sezzjoni 4. 5.
Abacavir and zidovudine:
Abacavir u zidovudine: L- użu konġunt ta 'APTIVUS, mogħti flimkien ma ’ doża baxxa ta' ritonavir, ma 'zidovudine jew abacavir, jirriżulta fi tnaqqis sinifikanti fil- konċentrazzjoni tal- plażma ta' dawn
The concomitant use of APTIVUS, co-administered with low dose ritonavir, with zidovudine or abacavir, results in a significant decrease in plasma concentration of these nucleoside reverse transcriptase inhibitors (NRTIs).
6 l- impedituri tat- tip nucleoside reverse transcriptase (NRTIs).
Therefore, the concomitant use of zidovudine or abacavir with APTIVUS, co-administered with low dose ritonavir, is not-recommended unless there are no other available NRTIs suitable for patient management (see section 4.5).
Għalhekk, l- użu konġunt ta 'zidovudine jew abacavir ma' APTIVUS, li jingħata f' doża baxxa ta 'ritonavir, mhux rakkomandat sakemm ma jkunx hemm NRTIs oħra disponibbli li huma adattati għal ġestjoni tal- pazjent (ara sezzjoni 4. 5).
Protease inhibitors:
Impedituri ta ’ enżimi protease:
Concomitant use of APTIVUS, co-administered with low dose ritonavir, with the protease inhibitors amprenavir, lopinavir or saquinavir (each co-administered with low dose ritonavir) in a dual-boosted regimen, results in significant decreases in plasma concentrations of these protease inhibitors.
L- użu konġunt ta 'APTIVUS, mogħti flimkien ma ’ doża baxxa ta' ritonavir, ma ’ l- impedituri ta ’ enżimi protease amprenavir, lopinavir jew saquinavir (kull wieħed jingħata flimkien ma ’ ritonavir b’ doża baxxa), f' reġimen ta 'żewġ dożi booster, jirriżulta f' konċentrazzjonijiet sinifikanti mnaqqsa ta ’ dawn l- impedituri ta ’ enżimi protease.
A significant decrease in plasma concentrations of atazanavir and a marked increase of tipranavir and ritonavir concentrations was observed when APTIVUS, associated with low dose ritonavir, was co-administered with atazanavir (see section 4.5).
Tnaqqis sinifikanti fil- konċentrazzjonijiet tal- plażma ta 'atazanavir u żjieda notevoli fil- konċentrazzjonijiet ta' tipranavir u ritonavir ġiet osservata meta APTIVUS, assoċjat ma 'doża baxxa ta' ritonavir, ġew mogħtija flimkien ma ’ atazanavir (ara sezzjoni 4. 5).
No data are currently available on interactions of APTIVUS, co-administered with low dose ritonavir, with protease inhibitors other than those listed above.
Attwalment, għad m’ hemmx ċifri dwar ir- reazzjonijiet ta ’ meta APTIVUS jingħata flimkien ma ’ ritonavir b’ doża baxxa, u jintuża ma ’ impedituri ta ’ enżimi protease, minbarra dawk li hemm elenkati fuq.
Therefore, the co-administration of APTIVUS, co-administered with low dose ritonavir, with protease inhibitors is not recommended.
Għalhekk, l- aministrazzjoni konġunta ta 'APTIVUS, mogħti flimkien ma' doża baxxa ta 'ritonavir, ma ’ impedituri ta ’ l- enżimi protease mhix rakkomandata.
6 Oral contraceptives and oestrogens:
Kontraċettivi orali u oestrogens:
Since levels of ethinyl oestradiol are decreased, the co- administration of APTIVUS co-administered with low dose ritonavir is not recommended.
Peress li l- livelli ta 'ethinyl oestradiol huma mnaqqsa, l- amministrazzjoni konġunta tagħhom ma ’ APTIVUS mogħti flimkien ma' ritonavir mhix rakkomandata.
Alternative or additional contraceptive measures are to be used when oestrogen based oral contraceptives are co- administered with APTIVUS co-administered with low dose ritonavir (see section 4.5).
Miżuri alternattivi jew addizzjonali ta 'kontraċezzjoni għandhom jittieħdu meta kontraċettivi orali bbażati fuq oestrogen huma mogħtija flimkien ma' APTIVUS mogħti flimkien ma ’ doża baxxa ta 'ritonavir (ara sezzjoni 4. 5).
Patients using oestrogens as hormone replacement therapy should be clinically monitored for signs of oestrogen deficiency.
Pazjenti li jużaw oestrogens bħala terapija ta 'sostituzzjoni ormonali għandhom jiġu monitorati b' mod kliniku għal sinjali ta' defiċjenza fl- oestrogen.
Women using oestrogens may have an increased risk of non serious rash.
Nisa li jużaw oestrogens ikollhom riskju akbar li jiżvillupaw raxx li ma jkunx serju.
Caution should be used when prescribing carbamazepine, phenobarbital, and phenytoin.
Antikonvulsanti: Għandha tintuża l- kawtela meta jinkitbu fuq ir- riċetta carbamazepine, phenobarbital u phenytoin.
APTIVUS may be less effective due to decreased tipranavir plasma concentrations in patients taking these agents concomitantly.
APTIVUS jista ’ jkun inqas effettiv minħabba konċentrazzjonijiet mnaqqsa ta ’ tipranavir fil- plażma f’ pazjenti li jieħdu dawn il- mediċini flimkien.
Due to their metabolic profile and inherent risk of inducing torsades de pointes, administration of halofantrine and lumefantrine with APTIVUS co-administered with low dose ritonavir, is not recommended.
Minħabba l- profil metaboliku tagħhom u r- riskju inerenti li jiġi indott torsades de pointes, l- għoti ta 'halofantrine u lumefantrine ma' APTIVUS mogħti flimkien ma ’ doża baxxa ta 'ritonavir, mhux rakkomandat.
Disulfiram/ metronidazole:
Disulfiram/ metronidazole:
APTIVUS soft capsules contain alcohol (7% ethanol, ie 100 mg per capsule or up to 200 mg per dose) which can produce disulfiram-like reactions when co-administered with disulfiram or other medicinal products which produce this reaction (eg metronidazole).
Il- kapsuli rotob ta 'APTIVUS fihom l- alkoħol (7% ethanol, ie 100 mg kull kapsula jew sa 200 mg kull doża) li jistgħu jikkaġunaw reazzjonijiet simili għal ta ’ disulfiram meta jiġu mogħtija flimkien ma' disulfiram jew prodotti mediċinali oħra li jipproduċu din ir- reazzjoni (eż metronidazole).
Concomitant use of APTIVUS, co-administered with low dose ritonavir, and fluticasone or other glucocorticoids that are metabolised by CYP3A4 is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression (see section 4.5).
L- użu konġunt ta 'APTIVUS, mogħti flimkien ma ’ doża baxxa ta' ritonavir, u fluticasone jew glucocorticoids oħrajn li huma metabolizzati b' CYP3A4 mhux rakkomandat għajr meta s- siwi potenzjali jisboq ir- riskju minn effetti sistematiċi ta 'corticosteroids inkluż is- sindromu ta' Cushing u t- trażżin adrenali (ara sezzjoni 4. 5).
APTIVUS, co-administered with low dose ritonavir, increases the plasma concentrations of atorvastatin (see section 4.5).
APTIVUS, mogħti flimkien ma ’ doża baxxa ta 'ritonavir, jgħolli l- konċentrazzjonijiet ta ’ atorvastatin fil- plażma (ara sezzjoni 4. 5).
The combination is not recommended.
Il- kombinazzjoni tagħhom mhix rakkomandata.
Other HMG-CoA reductase inhibitors should be considered such as pravastatin, fluvastatin or rosuvastatin.
Impedituri HMG- CoA reductase oħrajn għandhom jiġu konsidrati bħal pravastatin, fluvastatin jew rosuvastatin.
However, if atorvastatin is specifically required for patient management, careful monitoring is necessary.
Madankollu, jekk atorvastatin huwa speċifikament meħtieġ għal ġestjoni tal- pazjent, monitoraġġ b' kawtela huwa meħtieġ.
APTIVUS co-administered with low dose ritonavir decreases the plasma concentrations of omeprazole and esomeprazole (see section 4.5).
APTIVUS li jingħata ma ’ doża baxxa ta ’ ritonavir inaqqas l- konċentrazzjonijiet fil- plażma ta ’ omeprazole u esomeprazole (ara sezzjoni 4. 5).
Therefore, the combined use of APTIVUS/ ritonavir with either omeprazole or esomeprazole is not recommended.
Għalhekk, l- użu kkombinat ta ’ APTIVUS/ ritonavir ma ’ omeprazole jew ma ’ esomeprazole mhux rakkomandat.
If unavoidable, upward dose adjustments for either omeprazole or esomeprazole may be considered based on clinical response to therapy.
Jekk dan ma jistax jiġi evitat, aġġustamenti ’ l fuq fid- doża ta ’ omeprazole jew esomeprazole għandhom jiġu kkonsidrati skond ir- rispons kliniku għat- terapija.
Recommendations for maximal doses of omeprazole or esomeprazole are found in the corresponding product information.
Rakkomandazzjonijiet għal dożi massimi ta ’ omeprazole jew esomeprazole jinsabu fl- informazzjoni korrispondenti għal prodott.
Due to APTIVUS containing small amounts of sorbitol, patients with rare hereditary problems of fructose intolerance should not take this medicine.
Minħabba li APTIVUS fih ammonti żgħar ta 'sorbitol, pazjenti li għandhom problemi ereditarji rari ta' intolleranza tal- fruttożju m' għandhomx jieħdu din il- mediċina.
The interaction profile of APTIVUS, co-administered with low dose ritonavir, is complex and requires special attention in particular in combination with other antiretroviral agents.
Il- profil ta 'l- interazzjonijiet ta' APTIVUS, mogħti flimkien ma ’ doża baxxa ta 'ritonavir, huwa kumpless u jeħtieġ attenzjoni speċjali b' mod partikolari meta jingħata ma' mediċini anti- retrovirali oħra.
Interaction studies have only been performed in adults.
Studji dwar effetti farmaċewtiċi ma ’ prodotti mediċinali oħra saru biss fuq adulti.
Metabolic profile of tipranavir:
Profil metaboliku ta 'tipranavir:
Tipranavir is a substrate, an inducer and an inhibitor of cytochrome P450 CYP3A.
Tipranavir huwa sustrat, stimulant u impeditur tas- cytochrome P450 CYP3A.
When co- administered with ritonavir at the recommended dosage (see section 4.2) there is a net inhibition of P450 CYP3A.
Meta jingħata ma ’ ritonavir bid- doża rakkomandata (ara sezzjoni 4. 2), ikun hemm impediment nett ta ’ P450 CYP3A.
Co-administration of APTIVUS and low dose ritonavir with agents primarily metabolised by CYP3A may result in changed plasma concentrations of tipranavir or the other agents, which could alter their therapeutic and adverse effects (see list and details of considered agents, below).
Meta APTIVUS jingħata flimkien ma ’ ritonavir f’ doża baxxa, ma ’ mediċini li jkunu metabolizzati permezz ta ’ CYP3A, jista ’ jkun hemm bidla fil- livelli tal- plażma ta ’ tipranavir jew mediċini oħrajn, u b’ hekk jistgħu jinbidlu l- effetti terapewtiċi u l- effetti avversi tal- mediċini konċernati (ara lista u dettalji ta 'mediċini kkonsidrati hawn isfel).
Agents that are contraindicated specifically due to the expected magnitude of interaction and potential for serious adverse reactions are detailed in this section, and listed in section 4.3.
Mediċini li huma kontra- indikati b’ mod partikolari minħabba l- qawwa ta ’ l- interazzjoni tagħhom u l- potenzjal li jikkaġunaw reazzjonijiet avversi ta ’ natura serja, huma iddettaljati f’ din is- sezzjoni u elenkati f’ sezzjoni 4. 3.
7 (caffeine), 2C9 (warfarin), 2D6 (dextromethorphan), both intestinal/ hepatic CYP 3A4 (midazolam) and P-glycoprotein (Pgp) (digoxin).
Sar studju koktejl fuq 16- il volutier b’ saħħithom b’ għoti darbtejn kuljum ta ’ kapsula ta ’ APTIVUS/ ritonavir 500/ 200 mg għal 10 ijiem sabiex jiġi assessjat l- effett nett fuq l- attività ta ’ CYP 1A2 epatiku (kaffeina), 2C9 (warfarina), 2DG (dextromethorphan), CYP 3A4 (midazolam) kemm ta ’ l- imsaren/ fwied u P- glycoprotein (Pgp) (digoxin).
At steady state, there was a significant induction of CYP 1A2 and a slight induction on CYP 2C9.
Fl- istat fiss kien hemm sensibilazzjoni sinifikanti ta ’ CYP 1A2 u induzzjoni żgħira ta ’ CYP 2C9.
Potent inhibition of CYP 2D6 and both hepatic and intestinal CYP 3A4 activities were observed.
Kien osservat li kien hemm impediment qawwi ta ’ CYP 2D6 u ta ’ l- attivitajiet ta ’ CYP 3A4 kemm tal- fwied u ta ’ l- imsaren.
Pgp activity is significantly inhibited after the first dose, but there was a slight induction at steady state.
L- attività PgP hija impeduta b’ mod sinifikanti wara l- ewwel doża, iżda kien hemm induzzjoni żgħira fl- istat fiss.
Practical recommendations deriving from this study are displayed below.
Rakkomandazzjonijiet prattiċi li joħorġu minn dan l- istudju huma murija taħt.
Studies in human liver microsomes indicated tipranavir is an inhibitor of CYP 1A2, CYP 2C9, CYP 2C19 and CYP 2D6.
Studji fil- mikrożomi tal- fwied uman indikaw li tipranavir huwa impeditur għal CYP 1A2, CYP 2C9, CYP 2C19 u CYP 2D6.
The potential net effect of tipranavir/ ritonavir on CYP 2D6 is inhibition, because ritonavir is also a CYP 2D6 inhibitor.
L- effett potenzjali nett ta 'tipranavir/ ritonavir fuq CYP 2D6 hu ta' impediment, peress li ritonavir huwa impeditur CYP 2D6.
The in vivo net effect of tipranavir/ ritonavir on CYP 1A2, CYP 2C9 and CYP 2C19, indicates, through a preliminary study, an inducing potential of APTIVUS/ ritonavir on CYP1A2 and, to a lesser extent, on CYP2C9 and P-gp after several days of treatment.
L- effett nett in vivo ta 'tipranavir/ ritonavir fuq CYP 1A2, CYP 2C9 u CYP 2C19, jindika, minn studju preliminari, potenzjal li APTIVUS/ ritonavir jissensitizza CYP1A2 u, f’ każ aktar ristrett, lil CYP2C9 u P- gp wara diversi jiem ta ’ trattament.
Data are not available to indicate whether tipranavir inhibits or induces glucuronosyl transferases.
Għad mhemmx dejta disponibbli li tindika jekk tipranavir jimpedixxiex jew jistimulax glucuronosyl transferases.
In vitro studies show that tipranavir is a substrate and also an inhibitor of Pgp.
Studji in vitro juru li tipranavir huwa sustrat, kif ukoll impeditur ta 'Pgp.
It is difficult to predict the net effect of APTIVUS co-administered with low dose ritonavir on oral bioavailability and plasma concentrations of agents that are dual substrates of CYP3A and Pgp.
Huwa diffiċli li wieħed jipprevedi l- effett nett ta 'APTIVUS mogħti flimkien ma ’ doża baxxa ta' ritonavir fil- bijodisponibilità orali u l- konċentrazzjonijiet fil- plażma ta 'mediċini li huma sustrati kemm ta' CYP3A u Pgp.
The net effect will vary depending on the relative affinity of the co-administered drugs for CYP3A and Pgp, and the extent of intestinal first-pass metabolism/ efflux.
L- effett nett se jvarja skond l- affinità relattiva ta 'mediċini amministrati konġuntivament għal CYP3A u Pgp, u l- firxa ta' metaboliżmu intestinali fl- ewwel stadji/ efluss.
Co-administration of APTIVUS and agents that induce CYP3A and/ or Pgp may decrease tipranavir concentrations and reduce its therapeutic effect (see list and details of considered agents, below).
L- għoti konġunt ta 'APTIVUS u mediċini li jissensitizzaw CYP3A u/ jew Pgp jistgħu jnaqqsu l - konċentrazzjonijiet ta' tipranavir u jnaqqsu l- effett terapewtiku tiegħu (ara lista u dettalji ta 'mediċini kkonsidrati, hawn isfel).
Co- administration of APTIVUS and medicinal products that inhibit Pgp may increase tipranavir plasma concentrations.
L- għoti konġunt ta 'APTIVUS u prodotti mediċinali li jimpedixxu l- Pgp jistgħu jżidu l- konċentrazzjonijiet tal- plażma ta' tipranavir.
Nucleoside reverse transcriptase inhibitors:
Impedituri ta ’ l- enżima nucleotide reverse transcriptase:
Since there is no significant impact of nucleoside and nucleotide analogues on the P450 enzyme system no dosage adjustment of APTIVUS is required when co-administered with these agents.
Peress li m' hemmx impatt sinifikanti ta ’ nucleoside u ta ’ analogi ta 'nucleotide fuq is- sistema enżimatika ta' P450 l- ebda aġġustament fid- doża t' APTIVUS ma hu meħtieġ meta jiġi mogħti flimkien ma 'dawn l- aġenti.
APTIVUS, co-administered with low dose ritonavir, decreases the AUC of abacavir by approximately 40% and the AUC of zidovudine by approximately 35%.
APTIVUS, mogħti flimkien ma ’ doża baxxa ta 'ritonavir, inaqqas l- AUC ta' abacavir b' madwar 40% u l- AUC ta 'zidovudine b' madwar 35%.
There is no impact on glucuronidated-ZDV levels.
M' hemm l- ebda impatt fuq il- livelli glukorinati ta 'ZDV.
The clinical relevance of these reductions has not been established, but may decrease the efficacy of these antiretroviral agents.
Ir- rilevanza klinika ta 'dan it- tnaqqis ma ġietx stabbilita, imma jista' jnaqqas l- effikaċja ta 'dawn l- aġenti antiretrovirali.
Therefore the concomitant use of tipranavir, co-administered with low dose ritonavir, with either abacavir or zidovudine is not recommended unless there are no other available NRTIs suitable for patient management.
Għalhekk l- użu konġunt ta 'tipranavir, mogħti flimkien ma' doża baxxa ta 'ritonavir, kemm ma' abacavir jew ma ’ zidovudine mhux rakkomandat għajr meta ma
In such cases no dosage adjustment of abacavir or zidovudine can be recommended.
F' każijiet bħal dawn ma jistax jiġi rakkomandat aġġustament fid- doża ta 'abacavir jew zidovudine.
APTIVUS, co-administered with low dose ritonavir, causes a reduction in the AUC of didanosine.
APTIVUS mogħti flimkien ma ’ ritonavir b’ doża baxxa, jikkaġuna tnaqqis fl- AUC ta ’ didanosine.
The clinical relevance of the reduction in didanosine levels has not been established.
Ir- rilevanza klinika tat- tnaqqis fil- livelli ta 'didanosine għadha ma ġietx stabbilita.
Dosing of enteric-coated didanosine and APTIVUS soft capsules, co-administered with low dose ritonavir, should be separated by at least 2 hours to avoid formulation incompatibility.
Għandu jkun hemm intervall ta ’ mill- anqas sagħtejn bejn meta tingħata d- doża ta 'didanosine b’ kisja enterika u l- kapsula ratba ta' APTIVUS, li mogħti flimkien ma ’ doża baxxa ta 'ritonavir sabiex tiġi evitata inkompatibilità ta' formulazzjoni.
Lamivudine and stavudine:
Lamivudine u stavudine:
APTIVUS, co-administered with low dose ritonavir, does not cause a significant change in the AUC of lamivudine or stavudine.
APTIVUS, mogħti flimkien ma ’ ritonavir b’ doża baxxa, ma jikkaġunax tnaqqis sinifikanti fl- AUC ta ’ lamivudine jew stavudine.
No dosage adjustment of lamivudine or stavudine is recommended.
L- ebda aġġustament fid- doża ta ’ lamivudine m’ hu rakkomandat.
Nucleotide reverse transcriptase inhibitors:
Impedituri ta ’ l- enżima nucleotide reverse transcriptase:
APTIVUS, co-administered with low dose ritonavir, did not cause a significant change in the plasma concentrations of tenofovir.
APTIVUS mogħti flimkien ma ’ ritonavir b’ doża baxxa, ma kkaġunax tnaqqis sinifikanti fil- konċentrazzjoni ta ’ tenofovir fil- plażma.
No dosage adjustment of tenofovir is recommended.
L- ebda aġġustament fid- doża ta ’ tenofovir m’ hu rakkomandat.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs):
Impedituri ta ’ l- enżima non- nucleotide reverse transcriptase (NNRTIs):
Steady-state efavirenz 600 mg qd co-administered with steady-state APTIVUS and low- dose ritonavir (500/ 200 mg bid) did not significantly alter tipranavir AUC and Cmax and increased Cp12h by 19.2% which is not considered as clinically relevant.
Efavirenz 600 mg qd mogħti flimkien ma ’ APTIVUS u doża baxxa ta ’ ritonavir (500/ 200 mg bid) fi stadju fiss ma biddlux b’ mod sinifikanti l- AUC u Cmax ta ’ tipranavir u żiedu b’ 19. 2% Cp12h li mhux ikkonsidrat bħala klinikament rilevanti.
APTIVUS, co-administered with low-dose ritonavir, had no significant impact on the Cmin of efavirenz.
APTIVUS, mogħti ma ’ doża baxxa ta ’ ritonavir, ma kellux impatt sinifikanti fuq Cmin ta ’ efavirenz.
No specific drug-drug interaction study has been performed between APTIVUS and low- dose ritonavir (500/ 200 mg bid) with nevirapine.
Nevirapine Ma sar ebda studju dwar l- effetti ta ’ bejn mediċina u oħra fil- każ ta ’ bejn APTIVUS u doża baxxa ta ’ ritonavir (500/ 200 mg bid) ma ’ nevirapine.
However, the limited data available from a phase IIa study in HIV-infected patients suggest that no significant interaction is expected between nevirapine and APTIVUS co-administered with low dose ritonavir.
Madankollu, dejta ristretta disponibbli dwar studju ta ’ fażi IIa f’ pazjenti infettati b’ HIV tissuġerixxi li l- ebda effett farmaċewtiku sinifikanti għal prodotti mediċinali m’ hu mistenni bejn nevirapine u APTIVUS li jingħata ma ’ doża baxxa ta ’ ritonavir.
Moreover a study with APTIVUS and low dose ritonavir and another NNRTI (efavirenz) did not show any clinically relevant interaction (see above).
Barra dan studju b’ APTIVUS u doża baxxa ta ’ ritonavir u NNRTI ieħor (efavirenz) ma wera ebda effett farmaċewtiku klinikament rilevanti (ara fuq).
Therefore no dose adjustments are necessary.
Għalhekk l- ebda aġġustament fid- doża m’ hu meħtieġ.
Protease Inhibitors:
Impedituri ta ’ enżimi protease:
In a clinical study of dual-boosted protease inhibitor combination therapy in multiple-treatment experienced HIV-positive adults, APTIVUS, co-administered with low dose ritonavir, caused a 55%, 70% and 78% reduction in the Cmin of amprenavir, lopinavir and saquinavir, respectively.
Fi studju kliniku li sar fuq adulti li rriżultaw pożittivi għat- test tal- HIV, u li kienu esperjenżaw aktar minn terapija waħda permezz ta ’ trattamenti b’ taħlita ta ’ impedituri doppji tal- protease, APTIVUS mogħti flimkien ma ’ ritonavir b’ doża baxxa, irriżulta fi tnaqqis ta '55%, 70% u 78% fis- Cmin ta' amprenavir, lopinavir u saquinavir, rispettivament.
Therefore the concomitant administration of APTIVUS, co-administered with low dose ritonavir, with amprenavir/ ritonavir, lopinavir/ ritonavir or saquinavir/ ritonavir, is not recommended, as the clinical relevance of the reduction in their levels has not been established.
Għalhekk, l- għoti konġunt ta 'APTIVUS, mogħti flimkien ma ’ doża baxxa ta' ritonavir, ma 'amprenavir/ ritonavir, lopinavir/ ritonavir jew saquinavir/ ritonavir, mhux rakkomandat, billi r- rilevanza klinika tat- tnaqqis fil - livelli tagħhom ma ġiex stabbilit.
If the combination is nevertheless considered necessary, a monitoring of the plasma levels of these protease inhibitors is strongly encouraged.
Madankollu, jekk il- kombinazzjoni hija kkonsidrata meħtieġa, huwa inkorraġit bil- qawwa li jkun hemm monitoraġġ tal- livelli tal- plażma ta 'dawn l- impedituri tal- protease.
Co-administration of Tipranavir/ ritonavir and Atazanavir/ ritonavir:
L- għoti konġunt ta 'Tipranavir/ ritonavir u Atazanavir/ ritonavir:
In a study performed in healthy volunteers co-administration of atazanavir 300 mg with TPV/ r 500/ 100 mg bid resulted on one hand in a marked increase of Tipranavir exposure (notably Cp12h ratio of 1.75 with 90% CI [1.39-2.20]) and ritonavir exposure (AUC ratio of 1.51 with 90% CI [1.24- 1.83] and Cmax ratio of 1.38 with 90% CI [1.13-1.67]) associated with a risk of over-toxicity and on the other hand on a marked decrease of atazanavir exposure associated with a risk of loss of efficacy (AUC0-24h ratio of 0.32 with 90% CI [0.29-0.36], Cmax ratio of 0.43 with 90% CI [0.38-0.50] and Cp24h ratio of 0.19 with 90% CI [0.15-0.24]).
Fi studju mwettaq fuq voluntiera b' saħħithom li ngħataw 300 mg atazanavir ma '500/ 100 mg TPV/ r darbtejn kuljum irriżulta minn naħa żjieda notevoli għall- espożizzjoni ta' Tipranavir (b' mod partikolari proporzjon ta 'Cp12h ta' 1. 75 b' 90% CI [1. 39- 2. 20]) u espożizzjoni għal ritonavir (proporzjon AUC ta '1. 51 b' 90% CI [1. 24- 1. 83] u proporzjon Cmax ta '1. 38 b' 90% CI [1. 13- 1. 67]) assoċjat b' riskju ta' tossiċità żejda u fuq in- naħa l- oħra bi tnaqqis notevoli għal espożizzjoni ta 'atazanavir assoċjata b' riskju ta' telf ta 'effikaċja (proporzjon AUC0- 24h ta' 0. 32 b' 90% CI [0. 29- 0. 36], proporzjon Cmax ta '0. 43 b' 90% CI [0. 38- 0. 50] u proporzjon Cp24h ta '0. 19 b' 90% CI [0. 15- 0. 24]).
Consequently, this co-administration is not recommended.
Minħabba f' hekk, dan l- għoti konġunt mhux rakkomandat.
If the co-administration is nevertheless considered necessary, a close monitoring of the safety of tipranavir and a monitoring of plasma concentrations of atazanavir are strongly encouraged.
Madankollu jekk l- għoti konġunt huwa kkonsidrat bħala meħtieġ, huwa inkorraġit b' mod qawwi li jkun hemm monitoraġġ mill- qrib tas- sigurtà ta 'tipranavir u monitoraġġ tal- konċentrazzjonijiet ta' atazanavir fil- plażma.
No data are currently available on interactions of APTIVUS, co-administered with low dose ritonavir, with protease inhibitors other than those listed above.
Attwalment, għad m’ hemmx ċifri dwar ir- reazzjonijiet ta ’ meta APTIVUS jingħata flimkien ma ’ ritonavir b’ doża baxxa, u jintuża ma ’ impedituri ta ’ enżimi protease, minbarra dawk li hemm elenkati
Hence their combination with tipranavir co- administered with low dose ritonavir, is not recommended (see section 4.4).
Għalhekk l- għoti flimkien ma 'tipranavir mogħti flimkien ma' doża baxxa ritonavir, mhux rakkomandat (ara sezzjoni 4. 4).
Fusion inhibitors:
Impedituri ta ’ fużjoni:
In studies where tipranavir co-administered with low-dose ritonavir was used with or without enfuvirtide, it has been observed that the steady-state plasma tipranavir trough concentration of patients receiving enfuvirtide were 45% higher as compared to patients not receiving enfuvirtide.
Fi studji meta tipranavir ingħata flimkien ma ’ doża baxxa ta ’ ritonavir bi jew mingħajr enfuvirtide, ġie osservat li l- konċentrazzjoni l- aktar baxxa fi stadju fiss ta ’ tipranavir fil- plażma f’ pazjenti li qed jirċievu enfuvirtide kienet 45% ogħla meta mqabbla ma ’ pazjenti li ma kienux qed jirċievu enfuvirtide.
No information is available for the parameters AUC and Cmax.
L- ebda tagħrif mhu disponibbli dwar il- parametri AUC u Cmax.
A pharmacokinetic interaction is mechanistically unexpected and the interaction has not been confirmed in a controlled interaction study.
Interazzjoni farmakokinetika b’ mod mekanistiku mhux mistennija li jkun hemm u l- interazzjoni ma ġiex ikkonfermata fi studju ta ’ interazzjoni kkontrollat.
The clinical impact of the observed data, especially regarding the tipranavir/ ritonavir safety profile, remains unknown.
L- impatt kliniku tad- dejta osservat, speċjalment il- profil tas- sigurtà ta ’ tipranavir/ ritonavir jibqa ’ mhux magħruf.
Nevertheless, the clinical data available from the RESIST trials did not suggest any significant alteration of the tipranavir/ ritonavir safety profile when combined with enfuvirtide as compared to patients treated with tipranavir/ ritonavir without enfuvirtide.
Madankollu, id- dejta klinika disponibbli mill- provi ta ’ RESIST ma ssuġġeritx bidla sinifikanti fil- profil tas- sigurtà ta ’ tipranavir/ ritonavir meta jiġu kkombinati ma ’ enfuvirtide meta hekk imqabbla ma ’ pazjenti kkurati b’ tipanavir/ ritonavir li ma ngħatawx enfuvirtide.
Anticonvulsants:
Antikonvulsanti:
Carbamazepine, phenobarbital, and phenytoin induce CYP3A4 and should be used with caution in combination with APTIVUS/ ritonavir.
Carbamazepine, phenobarbital u phenytoin jinduċu CYP3A4 u meta jintużaw flimkien ma ’ APTIVUS/ ritonavir għandhom jintużaw b’ kawtela.
Concomitant use of carbamazepine at a dose of 200mg BID resulted in decreased concentrations of tipranavir (Cmin decreased by 61% compared to historical controls), which may result in decreased effectiveness.
L- użu konkomitanti ta ’ carbamazepine f’ doża ta ’ 200 mg BID irriżultat f’ konċentrazzjonijiet imnaqqsa ta ’ tipranavir (Cmin naqas b’ 61% meta mqabbel ma ’ kontrolli storiċi), li tista ’ tirriżulta f’ effettività mnaqqsa.
Higher doses of carbamazepine may result in even larger decreases in tipranavir plasma concentrations.
Dożi ogħla ta ’ carbamazepine jistgħu jirriżultaw fi tnaqqis akbar fil- konċentrazzjonijiet ta ’ tipranavir fil- plażma.
The total Cmin of carbamazepine and its active metabolite Cmin is increased by 23% which is not expected to have clinical consequences.
Is- Cmin totali ta ’ carbamazepine u l- metabolit attiv tiegħu Cmin jistgħu jiżdiedu bi 23% li mhux mistenni li jkollu konsegwenzi kliniċi.
Antifungals:
Mediċini ta ’ kontra l- fungi:
Fluconazole increases the AUC and Cmin of tipranavir by
APTIVUS, mogħti flimkien ma ’ doża baxxa ta ’ ritonavir, m' għandux effett sinifikanti fuq il- farmakokinetika fissa ta ’ fluconazole.
9 56% and 104%, respectively, when compared to historical data.
Fluconazole jikkaġuna żjieda fl- AUC u Cmin ta ’ tipranavir b’ 56% u 104%, rispettivament, meta mqabbel ma ’ riżultati li gew miksuba qabel.
No dosage adjustments are recommended.
L- ebda aġġustament fid- doża m’ hu rakkomandat.
Fluconazole doses > 200 mg/ day are not recommended.
Dożi ta '> 200 mg/ kuljum ta' fluconazole m' humiex rakkomandati.
Itraconazole/ ketoconazole:
Itraconazole/ ketoconazole:
Based on theoretical considerations APTIVUS, co-administered with low dose ritonavir, is expected to increase itraconazole or ketoconazole concentrations.
Skond konsiderazzjonijiet teoretiċi APTIVUS, mogħti flimkien ma ’ doża baxxa ta 'ritonavir, hu mistenni li jżid l- konċentrazzjonijiet ta' itraconazole jew ta 'ketoconazole.
Itraconazole or ketoconazole should be used with caution (doses > 200 mg/ day are not recommended).
Itraconazole jew ketoconazole għandhom jintużaw b' kawtela (dożi > 200 mg/ kuljum mhux rakkomandati).
Due to multiple enzyme systems being involved in voriconazole metabolism, it is difficult to predict the interaction.
Minħabba d- diversi sistemi enżimatiċi li huma involuti fil- metaboliżmu ta 'voriconazole, huwa diffiċli li wieħed jipprevedi l- interazzjoni.
10 HMG CoA reductase inhibitors:
Impedituri ta 'HMG CoA reductase:
Simvastatin and lovastatin:
Simvastatin and lovastatin:
The HMG-CoA reductase inhibitors simvastatin and lovastatin are highly dependent on CYP3A for metabolism, thus concomitant use of APTIVUS co-administered with low dose ritonavir, with simvastatin or lovastatin are contra-indicated due to an increased risk of myopathy, including rhabdomyolysis (see section 4.3).
L- impedituri ta 'HMG- CoA reductase simvastatin u lovastatin jiddependu ħafna fuq CYP3A għal metaboliżmu, u għalhekk l- użu konkomitanti ta' APTIVUS mogħti flimkien ma 'doża baxxa ta' ritonavir, b' simvastatin jew lovastatin huwa kontra- indikat minħabba r- riskju ogħla ta 'mijopatija, li tinkludi rabdomijolisi (ara sezzjoni 4. 3).
APTIVUS, co-administered with low dose ritonavir, increases the plasma concentrations of single dose atorvastatin by approximately 8-10 fold and reduces the AUCs of its metabolites by approximately 85%.
APTIVUS, mogħti flimkien ma 'doża baxxa ta ’ ritonavir, jikkaġuna żjieda fil- livelli tal - plażma ta ’ atorvastatin b’ madwar 8- 10 darbiet, u jnaqqss l- AUCs tal- metaboliti tat- tip hydroxyl b’ madwar 85%.
Atorvastatin does not significantly change the AUC, Cmax or Cmin of tipranavir.
Atorvastatin ma jeffettwax wisq l- AUC, Cmax jew Cmin ta 'tipranavir.
The combination is not recommended.
Il- kombinazzjoni mhix rakkomandata.
Other HMG-CoA reductase inhibitors should be considered such as pravastatin, fluvastatin or rosuvastatin.
Għandhom jiġu kkonsidrati impedituri HMG- CoA reductase oħrajn bħal pravastatin, fluvastatin jew rosuvastatin.
However, if atorvastatin is specifically required for patient management, careful monitoring is necessary (see section 4.4).
Madankollu, jekk atorvastatin huwa speċifikament meħtieġ għal ġestjoni tal- pazjent, monitoraġġ b' kawtela huwa meħtieġ (ara sezzjoni 4. 4).
CYP isoenzyme inducers:
Mediċini stimulanti ta ’ l- isoenżimi CYP:
Rifampicin is a strong CYP3A4 inducer and has been shown to cause profound decreases in concentrations of other protease inhibitors which can result in virological failure and resistance development.
Rifampicin huwa induttur qawwi ta ’ CYP 3A4 u ntwera li jikkaġuna tnaqqis profond fil - konċentrazzjonijiet ta ’ impedituri oħra ta ’ protease li jista ’ jirriżulta f’ indeboliment viroloġiku u żvilupp ta ’ reżistenza.
During attempts to overcome the decreased exposure by increasing the dose of other protease inhibitors with ritonavir, a high frequency of liver reactions was seen.
Waqt tentattivi sabiex tingħeleb l- espożizzjoni mnaqqsa billi tiżdied id- doża ta ’ impedituri oħra ta ’ protease ma ’ ritonavir, dehret frekwenza għolja ta ’ reazzjonijiet tal- fwied.
The combination of rifampicin with APTIVUS with concomitant low-dose ritonavir is contraindicated (see section 4.3).
10 Il- kombinazzjoni ta ’ rifampicin ma ’ APTIVUS flimkien ma ’ doża baxxa ta ’ ritonavir hija kontra - indikata (ara sezzjoni 4. 3).
APTIVUS, co-administered with low dose ritonavir, increases plasma concentrations of rifabutin by up to 3 fold, and its active metabolite by up to 20 fold.
APTIVUS, mogħti flimkien ma 'doża baxxa ta ’ ritonavir jikkaġuna żjieda li tasal sa tliet darbiet fil- livelli ta' rifabutin fil- plażma kif ukoll ta '20 darba fil- metabolit attiv tiegħu.
Rifabutin increases the Cmin of tipranavir by 16%.
Rifabutin jikkaġuna żjieda f’ Cmin ta ’ tipranavir b’ 16%.
Dosage reductions of rifabutin by at least 75% of the usual 300 mg/ day are recommended (ie 150 mg on alternate days, or three times per week).
150 mg ġurnata iva u ġurnata le, jew tliet darbiet fil- ġimgħa).
Patients receiving rifabutin with APTIVUS/ ritonavir should be closely monitored for emergence of adverse events associated with rifabutin therapy.
Pazjenti li qed jirċievu rifabutin ma 'APTIVUS/ ritonavir għandhom jiġu monitorati mill- qrib għal ħruġ ta' effetti avversi assoċjati mat- terapija b' rifabutin.
Further dosage reduction may be necessary.
Jista 'jkun bżonn li titnaqqas aktar id- doża.
St John’ s wort (Hypericum perforatum):
St John’ s wort (Hypericum perforatum):
Plasma levels of tipranavir can be reduced by concomitant use of the herbal preparation St John’ s wort (Hypericum perforatum).
Preparazzjonijiet minn ħxejjex li fihom St John’ s wort (Hypericum perforatum) jistgħu jikkaġunaw tnaqqis fil- livell ta ’ tipranavir fil- plażma, meta jingħataw flimkien.
This is due to induction of drug metabolising enzymes by St John’ s wort.
Dan iseħħ minħabba li dawn il- preparazzjonijiet fihom stimulanti ta ’ enżimi li jaħdmu fil- metaboliżmu tal- mediċini.
Herbal preparations containing St John’ s wort should not be used concomitantly with APTIVUS.
Preparazzjonijiet minn ħxejjex li fihom St John’ s wort (Hypericum perforatum) m’ għandhomx jintużaw flimkien m ’ APTIVUS.
If a patient is already taking St John’ s wort, stop St John’ s wort, check viral levels and if possible tipranavir levels.
John’ s wort, u ċċekja l- livelli virali u jekk possibbli ta ’ tipranavir ukoll.
Tipranavir levels may increase on stopping St John’ s wort, and the dose of APTIVUS may need adjusting.
Il- livelli ta ’ tipranavir jistgħu jiżdiedu meta jitwaqqaf it- teħid ta ’ St John’ s wort, u jista ’ ikun hemm il- ħtieġa li d- doża ta ’ APTIVUS tiġi aġġustata.
The inducing effect of St John’ s wort may persist for at least 2 weeks after cessation of treatment (see section 4.3).
L- effett stimulanti ta ’ St John’ s wort jista ’ jippersisti għal ta ’ lanqas ġimagħtejn wara li jitwaqqaf it- trattament (ara sezzjoni 4. 3).
CYP isoenzyme inhibitors:
Impedituri ta ’ l- isoenżimi CYP:
APTIVUS, co-administered with low dose ritonavir, increases the AUC and Cmin of clarithromycin by 19% and 68%, respectively, and decreases the AUC of the 14-hydroxy active metabolite by over 95%.
APTIVUS, mogħti flimkien ma ’ doża baxxa ta ’ ritonavir, jikkaġuna żjieda fl- AUC u Cmin ta ’ clarithromycin b’ 19% u b’ 68%, rispettivament, kif ukoll tnaqqis ta 'aktar minn 95% fl- AUC tal- metabolit attiv 14- hydroxy.
Whilst the changes in clarithromycin parameters are not considered clinically relevant, the reduction in the 14-OH metabolite AUC should be considered for the treatment of infections caused by Haemophilus influenzae in which the 14-OH metabolite is most active.
Filwaqt li l- bidliet fil- parametri ta 'clarithromycin m' humiex ikkonsidrati bħala rilevanti klinikament, it- tnaqqis fl- AUC tal- metabolit 14- OH għandu jiġi kkonsdrat għal kura ta' infezzjonijiet li jirriżultaw minn Haemophilus influenzae fejn il- metabolit 14- OH huwa kkonsidrat l- aktar attiv.
Clarithromycin increases the Cmin of tipranavir by more than 100%.
Clarithromycin jgħolli l- livell ta 'Cmin ta' tipranavir b' aktar minn 100%.
This large increase in Cmin may be clinically relevant.
Din iż- żjieda kbira f' Cmin tista ’ tkun klinikament rilevanti.
Patients using clarithromycin at doses higher than 500 mg twice daily should be carefully monitored for signs of toxicity.
Pazjenti li jużaw clarithromycin b’ dożi fissi ta ’ aktar minn 500 mg darbtejn kuljum, għandhom ikunu osservati bir- reqqa għal xi sintomi ta ’ tossiċità.
For patients with renal impairment the following dosage adjustments should be considered:
Il- pazjenti li għandhom indeboliment tal- kliewi għandhom jikkunsidraw dawn l- aġġustamenti fid- dożi:
For patients with CLCR 30 to 60 ml/ min the dose of clarithromycin should be reduced by 50%.
Għal pazjenti b 'CLCR 30 sa 60 ml/ min id- doża ta' clarithromycin għandha titbaxxa b’ 50%.
For patients with CLCR < 30 ml/ min the dose of clarithromycin should be decreased by 75%.
Għal pazjenti b' CLCR < 30 ml/ min għandhom ibaxxu d- doża ta ’ clarithromycin b’ 75%.
No dosage adjustments for patients with normal renal function are necessary.
M’ hemmx bżonn ta ’ aġġustamenti fil- każ ta ’ pazjenti li għandhom l- kliewi jaħdmu normali.
Other agents:
Mediċini oħra: