qanastek/EMEA-V3 huggingface dataset:
Neuroleptic malignant syndrome Neuroleptic Malignant Syndrome (NMS), characterised by hyperthermia, muscle rigidity, autonomic instability, altered consciousness, and elevated serum creatine phosphokinase levels has been reported to occur with antipsychotics, including paliperidone.
Sindromu malinn newrolettiku Is- Sindromu malinn newrolettiku (NMS), li hu karatterizzat minn ipertermja, twebbis tal- muskoli, instabilità awtonomika, perċezzjoni mibdula, u livelli elevati ta ’ serum creatine phosphokinase, ġew irrapurtati li jseħħu bl- antipsikotiċi, inkluż paliperidone.
Additional clinical signs may include myoglobinuria (rhabdomyolysis) and acute renal failure.
Sinjali oħra kliniċi jistgħu ikunu majoglobinurja (rabdomajoliżi) u insuffiċjenza renali akuta.
If a patient develops signs or symptoms indicative of NMS, all antipsychotics, including INVEGA, should be discontinued.
Jekk il- pazjent jiżviluppa sinjali jew sintomi li jindikaw NMS, l- antipsikotiċi kollha, inkluż INVEGA, għandhom jitwaqqfu.
Tardive dyskinesia Medicines with dopamine receptor antagonistic properties have been associated with the induction of tardive dyskinesia characterised by rhythmical, involuntary movements, predominantly of the tongue and/ or face.
Diskajneżja Tardiva Mediċini bi propjetajiet antagonistiċi għal riċetturi tad- dopamina ġew assoċjati ma ’ l- induzzjoni ta ’ diskajneżja tardiva karatterizzata minn ċaqlieq ritmiku involontarju, l- iktar ta ’ l- ilsien u/ jew tal- wiċċ.
Hyperglycemia Rare cases of glucose related adverse reactions, e. g., increase in blood glucose, have been reported in clinical trials with INVEGA.
17 Fi provi kliniċi ta ’ INVEGA ġew irrapurtati każijiet rari avversi marbuta mal- glucose, e. ż., żieda fil - glucose tad- demm.
As with other antipsychotics, appropriate clinical monitoring is advisable in diabetic patients and in patients with risk factors for the development of diabetes mellitus.
Bħal fil- każ ta ’ antipsikotiċi oħrajn, jaqbel li jkun hemm monitoraġġ kliniku xieraq f’ pazjenti dijabetiċi u f’ pazjenti b’ riskju li jiżviluppaw dijabete mellitus.
Orthostatic hypotension Paliperidone may induce orthostatic hypotension in some patients based on its alpha-blocking activity.
Ipotensjoni ortostatika F’ xi pazjenti Paliperidone jista ’ jinduċi ipotensjoni ortostatika minħabba l- attività tagħha ta ’ mbokkar ta ’ l- alfa.
16 Based on pooled data from the three, placebo-controlled, 6-week, fixed-dose trials with INVEGA (3, 6, 9, and 12 mg), orthostatic hypotension was reported by 2.5% of subjects treated with INVEGA compared with 0.8% of subjects treated with placebo.
Skond t- tagħrif meqjus flimkien minn tliet provi bi INVEGA ta ’ sitt ġimgħat b’ doża fissa (3, 6, 9, U 12- il mg) u bl- użu ta ’ plaċebo ma ’ grupp ta ’ kontroll, l- ipotensjoni ortostatika ġiet irrapurtata fi 2. 5% tal- pazjenti kkurati bi INVEGA meta mqabbla ma ’ 0. 8% ta ’ suġġetti kkurati bil- plaċebo.
INVEGA should be used with caution in patients with known cardiovascular disease (e. g., heart failure, myocardial infarction or ischaemia, conduction abnormalities), cerebrovascular disease, or conditions that predispose the patient to hypotension (e. g., dehydration and hypovolemia).
INVEGA għandu jintuża b’ kawtela f’ pazjenti li għandhom mard kardjovaskolari (e. ż., insuffiċjenza tal- qalb, infart mijokardijaku jew iskemija, anormalitajiet fil- konduzzjoni), mard ċerebrovaskulari, jew kondizzjonijiet li jippredisponu lill- pazjent għall- ipotensjoni (e. ż., id- deidrazzjoni u l- ipovolemija).
Seizures INVEGA should be used cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold.
Aċċessjonijiet INVEGA għandu jintuża b’ mod kawt ma ’ pazjenti bi storja ta ’ aċċessjonijiet jew kondizzjonijiet oħra li għandhom il- potenzjal li jkabbru l- possibiltà ta ’ aċċessjoni.
Potential for gastrointestinal obstruction Because the INVEGA tablet is non-deformable and does not appreciably change shape in the gastrointestinal tract, INVEGA should not ordinarily be administered to patients with preexisting severe gastrointestinal narrowing (pathologic or iatrogenic) or in patients with dysphagia or significant difficulty in swallowing tablets.
Potenzjal għal ostruzzjoni gastrointestinali Billi l- pillola INVEGA ma tistax tiġi deformata u ma tbiddilx l- għamla tagħha b’ mod sinifikanti fl- apparat gastrointestinali, INVEGA normalment m’ għandux jiġi amministrat lill - pazjenti li diġà għandhom djuq gastrointestinali sever (patoloġiku jew jatroġeniku) jew f’ pazjenti b’ disfaġja jew diffikultà sinifikanti biex jibilgħu l- pilloli.
There have been rare reports of obstructive symptoms in patients with known strictures in association with the ingestion of medicines in non-deformable controlled-release formulations.
Kien hemm rapporti rari ta ’ sintomi ta ’ ostruzzjoni f’ pazjenti li kellhom problemi magħrufa biex jibilgħu l- mediċina fil- formulazzjonijiet non - deformabbli u li jerħu l- mediċina bil- mod.
Due to the controlled-release design of the dosage form, INVEGA should only be used in patients who are able to swallow the tablet whole.
Minħabba d- disinn tal- forma tad- dożaġġ li jerħi l- mediċina bil- mod, INVEGA għandu jintuża biss f’ pazjenti li jistgħu jibilgħu il- pillola sħiħa.
Conditions with decreased gastro-intestinal transit time Conditions leading to shorter gastrointestinal transit time, e. g., diseases associated with chronic severe diarrhoea, may result in a reduced absorption of paliperidone.
Kondizzjonijiet li jqassru ż- żmien ta ’ traġitt mill- apparat gastro- intestinali Kondizzjonijiet li jwasslu għal żmien iqsar tat- traġitt mill- apparat gastro- intestinali, e. ż., mard assoċjat ma ’ dijarea qawwija kronika, jista ’ jirriżulta f’ inqas assorbiment ta ’ paliperidone.
Renal impairment The plasma concentrations of paliperidone are increased in patients with renal impairment and, therefore, dosage adjustment may be required in some patients (see section 4.2 and 5.2).
Indeboliment renali IL- konċentrazzjonijiet ta ’ paliperidone fil- plażma jiżdiedu f’ pazjenti b’ insuffiċjenza renali u, għalhekk, jista ’ jkun hemm bżonn li tinbidel id- doża ta ’ xi pazjenti (ara sezzjoni 4. 2 u 5. 2).
Hepatic impairment No data are available in patients with severe hepatic impairment (Child-Pugh class C).
Indeboliment epatika M’ hemmx tagħrif dwar pazjenti b’ indeboliment epatiku qawwi (Child- Pugh class C).
Caution is recommended if paliperidone is used in such patients.
Hija rakkomandata l- kawtela fl- użu ta ’ paliperidone ma ’ pazjenti bħal dawn.
Overall mortality In a meta-analysis of 17 controlled clinical trials, elderly patients with dementia treated with other atypical antipsychotics, including risperidone, aripiprazole, olanzapine, and quetiapine had an increased risk of mortality compared to placebo.
Moralità ġenerali F’ meta- analiżi ta ’ 17- il prova klinika kkontrollata, pazjenti anzjani bid- dimenzja kkurati b’ antipsikotiċi atipiċi oħrajn, inkluż risperidone, aripiprazole, olanzapine, u quetiapine kellhom riskju ogħla ta ’ mortalità meta mqabbla ma ’ dawk li ħadu plaċebo.
Among those treated with risperidone, the mortality was 4% compared with 3.1% for placebo.
Fost dawk ikkurati b’ risperidone, il- mortalità hija 4% meta mqabbel ma ’ 3. 1% bil- plaċebo.
Cerebrovascular adverse reactions An approximately 3-fold increased risk of cerebrovascular adverse reactions have been seen in randomised placebo-controlled clinical trials in the dementia population with some atypical antipsychotics, including risperidone, aripiprazole, and olanzapine.
Reazzjonijiet ċerebrovaskulari avversi Fi provi kliniċi randomised li kienu jinkludu gruppi ta ’ kontroll bil- plaċebo, instab li kien hemm bejn wieħed u ieħor 3 darbiet iktar riskju ta ’ reazzjonijiet ċerebrovaskulari avversi fil - popolazzjoni bid- dimenzja b’ xi antipsikotiċi atipiċi, inkluż risperidone, aripiprazole, u olanzapine.
The mechanism for this increased risk is not known.
Il- mekkaniżmu tat- tkattir tar- riskju mhux magħruf.
INVEGA should be used with caution in elderly patients with dementia who have risk factors for stroke.
INVEGA għandu jintuża b’ kawtela f’ pazjenti anzjani b’ dimenzja b’ riskju ta ’ aċċessjoni
Parkinson’ s disease and dementia with Lewy bodies Physicians should weigh the risks versus the benefits when prescribing antipsychotic medicinal products, including INVEGA, to patients with Parkinson’ s Disease or Dementia with Lewy Bodies (DLB) since both groups may be at increased risk of Neuroleptic Malignant Syndrome as well as having an increased
18 Mard tal- Parkinson u dimenzja b’ Lewy bodies t- tobba għandhom iqisu r- riskji u l- benefiċċji meta jagħtu prodotti mediċinali antipsikotiċi, inkluż INVEGA, lil pazjenti bil- mard tal- Parkinson jew Dimenzja b’ Lewy Bodies (DLB) billi dawn iż- żewġ gruppi jista ’ jkollhom riskju ogħla tas- Sindromu Malinn Newrolettiku, kif ukoll sensittività ogħla għall- antipsikotiċi.
Manifestation of this increased sensitivity can include confusion, obtundation, postural instability with frequent falls, in addition to extrapyramidal symptoms.
Is- sensittività ogħla tintwera permezz ta ’ konfużjoni, tmewwit, instabilità li twassal għal waqgħat frekwenti, flimkien ma ’ sintomi extrapiramidali.
Priapism Medicines with alpha-adrenergic blocking effects have been reported to induce priapism.
Prijapiżmu Mediċini b’ effetti ta ’ mblukkar alfa- adrenerġiċi ġew irrapurati li jinduċu l- prijapiżmu.
Although no cases of priapism have been reported in clinical trials with INVEGA, paliperidone shares this pharmacologic activity and, therefore, may be associated with this risk.
Għalkemm ma ġewx irrapurtati każijiet ta ’ prijapiżmu fi provi kliniċi bi INVEGA, paliperidone għandu wkoll din l - attività farmakoloġika u, għalhekk, jista ’ jkun assoċjat ma ’ dan ir- riskju.
Body temperature regulation Disruption of the body’ s ability to reduce core body temperature has been attributed to antipsychotic medicines.
Regulazzjoni tat- temperatura tal- ġisem Disturbi fil- ħila tal- ġisem li jnaqqas it- temperatura tal- ġisem ġew attribwiti għall- mediċini antipsikotiċi.
Appropriate care is advised when prescribing INVEGA to patients who will be experiencing conditions which may contribute to an elevation in core body temperature, e. g., exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration.
Għandha ssir attenzjoni xierqa meta tingħata INVEGA lil pazjenti li se jkollhom kondizzjonijiet li jistgħu jikkontribwixxu għal żieda fit- temperatura tal- ġisem, e. ż., eżerċizzju qawwi, espożizzjoni għal sħana estrema, meta tittieħed ma ’ mediċina b’ attività antikolinerġika, jew li tkun suġġett għal deidrazzjoni.
Antiemetic effect An antiemetic effect was observed in preclinical studies with paliperidone.
Effett antiemetiku Ġie osservat effett antiemetiku fi studji kliniċi b’ paliperidone.
This effect, if it occurs in humans, may mask the signs and symptoms of overdosage with certain medicines or of conditions such as intestinal obstruction, Reye’ s syndrome, and brain tumour.
Dan l- effett, jekk iseħħ fil- bnedmin, jista ’ jostor sinjali u sintomi ta ’ doża eċċessiva b’ ċerti mediċini jew ta ’ kondizzjonijiet bħal ostruzzjoni intestinali, sindromu ta ’ Reye u tumur fil- moħħ.
Lactose content (pertains only to the 3 mg tablets) Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose- galactose malabsorption should not take this medicine.
Kontenut ta ’ lactuse (jgħodd biss għall- pilloli ta ’ 3 mg) Pazjenti bi problemi rari ereditarji ta ’ intolleranza tal- galactose, nuqqas ta ’ Lapp lactase jew assorbiment ħażin ta ’ glucose- galactose m’ għandhomx jieħdu din il- mediċina.
Caution is advised when prescribing INVEGA with medicines known to prolong the QT interval, e. g., class IA antiarrhythmics (e. g., quinidine, disopyramide) and class III antiarrhythmics (e. g., amiodarone, sotalol), some antihistaminics, some other antipsychotics and some antimalarials (e. g., mefloquine).
Għandha tintuża kawtela meta jingħata INVEGA ma ’ mediċini li huma magħrufa li jtawlu l- intervall QT, e. ż. antiarritmiċi tal- klassi IA, (e. ż. quinidine, disopyramide) u antiarritmiċi tal- klassi III (e. ż. amiodarone, sotalol), xi antistaminiċi, xi antipsikotiċi, u xi mediċini kontra l- malarja (e. ż. mefloquine).
If this combination is deemed necessary, particularly in end-stage Parkinson’ s disease, the lowest effective dose of each treatment should be prescribed.
Jekk dan it- teħid flimkien jitqies neċessarju, speċjalment fl- aħħar fażi tal- marda tal- Parkinson, għandha tingħata l- iktar doża baxxa effettiva.
Because of its potential for inducing orthostatic hypotension (see section 4.4), an additive effect may be observed when INVEGA is administered with other therapeutic agents that have this potential, e. g., other antipsychotics, tricyclics.
Minħabba l- potenzjal li għandha li tinduċi l- ipotensjoni ortostatika (ara sezzjoni 4. 4) jista ’ jiġi osservat effett kumulattiv meta INVEGA jiġi amministrat ma ’ aġenti terapewtiċi oħrajn li għandhom dan il - potenzjal e. ż antipsikotiċi oħra, triċikliċi.
Caution is advised if paliperidone is combined with other medicines know to lower the seizure threshold (i. e., phenothiazines or butyrophenones, tricyclics or SSRIs, tramadol, mefloquine, etc.).
Għandha jkun hemm kawtela jekk Paliperidone jittieħed ma ’ mediċini oħrajn li huma magħrufin li jkabbru l- possibiltà ta ’ attakk ta ’ aċċessjoni (bħal, e. ż., phenothiazines jew butyrophenones, triċikliċi jew SSRIs, tramadol, mefloquine eċċ.)
Potential for other medicines to affect INVEGA In vitro studies indicate that CYP2D6 and CYP3A4 may be minimally involved in paliperidone metabolism, but there are no indications in vitro nor in vivo that these isozymes play a significant role in the metabolism of paliperidone.
19 Studji in vitro jindikaw li CYP2D6 u CYP3A4 jistgħu ikun involuti b’ mod minimu fil- metaboliżmu ta ’ paliperidone, imma ma hemm l- ebda indikazzjoni in vitro jew in vivo li dawn l- isożimi għandhom sehem sinifikanti fil- metaboliżmu ta ’ paliperidone.
Concomitant administration of INVEGA with paroxetine, a potent CYP2D6 inhibitor, showed no clinically significant effect on the pharmacokinetics of paliperidone.
L- amminstrazzjoni konkomitanti ta ’ INVEGA ma ’ paroxetine, inibitur qawwi ta ’ CYP2D6, ma wera ebda effett klinikament sinifikanti fuq il - karatteristiċi farmakokinetiċi ta ’ paliperidone.
In vitro studies have shown that paliperidone is a P-glycoprotein (P-gp) substrate.
Studji in vitro wrew li paliperidone huwa sustrat ta ’ P - glycoprotein (P- gp).
18 Co-administration of INVEGA once daily with carbamazepine 200 mg twice daily caused a decrease of approximately 37% in the mean steady-state Cmax and AUC of paliperidone.
Meta INVEGA ngħata darba kuljum flimkien ma ’ 200 mg ta ’ carbamazepine darbtejn kuljum, dan wassal għal tnaqqis ta ’ bejn wieħed u ieħor 37% fil- medja ta ’ stat fiss ta ’ Cmax u l- AUC ta ’ paliperidone.
This decrease is caused, to a substantial degree, by a 35% increase in renal clearance of paliperidone likely as a result of induction of renal P-gp by carbamazepine.
Dan it- tnaqqis huwa kkawżat fil- parti l- kbira, minn tkabbir ta ’ 35% tat- tneħħija renali ta ’ paliperidone aktarx minħabba l- induzzjoni ta ’ P- gp renali b’ carbamazepine.
A minor decrease in the amount of active substance excreted unchanged in the urine suggests that there was little effect on the CYP metabolism or bioavailability of paliperidone during carbamazepine co-administration.
Tnaqqis żgħir fl- ammont tas- sustanza attiva li toħroġ ma ’ l- urina mhux mibdul jissuġġerixxi li ftit kien hemm effett fuq il - metaboliżmu ta ’ CYP jew il- bijodisponibiltà ta ’ paliperidone waqt il- ko- amministrazzjoni b’ carbamazepine.
On initiation of carbamazepine, the dose of INVEGA should be re-evaluated and increased if necessary.
Kif jibda jittieħed carbamazepine, id- doża ta ’ INVEGA għandha tiġi evalwata mill- ġdid u jekk hemm bżonn għandha tiżdied.
It takes 2-3 weeks for full induction to be achieved and upon discontinuation of the inducer the effect wears off over a similar time period.
L - induzzjoni sħiħa sseħħ fi 2- 3 ġimgħat, u wara li l- induċitur jitwaqqaf l- effett jispiċċa wara perjodu simili.
Other medicinal products or herbals which are inducers, e. g. rifampicin and St John´s wort (Hypericum perforatum) may have similar effects on paliperidone.
John’ s Wort (Hypericum perforatum) jista ’ jkollhom effetti simili għal paliperidone.
Concomitant use of INVEGA with risperidone Concomitant use of INVEGA with oral risperidone is not recommended as paliperidone is the active metabolite of risperidone and the combination of the two may lead to additive paliperidone exposure.
L- użu konkomitanti ta ’ INVEGA ma ’ risperidone L- użu konkomitanti ta ’ INVEGA ma ’ risperidone li jittieħed mill- ħalq mhux rakkomandat għaliex paliperidone huwa l- metabolit attiv ta ’ risperidone u meta jiġu kkombinati jista ’ jkun hemm espożizzjoni miżjuda ta ’ paliperidone.
Paliperidone is excreted in the breast milk to such an extent that effects on the breast-fed infant are likely if therapeutic doses are administered to breast-feeding women.
Paliperidone tant joħroġ mal- ħalib tas- sider li aktarx li jaffettwa t- trabi mredda jekk jingħataw dożi terapewtiċi lil nisa li qed ireddgħu.
Therefore, patients should be advised not to drive or operate machines until their individual susceptibility to INVEGA is known.
Għalhekk il- pazjenti għandhom jingħataw il- parir li ma jsuqux u jħaddmu makkinarju sakemm ikun magħruf kemm huma suxxettibbli għal INVEGA.
The ADRs that appeared to be dose-related included weight increased, headache, salivary hypersecretion, vomiting, dyskinesia, akathisia, dystonia, extrapyramidal disorder, hypertonia, and Parkinsonism.
L- ADRs li dehru li kienu marbuta mad- doża kienu żieda fil- piż, uġigħ ta ’ ras, ipersekrezzjoni tas - saliva, rimettar, diskajneżja, akatisja, distonja, disturbi ekstrapiramidali, ipertonja u l- Parkinsoniżmu.
The following are all ADRs that were reported in INVEGA-treated subjects in clinical trials.
20 Dawn li li ġejjin kienu kollha ADRs li ġew irrapurtarti f’ suġġetti kkurati bi INVEGA fi provi kliniċi.
19 System Organ Class
Klassifikazzjoni tas - Sistema ta ’ l- Organi Disturbi fis- sistema immuni
grand mal convulsion, syncope, dyskinesia, dizziness postural,,
konvulżjonijiet tal- grand mal, sinkope, diskajneżja, sturdament skond il - pożizzjoni,
Tachycardia, sinus tachycardia, bundle branch
takikardja, sinus takikardja, imblokkar ta ’ bundle branch, imblukkar atrijoventrikulari ta ’ l - ewwel grad, bradikardja,
block, atrioventricular block first degree, bradycardia, Vascular disorders Gastrointestinal disorders
Disturbi vaskulari Disturbi gastro - intestinali
System Organ Class Infections and infestations
Klassifikazzjoni
agitation, anorgasmia, anxiety, blunted affect, confusional state, insomnia, libido decreased, listless, mania, middle insomnia, nervousness, restlessness, sleep disorder 20
aġitazzjoni, anorgażmija, ansjetà, effett ‘ blunted ’, stat konfużjonali, insomnja, tnaqqis tal- libido, mitluq, manija, insomnja mezzana, nervożiżmu, bla kwiet, disturbi fl- irqad.
General disorders
22 Disturbi ġenerali
alanine aminotransferase increased, aspartate aminotransferase increased, blood creatine phosphokinase increased, blood glucose increased, blood pressure decreased, blood prolactin increased, body temperature decreased, body temperature increased, electrocardiogram QT prolonged, eosinophil count increased, haematocrit decreased, haemoglobin decreased, heart rate increased, transaminases increased, white blood cell count decreased
żieda ta ’ alanine aminotransferase, żieda ta ’ aspartate aminotransferase, żieda ta ’ kreatina phosphokinase tad- demm, żieda tal- glukosju tad- demm, tnaqqis ta ’ pressjoni tad- demm, żieda tal- prolaktin tad- demm, tnaqqis tat - temperatura tal- ġisem, żieda tat- temperatura tal- ġisem, prolongament tal - QT ta ’ l- elettrokardjogramma, zieda ta ’ l- għadd ta ’ eosinophil, tnaqqis ta ’ ematokrit, emoglobina mnaqqsa, żieda tar- rata tal- qalb, żieda ta ’ transaminases, tnaqqis ta ’ l- għadd taċ- ċelloli bojod tad- demm
21 Elderly In a study conducted in elderly subjects with schizophrenia, the safety profile was similar to that seen in non-elderly subjects.
Fi studju li sar f’ suġġetti anzjani bi skiżofrenja, il- profil ta ’ sigurtà kien simili għal suġġetti mhux anzjani.
In clinical trials with some other atypical antipsychotics, increased risks of death and cerebrovascular accidents have been reported (see section 4.4).
Fi provi kliniċi b’ xi antipsikotiċi atipiċi, ġew irrapurati riskji miżjuda ta ’ mewt u inċidenti ċerebrovaskulari (ara sezzjoni 4. 4).
Class effects QT prolongation, ventricular arrythmias (ventricular fibrillation, ventricular tachycardia), sudden unexplained death, cardiac arrest and Torsade de pointes may occur with antipsychotics.
Effetti tal- klassi B’ antipsikotiċi jista ’ jkun hemm prolongazzjoni tal- QT, arritmiji ventrikulari (fibrillazzjoni ventrikulari, takikardja ventrikulari), mewt f’ daqqa bla spjegazzjoni, attakk tal- qalb u Torsade de pointes
In the case of acute overdosage, the possibility of multiple medicinal product involvement should be considered.
Fil- każ ta ’ doża eċċessiva akuta għandha tiġi kkunsidrata l- possibiltà ta ’ l- użu ta ’ iktar minn prodott mediċinali wieħed.
Establish and maintain a clear airway and ensure adequate oxygenation and ventilation.
Il- passaġġ ta ’ l- arja għandu jitbattal u jinżamm miftuħ, u għandha tiġi assigurata ossiġenazjoni u ventilazzjoni adegwata.
In case of severe extrapyramidal symptoms, anticholinergic agents should be administered.
23 Fil- każ ta ’ sintomi extrapiramidali qawwija, għandhom jingħataw aġenti antikolinerġiċi.
22 Mechanism of Action Paliperidone is a selective blocking agent of monoamine effects, whose pharmacological properties are different from that of traditional neuroleptics.
Mekkaniżmu ta ’ Azzjoni Paliperidone huwa aġent li jimblokka b’ mod selettiv l- effetti monoamini, li l- propjetajiet farmakoloġiċi tagħhom huma differenti minn dawk ta ’ newrolettiċi tradizzjonali.
Even though paliperidone is a strong D2-antagonist, which is believed to relieve the positive symptoms of schizophrenia, it causes less catalepsy and decreases motor functions to a lesser extent than traditional neuroleptics.
Għalkemm paliperidone huwa antagonista D2 qawwi, li hi maħsuba li ttaffi s- sintomi pożittivi ta ’ l- iskizzofrenija, tikkawża inqas katalepsija u tnaqqas inqas il- funzjonijiet motorji meta mqabbel ma ’ newtrolettiċi tradizzjonali.
Dominating central serotonin antagonism may reduce the tendency of paliperidone to cause extrapyramidal side effects.
Il- ħila li tiddomina l- antagoniżmu b’ mod ċentrali tas- serotonin jista ’ jnaqqas it- tendenza ta ’ paliperidone li jikkawża l - effetti ekstrapiramidali mhux mixtieqa.
INVEGA doses, which varied across the three studies, ranged from 3 to 15 mg once daily.
Id- dożi ta ’ INVEGA, li kienu jvarjaw fit- tliet studji, kienu bejn 3 u 15- il mg kuljum.
The primary efficacy endpoint was defined as a decrease in total Positive and Negative Syndrome Scale (PANSS) scores as shown in the following table.
Il- kejl aħħari primarju ta ’ effiċjenza kien iddefinit bħala it- tnaqqis fl- iskala totali ta ’ Sindromi Pożittivi u Negattivi (PANSS) kif muri fit- tabelli li ġejja.
Predefined secondary endpoints included the Personal and Social Performance (PSP) scale and the Clinical Global Impression – Severity (CGI-S) scale.
Kejlijiet aħħarija sekondarji li kienu definiti minn qabel kienu jinkludu l- iskala ta ’ l - Imġieba Personali u Soċjali (PSP) u l- iskala ta ’ l- Impressjoni Klinika Globali – severità (CGI- S).
In all three studies, INVEGA was superior to placebo on PSP and CGI-S.
Fit - tliet studji, INVEGA kien aħjar mill- plaċebo mill- aspett ta ’ PSP u CGI- S.
Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Total Score - Change From Baseline to End Point- LOCF for Studies R076477-SCH-303, R076477-SCH-304, and R076477-SCH-305:
L- iSkala ta ’ Sindromi Pożittivi u Negattivi għal skiżofrenja (PANSS) Marka Totali – Bidla mill- Linja Bażi sal- Punt Finali- LOCF għall- istudji R076477- SCH- 303, R076477- SCH- 304, u R076477- SCH - 305:
Intent- to-Treat Analysis Set
Sett ta ’ Analiżi Intenzjoni- biex- tikkura.
In a long-term trial designed to assess the maintenance of effect, INVEGA was significantly more effective than placebo in maintaining symptom control and delaying relapse of schizophrenia.
Fi prova fit- tul imfassla biex iqis kemm idum l- effett, INVEGA kien iktar effettiv b’ mod sinifikanti mill- plaċebo fil- kontroll tas- sintomi u biex jitwal iż- żmien qabel terġa ’ toħroġ l- iskiżofrenja.
After having been treated for an acute episode for 6 weeks and stabilized for an additional 8 weeks with INVEGA (doses ranging from 3 to 15 mg once daily) patients were then randomised in a double-blind manner to either continue on INVEGA or on placebo until they experienced a relapse in schizophrenia
Wara li ġew ikkurati għal episodju akut għal 6 ġimgħat u ġew stabilizzati għal 8 ġimgħat oħra bi INVEGA (id - dożi kienu jvarjaw minn 3 sa 15- il mg darba kuljum) il- pazjenti tqassmu b’ mod randomised bil - metodu ‘ double blind ’ biex jew ikomplu INVEGA jew bi plaċebo sakemm reġgħu ħarġu s- sintomi ta ’ l- iskiżofrenja.
The trial was stopped early for efficacy reasons by showing a significantly longer time to relapse in patients treated with INVEGA compared to placebo (p=0.0053).
Il- prova twaqqfet kmieni għal raġunijiet ta ’ effikaċja billi nwera li l- pazjenti li kienu fuq INVEGA damu iktar b’ mod sinifikanti biex jirkadu meta mqabbla mal- plaċebo (p=0. 0053).
The pharmacokinetics of paliperidone following INVEGA administration are dose proportional within the available dose range.
Il- karatteristiċi farmakokinetiċi ta ’ paliperidone waqt l- amministrazzjoni ta ’ INVEGA huma proporzjonali għad- doża fil- medda ta ’ doża klinika rakkomandata (3 sa 12- il mg).
With once-daily dosing of INVEGA, steady-state concentrations of paliperidone are attained within 4-5 days of dosing in most subjects.
B’ doża kuljum ta ’ INVEGA, konċentrazzjonijiet fissi ta ’ paliperidone jintlaħqu fi żmien 4- 5 ijiem fil- maġġoranza tas - suġġetti.
The release characteristics of INVEGA result in minimal peak-trough fluctuations as compared to those observed with immediate-release risperidone (fluctuation index 38% versus 125%).
Il- karatteristiċi tal- ħruġ ta ’ mediċini ta ’ INVEGA iwasslu għal varjazzjoni minimi bejn l- ogħla punt u l- iktar wieħed baxx meta mqabbla ma ’ risperidone b’ rilaxx immedjat (indiċi ta ’ varjazzjoni ta ’ 38% kontra 125%).
Distribution Paliperidone is rapidly distributed.
25 Distribuzzjoni Paliperidone jiġi distribwit malajr.
Although in vitro studies suggested a role for CYP2D6 and CYP3A4 in the metabolism of paliperidone, there is no evidence in vivo that these isozymes play a significant role in the metabolism of paliperidone.
Għalkemm studji in vitro jissuġġerixxu li CYP2D6 u CYP3A4 għandhom sehem fil- metaboliżmu ta ’ paliperidone, m’ hemmx evidenza in vivo li dawn l - isożimi għandhom sehem sinifikanti fil- metaboliżmu ta ’ paliperidone.
Population pharmacokinetics analyses indicated no discernable difference on the apparent clearance of paliperidone after administration of INVEGA between extensive metabolisers and poor metabolisers of CYP2D6 substrates.
Diversi analiżi tal- karatteristiċi farmakokinetiċi fil- popolazzjoni ma wrew l- ebda differenza fit- tneħħija apparenti ta ’ paliperidone wara l- amministrrazzjoni ta ’ INVEGA bejn metabizzaturi estensivi u metabolizzaturi mhux tajbin ta ’ sustrati ta ’ CYP2D6.
In vitro studies have shown that paliperidone is a P-gp substrate and a weak inhibitor of P-gp at high concentrations.
Studji in vitro urew li paliperidone huwa sustrat ta ’ P- gp u inibitur dgħajjef ta ’ P- gp f’ konċentrazzjonijiet għolja.
No in vivo data are available and the clinical relevance is unknown.
M’ hemmx tagħrif in vivo u r- rilevanza klinika mhix magħrufa.
Hepatic Impairment Paliperidone is not extensively metabolized in the liver.
Indeboliment epatika Paliperidone mhux metabolizzat b’ mod estensiv fil- fwied.
No data are available in patients with severe hepatic impairment (Child-Pugh class C).
M’ hemmx tagħrif dwar pazjenti b’ indeboliment epatiku qawwi (Child- Pugh Klassi C).
24 Renal Impairment Elimination of paliperidone decreased with decreasing renal function.
Indeboliment Renali L- eliminazzjoni ta ’ paliperidone naqas bit- tnaqqis tal- funzjoni renali.
Total clearance of paliperidone was reduced in subjects with impaired renal function by 32% in mild (Creatinine Clearance [CrCl] = 50 to < 80 ml/ min), 64% in moderate (CrCl = 30 to < 50 ml/ min), and 71% in severe (CrCl = < 30 ml/ min) renal impairment.
It- tneħħija totali ta ’ paliperidone naqset bi 32% f’ suġġetti b’ indeboliment renali ħafif (Tneħħija tal- kreatinina [CrCl] = 50 to < 80 ml/ min), b’ 64% f’ indeboliment moderat (CrCl = 30 to < 50 ml/ min), u 71% f’ indeboliment sever (CrCl = < 30 ml/ min).
The mean terminal elimination half-life of paliperidone was 24, 40, and 51 hours in subjects with mild, moderate, and severe renal impairment, respectively, compared with 23 hours in subjects with normal renal function (CrCl ≥ 80 ml/ min).
Il- half- life tal- medja ta ’ l- eliminazzjoni terminali ta ’ paliperidone kienet ta ’ 24, 40 u 51 siegħa għal suġġetti b’ indeboliment renali ħafif, moderat u qawwi rispettivament, meta mqabbel ma ’ 23 siegħa f’ suġġetti b’ funzjoni renali normali (CrCl ≥ 80 ml/ min).
Elderly Data from a pharmacokinetic study in elderly subjects (≥ 65 years of age, n = 26) indicated that the apparent steady-state clearance of paliperidone following INVEGA administration was 20% lower compared to that of adult subjects (18-45 years of age, n = 28).
Anzjani Tagħrif minn studju farmakokinetiku f’ suġġetti anzjani (età ≥ 65 sena, n = 26) indika li t- tneħħija fissa apparenti ta ’ paliperidone wara l- amministrazzjoni ta ’ INVEGA kien 20% iktar baxx meta mqabbel ma ’ suġġetti adulti (età bein 18- 45 sena, n = 28).
However, there was no discernable effect of age in the population pharmacokinetic analysis involving schizophrenia subjects after correction of age-related decreases in CrCl.
Madankollu, ma deherx li kien hemm effett ta ’ età fl - analiżi farmakokinetika tal- popolazzjoni li kienet tinvolvi suġġetti bi skiżofrenja wara l- korrezzjoni tat- tnaqqis marbut ma ’ l- età fi CrCl.
Race Population pharmacokinetics analysis revealed no evidence of race-related differences in the pharmacokinetics of paliperidone following INVEGA administration.
Razza Analiżi farmakokinetika tal- popolazzjoni ma uriet l- ebda xiehda ta ’ differenzi marbuta mar- razza fil - karatteristiċi farmakokinetiċi ta ’ paliperidone wara l- amministrazzjoni ta ’ INVEGA.
This difference is largely explained by differences in lean body mass and creatinine clearance between men and women.
Ħafna minn din id- differenza hija dovuta għal differenzi bejn in- nisa u l- irġiel fil- massa tal- ġisem mingħajr xaħam u t- tneħħija tal- creatinina.
Smoking Status Based on in vitro studies utilising human liver enzymes, paliperidone is not a substrate for CYP1A2; smoking should, therefore, not have an effect on the pharmacokinetics of paliperidone.
26 Fuq il- bażi ta ’ studji in vitro li użaw enżimi tal- fwied uman, paliperidone mhux sustrat għal CYP1A2; għalhekk, it- tipjip mhux suppost ikollu effett fuq il- karatteristiċi farmakokinetiċi ta ’ paliperidone.
The difference is unlikely to be of clinical relevance, though.
Madankollu d- differenza aktarx li ma jkollhiex rilevanza klinika..
Repeat-dose toxicity studies of paliperidone in rat and dog showed mainly pharmacological effects, such as sedation and prolactin-mediated effects on mammary glands and genitals.
Studji tossikoloġiċi b’ doża repetuta ta ’ paliperidone fuq il- firien u l- klieb l- iktar li urew kienu effetti farmakoloġiċi, bħal sedazzjoni u effetti medjati mill- prolactin fuq il- glandoli mammarji u l- ġenitali.
Paliperidone was not teratogenic in rat and rabbit.
Paliperidone mhux teratoġeniku fuq il- firien u l- fniek.
These tumours can be related to prolonged dopamine D2 antagonism and hyperprolactinemia.
Dawn it - tumuri jistgħu jintrabtu ma ’ antagoniżmu tad- dopamina D2 fit- tul u iperprolactinemija.
For the 3 mg tablet:
Għall- pillola tat- 3 mg:
25 Stearic acid Butyl hydroxytoluene (E321) Ferric oxide (yellow) (E172) Polyethylene oxide 7000K Ferric oxide (red) (E172) Hydroxyethyl cellulose Polyethylene glycol 3350 Cellulose acetate
Polyethylene oxide 200K Sodium chloride Povidone (K29- 32) Stearic acid Butyl hydroxytoluene (E321) Ferric oxide (isfar) (E172) Polyethylene oxide 7000K Ferric oxide (aħmar) (E172) Hydroxyethyl cellulose Polyethylene glycol 3350 Cellulose acetate
Hypromellose Titanium dioxide (E171) Lactose monohydrate Triacetin Carnauba wax
Hypromellose Titanium dioxide (E171) Lactose monohydrate Triacetin Carnauba wax
Iron oxide (black) (E172) Propylene glycol Hypromellose
Iron oxide iswed (E172) Propylene glycol Hypromellose
Keep the bottle tightly closed in order to protect from moisture.
Żomm il- flixkun magħluq biex tipproteġi mill - umdità.
Store in the original package in order to protect from moisture.
Aħżen fil- pakkett oriġinali biex tipproteġi mill- umdità.
Pack sizes of 30 and 350 prolonged-release tablets.
Pakketti ta ’ 30 u 350 pillola li jerħu l- mediċina bil- mod.
• Polyvinyl chloride (PVC) laminated with polychloro-trifluoroethylene (PCTFE)/ aluminium push- through layer.
• Polyvinyl chloride (PVC) laminat b’ saff ta ’ polychloro- trifluoroethylene (PCTFE) / aluminju li tinbotta b’ subgħajk.
Pack sizes of 14, 28, 30, 49, 56, and 98 prolonged-release tablets.
Pakketti ta ’ 14, 28, 30, 49, 56, u 98 pillola li jerħu l- mediċina bil- mod.
26 • Oriented polyamide (OPA)-aluminium-polyvinyl chloride (PVC)/ aluminium push-through layer.
• Oriented polyamide (OPA) - aluminium- polyvinyl chloride (PVC) / aluminju li tinbotta b’ subgħajk.
Pack sizes of 14, 28, 49, 56, and 98 prolonged-release tablets.
Pakketti ta ’ 14, 28, 30, 49, 56, u 98 pillola li jerħu l- mediċina bil- mod.
EU/ 1/ 07/ 395/ 001-005 EU/ 1/ 07/ 395/ 021-025 EU/ 1/ 07/ 395/ 041-044 EU/ 1/ 07/ 395/ 057-058 EU/ 1/ 07/ 395/ 065-067
NUMRU( I) TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ EU/ 1/ 07/ 395/ 001- 005 EU/ 1/ 07/ 395/ 021- 025 EU/ 1/ 07/ 395/ 041- 044 EU/ 1/ 07/ 395/ 057- 058 28 EU/ 1/ 07/ 395/ 065- 067
NAME OF THE MEDICINAL PRODUCT
29 ISEM TAL- PRODOTT MEDIĊINALI
INVEGA 6 mg prolonged-release tablets
INVEGA pilloli tas- 6 mg li jerħu l- mediċina bil- mod
Each prolonged-release tablet contains 6 mg of paliperidone.
Kull pillola li terħi l- mediċina bil- mod fiha 6 mg ta ’ paliperidone.
Trilayer capsule-shaped beige tablets printed with “ PAL 6”
Pilloli b’ forma ta ’ kapsula kannella jagħtu fl- isfar bi tliet saffi stampati b ’ “ PAL 6 ”
INVEGA must be swallowed whole with liquid, and must not be chewed, divided, or crushed.
INVEGA għandu jinbela ’ sħiħ ma ‘ likwidu, u m’ għandux jiġi magħmud, maqsum jew imfarrak.
As INVEGA has not been studied in patients with severe hepatic impairment, caution is recommended in such patients.
Billi INVEGA ma ġiex studjat f’ pazjenti b’ indeboliment epatiku qawwi, l- amministrazzjoni f’ dawn il - pazjenti għandha ssir b’ kawtela.
For patients with moderate to severe renal impairment (creatinine clearance ≥ 10 to < 50 ml/ min), the recommended initial dose of INVEGA is 1.5 mg every day, which may be increased to 3 mg once daily after clinical reassessment.
Għal pazjenti b’ indeboliment renali moderat għal qawwi (tneħħija tal- kreatinina ≥ 10 sa < 50 ml/ min), id- doża inizzjali rakkomandata ta ’ INVEGA hija 1. 5 mg kuljum, li tista ’ tiżdied għal 3 mg kuljum
28 Elderly Dosing recommendations for elderly patients with normal renal function (≥ 80 ml/ min) are the same as for adults with normal renal function.
Anzjani Ir- rakkomandazzjoni għad- dożaġġ għal pazjenti anzjani li għandhom funzjoni renali normali (≥ 80 ml/ min) hija l- istess għall- adulti b’ funzjoni renali normali.
Hyperglycemia Rare cases of glucose related adverse reactions, e. g., increase in blood glucose, have been reported in clinical trials with INVEGA.
Ipergliċemija Fi provi kliniċi ta ’ INVEGA ġew irrapurtati każijiet rari avversi marbuta mal- glucose, e. ż., żieda fil - glucose tad- demm.
Based on pooled data from the three, placebo-controlled, 6-week, fixed-dose trials with INVEGA (3, 6, 9, and 12 mg), orthostatic hypotension was reported by 2.5% of subjects treated with INVEGA compared with 0.8% of subjects treated with placebo.
Skond t- tagħrif meqjus flimkien minn tliet provi bi INVEGA ta ’ sitt ġimgħat b’ doża fissa (3, 6, 9, U 12- il mg) u bl- użu ta ’ plaċebo ma ’ grupp ta ’ kontroll, l- ipotensjoni ortostatika ġiet irrapurtata
INVEGA should be used with caution in patients with known
31 fi 2. 5% tal- pazjenti kkurati bi INVEGA meta mqabbla ma ’ 0. 8% ta ’ suġġetti kkurati bil- plaċebo.
29 cardiovascular disease (e. g., heart failure, myocardial infarction or ischaemia, conduction abnormalities), cerebrovascular disease, or conditions that predispose the patient to hypotension (e. g., dehydration and hypovolemia).
INVEGA għandu jintuża b’ kawtela f’ pazjenti li għandhom mard kardjovaskolari (e. ż., insuffiċjenza tal- qalb, infart mijokardijaku jew iskemija, anormalitajiet fil- konduzzjoni), mard ċerebrovaskulari, jew kondizzjonijiet li jippredisponu lill- pazjent għall- ipotensjoni (e. ż., id- deidrazzjoni u l- ipovolemija).
30 Priapism Medicines with alpha-adrenergic blocking effects have been reported to induce priapism.
32 Mediċini b’ effetti ta ’ mblukkar alfa- adrenerġiċi ġew irrapurati li jinduċu l- prijapiżmu.
Given the primary CNS effects of paliperidone (see section 4.8), INVEGA should be used with caution in combination with other centrally acting medicines e. g. anxiolytics, most antipsychotics, hypnotics, opiates, etc. or alcohol.
Meta wieħed iqis l- effetti primarji CNS ta ’ paliperidone (ara sezzjoni 4. 8), INVEGA għandu jintuża b’ kawtela meta jittieħed flimkien ma ’ mediċini oħra li għandhom azzjoni ċentrali e. ż. anksjolitiċi, il - biċċa l- kbira ta ’ l- antipsikotiċi, ipnotiċi, opjejts, etc. jew l- alkoħol.
Because of its potential for inducing orthostatic hypotension (see section 4.4), an additive effect may be observed when INVEGA is administered with other therapeutic agents that have this potentiale. g. other antipsychotics, tricyclics.
Minħabba l- potenzjal li għandha li tinduċi l- ipotensjoni ortostatika (ara sezzjoni 4. 4) jista ’ jiġi osservat effett kumulattiv meta INVEGA jiġi amministrat ma ’ aġenti terapewtiċi oħrajn li għandhom dan il - potenzjal e. ż antipsikotiċi oħra, triċikliċi.
Caution is advised if paliperidone is combined with other medicines know to lower the seizure threshold (i. e. phenothiazines or butyrophenones, tricyclics or SSRIs, tramadol, mefloquine, etc.).
Għandha jkun hemm kawtela jekk Paliperidone jittieħed ma ’ mediċini oħrajn li huma magħrufin li jkabbru l- possibiltà ta ’ attakk ta ’ aċċessjoni (bħal, e. ż., phenothiazines jew butyrophenones, triċikliċi jew SSRIs, tramadol, mefloquine eċċ.)
Potential for other medicines to affect INVEGA In vitro studies indicate that CYP2D6 and CYP3A4 may be minimally involved in paliperidone metabolism, but there are no indications in vitro nor in vivo that these isozymes play a significant role in the metabolism of paliperidone.
Il- potenzjal li mediċini oħrajn jaffettwaw INVEGA Studji in vitro jindikaw li CYP2D6 u CYP3A4 jistgħu ikun involuti b’ mod minimu fil- metaboliżmu ta ’ paliperidone, imma ma hemm l- ebda indikazzjoni in vitro jew in vivo li dawn l- isożimi għandhom sehem sinifikanti fil- metaboliżmu ta ’ paliperidone.
Co-administration of INVEGA once daily with carbamazepine 200 mg twice daily caused a decrease of approximately 37% in the mean steady-state Cmax and AUC of paliperidone.
Meta INVEGA ngħata darba kuljum flimkien ma ’ 200 mg ta ’ carbamazepine darbtejn kuljum, dan wassal għal tnaqqis ta ’ bejn wieħed u ieħor 37% fil- medja ta ’ stat fiss ta ’ Cmax u l- AUC ta ’ paliperidone.
A minor decrease in the amount of active substance excreted unchanged in the urine suggests that there was little effect on the CYP metabolism or bioavailability of paliperidone during carbamazepine co-administration.
Tnaqqis żgħir fl- ammont tas- sustanza attiva li toħroġ ma ’ l- urina mhux mibdul jissuġġerixxi li ftit kien hemm effett fuq il - metaboliżmu ta ’ CYP jew il- bijodisponibiltà ta ’ paliperidone waqt il- ko- amministrazzjoni
On initiation of carbamazepine, the dose of INVEGA should 31 be re-evaluated and increased if necessary.
Kif jibda jittieħed carbamazepine, id- doża ta ’ INVEGA għandha tiġi evalwata mill- ġdid u jekk hemm bżonn għandha tiżdied.
Medicinal products affecting gastrointestinal transit time may affect the absorption of paliperidone, e. g. metoclopramide.
Prodotti mediċinali li jaffettwaw iż- żmien ta ’ tranżitu gastrointestinali jistgħu jaffettwaw l- assorbiment ta ’ paliperidone, e. ż. metoclopramide.
32 System Organ Class
34 Klassifikazzjoni tas - Sistema ta ’ l- Organi Disturbi fis- sistema immuni
extrapyramidal disorder, parkinsonism, tremor, hypertonia, dystonia, akathisia, dizziness,, sedation, somnolence,
mard ekstrapiramidali, parkinsoniżmu, rogħda, ipertonja, distonja, akatisja, sturdament, sedazzjoni, ħedla,
grand mal convulsion, syncope, dyskinesia,, dizziness postural,
konvulżjonijiet tal- grand mal, sinkope, diskajneżja, sturdament skond il - pożizzjoni,
tachycardia, sinus tachycardia, bundle branch block, atrioventricular block first degree, bradycardia,
takikardja, sinus takikardja, imblokkar ta ’ bundle branch, imblukkar atrijoventrikulari ta ’ l - ewwel grad, bradikardja,
hyperprolactaemia, inappropriate antidiuretic hormone secretion
35 Disturbi fil- metaboliżmu u n- nutrizzjoni
Metabolism and nutrition anorexia, decreased appetite, diabetic ketoacidosis, polydipsia disorders
anoressja, tnaqqis ta ’ l- aptit, ketoaċidożi dijabetika, polidipsja
33 Psychiatric disorders
Disturbi psikjatriċi
agitation, anorgasmia, anxiety, blunted affect, confusional state, insomnia, libido decreased, listless, mania, middle insomnia, nervousness, restlessness, sleep disorder
aġitazzjoni, anorgażmija, ansjetà, effett ‘ blunted ’, stat konfużjonali, insomnja, tnaqqis tal- libido, mitluq, manija, insomnja mezzana, nervożiżmu, bla kwiet, disturbi fl- irqad.
34 Investigations
36 Investigazzjonijiet
Elderly
Anzjani
In a study conducted in elderly subjects with schizophrenia, the safety profile was similar to that seen in non-elderly subjects.
Fi studju li sar f’ suġġetti anzjani bi skiżofrenja, il- profil ta ’ sigurtà kien simili għal suġġetti mhux anzjani.
5.1 Pharmacodynamic properties
37 5. 1 Tagħrif farmakodinamiku
Mechanism of Action Paliperidone is a selective blocking agent of monoamine effects, whose pharmacological properties are different from that of traditional neuroleptics.
Mekkaniżmu ta ’ Azzjoni Paliperidone huwa aġent li jimblokka b’ mod selettiv l- effetti monoamini, li l- propjetajiet farmakoloġiċi tagħhom huma differenti minn dawk ta ’ newrolettiċi tradizzjonali.
The primary efficacy endpoint was defined as a decrease in total Positive and Negative Syndrome Scale (PANSS) scores as shown in the following table.
Il- kejl aħħari primarju ta ’ effiċjenza kien it- tnaqqis fl- iSkala totali ta ’ Sindromi Pożittivi u Negattivi (PANSS) kif muri fit- tabelli li ġejja.
Predefined secondary endpoints included the Personal and Social Performance (PSP) scale and the Clinical Global Impression – Severity (CGI-S) scale.
Kejlijiet aħħarija sekondarji li kienu definiti minn qabel kienu jinkludu l- iskala ta ’ l- Imġieba Personali u Soċjali (PSP) u l- iskala ta ’ l- Impressjoni Klinika Globali – severità (CGI- S).
In all three studies, INVEGA was superior to placebo on PSP and CGI-S.
Fit- tliet studji, INVEGA kien aħjar mill- plaċebo mill- aspett ta ’ PSP u CGI- S.
36 Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Total Score - Change From Baseline to End Point- LOCF for Studies R076477-SCH-303, R076477-SCH-304, and R076477-SCH-305:
L- iSkala ta ’ Sindromi Pożittivi u Negattivi għal skiżofrenja (PANSS) Marka Totali – Bidla mill- Linja Bażi sal- Punt Finali- LOCF għall- istudji R076477- SCH- 303, R076477- SCH- 304, u R076477- SCH - 305:
After having been treated for an acute episode for 6 weeks and stabilized for an additional 8 weeks with INVEGA (doses ranging from 3 to 15 mg once daily) patients were then randomised in a double-blind manner to either continue on INVEGA or on placebo until they experienced a relapse in schizophrenia symptoms.
Wara li ġew ikkurati għal episodju akut għal 6 ġimgħat u ġew stabilizzati għal 8 ġimgħat oħra bi INVEGA (id - dożi kienu jvarjaw minn 3 sa 15- il mg darba kuljum) il- pazjenti tqassmu b’ mod randomised bil - metodu ‘ double blind ’ biex jew ikomplu INVEGA jew bi plaċebo sakemm reġgħu ħarġu s- sintomi ta ’ l- iskiżofrenja.
Administration of paliperidone prolonged-release tablets with a standard high-fat/ high-caloric meal
L- amministrazzjoni ta ’ pilloli ta ’ paliperidone li jerħu l- mediċini bil- mod ma ’ ikla normali b’ livell għoli ta ’ xaħam/ kaloriji jgħolli Cmax u AUC ta ’ paliperidone sa 50- 60% meta mqabbel ma ’ l - amministrazzjoni fi stat ta ’ sawm.
37 increases Cmax and AUC of paliperidone by up to 50-60% compared with administration in the fasting state.
Distribuzzjoni
Distribution Paliperidone is rapidly distributed.
39 Paliperidone jiġi distribwit malajr.
Biotransformation and elimination One week following administration of a single oral dose of 1 mg immediate-release 14C-paliperidone, 59% of the dose was excreted unchanged into urine, indicating that paliperidone is not extensively metabolised by the liver.
Bijotrasformazzjoni u eliminazzjoni Ġimgħa wara l- amministrazzjoni ta ’ doża waħda orali ta ’ 1 mg 14C- paliperidone li jerħi l- mediċina b’ mod immedjat, 59% tad- doża tneħħiet bla bdil ma ’ l- awrina, li jindika li paliperidone ma jiġix metabolizzat b’ mod estensiv fil- fwied.
Renal Impairment Elimination of paliperidone decreased with decreasing renal function.
Indeboliment Renali L- eliminazzjoni ta ’ paliperidone naqas bit- tnaqqis tal- funzjoni renali.
Total clearance of paliperidone was reduced in subjects with impaired renal function by 32% in mild (Creatinine Clearance [CrCl] = 50 to < 80 ml/ min), 64% in moderate (CrCl = 30 to < 50 ml/ min), and 71% in severe (CrCl = < 30 ml/ min) renal impairment.
It- tneħħija totali ta ’ paliperidone naqset bi 32% f’ suġġetti b’ indeboliment renali ħafif (Tneħħifa tal- kreatinina [CrCl] = 50 to < 80 ml/ min), b’ 64% f’ indeboliment moderat (CrCl = 30 to < 50 ml/ min), u 71% f’ indeboliment sever (CrCl = < 30 ml/ min).
38 Smoking Status Based on in vitro studies utilising human liver enzymes, paliperidone is not a substrate for CYP1A2; smoking should, therefore, not have an effect on the pharmacokinetics of paliperidone.
Tipjip Fuq il- bażi ta ’ studji in vitro li użaw enżimi tal- fwied uman, paliperidone mhux sustrat għal CYP1A2; għalhekk, it- tipjip mhux suppost ikollu effett fuq il- karatteristiċi farmakokinetiċi ta ’ paliperidone.
A population pharmacokinetic analysis showed a slightly lower exposure to paliperidone in smokers compared with non-smokers.
40 Analiżi farmakokinetika tal- popolazzjoni uriet espożizzjoni kemmxejn inqas għal paliperidone f’ min ipejjep meta mqabbla ma ’ min ma jpejjipx.
In rat reproduction studies using risperidone, which is extensively converted to paliperidone in rats and humans, a reduction was observed in the birth weight and survival of the offspring.
Fi studji dwar riproduzzjoni fil- firien fejn użaw risperidone, li jiġi konvertit b’ mod estensiv għal paliperdone fil- firien u l- bnedmin, ġew osservati tnaqqis fil- piż fit- twelid u s- sopravivenza tal- friegħ.
Other dopamine antagonists, when administered to pregnant animals, have caused negative effects on learning and motor development in the offspring.
Meta antagonisti oħrajn tad- dopamina ġew amministrati lil annimali ħobla, kellhom effetti negattivi fuq it- tagħlim u l- iżvilupp motorju tal- friegħ.
For the 6 mg tablet:
Għall- pillola tas- 6 mg::