natgillin/translations-raw huggingface dataset:
Consult the Summary of Product Characteristics of atazanavir or darunavir for further information on use in combination with these medicinal products.
Za več informacij o uporabi v kombinaciji s temi zdravili glejte povzetek glavnih značilnosti zdravila za atazanavir ali darunavir.
Amlodipine Diltiazem Felodipine Nicardipine Nifedipine Verapamil
Priporočilo glede sočasne uporabe s kobicistatom 150 mg in atazanavirjem ali darunavirjem amlodipin diltiazem felodipin nikardipin nifedipin verapamil
Timolol
ritonavira
Sunset yellow FCF aluminium lake (E110) Macrogol 3350 (E1521)
Filmska obloga sončno rumeno FCF (E110) makrogol 3350 (E1521) polivinilalkohol (delno hidroliziran) (E1203) smukec (E553B) titanov dioksid (E171) rumeni železov oksid (E172)
Other special population(s)
Druge posebne skupine bolnikov
Pitavastatin
kobicistatf
Atazanavir 300 mg once daily Darunavir 800 mg once daily
Odmerek zdravila Tybost Odmerek zaviralca proteaze HIV-1 150 mg enkrat na dan atazanavir 300 mg enkrat na dan darunavir 800 mg enkrat na dan
NARCOTIC ANALGESICS Methadone
ciklosporin sirolimus takrolimus
Atazanavir + cobicistatf (n = 344)
atazanavir + kobicistata
• etravirine
• srbečica
Clorazepate
kolhicin
depression, sleep disorder Nervous system disorders: Common:
Bolezni živčevja: Pogosti:
Norgestimate/Ethinyloestradiol Interaction not studied.
norgestimat/ etinilestradiol
GLUCOCORTICOIDS
metoprolol timolol
Uncommon side effects
Neželeni učinek
Cobicistat:
kobicistat:
Clinical monitoring is recommended and a dose reduction may be necessary when these beta-blockers are co-administered with Tybost.
Pri sočasni uporabi antagonistov adrenergičnih receptorjev beta z zdravilom Tybost se priporoča klinično spremljanje in morebiti bo potrebno zmanjšanje odmerka.
Contents of the pack and other information What Tybost contains
Shranjevanje zdravila Tybost Vsebina pakiranja in dodatne informacije
Cmin: NC Ethinyloestradiol: AUC: ↓ 30%
etinilestradiol: AUC: ↓ 30 % Cmax: ↔ Cmin: NI
Plasma concentrations of drospirenone are increased following administration of drospirenone/ethinyloestradiol with atazanavir/cobicistat or with darunavir/cobicistat.
Po dajanju drospirenona/etinilestradiola z atazanavirjem/kobicistatom ali z darunavirjem/kobicistatom so koncentracije drospirenona v plazmi povišane.
• fever
• kobicistat
Drospirenone:
Inhibitors):
nausea
bosentan
For additional drug-drug interactions with atazanavir or darunavir, consult their respective Summary of Product Characteristics when using Tybost.
Ob sočasni uporabi z zdravilom Tybost za dodatne interakcije med zdravili in atazanavirjem ali darunavirjem glejte povzetek glavnih značilnosti teh dveh zdravil.
Cmax: ↑ 958% Cmin: NC
rosuvastatin: AUC: ↑ 242 % Cmax: ↑ 958 % Cmin: NI
l t o r d
o ā t
Invented name Strength Pharmaceutical Form Route of administration Packaging Content (concentration)
Številka EU zaščiteno ime jakost farmacevtska oblika pot uporabe ovojnina vsebina (koncentracija)
The Member States should ensure that all conditions or restrictions with regard to the safe and effective use of the medicinal product described below i.e. the details of a prescription checklist are implemented:
Države članice morajo zagotoviti, da so vsi pogoji ali omejitve glede varne in učinkovite uporabe zdravila, tj. podrobnosti seznama za preverjanje ob predpisovanju, uvedene:
• Patients should be carefully monitored for liver damage and for worsening of renal function.
• Bolnike je treba pozorno spremljati zaradi možnih poškodb jeter in poslabšanja v delovanju ledvic.
ANNEX 127a CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT TO BE IMPLEMENTED BY THE MEMBER STATES
DODATEK 127a
• To minimise the risk of adaptive regeneration and potentially subsequent liver tumour formation, early discontinuation in the presence of significant and persistent elevation of ALT/AST is recommended.
• Za zmanjšanje tveganja adaptivne regeneracije in morebiten posledičen razvoj jetrnih tumorjev na najmanjšo možno mero, je v primeru značilnega in trajnega povišanja ALT/AST
• Caution must be demonstrated if the patient: - has severe liver function impairment - has chronic liver diseases known to represent preneoplastic conditions (e.g. advanced liver fibrosis, cirrhosis, viral hepatitis, neonatal liver disease or congenital enzyme defects) - is receiving a concomitant therapy including hepatotoxic and/or genotoxic properties - is receiving concomitant therapy with amphotericin B desoxycholate - has history of haemolysis, haemolytic anaemia or renal impairment.
- ima bolnik kronično bolezen jeter, za katero je znano, da predstavlja preneoplastično stanje (npr. napredovalo jetrno fibrozo, cirozo, virusni hepatitis, neonatalno jetrno bolezen ali prirojeni encimski defekt)
• Patients receiving sirolimus, nifedipine or itraconazole in combination with Mycamine should be monitored for sirolimus, nifedipine or itraconazole toxicity and the sirolimus, nifedipine or itraconazole dosage should be reduced if necessary.
Mycamine, je treba spremljati zaradi možnosti pojava toksičnosti sirolimusa, nifedipina ali itrakonazola ter po potrebi zmanjšati njihove odmerke.
• Mycamine should not be used during pregnancy unless clearly necessary.
• Zdravilo Mycamine je kontraindicirano, če ima bolnik anamnezo preobčutljivosti na mikafungin, druge ehinokandine ali pomožne snovi • Zdravila Mycamine se ne sme uporabljati med nosečnostjo, razen če je nujno potrebno.
The study started on the 1st of June 2009 and results are expected to be available in 2013.
Študija se je začela 1. junija 2009, izsledki pa bodo po pričakovanjih na voljo leta 2013.
This information is very limited not allowing a conclusion with regards the cardiovascular risks.
Te informacije so zelo omejene in ne omogočajo zaključka v zvezi s kardiovaskularnim tveganjem.
Overall mortality risk was small, with an excess of 23 deaths over the 70 expected.
Tveganje splošne umrljivosti je bilo majhno, s presežkom 23 smrtnih primerov nad 70 pričakovanimi.
This information was circulated in a rapid alert triggering a procedure under Article 107 of Directive 2001/83/EC, as amended.
Te informacije so bile objavljene prek sistema hitrega obveščanja, na podlagi katerega je bil sprožen postopek iz člena 107 Direktive 2001/83/ES, kakor je bila spremenjena.
• The Committee considered the procedure under Article 107 of Directive 2001/83/EC, as amended for somatropin-containing medicinal products;
• Odbor je obravnaval postopek iz člena 107 Direktive 2001/83/ES, kakor je bila spremenjena, za zdravila, ki vsebujejo somatropin.
All 10,330 patients were assigned to three risk categories for long-term mortality based on the clinical condition.
Vseh 10 330 bolnikov je bilo na podlagi kliničnega stanja razporejenih v tri kategorije tveganja dolgoročne umrljivosti.
This long-term surveillance study collected data from all patients that were treated with rhGH in the period from 1985 to 1996 and who were older than 18 years of age at the time of data collection in 2007.
V okviru te dolgoročne spremljevalne študije so bili zbrani podatki o vseh bolnikih, ki so bili med letoma 1985 in 1996 zdravljeni z rhGH ter ki so bili v času zbiranja podatkov leta 2007 starejši od 18 let.
However, this study presents significant methodological limitations that preclude these results to be regarded as robust.
Vendar ta študija vključuje precejšnje metodološke omejitve, zaradi katerih se ti izsledki ne morejo šteti za zanesljive.
The SAGHE study in Europe is part of the FP7 Health work programme and approximatelly the sample size is of 30,000 patients will be included in the 8 involved countries (France, Belgium, United Kingdom, Netherlands, Switzerland, Italy, Germany and Sweden).
Evropska študija SAGHE je del delovnega programa za zdravje v okviru sedmega okvirnega programa, vanjo pa bo vključen vzorec približno 30 000 bolnikov v 8 sodelujočih državah (Francija, Belgija, Združeno kraljestvo, Nizozemska, Švica, Italija, Nemčija in Švedska).
• The Committee agreed that the French SAGHE study has significant methodological limitations (e.g. general population used as reference for the calculation of mortality).
• Odbor je sklenil, da ima francoska študija SAGHE precejšnje metodološke omejitve (npr. uporaba splošne populacije kot referenčne skupine za izračun umrljivosti).
Overall summary of the scientific evaluation of somatropin-containing medicinal products (see Annex I)
Splošni povzetek znanstvene ocene zdravil, ki vsebujejo somatropin (glejte Prilogo I)
The primary objective of the study was to evaluate the overall and cancer-related mortality and morbidity risks in comparison with risks in the general population.
Glavni cilj študije je bil oceniti tveganja splošne in z rakom povezane umrljivosti in obolevnosti v primerjavi s tveganji v splošni populaciji.
No information on the presence of cardiovascular risk factors was available for 3 out of 9 patients.
Pri treh od devetih bolnikov podatki o obstoju dejavnikov kardiovaskularnega tveganja niso bili na voljo.
Finally, data from the patient group that died due to diseases of the circulatory system showed that all but one had been treated for a diagnosis of growth hormone deficiency.
Nazadnje so podatki o skupini bolnikov, ki so umrli zaradi bolezni cirkulacijskega sistema, pokazali, da so bili vsi razen enega zdravljeni zaradi diagnoze pomanjkanja rastnega hormona.
Furthermore, the Committee agreed to emphasise in the Product Information (section 4.4) the need for the maximum recommended dose not to be exceeded.
Poleg tega se je Odbor dogovoril, da se v informacijah o zdravilu (poglavje 4.4) poudari, da se največji priporočeni dnevni odmerek ne sme preseči.
Of the 93 allcause mortality cases, 21 classified as resulting from “ill-defined conditions” are of unknown cause.
Od 93 smrtnih primerov zaradi vseh vzrokov je bil v 21 primerih, ki naj bi bili posledica „slabo opredeljenih stanj“, vzrok smrti neznan.
Therefore, limited information on long-term safety of somatropin treatment is currently available.
Zato so podatki, ki so trenutno na voljo o dolgoročni varnosti zdravljenja s somatropinom, omejeni.
In addition the risk increased with short duration of treatment, nevertheless a sub-analysis by cumulative doses did not confirm this finding.
Poleg tega se je tveganje povečalo s kratkotrajnostjo zdravljenja, vendar podanaliza kumulativnih odmerkov te ugotovitve ni potrdila.
However, the results of the French SAGHE study are regarded as potential safety signal to be further considered in light of long term safety data that will become available in 2 years time, namely the results of the European SAGHE consortium study.
Vendar izsledki francoske študije SAGHE pomenijo morebitno varnostno opozorilo, ki ga je treba nadalje preučiti ob upoštevanju dolgoročnih podatkov o varnosti, ki bodo na voljo čez dve leti, tj. izsledkov evropske študije konzorcija SAGHE.
The safety of growth hormone therapy has been mainly based on large samples of patients followed in post-marketing databases during or not for long after treatment.
Varnost zdravljenja z rastnim hormonom temelji predvsem na velikih vzorcih bolnikov, ki so bili spremljani v postmarketinških podatkovnih zbirkah med zdravljenjem ali malo po njem.
Some indications are not approved for all somatropin containing medicines.
Nekatere indikacije niso odobrene za vsa zdravila, ki vsebujejo somatropin.
Somatropin (rhGH) products have been available in Europe since the late 1980's for the treatment of several conditions associated with growth hormone deficiency and/or short stature.
Zdravila s somatropinom (rhGH) so v Evropi na voljo od poznih osemdesetih let prejšnjega stoletja za zdravljenje različnih obolenj, povezanih s pomanjkanjem rastnega hormona in/ali nizko rastjo.
The suggested increased risk with the higher doses is only statistically significant in the group treated with mean doses above 50 µg/kg/day (n=281).
Nakazano povečano tveganje pri večjih odmerkih je bilo statistično značilno samo v skupini, zdravljeni s povprečnimi odmerki nad 50 µg/kg/dan (n = 281).
On 9 December 2010, the French National Competent Authority (AFSSAPS) informed the European Commission, the European Medicines Agency and all Member States of unpublished results of the SAGHE study that showed an all-cause mortality significantly higher in children treated with rhGH (standard mortality ratio - SMR of 1.33, 95% CI 1.08;1.64).
Francoski nacionalni pristojni organ (AFSSAPS) je 9. decembra 2010 obvestil Evropsko komisijo, Evropsko agencijo za zdravila in vse države članice o neobjavljenih izsledkih študije SAGHE, ki so pokazali, da je umrljivost zaradi vseh vzrokov precej večja pri otrocih, zdravljenih z rhGH (standardizirana stopnja umrljivosti (SSU) 1,33, 95 % interval zaupanja 1,08-1,64).
There were concerns on the impact of the results of this study on the benefit-risk balance of somatropin-containing medicinal products.
Pojavile so se skrbi glede učinka izsledkov te študije na razmerje med koristmi in tveganji zdravil, ki vsebujejo somatropin.
• The Committee agreed however, that the results of the French SAGHE study are regarded as potential safety signal.
• Vendar je Odbor sklenil, da izsledki francoske študije SAGHE pomenijo morebitno varnostno opozorilo.
It is noted that in this group, 225 (80%) patients were part of a company-sponsored study conducted in children born short for gestational age (SGA) and overall this is considered a very small subpopulation for a clear association of the suggested risk with the dose.
Omeniti je treba, da je v tej skupini 225 (80 %) bolnikov sodelovalo v študiji po naročilu podjetja, opravljeni na otrocih, ki so se rodili majhni za svojo gestacijsko starost (MGS), kar je na splošno zelo majhna podpopulacija za jasno povezavo med navedenim tveganjem in odmerki.
A large epidemiological study based on data from the Association France-Hypophyse registry was ongoing since 2007 - the French Santé Adulte GH Enfant (SAGHE) study.
Vse od leta 2007 je na podlagi podatkov iz registra združenja France-Hypophyse potekala obsežna francoska epidemiološka študija, imenovana Santé Adulte GH Enfant (SAGHE).
In children with inadequate endogenous growth hormone, somatropin stimulates linear growth and increases growth rate.
Pri otrocih z nezadostno količino endogenega rastnega hormona pospešuje linearno rast in povečuje hitrost rasti.
Finally, to address the potential signal of an increased risk with increased dose as suggested by the results of the French SAGHE study, it was agreed to emphasize in the product information of all somatropin-containing medicinal products that the maximum recommended daily dose should not be exceeded.
Nazadnje, za preučitev morebitnega opozorila glede povečanega tveganja pri večjih odmerkih, na katero kažejo izsledki francoske študije SAGHE, je bilo dogovorjeno, da se v informacijah o zdravilu pri vseh zdravilih, ki vsebujejo somatropin, poudari, da se največji priporočeni dnevni odmerek ne sme preseči.
All other data reviewed by the CHMP did not corroborate the results of the SAGHE study or did provide new or additional safety concerns.
Drugi podatki, ki jih je pregledal odbor CHMP, niso potrdili izsledkov študije SAGHE in niso vzbudili novih ali dodatnih skrbi glede varnosti.
In view of the above, the CHMP has recommended the variation to the terms of the Marketing Authorisations for somatropin-containing medicinal products (see Annex I), for which the relevant sections of the Summary of Product Characteristics and Package Leaflet are set out in Annex III and subject to the conditions set out in Annex IV of this Opinion.
Ob upoštevanju naslednjega je odbor CHMP priporočil spremembo pogojev dovoljenj za promet z zdravili, ki vsebujejo somatropin (glejte Prilogo I), katerih ustrezna poglavja povzetka glavnih značilnosti zdravila in navodila za uporabo so določena v Prilogi III, zanjo pa veljajo pogoji, določeni v Prilogi IV tega mnenja.
Considering previously published data and information already included in the Product Information for some somatropins, the Committee considered that it is justified to harmonise existing contraindications for all somatropin containing medicines when there is any evidence of activity of a tumour.
Glede na predhodno objavljene podatke in informacije, ki so pri nekaterih zdravilih s somatropinom že vključene v informacije o zdravilu, je Odbor menil, da je upravičeno uskladiti obstoječe kontraindikacije za vsa zdravila, ki vsebujejo somatropin, če obstaja kakršen koli dokaz o aktivnosti tumorja.
Somatropin is a recombinant human growth hormone (rhGH) acting on the metabolism of lipids, carbohydrates and proteins.
Somatropin je rekombinantni humani rastni hormon (rhGH), ki vpliva na presnovo maščob, ogljikovih hidratov in beljakovin.
• Other data reviewed did not corroborate the results of the SAGHE study, or provided additional safety concerns.
• Drugi preučeni podatki niso potrdili izsledkov študije SAGHE in niso vzbudili dodatnih skrbi glede varnosti.
In adults, somatropin maintains a normal body composition by increasing nitrogen retention and stimulation of skeletal muscle growth, and by mobilisation of body fat.
Pri odraslih vzdržuje normalno zgradbo organizma, tako da povečuje retencijo dušika, spodbuja rast skeletnih mišic in mobilizira telesno maščobo.
• The Committee considered the results of the French SAGHE study and all available data submitted from clinical trials, registries, cohorts and safety databases in relation to the cardiovascular risk and risk of neoplasm associated with somatropin-treatment.
• Odbor je preučil izsledke francoske študije SAGHE ter vse predložene podatke iz kliničnih preskušanj, registrov, kohortnih študij in podatkovnih zbirk o varnosti zdravil v zvezi s kardiovaskularnim tveganjem in tveganjem novotvorb, ki se povezujeta z zdravljenjem s somatropinom.
In view of all the above discussed, the Committee considered justified to harmonise or include , as appropriate, contraindications for all somatropin containing medicinal products with regards the potential for tumour-promoting associated with treatment.
Glede na zgoraj navedeno je Odbor menil, da je upravičeno uskladiti ali po potrebi vključiti kontraindikacije za vsa zdravila, ki vsebujejo somatropin, kar zadeva možnost za pospešeno rast tumorjev, ki se povezuje z zdravljenjem.
This also needs to be reflected in the Risk Management Plans as well as the potential risk linked to subarachnoid or intracerebral haemorrhage.
To je treba navesti tudi v načrtih za obvladovanje tveganj skupaj z možnim tveganjem, povezanim s subarahnoidno ali intracerebralno krvavitvijo.
No data on the occurrence of non-fatal neoplasms in patients of the SAGHE study is, at the moment, available and the morbidity results are still is on-going.
Za bolnike iz študije SAGHE trenutno ni na voljo podatkov o pogostnosti nesmrtnih novotvorb, izsledki glede obolevnosti pa so še v pripravi.
Currently there are nine approved somatropin-medicinal products in the Union: Genotropin, Humatrope, Maxomat, Norditropin, Saizen, Zomacton approved via Mutual Recognition procedure (MRP) or Nationally (NAP) and Omnitrope, NutropinAq and Valtropin approved centrally (CAP).
Trenutno je v Uniji odobrenih devet zdravil, ki vsebujejo somatropin: zdravila Genotropin, Humatrope, Maxomat, Norditropin, Saizen in Zomacton so bila odobrena po postopku z medsebojnim priznavanjem ali nacionalnem postopku, zdravila Omnitrope, NutropinAq in Valtropin pa po centraliziranem postopku.
3 Ergun Longmire B, Mertens AC, Mitby P, Qin J, Heller G, Shi W et al. Growth hormone treated and risk of second malignant neoplasms in the childhood cancer survivor.
3 Ergun-Longmire, B., Mertens, A. C., Mitby, P., Qin, J., Heller, G., Shi, W. in drugi, Growth hormone treated and risk of second malignant neoplasms in the childhood cancer survivor, J. Clin.
In the Union, somatropin is approved to be used in children for growth hormone deficiency (including idiopathic growth hormone deficiency), growth failure in patients with Turner syndrome, chronic renal insufficiency or short stature homebox-containing gene (SHOX) deficiency, PraderWilli syndrome and in patients born small for gestational age (SGA).
V Uniji je uporaba somatropina dovoljena pri otrocih s pomanjkanjem rastnega hormona (vključno z idiopatskim pomanjkanjem rastnega hormona), bolnikih z zaostankom v rasti zaradi Turnerjevega sindroma, kronične ledvične insuficience, haploinsuficience gena SHOX ali Prader-Willijevega sindroma in bolnikih, ki so se za svojo gestacijsko starost rodili majhni (MGS).
The CHMP reviewed all data submitted including data from the French SAGHE study and from clinical trials, registries, cohorts and safety databases (pharmacovigilance) as well as data available in the literature relating to the cardiovascular risk and risk of neoplasm associated with somatropin-treatment.
Odbor CHMP je pregledal vse predložene podatke, vključno s podatki iz francoske študije SAGHE in iz kliničnih preskušanj, registrov, kohortnih študij in podatkovnih zbirk o varnosti zdravil (farmakovigilanca) ter podatki iz literature v zvezi s kardiovaskularnim tveganjem in tveganjem novotvorb pri zdravljenju s somatropinom.
Somatropin-treatment has been associated with tumour-promoting potential and this is currently reflected in the product information of all somatropin-containing medicinal products.
Zdravljenje s somatropinom se povezuje z možnostjo za pospešeno rast tumorjev, kar se trenutno navaja v informacijah o zdravilu pri vseh zdravilih, ki vsebujejo somatropin.
2 Sklar CA, Mertens AC, Mitby P, et al. Risk of disease recurrence and second neoplasms in survivors of childhood cancer treated with growth hormone: A report from the Childhood Cancer Survivor Study.
2 Sklar, C. A., Mertens, A. C., Mitby, P. in drugi, Risk of disease recurrence and second neoplasms in survivors of childhood cancer treated with growth hormone: A report from the Childhood Cancer Survivor Study, J. Clin.
Results of the French SAGHE study, a long-term surveillance study in a high number of patients and with a mean follow up of 17 years suggested an overall increase of mortality in patients treated with somatropin for isolated growth hormone deficiency (GDH), idiopathic short stature (ISS) and short for gestational age (SGA) compared to the general population.
Izsledki francoske študije SAHGE, tj. dolgoročne spremljevalne študije na velikem številu bolnikov in s povprečnim 17-letnim spremljanjem, so v primerjavi s splošno populacijo pokazali splošno povečanje umrljivosti pri bolnikih, zdravljenih s somatropinom zaradi izoliranega pomanjkanja rastnega hormona, idiopatske nizke rasti in majhnosti za gestacijsko starost (MGS).
The specific wording to be include in section 4.3 of the SmPCs and reflected in the package leaflets of all somatropin-containing medicinal products was agreed (see Annex II).
Dogovorjeno je bilo natančno besedilo, ki mora biti vključeno v poglavje 4.3 povzetkov glavnih značilnosti in v navodila za uporabo vseh zdravil, ki vsebujejo somatropin (glejte Prilogo II).
Scientific conclusions and grounds for the amendment of the summaries of product characteristics and package leaflets presented by the EMA
Priloga II Znanstveni zaključki in podlaga za dopolnilo povzetkov glavnih značilnosti zdravila in navodil za uporabo, ki jih je predstavila Evropska agencija za zdravila
The low risk population defined as treatment for idiopathic growth hormone deficiency, idiopathic short stature, short stature in children born short for gestational age, or isolated growth hormone deficiency was included in the mortality analysis (n=6,892 patients corresponding to 116,403 person-years of observation).
V analizo umrljivosti je bila vključena populacija z majhnim tveganjem, opredeljena kot zdravljenje zaradi idiopatskega pomanjkanja rastnega hormona, idiopatske nizke rasti, nizke rasti pri otrocih, ki so se za svojo gestacijsko starost rodili majhni, ali izoliranega pomanjkanja rastnega hormona (n = 6 892 bolnikov, kar je 116 403 oseb-let opazovanja).
Increased mortality was apparent when higher doses were used and due to subarachnoid or intracerebral haemorrhage and bone tumours.
Povečana umrljivost je bila razvidna pri uporabi večjih odmerkov ter zaradi subarahnoidne ali intracerebralne krvavitve in kostnih tumorjev.