qanastek/EMEA-V3 huggingface dataset:
No dose recommendations can be made regarding this combination.
M’ hemmx doża rakkomandabbli għal din it- taħlita.
Concomitant administration should be used with caution in patients with mild and moderate hepatic impairment and is contraindicated in patients with severe hepatic impairment (see section 4.3).
4. 3 Kontra- indikazzjonijiet
Hypersensitivity to the active substance or to any of the excipients.
Sensittività eċċessiva għas- sustanzi attivi jew għal xi sustanzi mhux attivi.
Agenerase must not be administered concurrently with medicinal products with narrow therapeutic windows that are substrates of cytochrome P450 3A4 (CYP3A4).
Agenerase m’ għandux jiġi mogħti ma ’ mediċini li għandhom meded terapewtiċi dojoq u li huma substrati taċ- citokromju P450 3A4 (CYP3A4).
Co-administration may result in competitive inhibition of the metabolism of these medicinal products and create the potential for serious and/ or life-threatening adverse events such as cardiac arrhythmia (e. g. amiodarone, bepridil, quinidine, terfenadine, astemizole, cisapride, pimozide), respiratory depression and / or prolonged sedation (e. g. oral triazolam and oral midazolam (for caution on parenterally administered midazolam, see section 4.5)) or peripheral vasospasm or ischaemia and ischaemia of other tissues, including cerebral or myocardial ischaemia (e. g. ergot derivatives).
It- teħid flimkien jista ’ jirriżulta f’ inibizzjoni kompetitiva tal- metaboliżmu ta ’ dawn il- mediċini, li jista ’ jwassal għal possibbiltà ta ’ reazzjonijiet avversi li huma serji jew li jpoġġu l- ħajja tal- pazjent f’ periklu, bħal arritmija kardijaka (eż. amiodarone, beprdil, quinidine, terfenadine, astemizole, cisapride, pimozide), dipressjoni respiratorja u/ jew sedazzjoni fit- tul (eż triazolam mill- ħalq u midazolam mill- ħalq (ara sezzjoni 4. 5 għal kawtela ta ’ kif tuża midazolam fil- vina) jew vasospażmu periferali jew iskemija u iskemija ta ’ tessuti oħra tal - ġisem, inkluż iskemija ċerebrali jew mijokardjali (eż. derivati ta ’ ergot).
Agenerase in combination with ritonavir is contraindicated in patients with severe hepatic impairment.
L- użu ta ’ Agenerase flimkien ma ’ ritonavir huwa kontra- indikat f’ dawk il- pazjenti li jbatu minn ħsara kbira fil- fwied.
(see section 4.5).
Il- kombinazzjoni ta ’ rifampicin ma ’ Agenerase flimkien ma ’ doża baxxa ta ’ ritonavir hija kontraindikata (ara sezzjoni 4. 5).
Agenerase with ritonavir must not be co-administered with medicinal products with narrow therapeutic windows that are highly dependent on CYP2D6 metabolism, e. g. flecainide and propafenone (see section 4.5).
Agenerase ma ’ ritonavir m’ għandux jiġi amministrat flimkien ma ’ prodotti mediċinali b’ therapeutic windows ristretti li huma dipendenti ħafna fuq il- metaboliżmu ta ’ CYP2D6, eż flecainide u propafenone (ara sezzjoni 4. 5).
Herbal preparations containing St John’ s wort (Hypericum perforatum) must not be used while taking amprenavir due to the risk of decreased plasma concentrations and reduced clinical effects of amprenavir (see section 4.5).
3 Sustanzi mediċinali ppreparati mill- ħxejjex li fihom Fexfiexa tar- raba ’ (Hypericum perforatum) m’ għandhomx jintużaw fl- istess waqt li qed jintuża amprenavir minħabba r- riskju ta ’ tnaqqis fil - konċentrazzjoni tal- plażma u fl- effetti kliniċi ta ’ amprenavir (ara 4. 5).
Patients should be advised that Agenerase, or any other current antiretroviral therapy does not cure HIV and that they may still develop opportunistic infections and other complications of HIV infection.
Il- pazjenti għandhom jiġu mgħarrfa li Agenerase, jew kull xorta ta ’ terapija antiretrovirali li teżisti bħalissa, ma tistax tfejjaq l- HIV u li xorta waħda jistgħu jiżviluppaw infezzjonijiet opportunistiċi jew kumplikazzjonijiet oħra marbuta mal- HIV.
Current antiretroviral therapies, including Agenerase, have not been proven to prevent the risk of transmission of HIV to others through sexual contact or blood contamination.
Bħalissa, l- ebda terapija antiretrovirali ma ġiet ippruvata li tnaqqas ir- riskju tat- tixrid tal- HIV permezz ta ’ kuntatti sesswali jew permezz tad- demm.
Appropriate precautions should continue to be taken.
Kull prekawzjoni possibli għandha tibqà tittieħed.
On the basis of current pharmacodynamic data, amprenavir should be used in combination with at least two other antiretrovirals.
Fuq it- tagħrif farmakodinamiku li jeżisti bħalissa, amprenavir għandu dejjem jintuża flimkien ma ’ ta ’ l- anqas żewġ mediċini antiretrovirali oħra.
When amprenavir is administered as monotherapy, resistant viruses rapidly emerge (see section 5.1).
Meta dan jingħata waħdu malajr jitfaċċaw vajruses reżistenti (ara 5. 1).
Agenerase capsules should normally be given in combination with low dose ritonavir and in combination with other antiretroviral agents (see section 4.2).
Il- kapsuli ta ’ Agenerase huma normalment mogħtija flimkien ma ’ doża baxxa ta ’ ritonavir, flimkien ma ’ mediċini antiretrovirali oħra (ara 4. 2).
Liver Disease:
Mard tal- Fwied:
The safety and efficacy of amprenavir has not been established in patients with significant underlying liver disorders.
Is- sigurtà u l- effikaċja marbutin ma ’ l- użu ta ’ Agenerase f’ pazjenti li jbatu minn mard serju fil- fwied m’ humiex magħrufa.
Agenerase capsules are contraindicated in patients with severe hepatic impairment when used in combination with ritonavir (see section 4.3).
L- użu ta ’ Agenerase flimkien ma ’ ritonavir huwa kontra - indikat f’ dawk il- pazjenti li jbatu minn ħsara kbira fil- fwied (ara 4. 3).
Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an increased risk of severe and potentially fatal hepatic adverse events.
Pazjenti li huma morda bl - epatite B jew C b’ mod kroniku, u li jingħataw taħlita ta ’ mediċini antivirali, jinsabu f’ riskju akbar li jsofru minn reazzjonijiet epatiċi avversi u li jistgħu jkunu fatali.
In case of concomitant antiviral therapy for hepatitis B or C, please refer also to the relevant product information for these medicinal products.
F’ każ ta ’ pazjenti li huma morda bl - epatite B jew C b’ mod kroniku u li ser jingħataw taħlita ta ’ mediċini antivirali, wieħed għandu dejjem jikkonsulta l- informazzjoni li jsib ma dawn il- mediċini.
Patients with pre-existing liver dysfunction, including chronic active hepatitis, have an increased frequency of liver function abnormalities during combination antiretroviral therapy and should be monitored according to standard practice.
Pazjenti li jsofru minn anormalità jew taħsir tal- funzjonijiet tal- fwied, inkluż l- epatite attiva u kronika, jbatu minn rata aktar frekwenti ta ’ problemi tal- funzjonijiet tal- fwied meta jirċievu terapija li tinkludi taħlita ta ’ mediċini antiretroviralii u għalhekk għandhom jinżammu taħt osservazzjoni kif meħtieġ.
If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered.
Jekk ikun hemm sinjali li juru li s- sitwazzjoni tal- fwied qalbet għall- agħar, wieħed għandu jikkunsidra jwaqqafx it- terapija għal ftit taż- żmien jew anke għal dejjem.
Medicinal products – interactions
Prodotti mediċinali – interazzjonijiet
Concomitant use of Agenerase with 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).
Mhuwiex rakkomandat l- użu ta ’ Agenerase flimkien ma ’ ritonavir u fluticasone u glukokortikojdi oħra li jiġu mmetaboliżżati minn CYP3A4 sakemm il- benefiċċju potenzjali tal- kura mhuwiex akbar mir - riskju ta ’ l- effetti tal- kortikosterojdi fid- demm, li jinkludi s- sindromu ta ’ Cushing u trażżin tal - glandola adrenali (ara sezzjoni 4. 5).
The HMG-CoA reductase inhibitors lovastatin and simvastatin are highly dependent on CYP3A4 for metabolism, thus concomitant use of Agenerase with simvastatin or lovastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis.
Il- mediċini lovastatin u simvastatin, li jinibixxu l’ HMG- CoA reductase, jiddependu ħafna fuq CYP3A4 biex jiġu metabolizzati; għalhekk l- użu tagħhom fl- istess waqt ma ’ Agenerase m’ huwiex rakkomandat minħabba riskju kbir ta ’ mijopatija, inkluż rhabdomyolysis.
Caution must also be exercised if Agenerase is used concurrently with atorvastatin, which is metabolized to a lesser extent by CYP3A4.
Għandha tingħata attenzjoni meta Agenerase jiġi wżat fl- istess ħin ma ’ atorvastatin, li jiġi metabolizzat ukoll mis- CYP3A4, għalkemm fi kwantità iżgħar.
In this situation, a reduced dose of atorvastatin should be considered.
F’ każ bħal dan doża iżgħar ta ’ atorvastatin għandha tiġi kkunsidrata.
If treatment with a HMG-CoA reductase inhibitor is indicated, pravastatin or fluvastatin are recommended (see section 4.5).
Jekk ikun hemm bżonn l- użu ta ’ mediċina li tinibixxi l’ HMG- CoA reductase, wieħed għandu juża pravastatin jew fluvastatin (ara 4. 5).
For some medicinal products that can cause serious or life-threatening undesirable effects, such as carbamazepine, phenobarbital, phenytoin, tricyclic antidepressants and warfarin (monitor International Normalised Ratio), concentration monitoring is available; this should minimise the risk of potential safety problems with concomitant use.
F’ dawk il- każi fejn qegħdin jintużaw mediċini li jistgħu jikkawżaw reazzjonijiet avversi li huma serji jew li jpoġġu l- ħajja tal- pazjent f’ periklu, bħal carbamezapine, phenobarbital, tricyclic antidepressants u warfarin (wieħed għandu josserva l- International Normalised Ratio), wieħed għandu jżomm il - konċentrazzjoni taħt osservazzjoni; dan għandu jwassal biex ikun hemm tnaqqis fir- riskju li jiżviluppaw problemi relatati mas- sigurtà meta jingħataw dawn il- mediċini fl- istess ħin.
The use of Agenerase concomitantly with halofantrine or lidocaine (systemic) is not recommended (see section 4.5).
Mhuwiex rakkomandat l- użu ta ’ Agenerase flimkien ma ’ halofantrine jew lidocaine (sistemiku) (ara sezzjoni 4. 5).
Anticonvulsants (carbamazepine, phenobarbital, phenytoin) should be used with caution.
4 Antikonvulżivi (carbamezapine, phenobarbital, phenytoin) għandhom jintużaw b’ kawtela.
Agenerase may be less effective due to decreased amprenavir plasma concentrations in patients taking these medicinal products concomitantly (see section 4.5).
Agenerase jista ’ jkun anqas effettiv minħabba konċentrazzjonijiet fil- plażma anqas f’ pazjenti li qed jieħdu dawn il- prodotti mediċinali flimkien (ara sezzjoni 4. 5)
Therapeutic concentration monitoring is recommended for immunosuppressant medicinal products (cyclosporine, tacrolimus, rapamycin) when co-administered with Agenerase (see section 4.5).
Hija rrakkomandata osservazzjoni tal- konċentrazzjoni terapewtika għall- prodotti mediċinali li jrażżnu l- immunità (cyclosporin, tacrolimus, rapamycin) meta ’ jingħataw flimkien ma ’ Agenerase (ara sezzjoni 4. 5).
Caution is advised when Agenerase is used concomitantly with PDE5 inhibitors (e. g. sildenafil and vardenafil) (see section 4.5).
Hi rrakkomandata l- kawtela meta Agenerase jintuża flimkien ma ’ inibituri ta ’ PDE5 (eż sildenafil u vardenafil) (ara sezzjoni 4. 5) Hi rrakkomandata l- kawtela meta Agenerase jintuża flimkien ma ’ delavirdine (ara sezzjoni 4. 5).
A reduction of rifabutin dosage of at least 50% is recommended when administered with Agenerase.
Hu rrakkomandat tnaqqis fid- doża ta ’ rifabutin ta ’ almenu 50% meta jingħata flimkien ma 'Agenerase.
When ritonavir is co-administered further dose reduction may be necessary (see section 4.5).
Meta ritonavir jingħata miegħu jista 'jkun hemm bżonn aktar tnaqqis fid- doża (ara sezzjoni 4. 5).
Because of the potential for metabolic interactions with amprenavir, the efficacy of hormonal contraceptives may be modified, but there is insufficient information to predict the nature of the interactions.
Minħabba r- riskju ta ’ interazzjonijiet metaboliċi meta jingħataw ma ’ amprenavir, l- effikaċja tal - kontraċettivi ormonali tistà tinbidel, iżda m’ hemmx tagħrif biżżejjed biex wieħed jkun jistà jbassar x’ tip ta ’ effetti dawn jistgħu jkunu.
Therefore, alternative reliable methods of contraception are recommended for women of childbearing potential (see section 4.5).
Għalhekk għandhom jinstabu mezzi oħra ta ’ kontraċezzjoni oħra li wieħed jistà joqgħod fuqhom f’ dawk in- nisa li għad jistà jkollhom it- tfal (ara 4. 5).
Co-administration of amprenavir with methadone leads to a decrease of methadone concentrations.
Meta jiġu mogħtija flimkien amprenavir u methadone jkun hemm tnaqqis fil- konċentrazzjoni ta ’ methadone fid- demm.
Therefore, when methadone is co-administered with amprenavir, patients should be monitored for opiate abstinence syndrome, in particular if low-dose ritonavir is also given.
Għalhekk meta dawn jiġu mogħtija flimkien, il- pazjenti għandhom jiġu osservati għas- sindromu ta ’ astinenza mill opiate, speċjalment jekk tkun ingħatat doża baxxa ta ’ ritonavir.
No recommendations can currently be made regarding adjustment of amprenavir dose when amprenavir is co-administered with methadone.
Bħalissa ma tistax tingħata informazzjoni dwar tibdil fid- doża ta ’ amprenavir meta dan jiġi mogħti fl- istess ħin ma ’ methadone.
Agenerase capsules contain vitamin E (36 IU/ 50 mg capsule), therefore additional vitamin E supplementation is not recommended.
Il- kapsuli ta ’ Agenerase fihom il- vitamina E (36IU/ 50 mg kull kapsula) u għalhekk huwa rakkomandat li m’ għandiex tingħata aktar vitamina E.
Agenerase capsules also contain sorbitol (E420).
Il- kapsoli ta ’ Agenerase fihom ukoll sorbitol (E420).
Patients with rare hereditary problems of fructose intolerance should not take this medicine.
Pazjenti bi problemi rari ereditarji ta ’ intolleranza ta ’ fructose m’ għandhomx jieħdu din il- mediċina.
Due to the potential risk of toxicity from the high propylene glycol content of Agenerase oral solution, this formulation is contraindicated in children below the age of four years and should be used with caution in certain other patient populations.
Minħabba r- riskju ta ’ tossiċità kawża tal- livell għoli ta ’ propylene glycol li hemm fis- soluzzjoni orali ta ’ Agenerase, din it- taħlita hija kontra- indikata fi tfal taħt l- 4 snin u għandha tiġi użata b’ attenzjoni f’ ċerti gruppi ta ’ pazjenti.
The Summary of Product Characteristics of Agenerase oral solution should be consulted for full prescribing information.
Wieħed għandu jikkonsulta mal- Karatteristiċi tal- Prodott fil- Qosor tas - soluzzjoni orali ta ’ Agenerase sabiex ikollu l- informazzjoni kollha meħtieġa.
Rash / cutaneous reactions
Raxx/ effetti fuq il- ġilda:
Most patients with mild or moderate rash can continue Agenerase.
Ħafna pazjenti li jsofru minn raxx ħafif jew moderat jistgħu jibqgħu jieħdu Agenerase.
Appropriate antihistamines (e. g. cetirizine dihydrochloride) may reduce pruritus and hasten the resolution of rash.
Jistgħu jintużaw antiistaminiċi adattati (eż. cetirizine dihydrochloride) sabiex itaffu l- ħakk u jħaffu l- fejqan mir- raxx.
Agenerase should be permanently discontinued when rash is accompanied with systemic symptoms or allergic symptoms or mucosal involvement (see section 4.8).
Agenerase għandu jiġi mwaqqaf għal dejjem jekk ir- raxx ikun akkompanjat minn sintomi fil- ġisem kollu, sintomi allerġiċi jew involviment tal- mukoża (ara 4. 8).
Hyperglycaemia
Ipergliċemija
New onset of diabetes mellitus, hyperglycaemia or exacerbations of existing diabetes mellitus have been reported in patients receiving antiretroviral therapy, including protease inhibitors.
Każijiet ġodda ta ’ dijabete, ipergliċemija jew taħrix ta ’ każi eżistenti ta ’ dijabete ġew irrapurtati f’ pazjenti li kienu qed jirċievu terapija antiretrovirali, inkluż bil- inibituri protease.
In some of these, the hyperglycaemia was severe and in some cases also associated with ketoacidosis.
F’ xi wħud minn dawn, l- ipergliċemija kienet severa u f’ xi każi kienet assoċjata ma ’ ketoacidosis.
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.
Ħafna mill- pazjenti kellhom kundizzjonijiet ta ’ mard mhux daqshekk ċari, fejn xi wħud kellhom bżonn terapija b’ mediċini li kienu magħrufa li jistgħu jikkawżaw id- dijabete jew l- ipergliċemija.
Combination antiretroviral therapy has been associated with the redistribution of body fat (lipodystrophy) in HIV patients.
It- terapija kombinata antiretrovirali ġiet assoċjata ma ’ lipodistrofija (lipodystrophy) ta ’ dawk il - pazjenti infettati bl- HIV.
The long-term consequences of these events are currently unknown.
Fil- preżent mhux magħruf x’ jistgħu jkunu il- konsegwenzi fit- tul ta ’ dan il - proċess.
Knowledge about the mechanism is incomplete.
It- tagħrif dwar dan il- proċess għadu mhux komplut.
A connection between visceral lipomatosis and protease inhibitors and lipoatrophy and nucleoside reverse transcriptase inhibitors has been hypothesised.
5 visceral lipomatosis, il- inibituri protease, il- lipoatrophy u inibituri nuklejosajd rivers transkriptejż.
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 ’ lipodystrophy huwa assoċjat ma ’ fatturi individwali bħal età kbira, u ma ’ fatturi li għandhom x’ jaqsmu mal- mediċina bħal ma huma terapija antiretrovirali li tkun ilha għaddejja għal żmien twil u problemi metaboliċi li jirriżultaw minn dan kollu.
Clinical examination should include evaluation for physical signs of fat redistribution.
Waqt il- viżta l- pazjent għandu jiġi eżaminat għal sinjali fiżiċi li juru li hemm minn dan it- taqsim mod ieħor tax- xaħam tal- ġisem.
Consideration should be given to the measurement of fasting serum lipids and blood glucose.
Wieħed għandu wkoll jikkunsidra li jiġu mkejla il- livelli tal- lipidi fis- serum waqt is- sawm kif ukoll il- livell taz- zokkor fid- demm.
Lipid disorders should be managed as clinically appropriate (see section 4.8).
Il- mard fil- metaboliżmu tal- lipidi għandu jiġi kkontrollat skond il- bżonn (ara 4. 8).
5 Haemophiliac patients
Pazjenti li jbatu minn emofilja
There have been reports of increased bleeding, including spontaneous skin haematomas and haemarthroses, in haemophiliac patients type A and B treated with protease inhibitors.
F’ pazjenti li jbatu mill- emofilja tip A u B, u li kienu jieħdu l- inibituri protease, ġew irrapportati każijiet fejn kien hemm żieda fil- fsada u li kienu jinkludu ematomi spontanji fil- ġilda u haemarthroses.
In some patients, additional factor VIII was given.
Xi wħud minn dawn il- pazjenti ingħataw aktar factor VIII.
In more than half of the reported cases, treatment with protease inhibitors was continued, or reintroduced if treatment had been discontinued.
F’ aktar minn nofs il- każi li ġew irrapurtati, l- użu tal- inibituri protease tkompla jew inkella reġa ġie mibdi.
A causal relationship has been evoked, although the mechanism of action has not been elucidated.
Ġie maħsub li jista jkun rabta kawżali, għalkemm il- mod ta ’ kif dan setà seħħ ma ’ setax jigi spjegat.
Haemophiliac patients should therefore be made aware of the possibility of increased bleeding.
Huwa għalhekk li pazjenti li jbatu mill- emofilja għandhom jiġu avżati li jista jkun hemm possibiltà ta ’ żieda fil- fsada.
Immune Reactivation Syndrome
Sindromu ta ’ Rijattivazzjoni Immuni:
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.
F’ pazjenti infettati bl- HIV, b’ defiċjenza immuni severa fiż- żmien li tkun inbdiet it- terapija antiretrovirali kombinata (TARK), jista ’ jkun hemm reazzjoni nfjammatorja għall- mikrobi opportunistiċi asintomatiċi jew residwali li jwasslu għall- kundizzjonijiet kliniċi serji jew li sintomi jmorru għall- agħar.
Typically, such reactions have been observed within the first few weeks or months of initiation of CART.
Dawn ir- reazzjonijiet ġew osservati l- aktar spiss fl- ewwel ftit ġimgħat jew xhur mill- bidu tat- TARK.
Relevant examples are cytomegalovirus retinitis, generalised and/ or focal mycobacterium infections, and Pneumocystis carinii pneumonia.
Eżempji rilevanti jinkludu retinite ċitomegalovirus, infezzjonijiet mikobatterjali lokali jew mifruxa, u pulmonite b’ Pneumocystis carinii.
Any inflammatory symptoms should be evaluated and treatment instituted when necessary.
Kull sintomi ta ’ nfammazzjoni għandhom ikunu evalwati u t- trattament jinbeda fejn hemm bżonn.
Osteonecrosis
Ostejonekrożi:
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 il- kawża tista ’ tkun minħabba ħafna fatturi, (li jinkludu l- użu ta ’ kortikosterojdi, il- konsum ta ’ alkoħol, immunosoppressjoni qawwija, indiċi ogħla ta ’ piż tal- ġisem), każijiet ta ’ ostejonekrożi nstabu li huwa partikolarment aktar komuni f’ pazjenti b’ HIV avvanzat u/ jew użu ta ’ terapija antiretrovirali kombinata (TARK) fit- tul.
Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.
Il- pazjenti għandhom ifittxu parir mediku jekk iħossu xi uġigħ jew egħbusija fil- ġogi jew isibuha diffiċli biex jiċċaqilqu.
Interaction studies have been performed with amprenavir as the sole protease inhibitor.
Saru studji dwar interazzjonijiet ma ’ mediċini oħra fejn amprenavir kien l- uniku inibitur protease.
When amprenavir and ritonavir are co-administered, the ritonavir metabolic drug interaction profile may predominate because ritonavir is a more potent CYP3A4 inhibitor.
Meta amprenavir u ritonavir jiġu mogħtija flimkien, il- profil ta ’ l- interazzjonijiet metaboliċi ta ’ ritonavir jippredomina minħabba l- fatt li ritonavir huwa inibitur aktar b’ saħħtu ta ’ CYP3A4.
Ritonavir also inhibits CYP2D6 and induces CYP3A4, CYP1A2, CYP2C9 and glucuronosyl transferase.
Ritonavir jinibixxi wkoll CYP2D6 u jistimola CYP3A4, CYP1A2, CYP2C9 u glucuronosyl transferase.
The full prescribing information for ritonavir must therefore be consulted prior to initiation of therapy with Agenerase and ritonavir.
Qabel ma ’ wieħed jiddeċiedi li jibda juża flimkien Agenerase u ritonavir għandu jikkonsulta u jaqra tajjeb l - informazzjoni li wieħed isib ma ’ ritonavir.
Amprenavir and ritonavir are primarily metabolised in the liver by CYP3A4.
Amprenavir u ritonavir jiġu l- biċċa l- kbira metabolizzati fil- fwied minn CYP3A4.
Therefore, medicinal products that either share this metabolic pathway or modify CYP3A4 activity may modify the pharmacokinetics of amprenavir.
Għalhekk dawk il - mediċini li jgħaddu minn dan l- istess proċess jew li jħallu xi effett fuq l- attività ta ’ CYP3A4, jistgħu jikkaġunaw tibdil fil- proprjetajiet farmakokinetiċi ta ’ amprenavir.
Similarly, amprenavir and ritonavir might also modify the pharmacokinetics of other medicinal products that share this metabolic pathway.
Bl- istess raġuni kemm amprenavir, kif ukoll ritonavir, jistgħu jħallu effett fuq il- proprjetajiet farmakokinetiċi ta ’ dawk il- mediċini li bħalhom jgħaddu minn dan l- istess proċess.
Associations contraindicated (see section 4.3)
Assoċjazzjonijiet kontraindikati (ara sezzjoni 4. 3)
CYP3A4 substrates with narrow therapeutic index Agenerase must not be administered concurrently with medicinal products with narrow therapeutic windows containing active substances that are substrates of cytochrome P450 3A4 (CYP3A4).
Meta jingħataw flimkien
Co-administration may result in competitive inhibition of the metabolism of these active substances thus increasing their plasma level and leading to serious and / or life-threatening adverse reactions such as cardiac arrhythmia (e. g. amiodarone, astemizole, bepridil, cisapride, pimozide, quinidine, terfenadine) or peripheral vasospasm or ischaemia (e. g. ergotamine, dihydroergotamine).
6 dan jista ’ jwassal għal inibizzjoni kompetitiva tal- metaboliżmu ta ’ dawn is- sustanzi attivi u b’ hekk iżid il- livell tagħhom fil- plażma u jwassal għal reazzjonijiet avversi serji u / jew ta ’ periklu għas- saħħa bħal arritmija tal- qalb (eż amiodarone, astemizole, bepridil, cisapride, pimozide, quinidine, terfenadine) jew spażmu ta 'l- arterji periferali jew iskemija (eż ergotamine, dihydroergotamine).
CYP2D6 substrates with narrow therapeutic index Agenerase with ritonavir must not be co-administered with medicinal products containing active substances that are highly dependent on CYP2D6 metabolism and for which elevated plasma concentrations are associated with serious and / or life-threatening adverse reactions.
Is- sustanzi li jaġixxi fuqhom CYP2D6 b’ therapeutic index zgħir Agenerase ma 'ritonavir m' għandux jingħata flimkien ma' prodotti mediċinali li fihom sustanzi attivi li jiddependu ħafna fuq il- metaboliżmu ta ’ CYP2D6 u fejn żieda fil- konċentrazzjoni tal- plażma huma assoċjati ma ’ reazzjonijiet avversi serji jew/ u ta ’ periklu għas- saħħa.
Rifampicin
Dawn is- sustanzi attivi jinkludu fost oħrajn flecainide u propafenone.
6 Rifampicin is a strong CYP3A4 inducer and has been shown to cause an 82% decrease in amprenavir AUC, which can result in virological failure and resistance development.
Rifampicin Rifampicin huwa induttur qawwi ta ’ CYP3A4 u intwera li jikkawża tnaqqis ta '82% fl- AUC ta ’ amprenavir, li jista ’ jirriżulta f’ falliment 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 attentati biex jingħelbu it- tnaqqis fl- espożizzjoni billi tiżdied id- doża ta ’ inibituri protease ma ’ ritonavir, kienet innutata frekwenza għolja ta ’ reazzjonijiet fil- fwied.
The combination of rifampicin and Agenerase with concomitant low-dose ritonavir is contraindicated (see section 4.3).
Il- kumbinazzjoni ta ’ rifampicin u Agenerase flimkien ma ’ doża baxxa ta ’ ritonavir hija kontraindikata (ara sezzjoni 4. 3)
St John’ s wort (Hypericum perforatum) Serum levels of amprenavir can be reduced by concomitant use of the herbal preparation St John’ s wort (Hypericum perforatum).
St John’ s wort (Hypericum perforatum) Il- livell ta ’ amprenavir fis- serum jistà jitnaqqas meta fl- istess ħin tingħata il- mediċina tal- ħxejjex Fexfiexa tar- raba ’ (Hypericum perforatum).
This is due to induction of drug metabolising enzymes by St John’ s wort.
Dan jiġri minħabba li jkun hemm stimulazzjoni ta ’ enzimi li jimmetabolizzaw il- mediċini permezz ta ’ St John’ s wort.
Herbal preparations containing St John’ s wort should therefore not be combined with Agenerase.
Mediċini tal- ħxejjex li fihom St John’ s wort m’ għandhomx jingħataw ma ’ Agenerase.
If a patient is already taking St John’ s wort, check amprenavir and if possible viral levels and stop St John’ s wort.
Jekk xi pazjent ikun qiegħed jieħu St John’ s wort, wieħed irid jiċċekja l- livell ta ’ amprenavir kif ukoll il- livell tal- vajrus, filwaqt li St Johns Wort jitwaqqaf.
Amprenavir levels may increase on stopping St John’ s wort.
Meta din tiġi mwaqqfa għandu mnejn jogħla l- livell ta ’ amprenavir.
The dose of amprenavir may need adjusting.
Jista ’ jkun hemm bżonn ta ’ bidla fid- doża ta’ amprenavir.
The inducing effect may persist for at least 2 weeks after cessation of treatment with St John’ s wort.
L- effett stimulanti jistà jdum għal ta ’ l- inqas ġimagħtejn wara li St John’ s wort ikun twaqqaf.
• Other combinations
• Kombinazzjonijiet oħra
Of note, the following interaction data was obtained in adults.
L- informazzjoni siewja li jmiss hija dwar interazzjonijiet u saret magħrufa minn studji li saru f’ nies adulti.
Antiretroviral agents
Mediċini Antiretrovirali
• Protease inhibitors (PIs):
● Inibituri protease (PIs):
Indinavir: the AUC, Cmin and Cmax of indinavir were decreased by 38%, 27%, and 22%, respectively, when given with amprenavir.
Indinavir: l- AUC, Cmin u Cmax ta ’ indinavir naqsu bi 38%, 27% u 22% rispettivament meta ġie mogħti flimkien ma ’ amprenavir.
The clinical relevance of these changes is unknown.
L- importanza klinika ta ’ dawn il- bidliet mhix magħrufa.
The AUC, Cmin and Cmax of amprenavir were increased by 33%, 25%, and 18%, respectively.
L- AUC, Cmin u Cmax ta ’ amprenavir żdiedu bi 33%, 25% u 18% rispettivament.
No dose adjustment is necessary for either medicinal product when indinavir is administered in combination with amprenavir.
M’ hemmx bżonn ta ’ ċaqliq fid- doża ta ’ l- ebda waħda minn dawn iż- żewġ mediċini meta indinavir jiġi mogħti flimkien ma ’ amprenavir.
Saquinavir: the AUC, Cmin and Cmax of saquinavir were decreased by 19% and 48% and increased by 21%, respectively, when given with amprenavir.
Saquinavir: l- AUC, Cmin u Cmax ta ’ saquinavir naqsu b’ 19% u 48% u żdiedu b’ 21% rispettivament meta ġie mogħti flimkien ma ’ amprenavir.
The AUC, Cmin and Cmax of amprenavir were decreased by 32%, 14%, and 37%, respectively.
L - AUC, Cmin u Cmax ta ’ amprenavir naqsu bi 32%, 14% u 37% rispettivament.
No dose adjustment is necessary for either medicinal product when saquinavir is administered in combination with amprenavir.
Ma ’ hemmx bżonn ta ’ ċaqliq fid- doża ta ’ l- ebda waħda minn dawn iż- żewġ mediċini meta saquinavir jiġi mogħti flimkien ma ’ amprenavir.
Nelfinavir: the AUC, Cmin and Cmax of nelfinavir were increased by 15%, 14%, and 12%, respectively, when given with amprenavir.
Nelfinavir: l- AUC, Cmin u Cmax ta ’ nelfinavir żdiedu bi 15%, 14% u 12% rispettivament meta ġie mogħti flimkien ma ’ amprenavir.
The Cmax of amprenavir was decreased by 14% whilst the AUC and Cmin were increased by 9% and 189%, respectively.
Is- Cmax ta ’ amprenavir naqas b’ 14%, filwaqt li l- AUC u Cmin żdiedu b’ 9% u 189% rispettivament.
No dose adjustment is necessary for either medicinal product when nelfinavir is administered in combination with amprenavir (see also efavirenz below).
M’ hemmx bżonn ta ’ ċaqliq fid- doża ta ’ l- ebda waħda minn dawn iż - żewġ mediċini meta nelfinavir jiġi mogħti flimkien ma ’ amprenavir (ara wkoll efavirenz aktar l’ isfel).
Ritonavir: the AUC and Cmin of amprenavir were increased by 64% and 508% respectively and the Cmax decreased by 30% when ritonavir (100 mg twice daily) was co-administered with amprenavir capsule (600 mg twice daily) compared to values achieved after 1200 mg twice daily doses of amprenavir capsules.
Fi studji kliniċi li saru intużat doża ta ’ 600 mg amprenavir darbtejn
In clinical trials, doses of amprenavir 600 mg twice daily and ritonavir 100 mg twice daily have been used; confirming the safety and efficacy of this regimen.
Dawn l- istudji kkonfermaw li din it - taħlita ta ’ dawn iż- żewġ mediċini hija effettiva u ma tipperikolax saħħet il- pazjent.
Lopinavir / ritonavir (Kaletra): in an open-label, non-fasting pharmacokinetic study, the AUC, Cmax and Cmin of lopinavir were decreased by 38%, 28% and 52% respectively when amprenavir (750 mg twice daily) was given in combination with Kaletra (400 mg lopinavir + 100 mg ritonavir twice daily).
Fi studju li sar (studju farmakokinetiku tat- tip open- label u li sar f’ nies li ma kienux qed isumu) l- AUC, Cmin u Cmax ta ’ lopinavir naqsu bi 38%, 28% u 52% rispettivament meta amprenavir (750 mg darbtejn kuljum) ġie mogħti flimkien ma ’ Kaletra (400 mg lopinavir u 100 mg ritonavir darbtejn kuljum).
In the same study, the AUC, Cmax, and Cmin of amprenavir were increased 72%, 12%, and 483%, respectively, when compared to values after standard doses of amprenavir (1200 mg twice daily).
Fl- istess studju, l- AUC, Cmin u Cmax ta ’ amprenavir żdiedu b’ 72%, 12% u 483% rispettivament meta mqabbla ma ’ valuri milħuqa wara doża normali ta ’ amprenavir (1200 mg darbtejn kuljum).
The amprenavir plasma Cmin values achieved with the combination of amprenavir (600 mg twice daily) in combination with Kaletra (400 mg lopinavir + 100 mg ritonavir twice daily) are approximately 40- 50% lower than when amprenavir (600 mg twice daily) is given in combination with ritonavir 100 mg twice daily.
Il- valuri ta ’ Cmin fil- plażma għal amprenavir milħuqa permezz tat- taħlita ta ’ amprenavir (600 mg darbtejn kuljum) flimkien ma ’ Kaletra (400 mg lopinavir + 100 mg ritonavir darbtejn kuljum) huma bejn wieħed u ieħor 40- 50% anqas minn meta amprenavir (600 mg darbtejn kuljum) jiġi mogħti flimkien ma ’ 100 mg darbtejn kuljum ta ’ ritonavir.
No dose recommendation can be given for the co-
Jekk jingħata aktar ritonavir ma ’ taħlita ta ’ amprenavir u Kaletra, jkun hemm żieda fil- valuri tas- Cmin ta ’ lopinavir iżda mhux f’ dawk ta ’ amprenavir.
7 administration of amprenavir and Kaletra, but close monitoring is advised because the safety and efficacy of this combination is unknown.
M’ hemmx doża rakkomandabbli li tista ’ tintuża meta jingħataw flimkien amprenavir u Kaletra iżda huwa għaqli li l- pazjent jinżamm taħt osservazzjoni minħabba li s- sigurtà u l- effikaċja ta’ din it- taħlita mhumiex magħrufa.
• Nucleoside analogue reverse transcriptase inhibitors (NRTIs):
● Analogi ta ’ l- Inibituri nuklejosajd rivers transkriptejż (NRTIs):
Zidovudine: the AUC and Cmax of zidovudine were increased by 31% and 40%, respectively, when given with amprenavir.
Zidovudine: l- AUC u Cmax ta ’ zidovudine żdiedu b’ 31% u 40% rispettivament meta ġie mogħti flimkien ma ’ amprenavir.
The AUC and the Cmax of amprenavir were unaltered.
Ma ’ kienx hemm bidla fl- AUC u fis- Cmax ta ’ amprenavir.
No dose adjustment for either medicinal product is necessary when zidovudine is administered in combination with amprenavir.
Ma ’ hemmx bżonn li jsir ċaqliq fid- doża ta ’ l- ebda waħda minn dawn iż- żewġ mediċini meta zidovudine jiġi mogħti flimkien ma ’ amprenavir.
Lamivudine: the AUC and Cmax of lamivudine and amprenavir, respectively, were both unaltered when these two medicinal products were given concomitantly.
Kemm fil- każ ta ’ lamivudine, kif ukoll fil- każ ta ’ amprenavir, l- AUC u Cmax ma nbidlux meta ż- zewġ mediċini ġew mogħtija flimkien.
No dose adjustment is necessary for either medicinal product when lamivudine is administered in combination with amprenavir.
Ma hemmx bżonn li jsir ċaqliq fid- doża ta ’ l- ebda waħda minn dawn iż- żewġ mediċini meta lamivudine jiġi mogħti flimkien ma ’ amprenavir.
Abacavir: the AUC, Cmin and Cmax of abacavir were unaltered when given with amprenavir.
Abacavir: l- AUC, Cmin u Cmax ta ’ abacavir ma nbidlux meta ġie mogħti flimkien ma ’ amprenavir.
The AUC, Cmin and Cmax of amprenavir were increased by 29%, 27%, and 47%, respectively.
L - AUC, Cmin u Cmax ta ’ amprenavir żdiedu bi 29%, 27% u 47% rispettivament.
No dose adjustment is necessary for either medicinal product when abacavir is administered in combination with amprenavir.
Ma ’ hemmx bżonn ta ’ ċaqliq fid- doża ta ’ l- ebda waħda minn dawn iż- żewġ mediċini meta abacavir jiġi mogħti flimkien ma ’ amprenavir.
Didanosine: no pharmacokinetic study has been performed with Agenerase in combination with didanosine, however, due to its antacid component, it is recommended that didanosine and Agenerase should be administered at least one hour apart (see Antacids below).
Iżda minħabba li didanosine għandu parti minnu li hija mediċina ta ’ kontra l- aċidu fl - istonku, għandu jitħalla jgħaddi perjodu ta ’ siegħa bejn Agenerase u didanosine (ara Mediċini kontra l - aċidu fl- istonku aktar ‘ l isfel).
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs):
● Inibituri non- nuklejosajd rivers transkriptejż (NNRTIs):
Efavirenz: efavirenz has been seen to decrease the Cmax, AUC and Cmin, ss of amprenavir by approximately 40% in adults.
Efavirenz: ġie muri li efavirenz inaqqas is- Cmax, AUC u Cmin, ss ta ’ amprenavir b’ madwar 40% f’ pazjenti adulti.
When amprenavir is combined with ritonavir, the effect of efavirenz is compensated by the pharmacokinetic booster effect of ritonavir.
Meta amprenavir jingħata flimkien ma ’ ritonavir, l- effetti ta ’ efavirenz jiġu kkumpensati mill- effett farmakokinetiku ta ’ ritonavir li jsaħħaħ dak ta ’ amprenavir.
Therefore, if efavirenz is given in combination with amprenavir (600 mg twice daily) and ritonavir (100 mg twice daily), no dose adjustment is necessary.
Għalhekk, jekk l - efavirenz jingħata flimkien ma ’ amprenavir (600 mg darbtejn kuljum) u ritonavir (100 mg darbtejn kuljum), m’ hemmx bżonn ta ’ ċaqliq fid- doża.
Further, if efavirenz is given in combination with amprenavir and nelfinavir, no dosage adjustment is necessary for any of the medicinal products.
Ma jkunx hemm bżonn ta ’ ċaqliq fid- doża ta ’ l- ebda waħda mill- mediċini.
Treatment with efavirenz in combination with amprenavir and saquinavir is not recommended, as the exposure to both protease inhibitors would be decreased.
Taħlita ta ’ efavirenz flimkien ma ’ amprenavir u saquinavir m’ hijiex rakkomandata, minħabba li ż - żewġ inibituri protease ma jilħaqx ikollhom ħin biżżejjed biex jagħmlu l- effett tagħhom.
No dose recommendation can be given for the co-administration of amprenavir with another protease inhibitor and efavirenz in children.
M’ hemmx doża rakkomandabbli li tista tintuża meta jingħataw fl- istess waqt amprenavir u inibitur protease flimkien ma ’ efavirenz fit- tfal.
Such combinations should be avoided in patients with hepatic impairment.
Taħlit ta ’ din l- għamla għandu jiġi evitat f’ pazjenti li jbatu minn indeboliment tal- fwied.
Nevirapine:
8 Nevirapine:
The effect of nevirapine on other protease inhibitors and the limited evidence available suggest that nevirapine may decrease the serum concentrations of amprenavir.
L- effett li jħalli nevirapine fuq inibituri protease oħra flimkien ma ’ n- nuqqas ta ’ provi li hemm jisuġġerixxu li nevirapine jista jnaqqas il- konċentrazzjoni ta ’ amprenavir fis- serum.
Delavirdine: the AUC, Cmax and Cmin of delavirdine were decreased by 61%, 47% and 88% respectively when given with amprenavir.
Delavirdine: l- AUC, Cmax u Cmin ta ’ delavirdine naqsu b’ 61%, 47% u 88% rispettivament meta ġie mogħti flimkien ma ’ amprenavir.
The AUC, Cmax and Cmin of amprenavir were increased by 130%, 40% and 125% respectively.
L- AUC, Cmax u Cmin ta ’ amprenavir żdiedu bi 130%, 40% u 125% rispettivament.
No dose recommendations can be given for the co-administration of amprenavir and delavirdine.
M’ hemmx doża rakkomandabbli li tistà tintuża meta jingħataw fl- istess waqt amprenavir u delavirdine.
If these medicinal products are used concomitantly care is advised, as delavirdine may be less effective due to decreased and potentially sub-therapeutic plasma concentrations.
Jekk dawn il- mediċini jintużaw flimkien, dan għandu jsir b’ attenzjoni, minħabba li delavirdine jista jkun inqas effettiv kawża tal- fatt li l- konċentrazzjoni tiegħu fil- plażma tistà tonqos jew ma tkunx għolja biżżejjed.
No dose recommendations can be given for the co-administration of amprenavir and low dose ritonavir with delavirdine.
M’ hemmx doża rakkomandabbli li tistà tintuża meta jingħataw fl- istess waqt amprenavir u doża baxxa ta ’ ritonavir flimkien ma ’ delavirdine.
If these medicinal products are used concomitantly care is advised, and close clinical and virological monitoring should be performed since it is difficult to predict the effect of the combination of amprenavir and ritonavir on delavirdine.
Fl- istess waqt għandu jkun hemm osservazzjoni mill- qrib tal- pazjent, flimkien ma ’ osservazzjoni viroloġika, minħabba li huwa diffiċli tbassar l- effett tat- taħlita ta ’ amprenavir u ritonavir fuq delavirdine.
8 Antibiotics/ antifungals
Antibijotiċi/ antifungals
Rifabutin: co-administration of amprenavir with rifabutin resulted in a 193% increase in rifabutin AUC and an increase of rifabutin-related adverse events.
Rifabutin: meta amprenavir ingħata flimkien ma ’ rifabutin kien hemm żieda ta ’ 193% fl- AUC ta ’ rifabutin u żieda f’ effetti mhux mixtieqa relatati ma ’ rifabutin.
The increase in rifabutin plasma concentration is likely to result from inhibition of rifabutin CYP3A4 mediated metabolism by amprenavir.
Iż- żieda fil- konċentrazzjoni ta ’ rifabutin fil- plażma x’ aktarx li tiġri minħabba li amprenavir jinibixxi il- metaboliżmu ta ’ rifabutin permezz ta ’ CYP3A4.
When it is clinically necessary to co-administer rifabutin with Agenerase, a dosage reduction of at least half the recommended dose of rifabutin is advised, although no clinical data are available.
Meta jkun hemm bżonn li jingħata rifabutin flimkien ma ’ Agenerase, id- doża irrikmandata ta ’ rifabutin għandha ta ’ l- anqas tiġi mnaqqsa bin- nofs, minkejja li m’ hemmx studji kliniċi dwar dan.
When ritonavir is co-administered a larger increase in rifabutin concentration may occur.
Meta flimkien ma ’ dawn jingħata wkoll ritonavir jistà jkun hemm żieda akbar fil- konċentrazzjoni ta ’ rifabutin.
Clarithromycin: the AUC and Cmin of clarithromycin were unaltered and the Cmax decreased by 10% when given with amprenavir.
Clarithromycin: ma ’ kien hemm l- ebda bidla fl- AUC u Cmin ta ’ clarithromycin, filwaqt li Cmax naqas b’ 10% meta ġie mogħti flimkien ma ’ amprenavir.
The AUC, Cmin and Cmax of amprenavir were increased by 18%, 39% and 15%, respectively.
L- AUC, Cmin u Cmax ta ’ amprenavir żdiedu bi 18%, 39% u 15% rispettivament.
No dose adjustment is necessary for either medicinal product when clarithromycin is administered in combination with amprenavir.
M’ hemmx bżonn ta ’ ċaqliq fid- doża ta ’ l- ebda waħda minn dawn iż- żewġ mediċini meta clarithromycin jiġi mogħti flimkien ma ’ amprenavir.
When ritonavir is co-administered an increase in clarithromycin concentrations may occur.
Meta jingħata ritonavir jistà jkun hemm żieda fil- konċentrazzjoni ta ’ clarithromycin.
Erythromycin: no pharmacokinetic study has been performed with Agenerase in combination with erythromycin, however, plasma levels of both medicinal products may be increased when co-administered.
Erythromycin: ma sar l- ebda studju farmakokinetiku ta ’ Agenerase flimkien ma ’ erythromycin iżda jistà jagħti l- każ li l- konċentrazzjoni fil- plażma taż- żewġ mediċini tista ’ togħla meta jingħataw flimkien.
Ketoconazole / Itraconazole: the AUC and Cmax of ketoconazole were increased by 44% and 19%, respectively when given with amprenavir alone.
Ketoconazole/ Itraconazole: l- AUC u Cmax ta ’ ketoconazole żdiedu b’ 44% u 19% rispettivament meta ġie mogħti flimkien ma ’ amprenavir waħdu.
The AUC and Cmax of amprenavir were increased by 31% and decreased by 16%, respectively.
L- AUC u Cmax ta ’ amprenavir żdied b’ 31% u naqas b’ 16% rispettivament.
Itraconazole concentrations are expected to increase in the same manner as ketoconazole.
Il- konċentrazzjoni ta ’ itraconazole hija mistennija li tiżdied bl- istess mod ta ’ ketoconazole.
No dose adjustment for any of the medicinal products is necessary when either ketoconazole or itraconazole is administered in combination with amprenavir.
M’ hemmx bżonn li jsir ċaqliq fid- doża ta ’ l- ebda waħda minn dawn iż- żewġ prodotti mediċinali meta jew ketoconazole jew itraconazole jiġu mogħtija flimkien ma ’ amprenavir.
Co- administration of fosamprenavir 700 mg with ritonavir 100 mg twice daily and ketoconazole 200 mg once daily increased plasma ketoconazole Cmax by 25% and increased AUC(0-τ) to values 2.69-fold those observed on administration of ketoconazole 200 mg once daily without concurrent fosamprenavir with ritonavir.
L- għoti flimkien ta ’ fosamprenavir 700mg ma ’ ritonavir 100mg darbtejn kuljum u ketoconazole 200mg darba kuljum żied il- konċentrazzjoni ta ’ ketoconazole fil- plażma Cmax b’ 25% u żied il- valuri ta ’ AUC (0- τ) għal valuri ta ’ 2. 69 ‘ il darba aktar minn dawk osservati meta ittieħed ketoconazole 200mg darba kuljum mingħajr ma ’ ingħata flimkien ma ’ fosamprenavir ma ’ ritonavir.
The Cmax, AUC and Cmin of amprenavir were unchanged.
Ma nbidlux Cmax, AUC u Cmin ta ’ amprenavir.
When used with Agenerase with ritonavir, high doses (> 200 mg/ day) of ketoconazole or itraconazole are not recommended.
Meta jintuża ma ’ Agenerase flimkien ma ’ ritonavir, m’ humiex rakkomandati dożi għoljin (> 200mg/ kuljum) ta ’ ketoconazole u itraconazole.
Other possible interactions
Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott
Other medicinal products, listed below, including examples of substrates, inhibitors or inducers of CYP3A4, may lead to interactions when administered with Agenerase.
Prodotti mediċinali oħra, msemmija hawn taħt u li jinkludu substrati, inibituri jew stimulanti ta ’ CYP3A4, jistgħu jwasslu għal interazzjonijiet meta jingħataw ma ’ Agenerase.
The clinical significance of these possible interactions is not known and has not been investigated.
Kull pazjent għandu
Patients should therefore be monitored for toxic reactions associated with these medicinal products when these are administered in combination with Agenerase.
9 għalhekk jiġi mpoġġi taħt osservazzjoni għal kull effett tossiku marbut ma ’ dawn il- prodotti u li jistà jinqalà meta dawn jingħataw ma ’ Agenerase.
Antacids: on the basis of the data for other protease inhibitors, it is advisable not to take antacids at the same time as Agenerase, since its absorption may be impaired.
Mediċini kontra l- aċidu fl- istonku: fuq tagħrif miġbur dwar inibituri protease oħra, huwa rakkomandabbli li wieħed m’ għandux jieħu mediċini kontra l- aċidu fl- istonku fl- istess ħin ma ’ Agenerase, minħabba li jistà jkun hemm problemi biex dan jiġi assorbit.
It is recommended that antacids and Agenerase should be administered at least one hour apart.
Huwa tajjeb li jitħalla perjodu ta ’ l- anqas siegħa minn bejn x’ ħín wieħed jieħu dawn il- mediċini u Agenerase.
Anticonvulsant active substances: concomitant administration of anticonvulsant active substances known as enzymatic inductors (phenytoin, phenobarbital, carbamazepine) with amprenavir may lead to a decrease in the plasma concentrations of amprenavir.
Sustanzi attivi kontra l- konvulżjonijiet: l- għoti flimkien ta ’ sustanzi attivi kontra l- konvulżjonijiet magħrufa bħala inductors ta ’ l- enżimi (phenytoin, phenobarbital, carbamazepine) ma ’ amprenavir jistgħu iwasslu għal tnaqqis fil- konċentrazzjoni tal- plażma ta ’ amprenavir.
These combinations should be used with caution and therapeutic concentration monitoring is recommended (see section 4.4).
(ara sezzjoni 4. 4)
Calcium-channel blockers: amprenavir may lead to increased serum concentrations of calcium channel blockers such as amlodipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine and verapamil, possibly resulting in enhanced activity and toxicity of these medicinal products.
Imblokkaturi tal- kanali tal- kalċju: l- użu ta ’ amprenavir jistà jwassal għal żieda fil- konċentrazzjoni fis - serum ta ’ imblokkaturi tal- kanali tal- kalċju bħal amlopidine, diltiazem, felopidine, isradipine, nicardipine, nifedipine nimodipine, nisolpidine u verapamil li possibilment jirriżulta f’ attività u effetti tossiċi aktar qawwija minn naħa ta’ dawn il- prodotti mediċinali.
Erectile dysfunction agents: based on data for other protease inhibitors caution should be used when prescribing PDE5 inhibitors (e. g. sildenafil and vardenafil) to patients receiving Agenerase.
Erectile Dysfunction Agents: fuq tagħrif miġbur dwar inibituri protease oħra, huwa għaqli li wieħed jippreskrivi b’ attenzjoni inibituri ta ’ PDE5 (eż sildenafil u vardenafil) f’ pazjenti li qed jirċievu Agenerase.
Co- administration with Agenerase may substantially increase PDE5 inhibitor plasma concentrations and associated adverse events, including hypotension, visual changes and priapism (see section 4.4).
Meta Agenerase jingħata flimkien, jistà jkun hemm żieda konsiderevoli fil- konċentrazzjoni fil- plażma ta ’ inibitur ta ’ PDE5 u effetti mhux mixtieqa bħal pressjoni baxxa, bdil fil- vista u prijapiżmu.