FrancophonIA/ELRC3.0 huggingface dataset:
English: Food intake has no effect on the extent of absorption but may delay the peak concentrations by 1.5 - 2 hours.
Slovenian: Vnos hrane ne vpliva na obseg absorpcije, lahko pa zakasni doseganje največje koncentracije za 1,5 do 2 uri.
English: The changes due to food intake are not clinically significant.
Slovenian: Spremembe zaradi uživanja hrane niso klinično pomembne.
English: Your doctor will conduct regular medical check-ups.
Slovenian: Vaš zdravnik vas bo redno pregledoval.
English: If you miss one dose take the next tablet as usual and continue treatment as recommended.
Slovenian: Če pozabite en odmerek, vzemite naslednjo tableto kot običajno in nadaljujte z zdravljenjem v skladu z navodili.
English: If the QTc interval is > 500 ms, Fareston should not be used.
Slovenian: Če je interval QTc > 500 ms, se zdravilo Fareston ne sme uporabljati.
English: Toremifene binds extensively (> 99.5%) to serum proteins, mainly to albumin.
Slovenian: Toremifen se obsežno veže (> 99,5 %) na serumske proteine, v glavnem na albumin.
English: Tell your doctor if you are taking, have recently taken or might take any other medicines.
Slovenian: Obvestite zdravnika ali farmacevta, če jemljete, ste pred kratkim jemali ali pa boste morda začeli jemati katero koli drugo zdravilo.
English: These results strongly suggest an important dose-dependent effect.
Slovenian: Ti rezultati jasno kažejo na pomemben učinek, povezan z odmerkom.
English: Do not use this medicine after the expiry date which is stated on the label.
Slovenian: Tega zdravila ne smete uporabljati po datumu izteka roka uporabnosti, ki je naveden na ovojnini.
English: This may be due to the underlying mechanism/estrogenic stimulation (see also section 4.4).
Slovenian: To je lahko posledica osnovnega mehanizma/estrogenske stimulacije (oglejte si tudi poglavje 4.4 ).
English: Although they have theoretically interesting hormonal effects, their concentrations during toremifene treatment are too low to have any major biological importance.
Slovenian: Četudi imajo ti teoretično zanimive hormonske učinke, pa so njihove koncentracije med zdravljenjem s toremifenom prenizke, da bi lahko imeli kak večji biološki pomen.
English: Pharmacotherapeutic group: Anti-estrogens, ATC code: L02BA02
Slovenian: Farmakoterapevtska skupina: antiestrogeni, oznaka ATC: L02BA02.
English: Afterwards gynaecological examination should be repeated at least once a year.
Slovenian: Kasneje mora imeti bolnica ginekološke preglede najmanj enkrat na leto.
English: The recommended dose is 60 mg daily.
Slovenian: Priporočeni odmerek je 60 mg na dan.
English: There is a risk of increased endometrial changes including hyperplasia, polyps and cancer.
Slovenian: Obstaja tudi tveganje za povečanje pogostnosti sprememb endometrija, vključno s hiperplazijo, polipi in rakom.
English: The half-life of the first (distribution) phase is 4 (range 2 - 12) hours, and of the second (elimination) phase 5 (range 210) days.
Slovenian: Razpolovna doba prve faze (porazdelitve) je 4 ure (razpon od 2 do 12 ur), razpolovna doba druge faze (izločanja) pa 5 dni (razpon od 2 do 10 dni).
English: DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorisation: 14 February 1996
Slovenian: DATUM PRIDOBITVE/PODALJŠANJA DOVOLJENJA ZA PROMET Z ZDRAVILOM Datum prve odobritve: 14. februar 1996 Datum zadnjega podaljšanja: 2. februar 2006
English: The following information regarding QT-prolongation is of special importance (for contraindications see section 4.3).
Slovenian: Naslednje informacije o podaljšanju intervala QT so še posebej pomembne (za kontraindikacije glejte poglavje 4.3).
English: The serum concentration curve can be described by a biexponential equation.
Slovenian: Krivuljo serumske koncentracije lahko opišemo z bieksponentno enačbo.
English: No information is available concerning polymorphic metabolism.
Slovenian: Ni podatkov glede polimorfne presnove zdravila.
English: In the acute and chronic toxicity studies most of the findings are related to the hormonal effects of toremifene.
Slovenian: V študijah akutne in kronične toksičnosti je bila večina izsledkov povezana s hormonskimi učinki toremifena.
English: The acute toxicity of toremifene is low with LD-50 in rats and mice of more than 2000 mg/kg.
Slovenian: Akutna toksičnost toremifena je majhna in z vrednostjo LD-50 pri podganah in miših večjo od 2.000 mg/kg.
English: Patients with non-compensated cardiac insufficiency or severe angina pectoris should be closely monitored.
Slovenian: Bolnice z nekompenzirano srčno insuficienco ali hudo angino pektoris morate skrbno spremljati.
English: Symptoms of overdose may be dizziness and headache.
Slovenian: Med simptomi prevelikega odmerjanja sta lahko omotica in glavobol.
English: Toremifene has not shown any genotoxicity and has not been found to be carcinogenic in rats.
Slovenian: Toremifen ni pokazal nobene genotoksičnosti in se ni pokazal kot kancerogen pri podganah.
English: Neoplasms beningn, malignant and unspecified (including cysts and polyps)
Slovenian: Benigne, maligne in neopredeljene novotvorbe (vključno s cistami in polipi)
English: About 10% of the administered dose is eliminated via urine as metabolites.
Slovenian: Približno 10 % danega odmerka se izloči z urinom v obliki presnovkov.
English: If signs or symptoms that may be associated with cardiac arrhythmia occur during treatment with Fareston, treatment should be stopped and an ECG should be performed.
Slovenian: Če se znaki ali simptomi, ki bi lahko bili povezani s srčno aritmijo, pojavijo med zdravljenjem z zdravilom Fareston, je treba zdravljenje prekiniti in izvesti EKG.
English: Elderly patients may also be more susceptible to drug-associated effects on the QT interval.
Slovenian: Starejši bolniki so prav tako lahko bolj dovzetni na z odmerkom povezane učinke na interval QT.
English: Toremifene has no influence on the ability to drive and use machines.
Slovenian: Toremifen nima vpliva na sposobnost vožnje in upravljanja strojev.
English: If you are admitted to the hospital or if you are prescribed a new medicine, please tell your doctor that you are taking Fareston.
Slovenian: Če ste sprejeti v bolnišnico ali če vam predpišejo novo zdravilo, povejte zdravniku, da jemljete zdravilo Fareston.
English: In vivo, high plasma concentrations in monkeys caused a 24% prolongation in QTc, which is in line with QTc findings in humans.
Slovenian: In vivo so visoke plazemske koncentracije pri opicah povzročile 24-odstotno podaljšanje intervala QTc, kar je skladno z izsledki o intervalih QTc pri človeku.
English: These findings are postulated to be of little relevance for the safety in man, where toremifene acts mainly as an anti-estrogen.
Slovenian: Trdijo, da so ti izsledki le malo pomembni za varnost zdravila pri človeku, kjer toremifen deluje v glavnem kot antiestrogen.
English: If you have missed several doses, please inform your doctor and follow his instructions.
Slovenian: Če pozabite več odmerkov, obvestite zdravnika in sledite njegovim navodilom.
English: Concomitant use of those drugs with toremifene should be carefully considered.
Slovenian: O sočasni uporabi teh zdravil s toremifenom morate skrbno premisliti.
English: Owing to the slow elimination, steady-state concentrations in serum are reached in 4 to 6 weeks.
Slovenian: Zaradi počasnega izločanja so koncentracije v serumu v stanju dinamičnega ravnovesja dosežene v 4 do 6 tednih.
English: Do not take Fareston - if you are allergic to toremifene or any of the other ingredients of this medicine (listed in section
Slovenian: Ne jemljite zdravila Fareston - če ste alergični na toremifen ali katero koli sestavino tega zdravila (navedeno v poglavju 6).
English: The basal disposition parameters (CL and V) could not be estimated due to the lack of intravenous study.
Slovenian: Osnovnih parametrov porazdelitve (očistek in volumen) ni bilo mogoče oceniti, ker študija intravenske uporabe ni bila opravljena.
English: There is a known interaction between anti-estrogens and warfarin-type anticoagulants leading to a seriously increased bleeding time.
Slovenian: Obstaja znano medsebojno delovanje med antiestrogenskimi zdravili in antikoagulanti tipa varfarina, ki lahko vodi do močnega podaljšanja časa krvavitve.
English: Endometrial hypertrophy may develop during the treatment due to the partial estrogenic effect of toremifene.
Slovenian: Med zdravljenjem se lahko razvije hipertrofija endometrija zaradi delnega estrogenskega učinka toremifena.
English: It is bound to plasma proteins even more extensively than toremifene, the protein bound fraction being > 99.9%.
Slovenian: N-demetiltoremifen se veže na plazemske beljakovine še bolj obsežno kot toremifen, na beljakovine vezana frakcija pa je > 99,9 %.
English: An additive effect on QT interval prolongation between Fareston and the following drugs and other medicinal products that may prolong the QTc interval cannot be excluded.
Slovenian: Dodatnih učinkov na podaljšanje intervala QT med zdravilom Fareston in zdravili, navedenimi v nadaljevanju ter drugimi zdravili, ki lahko podaljšujejo interval QTc, ni mogoče izključiti.
English: White, round, flat, bevelled edge tablet with TO 60 on one side.
Slovenian: Bele, okrogle, ravne tablete z zaobljenim robom in napisom TO 60 na eni strani.
English: 30 and 100 tablets.
Slovenian: 30 in 100 tablet.
English: As other members of this class, e.g. tamoxifen and clomifene, toremifene binds to estrogen receptors and may produce estrogenic, anti-estrogenic or both effects, depending upon the duration of treatment, animal species, gender, target organ and variable selected.
Slovenian: Kot druga zdravila iz te skupine, npr. tamoksifen in klomifen, se tudi toremifen veže na estrogenske receptorje in lahko povzroči estrogenske ali antiestrogenske učinke ali oboje, odvisno od trajanja zdravljenja, živalske vrste, spola, tarčnega organa in izbrane spremenljivke.
English: In some experimental cancers and/or using high-dose, toremifene displays anti-tumour effects which are not estrogen-dependent.
Slovenian: Pri nekaterih oblikah eksperimentalno povzročenega raka in/ali pri uporabi velikih odmerkov ima toremifen protitumorske učinke, ki niso odvisni od estrogena.
English: Toremifene binds specifically to estrogen receptors, competitively with oestradiol, and inhibits estrogeninduced stimulation of DNA synthesis and cell replication.
Slovenian: Toremifen se specifično veže na estrogenske receptorje, kompetitivno z estradiolom, in zavira z estrogeni inducirano stimulacijo sinteze DNA in celično replikacijo.
English: You should have gynaecological examinations before you start treatment with Fareston and at least once a year following the start of treatment with Fareston.
Slovenian: Pred začetkom zdravljenja z zdravilom Fareston vas je treba ginekološko pregledati, nato pa vsaj enkrat na leto, ko se začnete zdraviti z zdravilom Fareston.
English: Fareston can be taken with or without food.
Slovenian: Zdravilo Fareston lahko zaužijete s hrano ali brez nje.
English: Characteristics in patients
Slovenian: Značilnosti pri bolnicah
English: Therefore, the concomitant use of toremifene with such drugs should be avoided.
Slovenian: Sočasni uporabi toremifena s tovrstnimi zdravili se morate torej izogibati.
English: Other medicines and Fareston
Slovenian: Druga zdravila in zdravilo Fareston
English: The results of this study show a clear positive effect of toremifene in the 80 mg group with mean prolongations of 21 - 26 ms.
Slovenian: Rezultati te študije kažejo jasen pozitivni učinek učinkovine toremifen v skupini, v kateri so bolniki prejemali 80 mg zdravila in pri katerih je znašalo povprečno podaljšanje intervala od 21-26 ms.
English: - Pre-existing endometrial hyperplasia and severe hepatic failure are contra-indications in long term use of toremifene.
Slovenian: - Obstoječa hiperplazija endometrija in huda jetrna odpoved sta kontraindikaciji za dolgotrajno uporabo toremifena.
English: If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Slovenian: Če vam je zdravnik povedal, da ne prenašate nekaterih sladkorjev, se posvetujte z zdravnikom, preden začnete jemati to zdravilo.
English: Toremifene has a species-specific estrogen-like effect in mice and causes similar tumours.
Slovenian: Toremifen ima za vrsto posebne estrogenom podobne učinke pri miših in povzroča podobne tumorje.
English: PHARMACEUTICAL FORM Tablet.
Slovenian: FARMACEVTSKA OBLIKA tableta
English: Toremifene is a nonsteroidal triphenylethylene derivative.
Slovenian: Toremifen je nesteroidni derivat trifeniletilena.
English: Action potential studies in isolated rabbit heart have shown that toremifene induce cardiac electrophysiological changes which start to develop at concentrations approximately 10 fold compared to the calculated free therapeutic plasma concentration in human.
Slovenian: Študije z vzdrževanjem aktivnosti izoliranih kunčjih src kažejo, da učinkovina toremifen povzroča elektrofiziološke spremembe srca, ki se začnejo razvijati pri približno 10-kratnih koncentracijah v primerjavi z izračunano prosto terapevtsko plazemsko koncentracijo pri ljudeh.
English: Hepatic impairment Toremifene should be used cautiously in patients with liver impairment (see section 5.2).
Slovenian: Jetrna okvara Toremifen je treba uporabljati previdno pri bolnicah z jetrno okvaro (oglejte poglavje 5.2).
English: Package sizes: 30 and 100 tablets.
Slovenian: Velikosti pakiranj: 30 in 100 tablet.
English: In human serum the main metabolite is N-demethyltoremifene with mean half-life of 11 (range 4 - 20) days.
Slovenian: V človeškem serumu je poglavitni presnovek N-demetiltoremifen s srednjo razpolovno dobo 11 dni (razpon od 4 do 20 dni).
English: The pattern of the liver damage was predominantly hepatocellular.
Slovenian: Okvara jeter je bila predvsem hepatocelularna.
English: Psychiatric disorders depression insomnia
Slovenian: Psihiatrične motnje depresija nespečnost
English: Pediatric population There is no relevant use of Fareston in the paediatric population.
Slovenian: Pediatrična populacija Zdravilo Fareston ni primerno za uporabo pri pediatrični populaciji.
English: The anti-tumour effect of toremifene in breast cancer is mainly due to the anti-estrogenic effect, although other mechanisms (changes in oncogene expression, growth factor secretion, induction of apoptosis and influence on cell cycle kinetics) may also be involved in the anti-tumour effect.
Slovenian: Protitumorski učinek toremifena pri raku dojke je predvsem posledica njegovega antiestrogenskega učinka, četudi so lahko pri tem vpleteni tudi drugi mehanizmi (spremembe ekspresije onkogenov, sekrecija rastnega faktorja, sproženje apoptoze in vpliv na kinetiko celičnega ciklusa).
English: Peak concentrations in serum are obtained within 3 (range 2 - 5) hours.
Slovenian: Največjo koncentracijo v serumu doseže v 3 urah (razpon od 2 do 5 ur).
English: If you forget to take Fareston
Slovenian: Če ste pozabili vzeti zdravilo Fareston
English: The elimination of toremifene and its metabolites was significantly increased in patients with activated liver function and decreased in patients with impaired liver function.
Slovenian: Izločanje toremifena in njegovih presnovkov je bilo bistveno povečano pri bolnicah z aktiviranim delovanjem jeter in zmanjšano pri bolnicah z okvarjenim jetrnim delovanjem.
English: Drugs which decrease renal calcium excretion, e.g. thiazide diuretics, may increase the risk of hypercalcaemia.
Slovenian: Zdravila, ki zmanjšajo ledvično izločanje kalcija, npr. tiazidni diuretiki, lahko povečajo tveganje za pojav hiperkalciemije.
English: Frequency not known (cannot be estimated from the available data) - low number of white blood cells, which are important in fighting infection (leukopenia) - low number of red blood cells (anaemia) - low number of platelets (thrombocytopenia)
Slovenian: Neznana pogostnost (ni mogoče oceniti iz razpoložljivih podatkov) - nizko število belih krvnih celic, ki so pomembne v boju proti okužbam (levkopenija) - nizko število rdečih krvnih celic (anemija) - nizko število krvnih ploščic (trombocitopenija) - vnetje jeter (hepatitis)
English: Your doctor will conduct regular medical checkups if you have high blood pressure, diabetes, have taken hormone replacement therapy or if you are obese (BMI over 30).
Slovenian: Vaš zdravnik vas bo redno pregledoval, če imate visok krvni tlak, sladkorno bolezen, če ste jemali hormonsko nadomestno zdravljenje ali če ste debeli (indeks telesne mase čez 30).
English: As women tend to have a longer baseline QTc interval compared with men, they may be more sensitive to QTc-prolonging medications.
Slovenian: Ker so ženske v primerjavi z moškimi bolj nagnjene k daljšemu osnovnemu intervalu QTc, so lahko tudi bolj občutljive na zdravila, ki podaljšujejo interval QTc.
English: One tablet contains 28.5 mg of lactose.
Slovenian: Ena tableta vsebuje 28,5 mg laktoze.
English: Fareston causes certain abnormal changes in the electrical recording of the heart (electrocardiogram or ECG).
Slovenian: Zdravilo Fareston povzroča nekatere nenormalne spremembe v električnem spremljanju delovanja srca (elektrokardiogramu ali EKG).
English: Patients with additional risk of endometrial cancer, e.g. patients suffering from hypertension or diabetes, having high BMI (> 30) or history of hormone replacement therapy should be closely monitored (see also section 4.8).
Slovenian: Bolnice z dodatnim tveganjem za raka endometrija, npr. tiste s hipertenzijo ali sladkorno boleznijo, velikim indeksom telesne mase (BMI > 30) ali anamnezo hormonske nadomestne terapije, morate skrbno spremljati (glejte tudi poglavje 4.8 ).
English: - if you have been told by your doctor that you have an intolerance to certain sugars, like lactose (see section 2 Fareston contains lactose).
Slovenian: - če vam je zdravnik povedal, da ne prenašate nekaterih sladkorjev, kot je laktoza (glejte poglavje 2 Zdravilo Fareston vsebuje laktozo)
English: What Fareston is and what it is used for
Slovenian: Kaj je zdravilo Fareston in za kaj ga uporabljamo 2.
English: This might lead to an increased risk of ventricular arrhythmias, including Torsade de pointes.
Slovenian: To lahko vodi do povečanega tveganja za vertikularno aritmijo, vključno s tveganjem za Torsade de pointes.
English: Thromboembolic events include deep venous thrombosis, thrombophlebitis and pulmonary embolism (see also section 4.4).
Slovenian: Med trombemboličnimi pojavi so poročali o globoki venski trombozi, tromboflebitisu in pljučni emboliji (glejte tudi poglavje 4.4).
English: Vertigo, headache and dizziness were observed in healthy volunteer studies at daily dose of 680 mg.
Slovenian: V študijah pri zdravih prostovoljcih so opažali vrtoglavico, glavobol in omotico pri dnevnem odmerku 680 mg.
English: There are no adequate data from the use of Fareston in pregnant women.
Slovenian: Ustreznih podatkov o uporabi zdravila Fareston pri nosečnicah ni.
English: LIST OF EXCIPIENTS lactose monohydrate
Slovenian: SEZNAM POMOŽNIH SNOVI laktoza monohidrat
English: The mean concentration of toremifene at steady-state is 0.9 (range 0.6 - 1.3) µg/ml at the recommended dose of 60 mg per day.
Slovenian: Srednja koncentracija toremifena v stanju dinamičnega ravnovesja je 0,9 mg/ml (razpon od 0,6 do 1,3 mg /ml) pri priporočenem odmerku 60 mg na dan.
English: Theoretically the metabolism of toremifene is inhibited by drugs known to inhibit the CYP3A enzyme system which is reported to be responsible for its main metabolic pathways.
Slovenian: Teoretično bi lahko presnovo toremifena zavirala zdravila, za katera je znano, da zavirajo encimski sistem CYP 3A, ki je opisan kot odgovoren za glavne presnovne poti toremifena.
English: Enzyme inducers, like phenobarbital, phenytoin and carbamazepine, may increase the rate of toremifene metabolism thus lowering the steady-state concentration in serum.
Slovenian: Encimski induktorji, npr. fenobarbital, fenitoin in karbamazepin, lahko povečajo hitrost presnove toremifena in tako zmanjšajo njegovo serumsko koncentracijo v stanju dinamičnega ravnovesja.
English: The usual dose is one 60 mg tablet taken orally, once daily.
Slovenian: Priporočeni odmerek je ena 60 mg tableta, zaužita peroralno enkrat na dan.
English: The main metabolic pathway, N-demethylation, is mediated mainly by CYP3A.
Slovenian: Glavno presnovno reakcijo, N-demetilacijo, pa v glavnem povzroči encim CYP 3A.
English: In post-menopausal breast cancer patients, toremifene treatment is associated with modest reductions in both total serum cholesterol and low density lipoprotein (LDL).
Slovenian: Pri bolnicah z rakom dojk po menopavzi je zdravljenje s toremifenom povezano z majhnim zmanjšanjem tako celotne serumske vrednosti holesterola kot lipoproteinov majhne gostote (LDL).
English: Toremifene should not be used concurrently with other drugs that prolong the QT interval (see also section 4.5).
Slovenian: Toremifena ne smete uporabljati sočasno z drugimi zdravili, ki podaljšujejo interval QT (glejte tudi poglavje 4.5).
English: If you stop taking Fareston The treatment with Fareston should only be stopped when advised by your doctor.
Slovenian: Če ste prenehali jemati zdravilo Fareston: Zdravljenje z zdravilom Fareston smete prekiniti le po nasvetu zdravnika.
English: Its steady-state concentrations are about twice compared to those of the parent compound.
Slovenian: Njegove koncentracije v stanju dinamičnega ravnovesja je približno dvakrat večja od koncentracije matične spojine.
English: Fareston contains lactose
Slovenian: Zdravilo Fareston vsebuje laktozo
English: What you need to know before you take Fareston
Slovenian: Kaj morate vedeti, preden boste vzeli zdravilo Fareston
English: Very common side effects (may affect more than 1 in 10 people ) - hot flushes, sweating.
Slovenian: Zelo pogosti neželeni učinki (pojavijo se lahko pri več kot 1 od 10 bolnikov) - vročinski oblivi, znojenje.
English: First line hormone treatment of hormone-dependent metastatic breast cancer in postmenopausal patients.
Slovenian: Hormonsko zdravljenje prve izbire hormonsko odvisnega metastatskega raka dojk pri bolnicah po menopavzi.
English: Breast-feeding In rats, decreased body weight gain of the offspring during lactation was observed.
Slovenian: Dojenje Pri podganah so opažali zmanjšan prirastek telesne mase mladičev v času laktacije.
English: EU/1/96/004/002 100 tablets
Slovenian: EU/1/96/004/002 100 tablet
English: Toremifene treatment has been associated with changes in liver enzyme levels (increases of transaminases) and in very rare occasions with more severe liver function abnormalities (jaundice).
Slovenian: Zdravljenje s toremifenom je bilo povezano s spremembami vrednosti jetrnih encimov (povečanje vrednosti transaminaz) in v zelo redkih primerih s hudimi motnjami delovanja jeter (zlatenica).
English: Pharmacokinetics of toremifene were investigated in an open study with four parallel groups of ten subjects: normal subjects, patients with impaired (mean AST 57 U/L - mean ALT 76 U/L - mean gamma GT 329 U/L) or activated liver function (mean AST 25 U/L - mean ALT 30 U/L - mean gamma GT 91 U/L - patients treated with antiepileptics) and patients with impaired renal function (creatinine: 176 µmol/L).
Slovenian: Farmakokinetiko toremifena so raziskovali v odprti študiji s štirimi paralelnimi skupinami desetih preiskovank: normalne preiskovanke, bolnice z jetrno okvaro (srednja vrednost AST 57 enot/l - srednja vrednost ALT 76 enot/l - srednja vrednost gama-GT 329 enot/l), bolnice z aktiviranim delovanjem jeter (srednja vrednost AST 25 enot/l - srednja vrednost ALT 30 enot/l - srednja vrednost gama-GT 91 enot/l - bolnice zdravljene z antiepileptiki) ter bolnice z ledvično okvaro (vrednost kreatinina: 176 mg/l).
English: Metabolism and nutrition disorders loss of appetite
Slovenian: Presnovne in prehranske motnje izguba apetita
English: Toremifene obeys linear serum kinetics at oral daily doses between 11 and 680 mg.
Slovenian: Kinetika toremifena v serumu je linearna pri peroralnih dnevnih odmerkih od 11 do 680 mg.