qanastek/EMEA-V3 huggingface dataset:
Ritonavir was not found to be mutagenic or clastogenic in a battery of in vitro and in vivo assays including the Ames bacterial reverse mutation assay using S. typhimurium and E. coli, the mouse lymphoma assay, the mouse micronucleus test and chromosomal aberration assays in human lymphocytes.
F’ serje sħiha ta ’ provi in vitro u in vivo inkluża l- prova ‘ Ames bacterial reverse mutation ’ bl- użu ta ’ S. typhimurium u ta ’ E. coli, il- prova tal- linfoma fil- ġurdien, it- test mikronukleju fil- ġurdien u provi ta ’ aberrazzjoni kromosomali f’ linfoċiti umani, ma ġiex misjub li ritonavir huwa mutaġeniku jew klastoġeniku.
Long term carcinogenicity studies of ritonavir in mice and rats revealed tumourigenic potential specific for these species, but are regarded as of no relevance for humans.
Studji karċinoġeniċi fit- tul ta ’ ritonavir fuq ġrieden u fuq l- firien żvelaw potenzjal tumoriġeniku speċifikatament f’ din l- ispeċje, iżda huma kkunsidrati bħala ta ’ mingħajr rilevanza fil- każ tal- bniedem.
Norvir oral solution contains: alcohol, purified water, polyoxyl 35 castor oil, propylene glycol, anhydrous citric acid, saccharin sodium, peppermint oil, creamy caramel flavour, sunset yellow E110
Is- soluzzjoni orali Norvir fiha: alcoħol, ilma purifikat, polyoxyl 35 żejt ir- riġnu, propylene glycol, aċidu ċitriku mingħajr ilma sakkarina tas- sodju, żejt tal- pepermint, togħma tal- krema tal- karamel, Isfar lewn inżul ix- xemx (E110)
Norvir should not be diluted with water.
Norvir m’ għandux jiġi miżjud bl- ilma.
6 months
6 xhur
Store below 25°C and use within the expiry date shown on the bottle.
Aħżen f’ temperatura taħt 25ºC u uża sa qabel id- data ta ’ l- iskadenza murija fuq il- flixkun.
Avoid exposure to excessive heat.
Evita esponiment għal sħana eċċessiva.
Norvir oral solution is supplied in amber coloured multiple-dose polyethylene terephthalate (PET) bottles in a 90 ml size.
Is- soluzzjoni orali Norvir hija fornuta fi fliexken ta ’ aktar minn doża waħda, polyethylene terephthalate (PET) ta ’ kulur l- ambra tal- qies ta ’ 90 ml.
Each pack contains 5 bottles of 90 ml (450 ml).
Kull pakkett fih 5 fliexken ta ’ 90 ml (450 ml).
A dosage cup containing graduations at 3.75 ml (300 mg dose), 5 ml (400 mg dose), 6.25 ml (500 mg dose) and 7.5 ml (600 mg dose) is provided.
Tazza għall- kejl tad- doża li fiha l- kejl ta ’ 3. 75 ml (doża ta ’ 300 mg), 5 ml (doża ta ’ 400), 6. 25 ml (doża ta ’ 500 mg) u 7. 5 ml (doża ta ’ 600 mg) hija provduta.
Shake well before each use.
Ħawwad sewwa qabel kull darba li tuża.
If, after shaking, particles or precipitate can be seen in the solution, the patient should take the next dose and see their doctor about a fresh supply.
Jekk, wara li tħawwad, ikunu jidhru partiċelli jew materji sodi fis- soluzzjoni, ħu d- doża li jkun imiss u kellem lit- tabib dwar provvista ġdida.
The dosage cup or oral syringe should be cleaned immediately with hot water and dish soap after use.
It- tazza għall- kejl tad- doża jew is- siringa tal- ħalq għandha titnaddaf mill- ewwel wara l- użu bl- ilma sħun u bis- sapun tal- platti.
When cleaned immediately, drug residue is removed.
Meta mnaddfa mill- ewwel, il- fdal tal- mediċina jitneħħa.
The device must be dry prior to use
L- apparat għandu jkun xotta qabel l- użu.
MARKETING AUTHORISATION HOLDER
30 7 ID- DETENTUR TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ
26 August 1996 Date of last renewal:
26 ta ’ Awissu 1996 Data ta ’ l- aħħar tiġdid ta ’ l- awtorizzazzjoni:
27 August 2006
27 ta ’ Awissu 2006
Norvir 100 mg soft capsules
Norvir 100 mg kapsuli rotob
Each soft capsule contains 100 mg ritonavir.
Kull kapsula ratba fiha 100 mg ritonavir.
Excipients (per soft capsule):
Sustanzi mhux attivi (kull kapsula ratba):
Alcohol (12%w/w) Castor Oil Polyoxyl 35
Alkoħol (12% w/ w) Polyoxyl 35 żejt ir- riġnu
The capsule is white with “Abbott A” and the code “DS100” imprinted on the shell in black ink.
Il- kapsula hija bajda b ’ ” Abbott A ” u l- kodiċi “ DS100 ” stampati fuq il- qoxra ta ’ barra b’ linka sewda.
Ritonavir soft capsules are administered orally and should preferably be ingested with food.
Il- kapsuli rotob Norvir jittieħdu mill- ħalq, u preferibbilment għandhom jinbelgħu ma ’ l- ikel
Amprenavir 600 mg twice daily with ritonavir 100 mg twice daily Atazanavir 300 mg daily with ritonavir 100 mg daily Fosamprenavir 700 mg twice daily with ritonavir 100 mg twice daily Lopinavir 400 mg co-formulated with ritonavir 100 mg twice daily Saquinavir 1000 mg twice daily with ritonavir 100 mg twice daily Tipranvir 500 mg twice daily with ritonavir 200 mg twice daily Darunavir 600 mg twice daily with ritonavir 100 mg twice daily
600 mg ampremavir darbtejn kuljum flimkien ma ’ 100 mg ritonavir darbtejn kuljum 300 mg atazanavir kuljum flimkien ma ’ 100 mg ritonavir kuljum 700 mg fosamprenavir darbtejn kuljum flimkien ma ’ 100 mg ritonavir darbtejn kuljum 400 mg lopinavir imħallta ma ’ 100 mg ritonavir darbtejn kuljum f’ taħlita waħda 1000 mg saquinavir darbtejn kuljum ma ’ 100 mg ritonavir darbtejn kuljum 500 mg tipranvir darbtejn kuljum flimkien ma ’ 200 mg ritonavir darbtejn kuljum 600 mg darunavir darbtejn kuljum flimkien ma ’ 100 mg ritonavir darbtejn kuljum
Lopinavir co-formulated with ritonavir is recommended for children 2 years of age and older.
Lopinavir imħallat f’ taħlita waħda ma ’ ritonavir huwa rrakkomandat ghal tfal ta ’ sentejn jew aktar fl- età.
As ritonavir is primarily metabolised by the liver, ritonavir may be appropriate for use with caution as a pharmacokinetic enhancer in patients with renal insufficiency depending on the
Peress illi ritonavir jiġi primarjament imetabolizzat mill- fwied, ritonavir jista ’ jkun adattat, bħala dak illi jżid l- effett farmakokinetiku, ghal użu b’ attenzjoni minn pazjenti li jbatu minn insuffiċjenza renali, u dan skond l- impeditur protejaż speċifiku li miegħu jkun qiegħed jingħata
29 specific protease inhibitor with which it is co-administered.
32 ritonavir.
In the absence of pharmacokinetic studies in patients with stable severe hepatic impairment (Child Pugh Grade C) without decompensation, caution should be exercised when ritonavir is used as a pharmacokinetic enhancer as increased levels of the co-administered PI may occur.
Peress illi m’ hemmx studji farmakokinetiċi fuq pazjenti illi jbatu minn indeboliment tal- fwied minghajr kumpens, stabbli u sever (Child Pugh Grad C), ritonavir għandu jintuża b’ attenzjoni meta huwa jintuża biex jżid l- effett farmakokinetiku u dana minħabba l- fatt illi jistgħu jiżdiedu l- livelli tal- PI illi jingħata ma ’ ritonavir.
The recommended dosage of Norvir soft capsules is 600 mg (6 capsules) twice daily by mouth.
Id- doża rrakkomandata tal- kapsuli rotob Norvir hija ta ’ 600 mg (6 kapsuli) darbtejn kuljum mill- ħalq.
Treatment should be initiated at 300 mg (3 capsules) twice daily for a period of three days and increased by 100 mg (1 capsule) twice daily increments up to 600 mg twice daily over a period of no longer than 14 days.
Il- kura għandha tinbeda bi 300 mg (3 kapsuli) darbtejn kuljum għal perijodu ta ’ tlett ijiem, u tiżdied b’ 100 mg (kapsula waħda) darbtejn kuljum sakemm wieħed jasal sa 600 mg darbtejn kuljum, u dana fuq perijodu ta ’ mhux akatr minn 14 il - ġurnata.
Paediatric use (2 years of age and above): the recommended dosage of Norvir in children is 350 mg/m² by mouth twice daily and should not exceed 600 mg twice daily.
Użu pedjatriku (sentejn jew aktar fl- eta`): id- doża tas- soluzzjoni Norvir irrakkomandata għat- tfal hija ta ’ 350 mg/ m² mill- ħalq darbtejn kuljum, u m’ għandhiex teċċedi 600 mg darbtejn kuljum.
Norvir should be started at 250 mg/m² and increased at 2 to 3 day intervals by 50 mg/m² twice daily (please refer to the Norvir 80 mg/ml oral solution Summary of Product Characteristics)
Jekk jogħġbok irreferi għas- Sommarju tal- Karatteristiċi tal- Prodott tas- soluzzjoni orali Norvir ta ’ 80 mg/ ml).
For older children it may be feasible to substitute soft capsules for the maintenance dose of the oral solution.
Għal tfal akbar fl- età jista ’ jkun aktar vijabli li taqleb għal kapsuli rotob mis- soluzzjoni orali għad - doża tal- manteniment.
Dosage conversion from oral solution to soft capsules for children
Doża ta ’ soluzzjoni orali 175 mg (2. 2 ml) darbtejn kuljum
Oral solution dose 175 mg (2.2 ml) twice daily 350 mg (4.4 ml) twice daily 437.5 mg (5.5 ml) twice daily 525 mg (6.6 ml) twice daily
Doża tal- kapsuli 200 mg filgħodu u 200 mg filgħaxija
Capsule dose 200 mg in the morning and 200 mg in the evening 400 mg in the morning and 300 mg in the evening 500 mg in the morning and 400 mg in the evening 500 mg in the morning and 500 mg in the evening
500 mg filgħodu u 500 mg filgħaxija
The safety and efficacy of ritonavir in children under the age of 2 have not been established.
Is- sigurtà u l- effikaċja ta ’ ritonavir fit- tfal ta ’ taħt is- sentejn għadhom ma ġewx stabbiliti.
The renal clearance of ritonavir is negligible, therefore, a decrease in the total body clearance is not expected in patients with renal impairment.
Huwa ammont żgħir ħafna ta ’ ritonavir li jiġi eliminat permezz tal- kliewi, għalhekk m’ huwiex mistenni tnaqqis fl - eliminazzjoni totali ta ’ rinovir mill- ġisem f’ pazjenti illi jbatu minn indeboliment renali.
Because ritonavir is highly protein bound it is unlikely that it will be significantly removed by haemodialysis or peritoneal dialysis.
Minħabba l - fatt li ritonavir jeħel ħafna mal- proteini tad- demm, m’ huwiex probabbli li ammont kbir minnu jiġi mneħħi bil- ħemodijaliżi jew bid- dijaliżi peritonejali.
Hepatic impairment:
33 Indeboliment tal- fwied:
Ritonavir is principally metabolised and eliminated by the liver.
Ritonavir huwa prinċipalment imetabolizzat u eliminat permezz tal- fwied.
Pharmacokinetic data indicate that no dose adjustment is necessary in patients with mild to moderate hepatic impairment (see section 5.2).
Informazzjoni farmakokinetika tindika li m’ hemmx bżonn ta ’ aġġustament tad- doża f’ pazjenti li jbatu minn indeboliment tal- fwied li jvarja minn ħafif għal moderat (ara sezzjoni 5. 2).
30 4.3 Contraindications
4. 3 Kontra- indikazzjonijiet
Concomitant Drug Levels Increased α1-Adrenoreceptor Antagonist
Żieda fil- livelli tal- Mediċini ji jingħataw b’ mod Konkomitanti Mediċini li jimblukkaw ir- riċettur α1 - Adrenoreceptor
Antibiotic
Mediċini Anti- bijotiċi
Antifungal
34 Mediċini li jaħdmu kontra il- fungi
31 Antimycobacterial
Mediċini li jaħdmu kontra l - mycobacteria
Recommendations regarding use of ritonavir dosed as a pharmacokinetic enhancer with rifabutin are noted in section 4.5
Rakkommandazzjonijiet għall- użu ta’ ritonavir meta dan jingħata biex iżid l- effett farmakokinetiku flimkien ma ’ rifabutin huma mniżżla f’ sezzjoni 4. 5
Sedatives/hypnotics
Mediċini Sedattivi/ Ipnotiċi
(For caution on parenterally administered midazolam, see section 4.5.)
(Sabiex tiġi eżerċitata kawtela meta midazolam jiġi mgħoti parenteralment, ara sezzjoni 4. 5).
John’s Wort
Fexfiex tar- raba ’
Herbal preparations containing St John’s wort (Hypericum perforatum) due to the risk of decreased plasma concentrations and reduced clinical effects of ritonavir (see section 4.5).
Preparazzjonijiet tal- ħxejjex illi jinkludu l - fexfiex tar- raba ’ (Hypericum perforatum) minħabba riskju ta ’ tnaqqis ta ’ konċentrazzjoni fil- plażma u tnaqqis fl- effetti kliniċi ta ’ ritonavir (ara sezzjoni 4. 5).
4.4 Special warnings and precautions for use
u prekawzjonijiet għall- użu
Patients receiving Ritonavir or any other antiretroviral therapy may continue to develop opportunistic infections and other complications of HIV-1 infection.
Pazjenti li jkunu qegħdin jirċievu ritonavir jew kwalunkwe kura antiretrovirali oħra, jistgħu jibqgħu jiżvillupaw infezzjonijiet opportunistiċi jew komplikazzjonijiet oħra ta ’ l- infezzjoni ta ’ l- HIV- 1.
Ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer 32 Patients with chronic diarrhoea or malabsorption:
Pazjenti illi jbatu minn dijarea kronika jew min- nuqqas ta ’ assorbiment:
The relatively high frequency of diarrhoea during treatment with ritonavir may compromise the absorption and efficacy (due to decreased compliance) of ritonavir or other concurrent medications.
Iż- żieda relattivament kbira ta’ dijarea waqt li tkun qiegħda tingħata l- kura b ’ ritonavir tista ’ jaffetwa l- assorbiment u l- effikaċja (minħabba nuqqas ta ’ osservanza mill- pazjent) ta ’ ritonavir jew mediċini oħra li jkunu qegħdin jittieħdu ma ’ ritonavir.
Serious persistent vomiting and/or diarrhoea associated with ritonavir use might also compromise renal function.
Ħafna rimettar u/ jew dijarea persistenti assoċjati ma ’ l- użu ta’ ritonavir jistgħu ukoll jaffetwaw l- funzjoni renali.
Patients who exhibit these signs or symptoms should be evaluated and Norvir therapy should be discontinued if a diagnosis of pancreatitis is made (see section 4.8).
36 għandhom ikunu evalwati, u l- kura b’ Norvir għandha titwaqqaf f’ każ illi jkun hemm dijanjosi ta ’ pankreatite (ara sezzjoni 4. 8).
Typically, such reactions have been observed within the first few weeks or months of initiation of CART.
Normalment, reazzjonijiet bħal dawn jiġu nnotati fl- ewwel ftit ġimgħat jew xhur minn meta tkun inbdiet t- terapija antiretrovirali kombinata (CART).
Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections, and Pneumocystis carinii pneumonia.
Eżempji relevati huma retinite ikkawzata minn cytomegalovirus, infezzjonijiet generalised u/ jew infezzjonijiet fokali kkawżati minn mycobacteria, u pnewmonja kkawżata minn Pneumocystis carinii.
33 Renal disease:
Mard Renali:
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 in patients with advanced HIV-disease and/or long-term exposure to combination antiretroviral therapy (CART).
Għalkemm ġew ikkunsidrati diversi fatturi bħala l- kawża (li jinkludu użu ta’ corticosteroids, il- konsum ta ’ l- alkoħol, immuno- soppressjoni severa, indiċi tal- massa tal- ġisem aktar għoli), każi ta ’ nekrosi ta ’ l- għadam ġew irraportati f’ pazjenti illi jbatu mill- marda ta ’ l- HIV fi stat avanzat u/ jew li kellhom esponiment għal tul ta ’ żmien għal terapija antiretrovirali kombinata (CART).
Rare reports of 2nd or 3rd degree atrioventricular block in patients with underlying structural heart disease and pre-existing conduction system abnormalities or in patients receiving drugs known to prolong the PR interval (such as verapamil or atazanavir) have been reported in patients receiving ritonavir.
F’ pazjenti bħal dawn, Norvir għandu jintuża b’ kawtela (ara sezzjoni 5. 1).
Norvir should be used with caution in such patients (see section 5.1).
Dan il- prodott mediċinali fih ammonti żgħar ta ’ ethanol (alkoħol), inqas minn 100 mg kull doża massima ta ’ 600 mg.
Interactions with other medicinal products
Effetti fuq prodotti mediċinali oħra
The following Warnings and Precautions should be considered when ritonavir is used as a antiretroviral agent.
It- Twissijiet u l- Prekawzjonijiet segwenti għandhom jiġu kkunsidrati meta ritonavir jintuża bħala aġent antiretrovirali.
When ritonavir is used as a pharmacokinetic enhancer, full details on the warnings and precautions relevant to that particular PI must be considered, therefore the Summary of Product Characteristics, section 4.4, for the particular PI must be consulted to determine if the information below is applicable.
Meta ritonavir jintuża biex iżid l- effett farmakokinetiku, id- dettalji kollha fuq it- twissijiet u l - prekawzjonijiet illi huma relevanti għal dak il- PI partikolari għandhom jiġu kkunsidrati, u għalhekk 37 sabiex jiġi determinat jekk l- informazzjoni t’ hawn tapplikax jew le, għandu jiġi kkonsultat is - Sommarju tal- Karrateristiċi tal- Prodott, sezzjoni 4. 4, għal dak il- PI partikolari.
PDE5 inhibitors:
Impedituri PDE5:
The metabolism of pravastatin and fluvastatin is not dependent of CYP3A, and interactions are not expected with ritonavir.
Il- metaboliżmu ta ’ pravastatin u fluvastatin ma jiddependix minn CYP3A, u interazzjonijiet ma ’ ritonavir m’ humiex mistennija.
In patients who are already taking digoxin when ritonavir is introduced, the digoxin dose should be reduced to one-half of the patients’ normal dose and patients need to be followed more closely than usual for several weeks after initiating co-administration of ritonavir and digoxin.
F’ każ ta ’ pazjenti li meta jinbeda ritonavir ikunu diġà qegħdin jieħdu digoxin, id- doża ta ’ digoxin għandha titnaqqas għal nofs id- doża normali illi jieħu l- pazjent, u wara li jinbdew jittieħdu ritonavir u digoxin flimkien, il- pazjent għandu jiġi osservat aktar mill- viċin mis- soltu għal ħafna ġimgħat.
34 In patients who are already taking ritonavir when digoxin is introduced, digoxin should be introduced more gradually than usual.
Digoxin għandu jiġi introdott aktar bil- mod mis- soltu f’ każ ta ’ pazjenti illi meta jiġi introdott digoxin huma jkunu diġà qegħdin jieħdu ritonavir.
Concomitant use of 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 flimkien ta ’ ritonavir u fluticasone jew glucocorticoids oħra li jiġu metabolizzati minn CYP3A4 m’ huwiex rakkommandat, ħlief jekk il- benefiċji potenzjali tal- kura huma akbar mir- riskju ta ’ effetti sistemiċi tal- corticosteroid, li jinkludu is- sindromu Cushing (Cushing’ s Syndrome) u soppressjoni adrenali (ara sezzjoni 4. 5).
Particular caution should be used when prescribing ritonavir in patients using trazodone.
Attenzjoni speċjali għandha tingħata meta ritonavir jingħata lil pazjenti li jużaw trazodone.
Trazodone is a CYP3A4 substrate and co-administration of ritonavir is expected to increase trazodone levels.
Trazodone huwa sustanza li fuqha taġixxi is- CYP3A4 u l- għoti ta ’ ritonavir miegħu huwa mistenni li jżid il- livelli ta ’ trazodone.
Adverse events of nausea, dizziness, hypotension and syncope have been observed in single dose interaction studies in healthy volunteers (see section 4.5)
Effetti avversi ta ’ nawseja, sturdament, pressjoni baxxa ħafna u sinkope ġew innotati fi studji dwar l- effett ta ’ mediċina fuq oħra b’ doża waħda fuq voluntiera b’ saħħithom (ara sezzjoni 4. 5)
For a description of the mechanisms and potential mechanisms contributing to the interaction profile of the PIs, see section 4.5.
38 Għal deskrizzjoni tal- mekkaniżmi u mekkaniżmi potenzjali li jikkontribwixxu għall- profil ta ’ interazzjonijiet tal- PIs, ara sezzjoni 4. 5.
Co-administration of saquinavir and ritonavir has led to severe adverse events, mainly diabetic ketoacidosis and liver disorders, especially in patients with pre-existing liver disease.
L- għotja flimkien ta’ saquinavir u ritonavir wasslu għall- reazzjonijiet severi, l- aktar kètosi dijabetika u disturbi fil- fwied, speċjalment f’ pazjenti illi kienu diġà jbatu minn mard tal- fwied.
The use of higher ritonavir doses might alter the safety profile of atazanavir (cardiac effects, hyperbilirubinemia) and therefore is not recommended.
L- użu ta ’ dożi ta ’ ritonavir akbar minn hekk jista ’ jbiddel il- profil tas - sigurta` ta ’ atazanavir (effetti kardijaċi, livelli għoljin ta ’ bilirubin fid- demm), u għalhekk m’ huwiex rrakkomandat.
35 Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent
Ritonavir dożat biex iżid l- effett farmakokinetiku jew bħala agent antiretrovirali
The inhibitory effect of ritonavir (with or without other protease inhibitors) on P-gp activity may decrease over time (eg digoxin and fexofenadine-see table “Ritonavir effects on non-antiretroviral drugs” below).
L- effett li ritonavir għandu li jimpedixxi (kemm ma ’, kif ukoll mhux ma ’ impedituri protejaż oħra) fuq l- attività P- gp jista ’ jonqos maż- żmien (eż digoxin u fexofenadine- ara t- tabella t’ hawn taħt – “ L- Effetti ta ’ ritonavir fuq mediċini li m’ humiex antiretrovirali ”).
Important information regarding drug interactions when ritonavir is used as a pharmacokinetic enhancer is also contained in the Summary of Product Characteristics of the co-administered protease inhibitor.
Informazzjoni importanti fuq interazzjonijiet bejn mediċini meta ritonavir jiġi użat biex iżid l- effett farmakokinetiku tinsab ukoll fis- Sommarju tal- Karatteristiċi tal- Prodott ta ’ l- impeditur protejaż li jingħata ma ’ ritonavir.
Serum levels of ritonavir can be reduced by concomitant use of herbal preparations containing St John’s wort (Hypericum perforatum).
Il- livelli fis- serum ta ’ ritonavir jistgħu jiġu mnaqqsa bl- użu ta ’ preparazzjonijiet tal- ħxejjex li jkollhom fihom il- fexfiex tar- raba ’ (Hypericum perforatum) flimkien ma ’ ritonavir.
This is due to the induction of drug metabolising enzymes by St John’s wort.
Dan huwa dovut lill - induzzjoni ta ’ enzimi li jimmetabolizzaw il- mediċina permezz tal- fexfiex tar- raba ’.
Herbal preparations containing St John’s wort must not be used in combination with ritonavir.
Preparazzjonijiet tal- ħxejjex li għandhom fihom il- fexfiex tar- raba ’ m’ għandhomx jintużaw flimkien ma ’ ritonavir.
If a patient is already taking St John’s wort, stop St John’s wort and if possible check viral levels.
39 Jekk pazjent diġà qiegħed jieħu l- fexfiex tar- raba ’, waqqaf il- fexfiex tar- raba ’ u jekk huwa possibbli iċċekja l- livelli virali.
Ritonavir levels may increase on stopping St John’s wort.
Il- livelli ta ’ ritonavir jistgħu jiżdiedu mat- twaqqif tal- fexfiex tar- raba ’.
The inducing effect may persist for at least 2 weeks after cessation of treatment with St John’s wort (see section 4.3).
L- effett induttiv jista ’ jippersisti għal mill - inqas ġimagħtejn wara t- twaqqif tal- kura bil- fexfiex tar- raba ’ (ara sezzjoni 4. 3).
Drugs that are affected by the use of ritonavir
Mediċini li huma affetwati bl- użu ta ’ ritonavir
36 Ritonavir increases the serum levels of darunavir as a result of CYP3A inhibition.
darba Bħala riżultat ta ’ impediment minn CYP3A, ritonavir iżid il- livelli tas- serum ta ’ darunavir.
Amprenavir
Amprenavir ↑ bi 2. 4 drabi ↑ bi
↑ 11 fold
11 - il darba
Fosamprenavir must be given with ritonavir to ensure its therapeutic effect.
Biex l- effett terapewtiku ta ’ fosamprenavir jiġi żgurat, fosamprenavir għandu jingħata ma ’ ritonavir.
Indinavir3 Ritonavir
Indinavir
Appropriate doses for this combination, with respect to efficacy and safety, have not been established.
B’ dożi
Minimal benefit of ritonavir-mediated pharmacokinetic enhancement is achieved with doses higher than 100 mg twice daily.
40 akbar minn 100 mg darbtejn kuljum, irriżulta biss benefiċju minimu medjat minn żieda farmakokinetika minn ritonavir.
100 q12h
100 q12
Ritonavir100 mg twice daily with saquinavir 1000 mg twice daily provides saquinavir systemic exposure over 24 hours similar to or greater than those achieved with saquinavir 1200 mg three times daily without ritonavir.
100 mg ritonavir darbtejn kuljum flimkien ma ’ 1000 mg saquinavir darbtejn kuljum jipprovdu esponiment sistemiku fuq 24 siegħa li huwa simili jew ikbar minn dak li jirrizulta b’ 1200 mg saquinavir tliet darbiet kuljum, mingħajr ritonavir.
37
jittieħdu ma ’ ritonavir
administered Drug
jittieħdu
600 q12h 2 h later
600 q12h
↑ 21%
Frekwenza ogħla ta ’ effetti avversi (eż, sturdament, nawseja, parasteżija) u abnormalitajiet fir -
A higher frequency of adverse events (eg, dizziness, nausea, paraesthesia) and laboratory abnormalities (elevated liver enzymes) have been observed when efavirenz is co-administered with ritonavir dosed as an antiretroviral agent.
41 riżultati tal- laboratorju (enzimi tal- fwied għoljin) ġew innotati meta efavirenz jingħata ma ’ ritonavir f’ doża bħala aġent antiretrovali.
100 q12h 100 q12h Maraviroc ↑ 161%
100 q12h 100 q12h Maraviroc ↑161%
Ritonavir increases the serum levels of maraviroc as a result of CYP3A inhibition.
Bħala riżultat ta ’ impediment minn CYP3A, ritonavir iżid il- livelli tas- serum ta ’ maraviroc.
↓ 25%
Zidovudine ↓ 25% MD
Alpha1-Adrenoreceptor Antagonist
Antagonist Alpha1- Adrenoreceptor Alfuzosin
Ritonavir co-administration is likely to result in increased plasma concentrations of alfuzosin and is therefore contraindicated (see section 4.3).
It- teħid ta ’ ritonavir flimkien ma ’ alfuzosin x’ aktarx illi jirriżulta f’ żieda fil- konċentrazzjoni fil- plażma ta ’ alfuzosin, u għalhekk huwa kontro - indikat (ara sezzjoni 4. 3).
Amphetamine Derivatives Amphetamine
Derivattivi ta ’ l- Amfetamina Amfetamina
Ritonavir dosed as an antiretroviral agent is likely to inhibit CYP2D6 and as a result is expected to increase concentrations of amphetamine and its derivatives.
Ritonavir f’ doża bħala aġent antiretrovirali x’ aktarx li jimpedixxi CYP2D6 u għalhekk huwa mistenni illi jżid il- konċentrazzjoni ta ’ l- amfetamina u d - derivattivi tagħha.
Careful monitoring of therapeutic and adverse effects is recommended when these medicines are concomitantly administered with antiretroviral doses of ritonavir (see section 4.4).
Meta dawn il- mediċini jittieħdu flimkien ma ’ dożi antiretrovirali ta ’ ritonavir, hija rrakkomandata osservazzjoni b’ attenzjoni ta ’ effetti terapewtiċi u avversi (ara sezzjoni 4. 4).
Analgesics Buprenorphine Norbuprenorphine Glucuronide metabolites
42 Mediċini Anaġesiċi Buprenorphine Norbuprenorphine Metabolati Glucuronide
When ritonavir is used in combination with another protease inhibitor and buprenorphine, the SPC of the co-administered protease inhibitor should be reviewed for specific dosing information.
Meta ritonavir ikun użat flimkien ma ’ impeditur protejaż ieħor u ma ’ buprenorphine, l- SPF ta ’ l- impeditur protejaż li jingħata miegħu għandu jkun rivedut għal informazzjoni speċifika dwar id- dożaġġ.
0.5 single IV dose 300 q12h, 3 days ↑ 86% ND 0.4 single oral 200 q12h, 13 days ↑ 22% ↔ dose This interaction may be due to modification of P-glycoprotein mediated digoxin efflux by ritonavir dosed as an antriretroviral agent or as a pharmacokinetic enhancer.
0. 5 doża waħda IV 300 q12h, 3 jiem ↑ 86% MD ↔ 0. 4 doża waħda orali 200 q12h, 13 jiem ↑ 22% Din l- interazzjoni tista ’ tkun ikkaġunata mill- modifikazzjoni ta ’ effluss ta ’ digoxin medjat b’ P - glycoprotein minn ritonavir f’ doża bħala aġent antiretrovirali jew biex iżid l- effett farmakokinetiku.
An increased dose of theophyline may be required when co- administered with ritonavir, due to induction of CYP1A2.
43
3 9 Ritonavir effects on Non-antiretroviral Co-administered Drugs Co-administered Drug
Minħabba l- induzzjoni ta ’ CYP1A2, jista ’ jkun hemm bżonn ta ’ doża akbar ta ’ theophylline meta dan jittieħed flimkien ma ’ ritronavir.
Dose of Co- administered Drug (mg)
Aġenti kontra l- kanċer Vincristine, vinblastine
Effect on Co- administered Drug AUC
Il- konċentrazzjonijiet tal- mediċina fis- serum jistgħu jiżdiedu meta dawn l- aġenti jittieħdu flimkien ma ’ ritonavir, b’ konsegwenza li jkun hemm potenzjal ta ’ żieda fl- inċidenza ta ’ effetti avversi.
Effect on Co- administered Drug Cmax
Mediċini kontra l- koagulazzjoni tad - demm
Antidepressants Amitriptyline, fluoxetine, imipramine, nortriptyline, paroxetine, sertraline
Mediċini għal kontra d- Dipressjoni Amitriptyline, fluoxetine, imipramine, nortriptyline, paroxetine, sertraline
An increase in the incidence in trazodone-related adverse events was noted when co-administered with ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer.
44 Meta trazodone ittieħed ma ’ ritonavir dożat bħala aġent antiretrovirali jew biex iżid l- effett farmakokinetiku, ġiet osservata żieda fl- inċidenza ta ’ l - effetti avversi relatati ma ’ trazodone.
If trazodone is co- administered with ritonavir, the combination should be used with caution, initiating trazodone at the lowest dosage and monitoring for clinical response and tolerability.
Jekk trazodone jingħata flimkien ma ’ ritonavir, it- taħlita għandha tintuża b’ attenzjoni, b ’ trazodone jinbeda bl - inqas doża, u għandha ssir ukoll osservazzjoni tar- rispons kliniku u tat - tolleranza.
Ritonavir co-administration is likely to result in increased plasma concentrations of both fusidic acid and ritonavir and is therefore contraindicated (see section 4.3).
L- użu ta ’ fusidic acid flimkien ma ’ ritonavir x’ aktarx iwassal fil- konċentrazzjoni fil- plażma kemm ta ’ fusidic acid kif ukoll u għalhekk huwa kontro- indikat (ara sezzjoni 4. 3).
150 daily 500 q12h, ↑ 4-fold ↑ 2.5-fold
150 kuljum 500 q12h, ↑b ’ 4 darbiet
The Summary of Product Characteristics of the co-administered protease inhibitor should be consulted for specific recommendations.
Is- Sommarju tal - Karatteristiċi tal- Prodott ta ’ l- impeditur protejaż li jkun qiegħed jittieħed għandha tiġi konsultata.
200 q12h 400 q12h ↓ 82% ↓ 66% 200 q12h 100 q12h ↓ 39% ↓ 24%
200 q12h 400 q12h ↓ 82% ↓ 66% 200 q12h 100 q12h ↓ 39% ↓ 24%
Concomitant use of ritonavir dosed as an antiretroviral agent and voriconazole is contraindicated due to reduction in voriconazole concentrations (see section 4.3).
45 L- użu ta ’ ritonavir dożat bħala aġent antiretrovirali flimkien ma ’ voriconazole huwa kontro- indikat minħabba tnaqqis fil- konċentrazzjoni ta ’ voriconazole (ara sezzjoni 4. 3).
Careful monitoring of therapeutic and adverse effects is recommended when erythromycin or itraconazole is used concomitantly administered with ritonavir.
Ritonavir dożat biex iżid l- effett farmakokinetiku jew bħala aġent antiretrovirali jimpedixxi s- CYP3A4, u għalhekk huwa mistenni li jżid il - konċentrazzjoni fil- plażma ta ’ erythromycin u itraconazole. Meta erythromycin jew itraconazole jiġu użati flimkien ma ’ ritonavir, huwa rrakkomandat li ssir osservazzjoni b’ attenzjoni ta ’ l- effetti terapewtiċi u ta ’ l- effetti avversi.
200 daily 500 q12h ↑ 3.4-fold ↑ 55% Ritonavir inhibits CYP3A-mediated metabolism of ketoconazole.
200 kuljum 500 q12h ↑ bi 3. 4 drabi ↑ 55% Ritonavir jimpedixxi l- metaboliżmu medjat b ’ CYP3A ta ’ ketoconazole.
Due to an increased incidence of gastrointestinal and hepatic adverse events, a dose reduction of ketoconazole should be considered when co- administered with ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer.
Minħabba żieda fl- inċidenza ta ’ l- effetti avversi gastrointestinali u epatiċi, għandu jiġi kkunsidrat tnaqqis fid- doża ta ’ ketoconazole meta dan jingħata flimkien ma ’ ritonavir dożat bħala aġent antiretrovirali jew iżid l- effett farmakokinetiku.
Dose alteration of sulfamethoxazole/trimethoprim during concomitant ritonavir therapy should not be necessary.
800/ 160, doża 500 q12h ↓ 20% / ↑ 20% ↔ waħda M’ għandux għalfejn ikun hemm bżonn ta ’ tibdil fid- doża ta ’ sulfamethoxazole/ trimethoprim meta dan jingħata fl- istess żmien illi tkun qiegħda tingħata t- terapija b’ ritonavir
Haloperidol, risperidone, thioridazine
46 Haloperidol, risperidone, thioridazine
Amlodipine, diltiazem, nifedipine
Mediċini li jinblukkaw ir- riċetturi tal - kanali tal kalċju Amlodipine, diltiazem, nifedipine
Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent inhibits CYP3A4 and as a result is expected to increase the plasma concentrations of calcium channel antagonists.
Ritonavir dożat biex iżid l- effett farmakokinetiku jew bħala aġent antiretrovirali jimpedixxi s - CYP3A4, u għalhekk huwa mistenni li jżid il - konċentrazzjoni fil- plażma tal - mediċini li jimblukkaw ir- riċetturi tal - kanali tal- kalċju.
Dihydroergotamine, ergonovine, ergotamine, methylergonovine
Derivattivi ta ’ l- Ergotina Dihydroergotamine, ergonovine, ergotamine, methylergonovine
Ritonavir co-administration is likely to result in increased plasma concentrations of ergot derivatives and is therefore contraindicated (see section 4.3).
L- għotja ta ’ ritonavir flimkien ma ’ dihydroergotamine, ergonovine, ergotamine, methylergonovine aktarx li twassal għal żieda fil - konċentrazzjoni fil- plażma tad- derivattivi ta ’ l- ergotina, u għalhekk hija kontra- indikata (ara sezzjoni 4. 3).
Ritonavir co-administration is likely to result in increased plasma concentrations of cisapride and is therefore contraindicated (see section 4.3).
L- għotja ta ’ ritonavir flimkien ma ’ Cisapride aktarx li twassal għal żieda fil- konċentrazzjoni fil- plażma ta ’ cisapride, u għalhekk hija kontra - indikata (ara sezzjoni 4. 3).
HMG Co-A Reductase Inhibitors Atorvastatin, Fluvastatin, Lovastatin, Pravstatin, Rosuvastatin, Simvastatin
Impedituri HMG Co- A Reductase Atorvastatin, Fluvastatin, Lovastatin, Pravstatin, Rosuvastatin, Simvastatin
50 µg single dose
50 µg doża waħda 500 q12h ↓ 40% ↓ 32%
Due to reductions in ethinyl estradiol concentrations, barrier or other non-hormonal methods of contraception should be considered with concomitant ritonavir use when dosed as an antiretroviral agent or as a pharmacokinetic enhancer.
47 Minħabba tnaqqis fil- konċentrazzjoni ta ’ ethinyl estradiol, għandhom jiġu kkunsidrati metodi ta ’ barriera jew metodi oħra ta ’ kontraċezzjoni li ma fihomx ormoni meta dawn ikunu qegħdin jiġu użati flimkien ma ’ ritonavir dożat bħala aġent antiretrovirali jew biex iżid l- effett farmakokinetiku.
Ritonavir is likely to change the uterine bleeding profile and reduce the effectiveness of estradiol-containing contraceptives (see section 4.4).
X’ aktarx li ritonavir ibiddel il- profil ta ’ telf ta ’ demm mill- ġuf u jnaqqas l - effettività ta ’ kontraċettivi li jkun fihom estradiol (ara sezzjoni 4. 4).
Cyclosporine, tacrolimus, everolimus
Mediċini Immuno- Suppressanti Cyclosporine, tacrolimus, everolimus
↑ 11-fold
↑ bi 11 - il darba ↑ b’ 4 darbiet
The concomitant use of vardenafil and ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer should be with caution at reduced doses of no more than 2.5 mg every 72 hours with increased monitoring for adverse events (see section 4.4).
L- użu flimkien ta ’ vardenafil ma ’ ritonavir dożat bħala aġent antiretrovirali jew biex iżid l- effett farmakokinetiku għandu jsir b’ attenzjoni u b’ dożi mnaqqsa ta ’ mhux aktar minn 2. 5 mg kull 72 siegħa, u għandu jkun hemm aktar osservazzjoni għall- effetti avversi (ara sezzjoni 4. 4).
Sedatives/hynoptics Clorazepate, diazepam, estazolam, flurazepam, oral and parenteral midazolam and triazolam
48 Mediċina Sedattiva / Ipnotika Clorazepate, diazepam, estazolam, flurazepam, L- għoti ta ’ ritonavir ma ’ clorazepate, diazepam, estazolam, flurazepam, midazolam mittieħed mill- ħalq u parenterali u midazolam u triazolam x’ aktarx li jwassal għal żieda fil- konċentrazzjoni triazolam
Based on data for other CYP3A4 inhibitors, plasma concentrations of midazolam are expected to be significantly higher when midazolam is given orally.
Skond informazzjoni dwar impedituri CYP3A4 oħra, il- konċentrazzjoni plażma ta ’ midazolam hija mistennija li tkun ogħla b’ mod sinifikanti meta midazolam jingħata mill - ħalq.
Ritonavir co-administration is likely to result in increased plasma concentrations of triazolam and is therefore contraindicated (see section 4.3).
0. 125 doża waħda 200, 4 dożi ↑ > 20 darba ↑ 87% L- għoti ta ’ ritonavir ma ’ triazolam x’ aktarx li jwassal għal żieda fil - konċentrazzjoni fil- plażma ta ’ triazolam, u għalhekk huwa kontro- indikat (ara sezzjoni 4. 3).
The use of meperidine and ritonavir is contraindicated due to the increased concentrations of the metabolite, normeperidine, which has both analgesic and CNS stimulant activity.
L- użu ta ’ meperidine u ritonavir huwa kontro- indikat minħabba ż- żieda fil- konċentrazzjoni tal- metabolit normeperidine, li għandu attività analġesika, kif ukoll attività stimulanti fuq is- sistema nervuża (CNS).
Elevated normeperidine concentrations may increase the risk of CNS effects (eg, seizures), see section 4.3.
Konċentrazzjoni għolja ta ’ normeperidine jistgħu jżidu r- riskju ta ’ l- effetti tas- CNS (eż attakki tal - epilessija), ara sezzjoni 4. 3.
↑2.5 fold
↑bi 2. 5 drabi
Alprazolam metabolism was inhibited following the introduction of ritonavir.
Il- metaboliżmu ta ’ alprazolam ġie imwaqqaf meta ritonavir ġie introdott.
After ritonavir use for 10 days, no inhibitory effect of ritonavir was observed.
Wara l- użu ta ’ ritonavir għal 10 ijiem, ma ġie osservat l- ebda effett ta ’ impediment ta ’ ritonavir.
Caution is warranted during the first several days when alprazolam is co-administered with ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer, before induction of alprazolam metabolism develops.
Hemm bżonn li wieħed juża kawtela fl- ewwel diversi ġranet meta alprazolam jiġi mogħti flimkien ma ’ ritonavir dożat bħala aġent antiretrovirali jew biex iżid l- effett farmakokinetiku, qabel ma jibda l- induzzjoni biex jiġi metabolizzat alprazolam.
Sleeping agent Zolpidem
49 Mediċini li jraqqdu Zolpidem
86% in the above study) have been reported in patients receiving ritonavir and inhaled or intranasal fluticasone propionate; similar effects could also occur with other corticosteroids metabolised by CYP3A eg, budesonide.
Effetti tal- corticosteroids sistematiċi inkluż is- sindromu Cushing u soppressjoni adrenali (fl- istudju t’ hawn fuq ġie nnotat li l- livelli tal - cortisol fil- plażma naqsu 86%) ġew rapportati f’ pazjenti illi jieħdu ritonavir u li jiġbdu f’ imnifsejhom jew idaħħlu fl- imnieħer fluticasone propionate; jistgħu jirriżultaw effetti simili b’ corticosteroids oħra metabolati b ’ CYP3A eż, budesonide.
Consequently, concomitant administration of ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer and these glucocorticoids is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects (see section 4.4).
Għalhekk, l- għoti flimkien ta ’ ritonavir dożat bħala aġent antiretrovirali jew biex iżid l- effett farmakokinetiku u dawn il- glucocorticoids, m’ huwiex irrakkomandat, ħlief jekk il- benefiċju potenzjali li jista ’ jkollu t- trattament ikun jiżboq ir- riskju ta ’ l- effetti tal- corticosteroids sistematiċi (ara sezzjoni 4. 4).
Moreover, in case of withdrawal of glucocorticoids progressive dose reduction may be required over a longer period.
Għandu jiġi kkunsidrat tnaqqis fid- doża tal- glucocorticoid u ssir osservazzjoni mill - qrib ta ’ l- effetti lokali u sistematiċi, jew jingħata glucocorticoid ieħor minflok, li m’ huwiex sustanza li fuqa taħdem is- CYP3A4 (eż, beclomethasone). Barra minn hekk, f’ każ illi jitwaqqfu l- glucocorticoids, għandu jkun hemm tnaqqis progressiv tad- doża fuq tul ta ’ żmien.
Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent inhibits CYP3A and as a result is expected to increase the plasma concentrations of dexamethasone.
Ritonavir dożat biex iżid l- effett farmakokinetiku jew bħala aġent antiretrovirali jimpedixxi CYP3A, u għalhekk huwa mistenni li jżid il - konċentrazzjoni fil- plażma ta ’ dexamethasone.
Careful monitoring of therapeutic and adverse effects is recommended when dexamethasone is concomitantly administered with ritonavir.
Meta dexamethasone jingħata flimkien ma ’ ritonavir, huwa rrakkomandat li ssir osservazzjoni b’ attenzjoni ta ’ l- effetti terapewtiċi u ta ’ l- effetti avversi.
20 200 q12h ↑ 28% ↑ 9% Careful monitoring of therapeutic and adverse effects is recommended when prednisolone is concomitantly administered with ritonavir.
20 200 q12h ↑ 28% ↑ 9% Meta prednisolone jingħata flimkien ma ’ ritonavir, huwa rrakkomandat li ssir osservazzjoni b’ attenzjoni ta ’ l- effetti terapewtiċi u ta ’ l- effetti avversi.
ND:
50 MD:
Not determined 3.
Mhux determinat 1.
Based on a parallel group comparison 4.
Ibbażat fuq paragun ta ’ gruppi paralleli.
In addition to the interactions listed above, as ritonavir is highly protein bound, the possibility of increased therapeutic and toxic effects due to protein binding displacement of concomitant medications should be considered.
Ma ’ l - interazzjonijiet imniżżla hawn fuq, peress illi ritonavir jeħel ħafna mal- proteini tad- demm, għandu jiġi kkunsidrat il- fatt li jista ’ jkun hemm żieda fl- effetti terapewtiċi u tossiċi riżultanti mit- tqanqil minn mal- proteini tad- demm ta ’ medikazzjonijiet li jkunu ingħataw flimkien ma ’ ritonavir.
Based on interaction studies with the ritonavir boosted protease inhibitors (lopinavir/ritonavir, atazanavir), concurrent administration of omeprazole or ranitidine does not significantly modify ritonavir efficacy as a pharmacokinetic enhancer despite a slight change of exposure (about 6 - 18%).
Skond studji li saru fuq l- interazzjoni ma ’ l - impedituri protejaż li huma msaħħa b’ ritonavir (lopinavir/ ritonavir, atazanavir), l- għoti flimkien ta ’ omeprazole jew ranitidine, minkejja li jkun hemm bidla żgħira fl- esponiment (madwar 6 - 18%), ma jbiddilx l- effikaċja ta ’ ritonavir bħala li jżid l- effett farmakokinetiku b’ mod sinifikanti.
A limited number (> 800) of pregnant women were exposed to ritonavir during pregnancy; a very limited number (< 300) were exposed during the first trimester.
Numru limitat (> 800) ta ’ nisa tqal ġew esposti għal ritonavir waqt it- tqala; numru limitat ħafna (< 300) kienu esposti waqt l- ewwel tliet xhur tat- tqala.
These limited data indicate no increase in the rate 46 of birth defects compared to rates observed in population-based birth defect surveillance systems.
Din l- informazzjoni limitata ma turi l- ebda żieda fir- rata tad- difetti tat- twelid meta mqabbla ma ’ rati osservati f’ sistemi ta ’ sorveljanza ta ’ difetti tat- twelid bażati fuq il- poplazzjoni.
Adverse events associated with the use of ritonavir as a pharmacokinetic enhancer are dependent on the specific co-administered PI.
51 L- effetti avversi assoċjati ma ’ l- użu ta ’ ritonavir f’ dożi biex iżid l- effett farmakokinetiku jiddependu fuq il- PI speċifiku li jkun ġie mogħti miegħu.
The following adverse reactions of moderate to severe intensity with possible or probable relationship to Ritonavir have been reported.
Ġew irrapportati l- effetti avversi segwenti b’ relazzjoni possibbli jew probabbli ma ’ ritonavir, u li huma ta ’ intensità minn moderata sa severa.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness: very common (> 1/10); common (> 1/100 to < 1/10); uncommon (> 1/1000 to < 1/100); rare (> 1/10,000 to < 1/1,000).
F’ kull klassifikazzjoni ta ’ frekwenza, l- effetti mhux mixtieqa huma preżentati f’ ordni li tibda mill- iktar effetti serji u tispiċċa fl- inqas effetti serji: komuni ħafna (> 1/ 10); komuni (> 1/ 100 sa < 1/ 10); mhux komuni (> 1/ 1000 sa < 1/ 100); rari (> 1/ 10, 000 sa < 1/ 1, 000).
Metabolic and nutritional disorders
mhux magħrufa Mhux komuni Disturbi fil- metaboliżmu u n - nutrizzjoni
Seizure, syncope
Attakk ta ’ l- epilessija, sinkope
Renal and urinary disorders
Disturbi fil- kliewi u fis- sistema
48 Combination antiretroviral therapy has been associated with redistribution of body fat (lipodystrophy) in HIV patients including the loss of peripheral and facial subcutaneous fat, increased intra-abdominal and visceral fat, breast hypertrophy and dorsocervical fat accumulation (buffalo hump).
It- terapija antiretrovirali kombinata ġiet assoċjata mar- ridistribuzzjoni tax- xaħam tal- ġisem (lipodistrofija) f’ pazjenti li jbatu mill- HIV, inkluż it- telf ta ’ xaħam periferali u ta ’ taħt il- ġilda fil - wiċċ, żieda fix- xaħam taż- żaqq u vixxerali, ipertrofija tas- sider u akkumulazzjoni ta ’ xaħam dorsoċervikali (buffalo hump).
In HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise (see section 4.4).
F’ pazjenti infettati bl- HIV li, meta tinbeda t- terapija antiretrovirali kombinata (CART), ikollhom defiċjenza immunitarja severa, tista ’ tirriżulta reazzjoni infjammatorja għall- patoġeni li ma jikkaġunawx sintomi jew li huma opportunisti residwali (ara sezzjonin 4. 4).
Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to combination antiretroviral therapy (CART).
53 Ġew irrapportati każi ta ’ nekrosi ta ’ l- għadam, partikolarment f’ pazjenti li għandhom fatturi ta ’ riskju magħrufa, li jbatu mill- marda ta ’ l- HIV fi stat avanzat jew li kienu soġġetti għall- esponimenti tat - terapija antiretrovirali kombinata (CART) għal żmien twil.
Pharmacotherapeutic group: antiviral for systemic use, ATC code:
Kategorija farmakoterapewtika: antiretrovirali għall- użu sistematiku, Kodiċi ATC:
Maximal inhibition of metabolism of the co-administered protease inhibitor is generally achieved with ritonavir doses of 100 mg daily to 200 mg twice daily, and is dependent on the co-administered protease inhibitor.
L- impediment massimali tal - metaboliżmu ta’ l- impeditur protejaż li jingħata ma ’ ritonavir ġeneralment jintlaħaq b’ dożi ta ’ ritonavir ta ’ minn 100 mg kuljum sa 200 mg darbtejn kuljum, u dan jiddependi fuq l- impeditur protejaż li jingħata ma ’ ritonavir.
For additional information on the effect of ritonavir on co-administered protease inhibitor metabolism, see Section 4.5 and refer to the Summary of Product Characteristics of the particular co-administered PIs.
Għal aktar informazzjoni fuq l- effett ta ’ ritonavir fuq il metaboliżmu ta ’ l - impeditur protejaż li jingħata miegħu, ara Sezzjoni 4. 5 u irreferi għas- Sommarju tal- Karatteristiċi tal - Prodott tal- PIs partikolari li jkunu ngħataw ma ’ ritonavir.
49 Ritonavir is an orally active peptidomimetic inhibitor of the HIV-1 and HIV-2 aspartyl proteases.
Ritonavir huwa impeditur attiv peptidomimetiku tal- protejaż aspartil HIV- 1 u HIV- 2 li jittieħed mill - ħalq.
However, due to ritonavir’s metabolic inhibitory properties its use as a pharmacokinetic enhancer of other protease inhibitors is the prevalent use of ritonavir in clinical practice (see section 4.2).
Madanakollu, minħabba l- kwalitajiet li ritonavir għandu li jimpedixxi, l- akbar użu illi ritonavir għandu fil- prattika klinika huwa l- użu tiegħu biex iżid l- effett farmakokinetiku ta ’ impedituri protejaż oħra (ara sezzjoni 4. 2).
QTcF interval was evaluated in a randomised, placebo and active (moxifloxacin 400 mg once daily) controlled crossover study in 45 healthy adults, with 10 measurements over 12 hours on Day 3.
54 L- intervall QTcF ġie evalwat fi studju tat- tip crossover li sar b’ ordni addoċċ li kien ikkontrollat mill - plaċebo u attiv (moxifloxacin 400mg darba kuljum) li sar fuq 45 adult f’ saħħtu, fejn f’ Ġurnata 3, ġie mkejjel 10 darbiet fi 12- il siegħa.
The Day 3 ritonavir exposure was approximately 1.5 fold higher than that observed with the 600 mg twice daily dose at steady state.
L - esponiment ta ’ ritonavir f’ Ġurnata 3 kien ta ’ bejn wieħed u ieħor 1. 5 drabi aktar għoli minn dak osservat meta ngħatat doża fissa ta ’ 600 mg darbtejn kuljum.
Reduction in the antiretroviral activity of ritonavir is primarily associated with the protease mutations V82A/F/T/S and I84V.
Nuqqas fl- attività antiretrovirali ta ’ ritonavir huwa primarjament assoċjat mal- mutazzjoni tal - preotejażi V82A/ F/ T/ S u I84V.
Accumulation of other mutations in the protease gene (including at positions 20, 33, 36, 46, 54, 71, and 90) can also contribute to ritonavir resistance.
L- akkumulazzjoni ta ’ mutazzjonijiet oħra fil- ġene tal- protejazi (inkluż f’ pożizzjonijiet 20, 33, 36, 46, 54, 71, u 90) tista ’ tikkontribwixxi ukoll għar- resistenza għal ritonavir.
In general, as mutations associated with ritonavir resist ance accumulate, susceptibility to select other PIs may decrease due to cross-resistance.
B’ mod ġenerali, hekk kif jakkumula t- tibdil assoċjat ma ’ l- akkumulant tar- reżistenza għal ritonavir, is - suxxettibilità biex jagħżel PIs oħra tista ’ tonqos minħabba cross- resistance.
The effects of ritonavir (alone or combined with other antiretroviral agents) on biological markers of disease activity such as CD4 cell count and viral RNA were evaluated in several studies involving HIV-1 infected patients.
L- effetti ta ’ ritonavir (waħdu jew flimkien ma ’ aġenti antietrovirali oħra) fuq werrejja bijoloġiċi ta ’ l - attivita ’ tal- mard, bħal għadd ta ’ ċelluli CD4 u RNA virali, ġew evalwati f’ diversi studji li kienu jinvolvu pazjenti infettati bl- HIV- 1.