qanastek/EMEA-V3 huggingface dataset:
This value is consistent with data from pivotal clinical studies, where mean changes from baseline in QTcF (Fridericia’ s correction) after doses of 500 and 750 mg twice daily were 1.9 and 4.9 msec, respectively.
Dan il- valur huwa konsistenti ma ’ dejta minn studji kliniċi tal- pern, fejn tibdiliet medji mil- linja bażi fil- QTcF (korrezzjoni ta ’ Fridericia), wara dożi ta ’ 500 u 750 mg darbtejn kuljum, kienu 1. 9 u 4. 9 msec, rispettivament.
The slope is higher in patients with clinically significant hepatic impairment.
Iż - żurżieqa hija aktar għolja f’ pazjenti b’ indeboliment tal- fwied klinikament sinifikattiv.
In a large outcome study (MERLIN-TIMI 36) in 6,560 patients with UA/ NSTEMI ACS, there was no difference between Ranexa and placebo in the risk of all-cause mortality (relative risk ranolazine: placebo 0.99), sudden cardiac death (relative risk ranolazine: placebo 0.87), or the frequency of symptomatic documented arrhythmias (3.0% versus 3.1%).
Fi studju (MERLIN- TIMI 36) ta ’ effett kbir f’ 6, 560 pazjent b’ UA/ NSTEMI ACS, ma kien hemm l- ebda differenza bejn Ranexa u plaċebo fir- riskju ta ’ mortalità mill- kaġunijiet kollha (riskju relattiv ranolazine: plaċebo 0. 99), mewt kardijaka f’ daqqa waħda (riskju relattiv ranolazine: plaċebo 0. 87), jew il- frekwenza ta ’ arritmiji sintomatiċi dokumentati (3. 0% kontra 3. 1%).
No proarrhythmic effects were observed in 3,162 patients treated with Ranexa based on 7-day Holter monitoring in the MERLIN-TIMI 36 study.
L- ebda effetti proarritmiċi ma kienu osservati fi 3, 162 pazjent ikkurati b’ Ranexa abbażi ta ’ monitoraġġ Holter ta ’ 7 ijiem fl- istudju MERLIN- TIMI 36.
There was a significantly lower incidence of arrhythmias in patients treated with Ranexa (74%) versus placebo (83%), including ventricular tachycardia ≥ 8 beats (5% versus 8%).
Kien hemm inċidenza ferm aktar baxxa ta ’ arritmiji f’ pazjenti kkurati b’ Ranexa (74%) kontra plaċebo (83%), inklużi takikardja ventrikulari ≥ 8 taħbitiet (5% kontra 8%).
Clinical studies have demonstrated the efficacy and safety of Ranexa in the treatment of patients with chronic angina, either alone or when the benefit from other antianginal medicinal products was sub-optimal.
Studji kliniċi wrew l- effikaċja u s- sigurtà ta ’ Ranexa fil- kura ta ’ pazjenti b’ anġina kronika, kemm waħidha jew meta l- benefiċċju ta ’ prodotti mediċinali kontra l- anġina oħra ma kienx tajjeb biżżejjed.
In the pivotal study, CARISA, Ranexa was added to treatment with atenolol 50 mg once daily, amlodipine 5 mg once daily, or diltiazem 180 mg once daily.
Fl- istudju ewlieni, CARISA, Ranexa kienet miżjuda ma ’ kura b’ atenolol 50 mg darba kuljum, amlodipine 5 mg darba kuljum, jew diltiazem 180 mg darba kuljum.
Eight-hundred and twenty-three patients (23% women) were randomised to receive 12 weeks of treatment with Ranexa 750 mg twice daily, 1000 mg twice daily, or placebo.
Tmien mija u tlieta u għoxrin pazjent (23% nisa) kienu randomizzati li jirċievu 12- il ġimgħa ta ’ kura b’ Ranexa 750 mg darbtejn kuljum, 1000 mg darbtejn kuljum, jew plaċebo.
Ranexa demonstrated greater efficacy than placebo in prolonging exercise time at trough at 12 weeks for both doses studied when used as an add-on therapy.
Ranexa wriet effikaċja akbar minn plaċebo fit- titwil taż- żmien ta ’ eżerċizzju f’ livelli minimi, f’ ġimgħa 12 għaż- żewġ dożi studjati meta wżata bħala terapija add- on.
However, there was no difference in exercise duration between the two doses (24 seconds compared to placebo; p ≤ 0.03).
Madankollu, ma kien hemm l- ebda differenza fit- tul ta ’ żmien ta ’ l- eżerċizzju bejn iż - żewġ dożi (24 sekonda meta mqabbla ma ’ plaċebo; p ≤ 0. 03).
Ranexa resulted in significant decreases in the number of angina attacks per week and consumption of short-acting nitroglycerin compared to placebo.
Ranexa irriżultat fi tnaqqis sinifikanti fin- numru ta ’ attakki ta ’ anġina kull ġimgħa u l- konsum ta ’ nitrogliċerina li taħdem għal qasir żmien meta mqabbla ma ’ plaċebo.
Tolerance to ranolazine did not develop during treatment and a rebound increase in angina attacks was not observed following abrupt discontinuation.
Ma żviluppatx tolleranza għal ranolazine waqt il- kura u żieda rebound fl- attakki ta ’ l- anġina ma kinitx osservata wara twaqqif ta ’ f’ daqqa waħda.
The improvement in exercise duration in women was about 33% of the improvement in men at the 1000 mg twice-daily dose level.
It- titjib fit- tul ta ’ ħin ta ’ l- eżerċizzju fin- nisa kien ta ’ madwar 33% tat- titjib fl- irġiel fil - livell ta ’ doża ta ’ 1000 mg darbtejn kuljum.
However, men and women had similar reductions in frequency of angina attacks and nitroglycerin consumption.
Madankollu, l- irġiel u n- nisa kellhom tnaqqis simili fil- frekwenza ta ’ attakki ta ’ anġina u konsum ta ’ nitroġliċerina.
Given the dose-dependent side effects and similar efficacy at 750 and 1000 mg twice daily, a maximum dose of 750 mg twice daily is recommended.
Minħabba l- effetti sekondarji dipendenti fuq id- doża u effikaċja simili f’ 750 u 1000 mg darbtejn kuljum, hija rrakkomandata doża massima ta ’ 750 mg darbtejn kuljum.
In a second study, ERICA, Ranexa was added to treatment with amlodipine 10 mg once daily (the maximum labelled dose).
Fit- tieni studju, ERICA, Ranexa kienet miżjuda ma ’ kura ta ’ amlodipine 10 mg darba kuljum (id- doża massima ittikkettjata).
Five-hundred and sixty-five patients were randomised to receive an initial dose of Ranexa 500 mg twice daily or placebo for 1 week, followed by 6 weeks of treatment with Ranexa 1000 mg twice daily or placebo, in addition to concomitant treatment with amlodipine 10 mg once daily.
Ħames mija u ħamsa u sittin pazjent kienu randomizzati biex jirċievu doża tal- bidu ta ’ Ranexa 500 mg darbtejn kuljum jew plaċebo għal ġimgħa, segwiti b’ 6 ġimgħat ta ’ kura b’ Ranexa 1000 mg darbtejn kuljum jew plaċebo, f’ addizjoni ma ’ kura konkomittanti b’ amlodipine 10 mg darba kuljum.
Additionally, 45% of the study population also received long-acting nitrates.
Barra minn hekk, 45% mill- popolazzjoni ta ’ l- istudju rċiviet ukoll nitrati li jaħdmu fit- tul.
Ranexa resulted in significant decreases in the number of angina attacks per week (p = 0.028) and consumption of short-acting nitroglycerin (p = 0.014) compared to placebo.
Ranexa rriżultat fi tnaqqis sinifikanti fin- numri ta ’ attakki ta ’ l- anġina kull ġimgħa (p = 0. 028) u l- konsum ta ’ nitrogliċerina (p = 0. 014) li taħdem għal qasir żmien meta mqabbla ma ’ plaċebo.
Both the average number of angina attacks and nitroglycerin tablets consumed decreased by approximately one per week.
8 Kemm in- numru ta ’ attakki ta ’ anġina u l- pilloli ta ’ nitrogliċerina kkunsmati naqsu b’ madwar wieħed fil- ġimgħa.
In the main dose-finding study, MARISA, ranolazine was used as monotherapy.
Fl- istudju ewlieni ta ’ sejbien tad- doża, MARISA, ranolazine intuża bħala monoterapija.
One-hundred and ninety-one patients were randomised to treatment with Ranexa 500 mg twice daily, 1000 mg twice daily, 1500 mg twice daily, and matching placebo, each for 1 week in a crossover design.
Mija u wieħed u disgħin pazjent kienu rrandomizzati għal kura b’ Ranexa 500 mg darbtejn kuljum, 1000 mg darbtejn kuljum, 1500 mg darbtejn kuljum, u plaċebo li jaqbel, kollha għal ġimgħa f’ disinn crossover.
Ranexa was significantly superior to placebo in prolonging exercise time, time to angina, and time to 1 mm ST segment depression at all doses studied with an observed dose-response relationship.
Ranexa kienet superjuri b’ mod sinjifikanti għal plaċebo fid- dożi kollha studjati f’ li ttawwal il- ħin ta ’ l- eżerċizzju, żmien għal anġina, u żmien għal depressjoni tas- segment ST b’ mm 1 b’ relazzjoni osservata ta ’ doża- rispons.
Improvement of exercise duration was statistically significant compared to placebo for all three doses of ranolazine from 24 seconds at 500 mg twice daily to 46 seconds at 1500 mg twice daily, showing a dose-related response.
It- titjib f’ kemm idum l- eżerċizzju kien statistikament sinjifikanti meta mqabbel ma ’ plaċebo għat- tliet dożi l- oħrajn kollha ta ’ ranolazine minn 24 sekonda b’ 500 mg darbtejn kuljum għal 46 sekonda b’ 1500 mg darbtejn kuljum, u dan juri rispons relatat mad- doża.
In this study, exercise duration was longest in the 1500 mg group; however, there was a disproportional increase in side effects, and the 1500 mg dose was not studied further.
F’ dan l- istudju, it- tul ta ’ ħin ta ’ l- eżerċizzju kien l- itwal fil- grupp ta ’ 1500 mg; madankollu, kien hemm żieda sproporzjonali fl- effetti sekondarji, u d- doża 1500 mg ma kinitx studjata aktar.
8 death (relative risk ranolazine: placebo 0.87), or the frequency of symptomatic documented arrhythmias (3.0% versus 3.1%) between Ranexa and placebo when added to standard medical therapy (including beta-blockers, calcium channel blockers, nitrates, anti-platelet agents, lipid-lowering medicinal products, and ACE inhibitors).
Fi studju ta ’ riżultat kbir (MERLIN- TIMI 36) f’ 6, 560 pazjent b’ UA/ NSTEMI ACS, ma kien ebda differenza fir- riskju tal- mortalità b’ kull kawża (riskju relattiv ranolazine: plaċebo 0. 99), mewta kardijaka f’ daqqa (riskju relattiv ranolazine: plaċebo 0. 87), jew il- frekwenza ta ’ l- arritmiji sintomatiċi dokumentati (3. 0% kontra 3. 1%) bejn Ranexa u placebo meta miżjuda ma ’ terapija medika standard (inklużi mblokkaturi- beta, imblokkaturi tal- kanali tal- kalċju, nitrati, mediċini kontra l- pjastrini, prodotti mediċinali li jbaxxu l- lipidi u impedituri ACE).
Approximately one-half of the patients in MERLIN-TIMI 36 had a history of angina.
Madwar nofs il- pazjenti f’ MERLIN- TIMI 36 kellhom storja ta ’ anġina.
The results showed that exercise duration was 31 seconds longer in ranolazine patients versus placebo patients (p = 0.002).
Ir- riżultati wrew li t- tul ta ’ l- eżerċizzju kien 31 sekonda itwal f’ pazjenti b’ ranolazine meta mqabbla ma ’ pazjenti bi plaċebo (p = 0. 002).
The Seattle Angina Questionnaire showed significant effects on several dimensions, including angina frequency (p < 0.001), compared to placebo-treated patients.
Il- Kwestjonarju ta ’ Seattle dwar l - Anġina wera effetti sinjifikanti fuq bosta dimensjonijiet, inkluż il- frekwenza ta ’ l- anġina (p < 0. 001), meta mqabbel ma ’ pazjenti ttrattati bi plaċebo.
A small proportion of non-Caucasians was included in the controlled clinical studies; therefore, no conclusions can be drawn regarding the effect and safety in non-Caucasians.
Proporzjon żgħir ta’ nies mhux Kawkasi kienu inklużi fl- istudji kliniċi kkontrollati; għaldaqstant, l- ebda konklużjoni ma setgħet tinġibed rigward l- effett u s- sigurtà f’ nies mhux Kawkasi.
After oral administration of Ranexa, peak plasma concentrations (Cmax) are typically observed between 2 and 6 hours.
Wara għoti orali ta ’ Ranexa, konċentrazzjonijiet massimi fil- plażma (Cmax) huma tipikament osservati bejn 2 sa 6 sigħat.
Steady state is generally achieved within 3 days of twice-daily dosing.
Ġeneralment stat fiss jintlaħaq fi żmien 3 ijiem ta ’ dożaġġ ta ’ darbtejn kuljum.
The mean absolute bioavailability of ranolazine after oral administration of immediate- release ranolazine tablets ranged from 35− 50%, with large inter-individual variability.
Il- bijodisponibilità ta ’ wara għoti orali ta ’ pilloli ranolazine li jerħuha immedjatament varjat minn 35−50%, b’ varjabbilità kbira bejn l- individwi.
Ranexa exposure increases more than in proportion to dose.
L- espożizzjoni ta ’ Ranexa tiżdied aktar milli fi proporzjon mad- doża.
There was a 2.5- to 3-fold increase in steady-state AUC as the dose was increased from 500 mg to 1000 mg twice daily.
Kien hemm żieda ta ’ 2. 5 sa 3 darbiet f’ AUC ta ’ stat fiss hekk kif id- doża żdiedet minn 500 mg għal 1000 mg darbtejn kuljum.
In a pharmacokinetic study in healthy volunteers, steady-state Cmax was, on average, approximately 1770 (SD 1040) ng/ ml, and steady-state AUC0-12 was, on average, 13,700 (SD 8290) ng x h/ ml following a dose of 500 mg twice daily.
Fi studju farmakokinetiku f’ voluntieri f’ saħħithom, is - Cmax ta ’ stat fiss kienet, bejn wieħed u ieħor, medja ta ’ 1770 (SD 1040) ng/ ml, u l- AUC0- 12 ta ’ stat fiss kienet, medja ta ’, 13, 700 (SD 8290) ng x h/ ml, wara doża ta ’ 500 mg darbtejn kuljum.
Food does not affect the rate and extent of absorption of ranolazine.
L- ikel ma jaffettwax ir- rata u l- medda ta ’ assorbiment ta ’ ranolazine.
Approximately 62% of ranolazine is bound to plasma proteins, mainly alpha-1 acid glycoprotein and weakly to albumin.
Madwar 62% ta ’ ranolazine jeħel ma ’ proteini fil- plażma, prinċipalment alpha- 1 acid glycoprotein u b’ mod dgħajjef ma ’ albumin.
The mean steady-state volume of distribution (Vss) is about 180 l.
Il- volum ta ’ distribuzzjoni ta ’ stat fiss (Vss) medju huwa madwar 180 l.
Ranolazine is eliminated primarily by metabolism.
Ranolazine huwa eliminat primarjament permezz tal- metaboliżmu.
Less than 5% of the dose is excreted unchanged in the urine and faeces.
Inqas minn 5% tad- doża hija eliminata mhux mibdula fl- awrina u l- ippurgar.
Following oral administration of a single 500 mg dose of [14C]-ranolazine to healthy subjects, 73% of the radioactivity was recovered in urine and 25% in faeces.
Wara l- għoti orali ta ’ doża waħdanija ta ’ 500 mg ta ’ [14C] - ranolazine lil suġġetti f’ saħħithom, 73% tar- radjuattività kienet irkuprata fl- awrina u 25% fl- ippurgar.
Clearance of ranolazine is dose-dependent, decreasing with increased dose.
Ir- rata ta ’ eliminazzjoni ta ’ ranolazine hija dipendenti fuq id- doża, li tonqos b’ żieda fid- doża.
The elimination half-life is about 2− 3 hours after intravenous administration.
Il- half - life ta ’ l- eliminazzjoni hija madwar 2−3 sigħat wara għoti intravenuż.
The terminal half-life at steady state after oral administration of ranolazine is about 7 hours, due to the absorption rate-limited elimination.
Il- half- life terminali fi stat fiss wara għoti orali ta ’ ranolazine huwa madwar 7 sigħat, minħabba r- rata ta ’ eliminazzjoni limitata mill- assorbiment.
Ranolazine undergoes rapid and extensive metabolism.
Ranolazine jgħaddi minn metaboliżmu rapidu u estensiv.
In healthy young adults, ranolazine accounts for approximately 13% of the radioactivity in plasma following a single oral 500 mg dose of [14C]-ranolazine.
9 waħda orali ta ’ 500 mg ta ’ [14C] - ranolazine.
A large number of metabolites has been identified in human plasma (47 metabolites), urine (> 100 metabolites), and faeces (25 metabolites).
Numru kbir ta ’ metaboliti ġew identifikati fil- plażma tal- bniedem (47 metabolit), fl- awrina (> 100 metabolit), u fl- ippurgar (25 metabolit).
Fourteen primary pathways have been identified of which O-demethylation and N-dealkylation are the most important.
Erbatax il- mogħdija primarja ġew identifikati mil- liema O- demethylation u N- dealkylation huma l- aktar importanti.
In vitro studies using human liver microsomes indicate that ranolazine is metabolised primarily by CYP3A4, but also by CYP2D6.
Studji in vitro permezz ta ’ l- użu ta ’ mikrożomi tal- fwied tal- bniedem jindikaw li ranolazine huwa metabolizzat primarjament minn CYP3A4, u wkoll minn CYP2D6.
At 500 mg twice daily, subjects lacking CYP2D6 activity (poor metabolisers, PM) had 62% higher AUC than subjects with CYP2D6 metabolising capacity (extensive metabolisers, EM).
F’ 500 mg darbtejn kuljum, suġġetti li m’ għandhomx attività CYP2D6 (metabolizzaturi dgħajfin, PM) kellhom l- AUC 62% aktar għolja minn suġġetti b’ kapaċità metabolizzanti CYP2D6 (metabolizzaturi estensivi, EM).
The corresponding difference at the 1000 mg twice-daily dose was 25%.
Id- differenza korrespondenti fid- doża ta ’ 1000 mg darbtejn kuljum kienet ta ’ 25%.
The influence of various factors on the pharmacokinetics of ranolazine was assessed in a population pharmacokinetic evaluation in 928 angina patients and healthy subjects.
L- influwenza ta ’ fatturi diversi fuq il- farmakokinetiċi ta ’ ranolazine kienu stmati f’ evalwazzjoni farmakokinetika tal- popolazzjoni f’ 928 pazjent b’ anġina u suġġetti b’ saħħithom.
Gender effects:
Effetti ta ’ sess:
Gender had no clinically relevant effect on pharmacokinetic parameters.
Is- sess m’ għandu l- ebda effett klinikament relevanti fuq parametri farmokokinetiċi.
Elderly patients:
Pazjenti annzjani:
Age alone had no clinically relevant effect on pharmacokinetic parameters.
L- età waħidha ma għandha l- ebda effett klinikament relevanti fuq parametri farmakokinetiċi.
However, the elderly may have increased ranolazine exposure due to age-related decrease in renal function.
Madankollu, l- anzjani jistgħu jkunu żiedu l- esponiment ta ’ ranolazine minħabba tnaqqis fil- funzjoni tal- kliewi relatat ma ’ l- età.
9 Body weight:
Piż korporali:
Compared to subjects weighing 70 kg, exposure was estimated to be about 1.4-fold higher in subjects weighing 40 kg.
Meta mqabbel ma ’ suġġetti li jiżnu 70 kg, l- esponiment kien stmat li huwa madwar 1. 4- il darba aktar għoli f’ suġġetti li jiżnu 40 kg.
CHF NYHA Class III and IV were estimated to have about 1.3-fold higher plasma concentrations.
CHF NYHA Klassi III u IV kienu stmati li għandhom konċentrazzjonijiet fil- plażma madwar 1. 3 darba aktar għoljin.
In a study evaluating the influence of renal function on ranolazine pharmacokinetics, ranolazine AUC was on average 1.7- to 2-fold higher in subjects with mild, moderate, and severe renal impairment compared with subjects with normal renal function.
Fi studju li evalwa l- influwenza tal- funzjoni tal- kliewi fuq farmakokinetiċi ta ’ ranolazine, l- AUC ta ’ ranolazine kienet bħala medja 1. 7 sa 2 drabi ogħla f’ suġġetti b’ indeboliment tal- kliewi ħafif, moderat, u sever, meta mqabblin ma ’ suġġetti b’ funzjoni tal- kliewi normali.
There was a large inter-individual variability in AUC in subjects with renal impairment.
Kien hemm varjabbilità kbira fl- AUC ta ’ bejn l- individwi f’ suġġetti b’ indeboliment tal- kliewi.
The AUC of metabolites increased with decreased renal function.
L- AUC tal- metaboliti żdiedet ma ’ tnaqqis fil- funzjoni tal- kliewi.
The AUC of one pharmacologically active ranolazine metabolite was 5-fold increased in patients with severe renal impairment.
L- AUC ta ’ wieħed mill- metaboliti farmakoloġikament attiv ta ’ ranolazine żdiedet b’ 5 darbiet f’ pazjenti b’ indeboliment tal- kliewi sever.
In the population pharmacokinetic analysis, a 1.2-fold increase in ranolazine exposure was estimated in subjects with moderate impairment (creatinine clearance 40 ml/ min).
F’ analiżi tal- farmakokinetiċi tal- popolazzjoni, żieda fl- esponiment ta ’ ranolazine ta ’ 1. 2- il darba kienet stmata f’ suġġetti b’ indeboliment moderat (rata ta ’ eliminazzjoni ta ’ kreatinina 40 ml/ min).
In subjects with severe renal impairment (creatinine clearance 10– 30 ml/ min), a 1.3- to 1.8-fold increase in ranolazine exposure was estimated.
F’ suġġetti b’ indeboliment tal- kliewi sever (rata ta ’ eliminazzjoni ta ’ kreatinina 10– 30 ml/ min), kienet stmata żieda ta ’ 1. 3 sa 1. 8 drabi fl- esponiment ta ’ ranolazine.
The influence of dialysis on the pharmacokinetics of ranolazine has not been evaluated.
L- influwenza ta ’ dijaliżi fuq il- farmakokinetiċi ta ’ ranolazine ma ġietx evalwata.
The pharmacokinetics of ranolazine have been evaluated in patients with mild or moderate hepatic impairment.
Il- farmakokinetiċi ta ’ ranolazine ġew evalwati f’ pazjenti b’ indeboliment tal- fwied ħafif jew moderat.
There are no data in patients with severe hepatic impairment.
Ma hemm l- ebda dejta f’ pazjenti b’ indeboliment tal- fwied sever.
Ranolazine AUC was unaffected in patients with mild hepatic impairment but increased 1.8-fold in patients with moderate impairment.
L- AUC ta ’ ranolazine ma kienitx influwenzata f’ pazjenti b’ indeboliment tal- fwied ħafif iżda żdiedet 1. 8- il darba f’ pazjenti b’ indeboliment moderat.
QT prolongation was more pronounced in these patients.
Titwil QT kien aktar prominenti f’ dawn il- pazjenti.
The pharmacokinetic parameters of ranolazine have not been studied in the paediatric population (< 18 years).
Il- parametri farmakokinetiċi ta ’ ranolazine ma ġewx studjati fil- popolazzjoni pedjatrika (< 18- il sena).
Ranolazine was associated with convulsions and increased mortality in rats and dogs at plasma concentrations approximately 3-fold higher than at the proposed maximum clinical dose.
Reazzjonijiet avversi mhux osservati fi studji kliniċi, iżda dehru f’ annimali f’ livelli simili għal esponiment kliniku kienu kif ġejjin, Ranolazine kien assoċjat ma ’ aċċessjonijiet u żieda fil- mortalità fil- firien u fil- klieb f’ konċentrazzjonijiet fil- plażma madwar 3 drabi aktar għoljin milli fid- doża klinika massima proposta.
Chronic toxicity studies in rats indicated that treatment was associated with adrenal changes at exposures slightly greater than those seen in clinical patients.
Tossiċità kronika fil- firien indikat li l- kura kienet assoċjata ma ’ bidliet adrenali f’ esponimenti ftit aktar għoljin minn dawk li dehru f’ pazjenti kliniċi.
This effect is associated with increased plasma cholesterol concentrations.
10 għoljin ta ’ kolesterol fil- plażma.
No similar changes have been identified in humans.
L- ebda bidla simili ma ġiet identifikata fil- bnedmin.
No effect on the adreno-cortical axis was noted in humans.
L- ebda effett fl- assi adreno- kortikali ma kien innotat fil- bnedmin.
In long-term carcinogenicity studies at doses of ranolazine up to 50 mg/ kg/ day (150 mg/ m2/ day) in mice and 150 mg/ kg/ day (900 mg/ m2/ day) in rats, no relevant increases in the incidence of any tumour types were seen.
Fi studji ta ’ karċinoġeniċità f’ dożi ta ’ ranolazine sa 50 mg/ kg/ kuljum (150 mg/ m2/ kuljum) fil- ġrieden u 150 mg/ kg/ kuljum (900 mg/ m2/ kuljum) fil- firien, ma ntwerew l- ebda żidiet relevanti fl- inċidenza ta ’ xi tipi ta ’ tumuri.
These doses are equivalent to 0.1 and 0.8 times, respectively, the maximum recommended human dose of 2 grams on a mg/ m2 basis, and represent the maximum tolerated doses in these species.
Dawn id- dożi huma ekwivalenti għal 0. 1 u 0. 8- il darba, rispettivament, id- doża massima rrakkomandata għal bniedem ta ’ 2 grammi fuq bażi ta ’ mg/ m2, u jirrappreżentaw id- dożi massimi ttollerati f’ dawn l- ispeċi.
Signs of embryonal and maternal toxicity, but not teratogenicity, were seen at doses of ranolazine up to 400 mg/ kg/ day (2400 mg/ m2/ day) in rats and 150 mg/ kg/ day (1275 mg/ m2/ day) in rabbits.
Sinjali ta ’ tossiċità embrijunali u materna, iżda mhux teratoġeniċità, dehru f’ dożi ta ’ ranolazine sa 400 mg/ kg/ kuljum (2400 mg/ m2/ kuljum) fil- firien u 150 mg/ kg/ kuljum (1275 mg/ m2/ kuljum) fil- fniek.
These doses represent 2 and 1 times, respectively, the maximum recommended human dose.
Dawn id- dożi jirrapreżentaw darbtejn u darba, id- doża massima rrakkomandata tal- bniedem, rispettivament.
Excipients for all ranolazine prolonged-release tablets:
Sustanzi mhux attivi għall- pilloli ta ’ ranolazine kollha li jerħu l- mediċina bil- mod:
Carnauba wax Hypromellose Magnesium stearate Methacrylic acid-ethyl acrylate copolymer (1:1) Microcrystalline cellulose Sodium hydroxide Titanium dioxide
Carnauba wax Hypromellose Magnesium stearate Methacrylic acid- ethyl acrylate copolymer (1: 1) Microcrystalline cellulose Sodium hydroxide Titanium dioxide
Additional excipients for 375 mg tablet:
Sustanzi mhux attivi għall- pilloli ta ’ 375 mg:
Polyethylene glycol Polysorbate 80 Blue #2/ Indigo Carmine Aluminium Lake (E132)
Polyethylene glycol Polysorbate 80 Blu # 2/ Indigo Carmine Aluminium Lake (E132)
This medicinal product does not require any special storage conditions.
Din il- mediċina m’ għandhiex bżonn ħażna l- speċjali.
PVC/ PVDC/ Aluminium blisters of 10 tablets per blister card.
Folji ta ’ PVC/ PVDC/ Aluminju ta ’ 10 pilloli kull folja.
Each carton contains 3, 6, or 10 blister cards (30, 60, or 100 tablets) or one HDPE bottle containing 60 tablets.
Kull kartuna fiha 3, 6, jew 10 folji (30, 60, jew 100 pillola) jew flixkun HDPE li fih 60 pillola.
Not all pack-sizes may be marketed.
Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għal skop kummerċjali.
1, Avenue de la Gare, L-1611 Luxembourg Luxembourg
1, Avenue de la Gare, L- 1611 Luxembourg Il- Lussemburgu
60 tablets in blister pack 60 tablets in bottle 30 tablets in blister pack 100 tablets in blister pack
60 pillola f’ pakkett ta ’ folji 60 pillola fi fliexkun 30 pillola f’ pakkett ta ’ folji 100 pillola f’ pakkett ta ’ folji
09 July 2008
9 ta ’ Lulju 2008
Ranexa 500 mg prolonged-release tablets
Ranexa 500 mg pilloli li jerħu l- mediċina bil- mod
Each tablet contains 500 mg of ranolazine.
Kull pillola fiha 500 mg ta ’ ranolazine.
Each tablet contains 0.12 mg azo colouring agent E110.
Għal- lista kompleta ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1.
Prolonged-release tablet Light orange oval-shaped tablet engraved with CVT500 on one side.
Pillola li terħi l- mediċina bil- mod Pillola b’ forma ovali oranġjo ċar imnaqqxa b’ CVT500 fuq naħa waħda.
13 Elderly:
13 Anzjani:
Therefore, caution should be observed
Analiżi bbażata fuq il- popolazzjoni ta ’ dejta kkumbinata minn pazjenti u voluntiera f’ saħħithom uriet li l- inżul tar- relazzjoni tal- konċentrazzjoni tal- plażma- QTc kienet stmata li hija 14 2. 4 msek kull 1000 ng/ ml, li hija bejn wieħed u ieħor daqs żieda ta ’ 2 - sa 7- msek fuq il- medda ta ’ konċentrazzjoni fil- plażma għal ranolazine 500 sa 1000 mg darbtejn kuljum.
14 when treating patients with a history of congenital or a family history of long QT syndrome, in patients with known acquired QT interval prolongation, and in patients treated with drugs affecting the QTc interval (see section 4.5 also).
Għaldaqstant, għandha tiġi osservata l- kawtela meta pazjenti bi storja ta ’ sindromu QT twil konġenitali jew bi storja fil- familja, meta pazjenti b’ titwil fl- interval QT akkwistat, u meta pazjenti li qegħdin jiġu kkurati b’ mediċini li jaffettwaw l- intervall QTc (ara wkoll sezzjoni 4. 5).
Azo colouring agent E110:
Is- sustanza kolorant azo E110:
This medicinal product contains the azo colouring agent E110 which may cause allergic reactions.
Dan il- prodott mediċinali fih is- sustanza kolorant azo E102 li tista ’ tikkawża reazzjonijiet allerġiċi.
Effects of ranolazine on other medicinal products
15 Effetti ta ’ ranolazine fuq prodotti mediċinali oħra
15 Available data suggest that ranolazine is a mild inhibitor of CYP2D6.
Dejta disponibbli tissuġġerixxi li ranolazine huwa impeditur ħafif ta ’ CYP2D6.
The potential for inhibition of CYP2B6 has not been evaluated.
Il- potenzjal għal impediment ta ’ CYP2B6 ma ġiex evalwat.
The potential risk for humans is unknown.
Ir- riskju li jista ’ jkun hemm fuq in- nies, mhux l- magħruf.
Metabolism and nutrition disorders Uncommon: anorexia, decreased appetite, dehydration.
16 Disturbi fil- metaboliżmu u n- nutrizzjoni Mhux komuni: anoressja, tnaqqis fl- aptit, deidratazzjoni
16 Nervous system disorders Common: dizziness, headache.
Disturbi fis- sistema nervuża Komuni: sturdament, uġigħ ta ’ ras.
Eye disorders Uncommon: blurred vision, visual disturbance.
Disturbi fl- għajnejn Mhux komuni: viżta mċajpra, disturbi fil- viżta.
Evaluations in patients who may be considered at higher risk of adverse events when treated with other antianginal medicinal products, e. g. patients with diabetes, Class I and II heart failure, or obstructive airway disease, confirmed that these conditions were not associated with clinically meaningful increases in the incidence of adverse events.
Evalwazzjonijiet f’ pazjenti li jistgħu jkunu kkunsidrati f’ riskju ogħla ta ’ avvenimenti avversi meta kkurati bi prodotti mediċinali kontra l- anġina oħra, eż. pazjenti bid- dijabete, falliment tal- qalb Klassi I u II, jew mard li
Of the most commonly reported, the following events occurred more often with Ranexa (placebo-corrected frequencies) in elderly
Fost l- aktar avvenimenti komuni rapportati, l- avvenimenti li ġejjin seħħew aktar ta ’ spiss b’ Ranexa (frekwenzi korretti bi plaċebo) fl- anzjani (età ≥ 75- il sena) milli f’ pazjenti aktar żgħar (età < 75- il sena): stitikezza (8% kontra 5%), dardir (6% kontra 3%), pressjoni tad- demm baxxa (5% kontra 1%), u remettar (4% kontra 1%).
In patients with mild or moderate renal impairment (creatinine clearance ≥ 30– 80 ml/ min) compared to those with normal renal function (creatinine clearance > 80 ml/ min), the most commonly reported events and their placebo-corrected frequencies included: constipation (8% versus 4%), dizziness (7% versus 5%), and nausea (4% versus 2%).
F’ pazjenti b’ indeboliment tal- kliewi ħafif jew moderat (rata ta ’ eliminazzjoni ta ’ kreatinina ≥ 30- 80 ml/ min u ≤ 80 ml/ min) meta mqabbla ma ’ dawk b’ funzjoni tal- kliewi normali (rata ta ’ eliminazzjoni ta ’ kreatinina > 80 ml/ min), l- aktar avvenimenti rrapportati b’ mod komuni u l- frekwenzi korretti bi plaċebo nkludew: stitikezza (8% kontra 4%), sturdament (7% kontra 5%), u dardir (4% kontra 2%).
Clinical evidence of inhibition of the late sodium current by ranolazine is provided by a significant shortening of the QTc interval and an improvement in diastolic relaxation in an open-label study of 5 patients with a long QT syndrome (LQT3 having the SCN5A ∆ KPQ gene mutation).
Evidenza klinika ta ’ impediment tal- kurrent ittardjat tas- sodju permezz ta ’ ranolazine hija pprovduta permezz ta ’ tqassir sinifikattiv ta ’ l- intervall QTc u titjib fir- rilassament 18 dijastoliku fi studju b’ tikketta miftuħa ta ’ 5 pazjenti b’ sindromu QT twil (LQT3 ikollu mutazzjoni ta ’ ġene SCN5A ∆KPQ).
18 Electrocardiographic effects:
Effetti elettrokardjografiċi:
These effects of ranolazine on the surface electrocardiogram are believed to result from inhibition of the fast-rectifying potassium current, which prolongs the ventricular action potential, and from inhibition of the late sodium current, which shortens the ventricular action potential.
Dawn l- effetti ta ’ ranolazine fuq l- elettrokardjogramma tal- wiċċ jinħasbu li jirriżultaw minn impediment tal- kurrent tal- potassju li jikkoregi malajr, li jtawwal il- potentzjal ta ’ l- azzjoni ventrikolari, u minn impediment tal- kurrent ittardjat tas- sodju, li jqassar l- potenzjal ta ’ l- azzjoni ventrikolari.
A population analysis of combined data from 1,308 patients and healthy volunteers demonstrated a mean increase in QTc from baseline of 2.4 msec per 1000 ng/ ml ranolazine plasma concentration.
Analiżi tal- popolazzjoni ta ’ dejta kkumbinata minn 1, 308- il pazjent u voluntiera f’ saħħithom urew żieda medja fil- QTc mil- linja bażi b’ 2. 4 msek kull 1000 ng/ ml konċentrazzjoni ta ’ ranolazine fil- plażma.
Five-hundred and sixty-five patients were randomised to receive an initial dose of Ranexa 500 mg twice daily or placebo for 1 week, followed by 6 weeks of treatment with Ranexa 1000 mg twice daily or placebo, in addition to concomitant treatment with amlodipine 10 mg once daily.
19 tal- bidu ta ’ Ranexa 500 mg darbtejn kuljum jew plaċebo għal ġimgħa, segwiti b’ 6 ġimgħat ta ’ kura b’ Ranexa 1000 mg darbtejn kuljum jew plaċebo, f’ addizjoni ma ’ kura konkomittanti b’ amlodipine 10 mg darba kuljum.
Both the average number of angina attacks and nitroglycerin tablets consumed decreased by approximately one per week.
Kemm in- numru ta ’ attakki ta ’ anġina u l- pilloli ta ’ nitrogliċerina kkunsmati naqsu b’ madwar wieħed fil- ġimgħa.
Improvement of exercise duration was statistically significant compared to placebo for all three doses of ranolazine
Ranexa kienet superjuri b’ mod sinjifikanti għal plaċebo fid- dożi kollha studjati f’ li ttawwal il- ħin ta ’ l- eżerċizzju, żmien għal anġina, u żmien għal depressjoni tas- segment ST b’ mm 1 b’ relazzjoni osservata ta ’ doża- rispons.
19 from 24 seconds at 500 mg twice daily to 46 seconds at 1500 mg twice daily, showing a dose-related response.
It- titjib f’ kemm idum l- eżerċizzju kien statistikament sinjifikanti meta mqabbel ma ’ plaċebo għat- tliet dożi l- oħrajn kollha ta ’ ranolazine minn 24 sekonda b’ 500 mg darbtejn kuljum għal 46 sekonda b’ 1500 mg darbtejn kuljum, u dan juri rispons relatat mad- doża.
In a large outcome study (MERLIN-TIMI 36) in 6,560 patients with UA/ NSTEMI ACS, there was no difference in the risk of all-cause mortality (relative risk ranolazine: placebo 0.99), sudden cardiac death (relative risk ranolazine: placebo 0.87), or the frequency of symptomatic documented arrhythmias (3.0% versus 3.1%) between Ranexa and placebo when added to standard medical therapy (including beta-blockers, calcium channel blockers, nitrates, anti-platelet agents, lipid-lowering medicinal products, and ACE inhibitors).
Fi studju ta ’ riżultat kbir (MERLIN- TIMI 36) f’ 6, 560 pazjent b’ UA/ NSTEMI ACS, ma kien ebda differenza fir- riskju tal- mortalità b’ kull kawża (riskju relattiv ranolazine: plaċebo 0. 99), mewta kardijaka f’ daqqa (riskju relattiv ranolazine: plaċebo 0. 87), jew il- frekwenza ta ’ l- arritmiji sintomatiċi dokumentati (3. 0% kontra 3. 1%) bejn Ranexa u placebo meta miżjuda ma ’ terapija medika standard (inklużi mblokkaturi- beta, imblokkaturi tal- kanali tal- kalċju, nitrati, mediċini kontra l- pjastrini, prodotti mediċinali li jbaxxu l- lipidi u impedituri ACE).
The terminal half-life at steady state after oral administration of ranolazine is about 7 hours, due to the absorption rate-limited elimination.
20 wara għoti orali ta ’ ranolazine huwa madwar 7 sigħat, minħabba r- rata ta ’ eliminazzjoni limitata mill- assorbiment.
In healthy young adults, ranolazine accounts for approximately 13% of the radioactivity in plasma following a single oral 500 mg dose of [14C]-ranolazine.
F’ adulti żgħar f’ saħħithom, ranolazine jagħti spjegazzjoni għal madwar 13% tar- radjuattività fil- plażma wara doża waħda orali ta ’ 500 mg ta ’ [14C] - ranolazine.
20 Gender effects:
Effetti ta ’ sess:
Body weight:
Piż korporali:
Adverse reactions not observed in clinical studies, but seen in animals at levels similar to clinical exposure, were as follows:
Reazzjonijiet avversi mhux osservati fi studji kliniċi, iżda dehru f’ annimali f’ livelli simili għal esponiment kliniku kienu kif ġejjin, Ranolazine kien assoċjat ma ’ aċċessjonijiet u żieda fil- mortalità
Ranolazine was associated with convulsions and increased mortality in rats and dogs at plasma concentrations approximately 3-fold higher than at the proposed maximum clinical dose.
21 fil- firien u fil- klieb f’ konċentrazzjonijiet fil- plażma madwar 3 drabi aktar għoljin milli fid- doża klinika massima proposta.
This effect is associated with increased plasma cholesterol concentrations.
Dan l- effett kien assoċjat ma ’ konċentrazzjonijiet aktar għoljin ta ’ kolesterol fil- plażma.
Additional excipients for 500 mg tablet:
Sustanzi mhux attivi addizzjonali għall- pilloli ta ’ 500 mg:
Polyethylene glycol Polysorbate 80 Yellow #6/ Sunset Yellow FCF Aluminium Lake (E110)
Polyethylene glycol Polysorbate 80 Isfar # 6/ Sunset Yellow FCF Aluminium Lake (E110)
6.6 Special precautions for disposal
22 6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema
Ranexa 750 mg prolonged-release tablets
Ranexa 750 mg pilloli li jerħu l- mediċina bil- mod
Each tablet contains 750 mg of ranolazine.
Kull pillola fiha 750 mg ta ’ ranolazine.
Each tablet contains 0.04 mg azo colouring agent E102 and 12.0 mg lactose monohydrate.
Għal- lista kompleta ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1.
Prolonged-release tablet Pale green oval-shaped tablet engraved with CVT750 on one side.
Pillola li terħi l- mediċina bil- mod Pillola b’ forma ovali ta ’ kulur aħdar ċar imnaqqxa b’ CVT750 fuq naħa waħda.
24 Elderly:
24 Anzjani:
QT prolongation:
25 Titwil QT:
Therefore, caution should be observed
Analiżi bbażata fuq il- popolazzjoni ta ’ dejta kkumbinata minn pazjenti u voluntiera f’ saħħithom uriet li l- inżul tar- relazzjoni tal- konċentrazzjoni tal- plażma- QTc kienet stmata li hija 2. 4 msek kull 1000 ng/ ml, li hija bejn wieħed u ieħor daqs żieda ta ’ 2 - sa 7- msek fuq il- medda ta ’ konċentrazzjoni fil- plażma għal ranolazine 500 sa 1000 mg darbtejn kuljum.
25 when treating patients with a history of congenital or a family history of long QT syndrome, in patients with known acquired QT interval prolongation, and in patients treated with drugs affecting the QTc interval (see section 4.5 also).
Għaldaqstant, għandha tiġi osservata l- kawtela meta pazjenti bi storja ta ’ sindromu QT twil konġenitali jew bi storja fil- familja, meta pazjenti b’ titwil fl- interval QT akkwistat, u meta pazjenti li qegħdin jiġu kkurati b’ mediċini li jaffettwaw l- intervall QTc (ara wkoll sezzjoni 4. 5).
This medicinal product contains lactose.
Dan il- prodott mediċinali fih lactose.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.
Pazjenti li għandhom problemi ereditarji rari ta ’ intoleranza għal galactose, nuqqas ta ’ Lapp lactase, jew malassorbiment glucose- galactose m’ għandhomx jieħdu dan il- prodott mediċinali.
Azo colouring agent E102:
Is- sustanza kolorant azo E102:
This medicinal product contains the azo colouring agent E102 which may cause allergic reactions.
Dan il- prodott mediċinali fih is- sustanza kolorant azo E102 li tista ’ tikkawża reazzjonijiet allerġiċi.
The potent CYP2D6 inhibitor paroxetine, at a dose of 20 mg once daily, increased steady-state plasma concentrations of ranolazine 1000 mg twice daily by an average of 1.2-fold.
Paroxetine, l- impeditur qawwi CYP2D6, f’ doża ta ’ 20 mg darba kuljum, żied il- konċentrazzjonijiet ta ’ stat fiss ta ’
26 Effects of ranolazine on other medicinal products
Effetti ta ’ ranolazine fuq prodotti mediċinali oħra
Available data suggest that ranolazine is a mild inhibitor of CYP2D6.
Dejta disponibbli tissuġġerixxi li ranolazine huwa impeditur ħafif ta ’ CYP2D6.
The adverse events, considered to be at least possibly related to treatment, are listed below by body system, organ class, and absolute frequency.
27 L- avvenimenti avversi, ikkunsidrati li huma possibbilment relatati mal- kura, huma elenkati hawn taħt permezz ta ’ sistema tal- ġisem, klassifika ta ’ l- organi, u frekwenza assoluta.
27 Psychiatric disorders Uncommon: anxiety, insomnia.
Disturbi psikjatriċi Mhux komuni: ansjetà, insomnja.
Nervous system disorders Common: dizziness, headache.
Disturbi fis- sistema nervuża Komuni: sturdament, uġigħ ta ’ ras.
The adverse event profile was generally similar in the MERLIN-TIMI 36 study.
28 Il- profil ta ’ l- avveniment avers kien ġeneralment simili fl- istudju MERLIN- TIMI 36.
28 Elderly, renal impairment, and low weight:
Anzjani, indeboliment tal- kliewi, u piż baxx:
Of the most commonly reported, the following events occurred more often with Ranexa (placebo-corrected frequencies) in elderly (≥ 75 years of age) than younger patients (< 75 years of age): constipation (8% versus 5%), nausea (6% versus 3%), hypotension (5% versus 1%), and vomiting (4% versus 1%).
Fost l- aktar avvenimenti komuni rapportati, l- avvenimenti li ġejjin seħħew aktar ta ’ spiss b’ Ranexa (frekwenzi korretti bi plaċebo) fl- anzjani (età ≥ 75- il sena) milli f’ pazjenti aktar żgħar (età < 75- il sena): stitikezza (8% kontra 5%), dardir (6% kontra 3%), pressjoni tad- demm baxxa (5% kontra 1%), u remettar (4% kontra 1%).
Ranolazine, via its action to decrease the late sodium current, is considered to reduce these intracellular ionic imbalances during ischaemia.
29 Ranolazine, permezz ta ’ l- azzjoni li jnaqqas il- kurrent ittardjat tas- sodju, huwa kkunsidrat li jnaqqas dawn l- iżbilanċi joniċi intraċellolari waqt l- iskemija.
29 Pharmacodynamic effects
Effetti farmakodinamiċi
Given the dose-dependent side effects and similar efficacy at 750 and 1000 mg twice daily, a maximum dose of 750 mg twice daily is recommended.
30 dipendenti fuq id- doża u effikaċja simili f’ 750 u 1000 mg darbtejn kuljum, hija rrakkomandata doża massima ta ’ 750 mg darbtejn kuljum.
30 In the main dose-finding study, MARISA, ranolazine was used as monotherapy.
Fl- istudju ewlieni ta ’ sejbien tad- doża, MARISA, ranolazine intuża bħala monoterapija.
Following oral administration of a single 500 mg dose of [14C]-ranolazine to healthy subjects, 73% of the radioactivity was recovered in urine and 25% in faeces.
31 500 mg ta ’ [14C] - ranolazine lil suġġetti f’ saħħithom, 73% tar- radjuattività kienet irkuprata fl- awrina u 25% fl- ippurgar.
At 500 mg twice daily, subjects lacking CYP2D6 activity (poor metabolisers,
Studji in vitro permezz ta ’ l- użu ta ’ mikrożomi tal- fwied tal- bniedem jindikaw li ranolazine huwa metabolizzat primarjament minn CYP3A4, u wkoll minn CYP2D6.
31 PM) had 62% higher AUC than subjects with CYP2D6 metabolising capacity (extensive metabolisers, EM).
F’ 500 mg darbtejn kuljum, suġġetti li m’ għandhomx attività CYP2D6 (metabolizzaturi dgħajfin, PM) kellhom l- AUC 62% aktar għolja minn suġġetti b’ kapaċità metabolizzanti CYP2D6 (metabolizzaturi estensivi, EM).
5.3 Preclinical safety data
32 5. 3 Tagħrif ta 'qabel l- użu kliniku dwar is- sigurtà tal- mediċina
These doses are equivalent to 0.1 and 0.8 times, respectively, the maximum
Fi studji ta ’ karċinoġeniċità f’ dożi ta ’ ranolazine sa 50 mg/ kg/ kuljum (150 mg/ m2/ kuljum) fil- ġrieden u 150 mg/ kg/ kuljum (900 mg/ m2/ kuljum) fil- firien, ma ntwerew l- ebda żidiet relevanti fl- inċidenza ta ’ xi tipi ta ’ tumuri.
32 recommended human dose of 2 grams on a mg/ m2 basis, and represent the maximum tolerated doses in these species.
Dawn id- dożi huma ekwivalenti għal 0. 1 u 0. 8- il darba, rispettivament, id- doża massima rrakkomandata għal bniedem ta ’ 2 grammi fuq bażi ta ’ mg/ m2, u jirrappreżentaw id- dożi massimi ttollerati f’ dawn l- ispeċi.
Additional excipients for 750 mg tablet:
Sustanzi mhux attivi addizzjonali għall- pilloli ta ’ 750 mg:
Glycerol triacetate Lactose monohydrate Blue #1/ Brilliant Blue FCF Aluminium Lake (E133) and Yellow #5/ Tartrazine Aluminium Lake (E102)
Glycerol triacetate Lactose monohydrate Blu # 1/ Brilliant Blue FCF Aluminium Lake (E133) u Isfar # 5/ Tartrazine Aluminium Lake (E102)
6.5 Nature and contents of container
33 6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
Pharos House Wye Valley Business Park Hay-on-Wye Hereford HR3 5PG United Kingdom
Pharos House Wye Valley Business Park Hay- on- Wye Hereford HR3 5PG Ir- Renju Unit
The MAH must agree the details of a Patient Alert Card (PAC) with the National Competent Authorities and must provide this PAC directly to the pharmacy with each Ranexa shipment.
Id- detentur ta ’ l- awtorizzazzjoni għat- tqegħid fis- suq għandu jaqbel fuq id- dettalji tal- Kard ta ’ Twissija tal- Pazjent (PAC) ma ’ l- Awtoritajiet Kompetenti Nazzjonali u għandu jipprovdi dan il- PAC direttament lill- ispiżerija ma ’ kull kunsinna ta ’ Ranexa.
Health Care Professional information The PAC should include the following information for the healthcare professional information regarding Ranexa: • To refer to the Ranexa SPC prior to prescribing any medications to the patient, as there are potential drug interactions which should be taken into consideration. • Ranexa is contraindicated in patients taking: • Potent CYP3A4 inhibitors (e. g. itraconazole, ketoconazole, voriconazol, posaconazol, HIV protease inhibitors, clarithromycin, telithromycin, nefazodone) • Class Ia (e. g. quinidine) or Class III (e. g. dofetilide, sotalol) antiarrhythmics other than amiodarone
Informazzjoni għall- professjonisti fil- kura tas- saħħa Il- PAC għandu jinkludi l- informazzjoni li ġejja għall- professjonisti tal- kura tas- saħħa fir- rigward ta ’ Ranexa: • Li ssir referenza għall- Sommarju tal- Karatteristiċi tal- Prodott ta ’ Ranexa qabel il- preskrizzjoni ta ’ kwalunkwe mediċina lill- pazjent, minħabba li hemm interazzjonijiet potenzjali tal- mediċina li għandhom jitqiesu. • Ranexa mhuwiex rakkomandat f’ pazjenti li qegħdin jieħdu: • Inibituri CYP3A4 qawwijin (eż. itraconazole, ketoconazole, voriconazol, posaconazol, inibituri tal- protease tal- HIV, clarithromycin, telithromycin, nefazodone) • Antiarrittmiċi ta ’ Kategorija Ia (eż. quinidine) jew Kategorija III (eż., dofetilide, sotalol) għajr amiodarone
• Caution should be exercised when prescribing Ranexa to patients: • Taking certain other drugs mentioned in the product information • With certain other risk factors listed in the product information
• Għandha tiġi eżerċitata l- kawtela meta Ranexa jingħata lill- pazjenti: • li jkunu qegħdin jieħdu ċerti mediċini oħrajn imsemmija fl- informazzjoni dwar il- prodott • B’ ċerti fatturi ta ’ riskju oħrajn elenkati fl- informazzjoni dwar il- prodott
• Inform the patient about the potential for an interaction with other prescribed medicinal products and to contact his/ her doctor in case of dizziness, nausea or vomiting.
• Informa lill- pazjent dwar il- potenzjal għal interazzjoni ma ’ prodotti mediċinali oħrajn li jingħataw b’ riċetta u li jikkuntattja lit- tabib/ a tiegħu/ tagħha fil- każ ta ’ sturdament, nawsea jew rimettar.
Patient information The PAC should include the following information for the patient: • That the card should be shown to any doctor involved in their treatment • That prior to Ranexa treatment the patient should tell their doctor if they have any of the following:
Informazzjoni għall- pazjent Il- PAC għandu jinkludi l- informazzjoni li ġejja għall- pazjent:
36 • Kidney problems • Liver problems • Have ever had an abnormal electrocardiogram (ECG) • Is taking medications to treat epilepsy, bacterial or fungal infections, HIV infection, depression or heart rhythm disorders • Is taking the herbal remedy St John’ s Wort • Is taking allergy medicines
36 • li l- kard għandha tintwera lil kwalunkwe tabib involut fit- trattament tiegħu/ tagħha • li qabel trattament b’ Ranexa, il- pazjent għandu jgħid lit- tabib tiegħu jekk huwa għandux xi ħaġa minn dawn li ġejjin: • problemi fil- kliewi • problemi fil- fwied • qatt kellu xi elettrokardjogramma (ECG) anormali • jekk hux qiegħed jieħu mediċina biex jikkura epilepsija, infezzjonijiet batterjali jew fungali, infezzjoni ta ’ l- HIV, depressjoni jew disturbi fir- rittmu tal- qalb • jekk hux qiegħed jieħu r- rimedju erbali St John’ s Wort • jekk hux qiegħed jieħu mediċini kontra l- allerġiji
• To refer to the Ranexa package leaflet for more information. • To ensure to take a list of all their other medicines with them at any visit to the health care professional.
• Biex jirreferi għall- fuljett ta ’ tagħrif ta ’ Ranexa għal aktar informazzjoni. • Biex ma kull viżta għand professjonista tal- kura tas- saħħa, jieħu miegħu lista tal- mediċini l- oħrajn kollha tiegħu
Pharmacovigilance system The MAH must ensure that the system of pharmacovigilance, as described in version 2 presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and whilst the product is on the market.
Sistema ta ’ farmakoviġilanza Id- detentur ta ’ l- awtorizzazzjoni għat- tqegħid fis- suq għandu jiżgura li s- sistema ta ’ farmakoviġilanza, kif deskritta fil- verżjoni 2 ippreżentata fil- Modulu 1. 8. 1. ta ’ l- Applikazzjoni ta ’ l- Awtorizzazzjoni għat- Tqegħid Fis- Suq, tkun fis- seħħ qabel u waqt li l- prodott ikun fis- suq.
Risk Management Plan The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan, as agreed in version 0005 of the Risk Management Plan (RMP) presented in Module 1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP agreed by the CHMP.
Pjan ta ’ Ġestjoni tar- Riskji Id- detentur ta ’ l- awtorizzazzjoni għat- tqegħid fis- suq jimpenja ruħu li jwettaq l- istudji u l- attivitajiet addizzjonali ta ’ farmakoviġilanza mogħtija fid- dettall fil- Pjan ta ’ Farmakoviġilanza, kif sar qbil fuqu fil- verżjoni 0005 tal- Pjan ta ’ Ġestjoni tar- Riskji (RMP) ippreżentat fil- Modulu 1. 8. 2. ta ’ l - Applikazzjoni għall- Awtorizzazzjoni għat- Tqegħid fis- Suq u għal kwalunkwe aġġornament sussegwenti tal- RMP li jsir qbil fuqu mill- CHMP.
In addition, an updated RMP should be submitted • When new information is received that may impact on the current Safety Specification, Pharmacovigilance Plan or risk minimisation activities • Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being reached • At the request of the EMEA
Barra minn hekk, għandu jiġi ppreżentat RMP aġġornat • Meta tasal informazzjoni ġdida li jista ’ jkollha impatt fuq l- Ispeċifikazzjoni tas- Sigurtà, il- Pjan ta ’ Farmakoviġilanza jew l- attivitajiet ta ’ minimizzazzjoni tar- riskji attwali • Fi żmien 60 jum minn meta tintlaħaq mira importanti (farmakoviġilanza jew minimizzazzjoni tar - riskji) • Fuq talba ta ’ l- EMEA
37 ANNEX III
37 ANNESS III
Carton containing blister strips or carton containing HDPE bottle and bottle label.
Kartuna li fiha folji jew kartuna li fiha flixkun HDPE u t- tikketta tal- flixkun.