qanastek/EMEA-V3 huggingface dataset:
REYATAZ/ ritonavir
Prodotti mediċinali mogħtija Prodott
(fasted)
AUC
with stavudine is not expected to
Cmax
atazanavir, dosed ↔ 1.03 ↑ 1.12 ↔ 1.03 1 hr after ddI+d4T (0.64, 1.67) (0.67, 1.18) (0.61, 1.73) (fasted) Atazanavir concentrations were greatly decreased when co-administered with didanosine (buffered tablets) and stavudine.
Cmin
significantly alter the exposure of stavudine.
Rakkomandazzjonijie
Co-administered medicinal products (dose in mg)
fl- istess ħin (doża f’ mg)
Medicinal AUC Cmax Cmin product assessed (90% CI) (90% CI) (90% CI)
mediċinali evalwat
Recommendations concerning co-administration
(90% CI) (90% CI) (90% CI)
Didanosine (enteric coated
t dwar l- għoti fl- istess ħin
Didanosine (with
Ma ġie osservat l- ebda effett sinifikanti fuq il- konċentrazzjonijiet ta 'didanosine u stavudine.
↑ 1.25
stavudine.
capsules) 400 mg single dose (atazanavir 300 mg QD with
Didanosine (kapsuli enteriċi miksija) 400 mg doża waħda (atazanavir 300 mg QD ma ’
food)
Didanosine (ma 'l - ↓0. 66 ↓0. 62 ↑1. 25 ikel) (0. 59, 0. 73) (0. 52, 0. 74) (0. 92, 1. 69)
No significant effect on atazanavir concentrations was observed when administered with enteric-coated didanosine, but administration with food decreased didanosine concentrations.
Ma ġie osservat l- ebda effett sinifikanti fuq il- konċentrazzjonijiet ta 'atazanavir meta ngħata ma didanosine enteriku miksi, iżda l- għoti ma' l- ikel naqqas il- konċentrazzjonijiet ta 'didanosine.
↓ 0.78 * ↓ 0.84 * ↓ 0.77 * atazanavir
↓0. 78 * ↓0. 84 * ↓0. 77 * atazanavir
300 mg QD (atazanavir 300 mg QD with ritonavir 100 mg QD) studies conducted in HIV- infected patients
300 mg QD (atazanavir 300 mg QD ma 'ritonavir 100 mg QD) studji mwettqa f' pazjenti infettati bl- HIV
(0.65, 0.94) (0.70, 1.00) (0.57-1.02) * In a combined analysis from several clinical studies, atazanavir/ ritonavir 300/ 100 mg co-administered with tenofovir disoproxil fumarate 300 mg (n=39) was compared to atazanavir/ ritonavir 300/ 100 mg (n=33).
(0. 65, 0. 94) (0. 70, 1. 00) (0. 57- 1. 02) * F' analiżi kombinata minn diversi studji kliniċi, atazanavir/ ritonavir 300/ 100 mg mogħti fl- istess ħin ma 'tenofovir disoproxil fumarate 300 mg (n=39) ġie mqabbel ma ’ atazanavir/ ritonavir 300/ 100 mg (n=33).
The efficacy of REYATAZ/ ritonavir in combination with tenofovir in treatment-experienced patients has been demonstrated in clinical study 045 and in treatment naive patients in clinical study 138 (see sections 4.8 and 5.1).
L- effikaċja ta 'REYATAZ/ ritonavir ma' tenofovir f' pazjenti esperjenzati bil- kura ġiet murija fl- istudju kliniku 045 u f' pazjenti li qatt ma ħadu kura qabel fl- istudju kliniku 138 (ara sezzjoni 4. 8 u 5. 1).
The mechanism of interaction between atazanavir and tenofovir is unknown.
Mhux magħruf il- mekkaniżmu ta 'interazzjoni bejn atazanavir u tenofovir.
Tenofovir disoproxil fumarate 300 mg QD (atazanavir 300
Tenofovir disoproxil fumarate 300 mg QD (atazanavir
Patients should be closely monitored for
Il- pazjenti għandhom jiġu mmonitorjati mill -
mg QD with ritonavir 100 mg
100 mg QD)
tenofovir-associated
(1. 30, 1. 45)
QD)
(1. 20, 1. 51)
(1.30, 1.45) (1.20, 1.51) (1.21, 1.36) fumarate
(1. 21, 1. 36)
adverse events, including renal disorders.
avversi assoċjati ma 'tenofovir, fosthom disturbi renali.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Efavirenz 600 mg QD
Non- nucleoside reverse transcriptase inhibitors (NNRTIs) Efavirenz 600 mg QD
Co-administration of
L- għoti fl- istess ħin ta '
(atazanavir 400 mg QD with
(atazanavir 400 mg QD ma ’
efavirenz with
efavirenz ma '
ritonavir 100 mg QD)
ilkoll mogħtija ma 'ritonavir 100 mg QD)
with food
l- ikel
REYATAZ/ ritonavir is not recommended (see
REYATAZ/ ritonavir mhuwiex rakkomandat (ara sezzjoni 4. 4)
section 4.4)
ilkoll mogħtija ma '
(0.90, 1.26)
(0. 90, 1. 26)
(0.95, 1.26)
(0. 95, 1. 26)
* When compared to REYATAZ 300 mg/ ritonavir 100 mg once daily in the evening without efavirenz.
* Meta mqabbel ma 'REYATAZ 300 mg/ ritonavir 100 mg darba kuljum filgħaxija mingħajr efavirenz.
This decrease in atazanavir Cmin, might negatively impact the efficacy of atazanavir.
Dan it- tnaqqis fil- Cmin ta 'atazanavir, jista' jaffettwa b' mod negattiv l- effikaċja ta 'atazanavir.
The mechanism of efavirenz/ atazanavir interaction is CYP3A4 induction. ** based on historical comparison.
Il- mekkaniżmu ta 'l - interazzjoni ta' efavirenz/ atazanavir huwa l- induzzjoni ta 'CYP3A4. ** ibbażat fuq tqabbil storiku.
Nevirapine 200 mg BID
Nevirapine 200 mg BID
nevirapine
nevirapine
(atazanavir 400 mg QD with ritonavir 100 mg QD) study
(atazanavir 400 mg QD ma ’ ritonavir 100 mg QD) studju
nevirapine with REYATAZ/ ritonavir is
nevirapine ma ’ REYATAZ/ ritonavir
conducted in HIV infected
mwettaq f' pazjenti infettati bl -
(0.65, 1.02)
mhuwiex rakkomandat
patients Antibiotics
(ara sezzjoni 4. 4)
* When compared to REYATAZ 300 mg and ritonavir 100 mg without nevirapine.
* Meta mqabbel ma 'REYATAZ 300 mg u ritonavir 100 mg mingħajr nevirapine.
The mechanism of nevirapine/ atazanavir interaction is CYP3A4 induction.
Il- mekkaniżmu ta 'interazzjoni ta' nevirapine/ atazanavir huwa l- induzzjoni ta 'CYP3A4.
Clarithromycin 500 mg BID
Antibijotiċi Clarithromycin 500 mg BID
↑ 1.94 ↑ 1.50 ↑ 2.60 clarithromycin
clarithromycin
No recommendation
Ma tista 'ssir ebda
(1.75, 2.16) (1.32, 1.71) (2.35, 2.88) 14-OH ↓ 0.30 ↓ 0.28 ↓ 0.38
(2. 35, 2. 88)
regarding dose reduction can be made;
rakkomandazzjoni dwar tnaqqis fid- doża;
clarithromycin (0.26, 0.34) (0.24, 0.33) (0.34, 0.42)
↓0. 28
therefore, caution should be exercised if
(0. 24, 0. 33)
↑ 1.28 ↔ 1.06 ↑ 1.91 atazanavir (1.16, 1.43) (0.93, 1.20) (1.66, 2.21)
(0. 34, 0. 42)
REYATAZ/ ritonavir is co-administered with
tintuża kawtela jekk REYATAZ/ ritonavir
clarithromycin.
↑1. 28
Antifungals
↔1. 06
Ketoconazole 200 mg QD (atazanavir 400 mg QD)
↑1. 91
No significant effect on atazanavir concentrations was observed.
jingħata fl- istess ħin
Ketoconazole and itraconazole should be used cautiously with
(1. 16, 1. 43)
Itraconazole
(0. 93, 1. 20)
Itraconazole, like ketoconazole, is a potent inhibitor as well as a substrate of CYP3A4.
(1. 66, 2. 21)
REYATAZ/ ritonavir.
ma 'clarithromycin.
High doses of ketoconazole and
Il- mekkaniżmu ta 'interazzjoni ta' clarithromycin/ atazanavir huwa l- inibizzjoni ta 'CYP3A4.
7 Co-administered medicinal
Antifungali
Medicinal
Prodotti mediċinali mogħtija Prodott
concerning
t dwar l- għoti fl- istess ħin
co-administration
Itraconazole
Based on data obtained with other boosted PIs and ketoconazole, where ketoconazole AUC showed a 3-fold increase, REYATAZ/ ritonavir is expected to increase ketoconazole or itraconazole concentrations.
Fuq il- bażi ta 'dejta miksuba b' PIs oħra msaħħa u ketoconazole, fejn ketoconazole wera żieda ta' tliet darbiet, REYATAZ/ ritonavir huwa mistenni li jżid il- konċentrazzjonijiet ta 'ketoconazole jew itraconazole.
itraconazole (> 200 mg/ day) are not recommended.
rakkomandati dożi għoljin ta 'ketoconazole u itraconazole (> 200 mg/ kuljum).
Co-administration of REYATAZ/ ritonavir and voriconazole has not been studied.
L- għoti fl- istess ħin ta 'REYATAZ/ ritonavir ma' voriconazole ma ġiex studjat.
Co-administration of voriconazole and REYATAZ/ ritonavir is
L- għoti fl- istess ħin ta 'voriconazole u REYATAZ/ ritonavir
The effect of co-administration of oral voriconazole and low dose (100 mg) oral ritonavir was investigated in healthy volunteers.
L- effett ta 'l- għoti fl- istess ħin ta' voriconazole orali u doża baxxa (100 mg) ta 'ritonavir orali ġie studjat f' voluntiera b' saħħithom.
Low doses of ritonavir (100 mg BID) decreased the Cmax and AUC of voriconazole (90% CI) by an average of 24% (↓ 9% to ↓ 36%) and 39% (↓ 22% to ↓ 52%), respectively.
Dożi baxxi ta 'ritonavir (100 mg BID) naqqsu l- Cmax u l- AUC ta ’ voriconazole (90% CI) b' medja ta' 24% (↓9% għal ↓36%) u 39% (↓22% għal ↓52%), rispettivament.
Administration of voriconazole resulted in a minor decrease in steady state Cmax and AUC of ritonavir (90% CI) with an average of 24% (↓ 6% to ↓ 39%) and 14% (↓ 26% to ↑ 1%), respectively.
L- għoti ta 'voriconazole rriżulta fi tnaqqis żgħir fil- Cmax u l- AUC fissi ta' ritonavir (90% CI) b' medja ta '24% (↓6% għal ↓39%) u 14% (↓26% għal ↑1%), rispettivament.
not recommended unless an assessment of the benefit/ risk to the patient justifies the use of voriconazole (see section 4.4).
mhuwiex rakkomandat sakemm evalwazzjoni tal- benefiċċju/ riskju għall- pazjenti ma tkunx tiġġustifika l- użu ta ’ voriconazole (ara sezzjoni 4. 4).
Patients should be carefully monitored for adverse events and/ or loss of efficacy during the co-administration of voriconazole and REYATAZ/ ritonavir.
Il - pazjenti għandhom jiġu mmonitorjati b' attenzjoni għal episodji avversi u/ jew telf ta 'l- effikaċja waqt l- għoti ta' voriconazole u REYATAZ/ ritonavir.
Fluconazole 200 mg QD (atazanavir 300 mg and ritonavir 100 mg QD) Antimycobacterial
Fluconazole 200 mg QD (atazanavir 300 mg u ritonavir 100 mg QD) Antimikobatteriċi
Atazanavir and fluconazole concentrations were not significantly modified when REYATAZ/ ritonavir was co-administered with fluconazole.
Il- konċentrazzjonijiet ta 'atazanavir u fluconazole ma nbidlux b' mod sinifikanti meta REYATAZ/ ritonavir ingħata fl- istess ħin ma' fluconazole.
No dosage adjustments are needed for REYATAZ/ ritonavir and fluconazole.
M' hemmx bżonn ta 'aġġustamenti fid- doża għal REYATAZ/ ritonavir u fluconazole.
↑ 1.15 ↑ 1.34 ↑ 1.13
↑1. 15 ↑1. 34 ↑1. 13
A rifabutin dose
Huwa rakkomandat
atazanavir (0.98, 1.34) (1.14, 1.59) (0.68, 1.87)
atazanavir (0. 98, 1. 34) (1. 14, 1. 59) (0. 68, 1. 87)
reduction of up to 75% (eg, 150 mg every
tnaqqis fid- doża sa 75% (eż.
↑ 2.10 ↑ 1.18 ↑ 3.43 rifabutin
↑2. 10 ↑1. 18 ↑3. 43 rifabutin
other day or 3 times
fil- ġimgħa) meta
(atazanavir 600 mg QD) This is not the recommended therapeutic dose of atazanavir.
(atazanavir 600 mg QD) Din mhijiex id- doża
(1.57, 2.79) (0.94, 1.48) (1.98, 5.96) 25-O-desacetyl- ↑ 22.01* ↑ 8.20* ↑ 75.6* rifabutin (15.97, 30.34) (5.90, 11.40) (30.1, 190.0) * When compared to rifabutin 300 mg QD.
rifabutin (15. 97, 30. 34) (5. 90, 11. 40) (30. 1, 190. 0) * Meta mqabbel ma 'rifabutin 300 mg QD.
The mechanism of rifabutin and atazanavir interaction is CYP3A4 inhibition
Il- mekkaniżmu ta 'l- interazzjoni ta' rifabutin u atazanavir huwa l - inibizzjoni ta 'CYP3A4
No dose adjustment is needed for REYATAZ/ ritonavir.
M' hemmx bżonn ta 'aġġustament fid- doża għal REYATAZ/ ritonavir.
Rifampicin ACID REDUCING AGENTS H2-Receptor antagonists
Rifampicin SUSTANZI LI JNAQQSU L- AĊIDU Antagonisti tar- Riċettur H2
Rifampicin is a strong CYP3A4 inducer and has been shown to cause a 72% decrease in atazanavir AUC which can result in virological failure and resistance development.
Rifampicin huwa induttur ta ’ CYP3A4 qawwi u intwera li jikkawża tnaqqis ta ’ 72% fl- AUC ta ’ atazanavir li tista ’ tirriżulta f’ indeboliment viroloġiku u f’ reżistenza għall- iżvilupp.
During attempts to overcome the decreased exposure by increasing the dose of REYATAZ or other protease inhibitors with ritonavir, a high frequency of liver reactions was seen.
Matul it- tentattivi biex jingħeleb l- esponiment imnaqqas billi tiżdied id- doża ta ’ REYATAZ jew inibituri ta ’ protease oħrajn b’ ritonavir, intweriet frekwenza għolja ta ’ reazzjonijiet tal- fwied.
The combination of rifampicin and REYATAZ with concomitant low-dose ritonavir is contraindicated (see section 4.3).
Il- kombinazzjoni ta ’ rifampicin u REYATAZ ma ’ ritonavir ta ’ doża baxxa konkomittanti hija kontro- indikata (ara sezzjoni 4. 3).
Famotidine 40 mg BID
Famotidine 40 mg BID
↓ 0.82 ↓ 0.86 ↓ 0.72 atazanavir
↓ 0. 82 ↓0. 86 ↓0. 72
No dosage adjustment
M' hemmx bżonn ta '
(atazanavir 300 mg QD with ritonavir 100 mg QD)
atazanavir (atazanavir 300 mg QD ma ’
Therefore, the magnitude of this effect may be more pronounced.
(0. 79, 0. 94)
The mechanism of interaction is decreased solubility of atazanavir as intra- gastric pH increases with H2 blockers.
(0. 64, 0. 81)
REYATAZ 300 mg with ritonavir 100 mg once daily with food, 2 hours before and at least 10 hours
aġġustament fid- doża
co-administration
ritonavir 100 mg QD) Inibituri tal- proton pump
following the administration of an H2-receptor antagonist.
ta 'REYATAZ/ ritonavir meta jingħata ma' antagonist tar- riċettur H2 antagonist, kollha bħala doża waħda ta 'kuljum ma' l- ikel.
Proton pump inhibitors Omeprazole 40 mg QD
Omeprazole 40 mg QD
hr after
0. 39 0. 44 0. 35 sagħtejn wara (0. 35, 0. 45) (0. 38, 0. 51) (0. 29, 0. 41)
REYATAZ/ ritonavir
REYATAZ/ ritonavir
ritonavir 100 mg QD)
ritonavir 100 mg QD) Omeprazole 20 mg QD
omeprazole
omeprazole
If the
ma 'inibituri tal- proton pump mhuwiex rakkomandat.
combination of
Jekk il - kombinazzjoni ta '
↓ 0.69*
atazanavir (am): ↓0. 70 * ↓0. 69 * ↓0. 69 *
with a proton pump
REYATAZ/ ritonavir
ritonavir 100 mg QD)
ritonavir 100 mg QD) Antaċidi
The decrease in AUC, Cmax, and Cmin was not mitigated when an increased dose of REYATAZ/ ritonavir (400/ 100 mg once daily) was temporally separated from omeprazole by 12 hours.
siegħa wara (0. 57, 0. 86) (0. 58, 0. 83) (0. 54, 0. 88) omeprazaole * Meta mqabbel ma ’ atazanavir 300 mg QD ma ’ ritonavir 100 mg QD It- tnaqqis fl- AUC, Cmax, u Cmin ma ttaffiex meta doża akbar ta 'REYATAZ/ ritonavir (400/ 100 mg darba kuljum) ġiet separata fil- ħin minn omeprazole bi 12- il siegħa.
Although not studied, similar results are expected with other proton pump inhibitors.
Għalkemm mhux studjat, huma mistennija riżultati simili b’ inibituri oħra tal- proton pump.
This decrease in atazanavir exposure might negatively impact the efficacy of atazanavir.
Dan it - tnaqqis fl- esponiment ta 'atazanavir jista' jaffettwa b' mod negattiv l - effikaċja ta 'atazanavir.
The mechanism of interaction is decreased solubility of atazanavir as intra-gastric pH increases with proton pump inhibitors.
Il- mekkaniżmu ta 'interazzjoni huwa solubilità mnaqqsa billi l- pH intra- gastriku jiżdied b’ inibituri tal- proton pump.
recommended in combination with an increase in the dose of REYATAZ to 400 mg with 100 mg of ritonavir; doses of proton pump inhibitors comparable to omeprazole 20 mg should not be exceeded (see section 4.4).
ma 'inibitur tal- proton pump tkun ikkunsidrata bħala mhix evitabbli, huwa rakkomandat monitoraġġ mill- viċin flimkien ma' żieda fid - doża ta 'REYATAŻ għal 400 mg ma' 100 mg ta 'ritonavir; m' għandhomx jinqabżu dożi ta' inibituri tal - proton pump komparabbli għal omeprazole 20 mg (ara sezzjoni 4. 4).
Antacids and medicinal products containing buffers ANTICOAGULANTS
Antaċidi u prodotti mediċinali li fihom baffers ANTIKOAGULANTI
Reduced plasma concentrations of atazanavir may be the consequence of increased gastric pH if antacids, including buffered medicinal products, are administered with REYATAZ/ ritonavir.
Il- konċentrazzjonijiet imnaqqsa ta 'atazanavir fil- plasma jistgħu jkunu l - konsegwenza ta' żieda fil- pH gastriku jekk jiġu mogħtija antaċidi, inklużi prodotti mediċinali bafferjati, ma 'REYATAZ/ ritonavir.
REYATAZ/ ritonavir should be administered 2 hours before or 1 hour after antacids or buffered medicinal products.
REYATAZ/ ritonavir għandu jingħata sagħtejn qabel jew siegħa wara antaċidi jew prodotti mediċinali bafferjati.
Co-administration with REYATAZ/ ritonavir has the potential to produce a decrease or, less often, an increase in INR (International Normalised Ratio).
L- għoti fl- istess ħin ma 'REYATAZ/ ritonavir għandu l- potenzjal li jipproduċi tnaqqis jew, anqas sikwit, żieda fl- INR (Proporzjon Normalizzat Internazzjonali).
It is recommended that the INR be monitored carefully during treatment with REYATAZ/ ritonavir, especially when commencing therapy.
Huwa rakkomandat li l- INR jiġi mmonitorjat b' attenzjoni waqt trattament b' REYATAZ/ ritonavir - speċjalment fil- bidu tat- terapija.
ANTINEOPLASTICS AND IMMUNOSUPRESSANTS Antineoplastics Irinotecan Immunosuppressants
ANTINEOPLASTIĊI U IMMUNOSUPPRESSANTI Antineoplastiċi Irinotecan
Atazanavir inhibits UGT and may interfere with the metabolism of irinotecan, resulting in increased irinotecan toxicities.
Atazanavir jimpedixxi l- UGT u jista 'jinterferixxi mal- metaboliżmu ta' irinotecan, li jirriżulta f' effetti tossiċi miżjuda ta 'irinotecan.
Cyclosporin Tacrolimus Sirolimus CARDIOVASCULAR AGENTS Antiarrhythmics
Jekk REYATAZ/ ritonavir jingħata fl- istess ħin ma '
co-administration
Il- konċentrazzjonijiet ta 'dawn l- immunosuppressanti jistgħu jiżdiedu meta jingħataw fl- istess ħin ma' REYATAZ/ ritonavir minħabba l - inibizzjoni ta 'CYP3A4.
Calcium channel blockers
Amiodarone, Systemic lidocaine, Quinidine
contraindicated due to potential inhibition of CYP3A by REYATAZ/ ritonavir.
Il- mekkaniżmu ta ’ amiodarone jew l- interazzjoni sistemika ta ’ lidocaine/ atazanavir hija l- inibizzjoni ta 'CYP3A.
recommended when available.
Hija mitluba kawtela u huwa rakkomandat monitoraġġ tal - konċentrazzjoni terapewtika jekk ikun disponibbli.
The concomitant use of quinidine is contraindicated (see section 4.3).
L- użu konkomitanti ta 'quinidine huwa kontra - indikat (ara sezzjoni 4. 3).
Bepridil
Sustanzi li jimblukkaw il - kanali tal- kalċju Bepridil
REYATAZ/ ritonavir should not be used in combination with medicinal products that are substrates of CYP3A4 and have a narrow therapeutic index.
REYATAZ/ ritonavir m' għandux jintuża ma 'prodotti mediċinali li substrati ta' CYP3A4 u għandhom indiċi terapewtiku dejjaq.
Co-administration with bepridil is contraindicated (see section 4.3)
L- għoti fl- istess ħin ma 'bepridil huwa kontra- indikat (ara sezzjoni 4. 3)
↑ 2.25 ↑ 1.98 ↑ 2.42 diltiazem
↑2. 25 ↑1. 98 diltiazem
An initial dose
Huwa rakkomandat
(2.09, 2.41 (1.78, 2.19) (2.14, 2.73) desacetyl- ↑ 2.65 ↑ 2.72 ↑ 2.21 diltiazem (2.45, 2.87) (2.44, 3.03) (2.02, 2.42)
tnaqqis inizjali tad - doża ta 'diltiazem
reduction of diltiazem by 50% is recommended, with subsequent titration as
suċċessiva kif meħtieġ u monitoraġġ ta 'l- ECG
No significant effect on atazanavir concentrations was observed.
Ma ġie osservat ebda effett sinifikanti fuq il- konċentrazzjonijiet ta 'atazanavir.
There was an increase in the maximum PR interval compared to atazanavir alone.
Kien hemm żieda fl- intervall massimu ta 'PR meta mqabbel ma' atazanavir waħdu.
Co-administration of diltiazem and REYATAZ/ ritonavir has not been studied.
L- għoti fl- istess ħin ta 'diltiazem u REYATAZ/ ritonavir ma ġiex studjat.
The mechanism of diltiazem/ atazanavir interaction is CYP3A4 inhibition.
Il- mekkaniżmu ta 'interazzjoni ta' diltiazem/ atazanavir huwa l- inibizzjoni ta 'CYP3A4.
Verapamil CORTICOSTEROIDS
Verapamil KORTIKOSTEROJDI
Serum concentrations of verapamil may be increased by REYATAZ/ ritonavir due to CYP3A4 inhibition..
Il- konċentrazzjonijiet ta 'verapamil fis- serum jistgħu jiżdiedu b' REYATAZ/ ritonavir minħabba l- inibizzjoni ta' CYP3A4.
Caution should be exercised when verapamil is co-administered with REYATAZ/ ritonavir
Għandha tintuża kawtela meta verapamil jingħata fl - istess ħin ma 'REYATAZ/ ritonavir
Fluticasone propionate intranasal 50 µg 4 times daily for 7 days (ritonavir 100 mg capsules BID) ERECTILE DYSUNCTION PDE5 Inhibitors
Fluticasone propionate minn ġo l- imnieħer 50 µg 4 darbiet kuljum għal 7 ijiem (kapsuli ritonavir 100 mg BID)
The fluticasone propionate plasma levels increased significantly, whereas the intrinsic cortisol levels decreased by approximately 86% (90% confidence interval 82-89%) Greater effects may be expected when fluticasone propionate is inhaled.
Jistgħu jiġu mistennija livelli 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 metabolized via the P450 3A pathway, eg, budesonide.
Effetti kortikosterojdi sistemiċi fosthom is- sindrome ta 'Cushing u suppressjoni adrenali ġew irrappurtati f' pazjenti li rċevew ritonavir u ħadu man- nifs jew ingħataw mill- imnieħer fluticasone propionate; dan jista' jseħħ ukoll b' kortikosterojdi oħra metabolizzati permezz tal- mogħdija P450 3A, eż. budesonide.
The effects of high fluticasone systemic exposure on ritonavir plasma levels are yet unknown.
L- effetti ta 'esponiment sistemiku għoli għal fluticasone fuq il- livelli ta' ritonavir fil- plasma għadhom mhumiex magħrufa.
The mechanism of interaction is CYP3A4 inhibition.
Il - mekkaniżmu ta 'interazzjoni huwa l- inibizzjoni ta' CYP3A4.
Co-administration of REYATAZ/ ritonavir and these glucocorticoids is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects (see section 4.4).
L- għoti fl- istess ħin ta 'REYATAZ/ ritonavir u dawn il - glukokortikojdi mhuwiex rakkomandat sakemm il- benefiċċju potenzjali tat - trattament ma jkunx jegħleb ir- riskju ta' effetti sistemiċi mill - kortikosterojdi (ara sezzjoni 4. 4).
A 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 (eg, beclomethasone).
Għandu jiġi kkunsidrat tnaqqis fid- doża tal - glukokortikojd b' monitoraġġ mill- qrib
Medicinal
Prodotti mediċinali mogħtija
Cmin
Prodott AUC Cmax Cmin
co-administration
DISFUNZJONI TA 'L- EREZZJONI Inibituri PDE5 Sildenafil
This effect may be due to an induction of CYP3A4.
Sildenafil huwa metabolizzat minn CYP3A4.
There is a risk of loss of therapeutic effect and development of resistance (see section 4.3).
Il- mekkaniżmu ta 'l - interazzjoni ta' sildenafil/ atazanavir hija l- inibizzjoni ta 'CYP3A4.
with products containing St.
L- użu konkomitanti ta 'St.
John's wort is contraindicated.
Hemm riskju ta 'telf ta' l- effett terapewtiku u żvilupp ta 'reżistenza (ara sezzjoni 4. 3).
HORMONAL CONTRACEPTIVES
KONTRAĊETTIVI ORMONALI
Ethinyloestradiol 35 μ g + norethindrone (atazanavir 400
Ethinyloestradiol 35 μg + norethindrone (atazanavir 400 mg QD)
The co-administration of
L- għoti fl- istess ħin ta 'REYATAZ/ ritonavir u kontraċettivi orali
The concentration of oral contraceptives was increased due to UGT inhibition.
Il- konċentrazzjoni tal- kontraċettivi orali żdiedet minħabba inibizzjoni ta 'għandu jiġi evitat (ara UGT.
In contrast, ritonavir may decrease ethinyloestradiol concentrations.
B' kuntrast, ritonavir jista 'jnaqqas il- konċentrazzjonijiet ta' sezzjoni 4. 4). ethinyloestradiol.
The effects of co-administration of oral contraceptives and REYATAZ/ ritonavir have not been studied.
L- effetti ta 'l- għoti fl- istess ħin ta' Għandhom jiġu REYATAZ/ ritonavir ma ġewx studjati. kkunsidrati metodi alternattivi affidabbli ta 'konċentrazzjoni.
Simvastatin Lovastatin
SUSTANZI LI JBAXXU L- LIPIDI Inibituri ta 'HMG- CoA reductase Simvastatin Lovastatin
Simvastatin and lovastatin are highly dependent on CYP3A4 for their metabolism and co-administration with REYATAZ/ ritonavir may result in increased concentrations.
Simvastatin u lovastatin jiddependu ħafna fuq CYP3A4 għall - metaboliżmu tagħhom u l- għoti fl- istess ħin ma 'REYATAZ/ ritonavir jista' jirriżulta f' konċentrazzjonijiet miżjuda.
Co-administration of simvastatin or lovastatin with REYATAZ/ ritonavir is not recommended due to an increased risk of myopathy including rhabdomyolysis.
L- għoti fl- istess ħin ta 'simvastatin jew lovastatin ma' REYATAZ/ ritonavir mhuwiex rakkomandat minħabba riskju akbar ta 'mijopatija li tinkludi rabdomijolisi.
The use of another HMG- CoA reductase inhibitor which does not undergo metabolism by CYP3A such as pravastatin or fluvastatin is recommended.
Huwa rakkomandat li jintuża inibitur HMG- CoA reductase ieħor li mhuwiex metabolizzat minn CYP3A bħal pravastatin jew fluvastatin.
Atorvastatin OPIOIDS
Atorvastatin OPJOJDI
The risk of myopathy including rhabdomyolysis may also be increased with atorvastatin, which is also metabolised by CYP3A4.
Ir- riskju ta 'mijopatija li tinkludi rabdomijolisi jista' jiżdied b' atorvastatin, li wkoll jiġi metabolizzat minn CYP3A4.
Caution should be exercised.
Għandha tintuża kawtela.
Buprenorphine, QD, stable maintenance dose,
Buprenorphine, QD, doża ta 'manteniment stabbli, (atazanavir 300 mg QD ma' ritonavir 100 mg QD)
buprenorphine ↑ 1.67 ↑ 1.37 ↑ 1.69
buprenorphine ↑1. 67 ↑1. 37 norbuprenorphine ↑2. 05 ↑1. 61
Co-administration warrants
↑1. 69 ↑2. 01
A dose reduction of buprenorphine may be considered
L- għoti fl- istess ħin jitlob monitoraġġ kliniku għal effetti ta 'sedazzjoni u
co-administration
M' hemmx bżonn ta 'aġġustament fid- doża jekk il- methadone jingħata fl- istess ħin ma' REYATAZ u ritonavir.
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 REYATAZ jingħata fl - istess ħin ma 'midazolam parenterali, dan għandu jsir f' taqsima tal- kura intensiva (ICU) jew ambjent simili li jiżgura monitoraġġ kliniku mill- viċin u ġestjoni medika xierqa f' każ ta' depressjoni respiratorja u/ jew sedazzjoni twila.
Dosage adjustment for midazolam should be considered, especially if more than a single dose of midazolam is administered.
Għandu jiġi kkunsidrat aġġustament fid- doża għal midazolam, speċjalment jekk jingħataw aktar minn doża waħda ta 'midazolam.
There are no adequate data from the use of atazanavir in pregnant women.
M' hemmx biżżejjed tagħrif dwar l- użu ta 'atazanavir f' nisa tqal.
Studies in animals have not shown evidence of selective developmental toxicity or effects on reproductive function and fertility (see section 5.3).
Skond studji fuq annimali ma deherx li kien hemm tossiċità selettiva fl- iżvilupp jew effetti fil- funzjoni riproduttiva u l- fertilità (ara sezzjoni 5. 3).
REYATAZ should be used during pregnancy only if the potential benefit justifies the potential risk.
REYATAZ għandu jintuża f’ nisa tqal biss jekk il- benefiċċju mistenni jiġġustifika r- riskju possibbli.
It is not known whether REYATAZ administered to the mother during pregnancy will exacerbate physiological hyperbilirubinaemia and lead to kernicterus in neonates and infants.
Mhux magħruf jekk meta REYATAZ jingħata lil mara tqila, dan iżidx l- iperbilirubinemja u jwassalx għal kernicterus fi trabi tat- twelid u fi tfal żgħar.
In the prepartum period, additional monitoring and alternative therapy to REYATAZ should be considered.
Matul iż- żmien ta ’ qabel it- twelid, għandu jsir aktar kontroll u għandha tinstab terapija alternattiva għal REYATAZ.
It is not known whether atazanavir is excreted in human milk.
Mhux magħruf jekk atazanavir joħroġx fil- ħalib tal- bniedem.
Studies in rats have demonstrated that atazanavir is excreted in the milk.
Minn studji li saru fil- firien sar magħruf li atazanavir joħroġ fil- ħalib.
It is therefore recommended that mothers being treated with REYATAZ not breast-feed their infants.
Għalhekk huwa rrakkomandat li nisa li jkunu jieħdu REYATAZ m’ għandhomx ireddgħu.
As a general rule, it is recommended that HIV infected women not breast-feed their infants in order to avoid transmission of HIV.
Bħala regola ġenerali, nisa infettati bl- HIV m’ għandhomx ireddgħu lit- tarbija biex b’ hekk jevitaw li jgħaddu l- HIV lit- tarbija.
Patients should be informed that dizziness has been reported during treatment with regimens containing REYATAZ (see section 4.8).
Il- pazjenti għandhom ikunu nfurmati li ġie rrappurtat sturdament waqt li wieħed kien qed jieħdu kura b' REYATAZ (ara sezzjoni 4. 8).
REYATAZ has been evaluated for safety in combination therapy with other antiretroviral medicinal products in controlled clinical trials in 1,806 adult patients receiving REYATAZ 400 mg once daily (1,151 patients, 52 weeks median duration and 152 weeks maximum duration) or REYATAZ 300 mg with ritonavir 100 mg once daily (655 patients, 48 weeks median duration and 101 weeks maximum duration).
REYATAZ ġie evalwat għas- sigurtà bħala terapija mogħtija flimkien ma ’ prodotti mediċinali antiretrovirali oħra fi provi kliniċi kkontrollati f’ 1, 806 pazjenti adulti li ħadu REYATAZ 400 mg darba kuljum (1, 151 pazjent, b’ tul ta ’ żmien medjan ta ’ 52 ġimgħa u b’ tul ta ’ żmien massimu ta ’ 152 ġimgħa) jew REYATAZ 300 mg b’ ritonavir 100 mg darba kuljum (655 pazjent, tul ta ’ żmien medjan ta ’ 48 ġimgħa u b’ tul ta ’ żmien medjan ta ’ 101 ġimgħa).
Adverse reactions were consistent between patients who received REYATAZ 400 mg once daily and patients who received REYATAZ 300 mg with ritonavir 100 mg once daily, except that jaundice and elevated total bilirubin levels were reported more frequently with REYATAZ plus ritonavir.
Ir- reazzjonijiet avversi kienu konsistenti bejn pazjenti li ħadu REYATAZ 400 mg u pazjenti li ħadu REYATAZ 300 mg ma ’ ritonavir 100 mg darba kuljum, ħlief għas- suffejra u livelli għolja ta ’ bilirubin li ġew irrapportati aktar ta ’ spiss f’ pazjenti li ħadu REYATAZ b' ritonavir.
Among patients who received REYATAZ 400 mg once daily or REYATAZ 300 mg with ritonavir 100 mg once daily, the only adverse reactions of any severity reported very commonly with at least a possible relationship to regimens containing REYATAZ and one or more NRTIs were nausea (20%), diarrhoea (10%), and jaundice (12%).
Fost il- pazjenti li ħadu REYATAZ 400 mg darba kuljum jew REYATAZ 300 mg ma ’ ritonavir 100 mg darba kuljum, l- uniċi reazzjonijiet avversi ta ’ xi severità li ġew irrappurtati b' mod komuni ħafna li għall- inqas kien possibli li kellhom x’ jaqsmu mat- terapija li kienet tinkludi REYATAZ u wieħed jew iktar NRTIs kienu nawsja (20%), dijarrea (10%) u suffejra (12%).
Among patients receiving REYATAZ 300 mg with ritonavir
Fost il- pazjenti li ħadu REYATAZ 300 mg ma ’ ritonavir 100 mg, il- frekwenza tas- suffejra kienet ta ’ 17%.
In the majority of cases, jaundice was reported within a few days to a few months after the initiation of treatment (see section 4.4).
Fil- maġġoranza tal- każijiet, is- suffejra kienet irrapurtata fi ftit jiem sa ftit xhur minn meta nbdiet il- kura (ara sezzjoni 4. 4).
Combination antiretroviral therapy has been associated with redistribution of body fat (lipodystrophy) in HIV patients, including loss of peripheral and facial subcutaneous fat, increased intra-abdominal and visceral fat, breast hypertrophy, and dorsocervical fat accumulation (buffalo hump).
Terapija kombinata antiretrovirali ġiet assoċjata ma ’ ridistribuzzjoni tax- xaħam fil- ġisem (lipodostrofija) f’ pazjenti bl- HIV, inkluż telf ta ’ xaħam periferali u subkutanju fil- wiċċ, żieda fix - xaħam intra- addome jew vixxerali, ipertrofija fis- sider, u akkumulazzjoni ta ’ xaħam fid- dorso - ċervikali (buffalo hump).
Combination antiretroviral therapy has been associated with metabolic abnormalities such as hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperglycaemia, and hyperlactataemia (see sections 4.4 and 5.1).
Terapija kombinata antiretrovirali ġiet assoċjata ma ’ anormalitajiet metaboliċi bħal ipertrigliċeridemija, reżistenza għall- insulina, ipergliċemija, u iperlaktemija (ara sezzjonijiet 4. 4 u 5. 1).
Adult patients The following adverse reactions of moderate intensity or greater with at least a possible relationship to regimens containing REYATAZ and one or more NRTIs have also been reported.
Pazjenti Adulti Dawn ir- reazzjonijiet avversi ta ’ intesità moderata jew iktar qawwija li għall- inqas kellhom xi possibiltà ta 'relazzjoni mal- kura li kien fiha REYATAZ u wieħed jew iżjed mill- NRTIs, ġew irrapportati.
The frequency of adverse reactions listed below is defined using the following convention: very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10), uncommon (≥ 1/ 1,000 to < 1/ 100), rare (≥ 1/ 10,000 to < 1/ 1,000), or very rare (< 1/ 10,000).
Il- frekwenza ta ’ l- effetti avversi msemmija hawn taħt hija definita bl- użu ta ’ din il - konvenzjoni: komuni ħafna (≥ 1/ 10), komuni (≥ 1/ 100 sa < 1/ 10), mhux komuni (≥ 1/ 1, 000 sa < 1/ 100), rari (≥ 1/ 10, 000 sa < 1/ 1, 000) jew rari ħafna (< 1/ 10, 000).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
F’ kull sezzjoni ta ’ frekwenza, l - effetti mhux mixtieqa għandhom jitniżżlu skond is- serjetà tagħhom.
rare: oedema, palpitation
L- effetti li huma aktar serji għandhom jitniżżlu l- ewwel, segwiti minn dawk inqas serji.
Nervous system disorders:
rari: edema, palpitazzjoni Disturbi fil- qalb:
common: headache; uncommon: peripheral neuropathy, syncope, amnesia, dizziness, somnolence, dysgeusia
komuni: uġigħ ta ’ ras; Disturbi fis- sistema nervuża: mhux komuni: newropatija periferali, sinkope, amnesija, sturdament, ngħas, togħma ħażina
common: ocular icterus
komuni: icterus fl- għajnejn Disturbi fl- għajnejn:
Respiratory, thoracic and mediastinal disorders:
mhux komuni: dispneja Disturbi respiratorji, toraċiċi u medjastinali:
common: vomiting, diarrhoea, abdominal pain, nausea, dyspepsia; uncommon: pancreatitis, gastritis, abdominal distension, stomatitis aphthous, flatulence, dry mouth
komuni: rimettar, dijarea, uġigħ addominali, dardir, Disturbi gastro- intestinali: dispepsja; mhux komuni: pankreatite, gastrite, distensjoni
Renal and urinary disorders:
13 addominali, stomatite aphthous, gass fl- istonku, ħalq xott
uncommon: nephrolithiasis, hematuria, proteinuria, pollakiuria; rare: kidney pain
mhux komuni: nefrolitjasi, ħematurja, proteinurja, Disturbi fil- kliewi u fis- sistema pollakurja; urinarja: rari: uġigħ fil- kliewi
common: rash; uncommon: urticaria, alopecia, pruritus; rare: vesiculobullous rash, eczema, vasodilatation
komuni: raxx; Disturbi fil- ġilda u fit- tessuti ta 'mhux komuni: urtikarja, alopeċja, ħakk; taħt il- ġilda: rari: raxx bl- infafet, ekżema, vażodilazzjoni
uncommon: muscle atrophy, arthralgia, myalgia; rare: myopathy
mhux komuni: atrofija tal- muskoli, artralġja, uġigħ fil - Disturbi muskolu- skeltrali u tal - muskoli; connective tissue: rari: mijopatija
uncommon: weight decreased, weight gain, anorexia, appetite increased
mhux komuni: tnaqqis fil- piż, żieda fil- piż, anoreksja, Disturbi fil- metaboliżmu u n - żieda fl- aptit nutrizzjoni:
uncommon: hypertension
mhux komuni: pressjoni għolja Disturbi vaskulari:
common: lipodystrophy syndrome, fatigue; uncommon: chest pain, malaise, pyrexia, asthenia; rare: gait disturbance
komuni: sindrome tal- lipodistrofija, għeja; Disturbi ġenerali u kundizzjonijiet mhux komuni: uġigħ fis- sider, telqa, deni, astenja; ta 'mnejn jingħata: rari: disturb fil- mixja
uncommon: hypersensitivity
mhux komuni: sensittività eċċessiva Disturbi fis- sistema immuni:
common: jaundice; uncommon: hepatitis; rare: hepatosplenomegaly
komuni: suffejra; Disturbi fil- fwied u fil- marrara: mhux komuni: epatite; rari: epatosplenomagalija
Reproductive system and breast disorders:
mhux komuni: ginekomastja Disturbi fis- sistema riproduttiva u fis- sider:
uncommon: depression, disorientation, anxiety, insomnia, sleep disorder, abnormal dream
mhux komuni: depressjoni, diżorjentament, ansjetà, Disturbi psikjatriċi: nuqqas ta 'rqad, disturb fl- irqad, ħolm abnormali
In HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise (see section 4.4).
F' pazjenti infettati bl- HIV b' defiċjenza gravi ta 'immunità fl- istess żmien li bdew taħlita ta' terapija antiretrovirali (CART), tista 'tinħoloq reazzjoni ta' infjammazzjoni għall- infezzjonijiet bla sintomi jew dawk opportunistiċi residwali (ara sezzjoni 4. 4).
Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to combination antiretroviral therapy (CART).
Każijiet ta 'ostjonekrosi ġew irrappurtati, b' mod partikulari f' pazjenti li ġeneralment hu magħruf li għandhom fatturi ta' riskju, marda avvanzata ta 'l- HIV jew espożizzjoni fit- tul għat - taħlita ta' terapija antiretrovirali (CART).
The frequency of this is unknown (see section 4.4).
Il- frekwenza ta 'dawn mhix magħrufa (ara sezzjoni 4. 4).
Laboratory abnormalities The most frequently reported laboratory abnormality in patients receiving regimens containing REYATAZ and one or more NRTIs was elevated total bilirubin reported predominantly as elevated indirect [unconjugated] bilirubin (84% Grade 1, 2, 3, or 4).
Anormalitajiet tal- laboratorju L- anormalità tal- laboratorju li l- aktar li ġiet irrapportata f’ pazjenti b' kura bi REYATAZ u NRTI wieħed jew iżjed kienet żieda ta ’ bilirubin totali rrapportata predominantament bħala bilirubin għoli indirett [mhux konjugat] (84% grad 1, 2, 3 jew 4).
Grade 3 or 4 elevation of total bilirubin was noted in 35% (5% Grade 4).
Żieda ta ’ bilirubin totali ta ’ grad 3 jew 4 ġiet innotata f’ 35% (5% Grad 4).
Among experienced patients treated with REYATAZ 300 mg once daily with 100 mg ritonavir once daily for a median duration of 95 weeks, 53% had Grade 3-4 total bilirubin elevations.
Fost il- pazjenti li kienu rċevew il- kura, ikkurati bi REYATAZ 300 mg darba kuljum ma '100 mg ritonavir darba kuljum għal żmien medju ta' 95 ġimgħa, 53% kellhom żidiet totali ta 'bilirubin ta' Grad 3- 4.
Among naive patients treated with REYATAZ 300 mg once daily with 100 mg ritonavir once daily for a median duration of 48 weeks, 39% had Grade 3-4 total bilirubin elevations (see section 4.4).
Fost pazjenti li qatt ma kienu ħadu l- kura qabel, ikkurati b’ REYATAZ 300 mg darba kuljum b’ 100 mg ta ’ ritonavir darba kuljum għal perjodu ta ’ żmien medju ta ’ 48 ġimgħa, 39% kellhom żieda fil- bilirubin totali ta ’ Grad 3- 4 (ara sezzjoni 4. 4).
Other marked clinical laboratory abnormalities (Grade 3 or 4) reported in ≥ 2% of patients receiving regimens containing REYATAZ and one or more NRTIs included: elevated creatine kinase (7%), elevated alanine aminotransferase/ serum glutamic-pyruvic transaminase (ALT/ SGPT) (4%), low neutrophils (4%), elevated aspartate aminotransferase/ serum glutamic-oxaloacetic transaminase (AST/ SGOT) (3%), and elevated lipase (2%).
Anormalitajiet oħra tal- laboratorju (Grad 3 jew 4) li ġew irrapportati f’ ≥ 2% tal- pazjenti li jirċievu l - kura bi REYATAZ flimkien ma ’ NRTI wieħed jew iżjed inkludew: kreatina kinasi elevata (7%), serum aminotransferasi/ glutamikpiruvik transaminasi elevata (ALT/ SGPT) (4%), newtrofili baxxi
One percent of patients treated with REYATAZ experienced concurrent Grade 3-4 ALT/ AST and Grade 3-4 total bilirubin elevations.
Wieħed fil- mija tal- pazjenti taħt il- kura b' REYATAZ kellhom fl- istess ħin ALT/ AST Grad 3- 4 u bilirubin totali ta ’ Grad 3- 4 elevati.
Patients co-infected with hepatitis B and/ or hepatitis C virus Among 1,151 patients receiving atazanavir 400 mg once daily, 177 patients were co-infected with chronic hepatitis B or C, and among 655 patients receiving atazanavir 300 mg once daily with ritonavir 100 mg once daily, 97 patients were co-infected with chronic hepatitis B or C.
Pazjenti infettati flimkien bil- virus ta 'l- epatite B u/ jew ta' l- epatite Ċ Fost l- 1, 151 pazjent li ħadu atazanavir 400 mg darba kuljum, 177 pazjent kienu infettati wkoll b’ epatite kronika B jew Ċ, u fost 655 pazjent li ħadu atazanavir 300 mg darba kuljum ma ’ ritonavir 100 mg darba kuljum, 97 pazjent ġew infettati wkoll b’ epatite kronika B jew Ċ.
Co-infected patients were more likely to have baseline hepatic transaminase elevations than those without chronic viral hepatitis.
Il- pazjenti nfettati biż - żewġ tipi ta ’ epatite flimkien għandhom aktar ċans li jkollhom livelli ta ’ linja bażi ta 'transaminasi epatika elevati minn dawk li ma kellhomx epatite kronika virali.
No differences in frequency of bilirubin elevations were observed between these patients and those without viral hepatitis.
Ma kienx hemm differenza fil - frekwenza tal- livelli elevati ta ’ bilirubin bejn dawn il- pazjenti u dawk li ma kellhomx epatite virali.
The frequency of treatment emergent hepatitis or transaminase elevations in co-infected patients was comparable between REYATAZ and comparator regimens (see section 4.4).
Il - frekwenza ta ’ epatite li tirriżulta mill- kura jew żieda ta ’ transaminasi f’ pazjenti ko- infettati kienet taqbel meta l- kura bi REYATAZ tqabblet ma ’ kura simili (ara sezzjoni 4. 4).
Postmarketing experience There have been postmarketing reports of unknown frequency for torsades de pointes, QTc prolongation, diabetes mellitus, hyperglycaemia, nephrolithiasis, and gallbladder disorders including cholelithiasis, cholecystitis, and cholestasis.
Esperjenza wara t- tqegħid fis- suq Wara t- tqegħid fis- suq, kien hemm rapporti ta 'frekwenza mhux magħrufa għal torsades de pointes, titwil tal- QTc, dijabete mellitus, ipergliċemija, nefrolitjażi, u disturbi fil- musrana inkluż kolelitjażi, koleċistite, u kolestażiu ta' ipergliċemija.
Human experience of acute overdose with REYATAZ is limited.
L- esperjenza ta ’ doża eċċessiva akuta fil- bniedem hija limitata.
At high doses that lead to
Voluntieri f’ saħħithom ħadu doża waħda sa 1, 200 mg mingħajr ma kellhom effetti sintomatiċi mhux mixtieqa.
14 high drug exposures, jaundice due to indirect (unconjugated) hyperbilirubinaemia (without associated liver function test changes) or PR interval prolongations may be observed (see sections 4.4 and 4.8).
B’ dożi għoljin li jwasslu għal riskju għoli għall- mediċina, ġiet innotata suffejra minħabba iperbilirubinemja indiretta (mhux konjugata) (mhux konnessa ma ’ tibdil fit- test tal- funzjoni tal- fwied) jew titwil ta ’ l- intervall PR (ara sezzjonijiet 4. 4. or 4. 8).
Treatment of overdose with REYATAZ should consist of general supportive measures, including monitoring of vital signs and electrocardiogram (ECG), and observations of the patient's clinical status.
Il- kura għal doża eċċessiva ta ’ REYATAZ għandha tkun magħmula minn kull mezz ta ’ għajnuna, inkluż il- monitoraġġ ta ’ sinjali vitali u elettrokardjogramm (ECG), u osservazzjonijiet tal- kondizzjoni klinika tal- pazjent.
If indicated, elimination of unabsorbed atazanavir should be achieved by emesis or gastric lavage.
Jekk indikat, atazanavir mhux assorbit għandu jitneħħa billi l- pazjent jiġi mġiegħel jirremetti jew b’ tindifa gastrika.
Administration of activated charcoal may also be used to aid removal of unabsorbed drug.
Jista ’ jintuża wkoll faħam attivat biex igħin fit- tneħħija tal- mediċina mhux assorbita.
There is no specific antidote for overdose with REYATAZ.
M’ hemmx antidot speċifiku għal doża eċċessiva ta ’ REYATAZ.
Since atazanavir is extensively metabolised by the liver and is highly protein bound, dialysis is unlikely to be beneficial in significant removal of this medicinal product.
Billi atazanavir huwa metabolizzat b’ mod estensiv fil- fwied u jeħel ħafna mal- proteini tad- demm, aktarx li dijalisi ma tkunx ta ’ benefiċċju b’ mod sinifikanti biex tneħħi din il- mediċina.
Pharmacotherapeutic group: protease inhibitor, ATC code:
Kategorija farmakoterapewtika: inibitur tal- proteasi, Kodiċi ATC:
Mechanism of action: atazanavir is an azapeptide HIV-1 protease inhibitor (PI).
Kif jaħdem: atazanavir huwa azapeptide HIV- 1 protease inhibitor (PI).
The compound selectively inhibits the virus-specific processing of viral Gag-Pol proteins in HIV-1 infected cells, thus preventing formation of mature virions and infection of other cells.
Is- sustanza tinibixxi b’ mod selettiv il- proċessar speċifiku għall- virus tal- proteini virali Gag- Pol fiċ- ċelluli infettati bl- HIV- 1, b’ hekk ifixkel il- formazzjoni ta ’ virjoli maturi u l- infezzjoni ta ’ ċelluli oħra.
Antiviral activity in vitro: atazanavir exhibits anti-HIV-1 activity (EC50 of 2 to 5 nM) in the absence of human serum against a variety of laboratory and clinical HIV isolates.
Attività antivirali in vitro: atazanavir jesibixxi attività anti- HIV- 1 (EC50 ta ’ 2 sa 5nM) fin- nuqqas ta ’ serum uman kontra varjetà ta ’ iżolati tal- HIV tal- laboratorju u kliniċi.
Atazanavir has activity against HIV-1 Group M subtype viruses A, B, C, D, AE, AG, F, G, and J isolates in cell culture.
Atazanavir għandu attività kontra iżolati A, B, C, D, AE, AG, F, G, u J ta ’ virusijiet ta ’ sottotip ta ’ Grupp M tal- HIV- 1 f’ kultura ta ’ ċelloli.
Atazanavir has activity against HIV-2 isolates (EC50 of 1.9 to 32 nM).
Atazanavir għandu attività kontra iżolati tal- HIV- 2 (EC50 of 1. 9 sa 32 nM).
Combinations of atazanavir with stavudine, didanosine, lamivudine, zidovudine, nelfinavir, indinavir, ritonavir, saquinavir, amprenavir, did not result in antagonistic anti-HIV activity or enhanced cytotoxic effects at the highest concentrations used for antiviral evaluation.
Terapija kombinata flimkien ta ’ atazanavir ma ’ stavudine, didanosine, lamivudine, zidovudine, nelfinavir, indinavir, ritonavir, saquinavir, amprenavir ma rriżultatx f’ attività antagonistika anti- HIV u lanqas ma żiedet l- effetti ċitotossiċi għall- ogħla livelli ta ’ konċentrazzjoni użata f’ valutazzjoni antivirali.
Resistance Antiretroviral treatment naive patients In antiretroviral treatment naive patients, the I50L substitution, sometimes in combination with an A71V change, is the signature resistance substitution for atazanavir.
15 Pazjenti li qatt qabel ma ħadu kura antiretroviraliF’ pazjenti li qatt qabel ma ħadu kura antiretrovirali, is- sostituzzjoni I50L, kultant flimkien ma ’ bidla fl- A71V, hija sostituzzjoni ta ’ reżistenza firmatarja għal atazanavir.
An atazanavir resistance phenotype is expressed in all recombinant viral clones containing the I50L substitution in a variety of genetic backgrounds.
Il- fenotip ta ’ reżistenza ta 'atazanavir jidher fil- kloni virali kollha rikombinati li għandhom is- sostituzzjoni ta' I50L f' firxa ta 'sfondi ġenetiċi.
Resistance levels ranged from 3.5- to 29-fold.
Il- livelli ta ’ reżistenza virali jvarjaw minn 3. 5 għal 29 drabi.
There was no evidence of cross-resistance between atazanavir and amprenavir, with the presence of the I50L and I50V substitutions yielding selective resistance to atazanavir and amprenavir, respectively.
Ma kienx hemm evidenza ta 'inkroċju ta ’ reżistenza bejn atazanavir u amprenavir, bil- preżenza ta' sostituzzjonijiet I50L u 150V li jagħtu reżistenza selettiva lil atazanavir u amprenavir, rispettivament.
The N88S substitution has been rarely observed in patients with virologic failure on atazanavir treatment.
Is- sostituzzjoni ta ’ N88S rari ġiet osservata f’ pazjenti b’ indeboliment viroloġiku malli tingħata kura b’ atazanavir.
While it may contribute to decreased susceptibility to atazanavir when it occurs with other protease substitutions, in clinical studies N88S by itself does not lead to phenotypic resistance to atazanavir or have a consistent impact on clinical efficacy.
Filwaqt li din tista ’ tikkontribiwxxi għal suxxettibbiltà mnaqqsa għal atazanavir meta jseħħ ma ’ sostituzzjonijiet ta ’ protease oħrajn, fi studji kliniċi, N88S waħdu ma jwassalx għal reżistenza fenotipika għal atazanavir jew ikollu impatt konsistenti fuq l - effikaċja klinika.
Antiretroviral treatment experienced patients In antiretroviral treatment experienced patients, 100 isolates from patients designated as virological failures on therapy that included either atazanavir, atazanavir + ritonavir, or atazanavir + saquinavir were determined to have developed resistance to atazanavir.
Pazjenti li kienu għaddew minn kura antiretrovirali F' pazjenti li kienu għaddew minn kura antiretrovirali, ġew stabbiliti 100 iżolati minn pazjenti nnominati bħala fallimenti viroloġiċi fuq kura li kienet tinkludi jew atazanavir, atazanavir + ritonavir, jew atazanavir + saquinavir li żviluppaw reżistenza għal atazanavir.
Of the 60 isolates from patients treated with either atazanavir or atazanavir + ritonavir, 18 (30%) displayed the I50L phenotype previously described in naive patients.
Mis- 60 iżolat mill- pazjenti kkurati jew b' atazanavir jew b' atazanavir + ritonavir, 18 (30%) urew il- fenotip ta 'I50L li qabel kien muri f' pazjenti li qatt qabel ma ħadu kura antiretrovirali.
The resistance in antiretroviral treatment experienced patients mainly occurs by accumulation of the primary and secondary resistance substitutions described previously to be involved in protease inhibitor resistance.
Ir- reżistenza f’ pazjenti li diġà ħadu kura antiretrovirali tiġri l- aktar minħabba akkumulazzjoni tas- sostituzzjonijiet għar- reżistenza primarja u sekondarja kif diġà spjegati li kienu involuti fir- reżistenza għall- inibituri ta 'proteasi.
These isolates developed higher levels of resistance to the other protease inhibitors.
Dawn l- iżolati żviluppaw livelli ogħla ta ’ reżistenza għal inibituri ta 'proteasi oħra