qanastek/EMEA-V3 huggingface dataset:
Ritonavir is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infected patients (adults and children of 2 years of age and older).
4. 1 Indikazzjonijiet terapewtiċi
Ritonavir should be administered by physicians who are experienced in the treatment of HIV infection.
Ritonavir għandu jingħata minn tobba illi għandhom esperjenza fil- kura ta ’ l- infezzjoni ta ’ l- HIV.
Norvir solution is administered orally and should preferably be ingested with food.
Is- soluzzjoni Norvir tittieħed mill- ħalq, u preferibbilment għandha tinbela ’ ma ’ l- ikel
Ritonavir dosed as a pharmacokinetic enhancer
Ritonavir mogħti biex iżid l- effett farmakokinetiku
The following HIV-1 protease inhibitors have been approved for use with ritonavir as a pharmacokinetic enhancer at the noted doses.
L- impedituri protejaż ta ’ l- HIV- 1 li ġejjin, ġew approvati sabiex jittieħdu fid- dożi hawn indikati flimkien ma ’ ritonavir biex iżidu l- effett farmakokinetiku.
Adult use:
Użu mill- adulti:
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 ’ 100mg 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
Paediatric use:
Użu pedjatriku:
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- eta`.
For further dosage recommendations, refer to the product information of other Protease Inhibitors approved for co-administered with ritonavir.
Għal aktar rakkomandazzjonijiet ta ’ dożaġġ, irreferi għall- informazzjoni tal - prodott ta ’ Impedituri Protejaż oħra illi ġew approvati sabiex jingħataw flimkien ma ’ ritonavir.
2 Renal impairment:
Indeboliment renali:
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 specific protease inhibitor with which it is co-administered.
Peress illi ritonavir jiġi primarjament metabolizzat mill- fwied, ritonavir jista ’ jkun adattat, bħala dak illi jżid l- effett farmakokinetiku, ghal użu b’ attenzjoni minn pazjenti li jbatu
However, since the renal clearance of ritonavir is negligible, the decrease in the total body clearance is not expected in patients with renal impairment.
2 minn insuffiċjenza renali, u dan skond l- impeditur protejaż speċifiku li miegħu jkun qiegħed jingħata ritonavir.
For specific dosing information in patients with renal impairment, refer to the Summary of Product Characteristics (SPC) of the co-administered protease inhibitor.
Madanakollu, peress illi huwa biss ammont żgħir ħafna ta ’ ritonavir illi jiġi eliminat permezz tal- kliewi, m’ huwiex mistenni tnaqqis fl- eliminazzjoni totali mill- ġisem f’ pazjenti li jbatu minn indeboliment renali. Għal informazzjoni speċifika dwar dożaġġ għal persuni illi jbatu minn indeboliment renali, irreferi għas- Sommarju tal- Karatteristiċi tal- Prodott (SPC) ta ’ l- impeditur protejaż illi jkun ingħata ma ’ ritonavir.
Ritonavir should not be given as a pharmacokinetic enhancer to patients with decompensated liver disease.
Ritonavir m’ għandux jingħata biex iżid l- effett farmakokinetiku lil pazjenti li jbatu minn mard mhux kumpensat tal- fwied.
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 iżid l- effett farmakokinetiku u dana minħabba l- fatt illi jistgħu jiżdiedu l- livelli tal- PI illi jingħata ma ’ ritonavir.
Specific recommendations for use of ritonavir as a pharmacokinetic enhancer in patients with hepatic impairment are dependent on the protease inhibitor with which it is co-administered.
Rakkomandazzjonijiet speċifiċi għall- użu ta ’ ritonavir biex iżid l- effett farmakokinetiku f’ pazjenti li jbatu minn indeboliment tal- fwied jiddependu mill- impeditur protejaż li jingħata ma ’ ritonavir.
The SPC of the co-administered PI should be reviewed for specific dosing information in this patient population.
Fil- każ ta ’ dan it- tip ta ’ persuni, l- SPC tal- PI illi jingħata ma ’ ritonavir għandha tiġi analiżżata għal xi informazzjoni speċifika fuq id - dożaġġ.
Ritonavir dosed as an antiretroviral agent
Ritonavir dożat bħala aġent antiretrovirali
The recommended dosage of Norvir solution is 600 mg (7.5 ml) twice daily by mouth.
Id- doża rrakkomandata tas- soluzzjoni Norvir hija ta ’ 600 mg (7. 5 ml) darbtejn kuljum mill- ħalq.
Gradually increasing the dose of ritonavir when initiating therapy may help to improve tolerance.
Meta tinbeda il- kura, żieda gradwali fid- doża ta ’ ritonavir tista ’ tgħin biex iżżid it- tolleranza.
Treatment should be initiated at 300 mg (3.75 ml) twice daily for a period of three days and increased by 100 mg (1.25 ml) 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. 75 ml) darbtejn kuljum għal perijodu ta ’ tlett ijiem, u tiżdied b’ 100 mg (1. 25 ml) darbtejn kuljum sakemm wieħed jasal sa 600 mg darbtejn kuljum, u dana fuq perijodu ta ’ mhux aktar minn 14 - il ġurnata.
Patients should not remain on 300 mg twice daily for more than 3 days.
Il- pazjenti m’ għandhomx jibqgħu jieħdu doża ta ’ 300 mg darbtejn kuljum għal aktar minn 3 ijiem.
Paediatric use (2 years of age and above): the recommended dosage of Norvir solution 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.
Norvir għandu jibda jittieħed b’ doża ta ’ 250 mg/ m² u jiżdied kull jumejn jew tlieta b’ 50 mg/ m² darbtejn kuljum.
When possible, dose should be administered using a calibrated dosing syringe.
Meta jkun possibbli d- doża għandha tiġi mogħtija b’ siringa kkalibrata bid- doża.
Paediatric Dosage Guidelines
Linji Gwida għal Dożaġġ Pedjatriku
Body Surface area* (m²) 0.25 0.50 1.00 1.25 1.50
L- erja tas- Superfiċje tal- ġisem * (m²) 0. 25 0. 50 1. 00 1. 25 1. 50
Twice daily dose 250 mg/ m² 0.8 ml (62.5 mg) 1.6 ml (125 mg) 3.1 ml (250 mg) 3.9 ml (312.5 mg) 4.7 ml (375 mg)
Doża darbtejn kuljum 250 mg/ m² 0. 8 ml (62. 5 mg) 1. 6 ml (125 mg) 3. 1 ml (250 mg) 3. 9 ml (312. 5 mg) 4. 7 ml (375 mg)
Twice daily dose 300 mg/ m² 0.9 ml (75 mg) 1.9 ml (150 mg) 3.8 ml (300 mg) 4.7 ml (375 mg) 5.6 ml (450 mg)
Doża darbtejn kuljum 300 mg/ m² 0. 9 ml (75 mg) 1. 9 ml (150 mg) 3. 8 ml (300 mg) 4. 7 ml (375 mg) 5. 6 ml (450 mg)
Twice daily dose 350 mg/ m² 1.1 ml (87.5 mg) 2.2 ml (175 mg) 4.4 ml (350 mg) 5.5 ml (437.5 mg) 6.6 ml (525 mg)
Doża darbtejn kuljum 350 mg/ m² 1. 1 ml (87. 5 mg) 2. 2 ml (175 mg) 4. 4 ml (350 mg) 5. 5 ml (437. 5 mg) 6. 6 ml (525 mg)
* Body surface area can be calculated with the following equation BSA (m²) = √ (Height (cm) X Weight (kg) / 3600)
* L- erja tas- superfiċje tal- ġisem tista ’ tiġi kkalkulata bl- ekwazzjoni segwenti BSA (m²) = √( Tul (cm) X Piż (kg) / 3600)
Doses for intermediate body surface areas not included in the above table can be calculated using the following equations:
Dożi għall- erji tas- superfiċje tal- ġisem intermedjarji li m’ humiex inklużi fit- tabella t’ hawn fuq jistgħu jiġu kkalkulati billi wieħed juża l- ekwazzjonijiet segwenti:
To calculate the volume to be administered (in ml) the body surface area should be multiplied by a factor of:
Biex wieħed jikkalkula l- volum li għandu jingħata (f’ ml), l- erja tas- superfiċje tal- ġisem għandha tiġi mmultiplikata b’ fattur ta ’:
3.1 for a dose of 250 mg/ m²; 3.8 for one of 300 mg/ m²; and by 4.4 for 350 mg/ m².
3. 1 għal doża ta ’ 250 mg/ m²; 3. 8 għal doża ta ’ 300 mg/ m²; u b’ 4. 4 għal doża ta ’ 350 mg/ m².
Currently, there are no data specific to this patient population and therefore specific dosage recommendations cannot be made.
Preżentement, m’ hemm l- ebda informazzjoni speċifika relatata ma ’ dan it- tip ta ’ pazjent, u għalhekk ma jistgħux isiru rakkomandazzjonijiet għal dożaġġ speċifiku.
The renal clearance of ritonavir is negligible; therefore, a decrease in the total body clearance is not expected in patients with renal impairment.
Minħabba l -
Because ritonavir is highly protein bound it is unlikely that it will be significantly removed by haemodialysis or peritoneal dialysis.
3 fatt li ritonavir jeħel ħafna mal- proteini tad- demm, m’ huwiex probabbli li ammont kbir minnu jiġi mneħħi bil- ħemodijaliżi jew bid- dijaliżi peritonejali.
Ritonavir is principally metabolised and eliminated by the liver.
Ritonavir huwa prinċipalment metabolizzat u eliminat permezz tal- fwied.
Pharmacokinetic data indicate that no dose adjustment is necessary in patients with mild to moderate 3 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).
Ritonavir should not be given to patients with severe hepatic impairment (see section 4.3).
Ritonavir m’ għandux jingħata lil pazjenti li jbatu minn indeboliment tal- fwied sever (ara sezzjoni 4. 3).
Special Populations:
Populazzjonijiet Speċjali:
Pharmacokinetic data indicated that no dose adjustment is necessary for elderly patients (see section 5.2).
Informazzjoni farmakokinetika indikat li m’ hemm l- ebda bżonn ta ’ aġġustament fid- doża f’ każ ta ’ persuni anzjani (ara sezzjoni 5. 2).
The bitter taste of Norvir solution may be lessened if mixed with chocolate milk.
It- togħma morra tas- soluzzjoni Norvir tista ’ tiġi mnaqqsa jekk din titħallat mal- ħalib taċ- ċikkulata.
When ritonavir is used as a pharmacokinetic enhancer of other PIs, consult the Summary of Product Characteristics of the co-administered protease inhibitor for contraindications.
Meta ritonavir jintuża biex iżid l- effett farmakokinetiku ta ’ PIs oħra, għall- kontra- indikazzjonijiet ikkonsulta s- Sommarju tal- Karatteristiċi tal- Prodott ta ’ l- impeditur protejaż illi jingħata flimkien ma ’ ritonavir.
Ritonavir should not be given as a pharmacokinetic enhancer or as an antiretroviral agent to patients with decompensated liver disease.
Ritonavir m’ għandux jingħata biex iżid l- effett farmakokinetiku jew bħala aġent antiretrovirali lil pazjenti li għandhom mard mhux kompensat tal- fwied.
In vitro and in vivo studies have demonstrated that ritonavir is a potent inhibitor of CYP3A- and CYP2D6- mediated biotransformations.
Studji in vitro u in vivo urew li ritonavir huwa impeditur potenti ta ’ bijotrasformazzjonijiet medjati b’ CYP3A u CYP2D6.
The following medicines are contraindicated when used with ritonavir and unless otherwise noted, the contraindication is based on the potential for ritonavir to inhibit metabolism of the co-administered drug, resulting in increased exposure to the co-administered drug and risk of clinically significant adverse effects.
Il- mediċini segwenti huma kontro- indikati meta jintużaw ma ’ ritonavir, u jekk mhux indikat xort’ oħra, il- kontra- indikazzjoni hija bbażata fuq il- potenzjal li ritonavir għandu li jimpedi l- metaboliżmu tal- mediċina l- oħra li tkun qiegħda tingħata miegħu, u dan jirriżulta f’ esponiment akbar għall- mediċina illi tittieħed ma ’ ritonavir, u riskju ta ’ effetti avversi li huma klinikament sinifikanti.
The enzyme-modulating effect of ritonavir may be dose dependent.
L- effett li ritonavir għandu li jimmodula l- enzimi jista ’ jkun dipendenti fuq id- doża.
For some products, contraindications may be more relevant when ritonavir is used as an antiretroviral agent than when ritonavir is used as a pharmacokinetic enhancer (eg rifabutin and voriconazole):
Għal xi prodotti, il- kontro- indikazzjonijiet jistgħu jkunu aktar rilevanti meta ritonavir jintuża bħala aġent antiretrovirali milli meta ritonavir jintuża biex iżid l- effett farmakokinetiku (eż rifabutin u voriconazole):
Drug Class
Klassi ta ’ Mediċina
Drugs within Class
Mediċini f’ din il - Klassi
Rationale
Raġuni
Concomitant Drug Levels Increased α 1-Adrenoreceptor Antagonist
Żieda fil- livelli tal- Mediċini ji jingħataw b’ mod Konkomitanti Mediċini li jimblukkaw ir- riċettur α1 - Adrenoreceptor
Increased plasma concentrations of alfuzosin which may lead to severe hypotension (see section 4.5).
Żieda fil- konċentrazzjoni fil- plażma ta’ alfuzosin, li tista ’ tikkaġuna pressjoni baxxa ħafna (ara sezzjoni 4. 5).
Analgesics
Mediċini Analġesiċi
Increased plasma concentrations of normeperidine, piroxicam and propoxyphene.
Żieda fil- konċentrazzjoni fil- plażma ta ’ normeperidine, piroxicam u propoxyphene.
Thereby, increasing the risk of serious respiratory depression or haematologic abnormalities, or other serious adverse effects from these agents.
Għalhekk, dan iżid ir- riskju ta ’ dipressjoni respiratorja severa jew ta ’ abnormalitajiet ematoloġiċi, jew effetti avversi oħra kkaġunati minn dawn l- aġenti.
Antiarrthymics
Mediċini li jaħdmu fuq ir- rittmu tat- tħabbit tal - qalb
Amiodarone, bepridil, encainide, flecanide, propafenone, quinidine
Amiodarone, bepridil, encainide, flecanide, propafenone, quinidine
Increased plasma concentrations of amiodarone, bepridil, encainide, flecanide, propafenone, quinidine.
Żieda fil- konċentrazzjoni fil- plażma ta ’ amiodarone, bepridil, encainide, flecanide, propafenone, quinidine.
Thereby, increasing the risk of arrhythmias or other serious adverse effects from these agents.
Għalhekk, dan iżid ir - riskju ta ’ tħabbit irregolari tal- qalb jew effetti avversi oħra kkaġunati minn dawn l- aġenti.
Antibiotic
4 Mediċini Anti- bijotiċi
Fusidic Acid
Fusidic Acid
Increased plasma concentrations of fusidic acid and ritonavir.
Żieda fil- konċentrazzjoni fil- plażma tal- fusidic acid u ritonavir.
Antifungal
Mediċini li jaħdmu kontra il- fungi
Concomitant use of ritonavir (400 mg twice daily and more) and voriconazole is contraindicated due to a reduction in voriconazole plasma concentrations and possible loss of effect (see section 4.5)
L- użu ta’ ritonavir (400 mg darbtejn kuljum jew aktar) flimkien ma ’ voriconazole huwa kontro - indikat minħabba li jkun hemm tnaqqis fil - konċentrazzjoni fil- plażma ta ’ voriconazole, u għalhekk huwa possibbli illi jintilef l- effett (ara sezzjoni 4. 5)
Antihistamines
Mediċini li jaħdmu kontra l- istamina
Increased plasma concentrations of astemizole and terfenadine.
Żieda fil- konċentrazzjoni fil- plażma ta ’ astemizole u terfenadine.
Thereby, increasing the risk of serious arrhythmias from these agents.
Għalhekk, dan iżid ir - riskju ta ’ tħabbit irregolari tal- qalb serju kkaġunat minn dawn l- aġenti.
Antimycobacterial
Mediċini li jaħdmu kontra l - mycobacteria
Concomitant use of ritonavir dosed as an antiretroviral agent (600 mg twice daily) and rifabutin due to an increase of rifabutin serum concentrations and risk of adverse events including uveitis (see section 4.4).
L- użu ta ’ ritonavir mogħti f’ doża bħala aġent antiretrovirali (600 mg darbtejn kuljum) flimkien ma ’ rifabutin minħabba żieda fil- konċentrazzjoni fis- serum ta ’ rifabutin u riskju ta ’ effetti avversi, li jinkludu l- inflammazzjoni ta ’ l- uvea (ara sezzjoni 4. 4).
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
Antipsychotics/ Neuroleptics
Mediċini Anti - Psikotiċi / Newrolettiċi
Increased plasma concentrations of clozapine and pimozide.
Żieda fil- konċentrazzjoni fil- plażma ta ’ clozapine u pimozide.
Thereby, increasing the risk of serious haematologic abnormalities, or other serious adverse effects from these agents.
Għalhekk, dan iżid ir- riskju ta ’ abnormalitajiet ematoloġiċi serji, jew effetti avversi serji oħra kkaġunati minn dawn l- aġenti.
Ergot Derivatives
Derivattivi ta ’ l - Ergotina
Increased plasma concentrations of ergot derivatives leading to acute ergot toxicity, including vasospasm and ischaemia.
Żieda fil- konċentrazzjoni fil- plażma ta ’ derivattivi ta ’ l- ergotina li twassal għal tossiċità akuta ta ’ l- ergotina, li tinkludi għeluq tal- vini u iskemija.
GI motility agent
Mediċini li jaħdmu fuq il- passaġġ ta ’ fluwidi fis- sistema gastrointestinali
Increased plasma concentrations of cisapride.
Żieda fil- konċentrazzjoni fil- plażma ta ’ cisapride.
Thereby, increasing the risk of serious arrhythmias from this agent.
Għalhekk, dan iżid ir- riskju ta ’ tħabbit irregolari tal- qalb serju kkaġunata minn dan l- aġent.
HMG Co-A Reductase Inhibitor
Impeditur Reductase HMG Co- A
Increased plasma concentrations of lovastatin and simvastatin; thereby, increasing the risk of myopathy including rhabdomyolysis (see section 4.5).
Żieda fil- konċentrazzjoni fil- plażma ta ’ lovastatin u simvastatin; għalhekk, dan iżid ir- riskju ta ’ mijopatija, li jinkludi rabdomijoli (ara sezzjoni 4. 5).
Sedatives/ hypnotics
Mediċini Sedattivi/ Ipnotiċi
Clorazepate, diazepam, estazolam, flurazepam, oral midazolam and triazolam
Clorazepate, diazepam, estazolam, flurazepam, midazolam mittieħed mill- ħalq u triazolam
Increased plasma concentrations of clorazepate, diazepam, estazolam, flurazepam, oral midazolam and triazolam.
Żieda fil- konċentrazzjoni fil- plażma ta ’ clorazepate, diazepam, estazolam, flurazepam, midazolam mittieħed mill- ħalq u triazolam.
Thereby, increasing the risk of extreme sedation and respiratory depression from these agents.
Għalhekk, dan iżid ir- riskju ta ’ sedazzjoni estrema u dipressjoni respiratorja kkaġunati minn dawn l- aġenti.
(For caution on parenterally administered midazolam, see section 4.5).
(Sabiex tiġi eżerċitata kawtela meta midazolam jiġi mgħoti parenteralment, ara sezzjoni 4. 5).
Ritonavir Drug Level Decreased Herbal Preparation
Tnaqqis fil- livell tal- mediċina ritonavir
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).
5 Preparazzjonijiet tal - Ħxejjex mediċinali
5 4.4 Special warnings and precautions for use
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).
Ritonavir is not a cure for HIV-1 infection or AIDS.
Ritonavir m’ huwiex fejqan għall- infezzjoni ta ’ l- HIV- 1 jew għall- AIDS.
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.
Patients should be advised that current antiretroviral therapy has not been proven to prevent the risk of transmission of HIV to others through blood or sexual contact.
Il- pazjenti għandhom ikunu infurmati li għad m’ hawnx provi li l- kura antiretrovirali li teżisti sal- lum, tippreveni r- riskju tat- tixrid ta ’ l- HIV minn persuna għal oħra permezz ta ’ kuntatti tad- demm jew kuntatti sesswali.
Appropriate precautions should continue to be used.
Prekawzjonijiet xierqa għandhom jibqgħu jittieħdu.
When ritonavir is used as a pharmacokinetic enhancer with other PIs, full details on the warnings and precautions relevant to that particular PI should be considered, therefore the Summary of Product Characteristics for the particular PI must be consulted.
Meta ritonavir jintuża biex iżid l- effett farmakokinetiku ma ’ PIs oħra, għandhom jiġu kkonsidrati d - dettalji kollha tat- twissijiet u tal- prekawzjonijiet relevanti għal dak il- PI partikolari, u għalhekk is - Sommarju tal- Karrateritiċi tal- Prodott ta’ dak il- PI partikolari għandu jiġi kkonsultat.
Ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer
Ritonavir dożat bħala aġent antiretrovirali jew biex iżid l- effett farmakokinetiku
Patients with chronic diarrhoea or malabsorption:
Pazjenti illi jbatu minn dijarea kronika jew min- nuqqas ta ’ assorbiment:
Extra monitoring is recommended when diarrhoea occurs.
F’ każ illi tiġi kkawżata d - dijarea, ikun hemm bżonn ta ’ aktar osservazzjoni mis- soltu.
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 ’ taffetwa 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 il- funzjoni renali.
It is advisable to monitor renal function in patients with renal function impairment.
F’ każ ta ’ pazjenti li jbatu minn indeboliment tal- funzjoni renali, huwa aħjar illi ssir osservazzjoni fuq il- funzjoni renali.
Haemophilia: there have been reports of increased bleeding, including spontaneous skin haematomas and haemarthroses, in haemophiliac patients type A and B treated with protease inhibitors.
Kien hemm rapporti ta ’ żieda fit- telf ta ’ demm, inkluz ematomi tal- ġilda spontanja u emartrożi, f’ każ ta ’ pazjenti li jbatu minn emofilja tat- tip A u B li rċevew kura b’ impedituri protejaż.
In some patients additional factor VIII was given.
F’ ċerti pazjenti ingħata l- fattur VIII addizzjonalment.
In more than a half of the reported cases, treatment with protease inhibitors was continued or reintroduced if treatment had been discontinued.
F’ aktar min- nofs il- każi li ġew irrapportati, il - kura bl- impedituri protejaż tkompliet, jew reġgħet inbdiet mill- ġdid fejn din kienet ġiet imwaqqfa.
A causal relationship has been evoked, although the mechanism of action has not been elucidated.
Relazzjoni każwali ġiet imsejħa, għalkemm il- mekkaniżmu ta ’ azzjoni ma ġietx iċċarata.
Haemophiliac patients should therefore be made aware of the possibility of increased bleeding.
Pażjenti emofilijaċi għandhom għalhekk jiġu infurmati bil- possibilità ta ’ żieda fit- telf ta ’ demm.
Diabetes mellitus and hyperglycaemia:
Dijabete mellitus u ipergliċemija:
New onset diabetes mellitus, hyperglycaemia or exacerbation of existing diabetes mellitus has been reported in patients receiving protease inhibitors.
Bidu ġdid ta’ dijabete mellitus, ipergliċemija jew tħarrix ta ’ dijabete mellitus eżistenti ġew irrapportati f’ pazjenti li qegħdin jirċievu impedituri protejaż.
In some of these the hyperglycaemia was severe and in some cases also associated with ketoacidosis.
F’ uħud minnhom, l- ipergliċemija kienet severa u f’ xi każi anki assoċjata mal- ketoaċidożi.
Many patients had confounding medical conditions, some of which required therapy with agents that have been associated with the development of diabetes mellitus or hyperglycaemia.
Ħafna mill- pazjenti kellhom kondizzjonijiet mediċi oħra, u xi wħud minn dawn il- kondizzjonijiet kellhom bżonn kura b’ aġenti li ġew assoċjati ma ’ l- iżvilupp tad- dijabete mellitus jew ta ’ l- ipergliċemija.
Combination antiretroviral therapy has been associated with redistribution of body fat (lipodystrophy) in HIV patients.
F’ pazjenti li jbatu bl- HIV, it- terapija antiretrovirali kombinata ġiet assoċjata mar - ridistribuzzjoni tax- xaħam tal- ġisem (lipodistrofija).
The long-term consequences of these events are currently unknown.
Il- konsegwenzi fit- tul ta ’ dawn il- fatti għadhom m’ humiex magħrufa.
Knowledge about the mechanism is incomplete.
It- tagħrif dwar il- mekkaniżmu m’ huwiex komplut.
A connection between visceral lipomatosis and PIs and lipoatrophy and nucleoside reverse transcriptase inhibitors (NRTIs) has been hypothesised.
Ġiet ipotiżżata konnessjoni bejn lipomatożi vixxerali u PIs u lipoatrofija u impedituri ‘ nucleoside reverse transcriptase ’ (NRTIs).
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 akbar ta ’ lipodistrofija ġie assoċjat ma ’ fatturi individwali, bħal età akbar, u fatturi relatati mal - mediċina, bħal kura antiretrovirali aktar fit- tul u disturbi metaboliċi assoċjati.
Clinical examination should include evaluation for physical signs of fat redistribution.
Eżami kliniku għandu jinkludi evalwazzjoni għal sinjali fiżiċi ta ’ ridistribuzzjoni tax- xaħam fil- ġisem.
Consideration should be given to measurement of fasting serum lipids and blood glucose.
Għandha tingħata konsiderazzjoni għat- tkejjil tal- lipidi tas- serum fis- sawm u glukows fid- demm fis- sawm.
Lipid disorders should be managed as clinically appropriate (see section 4.8).
Disturbi fil - lipidi għandhom jiġu trattati kif klinikament xieraq (ara sezzjoni 4. 8).
Pancreatitis should be considered if clinical symptoms (nausea, vomiting, abdominal pain) or abnormalities in laboratory values (such as increased serum lipase or amylase values) suggestive of pancreatitis should occur.
Pazjenti li juru dawn is- sinjali jew sintomi
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).
6 għandhom ikunu evalwati, u l- kura b’ Norvir għandha titwaqqaf f’ każ illi jkun hemm dijanjosi ta ’ pankreatite (ara sezzjoni 4. 8).
Immune Reactivation Syndrome: in HIV-infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymtomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms.
F’ pazjenti infettati bl- HIV li meta tinbeda t- terapija antiretrovirali kombinata (CART) ikollhom immunità defiċjenti ħafna, tista ’ tirriżulta reazzjoni għall - patoġeni li ma jikkaġunawx sintomi jew li huma opportunisti residwali, u tikkaġuna kundizzjonijiet kliniċi serji, jew tiggrava s- sintomi.
Typically, such reactions have been observed within the first few weeks or months of 6 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 kkawżata minn cytomegalovirus, infezzjonijiet generalised u/ jew infezzjonijiet fokali ikkawżati minn mycobacteria, u pnewmonja kkawżata minn Pneumocystis carinii.
Any inflammatory symptoms should be evaluated and treatment instituted when necessary.
Kull sintomu ta ’ infjammazzjoni għandu jiġi evalwat, u fejn ikun hemm bżonn tinbeda l- kura.
Liver disease:
Mard tal- Fwied:
Ritonavir should not be given to patients with decompensated liver disease.
Ritonavir m’ għandux jingħata lil pazjenti li jbatu minn mard mhux kompensat tal - fwied.
For patients with stable severe hepatic impairment (Child Pugh Grade C) without decompensation see section 4.2.
Għal pazjenti li jbatu minn indeboliment sever mhux kompensat tal- fwied (Child Pugh Grad C) ara sezzjoni 4. 2.
Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse events.
Pazjenti li jbatu minn epatite B jew C u li jkunu qeghdin jieħdu terapija antiretrovirali kombinata għandhom riskju akbar ta ’ konsegwenzi epatiċi avversi li huma severi u potenzjalment fatali.
In case of concomitant antiviral therapy for hepatitis B or C, please refer to the relevant product information for these medicinal products.
F’ kaz ta ’ terapija konkomitanti antiretrovirali għall- epatite B jew C, jekk jogħġbok irreferi għall- informazzjoni dwar il- prodott relatat ma ’ dawn il- prodotti mediċinali.
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 għandhom kundizzjoni ta ’ diżfunzjoni fil- fwied li kienet teżisti qabel, inkluża l- epatite attiva kronika, għandhom frekwenza akbar ta ’ abnormalitajiet fil- funzjonijiet tal- fwied waqt it- terapija antiretrovirali kombinata u għandhom jiġu monitorjati skond il- prattika normali.
If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered.
Jekk f’ dawn il - pazjenti jkun hemm prova li l- mard fil- fwied mar għall- agħar, l- interruzzjoni jew twaqqif tal- kura għandu jiġi kkunsidrat.
Renal disease:
Mard Renali:
Since the renal clearance of ritonavir is negligible, the decrease in the total body clearance is not expected in patients with renal impairment.
Peress illi huwa biss ammont żgħir ħafna ta ’ ritonavir li jiġi eliminat permezz tal- kliewi, m’ huwiex mistenni tnaqqis fl- eliminazzjoni totali mill- ġisem, f’ pazjenti illi jbatu minn indeboliment renali.
For specific dosing information in patients with renal impairment, refer to the Summary of Product Characteristics (SPC) of the co-administered protease inhibitor.
Għal informazzjoni speċifika dwar dożaġġ għal persuni li jbatu minn indeboliment renali, irreferi għas- Sommarju tal- Karatteristiċi tal- Prodott (SPC) ta ’ l- impeditur protejaż illi jkun ingħata ma ’ ritonavir.
See also section 4.2.
Ara ukoll sezzjoni 4. 2.
Ritonavir oral solution contains castor oil polyoxyl which may cause stomach upset and diarrhoea.
Is- soluzzjoni orali ritonavir fiha żejt ir- riġnu polyoxyl li jista ’ jikkaġuna taqlib fl- istonku u dijarea.
Ritonavir oral solution also contains the azo-colouring agent sunset yellow (E110) which may cause allergic reactions.
Is - soluzzjoni orali ritonavir fiha ukoll l- aġent illi jagħti l- kulur isfar lewn inżul ix- xemx (E110) li jista ’ jikkaġuna reazzjonijiet allerġiċi.
Ritonavir oral solution contains alcohol (43% v/ v), ie up to 258 mg per maximum dose of 600 mg, equivalent to 65 ml beer, 27 ml wine per dose.
Is- soluzzjoni orali ritonavir fiha l- alkoħol (43% v/ v), jiġifieri sa 258 mg kull doża massima ta ’ 600 mg, ekwivalenti għal 65 ml birra, 27 ml inbid kull doża.
Each 100 mg dose contains up to 43 mg alcohol and each 200 mg dose contains 86 mg alcohol.
Kull doża ta ’ 100 mg fiha sa 43 mg alkoħol u kull doża ta ’ 200 mg fiha 86 mg alkoħol.
Therefore concomitant administration of Norvir with disulfiram or medicines with disulfiram-like reactions (eg metronidazole) should be avoided.
Għalhekk l- għoti ta ’ Norvir flimkien ma ’ disulfiram jew mediċini li għandhom reazzjonijiet illi huma simili għal dawk ta ’ disulfiram (eż metronidazole) għandu jiġi evitat.
Also to be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease or epilepsy.
Għandhom jiġu ukoll meħuda in konsiderazzjoni nisa tqal jew nisa li jkunu jreddgħu, tfal u gruppi illi għandhom riskju għoli, bħal pazjenti li jbatu minn mard tal- fwied jew epilessija.
Osteonecrosis:
Nekrosi ta ’ l- għadam:
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 tal- 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).
Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.
Il- pazjenti għandhom jiġu infurmati biex huma jitolbu parir mediku jekk iħossu weġgħat fil - ġogi u uġigħ, ebusija tal- ġogi jew difikultà fil- movimenti.
PR interval prolongation: ritonavir has been shown to cause modest asymptomatic prolongation of the PR interval in some healthy adult subjects.
Titwil ta ’ l- intervall PR: ġie ppruvat li, f’ xi suġġetti adulti f’ saħħithom, ritonavir jikkawża titwil mhux kbir li ma jurix sintomi ta ’ l- intervall PR.
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 li jirċievu ritonavir ġew irrapportati każi rari ta ’ imblukkar atrioventrikulari tat- tieni jew tat- tielet grad f’ pazjenti b’ mard eżistenti fl- istruttura tal- qalb u li kellhom abnormalitajiet eżistenti fis- sistema tat- trasmissjoni ta ’ l- impulsi fin- nervituri jew f’ pazjenti li kienu qegħdin jingħataw mediċini magħrufa li jtawlu l- intervall PR (bħal verapamil jew atazanavir).
Norvir should be used with caution in such patients (see section 5.1).
F’ pazjenti bħal dawn, Norvir għandu jintuża b’ kawtela (ara sezzjoni 5. 1).
Interactions with other medicinal products
7 Effetti fuq prodotti mediċinali oħra
The following Warnings and Precautions should be considered when ritonavir is used as an 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 at the 100 mg and 200 mg level it cannot be assumed that the following warnings and precautions will also apply.
Meta ritonavir jintuża biex iżid l- effett farmakokinetiku fil- livell ta ’ 100 mg u 200 mg, wieħed ma jistax jassumi li t- twissijiet u l- prekawzjonijiet segwenti se japplikaw ukoll.
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 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.
7 PDE5 inhibitors:
Impedituri PDE5:
Particular caution should be used when prescribing sildenafil, tadalafil or vardenafil in patients receiving ritonavir.
Għandha tingħata attenzjoni speċjali meta jingħataw sildenafil, tadalafil jew vardenafil lil pazjenti li jkunu qegħdin jirċievu ritonavir.
Co-administration of ritonavir with these medicinal products is expected to substantially increase their concentrations and may result in associated adverse events such as hypotension and prolonged erection (see section 4.5).
L- għoti ta ’ ritonavir flimkien ma ’ dawn il - prodotti mediċinali huwa mistenni li jżid il- konċentrazzjoni tagħhom b’ mod sostanzjali, u dan jista ’ jirriżulta f’ effetti avversi assoċjati magħhom, bħal pressjoni baxxa ħafna u erezzjoni fit- tul tal- parti ġenitali maskili (ara sezzjoni 4. 5).
HMG-CoA reductase inhibitors:
Impedituri HMG- CoA reductase:
The HMG-CoA reductase inhibitors simvastatin and lovastatin are highly dependent on CYP3A for metabolism, thus concomitant use of ritonavir with simvastatin or lovastatin is not recommended due to an increased risk of myopathy including rhabdomyolysis.
L- impedituri HMG- CoA reductase simvastatin u lovastatin jiddependu ħafna fuq CYP3A għall- metaboliżmu, għalhekk l- użu ta ’ ritonavir flimkien ma ’ simvastatin jew lovastatin m’ huwiex irrakkomandat minħabba illi hemm riskju akbar ta ’ mijopatija li tinkludi r- rabdomijoliżi.
Caution must also be exercised and reduced doses should be considered if ritonavir is used concurrently with atorvastatin, which is metabolised to a lesser extent by CYP3A.
Għandha titieħed ukoll l- attenzjoni u għandhom jiġu kkunsidrati dożi mnaqqsa jekk ritonavir jiġi użat flimkien ma ’ atorvastatin, li jiġi metabolizzat kemmxejn inqas minn CYP3A.
While rosuvastatin elimination is not dependent on CYP3A, an elevation of rosuvastatin exposure has been reported with ritonavir co-administration.
Filwaqt li l- eliminazzjoni ta ’ rosuvastatin ma tiddependix minn CYP3A, kien irrapurtat li kien hemm żieda fl- esponiment ta ’ rosuvastatin meta jigi amministrat flimkien ma ritonavir.
The mechanism of this interaction is not clear, but may be the result of transporter inhibition.
Il - mekkaniżmu ta ’ din l- interazzjoni m’ huwiex ċar, iżda jista jkun riżultat ta ’ inibizzjoni tat- trasportatur.
When used with ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent, the lowest doses of atorvastatin or rosuvastatin should be administered.
Għandhom jintużaw l- aktar dożi baxxi ta ’ atorvastatin jew rosuvastatin meta jiġu użati ma ritonavir biex iżidu l- effett farmakokinetiku jew bħala agenti antiretrovirali.
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.
If treatment with an HMG-CoA reductase inhibitor is indicated, pravastatin or fluvastatin is recommended (see section 4.5).
Jekk tkun indikata kura b’ impeditur HMG- CoA reductase, pravastatin jew fluvastatin huma rrakkomandati (ara sezzjoni 4. 5).
Particular caution should be used when prescribing ritonavir in patients taking digoxin since co-administration of ritonavir with digoxin is expected to increase digoxin levels.
Attenzjoni speċjali għandha tingħata meta ritonavir jingħata lil persuni li jieħdu digoxin, għaliex it- teħid flimkien ta ’ ritonavir ma ’ digoxin huwa mistenni li jżid il- livelli ta ’ digoxin.
The increased digoxin levels may lessen over time (see section 4.5).
Il- livelli ogħla ta ’ digoxin jistgħu jonqsu maż- żmien (ara sezzjoni 4. 5).
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 patient 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.
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.
Digoxin levels should be monitored more intensively than usual during this period, with dose adjustments made, as necessary, based on clinical, electrocardiographic and digoxin level findings.
F’ dan il- perijodu, il- livelli ta ’ digoxin għandhom jiġu monitorjati b’ aktar attenzjoni mis- soltu, b’ aġġustamenti fid- doża, skond il- bżonn, ibbażati fuq il - livelli kliniċi, elettrokardjografiċi u ta ’ digoxin illi jinstabu.
Ethinyl estradiol:
Ethinyl estradiol:
Barrier or other non-hormonal methods of contraception should be considered when administering ritonavir at therapeutic or low doses as ritonavir is likely to reduce the effect and change the uterine bleeding profile when co-administered with estradiol-containing contraceptives.
Meta ritonavir jingħata f’ dożi terapewtiċi jew baxxi, għandhom jiġu kkunsidrati metodi ta ’ barriera jew metodi oħra ta ’ kontraċettivi li ma fihomx ormoni, u dan peress illi hemm probabilità li ritonavir inaqqas l- effett u jbiddel il- profil ta ’ telf ta ’ demm mill- ġuf meta huwa jingħata ma ’ kontraċettivi li jkun fihom estradiol.
Glucocorticoids:
Glucocorticoids:
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).
Trazodone:
8 Trazodone:
Particular caution should be used when prescribing ritonavir in patients using trazodone.
Attenzjoni speċjali għandħa 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 iżid 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).
Ritonavir dosed as a pharmacokinetic enhancer
Ritonavir dożat biex iżid l- effett farmakokinetiku
The interaction profiles of HIV-protease inhibitors, co-administered with low dose ritonavir, are dependant on the specific co-administered protease inhibitor.
Il- profili ta’ interazzjonijiet ta ’ impedituri protejaż ta ’ l- HIV, meta dawn jiġu mogħtija ma ’ doża żgħira ta ’ ritonavir, jiddependu fuq l- impeditur protejaż speċifiku li jkun ingħata ma ’ ritonavir.
For a description of the mechanisms and potential mechanisms contributing to the interaction profile of the PIs, see section 4.5.
Għal deskrizzjoni tal- mekkaniżmi u mekkaniżmi potenzjali li jikkontribwixxu għall- profil ta ’ interazzjonijiet tal- PIs, ara sezzjoni 4. 5.
Please also review the Summary of Product Characteristics for the particular boosted PI.
Jekk jogħġbok ara ukoll is- Sommarju tal- Karatteristiċi tal - Prodott għall- PI partikolari li qiegħed jiġi miżjud l- effett tiegħu.
Doses of ritonavir higher than 100 mg twice daily should not be used.
M’ għandhomx jintużaw dożi ta ’ ritonavir ta ’ aktar minn 100 mg darbtejn kuljum.
Higher doses of ritonavir have been shown to be associated with an increased incidence of adverse events.
Dożi akbar ta ’ ritonavir urew li huma relatati ma ’ inċidenza akbar ta ’ reazzjonijiet avversi.
Saquinavir/ ritonavir should not be given together with rifampicin, due to the risk of severe hepatotoxicity (presenting as increased hepatic transaminases) if the three medicines are given together (see section 4.5).
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.
Tipranavir: co-administered with 200 mg of ritonavir has been associated with reports of clinical hepatitis and hepatic decompensation including some fatalities.
Tipranavir: meta mogħti ma ’ 200 mg ta ’ ritonavir, ġie assoċjat ma ’ rapporti ta ’ epatite klinika u dikompensazzjoni epatika, inkluż xi fatalitajiet.
Extra vigilance is warranted in patients with chronic hepatitis B or hepatitis C co-infection, as these patients have an increased risk of hepatotoxicity.
Attenzjoni speċjali għandha tingħata lil pazjenti li jbatu ukoll mill- infezzjoni kronika ta ’ l- epatite B jew epatite C, minħabba li dawn il- pazjenti għandhom riskju akbar ta ’ ħsara fil- fwied.
Doses of ritonavir lower than 200 mg twice daily should not be used as they might alter the efficacy profile of the combination.
Dożi ta ’ ritonavir ta ’ inqas minn 200 mg darbtejn kuljum m’ għandhomx jintużaw għaliex dawn jistgħu jbiddlu il- profil ta ’ l- effikaċja tat- taħlita.
Co-administration of fosamprenavir with ritonavir in doses greater than 100 mg twice daily has not been clinically evaluated.
L- għoti flimkien ta ’ fosamprenavir u ritonavir f’ dożi akbar minn 100 mg darba kuljum ma ’ ġiex evalwat klinikament.
The use of higher ritonavir doses might alter the safety profile of the combination and therefore is not recommended.
L- użu ta ’ dożi aktar għoljin ta ’ ritonavir jista ’ jbiddel il- profil tas- sigurtà tat- taħlita, u għalhekk m’ huwiex rrakkomandat.
Co-administration of atazanavir with ritonavir in doses greater than 100 mg once daily has not been clinically evaluated.
L- għoti ta ’ atazanavir flimkien ma ’ ritonavir f’ dożi akbar minn 100 mg darba kuljum ma ġiex klinikament evalwat.
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 - sigurtà ta ’ atazanavir (effetti kardijaċi, livelli għoljin ta ’ bilirubin fid- demm), u għalhekk m’ huwiex rrakkomandat.
Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent
Ritonavir dożat biex iżid l- effett farmakokinetiku jew bħala agent antiretrovirali
Ritonavir has a high affinity for several cytochrome P450 (CYP) isoforms and may inhibit oxidation with the following ranked order:
Ritonavir għandu affinità għolja għal diversi isoformi ta’ ċitokromi P450 (CYP) u jista ’ jimpedixxi l - ossidazzjoni skond din l- ordni li ġejja:
Co-administration of Norvir and medicinal products primarily metabolised by CYP3A may result in increased plasma concentrations of the other medicinal product, which could increase or prolong its therapeutic and adverse effects.
L- għoti ta ’ Norvir flimkien ma ’ prodotti mediċinali li huma primarjament metabolizzati minn CYP3A jista ’ jirriżulta f’ żieda fil - konċentrazzjoni fil- plażma tal- prodott mediċinali l- ieħor, u dan jista ’ jżid jew itawwal l- effetti terapewtiċi u avversi tiegħu.
For select medicinal products (eg alprazolam) the inhibitory effects of ritonavir on CYP3A4 may decrease over time.
Għal xi prodotti mediċinali partikolari (eż alprazolam) l- effetti ta ’ impediment ta ’ ritonavir fuq CYP3A4 jistgħu jonqsu maż- żmien.
Ritonavir also has a high affinity for P-glycoprotein and may inhibit this transporter.
Ritonavir għandu ukoll affinità għolja għal P- glycoprotein u jista ’ jimpedixxi dan it- trasportatur.