qanastek/EMEA-V3 huggingface dataset:
Xyrem should not be used in people who may be hypersensitive (allergic) to sodium oxybate or any of the other ingredients.
Xyrem m’ għandux jintuża minn persuni li għandhom allerġija għal sodium oxybate jew għal xi sostanza oħra tiegħu.
It should not be used in patients with ‘ succinic semialdehyde dehydrogenase deficiency’ (a rare metabolic disease), or in patients being treated with opioids (such as some painkillers) or barbiturates (such as some anaesthetics and medicines used to prevent seizures [fits]).
M’ għandux jintuża lanqas minn pazjenti li jkollhom ‘ succinic semialdehyde dehydrogenase deficiency ’ (marda metabolika rari), jew minn pazjenti li jkunu qed jieħdu narkotiċi (bħal mediċini għal kontra l- uġigħ) jew barbiturati (bħal xi anestetiċi u mediċini użati fit- trattament ta ’ aċċessjonijiet [attakki tal- qamar]).
Because sodium oxybate can be abused, doctors must carefully monitor patients using Xyrem.
Billi hawn min jabbuża minn sodium oxybate, it- tobba għandhom jissorveljaw sew pazjenti li jkunu qed jieħdu Xyrem.
Why has Xyrem been approved?
Għaliex ġie approvat Xyrem?
The Committee for Medicinal products for Human Use (CHMP) decided that Xyrem’ s benefits are greater than its risks for the treatment of narcolepsy with cataplexy in adult patients.
Il- Kumitat għall- Prodotti Mediċinali għall- Użu mill- Bniedem (CHMP) iddeċieda li l- benefiċċji ta ’ Xyrem fit- trattement tal- kataplessja f’ pazjenti adulti huma ikbar mir- riskji marbuta miegħu.
Although the 9 g dose was the most effective, it was linked to high levels of side effects, so the committee recommended a starting dose of 4.5 g per day.
Għalkemm l- iktar doża effettiva kienet 9 g, din wasslet għal livelli għoljin ta ’ effetti sekondarji, u allura l- kumitat irrakkomanda doża inizjali ta ’ 4. 5 g kuljum.
Since the effective dose is close to the dose at which side effects become serious, increases in dose must be carried out strictly and under the supervision of a doctor specialised in the treatment of sleep disorders.
Billi d- doża effettiva hi qrib tad- doża li twassal għal effetti sekondarji serji, żidiet fid- doża għandhom isiru b’ attenzjoni kbira u taħt is - sorveljanza ta ’ tabib speċjalizzat fit- trattament ta ’ mard ta ’ l- irqad.
The committee recommended that Xyrem be given marketing authorisation.
Il- kumitat irrikmanda li tingħata l - awtorizzazzjoni għat- tqegħid fis- suq ta ’ Xyrem.
Which measures are being taken to ensure the safe use of Xyrem?
X’ miżuri qed jittieħdu biex Xyrem jintuża b’ mod sigur?
The company that makes Xyrem will minimise the risk of abuse of Xyrem by providing educational materials to healthcare workers and patients, strictly controlling the distribution of the medicine, and monitoring its use.
Il- kumpanija li tagħmel Xyrem sa timminimizza r- riskju ta ’ abbuż minn Xyrem billi tipprovdi materjali edukattivi għall- pazjenti u għall- professjonisti tas- saħħa, billi tikkontrolla d- distribuzzjoni tal- mediċina b’ attenzjoni kbira u billi tissorvelja l- użu tagħha.
Other information about Xyrem:
Informazzjoni oħra dwar Xyrem:
The full EPAR for Xyrem can be found here.
Dan is- sommarju kien aġġornat l- aħħar fi 02- 2007.
EU/ 1/ 05/ 312/ 001
Numru ta ’ l- EU EU/ 1/ 05/ 312/ 001
Xyrem
Isem inventat Xyrem
500 mg/ ml
Qawwa 500 mg/ ml
Oral solution
G amla farma ewtika Soluzzjoni orali
Oral use
Mnejn jing ata U u mill - alq
bottle (PET)
Il- pakkett Flixkun (PET)
500 mg/ ml
Kontenut 500 mg/ ml
1 bottle + 1 graduated 10 ml measuring device
Daqs tal- pakkett 1 flixkun 1 g odda bilmarki tal- kejl ta ’ 10ml
Xyrem 500 mg/ ml oral solution.
Xyrem 500 mg/ ml soluzzjoni orali.
One ml Xyrem contains 500 mg of sodium oxybate.
Kull ml ta ’ Xyrem fih 500 mg ta ’ sodium oxybate.
The oral solution is clear to slightly opalescent.
Is- soluzzjoni orali hija ċara għal kemmxejn tkanġi.
Treatment of narcolepsy with cataplexy in adult patients.
It- trattament ta ’ narkolessija b’ kataplessija f’ pazjenti adulti.
Treatment should be initiated by and remain under the guidance of a physician experienced in the treatment of sleep disorders.
It- trattament għandu jinbeda minn, kif ukoll jitkompla taħt il- gwida ta ’ tabib b’ esperjenza fit - trattament ta ’ mard ta ’ l- irqad.
Due to the well known potential of abuse of sodium oxybate, physicians should evaluate patients for a history of drug abuse (see section 4.4).
Minħabba li l- potenzjal ta ’ abbuż ta ’ sodium oxybate huwa magħruf, it - tobba għandhom jiċċekkjaw jekk il- pazjenti għandhomx storja ta ’ abbuż ta ’ droga (ara sezzjoni 4. 4).
The recommended starting dose is 4.5 g/ day sodium oxybate divided into two equal doses of 2.25 g/ dose.
Id- doża rikkmandata tal- bidu hija ta ’ 4. 5 g ta ’ sodium oxybate kuljum maqsuma f ’ żewġt dożi ugwali ta ’ 2. 25 g/ doża.
The dose should be titrated to effect based on efficacy and tolerability (see Section 4.4) up to a maximum of 9 g/ day divided into two equal doses of 4.5g/ dose by adjusting up or down in dose increments of 1.5 g/ day (i. e.
Għandha issir it- titrazzjoni tad- doża sakemm jintlaħqu l- effikaċja u t- tolerabilta` mixtieqa (ara Sezzjoni 4. 4), billi titnaqqas jew tiżdied id- doża b ’ 1. 5 g kuljum (i. e.
0.75 g/ dose).
0. 75 g/ doża) sa mhux iżjed mid- doża massima ta ’ 9 g / ġurnata maqsuma f’ żewġt dozi ndaqs ta ’ 4. 5 g/ doża.
A minimum of one to two weeks is recommended between dosage increments.
Minimu ta ’ ġimgħa jew ġimagħtejn huwa rikkmandat bejn iż- żiediet fid- doża.
The dose of 9g/ day should not be exceeded due to the possible occurrence of severe symptoms at doses of 18 g/ day or above (see section 4.4).
Id- doża ta ’ 9g / ġurnata m’ għandiex tinqabes minħabba l- possibbilta` ta ’ sintomi severi f’ dożi ta ’ 18 g jew aktar kuljum (ara sezzjoni 4. 4).
A 10ml measuring syringe and two 90 ml dosing cups are provided with Xyrem.
Siringa tal- kejl ta ’ 10ml u żewġt tazzi għad- dożaġġ ta ’ 90 ml huma provduti ma ’ Xyrem.
Each dose of Xyrem must be diluted with 60 ml of water in the dosing cup prior to ingestion.
Kull doża ta ’ Xyrem għandha tiġi dilwita ma ’ 60 ml ta ’ ilma fit- tazza tad- dożaġġ qabel ma ’ tittieħed.
Single doses of 4.5g should not be given unless the patient has been titrated previously to that dose level.
Dożi singoli ta ’ 4. 5 g m’ għandhomx jingħataw sakemm ma tkunx saret it- titrazzjoni tad- doża sa dak il- livell għal dak il- pazjent partikolari.
Because food significantly reduces the bioavailability of sodium oxybate, patients should eat at least several (2-3) hours before taking the first dose of Xyrem at bedtime.
L- ikel inaqqas sinifikament il- biodisponibilita` ta ’ sodium oxybate u għalhekk il- pazjenti għandhom jieklu mill- inqas ftit sigħat mhux ħażin (2- 3 sigħat) qabel ma jieħu l- ewwel doza ta ’ Xyrem qabel ma jitħlu jorqdu.
Patients should always observe the same timing of dosing in relation to meals.
Il- pazjenti għandhom dejjem iħallu l- istess ammont ta ’ ħin wara li jieklu biex jieħdu d - doża.
Using Xyrem
Meta tuża Xyrem
Xyrem should be taken orally upon getting into bed and again between 2.5 to 4 hours later.
Xyrem għandu jittieħed mill- ħalq l- ewwel meta wieħed jitħol jorqod u imbagħad wara 2. 5 sa 4 sigħat.
It is recommended that both doses of Xyrem should be made up at the same time upon retiring to bed.
Huwa rikkmandat li ż- żewgt dożi ta ’ Xyrem għandhom jiġu rikostitwiti f’ istess ħin meta wieħed imur jorqod.
Xyrem is provided for use with a graduated measuring syringe and dosing cup with child resistant cap.
Xyrem issibu b’ siringa bil- kejl u tazza tad- dożaġġ b’ għatu li ma jinfetaħx mit- tfal.
Each measured dose of Xyrem must be dispensed into the dosing cup and diluted with 60 ml of water prior to ingestion.
Kull doża mkejla ta ’ Xyrem għandha titferra ’ fit- tazza tat- dożaġġ u tiġi dilwita b ’ 60 ml ta ’ ilma qabel ma tittieħed.
2 Discontinuation of Xyrem
2 Meta jitwaqqaf Xyrem
The discontinuation effects of sodium oxybate have not been systematically evaluated in controlled clinical trials (see Section 4.4).
L- effetti ta ’ meta jitwaqqaf sodium oxybate ma kienux sistematikament evalwati f ’ provi kliniċi kontrollati (ara sezzjoni 4. 4).
If the patient stops medication for more than 14 consecutive days, titration should be restarted from the lowest dose Patients with hepatic impairment
Jekk il- pazjent iwaqqaf il- mediċina għal iktar minn 14 il- ġurnata konsekuttiva, id- dożaġġ irid jerġa ’ jinbeda mill- iżjed doża baxxa.
The starting dose should be halved in patients with hepatic impairment, and response to dose increments monitored closely (see section 4.4).
Id- doża tal- bidu għandha tiġi mnaqqsa bin- nofs f’ pazjenti b’ indeboliment tal- fwied, u r- rispons għaż - żiediet fid- dożi għandha tiġi osservata mill- qrib (ara sezzjoni 4. 4).
Patients with renal impairment
Pazjenti b ’ indeboliment tal- kliewi
Patients with impaired renal function should consider a dietary recommendation to reduce sodium intake (see section 4.4).
Pazjenti b ’ indeboliment tal- kliewi għandhom jikkunsidraw ir- rikkomandazzjoni li jieħdu inqas sodium fid- dieta tagħhom (ara sezzjoni 4. 4).
Elderly patients should be monitored closely for impaired motor and/ or cognitive function when taking Sodium oxybate (see section 4.4).
Anzjani fuq sodium oxybate għandhom jiġu osservati mill- qrib għal indeboliment fil- funzjoni tal - moviment u/ jew tal- konjizzjoni (ara sezzjoni 4. 4).
Safety and effectiveness in children and adolescents has not been established, therefore use in patients under 18 years of age is not recommended.
Mhux rikkmandat għall- użu fit- tfal ta ’ taħt it- 18 il- sena, peress li ma ġietx stabbilita s- sigurtà u l - effikaċja fit- tfal u l- addoloxenti.
Hypersensitivity to sodium oxybate or to any of the excipients.
Sensittività eċċessiva għal sodium oxybate jew għal xi sustanzi mhux attivi.
Sodium oxybate is contraindicated in patients with succinic semialdehyde dehydrogenase deficiency.
Sodium oxybate huwa kontra- indikat f’ pazjenti b’ defiċjenza ta ’ succinic semialdehyde dehydrogenase.
Sodium oxybate is contraindicated in patients being treated with opoids or barbiturates.
Sodium oxybate huwa kontraindikat f’ pazjenti fuq trattament b’ opoids jew barbiturati.
4.4 Special warnings and special precautions for use
Twissijiet speċjali u prekawzjonijiet għall- użu 4. 4
Xyrem has the potential to induce respiratory depression
Xyrem għandu l- potenzjal li jindotta depressjoni respiratorja.
Abuse potential and dependance The active substance in Xyrem is sodium oxybate, which is as the sodium salt of gamma hydroxybutyrate (GHB), a CNS depressant active substance with well known abuse potential.
Il- potenzjal ta ’ abbuż u d- dipendenza Sodium oxybate li huwa s- sustanza attiva ta ’ Xyrem, huwa sodium salt ta ’ gamma hydroxybutyrate (GHB), sustanza attiva u depressant tas- sistema nervuża ċentrali li hu magħruf għall- potenzjal għall - abbuż.
Physicians should evaluate patients for a history of drug abuse and follow such patients closely.
It- tobba għandhom jiċċekkjaw jekk il- pazjenti għandhomx storja ta ’ abbuż u jsegwu il- pazjenti mill- qrib.
There have been case reports of dependence after illicit use of GHB at frequent repeated doses (18 to 250 g/ day) in excess of the therapeutic dose range.
Kien hemm rapporti ta ’ każi ta ’ dependenza wara l- użu illeċitu ta ’ GHB b’ dożi frekwenti ripetuti (18 sa 250 g/ ġurnata) iżjed mill- marġini tad- dożaġġ terapewtiku.
Whilst there is no clear evidence of emergence of dependence in patients taking sodium oxybate at therapeutic doses, this possibility cannot be excluded.
Għalkemm m’ hemmx evidenza ċara li turi l- iżvillup ta ’ dipendenza f’ pazjenti fuq sodium oxybate b ’ dożi terapewtiċi, din il - possibbilta` ma tistax tiġi eskluża.
CNS depression The combined use of alcohol or any CNS depressant drug with sodium oxybate may result in potentiation of the CNS-depressant effects of sodium oxybate.
Depressjoni tas- sistema nervuża ċentrali( CNS) L- użu ta ’ alkoħol jew xi mediċina depressanti tas- CNS flimkien ma ’ sodium oxybate jista ’ jwassal biex l- effetti depressanti fuq is- sistema nervuża ċentrali ta ’ sodium oxybate jitqawwew.
Therefore, patients should be warned against the use of alcohol in conjunction with sodium oxybate.
Għalhekk, il - pazjenti għandhom jitwissew biex ma jixorbux alkoħol waqt trattament b ’ sodium oxybate.
Patients with porphyria Sodium oxybate is considered to be unsafe in patients with porphyria because it has been shown to be porphyrogenic in animals or in-vitro systems.
3 Pazjenti b ’ porfirja Sodium oxybate huwa meqjuż perikoluż f’ pazjenti b ’ porfirja għaliex ġie muri li jikkawża l- porfirja f’ annimali jew f’ sistemi in- vitro.
3 Respiratory depression Sodium oxybate also has the potential to induce respiratory depression.
Depressjoni respiratorja Sodium oxybate għandu wkoll il- potenzjal li jindotta depressjoni respiratorja.
Apnoea and respiratory depression have been observed in a fasting healthy subject after a single intake of 4.5g (twice the recommended starting dose).
Apnea u depressjoni respiratorja kienu osservati f’ persuni sajma f’ saħħithom wara li ħadu 4. 5 g f’ daqqa (d- doppju tad- doża rikkmandata tal- bidu).
Patients should be questioned regarding signs of CNS or respiratory depression.
Pazjenti għandhom jiġu mistoqsija dwar sinjali ta ’ depressjoni tas- CNS u tas - sistema respiratorja.
Special caution should be observed in patients with an underlying respiratory disorder.
Attenzjoni speċjali trid tittieħed ma ’ pazjenti li ġa għandhom mard respiratorju.
Approximately 80% of patients who received sodium oxybate during clinical trials maintained CNS stimulant use.
Madwar 80% tal- pazjenti li ħadu sodium oxybate waqt il- provi kliniċi baqgħu fuq stimulanti tas- CNS.
Whether this affected respiration during the night is unknown.
Mhux magħruf jekk dan kellux effett fuq ir- respirazzjoni waqt il- lejl.
Before increasing the sodium oxybate dose (see section 4.2), prescribers should be aware that sleep apnoea occurs in up to 50% of patients with narcolepsy.
Qabel ma ’ jżidu d- doża ta ’ sodium oxybate (ara sezzjoni 4. 2), it- tobba għandhom ikunu konxji li l- apnea waqt l- irqad iseħħ f ’ mhux aktar minn 50% tal- pazjenti b’ narkolessija.
Benzodiazepines Given the possibility of increasing the risk of respiratory depression, the concomitant use of benzodiazepines and Xyrem should be avoided.
Benzodiazepines Minħabba l- possibbilta` li jiżdied ir- riskju ta ’ depressjoni respiratorja, għandu jiġi evitat l- użu ta ’ benzodiazepines u Xyrem flimkien.
Neuropsychiatric events Patients may become confused while being treated with sodium oxybate.
Ġrajjiet newropsikjatriċi Pazjenti jistgħu jsiru konfużi meta jkunu fuq trattament b ’ sodium oxybate.
If this occurs, they should be evaluated fully, and appropriate intervention considered on an individual basis.
Jekk dan iseħħ, għandhom jiġu eżaminati sew, u għandha tittieħed ażzjoni xierqa fuq bażi individwali.
Other neuropsychiatric events include psychosis, paranoia, hallucinations, and agitation.
Ġrajjiet newropsikjatriċi oħrajn jinkludu psikożi, paranoja, alluċinazzjonijiet, u aġitazzjoni.
The emergence of thought disorders and/ or behavioural abnormalities when patients are treated with sodium oxybate requires careful and immediate evaluation.
Iridu jiġu eżaminati immedjatament u b’ attenzjoni dawk il- pazjenti li jibdew ibagħtu minn disturbi fil- ħsieb u/ jew mġieba abnormali waqt li jkunu fuq sodium oxybate.
Patients with a previous history of a depressive illness and/ or suicide attempt should be monitored especially carefully for the emergence of depressive symptoms while taking sodium oxybate.
Jekk pazjent ikollu inkontinenza ta ’ l- awrina jew tal- ħmieġ waqt terapija b’ sodium oxybate, it- tabib għandu jqis investigazzjonijiet biex jiġu eliminati kawżi oħra.
Sleepwalking has been reported in patients treated in clinical trials with sodium oxybate.
Fi provi kliniċi, ġiet rappurtata sonnambulanza f’ pazjenti trattati b’ sodium oxybate.
It is unclear if some or all of these episodes correspond to true somnambulism (a parasomnia occurring during non- REM sleep) or to any other specific medical disorder.
Mhix ċara jekk xi episodji jew jekk l- episodji kollha jikkorrispondu għal sonnambulanza vera (parasomnja li tiġri waqt irqad li mhux REM) jew għal xi mard mediku speċifiku ieħor.
The risk of injury or self-harm should be borne in mind in any patient with sleepwalking.
Ir- riskju ta ’ korriment jew li jagħmel ħsara lilu nnifsu għandu jitqis f’ kull pazjent b’ sonnambulanza.
Therefore, episodes of sleepwalking should be fully evaluated and appropriate interventions considered.
Għalhekk, episodji ta ’ sonnambulanza għandhom jiġu evalwati sew u għandhom jittieħdu l- azzjonijiet xierqa.
Sodium intake Patients taking sodium oxybate will have an additional daily intake of sodium that ranges from 0.82g (for a 4.5g/ day Xyrem dose) to 1.6g (for a 9g/ day Xyrem dose).
It- teħid ta ’ sodium Pazjenti fuq sodium oxybate jkunu qegħdin jieħdu bejn 0. 82g (għal doża ta ’ 4. 5g kuljum Xyrem) sa 1. 6g (għal doża ta ’ 9g kuljum Xyrem) ta ’ sodium iżjed kuljum.
(see section 4.2).
F’ pazjenti b ’ insuffiċjenza tal- qalb, pressjoni għolja jew funzjoni renali kompromett, għandha tiġi kunsidrata b’ attenzjoni r - rikkmandazzjoni li jitnaqqas sodium fid- dieta (ara sezzjoni 4. 2).
Patients with compromised liver function Patients with compromised liver function will have an increased elimination half-life and systemic exposure to sodium oxybate (see Section 5.2).
Pazjenti b’ funzjoni renali kompromett Pazjenti b’ funzjoni renali kompromett jkollhom żieda fil- half- life ta ’ eliminazzjoni u fl- esponiment sistemiku għal sodium oxybate (ara Sezzjoni 5. 2).
The starting dose should therefore be halved in such patients, and response to dose increments monitored closely (see section 4.2).
Għalhekk, f’ dawn il- pazjenti d- doża tal- bidu għandha titnaqqas bin- nofs, u r- rispons għaż- żiediet fid- doża għandu jiġi osservat mill- qrib (ara sezzjoni 4. 2).
Elderly There is very limited experience with sodium oxybate in the elderly.
L- anzjani Hemm esperjenza limitata b’ sodium oxybate fl- anzjani.
Therefore, elderly patients should be monitored closely for impaired motor and/ or cognitive function when taking sodium oxybate.
Għalhekk, pazjenti anzjani għandhom jiġu osservati mill- qrib għal indeboliment fil- funzjoni tal- moviment u tal- konjizzjoni waqt li jkunu fuq sodium oxybate.
Childhood and adolescence Safety and effectiveness in children and adolescents has not been established, therefore use in patients under 18 years of age is not recommended.
Tfulija u addoloxxenza Is- sigurta ’ u l- effettivita` ma ġietx stabbilita fit- tfal u fl- addoloxxenti, u għalhekk l- użu f’ pazjenti taħt it- 18 il- sena mhux rikkmandat.
4 Epileptic patients Seizures have been observed in patients treated with sodium oxybate.
4 Pazjenti b’ epilessija Kienu osservati aċċessjonijiet f ’ pazjenti fuq sodium oxybate.
In patients with epilepsy, the safety and efficacy of sodium oxybate has not been established, therefore use is not recommended.
Is- sigurta ’ u l- effikaċja ta ’ sodium oxybate ma ġietx stabbilita f ’ pazjenti b ’ epilessija, u għalhekk l- użu f ’ dawn il- pazjenti mhux rikkmandat.
Rebound effects and withdrawal syndrome The discontinuation effects of sodium oxybate have not been systematically evaluated in controlled clinical trials.
Effetti li jiggravaw mal- waqfien u sindromu ta ’ waqfien mill- mediċina L- effetti ta ’ meta jitwaqqaf sodium oxybate ma ġewx evalwati sistematikament f’ provi kliniċi kontrollati.
In some patients, cataplexy may return at a higher frequency on cessation of sodium oxybate therapy, however this may be due to the normal variability of the disease.
Meta titwaqqaf it- terapija b’ sodium oxybate, xi pazjenti jistaw jerġaw jibdew ibagħtu minn kataplessija b ’ frekwenza ogħla minn qabel, għalkemm din tista ’ tkun minħabba l- varjabilita` normali tal- marda.
Although the clinical trial experience with sodium oxybate in narcolepsy/ cataplexy patients at therapeutic doses does not show clear evidence of a withdrawal syndrome, in rare cases, events such as insomnia, headache, anxiety, dizziness, sleep disorder, somnolence, hallucination, and psychotic disorders were observed after GHB discontinuation.
Għalkemm l- esperjenza fi provi kliniċi b’ sodium oxybate f ’ pazjenti b ’ narkolessija / kataplessija b’ dożi terapewtiċi ma turiex evidenza ċara ta ’ sindromu ta ’ waqfien mill- mediċina, f’ każi rari, effetti bħal nuqqas ta ’ rqad, uġigħ ta ’ ras, anzjeta`, sturdament, mard ta ’ l- irqad, nagħas, alluċinazzjonijiet, u mard psikotiċi kienu osservati wara l- waqfien ta ’ GHB.
The combined use of alcohol with sodium oxybate may result in potentiation of the central nervous system-depressant effects of sodium oxybate.
L- użu ta ’ l- alkoħol flimkien ma ’ sodium oxybate jista ’ jwassal għal tisħieħ ta ’ l- effetti depressanti tas - sistema nervuża ċentrali ta ’ sodium oxybate.
Patients should be warned against the use of any alcoholic beverages in conjunction with sodium oxybate.
Għandu jkun hemm twissija biex il- pazjenti ma jixorbux alkohol flimkien ma sodium oxybate.
Sodium oxybate should not be used in combination with sedative hypnotics or other CNS depressants.
Sodium oxybate m’ għandux jintuża flimkien ma ’ ipnotiċi sedattivi jew depressanti oħra tas- sistema nervuża ċentrali.
Drug interaction studies in healthy adults demonstrated no pharmacokinetic interactions between sodium oxybate and protriptyline hydrochloride (an antidepressant), zolpidem tartrate (a hypnotic), and modafinil (a stimulant).
Studji dwar dwar l- effett ta ’ mediċini jew ta ’ affarijiet oħra fuq l- effett farmaċewtiku tal- prodott fuq pazjenti f’ saħħithom ma wrewx interazzjonijiet farmakokinetiċi bejn sodium oxybate u protriptyline hydrochloride (mediċina kontra d- depressjoni), zolpidem tartrate (ipnotiku), and modafinil (stimulant).
However, pharmacodynamic interactions with these drugs have not been assessed.
Madanakollu, ma ġewx studjati l- interazzjonijiet farmakodinamiċi b ’ dawn il- mediċini.
The co-administration of omeprazole (a drug that alters gastric pH) has no clinically significant effect on the pharmacokinetics of sodium oxybate.
Meta omeprazole (mediċina li tibdel il- pH ta ’ l- istonku) jittieħed flimkien ma ’ sodium oxybate, dan ma kellux effett klinikament sinifikattiv fuq il- farmakokinetika ta ’ sodium oxybate.
The dosage of sodium oxybate therefore does not require adjustment when given concomitantly with proton pump inhibitors.
Id- dożaġġ ta ’ sodium oxybate m’ għandiex bżonn aġġustament meta jingħata flimkien ma ’ inibituri tal- proton pump.
Studies in vitro with pooled human liver microsomes indicate that sodium oxybate does not significantly inhibit the activities of the human isoenzymes (see section 5.2).
Studji in vitro b’ mikrożomi miġbura tal- fwied uman juru li sodium oxybate ma jinibixxix sinifikament l- attivita` tal- iżoenżimi umani (ara sezzjoni 5. 2).
Since sodium oxybate is metabolised by GHB dehydrogenase there is a potential risk of an interaction with drugs that stimulate or inhibit this enzyme (e. g. valproate, phenytoin or ethosuximide).
Peress li sodium oxybate huwa metabolizzat minn GHB dehydrogenase, hemm possibbilta` ta ’ tibdil fl- effett farmaċewtiku ma ’ mediċini li jistimulaw jew jinibixxu dan l- enżim (eż. valproate, phenytoin jew ethosuximide).
No interaction studies have been conducted in human subjects
Ma sarux studji dwar l- effett ta ’ mediċini jew ta ’ affarijiet oħra fuq l- effett farmaċewtiku tal- prodott fil- bniedem.
Sodium oxybate has been administered concomitantly with CNS stimulant agents in approximately 80% of patients in clinical studies.
Fl- istudji kliniċi, sodium oxybate ngħata flimkien ma ’ mediċini stimulanti tas- sistema nervuża ċentrali f’ madwar 80% tal- pazjenti.
Whether this affected respiration during the night is unknown.
Mhux magħruf jekk dan kellux effett fuq ir- respirazzjoni bil- lejl.
Antidepressants have been used in the treatment of cataplexy.
Il- mediċini kontra d- depressjoni kienu użati fit- trattament tal- kataplessija.
A possible additive effect of antidepressants and sodium oxybate cannot be excluded.
Il- possibbilta` ta ’ effett miżjud tal- mediċina kontra d- depressjoni u ta ’ sodium oxybate ma tistax tiġi eskluża.
The rate of adverse events have increased when sodium oxybate is co-administered with tricyclic antidepressants.
Ir- rata ta ’ effetti mhux mixtieqa żiedu meta sodium oxybate ngħata flimkien ma ’ mediċini triċikliki ta ’ kontra d - depressjoni.
Pregnancy Animal studies have shown no evidence of teratogenicity but embryolethality was seen in both rat and rabbit studies (see section 5.3).
Tqala Studji fuq l- annimali ma wrew ebda evidenza ta ’ teratoġeniċita`, imma kien hemm imwiet tal- embriju kemm f’ studji fil- ġrieden u kemm studji fil- fniek (ara sezzjoni 5. 3).
There are no adequate data on the use of sodium oxybate during the first trimester of pregnancy.
5 M’ hemmx tagħrif adekwat dwar l- użu ta ’ sodium oxybate waqt l- ewwel trimester tat- tqala.
Limited data from pregnant patients during second and third trimester indicate no malformative nor foeto/ neonatal toxicity of sodium oxybate.
Tagħrif limitat miġbur minn pazjenti tqal waqt it- tieni u t- tielet trimester ma juri ebda malformazzjoni jew tossiċita` fil- fetu / fit- tarbija tat- twelid b’ sodium oxybate.
Sodium oxybate is not recommended during pregnancy.
Sodium oxybate mhux rikkmandat waqt it- tqala.
5 Lactation It is not known whether sodium oxybate is excreted into breast milk.
Treddigħ Mhux magħruf jekk sodium oxybate jgħaddix fil- ħalib tas- sider.
Breastfeeding is not recommended when treating with Xyrem.
It- treddigħ mhux rikmandat waqt trattament b ’ Xyrem.
Sodium oxybate has a major influence on the ability to drive and use machines.
Sodium oxybate għandu effett qawwi ħafna fuq il- ħila biex issuq u tħaddem magni.
For at least 6 hours after taking sodium oxybate, patients must not undertake activities requiring complete mental alertness or motor co-ordination, such as operating machinery or driving.
Għal mill- inqas 6 sigħat wara li jieħdu sodium oxybate, pazjenti m’ għandhomx jagħmlu attivitajiet fejn hemm bżonn li wieħed ikollu viġilanza mentali kompleta jew ko- ordinament komplet tal - moviment, bħal fit- tħaddim ta ’ magni u fis- sewqan.
When patients first start taking sodium oxybate, until they know whether this medicinal product will still have some carryover effect on them the next day, they should use extreme care while driving a car, operating heavy machines, or performing any other task that could be dangerous or require full mental alertness.
Meta l- pazjenti l- ewwel jibdew jieħdu sodium oxybate, għandhom joqgħodu attenti ħafna waqt li jsuqu karozza, jħaddmu magni, jew jagħmlu xi xogħol ieħor li jista ’ jkun perikoluż jew li jirrikjedi viġilanza mentali kompleta, sakemm isiru jafu jekk din il- mediċina jkunx ser ikollha effett li jibqa ’ fuqhom anke l- għada.
The most commonly reported adverse drug reactions are dizziness, nausea, and headache, all occurring in 10% to 20% of patients.
L- effetti mhux mixtieqa li l- iżjed ġew rappurtati huma sturdament, dardir, u uġigħ ta ’ ras, li kollha jidhru f ’ 10% sa 20% tal- pazjenti.
Frequency estimate: very common (≥ 1/ 10); common (≥ 1/ 100 to < 1/ 10); uncommon (≥ 1/ 1000 to < 1/ 100); rare (≥ 1/ 10,000 to < 1/ 1000); very rare (< 1/ 10,000); not known (cannot be estimated from the available data).
Estimu tal- frekwenza: komuni ħafna (≥ 1/ 10); komuni (≥ 1/ 100 to < 1/ 10); mhux komuni (≥ 1/ 1000 to < 1/ 100); rari (≥ 1/ 10, 000 to < 1/ 1000); rari ħafna (< 1/ 10, 000); mhux magħruf (ma jistax jitkejjel mit- tagħrif miġbur).
Not known: hypersensitivity
Mhux magħruf: ipersensitivita`
Metabolism and nutrition disorders:
Mard marbut mal- metaboliżmu u n- nutrizzjoni:
Common: anorexia
Komuni: anoressija
Psychiatric disorders:
Mard psikjatriku:
Common: abnormal dreams, confusion, disorientation, nightmares, sleepwalking, depression, sleep disorder, cataplexy, anxiety, insomnia, middle insomnia, nervousness Uncommon: psychosis, paranoia, abnormal thinking, hallucination, agitation, suicide attempt, initial insomnia Not known: suicidal ideation
Komuni: ħolm abnormali, konfużjoni, diżorjentament, ħolm tal- biża ’, sonnambulanza, depressjoni, mard ta ’ l- irqad, kataplessija, anzjeta`, insomnja, insomnja tan- nofs, nervożita` Mhux komuni: psikożi, paranoja, ħsieb abnormali, alluċinazzjonijiet, aġitazzjoni, attentat ta ’ suwiċidju, insomnja inizjali Mhux magħruf: ħsibijiet ta ’ suwiċidju
Nervous system disorders:
Mard tas- sistema nervuża:
Very common: dizziness, headache Common: sleep paralysis, somnolence, tremor, balance disorder, disturbance in attention, hypoaesthesia, paraesthesia, sedation Uncommon: myoclonus, amnesia, restless legs syndrome Not known: convulsion
Komuni ħafna: sturdament, uġigħ ta ’ ras Komuni: paraliżi ta ’ l- irqad, nagħas, rogħda, mard tal- bilanċ, disturbi fl- attenzjoni, ipo- estesija, para - estesija, sedazzjoni Mhux komuni: myoklonus, amnesija, sindromu hekk msajjaħ restless legs Mhux magħruf: aċċessjoni
Common: blurred vision
Komuni: viżjoni mċajpra
Vascular disorders:
Mard vaskulari:
Common: hypertension
Komuni: ipertensjoni
Respiratory, thoracic and mediastinal disorders:
6 Mard respiratorju, toraċiku u medjastinali:
Common: dyspnoea, snoring Not known: respiratory depression
Komuni: qtugħ ta ’ nifs, inħir Mhux magħruf: depressjoni respiratorja
Gastrointestinal disorders:
Mard ġastro- intestinali:
Very common: nausea (the frequency of nausea is higher in women than men) Common: vomiting, upper abdominal pain, diarrhoea
Komuni ħafna: dardir (il- frekwenza ta ’ dardir hija ogħla fin- nisa milli fl- irġiel) Komuni: rimettar, uġigħ fil- parti ta ’ fuq ta ’ l- addomenu, dijareja Mhux komuni: inkontinenza tal- ħmieġ
Skin and subcutaneous tissue disorders:
Mard tal- ġilda u tat- tessut ta ’ taħt il- ġilda:
Common: sweating Uncommon: rash Not known: urticaria
Komuni: għaraq Mhux komuni: raxx Mhux magħruf: urtikarja
Musculoskeletal, connective tissue and bone disorders:
Mard muskolu- skeltrali, tal- connective tissue u tal- għadam:
Common: muscle cramps, arthralgia
Komuni: bugħawwieġ, artralġja
Renal and urinary disorders:
Mard tal- kliewi u tas- sistema urinarja:
Common: enuresis nocturna, urinary incontinence
Komuni: enuresi ta ’ bil- lejl, inkontinenza urinarja
Common: asthenia, fatigue, feeling drunk, oedema peripheral
Komuni: astenja, għajja, sensazzjoni ta ’ sakra, edima periferali
Uncommon: weight decreased, blood pressure increased
Mhux komuni: żieda fil- piz, żieda fil- pressjoni tad- demm
Injury, poisoning and procedural complications Common: fall
Korriment, avvelenament u komplikazzjonijiet ta ’ xi proċedura:
In some patients, cataplexy may return at a higher frequency on cessation of sodium oxybate therapy, however this may be due to the normal variability of the disease.
Wara l- waqfien tat- trattament b ’ sodium oxybate, xi pazjenti jistgħu jerġgħu jibdew ibagħtu minn kataplessija bi frekwenza ogħla minn qabel, għalkemm din tista ’ tkun minħabba l- varjabilita` normal tal- marda.
Although the clinical trial experience with sodium oxybate in narcolepsy/ cataplexy patients at therapeutic doses does not show clear evidence of a withdrawal syndrome, in rare cases, adverse events such as insomnia, headache, anxiety, dizziness, sleep disorder, somnolence, hallucination, and psychotic disorders were observed after GHB discontinuation.
Għalkemm l- esperjenza minn provi kliniċi b ’ sodium oxybate f’ dożi terapewtiċi f’ pazjenti b ’ narkolessija / kataplessija ma jurux evidenza ċara ta ’ sindromu ta ’ waqfien mill- mediċina, f’ każi rari, effetti mhux mixtieqa bħal insomnja, uġigħ ta ’ ras, anzjeta`, sturdament, mard ta ’ l- irqad, nagħas, alluċinazzjoni, u mard psikotiku kienu osservati wara il- waqfien ta ’ GHB.
Information about signs and symptoms associated with overdosage with sodium oxybate is limited.
L- informazzjoni dwar is- sinjali u s- sintomi marbuta ma ’ doża eċċessiva b’ sodium oxybate hija limitata.
Most data derives from the illicit use of GHB.
L- biċċa l- kbira tat- tagħrif ġej mill- użu illeċitu ta ’ GHB.
Sodium oxybate is the sodium salt of GHB.
Sodium oxybate huwa s- sodium salt ta ’ GHB.
Events associated with withdrawal syndrome have been observed outside the therapeutic range.
Kienu osservati ġrajjiet marbuta mas- sindromu ta ’ waqfien f’ dożi ogħla minn dawk terapewtiċi.
Patients have exhibited varying degrees of depressed consciousness that may fluctuate rapidly between a confusional, agitated combative state with ataxia and coma.
Pazjenti wrew gradi varji ta ’ koxjenza depressa li setgħu nbiddlu malajr minn stat konfużjonali, aġitat u kombattiv b’ ataxja għal koma.
Emesis (even with impaired consciousness), diaphoresis, headache, and impaired psychomotor skills may be observed.
Jista ’ jiġi osservat rimettar (anke ma ’ kuxjenza mnaqqsa), djaforesi, uġigħ ta ’ ras, u ħiliet psikomuturi mnaqqsa.
Blurred vision has been reported.
Kien rapportat viżżjoni mċajpra.
An increasing depth of coma has been observed at higher doses.
F’ dożi għolja, kien osservat koma iżjed fil- fond.
Myoclonus and tonic-clonic seizures have been reported.
Kienu rapportati aċċessjonijiet tat- tip myoclonus u tonic- clonic.
Cheyne-Stokes respiration and apnoea have been observed.
Hemm rapporti ta ’ kompromess fir- rata u l- fond tar- respirazzjoni kif ukoll ta ’ depressjoni respiratorja fejn ikun hemm theddida għall- ħajja, tant li kien hemm bżonn ta ’ intubazzjoni u ventilazzjoni.
Bradycardia and hypothermia may accompany unconsciousness, as well as muscular hypotonia, but tendon reflexes remain intact.
Jista ’ jkun hemm bradikardja u ipotermja flimkien ma ’ l- inkoxjenza, kif ukoll ipotonja muskolari, mingħajr ma jkun hemm bidla fir- riflessi tal- għerq.
Bradycardia has been responsive to atropine intravenous administration.
Il- bradikardja tirrispondi għal atropine meta jingħata mill- vina.
Gastric lavage may be considered if co-ingestants are suspected.
Jekk ikun hemm suspett li kien hemm teħid ta ’ mediċini oħra, jista ’ jiġi kunsidrat il- ħasil ta ’ l- istonku.
Because emesis may occur in the presence of impaired consciousness, appropriate posture (left lateral recumbent position) and protection of the airway by intubation may be warranted.
Peress li jista ’ jkun hemm rimettar meta jkun hemm nuqqas ta ’ koxjenza, jista ’ jkun hemm bżonn li tinżamm il- pożizzjoni xierqa tal- ġisem (il- pożizzjoni fejn wieħed ikun mimdud fuq il- ġenb tax- xellug) u l- intubazzjoni tat- toqob ta ’ l- imnieħer sabiex dawn jibqgħu miftuħin.
Although gag reflex may be absent in deeply comatose patients, even unconscious patients may become combative to intubation, and rapid sequence induction (without the use of sedative) should be considered.
7 intubazzjoni, u induzzjoni ta ’ sekwenza mgħaġġla (mingħajr l- użu ta ’ sedattiv) għandha tiġi kunsidrata.
No reversal of the central depressant effects of sodium oxybate can be expected from flumazenil administration.
It- teħid ta ’ flumazenil mhux mistenni li jneħħi l- effetti fuq is- sistema nervuża ċentrali ta ’ sodium oxybate.
There is insufficient evidence to recommend the use of naloxone in the treatment of overdose with GHB.
M’ hemm evidenza suffiċjenti li tirrikmanda l- użu ta ’ naloxone fit- trattament ta ’ doża eċċessiva b’ GHB.
The use of haemodialysis and other forms of extracorporeal drug removal have not been studied in sodium oxybate overdose.
L- użu ta ’ emodijaliżi u metodi oħrajn fejn titneħħa l- mediċina minn ġol- ġisem ma kienux studjati b’ dożi eċċessivi ta ’ sodium oxybate.
However, due to the rapid metabolism of sodium oxybate, these measures are not warranted.
Madanakollu, minħabba l- metaboliżmu mgħaġġel ta ’ sodium oxybate, m’ hemmx bżonn dawn il- miżuri.
Other Nervous System Drugs, ATC code:
Mediċini Oħra tas- Sistema Nervuża, Kodiċi ATC:
N07XX04 hydroxybutyric acid
N07XX04 hydroxybutyric acid
Sodium oxybate is a central nervous system depressant which reduces excessive daytime sleepiness and cataplexy in patients with narcolepsy and modifies sleep architecture reducing fragmented nighttime sleep.
Sodium oxybate huwa depressant tas- sistema nervuża ċentrali li jnaqqas nagħas eċċessiv ta ’ bi nhar u u kataplessija f’ pazjenti b’ narkolessija u jbiddel l- istruttura ta ’ l- irqad billi jnaqqas l- irqad mkisser waqt il- lejl.
The precise mechanism by which sodium oxybate produces an effect is unknown, however sodium oxybate is thought to act by promoting slow (delta) wave sleep and consolidating night-time sleep.
Mhux magħruf il- mekkaniżmu preċiż li biħ ikollu effett sodium oxybate, imma sodium oxybate huwa maħsub li jaħdem billi jżid slow (delta) wave sleep u jsaħħaħ l- irqad ta ’ bil- lejl.
Sodium oxybate administered before nocturnal sleep increases Stages 3 and 4 sleep and increases sleep latency, whilst reducing the frequency of sleep onset REM periods (SOREMPs).
Sodium oxybate meta jingħata qabel l- irqad ta ’ bil- lejl iżid l- irqad ta ’ Stadju 3 u Stadju 4 u jżid l- istadju ta ’ qabel l- irqad, waqt li jnaqqas il- frekwenza ta ’ perjodi ta ’ sleep onset REM (SOREMPs).
Other mechanisms, which have yet to be elucidated, may also be involved.
Jista ’ jkun hemm mekkaniżmi oħra involuti li għadhom mhux ċari.
In the clinical trial database, greater than 80% of patients maintained concomitant stimulant use.
Mit- tagħrif miġbur mill- provi kliniċi, iżjed minn 80% tal- pazjenti baqgħu jieħdu ukoll stimulant waqt li kienu fuq sodium oxybate.
The effectiveness of sodium oxybate for the treatment of narcolepsy symptoms was established in four multicentre, randomised, double-blind, placebo-controlled, parallel-group trials (Trial 1, 2, 3 and 4) in patients with narcolepsy with cataplexy except for trial 2 where cataplexy was not required for enrolment Concomitant stimulant use was permitted in all trials (except for the active-treatment phase of Trial 2); antidepressants were withdrawn prior to active treatment in all trials with the exception of Trial 2.
Kien permess it- teħid ukoll ta ’ stimulant f’ kull prova (ħlief fil- fażi ta ’ trattament attiv f’ Prova 2); mediċina kontra d- depressjoni kienu mwaqqfa qabel it- trattament attiv f’ kull prova minbarra Prova 2.
In each trial, the daily dose was divided into two equal doses.
F’ kull prova, id- doża ta ’ kuljum kienet maqsuma f’ żewġt dożi indaqs.
The first dose each night was taken at bedtime and the second dose was taken 2.5 to 4 hours later.
L- ewwel doża kull lejl ittieħded fil- ħin ta ’ l- irqad u t- tieni doża ttieħded 2. 5 sa 4 sigħat wara.
Table 1 Narcolepsy
Skeda 1 Narkolessija
Summary of Clinical Trials Performed Using Sodium Oxybate for the Treatment of
Ġabra fil- Qosor tal- Provi Kliniċi li saru b’ Sodium Oxybate fit- Trattament ta ’
Trial
Prova
Primary N= Secondary Efficacy Duration
Effiċjenza Sekondarja
Active
Trattament
Efficacy
Primarja
treatment and Dose (g/ d)
Attiv u Doża (g/ ġurnata)
Trial 1
Prova 1
MWT/ Sleep Architecture/ Cataplexy/ Naps/ FOSQ
MWT/ Struttura ta ’ L’ Irqad /
8 weeks
8 ġimgħat
Xyrem 4.5 - 9
4. 5 - 9
Trial 2
Kataplessija / Naps/ FOSQ Prova 2
Sleep Architecture/ ESS/ CGIc/ Naps
Struttura ta ’ L’ Irqad /
8 weeks
8 ġimgħat Xyrem 6 – 9
Xyrem 6 – 9 Modafinil 200-600 mg
Modafinil 200- 600 mg
Trial 3
Prova 3 Kataplessija Prova 4 Kataplessija
EDS (ESS)/ CGIc/ Naps
EDS (ESS) / CGIc/ Naps Xejn
4 weeks
4 ġimgħat 4 ġimgħat
Xyrem 3 - 9
Xyrem 3 - 9 Xyrem 3 - 9
EDS – Excessive daytime sleepiness; ESS – Epworth Sleepiness Scale; MWT – Maintenance of Wakefulness Test; Naps – Number of inadvertent daytime naps; CGIc – Clinical Global Impression of Change; FOSQ – Functional Outcomes of Sleep Questionnaire
EDS – nagħas ta ’ bi nhar eċċessiv; ESS – skala tan- nagħas Epworth; MWT – Test ta ’ kemm iżżomm imqajjem; Naps – Numru ta ’ nagħsiet involontarji ta ’ bi nhar; CGIc – L- Impressjoni Globali Klinika tal- Bidla; FOSQ – Risultati Funzjonali tal- Kwestjonarju dwar l- Irqad
Trial 1 enrolled 246 patients with narcolepsy and incorporated a 1 week up-titration period.
F ’ Prova 1, li inkudiet ġimgħa fejn hemm żiediet fid- doża, ħadu sehem 246 pazjent b’ narkolessija.
The primary measures of efficacy were changes in excessive daytime sleepiness as measured by the Epworth Sleepiness Scale (ESS), and the change in the overall severity of the patient’ s narcolepsy symptoms as assessed by the investigator using the Clinical Global Impressions of Change (CGI-c) measure.
Il - kejl primarju ta ’ effiċjenza kienu t- tibdiliet fin- nagħas eċċessiv bi nhar kif imkejla min Epsworth
8 Table 2
8 Sleepiness Scale (ESS), u l- bidla fis- severita` totali tas- sintomi ta ’ narkolessija fil- pazjent kif imkejel mill- investigatur bil- kejl tal- Impressjoni Globali Klinika tal- Bidla (CGI- c).
Summary of ESS in Trial 1
Skeda 2 Ġabra fil- Qosor ta ’ ESS f’ Prova 1
Epworth Sleepiness Scale (ESS; range 0-24)
Skala ta ’ Nagħas Epworth (ESS; medda 0- 24)
Dose Group [g/ d (n)]
Grupp ta ’ Doża [g/ ġurnata (n)]
Baseline
Linja Bażi
Endpoint
Fl- aħħar
Median Change from Baseline
Bidla Medja mill - Linja Bażi
Change from Baseline Compared to Placebo (p-value)
Bidla mill- Linja Bażi mqabbla mall- Plaċebo (p- valur)
Placebo (60) 4.5 (68) 6 (63) 9 (55)
Plaċebo (60) 4. 5 (68) 6 (63) 9 (55)
Table 3
Skeda 3 Ġabra fil- Qosor ta ’ CGI- c f ’ Prova 1
Summary of CGI-c in Trial 1
Impressjonijiet Globali Kliniċi ta ’ Bidla (CGI- c)
Clinical Global Impressions of Change (CGI-c) Dose Group [g/ d (n)]
Grupp ta ’ Doża [g/ ġurnata (n)]
Responders* N (%)
Minn Irrisponda * N (%)
13 (21.7) 32 (47.1) 30 (47.6) 30 (54.4)
13 (21. 7) 32 (47. 1) 30 (47. 6) 30 (54. 4)
- 0.002 < 0.001 < 0.001
- 0. 002 < 0. 001 < 0. 001
* The CGI-c data were analysed by defining responders as those patients who were very much improved or much improved.
* It- tagħrif li nġabar b ’ CGI- c kien analiżżat billi dawn li rrispondew ġew definiti bħala dawk il - pazjenti li ġew l- quddiem ħafna jew dawk il- pazjenti li ġew l- quddiem ħafna iżjed.
Trial 2 compared the effects of orally administered sodium oxybate, modafinil and sodium oxybate + modafinil, with placebo in the treatment of daytime sleepiness in narcolepsy.
F ’ Prova 2 tqabblu l- effetti ta ’ sodium oxybate li jittieħed mill- ħalq, modafinil u sodium oxybate + modafinil, mal- plaċebo fit- trattament ta ’ nagħas bi nhar f’ narkolessija.
During the 8 week double-blind period, patients took modafinil at their established dose or placebo equivalent.
Waqt it- 8 ġimgħat tal- perjodu double blind, il- pazjenti ħadu modafinil fid- doża stabbilita tagħhom jew l- ekwivalenti bil- plaċebo.
The sodium oxybate or placebo equivalent dose was 6g/ day for the first 4 weeks and was increased to 9g/ day for the remaining 4 weeks.
Id - doża ta ’ sodium oxybate jew id- doża ekwivalenti għal plaċebo kienet ta ’ 6g/ ġurnata għall- ewwel 4 ġimgħat u kienet miżjudha għal 9g/ ġurnata għal bqija ta ’ l - 4 ġimgħat.
The primary measure of efficacy was excessive daytime sleepiness as measured by objective response in MWT.
Il- kejl primarju tal- effikaċja kien nagħas eċċessiv bi nhar kif mkejla b ’ risponse oġġettiv f ’ MWT.
Summary of MWT in Trial 2
Skeda 4 Ġabra fil- Qosor ta ’ MWT f ’ Prova 2
TRIAL 2
PROVA 2
Dose Group
Grupp ta ’ Doża
Baseline
Bidla Medja mill - Linja Bażi
Compared to Placebo
L- aħħar mqabbel mall- Plaċebo
Trial 3 enrolled 136 narcoleptic patients with moderate to severe cataplexy (median of 21 cataplexy attacks per week) at baseline.
F’ prova 3 ħadu sehem 136 pazjenti b’ narkolessija u b’ kataplessija moderata jew severa (medja ta ’ 21 attakki ta ’ kataplessija kull ġimgħa) fil- linja bażi.
The primary efficacy measure in this trial was the frequency of cataplexy attacks.
Il- kejl primarju tal- effikaċja f’ din il- prova kien il - frekwenza ta ’ attakki ta ’ kataplessija.
9 Table 5
9 Skeda 5 Ġabra fil- Qosor tar- Risultati F’ Prova 3
Summary of Outcomes in Trial 3
Dożaġġ
Dosage
Numru Persuni
Number of Cataplexy Attacks Subjects
ta ’ Attakki ta ’ Kataplessija
Trial 3
Prova 3
Baseline
Linja Bażi Bidla mill- Linja Medja ta ’ attakki/ ġimgħa
Median Change from Baseline
Medja Bażi
Change Baseline Compared Placebo value)
Bidla mill- Linja Bażi mqabbla mall- Plaċebo (p- valur)
Median attacks/ week Placebo 3.0 g/ day 6.0 g/ day 9.0 g/ day
Plaċebo 3. 0 g/ ġurnata 6. 0 g/ ġurnata 9. 0 g/ ġurnata day
20.5 20.0 23.0 23.5
20. 5 - 4 20. 0 - 7 23. 0 - 10 23. 5 - 16
Trial 4 enrolled 55 narcoleptic patients who had been taking open-label sodium oxybate for 7 to 44 months.
F’ prova 4 ħadu sehem 55 pazjenti b’ narkolessija li kienu qegħdin jieħdu sodium oxybate f’ studju li kien open- label għal 7 sa 44 il- xahar.
Patients were randomised to continued treatment with sodium oxybate at their stable dose or to placebo.
Pazjenti kienu maqsuma mingħajr ma ġew magħżula biex ikomplu t- trattament b’ sodium oxybate fid- doża stabbli tagħhom jew fuq plaċebo.
Trial 4 was designed specifically to evaluate the continued efficacy of sodium oxybate after long-term use.
Il- prova 4 kienet iddiżinjata speċifikament biex tkejjel l- effikaċja kontinwa ta ’ sodium oxybate wara użu fit- tul.
The primary efficacy measure in this trial was the frequency of cataplexy attacks.
Il- kejl primarju tal- effikaċja f’ din il- prova kien il- frekwenza ta ’ attakki ta ’ kataplessija.
Table 6
Skeda 6 Ġabra fil- Qosor tar- Riżultati f’ Prova 4
Summary of outcome in Trial 4
Numru Persuni
Number of Baseline Subjects
ta ’ Linja Bażi
Change Baseline Compared Placebo (p-value)
Bidla mill- Linja Bażi mqabbla mall- Plaċebo (p- valur)
Trial 4
Prova 4
Median attacks/ two
Attakki medji / ġimagħtejn
21.0
4. 0 21. 0
1.9
1. 9 0
In Trial 4, the response was numerically similar for patients treated with doses of 6 to 9 g/ day, but there was no effect seen in patients treated with doses less than 6 g/ day.
F ’ prova 4, ir- rispons kien numerikament simili għal pazjenti b’ dożi ta ’ 6 sa 9 g/ ġurnata, imma ma kienx hemm effett fil- pazjenti fuq trattament b’ dożi inqas minn 6 g/ ġurnata.
Sodium oxybate is rapidly but incompletely absorbed after oral administration; absorption is delayed and decreased by a high fat meal.
Sodium oxybate huuwa assorbit rapidament iżda mhux kompletament wara li jittieħed mill- ħalq; l - assorbiment idum iżjed u jittnaqqas ma ’ ikla għolja fix- xaħam.
It is eliminated mainly by metabolism with a half-life of 0.5 to 1 hour.
Huwa l- biċċa l- kbira eliminat bil - metaboliżmu b’ half- life ta ’ 0. 5 sa 1 siegħa.
Pharmacokinetics are nonlinear with the area under the plasma concentration curve (AUC) versus time curve increasing 3.8-fold as dose is doubled from 4.5g to 9g.
Il- farmakokinetika mhix linejari, b’ erja taħt il- kurva tal - konċentrazzjoni tal- plażma (AUC) versus il- kurva tal- ħin li tiżdied 3. 8 l- darba waqt li tirdopplja d - doża minn 4. 5g to 9g.
The pharmacokinetics are not altered with repeat dosing.
Il- farmakokinetika ma tinbidilx b’ dożaġġ ripetut.
Sodium oxybate is absorbed rapidly following oral administration with an absolute bioavailability of about 25%.
Sodium oxybate huwa assorbit malajr wara li jittieħed mill- ħalq b’ bijodisponibilta` ta ’ madwar 25%.
The average peak plasma concentrations (1st and 2nd peak) following administration of a 9 g daily dose divided into two equivalent doses given four hours apart were 78 and 142 μ g/ ml, respectively.
Il- medja ta ’ l- ogħla konċentrazzjonijiet tal- plażma (l- ewwel u t- tieni l- ogħla) wara amministrazzjoni ta ’ doża kuljum ta ’ 9g maqsuma f’ żewġt dożi ekwivalenti li jingħataw erbgħa siegħat l- bogħod minn xulxin kienu ta ’ 78 u 142 μg/ ml, rispettivament.
The average time to peak plasma concentration (Tmax) ranged from 0.5 to 2 hours in eight pharmacokinetic studies.
Il- ħin medju biex jintlaħaq l - ogħla konċentrazzjonijiet tal- plażma (Tmax) kien ta ’ medda bejn il- 0. 5 sa 2 siegħat fi tmin studji farmakokinetiċi.
Following oral administration, the plasma levels of sodium oxybate increase more than proportionally with increasing dose.
Wara li ttieħed mill- ħalq, il- livelli fil- plażma ta ’ sodium oxybate żdiedu iżjed minn proporzjonalment meta mqabbla maż- żieda fid- doża.
Single doses greater than 4.5 g have not been studied.
Dożi singoli ta ’ iżjed minn 4. 5g ma kienux studjati.
Administration of sodium oxybate immediately after a high fat meal resulted in delayed absorption (average Tmax increased from 0.75 hr to 2.0 hr) and a reduction in peak plasma level (Cmax) by a mean of 58% and of systemic exposure (AUC) by 37%.
It- teħid ta ’ sodium oxybate immedjatament wara ikla għolja fix- xaħam irrisulta f’ assorbiment b’ dewwmien fl- assorbiment (Tmax medju żdied bejn 0. 75 siegħa sa 2. 0 siegħat) u t- tnaqqis fl- ogħla livell tal- plażma (Cmax) b’ medja ta ’ 58% u b’ esponiment sistemiku (AUC) ta ’ 37%.
10 Distribution:
10 Distribuzzjoni: