natgillin/translations-raw huggingface dataset:
Conversion from ciclosporin to Advagraf Care should be taken when converting patients from ciclosporin-based to tacrolimus-based therapy (see sections 4.4 and 4.5).
Prehod s ciklosporina na zdravilo Advagraf Pri prehodu s ciklosporinskega na takrolimsko zdravljenje je potrebna previdnost (glejte poglavji 4. 4 in 4. 5).
In practice, tacrolimus-based therapy has been initiated 12 - 24 hours after discontinuation of ciclosporin.
V praksi so takrolimsko zdravljenje začenjali od 12 do 24 ur po prekinitvi ciklosporina.
Target whole blood trough concentration recommendations Dosing should primarily be based on clinical assessments of rejection and tolerability in each individual patient aided by whole blood tacrolimus trough level monitoring.
Priporočila za ciljno najnižjo koncentracijo v polni krvi Odmerjanje mora v prvi vrsti temeljiti na klinični oceni zavrnitve in prenašanju vsakega posameznega bolnika s pomočjo nadziranja najnižjih koncentracij takrolimusa v polni krvi.
Comparisons of concentrations from the published literature to individual values in clinical practice should be assessed with care and knowledge of the assay methods employed.
4 praksi je treba primerjati previdno in ob poznavanju uporabljene metode.
The relationship between tacrolimus trough levels (C24) and systemic exposure (AUC 0-24) is similar between the two formulations Advagraf and Prograf.
Razmerje med najnižjimi koncentracijami takrolimusa (C24) in sistemsko izpostavljenostjo (AUC 0- 24) je pri obeh farmacevtskih oblikah, pri zdravilih Advagraf in Prograf, podobno.
Blood trough levels for Advagraf should be drawn approximately 24 hours post-dosing, just prior to the next dose.
Vzorce za določitev najnižje koncentracije zdravila Advagraf je treba vzeti približno 24 ur po uporabi zdravila, tik pred naslednjim odmerkom.
Frequent trough level monitoring in the initial two weeks post transplantation is recommended, 4 followed by periodic monitoring during maintenance therapy.
Med prvima dvema tednoma po presaditvi priporočamo pogosto nadziranje najnižjih koncentracij, med vzdrževalnim zdravljenjem pa nato periodično.
Blood trough levels of tacrolimus should also be monitored following conversion from Prograf to Advagraf, dose adjustment, changes in the immunosuppressive regimen, or co-administration of substances which may alter tacrolimus whole blood concentrations (see section 4.5).
Najnižje koncentracije takrolimusa v krvi je treba nadzirati tudi po zamenjavi zdravila Prograf z zdravilom Advagraf, prilagoditvi odmerka, spremembah imunosupresivnega režima ali sočasni uporabi učinkovin, ki lahko spremenijo koncentracije takrolimusa v polni krvi (glejte poglavje 4. 5).
As Advagraf is a medicinal product with low clearance, adjustments to the Advagraf dose regimen may take several days before steady state is achieved.
Zdravilo Advagraf je zdravilo z majhnim očistkom, zato lahko prilagajanje odmerka zdravila Advagraf za vzpostavitev ravnovesnega stanja traja več dni.
Clinical study analysis suggests that the majority of patients can be successfully managed if tacrolimus blood trough levels are maintained below 20 ng/ ml.
Analize kliničnih raziskav kažejo, da je mogoče večino bolnikov uspešno voditi, če je najnižja koncentracija takrolimusa v krvi vzdrževana pod 20 ng/ ml.
In clinical practice, whole blood trough levels have generally been in the range 5 - 20 ng/ ml in liver transplant recipients and 10 - 20 ng/ ml in kidney and heart transplant patients in the early post- transplant period.
V klinični praksi so bile najnižje koncentracije v polni krvi v zgodnjem obdobju po presaditvi pri prejemnikih jeter na splošno od 5 do 20 ng/ ml in pri prejemnikih ledvice ali srca od 10 do 20 ng/ ml.
During subsequent maintenance therapy, blood concentrations have generally been in the range of 5 - 15 ng/ ml in liver, kidney and heart transplant recipients.
Med poznejšim vzdrževalnim zdravljenjem, so bile koncentracije v krvi pri prejemnikih jeter, ledvic ali srca na splošno od 5 do 15 ng/ ml.
Hypersensitivity to tacrolimus or other macrolides or to any of the excipients.
Preobčutljivost za takrolimus, druge makrolide ali katerokoli pomožno snov.
This has led to serious adverse events, including graft rejection, or other side effects which could be a consequence of either under- or over- exposure to tacrolimus.
Pri tem so se pojavili resni neželeni učinki, vključno z zavrnitvijo presadka, ali drugi neželeni učinki, ki bi lahko bili posledica premajhne ali prevelike izpostavljenosti takrolimusu.
Patients should be maintained on a single formulation of tacrolimus with the corresponding daily dosing regimen; alterations in formulation or regimen should only take place under the close supervision of a transplant specialist (see sections 4.2 and 4.8).
Sprememba farmacevtske oblike zdravila ali režima odmerjanja lahko poteka le pod strogim nadzorom zdravnika specialista za zdravljenje bolnikov s presadki (glejte poglavji 4. 2 in 4. 8).
There is limited experience in non-Caucasian patients and patients at elevated immunological risk (e. g. retransplantation, evidence of panel reactive antibodies (PRA)).
Pri bolnikih nekavkazijskega porekla in bolnikih z večjim imunološkim tveganjem (npr. retransplantacija, dokaz panelnih reaktivnih protiteles (PRA)) je izkušenj malo.
For prophylaxis of transplant rejection in adult heart allograft recipients and for paediatric allograft recipients clinical data are not yet available for the prolonged-release formulation Advagraf.
Za preprečevanje zavrnitve presadka pri odraslih po alogenski presaditvi srca in otrocih z alogenskim presadkom klinični podatki za farmacevtsko obliko s podaljšanim sproščanjem zdravila Advagraf še niso na voljo.
Herbal preparations containing St.
Obstaja namreč nevarnost za
John’ s Wort (Hypericum perforatum) or other herbal preparations should be avoided when taking Advagraf due to the risk of interactions that lead to decrease in blood concentrations of tacrolimus and reduced clinical effect of tacrolimus (see section 4.5).
5 medsebojno delovanje, ki zniža koncentracijo takrolimusa v krvi in oslabi njegov klinični učinek (glejte poglavje 4. 5).
The combined administration of ciclosporin and tacrolimus should be avoided and care should be taken when administering tacrolimus to patients who have previously received ciclosporin (see sections 4.2 and 4.5).
Kombinirani uporabi ciklosporina in takrolimusa se je treba izogniti; pri bolnikih, ki so prej dobivali ciklosporin, je treba takrolimus uporabiti previdno (glejte poglavji 4. 2 in 4. 5).
Ventricular hypertrophy or hypertrophy of the septum, reported as cardiomyopathies, have been observed in Prograf treated patients on rare occasions and may therefore also occur with Advagraf.
Ventrikularno hipertrofijo ali hipertrofijo septuma, opisani kot kardiomiopatije, so opazili v redkih primerih zdravljenja bolnikov z zdravilom Prograf in zato se lahko to zgodi tudi pri uporabi zdravila Advagraf.
Other factors observed to increase the risk of these clinical 5 conditions included pre-existing heart disease, corticosteroid usage, hypertension, renal or hepatic dysfunction, infections, fluid overload, and oedema.
Drugi dejavniki, za katere je ugotovljeno, da povečujejo tveganje za te klinične motnje, so obstoječa bolezen srca, jemanje kortikosteroidov, hipertenzija, moteno delovanje ledvic ali jeter, okužbe, preobremenitev s tekočino in edemi.
Accordingly, high-risk patients receiving substantial immunosuppression should be monitored, using such procedures as echocardiography or ECG pre- and post-transplant (e. g. initially at 3 months and then at 9 -12 months).
Glede na to je treba zelo ogrožene bolnike, ki se zdravijo z intenzivno imunosupresijo, nadzorovati s preiskavami, kot sta ehokardiografija ali EKG, in sicer pred presaditvijo in po njej (npr. uvodoma po 3 mesecih in potem pri 9– 12 mesecih).
If abnormalities develop, dose reduction of Advagraf therapy, or change of treatment to another immunosuppressive agent should be considered.
Če se pojavijo nenormalnosti, je treba razmisliti o zmanjšanju odmerka zdravila Advagraf ali o prehodu na drugo imunosupresivno zdravilo.
Patients treated with tacrolimus have been reported to develop EBV-associated lymphoproliferative disorders.
Pri bolnikih, ki so se zdravili s takrolimusom, so poročali o pojavu z Epstein- Barr virusom (EBV) povezanih limfoproliferativnih bolezni.
A combination of immunosuppressives such as antilymphocytic antibodies given concomitantly increases the risk of EBV-associated lymphoproliferative disorders.
Pri kombiniranem zdravljenju z imunosupresivi, npr. sočasna uporaba antilimfocitnih protiteles, se tveganje za pojav z EBV povezanih limfoproliferativnih bolezni poveča.
Therefore, in this patient group, EBV-VCA serology should be ascertained before starting treatment with Advagraf.
Pri tej skupini bolnikov je pred začetkom zdravljenja z zdravilom Advagraf treba izvesti serološko testiranje na EBV- VCA.
During treatment, careful monitoring with EBV- PCR is recommended.
Med zdravljenjem je priporočljivo skrbno nadziranje z EBV- PCR.
Positive EBV-PCR may persist for months and is per se not indicative of lymphoproliferative disease or lymphoma.
Pozitiven EBV- PCR lahko traja mesece in sam po sebi ni kazalec limfoproliferativne bolezni ali limfoma.
As with other potent immunosuppressive compounds, the risk of secondary cancer is unknown (see section 4.8).
Tako kot pri drugih močnih imunosupresivih tudi pri tem zdravilu tveganje za sekundarnega raka ni znano (glejte poglavje 4. 8).
If patients taking tacrolimus present with symptoms indicating PRES such as headache, altered mental status, seizures, and visual disturbances, a radiological procedure (e. g.
Če se pri bolnikih, ki jemljejo takrolimus, pojavijo znaki, ki kažejo na PRES, kot so glavobol, spremenjeno duševno stanje, krči in motnje vida, je treba izvesti radiološko slikanje (npr.
If PRES is diagnosed, adequate blood pressure and seizure control and immediate discontinuation of systemic tacrolimus is advised.
Če se ugotovi prisotnost PRES, je potreben ustrezen nadzor krvnega pritiska in krčev ter takojšnja prekinitev sistemske uporabe takrolimusa.
Most patients completely recover after appropriate measures are taken.
Večina bolnikov si, po vpeljavi ustreznih ukrepov, popolnoma opomore.
As Advagraf prolonged-release capsules contain lactose, special care should be taken in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
Pri bolnikih z redko dedno intoleranco za galaktozo, laponsko obliko zmanjšane aktivnosti laktaze ali malabsorpcijo glukoze/ galaktoze je potrebna posebna previdnost.
Metabolic interactions Systemically available tacrolimus is metabolised by hepatic CYP3A4.
6 Presnovne interakcije Presnova sistemsko razpoložljivega takrolimusa poteka z jetrnim CYP3A4.
Concomitant use of medicinal products or herbal remedies known to inhibit or induce CYP3A4 may affect the metabolism of tacrolimus and thereby increase or decrease tacrolimus blood levels.
Sočasna uporaba zdravil ali zeliščnih pripravkov, ki zavirajo ali inducirajo CYP3A4, lahko vpliva na presnovo takrolimusa in poviša ali zniža njegovo koncentracijo v krvi.
It is therefore recommended to monitor tacrolimus blood levels whenever substances which have the potential to alter CYP3A metabolism are used concomitantly and to adjust the tacrolimus dose as appropriate in order to maintain similar tacrolimus exposure (see sections 4.2 and 4.4).
Zato je koncentracijo takrolimusa v krvi priporočljivo nadzirati, kadarkoli sočasno uporabljate učinkovine, ki lahko spremenijo presnovo CYP3A, in odmerek takrolimusa ustrezno prilagoditi, da bi izpostavljenost takrolimusu ohranili približno enako (glejte poglavji 4. 2 in 4. 4).
Inhibitors of metabolism Clinically the following substances have been shown to increase tacrolimus blood levels:
Zaviralci presnove Klinično je ugotovljeno, da koncentracijo takrolimusa v krvi zvišujejo naslednje snovi:
Strong interactions have been observed with antifungal agents such as ketoconazole, fluconazole, itraconazole and voriconazole, the macrolide antibiotic erythromycin or HIV protease inhibitors (e. g.
Močne interakcije so opazili z antimikotiki, kot so ketokonazol, flukonazol, itrakonazol in vorikonazol, makrolidnim antibiotikom eritromicinom ter zaviralci proteaz HIV (npr. ritonavir).
Weaker interactions have been observed with clotrimazole, clarithromycin, josamycin, nifedipine, nicardipine, diltiazem, verapamil, danazol, ethinylestradiol, omeprazole and nefazodone.
Šibkejše interakcije so opazili pri sočasni uporabi s klotrimazolom, klaritromicinom, z josamicinom, nifedipinom, nikardipinom, diltiazemom, verapamilom, danazolom, etinilestradiolom, omeprazolom in nefazodonom.
In vitro the following substances have been shown to be potential inhibitors of tacrolimus metabolism: bromocriptine, cortisone, dapsone, ergotamine, gestodene, lidocaine, mephenytoin, miconazole, midazolam, nilvadipine, norethindrone, quinidine, tamoxifen, (triacetyl)oleandomycin.
In vitro so se kot možni zaviralci presnove takrolimusa izkazale naslednje snovi: bromokriptin, kortizon, dapson, ergotamin, gestoden, lidokain, mefenitoin, mikonazol, midazolam, nilvadipin, noretindron, kinidin, tamoksifen, (triacetil) oleandomicin.
Lansoprazol and ciclosporin may potentially inhibit CYP3A4-mediated metabolism of tacrolimus and thereby increase tacrolimus whole blood concentrations.
Lansoprazol in ciklosporin lahko potencialno zavirata presnovo takrolimusa s CYP3A4 in tako povišata koncentracije takrolimusa v polni krvi.
Inducers of metabolism Clinically the following substances have been shown to decrease tacrolimus blood levels:
Induktorji presnove Klinično je ugotovljeno, da koncentracijo takrolimusa v krvi znižujejo naslednje snovi:
John’ s Wort (Hypericum perforatum) which may require increased tacrolimus doses in almost all patients.
Močne interakcije so opazili z rifampicinom, fenitoinom in šentjanževko (Hypericum perforatum), zato je potrebno v takšnem primeru odmerek takrolimusa skoraj pri vseh bolnikih povečati.
Effect of tacrolimus on the metabolism of other medicinal products Tacrolimus is a known CYP3A4 inhibitor; thus concomitant use of tacrolimus with medicinal products known to be metabolised by CYP3A4 may affect the metabolism of such medicinal products.
Vpliv takrolimusa na presnovo drugih zdravil Takrolimus je znan zaviralec CYP3A4, zato lahko njegova sočasna uporaba z zdravili, ki se presnavljajo s CYP3A4, vpliva na presnovo takšnih zdravil.
In addition, synergistic/ additive nephrotoxic effects can occur.
Poleg tega se lahko pojavijo sinergistični/ aditivni nefrotoksični učinki.
For these reasons, the combined administration of ciclosporin and tacrolimus is not recommended and care should be taken when administering tacrolimus to patients who have previously received ciclosporin (see sections 4.2 and 4.4).
Zato kombinirana uporaba ciklosporina in takrolimusa ni priporočljiva; pri bolnikih, ki so prej dobivali ciklosporin, je treba takrolimus uporabiti previdno (glejte poglavji 4. 2 in 4. 4).
As tacrolimus may reduce the clearance of steroid-based contraceptives leading to increased hormone exposure, particular care should be exercised when deciding upon contraceptive measures.
Zato je pri odločanju za kontracepcijsko zaščito potrebna posebna previdnost.
Other potential interactions that may increase systemic exposure of tacrolimus Prokinetic agents such as metoclopramide and cisapride.
Druge možne interakcije, ki lahko povečajo sistemsko izpostavljenost takrolimusa Propulzivi, kot sta metoklopramid in cisaprid.
Magnesium-aluminum-hydroxide.
7 Magnezijev/ aluminijev hidroksid.
Other interactions which have led to clinically detrimental effects Concurrent use of tacrolimus with medicinal products known to have nephrotoxic or neurotoxic effects may increase these effects (e. g., aminoglycosides, gyrase inhibitors, vancomycin, cotrimoxazole, NSAIDs, ganciclovir or aciclovir).
Druge interakcije, ki so povzročile klinično škodljive učinke Te učinke lahko poveča sočasna uporaba takrolimusa in zdravil z nefrotoksičnimi ali nevrotoksičnimi učinki (kot so aminoglikozidi, zaviralci giraze, vankomicin, kotrimoksazol, nesteroidni antirevmatiki, ganciklovir ali aciklovir).
As tacrolimus treatment may be associated with hyperkalaemia, or may increase pre-existing hyperkalaemia, high potassium intake, or potassium-sparing diuretics (e. g., amiloride, triamterene, or spironolactone) should be avoided.
Zato se je treba izogibati uživanju obilice kalija in uporabi diuretikov, ki varčujejo s kalijem (npr. amilorid, triamteren ali spironolakton).
Protein binding considerations 7 Tacrolimus is extensively bound to plasma proteins.
Vezava na beljakovine Takrolimus se izdatno veže na beljakovine v plazmi.
Possible interactions with other medicinal products known to have high affinity for plasma proteins should be considered (e. g., NSAIDs, oral anticoagulants, or oral antidiabetics).
Upoštevati je treba možnost medsebojnega delovanja z drugimi zdravili, ki imajo veliko afiniteto za beljakovine v plazmi (npr. nesteroidna protivnetna zdravila, peroralni antikoagulanti ali peroralni antidiabetiki).
4.6 Pregnancy and lactation
Nosečnost in dojenje 4. 6
Limited data from organ transplant recipients show no evidence of an increased risk of adverse events on the course and outcome of pregnancy under tacrolimus treatment compared with other immunosuppressive medicinal products.
Omejeni podatki prejemnic presajenih organov ne kažejo, da bi med zdravljenjem s takrolimusom obstajalo večje tveganje za neželene učinke na potek in izid nosečnosti v primerjavi z drugimi imunosupresivnimi zdravili.
In case of in utero exposure, monitoring of the newborn for the potential adverse events of tacrolimus is recommended (in particular effects on the kidneys). There is a risk for premature delivery (< 37 week) as well as for hyperkalaemia in the newborn (incidence 8 of 111 neonates, i. e.
V primeru izpostavljenosti in utero je novorojenčka priporočljivo nadzirati glede možnih neželenih učinkov takrolimusa (zlasti učinki na ledvice).
7.2%) which, however normalises spontaneously.
Obstaja tveganje za prezgoden porod (< 37 tednov) in za hiperkaliemijo pri novorojenčku (pri 8 od 111 novorojenčkov; pojavnost 7, 2%), ki pa se normalizira sama od sebe.
In rats and rabbits, tacrolimus caused embryofoetal toxicity at doses which demonstrated maternal toxicity (see section 5.3).
Pri podganah in kuncih je takrolimus povzročil embriofetalne toksične učinke v odmerkih, ki so imeli toksične učinke pri materah (glejte poglavje 5. 3).
Tacrolimus affected fertility in male rats (see section 5.3).
Pri podganah je takrolimus prizadel plodnost samcev (glejte poglavje 5. 3).
Lactation Human data demonstrate that tacrolimus is excreted in breast milk.
Dojenje Podatki pri ljudeh kažejo, da se takrolimus izloča v materinem mleku.
As detrimental effects on the newborn cannot be excluded, women should not breast-feed whilst receiving Advagraf.
Ker ni mogoče izključiti zelo škodljivih učinkov na novorojenčka, ženske med uporabo zdravila Advagraf ne smejo dojiti.
This effect may be enhanced if Advagraf is administered in association with alcohol.
Ta učinek se lahko stopnjuje, če se zdravilo Advagraf uporablja skupaj z alkoholom.
4.8 Undesirable effects
Neželeni učinki 4. 8
The adverse reaction profile associated with immunosuppressive agents is often difficult to establish owing to the underlying disease and the concurrent use of multiple medications.
Profil neželenih učinkov zdravila je pri imunosupresivih pogosto težko ugotoviti zaradi osnovne bolezni in sočasne uporabe več zdravil.
Many of the adverse reactions stated below are reversible and/ or respond to dose reduction.
Številni spodaj navedeni neželeni učinki so reverzibilni in/ ali se odzovejo na zmanjšanje odmerka.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Znotraj vsake razvrstitve po pogostnosti so neželeni učinki navedeni po padajoči resnosti.
Adverse reactions are listed below in descending order by frequency of occurrence: very common (≥ 1/ 10); common (≥ 1/ 100 to < 1/ 10); uncommon (≥ 1/ 1,000 to < 1/ 100); rare (≥ 1/ 10,000 to < 1/ 1,000); very rare (< 1/ 10,000), not known (cannot be estimated from the available data).
Neželeni učinki zdravila so v nadaljevanju navedeni v padajočem zaporedju pogostnosti pojavljanja: zelo pogosti (≥ 1/ 10); pogosti (≥ 1/ 100 do < 1/ 10); občasni (≥ 1/ 1. 000 do < 1/ 100); redki (≥ 1/ 10. 000 do < 1/ 1. 000); zelo redki (< 1/ 10. 000), neznana (ni mogoče oceniti iz razpoložljivih podatkov).
Cardiac disorders common: uncommon:
Srčne bolezni ishemična koronarna bolezen, tahikardija pogosti:
ischaemic coronary artery disorders, tachycardia ventricular arrhythmias and cardiac arrest, heart failures, cardiomyopathies, ventricular hypertrophy, supraventricular arrhythmias, palpitations, ECG investigations abnormal, heart rate and pulse investigations abnormal
ventrikularne aritmije in zastoji srca, srčno popuščanje, kardiomiopatije, hipertrofija prekatov, supraventrikularne aritmije, palpitacije, nenormalni izvidi preiskave EKG, nepravilnosti srčne frekvence in ritma
rare: very rare:
redki: zelo redki:
pericardial effusion echocardiogram abnormal
perikardialni izliv nenormalen ehokardiogram
anaemia, leukopenia, thrombocytopenia, leukocytosis, red blood cell analyses abnormal
anemija, levkopenija, trombocitopenija, levkocitoza, nenormalen izvid analize eritrocitov
uncommon:
občasni: redki:
coagulopathies, coagulation and bleeding analyses abnormal, pancytopenia, neutropenia
koagulopatije, nenormalni izvidi analiz koagulacije in krvavitve, pancitopenija, nevtropenija trombotična trombocitopenična purpura, hipoprotrombinemija
rare:
Bolezni živčevja
Nervous system disorders very common: common:
zelo pogosti: pogosti:
tremor, headache seizures, disturbances in consciousness, paraesthesias and dysaesthesias, peripheral neuropathies, dizziness, writing impaired, nervous system disorders 8
tremor, glavobol epileptični napadi, motnje zavesti, parestezije in disestezije, periferne nevropatije, omotica, motena sposobnost pisanja, bolezni živčevja
uncommon:
občasni:
coma, central nervous system haemorrhages and cerebrovascular accidents, paralysis and paresis, encephalopathy, speech and language abnormalities, amnesia
koma, krvavitve v osrednje živčevje in cerebrovaskularni incidenti, paraliza in pareza, encefalopatija, motnje govora in jezika, amnezija
hypertonia myasthenia
hipertonija miastenija
Eye disorders
Očesne bolezni pogosti:
common: uncommon: rare:
občasni: redki:
vision blurred, photophobia, eye disorders cataract blindness
katarakta slepota
Ear and labyrinth disorders common: uncommon: rare: very rare:
Ušesne bolezni, vključno z motnjami labirinta pogosti: občasni: redki:
tinnitus hypoacusis deafness neurosensory hearing impaired
tinitus hipakuza nevrosenzorična naglušnost
Respiratory, thoracic and mediastinal disorders common:
Bolezni dihal, prsnega koša in mediastinalnega prostora dispneja, parenhimske bolezni pljuč, plevralni izliv, faringitis, kašelj, zamašenost pogosti: nosu in vnetja občasni: redki:
dyspnoea, parenchymal lung disorders, pleural effusion, pharyngitis, cough, nasal congestion and inflammations
dihalna odpoved, bolezni dihal, astma akutni respiratorni distresni sindrom
uncommon: rare:
Bolezni prebavil
Gastrointestinal disorders very common: common:
zelo pogosti: pogosti:
diarrhoea, nausea gastrointestinal inflammatory conditions, gastrointestinal ulceration and perforation, gastrointestinal haemorrhages, stomatitis and ulceration, ascites, vomiting, gastrointestinal and abdominal pains, dyspeptic signs and symptoms, constipation, flatulence, bloating and distension, loose stools, gastrointestinal signs and symptoms
driska, navzea vnetja v prebavilih, razjede in perforacije v prebavilih, krvavitve v prebavilih, stomatitis in razjede, ascites, bruhanje, bolečine v prebavilih in trebuhu, dispepsija, zaprtje, flatulenca, napenjanje in napihnjenost, mehko blato, gastrointestinalne motnje