qanastek/EMEA-V3 huggingface dataset:
Therefore, medicinal products that either share this metabolic pathway or modify CYP3A4 and/ or P-gp activity (see "Other potential interactions") may modify the pharmacokinetics of saquinavir.
Għalhekk, prodotti mediċinali li jew jaqsmu l- istess passaġġ metaboliku jew jimmodifikaw lil CYP3A4 u/ jew l- attività ta ’ P- gpn (ara “ Interazzjonijiet potenzjali oħra ”) jistgħu jimmodifikaw il- farmakokinetika ta ’ saquinavir.
Similarly, saquinavir might also modify the pharmacokinetics of other medicinal products that are substrates for CYP3A4 or P-gp.
B’ mod simili, saquinavir jista ’ wkoll jimmodifika il- farmakokinetika ta ’ prodotti mediċinali oħra li huma sottostrati ta ’ CYP3A4 jew P- gp.
Ritonavir can affect the pharmacokinetics of other medicinal products because it is a potent inhibitor of CYP3A4 and P-gp.
Ritonavir jista ’ jaffettwa l- farmakokinetika ta ’ prodotti mediċinali oħra minħabba li huwa inibitur qawwi ta ’ CYP3A4 u P- gp.
Therefore, when saquinavir is co-administered with ritonavir, consideration should be given to the potential effects of ritonavir on other medicinal products (see the Summary of Product Characteristics for Norvir).
Għalhekk, meta saquinavir jingħata flimkien ma ’ ritonavir, iridu jiġu kkunsidrati l- effetti potenzjali ta ’ ritonavir fuq prodotti mediċinali oħra (ara s- Sommarju ta ’ Karatteristiċi tal- Prodott għal Norvir).
Interactions and dose recommendations with other medicinal products
Interazzjonijiet u rakkomandazzjonijiet tad- doża ma ’ prodotti mediċinali oħra
Medicinal product by therapeutic area (dose of Invirase used in study) Antiretroviral agents
Prodott mediċinali skond Interazzjoni is- settur terapewtiku (doża ta ’ Invirase użata fl- istudju) Sustanzi antiretrovirali Inibituri ta ’ nucleoside reverse transcriptase (NRTIs) - Zalcitabine u/ jew - Ma ntemmewx studji dwar l - Zidovudine interazzjoni farmakokinetika.
The pharmacokinetics of ritonavir remained unchanged.
(saquinavir/ ritonavir) Interazzjoni ma ’ zalcitabine mhux probabbli minħabba rotot differenti ta ’ metaboliżmu u tneħħija. Għal zidovudine (200 mg kull 8 sigħat), kien irrapportat tnaqqis ta ’ 25% fl - AUC ta ’ zidovudine meta kkombinat ma ’ ritonavir (300 mg kull 6 sigħat).
Zalcitabine and/ or Zidovudine (unboosted saquinavir)
Il- farmakokinetika ta ’ ritonavir baqgħet ma nbidlitx - Saquinavir ↔ - Zalcitabine u/ jew Zidovudine Zalcitabine ↔ (saquinavir mhux Zidovudine ↔ imsaħħaħ) Saquinavir AUC ↓ 30%
No dose adjustment required.
Rakkomandazzjonijiet li jikkonċernaw l- għoti fl- istess waqt - M’ hemmx bżonn ta ’ aġġustament fid- doża.
Saquinavir AUC ↓ 1% Saquinavir Cmax ↓ 7% Saquinavir Cmin ↔
Didanosine doża waħda ta ’ 400 mg Saquinavir Cmax ↓ 25% (saquinavir/ ritonavir Saquinavir Cmin ↔ 1600/ 100 mg qd) Saquinavir AUC ↓ 1%
No dose adjustment required.
M’ hemmx bżonn ta ’ aġġustament fid- doża.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) -
Tenofovir disoproxil fumarate 300 mg qd Saquinavir Cmax ↓ 7% (saquinavir/ ritonavir Saquinavir Cmin ↔ 1000/ 100 mg bid) Inibituri ta ’ non- nucleoside reverse transcriptase (NNRTIs) - Delavirdine - L- interazzjoni ma ’ Invirase/ ritonavir (saquinavir/ ritonavir) ma ’ ġietx studjata. - Saquinavir AUC ↑ 348%. - Delavirdine Hemm tagħrif limtat dwar is- sigurtà (saquinavir mhux u m’ hemmx tagħrif disponibbli dwar imsaħħaħ) l- effikaċja mill- użu ta ’ din it- taħlita.
In a small, preliminary study, hepatocellular enzyme elevations occurred in 13% of subjects during the first several weeks of the delavirdine and saquinavir combination (6% Grade 3 or 4).
Saquinavir ↔
Hepatocellular changes should be monitored frequently if this combination is prescribed.
M’ hemmx bżonn ta ’ aġġustament fid- doża. - Bidliet epatoċellulari għandhom jiġu sorveljati ta ’ spiss jekk din it - taħlita tiġi preskritta.
Efavirenz 600 mg qd (saquinavir/ ritonavir 1600/ 200 mg qd, or saquinavir/ ritonavir 1000/ 100 mg bid, or saquinavir/ ritonavir 1200/ 100 mg qd)
Efavirenz 600 mg qd (saquinavir/ ritonavir Efavirenz ↔ 1600/ 200 mg qd, jew saquinavir/ ritonavir 1000/ 100 mg bid, jew saquinavir/ ritonavir 1200/ 100 mg qd) - Nevirapine - L- interazzjoni ma ’ (saquinavir/ ritonavir) Invirase/ ritonavir ma ’ ġietx studjata.
- Saquinavir AUC ↓ 24% Nevirapine AUC ↔
- Saquinavir AUC ↓ 24% - Nevirapine (saquinavir mhux Nevirapine AUC ↔ imsaħħaħ) Indiċi: ↓ tnaqqis, ↑ żjieda, ↔ mhux mibdul, ↑↑ żjieda sostanzjali
- No dose adjustment required.
- M’ hemmx bżonn ta ’ aġġustament fid- doża.
6 Medicinal product by therapeutic area (dose of Invirase used in study)
7 Prodott mediċinali skond is- settur terapewtiku (doża ta ’ Invirase użata fl- istudju)
Recommendations concerning co- administration
Rakkomandazzjonijiet li jikkonċernaw l- għoti fl- istess waqt
HIV protease inhibitors (PIs) Atazanavir 300 mg qd (saquinavir/ ritonavir 1600/ 100 mg qd)
Saquinavir AUC ↓ 15% Fosamprenavir
Saquinavir AUC ↑ 60% Saquinavir Cmax ↑ 42% Ritonavir AUC ↑ 41% Ritonavir Cmax ↑ 34% Atazanavir ↔ No clinical data available for the combination of saquinavir/ ritonavir 1000/ 100 mg bid and atazanavir.
M’ hemmx bżonn ta ’ aġġustament
Fosamprenavir 700 mg bid (saquinavir/ ritonavir 1000/ 100 mg bid)
700 mg bid (saquinavir/ ritonavir 1000/ 100 mg bid)
Saquinavir AUC ↓ 15% Saquinavir Cmax ↓ 9% Saquinavir Cmin ↓ 24% (remained above the target threshold for effective therapy.)
Saquinavir Cmax ↓ 9% Saquinavir Cmin ↓ 24% (baqgħet il - fuq mil- livell immirat għal terapija effettiva.)
No dose adjustment required for Invirase/ ritonavir.
fid- doża għal Invirase/ ritonavir.
- Indinavir (saquinavir/ ritonavir) - Indinavir 800 mg tid (saquinavir 600-1200 mg single dose)
- Indinavir (saquinavir/ ritonavir) - Indinavir 800 mg tid (saquinavir 600- 1200 mg
- Low dose ritonavir increases the concentration of indinavir. - Saquinavir AUC ↑ 4.6-7.2 fold Indinavir ↔ No safety and efficacy data available for this combination.
- Doża baxxa ta ’ ritonavir iżżid il - konċentrazzjoni ta ’ indinavir. - Saquinavir AUC ↑ 4. 6- 7. 2 darbiet Indinavir ↔
Appropriate doses of combination not established.
Żjidiet fil- konċentrazzjonijiet ta ’ indinavir jistgħu jwasslu għal nefrolitijasi.
Increased concentrations of indinavir may result in nephrolithiasis.
M’ hemmx tagħrif disponibbli dwar is- sigurtà u l- effikaċja mill- użu ta ’ din it- taħlita.
Lopinavir/ ritonavir 400/ 100 mg bid (saquinavir/ ritonavir 1000/ 100 mg bid in combination with 2 or 3 NRTIs)
(saquinavir/ ritonavir 1000/ 100 mg bid f’ taħlita
Saquinavir ↔ Ritonavir ↓ (effectiveness as boosting agent not modified).
sustanza li ssaħħaħ ma nbidlitx).
Lopinavir ↔ (based on historical comparison with unboosted lopinavir)
Lopinavir ↔ (ibbażat fuq paragun
No dose adjustment required.
storiku b’ lopinavir mhux imsaħħaħ)
- Nelfinavir 1250 mg bid (saquinavir/ ritonavir 1000/ 100 mg bid)
Saquinavir AUC ↑ 13% Nelfinavir 1250 mg bid (saquinavir/ ritonavir
- Saquinavir AUC ↑ 13% (90% CI:
27↓ - 74↑)
27 ↓ - 74↑) Saquinavir Cmax ↑ 9% (90% CI:
Saquinavir Cmax ↑ 9% (90% CI:
- No dose adjustment required.
- Nelfinavir 750 mg tid -
- Nelfinavir 750 mg tid (unboosted saquinavir 1200 mg tid)
imsaħħaħ 1200 mg tid)
- Quadruple therapy, including saquinavir soft capsules and nelfinavir in addition to two nucleoside reverse transcriptase inhibitors gave a more durable response (prolongation of time to virological relapse) than triple therapy with either single protease inhibitor.
inibituri ta ’ nucleoside reverse transcriptase urew rispons aktar fit- tul (titwil taż- żmien sa rikaduta viroloġika) minn terapija tripla b’ xi wieħed mill- inibituri tal- protease waħdu.
Concomitant administration of nelfinavir and saquinavir soft capsules resulted in a moderate increase in the incidence of diarrhoea.
L- għoti ta ’ nelfinavir flimkien ma ’ kapsuli rotob ta ’ saquinavir wasslet għal żjieda moderata fl- inċidenza ta ’ dijarea.
7 Medicinal product by therapeutic area (dose of Invirase used in study)
Ritonavir 100 mg bid
Recommendations concerning co- administration
Dan huwa l- kors ta ’ taħlita approvat.
Ritonavir 100 mg bid (saquinavir 1000 mg bid)
(saquinavir 1000 mg bid)
Saquinavir ↑ Ritonavir ↔ In HIV-infected patients, Invirase or saquinavir soft capsules in combination with ritonavir at doses of 1000/ 100 mg twice daily provide a systemic exposure of saquinavir over a 24 hour period similar to or greater than that achieved with saquinavir soft capsules 1200 mg three times daily (see section 5.2).
F’ pazjenti infettati b’ HIV, Invirase jew kapsuli rotob ta ’ saquinavir flimkien ma ’ ritonavir f’ dożi ta ’ 1000/ 100 mg darbtejn kuljum jipprovdu esponiment sistemiku ta ’ saquinavir tul perijodu ta ’ 24 siegħa simili jew aktar minn dak li ntlaħaq b’ kapsuli rotob ta ’ saquinavir 1200 mg tliet darbiet kuljum (ara sezzjoni 5. 2).
No dose adjustment is recommended.
Mhux irrakkomandat aġġustament fid- doża.
Tipranavir/ ritonavir (saquinavir/ ritonavir) HIV fusion inhibitor
Tipranavir/ ritonavir
Concomitant administration of tipranavir, co-administered with low dose ritonavir, with saquinavir/ ritonavir, is not recommended.
ritonavir, ma ’ saquinavir/ ritonavir, mhux irrakkomandat.
If the combination is considered necessary, monitoring of the saquinavir plasma levels is strongly encouraged.
Jekk din it - taħlita hija meqjusa bħala neċessarja, sorveljanza tal- livelli ta ’ saquinavir fil- plażma hija inkoraġġuta ħafna.
Enfuvirtide (saquinavir/ ritonavir 1000/ 100 mg bid) Other medicinal products Antiarrhythmics
Inibitur tal- fużjoni ta ’ l- HIV Saquinavir ↔ Enfuvirtide
No dose adjustment required.
M’ hemmx bżonn ta ’ aġġustament
Bepridil Lidocaine (systemic) Quinidine (saquinavir/ ritonavir) Amiodarone flecainide propafenone (saquinavir/ ritonavir) Anticoagulant
(saquinavir/ ritonavir 1000/ 100 mg bid) Prodotti mediċinali oħra Anti- arritmijaċi Bepridil Lidocaine (sistemiku) Quinidine (saquinavir/ ritonavir) Amiodarone flecainide propafenone (saquinavir/ ritonavir)
Concentrations of bepridil, systemic lidocaine or quinidine may be increased when co-administered with Invirase/ ritonavir.
Konċentrazzjonijiet ta ’ bepridil, lidocaine sistemiku jew quinidine jistgħu jiżdiedu meta jingħataw flimkien ma ’ Invirase/ ritonavir.
Concentrations of amiodarone, flecainide or propafenone may be increased when co-administered with Invirase/ ritonavir.
Konċentrazzjonijiet ta ’ amiodarone, flecainide jew propafenone jistgħu jiżdiedu meta jingħataw flimkien ma ’ Invirase/ ritonavir.
Caution is warranted.
Kawtela hija meħtieġa.
Therapeutic concentration monitoring is recommended, if available.
Jekk disponibbli, huwa rrakkomandat li ssir sorveljanza tal - konċentrazzjoni terapewtika.
Contraindicated in combination with saquinavir/ ritonavir due to potentially life threatening cardiac arrhythmia (see section 4.3).
Kontra- indikat flimkien ma ’ saquinavir/ ritonavir minħabba arritmija kardijaka b’ potenzjal ta ’ periklu għal ħajja (ara sezzjoni 4. 3).
Warfarin (saquinavir/ ritonavir) Anticonvulsants
Sustanzi kontra il- koagulazzjoni tad- demm Huwa rrakkomandat li l- INR (il - Warfarin
Concentrations of warfarin may be affected.
Konċentrazzjonijiet ta ’ warfarin
INR (international normalised ratio) monitoring recommended.
proporzjon normalizzat
- Carbamazepine Phenobarbital Phenytoin (saquinavir/ ritonavir)
(saquinavir/ ritonavir)
- Interaction with Invirase/ ritonavir not studied.
jistgħu jiġu affettwati.
- Carbamazepine Phenobarbital Phenytoin (unboosted saquinavir) Antidepressants
internazzjonali) jiġi sorveljat.
- These medicinal products will induce CYP3A4 and may therefore decrease saquinavir concentrations.
9 Prodott mediċinali skond is- settur terapewtiku (doża ta ’ Invirase użata fl- istudju)
Tricyclic antidepressants (e. g. amitriptyline, imipramine) (saquinavir/ ritonavir)
Rakkomandazzjonijiet li jikkonċernaw l- għoti fl- istess waqt
Invirase/ ritonavir may increase concentrations of tricyclic antidepressants.
- L- interazzjoni ma ’
Therapeutic concentration monitoring recommended.
Invirase/ ritonavir ma ’ ġietx Phenobarbital studjata.
8 Medicinal product by therapeutic area (dose of Invirase used in study)
Carbamazepine Phenobarbital Phenytoin (saquinavir mhux imsaħħaħ)
Interaction
- Dawn il- prodotti mediċinali jinduċu CYP3A4 u għalhekk jistgħu jnaqqsu l - konċentrazzjonijiet ta ’ saquinavir.
Recommendations concerning co- administration
Anti- depressanti Hija rrakkomandata sorveljanza tal - Invirase/ ritonavir jista ’ jżid il - Anti- depressanti triċikliċi konċentrazzjoni terapewtika. konċentrazzjonijiet ta ’ anti - (e. ż. amitriptyline, depressanti triċikliċi. imipramine) (saquinavir/ ritonavir) -
- Nefazodone (saquinavir/ ritonavir)
Nefazodone (saquinavir/ ritonavir)
- Interaction with saquinavir/ ritonavir not evaluated.
- L- interazzjoni ma ’ saquinavir/ ritonavir ma ġietx stmata.
- Nefazodone (unboosted saquinavir) Antihistamines
Nefazodone (saquinavir mhux imsaħħaħ
- Nefazodone inhibits CYP3A4.
- Nefazodone jinibixxi lil CYP3A4.
Saquinavir concentrations may be increased.
Il- konċentrazzjonijiet ta ’ saquinavir jistgħu jiżdiedu.
- Monitoring for saquinavir toxicity recommended.
Sorveljanza għat- tossiċità ta ’ saquinavir hija rrakkomandata.
Terfenadine Astemizole (saquinavir/ ritonavir) Anti-infectives
Antistaminiċi Terfenadine Astemizole (saquinavir/ ritonavir) Anti- infettivi
Terfenadine AUC ↑, associated with a prolongation of QTc intervals.
Terfenadine AUC ↑, assoċjata ma ’ titwil ta ’ l- intervalli ta ’ QTc.
A similar interaction with astemizole is likely.
Interazzjoni simili ma ’ astemizole hija probabbli.
Terfenadine and astemizole are contraindicated with boosted or unboosted saquinavir (see section 4.3).
Terfenadine u astemizole huma kontra- indikati ma ’ saquinavir imsaħħaħ jew mhux imsaħħaħ (ara sezzjoni 4. 3).
- Interaction with Invirase/ ritonavir not studied.
- L- interazzjoni ma ’ Invirase/ ritonavir ma ’ ġietx studjata. - Saquinavir AUC ↑ 177%
- Clarithromycin 500 mg bid (unboosted saquinavir 1200 mg tid) - Erythromycin (saquinavir/ ritonavir)
(saquinavir mhux imsaħħaħ 1200 mg tid) - Erythromycin (saquinavir/ ritonavir)
- Saquinavir AUC ↑ 177% Saquinavir Cmax ↑ 187% Clarithromycin AUC ↑ 40% Clarithromycin Cmax ↑ 40% - Interaction with Invirase/ ritonavir not studied.
Clarithromycin AUC ↑ 40% Clarithromycin Cmax ↑ 40% - L- interazzjoni ma ’ Invirase/ ritonavir ma ’ ġietx studjata. - Saquinavir AUC ↑ 99%
- No dose adjustment is required when co-administered for a limited time at the doses studied.
flimikien għal żmien limitat fid - dożi studjati.
- Erythromycin 250 mg qid (unboosted saquinavir 1200 mg tid)
- Erythromycin
- Saquinavir AUC ↑ 99% Saquinavir Cmax ↑ 106%
Saquinavir Cmax ↑ 106%
- No dose adjustment required.
- M’ hemmx bżonn ta ’ aġġustament
- Streptogramin antibiotics (saquinavir/ ritonavir)
250 mg qid (saquinavir mhux imsaħħaħ 1200 mg tid)
- Interaction with Invirase/ ritonavir not studied.
fid- doża.
- Streptogramin antibiotics (unboosted saquinavir) Antifungals
- Anti- bijotiċi streptogramin (saquinavir/ ritonavir) - Anti- bijotiċi streptogramin (saquinavir mhux imsaħħaħ) Sustanzi kontra l- moffa
- Streptogramin antibiotics such as quinupristin/ dalfopristin inhibit CYP3A4.
- L- interazzjoni ma ’ Invirase/ ritonavir ma ’ ġietx studjata. - Anti- bijotiċi streptogramin bħal quinupristin/ dalfopristin jinibixxu lil CYP3A4.
Saquinavir concentrations may be increased.
Il- konċentrazzjonijiet ta ’ saquinavir jistgħu jiżjiedu.
- Monitoring for saquinavir toxicity recommended.
- Sorveljanza għat- tossiċità ta ’ saquinavir hija rrakkomandata.
Ketoconazole 200 mg qd (saquinavir/ ritonavir 1000/ 100 mg bid)
Ketoconazole 200 mg qd (saquinavir/ ritonavir
Saquinavir AUC ↔ Saquinavir Cmax ↔ Ritonavir AUC ↔ Ritonavir Cmax ↔ Ketoconazole AUC ↑ 168% (90% CI 146%-193%) Ketoconazole Cmax ↑ 45% (90% CI 32%-59%)
Ritonavir AUC ↔ Ritonavir Cmax ↔ Ketoconazole AUC ↑ 168% (90% CI 146% - 193%) Ketoconazole Cmax ↑ 45% (90% CI 32% - 59%) 10
No dose adjustment required when saquinavir/ ritonavir combined with ≤ 200 mg/ day ketoconazole.
jingħata flimkien ma ’ ketoconazole ≤ 200 mg/ kuljum.
High doses of ketoconazole (> 200 mg/ day) are not recommended.
Dożi għolja ta ’ ketoconazole (> 200 mg/ kuljum) mhux irrakkomandati.
- Interaction with Invirase/ ritonavir not studied.
- L- interazzjoni ma ’ Invirase/ ritonavir ma ’ ġietx studjata. - Itraconazole huwa inibitur qawwi
- Itraconazole (unboosted saquinavir)
- Itraconazole
- Itraconazole is a moderately potent inhibitor of CYP3A4.
b’ mod moderat ta ’ CYP3A4.
An interaction is possible.
Interazzjoni hija possibbli.
Monitoring for saquinavir toxicity recommended.
saquinavir hija rrakkomandata.
Fluconazole/ miconazole (saquinavir/ ritonavir) Antimycobacterials
Fluconazole/ miconazole (saquinavir/ ritonavir)
Interaction with Invirase/ ritonavir not studied.
L- interazzjoni ma ’ Invirase/ ritonavir ma ’ ġietx studjata.
Rifampicin 600 mg qd (saquinavir/ ritonavir 1000/ 100 mg bid)
Sustanzi kontra l- mycobacteria Rifampicin 600 mg qd
In a clinical study 11 of 17 (65%) healthy volunteers developed severe hepatocellular toxicity with transaminase elevations up to > 20- fold the upper limit of normal after 1 to 5 days of co-administration.
Fi studju kliniku 11 minn 17- il
Rifampicin is contraindicated in combination with Invirase/ ritonavir (see section 4.3).
Rifampicin huwa kontra- indikat
9 Medicinal product by therapeutic area (dose of Invirase used in study)
(saquinavir/ ritonavir
Interaction
voluntier b’ saħħithom (65%)
Recommendations concerning co- administration
flimkien ma ’ Invirase/ ritonavir
Rifabutin (saquinavir/ ritonavir 1000/ 100 mg bid) Benzodiazepines
1000/ 100 mg bid) Rifabutin (saquinavir/ ritonavir 1000/ 100 mg bid) Benzodiazepines
Interaction with saquinavir/ ritonavir 1000/ 100 mg not studied.
L- interazzjoni ma ’ saquinavir/ ritonavir 1000/ 100 mg ma ’ ġietx studjata.
A dosage reduction to rifabutin 150 mg every three days is recommended based on experience with low dose ritonavir boosted protease inhibitors.
Tnaqqis fid- doża għal rifabutin 150 mg kull tliet ijiem huwa rrakkomandat ibbażat fuq esperjenza b’ inibituri tal- protease msaħħa b’ doża baxxa ta ’ ritonavir.
Patients receiving rifabutin with Invirase/ ritonavir should be closely monitored for liver function test elevations and emergence of adverse events associated with rifabutin therapy.
Pazjenti li qed jingħataw rifabutin ma ’ Invirase/ ritonavir għandhom jiġu sorveljati mill- viċin għal żjidiet fit - test tal- funzjoni tal- fwied u d- dehra ta ’ avvenimenti avversi assoċjati ma ’ terapija b’ rifabutin.
Further dosage reduction of rifabutin may be necessary.
Midazolam 7. 5 mg
Studies of other CYP3A modulators and i. v. midazolam suggest a possible 3- 4 fold increase in midazolam plasma levels.
Midazolam AUC ↑ 12. 4 darbiet
Co-administration of Invirase/ ritonavir with orally administered midazolam is contraindicated (see section 4.3).
Midazolam Cmax ↑ 4. 3 darbiet
Caution should be used with co- administration of Invirase and parenteral midazolam.
Konċentrazzjonijiet ta ’ dawn il -
If Invirase is co-administered with parenteral midazolam it should be done in an intensive care unit (ICU) or similar setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/ or prolonged sedation.
Jekk Invirase jingħata flimkien ma ’ midazolam parenterali dan għandu jsir f’ sala ta ’ kura intensiva (ICU) jew post simili li jista ’ jassigura sorveljanza klinika mill- viċin u mmaniġġjar mediku xieraq f’ każ ta ’ depressjoni respiratorja u/ jew sedazzjoni mtawwla.
Dosage adjustment should be considered, especially if more than a single dose of midazolam is administered.
Aġġustament fid - dożaġġ għandu jiġi kkunsidrat, speċjalment jekk tingħata aktar minn doża waħda ta ’ midazolam.
Alprazolam Clorazepate Diazepam Flurazepam (saquinavir/ ritonavir)
Flurazepam (saquinavir/ ritonavir)
Concentrations of these medicinal products may be increased when co- administered with Invirase/ ritonavir.
Konċentrazzjonijiet ta ’ triazolam
Careful monitoring of patients with regard to sedative effects is warranted.
Prodott mediċinali skond is- settur terapewtiku (doża ta ’ Invirase użata fl- istudju)
A decrease in the dose of the benzodiazepine may be required.
Rakkomandazzjonijiet li jikkonċernaw l- għoti fl- istess waqt saquinavir/ ritonavir, minħabba r -
Triazolam (saquinavir/ ritonavir) Calcium channel blockers
(saquinavir/ ritonavir)
Concentrations of triazolam may be increased when co-administered with Invirase/ ritonavir.
jistgħu jiżdiedu meta jingħata flimkien ma ’ Invirase/ ritonavir.
Contraindicated in combination with saquinavir/ ritonavir, due to the risk of potentially prolonged or increased sedation and respiratory depression (see section 4.3).
riskju potenzjali ta ’ titwil jew żjieda fis- sedazzjoni u depressjoni respiratorja (ara sezzjoni 4. 3).
Felodipine, nifedipine, nicardipine, diltiazem, nimodipine, verapamil, amlodipine, nisoldipine, isradipine (saquinavir/ ritonavir)
Imblokkaturi tal- kanali tal- kalċju Konċentrazzjonijiet ta ’ dawn il - Felodipine, nifedipine,
Concentrations of these medicinal products may be increased when co- administered with Invirase/ ritonavir.
prodotti mediċinali jistgħu jiżdiedu
Caution is warranted and clinical monitoring of patients is recommended.
Hija rrakkomandata kawtela u
10 Medicinal product by therapeutic area (dose of Invirase used in study) Corticosteroids
nicardipine, diltiazem, nimodipine, verapamil, amlodipine, nisoldipine, isradipine (saquinavir/ ritonavir) Kortikosterojdi
Interaction
meta jingħataw flimkien ma ’ Invirase/ ritonavir.
Recommendations concerning co- administration
sorveljanza klinika tal- pazjenti.
- Dexamethasone (saquinavir/ ritonavir)
- Dexamethasone (saquinavir/ ritonavir)
- Interaction with Invirase/ ritonavir not studied.
- L- interazzjoni ma ’ Invirase/ ritonavir ma ġietx studjata.
- Dexamethasone (unboosted saquinavir)
- Dexamethasone (saquinavir mhux imsaħħaħ) Fluticasone propionate
- Dexamethasone induces CYP3A4 and may decrease saquinavir concentrations.
- Dexamethasone jinduċi lil CYP3A4 u jista ’ jnaqqas il - konċentrazzjonijiet ta ’ saquinavir.
- Use with caution.
- Uża b’ kawtela.
Saquinavir may be less effective in patients taking dexamethasone.
Saquinavir jista ’ jkun inqas effettiv f’ pazjenti li qed jieħdu dexamethasone.
Fluticasone propionate 50 mcg qid, intranasal (ritonavir 100 mg bid)
L- għoti fl- istess waqt ta ’ saquinavir
Fluticasone propionate ↑ Intrinsic cortisol ↓ 86% (90% CI 82%-89%) Greater effects may be expected when fluticasone propionate is inhaled.
50 mcg qid, mill- imnieħer Cortisol intrinsiku ↓ 86% (ritonavir 100 mg bid) (90% CI 82% - 89%) Wieħed jista ’ jistenna effetti akbar meta fluticasone propionate jittieħed man- nifs.
Systemic corticosteroid effects including Cushing’ s syndrome and adrenal suppression have been reported in patients receiving ritonavir and inhaled or intranasally administered fluticasone propionate; this could also occur with other corticosteroids metabolised via the P450 3A pathway e. g. budesonide.
Effetti sistemiċi tal - kortikosterojdi inkluż is- sindrome ta ’ Cushing u soppressjoni adrenali kienu irrapportati f’ pazjenti li ngħataw ritonavir u fluticasone propionate mogħti man- nifs mill- ħalq jew mill - imnieħer; dan jista ’ jseħħ wkoll ma ’ kortikosterojdi oħra metabolizzati mir- rotta ta ’ P450 3A e. ż. budesonide.
Concomitant administration of boosted saquinavir and fluticasone propionate and other corticosteroids metabolised via the P450 3A pathway (e. g. budesonide) is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects (see section 4.4).
L- effetti ta ’ esponiment sistemiku għoli ta ’ fluticasone fuq il- livelli fil - plażma ta ’ ritonavir għadhom mhux magħrufa.
Dose reduction of the glucocorticoid should be considered with close monitoring of local and systemic effects or a switch to a glucocorticoid, which is not a substrate for CYP3A4 (e. g.
Prodotti mediċinali li huma substrati ta ’ P- glycoprotein Glycosides ta ’ Digitalis Digoxin 0. 5 mg Digoxin AUC0- 72 ↑ 49% doża waħda Digoxin Cmax ↑ 27% (saquinavir/ ritonavir Livelli ta ’ digoxin jistgħu jkunu 1000/ 100 mg bid) differenti maż- żmien.
Effects of high fluticasone systemic exposure on ritonavir plasma levels yet unknown.
Żidiet kbar ta ’ digoxin jistgħu jkunu mistennija meta saquinavir/ ritonavir jinbeda f’ pazjenti diġa kkurati b’ digoxin.
In case of withdrawal of glucocorticoids progressive dose reduction may have to be performed over a longer period.
Antagonisti tar- riċetturi H2 ta 'l- istamina - Ranitidine - L- interazzjoni ma ’ (saquinavir/ ritonavir) Invirase/ ritonavir ma ’ ġietx studjata.
Medicinal products that are substrates of P-glycoprotein Digitalis glycosides Digoxin 0.5 mg single dose (saquinavir/ ritonavir 1000/ 100 mg bid)
imsaħħaħ u fluticasone propionate u kortikosterojdi oħra metabolizzati permezz tar- rotta ta ’ P450 3A (e. ż. budesonide) mhux irrakkomandat sakemm il- benefiċċju potenzjali tal - kura ma jkunx akbar mir- riskju ta ’ effetti sistemiċi tal- kortikosterojdi (ara sezzjoni 4. 4).
Digoxin AUC0-72 ↑ 49% Digoxin Cmax ↑ 27% Digoxin levels may differ over time.
Tnaqqis fid- doża tal- glukokortikojd għandha tiġi kkunsidrata ma ’ sorveljanza mill- viċin ta ’ effetti lokali u sistemiċi jew bidla għall - glukokortikojd li mhux substrat għal CYP3A4 (e. ż. beclometasone).
Large increments of digoxin may be expected when saquinavir/ ritonavir is introduced in patients already treated with digoxin.
F’ każ ta ’ rtirar tal- glukokortikojdi, jista ’ jkun hemm bżonn ta ’ tnaqqis gradwali fid- doża fuq perijodu ta ’ żmien itwal.
Caution should be exercised when Invirase/ ritonavir and digoxin are co- administered.
Għandu jkun hemm kawtela meta Invirase/ ritonavir u digoxin jingħataw flimkien.
The serum concentration of digoxin should be monitored and a dose reduction of digoxin should be considered if necessary.
Il - konċentrazzjoni ta ’ digoxin fis- serum għandha tiġi sorveljata u jekk hemm bżonn għandha tiġi kkunsidrata tnaqqis fid- doża.
Histamine H2-receptor antagonist -
12
Ranitidine (saquinavir/ ritonavir)
Prodott mediċinali skond is- settur terapewtiku (doża ta ’ Invirase użata fl- istudju)
- Interaction with Invirase/ ritonavir not studied.
Interazzjoni
-
Rakkomandazzjonijiet li jikkonċernaw l- għoti fl- istess waqt
Ranitidine (unboosted saquinavir)
- Ranitidine (saquinavir mhux imsaħħaħ) ta ’ HMG- CoA reductase
- Saquinavir AUC ↑ 67%
- Saquinavir AUC ↑ 67% L- interazzjoni ma ’ ġietx studjata.
-
Il -
Increase not thought to be clinically relevant.
- Iż- żjieda mhix maħsuba li hija ta ’ rilevanza klinika.
No dose adjustment of saquinavir recommended.
L- ebda aġġustament fid- doża ta ’ saquinavir ma hija rrakkomandata.
HMG-CoA reductase inhibitors Pravastatin Fluvastatin (saquinavir/ ritonavir)
Pravastatin
Interaction not studied.
Jekk
Metabolism of pravastatin and fluvastatin is not dependent on CYP3A4.
fluvastatin mhux dipendenti fuq
Interaction via effects on transport proteins cannot be excluded.
Ma tistax tiġi eskluża interazzjoni permezz ta ’ effetti fuq proteini tat- trasport.
Interaction unknown.
disponibbli, uża flimkien ma ’ sorveljanza b’ attenzjoni.
If no alternative treatment is available, use with careful monitoring.
Konċentrazzjonijiet miżjuda ta ’
Simvastatin Lovastatin (saquinavir/ ritonavir)
Simvastatin
Simvastatin ↑↑ Lovastatin ↑↑ Plasma concentrations highly dependent on CYP3A4 metabolism.
Simvastatin ↑↑
Increased concentrations of simvastatin and lovastatin have been associated with rhabdomyolysis.
simvastatin u lovastatin ġew
These medicinal products are contraindicated for use with Invirase/ ritonavir (see section 4.3).
prodotti mediċinali huma kontra - indikati għall- użu flimkien ma ’ Invirase/ ritonavir (ara sezzjoni 4. 3).
Medicinal product by therapeutic area (dose of Invirase used in study)
Meta wżat ma ’ Invirase/ ritonavir,
Interaction
Atorvastatin
Recommendations concerning co- administration
Atorvastatin huwa inqas dipendenti
Atorvastatin (saquinavir/ ritonavir) Immunosuppressants
(saquinavir/ ritonavir) Immunosoppressanti
Atorvastatin is less dependent on CYP3A4 for metabolism.
minn CYP3A4 għall- metaboliżmu.
When used with Invirase/ ritonavir, the lowest possible dose of atorvastatin should be administered and the patient should be carefully monitored for signs/ symptoms of myopathy (muscle weakness, muscle pain, rising plasma creatinine kinase).
Sorveljanza terapewtika tal- mediċina
Ciclosporin Tacrolimus Rapamycin (saquinavir/ ritonavir) Narcotic analgesics
Ciclosporin
Concentrations of these medicinal products increase several fold when co-administered with Invirase/ ritonavir.
flimkien ma ’ Invirase/ ritonavir.
Careful therapeutic drug monitoring is necessary for immunosuppressants when co-administered with Invirase/ ritonavir.
Methadone AUC ↓ 19%
Methadone 60-120 mg qd (saquinavir/ ritonavir 1000/ 100 mg bid) Neuroleptics
Methadone 60- 120 mg qd (saquinavir/ ritonavir 1000/ 100 mg bid) Newroleptiċi
Methadone AUC ↓ 19% (90% CI 9% to 29%) None of the 12 patients experienced withdrawal symptoms.
(90% CI 9% sa 29%) L- ebda wieħed mit- 12- il pazjent ma kellu esperjenza ta ’ sintomi ta ’ rtirar.
No dosage adjustment required.
Mhux meħtieġ aġġustament fid- doża.
Pimozide (saquinavir/ ritonavir) Oral contraceptives
Pimozide (saquinavir/ ritonavir) Kontraċettivi orali
Concentrations of pimozide may be increased when co-administered with Invirase/ ritonavir.
Konċentrazzjonijiet ta ’ pimozide jistgħu jiżdiedu meta jingħata flimkien ma ’ Invirase/ ritonavir.
Due to a potential for life threatening cardiac arrhythmias, Invirase/ ritonavir is contra-indicated in combination with pimozide (see section 4.3).
Minħabba l- potenzjal ta ’ arritmija kardijaka ta ’ periklu għal ħajja, Invirase/ ritonavir huwa kontra - indikat għall- użu flimkien ma ’ pimozide (ara sezzjoni 4. 3).
Ethinyl estradiol (saquinavir/ ritonavir)
Ethinyl estradiol
Concentration of ethinyl estradiol may be decreased when co- administered with Invirase/ ritonavir.
Konċentrazzjoni ta ’ ethinyl estradiol
Alternative or additional contraceptive measures should be used when oestrogen-based oral contraceptives are co-administered.
tista ’ tonqos meta jingħata flimkien ma ’ Invirase/ ritonavir.
Phosphodiesterase type 5 (PDE5) inhibitors -
Inibituri ta ’ phosphodiesterase tat- tip 5 (PDE5)
Sildenafil 100 mg (single dose) (unboosted saquinavir
Sildenafil 100 mg
-
13
- Use sildenafil with caution at reduced doses of no more than 25 mg every 48 hours with
mnaqqsa ta ’ mhux aktar minn 25 mg kull 48 siegħa b’ sorveljanza
1200 mg tid)
imsaħħaħ 1200 mg tid)
-
Vardenafil
Sildenafil is a substrate of CYP3A4.
Konċentrazzjonijiet ta ’ vardenafil
increased monitoring of adverse events when administered concomitantly with Invirase/ ritonavir.
mnaqqsa ta ’ mhux aktar minn 2. 5 mg
Concentrations of vardenafil may be increased when co-administered with Invirase/ ritonavir.
jistgħu jiżdiedu meta jingħata flimkien ma ’ Invirase/ ritonavir.
Use vardenafil with caution at reduced doses of no more than 2.5 mg every 72 hours with increased monitoring of adverse events when administered concomitantly with Invirase/ ritonavir.
Uża tadalafil b’ kawtela f’ dożi
Concentrations of tadalafil may be increased when co-administered with Invirase/ ritonavir.
Konċentrazzjonijiet ta ’ tadalafil
Use tadalafil with caution at reduced doses of no more than 10 mg every 72 hours with increased monitoring of adverse events when administered concomitantly with Invirase/ ritonavir.
mnaqqsa ta ’ mhux aktar minn 10 mg
12 Medicinal product by therapeutic area (dose of Invirase used in study) Proton pump inhibitors
(saquinavir/ ritonavir) Inibituri tal- proton pump
Interaction
jistgħu jiżdiedu meta jingħata flimkien ma ’ Invirase/ ritonavir.
Recommendations concerning co- administration
kull 72 siegħa b’ sorveljanza miżjuda għall- effetti avversi meta dan jingħata flimkien ma ’ Invirase/ ritonavir.
Omeprazole 40 mg qd (saquinavir/ ritonavir 1000/ 100 mg bid)
Omeprazole 40 mg qd (saquinavir/ ritonavir 1000/ 100 mg bid)
Saquinavir AUC ↑ 82% (90% CI 44-131%) Saquinavir Cmax ↑ 75% (90% CI 38-123%) Ritonavir ↔
Saquinavir AUC ↑ 82% (90% CI 44- 131%) Saquinavir Cmax ↑ 75% (90% CI 38- 123%) Ritonavir ↔
Monitoring for potential saquinavir toxicities is recommended.
Sorveljanza għal tossiċitajiet potenzjali ta ’ saquinavir hija rrakkomandata.
Other proton pump inhibitors (saquinavir/ ritonavir 1000/ 100 mg bid) Others
1000/ 100 mg bid) Oħrajn
No data are available on the concomitant administration of Invirase/ ritonavir and other proton pump inhibitors.
L- użu ta ’ Invirase/ ritonavir flimkien
If omeprazole or other proton pump inhibitors are taken concomitantly with Invirase/ ritonavir, monitoring for potential saquinavir toxicities is recommended.
Invirase/ ritonavir jista ’ jżid l -
Ergot alkaloids (e. g. ergotamine, dihydroergotamine, ergonovine, and methylergonovine) (saquinavir/ ritonavir)
ergotamine,
Invirase/ ritonavir may increase ergot alkaloids exposure, and consequently, increase the potential for acute ergot toxicity.
espożizzjoni għall- alkalojdi ergot, u
The concomitant use of Invirase/ ritonavir and ergot alkaloids is contra-indicated (see section 4.3).
indikat (ara sezzjoni 4. 3).
- Grapefruit juice (saquinavir/ ritonavir)
dihydroergotamine, ergonovine, u methylergonovine) (saquinavir/ ritonavir)
- Interaction with Invirase/ ritonavir not studied.
b’ hekk iżid il- potenzjal għal tossiċità akuta ta ’ ergot.
- Grapefruit juice (single dose) (unboosted saquinavir)
- Meraq tal- grejpfrut (saquinavir/ ritonavir) - Meraq tal- grejpfrut (doża waħda) (saquinavir mhux imsaħħaħ)
- Saquinavir ↑ 50% (normal strength grapefruit juice) - Saquinavir ↑ 100% (double strength grapefruit juice)
- L- interazzjoni ma ’ Invirase/ ritonavir ma ’ ġietx studjata. - Saquinavir ↑ 50% (meraq tal - grejpfrut ta ’ qawwa normali) - Saquinavir ↑ 100% (meraq tal - grejpfrut ta ’ qawwa doppja)
- Increase not thought to be clinically relevant.
- Iż- żjieda mhix maħsuba li hija ta ’ rilevanza klinika.
No dose adjustment required.
Mhux meħtieġ aġġustament fid- doża.
- Garlic capsules (saquinavir/ ritonavir)
- Kapsuli tat- tewm (saquinavir/ ritonavir)
- Interaction with Invirase/ ritonavir not studied.
- L- interazzjoni ma ’ Invirase/ ritonavir ma ’ ġietx studjata. - Saquinavir AUC ↓ 51%
- Garlic capsules (dose approx. equivalent to two 4 g cloves of garlic daily) (unboosted saquinavir 1200 mg tid)
- Kapsuli tat- tewm (doża ekwivalenti għal
- Saquinavir AUC ↓ 51% Saquinavir Ctrough ↓ 49% (8 hours post dose) Saquinavir Cmax ↓ 54%.
Saquinavir Ctrough ↓ 49% (8 sigħat
- Patients on saquinavir treatment must not take garlic capsules due to the risk of decreased plasma concentrations and loss of virological response and possible resistance to one or more components of the antiretroviral regimen.
- Pazjenti fuq kura b’ saquinavir m’ għandhomx jieħdu kapsuli tat -
13 Medicinal product by therapeutic area (dose of Invirase used in study)
Prodott mediċinali skond is- settur terapewtiku (doża ta ’ Invirase użata fl- istudju)
Recommendations concerning co- administration
Rakkomandazzjonijiet li jikkonċernaw l- għoti fl- istess waqt antiretrovirali.
John’ s wort (saquinavir/ ritonavir)
John’ s wort (saquinavir/ ritonavir)
- Interaction with Invirase/ ritonavir not studied.
- L- interazzjoni ma ’ Invirase/ ritonavir ma ’ ġietx studjata.
John’ s wort (unboosted saquinavir) Other potential interactions
John’ s wort
- Plasma levels of saquinavir can be reduced by concomitant use of the herbal preparation St.
Jekk pazjent ikun St.
John’ s wort (Hypericum perforatum).
John’ s wort (Hypericum digà qed jieħu St.
John’ s wort.
John’ s wort, perforatum).
- Herbal preparations containing St.
Dan jiġri minħabba l - waqqaf St.
If a patient is already taking St.
John’ s wort, iċċekja l - induzzjoni ta ’ enżimi livelli virali u jekk possibbli l - metabolizzanti tal- mediċina u/ jew livelli ta ’ saquinavir.
John’ s wort, check viral levels and if possible saquinavir levels.
Il- livelli ta ’ proteini tat- trasport minn St. saquinavir jistgħu jiżdiedu kif John’ s wort. jitwaqqaf St.
John’ s wort, and the dose of saquinavir may need adjusting.
John’ s wort, u d - doża ta ’ saquinavir jista ’ jkollha bżonn tiġi aġġustata.
The inducing effect of St.
L- effett ta ’ induzzjoni ta ’ St.
John’ s wort may persist for at least 2 weeks after cessation of treatment.
John’ s wort jista ’ jippersisti għal mill- inqas ġimagħtejn wara li titwaqqaf il - kura.
Medicinal products that are substrates of CYP3A4 e. g. dapsone, disopyramide, quinine, fentanyl, and alfentanyl (unboosted saquinavir)
disopyramide, quinine, fentanyl, u alfentanyl (saquinavir mhux imsaħħaħ)
Although specific studies have not been performed, co-administration of Invirase/ ritonavir with medicinal products that are mainly metabolised by CYP3A4 pathway may result in elevated plasma concentrations of these medicinal products.
ma ’ prodotti mediċinali li fil- biċċa l - kbira huma metabolizzati mir- rotta ta ’ CYP3A4 jistgħu jwasslu għall - konċentrazzjonijiet elevati fil- plażma ta ’ dawn il- prodotti mediċinali.
These combinations should be given with caution.
jingħataw b’ kawtela.
It is unknown whether medicinal products which reduce the gastrointestinal transit time could lead to lower saquinavir plasma concentrations.
Prodotti mediċinali li jnaqqsu l- ħin ta ’ passaġġ mis- sistema gastro- intestinali Mhux magħruf, jekk prodotti Metoclopramide mediċinali li jnaqqsu l- ħin ta ’ passaġġ mis- sistema gastro- intestinali jistgħux iwasslu għall- konċentrazzjonijiet aktar baxxi ta ’ saquinavir fil- plażma.
Evaluation of experimental animal studies does not indicate direct or indirect harmful effects with respect to the development of the embryo or foetus, the course of gestation and peri- and post-natal development.
Il- valutazzjoni ta ’ studji esperimentali fl- annimali ma tindikax effetti li jagħmlu ħsara diretta jew indiretta f’ dak li jikkonċerna l- iżvilupp ta ’ l- embriju jew tal- fetu, iż- żmien tat- tqala u l- iżvilupp ta ’ qabel u wara t- twelid.
Clinical experience in pregnant women is limited:
Esperjenza klinika f’ nisa tqal hija limitata:
Congenital malformations, birth defects and other disorders (without a congenital malformation) have been reported rarely in pregnant women who had received saquinavir in combination with other antiretroviral agents.
Malformazzjonijiet konġenitali, difetti tat- twelid u mard ieħor (mingħajr xi malformazzjoni konġenitali) rarament kienu rappurtati f’ nisa tqal li kienu rċevew saquinavir flimkien ma ’ sustanzi antiretrovirali oħrajn.
However, so far the available data are insufficient and do not identify specific risks for the unborn child.
Madankollu, s’ issa, l- informazzjoni disponibbli hija insuffiċjenti u ma tidentifikax riskji speċifiċi għat- tarbija mhux imwielda.
Saquinavir should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus (see section 5.3).
Saquinavir għandu jintuża waqt it- tqala biss jekk il- benefiċċju potenzjali jiġġustifika r - riskju potenzjali għall- fetu (ara sezzjoni 5. 3).
There are no laboratory animal or human data available on secretion of saquinavir in breast milk.
Ma hemmx informazzjoni disponibbli minn annimali tal- laboratorju jew mill- bniedem dwar il- ħruġ ta ’ saquinavir fil- ħalib tas- sider.
The potential for adverse reactions to saquinavir in nursing infants cannot be assessed, and therefore, breast-feeding should be discontinued prior to receiving saquinavir.
Il- potenzjal ta ’ reazzjonijiet avversi għal saquinavir fit- trabi li qed jerdgħu ma ’ jistax ikun stmat, għalhekk it- treddigħ għandu jitwaqqaf qabel ma jittieħed saquinavir.
It is recommended that HIV-infected women do not breast feed their infants under any circumstances in order to avoid transmission of HIV.
Esperti tas- saħħa jirrakkomandaw li nisa infettati bl- HIV ma jreddgħux lit- trabi tagħhom fl- ebda ċirkustanza sabiex jevitaw trasmissjoni ta ’ l- HIV.
4.7 Effects on ability to drive and use machines
15 4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
Invirase may have a minor influence on the ability to drive and use machines.
Invirase jista ’ jkollu influwenza ħafifa fuq il- ħila biex issuq jew tħaddem magni.
Dizziness and fatigue have been reported during treatment with Invirase.
Sturdament u għejja ġew irrappurtati waqt kura b’ Invirase.
14 4.8 Undesirable effects
4. 8 Effetti mhux mixtieqa
The following adverse events with an at least possible relationship to ritonavir boosted saquinavir (i. e. adverse reactions) were reported most frequently: nausea, diarrhoea, fatigue, vomiting, flatulence, and abdominal pain.
L- effetti avversi li ġejjin li għandhom ta ’ l- inqas relazzjoni possibbli ma ’ saquinavir msaħħaħ b’ ritonavir (i. e. reazzjonijiet avversi) kienu rrappurtati l- aktar frekwenti: dardir, dijareja. għejja, remettar, gass u uġigħ ta ’ żaqq.
For comprehensive dose adjustment recommendations and drug-associated adverse reactions for ritonavir and other medicinal products used in combination with saquinavir, physicians should refer to the Summary of Product Characteristics for each of these medicinal products.
Għar- rakkomandazzjonijiet komprensivi dwar aġġustament fid- doża u reazzjonijiet avversi assoċjati mal- mediċina ritonavir, u prodotti mediċinali oħra wżati flimkien ma ’ saquinavir, t- tobba għandhom jirreferu għas- Sommarju tal- Karatteristiċi tal- Prodott ta ’ kull wieħed mill- prodotti mediċinali.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
F’ kull sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa huma mniżżla skond is- serjetà tagħhom: l- aktar serji huma mniżżla l- ewwel, segwiti minn dawk anqas serji.
Adverse reactions from clinical trials where saquinavir was boosted with ritonavir
Reazzjonijiet avversi minn provi kliniċi fejn saquinavir kien msaħħaħ b’ ritonavir
Limited data is available from two studies where the safety of saquinavir soft capsule (1000 mg twice daily) used in combination with low dose ritonavir (100 mg twice daily) for at least 48 weeks was studied in 311 patients.
Tagħrif limitat huwa disponibbli minn żewġ studji fejn is- sikurtà ta ’ kapsoli rotob ta ’ saquinavir (1000 mg darbtejn kuljum) użat flimkien ma ’ doża baxxa ta ’ ritonavir (100 mg darbtejn kuljum) għal ta ’ l - inqas 48 ġimgħa kienet studjata f’ 311 pazjent.
Adverse reactions in these two pivotal studies are summarised in Table 2.
Reazzjonijiet avversi f’ dawn iż- żewġ studji pivitali huma miġbura f’ Tabella 2.
The list also includes marked laboratory abnormalities that have been observed with the saquinavir soft capsule in combination with ritonavir (at 48 weeks).
Il- lista tinkludi wkoll abnormalitajiet sinnifikanti tal- laboratorju li ġew osservati b’ kapsoli rotob ta ’ saquinavir f’ taħlita ma ’ ritonavir (wara 48 ġimgħa).
15 Table 2:
16 Tabella 2:
Incidences of Adverse Reactions and marked laboratory abnormalities from the MaxCmin1 and MaxCmin2 study.
Inċidenza ta ’ Reazzjonijiet Avversi u abnormalitajiet sinnifikanti tal- laboratorju mill- istudji MaxCmin1 u MaxCmin2.
(Very common (≥ 10%); common (≥ 1% and < 10%))
(Komni ħafna (≥ 10%); komuni (≥ 1% and < 10%))
Adverse Reactions
Reazzjonijiet Avversi Sistema tal- Ġisem Frekwenza tar- Reazzjoni
All Grades
Kull Grad
Blood and the lymphatic system disorders Common Immune system disorders
Mard tad- demm u tas- sistema limfatika Komuni Mard tas- sistema Immunitarja
Hypersensitivity
Ipersensitività
Metabolism and nutrition disorders Common Psychiatric disorders
Mard tal- metaboliżmu u n- nutrizzjoni Komuni Mard psikjatriku
Diabetes mellitus
Dijabete mellitus
Diabetes mellitus, anorexia, increased appetite
Dijabete mellitus, anoressija, żjieda fl - aptit
Common Nervous System Disorders
Komuni Mard tas- Sistema Nervuża
Decreased libido, sleep disorder
Tnaqqis fil- libido, problem fl- irqad
Paraesthesia, peripheral neuropathy, dizziness, dysgeusia, headache
Parastesija, newropatija periferali, sturdament, dysgeusia, uġigħ ta ’ ras
Respiratory, thoracic and mediastinal disorders Common Gastrointestinal disorders
Mard respiratorju, toraċiku u medjastinali Komuni Mard gastrointestinali
Diarrhoea, nausea
Dijareja, dardir
Diarrhoea, nausea, vomiting
Dijareja, dardir, remettar
Vomiting, abdominal distension, abdominal pain, upper abdominal pain, constipation, dry mouth, dyspepsia, eructation, flatulence, lip dry, loose stools
Remettar, nefħa fiż- żaqq, uġigħ ta ’ żaqq, uġigħ fin- naħa ta ’ fuq taż- żaqq, stitikezza, ħalq xott, ħruq ta ’ stonku, tifwieq, gass, xoftejn xotti, ħmieġ maħlul
Skin and subcutaneous tissue disorders Common
Mard tal- ġilda u tat- tessut ta ’ taħt il- ġilda Komuni
Acquired lipodystrophy
Lipodistrofija miksuba
Acquired lipodystrophy, alopecia, dry skin, eczema, lipoatrophy, pruritus, rash
Lipodistrofija miksuba, alopeċja, ġilda xotta, ekżema, lipoatrofija, ħakk, raxx
Musculoskeletal and connective tissue disorders Common General disorders and administration site conditions
Mard muskoloskeletari u tat- tessut konnettiv Komuni Mard ġenerali u fis- sit ta ’ l- għotja
Muscle spasms
Spażmi muskolari
Common Fatigue Investigations
Għejja
Asthenia, fatigue, increased fat tissue, malaise
Astenja, għejja, żjieda fit- tessut tax - xaħam, tħossok ma tiflaħx
Increased alanine aminotransferase, increased aspartate aminotransferase, increased blood cholesterol, increased blood triglycerides, increased low density lipoprotein, decreased platelet count
Żjieda f’ alanine aminotransferase, żjieda fl- aspartate aminotransferase, żjieda fil- kolesterol fid- demm, żjieda fit- trigliċeridi fid- demm, żjieda fil - lipoproteini ta ’ densità baxxa, tnaqqis fl- għadd tal- plejtlets
Increased blood amylase, increased blood bilirubin, increased blood creatinine, decreased haemoglobin, decreased lymphocyte count, decreased white blood cell count
Żjieda fl- amylase fid- demm, żjieda fil - bilirubin fid- demm, żjieda tal- creatinine fid- demm, tnaqqis fl- emoglobina, tnaqqis fl- għadd tal- limfoċiti, tnaqqis fl - għadd ta ’ ċelluli bojod
Post-marketing experience with saquinavir
Esperjenza ta ’ wara t- tqegħid fuq is- suq b’ saquinavir
Serious and non-serious adverse reactions from post-marketing spontaneous reports (where saquinavir was taken as the sole protease inhibitor or in combination with ritonavir), not mentioned previously in section 4.8, for which a causal relationship to saquinavir cannot be excluded, are summarised below.
Reazzjonijiet avversi serji u mhux serji mir- rapporti spontanji ta ’ wara t- tqegħid fuq is- suq (fejn saquinavir ingħata bħala l- uniku inibitur ta ’ protease jew flimkien ma ’ ritonavir), mhux imsemmija qabel f’ sezzjoni 4. 8, għal liema, relazzjoni każwali ma ’ saquinavr ma tistax tiġi eskluża, huma mniżżla hawn taħt.
As these data come from the spontaneous reporting system, the frequency of the adverse reactions is unknown.
Minħabba li dan it- tagħrif ġej minn sistema ta ’ rapport spontanju, il- frekwenza ta ’ l- effetti avversi mhix magħrufa.
16 • Immune system disorders:
• Mard tas- sistema mmunitarja:
Hypersensitivity.
Ipersensitività.
• Metabolism and nutrition disorders:
17 • Mard tal- metaboliżmu u nutrizzjoni:
- Diabetes mellitus or hyperglycaemia sometimes associated with ketoacidosis (see section 4.4).
- Diabetes mellitus jew ipergliċemija xi kultant assoċjata ma ’ ketoacidosis (ara sezzjoni 4. 4).
- Lipodystrophy:
- Lipodistrofija:
Combination antiretroviral therapy has been associated with redistribution of
Kura antiretrovirali kombinata ġiet assoċjata ma ’ ridistribuzzjoni tax- xaħam
body fat (lipodystrophy) in HIV infected patients including the loss of peripheral and facial subcutaneous fat, increased intra-abdominal and visceral fat, breast hypertrophy and dorsicervical fat accumulation (buffalo hump).
fil- ġisem (lipodistrofija) f’ pazjenti infettati bl- HIV inkluż telf tax- xaħam ta ’ taħt il- ġilda periferali u fil- wiċċ, żjieda fix- xaħam intra- addominali u fil- vixxri, ipertrofija tas- sider u akkumulazzjoni dorsiċervikali tax- xaħam (buffalo hump).
- Combination antiretroviral therapy has been associated with metabolic abnormalities such as
- Kura antiretrovirali kombinata ġiet assoċjata ma ’ abnormalitajiet metaboliċi bħal
hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperglycaemia and hyperlactataemia (see section 4.4).
ipertrigliċerimja, iperkolesterolemja, reżistenza għall- insulina, ipergliċemja u iperlactemja (ara sezzjoni 4. 4).
• Nervous system disorders:
• Mard tas- sitema nervuża:
Somnolence, convulsions.
Ngħas, attakki epilettiċi.
• Vascular disorders:
Mard vaskulari: