FrancophonIA/ELRC3.0 huggingface dataset:
English: Posaconazole Accord must not be administered with medicinal products that are substrates for CYP3A4 and are known to prolong the QTc interval (see sections 4.3 and 4.5).
Danish: Posaconazole Accord må ikke administreressammen med lægemidler, som er substrater for CYP3A4, og som er kendt for at forlænge QTc-intervallet (se pkt.
English: Q2
Danish: K2
English: Posaconazole Accord contains a medicine called posaconazole.
Danish: Posaconazole Accord indeholder et lægemiddelstof, der hedder posaconazol.
English: - Candida albicans: S ≤0.06 mg/L, R >0.06 mg/L - Candida tropicalis: S ≤0.06 mg/L, R >0.06 mg/L - Candida parapsilosis: S ≤0.06 mg/L, R >0.06 mg/L
Danish: EUCAST-MIC-grænseværdier for posaconazol [følsomme (S); resistente (R)]: - Candida albicans:S≤0,06 mg/l,R>0,06 mg/l - Candida tropicalis:S≤0,06 mg/l,R>0,06 mg/l - Candida parapsilosis:S≤0,06 mg/l,R>0,06 mg/l
English: Following administration of 800 mg per day of posaconazole oral suspension as a divided dose for treatment of invasive fungal infections, mean trough plasma concentrations from 12 patients 8-17 years of age (776 ng/mL) were similar to concentrations from 194 patients 18-64 years of age (817 ng/mL).
Danish: Efter administration af 800 mg posaconazol oral suspension dagligt fordelt på flere doser til behandling af invasive svampeinfektioner svarede de gennemsnitlige dalplasmakoncentrationer fra 12 patienteri alderen 8-17 år (776 ng/ml) til koncentrationerne fra 194 patienterialderen18-64 år (817 ng/ml).
English: Rifabutin (300 mg once a day) decreased the Cmax (maximum plasma concentration) and AUC (area under the plasma concentration time curve) of posaconazole to 57% and 51%, respectively.
Danish: Rifabutin(300 mgen gangdagligt)nedsatte Cmax(maksimalplasmakoncentration)og AUC(arealetunder kurven for plasmakoncentration som funktion af tiden) for posaconazol til henholdsvis 57 % og51 %.
English: Dose adjustment of benzodiazepines metabolised by CYP3A4 should be considered (see section 4.5).
Danish: Dosisjustering af benzodiazepiner, som metaboliseres af CYP3A4, bør overvejes (se pkt.
English: PHARMACEUTICAL FORM AND CONTENTS 24 gastro-resistant tablets
Danish: LÆGEMIDDELFORM OG INDHOLD (PAKNINGSSTØRRELSE) 24gastroresistentetabletter
English: In subjects with severe renal impairment (n=6, Clcr< 20 mL/min/1.73 m2), the AUC of posaconazole was highly variable [> 96% CV (coefficient of variance)] compared to other renal groups [< 40% CV].
Danish: Hos patienter med svært nedsat nyrefunktion(n=6, Clcr< 20 ml/min/1,73m2)varAUC forposaconazolmegetvariabel[>96 % CV(varianskoefficient)] sammenlignet med andre grupper med nyrelidelse [<40 % CV].
English: A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
Danish: A. FREMSTILLERE ANSVARLIGE FORBATCHFRIGIVELSE
English: Since certain adverse reactions (e.g. dizziness, somnolence, etc.) have been reported with posaconazole use, which potentially may affect driving/operating machinery, caution needs to be used.
Danish: Da visse bivirkninger(f.eks. svimmelhed, døsighed osv.), som potentielt kan påvirke evnen til at føremotorkøretøjog betjene maskiner, er set ved anvendelse af posaconazol, skal der udvises forsigtighed.
English: There is no information regarding cross-sensitivity between posaconazole and other azole antifungal agents.
Danish: Der findes ingen data om krydsallergi mellem posaconazol og andre antimykotiske azolderivater.
English: ANNEX III LABELLING AND PACKAGE LEAFLET
Danish: BILAGIII ETIKETTERING OG INDLÆGSSEDDEL
English: Both doses of posaconazole increased Cmax and AUC of oral midazolam (2 mg single oral dose) by 2.2 and 4.5-fold, respectively.
Danish: Begge doseraf posaconazol øgede Cmaxog AUCfor oralt midazolam (2 mgoralenkeltdosis)medhenholdsvis2,2og4,5 gange.
English: See “Other medicines and Posaconazole Accord” below for more information including information on other medicines which may interact with Posaconazole Accord.
Danish: Læs“BrugafandenmedicinsammenmedPosaconazole Accord”nedenforfor information om andre lægemidler,som kan påvirke virkningen af Posaconazole Accord.
English: The safety of posaconazole oral suspension has been assessed in > 2,400 patients and healthy volunteers enrolled in clinical trials and from post-marketing experience.
Danish: Sikkerheden af posaconazol tabletter og posaconazol oral suspension Sikkerhedenafposaconazol oral suspension er vurderet hos >2.400 patienter og frivillige raskeforsøgspersoner i kliniske studier og på baggrund af erfaring efter markedsføring.
English: electrolyte imbalance, anorexia, decreased appetite, hypokalaemia, hypomagnesaemia
Danish: Elektrolytforstyrrelser, anoreksi, nedsat appetit, hypokalæmi, hypomagnesiæmi
English: mouth ulceration, alopecia, dermatitis, erythema, petechiae
Danish: Mundsår, alopeci, dermatitis, erytem, petekkier
English: No effects on electrocardiograms, including QT and QTc intervals, were seen in a repeat dose safety pharmacology study in monkeys at maximal plasma concentrations 8.5-fold greater than the concentrations obtained at therapeutic doses in humans.
Danish: Der blev ikke konstateret virkning på elektrokardiogrammer, inklusive QT-og QTcintervaller,ietsikkerhedsfarmakologiskstudiemedgentagnedosertilabervedmaksimaleplasmakoncentration er,der var 8,5 gange større end de koncentrationer, der blev opnået ved terapeutiske doser hosmennesker.
English: During post-marketing surveillance of posaconazole oral suspension, severe hepatic injury with fatal outcome has been reported (see section 4.4).
Danish: Eftermarkedsføring af posaconazol oral suspension er der set alvorlige hepatiske skader med letaltudfald (se pkt.
English: Some patients have also reported feeling confused after taking Posaconazole Accord, the frequency of this is not known.
Danish: Nogle patienter har også oplevet at føle sig forvirrede efter brug af Posaconazole Accord.
English: Sulfonylureas
Danish: Sulfonylurinstoffer
English: Co-administration with the CYP3A4 substrates terfenadine, astemizole, cisapride, pimozide, halofantrine or quinidine since this may result in increased plasma concentrations of these medicinal products, leading to QTc prolongation and rare occurrences of torsades de pointes (see sections 4.4 and 4.5).
Danish: Samtidig administration med CYP3A4-substraterneterfenadin, astemizol, cisaprid, pimozid,halofantrin eller quinidin, da dette kan resultere i forhøjede plasmakoncentrationer af disse lægemidler med forlænget QTc og sjældne forekomster af torsades de pointestil følge (se pkt.
English: As shown in Table 4, a successful response (complete or partial resolution) at the end of treatment was seen in 42% of posaconazole-treated patients compared to 26% of the external group.
Danish: Somvist i tabel 4såsettilfredsstillenderespons(fuldstændig eller delvis bedring) efter endtbehandling hos 42 % afdepatienter,somblevbehandletmedposaconazol,sammenlignetmed26%iden eksterne gruppe.
English: Posaconazole Accord should be administered with caution to patients with pro-arrhythmic conditions such as: - Congenital or acquired QTc prolongation - Cardiomyopathy, especially in the presence of cardiac failure - Sinus bradycardia - Existing symptomatic arrhythmias - Concomitant use with medicinal products known to prolong the QTc interval (other than those mentioned in section 4.3).
Danish: Posaconazole Accord bør administreres med forsigtighed til patienter medproarytmiske tilstande såsom: - Kongenital eller erhvervet QTc-forlængelse - Kardiomyopati, især hvis hjerteinsufficiens er til stede - Sinusbradykardi - Eksisterende symptomatiske arytmier - Samtidigbehandlingmedlægemidler,somerkendtforatforlængeQTc-intervallet (ud overdem,derernævntunderpkt.
English: The mean duration of therapy was 80 days for posaconazole and 77 days for fluconazole.
Danish: Den gennemsnitligebehandlingsvarighed var80 dageforposaconazolog77 dage for fluconazol.
English: You can also report side effects directly via the national reporting system listed in Appendix V By reporting side effects you can help provide more information on the safety of this medicine.
Danish: Du eller dine pårørende kanogså indberette bivirkninger direkte til Lægemiddelstyrelsen via det nationale rapporteringssystemanførti Appendiks V.Ved at indrapportere bivirkninger kan du hjælpe med at fremskaffe mereinformationomsikkerhedenafdettelægemiddel.
English: Immune system disorders Uncommon:
Danish: Immunsystemet Ikke almindelig
English: At exposures lower than those obtained at therapeutic doses in humans, posaconazole caused skeletal variations and malformations, dystocia, increased length of gestation, reduced mean litter size and postnatal viability.
Danish: Ved lavereeksponering end den, der blev opnået ved terapeutiske doser hos mennesker, forårsagede posaconazol skeletforandringer og misdannelser, dystoki, forlænget drægtighedsperiode, reduceret gennemsnitligkuldstørrelseogpostnataloverlevelse.Hoskaninervarposaconazolembryotoksiskvedeksponer ing,der var større end den, der blev opnået med terapeutiske doser.
English: Posaconazole is not removed by haemodialysis.
Danish: Posaconazol fjernes ikke ved hæmodialyse.
English: hypersensitivity reaction
Danish: Overfølsomhedsreaktion
English: QUALITATIVE AND QUANTITATIVE COMPOSITION Each gastro-resistant tablet contains 100 mg of posaconazole.
Danish: KVALITATIV OG KVANTITATIV SAMMENSÆTNING Hver gastroresistent tablet indeholder 100 mg posaconazol.
English: Certain medicines may increase the risk of side effects of Posaconazole Accord by increasing the amount of Posaconazole Accord in the blood.
Danish: Følgende lægemidler kan nedsætte virkningen af Posaconazole Accord ved at nedsætte mængden af Posaconazole Accord i blodet:
English: Frequent monitoring for adverse reactions and toxicity related to antiretroviral agents that are substrates of CYP3A4 is recommended during coadministration with posaconazole.
Danish: Der anbefales hyppig monitorering for bivirkninger og toksicitet relateret til antiretrovirale midler, der er CYP3A4-substrater, vedadministration samtidig med posaconazol.
English: Combining fosamprenavir with posaconazole may lead to decreased posaconazole plasma concentrations.
Danish: Kombination af fosamprenavir og posaconazol kan medføre lavere plasmakoncentration af posaconazol.
English: Q3
Danish: K3
English: 24x1 gastro-resistant tablet 96x1 gastro-resistant tablet
Danish: 96x1 gastroresistente tabletter
English: cerebrovascular accident, encephalopathy, peripheral neuropathy, syncope
Danish: Hjerneblødning, encefalopati, perifer neuropati, synkope
English: 11 of 24 patients who had proven or probable fusariosis were successfully treated with posaconazole oral suspension 800 mg/day in divided doses for a median of 124 days and up to 212 days.
Danish: 11 ud af 24 patienter med påvist eller sandsynlig fusariose blev tilfredsstillende behandlet med posaconazol oral suspension 800 mg dagligt fordelt på flere doser i op til 212 dage med en median på124 dage.
English: A key secondary endpoint was the incidence of proven/probable IFIs at 100 days post-randomization.
Danish: Et centralt sekundært endepunkt var forekomstaf verificeret/sandsynligIFI100 dage efterrandomisering.
English: Patients were immunocompromised with underlying conditions including haematological malignancy, neutropenia post-chemotherapy, GVHD, and post HSCT.
Danish: Patienternevarimmunkompromitteretmedtilgrundliggendetilstande,herunderhæmatologiskmalignitet, neutropeni efter kemoterapi, GVHD og efter HSCT.
English: Efavirenz (400 mg once a day) decreased the Cmax and AUC of posaconazole by 45% and 50%, respectively.
Danish: Efavirenz(400 mg en gang dagligt) nedsatte Cmaxog AUC for posaconazol med henholdsvis45 % og50 %.
English: Co-administration with the HMG-CoA reductase inhibitors simvastatin, lovastatin and atorvastatin (see section 4.5).
Danish: Samtidig administration med HMG-CoAreduktasehæmmerne simvastatin, lovastatin og atorvastatin(se pkt.
English: Concomitant use of posaconazole and efavirenz should be avoided unless the benefit to the patient outweighs the risk.
Danish: Samtidig anvendelse af posaconazol og efavirenz bør undgås, medmindre fordelen for patienten opvejer risikoen.
English: 11 of 16 patients were successfully treated (at the end of treatment complete or partial resolution of signs and symptoms present at baseline) with posaconazole oral suspension 800 mg/day in divided doses for a median of 296 days and up to 460 days.
Danish: 11 ud af 16 patienter blev tilfredsstillende behandlet (efter endt behandling fuldstændig eller delvis bedring af alle tegn og symptomer på infektion, der var til stede ved behandlingsstart (baseline)) medposaconazol oral suspension 800 mg dagligt fordelt på flere doser i op til 460 dage med en median på296 dage.
English: Posaconazole oral suspension External control group
Danish: Posaconazol oral suspension Ekstern kontrolgruppe
English: Prophylaxis of invasive fungal infections
Danish: Forebyggelse af invasivesvampeinfektioner
English: Serial PK samples were collected on Day 1 and at steady-state on Day 8 for all Part 1 subjects and a subset of Part 2 subjects.
Danish: Seriellefarmakokinetiskeprøverblevudtagetpådag 1 ogvedsteady-state på dag 8 for alleforsøgspersoner i del 1 og en delgruppe af forsøgspersonerne i del2.
English: 200 mg four times daily (hospitalized) then 400 mg twice daily
Danish: 200 mgfiregange dagligt (indlagt), herefter400 mg to gange dagligt
English: Please make sure you tell your doctor about all the medicines you are taking (prescribed or non-prescribed).
Danish: Sørg for at fortælle din lægeomalledelægemidler,dutager(bådereceptpligtigeogikke-receptpligtige).
English: convulsions, neuropathy, hypoaesthesia, tremor, aphasia, insomnia
Danish: Kramper, neuropati, hypoesthesi, tremor, afasi, insomni
English: torsade de pointes, sudden death, ventricular tachycardia, cardio-respiratory arrest, cardiac failure, myocardial infarction
Danish: Torsades de pointes, pludselig død, ventrikulær takykardi, hjertestop/respirationsstop, nedsat hjertefunktion, myokardieinfarkt
English: There were fewer breakthrough Aspergillus infections in patients receiving posaconazole prophylaxis when compared to control patients.
Danish: Der var færre udbrud afAspergillus-infektion hos patienter, der fik posaconazol forebyggende,sammenlignetmedpatienter i kontrolgruppen.
English: Clinically significant interactions resulting in hospitalisation and/or posaconazole discontinuation were reported in clinical efficacy studies.
Danish: I kliniske effektstudier blev der rapporteret klinisk signifikanteinteraktioner, som resulterede i hospitalsindlæggelse og/eller afbrydelse af behandling med posaconazol.
English: acute renal failure, renal failure, blood creatinine increased
Danish: Akut nyresvigt, nyresvigt, forhøjet kreatininkoncentration i blodet
English: breast pain
Danish: • brystsmerter
English: Patients, in particular those receiving posaconazole after HSCT, who have a low body weight (< 60 kg) are more likely to experience higher plasma concentrations of posaconazole and should be closely monitored for adverse events.
Danish: Isærpatienter,derfår posaconazol efter HSCT og som haren lav kropsvægt (<60kg), harstørresandsynlighed for at opleve højere plasmakoncentration af posaconazologbørmonitoreresnøjeforbivirkninger.
English: Thereafter blood levels of ciclosporin should be monitored carefully during co-administration, and upon discontinuation of posaconazole treatment, and the dose of ciclosporin should be adjusted as necessary.
Danish: Niveauet af ciclosporin i blodet bør derefter følges omhyggeligt under samtidig administrationog efter afbrydelse af behandling med posaconazol, og dosis af ciclosporin bør om nødvendigt justeres.
English: The external control group included 86 patients treated with available therapy (as above) mostly at the same time and at the same sites as the patients treated with posaconazole.
Danish: Den eksterne kontrolgruppe bestod af 86patienterbehandletmedtilgængeligterapi(somovennævnt)påomtrentsammetidspunktogpådesamme afdelinger, som patienterne behandlet med posaconazol.
English: Posaconazole is an inhibitor of CYP3A4 and should only be used under specific circumstances during treatment with other medicinal products that are metabolised by CYP3A4 (see section 4.5).
Danish: Posaconazol er en hæmmer af CYP3A4 og bør kun anvendes under særlige omstændigheder vedbehandlingmedandrelægemidler,sommetaboliseresafCYP3A4(sepkt.
English: Posaconazole Accord is indicated for use in the treatment of the following fungal infections in adults (see section 5.1): - Invasive aspergillosis in patients with disease that is refractory to amphotericin B or itraconazole or in patients who are intolerant of these medicinal products; - Fusariosis in patients with disease that is refractory to amphotericin B or in patients who are intolerant of amphotericin B; - Chromoblastomycosis and mycetoma in patients with disease that is refractory to itraconazole or in patients who are intolerant of itraconazole; - Coccidioidomycosis in patients with disease that is refractory to amphotericin B, itraconazole or fluconazole or in patients who are intolerant of these medicinal products.
Danish: 5.1): - Invasiv aspergillose hos patienter med sygdom, hvor behandling med amphotericin B elleritraconazol har været utilstrækkelig, eller hos patienter med intolerans over for disse lægemidler; - Fusariose hos patienter med sygdom, hvor behandling med amphotericin B har væretutilstrækkelig, eller hos patienter med intolerans over for amphotericin B; - Chromoblastomykoseog mycetoma hos patienter med sygdom, hvor behandling meditraconazol har været utilstrækkelig, eller hos patienter med intolerans over for itraconazol; - Coccidioidomykose hos patienter med sygdom, hvor behandlingmedamphotericinB,itraconazol eller fluconazol har været utilstrækkelig, eller hos patienter med intolerans over for disse lægemidler.
English: Overall Response Success by Species All mycologically confirmed Aspergillus spp.1
Danish: Samlet respons Virkning per art Alle mykotisk bekræftet Aspergillus-arter.2 A. fumigatus
English: Study 5615 was a non-comparative multi-center study performed to evaluate the pharmacokinetic properties, safety, and tolerability of posaconazole tablet.
Danish: Sammendrag af bridging-studiet med posaconazol tabletten Studie5615varetikke-sammenlignende multicenterstudie, som blev udført for at vurdere defarmakokinetiske egenskaber, sikkerheden og tolerabiliteten af posaconazol tabletten.
English: Co-administration may result in increased plasma concentrations of these medicinal products, leading to QTc prolongation and rare occurrences of torsades de pointes (see section 4.3).
Danish: Samtidig administration kan resultere i forhøjede plasmakoncentrationer afdisselægemidler,somkanmedføreQTc-forlængelse og sjældne forekomster af torsades de pointes(se pkt.
English: Study 1899 was a randomised, evaluator-blinded study of posaconazole oral suspension (200 mg three times a day) versus fluconazole suspension (400 mg once daily) or itraconazole oral solution (200 mg twice a day) in neutropenic patients who were receiving cytotoxic chemotherapy for acute myelogenous leukaemia or myelodysplastic syndromes.
Danish: Studie 1899 var et randomiseret, evaluator-blindet studie af posaconazol oral suspension (200 mgtregange dagligt) versus fluconazol suspension (400 mg en gang dagligt) eller itraconazol oral opløsning(200 mg to gange dagligt) hos patienter medneutropeni,derfikcytotoksiskkemoterapiforakutmyeloid leukemi eller myelodysplastisk syndrom.
English: Cav Range (ng/mL)
Danish: Cavområde(ng
English: paresthesia, dizziness, somnolence, headache, dysgeusia
Danish: Parestesi, svimmelhed, døsighed, hovedpine, dysgeusi
English: Posaconazole increased the Cmax and AUC of rifabutin by 31% and 72%, respectively.
Danish: Posaconazol øgedeCmaxog AUC forrifabutin med henholdsvis 31% og72%.
English: Concomitant use of posaconazole and phenytoin and similar inducers (e.g. carbamazepine, phenobarbital, primidone) should be avoided unless the benefit to the patient outweighs the risk.
Danish: Samtidig administration af posaconazol ogphenytoin og lignende induktorer (f.eks.carbamazepin, phenobarbital, primidon) bør undgås, medmindre fordelen for patienten opvejerrisikoen.
English: HIV Protease inhibitors
Danish: Hiv-proteasehæmmere
English: Due to the risk of prolonged sedation it is recommended that dose adjustments should be considered when posaconazole is administered concomitantly with any benzodiazepine that is metabolised by CYP3A4 (e.g. midazolam, triazolam, alprazolam) (see section 4.4).
Danish: Som følge af risikoen for forlænget sedering, anbefales det at dosisjustering bør overvejes, nårposaconazolgivessamtidigmedethvilkensomhelstbenzodiazepin,dermetaboliseresafCYP3A4(f.eks. midazolam, triazolam, alprazolam) (se pkt.
English: Posaconazole Accord contain sodium
Danish: Posaconazole Accord indeholder natrium
English: Posaconazole tablets
Danish: Posaconazoltabletter
English: Cases of elevated ciclosporin levels resulting in serious adverse reactions, including nephrotoxicity and one fatal case of leukoencephalopathy, were reported in clinical efficacy studies.
Danish: I kliniske effektstudier blev der rapporteret tilfælde af stigning i ciclosporinniveauer med alvorlige bivirkninger til følge, inklusive nefrotoksicitet samt et letalt tilfælde af leukoencephalopati.
English: Summary of posaconazole oral suspension studies
Danish: Sammendrag af studier med posaconazol oral suspension
English: Following a single dose administration of 300 mg posaconazole tablets after a high fat meal to healthy volunteers, the AUC0-72 hours and Cmax were higher compared to administration under fasted condition (51% and 16% for AUC0-72 hours and Cmax respectively).
Danish: Efter administration af en enkeltdosis af 300 mg posaconazol-tabletter efter et måltid med højt fedtindhold tilraskeforsøgspersoner var AUC0-72timerogCmaxhøjeresammenlignetmed administrationunderfaste(henholdsvis51 %og16 %for AUC0-72timerog Cmax).
English: MARKETING AUTHORISATION HOLDER Accord Healthcare S.L.U.
Danish: Indehaver af markedsføringstilladelsen Accord Healthcare S.L.U.
English: Posaconazole may increase the plasma concentrations of vinca alkaloids which may lead to neurotoxicity and other serious adverse reactions.
Danish: Posaconazol kan øge plasmakoncentrationen af vinkaalkaloider,hvilket kan føretilneurotoksicitetogandrealvorligebivirkninger.
English: Based on average Cmin concentrations, a predicted average concentration (Cav) could be calculated for 186 subjects dosed with 300 mg. PK analysis in patients of Cav found that 81% of the subjects treated with the 300 mg once daily dose attained steady state predicted Cav between 500-2,500 ng/mL.
Danish: Påbasis af gennemsnitlige Cmin-koncentrationer kunnederudregnes en formodet gennemsnitlig koncentration (Cav) for 186 forsøgspersoner, som havde fået endosis på 300 mg.FarmakokinetiskanalysehospatientermedCavkonstaterede,at81%afforsøgspersonerne behandlet med en dosis på 300 mg en gang dagligt opnåede en formodet Cav vedsteady-state på mellem 5002.500ng/ml.Enforsøgsperson(<1 %) havde en formodet Cav på under500 ng/l, og 19 % af forsøgspersonerne havde en formodet Cav på over 2.500 ng/ml.
English: In addition to the medicines named above there are other medicines that carry a risk of rhythm problems that may be greater when they are taken with Posaconazole Accord.
Danish: I tillæg tildenmedicin,somernævntovenfor,erderandenmedicin,somindebæreren risiko forhjerterytmeproblemer, som kan være større, når de tages med Posaconazole Accord.
English: Concomitant administration of azole antifungals, including posaconazole, with vincristine has been associated with serious adverse reactions (see section 4.4).
Danish: Samtidig administration af azol-antimykotika, inklusive posaconazol, og vincristin er blevet associeret medalvorligebivirkninger (se pkt.
English: An effect of renal impairment on the pharmacokinetics of posaconazole is not expected and no dose adjustment is recommended (see section 5.2).
Danish: Farmakokinetikken for posaconazol formodes ikke at blive påvirket af nedsat nyrefunktion, og deranbefales ikke dosisjustering (se pkt.