natgillin/translations-raw huggingface dataset:
Important information about some of the ingredients of ViraferonPeg Patients with rare hereditary problems of fructose intolerance, glucose galactose malabsorption or sucraseisomaltase insufficiency should not take this medicine.
Pomembne informacije o nekaterih sestavinah zdravila ViraferonPeg Bolniki z redko dedno intoleranco za fruktozo, malabsorpcijo glukoze in galaktoze ali pomanjkanjem saharaza-izomaltaze ne smejo jemati tega zdravila.
HCV-RNA should be measured periodically during treatment (see section 4.2).
Vrednost HCV-RNA morate med zdravljenjem periodično meriti (glejte poglavje 4.2).
- have advanced, uncontrolled liver disease (other than hepatitis C).
- imate napredovalo, nenadzorovano jetrno bolezen (razen hepatitisa C).
If you are injecting this medicine yourself, you will be instructed how to prepare and give the injection.
Če si zdravilo injicirate sami, boste dobili navodila, kako pripraviti in si ga injicirati.
However, if a week 12 response was achieved, there was little difference in SVR regardless of prior treatment or prior response.
Če pa so se v 12. tednu odzvali na zdravljenje, je bila razlika v trajnem virološkem odzivu (SVR) majhna, ne glede na predhodno zdravljenje ali predhodni odziv na zdravljenje.
No response at treatment week
Ni odziva v tednu zdravljenja
Ribavirin causes serious birth defects when administered during pregnancy, therefore ribavirin therapy is contraindicated in women who are pregnant.
Ribavirin povzroča hude poškodbe ploda, če se uporablja med nosečnostjo, zato je zdravljenje z ribavirinom kontraindicirano pri nosečnicah.
It is not known whether this medicine is present in human milk.
Ni znano, ali je to zdravilo prisotno v materinem mleku.
Treatment regimen
Režim zdravljenja
The mechanism behind these events is not known (see sections 4.3, 4.4 and 4.5 of the telbivudine SmPC).
Mehanizem nastanka periferne nevropatije v tem primeru ni znan (glejte poglavja 4.3, 4.4 in 4.5 v SmPC-ju za telbivudin).
Male patients or their female partners must use an effective contraceptive during treatment and for 7 months after treatment has been concluded (see ribavirin SmPC).
Moški bolniki ali njihove partnerke morajo uporabljati učinkovito kontracepcijo med zdravljenjem in še 7 mesecev po zaključku zdravljenja (glejte SmPC za ribavirin).
Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface.
Interferoni kažejo svoje celične učinke preko vezave na specifične membranske receptorje na celični površini.
If your female partner is not pregnant but is of childbearing age, she must be tested for pregnancy each month during treatment and for the 7 months after treatment has stopped.
Če vaša partnerka sicer trenutno ni noseča, a je v rodni dobi, mora opraviti test nosečnosti vsak mesec med vašim zdravljenjem in še 7 mesecev po koncu zdravljenja.
Among 480 patients with > 2 log viral reduction but detectable virus at week 12, altogether 188 patients continued therapy.
Med 480 bolniki z zmanjšanjem količine virusa za > 2 log enoti, vendar še vedno z zaznavnim virusom v 12. tednu zdravljenja, je z zdravljenjem nadaljevalo skupaj 188 bolnikov.
Sustained response
Trajni odziv
Diabetic ketoacidosis
diabetična ketoacidoza
Growth rate decrease (height and/or weight decrease for age)
zmanjšana hitrost rasti (glede na leta manjša telesna masa in/ali višina)
However, an overall 24 weeks treatment duration may be associated with a higher risk of relapse than a 48 weeks treatment duration (see section 5.1).
Skupna dolžina zdravljenja 24 tednov pa je lahko povezana z večjim tveganjem za ponovitev bolezni kot pri skupni dolžini zdravljenja 48 tednov (glejte poglavje 5.1).
No studies have been conducted in juvenile animals to examine the effects of treatment with ViraferonPeg on growth, development, sexual maturation, and behaviour.
Študij pri mladih živalih, pri katerih bi spremljali vpliv zdravljenja z zdravilom ViraferonPeg na rast, razvoj, spolno dozorevanje in obnašanje, niso izvedli.
These adverse reactions were common (≥1/100 to < 1/10) in clinical trials in patients treated with ViraferonPeg monotherapy.
Ti neželeni učinki so bili pogosti (≥1/100 do < 1/10) v kliničnih preskušanjih pri bolnikih, zdravljenih z zdravilom ViraferonPeg v monoterapiji.
If necessary, an inter-disciplinary approach including a mental health care provider or addiction specialist should be considered to evaluate, treat and follow the patient.
Če je potrebno, uporabite interdisciplinarni pristop z vključitvijo specialista s področja duševnega zdravja ali odvisnosti za oceno stanja, zdravljenje in spremljanje takega bolnika.
• Lay the pre-filled pen on a flat clean surface and wait until it reaches room temperature (but not more than 25
• Napolnjeni injekcijski peresnik položite na ravno, čisto površino in počakajte, da doseže sobno temperaturo (vendar ne več kot 25 °C).
These time points (treatment week 4 and treatment week 12) have been shown to be predictive for sustained response (Table 12).
Za navedene časovne točke (4. teden zdravljenja in 12. teden zdravljenja) so pokazali, da napovedujejo trajni virološki odziv (preglednica 12).
General information about taking this medicine
Splošni podatki o uporabi tega zdravila
This medicinal product should only be reconstituted with the solvent provided (see section 6.6).
To zdravilo lahko rekonstituirate samo s priloženim vehiklom (glejte poglavje 6.6).
If you are injecting this medicine yourself, please be sure that the dose that has been prescribed is clearly provided on the package of medicine you receive.
Če si to zdravilo injicirate sami, morate vedno preveriti, ali je na pakiranju zdravila, ki ste ga prejeli, jasno naveden odmerek, ki ga je predpisal zdravnik.
Prepare the dose by adding water for injection to ViraferonPeg powder just before you intend to inject it and use it immediately.
Odmerek si pripravite z dodajanjem vode za injekcije v ViraferonPeg prašek, tik preden ga nameravate injicirati, in ga uporabite takoj.
There are no adequate data from the use of interferon alfa-2b in pregnant women.
Ni zadostnih podatkov o uporabi interferona alfa-2b pri nosečnicah.
Events were reported at various time points typically several months after starting treatment with interferon alfa.
O dogodkih so poročali ob različnih časovnih točkah, običajno nekaj mesecev po začetku zdravljenja z interferonom alfa.
ViraferonPeg vials are for single use only.
Viale ViraferonPeg so le za enkratno uporabo.
The biologic activity of the pegylated isomers is qualitatively similar, but weaker than free interferon alfa-2b.
Biološki učinek pegiliranih izomerov je kvalitativno podoben, vendar šibkejši od učinka prostega interferona alfa-2b.
The pre-filled pen, needle and all injection materials are intended for single use and must be discarded after the injection.
Napolnjeni injekcijski peresnik, igla in ves material za injiciranje so namenjeni za enkratno uporabo in jih je po injiciranju treba zavreči.
Sustained response was assessed by the response rate six months after the cessation of treatment.
Trajen virološki odziv so ocenjevali na podlagi odziva šest mesecev po prenehanju zdravljenja.
No specific antidote for ViraferonPeg is available; therefore, symptomatic treatment and close observation of the patient are recommended in cases of overdose.
Specifičen antidot za zdravilo ViraferonPeg ni na voljo, zato v primeru prevelikega odmerjanja priporočamo simptomatsko zdravljenje in skrbno opazovanje bolnika.
Patients predisposed to the development of autoimmune disorders may be at increased risk.
Bolniki, ki so nagnjeni k pojavu avtoimunih bolezni, so lahko bolj ogroženi.
This action inhibits viral replication or if replication occurs, the progeny virions are unable to leave the cell.
To delovanje zavira razmnoževanje virusa, če pa do razmnoževanja vseeno pride, potomski virioni ne morejo zapustiti celice.
Injecting it at the same time of day each week will help you not to forget to take it.
To zdravilo si injicirajte enkrat na teden, vedno na isti dan. Injiciranje vedno ob istem času na določeni dan v tednu vam bo pomagalo, da ne pozabite na zdravilo.
For patients who exhibit virological response at week 12, treatment should be continued for at least another three-month period (i.e., a total of six months).
Pri bolnikih, ki imajo virološki odziv v 12. tednu, se mora zdravljenje nadaljevati še najmanj tri mesece (tj. skupaj šest mesecev).
A complete and illustrated set of instructions is provided in the Annex to the Package Leaflet.
Natančna in ilustrirana navodila za to so podana v prilogi k Navodilu za uporabo.
- have cirrhosis or other liver problems (other than hepatitis C).
- imate cirozo ali druge težave z jetri (razen hepatitisa C).
Your other hand will be free to move the plunger.
Drugo roko imejte prosto za premikanje bata.
Therefore the use of zidovudine with this medicine and ribavirin combination therapy is not recommended.
Zato sočasne uporabe zidovudina in kombinacije tega zdravila in ribavirina ne priporočamo.
Cardiac arrhythmias (primarily supraventricular) usually respond to conventional therapy but may require discontinuation of ViraferonPeg therapy.
Srčne aritmije (predvsem supraventrikularne) se običajno odzovejo na konvencionalno zdravljenje, vendar pa lahko zahtevajo prekinitev zdravljenja z zdravilom ViraferonPeg.
Suicide, suicide attempt, suicidal ideation, psychosis, hallucination, panic attack
samomor, poskus samomora, samomorilne misli, psihoza, halucinacije, napad panike
Paediatric population - Existence of, or history of severe psychiatric condition, particularly severe depression, suicidal ideation or suicidal attempt.
Pediatrična populacija - Obstoječa huda psihiatrična bolezen ali huda psihiatrična bolezen v anamnezi, še posebej huda depresija, samomorilne misli ali poskus samomora.
Push up the plunger slowly back to the correct dose.
Bat počasi potisnite navzgor do pravilnega odmerka.
The purpose of the study was to annually evaluate the durability of sustained virologic response (SVR) and assess the impact of continued viral negativity on clinical outcomes for patients who were sustained responders 24 weeks post-treatment with 24 or 48 weeks of peginterferon alfa-2b and ribavirin treatment.
Namen študije je bilo letno ocenjevanje trajanja trajnega virološkega odziva (SVR - sustained virologic response) in ugotavljanje vpliva nadaljnje virološke negativnosti na klinične izide pri bolnikih, ki so imeli trajen odziv 24 tednov po 24- ali 48-tedenskem zdravljenju s peginterferonom alfa-2b in ribavirinom.
Anaemia (hemoglobin < 9.4 g/dl) was reported in 12 % (23/194) of patients treated with ViraferonPeg in combination with ribavirin.
O anemiji (hemoglobin < 9,4 g/dl) so poročali pri 12 % (23/194) bolnikov, zdravljenih z zdravilom ViraferonPeg v kombinaciji z ribavirinom.
Adults: Haemoglobin in Patients with history of stable cardiac disease
Odrasli: Hemoglobin pri: bolnikih s stabilno srčno boleznijo v anamnezi
• Press the pre-filled pen against the skin as shown in Figure 10.
• Napolnjeni injekcijski peresnik pritisnite na kožo, kot prikazuje slika 10.
- have the skin disorders, psoriasis or sarcoidosis, which may become worse while you are using this medicine.
- imate kožne bolezni, luskavico ali sarkoidozo, ker se lahko poslabšajo med uporabo tega zdravila.
• Take the pre-filled pen out of the refrigerator.
• Vzemite napolnjeni injekcijski peresnik iz hladilnika.
Theophylline, Antipyrine, Warfarin
teofilin, antipirin, varfarin
- have thyroid disease that is not well controlled with medicines.
- imate bolezen ščitnice, ki z zdravili ni dobro nadzorovana.
The recommended duration of treatment with bitherapy is 1 year.
Priporočeno trajanje zdravljenja z dvojno terapijo je 1 leto.
• Pinch a fold of loose skin in the area you have cleaned for injection.
• Rahlo stisnite gubo ohlapne kože v predelu, ki ste ga očistili za injiciranje.
ViraferonPeg increases the risk of hepatic decompensation and death in patients with cirrhosis.
Zdravilo ViraferonPeg poveča tveganje za jetrno dekompenzacijo in smrt pri bolnikih s cirozo.
Women of childbearing potential/contraception in males and females ViraferonPeg is recommended for use in fertile women only when they are using effective contraception during the treatment.
Ženske v rodni dobi/kontracepcija pri moških in ženskah Zdravilo ViraferonPeg priporočamo za uporabo pri plodnih ženskah le, če med zdravljenjem uporabljajo učinkovito kontracepcijo.
When administered in combination therapy, patients with impaired renal function should be more carefully monitored with respect to the development of anaemia.
Pri kombinirani terapiji je treba bolnike z okvarjeno ledvično funkcijo bolj skrbno spremljati glede pojava anemije.
Among patients with undetectable HCV-RNA at the end of treatment, the relapse rate was 24 %.
Med bolniki z nemerljivimi koncentracijami HCV-RNA ob koncu zdravljenja je bil delež ponovnih izbruhov bolezni 24 %.
9/l (children and adolescents)
9/l (otroci in mladostniki)
Ribavirin capsules are to be administered orally each day in two divided doses with food (morning and evening).
Kapsule ribavirina bolnik jemlje peroralno vsak dan, v dveh deljenih odmerkih s hrano (zjutraj in zvečer).
The negative predictive value for sustained response in patients treated with ViraferonPeg in monotherapy was 98 %.
Negativna napovedna vrednost za trajni odziv pri bolnikih, zdravljenih z zdravilom ViraferonPeg v monoterapiji, je bila 98 %.
• Wipe the injection site with a new alcohol swab.
• Mesto injiciranja obrišite z novim alkoholnim tamponom.
Uncommon side effects (may affect up to 1 in 100 people): - wanting to harm yourself, - hallucinations,
Občasni neželeni učinki (pojavijo se lahko pri največ 1 od 100 bolnikov): želja škodovati sebi, halucinacije.
The solution may appear cloudy or bubbly for a few minutes.
Raztopina je lahko nekaj minut videti motna ali polna mehurčkov.
- are being treated for a mental illness or had treatment in the past for any other nervous or mental disorder, including depression (such as feelings of sadness, dejection) or suicidal or homicidal behaviour (see section 4 “Possible side effects”).
- se zdravite zaradi duševne bolezni ali ste se v preteklosti zdravili zaradi katere koli bolezni živčevja ali duševne motnje, vključno z depresijo (kot je občutek žalosti, potrtosti) ali s samomorilnim ali morilskim vedenjem (glejte poglavje 4.
Laboratory evaluations are to be conducted at weeks 2 and 4 of therapy, and periodically thereafter as clinically appropriate.
Laboratorijske preiskave opravite v 2. in 4. tednu zdravljenja in periodično tudi kasneje, glede na klinično stanje bolnika.
Once all bubbles have risen to the top of the solution, you should have a clear solution with a small ring of tiny bubbles around the top.
Ko so vsi mehurčki splavali na vrh raztopine, bi morali imeti bistro raztopino z majhnim obročem drobnih mehurčkov okoli vrha raztopine.
After injection of the dose, discard the pen in an appropriate container.
Po injiciranju odmerka zavrzite peresnik v ustrezno posodo.
- have epilepsy, a condition that causes convulsions (seizures, or “fits”).
- imate epilepsijo, bolezen, ki povzroča konvulzije (napade krčev).
Table 1 Dosing for combination therapy* Body weight (kg)
Preglednica 1 Odmerjanje pri kombinirani terapiji* Telesna masa (kg)
Mean (SD) ViraferonPeg elimination half-life is approximately 40 hours (13.3 hours), with apparent clearance of 22.0 ml/hr/kg.
Srednja (SD) razpolovna doba eliminacije zdravila ViraferonPeg je približno 40 ur (13,3 ure), navidezni očistek zdravila pa je 22,0 ml/h/kg.
Although the exact antiviral mode of action of recombinant interferon alfa-2b is unknown, it appears to alter the host cell metabolism.
Čeprav natančen mehanizem protivirusnega delovanja rekombinantnega interferona alfa-2b ni znan, pa kaže, da spremeni presnovo gostiteljske celice.
There are no data available regarding potential effects of ViraferonPeg treatment on male or female fertility.
Podatki o možnih učinkih zdravljenja z zdravilom ViraferonPeg na plodnost moških in žensk niso na voljo.
Co-infected patients receiving both antiretroviral (ARV) and anti-hepatitis treatment should be closely monitored, assessing their Child-Pugh score during treatment.
Sočasno okužene bolnike, ki prejemajo tako antiretrovirusno zdravljenje (ARV) kot zdravila za hepatitis, je treba skrbno spremljati in jim določati oceno po Child-Pughu v teku zdravljenja.
- This risk should be weighed against the disease characteristics of the child, such as evidence of disease progression (notably fibrosis), co-morbidities that may negatively influence the disease progression (such as HIV co-infection), as well as prognostic factors of response (HCV genotype and viral load).
To tveganje je treba pretehtati glede na značilnosti bolezni pri otroku, na primer glede na znake napredovanja bolezni (predvsem fibrozo), druge sočasne bolezni, ki bi lahko negativno vplivale na napredovanje bolezni (npr. sočasno okužbo s HIV), pa tudi prognostične dejavnike odziva na zdravljenje (genotip HCV in virusno breme).
Do not inject ViraferonPeg into an area where the skin is irritated, red, bruised, infected, or has scars, stretch marks, or lumps.
Zdravila ViraferonPeg ne injicirajte v predele, kjer je koža razdražena, pordela, podpluta, okužena, ali kjer so brazgotine, proge (strije) ali bule.
Signs, Symptoms, and Treatment Mechanism and Risk Factors
Znaki, simptomi in zdravljenje Mehanizem in dejavniki tveganja teofilin
If this medicine is used in combination with ribavirin, your doctor should monitor you, or the child you are caring for more carefully for a decrease in red blood cell count.
Če uporabljate to zdravilo v kombinaciji z ribavirinom, bo moral zdravnik vas ali otroka, za katerega skrbite, bolj skrbno spremljati, da ugotovi morebitno zmanjšanje števila rdečih krvnih celic.
Patients with advanced liver disease receiving HAART may be at increased risk of worsening liver function, therefore adding treatment with this medicine alone or in combination with ribavirin may increase their risk.
Pri bolnikih z napredovalo boleznijo jeter, ki prejemajo HAART, je tveganje za poslabšanje delovanja jeter lahko večje, zato lahko dodatek tega zdravila samega ali v kombinaciji z ribavirinom to tveganje še poveča.
Although, the majority of them could be managed by dose reduction, close monitoring of haematological parameters should be undertaken in this population of patients (see section 4.2 and below “Laboratory tests” and section 4.8).
Čeprav bi lahko pri večini teh bolnikov zadostovalo zmanjšanje odmerka, je pri tej skupini bolnikov potrebno skrbno spremljanje hematoloških parametrov (glejte poglavje 4.2, poglavje “Laboratorijske preiskave” v nadaljevanju in poglavje 4.8).
Following subcutaneous administration, maximal serum concentrations occur between 15-44 hours post-dose, and are sustained for up to 48-72 hours post-dose.
Po subkutani uporabi se največja koncentracija v serumu pojavi 15 do 44 ur po odmerku in se ohrani do 48 - 72 ur po odmerku.
Your doctor will determine the correct dose for you, or the child you are caring for.
Zdravnik bo določil pravi odmerek za vas ali otroka, za katerega skrbite.
- have kidney disease, your doctor may prescribe a lower than usual dose and monitor your kidney blood values regularly during treatment.
- imate ledvično bolezen; zdravnik vam bo morda predpisal manjši odmerek od običajnega in bo med zdravljenjem redno spremljal ledvične parametre v vaši krvi.
If there is bleeding, cover with an adhesive bandage.
Če krvavi, ga pokrijte z obližem.
If you are uncertain, contact your doctor or pharmacist or the doctor or pharmacist of the child you are caring for.
Če ste negotovi, se posvetujte z zdravnikom ali farmacevtom ali z zdravnikom ali farmacevtom otroka, za katerega skrbite.
There are no data in children or adolescents with a history of cardiac disease.
Za otroke in mladostnike z boleznijo srca v anamnezi ni podatkov.
Study Population
Raziskovana populacija
Caucasian patients had a higher sustained virologic response rate compared to the African Americans.
Pri belcih je bil delež trajnega virološkega odziva večji kot pri Afro-Američanih.
- pulmonary fibrosis (scarring of the lungs).
- pljučna fibroza (brazgotinjenje pljuč).
ViraferonPeg 1.5 micrograms/kg/week in combination with ribavirin capsules.
ViraferonPeg 1,5 mikrogramov/kg/teden v kombinaciji s kapsulami ribavirina.
As in adult patients, children and adolescents experienced other psychiatric adverse events (e.g. depression, emotional lability, and somnolence).
Tako kot pri odraslih pa so se pri otrocih in mladostnikih pojavili tudi ostali psihiatrični neželeni učinki (npr. depresija, čustvena nestabilnost in zaspanost).
The high sustained response rate in this subgroup of patients was identified in an interim analysis (n=49) and prospectively confirmed (n=48).
Vmesna analiza je pokazala visoko stopnjo trajnega virološkega odziva pri tej podskupini (n=49), kar je bilo tudi prospektivno potrjeno (n=48).
The potential interaction of peginterferon alfa-2b (ViraferonPeg) on substrates of metabolic enzymes was evaluated in 3 multiple-dose clinical pharmacology studies.
Morebitno medsebojno delovanje peginterferona alfa-2b (zdravila ViraferonPeg) in substratov metabolnih encimov so ocenili v 3 kliničnih farmakoloških študijah večkratnih odmerkov.
All Genotypes Genotype 1 Genotype 2 Genotype 3
Vsi genotipi Genotip 1 Genotip 2 Genotip 3 Genotip 4
The recommended dose of ViraferonPeg is 60 g/m2/week subcutaneously in combination with ribavirin 15 mg/kg/day orally in two divided doses with food (morning and evening).
Priporočeni odmerek zdravila ViraferonPeg je 60 g/m²/teden subkutano v kombinaciji z ribavirinom 15 mg/kg/dan peroralno v dveh ločenih odmerkih s hrano (zjutraj in zvečer).
With up to one year of treatment with this medicine in combination with ribavirin, some children and adolescents did not grow or gain weight as much as expected.
V času enoletnega zdravljenja s tem zdravilom v kombinaciji z ribavirinom nekateri otroci in mladostniki niso zrasli in niso pridobili na telesni masi toliko, kot bi pričakovali.
The negative predictive value for sustained response in HCV/HIV co-infected patients treated with ViraferonPeg in combination with ribavirin was 99 % (67/68; Study 1) (see section 5.1).
Negativna napovedna vrednost stalnega virološkega odziva pri bolnikih, ki so bili sočasno okuženi s HCV/HIV in so se zdravili z zdravilom ViraferonPeg v kombinaciji z ribavirinom, je bila 99 % (67/68, študija 1) (glejte poglavje 5.1).
The reconstituted solution should be clear and colourless.
Rekonstituirana raztopina mora biti bistra in brezbarvna.
Guidelines were developed in clinical trials for dose modification.
V kliničnih preskušanjih so določili smernice za prilagoditev odmerka.
Mean apparent volume of distribution is 0.99 l/kg.
Srednji navidezni volumen porazdelitve je 0,99 l/kg.
A clinical trial investigating the combination of telbivudine, 600 mg daily, with pegylated interferon alfa-2a, 180 micrograms once weekly by subcutaneous administration, indicates that this combination is associated with an increased risk of developing peripheral neuropathy.
Klinično preskušanje, v katerem so raziskali uporabo kombinacije telbivudina v odmerku 600 mg na dan in pegiliranega interferona alfa-2a v odmerku 180 mikrogramov subkutano enkrat na teden, kaže, da je ta kombinacija povezana s povečanim tveganjem za pojav periferne nevropatije.
- loss of consciousness has occurred very rarely with alpha interferons, mostly in elderly patients treated at high doses.
- zelo redko se je pri zdravljenju z alfa interferoni pojavila izguba zavesti, večinoma pri starejših bolnikih, ki so se zdravili z visokimi odmerki.
If your doctor prescribes this medicine with ribavirin or with ribavirin and boceprevir, please read the Package Leaflets of ribavirin and boceprevir before you begin combination treatment.
Če vam zdravnik predpiše to zdravilo z ribavirinom ali z ribavirinom in boceprevirjem, prosimo, preberite navodili za uporabo ribavirina in boceprevirja, preden začnete s kombiniranim zdravljenjem.
All subjects HCV 2  600,000 IU/ml > 600,000 IU/ml HCV 3  600,000 IU/ml > 600,000 IU/ml
Vsi preiskovanci HCV 2  600.000 i.e./ml > 600.000 i.e./ml HCV 3  600.000 i.e./ml > 600.000 i.e./ml