qanastek/EMEA-V3 huggingface dataset:
Genetic and pharmacologic studies in animal models have provided evidence that PGD2, acting through DP1, one of the two receptors for PGD2, plays a key role in nicotinic acid-induced flushing.
Studji ġenetiċi u farmakoloġiċi f’ mudelli ta ’ l- annimali taw evidenza li l- PGD2, li jaħdem permezz tad- DP1, wieħed miż- żewġ riċetturi għall- PGD2, għandu rwol prinċipali fit- tifwir indott mill- aċidu nikotiniku.
Laropiprant is a potent and selective antagonist of DP1.
Laropiprant huwa antagonist qawwi u selettiv tad- DP1.
Laropiprant is not expected to inhibit the production of prostaglandins.
Laropiprant mhux mistenni li jimpedixxi l- produzzjoni tal- prostaglandins.
Pharmacodynamic effects Laropiprant has been shown to be effective in reducing flushing symptoms induced by nicotinic acid.
Effetti farmakodinamiċi Laropiprant ġie muri li huwa effettiv biex inaqqas is- sintomi ta ’ fawra indotti mill- aċidu nikotiniku.
The reduction in flushing symptoms (assessed by patient questionnaires) was correlated with a reduction in nicotinic acid-induced vasodilatation (assessed by measurements of skin blood flow).
It - tnaqqis fis- sintomi ta ’ fawra (evalwati mill- kwestjonarji fil- pazjenti) kien korrelat ma ’ tnaqqis fil - vażodilatazzjoni indotta mill- aċidu nikotiniku (evalwata bil- kejl tal- fluss tad- demm fil- ġilda).
In healthy subjects receiving Pelzont, pretreatment with acetylsalicylic acid 325 mg had no additional beneficial effects in reducing nicotinic acid-induced flushing symptoms compared to Pelzont alone (see section 4.8).
F’ individwi b’ saħħithom li rċevew Pelzont, it- trattament ta ’ qabel bl- aċidu aċetilsaliċiliku 325 mg ma kellu ebda effetti benefiċi addizzjonali fit- tnaqqis tas- sintomi ta ’ fawra indotti mill- aċidu nikotiniku meta mqabbel ma ’ Pelzont waħdu (ara sezzjoni 4. 8).
Laropiprant also has affinity for the thromboxane A2 receptor (TP) (although it is substantially less potent at TP as compared to DP1).
Laropiprant għandu affinità wkoll għar- riċettur tat- thromboxane A2 (TP) (għalkemm huwa sostanzjalment anqas b’ saħħtu fit- TP meta mqabbel mad- DP1).
TP plays a role in platelet function; however, therapeutic doses of laropiprant had no clinically relevant effect on bleeding time and collagen-induced platelet aggregation (see section 4.5).
TP għandu rwol fil- funzjoni tal - plejtlits; madankollu, dożi terapewtiċi ta ’ laropiprant ma kellhom ebda effett kliniku rilevanti fuq il - ħin tal- fsada u l- aggregazzjoni tal- plejtlits indotta mill- collagen (ara sezzjoni 4. 5).
Clinical studies Effect on lipids Pelzont was consistently efficacious across all prespecified patient subpopulations defined by race, gender, baseline LDL-C, HDL-C and TG levels, age and diabetes status.
Studji kliniċi Effetti fuq il- lipidi Pelzont kien effikaċji b’ mod konsistenti fis- subpopolazzjonijiet ta ’ pazjenti prespeċifikati kollha definiti permezz tar- razza, is- sess, il- livelli bażiċi ta ’ LDL- C, HDL- C u TG, jew l- età u l- istejtus tad - dijabete.
Patients taking Pelzont (2000 mg/ 40 mg) with or without a statin, versus placebo, had significantly decreased LDL-C (-18.9% vs. -0.5%), TG (-21.7% vs.
Il- pazjenti li ħadu Pelzont (2000 mg/ 40 mg) bi jew mingħajr statin, kontra l- plaċebo, kellhom tnaqqis sinifikanti fl- LDL- C (- 18. 9% vs. - 0. 5%), TG (- 21. 7% vs.
3.6%), LDL-C: HDL-C (-28.9% vs.
3. 6%), LDL- C: HDL- C (- 28. 9% vs.
2.3%), non-HDL-C (-19.0% vs.
2. 3%), non- HDL- C (- 19. 0% vs.
0.8%), apo B (-16.4% vs.
0. 8%), apo B (- 16. 4% vs.
2.5%), TC (-9.2% vs. -0.6%), Lp(a) (-17.6% vs.
2. 5%), TC (- 9. 2% vs. - 0. 6%), Lp( a) (- 17. 6% vs.
1.1%), and TC: HDL-C (-21.2% vs.
1. 1%), u TC: HDL- C (- 21. 2% vs.
1.9%) and also had significantly increased HDL-C (18.8% vs. -1.2%), and apo A-I (11.2% vs.
1. 9%) kif ukoll żidiet sinifikanti fl- HDL- C (18. 8% vs. - 1. 2%), u l- apo A- I (11. 2% vs.
4.3%) as measured by percent change from baseline.
4. 3%) kif imkejla mill- bidla perċentwali mil- linja bażi.
In general, the between-group treatment effects on all lipid parameters were consistent across all patient subgroups examined.
B’ mod ġenerali, l- effetti tat- trattament bejn il- gruppi fuq il- parametri kollha tal- lipidi kienu konsistenti tul is - sottogruppi kollha tal- pazjenti eżaminati.
Patients receiving Pelzont, nicotinic acid (prolonged-released formulation), or placebo were also taking statins (29% atorvastatin [5-80 mg], 54% simvastatin [10-80 mg], 17% other statins [2.5-180 mg] (pravastatin, fluvastatin, rosuvastatin, lovastatin)), of which 9% were also taking ezetimibe [10 mg].
Il- pazjenti li kienu qegħdin jirċievu Pelzont, aċidu nikotiniku (formulazzjoni li terħi l- mediċina bil- mod), jew plaċebo kienu qegħdin jieħdu wkoll statins (29% atorvastatin [5- 80 mg], 54% simvastatin [10- 80 mg], 17% statins oħra [2. 5- 180 mg] (pravastatin, fluvastatin, rosuvastatin, lovastatin)), li 9% minnhom kienu qegħdin jieħdu wkoll ezetimibe [10 mg].
The effect on lipids was similar whether Pelzont was given as monotherapy or was added to ongoing statin therapy with or without ezetimibe.
L- effett fuq il- lipidi kien simili kemm jekk Pelzont ingħata bħala monoterapija kif ukoll jekk żdied ma ’ terapija kontinwa bl- istatins bi jew mingħajr ezetimibe.
The placebo-adjusted LDL-C, HDL-C and TG responses appeared greater among women compared to men and appeared greater among elderly patients (≥ 65 years) compared to younger patients (< 65 years).
Ir- risponsi tal- LDL- C, HDL- C u TG aġġustati għall- plaċebo dehru akbar fost in- nisa meta mqabbla ma ’ l- irġiel u dehru akbar fost pazjenti anzjani (≥65 sena) meta mqabbla ma ’ pazjenti iżgħar fl- età (< 65 sena).
In a multicentre, double-blind, 12-week factorial study, Pelzont 1000 mg/ 20 mg co-administered with simvastatin, when compared with simvastatin alone or Pelzont 1000 mg/ 20 mg alone, for 4 weeks, significantly lowered LDL-C (-44.2%, -37.4%, -8.2% respectively), TG (-25.8%, -15.7%, -18.7% respectively), TC (-27.9%, -25.8%, -4.9% respectively) and significantly increased HDL-C (19.2%, 4.2%, 12.5% respectively).
Fi studju fattorjali, multi- ċentri, double- blind, ta ’ 12- il ġimgħa, Pelzont 1, 000 mg/ 20 mg mogħti fl - istess ħin ma ’ simvastatin, meta mqabbel ma ’ simvastatin waħdu jew Pelzont 1, 000 mg/ 20 mg waħdu, għal 4 ġimgħat, naqqas b’ mod sinifikanti l- LDL- C (- 44. 2%, - 37. 4%, - 8. 2% rispettivament), it- TG (- 25. 8%, - 15. 7%, - 18. 7% rispettivament), it- TC (- 27. 9%, - 25. 8%, - 4. 9% rispettivament) u żied b’ mod sinifikanti l- HDL- C (19. 2%, 4. 2%, 12. 5% rispettivament).
Pelzont (2000 mg/ 40 mg) co-administered with simvastatin when compared with simvastatin alone or Pelzont (2000 mg/ 40 mg) alone for 12 weeks, significantly lowered LDL-C (-47.9%, -37.0%, -17.0% respectively), TG (-33.3%, -14.7%, -21.6% respectively), apo B (-41.0%, -28.8%, -17.1%
Pelzont 2, 000 mg/ 40 mg mogħti flimkien ma ’ simvastatin, meta mqabbel ma ’ simvastatin waħdu jew ma ’ Pelzont 2, 000 mg/ 40 mg waħdu għal 12- il ġimgħa, naqqas b’ mod sinjifikanti LDL- C (- 47. 9%, - 37. 0%, - 17. 0% rispettivament), TG (- 33. 3%, - 14. 7%, - 21. 6% rispettivament), apo B (- 41. 0%, - 28. 8%, - 17. 1% rispettivament), u TC (- 29. 6%, - 24. 9%, 9. 1% rispettivament), kif ukoll LDL- C: HDL- C (- 57. 1%, - 39. 8%, - 31. 2% rispettivament), non- HDL- C (- 45. 8%, - 33. 4%, - 18. 1% rispettivament), u TC: HDL- C (- 43. 0%, - 28, 0%, - 24. 9% rispettivament), u żied b’ mod sinjifikanti HDL- C (27. 5%, 6. 0%, 23. 4% rispettivament).
Further analysis showed Pelzont (2000 mg/ 40 mg) co-administered with simvastatin when compared with simvastatin alone significantly increased apo A-I (8.6%, 2.3% respectively) and significantly decreased Lp(a) (-19.8%, 0.0% respectively).
Analiżi addizzjonali wriet li Pelzont 2000 mg/ 40 mg mogħti fl- istess ħin ma ’ simvastatin meta mqabbel ma ’ simvastatin waħdu żied b’ mod sinifikanti l- apo A- I (8. 6%, 2. 3% rispettivament) u naqqas b’ mod sinifikanti l- Lp( a) (- 19. 8%, 0. 0% rispettivament).
Efficacy and safety of Pelzont in combination with simvastatin > 40 mg were not included in this study.
L- effikaċja u s- sigurtà ta ’ Pelzont f’ kombinazzjoni ma ’ simvastatin > 40 mg ma kinux inklużi f’ dan l- istudju.
Flushing In two large clinical trials measuring patient-reported flushing symptoms, patients taking Pelzont experienced less flushing than those taking nicotinic acid (prolonged-release formulations).
10 Fwawar F’ żewġ provi kliniċi kbar li kejlu s- sintomi ta ’ fawra rrappurtati mill- pazjenti stess, il- pazjenti li ħadu Pelzont esperjenzaw anqas fawra minn dawk li ħadu l- aċidu nikotiniku (formulazzjonijiet li jerħu l - mediċina bil- mod).
In patients continuing in the first study (24 weeks), the frequency of moderate or greater flushing in patients treated with Pelzont declined and approached that of patients receiving placebo (see Figure 1), whereas in patients treated with nicotinic acid (prolonged-release formulation) the flushing frequency remained constant (after Week 6).
Fil- pazjenti li komplew fl- ewwel studju (24 ġimgħa), il- frekwenza ta ’ fawra moderata jew akbar f’ pazjenti trattati bi Pelzont naqset jew avviċinat dik tal- pazjenti li rċevew plaċebo (ara Figura 1), filwaqt li fil- pazjenti trattati bl- aċidu nikotiniku (formulazzjoni li terħi l- mediċina bil - mod) il- frekwenza tal- fwawar baqgħet kostanti (wara Ġimgħa 6).
Flushing efficacy of laropiprant has not been established past 24 weeks.
L- effikaċja kontra l- fwawar ta ’ laropiprant għadha ma ġietx stabbilita wara l- 24 ġimgħa.
Average number of days per week with moderate or greater* flushing symptoms across weeks 1-24 2 Number of Days per Week
Ammont medju ta ’ ġranet fil- ġimgħa b’ sintomi moderati jew akbar * ta ’ fawra minn ġimgħa 1- 24 2 Number of Days per Week
● Pelzont (1000 mg/ 20 mg to 2000 mg/ 40 mg at week 5) ▲ Nicotinic acid (prolonged-release 1000 mg to 2000 mg at week 5) ○ Placebo *Includes patients with moderate, severe, or extreme flushing symptoms † Dose advancement at Week 5
●Pelzont (1, 000 mg/ 20 mg għal 2000 mg/ 40 mg f’ Ġimgħa 5) ▲Aċidu nikotiniku (rilaxx bil- mod 1000 mg għal 2000 mg f’ Ġimgħa 5) ○Plaċebo * Jinkludi pazjenti b’ sintomi moderati, severa, jew estremi ta ’ fawra † Avvanzament tad- doża f’ Ġimgħa 5
In the second study (16 weeks) where acetylsalicylic acid was allowed, patients taking Pelzont experienced significantly fewer days per week with moderate or greater flushing compared to nicotinic acid (prolonged-release formulation taken as a 12-week multi-step 500 mg to 2000 mg titration) (p < 0.001).
Fit- tieni studju (16- il ġimgħa) fejn kien permess l- aċidu aċetilsaliċiliku, il- pazjenti li ħadu Pelzont esperjenzaw ġranet konsiderevolment inqas fil- ġimgħa b’ fawra moderata jew akbar meta mqabbel ma ’ l- aċidu nikotiniku (formulazzjoni li terħi l- mediċina bil- mod meħuda bħala titrazzjoni multi- step ta ’ 500 mg għal 2000 mg fuq tnax- il ġimgħa) (p < 0. 001).
Absorption Nicotinic acid Following a 2000 mg dose of nicotinic acid administered orally as two modified-release tablets of nicotinic acid/ laropiprant with food, nicotinic acid was absorbed with a median time to peak plasma concentration (Tmax) of 4 hours, a mean area under the plasma concentration-time curve (AUC0-last) of approximately 58.0 μ M·hr and a mean peak plasma concentration (Cmax) of approximately 20.2 μ M.
Assorbiment L- aċidu nikotiniku Wara doża ta ’ 2000 mg ta ’ aċidu nikotiniku mogħtija mill- ħalq bħala żewġ pilloli li jerħu l- mediċina b’ mod modifikat ta ’ l- aċidu nikotiniku/ laropiprant ma ’ l- ikel, l- aċidu nikotiniku b’ ħin medjan sa l - ogħla konċentrazzjoni fil- plażma (Tmax) ta ’ 4 sigħat, arja medja taħt il- kurva tal- konċentrazzjoni fil - plażma mal- ħin (AUC0- last) ta ’ madwar 58. 0 μM· hr u konċentrazzjoni massima medja fil- plażma (Cmax) ta ’ madwar 20. 2 μM.
Bioavailability with or without food is at least 72% based on the recovery of the nicotinic acid dose in the urine.
Il- bijodisponibilità ma ’ l- ikel jew fuq stonku vojt hija ta ’ mill- anqas 72% fuq il - bażi ta ’ l- irkupru tad- doża ta ’ l- aċidu nikotiniku fl- awrina.
The oral bioavailability of nicotinic acid is not altered when it is taken with a high-fat meal.
Il- bijodisponibilità orali ta ’ l- aċidu nikotiniku ma tinbidilx meta jittieħed ma ’ ikla b’ kontenut għoli ta ’ xaħam.
Laropiprant Following a 40 mg dose of laropiprant administered orally as two modified-release tablets of nicotinic acid/ laropiprant with food, laropiprant is rapidly absorbed with a median Tmax of 1 hour, a mean AUC0- ∞ of approximately 13 μ M·hr, and a mean Cmax of approximately 1.6 μ M.
Laropiprant Wara doża ta ’ 40 mg ta ’ laropiprant mogħtija mill- ħalq bħala żewġ pilloli ta ’ l- aċidu nikotiniku/ laropiprant li jerħu l- mediċina b’ mod modifikat ma ’ l- ikel, laropiprant jiġi assorbit malajr b’ Tmax medjan ta ’ siegħa, AUC0- ∞ medju ta ’ madwar 13 μM· hr, u Cmax medju ta ’ madwar 1. 6 μM.
The rate and extent of absorption are not altered with a high-fat meal.
Ir - rata u l- livell ta ’ l- assorbiment ma jinbidlux b’ ikla li jkollha kontenut għoli ta ’ xaħam.
The pharmacokinetics of laropiprant are linear, displaying approximately dose-proportional increases in AUC and Cmax and no evidence of time-dependent clearance.
Il - farmakokinetika ta ’ laropiprant hija lineari, u turi żidiet kważi proporzjonali mad- doża fl- AUC u l - Cmax u l- ebda evidenza ta ’ tneħħija dipendenti mill- ħin.
The mean absolute bioavailability of laropiprant is approximately 71% following a 40 mg dose when administered as two modified-release tablets of nicotinic acid/ laropiprant after an overnight fast.
11 Il- bijodisponibilità assoluta medja ta ’ laropiprant hija ta ’ madwar 71% wara doża ta ’ 40 mg meta mogħtija bħala żewġ pilloli ta ’ l- aċidu nikotiniku/ laropiprant li jerħu l- mediċina b’ mod modifikat wara sawma ta ’ lejl.
Distribution Nicotinic acid Nicotinic acid is less than 20% bound to serum proteins.
Distribuzzjoni L- aċidu nikotiniku L- aċidu nikotiniku jeħel anqas minn 20% mal- proteini tas- serum.
Laropiprant The mean volume of distribution at steady state following a single 40 mg intravenous dose of laropiprant to healthy subjects is approximately 70 litres.
Laropiprant Il- volum medju ta ’ distribuzzjoni fl- istat fiss wara doża waħda ta ’ 40 mg laropiprant fil- vini lil individwi b’ saħħithom huwa madwar 70 litru.
Laropiprant is highly bound (> 99%) to plasma proteins, and its binding is independent of concentration.
Laropiprant jeħel ħafna (> 99%) mal- proteini tal - plażma, u l- irbit tiegħu huwa indipendenti mill- konċentrazzjoni.
Laropiprant crosses the placenta in rats and rabbits.
Laropiprant jgħaddi mill- plaċenta fil - firien u l- fniek.
Metabolism Nicotinic acid Nicotinic acid undergoes extensive first-pass metabolism through two pathways that are dose and dose-rate dependent.
Metaboliżmu L- aċidu nikotiniku L- aċidu nikotiniku jgħaddi minn metaboliżmu first- pass estensiv minn żewġ passaġġi li huma dipendenti fuq id- doża u fuq ir- rata tad- doża.
The first pathway results in the formation of nicotinamide adenine dinucleotide (NAD) and nicotinamide.
L- ewwel passaġġ jirriżulta fil- formazzjoni ta ’ nicotinamide adenine dinucleotide (NAD) u nicotinamide.
In humans, nicotinamide is further predominantly metabolised to N-methylnicotinamide (MNA) and to N-methyl-2-pyridone-5-carboxamide (2PY).
Fil- bnedmin, nicotinamide jiġi metabolizzat aktar prinċipalment f’ N- methylnicotinamide (MNA) u f’ N- methyl- 2- pyridone- 5- carboxamide (2PY).
In the second pathway, glycine is conjugated with nicotinic acid to form nicotinuric acid (NUA).
Fit- tieni passaġġ, il- gliċina tingħaqad ma ’ l- aċidu nikotiniku biex tifforma l- aċidu nikotinuriku (NUA).
With low doses of nicotinic acid or lower rates of absorption, the first pathway predominates.
B’ dożi baxxi ta ’ aċidu nikotiniku jew rati aktar baxxi ta ’ assorbiment, l- ewwel passaġġ jippredomina.
At higher doses or higher rates of absorption, the NAD pathway is saturable, and an increasing fraction of the oral dose reaches the bloodstream unchanged as nicotinic acid.
B’ dożi aktar għoljin jew rati ogħla ta ’ assorbiment, il- passaġġ tan- NAD ikun saturabbli, u frazzjoni dejjem akbar tad- doża orali tilħaq in- nixxiegħa tad- demm fil- ġisem mhux mibdula bħala aċidu nikotiniku.
The glycine conjugation pathway is not saturated across the clinically relevant dose range, based on the dose-proportional increase in the plasma concentrations of NUA from 1000 mg to 2000 mg.
Il- passaġġ fejn tingħaqad il- gliċina ma jiġix saturat tul il- medda ta ’ dożi klinikament rilevanti, fuq il- bażi taż- żieda proporzjonali mad- doża fil- konċentrazzjoni ta ’ NUA fil- plażma minn 1, 000 mg għal 2000 mg.
In in vitro studies, nicotinic acid and its metabolites did not inhibit CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4-mediated reactions or UGT1A1-mediated 3-glucuronidation of estradiol.
Fi studji in vitro, l- aċidu nikotiniku u l- metaboliti tiegħu ma waqqfux reazzjonijiet medjati b’ CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, jew CYP3A4 jew 3- glucuronidation medjat b’ UGT1A1 ta ’ estradiol.
13 Laropiprant Laropiprant is metabolised primarily via acyl glucuronidation, with a smaller component of oxidative metabolism, followed by excretion of the glucuronide into faeces (via bile) and urine.
Laropiprant Laropiprant huwa metabolizzat prinċipalment permezz ta ’ acyl glucuronidation, b’ komponent iżgħar ta ’ metaboliżmu ossidattiv, segwit mill- eskrezzjoni tal- glucuronide fl- ippurgar (permezz tal- bile) u l - awrina.
Laropiprant and its acyl glucuronide conjugate are the major circulating components in human plasma.
Laropiprant u l- acyl glucuronide conjugate tiegħu huma l- komponenti prinċipali li jiċċirkolaw fil- plażma umana.
In vitro studies have shown that the acyl glucuronide conjugate of laropiprant had at least a 65-fold reduced affinity for DP1 as compared to laropiprant; thus, it is not expected to contribute to the overall DP1 activity of laropiprant.
Studji in vitro wrew li l- acyl glucuronide conjugate ta ’ laropiprant kellu mill- anqas 65 darba anqas affinità għad- DP1 meta mqabbel ma ’ laropiprant; għaldaqstant, mhuwiex mistenni li jikkontribwixxi għall- attività DP1 globali ta ’ laropiprant.
The major component (73% of radioactivity) in faeces is laropiprant (comprising unabsorbed active substance and/ or hydrolysed glucuronic acid conjugate).
Il- komponent prinċipali (73% tar - radjuattività) fl- ippurgar huwa laropiprant (inkluża s- sustanza attiva mhux assorbita u/ jew il- konjugat idrolizzat ta ’ l- aċidu glukoroniku).
In urine, the primary component is the acyl glucuronide conjugate (64% of radioactivity) with smaller contributions from the parent compound (5%).
Fl- awrina, il- komponent primarju huwa l- acyl glucuronide conjugate (64% tar- radjuattività) b’ kontribuzzjonijiet iżgħar mill- kompost oriġinali (5%).
The oxidative metabolism of laropiprant is catalysed primarily by CYP3A4, whereas several UGT isoforms (1A1, 1A3, 1A9 and 2B7) catalysed the acyl glucuronidation.
Il - metaboliżmu ossidattiv ta ’ laropiprant huwa katalizzat prinċipalment minn CYP3A4, filwaqt li diversi isoformi UGT (1A1, 1A3, 1A9 and 2B7) ikkatalizzaw l- acyl glucuronidation.
Elimination Nicotinic acid Nicotinic acid is predominantly excreted in the urine as metabolites.
Eliminazzjoni L- aċidu nikotiniku L- aċidu nikotiniku jitneħħa prinċipalment fl- awrina bħala metaboliti.
Laropiprant Laropiprant is eliminated primarily via acyl glucuronidation, followed by excretion of the glucuronide in faeces (via bile) and urine.
Laropiprant Laropiprant jitneħħa prinċipalment permezz ta ’ acyl glucuronidation, segwita mill- eskrezzjoni tal - glucuronide fl- ippurgar (permezz tal- bile) u l- awrina.
Following oral administration of 14C-laropiprant in humans, approximately 68% of the dose was recovered in faeces (primarily as parent compound, comprising unabsorbed active substance and/ or hydrolysed glucuronic acid conjugate) and 22% was recovered in urine (primarily as metabolites).
Wara l- għoti mill- ħalq ta ’ 14C- laropiprant fil - bnedmin, madwar 68% tad- doża kienet irkuprata fl- ippurgar (prinċipalment bħala kompost oriġinali, li kien jinkludi sustanza attiva mhux assorbita u/ jew il- konjugat idrolizzat ta ’ l- aċidu glukoroniku) u 22% kien irkuprat fl- awrina (primarjament bħala metaboliti).
The majority of the dose was excreted within 96 hours.
Il- maġġoranza tad- doża tneħħiet fi żmien 96 siegħa.
The apparent terminal half-life (t1/ 2) following a 40 mg dose of laropiprant administered as two modified-release tablets of nicotinic acid/ laropiprant with food was approximately 17 hours.
Il- half- life terminali apparenti (t1/ 2) wara doża ta ’ 40 mg laropiprant mogħtija bħala żewġ pilloli ta ’ l- aċidu nikotiniku/ laropiprant li jerħu l- mediċina b’ mod modifikat ma ’ l- ikel kienet ta ’
Pharmacokinetic steady state is achieved within 2 days of once-daily dosing of laropiprant, with minimal accumulation in AUC (approximately 1.3-fold) and Cmax (approximately 1.1-fold).
Stat farmakokinetiku fiss jinkiseb fi żmien jumejn ta ’ dożaġġ darba kuljum ta ’ laropiprant, b’ akkumulazzjoni minima fl- AUC (madwar 1. 3 darbiet) u fil- Cmax (madwar 1. 1 darbiet).
Characteristics in patients Renal insufficiency Pelzont:
Karatteristiċi fil- pazjenti Insuffiċjenza tal- kliewi Pelzont:
Use in patients with renal insufficiency has not been studied.
L- użu f’ pazjenti b’ insuffiċjenza tal- kliewi ma ġiex studjat.
Nicotinic acid: see section 4.4.
L- aċidu nikotiniku: ara sezzjoni 4. 4.
Administration of laropiprant 40 mg in non-dialysed patients with severe renal insufficiency resulted in no clinically meaningful change in the AUC and Cmax of laropiprant, compared to healthy control subjects.
L- għoti ta ’ laropiprant 40 mg f’ pazjenti mhux fuq dijalisi b’ insuffiċjenza renali severa ma rriżulta f’ ebda bidla klinikament sinifikanti fl- AUC u l- Cmax ta ’ laropiprant, meta mqabbel ma ’ individwi ta ’ kontroll b’ saħħithom.
As no effect was observed in severe renal insufficiency, no effect is expected in patients with mild and moderate renal insufficiency; however, the effects of end-stage renal failure and dialysis on laropiprant pharmacokinetics cannot be inferred from this study.
Billi ma kien osservat l- ebda effett f’ insuffiċjenza renali severa, ma huwa mistenni l- ebda effett f’ pazjenti b’ insuffiċjenza tal- kliewi ħafifa u moderata; madankollu, l - effetti ta ’ insuffiċjenza renali ta ’ l- aħħar stadju u dijalisi fuq il- farmakokinetika ta ’ laropiprant ma jistgħux jiġu inferiti minn dan l- istudju.
Hepatic insufficiency Pelzont:
Insuffiċjenza tal- fwied Pelzont:
Use in patients with hepatic insufficiency has not been studied.
L- użu f’ pazjenti b’ insuffiċjenza tal- fwied ma ġiex studjat.
Nicotinic acid: see sections 4.3 and 4.4.
(ara sezzjonijiet 4. 3 u 4. 4.)
Consistent with the characteristics of a medicinal product that is primarily cleared by metabolism, moderate hepatic disease has a significant impact on laropiprant pharmacokinetics, with an increase in AUC and Cmax of approximately 2.8- and 2.2-fold respectively.
Konsistenti mal- karatteristiċi ta ’ prodott mediċinali li jitneħħa primarjament bil - metaboliżmu, mard tal- fwied moderat għandu impatt sinifikanti fuq il- farmakokinetika ta ’ laropiprant, b’ żieda fl- AUC u l- Cmax ta ’ madwar 2. 8 u 2. 2 darbiet rispettivament.
14 Gender Nicotinic acid:
Sess tal- persuna L- aċidu nikotiniku:
No dose adjustment is necessary based on gender.
M’ hemmx bżonn ta ’ aġġustament fid- doża bbażat fuq is- sess tal- persuna.
Gender has no clinically meaningful effect on pharmacokinetics of nicotinic acid (prolonged-release formulation).
Is- sess tal- persuna m’ għandu l- ebda effett kliniku sinifikanti fuq il- farmakokinetika ta ’ l- aċidu nikotiniku (formulazzjoni li terħi l- mediċina bil- mod).
There is no difference in the oral bioavailability of nicotinic acid in men and women receiving Pelzont.
M’ hemmx differenza fil- bijodisponibilità orali ta ’ l- aċidu nikotiniku fl- irġiel u n- nisa li jirċievu Pelzont.
Women have a modest increase in plasma concentrations of nicotinuric acid and nicotinic acid compared to men.
In- nisa kellhom żieda modesta fil- konċentrazzjonijiet ta ’ aċidu nikotinuriku u aċidu nikotiniku fil- plażma meta mqabbel ma ’ l- irġiel.
Gender had no clinically meaningful effect on the pharmacokinetics of laropiprant.
Is- sess tal - persuna ma kellu ebda effett kliniku sinifikanti fuq il- farmakokinetika ta ’ laropiprant.
Elderly Nicotinic acid:
Anzjani L- aċidu nikotiniku:
There is no pharmacokinetic data in the elderly (≥ 65 years).
M’ hemmx dejta farmakokinetika dwar l- anzjani (≥ 65 sena).
Age has no clinically meaningful effect on pharmacokinetics of nicotinic acid (prolonged-release formulation) based on a composite analysis of subjects ages 18-65 years.
L- età tal- persuna ma għandha ebda effett kliniku sinifikanti fuq il- farmakokinetika ta ’ l- aċidu nikotiniku (formulazzjoni li terħi l- mediċina bil- mod) skond analiżi komposta ta ’ individwi ta ’ bejn 18 u 65 sena.
There is no change in the oral bioavailability of nicotinic acid with age.
M’ hemm ebda tibdil fil- bijodisponibilità orali ta ’ l- aċidu nikotiniku ma ’ l- età.
No dose adjustment is necessary in the elderly.
M’ hemmx bżonn ta ’ aġġustament fid- doża għall- anzjani.
Age had no clinically meaningful effect on the pharmacokinetics of laropiprant.
L- età tal- persuna ma għandha ebda effett kliniku sinifikanti fuq il- farmakokinetika ta ’ laropiprant.
Paediatric Pelzont:
Pedjatriċi Pelzont:
No studies have been performed in paediatric patients.
Ma sarux studji fuq pazjenti pedjatriċi.
Race Nicotinic acid:
Razza Aċidu Nikotiniku:
No dose adjustment is necessary based on race.
M’ hemmx bżonn ta ’ aġġustament fid- doża bbażat fuq ir- razza.
Race has no clinically meaningful effect on the pharmacokinetics of nicotinic acid (prolonged-release formulation) based on pharmacokinetic data including subjects of Hispanic, White, Black, and Native American racial groups.
Ir- razza ma għandha l- ebda effett kliniku sinifikanti fuq il- farmakokinetika ta ’ l- aċidu nikotiniku (formulazzjoni li terħi l - mediċina bil- mod) fuq il- bażi ta ’ informazzjoni farmakokinetika li kienet tinkludi individwi ta ’ gruppi razzjali Ispaniċi, Bojod, Suwed, u Amerikani Nattivi.
Race had no clinically meaningful effect on the pharmacokinetics of laropiprant based on a composite analysis of pharmacokinetic data including subjects of White, Hispanic, Black, Asian, and Native American racial groups.
Ir- razza ma kellha ebda effett kliniku sinifikanti fuq il- farmakokinetika ta ’ laropiprant skond analiżi komposta ta ’ informazzjoni farmakokinetika li kienet tinkludi individwi ta ’ gruppi razzjali Bojod, Ispaniċi, Suwed, Asjatiċi, u Amerikani Nattivi.
5.3 Preclinical safety data
13 5. 3 Tagħrif ta ’ qabel l- użu kliniku dwar is- sigurtà tal- mediċina
Pelzont Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the maximum human exposure, indicating little relevance to human use.
Pelzont Fi studji li m’ humiex kliniċi, effetti dehru biss wara esponimenti meqjusa ferm aktar għolja mill - massimu ta ’ l- esponimenti fil- bnedmin, li juru ftit li xejn rilevanza ma ’ l- użu fil- bnedmin.
The safety of concomitant administration of nicotinic acid and laropiprant was assessed in dogs and rats.
Is- sigurtà ta ’ l- għoti fl- istess ħin ta ’ l- aċidu nikotiniku u laropiprant ġiet evalwata fil- klieb u l- firien.
Toxicologic findings in these co-administration studies were consistent with those seen with nicotinic acid and laropiprant administered individually.
Is- sejbiet tossikoloġiċi f’ dawn l- istudji dwar l- għoti fl- istess ħin kienu konsistenti ma ’ dawk li dehru meta l- aċidu nikotiniku u laropiprant ingħataw b’ mod individwali.
Nicotinic acid Degeneration in the stomach and hepatocyte vacuolation were observed in rats following 6 months of dosing at systemic exposure values at least 179 times the human exposure based on the AUC of the recommended daily human dose.
Aċidu nikotiniku Kienet osservata deġenerazzjoni fl- istonku u vakwolazzjoni ta ’ l- epatoċiti fil- firien wara 6 xhur ta ’ dożaġġ b’ valuri ta ’ esponiment sistemiku ta ’ mill- anqas 179 darba l- esponiment uman ibbażat fuq l - AUC tad- doża ta ’ kuljum rakkomandata għall- bnedmin.
Retinopathy and/ or corneal lesions were observed in dogs following 6 months of dosing at systemic exposure values at least 240 times the human exposure based on the AUC of the recommended daily human dose.
Fil- klieb kienu osservati retinopatija u/ jew leżjonijiet fil- kornea wara sitt xhur ta ’ dożaġġ b’ valuri ta ’ esponiment sistemiku ta ’ mill- anqas 240 darba l- esponiment uman ibbażat fuq l- AUC tad- doża ta ’ kuljum rakkomandata għall- bnedmin.
15 Nicotinic acid was not carcinogenic in mice when administered for the duration of their life.
L- aċidu nikotiniku ma kienx karċinoġeniku fil- ġrieden meta ngħata għat- tul kollu ta ’ ħajjithom.
Mice in this study received approximately 9 to 13 times a human nicotinic acid dose of 2000 mg/ day as determined on a mg/ m2 basis.
Il - ġrieden f’ dan l- istudju rċevew madwar 9 sa 13- il darba d- doża umana ta ’ 2000 mg/ kuljum ta ’ aċidu nikotiniku kif stabbilita fuq bażi ta ’ mg/ m2.
Nicotinic acid showed no mutagenic effects in the in vitro assays.
L- aċidu nikotiniku ma wera ebda effetti mutaġeniċi fl - assaġġi in vitro.
No studies are available on possible effects of high dose nicotinic acid on fertility or on postnatal development after in utero exposure.
M’ hemm ebda studju disponibbli fuq l- effetti possibbli ta ’ aċidu nikotiniku ta ’ doża għolja fuq il - fertilità jew fuq l- iżvilupp wara t- twelid wara espożizzjoni in utero.
Nicotinic acid induced reproduction toxic effects in rats when dosed at 1000 mg/ kg/ day during days 5-16 of gestation.
L- aċidu nikotiniku ġab miegħu effetti tossiċi għar- riproduzzjoni fil- firien meta ddożat b’ 1000 mg/ kg/ day matul jiem 5- 16 tat- tqala.
Decreased placental and fetal weights were observed.
Ġie osservat tnaqqis fil- piż tal- plaċenta kif ukoll tal- fetu.
Laropiprant Ketonuria and hepatocellular centrilobular hypertrophy were observed in rats in repeated dose toxicity studies for up to 6 months dosing.
Laropiprant Fi studji dwar l- effett tossiku minn dożi ripetuti fuq il- firien b’ dożi li damu jingħataw sa 6 xhur dehru ketonurja u ipertrofija ċentrilobulari epatoċellulari.
The hepatocellular centrilobular hypertrophy was consistent with rodent specific enzyme induction.
L- ipertrofija ċentrilobulari epatoċellulari kienet konsistenti ma ’ l- induzzjoni ta ’ l- enzimi speċifiċi għall- annimali gerriema.
The no-observed-adverse-effect level (NOAEL) was at least 118 times the human exposure based on the AUC of the recommended daily human dose.
Il- livell ta ’ l- ebda effett avvers osservat (NOAEL – no- observed- adverse- effect level) kien mill- anqas 118- il darba l - esponiment uman ibbażat fuq l- AUC tad- doża ta ’ kuljum rakkomandata għall- bnedmin.
Increases in serum alanine aminotransferase (ALT) levels were observed in all dog studies, at systemic exposure levels at least 14 times the human exposure based on the AUC of the recommended daily human dose.
Fl- istudji kollha fuq il- kelb kienu osservati żidiet fil- livelli ta ’ alanine aminotransferase fis- serum (ALT), f’ livelli ta ’ esponiment sistemiku ta ’ mill- anqas 14- il darba l- esponiment uman ibbażat fuq id - doża ta ’ kuljum rakkomandata għall- bniedem.
No other effects were observed in dog studies with exposures at least 100 times the human exposure based on the AUC of the recommended daily human dose.
Ebda effett ieħor ma kien osservat fl- istudji fuq il- klieb b’ esponiment ta ’ mill- inqas 100 darba l- esponiment uman ibbażat fuq l- AUC tad- doża ta ’ kuljum rakkomandata għall- bnedmin.
Laropiprant was not carcinogenic in 2 year studies in mice and rats at the highest doses tested, which represents at least 218 to 289 times the human exposure based on the AUC of the recommended daily human dose.
Laropiprant ma kienx karċinoġeniku fi studji ta ’ sentejn fuq il- ġrieden u l- firien bl- ogħla dożi ttestjati, li jirrappreżentaw mill- anqas 218 sa 289 darba l- esponiment uman ibbażat fuq l- AUC tad- doża ta ’ kuljum rakkomandata għall- bnedmin.
Laropiprant was not mutagenic or clastogenic in a series of genetic toxicology studies.
Laropiprant ma kienx mutaġeniku jew klastoġeniku f’ sensiela ta ’ studji dwar l- effett tossiku fuq il - ġeni.
No adverse effects on fertility were observed in male or female rats given laropiprant prior to mating and throughout mating, at systemic exposure levels at least 289 times the human exposure based on the AUC of the recommended daily human dose.
Ma kienu osservati ebda effetti avversi fil- firien irġiel jew nisa li ngħataw laropiprant qabel it - tgħammir jew waqt it- tgħammir, b’ livelli ta ’ esponiment sistemiku ta ’ mill- anqas 289 darba l - esponiment uman ibbażat fuq l- AUC tad- doża ta ’ kuljum rakkomandata għall- bnedmin.
Laropiprant was not teratogenic in rats or in rabbits at least 153 and 438 times the human exposure based on the AUC of the recommended daily human dose.
Laropiprant ma kienx teratoġeniku fil- firien jew fil- fniek f’ livelli ta ’ mill- anqas 153 u 438 darba l - esponiment uman ibbażat fuq l- AUC tad- doża ta ’ kuljum rakkomandata għall- bnedmin.
Reproduction toxicity studies showed slight treatment-related decreases in mean maternal weight gain and foetal body weight, slight increases in pup mortality, and increased incidence of supernumerary rib and incomplete ossification of the sternebra in the foetus were observed in rats at systemic exposure levels at least 513 times the human exposure based on the AUC of the recommended daily human dose.
Studji ta ’ l - effett tossiku fuq is- sistema riproduttiva wrew tnaqqis żgħir relatat mat- trattament fiż- żieda medja fil - piż ta ’ l- omm u l- piż tal- ġisem tal- fetu, żidiet żgħar fil- mortalità tal- frieħ, u inċidenza akbar ta ’ kustilja żejda u ossifikazzjoni inkompleta ta ’ l- isternebra fil- fetu kienu osservati fil- firien f’ livelli ta ’
Hypromellose (E464) Colloidal anhydrous silica (E551) Sodium stearyl fumarate Hydroxypropylcellulose (E463) Microcrystalline cellulose (E460) Croscarmellose sodium Lactose monohydrate Magnesium stearate
Hypromellose (E464) Colloidal anhydrous silica (E551) Sodium stearyl fumarate Hydroxypropylcellulose (E463) Microcrystalline cellulose (E460) Croscarmellose sodium Lactose monohydrate Magnesium stearate
PVC/ Aclar blisters:
Folji tal- PVC/ Aclar:
Aluminium/ Aluminium blisters:
Aluminju/ Folji ta ’ l- aluminju:
Do not store above 30 C.
Taħżinx f’ temperatura ’ l fuq minn 30 C.
Opaque PVC/ Aclar blister with push-through aluminium lidding containing 14 modified-release tablets.
Folja opaka tal- PVC/ Aclar b’ għeluq ta ’ l- aluminju push- through li fiha 14- il pillola li jerħu l - mediċina.
Pack sizes of 14, 28, 56, 84, 98, 168, 196 modified-release tablets, multi-packs containing 196 (2 packs of 98) modified-release tablets and 49 x 1 modified-release tablets in a perforated unit dose blister.
Pakketti ta ’ 14, 28, 56, 84, 98, 168, 196 pillola li terħi l- mediċina b’ mod modifikat, pakketti multipli li fihom 196 (2 pakketti ta ’ 98) pillola li terħi l- mediċina b’ mod modifikat u 49 x 1 pillola li terħi l- mediċina b’ mod modifikat f’ folja unit dose perforata.
Aluminium/ Aluminium blister with push-through lidding containing 7 modified-release tablets.
Folja ta ’ l- Aluminju/ Aluminju b’ għeluq push- through li fiha 7 pilloli li jerħu l- mediċina b’ mod modifikat.
Pack sizes of 14, 28, 56, 168 modified-release tablets and 32 x 1 modified-release tablets in a perforated unit dose blister.
Pakketti ta ’ 14, 28, 56, 168 pillola li terħi l- mediċina b’ mod modifikat u 32 x 1 pillola li terħi l- mediċina b’ mod modifikat f’ folja ta ’ doża waħda perforata.
3 July 2008
3 ta ’ Lulju 2008
Detailed information on this product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/.
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropea dwar il - Mediċini (EMEA) http: // www. emea. europa. eu /.
18 ANNEX II
16 ANNESS II
Shotton Lane Cramlington Northumberland NE23 3JU United Kingdom
Shotton Lane Cramlington Northumberland NE23 3JU Ir- Renju Unit
The MAH must ensure that the system of pharmacovigilance, as described in version 3 dated September 2007 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.
Id- detentur ta ’ l- awtorizzazzjoni għat- tqegħid fis- suq għandu jiżgura li s- sistema ta ’ farmakoviġilanza, kif deskritta fil- verżjoni 3 datata Settembru 2007 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.
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan, as agreed in version 3.1 dated 23 April 2008 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.
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 3. 1 datata 23 ta ’ April 2008 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.
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the updated RMP should be submitted at the same time as the next Periodic Safety Update Report (PSUR).
Skond il- Linja gwida tal- CHMP dwar Sistemi ta ’ Ġestjoni tar- Riskji għal prodotti mediċinali għal użu mill- bniedem, l- RMP aġġornat għandu jiġi ppreżentat fl- istess ħin tar- Rapport Perjodiku ta ’ Aġġornament dwar is- Sigurtà (PSUR) li jmiss.
20 ANNEX III
18 ANNESS III
22 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
20 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA
OUTER CARTON (for Alu/ Alu blister)
KARTUNA TA ’ BARRA (għal folja Alu/ Alu)
Pelzont 1000 mg/ 20 mg modified-release tablets Nicotinic acid/ laropiprant
Pelzont 1, 000 mg/ 20 mg pilloli li jerħu l- mediċina b’ mod modifikat Aċidu nikotiniku/ laropiprant
Each modified-release tablet contains 1000 mg of nicotinic acid and 20 mg of laropiprant.
Kull pillola li terħi l- mediċina b’ mod modifikat fiha 1, 000 mg ta ’ aċidu nikotiniku u 20 mg laropiprant.
14 modified-release tablets 28 modified-release tablets 56 modified-release tablets 168 modified-release tablets 32 x 1 modified-release tablets
14- il pillola li terħi l- mediċina b’ mod modifikat 28 pillola li terħi l- mediċina b’ mod modifikat 56 pillola li terħi l- mediċina b’ mod modifikat 168 pillola li terħi l- mediċina b’ mod modifikat 32 x 1 pillola li terħi l- mediċina b’ mod modifikat
EU/ 1/ 08/ 460/ 009 14 modified-release tablets EU/ 1/ 08/ 460/ 010 28 modified-release tablets EU/ 1/ 08/ 460/ 011 56 modified-release tablets EU/ 1/ 08/ 460/ 013 168 modified-release tablets EU/ 1/ 08/ 460/ 014 32 x 1 modified-release tablets
EU/ 1/ 08/ 460/ 009 14- il pillola li terħi l- mediċina b’ mod modifikat EU/ 1/ 08/ 460/ 010 28 pillola li terħi l- mediċina b’ mod modifikat EU/ 1/ 08/ 460/ 011 56 pillola li terħi l- mediċina b’ mod modifikat EU/ 1/ 08/ 460/ 013 168 pillola li terħi l- mediċina b’ mod modifikat EU/ 1/ 08/ 460/ 014 32 x 1 pillola li terħi l- mediċina b’ mod modifikat
24 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
22 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA
OUTER CARTON (for PVC/ Aclar blister)
KARTUNA TA ’ BARRA (għal folja PVC/ Aclar)
14 modified-release tablets 28 modified-release tablets 56 modified-release tablets 84 modified-release tablets 98 modified-release tablets 168 modified-release tablets 196 modified-release tablets Multi-pack containing 196 (2 packs of 98) modified-release tablets 49 x 1 modified-release tablets
14- il pillola li terħi l- mediċina b’ mod modifikat 28 pillola li terħi l- mediċina b’ mod modifikat 56 pillola li terħi l- mediċina b’ mod modifikat 84 pillola li terħi l- mediċina b’ mod modifikat 98 pillola li terħi l- mediċina b’ mod modifikat 168 pillola li terħi l- mediċina b’ mod modifikat 196 pillola li terħi l- mediċina b’ mod modikfikat Pakkett multiplu li fih 196 (2 pakketti ta ’ 98) pillola li terħi l- mediċina b’ mod modifikat 49 x 1 pillola li terħi l- mediċina b’ mod modifikat
EU/ 1/ 08/ 460/ 001 14 modified-release tablets EU/ 1/ 08/ 460/ 002 28 modified-release tablets EU/ 1/ 08/ 460/ 003 56 modified-release tablets EU/ 1/ 08/ 460/ 004 84 modified-release tablets EU/ 1/ 08/ 460/ 005 98 modified-release tablets EU/ 1/ 08/ 460/ 006 168 modified-release tablets EU/ 1/ 08/ 460/ 007 196 modified-release tablets EU/ 1/ 08/ 460/ 008 49 x 1 modified-release tablets EU/ 1/ 08/ 460/ 012 196 (2 packs of 98) modified-release tablets
EU/ 1/ 08/ 460/ 001 14- il pillola li terħi l- mediċina b’ mod modifikat EU/ 1/ 08/ 460/ 002 28 pillola li terħi l- mediċina b’ mod modifikat EU/ 1/ 08/ 460/ 003 56 pillola li terħi l- mediċina b’ mod modifikat EU/ 1/ 08/ 460/ 004 84 pillola li terħi l- mediċina b’ mod modifikat EU/ 1/ 08/ 460/ 005 98 pillola li terħi l- mediċina b’ mod modifikat EU/ 1/ 08/ 460/ 006 168 pillola li terħi l- mediċina b’ mod modifikat EU/ 1/ 08/ 460/ 007 196 pillola li terħi l- mediċina b’ mod modifikat EU/ 1/ 08/ 460/ 008 49 x1 pillola li terħi l- mediċina b’ mod modifikat EU/ 1/ 08/ 460/ 012 196 (2 pakketti ta ’ 98) pillola li terħi l- mediċina b’ mod modifikat
27 PARTICULARS TO APPEAR ON THE INTERMEDIATECARTON
24 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT LI JMISS MAL- PRODOTT
Multi-packs of 196 (2 packs of 98 modified-release tablets) – without blue box (for PVC/ Aclar blister)
Pakketti multipli ta ’ 196 (2 pakketti ta ’ 98 pillola li jerħu b’ mod modifikat) - mingħajr kaxxa blu (għal folja tal- PVC/ Aclar)
Pelzont 1000 mg/ 20 mg modified-release tablets Nicotinic acid/ laropiprant
Pelzont 1000 mg/ 20 mg pilloli li jerħu l- mediċina b’ mod modifikat Nicotinic acid/ laropiprant
Each modified-release tablet contains 1000 mg of nicotinic acid and 20 mg of laropiprant.
Kull pillola li terħi l- mediċina b’ mod modifikat fiha 1000 mg ta ’ nicotinic acid u 20 mg ta ’ laropiprant.
Component of a multi-pack comprising 2 packs, each containing 98 modified-release tablets.
Il- komponenti fil- pakkett multiplu jikkonsistu minn 2 pakketti li kull wieħed fih 98 pillola li terħi b’ mod modifikat.
Read the package leaflet before use.
Użu orali Aqra l- pakkett ta ’ tagħrif qabel l- użu.
29 MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS
26 TAGĦRIF MINIMU LI GĦANDU JIDHER FUQ IL- FOLJI JEW FUQ L- ISTRIXXI
31 PACKAGE LEAFLET:
28 FULJETT TA ’ TAGĦRIF:
Pelzont 1000 mg/ 20 mg modified-release tablets nicotinic acid/ laropiprant
Pelzont 1, 000 mg/ 20 mg pilloli li jerħu l- mediċina b’ mod modifikat aċidu nikotiniku/ laropiprant
Read all of this leaflet carefully before you start taking this medicine.
Aqra sewwa dan il- fuljett kollu qabel tibda tieħu din il- mediċina. − Żomm dan il- fuljett.
- If you have any further questions, ask your doctor or pharmacist.
Jista ’ jkollok bżonn terġa ’ taqrah. − Jekk ikollok aktar mistoqsijiet, staqsi lit- tabib jew lill- ispiżjar tiegħek. − Din il- mediċina ġiet mogħtija lilek.
- If any of the side effects gets serious, or if you notice any side effects not listed in this
Tista ’ tagħmlilhom il- ħsara, anki jekk ikollhom l- istess sintomi bħal tiegħek. − Jekk xi wieħed mill- effetti sekondarji jiggrava, jew jekk tinnota xi effetti sekondarji li mhumiex imsemmijin f’ dan il- fuljett, jekk jogħġbok għid lit- tabib jew lill- ispiżjar tiegħek.
What Pelzont is and what it is used for 2.
X’ inhu Pelzont u għaliex jintuża 2.
Before you take Pelzont 3.
Qabel ma tieħu Pelzont 3.
How to take Pelzont 4.
Kif għandek tieħu Pelzont 4.
How to store Pelzont 6.
Kif taħżen Pelzont 6.
WHAT PELZONT IS AND WHAT IT IS USED FOR
X’ INHU PELZONT U GĦALIEX JINTUŻA
The name of your medicine is Pelzont.
L- isem tal- mediċina tiegħek huwa Pelzont.
It contains two different active substances: • nicotinic acid, a lipid modifying medicine, and • laropiprant, which reduces symptoms of flushing, a common side effect of nicotinic acid.
Huwa fih żewġ sustanzi attivi differenti: • aċidu nikotiniku, mediċina li timmodifika ix- xaħmijiet u • laropiprant, li jnaqqas is- sintomi ta ’ fawra, effett sekondarju komuni ta ’ l- aċidu nikotiniku.
The medicine comes as a modified-release tablet.
Din il- mediċina tiġi bħala pillola li terħi l- mediċina b’ mod modifikat.
This means one or more active substances are released slowly over a period of time.
Dan ifisser li sustanza attiva waħda jew aktar jiġu merħija bil- mod fuq perjodu ta ’ ħin.
Pelzont is used in addition to diet • to lower your ‘ bad’ cholesterol level.
Pelzont jintuża mad- dieta: • biex ibaxxi l- livell tal- kolesterol ‘ ħażin ’ tiegħek.
It does this by lowering the levels of total cholesterol, LDL cholesterol, fatty substances called triglycerides and apo B (a part of LDL) in the blood; • to raise levels of ‘ good’ cholesterol (HDL cholesterol) and apo A-I (a part of HDL).
Huwa jagħmel dan billi jbaxxi l- livelli ta ’ kolesterol totali, kolesterol LDL, sustanzi xaħmija msejħa trigliċeridi u apo B (parti mil- LDL) fid- demm. • biex jgħolli l- livelli tal- kolesterol ‘ tajjeb ’ (kolesterol HDL) u apo A- I (parti mill- HDL).
What should I know about cholesterol?
X’ għandi nkun naf dwar il- kolesterol?
Cholesterol is one of several fats found in your blood.
Il- kolesterol huwa wieħed mill- bosta xaħmijiet li hemm f’ ġismek.
Your total cholesterol is made up mainly of ‘ bad’ (LDL) and ‘ good’ (HDL) cholesterol.
Il- kolesterol totali tiegħek huwa magħmul prinċipalment minn kolesterol ‘ ħażin ’ (LDL) u ‘ tajjeb ’ (HDL).
LDL cholesterol is often called ‘ bad’ cholesterol because it can build up in the walls of your arteries and form plaque.
Kolesterol LDL huwa xi kultant imsejjaħ kolesterol ‘ ħażin ’ minħabba li jista ’ jinġema ’ mal- ħitan ta ’ l - arterji tiegħek u jifforma plakka.
Over time, this plaque build-up can lead to a clogging of your arteries.
Maż- żmien, din l- akkumulazzjoni tal- plakka tista ’ twassal għal imblukkar ta ’ l- arterji tiegħek.
This clogging can slow or block blood flow to vital organs such as the heart and brain.
Dan l- imblukkar jista ’ jnaqqas jew jimblokka l- fluss tad- demm lejn l - organi vitali bħall- qalb u l- moħħ.
When the blood flow is blocked, the result can be a heart attack or stroke.
Meta l- fluss tad- demm jiġi imblokkat, ir- riżultat jista ’ jkun jew attakk tal- qalb jew puplesija.
HDL cholesterol is often called ‘ good’ cholesterol because it helps keep the ‘ bad ’ cholesterol from building up in the arteries and because it protects against heart disease.
Il- kolesterol HDL huwa xi kultant imsejjaħ kolesterol ‘ tajjeb ’ minħabba li jżomm lill- kolesterol ‘ ħażin ’ milli jinġema ’ fl- arterji u minħabba li jipproteġi kontra l- mard tal- qalb.
Triglycerides are another fat in your blood.
It- tirgliċeridi huma xaħam ieħor li jinsab f’ demmek.
They may raise your risk of having heart problems.
Jistgħu jżidu r- riskju tiegħek li tiżviluppa problemi tal- qalb.
32 In most people, at first there are no signs of cholesterol problems.
29 F’ ħafna min- nies, għall- ewwel ma jkun hemm ebda sinjal ta ’ problemi bil- kolesterol.
Your doctor can measure your cholesterol with a simple blood test.
It- tabib jista ’ jkejjel il- kolesterol tiegħek b’ test sempliċi tad- demm.
Visit your doctor regularly to keep track of your cholesterol and discuss your goals with your doctor.
Żur it- tabib tiegħek b’ mod regolari sabiex iżżomm kontroll tal- kolesterol tiegħek u ddiskuti l- miri tiegħek mat- tabib tiegħek.