natgillin/translations-raw huggingface dataset:
Every effort should be made to switch to appropriate alternative treatment prior to conception, and before contraception is discontinued.
Treba je storiti vse potrebno za prehod na ustrezno drugo zdravilo pred spočetjem in pred prekinitvijo jemanja kontracepcije.
The potential impact of paternal use of valproate, the potential effect on the third generation offspring and the potential effects on mitochondria (mitochondrial toxicity) were discussed.
Razpravljali so o morebitnem vplivu uporabe valproata pri očetu, morebitnem vplivu na tretjo generacijo potomcev in morebitnem vplivu na mitohondrije (mitohondrijski toksičnosti).
The MAHs are strongly encouraged to collaborate on the requested measures and to perform joint studies.
Imetnikom dovoljenja za promet z zdravilom zelo priporočamo, da sodelujejo pri zahtevanih ukrepih in izvajajo skupne študije.
In addition to the measures to increase awareness about risks of valproate, the different expert consultations provided clear recommendations to restrict the use of valproate.
Poleg ukrepov za krepitev zavedanja o tveganjih valproata so bila prek posvetovanj z različnimi strokovnjaki podana jasna priporočila za omejevanje uporabe valproata.
Genetic changes can be divided in gene mutations and chromosome aberrations.
Genetske spremembe je mogoče razdeliti v mutacije genov in kromosomske aberacije.
This guide should be handed over to the patient.
Ta vodnik je treba predati bolnici.
Core elements of a direct healthcare professional communication were agreed, together with the timelines for its distribution.
Dogovorili so se o bistvenih elementih neposrednih sporočil za zdravstvene delavce in časovnih okvirih za njihovo razširjanje.
In view of the safety issues in discussion and the whole set of conditions for the risk minimisation aiming at minimising exposure in pregnancy, all MAHs need to have in place a risk management plan.
Ob upoštevanju varnostnih vprašanj pri razpravi in celotnega nabora pogojev za zmanjševanje tveganja, ki so namenjeni zmanjševanju tveganja za nosečnost, morajo imeti vsi imetniki dovoljenja za promet z zdravilom vzpostavljen načrt za obvladovanje tveganja.
For their use in the treatment of bipolar disorders and prophylaxis of migraine these products are contraindicated in pregnancy.
Za uporabo pri zdravljenju bipolarnih motenj in profilaksi migrene so ta zdravila v nosečnosti kontraindicirana.
The PRAC taking into account all the evidence as well the areas where information is limited requested several measures in order to further characterise the risks, increase the awareness of the risks, restrict the use and measure the effectiveness of the currently proposed measures.
Ob upoštevanju vseh dokazov in področij, na katerih so informacije omejene, je odbor PRAC zahteval več ukrepov za nadaljnje prepoznavanje tveganj, povečanje zavedanja o tveganjih ter omejevanje uporabe in merjenje učinkovitosti trenutno predlaganih ukrepov.
Furthermore, in a literature overview regarding effects on mitochondria, known side effects were described such as liver toxicity, Reye-like syndrome, pancreatitis and immune deficiency (leukopenia).
Poleg tega so bili v pregledu literature o učinkih na mitohondrije opisani znani neželeni učinki, kot so toksičnost za jetra, Reyevemu podoben sindrom, pankreatitis in imunska pomanjkljivosti (levkopenija).
The epigenetic mechanism refers to the possibility that changes in the gene expression in the gametes are transmitted to the gene expression in the embryo (for example by changes in DNA methylation).
Epigenetski mehanizem se nanaša na možnost, da se spremembe izražanja genov v gametah prenašajo na izražanje genov v zarodku (na primer s spremembami metilacije DNA).
In one experiment it was shown that a change in gene expression (one gene) in male mice after exposure to a histone deacetylases (HDAC) inhibitor (not valproate) was observed also in the offspring of these mice (Jia et al, 2015)1, so possible in principle.
V enem preskusu so dokazali, da je spremembo izražanja genov (enega gena) pri mišjih samcih po izpostavljenosti zaviralcu histonske deacetilaze (HDAC) (ne pri valproatu) mogoče opaziti tudi pri potomcih teh miši (Jia et al., 2015)1, zato je načeloma možna.
The PRAC is of the opinion that the currently available data do not warrant further investigation regarding the potential association between mitochondrial dysfunction and autism.
Na podlagi podatkov, ki so trenutno na voljo, odbor PRAC meni, da nadaljnje raziskovanje morebitne povezave med mitohondrijsko disfunkcijo in avtizmom ni upravičeno.
In the course of the consultations that PRAC had in this procedure, some additional concerns have arisen, other than the well-known and documented harm to the foetus during in utero exposure.
Med posvetovanji, ki jih je odbor PRAC opravil v tem postopku, se je poleg dobro znanih in dokumentiranih škodljivih učinkov na plod med izpostavljenostjo in utero pojavilo nekaj dodatnih pomislekov.
• For their use in pregnancy for the treatment of epilepsy, the PRAC concluded that these medicinal products are contraindicated unless there is no suitable alternative treatment option.
• Pri uporabi teh zdravil za zdravljenje epilepsije med nosečnostjo je odbor PRAC zaključil, da so kontraindicirana, razen če ni druge primerne možnosti zdravljenja.
As the injectable formulations are indicated only for short use, the patient card is most likely to be of limited value.
Ker so farmacevtske oblike za injiciranje indicirane le za kratkotrajno uporabo, ima kartica za bolnika najverjetneje le omejen pomen.
The PRAC therefore recommends that other tests could be performed (e.g. in vitro mouse lymphoma assay) to further explore this hypothesis.
Odbor PRAC zato priporoča, da bi se za nadaljnjo raziskovanje te hipoteze lahko opravila druga preskušanja (npr. in vitro mišji limfomski preskus).
On 08 March 2017 France triggered a procedure under Article 31 of Directive 2001/83/EC, and requested the PRAC to assess the impact on the concerns regarding the effectiveness of the risk minimisation measures on the benefit-risk balance of medicinal products containing substances related to valproate and issue a recommendation on whether the marketing authorisation(s) of these products should be maintained, varied, suspended or revoked.
Francija je 8. marca 2017 sprožila postopek v skladu s členom 31 Direktive 2001/83/ES in svetovalni odbor za oceno tveganja na področju farmakovigilance (PRAC) zaprosila, naj oceni utemeljenost pomislekov v zvezi z učinkovitostjo ukrepov za minimizacijo tveganja na razmerje med tveganji in koristmi zdravil, ki vsebujejo valproatu sorodne snovi, ter izda priporočilo, ali naj se dovoljenje(-a) za promet z zdravilom ohrani(-jo), spremeni(-jo), začasno umakne(-jo) ali prekliče(-jo).
The MAHs are encouraged to collaborate and liaise with the national competent authorities to facilitate the dissemination of the agreed educational material.
Imetnike dovoljenja za promet z zdravilom se spodbuja, da za lažje razširjanje dogovorjenega izobraževalnega gradiva sodelujejo s pristojnimi nacionalnimi organi in se povežejo z njimi.
Regarding exposure via seminal fluid, estimation was made of the area under curve (AUC) for valproate in a woman following vaginal exposure to valproate via seminal fluid of a man treated with valproate.
V zvezi z izpostavljenostjo prek semenske tekočine je bilo za valproat ocenjena površina pod krivuljo („area under curve“ - AUC) pri ženski po vaginalni izpostavljenosti valproatu prek semenske tekočine moškega, zdravljenega z valproatom.
The current ongoing drug utilisation study (DUS) should be adapted and continued to assess the effectiveness of the updated risk minimisation measures including the pregnancy prevention programme conditions and to further characterise the prescribing patterns for valproate.
Študijo o uporabi zdravil (DUS), ki trenutno poteka, je treba prilagoditi in še naprej ocenjevati učinkovitost posodobljenih ukrepov za zmanjševanje tveganj, vključno s pogoji programa za preprečevanje nosečnosti, ter še naprej prepoznavati vzorce predpisovanja valproata.
PRAC also recommended postauthorisation studies to assess the effectiveness of the risk minimisation measures.
Odbor PRAC je priporočil tudi študije po izdaji dovoljenja za promet z zdravilom za oceno učinkovitosti ukrepov za zmanjševanje tveganj.
It seems theoretically possible that gene mutations in sperm cells could be transmitted to the offspring.
Teoretično se zdi mogoče, da bi se mutacije genov v celicah spermijev lahko prenesle na potomce.
It was shown in a transgenerational experiment in mice that administration of valproate during pregnancy (day 10) produced autism-like symptoms and increased expression of several proteins in the brains up to the third generation offspring.
V transgeneracijskem preskusu pri miših so dokazali, da je dajanje valproata med brejostjo (10. dan) povzročilo avtizmu podobne simptome in povečano izražanje več proteinov v možganih vse do tretje generacije potomcev.
• The PRAC concluded that the minimisation measures for medicinal products containing valproate or related substances should be strengthened through contraindication in all indications (epilepsy, bipolar disorders and prophylaxis of migraine) in women/girls of childbearing potential unless the conditions of the pregnancy prevention programme are complied with.
• Odbor PRAC je sklenil, da je treba ukrepe za zmanjševanje tveganj za zdravila, ki vsebujejo valproat ali sorodne snovi, poostriti s kontraindikacijami pri vseh indikacijah (epilepsiji, bipolarnih motnjah in profilaksi migrene) pri ženskah/dekletih v rodni dobi, razen če so upoštevani pogoji programa za preprečevanje nosečnosti.
• The PRAC concluded that the risk minimisation measures in place have not been sufficiently effective to prevent unintended in utero exposure to valproate and related substances in all indications.
• Odbor PRAC je zaključil, da vzpostavljeni ukrepi za zmanjševanje tveganj niso bili dovolj učinkoviti, da bi pri vseh indikacijah preprečili izpostavljenost in utero valproatu in sorodnim snovem.
Among the requests from the patients and family members who were consulted was the implementation of a visual reminder on the outer package to warn the women on the harm to the unborn baby and to also promptly advise them to use effective contraception.
Med zahtevami bolnic in družinskih članov, s katerimi so bili opravljeni posveti, je bila uvedba vizualnega opomnika na zunanji ovojnini, da so ženske opozorjene na škodo za nerojenega dojenčka in da jim je pravočasno svetovana uporaba učinkovite kontracepcije.
The PRAC recommended that a patient card to be made available in all MSs and for all patients who receive valproate.
Odbor PRAC je priporočil, da je treba v vseh državah članicah in za vse bolnike, ki prejemajo valproat, priskrbeti kartice za bolnika.
With regards to the other pharmacovigilance activities and the studies are required to further investigate potential risks with products containing valproate and related substances and to measure the effectiveness of the RMMs, the CMDh clarified that these studies would not be relevant for the injectable products as the information that could be collected for these products would be limited and unlikely to be meaningful in view of the short duration of use, often in urgent situations and only when the oral formulations cannot be administered.
V zvezi z drugimi dejavnostmi na področju farmakovigilance in potrebnimi študijami za dodatno raziskavo morebitnih tveganj pri zdravilih, ki vsebujejo valproat in sorodne snovi, in za merjenje učinkovitosti ukrepov za zmanjševanje tveganj je skupina CMDh pojasnila, da te študije ne bi bile relevantne za zdravila za injiciranje, saj bi bile informacije, ki bi jih bilo mogoče za ta zdravila zbrati, omejene in najverjetneje ne bi imele pomena glede na kratkotrajnost uporabe, do katere pogosto pride v nujnih situacijah in le, če peroralnih farmacevtskih oblik ni mogoče uporabiti.
• The PRAC also reviewed the available scientific evidence on the risk of malformations and neurodevelopmental disorders to offspring after paternal exposure, the risk of malformations and neurodevelopmental disorders to the third generation offspring and considered that further research is needed before conclusions can be drawn.
• Odbor PRAC je pregledal tudi razpoložljive znanstvene dokaze o tveganju za okvare in motnje razvoja živčevja pri potomcih po izpostavljenosti pri očetu ter tveganju za okvare in motnje živčevja pri potomcih tretje generacije in menil, da so potrebne dodatne raziskave, preden bo mogoče priti do zaključkov.
Additionally, such patient card is to be attached to the packaging of valproate and related substances containing medicines, and serve as an additional reminder during the dispensing.
Poleg tega je treba takšno kartico za bolnika pritrditi na ovojnino zdravil, ki vsebujejo valproat in sorodne snovi, služi pa kot dodatno opozorilo med izdajanjem.
Theoretically this is possible by changes to the gene expression in sperm cells of adult males or by changes to the developing germ cells in the embryo.
Teoretično je to možno zaradi sprememb pri izražanju genov v celicah spermijev odraslih moških ali sprememb razvijajočih se zarodnih celic v zarodku.
The PRAC agreed that such visual reminder on the outer carton is important to warn the patient on the risk and to prompt to consult a physician and requested the inclusion of a visual reminder on the outer packaging.
Odbor PRAC se je strinjal, da je takšen vizualni opomnik na zunanji ovojnini pomemben za opozarjanje bolnice na tveganje in za poziv k posvetu z zdravnikom, ter je zahteval vključitev vizualnega opomnika v zunanjo ovojnino.
Therefore, this type of transmission is not likely to occur for valproate.
Zato je malo verjetno, da bi pri valproatu prišlo do te vrste prenosa.
A survey among HCP to assess their knowledge and behaviour with regard to the new product information restrictions and whether they received the direct healthcare professional communication (DHPC) and educational materials, and another survey among patients to assess the receipt of the educational materials should be performed.
Izvesti je treba raziskavo med zdravstvenimi delavci, da se oceni njihovo znanje in ravnanje glede novih omejitev informacij o zdravilu ter izve, ali so prejeli neposredno obvestilo za zdravstvene delavce (DHPC) in izobraževalna gradiva, ter še dodatno raziskavo med bolniki, da se oceni prejemanje izobraževalnih gradiv.
In view of the above, the PRAC recommended amendments to the product information, in particular to contraindicate its use to women of childbearing potential that do not fulfil the conditions of a pregnancy prevention program, and communication to healthcare professionals through a direct healthcare professional communication (DHPC).
Ob upoštevanju navedenega je odbor PRAC priporočil spremembe informacij o zdravilu, še posebej s kontraindiciranjem njegove uporabe pri ženskah v rodni dobi, ki ne izpolnjujejo pogojev programa za preprečevanje nosečnosti, in komunikacijo z zdravstvenimi delavci z neposrednimi sporočili za zdravstvene delavce (DHPC).
A wide consultation was done on the request of PRAC to gather all the latest information in terms of scientific and clinical knowledge with the consultation of two scientific groups (neurology and psychiatry), and to collect information from healthcare professionals, female patients themselves as well their families, from patient organisations (public hearing, stake holders meeting) who are advocating to better characterise and increase the awareness on the risk of harm to the foetus when using valproate during pregnancy.
Na zahtevo odbora PRAC je bilo opravljeno obsežno posvetovanje z dvema znanstvenima skupinama (s področja nevrologije in psihiatrije) za zbiranje vseh najnovejših informacij glede znanstvenega in kliničnega znanja ter zbiranje informacij zdravstvenih delavcev, bolnikov in njihovih družin ter organizacij bolnikov (prek javne obravnave, sestankov z deležniki), ki zagovarjajo boljše prepoznavanje in zavedanje tveganja poškodb ploda pri uporabi valproata med nosečnostjo.
This may be particularly important as the prescribers of IV formulations of valproate are expected to be different from the usual prescribers targeted during the implementation of additional risk minimisation measures.
To je lahko še posebej pomembno, saj se pričakuje, da zdravniki, ki predpisujejo intravenske farmacevtske oblike valproata, niso isti kot zdravniki, ki običajno predpisujejo zdravilo in na katere se cilja med uvedbo dodatnih ukrepov za zmanjševanje tveganj.
The guide should explain the pregnancy prevention programme and the conditions to be met prior to starting treatment with valproate.
V vodniku morajo biti pojasnjeni program preprečevanja nosečnosti in pogoji, ki jih je treba pred začetkom zdravljenja z valproatom izpolniti.
• The PRAC considered the totality of the data submitted for valproate and related substances with regard to the teratogenic and neurodevelopmental risks, the use in clinical practice and the effectiveness of the risk minimisation measures in place.
• Odbor PRAC je upošteval vse podatke, predložene za valproat in sorodne snovi, v zvezi s teratogenimi tveganji in tveganji za razvoj živčevja, uporabo v klinični praksi in učinkovitostjo pri vzpostavljenih ukrepih za zmanjševanje tveganja.
With regards to the educational materials (i.e. HCP guide and patient guide), these are also considered relevant for the injectable forms of products containing valproate and related substances and therefore should be implemented.
V zvezi z izobraževalnimi gradivi (npr. vodnikom za zdravstvene delavce in vodnikom za bolnike) velja, da so tudi primerni za farmacevtske oblike zdravil za injiciranje, ki vsebujejo valproat in sorodne snovi, in jih je zato treba uvesti.
Since the injectable formulations are indicated for short-term use with a short treatment duration, this annual risk acknowledgement form is not considered relevant therefore not applicable.
Ker so farmacevtske oblike za injiciranje indicirane za kratkotrajno uporabo pri kratkotrajnem zdravljenju, ta obrazec za letno potrjevanje seznanjenosti s tveganjem ne velja za relevantnega, torej ni smiseln.
Regarding pregnancy/family planning in epilepsy, the PRAC also highlighted that, a specialist experienced in the management of epilepsy, must reassess valproate therapy and consider alternative treatment options.
Glede nosečnosti/načrtovanja družine pri epilepsiji je odbor PRAC tudi poudaril, da mora strokovnjak z izkušnjami pri zdravljenju epilepsije ponovno oceniti zdravljenje z valproatom in pretehtati druge možnosti zdravljenja.
In order to provide adequate information, it should be tailored for different situations in the life-time of a woman and be age-appropriate: the first prescription, women continuing valproate treatment and not trying to have a child, women of childbearing potential continuing valproate treatment and considering trying to have a child, pregnant women (unplanned pregnancy) whilst continuing valproate treatment.
Da bodo informacije ustrezne, mora biti prilagojen različnim situacijam v življenju ženske in ustrezati starosti: prvemu predpisovanju, ženskam, ki nadaljujejo zdravljenje z valproatom in ne skušajo zanositi, ženskam v rodni dobi, ki nadaljujejo zdravljenje z valproatom in razmišljajo, da bi poskusile zanositi, ter nosečnicam (nenačrtovana nosečnost), ki nadaljujejo zdravljenje z valproatom.
The CMDh therefore clarified that the amendments to the product information and the other routine measures to inform on the risk to the foetus when valproate is taken in pregnancy to all Healthcare professionals (HCP) and patients are applicable to all medicinal products containing valproate and related substances, irrespective of the route of administration.
Zato je skupina CMDh pojasnila, da spremembe informacij o zdravilu in drugih rutinskih ukrepov za obveščanje vseh zdravstvenih delavcev in bolnikov o tveganju za plod pri jemanju valproata v nosečnosti veljajo za vsa zdravila, ki vsebujejo valproat in sorodne snovi, ne glede na pot uporabe.
In particular, experience from HCPs regarding the discontinuation of valproate or switch to other treatment was provided.
Zlasti so bile podane izkušnje zdravstvenih delavcev s prekinitvijo uporabe valproata ali s prehodom na druga zdravila.
This patient card should be attached at the outer carton to prompt as a reminder the discussion between the pharmacist and the patient at the time of the product dispensing.
Na zunanji ovojnini mora biti pritrjena ta kartica za bolnika, ki služi kot opomnik na razgovor med farmacevtom in bolnico v času izdajanja zdravila.
It is unknown whether slight chromosome damage might be transmitted to the offspring.
Ni znano, ali se rahle okvare kromosomov lahko prenašajo na potomce.
The CMDh acknowledges correspondence received from a MAH (Laboratoires Aguettant, France) of medicinal products containing valproate injectable (intravenous; IV) formulations, and requesting further clarity for the implementation of the pharmacovigilance activities and risk minimization measures adopted by the PRAC for these IV formulation indicated for the temporary management of epilepsy when administration via oral route is not possible.
Skupina CMDh potrjuje korespondenco, ki jo je prejela od imetnika dovoljenja za promet z zdravilom (Laboratoires Aguettant, Francija) za zdravila, ki vsebujejo farmacevtske oblike valproata za injiciranje (intravensko; IV), ter zahteva dodatna pojasnila za uvedbo dejavnosti na področju farmakovigilance in ukrepe za zmanjševanje tveganj, ki jih je sprejel odbor PRAC za te intravenske farmacevtske oblike, indicirane za začasno zdravljenje epilepsije, kadar peroralno dajanje ni mogoče.
• The PRAC also concluded that there was a need to update the educational materials aimed to fully inform patients and healthcare professionals on the risks to the unborn child when exposed in utero to valproate, and to implement some further risk minimisation measures such as a visual reminder on the outer packaging, a patient card and an acknowledgment form to raise awareness about the risks and the need for contraception.
• Odbor PRAC je tudi zaključil, da obstaja potreba po posodobitvi izobraževalnih gradiv, namenjenih izčrpnem obveščanju bolnikov in zdravstvenih delavcev o tveganjih za nerojenega otroka ob izpostavljenosti valproatu in utero , ter uvajanju določenih dodatnih ukrepov za zmanjševanje tveganja, kot so vizualno opozorilo na zunanji ovojnini, kartica za bolnika ter obrazec za potrditev seznanjenosti za povečanje osveščenosti o tveganjih in potrebi po kontracepciji.
The PRAC also reviewed the annual risk acknowledgement form which should be used and documented at initiation and during each annual review of valproate treatment by a specialist.
Odbor PRAC je pregledal tudi obrazec za letno potrditev seznanjenosti s tveganjem, ki ga mora zdravstveni delavec uporabiti in izpolniti ob začetku zdravljenja z valproatom ter ob vsakem letnem pregledu zdravljenja z valproatom.
The PRAC recommended the improvement of a HCP guide to make sure that valproate prescribers are aware of the risks associated with the use of this product in female children, women of childbearing potential and pregnant women and requested that the patients are also informed about these risks appropriately.
Odbor PRAC je priporočil izboljšanje vodnika za zdravstvene delavce, da se bodo zdravniki, ki predpisujejo valproat, zagotovo zavedali tveganj, povezanih z uporabo tega zdravila pri deklicah, ženskah v rodni dobi in nosečnicah, ter zahteval, da so o teh tveganjih ustrezno obveščene tudi bolnice.
In cases of patients for whom treatment is initiated with IV valproate formulations and then transferred to oral forms of valproate products, the patient card will be disclosed at the time of dispensing the oral valproate-containing products.
Pri bolnikih, pri katerih se zdravljenje začne z intravenskimi farmacevtskimi oblikami valproata in ki nato preidejo na peroralne oblike zdravil z valproatom, bo kartica za bolnika razkrita ob izdaji peroralnih zdravil, ki vsebujejo valproat.