natgillin/translations-raw huggingface dataset:
• feeling tired, lack of energy, difficulty in sleeping (insomnia)
• umor, nedostatak energije, poteškoće sa spavanjem (nesanica)
• Women with HIV should not breast-feed their infants because babies can be infected with HIV
• Žene zaražene HIV-om ne smiju dojiti svoju djecu jer mlijekom mogu prenijeti zarazu na dijete.
This means that you may keep getting infections or other illnesses associated with HIV, if you don't take DUTREBIS as your doctor has instructed you.
To znači da i dalje možete obolijevati od infekcija ili drugih bolesti povezanih s HIV-om ako ne uzimate DUTREBIS prema uputama svog liječnika.
When used with other medicines, DUTREBIS may:
Kada se primjenjuje s drugim lijekovima, DUTREBIS može:
Effects at exposure levels sufficiently in excess of clinical exposure levels indicate no special hazard for humans.
Učinci lijeka pri razinama izloženosti dovoljno višima od kliničkih razina izloženosti ne ukazuju na poseban rizik za ljude.
• Do not take this medicine after the expiry date which is stated on the bottle after EXP.
• Ovaj lijek se ne smije upotrijebiti nakon isteka roka valjanosti navedenog na boci iza oznake
These studies were terminated after the primary efficacy analysis at Week 24 because they failed to demonstrate non-inferiority of raltegravir versus lopinavir (+) ritonavir.
Ova su ispitivanja obustavljena nakon primarne analize djelotvornosti u 24. tjednu jer nije dokazana neinferiornost raltegravira naspram lopinavir (+) ritonavir.
Patients at increased risk should be followed closely.
Bolesnike u kojih postoji povećan rizik potrebno je pomno nadzirati.
In vitro susceptibility testing has not been standardised and results may vary according to methodological factors.
Testovi osjetljivosti in vitro nisu standardizirani i rezultati mogu varirati ovisno o metodološkim čimbenicima.
Therefore DUTREBIS should be used with caution in this population.
Stoga DUTREBIS u ovoj populaciji treba primjenjivati uz oprez.
DUTREBIS must not be used with the following medicines.
DUTREBIS se ne smije uzimati sa sljedećim lijekovima.
Lamivudine is well absorbed from the gastrointestinal tract, and the bioavailability of oral lamivudine in adults is normally between 80 and 85 %.
Lamivudin se dobro apsorbira iz gastrointestinalnog trakta, a bioraspoloživost peroralno primijenjenog lamivudina u odraslih obično je između 80 i 85%.
• abnormal dreams; nightmare; abnormal behaviour; feelings of deep sadness and
• neuobičajeni snovi; noćne more; neuobičajeno ponašanje; osjećaj duboke tuge i bezvrijednosti
For storage conditions after first opening of the medicinal product, see section 6.3.
Uvjeti čuvanja nakon prvog otvaranja lijeka navedeni su u dijelu 6.3.
Studies with raltegravir in animals have shown reproductive toxicity (see section 5.3).
Istraživanja raltegravira na životinjama pokazala su reproduktivnu toksičnost (vidjeti dio 5.3).
DUTREBIS can cause some side effects that you need to talk to your doctor, pharmacist or nurse about.
DUTREBIS može uzrokovati neke nuspojave o kojima trebate razgovarati sa svojim liječnikom, ljekarnikom ili medicinskom sestrom.
These median proportions are approximately 3- to 6-fold lower than the free fraction of raltegravir in plasma.
Ti proporcionalni medijani približno su 3 do 6 puta niži od slobodne frakcije raltegravira u plazmi.
These changes are not considered clinically meaningful; therefore, DUTREBIS may be administered with or without food.
Te se promjene ne smatraju klinički značajnima, stoga se DUTREBIS može primjenjivati s hranom ili bez
• certain kinds of kidney problems, including conditions in which the kidneys lose the ability to remove waste and excess water from the bloodstream.
• određene vrste bubrežnih tegoba, uključujući stanja kod kojih bubrezi gube sposobnost uklanjanja otpadnih tvari i viška vode iz krvotoka.
It is rare (may affect up to 1 in 1,000 people) and if it does happen, it usually happens after a few months of treatment.
Laktacidoza je rijetka (može se javiti u do 1 na 1000 osoba), a ako se pojavi, to je obično nakon nekoliko mjeseci liječenja.
• you have a history of depression or psychiatric illness.
• ako ste imali depresiju ili neku psihijatrijsku bolest.
In case of concomitant antiviral therapy for hepatitis B or C, please refer also to the relevant product information for these medicinal products.
U slučaju istodobne antivirusne terapije za hepatitis B ili C, pročitajte odgovarajuće informacije o lijeku i za te lijekove.
• Swallow the tablet whole (do not crush or chew).
• Tabletu progutajte cijelu (nemojte je drobiti niti žvakati).
During your treatment, your doctor will check you for signs of lactic acidosis.
Tijekom liječenja Vaš liječnik će provjeravati pojavu znakova laktacidoze.
No specific signs or symptoms have been identified following such overdose.
Nakon takvog predoziranja nisu zabilježeni nikakvi posebni znakovi ili simptomi.
• rash (more often when used in combination with darunavir)
• osip (češće se javlja kad se lijek uzima u kombinaciji s darunavirom)
Percent of patients with response and associated 95 % confidence interval (CI) are reported.
Prijavljen je postotak bolesnika koji su odgovorili na liječenje uz pripadajući 95%-tni interval pouzdanosti (CI).
Some clinical findings also support a possible interaction between lamivudine and cladribine.
Neki klinički nalazi također podržavaju moguću interakciju između lamivudina i kladribina.
A modest increase in Cmax (28 %) was observed for zidovudine when administered with lamivudine, however overall exposure (AUC) is not significantly altered.
Primijećen je blagi porast Cmax (28%) zidovudina kada se primjenjivao s lamivudinom, no ukupna izloženost (AUC) nije se značajno promijenila.
Any inflammatory symptoms should be evaluated and treatment instituted when necessary.
Bilo koji simptom upale treba procijeniti i po potrebi započeti liječenje.
• erectile dysfunction; breast enlargement in men; menopausal symptoms
• poremećaj erekcije; povećanje dojki u muškaraca; simptomi menopauze
NL-2031 BN Haarlem The Netherlands
NL-2031 BN Haarlem Nizozemska
126 treatment experienced children and adolescents 2 to 18 years of age.
U ispitivanje je uključeno 126 prethodno liječene djece i adolescenata u dobi od 2 do 18 godina.
• rifampicin - used to treat some infections such as tuberculosis.
• rifampicin - koristi se za liječenje nekih infekcija poput tuberkuloze.
Following oral administration, lamivudine pharmacokinetics in late pregnancy were similar to non-pregnant women.
Nakon peroralne primjene farmakokinetika lamivudina u kasnoj trudnoći bila je slična kao i u žena koje nisu bile trudne.
DUTREBIS film-coated tablets contain lactose.
DUTREBIS filmom obložene tablete sadrže laktozu.
See section 4 for more information about side effects.
Pogledajte dio 4. za više informacija o nuspojavama.
Raltegravir is approximately 83 % bound to human plasma protein over the concentration range of 2 to 10 µM.
Oko 83% raltegravira veže se za proteine u ljudskoj plazmi pri rasponu koncentracija od 2 do 10 µM.
However, the magnitude of the effect seems unlikely to result in clinically important drug-drug interactions.
Međutim, nije vjerojatno da bi učinci tog opsega mogli dovesti do klinički važnih interakcija lijekova.
Excipient with known effect: Each tablet contains 39.70 mg lactose (as monohydrate).
Pomoćna tvar s poznatim učinkom: Jedna tableta sadrži 39,70 mg laktoze (u obliku hidrata).
The likelihood of metabolic interactions of lamivudine with other medicinal products is low due to the small extent of hepatic metabolism (5-10 %) and low plasma protein binding.
Vjerojatnost metaboličke interakcije lamivudina s drugim lijekovima je mala zbog malog opsega metabolizma u jetri (5-10%) i slabog vezivanja za proteine plazme.
Patients were stratified by age, enrolling adolescents first and then successively younger children.
Bolesnici su stratificirani prema dobi tako da su najprije uključivani adolescenti, a zatim sukcesivno mlađa djeca.
HIV is the virus that causes Acquired Immune Deficiency Syndrome (AIDS).
HIV je virus koji uzrokuje sindrom stečene imunodeficijencije (SIDA).
Clinical examination should include evaluation for physical signs of fat redistribution.
Klinički pregled treba uključivati procjenu fizičkih znakova preraspodjele masnog tkiva.
Of the 126 patients, 96 received the recommended dose of raltegravir (see section 4.2).
Od 126 bolesnika, 96 ih je primalo preporučenu dozu raltegravira (vidjeti dio 4.2).
Clinical status including liver aminotransferases should be monitored and appropriate therapy initiated.
Treba pratiti klinički status uključujući jetrene aminotransferaze te započeti odgovarajuću terapiju.
Standard genotoxicity studies to evaluate mutagenicity and clastogenicity were negative.
Standardna ispitivanja genotoksičnosti radi procjene mutagenosti i klastogenosti bila su negativna.
In these 96 children and adolescents, frequency, type and severity of drug related adverse reactions through Week 48 were comparable to those observed in adults.
U tih su 96 djece i adolescenata učestalost, vrsta i težina nuspojava povezanih s primjenom lijeka tijekom 48 tjedana bile usporedive s onima opaženima u odraslih.
Most had a signature mutation at amino acid 155 (N155 changed to H), amino acid 148 (Q148 changed to H, K, or R), or amino acid 143 (Y143 changed to H, C, or R), along with one or more additional integrase mutations (e.g., L74M, E92Q, T97A, E138A/K, G140A/S, V151I, G163R, S230R).
Većina ih je imala karakterističnu mutaciju na aminokiselini 155 (N155 se mijenja u H), aminokiselini 148 (Q148 se mijenja u H, K ili R) ili aminokiselini 143 (Y143 se mijenja u H, C ili R), uz jednu ili više dodatnih mutacija integraze (npr. L74M, E92Q, T97A, E138A/K, G140A/S, V151I, G163R, S230R).
Randomization was stratified by screening HIV RNA level (≤50,000 copies/ml; and > 50,000 copies/ml) and by hepatitis B or C status (positive or negative).
Randomizacija je bila stratificirana probirom na temelju razine HIV-RNK (≤ 50 000 kopija/ml i > 50 000 kopija/ml) i statusa hepatitisa B ili C (pozitivan ili negativan).
Based on these data, raltegravir is not expected to affect the pharmacokinetics of medicinal products that are substrates of these enzymes or P-glycoprotein.
Na osnovu ovih podataka ne očekuje se da raltegravir utječe na farmakokinetiku lijekova koji su supstrati tih enzima ili P-glikoproteina.
If you are the parent of a child taking DUTREBIS, please read this information carefully with your child.
Ako ste roditelj djeteta koje uzima lijek DUTREBIS, pažljivo pročitajte cijelu uputu zajedno s djetetom.
No specific information is available on the treatment of overdose with raltegravir.
Nema specifičnih podataka o liječenju predoziranja raltegravirom.
Exposure (AUC∞), Cmax, and half-life increased with diminishing renal function (as expressed by creatinine clearance).
Izloženost (AUC∞), Cmax i poluvijek povećavali su se sa smanjenjem funkcije bubrega (izraženim klirensom kreatinina).
In intravenous studies with lamivudine, the mean volume of distribution is 1.3 l/kg.
U ispitivanjima intravenske primjene lamivudina, srednja vrijednost volumena raspodjele iznosila je 1,3 l/kg.
For observed C12 hr in BENCHMRK 1 and 2 the coefficient of variation (CV) for inter-subject variability = 212 % and the CV for intra-subject variability = 122 %.
Za C12h opažen u ispitivanjima BENCHMRK 1 i 2 koeficijent varijacije (CV) za interindividualnu varijabilnost iznosio je 212%, dok je CV za intraindividualnu varijabilnost iznosio 122%.
The results of long-term carcinogenicity studies with lamivudine in rats and mice did not show any carcinogenic potential relevant for humans.
Rezultati dugoročnih ispitivanja karcinogenosti lamivudina na štakorima i miševima nisu pokazali karcinogeni potencijal koji bi bio relevantan za ljude.
This is slightly faster than the raltegravir poloxamer formulation, which has a Tmax of approximately 3 hours.
To je nešto brže nego kod formulacije raltegravira s poloksamerom, kod koje tmax iznosi približno 3 sata.
Administration of trimethoprim/sulfamethoxazole 160 mg/800 mg results in a 40 % increase in lamivudine exposure, because of the trimethoprim component; the sulfamethoxazole component did not interact.
Primjena trimetoprima/sulfametoksazola u dozi od 160 mg/800 mg rezultira 40%-tnim povećanjem izloženosti lamivudinu zbog komponente trimetoprima; komponenta sulfametoksazola nije ulazila u interakciju.
People taking anti-retroviral medicines may find that their body shape changes.
Osobe koje uzimaju antiretrovirusne lijekove mogu primijetiti promjene u obliku tijela uzrokovane promjenama u
The pharmacokinetics of lamivudine after administration to patients over 65 years of age have not been studied; however, there was no clinically meaningful effect of age on raltegravir pharmacokinetics over the age range studied (19 to 71 years, with few (8) subjects over the age of 65).
Farmakokinetika lamivudina nakon primjene u bolesnika starijih od 65 godina nije ispitivana; međutim, dob nije imala klinički značajnog učinka na farmakokinetiku raltegravira u ispitanom rasponu dobi (od 19 do 71 godine uz nekoliko (8) ispitanika starijih od 65 godina).
Most viruses isolated from patients failing raltegravir had high-level raltegravir resistance resulting from the appearance of two or more mutations.
Većina virusa izoliranih iz bolesnika koji nisu odgovarali na liječenje raltegravirom imala je visok stupanj rezistencije na raltegravir zbog pojave dviju ili više mutacija.
As waste and fluids accumulate, other body systems are affected, potentially leading to complications
Nakupljanje otpadnih tvari i tekućina utječe i na druge tjelesne sustave, a to može uzrokovati komplikacije
The rashes observed in clinical studies were mild to moderate in severity and did not result in discontinuation of therapy (see section 4.4).
Osipi opaženi u kliničkim ispitivanjima bili su blagog do umjerenog intenziteta i nisu doveli do prekida terapije (vidjeti dio 4.4).
No dosage adjustment required for DUTREBIS or hormonal contraceptives (oestrogen- and/or progesterone-based).
Nije potrebno prilagođavati dozu lijeka DUTREBIS ili hormonskih kontraceptiva (na bazi estrogena i/ili progesterona).
If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment should be considered.
Pojave li se u tih bolesnika znakovi pogoršanja bolesti jetre, mora se razmotriti privremen ili trajan prekid liječenja.
Cases of pancreatitis have occurred rarely with lamivudine.
Pri primjeni lamivudina rijetko su nastupili slučajevi pankreatitisa.
In addition, higher C12h levels (20 % for raltegravir and 53 % for lamivudine) were observed.
Osim toga, primijećene su i više vrijednosti C12h (20% više za raltegravir i 53% više za lamivudin).
> 200 cells/mm Sensitivity score (GSS)
> 200 stanica/mm Indeks genotipske osjetljivosti (GSS)
The most frequently reported adverse reactions during treatment with raltegravir were headache and nausea.
Najčešće prijavljivane nuspojave tijekom liječenja raltegravirom bile su glavobolja i mučnina.
Other medicinal products (e.g. ranitidine, cimetidine) are eliminated only in part by this mechanism and were shown not to interact with lamivudine.
Drugi lijekovi (npr. ranitidin, cimetidin) samo se djelomično eliminiraju tim mehanizmom i pokazalo se da ne ulaze u interakciju s lamivudinom.
The types and rates of specific cancers were those expected in a highly immunodeficient population.
Vrste i stope učestalosti pojedinih vrsta raka bile su u okviru očekivanih za populaciju s izraženom imunodeficijencijom.
Sources of variability within the BENCHMRK study may include differences in co-administration with food and concomitant medicines.
Uzroci varijabilnosti u ispitivanju BENCHMRK mogu uključivati razlike u istodobnoj primjeni s hranom i drugim lijekovima.
Adults, adolescents, and children (6 through 11 years of age weighing at least 30 kg) The recommended dosage is one tablet (150 mg lamivudine/300 mg raltegravir) twice daily.
Odrasli, adolescenti i djeca (u dobi od 6 do 11 godina i tjelesne težine najmanje 30 kg) Preporučena doza je jedna tableta (150 mg lamivudina/300 mg raltegravira) dvaput na dan.
Non-clinical toxicology studies, including conventional studies of safety pharmacology, repeated-dose toxicity, genotoxicity, developmental toxicity and juvenile toxicity, have been conducted with raltegravir, in mice, rats, dogs and rabbits.
Neklinička toksikološka istraživanja raltegravira, uključujući konvencionalna ispitivanja sigurnosne farmakologije, toksičnosti ponovljenih doza, genotoksičnosti, razvojne toksičnosti i juvenilne toksičnosti provedena su na miševima, štakorima, psima i kunićima.
Lamivudine was not genotoxic in vivo at doses that gave plasma concentrations around 40-50 times higher than the anticipated clinical plasma levels.
Lamivudin nije bio genotoksičan u ispitivanjima in vivo, pri dozama kojima se postižu koncentracije u plazmi 40 do 50 puta više od predviđenih koncentracija u plazmi kod kliničke primjene.
DUTREBIS contains two medicines: lamivudine and raltegravir.
DUTREBIS sadrži dva lijeka: lamivudin i raltegravir.
Caution should be exercised when administering NRTIs to any patient (particularly obese women) with hepatomegaly, hepatitis or other known risk factors for liver disease and hepatic steatosis (including certain medicinal products and alcohol).
Potreban je oprez kada se NRTI primjenjuju u bilo kojeg bolesnika (osobito u pretilih žena) s hepatomegalijom, hepatitisom ili drugim poznatim faktorima rizika za bolesti jetre i steatozu jetre (uključujući neke lijekove i alkohol).
Typically, such reactions have been observed within the first few weeks or months of initiation of CART.
Ovakve su se reakcije u pravilu opažene unutar prvih nekoliko tjedana ili mjeseci nakon početka kombinirane antiretrovirusne terapije.
Therefore, whenever possible, DUTREBIS should be administered with another active ART to minimise the potential for virological failure and the development of resistance (see section 5.1).
Stoga se, kad god je to moguće, DUTREBIS mora primjenjivati s još jednim aktivnim ART-om kako bi se potencijalan izostanak virološkog odgovora i razvoj rezistencije sveli na najmanju moguću mjeru (vidjeti dio 5.1).
In addition, tenofovir may increase plasma levels of raltegravir, however, the mechanism for this effect is unknown (see Table 1).
Nadalje, tenofovir može povisiti koncentraciju raltegravira u plazmi, ali mehanizam tog učinka nije poznat (vidjeti Tablicu 1).
At the highest dosage levels, minor effects on indicators of liver and kidney function were seen together with occasional reductions in liver weight.
Pri najvišim dozama primijećen je manji učinak na pokazatelje funkcije jetre i bubrega uz povremeno smanjenje težine jetre.
If DUTREBIS is missed within 6 hours of the time it is usually taken, patients should be instructed to take the prescribed dose of DUTREBIS as soon as possible.
Ako je do propuštanja doze lijeka DUTREBIS došlo unutar 6 sati od uobičajenog vremena uzimanja, bolesnika treba uputiti da uzme propisanu dozu lijeka DUTREBIS što je prije moguće.
The mean (CV) AUC over a dosing interval of 12 hours is 4.7 μg•h/ml (18 %).
Srednja vrijednost (CV) AUC-a tijekom intervala doziranja od 12 sati je 4,7 µg•h/ml (18%).
This is not considered to be of significance to patient safety and therefore no dosage adjustments are necessary.
Budući da se smatra da to nije značajno za sigurnost bolesnika, nije potrebno prilagođavati dozu.
Treatment with NRTIs should be discontinued in the setting of symptomatic hyperlactatemia and metabolic/lactic acidosis, progressive hepatomegaly, or rapidly elevating aminotransferase levels.
Liječenje NRTI-ma mora se prekinuti u slučaju simptomatske hiperlaktatemije i metaboličke acidoze/laktacidoze, progresivne hepatomegalije ili brzog porasta razina aminotransferaza.
Mutations at amino acid 143 confer greater resistance to raltegravir than to elvitegravir, and the E92Q mutation confers greater resistance to elvitegravir than to raltegravir.
Mutacije na aminokiselini 143 uzrokuju veću rezistenciju na raltegravir nego na elvitegravir, dok mutacija E92Q uzrokuje veću rezistenciju na elvitegravir nego na raltegravir.
Patients with a prior history of virological failure were not excluded and the number of previous antiretroviral therapies was not limited.
Bolesnici koji nisu odgovorili na prethodno liječenje nisu bili isključeni iz ispitivanja, a broj prethodno primljenih antiretrovirusnih terapija nije bio ograničen.
These results indicate that raltegravir is not an inducer or inhibitor of CYP3A4, and raltegravir is thus not anticipated to affect the pharmacokinetics of medicinal products which are CYP3A4 substrates.
Ovi rezultati ukazuju da raltegravir nije ni induktor ni inhibitor CYP3A4 i stoga se ne očekuje da utječe na farmakokinetiku lijekova koji su supstrati CYP3A4.
Patients received either the 400 mg tablet formulation (6 to 18 years of age) or the chewable tablet formulation (2 to less than 12 years of age).
Bolesnici su primali lijek ili u obliku tablete od 400 mg (u dobi od 6 do 18 godina) ili u obliku tablete za žvakanje (u dobi od 2 do manje od 12 godina).
However, the effect of raltegravir on darunavir plasma concentrations does not appear to be clinically meaningful.
Međutim, učinak raltegravira na plazmatske koncentracije darunavira ne doima se klinički značajnim.
Lactic acidosis has a high mortality and may be associated with pancreatitis, liver failure, or renal
Laktacidoza ima visoku smrtnost, a može biti udružena s pankreatitisom, zatajenjem jetre ili
This may mean that the HIV virus will develop resistance to DUTREBIS and become harder to treat.
To može značiti da je virus HIV-a postao otporan na DUTREBIS i postaje ga teže liječiti.
Therapy should be initiated by a physician experienced in the management of HIV infection.
Terapiju mora započeti liječnik s iskustvom u liječenju HIV infekcije.
Based on modelling and simulation using raltegravir pharmacokinetic data in adults, the pharmacokinetics of raltegravir in DUTREBIS in children was projected to result in exposures that have been previously shown to be safe and efficacious in adults.
Na temelju modeliranja i simulacije farmakokinetičkih podataka raltegravira u odraslih, projicirana farmakokinetika raltegravira, kao komponente lijeka DUTREBIS, u djece rezultira razinama izloženosti za koje je prethodno dokazano da su sigurne i djelotvorne u odraslih.
As the in vitro mutagenic activity of lamivudine could not be confirmed in in vivo tests, it is concluded that lamivudine should not represent a genotoxic hazard to patients undergoing
Budući da se mutagena aktivnost lamivudina in vitro nije mogla potvrditi testovima in vivo, zaključeno je da lamivudin ne bi trebao predstavljati genotoksični rizik za bolesnika koji se liječi.
In vitro studies indicate that raltegravir is not a substrate of cytochrome P450 (CYP) enzymes, does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A, does not induce CYP3A4 and does not inhibit P-glycoprotein-mediated transport.
Istraživanja in vitro ukazuju da raltegravir nije supstrat enzima citokroma P450 (CYP), ne inhibira CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 ni CYP3A, ne inducira CYP3A4 niti inhibira transport posredovan P-glikoproteinom.
With twice-daily dosing of raltegravir, pharmacokinetic steady state is achieved rapidly, within approximately the first 2 days of dosing.
Primjenom raltegravira dvaput na dan farmakokinetičko stanje dinamičke ravnoteže postiže se brzo, priblližno unutar prva 2 dana primjene.
Lamivudine is also available as an oral solution for children over three months of age and who weigh less than 14 kg or for patients who are unable to swallow tablets.
Lamivudin je dostupan i u obliku oralne otopine za djecu stariju od 3 mjeseca i tjelesne težine manje od 14 kg ili za bolesnike koji ne mogu progutati tablete.
In interaction studies, raltegravir did not have a clinically meaningful effect on the pharmacokinetics of etravirine, maraviroc, tenofovir, hormonal contraceptives, methadone, midazolam, or boceprevir.
U ispitivanjima interakcija raltegravir nije imao klinički značajan učinak na farmakokinetiku etravirina, maraviroka, tenofovira, hormonskih kontraceptiva, metadona, midazolama ili boceprevira.