qanastek/EMEA-V3 huggingface dataset:
Apart from the specific medicinal product interaction information described above, interaction studies with clopidogrel and some medicinal products commonly administered in patients with atherothrombotic disease have not been performed.
Apparti mill- informazzjoni dwar l- interazzjoni ta ’ prodotti mediċinali speċifiċi kif spjegat qabel, ma sarux studji dwar l- interazzjoni ta ’ clopidogrel ma ’ xi prodotti mediċinali li s- soltu jingħataw lill - pazjenti li jkollhom mard tat- trombożi ta ’ l- arterji.
However, patients entered into clinical trials with clopidogrel received a variety of concomitant medicinal products including diuretics, beta blockers, ACEI, calcium antagonists, cholesterol lowering agents, coronary vasodilators, antidiabetic agents (including insulin), antiepileptic agents, and GPIIb/ IIIa antagonists without evidence of clinically significant adverse interactions.
Madankollu, pazjenti li daħlu fi studji kliniċi bi clopidogrel ngħataw varjeta` ta ’ prodotti mediċinali fl- istess ħin u dawn kienu jinkludu dijuretiċi, beta blockers, ACEI, antagonisti tal- kalċju, sustanzi li jbaxxu l- kolesterol, vasodilataturi koronarji, sustanzi kontra d- dijabete (inkluża l- insulina), sustanzi antiepilettiċi, u antagonisti GPIIb/ IIIa mingħajr ma kien hemm evidenza ta ’ interazzjonijiet avversi klinikament sinifikanti.
As no clinical data on exposure to clopidogrel during pregnancy are available, it is preferable not to use clopidogrel during pregnancy as a precautionary measure.
Billi m’ hemmx tagħrif kliniku dwar l- espożizzjoni għal clopidogrel waqt it- tqala, aħjar li bħala prekawzjoni ma jsirx użu ta ’ clopidogrel waqt it- tqala.
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/ foetal development, parturition or postnatal development (see section 5.3).
Studji fuq il- bhejjem ma jurux effetti ħżiena diretti jew indiretti fuq it- tqala, fuq l- iżvilupp ta 'l - embriju/ fetu, ħlas jew żvilupp wara t- twelid (ara sezzjoni 5. 3).
Animal studies have shown excretion of clopidogrel in breast milk.
Mhux magħruf jekk clopidogrel joħroġx fil- ħalib tas- sider uman.
As a precautionary measure, breast-feeding should not be continued during treatment with Clopidogrel BMS.
Studji fuq il- bhejjem urew li clopidogrel joħroġ fil- ħalib tas- sider.. Bħala miżura ta ’ prekawzjoni, id- treddigħ m’ għandux jitkompla waqt il- kura b ’ Clopidogrel BMS.
Clopidogrel has no or negligible influence on the ability to drive and use machines.
Clopidogrel m’ għandu l- ebda effett jew ftit li xejn fuq il- ħila ta 'sewqan u l- użu ta ’ magni.
Clopidogrel has been evaluated for safety in more than 42,000 patients who have participated in clinical studies, including over 9,000 patients treated for 1 year or more.
Clopidogrel ġie evalwat għas- sigurta` f’ iktar minn 42, 000 pazjent li pparteċipaw fi studji kliniċi, inklużi iktar minn 9, 000 pazjent li kienu kkurati bih għal sena jew iktar.
The clinically relevant adverse reactions observed in the CAPRIE, CURE, CLARITY and COMMIT studies are discussed below.
Ir- reazzjonijiet avversi klinikament rilevanti li ntwerew fl- istudji CAPRIE, CURE, CLARITY u COMMIT huma diskussi hawn taħt.
Overall, clopidogrel 75 mg/ day was comparable to ASA 325 mg/ day in CAPRIE regardless of age, gender and race.
In ġenerali, clopidogrel 75 mg/ jum kien jikkompara ma 'ASA 325 mg/ jum f' CAPRIE irrispettivament mill- età, sess u razza.
In addition to clinical studies experience, adverse reactions have been spontaneously reported.
Minbarra l- esperjenza ta 'l- istudji kliniċi, reazzjonijiet avversi ġew ukoll irrapportati b' mod spontanju.
Bleeding is the most common reaction reported both in clinical studies as well as in post-marketing experience where it was mostly reported during the first month of treatment.
Il- fsada hija r- reazzjoni l- aktar kommuni li ġiet irraportata kemm fl- istudji kliniċi kif ukoll wara li l - prodott tpoġġa fis- suq fejn l- aktar li ġiet rraportata kienet fl- ewwel xahar tal- kura.
In CAPRIE, in patients treated with either clopidogrel or ASA, the overall incidence of any bleeding was 9.3%.
F’ CAPRIE, f’ pazjenti li ngħataw jew clopidogrel jew ASA, l- inċidenza totali ta 'kull tip ta ’ fsada kienet ta' 9. 3%.
The incidence of severe cases was 1.4% for clopidogrel and 1.6% for ASA.
L- inċidenza ta ’ każi severi kienet ta ’ 1. 4% għal clopidogrel u ta ’ 1. 6% għal ASA.
In CURE, the major bleeding event rate for clopidogrel+ASA was dose-dependent on ASA (< 100mg:
F' CURE, ir- rata ta ’ avvenimenti ta 'fsada maġġuri għal clopidogrel+ASA kienet tiddependi fuq id - doża ta ’ ASA (< 100 mg:
2.6%; 100-200mg:
2. 6%; 100- 200 mg:
3.5%; > 200mg:
3. 5%; > 200 mg:
4.9%) as was the major bleeding event rate for placebo+ASA (< 100mg:
4. 9%) bħal ma 'kienet ukoll ir- rata ta ’ avvenimenti ta' fsada maġġuri għal plaċebo+ASA (< 100 mg:
2.0%; 100-200mg:
2. 0%; 100- 200 mg:
2.3%; > 200mg:
2. 3%; > 200 mg:
4.0%).
4. 0%).
The risk of bleeding (life-threatening, major, minor, other) decreased during the course of the trial:
Ir- riskju ta ’ fsada (ta ’ theddida għall- ħajja, maġġuri, minuri, ta ’ tip ieħor) naqas matul l- istudju:
0-1 months (clopidogrel:
0- 1 xahar (clopidogrel:
9.6%; placebo:
9. 6%; plaċebo:
6.6%), 1-3 months (clopidogrel:
6. 6%), 1- 3 xhur (clopidogrel:
4.5%; placebo:
4. 5%; plaċebo:
2.3%), 3-6 months (clopidogrel:
2. 3%), 3- 6 xhur (clopidogrel:
3.8%; placebo:
3. 8%; plaċebo:
1.6%), 6-9 months (clopidogrel:
1. 6%), 6- 9 xhur (clopidogrel:
3.2%; placebo:
3. 2%; plaċebo:
1.5%), 9-12 months (clopidogrel:
1. 5%), 9- 12 xhur (clopidogrel:
1.9%; placebo:
1. 9%; plaċebo:
1.0%).
1. 0%).
There was no excess in major bleeds with clopidogrel + ASA within 7 days after coronary bypass graft surgery in patients who stopped therapy more than five days prior to surgery (4.4% clopidogrel+ASA vs.
Ma kienx hemm eċċessi fi fsada maġġuri b' clopidogrel+ASA fis- 7 ijiem ta ’ wara operazzjoni ta ’ trapjant ta 'bajpass koronarju f’ pazjenti li waqqfu l- kura iktar minn ħamest ijiem qabel l- operazzjoni (4. 4% clopidogrel+ASA kontra 5. 3% plaċebo + ASA).
In patients who remained on therapy within five days of bypass graft surgery, the event rate was 9.6% for clopidogrel+ASA, and 6.3% for placebo+ASA.
F’ pazjenti li baqgħu jieħdu l- kura fil- ħamest ijiem ta ’ qabel l- operazzjoni ta ’ trapjant ta 'bajpass, ir- rata ta ’ avvenimenti kienet ta' 9. 6% għal clopidogrel+ASA, u 6. 3% għal placebo+ASA.
This was
L- inċidenza ta ’ fsada maġġuri kienet simili bejn il- gruppi (1. 3% kontra 1. 1% għal gruppi clopidogrel + ASA u l- plaċebo + ASA, rispettivament).
5 consistent across subgroups of patients defined by baseline characteristics, and type of fibrinolytic or heparin therapy.
Dan kien konsistenti fil- firxa ta ’ sottogruppi ta ’ pazjenti migbura skond linja bażi ta ’ karatteristiċi u t- tip ta ’ terapija fibrinolitika jew bil- heparin.
In COMMIT, the overall rate of noncerebral major bleeding or cerebral bleeding was low and similar in both groups (0.6% versus 0.5% in the clopidogrel + ASA and the placebo + ASA groups, respectively).
F’ COMMIT, ir- rata totali ta ’ fsada maġġuri mhux ċerebrali jew ta ’ fsada ċerebrali kienet baxxa u simili fiż- zewġ gruppi (0. 6% kontra 0. 5% fil- gruppi clopidogrel + ASA u l- plaċebo + ASA, rispettivament).
Adverse reactions that occurred either during clinical studies or that were spontaneously reported are presented in the table below.
Reazzjonijiet avversi oħra li seħħew jew waqt l- istudji kliniċi jew li ġew irrapportati b' mod spontanju huma mniżżlin fit- tabella hawn taħt.
Their frequency is defined using the following conventions: common (≥ 1/ 100 to < 1/ 10); uncommon (≥ 1/ 1,000 to < 1/ 100); rare (≥ 1/ 10,000 to < 1/ 1,000); very rare (< 1/ 10,000).
Il- frekwenza tagħhom hija definita skond dawn il - konvenzjonijiet: komuni (≥1/ 100 sa < 1/ 10); mhux komuni (≥/ 1, 000 sa < 1/ 100); rari (≥1/ 10, 000 sa < 1/ 1, 000); rari ħafna (< 1/ 10, 000).
Within each system organ class, adverse drug reactions are presented in order of decreasing seriousness.
F’ kull sistema tal- klassifika ta 'l- organi, l- effetti mhux mixtieqa huma mniżżla skond is- serjeta ’ tagħhom, bl- aktar serji jitniżżlu l- ewwel.
System Organ Class
Sistema tal- klassifika ta ’ l- organi
Very rare
Rari Ħafna
Blood and the lymphatic system disorders
Disturbi tad- demm u tas- sistema limfatika
Thrombocytopenia, leucopenia, eosinophilia
Tromboċitopenja, lewkopenja, eosinofilja
Neutropenia, including severe neutropenia
Newtropenja, inkluża newtropenja severa
Thrombotic thrombocytopenic purpura (TTP) (see section 4.4), aplastic anaemia, pancytopenia, agranulocytosis, severe thrombocytopenia, granulocytopenia, anaemia
Purpura tromboċitopenika trombotika (TTP) (ara sezzjoni 4. 4), anemija aplastika, panċitopenja, agranuloċitosi, tromboċitopenja severa, granuloċitopenja, anemija
Serum sickness, anaphylactoid reactions
Mard minn seru barrani, reazzjonijiet simili għal dawk anafilattiċi
Hallucinations, confusion
Alluċinazzjonijiet, konfużjoni
Nervous system disorders
Disturbi fis- sistema
Intracranial bleeding (some cases were
Tibdiliet fit- togħma
Taste disturbances
nervuża
reported with fatal outcome), headache, paraesthesia, dizziness Eye disorders
intrakranjali (ġew irrapportati xi każijiet b’ eżitu fatali), uġigħ ta ’ ras, parestiżja, sturdament
Eye bleeding (conjunctival, ocular, retinal)
Fsada fl- għajn (tal- konġuntiva, okulari, tar - retina)
Ear and labyrinth disorders
Disturbi fil- widnejn u fis- sistema labirintika
Serious haemorrhage, haemorrhage of operative wound, vasculitis, hypotension
Emorraġija serja, emorraġija ta ’ ferita minn operazzjoni, vaskulite, pressjoni baxxa
Respiratory tract bleeding (haemoptysis, pulmonary haemorrhage), bronchospasm, interstitial pneumonitis
Fsada fil- passaġġ respiratorju (emoptisi, emorraġija fil- pulmun), bronkospażmu, pulmonite interstizjali
6
6 Sistema tal- klassifika ta ’ l- organi
Retroperitoneal Gastrointestinal and
Disturbi gastro - intestinali Disturbi fil- fwied u fil - marrara
haemorrhage, diarrhoea, abdominal pain, dyspepsia
Emorraġija gastro - intestinali, dijarea, uġigħ addominali, dispepsja
duodenal ulcer, haemorrhage gastritis, vomiting, nausea, constipation, flatulence
Ulċera gastrika u Emorraġija ulċera dwodenali, tar - gastrite, rimettar, retroperitonew tqalligħ, stitikezza, gas fl - istonku
retroperitoneal haemorrhage with fatal outcome, pancreatitis, colitis (including ulcerative or lymphocytic colitis), stomatitis
Emorraġija gastro - intestinali u tar - retroperitonew b’ eżitu fatali, pankreatite, kolite (inklużi kolite ulċerattiva jew limfoċitika), stomatite Insuffiċjenza akuta tal - fwied, epatite, test tal - funzjoni tal- fwied anormali
Skin and subcutaneous tissue disorders
Disturbi fil- ġilda u fit - tessuti ta ’ taħt il- ġilda
Bruising
Tbenġil
Rash, pruritus, skin bleeding (purpura)
Raxx, ħakk, fsada fil- ġilda (purpura)
Bullous dermatitis (toxic epidermal necrolysis, Stevens Johnson Syndrome, erythema multiforme), angioedema, rash erythematous, urticaria, eczema, lichen planus
Dermatite bulloża (nekroliżi tossika ta ’ l - epidermide, Sindromu ta ’ Stevens Johnson, eritema multiforme), anġjoedima, raxx eritematika, urtikarja, ekżema, lichen planus
Musculoskeletal, connective tissue and bone disorders
Disturbi muskolu - skeltrali, tat- tessut konnettiv u fl- għadam
Musculo-skeletal bleeding (haemarthrosis), arthritis, arthralgia, myalgia
Fsada muskolu- skeltrali (emartrożi), artrite, artralġja, majalġja
Renal and urinary disorders
Disturbi fil- kliewi u fis- sistema urinarja
Haematuria
Ematurja
Glomerulonephritis, blood creatinine increased
Glomerulonefrite, żieda tal- kreatinina fid- demm
General disorders and administration site conditions
Disturbi ġenerali u kundizzjonijiet ta ’ mnejn jingħata
Bleeding at puncture site
Fsada fis- sit tat- titqib
Bleeding time prolonged, neutrophil count decreased, platelet count decreased
Id- demm idum iżjed biex jikkoagula, l - għadd tan - newtrofili jonqos, l- għadd tal - plejtlits jonqos
Overdose following clopidogrel administration may lead to prolonged bleeding time and subsequent bleeding complications.
Doża eċċessiva wara teħid ta ’ clopidrogel tista ’ twassal għal- żieda fil- ħin ta ’ dmija u komplikazzjonijiet ta ’ dmija sussegwenti.
Appropriate therapy should be considered if bleedings are observed.
Terapija adekwata għandha tiġi kkunsidrata jekk dmija tiġi osservata.
No antidote to the pharmacological activity of clopidogrel has been found.
Ma nstabx antidotu għall- attivita` farmakoloġika ta ’ clopidogrel.
If prompt correction of prolonged bleeding time is required, platelet transfusion may reverse the effects of clopidogrel.
Jekk hemm bżonn tittieħed azzjoni malajr minħabba li l- ħin tad- dmija jkun qed jitwal, it- trasfużjoni tal- plejtlets jista ’ jaqleb l - effetti ta ’ clopidogrel.
Pharmacotherapeutic group: platelet aggregation inhibitors excl. heparin, ATC Code:
Kategorija farmakoterapewtika: inibituri ta ’ l- aggregazzjoni tal- plejtlets eskl. heparin, Kodiċi ATC:
Clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor, and the subsequent ADP-mediated activation of the GPIIb/ IIIa complex, thereby inhibiting platelet aggregation.
Cloipidogrel jinibixxi b’ mod selettiv l- irbit ta ’ adenosine diphosphate (ADP) mar- riċettur tal- plejtlets, u l- attivazzjoni wara tal- kumpless GPIIb/ IIIa permezz ta ’ ADP, u għalhekk l- aggregazzjoni tal- plejtlet tiġi inibita.
Biotransformation of clopidogrel is necessary to produce inhibition of platelet aggregation.
Clopidogrel irid jiġi bijotrasformat biex jinibixxi l- aggregazzjoni tal- plejtlets.
Clopidogrel also inhibits platelet aggregation induced by other agonists by blocking the
Clopidogrel jinibixxi wkoll l- aggregazzjoni tal- plejtlets li tkun indotta minn agonisti oħra billi jibblukka l -
7 amplification of platelet activation by released ADP.
7 amplifikazzjoni ta ’ l- attivazzjoni tal- plejtlets li sseħħ permezz ta ’ l- ADP meħlus.
Clopidogrel acts by irreversibly modifying the platelet ADP receptor.
Clopidogrel jaġixxi billi jimmodifika b’ mod irriversibbli r- riċettur tal- plejtlet ADP.
Consequently, platelets exposed to clopidogrel are affected for the remainder of their lifespan and recovery of normal platelet function occurs at a rate consistent with platelet turnover.
B’ konsegwenza ta ’ dan, il- plejtlets esposti għal clopidogrel huma affettwati għall- bqija tal- ħajja tagħhom u l- plejtlets jerġgħu jibdew jiffunzjonaw b’ mod normali b’ rata li hija konsistenti mal- bidla fil- plejtlets.
Repeated doses of 75 mg per day produced substantial inhibition of ADP-induced platelet aggregation from the first day; this increased progressively and reached steady state between Day 3 and Day 7.
Dożi repetuti ta ’ 75 mg kuljum ipproduċew inibizzjoni sostanzjali ta ’ l- aggregazzjoni tal- plejtlets indotti minn ADP mill- ewwel ġurnata; dan żied progressivament u laħaq livell fiss bejn Jum 3 u Jum 7.
At steady state, the average inhibition level observed with a dose of 75 mg per day was between 40% and 60%.
Fi stat fiss, il- livell medju ta ’ inibizzjoni osservat b’ doża ta ’ 75 mg kuljum kien bejn 40% u 60%.
Platelet aggregation and bleeding time gradually returned to baseline values, generally within 5 days after treatment was discontinued.
L - aggregazzjoni tal- plejtlets u l- ħin tad- dmija reġgħu marru bil- mod għall- valuri tal- linja bażi, ġeneralment fi żmien 5 ijiem wara li kienet twaqqfet il- kura.
The safety and efficacy of clopidogrel have been evaluated in 4 double-blind studies involving over 80,000 patients: the CAPRIE study, a comparison of clopidogrel to ASA, and the CURE, CLARITY and COMMIT studies comparing clopidogrel to placebo, both medicinal products given in combination with ASA and other standard therapy.
Is- sigurtà u l- effikaċja ta ’ clopidogrel kienu evalwati f’ 4 studji double blind li involvew ’ il fuq minn 80, 000 pazjent: fl- istudju CAPRIE, paragun ta ’ clopidogrel ma ’ ASA, u fl- istudji CURE, CLARITY u COMMIT kienu mqabblin clopidogrel mal- plaċebo, fejn iż- żewġ prodotti mediċinali ngħataw flimkien ma ’ ASA u terapija oħra li soltu tingħata.
Recent myocardial infarction (MI), recent stroke or established peripheral arterial disease
Infart mijokardijaku reċenti (MI), puplesija reċenti jew mard periferali stabbilit ta ’ l- arterji
The CAPRIE study included 19,185 patients with atherothrombosis as manifested by recent myocardial infarction (< 35 days), recent ischaemic stroke (between 7 days and 6 months) or established peripheral arterial disease (PAD).
L- istudju CAPRIE kien jinkludi 19, 185 pazjent bi trombożi fil- vini li ntweriet permezz ta ’ infart mijokardijaku reċenti (< 35 jum), puplesija iskemika reċenti (bejn 7 ijiem u 6 xhur) jew mard stabbilit ta ’ l- arterji periferali (PAD).
Patients were randomised to clopidogrel 75 mg/ day or ASA 325 mg/ day, and were followed for 1 to 3 years.
Il- pazjenti kienu randomised għal clopidogrel 75 mg/ jum jew ASA 325 mg/ jum, u ġew osservati għal bejn sena u 3 snin.
In the myocardial infarction subgroup, most of the patients received ASA for the first few days following the acute myocardial infarction.
Fis- sottogrupp ta ’ l- infart mijokardijaku, il- biċċa l- kbira tal- pazjenti ngħataw ASA għall- ewwel jiem wara infart mijokardijaku akut.
Clopidogrel significantly reduced the incidence of new ischaemic events (combined end point of myocardial infarction, ischaemic stroke and vascular death) when compared to ASA.
Clopidogrel naqqas b’ mod sinifikanti l- inċidenza ta ’ avvenimenti iskemiċi ġodda (infart mijokardijaku ta ’ l- aħħar kombinat, puplesija iskemika u mewt vaskulari) meta mqabbel ma ’ ASA.
0 to 20] additional patients being prevented from experiencing a new ischaemic event.
Fl- analiżi ta ’ l - intenzjoni tal- kura, ġew osservati 939 avveniment fil- grupp ta ’ clopidogrel u 1 020 avveniment b’ ASA (tnaqqis tar- riskju relattiv (RRR) ta ’ 8. 7%, [95% CI: minn 0. 2 għal 16. 4]; p = 0. 045), li jikkorrispondi, għal kull 1 000 pazjent ttrattati għal għal sentejn, ma ’ 10 [CI: minn 0 sa 20] pazjenti oħra li evitaw avveniment iskemiku ġdid.
Analysis of total mortality as a secondary endpoint did not show any significant difference between clopidogrel (5.8%) and ASA (6.0%).
L- analiżi tal- mortalita` totali bħala punt sekondarju ta ’ tmiem m’ urietx xi differenza sinifikanti bejn clopidogrel (5. 8%) u ASA (6. 0%).
In a subgroup analysis by qualifying condition (myocardial infarction, ischaemic stroke, and PAD) the benefit appeared to be strongest (achieving statistical significance at p = 0.003) in patients enrolled due to PAD (especially those who also had a history of myocardial infarction) (RRR = 23.7%; CI:
F’ analiżi tas- sottogrupp permezz ta ’ kundizzjoni qwalifikanti (infart mijokardijaku, puplesija iskemika, u PAD) il- benefiċċju jidher li kien l- ikbar (b’ relevanza statistika ta ’ p = 0. 003) f’ pazjenti li ddaħħlu minħabba PAD (speċjalment dawk li kellhom ukoll storja medika ta ’ infart mijokardijaku) (RRR = 23. 7%; CI: minn 8. 9 sa 36. 2) u inqas (mhux differenti b’ mod sinifikanti minn ASA) f’ pazjenti b’ puplesija (RRR = 7. 3%; CI: minn - 5. 7 sa 18. 7 [p=0. 258]).
8.9 to 36.2) and weaker (not significantly different from ASA) in stroke patients (RRR = 7.3%; CI: -5.7 to 18.7 [p=0.258]).
F’ pazjenti li ddaħħlu fil- prova minħabba infart mijokardijaku reċenti biss, clopidogrel kien numerikament inqas, imma mhux statistikament differenti minn ASA.
In patients who were enrolled in the trial on the sole basis of a recent myocardial infarction, clopidogrel was numerically inferior, but not statistically different from ASA (RRR = -4.0%; CI: -22.5 to 11.7 [p=0.639]).
(RRR = - 4. 0%; CI: minn - 22. 5 sa 11. 7 [p=0. 639]).
In addition, a subgroup analysis by age suggested that the benefit of clopidogrel in patients over 75 years was less than that observed in patients ≤ 75 years.
Barra minn hekk, l- analiżi tas- sottogrupp skond l- eta` ssuġġeriet li l- benefiċċju ta ’ clopidogrel għal pazjenti li kellhom iktar minn 75 sena kien inqas minn dak osservat f’ pazjenti ≤75 sena.
Since the CAPRIE trial was not powered to evaluate efficacy of individual subgroups, it is not clear whether the differences in relative risk reduction across qualifying conditions are real, or a result of chance.
Billi l- prova CAPRIE ma kellhiex is- saħħa li tevalwa l- effikaċja ta ’ sottogruppi individwali, mhux ċar jekk id- differenzi fit- tnaqqis relattiv fir- riskju bejn kondizzjonjiet kwalifikanti differenti humiex vera jew kumbinazzjoni.
Acute coronary syndrome
Sindromu koronarju akut
The CURE study included 12,562 patients with non-ST segment elevation acute coronary syndrome (unstable angina or non-Q-wave myocardial infarction), and presenting within 24 hours of onset of the most recent episode of chest pain or symptoms consistent with ischaemia.
L- istudju CURE kien jinkludi 12, 562 pazjent bis- sindromu koronarju akut tas- segment mhux- ST elevat (anġina instabbli jew infart mijokardijaku li mhux- mewġa- Q), u li ddaħħlu fl- istudju f’ 24 siegħa mill- iktar episodju reċenti ta ’ uġigħ fis- sider jew sintomi konsistenti ma ’ l- iskemija.
Patients were required to have either ECG changes compatible with new ischaemia or elevated cardiac enzymes or troponin I or T to at least twice the upper limit of normal.
Biex jiddaħħlu fl - istudju, il- pazjenti riedu jkollhom jew bidliet fl- ECG li kienu kompatibbli ma ’ iskemija ġdida jew enzimi kardijaċi elevati jew troponin I jew T għall- inqas sa darbtejn l- ogħla livell tan- normal.
Patients were randomised to clopidogrel (300 mg loading dose followed by 75 mg/ day, N=6,259) or placebo (N=6,303), both given in combination with ASA (75-325 mg once daily) and other standard therapies.
Il - pazjenti kienu randomised għal clopidogrel (doża qawwija tal- bidu ta ’ 300 mg u wara 75 mg/ jum, N = 6, 259) jew il- plaċebo (N = 6, 303), u t- tnejn ingħataw flimkien ma ’ ASA (75- 325 mg darba kuljum) u terapiji oħra standard.
Patients were treated for up to one year.
Il- pazjenti kienu kkurati sa sena.
In CURE, 823 (6.6%) patients received concomitant GPIIb/ IIIa receptor antagonist therapy.
F’ CURE, 823 pazjent ingħataw terapija ta ’ antagonista għar- riċettur GPIIb/ IIIa fl- istess ħin.
Heparins were administered in more than 90% of the patients and the relative rate of bleeding between clopidogrel and placebo was not significantly affected by the concomitant heparin therapy.
Ngħataw heparins lil iktar minn 90% tal- pazjenti u r -
8 The number of patients experiencing the primary endpoint [cardiovascular (CV) death, myocardial infarction (MI), or stroke] was 582 (9.3%) in the clopidogrel-treated group and 719 (11.4%) in the placebo-treated group, a 20% relative risk reduction (95% CI of 10%-28%; p=0.00009) for the clopidogrel-treated group (17% relative risk reduction when patients were treated conservatively, 29% when they underwent percutaneous transluminal coronary angioplasty (PTCA) with or without stent and 10% when they underwent coronary artery bypass graft (CABG)).
In- numru ta ’ pazjenti li għaddew mill- punt primarju ta ’ tmiem [mewt kardjovaskulari (CV), infart mijokardijaku (MI) jew puplesija] kien 582 (9. 3%) fil- grupp ikkurat bi clopidogrel u 719 (11. 4%) fil - grupp ikkurat bil- plaċebo, li jissarraf fi tnaqqis fir- riskju relattiv ta ’ 20% (95% CI ta ’ 10% - 28%; p=0. 00009) għall- grupp ikkurat bi clopidogrel (tnaqqis fir- riskju relattiv ta ’ 17% f’ pazjenti li kienu kkurati b’ mod konservattiv, 29% meta kellhom anġoplastija koronarja transluminali perkutanja (PTCA) bi stent jew mingħajru u 10% meta kellhom trapjant ta 'bajpass f' arterja koronarja (CABG)).
New cardiovascular events (primary endpoint) were prevented, with relative risk reductions of 22% (CI:
Twaqqfu avvenimenti kardjovaskulari ġodda (punt primarju ta ’ tmien), bi tnaqqis fir- riskju relattiv ta ’ 22% (CI:
8.6, 33.4), 32% (CI:
8. 6, 33. 4), 32% (CI:
12.8, 46.4), 4% (CI: -26.9, 26.7), 6% (CI: -33.5, 34.3) and 14% (CI: -31.6, 44.2), during the 0-1, 1-3, 3-6, 6-9 and 9-12 month study intervals, respectively.
12. 8, 46. 4), 4% (CI: - 26. 9, 26. 7), 6% (CI: - 33. 5, 34. 3) u 14% (CI: - 31. 6, 44. 2), waqt l- intervalli ta ’ studju ta ’ 0- 1, 1- 3, 3- 6, 6- 9 u 9- 12 xhur, rispettivament.
Thus, beyond 3 months of treatment, the benefit observed in the clopidogrel + ASA group was not further increased, whereas the risk of haemorrhage persisted (see section 4.4).
Għalhekk, wara tliet xhur ta ’ kura, il- benefiċċju osservat fil- grupp ta ’ clopidogrel + ASA ma kibirx, fil- waqt li kompla r - riskju ta ’ emorraġija (ara sezzjoni 4. 4).
The use of clopidogrel in CURE was associated with a decrease in the need of thrombolytic therapy (RRR = 43.3%; CI:
L- użu ta ’ clopidogrel fi CURE kien assoċjat mat- tnaqqis fil- bżonn ta ’ kura trombolitika (RRR = 43. 3%; CI:
24.3%, 57.5%) and GPIIb/ IIIa inhibitors (RRR = 18.2%; CI:
24. 3%, 57. 5%) u inibituri ta ’ GPIIb/ IIIa (RRR = 18. 2%; CI:
6.5%, 28.3%).
6. 5%, 28. 3%).
The number of patients experiencing the co-primary endpoint (CV death, MI, stroke or refractory ischaemia) was 1,035 (16.5%) in the clopidogrel-treated group and 1,187 (18.8%) in the placebo- treated group, a 14% relative risk reduction (95% CI of 6%-21%, p=0.0005) for the clopidogrel- treated group.
In- numri ta ’ pazjenti li kellhom punt ko- primarju ta ’ tmiem (mewt b’ CV, MI, puplesija jew iskemija li mhux qed tirrisondi għall- kura) kien 1 035 (16. 5%) fil- grupp ikkurat bi clopidogrel u 1 187 (18. 8%) fil- grupp ikkurat bil- plaċebo, tnaqqis ta ’ 14% fir- riskju relattiv) (95% CI ta ’ 6% - 21%, p= 0. 0005) għall- grupp ikkurat bi clopidogrel.
This benefit was mostly driven by the statistically significant reduction in the incidence of MI [287 (4.6%) in the clopidogrel treated group and 363 (5.8%) in the placebo treated group].
Dan il- benefiċċju ġie l- iktar mit- tnaqqis li kien statistikament sinifikanti ta ’ l- inċidenza ta ’ MI [287 (4. 6%) fil- grupp ikkurat bi clopidogrel u 363 (5. 8%) fil- grupp ikkurat bil- plaċebo].
There was no observed effect on the rate of rehospitalisation for unstable angina.
Ma ġiex osservat effett fuq ir- rata ta ’ kemm il- pazjenti kellhom jerġgħu jiddaħħlu l- isptar għall- anġina instabbli.
The results obtained in populations with different characteristics (e. g. unstable angina or non-Q-wave MI, low to high risk levels, diabetes, need for revascularisation, age, gender, etc.) were consistent with the results of the primary analysis.
Ir- riżultati f’ popolazzjonijiet b’ karatteristiċi differenti (eż. anġina instabbli jew MI ta ’ mewġa mhux Q, minn livelli baxxa sa għolja ta ’ riskju, dijabete, il- bżonn ta ’ revaskularizzazzjoni, eta`, sess eċċ.) kienu konsistenti mar- riżultati ta ’ l- analiżi primarja.
In particular, in a post-hoc analysis in 2,172 patients (17% of the total CURE population) who underwent stent placement (Stent-CURE), the data showed that clopidogrel compared to placebo, demonstrated a significant RRR of 26.2% favouring clopidogrel for the co-primary endpoint (CV death, MI, stroke) and also a significant RRR of 23.9% for the second co-primary endpoint (CV death, MI, stroke or refractory ischaemia).
Partikularment, f’ analiżi post- hoc f ’ 2172 pazjent (17% tal- popolazzjoni kollha CURE) li kellhom stent impoġġija (Stent- CURE), id- data wriet li clopidogrel, imqabbel ma plaċebo, wera RRR sinifikanti ta ’ 26. 2% favur clopidogrel għal punt ko- primarju ta ’ tmiem (mewt b ’ CV, MI, puplesija) u wkoll RRR sinifikanti ta ’ 23. 9% għat- tieni punt ko- primarju ta ’ tmiem (mewt b ’ CV, MI, puplesija jew iskemija li mhux qed tirrispondi ghall- kura).
Moreover, the safety profile of clopidogrel in this subgroup of patients did not raise any particular concern.
Barra dan, il - profil tas- sigurtà ta ’ clopidogrel f’ dan is- sottogrup ta ’ pazjenti ma qajjemx tħassib partikulari.
Thus, the results from this subset are in line with the overall trial results.
Għalhekk, ir- riżultati minn din il- parti sekondarja tas- sett jixbħu lil- risultati totali ta ’ l- istudju.
The benefits observed with clopidogrel were independent of other acute and long-term cardiovascular therapies (such as heparin/ LMWH, GPIIb/ IIIa antagonists, lipid lowering medicinal products, beta blockers, and ACE-inhibitors).
Il- benefiċċji osservati bi clopidogrel kienu indipendenti minn terapiji kardjovaskulari oħra akuti u fit - tul (bħall - heparin/ LMWH, antagonisti ta ’ GPIIb/ IIIa, prodotti mediċinali li jbaxxu l- lipidi, imblokkaturi tar- riċetturi beta, u inibituri ta ’ ACE).
The efficacy of clopidogrel was observed independently of the dose of ASA (75-325 mg once daily).
L- effikaċja ta ’ clopidogrel kienet osservata b’ mod indipendenti mid- doża ta ’ ASA (75- 325 mg darba kuljum).
In patients with acute ST-segment elevation MI, safety and efficacy of clopidogrel have been evaluated in 2 randomised, placebo-controlled, double-blind studies, CLARITY and COMMIT.
F’ pazjenti b’ MI akut bl- ST segment elevat, is- sigurtà u l- effikaċja ta ’ clopidogrel kienu evalwati f’ 2 studji randomised, ikkontrollati bil- plaċebo, u double- blind, CLARITY u COMMIT.
The CLARITY trial included 3,491 patients presenting within 12 hours of the onset of a ST elevation MI and planned for thrombolytic therapy.
Il- prova CLARITY inkludiet 3, 491 pazjenti li daħlu fi żmien 12- il siegħa mill- bidu ta ’ infart mijokardijaku b’ ST elevat, fejn kien ippjanat li tingħata t- terapija trombolitika.
Patients received clopidogrel (300 mg loading dose, followed by 75 mg/ day, n=1,752) or placebo (n=1,739), both in combination with ASA (150 to 325 mg as a loading dose, followed by 75 to 162 mg/ day), a fibrinolytic agent and, when appropriate, heparin.
Il- pazjenti rċevew clopidogrel (300 mg bħala d- doża qawwija inizjali segwita minn 75 mg / kuljum, n=1752) jew il - plaċebo (n=1739), it- tnejn ma ’ ASA (150 sa 325 mg bħala doża qawwija inizjali segwita minn 75 sa 162 mg/ kuljum), sustanza fibrinolitika u, fejn kien xieraq, heparin.
The patients were followed for 30 days.
Il- pazjenti kienu eżaminati għal 30 jum.
The primary endpoint was the occurrence of the composite of an occluded infarct-related artery on the predischarge angiogram, or death or recurrent MI before coronary angiography.
Il- punt primarju u aħħari kien il- ġrajja ta’ arterja miżduda relatata ma ’ infart fl- anġjogram qabel ma l- pazjent kien liċenzjat biex joħrog mill- isptar, jew il- mewt jew MI rikurrenti qabel ma saret l - anġjografija tal- koronarji.
For patients who did not undergo angiography, the primary endpoint was death or recurrent myocardial infarction by Day 8 or by hospital discharge.
Għal dawk il- pazjenti li ma saritilhomx l- anġjografija, l- punt primarju u aħħari kien il- mewt jew infart mijokardijaku rikurrenti mat- 8 jum jew meta l- pazjent kien liċenzjat li joħrog mill- isptar.
The patient population included 19.7% women and 29.2% patients ≥ 65 years.
Il- grupp ta ’ pazjenti studjati kien jinkludi 19. 7% nisa u 29. 2% pazjenti ≥65 sena.
A total of 99.7% of patients received fibrinolytics (fibrin specific:
It - total ta ’ 99. 7% tal- pazjenti rċevew is- sustanzi fibrinolitiċi (speċifiċi ghall- fibrin:
68.7%, non-fibrin specific:
68. 7%, mhux speċifiċi għall- fibrin:
31.1%), 89.5% heparin, 78.7% beta blockers, 54.7% ACE inhibitors and 63% statins.
31. 1%), 89. 5% heparin, 78. 7% imblokkaturi tar- riċetturi beta, 54. 7% inibituri ta ’ ACE u 63% statins.
Fifteen percent (15.0%) of patients in the clopidogrel group and 21.7% in the placebo group reached the primary endpoint, representing an absolute reduction of 6.7% and a 36% odds reduction in favor of clopidogrel (95% CI:
9 Ħmistax fil- mija (15. 0%) tal- pazjenti fil- grupp tal- clopidogrel u 21. 7% tal- grupp bil- plaċebo laħqu l - punt primarju u aħħari, li jirrappreżentaw tnaqqis assolut ta ’ 6. 7% u 36% ta ’ tnaqqis probabbli favur clopidogrel (95% CI:
24, 47%; p < 0.001), mainly related to a reduction in occluded infarct-related arteries.
24, 47%; p < 0. 001), relatat prinċipalment għal tnaqqis fis- sadd ta ’ l- arterji assoċjati ma ’ infart.
This benefit was consistent across all prespecified subgroups including patients’ age and gender, infarct location, and type of fibrinolytic or heparin used.
Dan il- benefiċċju kien konsistenti fis- sottogruppi speċifikati minn qabel li jinkludu l- età tal- pazjent, is- sess maskil jew dak femminil, il- post fejn qiegħed l- infart u t- tip ta ’ sustanza fibrinolitika jew heparin użat.
ST elevation, ST depression or left bundle-branch block).
L- għamla ta ’ 2x2 factorial tal- prova COMMIT inkludiet 45, 852 pazjent li daħlu fi żmien 24 siegħa mill- ħin li bdew is- sintomi suspettużi ta ’ MI b’ abnormalitajiet fl- ECG suġġestivi t’ hekk (iġifieri ST elevat, ST imniżżel jew bundle branch block tax- xellug).
Patients received clopidogrel (75 mg/ day, n=22,961) or placebo (n=22,891), in combination with ASA (162 mg/ day), for 28 days or until hospital discharge.
Il- pazjenti ngħataw clopidogrel (75 mg/ kuljum, n=22, 961) jew il- plaċebo (n=22, 891), flimkien ma ’ ASA (162 mg/ kuljum), għal 28 jum jew sakemm ġew illiċenzjati mill- isptar.
The co-primary endpoints were death from any cause and the first occurrence of re-infarction, stroke or death.
Iż- zewġ punti primarji ta ’ l- aħħar kienu l- mewt minn kwalunkwe kawża u l- ewwel darba li jiġri infart ieħor, il- puplesija jew il- mewt.
The population included 27.8% women, 58.4% patients ≥ 60 years (26% ≥ 70 years) and 54.5% patients who received fibrinolytics.
Il- grupp studjat inkluda 27. 8% nisa, 58. 4% pazjenti ≥60 sena (26% ≥70 sena) u 54. 5% tal- pazjenti li rċevew is - sustanzi fibrinolitiċi.
Clopidogrel significantly reduced the relative risk of death from any cause by 7% (p = 0.029), and the relative risk of the combination of re-infarction, stroke or death by 9% (p = 0.002), representing an absolute reduction of 0.5% and 0.9%, respectively.
Clopidogrel naqqas b’ mod sinifikanti r- riskju relattiv tal- mewt minn kwalunkwe kawża b’ 7% (p=0. 029), u r- riskju relattiv ta ’ infart ġdid, puplesija jew il- mewt b’ 9% (p=0. 002), li jirrappreżentaw tnaqqis assolut ta ’ 0. 5% u 0. 9%, rispettivament.
This benefit was consistent across age, gender and with or without fibrinolytics, and was observed as early as 24 hours.
Dan il- benefiċċju kien konsistenti meta wieħed iqies l - eta, is- sess maskil few femminil, il- kura bis- sustanzi fibrinolitiċi jew mingħajrha, u kien innotat kmieni sa minn 24 siegħa.
After repeated oral doses of 75 mg per day, clopidogrel is rapidly absorbed.
Wara dożi orali ripetuti ta ’ 75 mg kuljum, clopidogrel kien assorbit b’ rata mgħaġġla.
However, plasma concentrations of the parent compound are very low and below the quantification limit (0.00025 mg/ l) beyond 2 hours.
Madankollu, il - konċentrazzjonijiet fil- plażma tas- sustanza oriġinali huma baxxi ħafna u taħt il- limitu kwalifikanti (0. 00025 mg/ l) wara sagħtejn.
Absorption is at least 50%, based on urinary excretion of clopidogrel metabolites.
L- assorbiment huwa mill- inqas ta ’ 50%, skond l- eskrezzjoni fl- urina ta ’ metaboliti ta ’ clopidogrel.
Clopidogrel is extensively metabolised by the liver and the main metabolite, which is inactive, is the carboxylic acid derivative, which represents about 85% of the circulating compound in plasma.
Clopidogrel huwa metabolizzat b’ mod estensiv fil- fwied u l- metabolit prinċipali, li mhux attiv, huwa d- derivattiv ta ’ carboxylic acid, li jirrappreżenta madwar 85% tal- kompost li qed jiċċirkola fil- plażma.
3mg/ l after repeated 75 mg oral doses) occurred approximately 1 hour after dosing.
Il- livelli massimi fil- plażma ta ’ dan il- metabolit (bejn wieħed u ieħor 3 mg/ l wara dożi ripetuti ta ’ 75 mg mill- ħalq) seħħew bejn wieħed u ieħor siegħa wara d- dożaġġ.
Clopidogrel is a prodrug.
Clopidogrel huwa pro- mediċina.
The active metabolite, a thiol derivative, is formed by oxidation of clopidogrel to 2-oxo-clopidogrel and subsequent hydrolysis.
Il- metabolit attiv, derivattiv ta ’ thiol, huwa ffurmat bl- ossidazzjoni ta ’ clopidogrel għal 2- oxo- clopidogrel u l- idroliżi ta ’ wara.
The oxidative step is regulated primarily by Cytochrome P450 isoenzymes 2B6 and 3A4 and to a lesser extent by 1A1, 1A2 and 2C19.
Il- pass ta ’ ossidazzjoni huwa rregolat primarjament minn Cytochrome P450 isoenżimi 2B6 u 3A4 u b’ mod inqas minn 1A1, 1A2 u 2C19.
The active thiol metabolite, which has been isolated in vitro, binds rapidly and irreversibly to platelet receptors, thus inhibiting platelet aggregation.
Il - metabolit attiv ta ’ thiol, li ġie iżolat in vitro, jintrabat malajr u b’ mod irreversibbli mar- riċetturi tal - plejtlets, u hekk l- agreggazzjoni tal- plejtlets tiġi inibita.
This metabolite has not been detected in plasma.
Dan il- metabolit ma nstabx fil- plażma.
The kinetics of the main circulating metabolite were linear (plasma concentrations increased in proportion to dose) in the dose range of 50 to 150 mg of clopidogrel.
Il- karatteristiċi kinetiċi tal- metabolit ċirkolanti prinċipali kienu lineari (il- konċentrazzjonijiet fil - plażma żdiedu b’ mod proporzjonali mad- doża) fil- medda tad- doża ta ’ bejn 50 u 150 mg ta ’ clopidogrel.
Clopidogrel and the main circulating metabolite bind reversibly in vitro to human plasma proteins (98% and 94% respectively).
Clopidogrel u l- metabolit prinċipali ċirkolanti jintrabtu b’ mod reversibbli in vitro mal- proteini umani tal- plażma (98% u 94% rispettivament).
The binding is non-saturable in vitro over a wide concentration range.
L- irbit mhux saturabbli in vitro f’ medda wiesgħa ta ’ konċentrazzjoni.
Following an oral dose of 14C-labelled clopidogrel in man, approximately 50% was excreted in the urine and approximately 46% in the faeces in the 120-hour interval after dosing.
Wara doża orali ta ’ clopidogrel 14C- tikkettat fil- bniedem, bejn wieħed u ieħor 50% kien mneħħi fl - urina u bejn wieħed u ieħor 46% ħareġ fl- ippurgar fl- intervall ta ’ 120 siegħa wara d- dożaġġ.
The elimination half- life of the main circulating metabolite was 8 hours after single and repeated administration.
Il- half - life tat- tneħħija tal- metabolit prinċipali ċirkolanti kien 8 sigħat wara amministrazzjoni waħda u ripetuta.
After repeated doses of 75 mg clopidogrel per day, plasma levels of the main circulating metabolite were lower in subjects with severe renal disease (creatinine clearance from 5 to 15 ml/ min) compared to subjects with moderate renal disease (creatinine clearance from 30 to 60 ml/ min) and to levels observed in other studies with healthy subjects.
Wara dożi ripetuti ta ’ 75 mg ta ’ clopidogrel kuljum, il- livelli fil- plażma tal- metabolit prinċipali ċirkolanti kienu iktar baxxi f’ persuni b’ mard sever tal- kliewi (tneħħija tal- kreatinina minn 5 sa 15 ml/ min) meta mqabbla ma ’ persuni b’ mard moderat tal- kliewi (tneħħija tal- kreatitina minn 30 sa
Although inhibition of ADP-induced platelet aggregation was lower (25%) than that observed in healthy subjects, the prolongation of bleeding was similar to that seen in healthy subjects receiving 75 mg of clopidogrel per day.
Għalkemm l- inibizzjoni ta ’ l - agreggrazzjoni tal- plejtlets indotti minn ADP kien iktar baxx (25%) minn dak osservat f’ persuni f’ saħħithom, it- titwil tad- dmija kien simili għal dak osservat f’ persuni f’ saħħithom li kienu qed jingħataw 75 mg ta ’ clopidogrel kuljum.
In addition, clinical tolerance was good in all patients.
Barra minn hekk, it- tolleranza klinika kienet tajba fil- pazjenti kollha.
The pharmacokinetics and pharmacodynamics of clopidogrel were assessed in a single and multiple dose study in both healthy subjects and those with cirrhosis (Child-Pugh class A or B).
Il- karatteristiċi farmakokinetiċi u farmakodinamiċi ta ’ clopidogrel tqiesu fi studju dwar dożi singoli u multipli kemm f’ persuni f’ saħħithom u f’ dak li kellhom ċirrożi (Child- Pugh klassi A jew B).
Daily dosing for 10 days with clopidogrel 75 mg/ day was safe and well tolerated.
Kienet aċċertata s- sigurta` tad- dożaġġ ta ’ kuljum għal 10 ijiem bi clopidogrel 75 mg/ jum, u kienet ittollerata sew.
Clopidogrel Cmax for both single dose and steady state for cirrhotics was many fold higher than in normal subjects.
Clopidogrel Cmax kemm għal doża waħda u għal stat fiss għaċ- ċirrotiċi kien ogħla għal kemm- il darba milli f’ persuni normali.
However, plasma levels of the main circulating metabolite together with the effect of clopidogrel on ADP-induced platelet aggregation and bleeding time were comparable between these groups.
Madankollu, il- livelli fil- plażma tal- metabolit ċirkolanti prinċipali flimkien ma ’ l- effett ta ’ clopidogrel fuq l- agreggazzjoni tal- plejtlets indotti minn ADP u l- ħin tad - dmija setgħu komparabbli bejn dawn il- gruppi.
10 5.3 Preclinical safety data
5. 3 Tagħrif ta 'qabel l- użu kliniku dwar is- sigurtà tal- mediċina
During non clinical studies in rat and baboon, the most frequently observed effects were liver changes.
Waqt studji mhux kliniċi fil- firien u l- babwini, l- iktar effetti li kienu osservati b’ mod frekwenti kienu bidliet fil- fwied.
These occurred at doses representing at least 25 times the exposure seen in humans receiving the clinical dose of 75 mg/ day and were a consequence of an effect on hepatic metabolising enzymes.
Dawn seħħew f’ dożi li jirrappreżentaw mill- inqas 25 darba l- espożizzjoni li ġiet osservata fil- bnedmin li ngħataw doża klinika ta ’ 75 mg/ jum u kienu bħala konsegwenza ta ’ effett fuq l- enzimi metabolizzanti fil- fwied.
No effect on hepatic metabolising enzymes was observed in humans receiving clopidogrel at the therapeutic dose.
Ma ġiex osservat effett fuq l- enzimi metabolizzanti tal- fwied fi bnedmin li kienu qed jingħataw clopidogrel b’ doża terapewtika.
At very high doses, a poor gastric tolerability (gastritis, gastric erosions and/ or vomiting) of clopidogrel was also reported in rat and baboon.
F’ dożi għolja ħafna, ġiet irrapurtata tollerabilita` baxxa fiż- żaqq (gastrite, erożjonijiet gastriċi u/ jew rimettar) ta ’ clopidogrel fil- firien u l- babwini.
There was no evidence of carcinogenic effect when clopidogrel was administered for 78 weeks to mice and 104 weeks to rats when given at doses up to 77 mg/ kg per day (representing at least 25 times the exposure seen in humans receiving the clinical dose of 75 mg/ day).
Ma kienx hemm evidenza ta ’ riskju ta ’ kanċer meta clopidogrel ingħata għal 78 ġimgħa lill- ġrieden u 104 ġimgħa lill- firien meta dawn ingħataw dożi sa 77 mg/ kg kuljum (li jirrappreżenta espożizzjoni mill- inqas 25 darba dik osservata fil- bnedmin li kienu qed jingħataw doża klinika ta ’ 75 mg/ jum).
Clopidogrel has been tested in a range of in vitro and in vivo genotoxicity studies, and showed no genotoxic activity.
Clopidogrel ġie ttestajt f’ medda ta ’ studji in vitro u in vivo dwar l- effett tossiku fuq il- ġeni, u ma tax indikazzjoni ta ’ attivita` tossika fuq il- ġeni.
Clopidogrel was found to have no effect on the fertility of male and female rats and was not teratogenic in either rats or rabbits.
Clopidogrel ma ntwera li kellu l- ebda effett fuq il- fertilita` tal- firien irġiel u nisa u ma kellux effett tossiku fuq is- sistema riproduttiva la fil- firien u lanqas fil- fniek.
When given to lactating rats, clopidogrel caused a slight delay in the development of the offspring.
Meta clopidogrel ngħata lill- firien li kienu qed ireddgħu, dan ikkawża dewmien żgħir fl- iżvilupp tat- trabi.
Specific pharmacokinetic studies performed with radiolabelled clopidogrel have shown that the parent compound or its metabolites are excreted in the milk.
Saru studji farmakokinetiċi speċifiċi bi clopidogrel radjutikkettat li wrew li s- sustanza oriġinali jew il- metaboliti tagħha joħorġu fil- ħalib.
Consequently, a direct effect (slight toxicity), or an indirect effect (low palatability) cannot be excluded.
Għalhekk, ma jistgħux jiġu esklużi effett dirett (ftit tossiċita`), jew effett indirett (ma jintiegħemx tajjeb).
Core:
Qalba:
Mannitol (E421) Macrogol 6000 Microcrystalline cellulose Hydrogenated castor oil Low substituted hydroxypropylcellulose
Mannitol (E421) Macrogol 6000 Microcrystalline cellulose Hydrogenated castor oil Low- substituted hydroxypropylcellulose
Coating:
Rita:
Hypromellose (E464) Lactose Triacetin (E1518) Titanium dioxide (E171) Red iron oxide (E172) Carnauba wax
Hypromellose (E464) Lactose Triacetin (E1518) Titanium dioxide (E171) iron oxide aħmar (E172)
6.2 Incompatibilities
11 Carnauba wax
Not applicable
6. 2 Inkompatibilitajiet
6.3 Shelf-life
Ma jgħoddx f’ dan il- każ.
In PVC/ PVDC/ aluminium blisters, store below 30°C.
Fil- folji tal- PVC/ PVDC/ Aluminju, aħżen f’ temperatura taħt 30°C.
In all aluminium blisters, this medicinal product does not require any special storage conditions.
Fil- folji kollha kemm huma ta ’ l- aluminju, din il- mediċina m’ għandhiex bżonn ħażna speċjali.
11 6.5 Nature and content of container
6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
PVC/ PVDC/ Aluminium blisters or all aluminium blisters in cardboard cartons containing 7, 14, 28, 30, 84, 90 and 100 film-coated tablets.
Folji tal- PVC/ PVDC/ Aluminju jew folji kollha kemm huma ta ’ l- aluminju f’ kaxxi tal- kartun li fihom 7, 14, 28, 30, 84, 90 u 100 pillola miksija b’ rita.
PVC/ PVDC/ Aluminium or all aluminium perforated unit-dose blister packs in cardboard cartons containing 50x1 film-coated tablets.
Pakketti ta ’ folji mtaqqbin ta ’ doża waħda tal- PVC/ PVDC/ Aluminju jew kollha kemm huma ta ’ l - aluminju f’ kaxxi tal- kartun li fihom 50x1 pilloli miksijin b’ rita.
Bristol Myers Squibb Pharma EEIG Uxbridge Business Park Sanderson Road Uxbridge UB8 1DH United Kingdom
Bristol Myers Squibb Pharma EEIG Uxbridge Business Park Sanderson Road Uxbridge UB8 1DH Ir- Renju Unit
MARKETING AUTHORISATION NUMBERS
NUMRU( I) TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ
EU/ 1/ 08/ 464/ 001 - Cartons of 14 film-coated tablets in PVC/ PVDC/ Alu blisters EU/ 1/ 08/ 464/ 002 - Cartons of 14 film-coated tablets in all aluminium blisters EU/ 1/ 08/ 464/ 003 - Cartons of 28 film-coated tablets in PVC/ PVDC/ Alu blisters EU/ 1/ 08/ 464/ 004 - Cartons of 28 film-coated tablets in all aluminium blisters EU/ 1/ 08/ 464/ 005 - Cartons of 30 film-coated tablets in PVC/ PVDC/ Alu blisters EU/ 1/ 08/ 464/ 006 - Cartons of 30 film-coated tablets in all aluminium blisters EU/ 1/ 08/ 464/ 007 - Cartons of 50x1 film-coated tablets in PVC/ PVDC/ Alu blisters EU/ 1/ 08/ 464/ 008 - Cartons of 50x1 film-coated tablets in all aluminium blisters EU/ 1/ 08/ 464/ 009 - Cartons of 84 film-coated tablets in PVC/ PVDC/ Alu blisters EU/ 1/ 08/ 464/ 010 - Cartons of 84 film-coated tablets in all aluminium blisters EU/ 1/ 08/ 464/ 011 - Cartons of 90 film-coated tablets in PVC/ PVDC/ Alu blisters EU/ 1/ 08/ 464/ 012 - Cartons of 90 film-coated tablets in all aluminium blisters EU/ 1/ 08/ 464/ 013 - Cartons of 100 film-coated tablets in PVC/ PVDC/ Alu blisters EU/ 1/ 08/ 464/ 014 - Cartons of 100 film-coated tablets in all aluminium blisters EU/ 1/ 08/ 464/ 018 - Cartons of 7 film-coated tablets in PVC/ PVDC/ Alu blisters EU/ 1/ 08/ 464/ 019 - Cartons of 7 film-coated tablets in all aluminium blisters
EU/ 1/ 08/ 464/ 001 - Kaxex ta ’ 14- il pillola miksija b’ rita fil- folji tal- PVC/ PVDC/ Alu EU/ 1/ 08/ 464/ 002 - Kaxex ta ’ 14- il pillola miksija b’ rita fil- folji kollha kemm huma ta ’ l- aluminjum EU/ 1/ 08/ 464/ 003 - Kaxex ta ’ 28 pillola miksija b’ rita fil- folji tal- PVC/ PVDC/ Alu EU/ 1/ 08/ 464/ 004 - Kaxex ta ’ 28 pillola miksija b’ rita fil- folji kollha kemm huma ta ’ l- aluminjum EU/ 1/ 08/ 464/ 005 - Kaxex ta ’ 30 pillola miksija b’ rita fil- folji tal- PVC/ PVDC/ Alu EU/ 1/ 08/ 464/ 006 - Kaxex ta ’ 30 pillola miksija b’ rita fil- folji kollha kemm huma ta ’ l- aluminjum EU/ 1/ 08/ 464/ 007 - Kaxex ta ’ 50x1 pillola miksija b’ rita fil- folji tal- PVC/ PVDC/ Alu EU/ 1/ 08/ 464/ 008 - Kaxex ta ’ 50x1 pillola miksija b’ rita fil- folji kollha kemm huma ta ’ l- aluminjum EU/ 1/ 08/ 464/ 009 - Kaxex ta ’ 84 pillola miksija b’ rita fil- folji tal- PVC/ PVDC/ Alu EU/ 1/ 08/ 464/ 010X/ X/ X/ XXX - Kaxex ta ’ 84 pillola miksija b’ rita fil- folji kollha kemm huma ta ’ l - aluminjum EU/ 1/ 08/ 464/ 011 - Kaxex ta ’ 90 pillola miksija b’ rita fil- folji tal- PVC/ PVDC/ Alu EU/ 1/ 08/ 464/ 012 - Kaxex ta ’ 90 pillola miksija b’ rita fil- folji kollha kemm huma ta ’ l- aluminjum EU/ 1/ 08/ 464/ 013 - Kaxex ta ’ 100 pillola miksija b’ rita fil- folji tal- PVC/ PVDC/ Alu
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 tinstab fuq il- website ta ’ l- Agenzija Ewropea dwar il - Mediċini (EMEA): http: // www. emea. europa. eu /
Clopidogrel BMS 300 mg film-coated tablets
Clopidogrel BMS 300 mg pilloli miksija b’ rita