natgillin/translations-raw huggingface dataset:
65 This leaflet was last approved in {MM/YYYY}.
Navodilo je bilo odobreno {MM/ LLLL}.
TARGRETIN EPAR summary for the public
TARGRETIN Povzetek EPAR za javnost
Targretin is used for the treatment of the visible signs on the skin of cutaneous T-cell lymphoma (CTCL).
Zdravilo Targretin se uporablja za zdravljenje vidnih znakov kožnega T- celičnega limfoma (CTCL) na koži.
Treatment with Targretin should only be initiated and maintained by a doctor who has experience in the treatment of patients with CTCL.
Zdravljenje z zdravilom Targretin sme začeti in ga izvajati samo zdravnik z izkušnjami pri zdravljenju bolnikov s kožnim T- celičnim limfomom.
The dose of Targretin is based on the patient’ s body surface area in square metres (m2).
Odmerek zdravila Targretin se določi glede na površino telesa bolnika v kvadratnih metrih (m2).
The recommended starting dose is 300 mg/ m2/ day.
Priporočen začetni odmerek je 300 mg/ m2/ dan.
The dose is adjusted depending on the patient ’ s response to treatment or side effects.
Odmerek se prilagaja glede na bolnikov odziv na zdravljenje ali glede na neželene učinke.
It belongs to the group of retinoids, substances that are derived from vitamin A.
Sodi v skupino retinoidov, snovi, ki so pridobljene iz vitamina A.
The exact way bexarotene works in CTCL is not known.
Natančen način delovanja beksarotena pri kožnem T- celičnem limfomu ni znan.
The effectiveness of Targretin has been examined in two studies involving a total of 193 patients with CTCL who had failed on at least two previous treatments.
Učinkovitost zdravila Targretin so preučevali v dveh študijah s skupno 193 bolniki s kožnim T - celičnim limfomom, pri katerih sta se najmanj dve predhodni zdravljenji izkazali za neuspešni.
Sixty-one patients were treated at the starting dose of 300 mg/ m2/ day.
Enainšestdeset bolnikov so zdravili z začetnim odmerkom 300 mg/ m2/ dan.
(44-20) 74 18 84 00 Fax (44-20) 74 18 84 16 E-mail: mail@emea. europa. eu http: / /www. emea. europa. eu  EMEA 2007 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged effectiveness was the response to treatment after 16 weeks.
(44- 20) 74 18 84 00 Fax (44- 20) 74 18 84 16 E- mail: mail@ emea. europa. eu http: // www. emea. europa. eu EMEA 2007 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged Kakšne koristi je zdravilo Targretin izkazalo med raziskavami?
Across the two studies, among the patients who received 300 mg/ m2, about half of them responded to treatment, according the doctor’ s grading.
V dveh študijah z bolniki, ki so prejemali 300 mg/ m2 zdravila, se jih je glede na zdravniško oceno na zdravljenje odzvala približno polovica.
The response rates according to the 5 skin scores were 36% and 27%, respectively.
27%.
Targretin should also not be used in the following situations:  women who are pregnant or breast-feeding  women who could become pregnant  anyone who has had pancreatitis (inflammation of the pancreas)  uncontrolled hypercholesterolaemia (high blood cholesterol).  uncontrolled hypertriglyceridaemia (high blood triglycerides [fat]).  hypervitaminosis A (high levels of vitamin A)  uncontrolled thyroid disease.  liver disease  where there is a body infection.
Zdravilo Targretin se prav tako ne sme uporabljati v naslednjih primerih:  pri ženskah, ki so noseče ali dojijo  pri ženskah, ki utegnejo zanositi  pri osebah, ki so imele pankreatitis (vnetje trebušne slinavke)  pri nekontrolirani hiperholesterolemiji (visoke koncentracije holesterola v krvi)  pri nekontrolirani hipertrigliceridemiji (visoke krvne vrednosti trigliceridov [maščob])  pri hipervitaminozi A (visoke koncentracije vitamina A)  pri nekontrolirani bolezni ščitnice  pri bolezni jeter  pri okužbi v telesu.
The Committee for Medicinal products for Human Use (CHMP) decided that Targretin’ s benefits are greater than its risks for the treatment of the skin manifestations of advanced stage cutaneous T-cell lymphoma patients refractory to at least one systemic treatment.
Odbor za zdravila za uporabo v humani medicini (CHMP) je odločil, da so koristi zdravila Targretin pri zdravljenju kožnih manifestacij pri bolnikih s kožnim T- celičnim limfomom v napredovalem stadiju, ki se ni odzval na najmanj eno sistemsko zdravljenje, večje od z njim povezanih tveganj.
EU/ 1/ 01/ 178/ 001
Številka EU EU/ 1/ 01/ 178/ 001
Targretin
Zaščiteno ime Targretin
75 mg
Jakost 75mg
Capsule, soft
Farmacevtska oblika Kapsula, mehka
Bottle (HDPE)
Ovojnina Steklenika (HDPE)
100
Velikost pakiranja 100
Each capsule contains 75 mg of bexarotene.
Vsaka kapsula vsebuje 75 mg beksarotena Za celoten seznam pomožnih snovi glejte poglavje 6. 1.
Off-white capsule, containing a liquid suspension and imprinted with “ Targretin”.
Kapsule bele kremne barve z natisnjenim napisom “ Targretin ”, ki vsebujejo tekočo suspenzijo.
Targretin capsules are indicated for the treatment of skin manifestations of advanced stage cutaneous T-cell lymphoma (CTCL) patients refractory to at least one systemic treatment.
Targretin kapsule so namenjene zdravljenju kožnih manifestacij pri bolnikih s kožnim T- celičnim limfomom (CTCL) v razvitem stadiju, ki se ni odzval na najmanj eno sistemsko zdravljenje.
Bexarotene therapy should only be initiated and maintained by physicians experienced in the treatment of patients with CTCL.
Terapijo z beksarotenom naj predpiše in nadzoruje le zdravnik specialist, ki ima izkušnje z zdravljenjem bolnikov s kožnim T- celičnim limfomom (CTCL).
The recommended initial dose is 300 mg/ m2/ day.
Priporočen začetni odmerek je 300 mg/ m2/ dan.
Targretin capsules should be taken as a single oral daily dose with a meal (see section 4.5).
Targretin kapsule naj se jemljejo enkrat dnevno peroralno pri jedi (glejte poglavje 4. 5).
Initial dose level (300 mg/ m2/ day) Number of 75 mg
Višina začetnega odmerka (300 mg/ m2/ dan) Število 75 mg
Surface Area (m2)
Površina telesa (m2)
Total daily dose (mg/ day)
Celokupni dnevni odmerek (mg/ dan)
0.88 – 1.12 1.13 - 1.37 1.38 - 1.62 1.63 - 1.87 1.88 - 2.12 2.13 - 2.37 2.38 - 2.62
0, 88 - 1, 12 1, 13 - 1, 37 1, 38 - 1, 62 1, 63 - 1, 87 1, 88 - 2, 12 2, 13 - 2, 37
300 375 450 525 600 675 750
300 375 450 525 600 675
4 5 6 7 8 9 10
10
Dose modification guidelines: the 300 mg/ m2/ day dose level may be adjusted to 200 mg/ m2/ day then to 100 mg/ m2/ day, or temporarily suspended, if necessitated by toxicity.
Smernice za prilagoditev odmerjanja: odmerek v višini 300 mg/ m2/ dan se lahko zmanjša na 200 mg/ m2/ dan in nato na 100 mg/ m2/ dan oz. zdravljenje se lahko začasno prekine, če je to potrebno zaradi toksičnosti.
With appropriate clinical monitoring, individual patients may benefit from doses above 300 mg/ m2/ day.
Pri ustreznem kliničnem spremljanju lahko odmerki nad 300 mg/ m2/ dan ugodno vplivajo na posamezne bolnike.
Doses greater than 650 mg/ m2/ day have not been evaluated in patients with CTCL.
Odmerki, ki presegajo 650 mg/ m2/ dan, še niso bili preučevani pri CTCL bolnikih.
2 Use in children and adolescents: the clinical safety and effectiveness of bexarotene in the paediatric population (below 18 years of age) have not been studied and this product should not be used in a paediatric population until further data become available.
Dokler ni na razpolago nadaljnjih podatkov, otroci in mladostniki tega zdravila ne smejo uporabljati.
Use in the elderly: of the total number of patients with CTCL in clinical studies, 61% were 60 years or older, while 30% were 70 years or older.
Od skupnega števila vseh bolnikov s CTCL, ki so sodelovali v kliničnih študijah, je bilo 61% starih 60 let ali več ter 30% 70 let ali več.
Renal insufficiency: no formal studies have been conducted in patients with renal insufficiency.
Formalnih študij pri bolnikih z ledvično insuficienco niso izvajali.
In all evaluated patients, the estimated renal clearance of bexarotene was less than 1 ml/ minute.
Pri vseh pregledanih bolnikih je bilo ocenjeno izločanje beksarotena preko ledvic manjše kot 1 ml/ minuta.
In view of the limited data, patients with renal insufficiency should be monitored carefully while on bexarotene therapy.
Zaradi omejenih podatkov o bolnikih z ledvično insuficienco je treba le- te v času terapije z beksarotenom skrbno nadzorovati.
Ongoing systemic infection.
Znana preobčutljivost za beksaroten ali katerokoli pomožno snov zdravila. nosečnost in dojenje plodne ženske, ki ne uporabljajo učinkovita kontracepcijska sredstva anamneza pankreatitisa nekontrolirana hiperholesterolemija nekontrolirana hipertrigliceridemija hipervitaminoza A nekontrolirane bolezni ščitnice jetrna insuficienca stalna sistemska infekcija
Lipids: hyperlipidaemia has been identified as an effect associated with the use of bexarotene in clinical studies.
Hiperlipidemija je bila ugotovljena kot učinek, povezan z uporabo beksarotena v kliničnih študijah.
Fasting blood lipid determinations (triglycerides and cholesterol) should be performed before bexarotene therapy is initiated and at weekly intervals until the lipid response to bexarotene is established, which usually occurs within two to four weeks, and then at intervals no less than monthly thereafter.
To je običajno med drugim in četrtim tednom.
Fasting triglycerides should be normal or normalised with appropriate intervention prior to bexarotene therapy.
Testiranje krvnih lipidov je nato treba opravljati še naprej, in sicer v najmanj enomesečnih intervalih.
Every attempt should be made to maintain triglyceride levels below 4.52 mmol/ l in order to reduce the risk of clinical sequelae.
V izogib posledični klinični bolezni mora biti posebna pozornost posvečena temu, da se vrednost trigliceridov nahaja pod nivojem 4, 52 mmol/ l.
If fasting triglycerides are elevated or become elevated during treatment, institution of antilipaemic therapy is recommended, and if necessary, dose reductions (from 300 mg/ m2/ day of bexarotene to 200 mg/ m2/ day, and if necessary to 100 mg/ m2/ day) or treatment discontinuation.
V primeru, da so trigliceridi (na tešče) zvišani ali če se vrednost trigliceridov v času zdravljenja poveča, je priporočena antilipidna terapija ali po potrebi tudi zmanjšanje odmerka (iz 300 mg/ m2/ dan beksarotena na 200 mg/ m2/ dan; če je nujno tudi do 100 mg/ m2/ dan) oz. prekinitev zdravljenja.
However, concomitant administration of gemfibrozil resulted in substantial increases in plasma concentrations of bexarotene and therefore, concomitant administration of gemfibrozil with bexarotene is not recommended (see section 4.5).
Iz tega razloga sočasno dajanje gemfibrozila skupaj z beksarotenom ni priporočljivo (glejte poglavje 4. 5).
Pancreatitis: acute pancreatitis associated with elevations of fasting serum triglycerides has been reported in clinical studies.
V poročilih kliničnih študij so akutni pankreatitis povezali z zvišanimi serumskimi trigliceridi (na tešče).
Patients with CTCL having risk factors for pancreatitis (e. g., prior episodes of pancreatitis, uncontrolled hyperlipidaemia, excessive alcohol consumption, uncontrolled diabetes mellitus, biliary tract disease, and medications known to increase triglyceride levels or to be associated with pancreatic toxicity) should not be treated with bexarotene, unless the potential benefit outweighs the risk.
CTCL bolniki, ki imajo dejavnike tveganja za pankreatitis (npr. predhodne epizode pankreatitisa, nekontrolirana hiperlipidemija, prekomerno uživanje alkohola, nekontroliran diabetes mellitus, bolezni žolčevodov ter zdravila, o katerih je znano, da povečajo nivo trigliceridov ali ki so povezani s toksičnostjo za pankreas), se ne smejo zdraviti z beksarotenom, razen če potencialne koristi presegajo tveganje.
3 Liver Function Test (LFT) abnormalities:
3 Anomalije pri testiranju jetrne funkcije (LFT):
Consideration should be given to a suspension or discontinuation of bexarotene if test results reach greater than three times the upper limit of normal values for SGOT/ AST, SGPT/ ALT, or bilirubin.
V primeru, da rezultati testiranja dosežejo trikratno vrednost ali celo višjo v primerjavi z zgornjo mejo normalne vrednosti za SGOT/ AST, SGPT/ ALT ali bilirubin, je treba razmišljati o začasni ali celotni prekinitvi jemanja beksarotena.
Thyroid function test alterations: changes in thyroid function tests have been observed in patients receiving bexarotene, most often noted as a reversible reduction in thyroid hormone (total thyroxine [total T4]) and thyroid-stimulating hormone (TSH) levels.
Spremembe pri testiranju delovanja ščitnice so opazili pri bolnikih, ki so jemali beksaroten, spremembe so bile najpogosteje vidne kot reverzibilna redukcija hormona ščitnice (skupni nivo tiroksina [skupno T4]) in tiroksin- stimulirajočega hormona (TSH).
Leucopenia: leucopenia associated with bexarotene therapy has been reported in clinical studies.
V kliničnih študijah so poročali o povezanosti levkopenije z beksarotensko terapijo.
Anaemia: anaemia associated with bexarotene therapy has been reported in clinical studies.
V kliničnih študijah so poročali o povezanosti anemije z beksaroten terapijo.
Lens opacities: following bexarotene treatment, some patients were observed to have previously undetected lens opacities or a change in pre-existing lens opacities unrelated to treatment duration or dose level of exposure.
Pri nekaterih bolnikih so po zdravljenju z beksarotenom opazili poprej neopažene motnosti očesne leče oz. spremembe že obstoječe motnosti očesne leče, ki pa niso bile povezane s trajanjem zdravljenja ali višino odmerka.
Vitamin A supplementation: because of the relationship of bexarotene to vitamin A, patients should be advised to limit vitamin A supplements to ≤ 15,000 IU/ day to avoid potential additive toxic effects.
Na ta način se preprečijo potencialni kumulativni toksični učinki.
Patients with diabetes mellitus: caution should be exercised when administering bexarotene in patients using insulin, agents enhancing insulin secretion (e. g. sulfonylureas), or insulin-sensitisers (e. g. thiazolidinediones).
Pri dajanju beksarotena bolnikom, ki uporabljajo inzulin, sredstva za izboljšanje izločanja inzulina (npr. sulfonil sečnine), ali inzulinske senzibilizatorje (npr. tiazolidinedion), je potrebna posebna previdnost.
Photosensitivity: the use of some retinoids has been associated with photosensitivity.
Uporabo nekaterih retinoidov so povezali z občutljivostjo za svetlobo.
Oral contraceptives: bexarotene can potentially induce metabolic enzymes and thereby theoretically reduce the efficacy of oestroprogestive contraceptives.
Beksaroten lahko potencialno povzroči nastajanje metaboličnih encimov ter zaradi tega teoretično zmanjša učinkovitost estroprogestivnih kontracepcijskih sredstev.
Effects of other substances on bexarotene: no formal studies to evaluate interactions with bexarotene have been conducted.
Učinki drugih snovi na beksaroten:
On the basis of the oxidative metabolism of bexarotene by cytochrome
Dosedaj ni bilo opravljenih študij za ovrednotenje medsebojnega delovanja beksarotena z drugimi zdravili.
4 P450 3A4 (CYP3A4), coadministration with other CYP3A4 substrates such as ketoconazole, itraconazole, protease inhibitors, clarithromycin and erythromycin may theoretically lead to an increase in plasma bexarotene concentrations.
Na osnovi oksidativnega metabolizma beksarotena zaradi citokroma P450 3A4 (CYP3A4) vodi sočasna uporaba CYP3A4 substratov, kot so ketokonazol, itrakonazol, proteazni inhibitorji, klaritromicin in eritromicin, teoretično do povečanja koncentracije beksarotena v plazmi.
Caution is advised in case of combination with CYP3A4 substrates having a narrow therapeutic margin i. e. immunosuppressive agents (cyclosporine, tacrolimus, sirolimus) as well as CYP3A4- metabolised cytotoxics, i. e. cyclophosphamide, etoposide, finasteride, ifosfamide, tamoxifen, vinca- alcaloids.
Previdnost je potrebna pri kombinacijah substratov za CYP3A4 z majhno terapevtsko širino, t. j. pri imunosupresivnih sredstvih (ciklosporin, takrolimus, sirolimus), pa tudi pri citotoksičnih sredstvih, ki jih presnavlja CYP3A4, kot so ciklofosfamid, etopozid, finasterid, ifosfamid, tamoksifen, alkaloidi vinca.
Effects of bexarotene on other substances: there are indications that bexarotene may induce CYP3A4.
Obstajajo znaki, da beksaroten lahko povzroči indukcijo CYP3A4.
Therefore, repeated administration of bexarotene may result in an auto-induction of its own metabolism and, particularly at dose levels greater than 300 mg/ m2/ day, may increase the rate of metabolism and reduce plasma concentrations of other substances metabolised by cytochrome P450 3A4, such as tamoxifen.
Iz tega razloga lahko večkratno dajanje beksarotena povzroči samoindukcijo lastnega metabolizma in (še posebej pri odmerkih, ki presegajo 300 mg/ m2/ dan) poveča stopnjo metabolizma ter zmanjša koncentracije drugih snovi v plazmi, katere presnavlja citokrom P450 3A4, kot je npr. tamoksifen.
For example bexarotene may reduce the efficacy of oral contraceptives (see sections 4.4 and 4.6).
Beksaroten lahko na primer zmanjša učinkovitost peroralnih kontracepcijskih sredstev (glejte poglavje 4. 4 in 4. 6).
Laboratory test interactions:
Vpliv na laboratorijske preiskave - medsebojno delovanje:
CA125 assay values in patients with ovarian cancer may be accentuated with bexarotene therapy.
Vrednosti CA125 v testih pri bolnikih z rakom jajčnikov so lahko izrazitejše.
Food interactions: in all clinical trials, patients were instructed to take Targretin capsules with or immediately following a meal.
V vseh kliničnih preskušanjih je bilo bolnikom dano navodilo, da vzamejo Targretin kapsule pri jedi oz. nemudoma po jedi.
Pregnancy: there are no adequate data from the use of bexarotene in pregnant women.
Ni zadostnih podatkov o uporabi beksarotena pri nosečnicah.
Based on the comparison of animal and patient exposures to bexarotene, a margin of safety for human teratogenicity has not been demonstrated (see section 5.3).
Na osnovi primerjave izpostavljenosti beksarotenu pri živalih in pri bolnikih ni bila demonstrirana meja varnosti glede na teratogenost pri ljudeh (glejte poglavje 5. 3).
Bexarotene is contraindicated in pregnancy (see section 4.3).
Beksaroten je kontraindiciran v nosečnosti (glejte poglavje 4. 3).
Women of childbearing potential must use adequate birth-control measures when bexarotene is used.
V času jemanja beksarotena si morajo plodne ženske zagotoviti učinkovito kontracepcijo.
A negative, sensitive, pregnancy test (e. g. serum beta-human chorionic gonadotropin, beta-HCG) should be obtained within one week prior to bexarotene therapy.
Teden pred začetkom terapije je treba opraviti občutljiv test za ugotavljanje nosečnosti (npr. serumski beta- humani horionski gonadotropin, beta- HCG), ki mora biti negativen.
Effective contraception must be used from the time of the negative pregnancy test through the initiation of therapy, during therapy and for at least one month following discontinuation of therapy.
Kadarkoli je potrebna
Whenever contraception is required, it is recommended that two reliable forms of contraception be used simultaneously.
5 kontracepcija, je priporočljivo, da se uporabita dve zanesljivi obliki kontracepcije hkrati.
Bexarotene can potentially induce metabolic enzymes and thereby theoretically reduce the efficacy of oestroprogestative contraceptives (see section 4.5).
Beksaroten lahko potencialno inducira metabolične encime in na ta način zmanjša učinkovitost estroprogestativnih kontracepcijskih sredstev (glejte poglavje 4. 5).
5 potentially become pregnant must use condoms during sexual intercourse while taking bexarotene and for at least one month after the last dose.
Moški bolniki s spolno partnerico, ki je noseča, eventualno noseča oz. lahko zanosi, morajo za koitus uporabiti kondom v času jemanja beksarotena, in sicer za čas najmanj enega meseca po zadnjem odmerku.
Lactation: it is not known whether bexarotene is excreted in human milk.
Ni znano, ali se beksaroten izloča preko materinega mleka.
The safety of bexarotene has been examined in clinical studies of 193 patients with CTCL who received bexarotene for up to 118 weeks and in 420 non-CTCL cancer patients in other studies.
Varnost beksarotena so analizirali v kliničnih študijah s 193 bolniki s CTCL, ki so dobivali beksaroten v času do 118 tednov ter v drugih študijah, v katerih je sodelovalo 420 bolnikov brez CTCL- a.
In 109 patients with CTCL treated at the recommended initial dose of 300 mg/ m2/ day, the most commonly reported adverse reactions to Targretin were hyperlipaemia ((primarily elevated triglycerides) 74%), hypothyroidism (29%), hypercholesterolaemia (28%), headache (27%), leucopenia (20%), pruritus (20%), asthenia (19%), rash (16%), exfoliative dermatitis (15%), and pain (12%).
109 bolnikov s CTCL, zdravljenih s priporočenim začetnim odmerkom 300 mg/ m2/ dan, je najpogosteje poročalo o sledečih neželenih učinkih: hiperlipemija ((na začetku zvišani trigliceridi) 74%), hipotiroidizem (29%), hiperholesterolemija (28%), glavobol (27%), levkopenija (20%), pruritus (20%), astenija (19%), izpuščaji (16%), eksfoliativni dermatitis (15%) in bolečina (12%).
The following Targretin-related adverse reactions were reported during clinical studies in patients with CTCL (N=109) treated at the recommended initial dose of 300 mg/ m2/ day.
Med kliničnimi študijami so poročali o sledečih neželenih učinkih pri bolnikih s CTCL (N=109), ki so se zdravili s priporočenim začetnim odmerkom 300 mg/ m2/ dan.
The frequencies of adverse reactions are classified as very common (> 1/ 10), common (> 1/ 100 ,< 1/10), uncommon (> 1/ 1,000 ,< 1/100), rare (> 1/ 10,000, < 1/ 1,000), and very rare (< 1/ 10,000).
Neželeni učinki so glede na pogostnost pojavljanja razvrščeni kot: zelo pogosti (> 1/ 10), pogosti (> 1/ 100, < 1/ 10), občasni (> 1/ 1. 000, < 1/ 100), redki (> 1/ 10. 000, < 1/ 1. 000) in zelo redki (< 1/ 10. 000).
Leucopenia Lymphoma Like Reaction, Lymphadenopathy, Hypochromic Anaemia1,2,3, Blood Dyscrasia, Purpura, Coagulation Disorder, Coagulation Time Increased2,3, Anaemia1, Thrombocytopenia3, Thrombocythemia, Eosinophilia1, Leukocytosis2, Lymphocytosis
levkopenija reakcija, podobna limfomu, limfadenopatija, hipokromna anemija1, 2, 3 krvna diskrazija, purpura, koagulacijske motnje, podaljšan čas koagulacije2, 3, anemija1, trombocitopenija3, trombocitemija, eozinofilija1, levkocitoza2, limfocitoza
Very common:
Bolezni endokrinega sistema Zelo pogosti:
Hypothyroidism Thyroid Disorder Hyperthyroidism
hipotiroidizem motnje delovanja ščitnice hipertiroidizem
Gout, Bilirubinemia1,3, BUN Increased1, High Density Lipoprotein Decreased
hiperlipemija, hiperholesterolemija povečanje telesne mase, zvišan SGOT, zvišan SGPT, zvišana laktat - dehidrogenaza, zvišan kreatinin, hipoproteinemija protin, bilirubinemija1, 3, zvišana stopnja dušika v krvi1, znižan HDL
Dizziness, Hypesthesia, Insomnia Ataxia, Neuropathy, Vertigo, Hyperaesthesia, Depression1,2,3, Agitation
omotica, hipestezija, nespečnost ataksija, nevropatija, vrtoglavica, hiperestezija, depresija1, 2, 3, agitacija
Uncommon:
suhe oči, očesne bolezni
6 Ear and labyrinth disorders Common:
6
Deafness Ear disorder
naglušnost ušesne bolezni
Peripheral Oedema Haemorrhage, Hypertension, Oedema3, Vasodilatation1,2,3, Varicose Vein
periferni edem hemoragija, hipertenzija, edem3, vazodilatacija1, 2, 3, krčne žile,
Pancreatitis1,3, Hepatic Failure, Gastrointestinal Disorder1
bruhanje, driska1, 3, slabost3, anoreksija1, nenormalni izvidi pri testiranju jetrne funkcije, vnetje ustnice2, suha usta2, 3, zaprtje, vetrovi pankreatitis1, 3, odpoved jeter, bolezni prebavil1
Serous Drainage1, Herpes Simplex, Pustular Rash, Skin Discoloration3 Hair Disorder1, Nail Disorder1,3
eksfoliativni dermatitis, pruritus, izpuščaji ulkus kože, alopecija1, kožna hipertrofija, kožni vozli, akne, znojenje, suha koža2, 3, bolezni kože močna izsušenost1, herpes simpleks, pustularni izpuščaji, sprememba barve kože3, težave z lasmi1, težave z nohti1, 3
Musculoskeletal and Common:
Bolezni mišično- skeletnega sistema in vezivnega tkiva Pogosti:
connective tissue disorders Bone Pain, Arthralgia, Myalgia Myasthaenia1
bolečine v kosteh, artralgija, mialgija miastenija1
Renal and urinary disorders Uncommon:
Bolezni sečil Občasni: