qanastek/EMEA-V3 huggingface dataset:
Dose increases should be carried out carefully in the elderly, in patients who weigh less than 60 kg, and in patients who have problems with their kidneys, liver or heart.
Żjiediet fid- doża għandhom jiġu amministrati b’ mod kawt f’ pazjenti anzjani li jiżnu anqas minn 60 kg u f’ pazjenti li għandhom problemi tal- kliewi, il- fwied jew il- qalb.
Ranexa tablets should be swallowed whole and should not be broken, crushed or chewed.
Pilloli Ranexa għandhom jinbelgħu sħaħ u ma għandhomx jiġi maqsuma, misħuqa jew magħmuda.
They can be taken with or without food.
Jistgħu jittieħdu kemm mal- ikel kif ukoll fuq stonku vojt.
Patients who are given Ranexa must also be given a ‘ patient alert card ’ that summarises the key safety information about the medicine.
Pazjenti li jingħataw Ranexa għandhom jingħataw ukoll ‘ skeda dwar is- saħħa tal- pazjent ’ li jkun fiha informazzjoni saljenti u fil- qosor dwar is- sigurtà tal- mediċina.
How does Ranexa work?
Kif jaħdem Ranexa?
The active substance in Ranexa, ranolazine, is thought to work by reducing the flow of sodium ions into the heart muscle cells.
Is- sustanza attiva f’ Ranexa, ranolazine hija maħsuba sabiex taħdem fuq it- tnaqqis tal- fluss ta ’ ijoni tas- sodju fiċ- ċelloli tal- muskoli tal- qalb.
Calcium ions normally cause the heart muscle to contract.
Dan jinterferixxi mal- attività ta ’ kanali speċjali fil- wiċċ taċ - ċellola li jissejħu ‘ kanali tal- kalċju li jiddependu fuq is- sodju ’ li minnhom normalment l- ijoni tal - kalċju jidħlu fiċ- ċelloli, li jnaqqsu n- numru ta ’ ijoni tal- kalċju li jidħlu fiċ- ċelloli.
By reducing the flow of calcium into the cells, ranolazine is thought to help the heart to relax, improving blood flow to the heart muscle and relieving the symptoms of angina pectoris.
Normalment l- ijoni tal- kalċju jikkawżaw rilassament tal- qalb, b’ hekk jitjieb il- fluss tad- demm lejn il- muskolu tal- qalb u jittaffew is- sintomi ta ’ anġina pectoris.
How has Ranexa been studied?
Kif ġie studjat Ranexa?
The effects of Ranexa were first tested in experimental models before being studied in humans.
L- effetti ta ’ Ranexa għall- ewwel ġew ittestjati f’ mudelli sperimentali qabel ma ’ ġew studjati fil - bniedem.
Ranexa has been studied in one main study including a total of 823 patients with an average age of 64 years who had had angina pectoris for at least three months.
Ranexa ġie studjat fi studju prinċipali li kien jinkludi total ta ’ 823 pazjent ta ’ età medja ta ’ 64 sena li kellhom anġina pectoris għal mill- anqas tliet xhur.
Two doses of Ranexa (750 and 1000 mg twice a day) were compared with placebo (a dummy treatment) as an add-on to commonly used medicines for angina pectoris (atenolol, amlodipine or diltiazem).
Żewġ dożi ta ’ Ranexa (750 u 1000 mg darbtejn kuljum) tqabblu ma ’ plaċebo (trattament finta) bħala trattament addizzjonali flimkien ma ’ mediċini użati b’ mod komuni għal anġina pectoris (atenolol, amlodipine jew diltiazem).
The main measure of effectiveness was how long patients could exercise after 12 weeks of treatment, compared with before treatment.
Il- kejl ewlieni tal - effikaċja kien it- tul ta ’ żmien li l- pazjenti setgħu jagħmlu eżerċizzju wara 12– il ġimgħa ta ’ trattament meta mqabbel ma ’ trattament preċedenti.
What benefit has Ranexa shown during the studies?
Liema benefiċċju wera Ranexa waqt l- istudji mwettqa?
Ranexa was more effective than placebo at increasing the length of time the patients could exercise.
Ranexa kien effikaċi aktar mill- plaċebo fiż- żieda fit- tul ta ’ ħin waqt liema l- pazjenti jistgħu jagħmlu eżerċizzju.
At the start of the study, the patients could exercise for about 7 minutes.
Fil- bidu tal- istudju il- pazjenti setgħu jagħmlu eżerċizzju għal madwar 7 minuti.
After 12 weeks, this increased by an average of 1 minute 56 seconds in the patients adding either dose of Ranexa, and by an average of 1 minute 32 seconds in those adding placebo.
Wara 12– il ġimgħa dan żdied b’ medja ta ’ minuta u 56 sekonda f’ pazjenti li jżidu kwalunkwe mid- dożi ta ’ Ranexa u b’ medja ta ’ minuta u 32 sekonda f’ dawk li jżidu l- plaċebo.
What is the risk associated with Ranexa?
X’ inhu r- riskju assoċjat ma ’ Ranexa?
The most common side effects with Ranexa (seen in between 1 and 10 patients in 100) are dizziness, headache, constipation, vomiting, nausea (feeling sick) and asthenia (weakness).
L- effetti sekondarji l- aktar komuni b’ Ranexa (dehru f’ madwar pazjent 1 u 10 pazjenti f’ 100) huma sturdament, uġigħ ta ’ ras, stitikezza, remettar, nawżea (dardir) u astenija (dgħufija).
For the full list of all side effects reported with Ranexa, see the Package Leaflet.
Għal- lista sħiħa tal- effetti sekondarji rrappurtati ma 'Ranexa, ara l- Fuljett ta' Tagħrif.
Ranexa should not be used in people who may be hypersensitive (allergic) to ranolazine or any of the other ingredients.
Ranexa m’ għandux jintuża minn persuni ipersensittivi (allerġiċi) għal ranolazine jew għal xi ingredjenti oħra tiegħu.
It must not be used in patients who have severe problems with their kidneys or moderate or severe problems with their liver.
M’ għandux jintuża f’ pazjenti li għandhom problemi severi bil- kliewi jew problemi moderati jew severi bil- fwied tagħhom.
It must also not be used in patients who are taking other medicines that are broken down in the same way as ranolazine, or certain other medicines that are used to correct the heart rhythm.
Ranexa ma għandux jintuża f’ pazjenti li qed jieħdu mediċini oħrajn li jinkisru bl- istess mod bħal ranolazine jew ċerti mediċini oħrajn li jintużaw sabiex tiġi kkoreġuta t- taħbita tal- qalb.
For the full list, see the Package Leaflet.
Għal- lista sħiħa, ara l- Fuljett ta ’ Tagħrif.
Why has Ranexa been approved?
Għaliex ġie approvat Ranexa?
The Committee for Medicinal Products for Human Use (CHMP) noted that the effectiveness of Ranexa in improving the symptoms of patients with stable angina pectoris is modest but that it could be of value in patients who have not responded fully to other medicines for angina pectoris.
Il- Kumitat għall- Prodotti Mediċinali għall- Użu mill- Bniedem (CHMP) innota li l- effikaċja ta ’ Ranexa fit- titjib tas- sintomi f’ pazjenti b’ anġina pectoris stabbli hija modesta iżda li tista ’ tkun ta ’ valur f’ pazjenti li ma rrispondewx għal mediċini oħrajn għal anġina pectoris.
The Committee decided that Ranexa’ s benefits are greater than its risks as an add-on treatment of the symptoms of patients with stable angina pectoris who are inadequately controlled or intolerant to first- line anti-anginal medicines (such as beta-blockers and calcium antagonists).
Il- Kumitat iddeċieda li l - benefiċċji ta ’ Ranexa huma akbar mir- riskji tiegħu bħala trattament addizzjonali tas- sintomi tal - pazjenti b’ anġina pectoris stabbli li huma kkontrollati b’ mod mhux xieraq jew li mhumiex intolleranti għal mediċini kontra l- anġina tat- tip tal- ewwel preferenza (bħal imblokkaturi beta u antagonisti tal - kalċju).
The Committee recommended that Ranexa be given marketing authorisation.
Il- Kumitat irrakkomanda li Ranexa jingħata awtorizzazzjoni għat- tqegħid fis- suq.
Which measures are being taken to ensure the safe use of Ranexa?
X’ miżuri qed jittieħdu biex ikun żgurat l- użu sigur ta ’ Ranexa?
The company that makes Ranexa will agree on the wording of the patient alert card in each Member State and ensure that the card is provided to all pharmacies that dispense Ranexa.
Il- kumpanija li tipproduċi Ranexa ser taqbel mal- kliem tal- iskeda tas- saħħa tal- pazjent f’ kull Stat Membru u tassigura li l- iskeda hija pprovduta fl- ispiżeriji kollha li jbiegħu Ranexa.
The card will include information for patients and healthcare workers explaining how to use the medicine safely.
L- iskeda ser tinkludi informazzjoni għal pazjenti u ħaddiema fil- qasam tas- saħħa li tispjega l- użu sigur tal - mediċina.
Other information about Ranexa:
Informazzjoni oħra dwar Ranexa:
The European Commission granted a marketing authorisation valid throughout the European Union for Latixa on 9 July 2008.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fis- suq valida madwar l- Unjoni Ewropea kollha għal Latixa fid- 9 ta ’ Lulju 2008.
The marketing authorisation holder is Menarini International Operations Luxembourg S. A.
Isem il- mediċina nbidel għal Ranexa fil- 11 ta ’ Awwissu 2008. id- detentur tal- awtorizzazzjoni għat- tqegħid fis- suq huwa Menarini International Operations Luxembourg S. A.
The full EPAR for Ranexa can be found here.
L- EPAR sħiħ għal Ranexa jista ’ jiġi kkonsultat hawn
EU Numbers EU/ 1/ 08/ 462/ 001 EU/ 1/ 08/ 462/ 002 EU/ 1/ 08/ 462/ 003 EU/ 1/ 08/ 462/ 004 EU/ 1/ 08/ 462/ 005 EU/ 1/ 08/ 462/ 006 EU/ 1/ 08/ 462/ 007 EU/ 1/ 08/ 462/ 008 EU/ 1/ 08/ 462/ 009 EU/ 1/ 08/ 462/ 010 EU/ 1/ 08/ 462/ 011 EU/ 1/ 08/ 462/ 012
Numru tal- EU EU/ 1/ 08/ 462/ 001 EU/ 1/ 08/ 462/ 002 EU/ 1/ 08/ 462/ 003 EU/ 1/ 08/ 462/ 004 EU/ 1/ 08/ 462/ 005 EU/ 1/ 08/ 462/ 006 EU/ 1/ 08/ 462/ 007 EU/ 1/ 08/ 462/ 008 EU/ 1/ 08/ 462/ 009 EU/ 1/ 08/ 462/ 010 EU/ 1/ 08/ 462/ 011 EU/ 1/ 08/ 462/ 012
Invented name Ranexa Ranexa Ranexa Ranexa Ranexa Ranexa Ranexa Ranexa Ranexa Ranexa Ranexa Ranexa
Isem inventat Ranexa Ranexa Ranexa Ranexa Ranexa Ranexa Ranexa Ranexa Ranexa Ranexa Ranexa Ranexa
Strength 375 mg 375 mg 500 mg 500 mg 750 mg 750 mg 375 mg 375 mg 500 mg 500 mg 750 mg 750 mg
Qawwa 375 mg 375 mg 500 mg 500 mg 750 mg 750 mg 375 mg 375 mg 500 mg 500 mg 750 mg 750 mg
Pharmaceutical Form Prolonged release tablet Prolonged release tablet Prolonged release tablet Prolonged release tablet Prolonged release tablet Prolonged release tablet Prolonged release tablet Prolonged release tablet Prolonged release tablet Prolonged release tablet Prolonged release tablet Prolonged release tablet
Għamla farmaċewtika Pillola li terħi l- mediċina bil- mod Pillola li terħi l- mediċina bil- mod Pillola li terħi l- mediċina bil- mod Pillola li terħi l- mediċina bil- mod Pillola li terħi l- mediċina bil- mod Pillola li terħi l- mediċina bil- mod Pillola li terħi l- mediċina bil- mod Pillola li terħi l- mediċina bil- mod Pillola li terħi l- mediċina bil- mod Pillola li terħi l- mediċina bil- mod Pillola li terħi l- mediċina bil- mod Pillola li terħi l- mediċina bil- mod
Route of administration Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use
Mnejn jingħata Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali
Packaging Blister (PVC/ PVDC/ alu) Bottle (HDPE) Blister (PVC/ PVDC/ alu) Bottle (HDPE) Blister (PVC/ PVDC/ alu) Bottle (HDPE) Blister (PVC/ PVDC/ alu) Blister (PVC/ PVDC/ alu) Blister (PVC/ PVDC/ alu) Blister (PVC/ PVDC/ alu) Blister (PVC/ PVDC/ alu) Blister (PVC/ PVDC/ alu)
Il- pakkett Folja (PVC/ PVDC/ alu) Fliexkun (HDPE) Folja (PVC/ PVDC/ alu) Fliexkun (HDPE) Folja (PVC/ PVDC/ alu) Fliexkun (HDPE) Folja (PVC/ PVDC/ alu) Folja (PVC/ PVDC/ alu) Folja (PVC/ PVDC/ alu) Folja (PVC/ PVDC/ alu) Folja (PVC/ PVDC/ alu) Folja (PVC/ PVDC/ alu)
Package size 60 tablets 60 tablets 60 tablets 60 tablets 60 tablets 60 tablets 30 tablets 100 tablets 30 tablets 100 tablets 30 tablets 100 tablets
Daqs tal- pakkett 60 pillola 60 pillola 60 pillola 60 pillola 60 pillola 60 pillola 30 pillola 100 pillola 30 pillola 100 pillola 30 pillola 100 pillola
Ranexa 375 mg prolonged-release tablets
Ranexa 375 mg pilloli li jerħu l- mediċina bil- mod
Each tablet contains 375 mg of ranolazine.
Kull pillola fiha 375 mg ta ’ ranolazine.
Prolonged-release tablet Pale blue oval-shaped tablet engraved with CVT375 on one side.
Pillola li terħi l- mediċina bil- mod Pillola ċelesti ovali mnaqqxa b’ CVT375 fuq naħa waħda.
Ranexa is indicated as add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled or intolerant to first-line antianginal therapies (such as beta- blockers and/ or calcium antagonists).
Ranexa hija indikata bħala terapija add- on għall- kura sintomatika ta ’ pazjenti b’ anġina pectoris stabbli li mhumiex ikkontrollati adegwatament jew mhumiex tolleranti għal terapiji ta ’ l- ewwel għażla kontra l- anġina (bħalma huma mblokkaturi- beta u/ jew antagonisti tal- kalċju).
Patients should be given the Ranexa package leaflet and the Patient Alert Card and instructed to present their Patient Alert Card and medication list to their health care professional at each visit.
Il- pazjenti għandhom jingħataw il- fuljett ta ’ tagħrif ta ’ Ranexa u l- Kard ta ’ Twissija tal- Pazjent u għandhom ikunu struwiti sabiex jippreżentaw il- Kard ta ’ Twissija tal- Pazjent u l- lista tal- medikazzjoni lill- professjonista tal- kura tas- saħħa f’ kull viżta.
Ranexa is available as 375 mg, 500 mg, and 750 mg prolonged-release tablets.
Ranexa tiġi bħala pilloli ta ’ 375 mg, 500 mg u 750 mg li jerħu l- mediċina bil- mod.
The recommended initial dose of Ranexa is 375 mg twice daily.
Id- doża tal- bidu rrakkomandata ta ’ Ranexa hija ta ’ 375 mg darbtejn kuljum.
After 2– 4 weeks, the dose should be titrated to 500 mg twice daily and, according to the patient’ s response, further titrated to a recommended maximum dose of 750 mg twice daily (see section 5.1).
Wara 2 – 4 ġimgħat, id- doża għandha tkun titrata għal 500 mg darbtejn kuljum u, skond ir- reazzjoni tal- pazjent, aktar titratazzjoni għal doża massima rakkomandata ta ’ 750 mg darbtejn kuljum (ara sezzjoni 5. 1).
If a patient experiences treatment-related adverse events (e. g. dizziness, nausea, or vomiting), down- titration of Ranexa to 500 mg or 375 mg twice daily may be required.
Jekk pazjent jesperjenza avvenimenti avversi relatati mal- kura (eż., sturdament, dardir, jew remettar) tista ’ teħtieġ titrazzjoni ’ l isfel ta ’ Ranexa għal 500 mg jew 375 mg darbtejn kuljum.
If symptoms do not resolve after dose reduction, treatment should be discontinued.
Jekk is- sintomi ma jirrisolvux wara tnaqqis fid- doża, il- kura għandha titwaqqaf.
Concomitant treatment with CYP3A4 and P-glycoprotein (P-gp) inhibitors:
Kura konkomittanti b’ impedituri CYP3A4 u P- glycoprotein (P- gp):
Careful dose titration is recommended in patients treated with moderate CYP3A4 inhibitors (e. g. diltiazem, fluconazole, erythromycin) or P-gp inhibitors (e. g. verapamil, ciclosporin) (see sections 4.4 and 4.5).
Hija rrakkomandata titrazzjoni bir- reqqa f’ pazjenti kkurati b’ impedituri CYP3A4 moderati (eż. diltiazem, fluconazole, erythromycin) jew impedituri P- gp (eż. verapamil, ciclosporin) (ara sezzjonijiet 4. 4 u 4. 5).
Concomitant administration of potent CYP3A4 inhibitors is contraindicated (see sections 4.3 and 4.5).
Għoti ta ’ impedituri CYP3A4 qawwija flimkien mhuwiex rakkomandat (ara sezzjonijiet 4. 3 u 4. 5).
Careful dose titration is recommended in patients with mild to moderate renal impairment (creatinine clearance 30– 80 ml/ min) (see sections 4.4, 4.8, and 5.2).
Titrazzjoni tad- doża bir- reqqa hija rrakkomandata f’ pazjenti b’ indeboliment tal- kliewi ħafif għal moderat (tneħħija tal- kreatinina 30– 80 ml/ min) (ara sezzjonijiet 4. 4, 4. 8, u 5. 2).
Ranexa is contraindicated in patients with severe renal impairment (creatinine clearance < 30 ml/ min) (see sections 4.3 and 5.2).
Ranexa mhijiex rakkomandata f’ pazjenti b’ indeboliment severi tal- kliewi (tneħħija tal- kreatinina < 30 ml/ min) (ara sezzjonijiet 4. 3 u 5. 2).
Careful dose titration is recommended in patients with mild hepatic impairment (see sections 4.4 and 5.2).
Titrazzjoni tad- doża bir- reqqa hija rrakkomandata f’ pazjenti b’ indeboliment tal- fwied ħafif (ara sezzjonijiet 4. 4 u 5. 2).
Ranexa is contraindicated in patients with moderate or severe hepatic impairment (see sections 4.3 and 5.2).
Ranexa mhijiex rakkomandata f’ pazjenti b’ indeboliment tal- fwied moderat jew severi (ara sezzjonijiet 4. 3 u 5. 2).
2 Elderly:
2 Anzjani:
Dose titration in elderly patients should be exercised with caution (see section 4.4).
Titrazzjoni tad- doża f’ pazjenti anzjani għandha ssir b’ kawtela (ara sezzjoni 4. 4).
Elderly may have increased ranolazine exposure due to age-related decrease in renal function (see section 5.2).
L- anzjani jista ’ jkollhom żieda fl- esponiment ta ’ ranolazine minħabba tnaqqis fil- funzjoni tal- kliewi relatat ma ’ l- età (ara sezzjoni 5. 2).
The incidence of adverse events was higher in the elderly (see section 4.8).
L- inċidenza ta ’ episodji avversi fl- anzjani kienet aktar għolja (ara sezzjoni 4. 8).
Low weight:
Piż baxx:
The incidence of adverse events was higher in patients with low weight (≤ 60 kg).
L- inċidenza ta ’ avvenimenti avversi f’ pazjenti b’ piż baxx (≤ 60 kg) kienet ogħla.
Dose titration in patients with low weight should be exercised with caution (see sections 4.4, 4.8, and 5.2).
Titrazzjoni tad- doża f’ pazjenti b’ piż baxx għandha ssir b’ kawtela (ara sezzjonijiet 4. 4, 4. 8, u 5. 2).
Congestive heart failure (CHF):
Falliment konġestiv tal- qalb (CHF):
Dose titration in patients with moderate to severe CHF (NYHA Class III– IV) should be exercised with caution (see sections 4.4 and 5.2).
Titrazzjoni tad- doża f’ pazjenti b’ CHF moderat sa severi (NYHA Klassi III– IV) għandha ssir b’ kawtela (ara sezzjonijiet 4. 4 u 5. 2).
Ranexa is not recommended for use in children below the age of 18 years due to a lack of data on safety and efficacy.
Ranexa mhijiex rakkomandata għal użu fi tfal taħt l- età ta ’ 18- il sena minħabba nuqqas ta ’ dejta dwar is- sigurtà u l- effikaċja.
Ranexa tablets should be swallowed whole and not crushed, broken, or chewed.
Pilloli Ranexa għandhom jinbelgħu sħaħ u mhux mgħaffġin, miksurin, jew magħmudin.
They may be taken with or without food.
Jistgħu jittieħdu ma ’ l- ikel jew fuq stonku vojt.
Severe renal impairment (creatinine clearance < 30 ml/ min) (see sections 4.2 and 5.2).
Indeboliment tal- kliewi severi (rata ta ’ tneħħija ta ’ kreatinina < 30 ml/ min) (ara sezzjonijiet 4. 2 u 5. 2).
Moderate or severe hepatic impairment (see sections 4.2 and 5.2).
Indeboliment tal- fwied moderat jew severi (ara sezzjonijiet 4. 2 u 5. 2).
Concomitant administration of potent CYP3A4 inhibitors (e. g. itraconazole, ketoconazole, voriconazol, posaconazol, HIV protease inhibitors, clarithromycin, telithromycin, nefazodone) (see sections 4.2 and 4.5).
Għoti ta ’ impedituri CYP3A4 qawwija flimkien (eż. itraconazole, ketoconazole, voriconazol, posaconazol, impedituri HIV protease, clarithromycin, telithromycin, nefazodone) (ara sezzjonijiet 4. 2 u 4. 5).
Concomitant administration of Class Ia (e. g. quinidine) or Class III (e. g. dofetilide, sotalol) antiarrhythmics other than amiodarone.
Għoti flimkien ta ’ antiarritmiċi Klassi Ia (eż. quinidine) jew Klassi III (eż. dofetilide, sotalol) barra minn amiodarone.
Caution should be exercised when prescribing or uptitrating ranolazine to patients in whom an increased exposure is expected: • Concomitant administration of moderate CYP3A4 inhibitors (see sections 4.2 and 4.5). • Concomitant administration of P-gp inhibitors (see sections 4.2 and 4.5). • Mild hepatic impairment (see sections 4.2 and 5.2). • Mild to moderate renal impairment (creatinine clearance 30– 80 ml/ min) (see sections 4.2, 4.8, and 5.2). • Elderly (see sections 4.2, 4.8, and 5.2). • Patients with low weight (≤ 60 kg) (see sections 4.2, 4.8, and 5.2). • Patients with moderate to severe CHF (NYHA Class III– IV) (see sections 4.2 and 5.2).
Meta ranolazine jingħata b’ riċetta ta ’ tabib jew f’ titrazzjoni ’ l fuq f’ pazjenti li fihom hija mistennija żieda fl- esponiment għandha tiġi eżerċitata l- kawtela: • Għoti ta ’ impedituri CYP3A4 moderati flimkien( ara sezzjonijiet 4. 2 u 4. 5). • Għoti ta ’ impedituri P- gp flimkien (ara sezzjonijiet 4. 2 u 4. 5). • Indeboliment tal- fwied ħafif (ara sezzjonijiet 4. 2 u 5. 2). • Indeboliment tal- kliewi ħafif għal moderat (tneħħija tal- kreatininae 30– 80 ml/ min) (ara sezzjonijiet 4. 2, 4. 8, u 5. 2). • Anzjani (ara sezzjonijiet 4. 2, 4. 8, u 5. 2). • Pazjenti b’ piż baxx (≤ 60 kg) (ara sezzjonijiet 4. 2, 4. 8, u 5. 2). • Pazjenti b’ CHF moderat sa severi (NYHA Klassi III– IV) (ara sezzjonijiet 4. 2 u 5. 2).
In patients with a combination of these factors, additional exposure increases are expected.
F’ pazjenti b’ taħlita ta ’ dawn il- fatturi huma mistennija żidiet addizzjonali fl- esponiment.
Dose- dependent side effects are likely to occur.
X’ aktarx li jseħħu effetti sekondarji relatati mad- doża.
If Ranexa is used in patients with a combination of several of these factors, monitoring of adverse events should be frequent, the dose reduced, and treatment discontinued, if needed.
Jekk Ranexa tintuża f’ pazjenti b’ taħlita ta ’ diversi minn dawn il- fatturi, is- sorveljanza ta ’ avvenimenti avversi għandha tkun frekwenti, id- doża għandha tkun imnaqqsa, u l- kura mwaqqfa, jekk meħtieġ.
The risk for increased exposure leading to adverse events in these different subgroups is higher in patients lacking CYP2D6 activity (poor metabolisers, PM) than subjects with CYP2D6 metabolising capacity (extensive metabolisers, EM) (see section 5.2).
Ir- riskju ta ’ żieda fl- esponiment li twassal għal avvenimenti avversi f’ dawn is- sottogruppi differenti hija aktar għolja f’ pazjenti b’ nuqqas ta ’ attività ta ’ CYP2D6 (metabolizzaturi dgħajfin, PM) milli f’ suġġetti b’ kapaċità metabolizzanti ta ’ CYP2D6 (metabolizzaturi estensivi, EM) (ara sezzjoni 5. 2).
The above precautions are based on the risk in a CYP2D6 PM patient, and are needed when the CYP2D6 status is unknown.
Il- prekawzjonijiet ta ’ hawn fuq huma bbażati fuq riskju f’ pazjent CYP2D6 PM, u huma meħtieġa meta l- istatus ta ’ CYP2D6 ma jkunx magħruf.
There is a lower need for precautions in patients with CYP2D6 EM status.
Hemm ħtieġa aktar baxxa għal prekawzjoniet f’ pazjenti bi status CYP2D6 EM.
If the CYP2D6 status of the patient has been determined (e. g. by genotyping) or is previously known to be EM, Ranexa can be used with caution in these patients when they have a combination of several of the above risk factors.
Jekk l- istatus CYP2D6 tal- pazjent ikun ġie stabbilit (eż. permezz ta ’ ġenotajping) jew huwa diġà magħruf li huwa EM, Ranexa għandha tintuża bil- kawtela f’ dawn il- pazjenti meta jkollhom taħlita ta ’ diversi mill- fatturi ta ’ riskju ta ’ hawn fuq.
QT prolongation:
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 ’ 3 konċentrazzjoni fil- plażma għal ranolazine 500 sa 1000 mg darbtejn kuljum.
3 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).
Drug-drug interactions:
Interazzjonijiet mediċina- mediċina:
Co-administration with CYP3A4 inducers is expected to lead to lack of efficacy.
Għoti konkomittanti ma ’ indutturi CYP3A4 huwa mistenni li jwassal għal nuqqas fl- effikaċja.
Ranexa should not be used in patients treated with CYP3A4 inducers (e. g. rifampicin, phenytoin, phenobarbital, carbamazepine, St.
Ranexa m’ għandhiex tintuża f’ pazjenti kkurati b’ indutturi CYP3A4 (eż. rifampicin, phenytoin, phenobarbital, carbamazepine, St.
John’ s Wort) (see section 4.5).
John’ s Wort) (ara sezzjoni 4. 5).
Renal function decreases with age and it is therefore important to check renal function at regular intervals during treatment with ranolazine (see sections 4.2, 4.3, 4.8, and 5.2).
Il- funzjoni tal- kliewi tonqos ma ’ l- età u huwa għaldaqstant importanti li tiċċekkja l- funzjoni tal- kliewi f’ intervalli regolari waqt il- kura b’ ranolazine (ara sezzjonijiet 4. 2, 4. 3, 4. 8, u 5. 2).
Effects of other medicinal products on ranolazine
Effetti ta ’ prodotti mediċinali oħra fuq ranolazine
CYP3A4 or P-gp inhibitors:
Impedituri CYP3A4 jew P- gp:
Ranolazine is a substrate of cytochrome CYP3A4.
Ranolazine huwa sottostrat ta ’ ċitokroma CYP3A4.
Inhibitors of CYP3A4 increase plasma concentrations of ranolazine.
Impedituri ta ’ CYP3A4 iżidu l- konċentrazzjoniet ta ’ ranolazine fil- plażma.
The potential for dose-related adverse events (e. g. nausea, dizziness) may also increase with increased plasma concentrations.
Il- potenzjal għal avvenimenti avversi relatati mad- doża (eż. dardir, sturdament) jistgħu wkoll jiżdiedu mal- konċentrazzjonijiet fil- plażma.
Concomitant treatment with ketoconazole 200 mg twice daily increased the AUC of ranolazine by 3.0- to 3.9-fold during ranolazine treatment.
Kura konkomittanti ma ’ 200 mg ketoconazole darbtejn kuljum żiedet l- AUC ta ’ ranolazine bi 3. 0 - sa 3. 9- il- darba waqt kura b’ ranolazine.
Combining ranolazine with potent CYP3A4 inhibitors (e. g. itraconazole, ketoconazole, voriconazole, posaconazole, HIV protease inhibitors, clarithromycin, telithromycin, nefazodone) is contraindicated (see section 4.3).
Mhuwiex rakkomandat li l- impedituri CYP3A4 qawwija (eż. itraconazole, ketoconazole, voriconazole, posaconazole, impedituri HIV protease, clarithromycin, telithromycin, nefazodone) jittieħdu flimkien ma ’ ranolazine (ara sezzjoni 4. 3).
Grapefruit juice is also a potent CYP3A4 inhibitor.
Il- meraq tal- grejpfrut huwa wkoll impeditur CYP3A4 qawwi.
Diltiazem (180 to 360 mg once daily), a moderately potent CYP3A4 inhibitor, causes dose-dependent increases in average ranolazine steady-state concentrations of 1.5- to 2.4-fold.
Diltiazem (180 sa 360 mg darba kuljum), impeditur CYP3A4 moderatament qawwi, jikkaġuna żidiet dipendenti fuq id- doża f’ konċentrazzjonijiet medji ta ’ ranolazine fi stati stabbli ta ’ 1. 5 - sa 2. 4- il darba.
Careful dose titration of Ranexa is recommended in patients treated with diltiazem and other moderately potent CYP3A4 inhibitors (e. g. erythromycin, fluconazole).
Titrazzjoni bir- reqqa tad- doża ta ’ Ranexa hija rrakkomandata f’ pazjenti kkurati b’ diltiazem jew impedituri CYP3A4 oħra moderatament qawwija (eż. erythromycin, fluconazole).
Down-titration of Ranexa may be required (see sections 4.2 and 4.4).
Jista ’ jkun hemm bżonn ta ’ titrazzjoni ’ l isfel ta ’ Ranexa (ara sezzjonijiet 4. 2 u 4. 4).
Ranolazine is a substrate for P-gp.
Ranolazine huwa sottostrat għal P- gp.
Inhibitors of P-gp (e. g. ciclosporin, quinidine, verapamil) increase plasma levels of ranolazine.
Impedituri ta ’ P- gp (eż. ciclosporin, quinidine, verapamil) iżidu livelli ta ’ ranolazine fil- plażma.
Verapamil (120 mg three times daily) increases ranolazine steady-state concentrations 2.2-fold.
Verapamil (120 mg tliet darbiet kuljum) iżid il- konċentrazzjonijiet ta ’ stat- fiss ta ’ ranolazine bi 2. 2- il darba.
Careful dose titration of Ranexa is recommended in patients treated with P-gp inhibitors.
F’ pazjenti kkurati b’ impedituri P- gp hija rrakkomandata titrazzjoni bir- reqqa tad- doża ta ’ Ranexa.
CYP3A4 inducers:
Indutturi CYP3A4:
Rifampicin (600 mg once daily) decreases ranolazine steady-state concentrations by approximately 95%.
Rifampicin (600 mg darba kuljum) inaqqas il- konċentrazzjonijiet ta ’ stat- fiss ta ’ ranolazine b’ madwar 95%.
Initiation of treatment with Ranexa should be avoided during administration of inducers of CYP3A4 (e. g. rifampicin, phenytoin, phenobarbital, carbamazepine, St.
Il- bidu tal- kura b’ Ranexa għandha tiġi evitata waqt l- għoti ta ’ indutturi ta ’ CYP3A4 (eż. rifampicin, phenytoin, phenobarbital, carbamazepine, St.
John’ s Wort) (see section 4.4).
John’ s Wort) (ara sezzjoni 4. 4).
CYP2D6 inhibitors:
Impedituri CYP2D6:
Ranolazine is partially metabolised by CYP2D6; therefore, inhibitors of this enzyme may increase plasma concentrations of ranolazine.
Ranolazine huwa parzjalment metabolizzat minn CYP2D6; għaldaqstant, impedituri ta ’ din l- enzima jistgħu jżidu l- konċentrazzjonijiet ta ’ ranolazine fil- plażma.
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 ’ 1000 mg ranolazine darbtejn kuljum fil- plażma b’ medja ta ’ 1. 2- il darba.
No dose adjustment is required.
Ma huwa meħtieġ l- ebda aġġustament fid- doża.
At the dose level 500 mg twice daily, co-administration of a potent inhibitor of CYP2D6 could result in an increase in ranolazine AUC of about 62%.
Fil- livell ta ’ doża ta ’ 500 mg darbtejn kuljum, għoti flimkien ma ’ impeditur qawwi ta ’ CYP2D6 jista ’ jirriżulta f’ żieda fl- AUC ta ’ ranolazine b’ madwar 62%.
Effects of ranolazine on other medicinal products
Effetti ta ’ ranolazine fuq prodotti mediċinali oħra
Ranolazine is a moderate to potent inhibitor of P-gp and a mild inhibitor of CYP3A4, and may increase plasma concentrations of P-gp or CYP3A4 substrates.
Ranolazine huwa impeditur ta ’ P- gp moderat għal qawwi u impeditur ħafif ta ’ CYP3A4, u jista ’ jżid il- konċentrazzjonijiet fil- plażma ta ’ sottostrati ta ’ P- gp jew CYP3A4.
Tissue distribution of drugs which are transported by P-gp may be increased.
Tista ’ tiżdied id- distribuzzjoni fit- tessuti ta ’ mediċini li huma trasportati minn P- gp.
Available data suggest that ranolazine is a mild inhibitor of CYP2D6.
4 Dejta disponibbli tissuġġerixxi li ranolazine huwa impeditur ħafif ta ’ CYP2D6.
The exposure of CYP2D6 substrates (e. g. tricyclic antidepressants and antipsychotics) may be increased during co-administration of Ranexa, and lower doses of these medicinal products may be required.
L- esponiment ta ’ sottostrati CYP2D6 (eż. antidepressanti triċikliċi u antipsikotiċi) jistgħu jiżdiedu waqt għoti konkomittanti ta ’ Ranexa, u jistgħu jeħtieġu dożi aktar baxxi ta ’ dawn il- prodotti mediċinali.
4 The potential for inhibition of CYP2B6 has not been evaluated.
Il- potenzjal għal impediment ta ’ CYP2B6 ma ġiex evalwat.
Caution is advised during co-administration with CYP2B6 substrates (e. g. bupropion, efavirenz, cyclophosphamide).
Huwa rrakkomandat li tintuża l- kawtela waqt għoti konkomittanti ma ’ sottostrati CYP2B6 (eż. bupropion, efavirenz, cyclophosphamide).
An increase in plasma digoxin concentrations by an average of 1.5-fold has been reported when Ranexa and digoxin are co-administered.
Żieda ta ’ konċentrazzjonijiet fil- plażma ta ’ digoxin b’ medja ta ’ 1. 5- il darba ġiet irrapportata meta Ranexa u digoxin jingħataw fl- istess ħin.
Therefore, digoxin levels should be monitored following initiation and termination of Ranexa therapy.
Għaldaqstant, il- livelli ta ’ digoxin għandhom jiġu sorveljati wara l- bidu u t- twaqqif ta ’ terapija Ranexa.
Simvastatin metabolism and clearance are highly dependent on CYP3A4.
Il- metaboliżmu u r- rata ta ’ eliminazzjoni ta ’ simvastatin huma dipendenti bil- bosta fuq CYP3A4.
Ranexa 1000 mg twice daily increased plasma concentrations of simvastatin lactone, simvastatin acid, and the HMG-CoA reductase inhibitor activity by 1.4- to 1.6-fold.
Ranexa 1000 mg darbtejn kuljum żiedet il- konċentrazzjonijiet ta ’ simvastatin lactone fil- plażma, aċidu simvastatin, u attività ta ’ l- impeditur HMG- CoA reductase b’ 1. 4 - sa 1. 6- il darba.
There is a theoretical risk that concomitant treatment of ranolazine with other drugs known to prolong the QTc interval may give rise to a pharmacodynamic interaction and increase the possible risk of ventricular arrhythmias.
Hemm riskju teoretiku li kura konkomittanti ta ’ ranolazine ma ’ mediċini oħra li huma magħrufin li jtawwlu l- intervall QTc jistgħu jagħtu lok għal interazzjoni farmakodinamika, iżidu r- riskju ta ’ interazzjoni farmakodinamika u jżidu r- riskju ta ’ arritmiji ventrikulari.
Examples of such drugs include certain antihistamines (e. g. terfenadine, astemizole, mizolastine), certain antiarrhythmics (e. g. quinidine, disopyramide, procainamide), erythromycin, and tricyclic antidepressants (e. g. imipramine, doxepin, amitriptyline).
Eżempji ta ’ mediċini minn dawn jinkludu ċerti antiħistamini (eż. terfenadine, astemizole, mizolastine), ċerti antiarritmiċi (eż. quinidine, disopyramide, procainamide), erythromycin, u antidepressanti triċikliċi (eż. imipramine, doxepin, amitriptyline).
There are no adequate data from the use of ranolazine in pregnant women.
M’ hemmx tgħarif biżżejjed dwar ll- l- użu ta ’ ranolazine waqt it- tqala.
Animal studies are insufficient with respect to effects on pregnancy and embryofoetal development (see section 5.3).
Studji fuq bhejjem m’ humiex biżżejjed rigward l- effetti fuq it- tqala u l- iżvilupp ta ’ l- embriju/ fetu (ara 5. 3).
The potential risk for humans is unknown.
Ir- riskju li jista 'jkun hemm fuq in- nies, mhux l- magħruf.
Ranexa should not be used during pregnancy unless clearly necessary.
Ranexa m’ għandhux jintuża waqt it- tqala jekk m’ hemmx bżonn ċar.
It is unknown whether ranolazine is excreted in human breast milk.
Mhuwiex magħruf jekk ranolazine huwiex eliminat fil- ħalib tas- sider tal- bniedem.
The excretion of ranolazine in milk has not been studied in animals.
L- eliminazzjoni ta ’ ranolazine fil- ħalib ma ġietx studjata fl- annimali.
Ranexa should not be used during breast-feeding.
Ranexa m’ għandhiex tintuża waqt it- treddigħ.
No studies on the effects of Ranexa on the ability to drive and use machines have been performed.
Ma sarux l- studji dwar l- effetti ta ’ Ranexa fuq il- ħila biex issuq jew tħaddem magni.
Ranexa may cause dizziness and blurred vision (see section 4.8), which may affect the ability to drive and use machines.
Ranexa tista ’ tikkaġuna sturdament u vista mċajjpra (ara sezzjoni 4. 8), li tista ’ taffettwa l- ħila biex issuq u tħaddem magni.
Undesirable effects in patients receiving Ranexa are generally mild to moderate in severity and often develop within the first 2 weeks of treatment.
Effetti mhux mixtieqa f’ pazjenti li qegħdin jirċievu Ranexa huma ġeneralment ħfief għal moderati fis- severità u ta ’ spiss jiżviluppaw fi żmien l- ewwel ġimgħatejn ta ’ kura.
These were reported during the Phase 3 clinical development programme, which included a total of 1,030 chronic angina patients treated with Ranexa.
Dawn kienu rrapportati waqt program ta ’ żvilupp kliniku Fażi 3, li nkludew total ta ’ 1, 030 pazjent b’ anġina kronika kkurati b’ Ranexa.
The adverse events, considered to be at least possibly related to treatment, are listed below by body system, organ class, and absolute frequency.
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.
Frequencies are defined as very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10), uncommon (≥ 1/ 1,000 to < 1/ 100), rare (≥ 1/ 10,000 to < 1/ 1,000), and very rare (< 1/ 10,000).
Il- frekwenzi huma ddefiniti bħala komuni ħafna (≥ 1/ 10), komuni (≥ 1/ 100 to < 1/ 10), mhux komuni (≥ 1/ 1, 000 to < 1/ 100), rari (≥ 1/ 10, 000 to < 1/ 1, 000), u rari ħafna (< 1/ 10, 000).
Metabolism and nutrition disorders Uncommon: anorexia, decreased appetite, dehydration.
Disturbi fil- metaboliżmu u n- nutrizzjoni Mhux komuni: anoressja, tnaqqis fl- aptit, deidratazzjoni
Psychiatric disorders Uncommon: anxiety, insomnia.
Disturbi psikjatriċi Mhux komuni: ansjetà, insomnja.
Rare: disorientation.
Rari: diżorjentazzjoni.
Nervous system disorders Common: dizziness, headache.
5 Disturbi fis- sistema nervuża Komuni: sturdament, uġigħ ta ’ ras.
Uncommon: lethargy, syncope, hypoaesthesia, somnolence, tremor, postural dizziness.
Mhux komuni: letarġija, ħass ħażin, ipoestiżja, ngħas, rogħda, sturdament posturali.
Rare: amnesia, depressed level of consciousness, loss of consciousness, parosmia.
Rari: amneżija, tnaqqis fil- livell tas- sensi, telf tas- sensi, parożmja.
5 Eye disorders Uncommon: blurred vision, visual disturbance.
Disturbi fl- għajnejn Mhux komuni: viżta mċajpra, disturbi fil- viżta.
Ear and labyrinth disorders Uncommon: vertigo, tinnitus.
Disturbi fil- widnejn u fis- sistema labirintika Mhux komuni: vertiġini, tinnitus.
Rare: impaired hearing.
Rari: indeboliment tas- smigħ.
Rare: peripheral coldness, orthostatic hypotension.
Disturbi vaskulari Mhux komuni: fwawar, pressjoni baxxa Rari: kesħa fl- estremitajiet, pressjoni baxxa ortostatika.
Rare: throat tightness.
Disturbi respiratorji, toraċiċi u medjastinali Mhux komuni: dispnija, sogħla, epitassi Rari: għafis fuq il- gerżuma.
Gastrointestinal disorders Common: constipation, vomiting, nausea.
Disturbi gastro- intestinali Komuni: stitikezza, remettar, dardir.
Uncommon: abdominal pain, dry mouth, dyspepsia, flatulence, stomach discomfort.
Mhux komuni: uġigħ addominali, ħalq xott, dispepsja, gass, dwejjaq fl- istonku.
Rare: pancreatitis, erosive duodenitis, oral hypoaesthesia.
Rari: pankrejatite, duwodenite erożiva, ipoestiżja orali.
Skin and subcutaneous tissue disorders Uncommon: pruritus, hyperhydrosis.
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Mhux komuni: prurite, raxx, iperidrożi.
Rare: allergic dermatitis, urticaria, cold sweat, rash.
Rari: dermatite allerġika, urtikarja, għaraq kiesaħ, raxx.
Musculoskeletal and connective tissue disorders Uncommon: pain in extremity, muscle cramp, joint swelling.
Disturbi muskolu- skeltrali u tal- connective tissue Mhux komuni: uġigħ fl- estremità, bugħawwieġ, nefħa fil- ġogi.
Renal and urinary disorders Uncommon: dysuria, haematuria, chromaturia.
Disturbi fil- kliewi u fis- sistema urinarja Mhux komuni: disurja, ematurja, kromaturja.
Reproductive system and breast disorders Rare: erectile dysfunction.
Disturbi fis- sistema riproduttiva u fis- sider Rari: funżjoni erettili ħażina.
General disorders and administration site conditions Common: asthenia.
Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata Komuni: astenja.
Uncommon: fatigue, peripheral oedema.
Mhux komuni: għeja kbira, edima periferali.
Investigations Uncommon: increased blood creatinine, increased blood urea, prolonged QT corrected interval, increased platelet or white blood cell count, decreased weight.
Investigazzjonijiet Mhux komuni: żieda fil- kreatinina fid- demm, żieda fil- ureja fid- demm, titwil fl- intervall QT ikkoreġut, żieda fl- għadd ta ’ plejtlits jew ta ’ ċelloli bojod tad- demm, tnaqqis fil- piż.
Rare: elevated levels of hepatic enzyme.
Rari: livelli għoljin ta ’ enżimi epatiċi.
The adverse event profile was generally similar in the MERLIN-TIMI 36 study.
Il- profil ta ’ l- avveniment avers kien ġeneralment simili fl- istudju MERLIN- TIMI 36.
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 jostakola l- passaġġi ta ’ l- arja, ikkonfermaw li dawn il- kondizzjonijiet ma kinux assoċjati ma ’ żidiet klinikament sinifikattivi fl- inċidenza ta ’ reazzjonijiet avversi.
Elderly, renal impairment, and low weight:
Anzjani, indeboliment tal- kliewi, u piż baxx:
In general, adverse events occurred more frequently among elderly patients and patients with renal impairment; however, the types of events in these subgroups were similar to those observed in the general population.
B’ mod ġenerali, avvenimenti avversi seħħew aktar frekwenti fost pazjenti anzjani u pazjenti b’ indeboliment tal- kliewi; madankollu, it- tipi ta ’ avvenimenti f’ dawn is- sottogruppi kienu simili għal dawk osservati fil- popolazzjoni ġenerali.
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
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
6 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%).
6 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%).
In general, the type and frequency of adverse events reported in patients with low body weight (≤ 60 kg) were similar to those of patients with higher weight (> 60 kg); however, the placebo- corrected frequencies of the following common adverse events were higher in low body weight than heavier patients: nausea (14% versus 2%), vomiting (6% versus 1%), and hypotension (4% versus 2%).
B’ mod ġenerali, it- tip u l- frekwenza ta ’ avvenimenti avversi rrapportati f’ pazjenti b’ piż korporali baxx (≤ 60 kg) kienu simili għal dawk ta ’ pazjenti b’ piż korporali aktar għoli (> 60 kg); madankollu, il- frekwenzi korretti bi plaċebo ta ’ l- avvenimenti avversi komuni li ġejjin kienu aktar għoljin f’ pazjenti b’ piż korporali baxx milli f’ pazjenti aktar tqal: dardir (14% kontra 2%), remettar (6% kontra 1%), u pressjoni tad- demm baxxa (4% kontra 2%).
Laboratory findings:
Sejbiet tal- laboratorju:
Small, clinically insignificant, reversible elevations in serum creatinine levels have been observed in healthy subjects and patients treated with Ranexa.
Elevazzjonijiet żgħar, klinikament insinifikanti, riversibbli f’ livelli ta ’ kreatinina fis- serum kienu osservati f’ suġġetti f’ saħħithom u pazjenti kkurati b’ Ranexa.
There was no renal toxicity related to these findings.
Ma kien hemm l- ebda tossiċità tal- kliewi relatata ma ’ dawn is- sejbiet.
A renal function study in healthy volunteers demonstrated a reduction in creatinine clearance with no change in glomerular filtration rate consistent with inhibition of renal tubular secretion of creatinine.
Studju ta ’ funzjoni tal- kliewi f’ voluntiera f’ saħħithom wera tnaqqis fir- rata ta ’ eliminazzjoni ta ’ kreatinina mingħajr l- ebda bidla fir- rata ta ’ filtrazzjoni glomerulari konsistenti ma ’ impediment ta ’ tnixxija tubulari tal- kliewi ta ’ kreatinina.
In an oral high-dose tolerability study in angina patients, the incidence of dizziness, nausea, and vomiting increased in a dose-dependent manner.
Fi studju ta ’ tolerabbilità ta ’ dożaġġ orali għoli f’ pazjenti b’ anġina, l- inċidenza ta ’ sturdament, dardir, u remettar żdiedu b’ mod dipendenti fuq id- doża.
In addition to these adverse events, diplopia, lethargy, and syncope were observed in an intravenous overdose study in healthy volunteers.
Barra dawn l- avvenimenti avversi, kienu osservati diplopja, letarġija, u ħass ħażin fi studju ta ’ dożaġġ eċċessiv intravenuż f’ voluntiera f’ saħħithom.
In the event of overdose, the patient should be closely monitored and the treatment should be symptomatic and supportive.
Fil- każ ta ’ teħid eċċessiv, il- pazjent għandu jkun sorveljat mill- qrib u l- kura għandha tkun sintomatika u sapportiva.
Approximately 62% of ranolazine is bound to plasma proteins, and therefore, complete clearance by haemodialysis is unlikely.
Madwar 62% ta ’ ranolazine jeħel ma ’ proteini fil- plażma, u għaldaqstant, x’ aktarx li ma sseħħx eliminazzjoni sħiħa permezz ta ’ l- emodijaliżi.
Pharmacotherapeutic group:
5. 1 Tagħrif farmakodinamiku
Other cardiac preparations, ATC code:
Preparazzjonijiet kardijaċi oħra, Kodiċi ATC:
The mechanism of action of ranolazine is largely unknown.
Il- mekkaniżmu ta ’ azzjoni ta ’ ranolazine huwa fil- parti l- kbira mhux magħruf.
Ranolazine may have some antianginal effects by inhibition of the late sodium current in cardiac cells.
Ranolazine jista ’ jkollu xi effetti kontra l- anġina permezz ta ’ impediment tal- kurrent ittardjat tas- sodju fiċ- ċelloli kardijaċi.
This reduces intracellular sodium accumulation and consequently decreases intracellular calcium overload.
Dan inaqqas l- akkumulazzjoni intraċellolari tas- sodju u konsegwentement inaqqas it- tagħbija żejda ta ’ kalċju intracellolari.
Ranolazine, via its action to decrease the late sodium current, is considered to reduce these intracellular ionic imbalances during ischaemia.
Ranolazine, permezz ta ’ l- azzjoni li jnaqqas il- kurrent ittardjat tas- sodju, huwa kkunsidrat li jnaqqas dawn l- iżbilanċi joniċi intraċellolari waqt l- iskemija.
This reduction in cellular calcium overload is expected to improve myocardial relaxation and thereby decrease left ventricular diastolic stiffness.
Dan it- tnaqqis fit- tagħbija żejda ta ’ kalċju ċellolari huwa mistenni li jtejjeb ir- rilassament majokardjali u b’ hekk inaqqas l- ebusija dijastolika ventrikolari xellugija.
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 dijastoliku fi studju b’ tikketta miftuħa ta ’ 5 pazjenti b’ sindromu QT twil (LQT3 ikollu mutazzjoni ta ’ ġene SCN5A ∆KPQ).
These effects do not depend upon changes in heart rate, blood pressure, or vasodilation.
Dawn l- effetti ma jiddependux fuq bidliet fir- rata ta ’ tħabbit tal- qalb, pressjoni tad- demm, jew vażodilatazzjoni.
Pharmacodynamic effects
7 Effetti farmakodinamiċi
Haemodynamic effects:
Effetti emodinamiċi:
Minimal decreases in mean heart rate (< 2 beats per minute) and mean systolic blood pressure (< 3 mm Hg) were observed in patients treated with ranolazine either alone or in combination with other antianginal medicinal products in controlled studies.
Tnaqqis minimu fir- rata tal- qalb medja (< 2 taħbitiet kull minuta) u fil- pressjoni tad- demm sistolika medja (< 3 mm Hg) kien osservat f’ pazjenti kkurati b’ ranolazine kemm waħdu jew f’ kumbinazzjoni ma ’ prodotti mediċinali kontra l- anġina fi studji kkontrollati.
Electrocardiographic effects:
Effetti elettrokardjografiċi:
Dose and plasma concentration-related increases in the QTc interval (about 6 msec at 1000 mg twice daily), reductions in T wave amplitude, and in some cases notched T waves, have been observed in patients treated with Ranexa.
Żidiet relatati mad- doża u mal- konċentrazzjoni fil- plażma fl- interval QTc (madwar 6 msek f’ 1000 mg darbtejn kuljum), tnaqqis fl- estensjoni tal- mewġa T, u f’ xi każijiet mewġiet T taljati, ġew osservati f’ pazjenti ikkurati b’ Ranexa.
A population analysis of combined data from
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.
7 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.