FrancophonIA/ELRC3.0 huggingface dataset:
English: In a small prospective study in women (n=64) who became inadvertently pregnant while taking leflunomide for no more than three weeks after conception and followed by a drug elimination procedure, no significant differences (p=0.13) were observed in the overall rate of major structural defects (5.4%) compared to either of the comparison groups (4.2% in the disease matched group [n=108] and 4.2% in healthy pregnant women [n=78]).
Croatian: U manjem prospektivnom ispitivanju u žena (n=64) koje su neplanirano ostale u drugom stanju dok su uzimale leflunomid u trajanju od ne više od tri tjedna nakon začeća i nakon postupka eliminacije lijeka nisu zabilježene značajne razlike (p=0,13) u cjelokupnoj stopi većih strukturalnih oštećenja (5,4%) u odnosu na bilo koju od komparativnih skupina (4,2% u bolesnih žena [n=108] i 4,2% u zdravih trudnica [n=78]).
English: If both plasma concentrations are below 0.02 mg/l no teratogenic risk is to be expected.
Croatian: Ako su obje koncentracije niže od 0,02 mg/l, ne očekuje se teratogeni rizik.
English: The MAH must ensure that the system of pharmacovigilance, as presented in Module 1.8.1. of the Marketing Authorisation, is in place and functioning before and whilst the medicinal product is on the market.
Croatian: Nositelj odobrenja mora osigurati da je farmakovigilancijski sustav prikazan u Modulu 1.8.1 odobrenja za stavljanje gotovog lijeka u promet, ustrojen i funkcionalan prije i za vrijeme dok je lijek na tržištu.
English: As leflunomide has a long persistence in the body, a switching to another DMARD (e.g. methotrexate) without performing the washout procedure (see below) may raise the possibility of additive risks even for a long time after the switching (i.e. kinetic interaction, organ toxicity).
Croatian: Kako se leflunomid dugo zadržava u tijelu, prijelaz na neki drugi DMARD (npr. metotreksat) bez provođenja postupka eliminacije (vidjeti nastavak teksta) može povećati mogućnost pojave dodatnih rizika, čak i dugo nakon promjene lijeka (npr. kinetička interakcija, organska toksičnost).
English: Women of childbearing potential have to use effective contraception during and up to 2 years after treatment (see “waiting period” below) or up to 11 days after treatment (see abbreviated “washout period” below).
Croatian: Žene reproduktivne dobi moraju koristiti učinkovitu metodu kontracepcije tijekom liječenja i do dvije godine nakon liječenja (vidjeti „razdoblje čekanja“ u nastavku teksta) ili do 11 dana nakon liječenja (vidjeti „skraćeni postupak eliminacije“ u nastavku teksta).
English: What you need to know before you take Leflunomide Teva
Croatian: Što morate znati prije nego što počnete uzimati Leflunomid Teva
English: As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, any updated RMP should be submitted at the same time as the following Periodic Safety Update Report
Croatian: Prema smjernicama CHMP-a za Sustave upravljanja rizicima za lijekove za humanu uporabu, dopunjeni RMP mora se podnijeti istovremeno uz sljedeće Periodičko izvješće o neškodljivosti lijeka (PSUR).
English: The active metabolite of leflunomide, A771726, has a long half-life, usually 1 to 4 weeks.
Croatian: Aktivni metabolit leflunomida, A771726, ima dugi poluvijek: obično od 1 do 4 tjedna.
English: For women receiving leflunomide treatment and who wish to become pregnant, one of the following procedures is recommended in order to ascertain that the foetus is not exposed to toxic concentrations of A771726 (target concentration below 0.02 mg/l):
Croatian: Za žene koje se liječe leflunomidom a planiraju trudnoću preporučuje se jedan od sljedećih postupaka kako bi se osiguralo da fetus ne bude izložen toksičnim koncentracijama A771726 (ciljna koncentracija niža od 0,02 mg/l):
English: SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
Croatian: POSEBNE MJERE ZA ZBRINJAVANJE NEISKORIŠTENOG LIJEKA ILI OTPADNIH MATERIJALA KOJI POTJEČU
English: Reproductive system and breast disorders marginal (reversible) decreases in sperm concentration, total sperm count and rapid
Croatian: Poremećaji reproduktivnog sustava i dojki granično (reverzibilno) smanjenje koncentracije spermija, ukupnog broja spermija i
English: Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Croatian: Bolesnici s rijetkim nasljednim poremećajem nepodnošenja galaktoze, nedostatkom Lapp-laktaze ili glukoza-galaktoza malapsorpcijom ne bi trebali uzimati ovaj
English: Very rare cases of Stevens Johnson syndrome or toxic epidermal necrolysis have been reported in patients treated with leflunomide.
Croatian: Vrlo rijetki slučajevi Stevens-Johnsonovog sindroma ili toksične epidermalne nekrolize zabilježeni su u bolesnika koji su liječeni leflunomidom.
English: Leflunomide Teva is contraindicated in pregnancy (see section 4.3).
Croatian: Leflunomid Teva je kontraindiciran u trudnoći (vidjeti dio 4.3).
English: PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties
Croatian: 5.2 Farmakokinetička svojstva
English: What Leflunoamide Teva is and what it is used for Leflunomide Teva belongs to a group of medicines called anti-rheumatic medicines.
Croatian: Što je Leflunomid Teva i za što se koristi Leflunomid Teva pripada skupini antireumatskih lijekova.
English: Pack sizes of 28, 30 and 100 film-coated tablets.
Croatian: Veličine pakovanja od 28, 30 i 100 filmom obloženih tableta.
English: The MAH shall perform the pharmacovigilance activities detailed in the Pharmacovigilance Plan, as agreed in the RMP presented in Module 1.8.2. of the Marketing Authorisation and any subsequent updates of the RMP agreed by the Committee for Medicinal Products for Human Use (CHMP).
Croatian: Nositelj odobrenja će provoditi ispitivanja i dodatne aktivnosti predviđene Farmakovigilancijskim planom, kako je dogovoreno RMP-om prikazanim u Modulu 1.8.2 odobrenja za stavljanje gotovog lijeka u promet te sve daljnje dopune RMP-a dogovorene od strane Povjerenstva za humane lijekove (CHMP).
English: Leflunomide was embryotoxic and teratogenic in rats and rabbits at doses in the human therapeutic range and exerted adverse effects on male reproductive organs in repeated dose toxicity studies.
Croatian: Leflunomid je bio embriotoksičan i teratogen u štakora i kunića u terapijskim dozama za ljude te je izazvao nuspojave na reproduktivnim organima mužjaka pri istraživanjima toksičnosti ponovljenih
English: Contains lactose (see leaflet for further information).
Croatian: Sadrži laktozu (vidjeti Uputu o lijeku za dodatne informacije).
English: • Patients with significantly impaired bone marrow function or significant anaemia, leucopenia,
Croatian: • Bolesnici sa značajno oštećenom funkcijom koštane srži ili izraženom anemijom, leukopenijom,
English: neutropenia or thrombocytopenia due to causes other than rheumatoid arthritis.
Croatian: neutropenijom ili trombocitopenijom, koje nisu uzrokovane reumatoidnim artritisom.
English: Leflunomide can be administered with food, since the extent of absorption is comparable in the fed and fasting state.
Croatian: Leflunomid se može uzimati s hranom jer se opseg apsorpcije može usporediti s onim kad se uzima natašte.
English: Physicians and patients should be made aware that there is an ad hoc advisory service available to provide information on leflunomide plasma
Croatian: Liječnici i bolesnici trebaju biti upoznati s postojanjem ad hoc savjetodavne službe za pružanje informacije o laboratorijskim pretragama
English: At steady state plasma levels accumulate about 33- to 35-fold compared with single dose.
Croatian: Koncentracija u plazmi u stanju dinamičke ravnoteže kumulira se oko 33 do 35 puta u usporedbi s koncentracijom kod primjene jedne doze.
English: - If you switch to another medicine to treat your rheumatoid arthritis or if you have recently taken medicines that may be harmful to your liver or blood, your doctor may advise you to take certain medicines to speed up the removal of Leflunomide Teva from your body or may closely monitor you when you start taking Leflunomide Teva.
Croatian: Ako počnete uzimati neki drugi lijek za liječenje reumatoidnog artritisa ili ste nedavno uzimali lijekove koji mogu biti štetni za jetru ili krv, liječnik Vam može savjetovati uzimanje određenih lijekova koji će ubrzati uklanjanje Leflunomida Teva iz tijela ili Vas može pomno nadzirati nakon što počnete uzimati Leflunomid Teva.
English: For ALT (SGPT) elevations between 2- and 3-fold the upper limit of normal, dose reduction from 20 mg to 10 mg may be considered and monitoring must be performed weekly.
Croatian: Kad se ALT (SGPT) poveća 2 do 3 puta u odnosu na gornju granicu normale, može se razmotriti smanjenje doze sa 20 mg na 10 mg, a vrijednosti se moraju kontrolirati jednom na tjedan.
English: This medicinal product contains lactose (see leaflet for further information).
Croatian: Ovaj lijek sadrži laktozu (vidjeti Uputu o lijeku za dodatne informacije).
English: Warnings and precautions Talk to your doctor, pharmacist or nurse before taking Leflunomide Teva
Croatian: Obratite se svom liječniku, ljekarniku ili medicinskoj sestri prije nego što uzmete Leflunomid Teva.
English: • Pregnant women, or women of childbearing potential who are not using reliable contraception during treatment with leflunomide and thereafter as long as the plasma levels of the active metabolite are above 0.02 mg/l (see section 4.6).
Croatian: • Trudnice i žene generativne dobi koje ne koriste učinkovitu kontracepciju tijekom liječenja leflunomidom i nakon njega, sve dok je koncentracija aktivnog metabolita u plazmi veća od 0,02 mg/l (vidjeti dio 4.6.).
English: It is known that medicinal products with immunosuppressive properties - like leflunomide - may cause patients to be more susceptible to infections, including opportunistic infections.
Croatian: Poznato je da lijekovi s imunosupresivnim svojstvima, poput leflunomida, mogu povećati osjetljivost bolesnika na infekcije, uključujući i oportunističke.
English: After this the dose is 10 mg or 20 mg once daily depending on the severity of the disease.
Croatian: Nakon toga doza iznosi 10 mg ili 20 mg jedanput na dan, ovisno o težini bolesti.
English: • Tablet coating: titanium dioxide, hypromellose, macrogol 400, iron oxide yellow, polysorbate, quinoline yellow aluminium lake and indigo carmine aluminium Lake.
Croatian: • Ovojnica tablete: titanijev dioksid, hipromeloza, makrogol 400, željezov oksid žuti, polisorbat, quinoline yellow aluminium lake i indigo carmine aluminium lake.
English: However, also following either of the washout procedures, verification by 2 separate tests at an interval of at least 14 days and a waiting period of one-and-a-half months between the first occurrence of a plasma concentration below 0.02 mg/l and fertilisation is required.
Croatian: Međutim, nakon primjene bilo kojeg navedenog ispiranja ("washout" postupak) potrebno je provjeriti koncentraciju u plazmi na osnovi dva testa provedena u razmaku od najmanje 14 dana i uz razdoblje čekanja od najmanje mjesec i pol između prvog nalaza koncentracije u plazmi niže od 0,02 mg/l i
English: The enzymes involved in the metabolism of leflunomide and its metabolites are not exactly known.
Croatian: Nisu točno poznati enzimi koji su uključeni u metabolizam leflunomida i njegovih metabolita.
English: In these studies, the clinical effect was closely related to the plasma concentration of A771726 and to the daily dose of leflunomide.
Croatian: U tim ispitivanjima klinički učinak bio je usko povezan s koncentracijom A771726 u plazmi i dnevnim doziranjem leflunomida.
English: However, the minor metabolite TFMA (4-trifluoromethylaniline) caused clastogenicity and point mutations in vitro, whilst insufficient information was available on its potential to exert this effect in vivo.
Croatian: Međutim, sporedni metabolit TFMA (4trifluorometilanilin) uzrokovao je klastogenost i točkaste mutacije in vitro, dok su nedostatne informacije o njegovom potencijalu izazivanja tog učinka in vivo.
English: The results of a population pharmacokinetic analysis of these trials have demonstrated that pediatric patients with body weights ≤ 40 kg have a reduced systemic exposure (measured by Css) of A771726 relative to adult rheumatoid arthritis patients (see section
Croatian: Rezultati populacijske farmakokinetičke analize tih ispitivanja pokazuju da su pedijatrijski bolesnici tjelesne težine ≤ 40 kg imali smanjenu sistemsku izloženost (mjerenu s Css) A771726 u odnosu na odrasle bolesnike s reumatoidnim artritisom (vidjeti dio 4.2.).
English: Increased side effects may occur in case of recent or concomitant use of hepatotoxic or haematotoxic drugs or when leflunomide treatment is followed by such drugs without a washout period (see also guidance concerning combination with other treatments, section 4.4).
Croatian: Više nuspojava može se pojaviti u slučaju nedavne ili istodobne primjene hepatotoksičnih ili hematotoksičnih lijekova ili kad se nakon primjene takvih lijekova leflunomid primjenjuje bez provedbe postupka eliminacije (vidjeti upute o kombinaciji s ostalim lijekovima, dio 4.4.).
English: ALT (SGPT) must be checked before initiation of leflunomide and at the same frequency as the complete blood cell count (every two weeks) during the first six months of treatment and every
Croatian: ALT (SGPT) se mora provjeriti prije početka liječenja leflunomidom te u jednakim razmacima kao i kompletnu krvnu sliku, odnosno svaka dva tjedna, tijekom prvih 6 mjeseci liječenja i nakon toga
English: Use of alternative contraceptive methods is recommended.
Croatian: Preporučuje se primjena alternativnih
English: The pharmacokinetics of A771726 in CAPD subjects appeared to be similar to healthy volunteers.
Croatian: Farmakokinetika A771726 u bolesnika na kontinuiranoj peritonealnoj dijalizi (CAPD) bila je slična onoj u zdravih dobrovoljaca.
English: Name and address of the manufacturers responsible for batch release TEVA Pharmaceutical Works Private Limited Company
Croatian: Nazivi i adrese proizvođača odgovornih za puštanje serije lijeka u promet TEVA Pharmaceutical Works Private Limited Company Pallagi út 13
English: In female mice an increased incidence, dose-dependent, of bronchiolo-alveolar adenomas and carcinomas of the lung was noted.
Croatian: ženki miševa zabilježena je povećana incidencija (ovisna o dozi) bronhiolo-alveolarnih adenoma i karcinoma pluća.
English: If ALT (SGPT) elevations of more than 2-fold the upper limit of normal persist or if ALT elevations of more than 3-fold the upper limit of normal are present, leflunomide must be discontinued and wash-out procedures initiated.
Croatian: Ako dvostruko veća koncentracija ALT (SGPT) u odnosu na gornju granicu normale potraje ili ako se ALT poveća više od 3 puta u odnosu na gornju granicu normale, liječenje leflunomidom valja prekinuti i započeti postupak eliminacije.
English: It is possible that rapidly lowering the blood level of the active metabolite, by instituting the drug elimination procedure described below, at the first delay of menses may decrease the risk to the foetus from leflunomide.
Croatian: Naime, brzo smanjenje koncentracije aktivnog metabolita leflunomida u krvi, uvođenjem kasnije opisanog postupka eliminacije lijeka, može pri prvom kašnjenju menstruacije smanjiti rizik za fetus.
English: In a carcinogenicity study in mice an increased incidence of malignant lymphoma occurred in males of the highest dose group, considered to be due to the immunosuppressive activity of leflunomide.
Croatian: ispitivanjima karcinogenosti u miševa zabilježena je povećana incidencija malignog limfoma u mužjaka koji su primali najviše doze, što se pripisuje imunosupresivnom djelovanju leflunomida.
English: Men wishing to father a child should contact their doctor who may advise them to stop taking Leflunomide Teva and take certain medicines to remove Leflunomide Teva rapidly and sufficiently from their body.
Croatian: Muškarci koji žele postati roditelji trebaju se obratiti svom liječniku koji im može savjetovati da prestanu uzimati Leflunomid Teva i uzmu određene lijekove koji će brzo i učinkovito ukloniti Leflunomid Teva iz tijela.
English: Leflunomide Teva tablets should be swallowed whole with sufficient amounts of liquid.
Croatian: Leflunomid Teva tablete treba progutati cijele s dovoljnom količinom tekućine.
English: Drinking alcohol while taking Leflunomide Teva may increase the chance of liver damage.
Croatian: Uzimanje alkohola za vrijeme liječenja Leflunomidom Teva može povećati mogućnost oštećenja jetre.
English: 14C-leflunomide in three healthy volunteers, no unchanged leflunomide was detected in plasma, urine or faeces.
Croatian: U ispitivanjima radioaktivno obilježenog 14C-leflunomida u tri zdrava dobrovoljca nije otkriven nepromijenjeni leflunomid u plazmi, mokraći ili stolici.
English: elevation of liver parameters (transaminases [especially ALT], less often gamma-GT, alkaline phosphatase, bilirubin)
Croatian: (transaminaze (osobito ALT), manje često gama-GT, alkalna fosfataza, bilirubin).
English: In the case of side effects such as dizziness the patient's ability to concentrate and to react properly may be impaired.
Croatian: U slučaju pojave nuspojava, poput omaglice, može biti oslabljena bolesnikova sposobnost koncentracije i reakcija.
English: Leflunomide Teva is contraindicated in patients with severe hypoproteinaemia or impairment of liver function (see section 4.3).
Croatian: Leflunomid Teva kontraindiciran je u bolesnika s teškom hipoproteinemijom ili oštećenom jetrenom funkcijom (vidjeti dio 4.3.).
English: • Patients with moderate to severe renal insufficiency, because insufficient clinical experience is
Croatian: • Bolesnici s umjerenom do teškom bubrežnom insuficijencijom zbog nedostatnih kliničkih
English: - Cutaneous lupus (characterized by rash/erythema on skin areas that are exposed to light)
Croatian: kožni lupus (karakteriziran osipom/crvenilom na područjima kože izloženima svjetlu);
English: Interaction studies with cimetidine (non-specific cytochrome P450 inhibitor) and rifampicin (non-specific cytochrome P450 inducer), indicate that in vivo CYP enzymes are involved in the metabolism of leflunomide only to a small extent.
Croatian: Ispitivanja interakcija s cimetidinom (nespecifični inhibitor citokroma P450) i rifampicinom (nespecifični induktor citokroma P450) pokazuju da CYP enzimi sudjeluju in vivo u metabolizmu leflunomida tek u manjoj mjeri.
English: If you think you may be pregnant while you are taking Leflunomide Teva, contact your doctor immediately for a pregnancy test.
Croatian: Ako sumnjate da ste zatrudnjeli za vrijeme uzimanja Leflunomida Teva, morate se odmah obratiti svom liječniku zbog testiranja na trudnoću.
English: A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE C. OTHER CONDITIONS AND REQUIREMENTS OF THE
Croatian: PROIZVOĐAČ ODGOVORAN ZA PUŠTANJE SERIJE LIJEKA U PROMET B. UVJETI ILI OGRANIČENJA VEZANI UZ OPSKRBU I PRIMJENU
English: For any information about this medicine, please contact the local representative of the Marketing
Croatian: Za sve informacije o ovom lijeku obratite se lokalnom predstavniku nositelja odobrenja za stavljanje
English: Leflunomide Teva tablets should be swallowed whole with plenty of water.
Croatian: Leflunomid Teva tablete treba progutati cijele s većom količinom vode.
English: • In rheumatoid arthritis: leflunomide therapy is usually started with a loading dose of 100 mg once daily for 3 days.
Croatian: • U bolesnika s reumatoidnim artritisom: terapiju leflunomidom započinje primjenom udarne doze od 100 mg jedanput na dan tijekom 3 dana.
English: After administration of a radiolabelled dose of leflunomide, radioactivity was equally excreted in faeces, probably by biliary elimination, and in urine.
Croatian: Nakon primjene radioaktivno obilježenog leflunomida, radioaktivnost se jednako pojavila u stolici, vjerojatno eliminacijom putem žuči, i u mokraći.
English: A771726 displaced ibuprofen, diclofenac and tolbutamide but the unbound fraction of these drugs is only increased by 10 % to 50 %.
Croatian: A771726 istiskuje ibuprofen, diklofenak i tolbutamid, ali se nevezana frakcija tih lijekova povećava za samo 10% do 50%.
English: The doctor that starts you on Leflunomide Teva and supervises you while you are on it should be experienced in the treatment of rheumatoid arthritis.
Croatian: Liječnik koji Vam uvede terapiju Leflunomidom Teva i koji Vas nadzire tijekom terapije treba imati iskustva u liječenju reumatoidnog artritisa.
English: The metabolic biotransformation of leflunomide to A771726 and subsequent metabolism of A771726 is not controlled by a single enzyme and has been shown to occur in microsomal and cytosolic cellular fractions.
Croatian: Metaboličku biotransformaciju leflunomida u A771726 i naknadni metabolizam A771726 ne kontrolira niti jedan enzim i pokazalo se da se odvijaju u mikrosomalnim i citosolnim staničnim dijelovima.
English: Most patients improved after discontinuation of Leflunomide Teva.
Croatian: Stanje se popravilo u većine bolesnika nakon prekida terapije Leflunomidom Teva.
English: - Other medicines that are broken down by an enzyme called CYP2C9 e.g. phenytoin (an epilepsy treatment), warfarin and phenprocoumon (blood thinners), and tolbutamide (a type 2 diabetes treatment).
Croatian: - Druge lijekove koji se razgrađuju putem enzima CYP2C9, npr. fenitoin (za liječenje epilepsije), varfarin i fenprokumon (za razrjeđivanje krvi) i tolbutamid (za liječenje šećerne bolesti tipa 2).
English: Patients were 3-17 years of age with active polyarticular course JRA regardless of onset type and naive to methotrexate or leflunomide.
Croatian: Bolesnici su bili u dobi između 3 i 17 godina, imali su aktivni poliartikularni oblik juvenilnog reumatoidnog artritisa, bez obzira na tip nastupa bolesti i do tada nisu primali metotreksat ili leflunomid.
English: Therefore, when such toxicities occur or if for any other reason A771726 needs to be cleared rapidly from the body, the washout procedure has to be followed.
Croatian: Stoga, pri pojavi tih toksičnosti ili potrebe za brzim uklanjanjem A771726 iz organizma zbog bilo kojeg drugog razloga treba obaviti ispiranje ("washout" postupak).
English: What Leflunomide Teva is and what it is used for 2.
Croatian: Što je Leflunomid Teva i za što se koristi
English: The Marketing Authorisation Holder (MAH) shall ensure that any changes to the safety profile of the reference medicinal product requiring changes to the Risk Management Plan or Product Information are immediately implemented for Leflunomide Teva.
Croatian: Nositelj odobrenja za stavljanje gotovog lijeka u promet dužan je odmah implementirati sve promjene sigurnosnog profila referentnog lijeka, koje iziskuju promjene u Planu upravljanja rizicima ili Informacijama o lijeku, u dokumentaciju za Leflunomid Teva.
English: Each tablet contains 97.25 mg of lactose monohydrate and 3.125 mg anhydrous lactose.
Croatian: Jedna tableta sadrži 97,25 mg laktoze hidrata i 3,125 mg laktoze, bezvodne.
English: If you are already taking non-steroidal anti-inflammatory drugs (NSAIDs) and/or corticosteroids, you may continue to use these after starting Leflunomide Teva.
Croatian: Ako već uzimate nesteroidne protuupalne lijekove (NSAIL) i/ili kortikosteroide, možete ih nastaviti uzimati nakon što počnete uzimati Leflunomid Teva.
English: Following concomitant administration of a single dose of leflunomide to subjects receiving multiple doses of rifampicin (non-specific cytochrome P450 inducer) A771726 peak levels were increased by approximately 40 %, whereas the AUC was not significantly changed.
Croatian: Nakon istodobne primjene pojedinačne doze leflunomida u osoba koje su primale višestruke doze rifampicina (nespecifičnog induktora citokroma P450), vršne koncentracije A771726 porasle su za 40%, dok se vrijednost AUC nije značajno promijenila.
English: General disorders and administration site conditions anorexia, weight loss (usually insignificant), asthenia
Croatian: Opći poremećaji i reakcije na mjestu primjene anoreksija, gubitak težine (obično neznačajan), astenija