natgillin/translations-raw huggingface dataset:
-for grade 3 and 4 toxicity, treatment should be discontinued and not resumed until events have been resolved.
Takšen način dajanja vzdržujte celoten čas zdravljenja; - pri 3. in 4. stopnji toksičnosti zdravljenje prekinite, dokler dogodki ne izzvenijo.
In addition, a number of typographical and QRD-related changes were made.
Izvedenih je bilo tudi več tipografskih sprememb in sprememb, povezanih s QRD.
Corresponding changes were made, where relevant, to the currently approved product information.
Kadar je bilo potrebno, so bile izvedene tudi pripadajoče spremembe trenutno odobrenih informacij o zdravilu.
The renin-angiotensin system (RAS) is a hormone system that regulates blood pressure and fluid balance.
Renin-angiotenzinski sistem (RAS) je hormonski sistem, ki uravnava krvni tlak in tekočinsko ravnovesje.
This is of particular concern, as
Ob upoštevanju naslednjega:
these patients and patients with renal impaired are already particularly prone to developing hyperkalaemia.
To je zlasti zaskrbljujoče, saj so ti bolniki in bolniki z ledvično okvaro še posebej nagnjeni k razvoju hiperkaliemije.
Changes were made to the heart failure indication in section 4.4 for candesartan-containing products and in sections 4.2 and 4.4 for valsartan-containing products, in order to further harmonise the wording for the two substances.
Spremembe so bile izvedene za indikacijo srčnega popuščanja v poglavju 4.4 za zdravila, ki vsebujejo kandesartan, in v poglavjih 4.2 in 4.4 za zdravila, ki vsebujejo valsartan, z namenom nadaljnje uskladitve besedila za obe učinkovini.
1 - Overall summary of the scientific evaluation by PRAC
1 - Splošni povzetek znanstvenega vrednotenja odbora PRAC
However, the CHMP considered that minor additional changes were necessary to the wording proposed for the Summary of Product Characteristics.
Vendar pa je menil, da so potrebne manjše dodatne spremembe besedila, predlaganega za povzetek glavnih značilnosti zdravila.
In particular the contraindication statements recommended by the PRAC were deleted from sections 5.1 (where proposed) and from section 4.4 for aliskiren, as these were already proposed in section 4.3 and therefore considered redundant.
Iz poglavja 5.1 (kjer je bilo predlagano) in poglavja 4.4 za aliskiren so bile izbrisane zlasti izjave o kontraindikacijah, ki jih je priporočil odbor PRAC, saj so bile že predlagane v poglavju 4.3 in zato nepotrebne.
RAS-acting agents include angiotensin-converting enzyme inhibitors (ACEinhibitors) such as benazepril, captopril, cilazapril, delapril, enalapril, fosinopril, imidapril, lisinopril, moexipril, perindopril, quinapril, ramipril, spirapril, trandolapril and zofenopril), angiotensin receptor blockers (ARBs) such as candesartan, telmisartan, valsartan, irbesartan, eprosartan, olmesartan, losartan and azilsartan and direct renin inhibitors such as aliskiren.
Med snovi, ki delujejo na renin-angiotenzinski sistem, spadajo zaviralci angiotenzin konvertirajočega encima (zaviralci ACE), kot so benazepril, kaptopril, cilazapril, delapril, enalapril, fosinopril, imidapril, lisinopril, moeksipril, perindopril, kvinapril, ramipril, spirapril, trandolapril in zofenopril, zaviralci angiotenzinskih receptorjev (ARB-ji), kot so kandesartan, telmisartan, valsartan, irbesartan, eprosartan, olmesartan, losartan in azilsartan, in neposredni zaviralci renina, kot je aliskiren.
Grounds for PRAC recommendation
Razlogi za priporočilo odbora PRAC
The PRAC therefore concluded that the product information of all RAS-acting agents should be revised to reflect the identified risks and provide guidance to prescribers and patients.
Zaključil je, da je treba informacije o zdravilu vseh snovi, ki delujejo na reninangiotenzinski sistem, spremeniti tako, da odražajo ugotovljena tveganja in zagotavljajo smernice za zdravnike, ki to zdravilo predpisujejo, in bolnike.
RAS-acting agents act by blocking different stages of the renin-angiotensin system, lowering blood pressure and their use in the treatment of hypertension and its complications (including acute myocardial infarction, congestive heart failure and chronic kidney disease) is recommended in many current clinical guidelines.
Snovi, ki delujejo na renin-angiotenzinski sistem, delujejo tako, da zavirajo različne faze renin-angiotenzinskega sistema ter tako znižujejo krvni tlak, njihova uporaba pri zdravljenju hipertenzije in z njo povezanih zapletov (vključno z akutnim miokardnim infarktom, kongestivnim srčnim popuščanjem in kronično boleznijo ledvic) pa je priporočena v mnogih trenutnih kliničnih smernicah.
It was noted that the Committee for Medicinal Products for Human Use (CHMP) had already conducted a review2 under Article 20 of Regulation (EC) No 726/2004 for aliskiren-containing products, concluding that these products should be contraindicated in patients with diabetes mellitus or moderate to severe renal impairment who take ACE-inhibitors or ARBs.
Zabeležili so, da je Odbor za zdravila za uporabo v humani medicini (CHMP) že izvedel pregled2 v skladu s členom 20 Uredbe (ES) št. 726/2004 za zdravila, ki vsebujejo aliskiren, in zaključil, da so ta zdravila kontraindicirana pri bolnikih s sladkorno boleznijo ali zmerno do hudo ledvično okvaro, ki jemljejo zaviralce ACE ali zaviralce angiotenzinskih receptorjev.
Having considered the new available evidence from the scientific literature and given the seriousness of the identified safety concerns, the Italian Medicines Agency (AIFA) decided to initiate a review under Article 31 of Council Directive 2001/83/EC on 17 April 2013, referring the matter to the Pharmacovigilance Risk Assessment Committee (PRAC) and requesting the PRAC to issue a recommendation on the benefit-risk of dual RAS blockade therapy through the combined use of ACEinhibitors, ARBs or aliskiren and whether any regulatory measures should be taken on the marketing authorisations of the products involved in this procedure.
Po preučitvi novih razpoložljivih dokazov iz znanstvene literature in glede na resnost ugotovljenih zadržkov v zvezi z varnostjo je italijanska agencija za zdravila (AIFA) 17. aprila 2013 sprožila pregled v skladu s členom 31 Direktive Sveta 2001/83/ES in zadevo napotila na Odbor za oceno tveganja na področju farmakovigilance (PRAC) ter od njega zahtevala, da izda priporočilo o razmerju med tveganji in koristmi zdravljenja z dvojnim zaviranjem renin-angiotenzinskega sistema s kombinirano uporabo zaviralcev ACE, zaviralcev angiotenzinskih receptorjev ali aliskirena in navede, ali bi bilo treba sprejeti kakršne koli regulativne ukrepe za dovoljenja za promet z zdravili, ki so predmet tega postopka.
The PRAC considered that the overall available data strongly suggests that the concerns identified with regard to safety and the lack of efficacy are a class effect and therefore considered that the conclusions of the review apply to all the active substances involved in the procedure.
Odbor PRAC je menil, da skupni razpoložljivi podatki jasno kažejo, da so ugotovljeni zadržki v zvezi z varnostjo in pomanjkanjem učinkovitosti razredni učinek, zato je menil, da zaključki pregleda veljajo za vse zdravilne učinkovine v tem postopku.
• The PRAC considered the procedure under Article 31 of Directive 2001/83/EC initiated by Italy following the emergence of new evidence on the efficacy and safety of dual RAS blockade therapy through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren, to determine whether any regulatory measures should be taken on the marketing authorisations of the products involved in this procedure;
• Odbor PRAC je preučil postopek v skladu s členom 31 Direktive 2001/83/ES, ki ga je sprožila Italija po pojavu novih dokazov o učinkovitosti in varnosti zdravljenja z dvojnim zaviranjem reninangiotenzinskega sistema s kombinirano uporabo zaviralcev ACE, zaviralcev angiotenzinskih receptorjev II ali aliskirena, da bi določili, ali bi bilo treba sprejeti kakršne koli regulativne ukrepe za dovoljenja za promet z zdravili, ki so predmet tega postopka;
In addition, the meta-analysis suggested that using multiple RAS-acting agents may not be more beneficial than using a single RAS-acting agent in terms of reducing overall mortality.
Poleg tega je metaanaliza pokazala, da uporaba več snovi, ki delujejo na renin-angiotenzinski sistem, morda ni koristnejša od uporabe ene snovi, ki deluje na renin-angiotenzinski sistem, kar zadeva zmanjšanje celokupne smrtnosti.
However, new data has emerged in the past years, raising doubts over the efficacy and identifying safety concerns associated with dual RAS blockade therapy through the combined use of ACE-inhibitors, ARBs or aliskiren.
Vendar so bili v zadnjih letih objavljeni novi podatki, ki so povečali dvome o učinkovitosti in prepoznavanju zadržkov v zvezi z varnostjo, povezanih z zdravljenjem z dvojnim zaviranjem renin-angiotenzinskega sistema s kombinirano uporabo zaviralcev ACE, zaviralcev angiotenzinskih receptorjev ali aliskirena.
3 ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial 4 Veterans Affairs Nephropathy in Diabetes 5 Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Endpoints
3 ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial 4 Veterans Affairs Nephropathy in Diabetes 5 Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Endpoints pod nadzorom zdravnika specialista in se pri njih pogosto skrbno spremlja delovanje ledvic, vrednosti elektrolitov in krvni tlak.
In particular, a number of trials in heart failure patients have shown that the addition of a second RASacting agent may reduce hospital admissions for heart failure in patients with heart failure, which is considered a meaningful clinical endpoint.
Zlasti številna preskušanja pri bolnikih s srčnim popuščanjem so pokazala, da lahko dodatek druge snovi, ki deluje na renin-angiotenzinski sistem, zmanjša število sprejemov v bolnišnico zaradi srčnega popuščanja pri bolnikih s srčnim popuščanjem, kar velja za pomembno klinično končno točko.
The PRAC was also of the opinion that the contraindication based on the ALTITUDE5 study data regarding the concomitant use of ACE-inhibitors or ARBs with aliskiren-containing products in patients with diabetes mellitus or renal impairment (glomerular filtration rate (GFR) < 60 ml/min/1.73 m2) was confirmed by the additional data reviewed and that it should also be implemented in the product information of ARBs and ACE-inhibitors.
Prav tako je menil, da dodatni pregledani podatki potrjujejo kontraindikacijo na podlagi podatkov iz študije ALTITUDE5 glede sočasne uporabe zaviralcev ACE ali zaviralcev angiotenzinskih receptorjev z zdravili, ki vsebujejo aliskiren, pri bolnikih s sladkorno boleznijo ali ledvično okvaro (stopnja glomerularne filtracije < 60 ml/min/1,73 m2) in da je treba to kontraindikacijo prav tako vključiti v informacije o zdravilu za zaviralce angiotenzinskih receptorjev in zaviralce ACE.
The PRAC reviewed the totality of the available data, including clinical trials, meta-analysis and publications, the MAHs' responses as well as the report from the Scientific Advisory Group in Cardiovascular Issues (SAG CVS).
Odbor PRAC je pregledal vse razpoložljive podatke, vključno s kliničnimi preskušanji, metaanalizami in publikacijami, odgovori imetnikov dovoljenj za promet z zdravili ter poročilom znanstveno svetovalne skupine za srčno-žilna vprašanja (SAG CVS).
Treatment should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure.
Zdravljenje se lahko izvaja samo pod nadzorom zdravnika specialista in med zdravljenjem je potrebno pogosto skrbno spremljanje delovanja ledvic, vrednosti elektrolitov in krvnega tlaka.
• The PRAC reviewed the totality of the available data, including clinical trials, meta-analysis and publications, the MAHs' responses as well as the report from the Scientific Advisory Group in Cardiovascular Issues;
• Odbor PRAC je pregledal vse razpoložljive podatke, vključno s kliničnimi preskušanji, metaanalizami in publikacijami, odgovori imetnikov dovoljenj za promet z zdravili ter poročilom znanstveno svetovalne skupine za srčno-žilna vprašanja;
The PRAC therefore concluded that dual RAS blockade therapy should not be routinely used in the treatment of heart failure and is not recommended in the general population although it may benefit certain patients who remain symptomatic while receiving monotherapy or who cannot otherwise use alternative therapies, including potentially patients with diabetic nephropathy.
Zato je zaključil, naj se zdravljenje z dvojnim zaviranjem renin-angiotenzinskega sistema ne uporablja rutinsko pri zdravljenju srčnega popuščanja in da to zdravljenje ni priporočeno pri splošni populaciji, čeprav lahko koristi določenim bolnikom, pri katerih simptomi med prejemanjem monoterapije ne izginejo ali pri katerih nadomestno zdravljenje ni mogoče, morebiti vključno z bolniki z diabetično nefropatijo.
The PRAC however clearly specified, based on data from the ONTARGET3 and VA NEPHRON-D4 studies that ACE-inhibitors and ARBs should not be used concomitantly in patients with diabetic nephropathy.
Vendar pa je jasno navedel, da na podlagi podatkov iz študij ONTARGET3 in VA NEPHRON-D4 sočasna uporaba zaviralcev ACE in zaviralcev angiotenzinskih receptorjev ni dovoljena pri bolnikih z diabetično nefropatijo.
The CHMP, having considered the PRAC recommendation, agrees with the overall scientific conclusions by the PRAC and is of the opinion that the marketing authorisations for RAS-acting agents should be varied.
Po preučitvi priporočila odbora PRAC se je odbor CHMP strinjal z njegovimi splošnimi znanstvenimi zaključki in menil, da je treba dovoljenja za promet z zdravili za snovi, ki delujejo na reninangiotenzinski sistem, spremeniti.
Scientific conclusions and detailed explanation of the scientific grounds for the differences from the PRAC recommendation
Znanstveni zaključki in podrobna obrazložitev znanstvenih razlogov za odstopanja od priporočila odbora PRAC
• The PRAC was of the view that there is considerable evidence, in particular from the ONTARGET, ALTITUDE and VA NEPHRON-D trials which conclusively demonstrates that dual RAS blockade therapy through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated with an increased risk of adverse events, including hypotension, hyperkalaemia and renal failure compared to monotherapy;
• Odbor PRAC je menil, da obstaja veliko dokazov, zlasti iz preskušanj ONTARGET, ALTITUDE in VA NEPHRON-D, ki jasno kažejo, da je zdravljenje z dvojnim zaviranjem renin-angiotenzinskega sistema s kombinirano uporabo zaviralcev ACE, zaviralcev angiotenzinskih receptorjev II ali aliskirena povezano s povečanim tveganjem za neželene dogodke, vključno s hipotenzijo, hiperkaliemijo in ledvično odpovedjo, v primerjavi z monoterapijo;
The concept of dual RAS blockade through the combined use of several RAS-acting agents, emerged in the late 1990's based on an experimental model hypothesising that the combined use of an ARB, an ACE-inhibitor or aliskiren could provide a more complete blockade of the RAS which could translate into better control of blood pressure and nephroprotective and cardioprotective effects.
Zasnova dvojnega zaviranja renin-angiotenzinskega sistema s kombinirano uporabo več snovi, ki delujejo na renin-angiotenzinski sistem, se je pojavil v poznih 90. letih 20. stoletja na eksperimentalnem modelu, katerega hipoteza je bila, da lahko kombinirana uporaba zaviralca angiotenzinskih receptorjev, zaviralca ACE ali aliskirena zagotovi močnejše zaviranje reninangiotenzinskega sistema, kar bi lahko pomenilo boljše obvladovanje krvnega tlaka ter nefroprotektivnih in kardioprotektivnih učinkov.
2 - Detailed explanation of the scientific grounds for differences from the PRAC recommendation
2 - Podrobna obrazložitev znanstvenih razlogov za odstopanja od priporočila odbora PRAC
• The PRAC considered that the available efficacy data indicates that dual RAS blockade therapy does not provide significant benefit in the general patient population although certain patient subpopulations may benefit from treatment, provided that it occurs only under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure;
• Odbor PRAC je menil, da razpoložljivi podatki o učinkovitosti nakazujejo, da zdravljenje z dvojnim zaviranjem renin-angiotenzinskega sistema ne zagotavlja pomembne koristi pri splošni populaciji bolnikov, čeprav lahko določeni podpopulaciji bolnikov to zdravljenje koristi, če poteka pod nadzorom zdravnika specialista in se pogosto skrbno spremlja delovanje ledvic, vrednosti elektrolitov in krvnega tlaka;
The PRAC was of the opinion that the concerns identified during this procedure with regard to the safety and the lack of efficacy of dual RAS blockade therapy could be adequately managed through changes to the product information, without the need for additional risk minimisation measures.
Odbor PRAC je menil, da je mogoče zadržke, ugotovljene med tem postopkom v zvezi z varnostjo in pomanjkanjem učinkovitosti zdravljenja z dvojnim zaviranjem renin-angiotenzinskega sistema, ustrezno obvladovati s spremembami informacij o zdravilu brez potrebe po dodatnih ukrepih za zmanjševanje tveganja.
The PRAC considered that the available efficacy data indicates that dual RAS blockade therapy does not provide significant benefit in the general patient population, although there is evidence to suggest that some selected patient subpopulations may benefit from this dual RAS blockade therapy.
Odbor PRAC je menil, da razpoložljivi podatki o učinkovitosti kažejo, da zdravljenje z dvojnim zaviranjem renin-angiotenzinskega sistema ne zagotavlja pomembne koristi pri splošni populaciji bolnikov, čeprav obstajajo dokazi, ki kažejo na to, da lahko nekaterim izbranim podpopulacijam bolnikov to zdravljenje z dvojnim zaviranjem renin-angiotenzinskega sistema koristi.
A warning was introduced to state that dual RAS blockade therapy through the combined use of ACE-inhibitors, ARBs or aliskiren is not recommended and, if considered absolutely necessary, should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure.
Uvedeno je bilo opozorilo, da zdravljenje z dvojnim zaviranjem renin-angiotenzinskega sistema s kombinirano uporabo zaviralcev ACE, zaviralcev angiotenzinskih receptorjev ali aliskirena ni priporočeno in da se lahko uporabi, če je nujno potrebno, samo pod nadzorom zdravnika specialista in ob stalnem skrbnem spremljanju delovanja ledvic, vrednosti elektrolitov in krvnega tlaka.
Annex IV Scientific conclusions, grounds for variation to the terms of the marketing authorisations and detailed explanation of the scientific grounds for the differences from the PRAC recommendation
Znanstveni zaključki, podlaga za spremembo pogojev dovoljenj za promet z zdravilom ter podrobna obrazložitev znanstvenih razlogov za odstopanja od priporočila odbora PRAC
• The PRAC was of the opinion that the concerns identified with regard to safety and the lack of additional efficacy of dual RAS blockade therapy are a class effect and that the conclusions of the review therefore apply to all the active substances involved in this procedure;
• Odbor PRAC je menil, da so zadržki, ugotovljeni v zvezi z varnostjo in pomanjkanjem dodatne učinkovitosti zdravljenja z dvojnim zaviranjem renin-angiotenzinskega sistema, razredni učinek in da zaključki pregleda zato veljajo za vse zdravilne učinkovine v tem postopku;
The PRAC concluded that the benefit-risk balance of RAS-acting agents remains favourable, including in the context of dual RAS blockade therapy, subject to the agreed revisions to the product information.
Odbor PRAC je zaključil, da razmerje med tveganji in koristmi za snovi, ki delujejo na reninangiotenzinski sistem, ostaja ugodno, tudi pri zdravljenju z dvojnim zaviranjem renin-angiotenzinskega sistema, ob upoštevanju dogovorjenega pregleda informacij o zdravilu.
Having considered the matter, the PRAC therefore recommended the variation of the marketing authorisations for RAS-acting agents.
Po preučitvi zadeve je priporočil spremembo dovoljenj za promet z zdravili za snovi, ki delujejo na reninangiotenzinski sistem.
The PRAC was of the opinion that there is considerable evidence from large clinical trials and meta-analyses which conclusively demonstrates that dual RAS blockade therapy through the combined use of ACE-inhibitors, ARBs or aliskiren is associated with an increased risk of adverse events, including hypotension, hyperkalaemia and renal failure compared to monotherapy, in particular in patients with diabetic nephropathy.
Menil je, da obstaja veliko dokazov iz obsežnih kliničnih preskušanj in metaanaliz, ki jasno kažejo, da je zdravljenje z dvojnim zaviranjem reninangiotenzinskega sistema s kombinirano uporabo zaviralcev ACE, zaviralcev angiotenzinskih receptorjev ali aliskirena povezano s povečanim tveganjem za neželene učinke, vključno s hipotenzijo, hiperkaliemijo in ledvično odpovedjo, v primerjavi z monoterapijo, zlasti pri bolnikih z diabetično nefropatijo.
The PRAC, as a consequence, concluded that the benefit-risk balance of RAS-acting agents remains favourable, provided that their product information is revised to reflect the concerns associated with dual RAS blockade therapy.
je odbor PRAC zaključil, da razmerje med tveganji in koristmi za snovi, ki delujejo na reninangiotenzinski sistem, ostaja ugodno, če se uvedejo spremembe informacij o zdravilu, tako da bodo odražale zadržke, povezane z zdravljenjem z dvojnim zaviranjem renin-angiotenzinskega sistema.
• The PRAC was of the opinion that the concerns identified with regard to the safety and the lack of additional efficacy of dual RAS blockade therapy can be adequately managed through changes to the product information, without the need for additional risk minimisation measures.
• Odbor PRAC je menil, da je mogoče zadržke, ugotovljene v zvezi z varnostjo in pomanjkanjem dodatne učinkovitosti zdravljenja z dvojnim zaviranjem renin-angiotenzinskega sistema, ustrezno obvladovati s spremembami informacij o zdravilu brez potrebe po dodatnih ukrepih za zmanjševanje tveganja;
For candesartan- and valsartan-containing products, which are also authorised in the treatment of heart failure, additional information was agreed upon to reflect the fact that dual RAS blockade therapy in combination with an ACE-inhibitor may be of benefit in certain patients who cannot use other heart failure treatments, provided that they are used under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure.
Za zdravila, ki vsebujejo kandesartan in valsartan, ki so prav tako odobrena za zdravljenje srčnega popuščanja, so sprejeli dodatne informacije, ki odražajo, da je lahko zdravljenje z dvojno blokado renin-angiotenzinskega sistema v kombinaciji z zaviralci ACE koristno pri določenih bolnikih, pri katerih ni mogoče uporabiti drugih vrst zdravljenja za srčno popuščanje, če so
In particular, the publication of a meta-analysis by Makani et al1 involving over 68,000 patients raised concerns that combining several RAS-acting agents may be associated with an increased risk of hyperkalaemia, hypotension and kidney failure, compared with the single use of one RAS-acting agent.
Zadržki, da je lahko kombinacija več snovi, ki delujejo na renin-angiotenzinski sistem, povezana s povečanim tveganjem za hiperkaliemijo, hipotenzijo in ledvično odpovedjo v primerjavi z uporabo samo ene snovi, ki deluje na reninangiotenzinski sistem, so se pojavili predvsem zaradi objave metaanalize, ki so jo izvedli Makani in sod.1 in je vključevala več kot 68 000 bolnikov.
Follow-up continued up to Day 77.
Spremljanje se je nadaljevalo do 77. dneva.
Date of first authorisation: 21 March 2002 Date of latest renewal: 21 March 2007
Datum pridobitve dovoljenja za promet: 21. marec 2002 Datum zadnjega podaljšanja dovoljenja za promet: 21. marec 2007
Conditions you need to look out for
Stanja, na katera morate biti pozorni
This is shown in Picture 3 at the beginning of these instructions
Opisano prikazuje slika 3 na začetku tega navodila.