FrancophonIA/ELRC3.0 huggingface dataset:
English: Difference of incidence between roflumilast and placebo was quantitatively greater with concomitant LAMA for weight decreased (7.2% vs 4.2%), decreased appetite (3.7% vs 2.0%), headache (2.4% vs 1.1%) and depression (1.4% vs -0.3%).
Croatian: Razlika u incidenciji između roflumilasta i placeba bila je kvantitativno veća uz istodobni LAMA za smanjenje težine (7,2% naspram 4,2%), smanjeni apetit (3,7 naspram 2,0), glavobolju (2,4% naspram 1,1%) i depresiju (1,4% naspram -0,3%).
English: The numbers of patients who died due to any reason were equal for those treated with placebo or roflumilast (42 deaths each group; 2.7% each group; pooled analysis).
Croatian: Broj bolesnika sa smrtnim ishodom bez obzira na uzrok bio je jednak u skupinama liječenim placebom ili roflumilastom (42 smrti u svakoj skupini; 2,7% u svakoj skupini; objedinjena analiza).
English: In Phase I studies, the following symptoms were observed at an increased rate after single oral doses of 2,500 micrograms and one single dose of 5,000 micrograms (ten times the recommended dose): headache, gastrointestinal disorders, dizziness, palpitations, light-headedness, clamminess and arterial hypotension.
Croatian: U ispitivanjima faze I sljedeći su se simptomi učestalije javljali nakon jednokratnih peroralnih doza od 2500 mikrograma i jedne jednokratne doze od 5000 mikrograma (deset puta veća doza od preporučene): glavobolja, gastrointestinalne smetnje, omaglica, palpitacije, ošamućenost, hladan, ljepljivi znoj i arterijska hipotenzija.
English: Therefore, the use of strong cytochrome P450 enzyme inducers (e.g. phenobarbital, carbamazepine, phenytoin) may reduce the therapeutic efficacy of roflumilast.
Croatian: Stoga se istodobnom primjenom snažnih induktora citokroma P450 (npr. fenobarbitala, karbamazepina, fenitoina) može smanjiti terapijsko djelovanje roflumilasta.
English: There was a trend towards a reduction in moderate or severe exacerbations in subjects treated with roflumilast compared with placebo over 52 weeks, which did not achieve statistical significance (Table 2).
Croatian: Zabilježen je trend smanjenja umjerenih i teških egzacerbacija u ispitanika liječenih roflumilastom u usporedbi s onima koji su uzimali placebo tijekom 52 tjedna, koji nije dosegao statističku značajnost (tablica 2).
English: Co-administration with an antacid (combination of aluminium hydroxide and magnesium hydroxide) did not alter the absorption or pharmacokinetics of roflumilast or its N-oxide.
Croatian: Istodobnom primjenom s antacidom (koji sadrži aluminijev hidroksid i magnezijev hidroksid) ne mijenjaju se apsorpcija i farmakokinetika roflumilasta ili njegovog N-oksida.
English: D-16515 Oranienburg Germany
Croatian: D-16515 Oranienburg
English: Daxas tablets contain lactose.
Croatian: Daxas tablete sadrže laktozu.
English: This helps to stop narrowing of airways occurring in chronic obstructive pulmonary disease (COPD).
Croatian: Time se zaustavlja sužavanje dišnih puteva koje se javlja u kroničnoj opstruktivnoj plućnoj bolesti (KOPB).
English: A combination of factors, such as in black, non-smoking females, might lead to an increase of exposure and persistent intolerability.
Croatian: U slučaju preklapanja više čimbenika, primjerice kod žena crne rase koje ne puše, moguća je povećana izloženost i trajna nepodnošljivost lijeka.
English: The most commonly reported adverse reactions were diarrhoea (5.9%), weight decreased (3.4%), nausea (2.9%), abdominal pain (1.9%) and headache (1.7%).
Croatian: Najčešće prijavljene nuspojave bile su proljev (5,9%), smanjenje tjelesne težine (3,4%), mučnina (2,9%), bol u trbuhu (1,9%) i glavobolja (1,7%).
English: Following intravenous or oral administration of radiolabelled roflumilast, about 20% of the radioactivity was recovered in the faeces and 70% in urine as inactive metabolites.
Croatian: Nakon intravenske ili peroralne primjene radiooznačenog roflumilasta oko 20% radioaktivnosti izlučeno je fecesom i 70% u mokraći u obliku neaktivnih metabolita.
English: The absolute bioavailability of roflumilast following a 500 micrograms oral dose is approximately 80%.
Croatian: Apsolutna bioraspoloživost roflumilasta nakon peroralne primjene 500 mikrograma je približno 80%.
English: You may also experience sleeplessness, anxiety, nervousness, or depressive mood.
Croatian: Također se mogu pojaviti i nesanica, tjeskoba, nervoza ili depresivno raspoloženje.
English: The plasma AUC of the N-oxide metabolite on average is about 10-fold greater than the plasma AUC of roflumilast.
Croatian: Plazmatski AUC (engl. area under the curve) metabolita N-oksida je prosječno oko 10 puta veći od plazmatskog AUC-a roflumilasta.
English: This mechanism of action and the selectivity also apply to roflumilast N-oxide, which is the major active metabolite of roflumilast.
Croatian: Jednaki mehanizam djelovanja i selektivnost vrijede i za roflumilast N-oksid koji je glavni aktivni metabolit roflumilasta.
English: Interim Study Reports - with each PSUR.
Croatian: Privremena izvješća ispitivanja - sa svakim
English: • insomnia, anxiety, depression, changes in behaviour or mood, suicidal ideation or behaviour
Croatian: • nesanicu, anksioznost, depresiju, promjene u ponašanju ili raspoloženju, suicidalne misli ili ponašanje
English: If you stop taking Daxas
Croatian: Ako prestanete uzimati Daxas
English: At screening, patients were required to have had at least one exacerbation in the previous year and on standard of care COPD maintenance treatment for at least 12 weeks.
Croatian: Bolesnici su pri probiru morali imati najmanje jednu egzacerbaciju tijekom prethodne godine i primati standardnu terapiju održavanja za KOPB tijekom najmanje 12 tjedana.
English: Prolongation of gestation was seen in mice.
Croatian: Kod miševa je opaženo produljenje trajanja gestacije.
English: Maximum plasma concentrations of roflumilast typically occur approximately one hour after dosing (ranging from 0.5 to 2 hours) in the fasted state.
Croatian: Maksimalna koncentracija roflumilasta u plazmi najčešće se postiže približno jedan sat nakon unosa (u rasponu od 0,5 do 2 sata) natašte.
English: The lack of clinical data to support the combination with theophylline and that such combination is not recommended.
Croatian: Nepostojanje kliničkih podataka u prilog istodobne primjene s teofilinom te da se takva kombinacija ne preporučuje.
English: 16515 Oranienburg Germany
Croatian: 16515 Oranienburg Njemačka
English: In one of three rat studies on fertility and embryofetal development, post-implantation losses were observed.
Croatian: U jednom od tri ispitivanja plodnosti i embriofetalnog razvoja štakora primijećeni su postimplantacijski prekidi trudnoće.
English: You may experience diarrhoea, nausea, stomach ache or headache during the first weeks of treatment with Daxas.
Croatian: Proljev, mučninu, bolove u trbuhu ili glavobolju možete osjetiti tijekom prvih tjedana liječenja lijekom Daxas.
English: Roflumilast is extensively metabolised in humans, with the formation of a major pharmacodynamically active metabolite, roflumilast N-oxide.
Croatian: Roflumilast se kod ljudi opsežno metabolizira uz stvaranje glavnog farmakodinamički aktivnog metabolita, roflumilast N-oksida.
English: An early distribution phase with marked penetration into tissues is followed by a marked elimination phase out of fatty tissue most probably due to pronounced break-down of parent compound to roflumilast N-oxide.
Croatian: Ranu fazu distribucije s naglašenim prodiranjem u tkiva slijedi eliminacijska faza iz masnog tkiva, najvjerojatnije zbog obilne razgradnje roflumilasta u roflumilast N-oksid.
English: A pre-specified sensitivity analysis using the negative binomial regression model treatment showed a statistically significant difference of -14.2% (rate ratio: 0.86; 95% CI: 0.74 to 0.99).
Croatian: Unaprijed definirana analiza osjetljivosti primjenom negativnog binomnog regresijskog modela pokazala je statistički značajnu razliku od -14,2% (omjer stope: 0,86; 95% CI: 0,74 do 0,99).
English: You may also experience sleeplessness (common), anxiety (uncommon), nervousness (rare), panic attack (rare) or depressive mood (rare).
Croatian: Također, možete patiti od nesanice (često), tjeskobe (manje često), nervoze (rijetko), napadaja panike (rijetko) ili depresivnog raspoloženja (rijetko).
English: Maximum concentrations of the N-oxide metabolite are reached after about eight hours (ranging from 4 to 13 hours).
Croatian: N-oksida postiže se nakon otprilike osam sati (u rasponu od 4 do 13 sati).
English: Post-bronchodilator FEV1 showed a clinically significant improvement in favour of roflumilast by 56 mL over placebo (95% CI: 38, 73 mL).
Croatian: Postbronhodilatacijski FEV1 pokazao je klinički značajno poboljšanje u korist roflumilasta za 56 ml u odnosu na placebo (95% CI: 38,73 ml).
English: Titanium dioxide (E171) Iron oxide yellow (E172)
Croatian: Ovojnica hipromeloza makrogol 4000 titanijev dioksid (E171) željezov oksid, žuti (E172)
English: Daxas contains the active substance roflumilast, which is an anti-inflammatory medicine called phosphodiesterase-4 inhibitor.
Croatian: Daxas sadrži djelatnu tvar roflumilast, a to je protuupalni lijek koji zovemo inhibitorom fosfodiesteraze-4.
English: In contrast to the two confirmative studies, a history of chronic bronchitis and of COPD exacerbations was not requested for patients' inclusion.
Croatian: Suprotno dvama potvrdnim ispitivanjima, kronični bronhitis i egzacerbacije KOPB-a nisu bili uvjet za uključenje bolesnika.
English: A total of 1935 patients were randomised to doubleblind medication and approximately 70% were also using a long-acting muscarinic antagonist (LAMA) through the course of the trial.
Croatian: Dvostruko-slijepo je randomizirano ukupno 1935 bolesnika, a za trajanja ispitivanja je približno 70% također primjenjivalo dugodjelujuće muskarinske antagoniste (LAMA).
English: Based on further in vitro results in human hepatic microsomes, therapeutic plasma concentrations of roflumilast and roflumilast N-oxide do not inhibit CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4/5, or 4A9/11.
Croatian: Temeljem in vitro rezultata na ljudskim jetrenim mikrosomima, terapijske plazmatske koncentracije roflumilasta i roflumilast N-oksida ne inhibiraju CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4/5 ili 4A9/11.
English: Do not take Daxas - if you are allergic to roflumilast or any of the other ingredients of this medicine (listed in section
Croatian: Nemojte uzimati Daxas - ako ste alergični na roflumilast ili neki drugi sastojak ovog lijeka (naveden u dijelu 6.) - ako imate umjerene ili teške tegobe s jetrom.
English: • Obligation to conduct post-authorisation measures
Croatian: •Obveza provođenja mjera nakon davanja odobrenja
English: The MAH shall perform the required pharmacovigilance activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent updates of the RMP.
Croatian: Nositelj odobrenja obavljat će zadane farmakovigilancijske aktivnosti i intervencije, detaljno objašnjenje u dogovorenom Planu upravljanja rizikom (RMP), koji se nalazi u Modulu 1.8.2
English: Moderate or severe hepatic impairment (Child-Pugh B or C).
Croatian: Umjereno ili teško oštećenje jetre (Child-Pugh B ili C).
English: • Copies of the patient card to be given to patients or caregivers before they receive Daxas
Croatian: • Edukacijski materijal za liječnike • Kopije kartice za bolesnike za uručiti bolesnicima prije nego dobiju Daxas
English: If you forget to take Daxas
Croatian: Ako ste zaboravili uzeti Daxas
English: In clinical studies and post-marketing experience, rare instances of suicidal thinking and behaviour (including suicide) were reported.
Croatian: U kliničkim ispitivanjima i prema iskustvu nakon stavljanja lijeka u promet, zabilježeni su rijetki slučajevi suicidalnih misli i ponašanja (uključujući suicid).
English: All patients should be informed about the risks of Daxas and the precautions for safe use and should be given a patient card before starting Daxas.
Croatian: Bolesnike treba obavijestiti o rizicima lijeka Daxas i mjerama predostrožnosti za sigurnu primjenu, te im prije početka terapije uručiti karticu za bolesnike.
English: Upon in vitro stimulation of human neutrophils, monocytes, macrophages or lymphocytes, roflumilast and roflumilast N-oxide suppress the release of inflammatory mediators e.g. leukotriene B4, reactive oxygen species, tumour necrosis factor α, interferon γ and granzyme B.
Croatian: Nakon in vitro stimulacije ljudskih neutrofila, monocita, makrofaga ili limfocita, roflumilast i roflumilast N-oksid zaustavljaju oslobađanje upalnih posrednika poput leukotriena B4, reaktivnih oblika kisika, faktora nekroze tumora α, interferona γ i granzima B.
English: Special clinical conditions
Croatian: Posebna klinička stanja
English: The tolerability of roflumilast was evaluated in a 12-week randomised, double-blind, parallel group trial (RO-2455-302-RD) in patients with severe COPD associated with chronic bronchitis.
Croatian: Podnošljivost roflumilasta ocjenjivala se u 12-tjednom randomiziranom, dvostruko slijepom ispitivanju s paralelnim skupinama (RO-2455-302-RD) provedenom kod bolesnika s teškim KOPB-om povezanim s kroničnim bronhitisom.
English: A major step in roflumilast metabolism is the N-oxidation of roflumilast to roflumilast N-oxide by CYP3A4 and CYP1A2.
Croatian: Značajni korak u metabolizmu roflumilasta je N-oksidacija roflumilasta u roflumilast N-oksid na CYP3A4 i CYP1A2.
English: Summary of COPD exacerbation endpoints in Study RO-2455-404-RD
Croatian: Tablica 2.Sažetak ishoda egzacerbacija KOPB-a u ispitivanju RO-2455-404-RD
English: Total PDE4 inhibitory activity was slightly decreased in smokers.
Croatian: Ukupna inhibicijska aktivnost PDE4 kod pušača je nešto niža.
English: It is not known whether roflumilast is dialysable by peritoneal dialysis.
Croatian: Nije poznato može li se ukloniti peritonealnom dijalizom.
English: The potential cardiac risk: Daxas has not been studied in patients in congestive heart failure (NYHA grade3 and 4); hence, it is not recommended in this population.
Croatian: Potencijalni kardiološki rizik: Daxas nije ispitan kod bolesnika s kongestivnim zatajenjem srca (NYHA stupanj 3 i 4) stoga se ne preporučuje kod takvih bolesnika.
English: OUTER CARTON FOR BLISTER
Croatian: KARTONSKA KUTIJA ZA BLISTERE
English: Patients should be advised to weigh themselves at regular intervals and record the weight in the patient card.
Croatian: Bolesnicima treba savjetovati da se sami redovito važu i bilježe težinu na kartici za bolesnike.
English: The clinical data with Daxas in patients with mild hepatic impairment classified as Child-Pugh A are insufficient to recommend a dose adjustment (see section 5.2) and therefore Daxas should be used with caution in these patients.
Croatian: Klinički podaci o primjeni lijeka Daxas kod bolesnika s blagim oštećenjem jetre klasificiranim kao Child-Pugh A nisu dovoljni da bi se preporučilo smanjenje doze (vidjeti dio 5.2), stoga Daxas kod tih bolesnika treba koristiti uz oprez.
English: The mechanism of action is the inhibition of PDE4, a major cyclic adenosine monophosphate (cAMP)-metabolizing enzyme found in structural and inflammatory cells important to the pathogenesis of COPD.
Croatian: Mehanizam djelovanja se temelji na inhibiciji PDE4, glavnog enzima koji metabolizira ciklički adenozin monofosfat (cAMP) i prisutan je u strukturnim i upalnim stanicama važnim za patogenezu KOPB-a.
English: The other ingredients are lactose monohydrate (see section 2 under “Daxas contains lactose”), maize starch, povidone, magnesium stearate.
Croatian: Drugi sastojci su laktoza hidrat (pogledajte odlomak „Daxas sadrži laktozu“ u dijelu 2.), kukuruzni škrob, povidon, magnezijev stearat.
English: In a human spermatogenesis study, roflumilast 500 micrograms had no effects on semen parameters or reproductive hormones during the 3-month treatment period and the following 3-month off-treatment period.
Croatian: U ispitivanju spermatogeneze kod ljudi, 500 mikrograma roflumilasta nije tijekom tromjesečnog razdoblja liječenja te tromjesečnog razdoblja nakon prestanka terapije, imalo utjecaja na obilježja sperme ili spolne hormone.
English: Long-term administration at the 250 micrograms dose level may not induce sufficient PDE4 inhibition to exert clinical efficacy.
Croatian: Dugoročnom primjenom doze od 250 mikrograma jedanput na dan možda se neće postići dovoljna razina inhibicije PDE4 da bi se ostvarila klinička djelotvornost.
English: The incidence observed was also higher in patients less than 75 years old, treated with roflumilast when compared to those treated with placebo (3.1% vs 2.0%).
Croatian: Incidencija je bila veća i u bolesnika mlađih od 75 godina liječenih roflumilastom u usporedbi s onima koji su uzimali placebo (3,1% naspram 2,0%).
English: Daxas is contraindicated in patients with moderate or severe liver impairment (Child-Pugh B or C).
Croatian: Daxas je kontraindiciran kod bolesnika s umjerenim ili teškim zatajenjem jetre (Child Pugh B ili C).
English: Pregnancy There are limited amount of data from the use of roflumilast in pregnant women.
Croatian: Trudnoća Podaci o primjeni roflumilasta u trudnica su ograničeni.
English: Since roflumilast is highly protein bound, haemodialysis is not likely to be an efficient method of its removal.
Croatian: Budući da se roflumilast opsežno veže za proteine, nije vjerojatno da se može ukloniti dijalizom.
English: Following an oral dose, the median plasma effective half-life of roflumilast and its N-oxide metabolite are approximately 17 and 30 hours, respectively.
Croatian: Nakon peroralne primjene srednji efektivni poluvijek roflumilasta i njegovog N-oksid metabolita u plazmi je približno 17, odnosno 30 sati.
English: Effects were similar, independent of previous treatment with inhaled corticosteroids or underlying treatment with LABAs.
Croatian: Učinak je bio jednak bez obzira na prethodno liječenje inhalacijskim kortikosteroidima ili temeljno liječenje s LABA.
English: Body weight of underweight patients should be checked at each visit.
Croatian: Kod bolesnika niske tjelesne težine potrebno je na svakoj kontrolnoj posjeti provjeriti tjelesnu težinu.
English: Both studies included moderate to severe patients with a non-reversible airway obstruction and a FEV1 of 40% to 70% of predicted.
Croatian: U oba ispitivanja sudjelovali su i umjereni i teški bolesnici s ireverzibilnom opstrukcijom dišnih puteva i FEV1 između 40% i 70% od predviđenog.
English: Daxas is indicated for maintenance treatment of severe chronic obstructive pulmonary disease (COPD) (FEV1 post-bronchodilator less than 50% predicted) associated with chronic bronchitis in adult patients with a history of frequent exacerbations as add on to bronchodilator treatment.
Croatian: Daxas je indiciran za terapiju održavanja teške kronične opstruktivne plućne bolesti (KOPB) (postbronhodilatacijski FEV1 manji od 50% predviđenog) povezane s kroničnim bronhitisom kod odraslih bolesnika s učestalim egzacerbacijama u anamnezi, kao dodatak liječenju bronhodilatatorima.
English: Description of selected adverse reactions * In clinical studies and post-marketing experience, rare instances of suicidal ideation and behaviour, including suicide, were reported.
Croatian: Opis odabranih nuspojava * U kliničkim ispitivanjima i iskustvu s lijekom nakon stavljanja u promet zabilježeni su rijetki primjeri suicidalnih misli i ponašanja uključujući i suicid.
English: Patient Card
Croatian: Kartica za bolesnike
English: The one-year studies included patients with a history of severe to very severe COPD [FEV1 (forced expiratory volume in one second) ≤50% of predicted] associated with chronic bronchitis, with at least one documented exacerbation in the previous year and with symptoms at baseline as determined by cough and sputum score.
Croatian: U jednogodišnjim ispitivanjima sudjelovali su bolesnici s teškim do vrlo teškim KOPB-om u anamnezi [FEV1 (forsirani ekspiratorni volumen u jednoj sekundi) ≤50% predviđenog] povezanim s kroničnim bronhitisom, s barem jednom dokumentiranom egzacerbacijom u proteklih godinu dana te sa simptomima kašlja i produkcije sputuma.
English: The recommended starting dose is one tablet of 250 micrograms roflumilast to be taken once daily, for 28 days.
Croatian: Preporučena početna doza je jedna tableta od 250 mikrograma roflumilasta primijenjena jedanput na dan tijekom 28 dana.
English: • insomnia, anxiety, depression, suicidal ideation or behaviour
Croatian: • nesanicu, anksioznost, depresiju, suicidalne misli ili ponašanje
English: Adverse events rates were independent of concomitant treatment with inhaled corticosteroids.
Croatian: Stopa nuspojava bila je neovisna o istodobnom liječenju inhalacijskim kortikosteroidima.
English: Adverse reactions with roflumilast in clinical COPD studies and post-marketing experience
Croatian: Nuspojave roflumilasta u kliničkim ispitivanjima KOPB i prema iskustvu nakon stavljanja lijeka u promet
English: After 28 days of treatment with the 250-micrograms starting dose, patients must be up-titrated to one tablet of 500 micrograms roflumilast, to be taken once daily.
Croatian: Nakon 28 dana liječenja početnom dozom od 250 mikrograma, bolesniku se mora povisiti doza na jednu tabletu od 500 mikrograma roflumilasta primijenjenu jedanput na dan.
English: Post-bronchodilator FEV1 increased for the roflumilast group by 52 mL (95% CI: 40, 65 mL) and decreased for the placebo group by 4 mL (95% CI: -16, 9 mL).
Croatian: Postbronhodilatacijski FEV1 povećao se za 52 ml u skupini koja je uzimala roflumilast (95% CI: 40, 65 ml) i smanjio za 4 ml u skupina koja je uzimala placebo (95% CI: -16,9 ml).
English: Steady state plasma concentrations of roflumilast and its N-oxide metabolite are reached after approximately 4 days for roflumilast and 6 days for roflumilast N-oxide following once-daily dosing.
Croatian: Koncentracije roflumilasta i njegovog N-oksid metabolita u plazmi u stanju dinamičke ravnoteže postižu se nakon približno 4 dana za roflumilast, odnosno 6 dana za roflumilast N-oksid, uz doziranje jednanput na dan.
English: The majority of these adverse reactions were mild or moderate.
Croatian: Većina nuspojava bile su blage do umjerene.
English: The study assessed the effect of roflumilast on COPD exacerbation rate in patients treated with fixed combinations of LABA and inhaled corticosteroids, compared to placebo.
Croatian: Ispitivanje je ocijenilo učinak roflumilasta na stopu egzacerbacija KOPB-a u bolesnika liječenih fiksnom kombinacijom LABA i inhalacijskih kortikosteroida, u usporedbi s placebom.
English: This might be the case in special populations that may have higher exposure, such as in black, non-smoking females (see section 5.2) or in patients concomitantly treated with CYP1A2/ 2C19/3A4 inhibitors (such as fluvoxamine and cimetidine) or the CYP1A2/3A4 inhibitor enoxacin (see section 4.5).
Croatian: To može biti slučaj kod posebnih skupina bolesnika kod kojih je izloženost lijeku povećana, poput žena crne rase koje ne puše (vidjeti dio 5.2) ili bolesnika koji se istodobno liječe inhibitorima CYP1A2/2C19/3A4 (kao što su fluvoksamin i cimetidin) ili inhibitorom CYP1A2/3A4 enoksacinom (vidjeti dio 4.5).
English: You may take this medicine with or without food.
Croatian: Lijek možete uzimati natašte ili uz jelo.
English: In vitro studies and clinical interaction studies suggest that the metabolism of roflumilast to its N-oxide metabolite is mediated by CYP1A2 and 3A4.
Croatian: In vitro ispitivanja i klinička ispitivanja interakcija pokazuju da se metabolizam roflumilasta u njegov N-oksid metabolit odvija posredstvom CYP1A2 i 3A4.
English: Since both roflumilast and roflumilast N-oxide contribute to PDE4 inhibitory activity in vivo, pharmacokinetic considerations are based on total PDE4 inhibitory activity (i.e. total exposure to roflumilast and roflumilast N-oxide).
Croatian: Budući da i roflumilast i roflumilast N-oksid pridonose inhibicijskoj aktivnosti PDE4 in vivo, farmakokinetički podaci odražavaju ukupnu inhibicijsku aktivnost PDE4 (odnosno ukupnu izloženost roflumilastu i roflumilast N-oksidu).