natgillin/translations-raw huggingface dataset:
This medicinal product contains lactose (see leaflet for further information).
Ovaj lijek sadrži laktozu (vidjeti Uputu o lijeku za dodatne informacije).
Warnings and precautions Talk to your doctor, pharmacist or nurse before taking Leflunomide Teva
Obratite se svom liječniku, ljekarniku ili medicinskoj sestri prije nego što uzmete Leflunomid Teva.
• 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).
• 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.).
It is known that medicinal products with immunosuppressive properties - like leflunomide - may cause patients to be more susceptible to infections, including opportunistic infections.
Poznato je da lijekovi s imunosupresivnim svojstvima, poput leflunomida, mogu povećati osjetljivost bolesnika na infekcije, uključujući i oportunističke.
After this the dose is 10 mg or 20 mg once daily depending on the severity of the disease.
Nakon toga doza iznosi 10 mg ili 20 mg jedanput na dan, ovisno o težini bolesti.
• Tablet coating: titanium dioxide, hypromellose, macrogol 400, iron oxide yellow, polysorbate, quinoline yellow aluminium lake and indigo carmine aluminium Lake.
• Ovojnica tablete: titanijev dioksid, hipromeloza, makrogol 400, željezov oksid žuti, polisorbat, quinoline yellow aluminium lake i indigo carmine aluminium lake.
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.
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
The enzymes involved in the metabolism of leflunomide and its metabolites are not exactly known.
Nisu točno poznati enzimi koji su uključeni u metabolizam leflunomida i njegovih metabolita.
In these studies, the clinical effect was closely related to the plasma concentration of A771726 and to the daily dose of leflunomide.
U tim ispitivanjima klinički učinak bio je usko povezan s koncentracijom A771726 u plazmi i dnevnim doziranjem leflunomida.
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.
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.
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
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.).
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).
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.).
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
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
Use of alternative contraceptive methods is recommended.
Preporučuje se primjena alternativnih
The pharmacokinetics of A771726 in CAPD subjects appeared to be similar to healthy volunteers.
Farmakokinetika A771726 u bolesnika na kontinuiranoj peritonealnoj dijalizi (CAPD) bila je slična onoj u zdravih dobrovoljaca.
Name and address of the manufacturers responsible for batch release TEVA Pharmaceutical Works Private Limited Company
Nazivi i adrese proizvođača odgovornih za puštanje serije lijeka u promet TEVA Pharmaceutical Works Private Limited Company Pallagi út 13
In female mice an increased incidence, dose-dependent, of bronchiolo-alveolar adenomas and carcinomas of the lung was noted.
ženki miševa zabilježena je povećana incidencija (ovisna o dozi) bronhiolo-alveolarnih adenoma i karcinoma pluća.
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.
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.
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.
Naime, brzo smanjenje koncentracije aktivnog metabolita leflunomida u krvi, uvođenjem kasnije opisanog postupka eliminacije lijeka, može pri prvom kašnjenju menstruacije smanjiti rizik za fetus.
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.
ispitivanjima karcinogenosti u miševa zabilježena je povećana incidencija malignog limfoma u mužjaka koji su primali najviše doze, što se pripisuje imunosupresivnom djelovanju leflunomida.
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.
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.
Leflunomide Teva tablets should be swallowed whole with sufficient amounts of liquid.
Leflunomid Teva tablete treba progutati cijele s dovoljnom količinom tekućine.
Drinking alcohol while taking Leflunomide Teva may increase the chance of liver damage.
Uzimanje alkohola za vrijeme liječenja Leflunomidom Teva može povećati mogućnost oštećenja jetre.
14C-leflunomide in three healthy volunteers, no unchanged leflunomide was detected in plasma, urine or faeces.
U ispitivanjima radioaktivno obilježenog 14C-leflunomida u tri zdrava dobrovoljca nije otkriven nepromijenjeni leflunomid u plazmi, mokraći ili stolici.
elevation of liver parameters (transaminases [especially ALT], less often gamma-GT, alkaline phosphatase, bilirubin)
(transaminaze (osobito ALT), manje često gama-GT, alkalna fosfataza, bilirubin).
In the case of side effects such as dizziness the patient's ability to concentrate and to react properly may be impaired.
U slučaju pojave nuspojava, poput omaglice, može biti oslabljena bolesnikova sposobnost koncentracije i reakcija.
Leflunomide Teva is contraindicated in patients with severe hypoproteinaemia or impairment of liver function (see section 4.3).
Leflunomid Teva kontraindiciran je u bolesnika s teškom hipoproteinemijom ili oštećenom jetrenom funkcijom (vidjeti dio 4.3.).
• Patients with moderate to severe renal insufficiency, because insufficient clinical experience is
• Bolesnici s umjerenom do teškom bubrežnom insuficijencijom zbog nedostatnih kliničkih
- Cutaneous lupus (characterized by rash/erythema on skin areas that are exposed to light)
kožni lupus (karakteriziran osipom/crvenilom na područjima kože izloženima svjetlu);
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.
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.
If you think you may be pregnant while you are taking Leflunomide Teva, contact your doctor immediately for a pregnancy test.
Ako sumnjate da ste zatrudnjeli za vrijeme uzimanja Leflunomida Teva, morate se odmah obratiti svom liječniku zbog testiranja na trudnoću.
A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE C. OTHER CONDITIONS AND REQUIREMENTS OF THE
PROIZVOĐAČ ODGOVORAN ZA PUŠTANJE SERIJE LIJEKA U PROMET B. UVJETI ILI OGRANIČENJA VEZANI UZ OPSKRBU I PRIMJENU
For any information about this medicine, please contact the local representative of the Marketing
Za sve informacije o ovom lijeku obratite se lokalnom predstavniku nositelja odobrenja za stavljanje
Leflunomide Teva tablets should be swallowed whole with plenty of water.
Leflunomid Teva tablete treba progutati cijele s većom količinom vode.
• In rheumatoid arthritis: leflunomide therapy is usually started with a loading dose of 100 mg once daily for 3 days.
• U bolesnika s reumatoidnim artritisom: terapiju leflunomidom započinje primjenom udarne doze od 100 mg jedanput na dan tijekom 3 dana.
After administration of a radiolabelled dose of leflunomide, radioactivity was equally excreted in faeces, probably by biliary elimination, and in urine.
Nakon primjene radioaktivno obilježenog leflunomida, radioaktivnost se jednako pojavila u stolici, vjerojatno eliminacijom putem žuči, i u mokraći.
A771726 displaced ibuprofen, diclofenac and tolbutamide but the unbound fraction of these drugs is only increased by 10 % to 50 %.
A771726 istiskuje ibuprofen, diklofenak i tolbutamid, ali se nevezana frakcija tih lijekova povećava za samo 10% do 50%.
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.
Liječnik koji Vam uvede terapiju Leflunomidom Teva i koji Vas nadzire tijekom terapije treba imati iskustva u liječenju reumatoidnog artritisa.
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.
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.
Most patients improved after discontinuation of Leflunomide Teva.
Stanje se popravilo u većine bolesnika nakon prekida terapije Leflunomidom Teva.
- 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).
- 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).
Patients were 3-17 years of age with active polyarticular course JRA regardless of onset type and naive to methotrexate or leflunomide.
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.
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.
Stoga, pri pojavi tih toksičnosti ili potrebe za brzim uklanjanjem A771726 iz organizma zbog bilo kojeg drugog razloga treba obaviti ispiranje ("washout" postupak).
What Leflunomide Teva is and what it is used for 2.
Što je Leflunomid Teva i za što se koristi
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.
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.
Each tablet contains 97.25 mg of lactose monohydrate and 3.125 mg anhydrous lactose.
Jedna tableta sadrži 97,25 mg laktoze hidrata i 3,125 mg laktoze, bezvodne.
If you are already taking non-steroidal anti-inflammatory drugs (NSAIDs) and/or corticosteroids, you may continue to use these after starting Leflunomide Teva.
Ako već uzimate nesteroidne protuupalne lijekove (NSAIL) i/ili kortikosteroide, možete ih nastaviti uzimati nakon što počnete uzimati Leflunomid Teva.
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.
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.
General disorders and administration site conditions anorexia, weight loss (usually insignificant), asthenia
Opći poremećaji i reakcije na mjestu primjene anoreksija, gubitak težine (obično neznačajan), astenija
The pharmacokinetics of A771726 following oral administration of leflunomide have been investigated in 73 pediatric patients with polyarticular course Juvenile Rheumatoid Arthritis (JRA) who ranged in age from 3 to 17 years.
Farmakokinetika A771726 nakon oralne primjene leflunomida ispitivana je u 73 pedijatrijska bolesnika u dobi od 3 do 17 godina s poliartikuliranim oblikom juvenilnog reumatoidnog artritisa
At a dose level of 20 mg/day, average plasma concentration of A771726 at steady state is approximately 35 μg/ml.
Pri dozi od 20 mg/dan prosječna koncentracija A771726 u plazmi u stanju dinamičke ravnoteže iznosila je oko 35 μg/ml.
Each tablet contains 194.5 mg of lactose monohydrate and 6.25 mg anhydrous lactose.
Jedna tableta sadrži 194,5 mg laktoze hidrata i 6,25 mg laktoze, bezvodne.
In vivo, it is rapidly and almost completely metabolised to A771726 which is active in vitro, and is presumed to be responsible for the therapeutic effect.
In vivo se brzo i gotovo potpuno metabolizira u A771726, koji je aktivan in vitro te se smatra
- If you have bone marrow problems, or if you have low numbers of red or white blood cells or a reduced number of blood platelets, due to causes other than rheumatoid or psoriatic arthritis.
Ako imate problema s koštanom srži ili ako imate smanjen broj crvenih ili bijelih krvnih stanica ili krvnih pločica (trombocita) koji nije uzrokovan reumatoidnim ili psorijatičnim artritisom.
If you are pregnant or become pregnant while taking Leflunomide Teva, the risk of having a baby with serious
Ako ste trudni ili zatrudnite dok uzimate Leflunomid Teva, rizik od ozbiljnih prirođenih mana u Vašeg djeteta
- An increase in some liver test results.
- porast vrijednosti određenih jetrenih enzima;
If both plasma concentrations are below 0.02 mg/l, and after a waiting period of at least 3 months, the risk of
Ako je u oba slučaja koncentracija u plazmi manja od 0,02 mg/l, a nakon stanke od najmanje 3 mjeseca, rizik od fetalne
Interstitial lung disease is a potentially fatal disorder, which may occur acutely during therapy.
Intersticijska plućna bolest može imati smrtni ishod, a smrt može nastupiti iznenada tijekom liječenja
In patients with pre-existing anaemia, leucopenia, and/or thrombocytopenia as well as in patients with impaired bone marrow function or those at risk of bone marrow suppression, the risk of haematological disorders is increased.
U bolesnika s postojećom anemijom, leukopenijom i/ili trombocitopenijom, kao i u bolesnika s oštećenom funkcijom koštane srži ili s rizikom od supresije koštane srži, povećan je rizik od pojave hematoloških poremećaja.
Not known side effects (frequency cannot be estimated from the available data): - Kidney failure.
Nepoznate nuspojave (učestalost se ne može procijeniti na osnovi raspoloživih podataka): zatajenje bubrega;
For washout procedures and other recommended actions in case of desired or unintended pregnancy
Za ispiranje ("washout" postupak) i ostale preporučene aktivnosti u slučaju željene ili neplanirane trudnoće vidjeti dio 4.6.
Cases of peripheral neuropathy have been reported in patients receiving Leflunomide Teva.
Slučajevi periferne neuropatije zabilježeni su u bolesnika koji su uzimali Leflunomid Teva.
If such effects occur, a washout (see below) to reduce plasma levels of A771726 should be considered.
Ako se ti učinci pojave, treba razmotriti postupak eliminacije (vidjeti nastavak teksta) kako bi se smanjila koncentracija A771726 u plazmi.
The ACR (American College of Rheumatology) response rates in study YU203 were 27.7 % for placebo, 31.9 % for 5 mg, 50.5 % for 10 mg and
Stope terapijskog odgovora prema ACR-u (American College of Rheumatology) u studiji YU203 bile su 27,7% za placebo, 31,9% za 5 mg/dan, 50,5% za 10 mg/dan i 54,5% za 25 mg/dan.
If a waiting period of up to approximately 2 years under reliable contraception is considered unpractical, prophylactic institution of a washout procedure may be advisable.
Ako nije moguće čekati dvije godine uz odgovarajuću kontracepciju, preporučuje se profilaktički započeti ispiranje ("washout" postupak).
In vitro plasma protein binding interaction studies with warfarin at clinically relevant concentrations, however, showed no interaction.
U in vitro ispitivanjima interakcija s varfarinom kod vezanja za proteine plazme nisu zabilježene interakcije pri klinički relevantnim koncentracijama.
Colestyramine given orally at a dose of 8 g three times a day for 24 hours to three healthy volunteers decreased plasma levels of A771726 by approximately 40 % in 24 hours and by 49 % to
Kolestiramin u dozi od 8 g primijenjen oralno tri puta tijekom 24 sata u tri zdrava dobrovoljca smanjio je koncentraciju A771726 u plazmi za oko 40% u 24 sata, te za 49% do 65% u 48 sati.
In a study in which leflunomide was given concomitantly with a triphasic oral contraceptive pill containing 30 μg ethinyloestradiol to healthy female volunteers, there was no reduction in contraceptive activity of the pill, and A771726 pharmacokinetics were within predicted ranges.
U ispitivanju u kojem se zdravim ženama leflunomid davao istodobno s trifaznim oralnim kontraceptivima koji su sadržavali 30 μg etiniloestradiola nije zabilježena smanjena kontracepcijska aktivnost pilule, dok je farmakokinetika A771726 bila u predvidljivim rasponima.
In the event that severe, uncontrolled infections occur, it may be necessary to interrupt leflunomide treatment and administer a washout procedure as described below.
U slučaju pojave teških nekontroliranih infekcija može biti potrebno prekinuti primjenu leflunomida i započeti eliminaciju, kako je opisano u nastavku teksta.
• colestyramine 8 g is administered 3 times daily for a period of 11 days,
• kolestiramin 8 g tri puta na dan tijekom 11 dana,
In multiple dose studies in patients with rheumatoid arthritis, the pharmacokinetic parameters of A771726 were linear over the dose range of 5 to 25 mg.
U ispitivanjima višekratnih doza u bolesnika s reumatoidnim artritisom, farmakokinetički parametri A771726 bili su linearni u rasponu doza od 5 do 25 mg.
It is recommended that patients receiving leflunomide are not treated with colestyramine or activated powdered charcoal because this leads to a rapid and significant decrease in plasma A771726 (the active metabolite of leflunomide; see also section 5) concentration.
Preporučuje se da se bolesnici koji uzimaju leflunomid ne liječe kolestiraminom ili aktivnim ugljenom u prahu jer oni utječu na brzo i značajno smanjenje koncentracije A771726 (aktivnog metabolita leflunomida; vidjeti dio 5) u plazmi.
Moreover, switching from leflunomide to another DMARD without following the washout procedure (see section 4.4) may also increase the risk of serious adverse reactions even for a long time after the
Osim toga, prijelaz s leflunomida na neki drugi DMARD, bez provedbe ispiranja ("washout" postupak) leflunomida (vidjeti dio 4.4.), također može povećati rizik od ozbiljnih nuspojava, čak i
- If you already have low red or white blood cells (anaemia or leucopenia), low blood platelets, which may increase your bleeding or bruising (thrombocytopenia), low bone marrow function or if you are at risk of your bone marrow not working properly your doctor may advise you to take certain medicines to speed up the removal of Leflunomide Teva from your body.
Ako već imate niske razine crvenih ili bijelih krvnih stanica (anemiju ili leukopeniju), niske razine trombocita, što može povećati rizik od krvarenja ili pojave modrica (trombocitopenija), odnosno ako imate smanjenu funkciju koštane srži ili ako postoji rizik od oštećenja funkcije koštane srži, liječnik Vam može savjetovati uzimanje određenih lijekova koji će ubrzati uklanjanje Leflunomida Teva iz tijela.
Marketing Authorisation Holder: Teva Pharma B.V.
NOSITELJ ODOBRENJA ZA STAVLJANJE GOTOVOG LIJEKA U PROMET Teva Pharma B.V.
Leflunomide is metabolised to one primary (A771726) and many minor metabolites including TFMA (4-trifluoromethylaniline).
Leflunomid se metabolizira u jedan glavni (A771726) i više manjih metabolita, uključujući (4-trifluorometilanilin).
This is thought to be achieved by a gastrointestinal dialysis mechanism and/or by interrupting enterohepatic recycling.
Smatra se da se taj učinak postiže gastrointestinalnom dijalizom i/ili prekidom
No clinical data are available on the efficacy and safety of vaccinations under leflunomide treatment.
Ne postoje klinički podaci o djelotvornosti i sigurnosti cijepljenja u osoba koje se istodobno liječe leflunomidom.
• The identified risk of synergistic hepato- or haematotoxicity associated with combination therapy with another Disease-Modifying Antirheumatic Drug (e.g. methotrexate).
• Prepoznat rizik od sinergije između hepatotoksičnosti ili hematotoksičnosti i kombinirane terapije s nekim drugim antireumatikom koji modificira tijek bolesti (primjerice
In a small (n=30) study with co-administration of leflunomide (10 to 20 mg per day) with methotrexate (10 to 25 mg per week) a 2- to 3-fold elevation in liver enzymes was seen on 5 of 30 patients.
U manjem ispitivanju (n=30) istodobne primjene leflunomida (10 do 20 mg na dan) i metotreksata (10 do 25 mg na tjedan) opaženo je povišenje jetrenih enzima dva do tri puta u 5 od 30 bolesnika.
HDPE containers: Do not store above 30°C.
HDPE spremnici: Ne čuvati na temperaturi iznad 30°C.
Do not use this medicine after the expiry date that is stated on the outer carton or foil after EXP.
Ovaj lijek ne smije se upotrijebiti nakon isteka roka valjanosti navedenog na vanjskom pakovanju ili foliji iza oznake „Rok valjanosti ili kratice „EXP“.
- Severe sometimes life-threatening reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme).
- teške reakcije koje ponekad mogu biti opasne po život (Stevens-Johnsonov sindrom, toksična epidermalna nekroliza, multiformni eritem);