natgillin/translations-raw huggingface dataset:
Risici og fordele ved yderligere behandling med RISPERDAL CONSTA bør vurderes, hvis klinisk relevant ortostatisk hypotension vedvarer.
The MAH provided further justifications, being of the position that restricting the use of Risperdal Consta to patients with an initial treatment response to oral risperidone would be unjustified and would introduce an unnecessary and potentially prolonged additional step for the prescribing physicians, delaying access of Risperdal Consta to those patients who may not be adherent to their oral medication and who may be among the most suitable candidates for a long-acting injectable medication.
Lægemidler med dopaminreceptorantagonistiske egenskaber er blevet sat i forbindelse med induktion af tardiv dyskinesi karakteriseret ved ufrivillige rytmiske bevægelser, overvejende i tungen og/ eller ansigtet.
Based on the submitted data, the CHMP was of the opinion that the presented clinical data show that patients stabilised with any antipsychotic medication (oral or depot formulations) can safely be switched to Risperdal Consta and achieve a clinical benefit similar to that seen in patients being switched from oral risperidone and without a higher incidence of clinical deterioration.
Forekomst af ekstrapyramidale symptomer er en risikofaktor for tardive dyskinesier.
The CHMP agreed that no non-inferiority study is required and the following wording for section 4.1 was adopted:
Hvis de nævnte symptomer opstår, skal alle antipsykotika, herunder RISPERDAL CONSTA, seponeres.
“ Risperdal Consta is indicated for the maintenance treatment of schizophrenia in patients currently stabilised with oral antipsychotics”.
Parkinsons sygdom kan forværres af risperidon.
The CHMP further assessed data from patients switched to Risperdal Consta without stabilisation on oral risperidone, and concluded that sufficient antipsychotic coverage should be ensured during a lag period following the first Risperdal Consta injection.
Denne øgede sensitivitet kan bl. a. manifestere sig ved konfusion, bevidsthedssvækkelse og postural ustabilitet med hyppige fald samt ekstrapyramidale symptomer.
The length of the oral supplementation period was also discussed and the CHMP concluded that 3 weeks is the most appropriate length, leading neither to an overdose at the end of the oral supplementation period in those patients who have a relatively early release, nor to clinically relevant ‘ underdosing’ in patients for whom the main release starts from 4 weeks onwards only, given the relatively long half-life of the active moiety following oral risperidone.
Hyperglycæmi eller forværring af eksisterende diabetes er rapporteret i meget sjældne tilfælde under behandling med RISPERDAL CONSTA.
The need for increased patient monitoring during the switch period was discussed and the CHMP considered that the data provided showed no worsening in clinical symptoms after the therapy with long-acting risperidone was initiated.
Relevant klinisk monitorering tilrådes af patienter med diabetes og patienter med risikofaktorer for udvikling af diabetes mellitus.
According to various treatment guidelines of schizophrenia, the switch of antipsychotic treatment in patients with schizophrenia requires “ per se” the increased
Selvom kliniske og epidemiologiske forsøg indtil videre ikke har vist nogen klar sammenhæng med administration af antipsykotika, bør der udvises forsigtighed hos patienter med relevant medicinsk anamnese.
15 monitoring of therapy by qualified physicians and the CHMP was therefore of the opinion that due to nature of the illness and long-term experience with treatment of schizophrenia by atypical antipsychotics, proper monitoring of therapy after switching antipsychotic treatment can be expected, without being explicitly mentioned in the SPC.
Dette skyldes at risperidon kan øge risikoen for arytmogene effekter.
For section 4.2, the CHMP discussed the Risperdal Consta starting dose (25 mg, intramuscular, every 2 weeks), considering the data provided by the MAH, and was of the opinion that the recommendation in the SPC that treatment should be started with the dose of 25 mg every two weeks should be maintained.
Der bør udvises forsigtighed ved ordination af RISPERDAL CONSTA til patienter, som skal udsættes for forhold, der kan bidrage til forhøjelse af kroppens kernetemperatur, f. eks. kraftig motion, eksponering for ekstrem varme, samtidig behandling med antikolinerg aktivitet eller ved udsættelse for dehydrering.
Relatively constant dose-response after Risperdal Consta treatment using doses from 25 to 75 mg is considered to be established and the CHMP agreed that good medical practice would be to start patients at the lowest effective dose and to increase the dose only if the response is insufficient.
Patienternes vægt bør kontrolleres regelmæssigt.
This was supported by results from the switching studies and since this product has been on the market for several years already, its efficacy and safety have been already confirmed.
4. 2).
The CHMP was also of the opinion that the proposed wording of the SPC gives enough flexibility to the treating physician to start with the dose of 25 mg or higher.
Der bør udvises forsigtighed, således at RISPERDAL CONSTA ikke utilsigtet injiceres i en blodåre.
Regarding the precise correspondence of an oral risperidone dose to a specific dose of Risperdal Consta, a wording in the SPC was adopted, reflecting the available efficacy and safety data and the results of clinical studies, to guide the choice of starting dose of Risperdal Consta:
Dette lægemiddel indeholder mindre end 1 mmol (23 mg) natrium pr. dosis, dvs. det er stort set natriumfrit.
“ For most patients the recommended dose is 25 mg intramuscular every two weeks.
Der er udført interaktionsundersøgelser med oral RISPERDAL.
For those patients on a fixed dose of oral risperidone for two weeks or more, the following conversion scheme should be considered.
Risperidon skal på grund af øget risiko for sedation anvendes med forsigtighed i kombination med andre centralt virkende stoffer, særligt alkohol, opioider, antihistaminer og benzodiazepiner.
Patients treated with a dosage of 4 mg or less oral risperidone should receive 25 mg Risperdal Consta, while patients treated with higher oral doses should be considered for the higher Risperdal Consta dose of 37.5 mg.
Hvis en sådan kombination vurderes nødvendig, særligt ved parkinsonisme på et sent stadie, bør den laveste effektive dosis af hvert lægemiddel gives.
Where patients are not currently taking oral risperidone, the oral pre-treatment dosage should be considered when choosing the i. m. starting dose.
25 Klinisk signifikant hypotension er observeret efter markedsføring ved samtidig brug af risperidon og antihypertensiva.
The recommended starting dose is 25 mg Risperdal Consta every two weeks.
Risperidon viser ikke en klinisk relevant effekt på lithiums, valproats, digoxins eller topiramats farmakokinetik.
Patients on higher dosages of the used oral antipsychotic should be considered for the higher Risperdal Consta dose of 37.5 mg .”
Andre lægemidlers potentiale for påvirkning af RISPERDAL CONSTA
The CHMP also assessed the proposed 12.5 mg dosing, in particular with regards to the elderly population, and considered that the 12.5 mg dose of Risperdal Consta would provide additional dosing flexibility but stressed that this dose is intended only as a lower initial dose to establish tolerability, to be used mainly for patients with a higher sensitivity to the effects of the drug, either because of reduced metabolism/ excretion, or in patients with an intrinsic lower tolerability to psychotropic medication.
Carbamazepin reducerer plasmakoncentrationen af risperidons aktive antipsykotiske fraktion.
This was reflected in the harmonised wording of the SPC, along with the statement “ The efficacy of the 12.5 mg dose has not been investigated in clinical trials”.
Lignende effekt kan observeres med andre stoffer, f. eks. rifampicin, phenytoin og phenobarbital, som også inducerer leverenzymet CYP 3A4 såvel som P- glykoprotein.
Furthermore, the PK of Risperdal Consta in the elderly population was adequately described, and it was shown that the pharmacokinetics in the population > 65 years are comparable to the population < 65 years.
Ved initiering eller seponering af carbamazepin eller andre andre stoffer, som inducerer leverenzymet CYP 3A4/ P- glykoprotein (P- gp), bør doseringen af RISPERDAL CONSTA reevalueres.
Due to the known efficacy and safety profile of risperidone, this additional dose is approvable without its own efficacy data and can be based solely on the PK data.
CYP 2D6- inhibitorerne fluoxetin og paroxetin øger plasmakoncentrationen af risperidon, men niveauet af den aktive antipsykotiske fraktion øges ikke i tilsvarende grad.
The CHMP assessed the need for a warning, advising against the use of Risperdal Consta in acute exacerbations of schizophrenia, but considered it to potentially raise a safety concern that is not valid or clinically justified and that there are no particular risks associated with using Risperdal Consta in acute exacerbations of schizophrenia that warrant a warning.
Det forventes, at andre CYP 2D6- inhibitorer som kinidin kan påvirke plasmakoncentrationen af risperidon tilsvarende.
If Risperdal Consta is used in accordance with the SPC recommendations for dosing, no particular safety or efficacy risks for the patient would be foreseen, even if acutely ill.
Ved initiering eller seponering af fluoxetin eller paroxetin bør doseringen af RISPERDAL CONSTA reevalueres.
The CHMP adopted the following text in section 4.2:
Verapamil, som er en inhibitor af CYP 3A4 og P- gp, øger plasmakoncentrationen af risperidon.
“ Risperdal Consta should not be used in acute exacerbations of schizophrenia without ensuring sufficient antipsychotic coverage with oral risperidone or the previous antipsychotic during the three- week lag period following the first Risperdal Consta injection .”
Galantamin og donepezil viser ikke klinisk relevant effekt på risperidons farmakokinetik eller den aktive antipsykotiske fraktion.
Finally, the CHMP discussed the use of Risperdal Consta in patients previously treated with oral risperidone at doses ≥ 6mg/ day and noted that the provided efficacy data of these patients, when
Amytriptylin påvirker hverken risperidons farmakokinetik eller den aktive antipsykotiske fraktion.
16 switched to Risperdal Consta, were not different from the data obtained after previous oral risperidone treatment, despite the high probability of lower plasma level of risperidone being reached.
Cimetidin og ranitidin øger biotilgængeligheden af risperidon, men den aktive antipsykotiske fraktions biotilgængelighed påvirkes kun marginalt.
In addition, long-acting risperidone offers an advantage in increased compliance to the treatment, which could result in more stable plasma levels of risperidone.
CYP 3A4 - inhibitoren erythromycin påvirker ikke risperidons farmakokinetik eller den aktive antipsykotiske fraktion.
The CHMP was also of the opinion that doses of risperidone > 8 mg/ day should not be routinely used and should be restricted to certain group of patients.
4. 6 Graviditet og amning
In conclusion, the CHMP was not in favour of restricting the use of long-acting risperidone for patients who were administered with 6 mg risperidone per day.
Ifølge data fra efter markedsføringen er der observeret reversible ekstrapyramidale symptomer hos neonatale, når risperidon har været brugt i det sidste trimester af graviditeten.
The CHMP assessed the data provided on the use of Risperdal Consta in elderly patients and was of the opinion that no significant trend of increased adverse events according to the age of patients or dose of Risperdal Consta were identified.
Nyfødte bør således monitoreres nøje.
All differences were accordingly justified and the proposed wording in the SPC is acceptable.
Risperidon var ikke teratogent i dyreforsøg, men der blev observeret andre former for reproduktionstoksicitet (se pkt.
The MAH presented a table summarising the results of total PANSS score from RIS-INT-61, broken down by dose level for the dose groups 25 mg, 50 mg and 75 mg.
Den potentielle risiko for mennesker er ukendt.
Two additional tables provided data showing that treatment is non-inferior to risperidone oral treatment for the changes in positive and negative symptoms subscales of PANSS.
RISPERDAL CONSTA bør derfor kun anvendes på tvingende indikation under graviditet.
The CHMP considered that the requested efficacy analysis had been provided and that the efficacy of Risperdal Consta was shown in all doses separately.
I dyreforsøg udskilles risperidon og 9- hydroxyrisperidon i modermælk.
For section 4.3, the CHMP discussed the relevance of a Contraindication warning for patients with high risk factors for cerebrovasular adverse events.
Det er påvist, at risperidon og 9- hydroxyrisperidon også udskilles i små mængder i human modermælk.
Because Risperdal Consta has not been studied in elderly patients with dementia, it is therefore not indicated for use in this group of patients, as stated in Section 4.4 of the proposed SPC and in line with the current CHMP SPC guideline.
Fordelene ved amning bør således vurderes i forhold til de potentielle risici for barnet.
The CHMP agreed that the presence of cerebrovascular risk factors is poorly predictive for a risperidone-mediated increased cerebrovascular risk and was therefore of the opinion that a contraindication for Risperdal Consta in patients with high risk factors for cerebrovascular events was not justified.
Patienterne bør
For section 4.4, the CHMP implemented the wording on tardive dyskinesia, agreed upon by the Pharmacovigilance Working Party.
26 derfor frarådes at føre motorkøretøj eller betjene maskiner, før den individuelle følsomhed over for lægemidlet er kendt.
The CHMP further assessed the need for special mention of hyperprolactinaemia and stimulation of cell growth in breast tumours linked to prolactin.
Søvnløshed, angst, hovedpine, infektion i de øvre luftveje, parkinsonisme, depression og akatisi.
The CHMP considered the MAH responses and agreed that although data may suggest that prolactin is involved in breast cancer etiology, further studies are required to establish a formal link, and therefore adopted the following wording, addressing the potential risks of hyperprolactinaemia, although without specific inclusion of prolactinoma and breast cancer:
Nedenfor anføres samtlige bivirkninger, som er rapporteret i kliniske forsøg og efter markedsføringen.
“ Tissue culture studies suggest that cell growth in human breast tumours may be stimulated by prolactin.
Følgende termer og hyppigheder anvendes: meget almindelig (≥ 1/ 10), almindelig (≥ 1/ 100 til < 1/ 10), ikke almindelig (≥ 1/ 1. 000 til < 1/ 100), sjælden (≥ 1/ 10. 000 til < 1/ 1. 000), meget sjælden (< 1/ 10. 000) og ikke kendt (kan ikke estimeres ud fra forhåndenværende data).
Although no clear association with the administration of antipsychotics has so far been demonstrated in clinical and epidemiological studies, caution is recommended in patients with a relevant medical history.
De alvorligste bivirkninger skal anføres først.
Risperdal should be used with caution in patients with pre-existing hyperprolactinaemia and in patients with possibly prolactin-dependent tumours .”
27 Bivirkninger efter systemorganklasse og hyppighed Undersøgelser Almindelig
For section 4.6, the CHMP discussed the wording, moving the mention of galactorrhea to section 4.8 and adopting the following harmonised wording:
Unormalt elektrokardiogram, forhøjet blodprolactina, stigning i blodglucose, stigning i leverenzymer, stigning i transaminaser, stigning i gammaglutamyltransferase, vægtøgning, vægttab
“ It has been demonstrated that risperidone and 9-hydroxy-risperidone are also excreted in human breast-milk in small quantities.
Almindelig Ikke almindelig Blod og lymfesystem
There are no data available on adverse effects in breast-feeding infants.
AV- blok, takykardi Grenblok, atrieflimren, bradykardi, sinusbradykardi, palpitationer
Therefore, the advantage of breast-feeding should be weighed against the potential risks for the child .”
Anæmi Trombocytopeni, neutropeni Agranulocytose
For section 4.8, the CHMP assessed and harmonised the wording.
Meget almindelig Parkinsonismeb, akatisib, hovedpine Almindelig
Furthermore, « Anxiety » and « nervousness » should be separated and not grouped by the term “ anxiety”.
Svimmelhed, sedation, somnolens, tremor, dystonib, tardiv dyskinesi, dyskinesib
Finally, « Extrapyramidal symptoms » should be the grouped term in the subparagraph Nervous System Disorders and the single symptoms should be mentioned with an
Ikke almindelig Øjne
17 asterix.
Kramper, synkope, postural svimmelhed, hypoæstesi, paræstesi, letargi, hypersomni
As already mentioned, hypersalivation/ drooling should be added to « EPS » as otherwise incidence of EPS is underestimated.
Sløret syn, konjunktivitis Retinal arterieokklusion
All sections of the SPC were thoroughly assessed and all revisions were implemented accordingly in the Labelling and in the Package Leaflet, achieving a harmonised Product Information text.
Luftveje, thorax og mediastinum Almindelig
Based on the available data, the CHMP is of the opinion that all raised question were adequately addressed and that the harmonised Product Information wording is acceptable.
Dyspnø, hoste, nasal kongestion, faryngolaryngeale smerter
GROUNDS FOR AMENDMENT OF THE SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET
Almindelig
Whereas
Opkastning, diaré, obstipation, kvalme, abdominalsmerter, dyspepsi, tandpine, mundtørhed, abdominalgener, gastritis
- the scope of the referral was the harmonisation of the Summaries of Products Characteristics,
Intestinal obstruktion, pankreatitis
labelling and package leaflet,
Udslæt, eksem Angioødem, pruritis, akne, alopeci, tør hud
- the Summaries of Products Characteristic, labelling and package leaflet proposed by the Marketing
Knogler, led, muskler og bindevæv Almindelig Ikke almindelig
Authorisation Holders has been assessed based on the documentation submitted and the scientific discussion within the Committee,
Artralgi, rygsmerter, smerter i ekstremiteterne, myalgi Muskelsvaghed, nakkesmerter, smerter i endeballen, muskuloskeletale smerter i brystet
the CHMP has recommended the amendment of the Marketing Authorisations for which the Summary of Product Characteristics, labelling and package leaflet are set out in Annex III for Risperdal Consta and associated names (see Annex I).
Det endokrine system Sjælden
18 ANNEX III
Uhensigtsmæssig ADH- sekretion
SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET
Metabolisme og ernæring Ikke almindelig Meget sjælden Ikke kendt
19 SUMMARY OF PRODUCT CHARACTERISTICS
Forøget appetit, nedsat appetit Diabetisk ketoacidose Vandintoksikation
NAME OF THE MEDICINAL PRODUCT
Infektioner og parasitære sygdomme Meget almindelig Infektion i de øvre luftveje Almindelig
RISPERDAL CONSTA and associated names (see Annex I) 12.5 mg powder and solvent for prolonged-release suspension for intramuscular injection [See Annex I – To be completed nationally]
Lungebetændelse, influenza, infektion i de nedre luftveje, bronkitis, urinvejsinfektion, øreinfektion, sinusitis, virusinfektion
RISPERDAL CONSTA and associated names (see Annex I) 25 mg powder and solvent for prolonged- release suspension for intramuscular injection
Cystitis, gastroenteritis, infektion, lokaliseret infektion, subkutan absces
RISPERDAL CONSTA and associated names (see Annex I) 37.5 mg powder and solvent for prolonged-release suspension for intramuscular injection
Traumer, forgiftninger og behandlingskomplikationer Almindelig
RISPERDAL CONSTA and associated names (see Annex I) 50 mg powder and solvent for prolonged- release suspension for intramuscular injection
28
2.
Ikke almindelig Vaskulære sygdomme
QUALITATIVE AND QUANTITATIVE COMPOSITION
Procedurerelaterede smerter
[To be completed nationally]
Hypertension, hypotension Ortostatisk hypotension
For a full list of excipients, see section 6.1.
Almindelig
3.
Ikke almindelig
PHARMACEUTICAL FORM
Sjælden Immunsystemet
[To be completed nationally]
Gulsot
4.
Det reproduktive system og mammae
CLINICAL PARTICULARS
Almindelig Ikke almindelig Ikke kendt Psykiske forstyrrelser
4.1 Therapeutic indications
Amenoré, erektil dysfunktion, galaktoré Seksuel dysfunktion, gynækomasti Priapisme
RISPERDAL CONSTA is indicated for the maintenance treatment of schizophrenia in patients currently stabilised with oral antipsychotics.
Meget almindelig Depression, søvnløshed, angst
4.2 Posology and method of administration
Almindelig Ikke almindelig a
Adults Starting dose:
Tremor omfatter tremor og parkinsons hviletremor.
For most patients the recommended dose is 25 mg intramuscular every two weeks.
Det bør bemærkes, at et bredere spektrum af symptomer, som ikke nødvendigvis har ekstrapyramidal oprindelse, er inkluderet.
For those patients on a fixed dose of oral risperidone for two weeks or more, the following conversion scheme should be considered.
Nedenfor følger en oversigt over yderligere bivirkninger, som er associeret med risperidon, og som er identificeret som bivirkninger i kliniske forsøg med den orale risperidonformulering (RISPERDAL), men som ikke er fastslået som bivirkninger i de kliniske forsøg med RISPERDAL CONSTA.
Patients treated with a dosage of 4 mg or less oral risperidone should receive 25 mg RISPERDAL CONSTA, while patients treated with higher oral doses should be considered for the higher RISPERDAL CONSTA dose of 37.5 mg.
Som ved andre antipsykotika er der efter markedsføringen rapporteret meget sjældne tilfælde af QT - forlængelse med risperidon.
Where patients are not currently taking oral risperidone, the oral pre-treatment dosage should be considered when choosing the i. m. starting dose.
25% af patienterne havde en vægtøgning på ≥ 7%.
The recommended starting dose is 25 mg RISPERDAL CONSTA every two weeks.
Selv om overdosis er mindre sandsynlig for parenterale lægemidler end for orale lægemidler, præsenteres information vedrørende oral indgift.
Patients on higher dosages of the used oral antipsychotic should be considered for the higher RISPERDAL CONSTA dose of 37.5 mg.
Disse omfatter døsighed og sedation, takykardi og hypotension samt ekstrapyramidale symptomer.
A lower initial dose of 12.5 mg may be appropriate when clinical factors warrant dose adjustment, such as in patients with hepatic or renal impairment, for certain drug interactions that increase risperidone plasma concentrations (see section 4.5), or in patients who have a history of poor tolerability to psychotropic medications.
Ved overdosering er der rapporteret QT- forlængelse og krampeanfald.
The efficacy of the 12.5 mg dose has not been investigated in clinical trials.
Kardiovaskulær monitorering bør påbegyndes straks og omfatte kontinuert EKG for at opdage mulige arytmier.
21 Sufficient antipsychotic coverage with oral risperidone or the previous antipsychotic should be ensured during the three-week lag period following the first RISPERDAL CONSTA injection (see section 5.2).
I tilfælde af svære ekstrapyramidale symptomer bør der indgives antikolinergika.
RISPERDAL CONSTA should not be used in acute exacerbations of schizophrenia without ensuring sufficient antipsychotic coverage with oral risperidone or the previous antipsychotic during the three- week lag period following the first RISPERDAL CONSTA injection.
Andre antipsykotika:
Maintenance dose:
Risperidon er en selektiv monoamin antagonist med unikke egenskaber.
For most patients the recommended dose is 25 mg intramuscular every two weeks.
Langtidssikkerheden og - effekten (50 uger) af RISPERDAL CONSTA blev også evalueret i et åbent forsøg med stabile psykotiske indlagte og ambulante patienter, som opfyldte DSM- IV- kriterierne for skizofreni eller skizoaffektiv lidelse.
Some patients may benefit from the higher doses of 37.5 mg or 50 mg.
Absorption Absorptionen af risperidon fra RISPERDAL CONSTA er fuldstændig.
Upward dosage adjustment should not be made more frequently than every 4 weeks.