FrancophonIA/ELRC3.0 huggingface dataset:
English: In the 22 patients less than 2 years old who received voriconazole in a compassionate use programme, the following adverse reactions (for which a relationship to voriconazole could not be excluded) were reported: photosensitivity reaction (1), arrhythmia (1), pancreatitis (1), blood bilirubin increased (1), hepatic enzymes increased (1), rash (1) and papilloedema (1).
Croatian: U 22 bolesnika mlađa od 2 godine koja su dobivala vorikonazol u okviru programa milosrdne primjene lijeka zabilježene su sljedeće nuspojave (za koje se nije mogla isključiti povezanost s vorikonazolom): reakcija fotoosjetljivosti (1), aritmija (1), pankreatitis (1), povišenje vrijednosti bilirubina u krvi (1), povišenje vrijednosti jetrenih enzima (1), osip (1), papiloedem (1).
English: Extended and frequent monitoring for respiratory depression and other opiateassociated adverse reactions is recommended.
Croatian: Preporučuju se opsežne i česte kontrole zbog moguće depresije disanja i drugih nuspojava povezanih s opijatima.
English: The safety of voriconazole was investigated in 288 paediatric patients aged 2 to <12 years (169) and 12 to <18 years (119) who received voriconazole for prophylaxis (183) and therapeutic use (105) in clinical trials.
Croatian: Sigurnost vorikonazola ispitana je u 288 pedijatrijskih bolesnika u dobi od 2 do < 12 godina (169) i 12 do <18 godina (119) koji su primili vorikonazol kao profilaksu (183) ili terapiju (105) u kliničkim ispitivanjima.
English: 2 Includes immune thrombocytopenic purpura.
Croatian: 2 Uključuje imunu trombocitopeničnu purpuru.
English: Voriconazole Hikma must not be administered simultaneously with any blood product or any short-term infusion of concentrated solutions of electrolytes, even if the two infusions are running in separate lines.
Croatian: Vorikonazol Hikma se ne smije primjenjivati u isto vrijeme s bilo kojim krvnim pripravkom ili kratkotrajnom infuzijom koncentriranih otopina elektrolita, čak ni ako se koriste dvije odvojene infuzijske linije.
English: Depending on the severity of symptoms, consideration should be given to stopping treatment (see section 4.8).
Croatian: Ovisno o težini simptoma, treba razmotriti potrebu za prestankom liječenja (vidjeti dio 4.8).
English: The doctor may decide to decrease the dose if you have mild to moderate cirrhosis.
Croatian: Liječnik će možda odlučiti smanjiti dozu ako imate blagu do umjerenu cirozu jetre.
English: The species most frequently involved in causing human infections include C. albicans, C. parapsilosis, C. tropicalis, C. glabrata and C. krusei, all of which usually exhibit minimum inhibitory concentration (MICs) of less than 1 mg/L for voriconazole.
Croatian: Vrste koje najčešće uzrokuju infekcije u ljudi uključuju C. albicans, C. parapsilosis, C. tropicalis, C. glabrata i C. krusei, a uobičajene minimalne inhibicijske koncentracije (MIK) vorikonazola za sve navedene vrste iznose manje od 1 mg/l.
English: You should avoid any sunlight and sun exposure while being treated.
Croatian: Tijekom liječenja morate izbjegavati sunčevu svjetlost i izlaganje suncu.
English: Voriconazole Hikma treatment will continue for as long as your doctor advises, however the duration of treatment with voriconazole should be no more than 6 months.
Croatian: Liječenje lijekom Vorikonazol Hikma nastavit će se onoliko dugo koliko to preporuči liječnik, no liječenje vorikonazolom ne smije trajati dulje od 6 mjeseci.
English: Candida Species
Croatian: Vrste iz roda Candida
English: The higher intravenous maintenance dose in paediatric patients relative to adults reflects the higher elimination capacity in paediatric patients due to a greater liver mass to body mass ratio.
Croatian: Viša intravenska doza održavanja u djece u odnosu na odrasle odražava veći kapacitet eliminacije lijeka u pedijatrijskih bolesnika zbog većeg omjera između jetrene mase i tjelesne mase.
English: All other adolescents (12 to 14 years and ≥50 kg; 15 to 17 years regardless of body weight) Voriconazole should be dosed as adults.
Croatian: Svi ostali adolescenti (12 do 14 godina i ≥ 50 kg; 15 do 17 godina neovisno o tjelesnoj težini) Vorikonazol se treba dozirati kao kod odraslih.
English: For patients with ICC the global response rate at EOT was 85.7% (6/7) and for patients with EC the global response rate at EOT was 70% (7/10).
Croatian: Kod bolesnika s ICC-om, stopa globalne reakcije po završetku liječenja bila je 85,7% (6/7), a za bolesnike s EC-om, stopa globalne reakcije po završetku liječenja bila je 70% (7/10).
English: • Indinavir and other HIV protease inhibitors (used for treating HIV)
Croatian: • indinavir i druge inhibitore HIV proteaze (koriste se za liječenje HIV-a)
English: 5 Includes akathisia and parkinsonism.
Croatian: 5 Uključuje akatiziju i parkinsonizam.
English: Dose reduction of methadone may be needed.
Croatian: Možda će biti potrebno smanjiti dozu metadona.
English: The absolute bioavailability of voriconazole after oral administration is estimated to be 96 %.
Croatian: Procjenjuje se da apsolutna bioraspoloživost vorikonazola nakon peroralne primjene iznosi oko 96%.
English: Voriconazole exposures in the majority of adolescent patients were comparable to those in adults receiving the same dosing regimens.
Croatian: Izloženost vorikonazolu u većine adolescenata bila je usporediva s onom u odraslih koji su primali isti režim doziranja.
English: Dosage adjustment (Children [2 to <12 years] and young adolescents with low body weight [12 to 14 years and <50 kg])
Croatian: Prilagodba doze (djeca [2 do <12 godina] i mladi adolescenti male tjelesne težine [12 do 14 godina i <50 kg])
English: For patients with IA the overall rates of global response at 6 weeks were 64.3% (9/14), the global response rate was 40% (2/5) for patients 2 to <12 years and 77.8% (7/9) for patients 12 to <18 years of age.
Croatian: Kod bolesnika s IA-om ukupne stope globalne reakcije nakon 6 tjedana bile su 64,3% (9/14), stopa globalne reakcije bila je 40% (2/5) za bolesnike u dobi od 2 do <12 godina i 77,8% (7/9) kod bolesnika u dobi od 12 do <18 godina.
English: Carcinogenicity studies were not performed with SBECD.
Croatian: Nisu provedena ispitivanja kancerogenosti SBECD-a.
English: The study comprised 55 patients with serious refractory systemic Candida infections (including candidaemia, disseminated and other invasive candidiasis) where prior antifungal treatment, particularly with fluconazole, had been ineffective.
Croatian: U ispitivanje je bilo uključeno 55 bolesnika s ozbiljnim refraktornim sistemskim infekcijama čiji je uzročnik bila Candida (uključujući kandidemiju, diseminiranu i druge oblike invazivne kandidijaze), u kojih prethodno liječenje drugim antimikoticima, posebice flukonazolom, nije bilo djelotvorno.
English: Dose reduction of methadone may be needed (see section 4.5).
Croatian: Možda će biti potrebno smanjiti dozu metadona (vidjeti dio 4.5).
English: Voriconazole Hikma must not be infused into the same line or cannula concomitantly with other drug infusions, including parenteral nutrition (e.g. Aminofusin 10% Plus).
Croatian: Hikma se ne smije primijeniti u istoj infuzijskoj liniji ili kanili istodobno s drugim lijekovima, uključujući i pripravke za parenteralnu prehranu (npr. Aminofusin 10% Plus).
English: In children experiencing photoaging injuries such as lentigines or ephelides, sun avoidance and dermatologic follow-up are recommended even after treatment discontinuation.
Croatian: U djece s lezijama uzrokovanih fotostarenjem, kao što su lentigo ili pjege, preporučuje se izbjegavanje sunca i dermatološki kontrolni pregledi čak i nakon prekida liječenja.
English: EU/1/15/1004/001 1 Pack EU/1/15/1004/002 5 Pack
Croatian: EU/1/15/1004/001 pakiranje s 1 bočicom EU/1/15/1004/002 pakiranje s 5 bočica
English: The recommended doses in children and adolescent patients are based on a population pharmacokinetic analysis of data obtained from 112 immunocompromised paediatric patients aged 2 to <12 years and 26 immunocompromised adolescent patients aged 12 to <17 years.
Croatian: Preporučene doze u djece i adolescenata temelje se na populacijskoj farmakokinetičkoj analizi podataka prikupljenih u 112 imunokompromitiranih pedijatrijskih bolesnika u dobi od 2 do < 12 godina i 26 imunokompromitiranih adolescentnih bolesnika u dobi 12 do < 17 godina.
English: The safety profile of voriconazole in adults is based on an integrated safety database of more than 2,000 subjects (including 1,603 adult patients in therapeutic trials) and an additional 270 adults in prophylaxis trials).
Croatian: Sigurnosni profil vorikonazola u odraslih temelji se na objedinjenoj bazi podataka o sigurnosti primjene u više od 2000 ispitanika (uključujući 1603 odrasla bolesnika u terapijskim kliničkim ispitivanjima) i dodatnih 270 odraslih ispitanika u ispitivanjima profilakse.
English: Clinical management should include laboratory evaluation of hepatic function (specifically AST and ALT) at the initiation of treatment with voriconazole and at least weekly for the first month of treatment.
Croatian: Kliničko zbrinjavanje trebalo bi uključivati laboratorijsku procjenu funkcije jetre (osobito AST-a i ALT-a) na samom početku uzimanja vorikonzola i zatim barem svaki tjedan tijekom prvog mjeseca uzimanja.
English: For storage conditions after reconstitution of the medicinal product, see section 6.3.
Croatian: Uvjete čuvanja nakon pripreme lijeka vidjeti u dijelu 6.3.
English: If you have liver disease, your doctor may prescribe a lower dose of Voriconazole Hikma.
Croatian: Ako imate bolest jetre, liječnik će Vam možda propisati nižu dozu lijeka Vorikonazol Hikma.
English: Voriconazole is rapidly and almost completely absorbed following oral administration, with maximum plasma concentrations (Cmax) achieved 1-2 hours after dosing.
Croatian: Vorikonazol se brzo i gotovo u potpunosti apsorbira nakon peroralne primjene, a vršne koncentracije u plazmi (Cmax) dostižu se 1-2 sata nakon primjene.
English: 8 See section 4.4.
Croatian: Vidjeti dio 4.4. 8 Vidjeti dio 4.4.
English: In the same study, no significant differences in Cmax and AUCτ were observed between healthy elderly males and healthy elderly females (≥ 65 years).
Croatian: U istom ispitivanju nisu zabilježene značajne razlike u Cmax i AUCτ između zdravih starijih muškaraca i žena (≥ 65 godina).
English: The safety profile of voriconazole in young and elderly patients was similar and, therefore, no dosage adjustment is necessary for the elderly (see section 4.2).
Croatian: Sigurnosni je profil vorikonazola podjednak u mladih i starijih bolesnika te stoga nije potrebno prilagođavati dozu u starijih osoba (vidjeti dio 4.2).
English: After administration of a radiolabelled dose of voriconazole, approximately 80 % of the radioactivity is recovered in the urine after multiple intravenous dosing and 83 % in the urine after multiple oral dosing.
Croatian: Nakon primjene doze radioaktivno obilježenog vorikonazola približno se 80% radioaktivnosti nađe u mokraći nakon višekratne intravenske primjene, a 83% u mokraći nakon višekratne peroralne primjene.
English: In case of treatment-related adverse events (hepatotoxicity, severe skin reactions including phototoxicity and SCC, severe or prolonged visual disorders and periostitis), discontinuation of voriconazole and use of alternative antifungal agents must be considered.
Croatian: U slučaju štetnih događaja povezanih s liječenjem (hepatotoksičnost, teške kožne reakcije uključujući fototoksičnost i SCC, teški ili produženi poremećaji vida i periostitis) treba razmisliti o prekidu liječenja vorikonazolom i primjeni zamjenskih antimikotika.
English: Infections and infestations sinusitis pseudomembranous colitis
Croatian: Infekcije i infestacije sinusitis pseudomembransk i kolitis
English: Voriconazole is indicated for paediatric patients aged two years or older.
Croatian: Vorikonazol je indiciran u pedijatrijskih bolesnika u dobi od 2 ili više godina.
English: The 84-day survival rate for voriconazole was statistically significantly higher than that for the comparator and a clinically and statistically significant benefit was shown in favour of voriconazole for both time to death and time to discontinuation due to toxicity.
Croatian: Stopa 84-dnevnog preživljenja je kod primjene vorikonazola bila statistički značajno veća od one kod primjene usporednog lijeka, a pokazala se i klinički i statistički značajna korist vorikonazola s obzirom na vrijeme do nastupa smrti i vrijeme do prekida terapije zbog toksičnih učinaka lijeka.
English: No pharmacokinetic data are available for patients with severe hepatic cirrhosis (Child-Pugh C) (see sections 4.2 and 4.4).
Croatian: Nema podataka o farmakokinetici u bolesnika s teškom cirozom jetre (Child-Pugh stadij C) (vidjeti dijelove 4.2 i 4.4).
English: The modified intent-to-treat (MITT) group included 465 allogeneic HSCT recipients with 45% of patients having AML.
Croatian: modified intent-to-treat, MITT) uključivala je 465 primatelja alogene HSCT, a 45% bolesnika imalo je akutnu mijeloičnu leukemiju (AML).
English: No subject experienced an interval exceeding the potentially clinically relevant threshold of 500 msec (see section 5.1).
Croatian: Niti u jednog ispitanika nije primijećeno produljenje intervala iznad potencijalno značajne kliničke granice od 500 ms (vidjeti dio 5.1).
English: Children (2 to <12 years) and young adolescents with low body weight (12 to 14 years and <50 kg) Voriconazole should be dosed as children as these young adolescents may metabolize voriconazole more similarly to children than to adults.
Croatian: Djeca (2 do < 12 godina) i mlađi adolescenti male tjelesne težine (12 do 14 godina i <50 kg) Vorikonazol se treba dozirati kao kod djece jer mlađi adolescenti mogu metabolizirati vorikonazol sličnije djeci nego odraslima.
English: Greater than proportional increase in exposure is observed with increasing dose.
Croatian: S povećanjem doze se izloženost lijeku povećava više nego proporcionalno dozi.
English: Other Candida spp.4
Croatian: Druge vrste iz roda Candida spp.4
English: Voriconazole has been associated with elevations in liver function tests and clinical signs of liver damage, such as jaundice, and must only be used in patients with severe hepatic impairment if the benefit outweighs the potential risk.
Croatian: Vorikonazol je povezan s povišenjem vrijednosti testova funkcije jetre i s kliničkim znakovima oštećenja jetre, kao što je žutica pa ga u bolesnika s teškim oštećenjem jetre treba primjenjivati samo ako korist od njegove primjene nadilazi mogući rizik.
English: Dosage adjustments in case of co-administration
Croatian: Prilagodba doze u slučaju istodobne primjene
English: The safety of voriconazole was also investigated in 158 additional paediatric patients aged 2 to <12 years in compassionate use programs.
Croatian: Sigurnost vorikonazola ispitana je također u 158 dodatnih pedijatrijskih bolesnika u dobi od 2 do <12 godina u programima milosrdne primjene lijeka.
English: The volume of distribution at steady state for voriconazole is estimated to be 4.6 L/kg, suggesting extensive distribution into tissues.
Croatian: Volumen distribucije vorikonazola u stanju dinamičke ravnoteže procjenjuje se na 4,6 l/kg, što ukazuje na opsežnu raspodjelu u tkiva.
English: • Patient Alert Card for Phototoxicity and SCC: - Reminds patients of the risk of phototoxicity and skin SCC.
Croatian: • Kartica s upozorenjima za bolesnika o fototoksičnosti i SCC-u: - Podsjeća bolesnike na rizik od fototoksičnosti i SCC kože.
English: In the clinical programme, no dosage adjustment was made on the basis of gender.
Croatian: U kliničkom programu doze se nisu prilagođavale s obzirom na spol.
English: • invasive aspergillosis (a type of fungal infection due to Aspergillus sp.),
Croatian: • invazivnu aspergilozu (vrstu gljivične infekcije uzrokovanu vrstama iz roda Aspergillus),
English: Preclinical data on the intravenous vehicle, SBECD indicated that the main effects were vacuolation of urinary tract epithelium and activation of macrophages in the liver and lungs in the repeated-dose toxicity studies.
Croatian: Pretklinički podaci o intravenskom vehikulumu SBECD-u pokazali su da su glavni učinci bili vakuolizacija epitela mokraćnog sustava i aktiviranje makrofaga u jetri i plućima u ispitivanjima toksičnosti ponovljenih doza.
English: - Reminds HCPs to provide a Patient Alert Card to the patient.
Croatian: - Podsjeća zdravstvene radnike da daju bolesniku karticu s upozorenjima za bolesnika..
English: Because of non-linear pharmacokinetics, the terminal half-life is not useful in the prediction of the accumulation or elimination of voriconazole.
Croatian: Zbog nelinearne farmakokinetike terminalni poluvijek nije koristan pretkazatelj kumulacije ni eliminacije vorikonazola.
English: In clinical trials, 705 patients received voriconazole therapy for greater than 12 weeks, with 164 patients receiving voriconazole for over 6 months.
Croatian: U kliničkim je ispitivanjima 705 bolesnika primalo vorikonazol dulje od 12 tjedana, a 164 bolesnika dulje od 6 mjeseci.
English: The efficacy and survival benefit of voriconazole versus conventional amphotericin B in the primary treatment of acute invasive aspergillosis was demonstrated in an open, randomised, multicentre study in 277 immunocompromised patients treated for 12 weeks.
Croatian: Djelotvornost vorikonazola i korist s obzirom na preživljenje, u odnosu na konvencionalni amfotericin B, u primarnom liječenju akutne invazivne aspergiloze dokazana je u otvorenom, randomiziranom, multicentričnom ispitivanju s 277 imunokompromitiranih bolesnika liječenih tijekom 12 tjedana.
English: Timepoint
Croatian: Vremenska točka
English: • Non-nucleoside reverse transcriptase inhibitors (e.g., efavirenz, delavirdine, nevirapine) (used for treating HIV) (some doses of efavirenz can NOT be taken at the same time as Voriconazole Hikma)
Croatian: • nenukleozidne inhibitore reverzne transkriptaze (npr. efavirenz, delavirdin, nevirapin) (koriste se za liječenje HIV-a) (neke doze efavirenza NE smiju se koristiti istovremeno s lijekom Vorikonazol Hikma)
English: Patients who did not have an assessment 12 weeks after EOT were counted as failures.
Croatian: Bolesnici u kojih nije učinjena procjena 12 tjedana po završetku liječenja ubrojeni su među one koji nisu odgovorili na liječenje.
English: Dose adjustments in prophylaxis studies have not been explored.
Croatian: Prilagodbe doze nisu istražene u ispitivanjima profilakse.
English: The reduced dose and/or frequency of voriconazole and fluconazole that would eliminate this effect have not been established.
Croatian: Nije utvrđeno koja bi smanjena doza i/ili učestalost primjene vorikonazola i flukonazola poništila ovaj učinak.
English: A satisfactory global response (complete or partial resolution of all attributable symptoms signs, radiographic/bronchoscopic abnormalities present at baseline) was seen in 53 % of voriconazole-treated patients compared to 31 % of patients treated with comparator.
Croatian: Zadovoljavajući opći odgovor (potpuno ili djelomično povlačenje svih simptoma bolesti kao i rendgenskih/bronhoskopskih promjena prisutnih na početku liječenja) uočen je u 53% bolesnika liječenih vorikonazolom u usporedbi s 31% bolesnika liječenih usporednim lijekom.
English: Pharmacokinetic-Pharmacodynamic analyses of clinical trial data identified positive associations between plasma voriconazole concentrations and both liver function test abnormalities and visual disturbances.
Croatian: Farmakokinetičko-farmakodinamičke analize podataka iz kliničkih ispitivanja otkrile su pozitivnu povezanost između koncentracija vorikonazola u plazmi i poremećaja testova funkcije jetre kao i poremećaja vida.
English: If you are already being treated with rifabutin, your blood counts and side effects to rifabutin will need to be monitored.
Croatian: Ako već primate rifabutin, morat će se kontrolirati krvna slika i nuspojave na rifabutin.
English: Photosensitivity reactions, such as ephelides, lentigo and actinic keratosis, have been reported, especially during long-term therapy (see section 4.4).
Croatian: Opisane su i reakcije fotoosjetljivosti, kao što su pjege, lentigo i aktinička keratoza, posebice tijekom dugotrajnog liječenja (vidjeti dio 4.4).
English: After an oral single dose (200 mg), AUC was 233 % higher in subjects with mild to moderate hepatic cirrhosis (Child-Pugh A and B) compared with subjects with normal hepatic function.
Croatian: Nakon primjene jedne peroralne doze (200 mg) AUC je bio 233% veći u ispitanika s blagom do umjereno teškom cirozom jetre (Child-Pugh stadij A i B) u usporedbi s ispitanicima s normalnom jetrenom funkcijom.
English: Infusion of total parenteral nutrition can occur silmultaneously with Voriconazole Hikma but not in the same line or cannula.
Croatian: Infuzija pripravka potpune parenteralne prehrane može se odvijati u isto vrijeme s primjenom lijeka Vorikonazol Hikma, ali ne u istoj infuzijskoj liniji ili kanili.
English: There is limited data on the safety of voriconazole in patients with abnormal liver function tests (aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), or total bilirubin >5 times the upper limit of normal).
Croatian: Podaci o sigurnosti vorikonazola u bolesnika s abnormalnim testovima funkcije jetre (aspartat transaminaza [AST], alanin transaminaza [ALT], alkalna fosfataza [ALP] ili ukupan bilirubin > 5 puta od gornje granice normalne vrijednosti) su ograničeni.
English: The second study enrolled 22 patients with invasive candidiasis including candidaemia (ICC), and esophageal candidiasis (EC) requiring either primary or salvage therapy, of whom 17 were included in the MITT efficacy analyses.
Croatian: Drugo je ispitivanje uključivalo 22 bolesnika s invazivnom kandidijazom, uključujući kandidemiju (ICC) i ezofagalnu kandidijazu (EC) koje zahtijevaju primarno liječenje ili postupke spašavanja života bolesnika, od kojih je 17 uključeno u analize djelotvornosti MITT.
English: The compatibility of voriconazole with diluents other than described above or in section 6.2 is unknown.
Croatian: Nije poznata kompatibilnost vorikonazola s drugim otopinama za razrjeđivanje, osim onih navedenih u prethodnom odlomku ili u dijelu 6.2.
English: Oral*
Croatian: Peroralno *
English: It may only be continued up to 180 days after transplantation in case of continuing immunosuppression or graft versus host disease (GvHD) (see section
Croatian: Smije se nastaviti najviše 180 dana nakon transplantacije u slučaju nastavka imunosupresije ili reakcije presatka protiv primatelja (GvHD) (vidjeti dio 5.1).
English: Safety and effectiveness in paediatric subjects below the age of two years has not been established (see sections 4.8 and 5.1).
Croatian: Sigurnost i djelotvornost vorikonazola u pedijatrijskih ispitanika mlađih od dvije godine nisu ustanovljene (vidjeti dijelove 4.8 i 5.1).
English: Monitoring of hepatic function should be carried out in both children and adults.
Croatian: Praćenje funkcije jetre treba provoditi i u djece i odraslih.
English: Indinavir Cmax ↔ Indinavir AUCτ ↔ Voriconazole Cmax ↔ Voriconazole AUCτ ↔
Croatian: Indinavir Cmax ↔ Indinavir AUCτ ↔ Vorikonazol Cmax ↔ Vorikonazol AUCτ
English: *Oral dosage forms of voriconazole are available from other manufacturers Note: Based on a population pharmacokinetic analysis in 112 immunocompromised paediatric patients aged 2 to <12 years and 26 immunocompromised adolescents aged 12 to <17 years.
Croatian: * oralni dozirni oblici vorikonazola su dostupni od drugih proizvođača Napomena: na temelju populacijske farmakokinetičke analize u 112 imunokompromitiranih pedijatrijskih bolesnika u dobi od 2 do <12 godina te 26 imunokompromitiranih adolescenata u dobi od 12 do <17 godina.
English: Voriconazole has been associated with QTc interval prolongation.
Croatian: Vorikonazol se povezuje s produljenjem QTc-intervala.
English: Duration of treatment The duration of treatment with the intravenous formulation should be no longer than 6 months (see section
Croatian: Trajanje liječenja Trajanje liječenje intravenskim oblikom ne smije biti dulje od 6 mjeseci (vidjeti dio 5.3).