natgillin/translations-raw huggingface dataset:
The management of adverse reactions may require dose reduction, treatment interruption or treatment discontinuation (see Tables 1 and 2).
Obvladovanje neželenih učinkov lahko zahteva znižanje odmerka, prekinitev zdravljenja ali prenehanje zdravljenja (glejte preglednici 1 in 2).
Fertility - both men and women Mekinist may impair fertility in both men and women.
Plodnost - moški in ženske Zdravilo Mekinist lahko poslabša plodnost pri moških in ženskah.
Your doctor will also check your head, neck, mouth and lymph glands and you will have scans of your chest and stomach area (called CT scans) regularly.
Zdravnik vam bo pregledal tudi glavo, vrat, usta in bezgavke, poleg tega boste redno opravljali slikanje (tako imenovano CT slikanje) prsnega koša in trebuha.
In some cases, patients were able to continue trametinib.
V nekaterih primerih so bolniki lahko nadaljevali zdravljenje s trametinibom.
The median time to first presentation of ILD or pneumonitis was 160 days (range: 60 to 172 days).
Mediani čas do prvega pojava IBP ali pnevmonitisa je bil 160 dni (razpon: od 60 do 172 dni).
Other medicines and Mekinist
Druga zdravila in zdravilo Mekinist
If possible, show them the Mekinist pack and this leaflet.
Če je mogoče, jim pokažite pakiranje zdravila Mekinist in to navodilo.
Physicians should be alert to the possibility of myocarditis in patients who develop new or worsening cardiac signs or symptoms.
Zdravniki naj bodo pozorni na možnost miokarditisa pri bolnikih, pri katerih se znaki ali simptomi težav s srcem pojavijo na novo oziroma se poslabšajo.
Table 14 Summary of efficacy in the combination treatment cohorts based on investigator and independent radiology review
Preglednica 14 Pregled učinkovitosti v kohortah s kombiniranim zdravljenjem po ocenah raziskovalcev in neodvisnih radiologov
Follow your doctor's instructions for what to do to help prevent rash.
Upoštevajte zdravnikova navodila za ukrepanje, s katerim boste pomagali preprečiti izpuščaj.
Your disease symptoms and treatment situation may also affect your ability to drive or use machines.
Vaša bolezen, simptomi in okoliščine zdravljenja lahko prizadenejo tudi vašo sposobnost za upravljanje vozil in strojev.
Prior to starting treatment with dabrafenib, talk to your doctor about options to improve your chances to have children in the future.
Pred začetkom zdravljenja z dabrafenibom se z zdravnikom posvetujte, na kakšen način bi lahko izboljšali možnost, da bi v prihodnje imeli otroke.
What you need to know before you take Mekinist
Kaj morate vedeti, preden boste vzeli zdravilo Mekinist
Grade 2-3 RPED that does not improve to at least Grade 1 within 3 weeks
RPED 2. do 3. stopnje, ki se v 3 tednih ne izboljša na vsaj 1. stopnjo
Table 2 Dose modification schedule based on the grade of any adverse reactions
Preglednica 2 Načrt prilagajanja odmerka glede na stopnjo resnosti posameznega neželenega učinka
It is recommended that the dose of trametinib is taken at a similar time every day.
Priporočljivo je, da bolnik odmerek trametiniba vzame vsak dan ob podobnem času.
Table 11 Investigator-assessed efficacy results (ITT population)
Preglednica 11 Rezultati učinkovitosti po oceni raziskovalcev (populacija ZNZ)
Baseline characteristics were balanced between treatment groups in the primary efficacy population and the ITT population.
Izhodiščne značilnosti so bile med zdravljenima skupinama v primarni populaciji učinkovitosti in populaciji ZNZ uravnotežene.
Carcinogenicity studies with trametinib have not been conducted.
Študij kancerogenosti s trametinibom niso izvedli.
Your doctor may ask you to stop taking Mekinist or refer you to a specialist, if you develop signs and symptoms in your vision that include:
Naroči vam lahko, da prenehajte jemati zdravilo Mekinist, ali vas napoti k specialistu, če se vam pojavijo znaki in simptomi, ki prizadenejo vid, na primer:
Mean terminal half-life is 127 hours (5.3 days) after single dose administration.
Povprečni terminalni razpolovni čas po uporabi enkratnega odmerka je 127 ur (5,3 dneva).
The European Medicines Agency has deferred the obligation to submit the results of studies with trametinib in all subsets of the paediatric population in melanoma and malignant neoplasms (see section 4.2 for information on paediatric use).
Evropska agencija za zdravila je začasno odložila zahtevo za predložitev rezultatov študij s trametinibom za vse podskupine pediatrične populacije pri melanomu in malignih novotvorbah (za podatke o uporabi pri pediatrični populaciji glejte poglavje 4.2).
Withhold trametinib for up to 3 weeks.
Prekinite uporabo trametiniba za obdobje do 3 tednov.
The tablets should not be chewed or crushed and they should be taken without food, at least 1 hour before or 2 hours after a meal.
Tablet se ne sme gristi ali drobiti, vzeti jih je treba brez hrane in sicer vsaj 1 uro pred jedjo ali vsaj 2 uri po jedi.
• Bleeding, at various sites in the body, which may be mild or serious
• krvavitve na različnih mestih v telesu; krvavitve so lahko blage ali resne
If RPED worsens follow instructions below and withhold trametinib for up to 3 weeks.
Če se RPED poslabša, upoštevajte spodnja navodila in prekinite uporabo trametiniba za obdobje do 3 tednov.
Possible side effects in patients taking Mekinist alone
Možni neželeni učinki pri bolnikih, ki jemljejo samo zdravilo Mekinist
Signs that your liver may not be working properly may include:
Znaki nezadostnega delovanja jeter lahko vključujejo:
Based on its mechanism of action, dabrafenib may increase the risk of non-cutaneous malignancies when RAS mutations are present.
Zaradi svojega mehanizma delovanja lahko dabrafenib poveča tveganje za razvoj nekožnih malignomov, če so prisotne mutacije RAS.
Based on the population pharmacokinetic analysis (range 19 to 92 years), age had no relevant clinical effect on trametinib pharmacokinetics.
Na podlagi populacijske farmakokinetične analize (razpon starosti: od 19 do 92 let) starost nima pomembnega kliničnega vpliva na farmakokinetiko trametiniba.
• Swelling around the eyes
• oteklost okrog oči
The majority of these cases were Grade 1 or 2 and did not require any dose interruptions or dose reductions (see sections 4.2 and 4.4).
Večina teh primerov je bila 1. ali 2. stopnje in niso zahtevali prekinitve uporabe ali znižanja odmerka (glejte poglavji 4.2 in 4.4).
In the first-line population, 68% of patients had not progressed after 9 months.
V skupini predhodno nezdravljenih bolnikov pri 68 % bolnikov v 9 mesecih ni prišlo do napredovanja bolezni.
Treatment with trametinib should only be initiated and supervised by a physician experienced in the administration of anti-cancer medicinal products.
Zdravljenje s trametinibom mora uvesti in nadzorovati zdravnik, ki ima izkušnje z uporabo zdravil proti raku.
If the missed dose is less than 12 hours late, take it as soon as you remember.
Če je zamuda s pozabljenim odmerkom krajša od 12 ur, odmerek vzemite, čim se spomnite.
Mekinist can cause heart problems, or make existing heart problems worse (see also “Heart conditions” in section 4) in people taking Mekinist in combination with dabrafenib.
Zdravilo Mekinist lahko povzroči težave s srcem, ali poslabša že obstoječe težave s srcem (glejte tudi "Srčne motnje" v poglavju 4) pri bolnikih, ki jemljejo zdravilo Mekinist v kombinaciji z dabrafenibom.
In rats, hypertrophy of the physis and increased bone turnover were observed, but the physeal hypertrophy is not expected to be clinically relevant for adult humans.
Pri podganah so opažali hipertrofijo fize in povečano premeno kosti, vendar ni verjetno, da bi bila hipertrofija fize klinično pomembna pri odraslih ljudeh.
Patients with left ventricular dysfunction, New York Heart Association Class II, III, or IV heart failure, acute coronary syndrome within the past 6 months, clinically significant uncontrolled arrhythmias, and uncontrolled hypertension were excluded from clinical trials; safety of use in this population is therefore unknown.
Bolniki z disfunkcijo levega prekata, srčnim popuščanjem II., III. ali IV. stopnje po New York Heart Association, akutnim koronarnim sindromom v preteklih 6 mesecih, klinično pomembnimi in neobvladanimi motnjami srčnega ritma ali z neurejeno hipertenzijo so bili izključeni iz kliničnih preskušanj; zato varnost uporabe v tej populaciji ni znana.
Grade 2 (Intolerable) or Grade 3
2. stopnja (neznosni) ali
Trametinib should be taken orally with a full glass of water.
Trametinib je treba zaužiti s polnim kozarcem vode.
Effect of trametinib on other medicinal products
Vpliv trametiniba na druga zdravila
There are insufficient data to evaluate the potential effect of race on trametinib pharmacokinetics as clinical experience is limited to Caucasians.
Podatkov za oceno možnega vpliva rase na farmakokinetiko trametiniba ni dovolj, ker so klinične izkušnje omejene na belce.
Of the patients with confirmed disease progression in the chemotherapy arm, a total of 51 (47%) crossed over to receive trametinib.
Med bolniki s potrjenim napredovanjem bolezni v skupini s kemoterapijo jih je skupno 51 (47 %) prešlo na zdravljenje s trametinibom.
Of the specimens from the non-clinical and clinical trials (n=876) that were mutation positive by the THxID BRAF assay and subsequently were sequenced using the reference method, the specificity of the assay was 94%.
Na vzorcih predkliničnih in kliničnih preskušanj (n = 876), ki so imeli s testom ThxID določeno mutacijo BRAF in so bili nato sekvencirani z referenčno metodo, je bila specifičnost testa 94 %.
Tell your doctor if you have any lung or breathing problems, including difficulty in breathing often accompanied by a dry cough, shortness of breath and fatigue.
Zdravniku povejte, če imate kakršnekoli težave s pljuči ali dihanjem, tudi če imate težave z dihanjem, ki jih pogosto spremlja suh kašelj, zadihanost in utrujenost.
Mekinist can cause serious bleeding problems, especially in your brain or stomach.
Zdravilo Mekinist lahko povzroči resne težave s krvavitvami, še posebno v možganih in želodcu.
To prevent pregnancy, female patients using hormonal contraception are advised to use an additional or alternative method during treatment and for 16 weeks following discontinuation of trametinib.
Za preprečitev nosečnosti se bolnicam, ki jemljejo hormonske kontraceptive svetuje, da uporabijo dodaten ali drug način kontracepcije med zdravljenjem in še 16 tednov po prekinitvi zdravljenja s trametinibom.
LVEF should be evaluated in all patients prior to initiation of treatment with trametinib, one month after initiation of therapy, and then at approximately 3-monthly intervals while on treatment (see section 4.2 regarding dose modification).
Vsem bolnikom je treba LVEF oceniti pred uvedbo zdravljenja s trametinibom, en mesec po uvedbi zdravljenja in nato v približno 3-mesečnih presledkih med zdravljenjem (glejte poglavje 4.2 glede prilagoditve odmerka).
It is used either on its own or in combination with another medicine containing dabrafenib to treat a type of skin cancer called melanoma that has spread to other parts of the body, or cannot be removed by surgery.
Uporabljamo ga bodisi samostojno ali v kombinaciji z drugim zdravilom, ki vsebuje dabrafenib, za zdravljenje vrste kožnega raka, imenovanega melanom, ki se je razširil v druge dele telesa ali ga ni mogoče odstraniti z operacijo.
The bottles also include a silica gel desiccant in a small cylinder shaped container.
Plastenke vsebujejo tudi silikagelsko sušilo v majhnem vsebniku cilindrične oblike.
One bottle contains either 7 or 30 tablets.
Ena plastenka vsebuje 7 ali 30 tablet.
However, in rat and dog toxicity studies up to 13 weeks in duration, there were no treatment effects observed in male reproductive tissues.
Toda v študijah toksičnosti na podganah in psih, ki so trajale do 13 tednov, niso opazili učinkov zdravila na reproduktivna tkiva samcev.
Figure 3 Kaplan-Meier curves of overall survival (OS -ad hoc analysis 20 May 2013)
Slika 3 Kaplan-Meierjeve krivulje celokupnega preživetja (celokupno preživetje - ad hoc analiza 20. maja 2013)
In the clinical trials only patients with cutaneous melanoma were studied.
V kliničnih preskušanjih so preučevali le bolnike s kožnim melanomom.
Pharmacotherapeutic group: Antineoplastic agents, protein kinase inhibitor, ATC code: L01XE25
Farmakoterapevtska skupina: zdravila z delovanjem na novotvorbe (citostatiki), zaviralci proteinskih kinaz, oznaka ATC: L01XE25
Determination of BRAF mutation status
Določanje mutacije BRAF
Mekinist can cause eye problems.
Zdravilo Mekinist lahko povzroči težave z očmi.
The primary endpoint was investigator-assessed relapse-free survival (RFS), defined as the time from randomisation to disease recurrence or death from any cause.
Primarni cilj opazovanja je bilo preživetje brez ponovitve bolezni (RFS - relapse-free survival) po oceni raziskovalca, ki je bilo opredeljeno kot čas od randomizacije do ponovitve bolezni ali smrti iz kateregakoli vzroka.
These checks are to detect if any other cancer, including squamous cell carcinoma, develops inside your body.
Namen teh preiskav je ugotoviti, ali se vam je v telesu razvil kakšen drug rak, med katere sodi tudi ploščatocelični karcinom.
Pack sizes: One bottle contains either 7 or 30 tablets.
Velikosti pakiranj: Ena plastenka vsebuje 7 ali 30 tablet.
• If you get side effects your doctor may decide that you should take lower doses of Mekinist and dabrafenib.
• Če pride do neželenih učinkov, se zdravnik lahko odloči za znižanje odmerka zdravila Mekinist in dabrafeniba.
Mekinist is not recommended while breast-feeding It is not known whether the ingredients of Mekinist can pass into breast milk.
Zdravilo Mekinist ni priporočljivo med obdobjem dojenja Ni znano, ali lahko sestavine zdravila Mekinist prehajajo v materino mleko.
What Mekinist is and what it is used for What you need to know before you take Mekinist How to take Mekinist
Kaj je zdravilo Mekinist in za kaj ga uporabljamo Kaj morate vedeti, preden boste vzeli zdravilo Mekinist Kako jemati zdravilo Mekinist Možni neželeni učinki
Trametinib has a volume of distribution of approximately 1200 L determined following administration of a 5 g intravenous microdose.
Volumen porazdelitve trametiniba je približno 1200 l, določeno po uporabi intravenskega mikroodmerka 5 g.
• Infection of the skin (cellulitis)
• okužba kože (celulitis)
A population pharmacokinetic analysis indicates that mildly elevated bilirubin and/or AST levels (based on National Cancer Institute [NCI] classification) do not significantly affect trametinib oral clearance.
Populacijska farmakokinetična analiza kaže, da blago zvišanje bilirubina in/ali AST (po klasifikaciji NCI - National Cancer Institute) ne vpliva pomembno na peroralni očistek trametiniba.
You and your doctor will decide whether you will take Mekinist or breast-feed.
Skupaj z zdravnikom se boste odločili, ali boste jemali zdravilo Mekinist ali boste dojili.
The median age was 54 years (22% were 65 years); all patients had an ECOG performance score of 0 or 1; and 3 % had history of brain metastases.
Mediana starost je bila 54 let (22 % je bilo starih  65 let); vsi so imeli stanje zmogljivosti 0 ali 1 po lestvici ECOG in 3 % so imeli anamnezo metastaz v možganih.
• after eating, you must wait at least 2 hours before taking Mekinist.
• morate po jedi počakati vsaj 2 uri, preden vzamete zdravilo Mekinist.
Some people taking Mekinist develop other conditions which can be serious.
Nekaterim bolnikom, ki so jemali zdravilo Mekinist, so se pojavila druga bolezenska stanja, ki so lahko resna.
• Lack of energy or feeling weak or tired
• pomanjkanje energije, občutek šibkosti ali utrujenosti
Administration of a single dose of trametinib with a high-fat, high-calorie meal resulted in a 70% and 10% decrease in Cmax and AUC, respectively compared to fasted conditions (see sections 4.2 and 4.5).
Uporaba enkratnega odmerka trametiniba z zelo mastnim, zelo kaloričnim obrokom je povzročila 70 % znižanje Cmax in 10 % znižanje AUC v primerjavi s stanjem na tešče (glejte poglavji 4.2. in 4.5).
In the Phase III study with trametinib in patients with unresectable or metastatic melanoma (n=211), 49 patients (23%) were ≥65 years of age, and 9 patients (4%) were ≥75 years of age.
V študiji trametiniba III. faze pri bolnikih z inoperabilnim ali metastatskim melanomom (n = 211) je bilo 49 bolnikov (23 %) starih ≥ 65 let, 9 bolnikov (4 %) pa ≥ 75 let.
Grade 2-3 RPED
RPED 2. do 3. stopnje
Therefore, before starting treatment your doctor will test for this mutation.
Zdravnik vas bo pred zdravljenjem testiral za to mutacijo.
The dabrafenib doses should be about 12 hours apart.
Presledek med odmerkoma dabrafeniba naj bo približno 12 ur.
Survival estimates at 1 and 2 years from randomisation were 97% and 91% in the combination arm and 94% and 83% in the placebo arm, respectively.
Ocenjeno preživetje po 1 oziroma 2 letih od randomizacije je bilo v skupini s kombiniranim zdravljenjem 97 % oziroma 91 %, v skupini s placebom pa 94 % oziroma 83 %.
The mean absolute bioavailability of a single 2 mg tablet dose is 72% relative to an intravenous (IV) microdose.
Povprečna absolutna biološka uporabnost posamičnega odmerka 2 mg v tableti je 72 % glede na intravenski mikroodmerek.
Mekinist can cause new or worsening high blood pressure (hypertension).
Zdravilo Mekinist lahko povzroči pojav visokega krvnega tlaka ali njegovo poslabšanje (hipertenzija).
Your doctor should check your heart function before and during treatment.
Zdravnik mora preveriti delovanje vašega srca pred začetkom in med potekom zdravljenja.
Efficacy in patients with ocular or mucosal melanoma has not been assessed.
Učinkovitosti pri bolnikih z očesnim ali sluzničnim melanomom niso ocenili.
The other side effects that you may see when you take Mekinist alone are as follows:
Drugi neželeni učinki, ki jih lahko opazite, če jemljete samo zdravilo Mekinist so:
Trametinib plasma IV clearance is 3.21 L/hr.
Plazemski očistek intravensko uporabljenega trametiniba je 3,21 l/uro.
If you forget to take Mekinist
Če ste pozabili vzeti zdravilo Mekinist
• Heart rate that is lower than the normal range and/or a decrease in heart rate
• srčni utrip, ki je nižji od normalnih vrednosti in/ali znižanje srčnega utripa
Please read the dabrafenib Package Leaflet for details of the side effects you may get when taking this medicine.
Preberite navodilo za uporabo za dabrafenib glede podrobnosti o neželenih učinkih, do katerih lahko pride pri jemanju tega zdravila.
In the previously-treated population, 38 patients (67%) had one line of systemic anti-cancer therapy for metastatic disease.
Med predhodno zdravljenimi bolniki je 38 bolnikov (67 %) prej prejelo eno linijo sistemskega zdravljenja proti raku za zdravljenje metastatske bolezni.
The safety of trametinib in subjects with predisposing factors for RVO, including uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, uncontrolled diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes, has not been established.
Varnost trametiniba pri osebah s predispozicijskimi dejavniki za RVO, vključno z neurejenim glavkomom ali očesno hipertenzijo, neurejeno hipertenzijo, neurejeno sladkorno boleznijo ali z anamnezo sindromov hiperviskoznosti ali hiperkoagulabilnosti ni ugotovljena.
It is not known whether trametinib is excreted in human milk.
Ni znano, ali se trametinib izloča v materino mleko.
Mekinist is not recommended for children and adolescents since the effects of Mekinist in people younger than 18 years old are not known.
Učinek zdravila Mekinist ni znan pri osebah, mlajših od 18 let.
• have or have ever had kidney problems.
• če imate ali ste kdaj imeli težave z ledvicami,
The risk of haemorrhage may be increased with concomitant use of antiplatelet or anticoagulant therapy.
Tveganje za krvavitve se lahko poveča v primeru sočasne uporabe antiagregacijskih ali antikoagulantnih zdravil.
• dark urine due to kidney damage
• temnim urinom zaradi okvare ledvic
However, based on the low dose and low clinical systemic exposure relative to the in vitro potency of inhibition or induction values, trametinib is not considered to be an in vivo inhibitor or inducer of these enzymes or transporters, although transient inhibition of BCRP substrates in the gut may occur (see section 4.5).
Toda zaradi nizkega odmerka in majhne klinične sistemske izpostavljenosti glede na in vitro moč zaviranja oziroma indukcijske vrednosti, trametinib ne velja za zaviralca ali induktorja teh encimov ali prenašalcev in vivo, lahko pa se pojavi prehodno zavrtje substratov BCRP v črevesu (glejte poglavje 4.5).
In repeat-dose studies the effects seen after trametinib exposure are found mainly in the skin, gastrointestinal tract, haematological system, bone and liver.
V študijah ponavljajočih se odmerkov so učinke po izpostavljenosti trametinibu našli v glavnem v koži, prebavilih, hematološkem sistemu, kosteh in jetrih.
Non-clinical and clinical trials with retrospective bi-directional Sanger sequencing analyses have shown that the test also detects the less common BRAF V600D mutation and V600E/K601E mutation with lower sensitivity.
Predklinična in klinična preskušanja z retrospektivnimi analizami obojestranskega sekvenciranja po Sangerju so pokazala, da ta test odkrije tudi manj pogosto mutacijo BRAF V600D in mutacijo V600E/K601E z manjšo senzitivnostjo.
• If you are a woman who could become pregnant, you must use reliable birth control (contraception) while you are taking Mekinist and for at least 16 weeks after you stop taking it.
• Če ste ženska, ki bi lahko zanosila, morate med jemanjem zdravila Mekinist in še vsaj 16 tednov po koncu njegovega jemanja uporabljati zanesljivo kontracepcijsko zaščito.
If trametinib is used during pregnancy, or if the patient becomes pregnant while taking trametinib, the patient should be informed of the potential hazard to the foetus.
Če je trametinib uporabljen med nosečnostjo, ali če bolnica med zdravljenjem s trametinibom zanosi, jo je treba seznaniti z možno nevarnostjo za plod.
Trametinib was not genotoxic in studies evaluating reverse mutations in bacteria, chromosomal aberrations in mammalian cells and micronuclei in the bone marrow of rats.
Trametinib ni bil genotoksičen v študijah, ki so ocenjevale reverzne mutacije pri bakterijah, kromosomske aberacije v celicah sesalcev in mikrojedra v kostnem mozgu podgan.
• after taking Mekinist, you must wait at least 1 hour before eating, or
• morate po zaužitju zdravila Mekinist počakati vsaj 1 uro, preden jeste, ali
Results for the primary analysis of RFS are presented in Table 13.
V preglednici 13 so prikazani rezultati primarne analize RFS.
Taking Mekinist with dabrafenib: Dabrafenib may permanently reduce male fertility.
Jemanje zdravila Mekinist skupaj z dabrafenibom: Dabrafenib lahko pri moških trajno zmanjša plodnost.
Studies in juvenile animals have shown adverse effects of trametinib which were not observed in adult animals (see section 5.3).
V študijah na mladih živalih so se pokazali neželeni učinki trametiniba, ki jih pri odraslih živalih niso opažali (glejte poglavje 5.3).
Continue treatment with retinal evaluation monthly until resolution.
Nadaljujte zdravljenje in vsak mesec opravite pregled mrežnice, dokler odstop ne izgine.
Kaplan-Meier curves of investigator-assessed OS (post-hoc analysis 20 May 2013) is presented in Figure 3.
Kaplan-Meierjeve krivulje celokupnega preživetja po oceni raziskovalcev (post-hoc analiza 20. maja 2013) so prikazane na sliki 3.
Take Mekinist once a day, on an empty stomach (at least 1 hour before a meal or 2 hours after a meal).
Zdravilo Mekinist vzemite enkrat na dan, na prazen želodec (vsaj 1 uro pred jedjo ali 2 uri po jedi).
• have or have ever had lung or breathing problems.
• če imate ali ste kdaj imeli težave s pljuči ali dihanjem,
It is recommended that patients continue treatment with trametinib until patients no longer derive benefit or the development of unacceptable toxicity (see Table 2).
Zdravljenje s trametinibom je priporočljivo nadaljevati, dokler bolniku koristi, oziroma do pojava nesprejemljivih toksičnih učinkov (glejte preglednico 2).