natgillin/translations-raw huggingface dataset:
Risk for abuse and dependence
Tveganje za zlorabo in odvisnost
Overall summary of the scientific evaluation of Dexamed (see Annex I)
Splošni povzetek znanstvenega vrednotenja zdravila Dexamed (glejte Prilogo I)
At the final CMDh discussion, there were two major issues where agreement could not be reached by Member States.
Na zadnji razpravi skupine CMDh sta ostali odprti dve pomembnejši vprašanji, v zvezi s katerima države članice niso mogle doseči soglasja.
However it is noted that overall very few data is available in clinical practice to support this.
Vendar je treba izpostaviti, da je na splošno v klinični praksi na voljo zelo malo podatkov, s katerimi bi to lahko potrdili.
Risks associated with long term use
Tveganja, povezana z dolgotrajno uporabo
The Netherlands considered that the granting of the marketing authorisation constitutes a potential serious risk to public health.
Nizozemska je menila, da bi lahko odobritev dovoljenja za promet pomenila resno tveganje za javno zdravje;
The number of patients was small and the statistical significance of the findings is uncertain.
Bolnikov je bilo malo, zato je statistična značilnost ugotovitev negotova.
In the Elia et al. study, approximately 30% of participants did not respond to one treatment but only 4% were non-responders to both.
V študiji, ki so jo izvedli Elia in sodelavci, se na eno vrsto zdravljenja ni odzvalo približno 30 % udeležencev, samo 4 % pa se niso odzvali na obe.
All of these measures, taken together with existing national laws concerning manufacture, distribution and prescription of controlled drugs are considered to balance the risk.
Vsi ti ukrepi skupaj z obstoječimi nacionalnimi zakonodajami glede izdelave, distribucije in predpisovanja nadzorovanih drog odtehtajo tveganje.
There are, however, methodological problems with this study.
Vendar pa so bile pri tej študiji ugotovljene metodološke pomanjkljivosti.
The CHMP was therefore asked to consider:
Odbor CHMP je bil zato zaprošen, da prouči naslednje:
During the assessment of the application at Member State level, advice from the PRAC on the risk management plan was sought and the applicant agreed with the recommendation to:
Med ocenjevanjem vloge na ravni držav članic je bil odbor PRAC zaprošen za nasvet glede načrta za obvladovanje tveganja, nato pa se je predlagatelj strinjal z naslednjim priporočilom:
While the review has methodological limitations, the conclusions reached are based on relevant evidence.
Čeprav je imel pregled metodološke omejitve, končni zaključki temeljijo na ustreznih dokazih.
It is a Central Nervous System stimulant, more potent than the racemic mixture.
Je stimulant centralnega živčnega sistema, ki je močnejši od racemne zmesi.
These data are further supported by the Arnold et al. (1978) study.
Te podatke je dodatno potrdila študija, ki so jo opravili Arnold in sodelavci (1978).
There is also evidence that amfetamines increase release and turnover of serotonin.
Prav tako obstajajo dokazi, da amfetamini povečajo sproščanje in pretvorbo serotonina.
Experimentation with recreational drugs generally starts during adolescence, whereas treatment of ADHD can begin at an earlier age.
Eksperimentiranje z rekreacijskimi drogami se običajno začne v mladostništvu, medtem ko se zdravljenje ADHD lahko začne v zgodnejših letih.
The experts' panel recognises this risk but considers its frequency to be low.
Skupina izvedencev je potrdila to tveganje, vendar je menila, da je pogostnost majhna.
This retrospective (new users) study will also compare the relative risk between dexamfetamine and other stimulants in the patient population.
Ta retrospektivna (novi uporabniki) študija bo primerjala tudi relativno tveganje pri deksamfetaminu in drugih stimulantih pri populaciji bolnikov.
Therefore, the assessment of efficacy is based on an intensive literature search as well as on current European treatment guidelines.
Ocena učinkovitosti zato temelji na izčrpnem pregledu literature in veljavnih evropskih smernicah za zdravljenje.
• Introduction of a statement in section 4.8 on reporting of suspected adverse reactions.
• vključitev navedbe v poglavje 4.8 glede poročanja o domnevnih neželenih učinkih.
The author concludes that the individual patient response profiles are non-congruent, and that non-response or intolerable side effects with one stimulant do not preclude a good response to the other.
Avtor je zaključil, da profili odzivov posameznih bolnikov niso skladni in da neodzivnost ali nevzdržni neželeni učinki pri enem stimulantu ne izključujejo dobrega odziva na drugega.
The CHMP therefore considered that this publication can be regarded as supportive of efficacy but does not provide conclusive evidence.
Odbor CHMP je zato menil, da se lahko upošteva, da ta publikacija podpira učinkovitost, vendar ne zagotavlja trdnih dokazov.
It was noted that increased blood pressure may occur as well as tachycardia.
Izpostavljeno je bilo, da se lahko pojavita tako povišan krvni tlak kot tudi tahikardija.
This publication also includes a comprehensive review of the preclinical pharmacodynamics of the two compounds, which may help explain the observed variability in response.
Ta publikacija vsebuje tudi izčrpen pregled predklinične farmakodinamike obeh spojin, ki bi lahko pomagal pojasniti opaženo variabilnost v odzivu.
In addition, the CHMP recommended that the risk management plan should be further updated (see annex IV).
Poleg tega je odbor CHMP priporočil dodatno posodobitev načrta za obvladovanje tveganja (glejte Prilogo IV).
During the referral procedure, the CHMP recommended safety related changes to the product information:
Med napotitvenim postopkom je odbor CHMP priporočil spremembe informacij o zdravilu, povezane z varnostjo:
Treatment optimisation may be also easier to achieve with immediate-release forms when an initial titration phase is needed to determine the correct dosing levels.
Prav tako je z oblikami s takojšnjim sproščanjem lažje doseči optimizacijo zdravljenja, kadar je potrebna začetna titracija, da se določijo pravilne velikosti odmerkov.
The proposed risk minimisation measures are a combination of routine activities (inclusion of warnings in the product information) and the following educational materials and tools:
Predlagani ukrepi za zmanjšanje tveganja združujejo običajne dejavnosti (vključitev opozoril v informacije o zdravilu) ter naslednja izobraževalna gradiva in orodja:
The identified risk of cardiomyopathy is mainly associated with chronic use, especially with high dose use.
Ugotovljeno tveganje za kardiomiopatijo je v glavnem povezano s kronično uporabo zlasti velikih odmerkov.
Dexamfetamine, (2S)-1-phenylpropan-2-amine, is the dextrorotatory, stereoisomer of amfetamine.
Deksamfetamin, (2S)-1-fenilpropan-2-amin, je desnosučni stereoizomer amfetamina.
This is acceptable as in well-established use applications it is not required that applicants provide results of pre-clinical tests and clinical trials, these are to be replaced by appropriate scientific literature.
To je sprejemljivo, ker v vlogi za pridobitev dovoljenja za promet na podlagi dobro uveljavljene uporabe predlagateljem ni treba predložiti rezultatov predkliničnih preskusov in kliničnih preskušanj, saj namesto tega predložijo ustrezno znanstveno literaturo.
It is noted that all the guidelines mentioned in this article are from countries where dexamfetamine is already marketed for ADHD.
Pri tem je bilo zabeleženo, da so bile vse smernice, omenjene v tem članku, iz držav, v katerih deksamfetamin že ima dovoljenje za promet za uporabo pri ADHD.
The CHMP, having considered the data submitted in the application is of the opinion that the above risk management activities are necessary for the safe and effective use of the medicinal product.
Odbor CHMP je po proučitvi podatkov, predloženih v okviru vloge, menil, da so zgoraj navedene dejavnosti za obvladovanje tveganja nujne za varno in učinkovito uporabo zdravila.
Dexamfetamine is currently used for treatment of narcolepsy and attention deficit hyperactivity disorder (ADHD) in several EU countries including the reference Member State (RMS) in this procedure.
Deksamfetamin se trenutno uporablja za zdravljenje narkolepsije ter primanjkljaja pozornosti in motnje hiperaktivnosti (attention deficit hyperactivity disorder - ADHD) v več državah EU, med drugim tudi v referenčni državi članici iz tega postopka.
From the publication alone it is difficult to assess the meaningfulness of the suggested effect sizes based on which the level of response was assessed, but despite some lack of clarity regarding methodology it is noted that the conclusions are in line with those of the Elia et al. study.
Iz same publikacije je težko oceniti pomembnost opisanega obsega učinka, na podlagi katerega je bila ocenjena stopnja odziva, vendar je kljub nekaterim nejasnostim v zvezi z metodologijo mogoče zabeležiti, da so zaključki skladni s tistimi iz študije, ki so jo opravili Elia in sodelavci.
In addition, at least seven evidence-based guidelines for the pharmacological treatment of ADHD recommend dexamfetamine as first-line therapy; others give an explicit favourable recommendation for use as a therapeutic option in ADHD (Seixas et al., 2012).
Poleg tega najmanj sedem z dokazi podprtih smernic za farmakološko zdravljenje ADHD priporoča deksamfetamin kot zdravilo prve izbire, ostale pa ga izrecno priporočajo za uporabo v okviru možnosti zdravljenja ADHD (Seixas in sod., 2012).
More importantly, the Arnold LE (2000) comparative review analysed six non-duplicative studies, from which a response rate of 66% was calculated for dexamfetamine sulphate, 56% for methylphenidate and 85% stimulant response if both are tried.
Še pomembnejši pa je primerjalni pregled, ki ga je opravil Arnold LE (2000) in v katerem je analiziral šest nepodvojenih študij, na podlagi katerih je bila izračunana stopnja odziva 66 % za deksamfetaminijev sulfat, 56 % za metilfenidat in 85-odstotni odziv na stimulant, kadar sta bila preskušena oba.
• Checklists for pre-screening and on-going monitoring of patients' blood pressure, heart rate, growth (weight, height, appetite) and emergence of psychoses.
• kontrolne sezname za predhodni presejalni pregled in redno spremljanje bolnikovega krvnega tlaka, srčnega utripa, rasti (telesne mase, višine, teka) ter pojava psihoz.
This meta-analysis identified a number of key issues that may explain the differences in outcome of the studies, and the authors noted that, while building on that of Wilens et al. (2003), is still relatively modest in terms of number of studies included.
Ta metaanaliza je razkrila številne ključne zadeve, ki bi lahko pojasnile razlike v rezultatih študij, avtorji pa so izpostavili, izhajajoč iz študije, ki so jo opravili Wilens in sodelavci (2003), da so ti še vedno sorazmerno skromni glede na število vključenih študij.
The two substances have similar efficacy in ADHD but different mechanisms of action.
Učinkovini sta podobno učinkoviti pri ADHD, vendar imata različna mehanizma delovanja.
Its mechanism of action in ADHD is not fully understood, but its efficacy in treatment of ADHD has not been disputed during this procedure.
Njegov mehanizem delovanja pri ADHD ni povsem pojasnjen, vendar njegova učinkovitost pri zdravljenju ADHD v tem postopku ni bila sporna.
It is acknowledged that abuse and dependence may occur, however there appears to be a difference between the population that abuses stimulants and the general ADHD population.
Da se lahko pojavita zloraba in odvisnost, je znano dejstvo, vendar se zdi, da obstaja razlika med populacijo, ki zlorablja stimulante, in splošno populacijo bolnikov z ADHD.
Moreover short acting treatments are expected to have some advantages compared to long-acting treatments.
Poleg tega naj bi imela kratkodelujoča zdravila določene prednosti v primerjavi z dolgodelujočimi zdravili.
It is noted that age can be a dominant factor in substance use disorder.
Ugotovljeno je bilo, da je starost lahko prevladujoč dejavnik pri motnji, povezani z zlorabo snovi.
With regards to other potential risks associated with long-term use of dexamfetamine such as possible impairment of neuro-cognitive development and risk of cardiomyopathy, there is no clinical evidence to support that long-term treatment has any negative influence on neuro-cognitive development.
Kar zadeva druga možna tveganja, povezana z dolgotrajno uporabo deksamfetamina, kot sta možna prizadetost nevrokognitivnega razvoja in tveganje za kardiomiopatijo, ni na voljo nobenih kliničnih dokazov, ki bi kazali na to, da ima dolgotrajno zdravljenje kakršen koli negativen vpliv na nevrokognitivni razvoj.
• Amendment to the section 4.1 to advise that “Treatment should be under the supervision of a specialist in childhood and/or adolescent behavioural disorders.” and that “Dexamfetamine is not indicated in all children with ADHD and the decision to use dexamfetamine must be based on a very thorough assessment of the severity and chronicity of the child's symptoms in relation to the child's age and potential for abuse, misuse or diversion.”
• spremembe poglavja 4.1, tako da se vključi priporočilo: „Zdravljenje mora nadzorovati specialist na področju vedenjskih motenj v otroštvu in/ali mladostništvu“ ter navedba, da „deksamfetamin ni indiciran pri vseh otrocih z ADHD, odločitev o uporabi deksamfetamina pa mora temeljiti na zelo natančni oceni resnosti in kroničnosti otrokovih simptomov ob upoštevanju starosti otroka in možnosti za zlorabo, napačno uporabo ali uporabo za rekreativne namene“;
Lisdexamfetamine was recently approved in some Member States as part of a comprehensive treatment programme for ADHD in children aged 6 years of age and over when response to previous methylphenidate treatment is considered clinically inadequate.
Lisdeksamfetamin je bil pred kratkim v nekaterih državah članicah odobren kot del celovitega programa zdravljenja ADHD pri otrocih, starih 6 let ali več, pri katerih je bil odziv na predhodno zdravljenje z metilfenidatom ocenjen kot klinično nezadosten.
In addition, ADHD patients are prescribed stimulants after an ADHD diagnosis has been made as opposed to deliberately seeking stimulants.
Poleg tega bolniki z ADHD dobijo stimulante na recept, potem ko se postavi diagnoza ADHD, v nasprotju s tistimi, ki namenoma poskušajo dobiti stimulante.
The relevant sections of the product information were updated accordingly.
Zadevna poglavja informacij o zdravilu so bila ustrezno spremenjena.
The CHMP took note of the fact that the proposed RMP is in line with existing risk management plans for other stimulants (methylphenidate and lisdexamfetamine), and also that dexamfetamine-containing products have been available in the EU for several decades without a risk management plan.
Odbor CHMP je upošteval dejstvo, da je predlagan načrt za obvladovanje tveganja skladen z že obstoječimi načrti za obvladovanje tveganja za druge stimulante (metilfenidat in lisdeksamfetamin) in da so zdravila, ki vsebujejo deksamfetamin, v EU že več desetletij na voljo brez načrta za obvladovanje tveganja.
The Committee also noted that dexamfetamine-containing products have been available in the EU for several years without a risk management plan and therefore the introduction of a dexamfetamine product with a risk management plan is expected to represent a significant improvement for patients.
Odbor je izpostavil tudi, da so zdravila, ki vsebujejo deksamfetamin, v EU že več let na voljo brez načrta za obvladovanje tveganja, zaradi česar je pričakovati, da bo odobritev deksamfetamina z načrtom za obvladovanje tveganja prinesla pomembno izboljšanje za bolnike.
Grounds for positive opinion, amendments of the summary of product characteristics and package leaflet, and conditions to the Marketing Authorisations
Podlaga za pozitivno mnenje, spremembe povzetka glavnih značilnosti zdravila in navodila za uporabo ter pogoji dovoljenj za promet z zdravili
Lastly, it is noted that lisdexamfetamine is an inactive prodrug which is absorbed to the bloodstream where it is gradually converted to dexamfetamine.
Prav tako je bilo zabeleženo, da je lisdeksamfetamin neaktivno predzdravilo, ki se absorbira v krvni obtok, kjer se postopoma pretvori v deksamfetamin.
Although it is acknowledged that misuse, abuse, dependence and diversion are events that will not always be reported to the prescribers, the search retrieved a very low event rate in the countries where dexamfetamine is available on the market for ADHD.
Čeprav je znano, da so napačna uporaba, zloraba, odvisnost in uporaba za rekreativne namene dogodki, o katerih zdravstveni delavci, ki predpisujejo zdravila, niso vedno obveščeni, je pregled razkril zelo majhno pogostnost dogodkov v državah, v katerih je deksamfetamin dostopen na trgu za uporabo pri ADHD.
Furthermore educational materials would also be made available for both physicians and patients, including the provision of checklists, and are in line with those for other ADHD medicines.
Prav tako bi zagotovili izobraževalno gradivo za zdravnike in bolnike, ki bi vključevalo kontrolne sezname in bi bilo skladno s tistimi, ki so na voljo za druga zdravila za ADHD.
The CHMP issued a positive opinion recommending the granting of the marketing authorisations for which the summary of product characteristics and package leaflet are as set out in Annex III of the CHMP opinion and conditions to the marketing authorisations in Annex IV of the CHMP Opinion for Dexamed and associated names (see Annex I).
Odbor CHMP je izdal pozitivno mnenje, v katerem je priporočil odobritev dovoljenj za promet z zdravili, za katera sta povzetek glavnih značilnosti zdravila in navodilo za uporabo opredeljena v Prilogi III k mnenju odbora CHMP, pogoji dovoljenj za promet z zdravili pa v Prilogi IV k mnenju odbora CHMP o zdravilu Dexamed in povezanih imen (glejte Prilogo I).
Therefore the introduction of a dexamfetamine product with a risk management plan is expected to provide significant improvement by collecting information about use of the product in real life setting, as well as introducing risk minimisation measures that are currently not in place.
Zato se pričakuje, da bo uvedba zdravila, ki vsebuje deksamfetamin, z načrtom za obvladovanje tveganja prinesla pomembne izboljšave, saj se bodo pridobili podatki o uporabi zdravila v realnem življenju in uvedli ukrepi za zmanjšanje tveganja, ki jih trenutno ni.
• Introduction of a statement in section 4.4 on “Abuse, misuse, and diversion” reporting that the risk is generally greater for short acting stimulants than for corresponding long-acting products.
• vključitev navedbe v poglavje 4.4 o „zlorabi, napačni uporabi in uporabi za rekreativne namene“, ki pojasnjuje, da je tveganje običajno večje pri kratkodelujočih stimulantih kot pri ustreznih dolgodelujočih zdravilih;
In other publications, authors seem to have further concluded that ADHD treatment with stimulants during childhood is associated with a reduction in the risk of substance use disorder later in life (Biederman et al. 1999; Wilens et al. 2003).
V drugih publikacijah so avtorji nadalje zaključili, da je zdravljenje ADHD s stimulanti v otroštvu povezano z zmanjšanjem tveganja za razvoj motnje, povezane z zlorabo snovi, kasneje v življenju (Biederman in sod.
During treatments regular evaluations should be performed regarding treatment necessity (see below) and possible occurrence of overuse, dependence or diversion.
Med zdravljenjem je treba redno ocenjevati potrebo po zdravljenju (glejte nadaljevanje) in morebiten pojav čezmerne uporabe, odvisnosti ali uporabe za rekreativne namene.
These and the other measures in the risk management plan are proposed to ensure that dexamfetamine is only made available to patients who really need it and can benefit from it, therefore mitigating the risk of misuse and diversion.
Ti in drugi ukrepi v načrtu za obvladovanje tveganja so bili predlagani, da bi se zagotovilo, da bo deksamfetamin dostopen samo tistim bolnikom, ki ga zares potrebujejo in imajo od njega lahko koristi, s čimer bi se zmanjšalo tveganje za napačno uporabo in uporabo za rekreativne namene.
In addition the applicant proposed to undertake a drug utilisation study (DUS) to monitor for reports of abuse and/or overdose, and a non-interventional post authorisation safety study (PASS) to monitor key adverse events.
Poleg tega je predlagatelj predlagal, da bi izvedli študijo o uporabi zdravila, namenjeno spremljanju poročil o zlorabi in/ali prevelikem odmerjanju, ter neintervencijsko študijo o varnosti zdravila po pridobitvi dovoljenja za promet (PASS) za spremljanje ključnih neželenih dogodkov.
However, a more recent meta-analysis by Humphreys et al. (2013) investigated both published and unpublished reports on a total of 15 different studies and concluded that effective treatment of ADHD, typically using methylphenidate, does not seem to have impact of substance abuse later in life.
Vendar pa so v novejši metaanalizi, ki so jo opravili Humphreys in sodelavci (2013), proučili tako objavljena kot neobjavljena poročila o skupno 15 različnih študijah in zaključili, da učinkovito zdravljenje ADHD, običajno z uporabo metilfenidata, ne vpliva na zlorabo snovi kasneje v življenju.
Therefore it is currently unclear whether treatment of ADHD patients with stimulants alters their risk of substance abuse disorder later in life, but evidence seems to indicate that the risk in the stimulant treated ADHD population is not higher than in the not treated ADHD population.
Trenutno torej ni jasno, ali zdravljenje bolnikov z ADHD s stimulanti vpliva na tveganje za motnjo, povezano z zlorabo snovi, kasneje v življenju, vendar dokazi kažejo, da tveganje pri populaciji bolnikov z ADHD, zdravljenih s stimulanti, ni večje kot pri nezdravljeni populaciji bolnikov z ADHD.
The experts consulted expressed the fact that ADHD is less likely to produce euphoria in children when the products are used as intended.
Izvedenci, ki so bili zaprošeni za mnenje, so izpostavili dejstvo, da je veliko manj verjetno, da bi ADHD povzročila evforijo pri otrocih, kadar se zdravila uporabljajo, kot je predvideno.
Therefore, the CHMP was of the opinion that the benefit/risk ratio of Dexamed and associated names is considered to be favourable.
Odbor CHMP je zato menil, da se razmerje med tveganji in koristmi zdravila Dexamed in povezanih imen lahko šteje za ugodno.
Ramtvedt et al. (2013) have reported that in a cross-over clinical study including 36 children with a diagnostic of ADHD (as per Norwegian diagnostic guidelines), who received, in sequence, 2 weeks each of methylphenidate, dexamfetamine and placebo, dexamfetamine and methylphenidate each produced a favourable response in 26 children (72%), but not always the same child.
Ramtvedt in sodelavci (2013) so poročali, da sta v navzkrižni klinični študiji, v katero so vključili 36 otrok z diagnosticirano ADHD (v skladu z norveškimi smernicami za diagnostiko), ki so po vrsti po 2 tedna prejemali metilfenidat, deksamfetamin in placebo, tako deksamfetamin kot metilfenidat povzročila ugoden odziv pri 26 otrocih (72 %), vendar ne vedno oba pri istem otroku.
Clinical studies show that there are ADHD patients who respond to methylphenidate and not to dexamfetamine and vice versa.
Klinične študije kažejo, da obstajajo bolniki z ADHD, ki se odzovejo na metilfenidat, vendar se ne odzovejo na deksamfetamin, in obratno.
During the procedure the MAH conducted further research in the literature, online, in databases from European Health Authorities and WHO and its own safety database.
Med postopkom je imetnik dovoljenja za promet z zdravilom dodatno raziskal literaturo, splet, podatkovne zbirke evropskih zdravstvenih organov in SZO ter lastno zbirko podatkov o varnosti.
In addition, the DUS should be expanded to actively obtain reports of abuse, misuse, diversion and dependence in children with ADHD from poison centres, drug monitoring centres, other databases, publicly available information in the literature and online.
Poleg tega je študijo o uporabi zdravila treba razširiti, tako da bo omogočala aktivno zbiranje poročil o zlorabi, napačni uporabi, uporabi za rekreativne namene in odvisnosti pri otrocih z ADHD iz centrov za zastrupitve, centrov za spremljanje drog, drugih podatkovnih zbirk, javno dostopnih informacij iz literature in spleta;