natgillin/translations-raw huggingface dataset:
By as-treated analysis, excluding missing values, the proportions of patients with HIV RNA < 400 copies/ ml (< 50 copies/ ml) in the REYATAZ + ritonavir arm and the lopinavir + ritonavir arm were 55% (40%) and 56% (46%), respectively.
Po analizi kot- so- bili- zdravljeni (z izključitvijo manjkajočih vrednosti) je bil delež bolnikov s HIV RNA < 400 kopij/ ml (< 50 kopij/ ml) v kraku z zdravilom REYATAZ + ritonavirjem 55% (40%) in v kraku z lopinavirjem + ritonavirjem 56% (46%).
The mean increases from baseline in CD4 cell count were 110 cells/ mm3 and 121 cells/ mm3 in the REYATAZ + ritonavir and lopinavir + ritonavir arms, respectively.
Povprečen porast števila celic CD4 od izhodišča je bil v kraku z zdravilom REYATAZ + ritonavirjem 110 celic/ mm3 in v kraku z lopinavirjem + ritonavirjem 121 celic/ mm3.
Analyses of data through 96 weeks of treatment demonstrated durability of antiviral activity.
Analize podatkov do 96 tednov zdravljenja so pokazale trajnost protivirusnega delovanja.
Mean HIV RNA changes from baseline at Week 96 (-2.29 log10 copies/ ml for REYATAZ + ritonavir and -2.08 log10 copies/ ml for lopinavir + ritonavir, time-averaged difference of 0.14, 97.5% confidence interval [-0.13, 0.41]) met criteria for non-inferiority based on observed cases.
Povprečne spremembe HIV RNA od izhodišča do 96. tedna (- 2, 29 log10 kopij/ ml za REYATAZ + ritonavir in - 2, 08 log10 kopij/ ml za lopinavir + ritonavir, časovno povprečna razlika 0, 14, 97, 5% interval zaupanja [- 0, 13, 0, 41]) so zadostile merilom neinferiornosti na podlagi opazovanih primerov.
The proportions of patients with HIV RNA < 400 copies/ ml (< 50 copies/ ml) for REYATAZ + ritonavir were 43% (32%) and for
Delež bolnikov s HIV RNA < 400 kopij/ ml (< 50 kopij/ ml) je bil za REYATAZ + ritonavir 43% (32%) in za lopinavir + ritonavir 46% (35%).
Patients completing treatment while in response after 48 weeks were censored.
Bolniki, ki so dokončali zdravljenje med obdobjem trajajočega odziva nanj po 48 tednih, so bili obravnavani kot krnjeni.
By as-treated analysis, excluding missing values, the proportions of patients with HIV RNA < 400 copies/ ml (< 50 copies/ ml) for REYATAZ + ritonavir were 84% (72%) and for lopinavir + ritonavir were 82% (72%).
Z analizo "kot so bili zdravljeni" in ob izključitvi manjkajočih vrednosti, je bil delež bolnikov s HIV RNA < 400 kopij/ ml (< 50 kopij/ ml) za REYATAZ + ritonavir 84% (72%) in za lopinavir + ritonavir 82% (72%).
It is important to note that at time of the 96-week analysis, 48% of patients overall remained on study.
Omeniti je treba, da je bilo v študiji v času analize po 96 tednih v celoti še 48% bolnikov.
Through 48 weeks of treatment, two types of analyses were performed based on baseline genotypic mutations.
Med 48 tedni zdravljenja sta bili narejeni dve vrsti analiz na podlagi izhodiščnih genotipskih mutacij.
10, 20, 24, 32, 33, 36, 46, 48, 50, 54, 63, 71, 73, 82, 84 and 90.
Prva je obsegala ugotavljanje sprememb HIV RNA od izhodišča v podskupini bolnikov z < ali ≥ 4 mutacijami iz skupine mutacij 10, 20, 24, 32, 33, 36, 46, 48, 50, 54, 63, 71, 73, 82, 84 in 90.
10, 46, 54, 82, 84, 90.
Druga je obsegala ugotavljanje sprememb HIV RNA od izhodišča v podskupini bolnikov z < ali ≥ 4 mutacijami iz bolj specifične skupine mutacij 10, 46, 54, 82, 84, 90.
In the analysis performed for patients with ≥ 4 protease gene mutations among the following set of mutations 10, 20, 24, 32, 33, 36, 46, 48, 50, 54, 63, 71, 73, 82, 84 and 90, the results significantly favoured the lopinavir + ritonavir arm.
Pri bolnikih, ki so imeli ≥ 4 mutacije proteaznega gena iz skupine mutacij 10, 20, 24, 32, 33, 36, 46, 48, 50, 54, 63, 71, 73, 82, 84 in 90, so bili rezultati analize značilno v prid kraku lopinavir + ritonavir.
There were too few patients with ≥ 4 of the second more specific set of mutations (i. e.
Bolnikov z ≥ 4 mutacijami iz druge, bolj specifične skupine mutacij (tj.
10, 46, 54, 82, 84, 90) to assess the comparability of the REYATAZ + ritonavir and lopinavir + ritonavir regimens, but reduced virologic activity may be anticipated among patients with this resistance profile.
10, 46, 54, 82, 84, 90) je bilo za oceno primerljivosti shem REYATAZ + ritonavir in lopinavir + ritonavir premalo, vendar je mogoče pri bolnikih s takšnim profilom odpornosti pričakovati manjšo virološko aktivnost.
5.2 Pharmacokinetic properties
18 5. 2 Farmakokinetične lastnosti
The pharmacokinetics of atazanavir were evaluated in healthy adult volunteers and in HIV-infected patients; significant differences were observed between the two groups.
Med skupinama so opazili pomembne razlike.
In healthy subjects, the AUC of atazanavir from the capsules and oral powder were similar.
Pri zdravih preiskovancih je bila AUC atazanavirja v kapsulah in peroralnem prašku enaka.
Absorption: in HIV-infected patients (n=33, combined studies), multiple dosing of REYATAZ 300 mg once daily with ritonavir 100 mg once daily with food produced a geometric mean (CV%) for atazanavir, Cmax of 4466 (42%) ng/ ml, with time to Cmax of approximately 2.5 hours.
Vrednost Cmax je bila dosežena približno po 2, 5 urah.
The geometric mean (CV%) for atazanavir Cmin and AUC was 654 (76%) ng/ ml and 44185 (51%) ng• h/ ml, respectively.
Geometrijska srednja vrednost Cmin (CV%) atazanavirja je bila 654 (76%) ng/ ml, geometrijska srednja vrednost AUC (CV%) atazanavirja pa 44. 185 (51%) ng• h/ ml.
Food effect: co-administration of REYATAZ and ritonavir with food optimizes the bioavailability of atazanavir.
Učinek hrane: pri uporabi zdravila REYATAZ in ritonavirja skupaj s hrano je biološka uporabnost atazanavirja optimalna.
Co-administration of a single 300-mg dose of REYATAZ and 100-mg dose of ritonavir with a light meal resulted in a 33% increase in the AUC and a 40% increase in both the Cmax and the 24-hour concentration of atazanavir relative to the fasting state.
V primerjavi z uporabo na tešče so se pri uporabi enkratnega 300 mg odmerka zdravila REYATAZ in 100 mg odmerka ritonavirja skupaj z lahkim obrokom vrednosti AUC, Cmax in 24- urne koncentracije atazanavirja povečale, in sicer AUC za 33%, Cmax in 24- urna koncentracija pa za 40%.
The 24-hour concentration following a high fat meal was increased by approximately 33% due to delayed absorption; the median Tmax increased from 2.0 to 5.0 hours.
Po obroku, bogatem z maščobami, se je zaradi zakasnele absorpcije 24- urna koncentracija povečala za približno 33%; srednji čas Tmax se je podaljšal iz 2, 0 na 5, 0 ur.
Distribution: atazanavir was approximately 86% bound to human serum proteins over a concentration range of 100 to 10,000 ng/ ml.
Porazdelitev: atazanavir je v koncentracijskem območju od 100 do 10. 000 ng/ ml približno 86% vezan na beljakovine v človeškem serumu.
Atazanavir binds to both alpha-1-acid glycoprotein (AAG) and albumin to a similar extent (89% and 86%, respectively, at 1,000 ng/ ml).
Atazanavir se v podobni meri veže na alfa- 1- kisli glikoprotein in na albumin (89% na prvega in 86% na drugega pri 1. 000 ng/ ml).
Additional minor metabolic pathways consist of N-dealkylation and hydrolysis.
Dodatna manj pomembna metabolne pot obsega N - dealkilacijo in hidrolizo.
18 Elimination: following a single 400-mg dose of 14C-atazanavir, 79% and 13% of the total radioactivity was recovered in the faeces and urine, respectively.
Izločanje: po enkratnem 400- mg odmerku s 14C - označenega atazanavirja se je 79% radioaktivnosti pojavilo v blatu in 13% v urinu.
In HIV-infected adult patients (n=33, combined studies) the mean half-life within a dosing interval for atazanavir was 12 hours at steady state following a dose of 300 mg daily with ritonavir 100 mg once daily with a light meal.
Pri bolnikih, okuženih s HIV (n = 33, kombinirane študije), je bil srednji razpolovni čas znotraj odmernega intervala atazanavirja v stanju dinamičnega ravnovesja 12 ur po uporabi 300 mg na dan s 100 mg ritonavirja enkrat na dan z lahkim obrokom.
Impaired renal function: in healthy subjects, the renal elimination of unchanged atazanavir was approximately 7% of the administered dose.
Okvarjeno delovanje ledvic: pri zdravih preiskovancih se je skozi ledvice izločilo v nespremenjeni obliki približno 7% uporabljenega odmerka atazanavirja.
There are no pharmacokinetic data available on patients with renal insufficiency (see section 4.2); however, the impact of renal impairment on atazanavir elimination is anticipated to be minimal.
Farmakokinetičnih podatkov za bolnike z ledvično insuficienco ni (glejte poglavje 4. 2), sklepamo pa lahko, da okvarjeno delovanje ledvic minimalno vpliva na izločanje atazanavirja.
Impaired hepatic function: atazanavir is metabolised and eliminated primarily by the liver.
Okvarjeno delovanje jeter: atazanavir se večinoma presnavlja in izloča v jetrih.
Concentrations of atazanavir with or without ritonavir are expected to be increased in patients with moderately or severely impaired hepatic function (see sections 4.2, 4.3, and 4.4).
Pričakovati je mogoče, da so koncentracije atazanavirja z ritonavirjem ali brez njega zvišane pri bolnikih z zmerno ali hudo okvarjenim delovanjem jeter (glejte poglavja 4. 2, 4. 3 in 4. 4).
Age/ Gender: a study of the pharmacokinetics of atazanavir was performed in 59 healthy male and female subjects (29 young, 30 elderly).
19 Starost/ spol: farmakokinetične študije atazanavirja so bile izvedene pri 59 zdravih preiskovancih in preiskovankah (29 mladih, 30 starejših).
Infants, toddlers, children, and adolescents: the pharmacokinetics of atazanavir is being studied after multiple doses in paediatric patients, stratified by age.
Dojenčki, malčki, otroci in mladostniki: farmakokinetiko atazanavirja so pri pediatričnih bolnikih, razdeljenih po starosti, raziskali po večkratnih odmerkih.
There are insufficient data at this time to recommend a dose (see section 4.2).
Trenutno ni dovolj podatkov, da bi priporočili odmerek (glejte poglavje 4. 2).
In female mice, atazanavir exposure at a dose that produced single-cell necrosis was 12 times the exposure in humans given 400 mg once daily.
Pri mišjih samicah je bila izpostavljenost atazanavirju ob odmerku, ki je povzročil nekrozo posameznih jetrnih celic, 12- krat tolikšna kot je izpostavljenost pri človeku ob uporabi 400 mg enkrat na dan.
During in vitro studies, cloned human cardiac potassium channel (hERG), was inhibited by 15% at a concentration (30 μ M) of atazanavir corresponding to 30-fold the free drug concentration at Cmax in humans.
Med študijami in vitro je prišlo do 15- odstotnega zavrtja kloniranih človeških srčnih kanalov za kalij, hERG, pri koncentraciji atazanavirja (30 μM), ki ustreza 30- kratni koncentraciji nevezane oblike učinkovine pri Cmax pri človeku.
Electrocardiographic changes (sinus bradycardia, prolongation of PR interval, prolongation of QT interval, and prolongation of QRS complex) were observed only in an initial 2-week oral toxicity study performed in dogs.
Elektrokardiografske spremembe (sinusna bradikardija, podaljšanje intervala PR, intervala QT in razširitev kompleksa QRS) so opazili samo v prvih 2 tednih študije peroralne toksičnosti pri psih.
Subsequent 9-month oral toxicity studies in dogs showed no drug-related electrocardiographic changes.
Nadaljnja 9- mesečna študija peroralne toksičnosti pri psih ni pokazala z zdravilom povezanih EKG- sprememb.
Potential cardiac effects of this product in humans cannot be ruled out (see sections 4.4 and 4.8).
Potencialnih učinkov tega zdravila na srce pri ljudeh ni mogoče izključiti (glejte poglavji 4. 4 in 4. 8).
The potential for PR prolongation should be considered in cases of overdose (see section4.9).
V primerih prevelikega odmerjanja je treba upoštevati možnost podaljšanja intervala PR (glejte poglavje 4. 9).
No teratogenic effects were observed in rats or rabbits at maternally toxic doses.
Pri podganah in kuncih niso opazili teratogenih učinkov v odmerkih, toksičnih za samice- matere.
In the pre- and postnatal development assessment in rats, atazanavir
Pri brejih kunčicah so pri poginulih ali moribundnih samicah ugotovili izrazite lezije na želodcu in črevesju ob maternalnih odmerkih, 2 - in 4- krat večjih od največjega odmerka, uporabljenega v definitivni študiji embrionalnega razvoja.
19 produced a transient reduction in body weight in the offspring at a maternally toxic dose.
Med pred - in postnatalno oceno razvoja pri podganah je atazanavir povzročil prehodno zmanjšanje telesne mase mladičev pri maternalno toksičnih odmerkih.
Systemic exposure to atazanavir at doses that resulted in maternal toxicity was at least equal to or slightly greater than that observed in humans given 400 mg once daily.
Sistemska izpostavljenost atazanavirju v odmerkih, ki so povzročili toksične učinke pri samicah- materah, je bila vsaj tolikšna ali pa rahlo večja kot pri ljudeh po odmerku 400 mg enkrat na dan.
The increased incidence of benign hepatic adenomas in female mice was likely secondary to cytotoxic liver changes manifested by single-cell necrosis and is considered to have no relevance for humans at intended therapeutic exposures.
Ocenjujejo, da to pri predvidenih terapevtskih izpostavljenostih za človeka ni pomembno.
Atazanavir increased opacity of bovine corneas in an in vitro ocular irritation study, indicating it may be an ocular irritant upon direct contact with the eye.
20 Atazanavir je v in vitro študiji očesnega draženja zvečal opalescenco goveje roženice, kar kaže, da bi ob neposrednem stiku z očesom lahko povzročil draženje.
Crospovidone Lactose monohydrate Magnesium stearate
Vsebina kapsul: krospovidon laktoza monohidrat magnezijev stearat
Gelatine Indigocarmin (E132) Titanium dioxide (E171)
Ovojnice kapsul: želatina indigotin (E132) titanov dioksid (E 171)
Shellac Propylene glycol Ammonium hydroxide Indigocarmin (E132)
Modro črnilo vsebuje: šelak propilenglikol amonijev hidroksid indigotin (E132)
Shellac Titanium dioxide (E171) Ammonium hydroxide Propylene glycol Simethicone
Belo črnilo vsebuje: šelak titanov dioksid (E 171) amonijev hidroksid propilenglikol simetikon
20 6.5 Nature and contents of container
6. 5 Vrsta ovojnine in vsebina
Each carton contains one high-density polyethylene (HDPE) bottle closed with child-resistant polypropylene closure.
Plastenka je zaprta s polipropilensko zaporko, varno za otroke.
Each carton contains 60 x 1 capsules; 10 blister cards of 6 x 1 capsules each in Alu/ Alu perforated unit dose blisters.
Ena škatla vsebuje 60 x 1 kapsulo; 10 pretisnih omotov s 6 x 1 kapsulo v enoodmernem alu/ alu perforiranem pretisnem omotu.
02 March 2004 Date of latest renewal:
2. marec 2004 Datum zadnjega podaljšanja dovoljenja:
{month year}
{datum}
Each capsule contains 150 mg of atazanavir (as sulphate)
Ena kapsula vsebuje 150 mg atazanavirja (v obliki sulfata).
82.18 mg of lactose per capsule.
82, 18 mg laktoze na kapsulo
Hard capsule Opaque blue and powder blue capsule printed with white and blue inks, with "BMS 150 mg" on one half and with "3624" on the other half.
Oznaki sta bele in modre barve.
22 Method of administration: for oral administration.
Način uporabe: za peroralno uporabo.
23 There have been reports of increased bleeding, including spontaneous skin haematomas and haemarthroses, in type A and B haemophiliac patients treated with protease inhibitors.
24 Pri bolnikih s hemofilijo A ali B, ki so dobivali zaviralce proteaz, so poročali o pogostejših krvavitvah, vključno s spontanimi kožnimi hematomi in hemartrozami.
24 Relevant examples are cytomegalovirus retinitis, generalised and/ or focal mycobacterial infections, and Pneumocystis carinii pneumonia.
25 mikobakterijami in s Pneumocystis carinii povzročena pljučnica.
Therefore, REYATAZ with ritonavir is contraindicated with medicinal products that are substrates of CYP3A4 and have a narrow therapeutic index: astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil, triazolam, orally administered midazolam, and ergot alkaloids, particularly ergotamine and dihydroergotamine (see section 4.3).
26 terapevtski indeks, npr. astemizol, terfenadin, cisaprid, pimozid, kinidin, bepridil, triazolam, peroralne oblike midazolama in alkaloidi ergot, zlasti ergotamin in dihidroergotamin (glejte poglavje 4. 3).
25 Other interactions Interactions between atazanavir/ ritonavir and protease inhibitors, antiretroviral agents other than protease inhibitors, and other non-antiretroviral medicinal products are listed in the tables below (increase is indicated as “↑”, decrease as “↓”, no change as “↔”, twice daily as “ BID” and once daily as “ QD”).
Druge interakcije V spodnji tabeli so navedene interakcije med atazanavirjem/ ritonavirjem in zaviralci proteaz, drugimi protiretrovirusnimi zdravili ter drugimi neprotiretrovirusnimi zdravili (zvišanje je navedeno kot “ ↑ ”, znižanje kot “ ↓ ”, brez spremembe kot “ ↔ ”, dvakrat na dan kot “ 2x/ dan ” in enkrat na dan kot “ 1x/ dan ”).
26
↔ 1, 03
27 Co-administered medicinal
ritonavir uporablja skupaj s
28 Co-administered medicinal
Sočasno uporabljena
29
Varfarin
Co-administration of diltiazem and REYATAZ/ ritonavir has not been studied.
Sočasne uporabe diltiazema in zdravila REYATAZ / ritonavirja niso raziskovali.
The mechanism of diltiazem/ atazanavir interaction is CYP3A4 inhibition.
Verapamil KORTIKOSTEROIDI
needed and ECG monitoring
Pri sočasni uporabi zdravila REYATAZ / ritonavirja in verapamila je potrebna previdnost.
Verapamil CORTICOSTEROIDS
Flutikazonpropionat za
Serum concentrations of verapamil may be increased by REYATAZ/ ritonavir due to CYP3A4 inhibition..
Plazemske vrednosti flutikazonpropionata so se znatno povečale,
Caution should be exercised when verapamil is co-administered with REYATAZ/ ritonavir
(90% IZ) (90% IZ) (90% IZ)
Fluticasone propionate intranasal 50 µg 4 times daily for 7 days (ritonavir 100 mg capsules BID) ERECTILE DYSUNCTION PDE5 Inhibitors
intranazalno uporabo 50 µg 4 krat na dan, 7 dni (ritonavir 100 mg kapsule 2x/ dan) ZDRAVILA ZA ZDRAVLJENJE EREKTILNE DISFUNKCIJE Zaviralci PDE5
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.
Večje učinke lahko pričakujemo pri uporabi inhalacijskih oblik flutikazonpropionata.
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.
Omenjeni sistemski kortikosteroidni učinki se lahko pojavijo tudi pri uporabi drugih kortikosteroidov, ki se presnavljajo s P450 3A, npr. budezonid.
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).
zdravila REYATAZ / ritonavirja in teh glukokortikoidov ne priporočamo, razen v primerih, ko možne koristi zdravljenja prevladajo nad tveganjem za pojav sistemskih kortikosteroidnih učinkov (glejte poglavje 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).
Razmisliti je treba o zmanjšanju odmerka glukokortikoida in skrbno nadzirati morebiten pojav lokalnih ali sistemskih učinkov ali glukokortikoid zamenjati s takšnim, ki ni substrat za CYP3A4 (npr. beklometazon).
Sildenafil is metabolised by CYP3A4.
Sildenafil se presnavlja s CYP3A4.
Co-administration with REYATAZ/ ritonavir may result in increased concentrations of sildenafil and an increase in sildenafil-associated adverse events, including hypotension, visual changes, and priapism.
Pri sočasni uporabi z zdravilom REYATAZ/ ritonavirjem se lahko koncentracije sildenafila povečajo in pojavijo neželeni učinki sildenafila, kot so hipotenzija, spremembe vida in priapizem.
The mechanism of the sildenafil/ atazanavir interaction is CYP3A4 inhibition.
Mehanizem interakcije med sildenafilom in atazanavirjem je zaviranje CYP3A4.
Patients should be warned about these possible side effects.
Bolnike je treba opozoriti na te možne neželene učinke.
HERBAL PRODUCTS
PRIPRAVKI RASTLINSKEGA IZVORA
John’ s wort (Hypericum perforatum):
Šentjanževka (Hypericum perforatum):
Concomitant use of St.
Ta učinek je lahko posledica indukcije CYP3A4.
John's wort with REYATAZ/ ritonavir may be expected to result in significant reduction in plasma levels of atazanavir.
Nasprotno po lahko ritonavir zmanjša koncentracije kontraceptivov se je etinilestradiola.
Co-administration of REYATAZ/ ritonavir
Presnova simvastatina in lovastatina je močno odvisna od CYP3A4.
30 Co-administered medicinal
Sočasno uporabljena
Co-administration of simvastatin or lovastatin with REYATAZ/ ritonavir is not recommended due to an increased risk of myopathy including rhabdomyolysis.
priporočljiva zaradi večjega tveganja za pojav miopatije, vključno z rabdomiolizo.
The use of another HMG- CoA reductase inhibitor which does not undergo metabolism by CYP3A such as pravastatin or fluvastatin is recommended.
Priporočljiva je uporaba drugega zaviralca reduktaze HMG- CoA, ki se ne presnavlja s CYP3A, kot sta pravastatin ali fluvastatin.
Atorvastatin OPIOIDS
Atorvastatin OPIOIDI
Buprenorphine, QD, stable maintenance dose,
Buprenorfin, 1x/ dan, stabilni vzdrževalni odmerek, (atazanavir 300 mg 1x/ dan z
buprenorphine ↑ 1.67 ↑ 1.37 ↑ 1.69
buprenorfin ↑ 1, 67 ↑ 1, 37 ↑ 1, 69 norbuprenorfin ↑ 2, 05 ↑ 1, 61 ↑ 2, 01
Co-administration warrants
Pri sočasni uporabi je potreben klinični nadzor sedacije in
(atazanavir 300 mg QD with ritonavir 100 mg QD)
ritonavirjem 100 mg 1x/ dan)
norbuprenorphine ↑ 2.05 ↑ 1.61 ↑ 2.01 The mechanism of interaction is CYP3A4 and UGT1A1 inhibition.
Mehanizem interakcije je zaviranje CYP3A4 in UGT1A1.
clinical monitoring for sedation and cognitive effects.
učinkov na kognitivno funkcijo.
Methadone, stable maintenance dose (atazanavir 400 mg QD) SEDATIVES Benzodiazepines
Metadon, stabilni vzdrževalni odmerek (atazanavir 400 mg 1x/ dan)
Given that low dose ritonavir (100 mg twice daily) has been shown to have no significant effect on methadone concentrations, no interaction is expected if methadone is co-administered with REYATAZ and ritonavir, based on these data.
Glede na to, da je bilo dokazano, da nizki odmerek ritonavirja (100 mg dvakrat na dan) nima pomembnega vpliva na koncentracije metadona, na osnovi teh podatkov pri sočasni uporabi metadona, zdravila REYATAZ in ritonavirja interakcij ne pričakujemo.
Midazolam and triazolam are extensively metabolized by CYP3A4.
Midazolam in triazolam se v veliki meri presnavljata s CYP3A4.
Co-administration with REYATAZ/ ritonavir may cause a large increase in the concentration of these benzodiazepines.
Pri sočasni uporabi zdravila REYATAZ/ ritonavirja se lahko koncentracije teh benzodiazepinov močno povečajo.
No drug interaction study has been performed for the co-administration of REYATAZ/ ritonavir with benzodiazepines.
Študije medsebojnega delovanja pri sočasni uporabi zdravila REYATAZ/ ritonavirja in benzodiazepinov niso bile izvedene.
Data from concomitant use of parenteral midazolam with other protease inhibitors suggest a possible 3-4 fold increase in midazolam plasma levels.
Podatki o sočasni uporabi parenteralnega midazolama z drugimi zaviralci proteaz kažejo, da se plazemske vrednosti midazolama lahko povečajo za 3 - do 4- krat.
If REYATAZ is
Zdravilo REYATAZ / ritonavir se ne sme uporabljati sočasno s triazolamom ali peroralnim midazolamom (glejte poglavje 4. 3).
co-administration
Pri sočasni uporabi zdravila REYATAZ / ritonavirja in parenteralnega midazolama je potrebna previdnost.
4.6 Pregnancy and lactation
33 4. 6 Nosečnost in dojenje
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.
34 Odrasli bolniki Poročali so tudi o naslednjih neželenih učinkih zmerne ali močneje jakosti, ki bi vsaj lahko bili povezani s terapevtskimi shemami, ki so vključevale zdravilo REYATAZ in enega ali več nukleozidnih/ nukleotidnih zaviralcev reverzne transkriptaze.