FrancophonIA/ELRC3.0 huggingface dataset:
English: Some new potential, very rare and reversible adverse effects were highlighted during the referral procedure, including trombocytopenia, agranulocytosis and liver dysfunction and have been included in the risk management plan (RMP) and reflected in the relative sections of the SmPC.
Slovenian: Med napotitvenim postopkom so bili izpostavljeni nekateri novi možni, zelo redki in reverzibilni neželeni učinki, vključno s trombocitopenijo, agranulocitozo in jetrno disfunkcijo, ki so bili vključeni v načrt obvladovanja tveganja (RMP) in navedeni v ustreznih poglavjih povzetka glavnih značilnosti zdravila.
English: It is considered that the study is only adequate to show the efficacy of trimetazidine with reference to the primary endpoint, time to onset of angina pectoris, as no significant difference between groups could be found for the other secondary endpoints (total exercise duration, total workload and clinical endpoints).
Slovenian: Študija se obravnava kot ustrezna le za prikaz učinkovitosti trimetazidina glede na primarni opazovani dogodek, čas do pojava angine pektoris, saj pomembnih razlik med skupinama za druge sekundarne opazovane dogodke ni bilo mogoče ugotoviti (skupno trajanje vadbe, skupna obremenitev in klinični opazovani dogodki).
English: Among these nine studies, three were non-comparative studies (Guillaumat, 1982; Millara, 1988; Nowak, 2007); three were comparative studies of short duration (up to 3 months) conducted against products used at the time of these studies e.g. cinnarizine, piridoxilate which are no more considered as therapies of choice to treat or prevent retinal or glaucoma diseases by the ophthalmologists; two studies were conducted against placebo (Couderc, 1984 and Aron-Rosa, 1988).
Slovenian: Med temi devetimi študijami so bile tri neprimerjalne (Guillaumat, 1982; Millara, 1988; Nowak, 2007); tri so bile primerjalne s kratkim trajanjem (do 3 mesece) in izvedene s primerjanjem z zdravili, ki so se takrat uporabljala, npr. cinarizin, piridoksilat, ki za oftalmologe niso več zdravila izbire za zdravljenje ali preprečevanje bolezni retine ali glavkoma; dve študiji sta bili izvedeni s primerjanjem s placebom (Couderc, 1984 in Aron-Rosa, 1988).
English: Although the methodology followed by the MAH may be regarded as not totally compliant to the currently accepted standards, no major bias affecting the interpretation of study results appears evident and all analyses show a beneficial effect of trimetazidine combined with metoprolol on exercise tolerance, myocardial ischemia and clinical symptoms.
Slovenian: Čeprav metodologija, ki jo je imetnik dovoljenja za promet z zdravilom uporabil, ni povsem v skladu s trenutno sprejetimi standardi, ni videti večjih pristranskosti, ki bi vplivale na razlago rezultatov študije, vse analize pa kažejo na koristne učinke trimetazidina, kombiniranega z metoprololom, na prenašanje vadbe, miokardno ishemijo in klinične simptome.
English: The Emeriau PK study has shown high plasma concentrations of trimetazidine in old patients, receiving the usual dose of 35 mg twice daily.
Slovenian: Farmakokinetična študija Emeriau je pokazala visoke koncentracije trimetazidina v plazmi pri starejših bolnikih, ki so prejemali običajni odmerek 35 mg dvakrat na dan.
English: In a 426-patients randomised, double blind, placebo-controlled study (TRIMPOL-II), trimetazidine (60mg/day) added to metoprolol 100mg daily (50 mg b.i.d) for 12 weeks significantly improved statistically exercise tests parameters and clinical symptoms as compared to placebo: total exercise duration +20.1s, p= 0.023, total workload +0.54 METs, p=0.001, time to 1-mm ST-segment depression +33.4s, p=0.003, time to onset of angina +33.9s, p<0.001, angina attacks/week -0.73, p=0.014 and short acting nitrates consumption/week, -0.63, p=0.032, without hemodynamic changes.
Slovenian: V randomizirani, dvojno slepi, s placebom kontrolirani študiji s 426 bolniki (TRIMPOL-II) je trimetazidin (60 mg/dan), dodajan 100 miligramom metoprolola na dan (50 mg dvakrat na dan) za 12 tednov, v primerjavi s placebom značilno izboljšal statistične parametre testov vadbe in klinične simptome: skupno trajanje vadbe +20,1 s, p = 0,023, skupna obremenitev +0,54 METs; p = 0,001, čas do 1-mm znižanje spojnice ST +33,4 s; p = 0,003, čas do nastopa angine pektoris +33,9 s; p <0,001, napadi angine pektoris/teden -0,73; p = 0,014 in poraba kratkodelujočih nitratov/teden -0,63; p = 0,032, brez hemodinamskih sprememb.
English: Indeed, it is well known that patients with proven coronary artery disease who are asymptomatic may not have inducible ischemia and that in these patients anti-anginal treatments are ineffective in improving exercise capacity.
Slovenian: Znano je, da asimptomatski bolniki z dokazano koronarno arterijsko boleznijo morda nimajo inducibilne ishemije in da zdravljenje proti angini pektoris pri teh bolnikih nima učinka na izboljšanje vadbene zmogljivosti.
English: • For the indications of symptomatic treatment of tinnitus, vertigo and of visual field disturbances, the CHMP concluded that in view of the newly available safety data and very limited efficacy, the benefits no longer outweigh the risks under normal conditions of use and therefore these therapeutic indications should be removed.
Slovenian: • Za indikacije simptomatskega zdravljenja tinitusa, vrtoglavice in motenj vidnega polja je CHMP sklenil, da ob upoštevanju na novo razpoložljivih podatkov o varnosti in zelo omejene učinkovitosti koristi ne odtehtajo več tveganj v običajnih pogojih uporabe, zato je treba ti terapevtski indikaciji črtati.
English: In addition, the SmPC has to be amended to include a warning about trimetazidine induced parkinsonism, its diagnosis and management.
Slovenian: Poleg tega je treba povzetek glavnih značilnosti zdravila popraviti tako, da bo vsebovalo opozorilo o parkinsonizmu zaradi trimetazidina, njegovo diagnozo in zdravljenje.
English: For the remaining two indications of symptomatic treatment of tinnitus, vertigo and of visual field disturbances, the CHMP concluded that in view of the newly available safety data and very limited efficacy, the benefits no longer outweigh the risks under normal conditions of use and therefore these therapeutic indications should be removed.
Slovenian: Za preostali dve indikaciji simptomatskega zdravljenja tinitusa, vrtoglavice in motenj vidnega polja je CHMP sklenil, da ob upoštevanju na novo razpoložljivih podatkov o varnosti in zelo omejene učinkovitosti koristi ne odtehtajo več tveganj v običajnih pogojih uporabe, zato je treba ti terapevtski indikaciji črtati.
English: In addition, a pharmacokinetics study was agreed with the MAH to investigate the effects of renal impairment and age on the trimetazidine safety profile.
Slovenian: Poleg tega je bilo dogovorjeno, da imetnik dovoljenja za promet z zdravilom opravi farmakokinetično študijo, da razišče učinke okvare ledvic in starosti na varnostni profil trimetazidina.
English: In a 1962 patients three-month randomised, double-blinded study (VASCO study, 2011) on top of atenolol 50 mg/d, two dosages of trimetazidine (70 mg/d and 140 mg/d) were tested versus placebo.
Slovenian: Pri 1962 bolnikih so opravili trimesečno, randomizirano, dvojno slepo študijo (študija VASCO, 2011), v kateri so preskušali atenolol 50 mg/danskupaj z dvema odmerkoma trimetazidina (70 mg/dan in 140 mg/dan) v primerjavi s placebom.
English: Caution should be exercised when prescribing trimetazidine to patients in whom an increased exposure is expected moderate due to renal impairment, or in elderly patients older than 75 years old.
Slovenian: Previdnost je potrebna pri predpisovanju trimetazidina bolnikom, pri katerih je pričakovana večja izpostavljenost zaradi zmerne okvare ledvic ali pri starejših bolnikih, starih več kot 75 let.
English: Trimetazidine (TMZ) is a metabolic agent whose aim is to protect against ischemia by increasing glucose metabolism relative to that of fatty acids.
Slovenian: Trimetazidin (TMZ) je presnovno zdravilo z nalogo zaščititi pred ishemijo s povečanjem presnove glukoze maščobnih kislin.
English: This risk has been identified in post marketing setting and in literature based on: positive dechallenge of Parkinson symptoms after the only withdrawal of TMZ, positive rechallenge, significant higher coprescription of antiparkinson drugs in TMZ group compared to control group (IMS study) and significant higher number of patients that begin antiparkinson drugs after the introduction of TMZ compared to control group (IMS study).
Slovenian: To tveganje je bilo opredeljeno v obdobju trženja in v literaturi na podlagi: pozitivnega okrevanja od simptomov parkinsonove bolezni po prenehanju uporabe trimetazidina, ponovitve simptomov pri ponovni uporabi, značilno višjega sočasnega predpisovanja zdravil proti parkinsonovi bolezni v skupini s trimetazidinom v primerjavi s kontrolno skupino (študija IMS) in značilno višjega števila bolnikov, ki začnejo po uvedbi trimetazidina uporabljati zdravila proti parkinsonovi bolezni v primerjavi s kontrolno skupino (študija IMS).
English: Caution should be exercised when prescribing trimetazidine to patients in whom an increased exposure is expected such as with moderate renal impairment and elderly patients older than 75 years old.
Slovenian: Previdnost je potrebna pri predpisovanju trimetazidina bolnikom, pri katerih je pričakovana večja izpostavljenost zaradi zmerne okvare ledvic in pri starejših bolnikih, starih več kot 75 let.
English: The three studies of short duration (up to 3 months) conducted against reference products of the time (e.g cinnarizine, piridoxilate ), included a small number of patients who presented very heterogeneous or poorly defined pathologies (n=19, n=24 and n=8 respectively for the Cornand (1982), Cordella (1982) and Perdriel (1988) studies).
Slovenian: Tri kratkotrajne študije (do 3 mesece), v katerih so primerjali referenčno zdravilo, ki se je takrat uporabljalo (npr. cinarizin, piridoksilat), so vključevale majhno količino bolnikov z zelo heterogenimi ali slabo opisanimi patologijami (št. = 19 za študijo Cornand (1982), št. = 24 za študijoCordella (1982) in št. = 8 za študijo Perdriel (1988)).
English: The main identified serious ADR is related to Parkinson syndrome and related symptoms.
Slovenian: Glavni opredeljeni resni neželeni učinek zdravila je povezan s parkinsonovim sindromom in povezanimi simptomi.
English: In the overall population, including both asymptomatic and symptomatic patients, trimetazidine failed to demonstrate a benefit on both ergometric (total exercise duration, time to onset of 1mm ST and time to onset angina) and clinical endpoints.
Slovenian: V celotni populaciji, ki vključuje asimptomatske in simptomatske bolnike, trimetazidin ni pokazal koristi za ergometrične (skupno trajanje vadbe, čas do 1-mm znižanja spojnice ST in čas do nastopa angine pektoris) in klinične opazovane dogodke.
English: The submitted data comparing TMZ to either placebo or the other reference products or based on cohorts without comparator provide insufficient demonstration of a relevant clinical benefit of trimetazidine in the ancillary treatment of visual acuity decrease and visual field disturbances due to vascular reasons.
Slovenian: Predloženi podatki, ki primerjajo trimetazidin s placebom ali drugim referenčnim zdravilom ali ki temeljijo na kohortah brez primerjalnega zdravila, ne zadoščajo za dokaz pomembnih kliničnih koristi trimetazidina pri dodatnem zdravljenju motenj ostrine vida in vidnega polja zaradi ožilja.
English: The CHMP also agreed on a study protocol to assess the effect of renal impairment and age on trimetazidine pharmacokinetics for the study to be conducted.
Slovenian: CHMP se je strinjal tudi s protokolom študije, ki jo je treba izvesti, da se oceni učinke okvare ledvic in starosti na farmakokinetiko trimetazidina.
English: • The Committee also considered the cumulative efficacy and safety data submitted for the indications of the prophylactic treatment of attacks of angina pectoris, ancillary symptomatic treatment of vertigo and tinnitus and ancillary treatment of visual acuity decrease and visual field disturbances due to vascular reasons.
Slovenian: • Odbor je obravnaval tudi kumulativne podatke o učinkovitosti in varnosti, predložene za indikacije profilaktičnega zdravljenja napadov angine pektoris, dodatnega simptomatskega zdravljenja vrtoglavice in tinitusa ter dodatnega zdravljenja motenj ostrine vida in vidnega polja zaradi ožilja.
English: The efficacy of trimetazidine is sufficiently demonstrated as add-on therapy in the shortmedium-term (weeks /months) treatment of symptomatic patients with angina who are inadequately controlled by or intolerant to first-line antianginal therapies.
Slovenian: Učinkovitost trimetazidina je zadostno dokazana kot dodatno zdravljenje h kratkotrajnemu ali srednje dolgemu (tedni/meseci) zdravljenju simptomatskih bolnikov z angino pektoris, pri katerih ni dosežen ustrezen nadzor ali ki ne prenašajo zdravil prve izbire proti angini pektoris.
English: However, in the subgroup of symptomatic patients (n= 1574) trimetazidine (140 mg) significantly improved total exercise duration (+23.8 s versus +13.1 s placebo; p=0.001) and time to onset of angina (+46.3 s versus +32.5 s placebo; p=0.005).
Slovenian: Vendar pa je v podskupini simptomatskih bolnikov (št. = 1574) trimetazidin (140 mg) pomembno izboljšal skupno trajanje vadbe (+23,8 s v primerjavi s +13,1 s za placebo; p = 0,001) in čas do nastopa angine pektoris (+46,3 s v primerjavi s +32,5 s za placebo; p = 0,005).
English: Thus, all of these elements deriving from post-approval data do not demonstrate a relevant clinical benefit of trimetazidine for patients suffering from tinnitus, dizziness or hearing loss.
Slovenian: Zato vsi ti elementi, ki so bili izpeljani po datumu odobritve, ne kažejo ustreznih kliničnih koristi trimetazidina za bolnike s tinitusom, vrtoglavico ali izgubo sluha.
English: This analysis showed that in patients with chronic stable angina trimetazidine given as add-on to atenolol significantly improved exercise tolerance (p<0.01), time to 1 mm ST segment depression and time to angina.
Slovenian: Slednja je pokazala, da je pri bolnikih s kronično stabilno angino pektoris, ki so trimetazidin prejemali kot dodatek k atenololu, pomembno izboljšal vadbeno toleranco (p < 0,01), čas do 1-mm znižanja spojnice ST in čas do pojava angine pektoris.
English: The CHMP concluded that the limited data generated by the clinical trials submitted for the ENT indication, insufficiently support the demonstration of a relevant clinical benefit of trimetazidine for patients suffering from tinnitus, vertigo or hearing loss and that either the currently ENT registered indication or the newly claimed indications cannot be supported.
Slovenian: CHMP je zaključil, da omejeni podatki iz kliničnih preskušanj, predloženi za indikacijo ORL, ne zadoščajo za podporo dokazov ustreznih kliničnih koristi trimetazidina za bolnike, ki imajo tinitus, vrtoglavico ali izgubo sluha, zato ni mogoče podpreti trenutno registrirane indikacije ORL ali na novo vloženih indikacij.
English: Therefore, considering these methodological weaknesses, the dossier is insufficient to conclude that trimetazidine has satisfactorily demonstrated a clinical benefit as adjuvant symptomatic treatment of dizziness, tinnitus or hearing loss.
Slovenian: Zato predložena dokumentacija, ob upoštevanju teh metodoloških slabosti, ne zadošča za zaključek, da ima trimetazidin dokazane ustrezne klinične koristi kot dodatno simptomatsko zdravljenje za vrtoglavico, tinitus ali izgubo sluha.
English: Favourable results from ‘Dizziness Handicap Inventory questionnaire' were suggested by the small Sterckers and Vitte studies.
Slovenian: Majhni študiji Sterckers in Vitte sta nakazovali ugodne rezultate iz „Vprašalnika o težavah zaradi vrtoglavice (Dizziness Handicap Inventory questionnaire)”.
English: Elderly patients may have increased trimetazidine exposure due to age-related decrease in renal function.
Slovenian: Pri starejših bolnikih je izpostavljenost trimetazidinu lahko večja zaradi starostno pogojenega poslabšanja delovanja ledvic.
English: Therefore, trimetazidine as add-on therapy may represent an optional treatment drug to be used in association with first-line anti-anginal drugs especially in those patients for whom optimally control of symptoms cannot be achieved with other anti-anginal drugs in monotherapy due to haemodynamic intolerance or chronotropic incompetence.
Slovenian: Zato lahko trimetazidin kot dodatno zdravljenje predstavlja možno zdravilo, ki se uporablja v povezavi z zdravili proti angini pektoris, ki so prva izbira zdravljenja, zlasti pri bolnikih, pri katerih ni mogoče doseči ustreznega nadzora simptomov z drugimi zdravili proti angini pektoris v monoterapiji zaradi hemodinamskega neprenašanja ali kronotropne inkompetence.
English: Trimetazidine-containing medicinal products are indicated for prophylactic treatment of angina pectoris crisis, ancillary symptomatic treatment of vertigo and tinnitus and ancillary treatment of visual acuity decrease and visual field disturbances due to vascular reasons.
Slovenian: Zdravila, ki vsebujejo trimetazidin, so indicirana za profilaktično zdravljenje krize zaradi angine pektoris, pomožno simptomatsko zdravljenje vrtoglavice in tinitusa ter pomožno zdravljenje zmanjšane ostrine vida in motenj vidnega polja zaradi ožilja.
English: Considering all currently available data, the CHMP concluded that trimetazidine-containing medicinal products should be contraindicated in patients with severe renal impairment (creatinine clearance < 30ml/min).
Slovenian: Ob upoštevanju vseh trenutno razpoložljivih podatkov je CHMP zaključil, da morajo biti zdravila, ki vsebujejo trimetazidin, kontraindicirana pri bolnikih s hudo okvaro ledvic (očistek kreatinina < 30 ml/min).
English: • The Committee is of the opinion that the benefits continue to outweigh the risks in patients with angina pectoris but that treatment should be restricted to add-on to existing treatments in patients who are not adequately controlled by or intolerant to other medicines for angina pectoris.
Slovenian: • CHMP je mnenja, da koristi še naprej odtehtajo tveganja pri bolnikih z angino pektoris, vendar pa je treba zdravljenje omejiti na dodatek že obstoječemu zdravljenju pri bolnikih, pri katerih angina pektoris ni pod ustreznim nadzorom ali ki drugih zdravil ne prenašajo.
English: The Committee, therefore, concluded that the benefit-risk balance of trimetazidine- containing medicinal products remains positive under normal conditions of use, subject to the restrictions, warnings, changes to the product information, additional pharmacovigilance activities and risk minimisation measures agreed, only as add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled by or intolerant to first-line anti-anginal therapies.
Slovenian: Odbor je zato sklenil, da ostaja razmerje med tveganji in koristmi za zdravila, ki vsebujejo trimetazidin, pozitivno v običajnih pogojih uporabe, ob upoštevanju dogovorjenih omejitev, opozoril, spremenjenih informacij o zdravilu, dodatnih farmakovigilančnih aktivnosti in ukrepov za zmanjševanje tveganja, vendar le kot dodatno zdravljenje za simptomatsko zdravljenje bolnikov s stabilno angino pektoris, pri katerih z zdravili prve izbire proti angini pektoris bolezni ni mogoče ustrezno nadzirati ali ki teh zdravil ne prenašajo.
English: Therefore, the Committee concluded that the benefit-risk balance of trimetazidine- containing medicinal products in the add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled by or intolerant to first-line antianginal therapies, remains positive under normal conditions of use, subject to the restrictions, warnings, changes to the product information, additional pharmacovigilance activities and risk minimisation measures agreed.
Slovenian: Odbor je torej sklenil, da ostaja razmerje med tveganji in koristmi za zdravila, ki vsebujejo trimetazidin kot dodatno zdravljenje za simptomatsko zdravljenje bolnikov s stabilno angino pektoris, pri katerih z zdravili prve izbire proti angini pektoris bolezni ni mogoče ustrezno nadzirati ali ki teh zdravil ne prenašajo, pozitivna v običajnih pogojih uporabe, ob upoštevanju dogovorjenih omejitev, opozoril, spremenjenih informacij o zdravilu, dodatnih farmakovigilančnih aktivnostih in ukrepov za zmanjševanje tveganja.
English: 223 patients were randomized for this double blind, placebo-controlled study where one 35 mg trimetazidine modified release tablet (b.i.d.)
Slovenian: 223 bolnikov je bilo randomiziranih v to dvojno slepo, s placebom kontrolirano študijo, v kateri so 50 mg atenolola (enkrat na dan) dodajali 35 mg trimetazidina v obliki tablet s prirejenim sproščanjem (dvakrat na dan) v obdobju 8 tednov.
English: Accordingly, the SmPC has been amended to include dose information in the elderly and in patients with moderate renal impairment (creatinine clearance [30-60] ml/min).
Slovenian: Povzetek glavnih značilnosti zdravila je bil ustrezno spremenjen in zdaj vključuje informacije o odmerjanju pri starejših bolnikih in bolnikih z zmerno okvaro ledvic (očistek kreatinina [30-60] ml/min).
English: study) to address all important, potential and identified risks, particularly Parkinsonism and a drug utilization study to verify the compliance of prescribers regarding the restricted indication after marketing authorisation changes was also agreed.
Slovenian: Dogovorjeno je bilo tudi, da se izvede študija po odobritvi dovoljenja za promet z zdravilom, ki bo obravnavala vsa pomembna, možna in opredeljena tveganja, zlasti parkinsonizem, in študija uporabe zdravila, ki bo potrdila skladnost predpisovalcev z omejitvijo indikacij po spremembah dovoljenja za promet z zdravilom.
English: Trimetazidine was shown to have an effect very similar to that of non-heart rate−lowering anti-anginal agents: nicorandil, ranolazine, long-acting nitrates and dihydropyridines, with less than a few seconds differences in exercise tolerance test (ETT) ergometric parameters.
Slovenian: ranolazinu, dolgodelujočim nitratom in dihidropiridinom, z manj kot nekaj sekundami razlike v ergonomskih parametrih testov vadbene tolerance.
English: In conclusion, the data submitted for trimetazidine with respect to ENT indications, insufficiently support the demonstration of a relevant clinical benefit for these patients suffering from tinnitus, vertigo or hearing loss symptomatology who were targeted by the ENT therapeutic indications as mentioned currently in the European marketing authorisations.
Slovenian: Podatki, predloženi za trimetazidin v zvezi z indikacijami ORL, torej ne zadoščajo za podporo dokazov o ustreznih kliničnih koristih za bolnike s, simptomatiko tinitusa, vrtoglavice ali izgube sluha, na katere ciljajo terapevtske indikacije ORL, ki jih trenutno vsebujejo dovoljenja za promet z zdravilom v Evropi.
English: A PASS study to address all important, potential and identified risks, particularly Parkinsonism, and a Drug utilization study to monitor whether the risk minimization measures put in place as results of the referral procedure are effective have been requested by the CHMP.
Slovenian: CHMP je zahteval, da se opravi študija varnosti po pridobitvi dovoljenja za promet z zdravilom, z namenom da se naslovijo vsa pomembna, možna in opredeljena tveganja, zlasti parkinsonizem, in študija uporabe zdravila, da se lahko nadzoruje, ali so ukrepi za zmanjšanje tveganja, uvedeni kot rezultat napotitvenega postopka, učinkoviti.
English: Considering all currently available data, the CHMP concluded that trimetazidine-containing medicines should be contraindicated in patients with Parkinson disease, parkinsonian symptoms, tremors, restless leg syndrome, and other related movement disorders.
Slovenian: Ob upoštevanju vseh trenutno razpoložljivih podatkov je CHMP sklenil, da morajo biti zdravila, ki vsebujejo trimetazidin, kontraindicirana pri bolnikih s parkinsonovo boleznijo, simptomi parkinsonove bolezni, tremorji, sindromom nemirnih nog in drugimi povezanimi motnjami gibanja.