qanastek/EMEA-V3 huggingface dataset:
As stiripentol inhibited CYP2D6 in vitro at concentrations that are achieved clinically in plasma, drugs that are metabolized by this isoenzyme like: beta-blockers (propranolol, carvedilol, timolol), antidepressants (fluoxetine, paroxetine, sertraline, imipramine, clomipramine), antipsychotics (haloperidol), analgesics (codeine, dextromethorphan, tramadol) may be subject to metabolic interactions with stiripentol.
Peress li stiripentol jinibixxi CYP2D6 in vitro f’ konċentrazzjonijiet li huma miksuba klinikament fil - plażma, mediċini li huma metabolizzati minn din l- iżoenzima bħal: imblokkaturi- beta (propranolol, carvedilol, timolol), antidepressanti (fluoxetine, paroxetine, sertraline, imipramine, clomipramine), antipsikotiċi (haloperidol), analġesici (codeine, dextromethorphan, tramadol) jistgħu jkunu suġġetti għal interazzjonijiet metaboliċi ma ’ stiripentol.
A dose-adjustment may be necessary for drugs metabolised by CYP2D6 and that are individually dose titrated.
Aġġustament fid- doża jista ’ jkun meħtieġ għal mediċini metabolizzati minn CYP2D6 u li għandhom doża ttitrata individwalment.
In the absence of available clinical data, caution should be taken with the following clinically relevant interactions with stiripentol:
Il- potenzjal għal stiripentol li jaffettwa prodotti mediċinali oħra Fin- nuqqas ta ’ dejta klinika disponibbli, għandha tittieħed il- kawtela ma ’ l- interazzjonijiet klinikament relevanti li ġejjin ma ’ stiripentol:
Undesirable combinations (to be avoided unless strictly necessary)
Kombinazzjonijiet mhux mixtieqa (li għandhom jiġu evitati kemm- il darba mhux strettament meħtieġ)
- Rye ergot alkaloids (ergotamine, dihydroergotamine)
- Alkalojdi ergot tas- segala (ergotamine, dihydroergotamine)
Ergotism with possibility of necrosis of the extremities (inhibition of hepatic elimination of rye ergot).
Ergotiżmu b’ possibbilità ta ’ nekrożi ta ’ l- estremitajiet (inibizzjoni ta ’ l- eliminazzjoni epatika ta ’ ergot tas- segala).
- Cisapride, halofantrine, pimozide, quinidine, bepridil
- Cisapride, halofantrine, pimozide, quinidine, bepridil
Increased risk of cardiac arrhythmias and torsades de pointes/ wave burst arrhythmia in particular.
Riskju miżjud ta ’ arritmiji kardijaċi u arritmija torsades de pointes/ wave burst in partikolari.
- Immunosuppressants (tacrolimus, cyclosporine, sirolimus)
- Immunosoppressanti (tacrolimus, cyclosporine, sirolimus)
Raised blood levels of immunosuppressants (decreased hepatic metabolism).
Livelli fid- demm mgħollija ta ’ l- immunosoppressanti (metaboliżmu epatiku mnaqqas).
- Statins (atorvastatin, simvastatin, etc.)
- Statins (atorvastatin, simvastatin, eċċ.)
Increased risk of dose-dependent adverse reactions such as rhabdomyolysis (decreased hepatic metabolism of cholesterol-lowering agent)
Riskju miżjud ta ’ reazzjonijiet avversi dipendenti fuq id- doża bħal ma huma rabdomijoliżi (metaboliżmu epatiku mnaqqas tal- mediċina li tbaxxi l- kolesterol).
Combinations requiring precautions
Kombinazzjonijiet li jinħtieġu prekawzjonijiet
Increased plasma benzodiazepine levels may occur via decreased hepatic metabolism leading to excessive sedation.
Livelli ta ’ benzodiazepine fil- plażma miżjuda jistgħu jseħħu permezz ta ’ metaboliżmu epatiku mnaqqas li jwassal għal sedazzjoni eċċessiva.
- Theophylline, caffeine
- Theophylline, caffeine
Increased plasma levels of theophylline and caffeine may occur via inhibition of their hepatic metabolism, potentially leading to toxicity.
Livelli ta ’ theophylline u kaffeina fil- plażma miżjuda jistgħu jseħħu permezz ta ’ inibizzjoni tal- metaboliżmu epatiku tagħhom, potenzjalment iwasslu għal tossiċità.
These combinations should be avoided.
Dawn il- kumbinazzjonijiet għandhom jiġu evitati.
Stiripentol enhances the central depressant effect of chlorpromazine.
Stiripentol ikabbar l- effett dipressanti ċentrali ta’ chlorpromazine.
In a French compassionate use program for Diacomit, topiramate was added to Diacomit, clobazam and valproate in 41% of 230 cases.
Fi programm ta ’ użu kompassjonanti Franċiż għal Diacomit, topiramate kien miżjud ma ’ Diacomit, clobazam u valproate f ’ 41% ta ’ 230 każijiet.
Based on the clinical observations in this group of patients, there is no evidence to suggest that a change in topiramate dose and dosage schedules is needed if co- administered with stiripentol.
Skond l- osservazzjonijiet kliniċi f’ dan il- grupp ta ’ pazjenti, ma ’ hemm l- ebda evidenza li tissuġġerixxi li bidla fid- dożaġġ u skedi ta ’ dożaġġ hija meħtieġa jekk amministrat flimkien ma ’ stiripentol.
With regard to topiramate, it is considered that potential competition of inhibition on CYP2C19 should not occur because it probably requires plasma concentrations 5 – 15 times higher than plasma concentrations obtained with the standard recommended topiramate dose and dosage schedules.
Fir- rigward ta ’ topiramate, huwa kkunsidrat li l- kompetizzjoni potenzjali ta ’ inibizzjoni fuq CYP2C19 m’ għandhiex isseħħ peress li probabbli teħtieġ konċentrazzjonijiet fil- plażma 5- 15 il- darba ogħla minn konċentrazzjonijiet fil- plażma miksuba bid- doża u skedi ta ’ dożaġġ standard irrakkomandati ta ’ topiramate.
Levetiracetam does not undergo hepatic metabolism to a major extent.
Levetiracetam ma ’ jgħaddix minn metaboliżmu epatiku ta ’ estensjoni maġġura.
As a result, no pharmacokinetic metabolic drug interaction between stiripentol and levetiracetam is anticipated.
B’ riżultat, l- ebda interazzjoni farmakokinetika, metabolika tal- mediċina bejn stiripentol u levitiracetam ma hija antiċipata.
Risk related to epilepsy and antiepileptic medicinal products in general:
Riskju relatat ma ’ l- epilessija u prodotti mediċinali anti- epilettiċi in ġenerali:
It has been shown that in the offspring of women with epilepsy, the prevalence of malformations is two to three times greater than the rate of approximately 3% in the general population.
Ġiet murija li l- prevalenza ta ’ malformazzjonijiet hija tnejn jew tliet darbiet akbar mir- rata ta ’ madwar 3% fil- popolazzjoni inġenerali fil- wild ta ’ nisa bl- epilessija.
Although other factors, e. g. the epilepsy, can contribute, available evidence suggests that this increase, to a large extent, is caused by the treatment.
Għalkemm fatturi oħra, eż. l- epilessija, jistgħu jikontribwixxu, l- evidenza li hemm tissuġġerixxi li din iż- żieda, fil- parti l- kbira, hija kkaġunata mit- trattament.
In the treated population, an increase in malformations has been noted with polytherapy.
Fil- popolazzjoni ttrattata, żieda fil- malformazzjonijiet ġiet innotata bil- politerapija.
However, effective anti-epileptic therapy should not be interrupted during pregnancy, since the aggravation of the illness may be detrimental to both the mother and the foetus.
Madankollu, terapija anti- epilettika (kontra l- aċċessjonijiet) effettiva m’ għandhiex tiġi interotta waqt it- tqala, peress li l- aggravament tal- marda jista ’ jkun detrimentali kemm għal omm u kemm għal fetu.
Risk related to Diacomit:
Riskju relatat ma ’ Diacomit:
No data on exposed pregnancies are available.
Ma hemm l- ebda dejta fuq tqaliet esposti.
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, foetal development, parturition or postnatal development at non-maternotoxic doses (See, section 5.3).
Studji fl- annimali ma jindikawx effetti ta ’ ħsara diretti jew indiretti b’ rispett għat- tqala, żvilupp fetali, ħlas u żvilupp ta ’ wara t- twelid f’ dożi li mhumiex tossiċi għal omm (Ara, sezzjoni 5. 3).
In view of the indication, administration of Diacomit during pregnancy and in women of childbearing potential would not be expected.
In vista ta ’ din l- indikazzjoni, l- għoti ta ’ Diacomit waqt it- tqala u f’ nisa b’ potenzjal li jista ’ jkollhom it- tfal mhix mistennija.
The clinical decision for use of Diacomit in pregnancy needs to be made on an individual patient basis taking into consideration the potential clinical benefits and risks.
Id- deċiżjoni klinika għall- użu ta ’ Diacomit fit - tqala jeħtieġ li tiġi magħmula fuq bażi ta ’ pazjenta individwali u jittieħdu inkonsiderazzjoni r- riskji u l- benefiċċji kliniċi potenzjali.
Caution should be exercised when prescribing to pregnant women and use of efficient methods of contraception is advisable.
Għandha tiġi eżerċitata l- kawtela meta tagħti b’ riċetta lill- nisa tqal u l - użu ta ’ metodi effiċjenti ta ’ kontraċezzjoni huma rrakkomandati.
During pregnancy:
Waqt it- tqala:
Effective anticonvulsant treatment with Diacomit must not be stopped during pregnancy as worsening of the disease is potentially harmful to both mother and foetus.
Trattament kontra l- aċċessjonijiet b’ Diacomit m’ ghandux jitwaqqa ’ waqt it- tqala għax deterjorament tal- marda huwa potenzjalment ta ’ ħsara kemm għall- omm u kemm għall- fetu.
In the absence of human studies on excretion in breast milk, and given that stiripentol passes freely from plasma into milk in the goat, breast-feeding is not recommended during treatment.
Fin- nuqqas ta ’ studji dwar l- eliminazzjoni fil- ħalib mis- sider uman, u mogħti li stiripentol jgħaddi mill- plażma għal ġol- ħalib fil- mogħża, it- treddigħ mhux rakkomandat waqt it- trattament.
In case Diacomit therapy is continued during breast-feeding, the breast-fed infant should be carefully observed for potential adverse effects.
F’ każ li terapija b’ Diacomit titkompla waqt it- treddigħ, it- tarbija li tkun qed terda ’ għandu tkun sorveljata mill - qrib għall- effetti avversi potenzjali.
4.7 Effects on ability to drive and use machines
6 4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
Patients with SMEI would not be expected to drive or operate machinery due to the nature of the underlying disease and the effects of long term administration of anticonvulsant drugs.
Pazjenti b’ SMEI m’ għandhomx ikunu mistennija li jsuqu jew iħaddmu inġenji minħabba n- natura tal- marda eżistenti u l- effetti ta ’ amministrazzjoni ta ’ mediċini kontra l- aċċessjonijiet fuq tul ta ’ żmien.
Diacomit may cause dizziness and ataxia that may affect ability to drive and use machines and patients should not drive or use machinery whilst on Diacomit therapy.
Diacomit jista ’ jikkaġuna sturdament u atassja li tista ’ teffettwa l- ħila li ssuq u li tuża l- inġenji u l - pazjenti m’ għandhomx isuqu jew jużaw inġenji waqt terapija b’ Diacomit.
Adverse reactions encountered most often are as follows: very common (≥ 1/ 10), common (≥ 1/ 100, < 1/ 10), uncommon (≥ 1/ 1,000, < 1/ 100), rare (≥ 1/ 10,000, < 1/ 1,000), very rare (< 1/ 10,000, including isolated cases), frequency not known (cannot be estimated from the available data).
Reazzjonijiet avversi li wieħed jiltaqa ’ magħhom ta ’ spiss huma kif ġej: komuni ħafna (≥ 1/ 10), komuni (≥ 1/ 100, < 1/ 10), mhux komuni (≥ 1/ 1, 000, < 1/ 100), rare (≥1/ 10, 000, < 1/ 1, 000), rari ħafna (< 1/ 10, 000, li jinkludu każijiet iżolati), frekwenza mhix magħrufa (ma tistax tiġi stmata mit- tagħrif disponibbli).
Within each frequency grouping, undesirable effects are presented in order of decreasing severity.
Fi ħdan kull ragruppament ta ’ frekwenzi, l- effetti mhux mixtieqa qegħdin jiġu ppreżentati skond severità li dejjem tonqos.
6 System/ organ classes
Klassifika tas- sistema ta ’ l- organi
System Organ Class (MedDRA terminology)
Sistema tal- Klassifika ta ’ l- Organi (Reġsitru ta ’ MedDRA)
Common
Komuni Ħafna
Neutropenia Persistent severe neutropenia usually resolves spontaneously when Diacomit is stopped.
Newtropenja Newtropenja severa u persistenti ġeneralment tirriżolvi b’ mod spontaneju meta Diacomit jitwaqqaf.
Metabolism and nutrition disorders
Disturbi fil- metaboliżmu u n- nutrizzjon
Anorexia, loss of appetite, weight loss (especially when combined with sodium valproate)
Anoreksja, telf ta ’ aptit, telf fil- piż (speċjalment meta kkombinat ma ’ sodium valproate)
Psychiatric Disorders
Disturbi psikjattriċi
Aggressiveness, irritability, behaviour disorders, opposing behaviour, hyperexcitability, sleep disorders
Aggressività, irritabilità, disturbi ta ’ mġieba, mġieba opposta, ipereċitabilità, disturbi fl- irqad
Nervous system disorders Eye disorders
Disturbi fis- sistema nervuża
Drowsiness, ataxia, hypotonia, dystonia
Ngħas, atassja, ipotonja, distonja
Hyperkinesias
Iperkinesi
Diplopia (when used in combination with carbamazepine)
Diplopja (meta użat flimkien ma ’ carbamazepine)
Gastrointestinal disorders
Disturbi gastro - intestinali
Nausea, vomiting
Nawsja, rimettar
Skin and subcutaneous tissue disorders General disorders
Disturbi fil- ġilda u t- tessut ta ’ taħt il- ġilda Disturbi ġenerali
Photosensitivity, rash, cutaneous allergy, urticaria Fatigue
Fotosensitività, raxx, allerġija tal- ġilda, urtikarja Għeja
Investigations
Investigazzjoniji et
Raised γ GT (notably when combined with carbamazepine and valproate).
γGT ogħla (b’ mod partikolari meta jingħata flimkien ma ’ carbamazepine u valproate).
Many of the above adverse reactions are often due to an increase in plasma levels of other anticonvulsant medicinal products (See, sections 4.4 and 4.5) and may regress when the dose of these medicinal products is reduced.
7 Ħafna mir- reazzjonijiet avversi t’ hawn fuq huma ta ’ spiss dovuti għal żieda fil- livelli ta ’ plażma ta ’ prodotti mediċinali anti- konvulsanti (Ara, sezzjonijiet 4. 4 u 4. 5) u jistgħu jonqsu meta d- doża ta ’ dawn il- prodotti mediċinali titnaqqas.
Data on clinical overdose are not available.
Dejta minn doża eċċessiva mhix disponibbli.
Treatment is supportive (symptomatic measures in intensive care units).
It- trattament hu t’ appoġġ (miżuri sintomatiċi fit - taqsimiet tal- kura intensiva).
Other Antiepileptics, ATC code:
Antiepilletiċi oħra, Kodiċi ATC:
N03AX17 In animal models, stiripentol antagonizes seizures induced by electric shock, pentetrazole and bicuculline.
N03AX17 F’ mudelli ta ’ annimali, stiripentol jantagonizza l- aċċessjonijiet sensitizzati permezz ta ’ xokk elettriku, pentetrazole u bicuculline.
In rodent models, stiripentol appears to increase brain levels of gamma-aminobutyric acid (GABA) - the major inhibitory neurotransmitter in mammalian brain.
F’ mudelli ta ’ annimali gerriema, stiripentol jidher li jżid il- livelli fil- moħħ ta’ gamma- aminobutyric acid (GABA) – in- newrotrasmittatur inibitur maġġur fil- moħħ tal- mammiferi.
This could occur by inhibition of synaptosomal uptake of GABA and/ or inhibition of GABA transaminase.
Dan jista ’ jseħħ permezz ta ’ inibizzjoni ta ’ teħid sinaptosomali ta ’ GABA u/ jew inibizzjoni ta ’ GABA transaminase.
Stiripentol potentiates the efficacy of other anticonvulsants, such as
Stiripentol ukoll deher li jtejjeb it- trasmissjoni medjata minn riċettaturi GABAA fil - ħippokampus tal- far immatur u jżid it- tul ta ’ żmien miftuħ medju (iżda mhux il- frekwenza) ta ’ kanali tal- klorur tar- riċettaturi GABA minn mekkaniżmu bħal tal- barbiturati.
7 carbamazepine, sodium valproate, phenytoin, phenobarbital and many benzodiazepines, as the result of pharmacokinetic interactions.
Stiripentol jqawwi l- effikaċja ta ’ antikonvulsanti oħra, bħal ma huma carbamazepine, sodium valproate, phenytoin, phenobarbital u ħafna benzodiazepines, bħala riżultat ta ’ interazzjonijiet farmakokinetiċi.
The second effect of stiripentol is mainly based on metabolic inhibition of several isoenzymes, in particular CYP450 3A4 and 2C19, involved in the hepatic metabolism of other anti-epileptic drugs.
It- tieni effett ta ’ stiripentol huwa bbażat prinċipalment fuq inibizzjoni metabolika ta ’ diversi iżoenzimi, in partikolari CYP450 u 2C19, involuti fil- metaboliżmu epatiku ta ’ mediċini anti- epilettiċi (kontra l- epilessija) oħra.
The pivotal clinical evaluation of Diacomit was in children of 3 years of age and over with SMEI.
L- evalwazzjoni klinika ewlenija ta ’ Diacomit kienet fi tfal ta ’ età ta ’ 3 snin jew aktar b’ SMEI.
A French compassionate use program included children from 6 months of age because the diagnosis of Dravet’ s syndrome may be made with confidence at that age in some patients.
Program ta ’ użu kompassjonanti Franċiż inkluda tfal minn età ta ’ 6 xhur minħabba li d- djanjożi tas - sidromu ta ’ Dravet jista ’ jsir b’ kunfidenza f’ dik l- età f’ xi pazjenti.
The clinical decision for use of Diacomit in children with SMEI less than 3 years of age needs to be made on an individual patient basis taking into consideration the potential clinical benefits and risks (See, section 4.2).
Id- deċiżjoni klinika għall- użu ta ’ Diacomit fit- tfal b’ SMEI ta ’ età anqas minn 3 snin għandha tiġi magħmula fuq bażi individwali billi jittieħdu inkonsiderazzjoni l- benefiċċji u r- riskji kliniċi potenzjali (Ara sezzjoni 4. 2).
41 children with SMEI were included in a randomised, placebo-controlled, add-on trial.
41 tfal b’ SMEI kienu inklużi fi studju add- on, randomizzat u kkontrollat bil- plaċebo.
After a baseline period of 1 month, placebo (n=20) or stiripentol (n=21) was added to valproate and clobazam during a double-blind period of 2 months.
Wara perijodu fil- linja bażi ta ’ riferiment ta ’ xahar, plaċebo (n=20) jew stiripentol (n=21) kienu miżjuda ma ’ valproate u clobazam waqt perijodu double- blind ta ’ xahrejn.
Patients then received stiripentol in an open fashion.
Il- pazjenti mbagħad ingħataw stiripentol b’ mod miftuħ.
Responders were defined as having more than 50% reduction in the frequency of clonic (or tonic- clonic) seizures during the second month of the double-blind period compared with baseline.
Dawk li rrispondew kienu mfissra bħala li kellhom aktar minn 50% tnaqqis fil - frekwenza ta ’ aċċessjonijiet kloniċi (jew toniċi- kloniċi) waqt it- tieni xahar tal- perijodu double- blind imqabbla mal- linja bażi.
15 (71%) patients were responders on stiripentol (including nine free of clonic or tonic-clonic seizures), whereas there was only one (5%) on placebo (none was seizure free; stiripentol 95% CI 52.1-90.7 vs. placebo 0-14.6).
15- il (71%) pazjent kienu dawk fuq stiripentol li rrispondew (inklużi disgħa ħielsa minn aċċessjonijiet kloniċi jew toniċi- kloniċi), filwaqt kien hemm wieħed biss (5%) fuq plaċebo (l- ebda minnhom ma ’ kienu ħielsa mill- aċċessjonijiet; stiripentol 95% CI 52. 1- 90. 7 vs. plaċebo 0- 14. 6).
The 95% CI of the difference was 42.2-85.7.
Il- 95% CI tad- differenza kien 42. 2- 85. 7.
Percentage of change from baseline was higher on stiripentol (-69%) than on placebo (+7%), p < 0.0001.
Il- persentaġġ ta ’ bidla mill- linja bażi kien ogħla fuq stiripentol (- 69%) milli fuq il- plaċebo (+7%), p < 0. 0001.
21 patients on stiripentol had moderate side- effects (drowsiness, loss of appetite) compared with eight on placebo, but side-effects disappeared when the dose of comedication was decreased in 12 of the 21 cases (Chiron et al, Lancet, 2000).
21 pazjent fuq stiripentol kellhom effetti mhux mixtieqa moderati (ngħas, telf ta ’ aptit) imqabbla ma ’ tmienja fuq il- plaċebo, imma l- effetti mhux mixtieqa sparrixew meta d- doża ta ’ medikazzjoni konkomitanti kienet imnaqqsa fi 12 mill- 21 każ (Chiron et al, Lancet, 2000).
This medicinal product has been authorised under a “ conditional approval” scheme.
Dan il- prodott mediċinali kien awtorizzat taħt dik li tissejjaħ skema ta ’ “ approvazzjoni ta ’ kondizzjoni ”.
This means that further evidence on this medicinal product is awaited, in particular about the efficacy of stiripentol in combination with the maximum safe dose of the add-on therapy.
Dan ifisser li għad tingħata aktar evidenza dwar dan il- prodott mediċinali, b’ mod partikolari dwar l- effikaċja ta ’ stiripentol meta jingħata bid- doża sikura massima tat- terapija add- on.
A study is being conducted to investigate this.
Qed isir studju biex dan jiġi mistħarreġ.
The European Medicines Agency (EMEA) will review new information on the product every year and this SPC will be updated as necessary.
L- Aġenzija Ewropeja dwar il- mediċini (EMEA) ser tirrevedi l- informazzjoni l- ġdida dwar il- prodott kull sena u ser taġġorna dan is- Sommarju tal- Karatteristiċi tal- Prodott, skond il- bżonn.
The following pharmacokinetic properties of stiripentol have been reported from studies in adult healthy volunteers and adult patients.
Il- proprjetajiet farmakokinetiċi li ġejjin dwar stiripentol ġie rraportat minn studju fuq voluntiera adulti b’ saħħithom u pazjenti adulti.
Absorption / Bioavailability:
Assorbiment / Bijodisponibilità:
Stiripentol is quickly absorbed, with a time to peak plasma concentration of about 1.5 hours.
Stiripentol huwa assorbit malajr, bil- ħin biex tintlaħaq il- konċentrazzjoni tal- quċċata fil- plażma ta ’ madwar 1. 5 sigħat.
The absolute bioavailability of stiripentol is not known since an intravenous formulation is not available for testing.
Il- bijodisponibbilità assoluta ta ’ stiripentol mhix magħrufa peress li formulazzjoni intravenuża ma teżistix biex tiġi ttestjata.
It is well absorbed by the oral route since the majority of an oral dose is excreted in urine.
Huwa assorbit tajjeb permezz tar- rotta orali peress li l - maġġoranza tad- doża orali hija eliminata fl- awrina.
Stiripentol binds extensively to circulating plasma proteins (about 99%).
Stiripentol jingħaqad b’ mod estensiv ma ’ proteini fil- plażma li qegħdin fiċ- ċirkolazzjoni (madwar 99%).
Systemic exposure to stiripentol increases markedly compared to dose proportionality.
L- esponiment sistemiku għal stiripentol jiżdied bil- bosta meta mqabbel ma ’ proporzjonalità tad- doża.
Plasma clearance decreases markedly at high doses; it falls from approximately 40 l/ kg/ day at the dose of 600 mg/ day to about 8 l/ kg/ day at the dose of 2400 mg.
Ir- rata ta ’ eliminazzjoni mill- plażma tonqos bil- bosta f’ dożi għoljin; hija taqgħa minn madwar 40l/ kg/ kuljum fid- doża ta ’ 600 mg/ kuljum għal madwar 8 l/ kg/ kuljum fid- doża ta ’ 2400 mg.
Clearance is decreased after repeated administration of stiripentol, probably due to inhibition of the cytochrome P450 isoenzymes responsible for its metabolism.
It - tneħħija tonqos wara amministrazzjoni ripetuta ta ’ stiripentol, probabbilment minħabba inibizzjoni tal - iżoenzimi cytochrome P450 risponsabbli għal metaboliżmu tiegħu.
The half-life of elimination was in the range of 4.5 hours to 13 hours, increasing with dose.
Il- half- life ta ’ l- eliminazzjoni kienet fuq medda ta ’ 4. 5 sigħat sa 13- il siegħa, u tiżdied mad- doża.
8 Metabolism:
Metaboliżmu:
Stiripentol is extensively metabolized, 13 different metabolites having been found in urine.
Stiripentol huwa metabolizzat b’ mod estensiv, b’ 13- il metabolit differenti jinstab fl- awrina.
The main metabolic processes are demethylenation and glucuronidation, although precise identification of the enzymes involved has not yet been achieved.
Il- proċessi metaboliċi ewlenin huma demetilazzjoni u glukorinidazzjoni, għalkemm identifikazzjoni preċiża ta ’ l - enzimi involuti għandha ma ġietx stabbilita.
On the basis of in vitro studies, the principal liver cytochrome P450 isoenzymes involved in phase 1 metabolism are considered to be CYP1A2, CYP2C19 and CYP3A4.
Fuq il- bażi ta ’ studji in vitro, l- isoenzimi prinċipali tal- fwied ta ’ ċitokrom P450 involuti fil - metaboliżmu ta ’ fażi 1 huma kkunsidrati li huma CYP1A2, CYP2C19 u CYP3A4.
Most stiripentol is excreted via the kidney.
Il- biċċa l- kbira ta ’ stiripentol huwa eliminat permezz tal- kliewi.
Urinary metabolites of stiripentol accounted collectively for the majority (73%) of an oral acute dose whereas a further 13-24% was recovered in faeces as unchanged drug.
Metaboliti mill- awrina ta ’ stiripentol kollettivament kienet tgħodd għal maġġoranza (73%) ta ’ doża akuta orali, filwaqt li 13- 24% aktar kienet irkuprata mill- ippurgar bħala mediċina mhix mibdula.
Bioavailability / Bioequivalence:
Bijodisponibilità / Bijoekwivalenza:
Relative bioavailabilty between the capsules and powder for oral suspension in sachet formulations has been studied in healthy male volunteers after a 1,000mg single oral administration.
Il- bijodisponibilità relattiva bejn il- kapsuli u t- trab għal suspensjoni orali f’ formulazzjonijiet tal- qratas ġiet studjata f’ voluntiera rġiel b’ saħħithom wara l- għoti ta ’ 1, 000 mg mill- ħalq f’ darba.
The two formulations were bioequivalent in terms of AUC but not in terms of Cmax.
Iż- żewġ formulazzjonijiet kienu bijoekwivalenti f’ termini ta ’ AUC imma mhux f’ termini ta ’ Cmax.
Cmax of the sachet was slightly higher (23%) compared with the capsule and did not meet the criteria for bioequivalence.
Il- Cmax tal- qartas kien kemxejn ogħla (23%) meta mqabbel mal- kapsula u ma ssodisfax il- kriterji dwar bijoekwivalenza.
Tmax was similar with both formulations.
Tmax kien simili għaż- żewġ formulazzjonijiet.
Clinical supervision is recommended if switching between the stiripentol capsule and powder for oral suspension in sachet formulations.
Is- superviżjoni klinika hija rakkomandata jekk pazjenti jinqalbu minn mal- kapsula stiripentol u t- trab għal suspensjoni orali fil- formulazzjonijiet tal- qratas.
5.3 Preclinical safety data Toxicity studies in animals (rat, monkey, mouse) have not revealed any consistent pattern of toxicity apart from liver enlargement associated with hepatocellular hypertrophy, which occurred when high doses of stiripentol were administered to both rodents and nonrodents.
Studji dwar it- tossiċità fl- annimali (far, xadina, ġurdien) ma rrevelaw l- ebda disinn konsistenti ta ’ tossiċità minbarra tkabbir fil- fwied assoċjat ma ’ ipertrofija epatoċellulari, li seħħet meta dożi għoljin ta ’ stiripentol kienu amministrati kemm lill- annimali gerriema u kemm lil dawk mhux gerriema.
This finding is considered to be an adaptive response to a high metabolic burden on the liver.
Dawn ir- riżultati huma kkunsidrati li huma reazzjoni ta ’ adattament għat- tagħbija metabolika għolja fuq il - fwied.
Stiripentol was not teratogenic when tested in the rat and rabbit; in one study in the mouse, but not in several other similar studies, a low incidence of cleft palate formation was observed at a maternotoxic dose (800 mg/ kg/ day).
Stiripentol ma kienx teratoġeniku meta ttestjat fil- far jew fil- fenek; f’ wieħed mill- istudji fil - ġurdien, iżda mhux f’ bosta studji oħra simili, inċidenza baxxa ta ’ formazzjoni tas- saqaf tal- ħalq maqsum kienet osservata f’ doża maternotossika (800mg/ kg/ kuljum).
These studies in mice and rabbits were undertaken prior to the introduction of Good Laboratory Practice requirements.
Dawn l- istudji fil- ġrieden u fil - fniek kienu magħmula qabel l- introduzzjoni ta ’ ħtiġijiet ta ’ Prattika tal- Laboratorju Tajba.
Studies in the rat on fertility and general reproductive performance and on pre- and postnatal development were uneventful except for a minor reduction in the survival of pups nursed by mothers exhibiting toxic responses to stiripentol at a dose of 800 mg/ kg/ day (See, section, 4.6).
9 kienu bla problemi ħlief għal tnaqqis żgħir fis- sopravivenza tal- ġriewi imreddgħin minn ommijiet li kienu qed juru reazzjonijiet tossiċi għal stiripentol f’ doża ta ’ 800 mg/ kg/ kuljum (Ara, sezzjoni, 4. 6).
Genotoxicity studies have not detected any mutagenic or clastogenic activity.
Studji ġenotossiċi ma wrew l- ebda attivita mutaġenika jew klastoġenika.
Carcinogenicity studies gave negative results in the rat.
Studji ta ’ karċinoġenetiċità taw riżultati negattivi għal far.
In the mouse there was only a small increase in the incidence of hepatic adenomas and carcinomas in animals treated with 200 or 600mg/ kg/ day for 78 weeks but not in those given 60mg/ kg/ day.
Fil- ġurdien kien hemm żieda żgħira fl - inċidenza ta ’ adenomi u karċinomi epatiċi f’ annimali ttrattati b’ 200 jew 600 mg/ kg/ kuljum għal 78- il ġimgħa iżda mhux f’ dawk mgħotija 60 mg/ kg/ kuljum.
In view of the lack of genotoxicity of stiripentol and the well known, special susceptibility of the mouse liver to tumour formation in the presence of hepatic enzyme induction, this finding is not considered to indicate a risk of tumorigenicity in patients.
Minħabba in- nuqqas ta ’ ġenotossiċità ta ’ stiripentol u s- suxxettibilità speċjali, magħrufa sewwa tal- fwied tal- ġurdien għal formazzjoni ta ’ tumur fil- preżenza ta ’ induzzjoni ta ’ l- enzima epatika, dawn ir- riżultati mhumiex ikkunsidrati li jindikaw riskju ta ’ tumuriġeneċità fil- pazjenti.
povidone K29/ 32 sodium starch glycolate (type A) magnesium stearate
povidone K29/ 32 sodium starch glycolate (tip A) magnesium stearate
Capsule shell Gelatin Titanium dioxide (E171) Erythrosine (E127) Indigotine (E132)
Il- qoxra tal- kapsula Gelatin Titanium dioxide (E171) Erythrosine (E127) Indigotine (E132)
Not applicable.
6. 2 Inkompatibilitajiet Ma jgħoddx f’ dan il- każ.
6.4 Special precautions for storage
6. 3 Żmien kemm idum tajjeb il- prodott mediċinali 3 snin
6.5 Nature and contents of container
6. 4 Prekawzjonijiet speċjali għall- ħażna Aħżen fil- pakkett oriġinali, sabiex tilqa ’ mid- dawl..
Polypropylene bottle with tamper-evident seal and polyethylene screw cap.
6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih Flixkun tal- polypropylene bottle b’ siġill ta ’ evidenza ta ’ meta jinfetaħ u b’ għatu tal- kamin tal - polyethylene.
Bottles of 30, 60 and 90 capsules in cardboard cartons.
Fliexken ta ’ 30, 60 u 90 kapsula f’ pakketti tal- kartun.
6.6 Special precautions for disposal and other handling
6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema u għal immaniġġar ieħor L- ebda ħtiġijiet speċjali.
Biocodex, 7 Avenue Gallieni, 94250 Gentilly, France.
Biocodex, 7 Avenue Gallieni, 94250 Gentilly, Franza.
MARKETING AUTHORISATION NUMBER(S)
NUMRU( I) TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ EU/ 1/ 06/ 367/ 001- 03
DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION
DATA TA ’ L- EWWEL AWTORIZZAZZJONI/ TIĠDID TA ’ L- AWTORIZZAZZJONI 04/ 01/ 2007
Diacomit 500 mg hard capsules
Diacomit 500 mg kapsuli iebsin
Each capsule contains 500 mg of stiripentol
Kull kapsula fiha 500 mg ta ’ stiripentol
0.32 mg sodium per capsule.
0. 32 mg sodium għal kull kapsula.
Size 0, white capsule
Daqs 0, kapsula bajda
There are no clinical study data to support the use of Diacomit as monotherapy in Dravet’ s syndrome.
M’ hemm l- ebda tagħrif minn studju kliniku li jissostanza l- użu ta ’ Diacomit bħala monoterapija fis - sindromu ta ’ Dravet.
Dose adjustments of other antiepileptics used in combination with Diacomit Despite the absence of comprehensive pharmacology data on potential drug interactions, the following advice regarding modification of the dose and dosage schedules of other anti-epileptic medicinal products administered in conjunction with Diacomit is provided based on clinical experience.
Aġġustamenti fid- doża ta ’ antielettiċi oħra użati flimkien ma ’ Diacomit Minkejja n- nuqqas ta ’ tagħrif dwar farmakoloġija komprensiva dwar l- effetti potenzjali fuq mediċini, ir- rakkomandazzjonijiet li ġejjin fir- rigward ta ’ modifiċi fid- doża u l- iskedi tad- dożaġġ ta ’ prodotti mediċinali anti- epilettiċi mogħtija flimkien ma ’ Diacomit qed tiġi mogħtija skond l- esperjenza klinika.
Abnormal Laboratory Findings In the event of an abnormal blood count or liver function test finding, the clinical decision for continuing use or adjusting the dose of Diacomit in conjunction with adjusting the doses of clobazam and valproate needs to be made on an individual patient basis taking into consideration the potential clinical benefits and risks (See, section 4.4).
Riżultati Abnormali tal- laboratorju Fil- każ ta ’ riżultati abnormali fl- għadd tad- demm jew fit- test tal- funzjoni tal- fwied, id- deċizjoni klinika biex jitkompla l- użu jew l- aġġustament tad- doża ta ’ Diacomit flimkien ma ’ l- aġġustament tad - dożi ta ’ clobazam u valproate għandha tiġi magħmula fuq bażi individwali u għandhom jittieħdu in konsiderazzjoni l- benefiċċji u r- riskji kliniċi potenzjali (Ara, sezzjoni 4. 4).
Data are limited about the use of Diacomit under 12 months of age.
Hemm dejta ristretta dwar l- użu ta ’ Diacomit f’ età taħt it- tnax- il xahar.
12 4.4 Special warnings and precautions for use
4. 4 Twissijiet speċjali u prekawzjonijiet għall- użu
Given the frequency of gastrointestinal adverse reactions to treatment with Diacomit and valproate (anorexia, loss of appetite, nausea, vomiting), the growth rate of children under this combination of treatment should be carefully monitored.
12 Minħabba l- frekwenza ta ’ reazzjonijiet avversi gastrointestinali għat- trattament b’ Diacomit u valproate (anoressja, telf t’ aptit, dardir, remettar), ir- rata ta ’ l- iżvilupp tat- tfal taħt din il- kombinazzjoni tat - trattament għandha tkun sorveljata bir- reqqa.
Stiripentol is an inhibitor of the enzymes CYP2C19, CYP3A4 and CYP2D6 and may markedly increase the plasma concentrations of drugs metabolised by these enzymes and increase the risk of adverse effects (See, section 4.5.).
Stiripentol huwa inibitur ta ’ l- enzimi CYP2C19, CYP3A4 u CYP2D6 u jista ’ jżid bil- bosta l - konċentrazzjonijiet fil- plażma ta ’ mediċini metabolizzati minn dawn l- enżimi u jżid ir- riskju ta ’ reazzjonijiet avversi (Ara, sezzjoni 4. 5).
Caution is advised when combining stiripentol with other drugs that inhibit or induce one or more of these enzymes.
L - attenzjoni hi rakkomandata meta tħallat stiripentol ma ’ mediċini oħrajn li jinibixxu jew jinduċu wieħed jew aktar minn dawn l- enzimi..
Caution must be exercised if clinical circumstances require combining stiripentol with drugs metabolised by CYP2C19 (e. g. citalopram, omeprazole) or CYP3A4 (e. g.
Għandha tintuża l- kawtela jekk ċirkostanzi kliniċi jeħtieġu li stiripentol jiġi kkombinat ma ’ mediċini metabolizzati minn CYP2C19 (e. ż. citalopram, omeprazole) jew CYP3A4 (e. ż. inibituri HIV protease, antistaminiċi bħal astemizole, chlorpheniramine, imblokkaturi tal- kanali tal- kalċju, statins, kontraċettivi orali, kodeina) minħabba r- riskju akbar ta ’ reazzjonijiet avversi (ara aktar f’ din is -
HIV protease inhibitors, antinistamines such as astemizole, chlorpheniramine, calcium channel blockers, statins, oral contraceptives, codeine) due to the increased risk of adverse events (see further in this section for 13 antiepileptic drugs).
13 sezzjoni għal mediċini antiepilettiċi).
Increased plasma levels of theophylline and caffeine may occur via inhibition of their hepatic metabolism, potentially leading to toxicity.
Livelli ta ’ theophylline u kaffeina fil- plażma miżjuda jistgħu jseħħu permezz ta ’ inibizzjoni tal - metaboliżmu epatiku tagħhom, potenzjalment iwasslu għal tossiċità.
- Effects on other AEDs
- Effects on other AEDs
Inhibition of CYP450 isoenzyme CYP2C19 and CYP3A4 may provoke pharmacokinetic interactions (inhibition of their hepatic metabolism) with phenobarbital, primidone, phenytoin, carbamazepine, clobazam (See, section 4.2), valproate (See, section 4.2), diazepam (enhanced myorelaxation), ethosuximide, and tiagabine.
Inibizzjoni ta ’ CYP450 iżoenzima CYP2C19 u CYP3A4 jistgħu jqanqlu interazzjonijiet farmakokinetiċi (inibitur tal- metaboliżmu epatiku tagħhom) ma ’ phenobarbital, primidone, phenytoin, carbamazepine, clobazam (Ara, sezzjoni 4. 2), valproate (Ara, sezzjoni 4. 2), diazepam (rilassjoni tal - muskoli mtejjba), ethosuximide, u tiagabine.
The consequences are increased plasma levels of these anticonvulsants with potential risk of overdose.
Hija
14
14 rrakkomandata sorveljanza klinika tal- livelli fil- plażma ta ’ anticonvulsants (mediċini kontra l - aċċessjonijiet) oħra meta kkumbinati ma ’ stiripentol b’ aġġustamenti fid- doża possibbli.
Risk related to epilepsy and antiepileptic medicinal products in general:
Riskju relatat ma ’ l- epilessija u prodotti mediċinali anti- epilettiċi b’ mod ġenerali:
Risk related to Diacomit:
Riskju relata ma ’ Diacomit:
4.8 Undesirable effects
15 4. 8 Effetti mhux mixtieqa
15 System/ organ classes
Klassifika tas- sistema ta ’ l- organi
Many of the above adverse reactions are often due to an increase in plasma levels of other anticonvulsant medicinal products (See, sections 4.4 and 4.5) and may regress when the dose of these medicinal products is reduced.
Ħafna mir- reazzjonijiet avversi t’ hawn fuq huma ta ’ spiss dovuti għal żieda fil- livelli ta ’ plażma ta ’ prodotti mediċinali anti- konvulsanti (Ara, sezzjonijiet 4. 4 u 4. 5) u jistgħu jonqsu meta d- doża ta ’ dawn il- prodotti mediċinali titnaqqas.
Stiripentol has also been shown to enhance GABAA receptor-mediated transmission in the immature rat hippocampus and increase the mean open-duration (but not the frequency) of GABAA receptor chloride channels by a
Stiripentol ukoll deher li jtejjeb it- trasmissjoni medjata minn riċettaturi GABAA fil - ħippokampus tal- far immatur u jżid it- tul ta ’ żmien miftuħ medju (iżda mhux il- frekwenza) ta ’ kanali tal- klorur tar- riċettaturi GABA minn mekkaniżmu bħal tal- barbiturati.
Stiripentol potentiates the efficacy of other anticonvulsants, such as carbamazepine, sodium valproate, phenytoin, phenobarbital and many benzodiazepines, as the result of pharmacokinetic interactions.
Stiripentol jqawwi l- effikaċja ta ’ antikonvulsanti oħra, bħal ma huma carbamazepine, sodium valproate, phenytoin, phenobarbital u ħafna benzodiazepines, bħala riżultat ta ’ interazzjonijiet farmakokinetiċi.
15 (71%) patients were responders on stiripentol (including nine free of clonic or tonic-clonic seizures), whereas there was only one (5%) on placebo (none was seizure free; stiripentol 95% CI 52.1-90.7 vs. placebo 0-14.6).
15- il (71%) pazjent kienu dawk fuq stiripentol li rrispondew (inklużi disgħa ħielsa minn aċċessjonijiet kloniċi jew toniċi- kloniċi), filwaqt kien hemm wieħed biss (5%) fuq plaċebo (l- ebda minnhom ma ’ kienu ħielsa mill- aċċessjonijiet; stiripentol 95% CI 52. 1- 90. 7 vs. plaċebo 0 - 14. 6).
The European Medicines Agency (EMEA) will review new information on the product every year and this SPC will be updated as necessary.
L- Aġenzija Ewropeja dwar il- mediċini (EMEA) ser tirrevedi l- informazzjoni l- ġdida dwar il- prodott kull sena u ser taġġorna dan is- Sommarju tal- Karatteristiċi tal - Prodott, skond il- bżonn.
The following pharmacokinetic properties of stiripentol have been reported from studies in adult healthy volunteers and adult patients.
Il- proprjetajiet farmakokinetici li ġejjin dwar stiripentol ġie rraportat minn studju fuq voluntiera adulti b’ saħħithom u pazjenti adulti.
Distribution:
17 Distribuzzjoni:
17 Metabolism:
Metaboliżmu:
5.3 Preclinical safety data Toxicity studies in animals (rat, monkey, mouse) have not revealed any consistent pattern of toxicity apart from liver enlargement associated with hepatocellular hypertrophy, which occurred when high doses of stiripentol were administered to both rodents and nonrodents.
5. 3 Tagħrif ta ’ qabel l- użu kliniku dwar is- sigurtà tal- mediċina Studji dwar it- tossiċità fl- annimali (far, xadina, ġurdien) ma rrevelaw l- ebda disinn konsistenti ta ’ tossiċità minbarra tkabbir fil- fwied assoċjat ma ’ ipertrofija epatoċellulari, li seħħet meta dożi għoljin ta ’ stiripentol kienu amministrati kemm lill- annimali gerriema u kemm lil dawk mhux gerriema.
Studies in the rat on fertility and general reproductive performance and on pre- and postnatal development were uneventful except for a minor reduction in the survival of pups nursed by mothers exhibiting toxic responses to stiripentol at a dose of 800 mg/ kg/ day (See, section, 4.6).
Studji fuq il- fertilità fil- far u l- eżekuzzjoni riproduttiva ġenerali u fuq l- iżvilupp ta ’ qabel u ta ’ wara t- twelid kienu bla problemi ħlief għal tnaqqis żgħir fis- sopravivenza tal- ġriewi imreddgħin minn ommijiet li kienu qed juru reazzjonijiet tossiċi għal stiripentol f’ doża ta ’ 800 mg/ kg/ kuljum (Ara, sezzjoni, 4. 6).
6.1 List of excipients povidone K29/ 32 sodium starch glycolate (type A) magnesium stearate
povidone K29/ 32 sodium starch glycolate (type A) magnesium stearate
Capsule shell Gelatin Titanium dioxide (E171)
Il- qoxra tal- kapsula Gelatin Titanium dioxide (E171)
18 6.3 Shelf life
6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
Store in the original package, in order to protect from light.
Aħżen fil- pakkett oriġinali, sabiex tilqa ’ mid- dawl,.
Polypropylene bottle with tamper-evident seal and polyethylene screw cap.
Flixkun tal- polypropylene bottle b’ siġill ta ’ evidenza ta ’ meta jinfetaħ u b’ għatu tal- kamin tal - polyethylene.
MARKETING AUTHORISATION NUMBER(S)
NUMRU( I) TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ EU/ 1/ 06/ 367/ 004- 006
Diacomit 250 mg powder for oral suspension in sachets.
Diacomit 250 mg trab għal sospensjoni orali fi qratas.
Each sachet contains 250 mg of stiripentol
Kull qartas fih 250 mg ta ’ stiripentol
0.11 mg sodium per sachet.
0. 11 mg sodju kull qartas.
Each sachet contains 2.5mg of aspartame, 500mg of glucose liquid spray and 2.4 mg of sorbitol.
Kull qartas fih 2. 5mg ta ’ aspartame, 500mg ta ’ sprej ta ’ likwidu ta ’ glukożju u 2. 4 mg ta ’ sorbitol.
For a full list of excipients, see section 6.1.
Għal- lista kompleta ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1
Powder for oral suspension Pale pink crystalline powder
Trab għal sospensjoni orali Trab roża ċar ikkristalizzat
The powder should be mixed in a glass of water and should be taken immediately after mixing during a meal.
It- trab għandu jitħallat f’ tazza ilma u għandu jittieħed eżatt wara li jitħallat waqt xi ikla.
The daily dosage may be administered in 2 or 3 divided doses.
Id- doża ta ’ kuljum tista ’ tingħata f’ 2 jew 3 dożi separate kuljum.
Dose adjustments of other antiepileptics used in combination with Diacomit Despite the absence of comprehensive pharmacology data on potential drug interactions, the following advice regarding modification of the dose and dosage schedules of other anti-epileptic medicinal products administered in conjunction with Diacomit is provided based on clinical experience.
Aġġustamenti fid- doża ta ’ antielettiċi oħrajn użati flimkien ma ’ Diacomit Minkejja n- nuqqas ta ’ tagħrif dwar farmakoloġija komprensiva dwar l- effetti potenzjali fuq mediċini, ir- rakkomandazzjonijiet li ġejjin fir- rigward ta ’ modifiċi fid- doża u l- iskedi tad- dożaġġ ta ’ prodotti mediċinali anti- epilettiċi mogħtija flimkien ma ’ Diacomit qed tiġi mogħtija skond l- esperjenza klinika.
Abnormal Laboratory Findings In the event of an abnormal blood count or liver function test finding, the clinical decision for continuing use or adjusting the dose of Diacomit in conjunction with adjusting the doses of clobazam and valproate needs to be made on an individual patient basis taking into consideration the potential clinical benefits and risks (See, section 4.4).
Riżultati Abnormali tal- Laboratorju Fil- każ ta ’ riżultati abnormali fl- għadd tad- demm jew fit- test tal- funzjoni tal- fwied, id- deċizjoni klinika biex jitkompla l- użu jew l- aġġustament tad- doża ta ’ Diacomit flimkien ma ’ l- aġġustament tad - dożi ta ’ clobazam u valproate għandha tiġi magħmula fuq bażi individwali u għandhom jittieħdu in konsiderazzjoni l- benefiċċji u r- riskji kliniċi potenzjali (Ara, sezzjoni 4. 4).
In this younger group of patients, adjunctive therapy with Diacomit should only be started when the diagnosis of SMEI has been clinically confirmed.
F’ dan il- grupp ta ’ pazjenti iżgħar, it- terapija miżjuda b’ Diacomit għandha tinbeda biss meta d- djanjożi ta ’ SMEI tkun ġiet klinikament ikkonfermata (Ara, sezzjoni 5. 1).
(See, section 5.1) Data are limited about the use of Diacomit under 12 months of age.
Hemm dejta ristretta dwar l- użu ta ’ Diacomit f’ età taħt it- 12- il xahar.
21 4.4 Special warnings and precautions for use
21 4. 4 Twissijiet speċjali u prekawzjonijiet għall- użu
Carbamazepine, phenytoin and phenobarbital should not be used in conjunction with Diacomit in the management of Dravet’ s syndrome.
Carbamazepine, iphenytoin u phenobarbital m’ għandomx jintużaw ma ’ Diacomit fis- sindromu ta ’ Dravet.
Unless otherwise clinically indicated, blood counts should be checked every 6 months.
L- għadd tad- demm għandu jiġu ċċekkjat kull 6 xhur, sakemm ma jkunx klinikament indikat b’ mod ieħor.
Caution is advised when combining stiripentol with other drugs that inhibit or induce one or more of these enzymes
L - attenzjoni hi rakkomandata meta tħallat stiripentol ma ’ mediċini oħrajn li jinibixxu jew jinduċu wieħed jew aktar minn dawn l- enzimi..
Diacomit powder for oral suspension in sachet contains aspartame, a source of phenylalanine.
It- trab Diacomit għal sospensjoni orali fi qratas fih l- aspartame, sors ta ’ phenylalanine.
Therefore it may be harmful for people with phenylketonuria.
Għalhekk, dan jista ’ jkun ta ’ ħsara għal persuni b’ phenylketonuria.
Patients with rare glucose-galactose malabsorption should not take this medicine, as the formulation contains glucose.
Pazjenti li għandhom assorbiment ħażin ta ’ glukows- galaktows rari m’ għandhomx jieħdu din il- mediċina, billi l- formulazzjoni fiha l- glukows.
As the flavouring component contains small amount of sorbitol, patients with hereditary problems of fructose intolerance should not take this medicine.
Peress li l- komponent tal- benna fiha ammonti żgħar ta ’ sorbitol, pazjenti li għandhom problemi ereditarji ta ’ intolleranza għal fruttożju m’ għandhomx jieħdu din il- mediċina.
Effect of stiripentol on cytochrome P450 enzymes.
22 L- effett ta ’ stiripentol fuq enżimi ta ’ cytochrome P450..
22 At therapeutic concentrations, stiripentol significantly inhibits several CYP450 isoenzymes: for example, CYP2C19, CYP2D6 and CYP3A4.
F’ konċentrazzjonijiet terapewtiċi, stiripentol jinibixxi sinifikattivament bosta iżoenzimi CYP450, per eżempju, CYP2C19, CYP2D6 u CYP3A4.
Caution must be exercised if clinical circumstances require combining stiripentol with drugs metabolised by CYP2C19 (e. g. citalopram, omeprazole) or CYP3A4 (e. g. several HIV protease inhibitors, antihistamines, astemizole, chlorpheniramine, calcium channel blockers, statins, oral contraceptives, codeine) due to the increased risk of adverse events (see further in this section for antiepileptic drugs).
Għandha tintuża l- kawtela jekk ċirkostanzi kliniċi jeħtieġu li stiripentol jiġi kkombinat ma ’ mediċini metabolizzati minn CYP2C19 (e. ż. citalopram, omeprazole) jew CYP3A4 (e. ż. inibituri HIV protease, antistaminiċi bħal astemizole, chlorpheniramine, imblokkaturi tal- kanali tal- kalċju, statins, kontraċettivi orali, kodeina) minħabba r- riskju akbar ta ’ reazzjonijiet avversi (ara aktar f’ din is - sezzjoni għal mediċini antiepilettiċi).
Combinations requiring precautions
23 Kombinazzjonijiet li jinħtieġu prekawzjonijiet
- Effects on other AEDs
- Effetti ta ’ AEDs oħra
The consequences are increased plasma levels of these anticonvulsants with potential risk of overdose.
Il- konsegwenzi huma livelli għola fil- plażma ta ’ dawn l - antikonvulsanti (mediċini kontra l- aċċessjonijiet) b’ riskju potenzjal ta ’ dożaġġ eċċessiv.
Clinical monitoring of plasma levels of other anticonvulsants when combined with stiripentol with possible dose adjustments is recommended.
Hija rrakkomandata sorveljanza klinika tal- livelli fil- plażma ta ’ anticonvulsants (mediċini kontra l - aċċessjonijiet) oħra meta kkumbinati ma ’ stiripentol b’ aġġustamenti fid- doża possibbli.
Risk related to epilepsy and antiepileptic medicinal products in general:
Riskju relatat ma ’ l- epilessija u prodotti mediċinali antiepilettiċi b’ mod ġenerali:
During pregnancy:
24 Waqt it- tqala:
24 4.7 Effects on ability to drive and use machines
4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
Within each frequency grouping, undesirable effects are presented in order of decreasing severity.
Fi ħdan kull ragruppament ta ’ frekwenzi, l- effetti mhux mixtieqa qegħdin jiġu ppreżentati skond severità li dejjem tonqos
System/ organ classes
Klassifika tas- sistema ta ’ l- organi
Photosensitivity, rash, cutaneous allergy, urticaria Fatigue
Fotosensitività, raxx, allerġija, tal- ġilda urtikarja Għeja
25 4.9 Overdose
4. 9 Doża eċċessiva
Stiripentol has also been shown to enhance GABAA receptor-mediated transmission in the immature rat hippocampus and increase the mean open-duration (but not the frequency) of GABAA receptor chloride channels by a barbiturate-like mechanism.
Stiripentol ukoll deher li jtejjeb it- trasmissjoni medjata minn riċettaturi GABAA fil - ħippokampus tal- far immatur u jżid it- tul ta ’ żmien miftuħ medju (iżda mhux il- frekwenza) ta ’ kanali tal- klorur tar- riċettaturi GABA minn mekkaniżmu bħal tal- barbiturati.
15 (71%) patients were responders on stiripentol (including nine free of clonic or tonic-clonic seizures), whereas there was only one (5%) on placebo (none was seizure free; stiripentol 95% CI 52.1-90.7 vs. placebo 0-14.6).
15- il (71%) pazjent kienu dawk fuq stiripentol li rrispondew (inklużi disgħa ħielsa minn aċċessjonijiet kloniċi jew toniċi- kloniċi), filwaqt kien hemm wieħed biss (5%) fuq plaċebo (l- ebda minnhom ma ’ kienu ħielsa
26 Distribution:
Distribuzzjoni: