qanastek/EMEA-V3 huggingface dataset:
These may be local or widespread rashes that may be itchy or blistering, swelling of the eyes and face, difficulty in breathing or swallowing, a sudden drop in blood pressure and loss of consciousness.
Dawn jistgħu jkunu raxx lokali jew mifrux li jista ’ jkun jieklok jew ikun bl- infafet, nefħa fl- għajnejn u l- wiċċ, qtugħ ta ’ nifs jew diffikultà biex tibla ’, pressjoni li titbaxxa f’ daqqa u tintilef min sensik.
Such reactions may occur before leaving the doctor’s surgery.
Dawn ir- reazzjonijiet jistgħu jiġru qabel ma titlaq mill- klinika tat- tabib.
However, you should seek immediate treatment in any event.
Madankollu għandek tfittex għajnuna medika immedjatament f’ kull każ.
Flu-like symptoms, including chills, and muscle and joint pains Fits, dizziness, pins and needles, multiple sclerosis, disease of the nerves of the eye, loss of sensation in, or of the ability to move some parts of the body, severe headache with stiff neck, disruption of the normal brain functions
Sintomi bħal ta 'l- influwenza li jinkludu tkexkix ta ’ bard, u uġigħ fil- muskoli u fil- ġogi Aċċessjonijiet, sturdament, tnemnim, sklerosi multipla, mard fin- nervituri ta ’ l- għajn, nuqqas ta ’ sensazzjoni f’ xi partijiet jew ta ’ l- abbilità li ċċaqlaq xi partijiet tal- ġisem, uġigħ ta ’ ras qawwi b’ ebusija fl- għonq, tfixkil fil- funzjoni normali tal- moħħ.
Faints Inflammation of some blood vessels Feeling or being sick, loss of appetite, diarrhoea and stomach pains Abnormal laboratory liver test results Swelling of the glands Bleeding or bruising more easily than normal due to a drop in a type of blood cell called platelets.
Nefħa tal- glandoli Fsada jew tbenġil aktar mis- soltu minħabba tnaqqis ta ’ ċelluli fid- demm magħrufa bħala plejtlits.
Do not be alarmed by this list of possible side effects.
Tieħux qatgħa b’ din il- lista ta ’ effetti sekondarji li jista ’ jkun hemm.
It is possible that your child has no side effects from vaccination.
Huwa possibbli li ibnek/ bintek ma jkollhomx effetti sekondarji mit- tilqim.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Jekk xi wieħed mill- effetti sekondarji jiggrava jew jekk tinnota xi effetti sekondarji li m’ humiex imsemmijin f’ dan il- fuljett, jekk jogħġbok għid lit- tabib jew lill- ispiżjar tiegħek.
HOW TO STORE AMBIRIX
KIF TAĦŻEN AMBIRIX
Do not use Ambirix after the expiry date which is stated on the carton.
Tużax Ambirix wara d- data ta ’ skadenza li tidher fuq il- kartuna.
Store in the original package in order to protect from light.
Żommu fil- pakket oriġinali sabiex tilqa ’ mid- dawl.
What Ambirix contains
X’ fih Ambirix
Hepatitis B surface antigen 3,4 1 Produced on human diploid (MRC-5) cells 2
Virus ta 'l- epatite A (inattivat) 1, 2 Antiġen tal- wiċċ ta' l- epatite B3, 4 1 Magħmul fuq ċelluli diplojdi (MRC- 5) umani 2
20 micrograms
720 Unitajiet ELISA 20 mikrogramma
Adsorbed on aluminium hydroxide, hydrated
0. 05 milligrammi Al3+ Adsorbit fuq aluminium hydroxide, idratat 3 Magħmul f’ ċelluli tal- ħmira (Saccharomyces cerevisiae) b’ teknoloġija rikombinanti tad- DNA 4 0. 4 milligrammi Al3+ Adsorbit fuq aluminium phosphate
Produced in yeast cells (Saccharomyces cerevsiae) by recombinant DNA technology 4
- Is- sustanzi l- oħra ta’ Ambirix huma: sodium chloride u ilma għall- injezzjonijiet.
- The other ingredients in Ambirix are: sodium chloride and water for injections.
Id- Dehra ta ’ Ambirix u l- kontenut tal- pakkett
What Ambirix looks like and contents of the pack
Suspensjoni għall- injezzjoni f’ siringa mimlija għal- lest.
(1 ml)
Ambirix huwa likwidu abjad qisu ħalib f’ siringa mimlija għal- lest (1ml).
Ambirix is available in packs of 1 and 10 with or without needles and in a pack size of 50 without needles.
Ambirix huwa disponibbli f’ pakketti b’ siringa waħda u b’ 10 siringi bil- labra jew mingħajrha u f’ pakkett b’ 50 siringa mingħajr labar.
Ambirix is a white, slightly milky liquid presented in a prefilled syringe.
Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għal skop kummerċjali.
Rue de l’Institut 89 B-1330 Rixensart Belgium
Rue de l`Institut 89 B- 1330 Rixensart Il- Belġju
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: http://www.emea.europa.eu/.
Informazzjoni dettaljata dwar din il- medicina tinsab fuq il- website ta ’ l- Aġenzija Ewropea dwar il- Mediċini (EMEA): http: // www. emea. europa. eu /. ------------------------------------------------------------------------------------------------------------------------------
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25 It- tagħrif li jmiss qed jingħata biss għall- professjonisti fil- qasam mediku:
The following information is intended for medical or healthcare professionals only:
Meta jinħażen, jista ’ jiġi osservat depożitu abjad fin b’ saff likwidu ċar bla kulur fil- wiċċ.
25 Upon storage, a fine white deposit with a clear colourless supernatant can be observed.
Qabel ma jingħata l- vaċċin għandu jitħawwad sew biex tinkiseb suspensjoni bajda u ftit opaka.
Before administration, the vaccine should be well shaken to obtain a slightly opaque, white suspension.
Il- vaċċin għandu jiġi mifli viżwalment kemm qabel kif ukoll wara ir- risuspensjoni għal xi frak u/ jew dehra fiżika mhux normali.
The vaccine should be visually inspected before or after resuspension for any foreign particulate matter and/or change in physical appearance The vaccine must not be used if any change in the appearance of the vaccine has taken place.
Il- vaċċin m’ għandux jintuża jekk ikun hemm xi tibdil fid- dehra tal- vaċċin.
Any unused vaccine or waste material should be disposed of in accordance with local requirements.
Kull fdal tal- vaċċin li ma jkunx intuża jew skart li jibqa wara l- użu tal- prodott għandu jintrema kif jitolbu l- liġijiet lokali. trema skond il- ħtiġijiet lokali
26 ANNEX IV
26
AMMONAPS 500 mg tablets.
AMMONAPS 500 mg pilloli.
Each tablet contains 500 mg sodium phenylbutyrate.
Kull pillola fiha 500 mg sodium phenylbutyrate.
Tablet.
Pilloli.
The tablets are off-white, oval and embossed with “ UCY 500”.
Il- pilloli huma ta ’ kulur off- wajt, ovali u bit- tinqix “ UCY 500 ”.
AMMONAPS is indicated as adjunctive therapy in the chronic management of urea cycle disorders, involving deficiencies of carbamylphosphate synthetase, ornithine transcarbamylase or argininosuccinate synthetase.
AMMONAPS hu intiż bħala terapija aġġuntiva fil- kura kronika ta ’ disturbi fiċ- ċiklu ta ’ l- urea, li jinvolvu nuqqas ta ’ carbamyl phosphate synthetase, ornithine transcarbamylase, jew argininosuccinate synthetase.
It is indicated in all patients with neonatal-onset presentation (complete enzyme deficiencies, presenting within the first 28 days of life).
Għandu jintuża fil- pazjenti kollha b’ neonatal- onset presentaion (nuqqasijiet sħaħ fl- enżimi li jidhru fl - ewwel 28 ġurnata tal- ħajja).
It is also indicated in patients with late-onset disease (partial enzyme deficiencies, presenting after the first month of life) who have a history of hyperammonaemic encephalopathy.
Għandu jintuża wkoll minn pazjenti fejn il- mard joħroġ aktar tard (nuqqasijiet parzjali fl- enżimi, li jidhru wara l- ewwel xahar ta ’ ħajja) li għandhom storja ta ’ enċefalopatija iperammonemika.
AMMONAPS treatment should be supervised by a physician experienced in the treatment of urea cycle disorders.
Il- kura permezz ta ’ AMMONAPS għandu jkun sorveljat minn tabib b’ esperjenza fil- kura ta ’ problemi fiċ- ċiklu ta ’ l- urea.
The use of AMMONAPS tablets is indicated for adults and children who are able to swallow tablets.
AMMONAPS hu indikat għal adulti u tfal li huma kapaċi jibilgħu l- pilloli.
AMMONAPS is also available as granules for infants, children who are unable to swallow tablets and for patients with dysphagia.
AMMONAPS hu disponibbli bħala granijiet għat- tfal żgħar u tfal li mhumiex kapaċi jibilgħu l- pilloli, u għal pazjenti li għadhom disfaġja.
The daily dose should be individually adjusted according to the patient ’ s protein tolerance and the daily dietary protein intake needed to promote growth and development.
Id- doża ta ’ kuljum għandha tkun maħduma b' mod individwali skond kemm il- pazjent jiflaħ jieħu proteini u l- ammont ta ’ proteini għad- dieta ta ’ kuljum li huma meħtieġa biex wieħed jikber u jiżviluppa.
The safety and efficacy of doses in excess of 20 g/ day (40 tablets) have not been established.
Id- doża totali ta ’ kuljum normali ta ’ sodium phenylbutyrate fl- esperjenza klinika hi: • 450 - 600 mg/ kg/ kuljum fi tfal li jiżnu anqas minn 20 kg 9. 9 - 13. 0 g/ m2/ kuljum fi tfal li jiżnu aktar minn 20 kg, adoloxxenti u adulti. • Is- sigurtà u l- effikaċja ta ’ dożi li jaqbżu l- 20 g/ kuljum (40 pillola) ma kienux stabbiliti.
The total daily dose should be divided into equal amounts and given with each meal (e. g. three times per day).
Id- doża totali ta ’ kuljum għandha titqassam fl- istess ammonti u mogħtija ma ’ kull ikla (i. e. tliet darbiet kuljum).
AMMONAPS tablets should be taken with a large volume of water.
Il- pilloli AMMONAPS għandhom jittieħdu ma ’ ammont kbir ta ’ ilma.
Therapeutic monitoring:
Osservazzjoni terapewtika:
Plasma levels of ammonia, arginine, essential amino acids (especially branched chain amino acids), carnitine and serum proteins should be maintained within normal limits.
Il- livelli fil- plażma ta ’ ammonia, arginine, l- amino aċidi essenzjali (speċjalment branched chain amino acids), carnitine u proteini tas- serum għandhom jinżammu fil - limiti normali.
Plasma glutamine should be maintained at levels less than 1,000 µmol/ l.
Glutamine tal- plażma għandha tinżamm f’ livelli ta ’ anqas minn 1, 000 µmol/ l.
Nutritional management:
2 Kura nutrizzjonali:
AMMONAPS must be combined with dietary protein restriction and, in some cases, essential amino acid and carnitine supplementation.
AMMONAPS għandu jingħata flimkien ma ’ restrizzjoni ta ’ proteini tad- dieta u, f’ ċertu każi, flimkien ma ’ għoti supplimentari ta ’ amino aċidi essenzjali u carnitine.
2 Citrulline or arginine supplementation is required for patients diagnosed with neonatal-onset form of carbamyl phosphate synthetase or ornithine transcarbamylase deficiency at a dose of 0.17 g/ kg/ day or 3.8 g/ m2/ day.
L- għoti supplimentari ta ’ ċitrullina jew arginine huma meħtieġa għall- pazjenti li fuqhom kien djanjostikat nuqqas mat- twelid / mill- ewwel ta ’ carbamyl synthetase tal- fosfat jew ornithine transcarbamylase b’ doża ta ’ 0. 17 g/ kg/ kuljum jew 3. 8 g/ m2/ kuljum.
Arginine supplementation is required for patients diagnosed with deficiency of argininosuccinate synthetase at a dose of 0.4-0.7 g/ kg/ day or 8.8 - 15.4 g/ m2/ day.
L- għoti supplimentari ta ’ arginine hu meħtieġ għall- pazjenti li fuqhom kien djanjostikat nuqqas ta ’ argininosuccinate synthetase b’ doża ta ’ 0. 4- 0. 7 g/ kg/ kuljum or 8. 8 - 15. 4 g/ m2/ kuljum.
If caloric supplementation is indicated, a protein-free product is recommended.
Jekk hu indikat għoti supplimentari ta ’ kaloriji, hu rakkomandat li jingħata prodott ħieles mill- proteini.
− Pregnancy − Breast-feeding − Hypersensitivity to the active substance or to any of the excipients.
Sensittività eċċessiva għas- sustanza attiva jew għal xi waħda mis- sustanzi mhux attivi. −
AMMONAPS tablets should not be used in patients with dysphagia due to the potential risk of oesophageal ulceration if tablets are not promptly delivered to the stomach.
Il- pilloli AMMONAPS m’ għandhomx jintużaw f’ pazjenti li għandhom disfaġja minħabba r- riskju potenzjali ta ’ ulċerazzjoni esofagali jekk il- pilloli ma jgħaddux direttament għal ġol- istonku.
Each AMMONAPS tablet contains 62 mg (2.7 mmol) of sodium, corresponding to 2.5 g (108 mmol) of sodium per 20 g of sodium phenylbutyrate, which is the maximum daily dose.
Kull pillola AMMONAPS fiha 62 mg (2. 7 mmol) ta ’ sodium, korrispondenti għal 2. 5 g (108 mmol) ta ’ sodium kull 20 g ta ’ sodium phenylbutyrate, li hi l- għola doża ta ’ kuljum.
AMMONAPS should therefore be used with caution in patients with congestive heart failure or severe renal insufficiency, and in clinical conditions where there is sodium retention with oedema.
AMMONAPS għalhekk għandu jintuża bl- attenzjoni f’ pazjenti b’ insuffiċjenza tal- qalb konġestiva jew insuffiċjenza serja fil - kliewi, u f’ kundizzjonijiet kliniċi fejn l- edema żżomm sodium.
Since the metabolism and excretion of sodium phenylbutyrate involves the liver and kidneys, AMMONAPS should be used with caution in patients with hepatic or renal insufficiency.
Minħabba li l- metaboliżmu u t- tneħħija mill- ġisem ta ’ sodium phenylbutyrate jinvolvi l- fwied u l - kliewi, AMMONAPS għandu jintuża b’ attenzjoni f’ pazjenti li għandhom insuffiċjenza tal- fwied jew tal- kliewi.
Serum potassium should be monitored during therapy since renal excretion of phenylacetylglutamine may induce a urinary loss of potassium.
Il- potassju fis- serum għandu jkun immonitorjat matul it- terapija minħabba li l- eskrezzjoni mill- kliewi ta ’ phenylacetylglutamine tista ’ tikkawża t- telf ta ’ potassju mill- urina.
Even on therapy, acute hyperammonaemic encephalopathy may occur in a number of patients.
Anki waqt it- terapija, l- enċefalopatija iperammonemika akuta tista ’ sseħħ f’ numru ta ’ pazjenti.
AMMONAPS is not recommended for the management of acute hyperammonaemia, which is a medical emergency.
AMMONAPS mhux rakkomandat għall- immaniġġjar ta ’ iperammonemija akuta, li hi emerġenza medika.
Concurrent administration of probenicid may affect renal excretion of the conjugation product of sodium phenylbutyrate.
L- għotja flimkien ma ’ probenicid tista ’ taffettwa t- tneħħija mill- kliewi tal- prodott ta ’ konġukazzjoni ta ’ sodium phenylbutyrate.
There have been published reports of hyperammonaemia being induced by haloperidol and by valproate.
Kienu ppubblikati rapporti li jsostnu li l- iperammonemja rriżultat kaġun ta ’ haloperidol u ta ’ valproate.
Corticosteroids may cause the breakdown of body protein and thus increase plasma ammonia levels.
Il- kortikosterojdi jistgħu jwasslu għat- tkissir tal- proteini tal- ġisem u b’ hekk jgħollu l- livelli ta ’ ammonia fil- plażma.
More frequent monitoring of plasma ammonia levels is advised when these medications have to be used.
Hu rakkomandat li jkun hemm osservazzjoni aktar frekwenti tal- livelli ta ’ ammonia fil- plażma meta jkun hemm bżonn li jintużaw dawn il- mediċini.
The safety of this medicinal product for use in human pregnancy has not been established.
Is- sigurtà ta ’ dan il- prodott mediċinali meta jintuża waqt it- tqala ma kienetx stabbilita.
Evaluation of experimental animal studies has shown reproductive toxicity, i. e. effects on the development of the embryo or the foetus.
Evalwazzjoni ta ’ studji sperimentali fuq l- annimali wrew tossiċità riproduttiva, i. e. effetti fuq l- iżvilupp ta ’ l- embriju jew il- fetu.
Prenatal exposure of rat pups to phenylacetate (the active metabolite of phenylbutyrate) produced lesions in cortical pyramidal cells; dendritic spines were longer and thinner than normal and reduced in number.
Espożizzjoni qabel it- twelid ta ’ frieħ tal- firien għal phenylacetate (il- metabolitu attiv ta ’ phenylbutyrate) ipproduċa feriti fiċ- ċelloli kortikali piramidali, l- ispina dendritika kienet itwal u irqaq
The significance of these data in pregnant women is not known; therefore the use of AMMONAPS is contra-indicated during pregnancy (see section 4.3).
3 min- normal u mnaqqsa fl- ammont.
3 Effective contraceptive measures must be taken by women of child-bearing potential.
Is- sinifikat ta ’ din l- informazzjoni għan- nisa tqal mhux magħruf; għalhekk AMMONAPS huwa kontra- indikat waqt it- tqala (ara sezzjoni 4. 3).
Lactation:
Treddiegħ:
When high doses of phenylacetate (190 - 474 mg/ kg) were given subcutaneously to rat pups, decreased proliferation and increased loss of neurons were observed, as well as a reduction in CNS myelin.
Meta dożi għolja ta ’ phenylacetate (190 - 474 mg/ kg) ingħataw minn taħt il- ġilda fi frieħ tal- firien, kien osservat tnaqqis tal- proliferazzjoni u żjieda fit- telf ta ’ newroni, kif ukoll tnaqqis ta ’ myelin ta ’ CNS.
Cerebral synapse maturation was retarded and the number of functioning nerve terminals in the cerebrum was reduced, which resulted in impaired brain growth.
Il- maturazzjoni tas- sinapsi ċerebrali ħadet aktar żmien, u kien hemm tnaqqis fin- numru ta ’ terminali nervużi li jaħdmu fiċ- ċerebru, li wassal għal difetti fl- iżvilupp fil- kobor tal- moħħ.
It has not been determined if phenylacetate is secreted in human milk and therefore the use of AMMONAPS is contra-indicated during lactation (see section 4.3).
Ma kienx stabbilit jekk- phenylacetate jitneħħa fil- ħalib ta ’ l- omm u għalhekk AMMONAPS huwa kontra - indikat waqt it- treddiegħ (ara sezzjoni 4. 3).
In clinical trials with AMMONAPS, 56% of the patients experienced at least one adverse event and 78% of these adverse events were considered as not related to AMMONAPS.
F’ eżamijiet kliniċi b’ AMMONAPS, 56% tal- pazjenti esperjenzaw ta ’ l- anqas effett avvers wieħed u 78% ta ’ dawn is- sintomi avversi ma kienux ikkunsidrati li huma marbuta ma ’ AMMONAPS.
Adverse reactions mainly involved the reproductive and gastrointestinal system.
Reazzjonijiet avversi involvew primarjament is- sistema riproduttiva u gastro- intestinali.
The adverse reactions are listed below, by system organ class and by frequency.
Ir- reazzjonijiet avversi huma elenkati hawn taħt, skond il- klassi ta ’ l- organi tas- sistema tal- ġisem u skond il- frekwenza.
Frequency is defined as very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10) and uncommon (≥ 1/ 1,000 to < 1/ 100).
Il- frekwenza hi definita bħala komuni ħafna (≥1/ 10), komuni (≥1/ 100 sa < 1/ 10) u mhux komuni (≥1/ 1, 000 sa < 1/ 100).
Decreased blood potassium, albumin, total protein and phosphate.
Tnaqqis fil- potassium, albumina, proteina totali u phosphate fid- demm.
Increased blood alkaline phosphatase, transaminases, bilirubin, uric acid, chloride, phosphate and sodium.
Żieda fl- alkaline phosphatase, transaminases, bilirubina, uric acid, chloride, phosphate u sodium fid- demm.
Increased weight.
Żieda fil - piż.
Oedema Uncommon:
Edema Mhux komuni:
Arrhythmia
Arritmija
Anaemia, thrombocytopenia, leukopenia, leukocytosis, thrombocytosis Uncommon:
Anemija, tromboċitopenja, lewkopenja, lewkoċitosi, tromboċitosi Mhux komuni:
Aplastic anaemia, ecchymosis
Anemija aplastika, ekkimosi
Syncope, headache
Sinkope, uġigħ ta ’ ras
Abdominal pain, vomiting, nausea, constipation, dysgeusia Uncommon:
Uġigħ ta ’ żaqq, rimettar, nawsja, konstipazzjoni, indeboliment fis- sens tat- togħma Mhux komuni:
Pancreatitis, peptic ulcer, rectal haemorrhage, gastritis
Pankreatite, ulċera peptika, emorraġija tar- rektum, gastrite
Renal tubular acidosis
Aċidożi tubulari tal- kliewi
Rash, abnormal skin odour
Raxx, riħa anormali fil- ġilda
Metabolism and nutrition disorders Common:
Disturbi fil- metaboliżmu u n- nutrizzjoni:
Metabolic acidosis, alkalosis, decreased appetite
Aċidożi metabolika, alkalosi, nuqqas t’ aptit
Reproductive system and breast disorders Very common:
4 Disturbi fis- sistema riproduttiva u fis- sider Komuni ħafna:
Amenorrhoea, irregular menstruation
Amenorrea, mestrwazzjoni irregolari
Depression, irritability
Dipressjoni, irritabilità
4 A probable case of toxic reaction to AMMONAPS (450 mg/ kg/ d) was reported in an 18-year old anorectic female patient who developed a metabolic encephalopathy associated with lactic acidosis, severe hypokalaemia, pancytopaenia, peripheral neuropathy, and pancreatitis.
Każ probabbli ta ’ reazzjoni tossika għal AMMONAPS (450 mg/ kg/ kuljum) kien irrappurtat f’ pazjenta anorettika ta ’ 18- il sena li żviluppat enċefalopatija metabolika assoċjata ma ’ aċidożi lattika, ipokalemija severa, panċitopenja, newropatija periferali, u pankreatite.
She recovered following dose reduction except for recurrent pancreatitis episodes that eventually prompted treatment discontinuation.
Hi rkuprat wara tnaqqis tad - doża ħlief għal episodji rikorrenti ta ’ pankreatite li eventwalment wasslu għat- twaqqif tal- kura.
One case of overdose occurred in a 5-month old infant with an accidental single dose of 10 g (1370 mg/ kg).
Każ wieħed ta ’ doża eċċessiva seħħ f’ tarbija ta ’ 5 xhur b’ doża aċċidentali waħda ta ’ 10 g (1370 mg/ kg).
The patient developed diarrhoea, irritability and metabolic acidosis with hypokalaemia.
Il- pazjent żviluppa dijarrea, irritabbiltà u aċidożi metabolika b’ ipokalemja.
The patient recovered within 48 hours after symptomatic treatment.
Il- pazjent irkupra wara 48 siegħa ta ’ kura sintomatika.
These symptoms are consistent with the accumulation of phenylacetate, which showed dose-limiting neurotoxicity when administered intravenously at doses up to 400 mg/ kg/ day.
Dawn is- sintomi huma konsistenti ma ’ l- akkumulazzjoni ta ’ phenylacetate, li wera newrotossiċità limitata mid- doża meta mogħti fil- vina f’ dożi li jwasslu sa 400 mg/ kg/ kuljum.
Manifestations of neurotoxicity were predominantly somnolence, fatigue and light-headedness.
L- aktar effetti predominanti ta ’ newrotossiċità kienu ħedla, għejja, nuqqas ta ’ konċentrazzjoni.
Less frequent manifestations were confusion, headache, dysgeusia, hypacusis, disorientation, impaired memory and exacerbation of a pre-existing neuropathy.
Manifestazzjonijiet inqas frekwenti kienu: konfużjoni, uġigħ ta ’ ras, disgewsja, ipakużi, nuqqas ta ’ orjentazzjoni, diffikultajiet fil- memorja u żjieda f’ newroapatija eżistenti minn qabel.
In the event of an overdose, discontinue the treatment and institute supportive measures.
F’ każ ta ’ doża eċċessiva, waqqaf il- kura u ibda miżuri ta ’ appoġġ.
Haemodialysis or peritoneal dialysis may be beneficial.
Tista ’ tkun ta ’ benefiċċju l- ħemodijaliżi jew dijaliżi peritonejali.
Pharmacotherapeutic group: alimentary tract and metabolism product, ATC code:
Kategorija farmakoterapewtika: prodott ta ’ l- apparat alimentari u tal- metaboliżmu, Kodiċi ATC:
Sodium phenylbutyrate is a pro-drug and is rapidly metabolised to phenylacetate.
Sodium phenylbutyrate hu pro- drug li jiġi metabolizzat malajr għal phenylacetate.
Phenylacetate is a metabolically active compound that conjugates with glutamine via acetylation to form phenylacetylglutamine which is then excreted by the kidneys.
Phenylacetate hija sustanza metabolikament attiva li tingħaqad ma ’ glutamine permezz ta ’ acetylation biex jifforma phenylacetylglutamine li mbagħad jitneħħa mill- kliewi.
On a molar basis, phenylacetylglutamine is comparable to urea (each containing 2 moles of nitrogen) and therefore provides an alternate vehicle for waste nitrogen excretion.
Fuq bażi molari, phenylacetylglutamine jista ’ jitqabbel ma ’ l- urea (it- tnejn fihom żewġ moles ta ’ nitrogen) u għalhekk jipprovdi metodu alternattiv għat- tneħħija mill- ġisem ta ’ nitrogen mhux meħtieġ.
Based on studies of phenylacetylglutamine excretion in patients with urea cycle disorders it is possible to estimate that, for each gram of sodium phenylbutyrate administered, between 0.12 and 0.15 g of phenylacetylglutamine nitrogen are produced.
Skond studji li saru b’ phenylacetateglutamine, it - tneħħija mill- ġisem f’ pazjenti bi problemi fiċ- ċiklu ta ’ l- urea, hu possibli li jkun stmat li, għal kull gramma ta ’ sodium phenylbutyrate mogħti, jiġi prodott bejn 0. 12 u 0. 15 g ta ’ phenylacetylglutamine nitrogen.
As a consequence, sodium phenylbutyrate reduces elevated plasma ammonia and glutamine levels in patients with urea cycle disorders.
Bħala riżultat ta ’ dan, sodium phenylbutyrate inaqqas il- livell ta ’ ammonia għolja fil- plażma u ta ’ glutamine f’ pazjenti bi problemi fiċ- ċiklu ta ’ l- urea.
It is important that the diagnosis is made early and treatment is initiated immediately to improve the survival and the clinical outcome.
Hu importanti li d- djanjosi ssir minn kmieni u l- kura tibda immedjatament biex tittejjeb il- qagħda klinika u ċ- ċans ta 'sopravivenza.
Previously, neonatal-onset presentation of urea cycle disorders was almost universally fatal within the first year of life, even when treated with peritoneal dialysis and essential amino acids or their nitrogen- free analogues.
Qabel, neonatal- onset presentation ta ’ disturbi taċ- ċiklu ta ’ l- urea kienu kważi universalment fatali fl - ewwel sena tal- ħajja, anke meta kkurata permezz ta ’ dijaliżi peritonejali u b ’ amino aċidi essenzjali jew l- analogi tagħhom li huma ħielsa minn nitrogen.
With haemodialysis, use of alternative waste nitrogen excretion pathways (sodium phenylbutyrate, sodium benzoate and sodium phenylacetate), dietary protein restriction, and, in some cases, essential amino acid supplementation, the survival rate in new-borns diagnosed after birth (but within the first month of life) increased to almost 80% with most deaths occurring during an episode of acute hyperammonaemic encephalopathy.
Permezz ħemodijaliżi, l- użu ta ’ rotot alternattivi għat- tneħħija mill- ġisem ta ’ nitrogen mhux meħtieġ, (sodium phenylbutyrate, sodium benzoate u sodium phenylacetate), restrizzjoni tal- proteini fid- dieta, u, f’ ċertu każi, l- għoti supplimentari ta ’ amino aċidi essenzjali, ir- rata ta ’ għajxien f’ trabi li għadhom kif jitwieldu djanjostikati wara t- twelid (iżda fl- ewwel xahar tal- ħajja) żdiedet sa kważi 80% bil- parti l- kbira ta ’ l- imwiet iseħħ matul episodju ta ’ enċefalopatija iperammonemika akuta.
Patients with neonatal-onset disease had a high incidence of mental retardation.
Pazjenti fejn il- marda ħarġet immedjatament mat- twelid, tirriżulta inċidenza għolja ta ’ nuqqas ta ’ żvilupp mentali.
In patients diagnosed during gestation and treated prior to any episode of hyperammonaemic encephalopathy, survival was 100%, but even in these patients, many subsequently demonstrated cognitive impairment or other neurologic deficits.
F’ pazjenti djanjostikati matul il- ġestazzjoni u kkurati qabel xi espisodju ta ’ enċefalopatija iperammonemika, ir- rata ta ’ għajxien kienet ta ’ 100%, imma anke f’ dawn il- pazjenti, ħafna eventwalment urew nuqqasijiet konjittivi jew nuqqasijiet newroloġiċi oħra.
In late-onset deficiency patients, including females heterozygous for ornithine transcarbamylase deficiency, who recovered from hyperammonaemic encephalopathy and were then treated chronically with dietary protein restriction and sodium phenylbutyrate, the survival rate was 98%.
5 F’ pazjenti fejn il- marda ħarġet tard, inklużi eterożigi femminili għal nuqqas ta ’ ornithine transcarbamylase, li rkupraw minn enċefalopatija iperammonemika u kienu kkurati b’ mod kroniku b’ restirizzjoni tal- proteini fid- dieta u sodium phenylbutyrate, ir- rata ta ’ għajxien kienet ta ’ 98%.
The majority of the patients who were tested had an IQ in the average to low average/ borderline mentally retarded range.
Il - maġġoranza tal- pazjenti li kienu eżaminati kellhom livell ta ’ IQ bejn medju u medju baxx/ borderline mentally retarded range.
Their cognitive performance remained relatively stable during phenylbutyrate therapy.
Ir- riżulati konjittivi tagħhom jibqgħu relattivament stabbli matul it- terapija permezz ta ’ phenylbutyrate.
5 Reversal of pre-existing neurologic impairment is not likely to occur with treatment, and neurologic deterioration may continue in some patients.
Hu diffiċli li l- kura twassal biex jingħelbu nuqqasijiet newroloġiċi eżistenti minn qabel, u deterjorazzjoni newroloġika tista ’ tkompli f’ xi pazjenti.
AMMONAPS may be required life-long unless orthotopic liver transplantation is elected.
AMMONAPS jista ’ jkun meħtieġ matul il- ħajja kollha sakemm ma jsirx trapjant ortotopiku tal- fwied.
Phenylbutyrate is known to be oxidised to phenylacetate which is enzymatically conjugated with glutamine to form phenylacetylglutamine in the liver and kidney.
Phenylbutyrate hu magħruf li jossida ruħu għal phenylacetate li jingħaqad b' mod enżimatiku ma ’ glutamine biex jifforma phenylacetylglutamine fil- fwied u l- kliewi.
Phenylacetate is also hydrolysed by esterases in liver and blood.
Phenylacetate jiġi idrolizzat ukoll mill- esterases fil- fwied u fid- demm.
Plasma and urine concentrations of phenylbutyrate and its metabolites have been obtained from fasting normal adults who received a single dose of 5 g of sodium phenylbutyrate and from patients with urea cycle disorders, haemoglobinopathies and cirrhosis receiving single and repeated oral doses up to 20 g/ day (uncontrolled studies).
Il- konċentrazzjonijiet fil- plażma u ta ’ l- awrina ta ’ phenylbutyrate u l- metaboliti tiegħu nkisbu minn adulti normali sajmin li ngħataw doża waħda ta ’ 5 g ta ’ sodium phenylbutyrate u minn pazjenti bi problemi fiċ- ċiklu ta ’ l- urea, emoglobinopatijiet u cirrhosis li ngħataw doża waħda u dożi orali ripetuti sa 20 g/ kuljum (studji mhux kontrollati).
The disposition of phenylbutyrate and its metabolites has also been studied in cancer patients following intravenous infusion of sodium phenylbutyrate (up to 2 g/ m²) or phenylacetate.
Id- dispożizzjoni ta ’ phenylbutyrate u l- metaboliti tiegħu kienet studjata wkoll f’ pazjenti b’ kanċer wara infużjoni fil- vina ta ’ sodium phenylbutyrate (sa 2 g/ m²) jew phenylacetate.
After a single oral dose of 5 g of sodium phenylbutyrate, in the form of tablets, measurable plasma levels of phenylbutyrate are detected 15 minutes after dosing.
Assorbiment Phenylbutyrate jiġi assorbit malajr waqt li tkun sajjem: wara doża waħda orali ta ’ 5 g ta ’ sodium phenylbutyrate, fil- forma ta ’ pilloli, livelli li jitkejjlu fil- plażma kienu osservati 15- il minuta wara l - għotja tad- doża.
The mean time to peak concentration is 1.35 hour and the mean peak concentration 218 µg/ ml.
Il- ħin medju biex tintlaħaq il- konċentrazzjoni massima hu ta ’ 1. 35 siegħa u l - konċentrazzjoni massima medja hi ta ’ 218 µg/ ml.
The elimination half-life was estimated to be 0.8 hours.
Il- half- life ta ’ l- eliminazzjoni hi 0. 8 siegħa.
The effect of food on absorption is unknown.
L- effett ta ’ l- ikel fuq l- assorbiment mhux magħruf.
Distribution The volume of distribution of phenylbutyrate is 0.2 l/ kg.
Distribuzzjoni Il- volum ta ’ distribuzzjoni ta ’ phenylbutyrate hu ta ’ 0. 2 l/ kg.
Metabolism After a single dose of 5 g of sodium phenylbutyrate, in the form of tablets, measurable plasma levels of phenylacetate and phenylacetylglutamine are detected 30 and 60 minutes respectively after dosing.
Metaboliżmu Wara doża waħda ta ’ 5 g ta ’ sodiumphenylbutyrate fil- forma ta ’ pillola, livelli li jitkejjlu fil- plażma ta ’ phenylacetate u phenylacetylglutamine kienu osservati 30 u 60 minuta rispettivament wara l- għotja tad- doża.
The mean time to peak concentration is 3.74 and 3.43 hours, respectively, and the mean peak concentration is 48.5 and 68.5 µg/ ml, respectively.
Il- perjodu medju biex tintlaħaq il- konċentrazzjoni massima hu ta ’ 3. 74 u 3. 43 siegħat, rispettivament, u l- konċentrazzjoni massima medja hi ta ’ 48. 5 and 68. 5 µg/ ml, rispettivament.
The elimination half-life was estimated to be 1.2 and 2.4 hours, respectively.
Il- half - life ta ’ l- eliminazzjoni hi 1. 2 u 2. 4 siegħat, rispettivament.
Studies with high intravenous doses of phenylacetate showed non linear pharmacokinetics characterised by saturable metabolism to phenylacetylglutamine.
Studji b’ għotja ta’ dożi għoljin fil- vina ta ’ phenylacetate urew farmokinetika mhux lineari kkaraterizzata minn metaboliżmu saturabbli għal phenylacetylglutamine.
Repeated dosing with phenylacetate showed evidence of an induction of clearance.
Dożaġġ ripetut b’ phenylacetate wera evidenza ta ’ induzzjoni tat- tneħħija.
In the majority of patients with urea cycle disorders or haemoglobinopathies receiving various doses of phenylbutyrate (300 - 650 mg/ kg/ day up to 20 g/ day) no plasma level of phenylacetate could be detected after overnight fasting.
Fil- maġġoranza tal- pazjenti b’ disturbi fiċ- ċiklu ta ’ l- urea jew b’ emoglobinopatiji li kienu qed jirċievu diversi dożi ta ’ phenylbutyrate (300 - 650 mg/ kg/ kuljum sa 20 g/ kuljum) ma seta ’ jkun osservat l- ebda livell ta ’ phenylacetate fil- plażma wara lejl li fih il- pazjent ma ħa xejn.
In patients with impaired hepatic function the conversion of phenylacetate to phenylacetylglutamine may be relatively slower.
F’ pazjenti b’ indeboliment fil - funzjoni epatika, il- konversjoni ta ’ phenylacetate għal phenylacetylglutamine tista ’ ddum relattivament aktar.
Three cirrhotic patients (out of 6) who received repeated oral administration of sodium phenylbutyrate (20 g/ day in three doses) showed sustained plasma levels of phenylacetate on the third day that were five times higher than those achieved after the first dose.
Tliet pazjenti ċirrotiċi (minn 6) li rċevew għotja orali ta ’ sodium phenylbutyrate (20 g/ kuljum fi tliet dożi) urew livelli sostenuti ta ’ phenylacetate fil- plażma fit- tielet ġurnata, li huma ta ’ ħames darbiet aktar minn dawk miksuba mill- ewwel doża.
In normal volunteers gender differences were found in the pharmacokinetic parameters of phenylbutyrate and phenylacetate (AUC and Cmax about 30-50% greater in females), but not phenylacetylglutamine.
F’ voluntiera normali, differenzi fis- sess instabu fil- parametri farmakokinetiċi ta ’ phenylbutyrate u phenylacetate (AUC u Cmax madwar 30- 50% akbar fin- nisa) iżda mhux phenylacetylglutamine.
This may be due to the lipophilicity of sodium phenylbutyrate and consequent differences in volume of distribution.
Dan jista ’ jkun minħabba l- lipofiliċità ta ’ sodium phenylbutyrate u differenzi konsegwenti fil- volum ta ’ distribuzzjoni.
Excretion Approximately 80-100% of the medicinal product is excreted by the kidneys within 24 hours as the conjugated product, phenylacetylglutamine.
6 Eskrezzjoni Madwar 80- 100% tal- prodott mediċinali jitneħħa mill- kliewi f’ 24 siegħa bħala prodott konjugat, phenylacetylglutamine.
6 5.3 Preclinical safety data
5. 3 Tagħrif ta ’ qabel l- użu kliniku dwar is- sigurtà tal- medicina
Sodium phenylbutyrate was negative in 2 mutagenicity tests, i. e. the Ames test and the micronucleus test.
Kien hemm riżultat negattiv f’ 2 studji fuq il- mutaġeniċita b’ sodium phenylbutyrate, i. e. l- eżami Ames u l- eżami tal- mikronukleju.
Results indicate that sodium phenylbutyrate did not induce any mutagenic effects in the Ames test with or without metabolic activation.
Ir- riżultati jindikaw li sodium phenylbutyrate ma jwassal għall- ebda effett mutaġeniku fl- eżami Ames kemm b’ attivazzjoni metabolika kif ukoll mingħajra.
Micronucleus test results indicate that sodium phenylbutyrate was considered not to have produced any clastogenic effect in rats treated at toxic or non-toxic dose levels (examined 24 and 48 hours after a single oral administration of 878 to 2800 mg/ kg).
Ir- riżultati ta ’ l- eżami tal- mikronukleju jindikaw li sodium phenylbutyrate ma kienx ikkunsidrat li jipproduċi l- ebda effett klastoġeniku fuq firien ikkurati b’ livelli ta ’ doża tossika jew mhux tossika (eżaminati 24 u 48 siegħa wara doża orali waħda ta ’ 878 sa 2800 mg/ kg).
Carcinogenicity and fertility studies have not been conducted with sodium phenylbutyrate.
Ma sarux studji dwar il - karċinoġeniċità u fertilità ta ’ sodium phenylbutyrate.
Microcrystalline cellulose Magnesium stearate Colloidal anhydrous silica
Microcrystalline cellulose Magnesium stearate Colloidal anhydrous silica
HDPE bottles containing 250 or 500 tablets.
Fliexken HDPE li fihom 250 jew 500 pillola.
The bottles are equipped with child resistant caps.
Dawn il- fliexken huma mgħammra b’ għotjien li ma jinfetħux mit- tfal.
Swedish Orphan International AB Drottninggatan 98 SE-111 60 Stockholm Sweden
Swedish Orphan International AB Drottninggatan 98 SE- 111 60 Stockholm L- Isvezja
EU/ 1/ 99/ 120/ 001 (250 tablets) EU/ 1/ 99/ 120/ 002 (500 tablets)
EU/ 1/ 99/ 120/ 001 (250 pillola) EU/ 1/ 99/ 120/ 002 (500 pillola)
08/ 12/ 1999 Date of latest renewal:
08/ 12/ 1999 Data ta ’ l- aħħar tiġdid:
AMMONAPS 940 mg/ g granules
AMMONAPS 940 mg/ g granijiet
Sodium phenylbutyrate:
Sodium phenylbutyrate:
940 mg/ g of granules
940 mg/ g ta ’ granijiet
Granules.
Granijiet
The granules are off-white.
Il- granijiet huma ta ’ kulur abjad jagħti fil- griż.
AMMONAPS is indicated as adjunctive therapy in the chronic management of urea cycle disorders, involving deficiencies of carbamylphosphate synthetase, ornithine transcarbamylase or argininosuccinate synthetase.
AMMONAPS hu intiż bħala terapija aġġuntiva fil- kura kronika ta ’ disturbi fiċ- ċiklu ta ’ l- urea, li jinvolvu nuqqas ta ’ carbamyl phosphate synthetase, ornithine transcarbamylase jew argininosuccinate synthetase.
AMMONAPS granules should be administered orally (to infants and children unable to swallow tablets and to patients with dysphagia) or via gastrostomy or nasogastric tube.
AMMONAPS granijiet għandhom jittieħdu mill- ħalq (lil trabi u tfal li ma jafux jibilgħu l- pilloli, u lil pazjenti li għandhom disfaġja) jew permezz ta ’ gastrostomy jew tubu nażogastriku.
The usual total daily dose of sodium phenylbutyrate in clinical experience is: • 450 - 600 mg/ kg/ day in neonates, infants and children weighing less than 20 kg • 9.9 - 13.0 g/ m2/ day in children weighing more than 20 kg, adolescents and adults.
Id- doża totali ta ’ kuljum normali ta ’ sodium phenylbutyrate fl- esperjenza klinika hi:
The safety and efficacy of doses in excess of 20 g/ day have not been established.
450 - 600 mg/ kg/ kuljum fi trabi li għadhom jitwieldu, trabi u tfal li jiżnu anqas minn 20 kg • 9. 9 - 13. 0 g/ m2/ kuljum fi tfal li jiżnu aktar minn 20 kg, adoloxxenti u adulti. • Is- sigurtà u l- effikaċja ta ’ dożi li jaqbżu l- 20 g/ kulum ma kienux stabbiliti.
The total daily dose should be divided into equal amounts and given with each meal or feeding (e. g.
Id- doża totali ta ’ kuljum għandha titqassam f’ ammonti ugwali u mogħtija ma ’ kull ikla jew tmiegħ (eż.
4- 6 times per day in small children).
4- 6 darbiet kuljum fit- tfal iż- żgħar).
When taken orally, the granules are to be mixed with solid foods (such as mashed potatoes or apple sauce) or liquid foods (such as water, apple juice, orange juice or protein-free infant formulas).
Meta jittieħed mill- ħalq, il- granijiet għandhom jitħalltu ma ’ ikel solidu (bħal patata mgħaffġa jew zalza tat- tuffieħ) jew ikel likwidu (bħal meraq tat- tuffieħ, meraq tal - larinġ jew ikel tat- trabi li ma jkunx fih proteini).
Three dosing spoons are provided which dispense 0.95 g, 2.9 g or 8.6 g of sodium phenylbutyrate.
Tlett imgħaref għad- doża huma provduti li jesgħu 0. 95 g, 2. 9 g jew 8. 6 g ta ’ sodium phenylbutyrate.
Lightly shake the bottle before dispensing.
Ċaqlaq il- flixkun bil- mod qabel ma tiftħu.
9 Therapeutic monitoring:
9 Osservazzjoni terapewtika:
Nutritional management:
Kura nutrizzjonali:
Citrulline or arginine supplementation is required for patients diagnosed with neonatal-onset form of carbamyl phosphate synthetase or ornithine transcarbamylase deficiency at a dose of 0.17 g/ kg/ day or 3.8 g/ m2/ day.
L- għoti supplimentari ta ’ ċitrullina jew arginine huma meħtieġa għall- pazjenti li fuqhom kien djanjostikat nuqqas mat- twelid / mill- ewwel ta ’ carbamyl synthetase tal- fosfat jew ornithine transcarbamylase b’ doża ta ’ 0. 17 g/ kg/ kuljum jew 3. 8 g/ m2/ kuljum.
AMMONAPS granules contain 124 mg (5.4 mmol) of sodium per gram of sodium phenylbutyrate, corresponding to 2.5 g (108 mmol) of sodium per 20 g of sodium phenylbutyrate, which is the maximum daily dose.
Il- granuli AMMONAPS jinkludu124 mg (5. 4 mmol) ta ’ sodju kull gramma ta ’ sodium phenylbutyrate, korrispondenti għal 2. 5 g (108 mmol) ta ’ sodium kull 20 g ta ’ sodium phenylbutyrate, li hi l- għola doża ta ’ kuljum.
AMMONAPS should therefore be used with caution in patients with congestive heart failure or severe renal insufficiency, and in clinical conditions where there is sodium retention with oedema.
AMMONAPS għalhekk għandu jintuża bl- attenzjoni f’ pazjenti b’ insuffiċjenza tal- qalb konġestiva jew insuffiċjenza serja fil- kliewi, u f’ kundizzjonijiet kliniċi fejn l - edema żżomm sodium.
4.6 Pregnancy and lactation
10 4. 6 Tqala u treddigħ
Prenatal exposure of rat pups to phenylacetate (the active metabolite of phenylbutyrate) produced lesions in cortical pyramidal cells; dendritic spines were longer and thinner
Espożizzjoni qabel it- twelid ta ’ frieħ tal- firien għal phenylacetate (il- metabolitu attiv ta ’ phenylbutyrate) ipproduċa feriti fiċ- ċelloli kortikali piramidali, l- ispina dendritika kienet itwal u irqaq min- normal u mnaqqsa fl- ammont.
The significance of these data in pregnant women is not known; therefore the use of AMMONAPS is contra-indicated during pregnancy (see section 4.3).
Is- sinifikat ta ’ din l- informazzjoni għan- nisa tqal mhux magħruf; għalhekk AMMONAPS huwa kontra- indikat waqt it- tqala (ara sezzjoni 4. 3).
Effective contraceptive measures must be taken by women of child-bearing potential.
Miżuri effettivi ta ’ kontraċezzjoni għandhom jittieħdu minn nisa li jistgħu jkollhom it- tfal.
Skin and subcutaneous tissue disorders Common:
11 Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Komuni:
Reproductive system and breast disorders Very common:
Disturbi fis- sistema riproduttiva u fis- sider Komuni ħafna:
11 Psychiatric disorders Common:
Disturbi psikjatriċi Komuni:
A probable case of toxic reaction to AMMONAPS (450 mg/ kg/ d) was reported in an 18-year old anorectic female patient who developed a metabolic encephalopathy associated with lactic acidosis, severe hypokalaemia, pancytopaenia, peripheral neuropathy, and pancreatitis.
Każ probabbli ta ’ reazzjoni tossika għal AMMONAPS (450 mg/ kg/ kuljum) kien irrappurtat f’ pazjenta anorettika ta ’ 18- il sena li żviluppat enċefalopatija metabolika assoċjata ma ’ aċidożi lattika, ipokalemija severa, panċitopenja, newropatija periferali, u pankreatite.
Less frequent manifestations were confusion, headache, dysgeusia, hypacusis, disorientation, impaired memory and exacerbation of a pre-existing neuropathy.
Manifestazzjonijiet inqas frekwentikienu konfużjoni, uġigħ ta ’ ras, disgewsja, ipakużi, nuqqas ta ’ orjentazzjoni, diffikultajiet fil- memorja u żjieda f’ newroapatija eżistenti minn qabel.
With haemodialysis, use of alternative waste nitrogen excretion pathways (sodium phenylbutyrate, sodium benzoate and sodium phenylacetate), dietary protein restriction, and, in some cases, essential amino acid supplementation, the survival rate in new-borns diagnosed after birth (but within the first month of life) increased to almost 80% with most deaths occurring during an episode of acute hyperammonaemic encephalopathy.
Permezz ħemodijaliżi, l- użu ta ’ rotot alternattivi għat- tneħħija mill- ġisem ta ’ nitrogen mhux meħtieġ, (sodium phenylbutyrate, sodium benzoate u sodium phenylacetate), restrizzjoni tal- proteini fid- dieta, u, f’ ċertu każi, l- għoti supplimentari ta ’ amino aċidi essenzjali, ir- rata ta ’ għajxien f’ trabi li għadhom kif jitwieldu djanjostikati wara t- twelid
Patients with neonatal-onset disease had a high incidence of mental retardation.
12 (iżda fl- ewwel xahar tal- ħajja) żdiedet sa kważi 80% bil- parti l- kbira ta ’ l- imwiet iseħħ matul episodju ta ’ enċefalopatija iperammonemika akuta.
The majority of
F’ pazjenti fejn il- marda ħarġet tard, inklużi eterożigi femminili għal nuqqas ta ’ ornithine transcarbamylase, li rkupraw minn enċefalopatija iperammonemika u kienu kkurati b’ mod kroniku b’ restirizzjoni tal- proteini fid- dieta u sodium phenylbutyrate, ir- rata ta ’ għajxien kienet ta ’ 98%.
12 the patients who were tested had an IQ in the average to low average/ borderline mentally retarded range.
Il - maġġoranza tal- pazjenti li kienu eżaminati kellhom livell ta ’ IQ bejn medju u medju baxx/ borderline mentally retarded range.
Reversal of pre-existing neurologic impairment is not likely to occur with treatment, and neurologic deterioration may continue in some patients.
Hu diffiċli li l- kura twassal biex jingħelbu nuqqasijiet newroloġiċi eżistenti minn qabel, u deterjorazzjoni newroloġika tista ’ tkompli f’ xi pazjenti.
After a single oral dose of 5 g of sodium phenylbutyrate, in the form of granules, measurable plasma levels of phenylbutyrate are detected 15 minutes after dosing.
Assorbiment Phenylbutyrate jiġi assorbit malajr waqt li tkun sajjem: wara doża waħda orali ta ’ 5 g ta ’ sodium phenylbutyrate, fil- forma ta ’ granuli, livelli li jitkejjlu fil- plażma kienu osservati 15- il minuta wara l - għotja tad- doża.
The mean time to peak concentration is 1 hour and the mean peak concentration 195 µg/ ml.
Il- ħin medju biex tintlaħaq il- konċentrazzjoni massima hu ta ’ 1 siegħa u l - konċentrazzjoni massima medja hi ta ’ 195 µg/ ml.
Distribution The volume of distribution of phenylbutyrate is 0.2 l/ kg.
Distribuzzjoni Il- volum ta ’ distribuzzjoni tal- fenajlbutirajt hu ta ’ 0. 2 l/ kg.
Metabolism After a single dose of 5 g of sodium phenylbutyrate, in the form of granules, measurable plasma levels of phenylacetate and phenylacetylglutamine are detected 30 and 60 minutes respectively after dosing.
Metaboliżmu Wara doża waħda ta ’ 5 g ta ’ fenajlbutirajt ta ’ sodju fil- forma ta ’ granijiet, livelli li jitkejjlu fil- plażma ta ’ phenylacetate u phenylacetylglutamine kienu osservati 30 u 60 minuta rispettivament wara l- għotja tad- doża.
The mean time to peak concentration is 3.55 and 3.23 hours, respectively, and the mean peak concentration is 45.3 and 62.8 µg/ ml, respectively.
Il- perjodu medju biex tintlaħaq il- konċentrazzjoni massima hu ta ’ 3. 55 u 3. 23 siegħat, rispettivament, u l- konċentrazzjoni massima medja hi ta ’ 45. 3 and 62. 8 µg/ ml, rispettivament.
The elimination half-life was estimated to be 1.3 and 2.4 hours, respectively.
Il- half - life ta ’ l- eliminazzjoni hi 1. 3 u 2. 4 siegħat, rispettivament.
In patients with impaired hepatic function the conversion of phenylacetate to phenylacetylglutamine may be relatively slower.
F’ pazjenti b’ indeboliment fil - funzjoni epatika il- konversjoni ta ’ phenylacetate għal phenylacetylglutamine tista ’ ddum relattivament
Excretion Approximately 80-100% of the medicinal product is excreted by the kidneys within 24 hours as the conjugated product, phenylacetylglutamine.
Eskrezzjoni Madwar 80- 100% tal- prodott mediċinali jitneħħa mill- kliewi f’ 24 siegħa bħala prodott konjugat, phenylacetylglutamine.
13 5.3 Preclinical safety data
5. 3 Tagħrif ta ’ qabel l- użu kliniku dwar is- sigurtà tal- medicina
Calcium stearate Colloidal anhydrous silica
Calcium stearate Colloidal anhydrous silica
During the shelf life the patient may store the finished product for a single period of 3 months at a temperature not above 25°C, after which the product must be discarded.
6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
HDPE bottles containing 266 g or 532 g of granules.
Fliexken HDPE li fihom 266 g jew 532g ta ’ granijiet.
The bottles are equipped with child resistant caps.
Dawn il- fliexken huma mgħammra b’ għotjin li ma jinfetħux mit- tfal.
Three dosage spoons of different measures are provided.
Tlett imgħaref ta ’ kejl differenti għad- doża huma provduti.
It is recommended that a heaped measuring spoon is removed from the container and a flat surface, e. g. the blade of a knife, is drawn across the top of the measure.
Ix - xafra ta ’ sikkina jitpoġġa fil- parti ta ’ fuq ta ’ fejn jintuża għat- tkejjil.
This will give the following doses: small measure 0.95 g, medium measure 2.9 g and large measure 8.6 g of sodium phenylbutyrate.
Dan se jagħti d- dożi segwenti: miżura żgħira 0. 95 g, miżura ta ’ daqs medju 2. 9 mg u miżura kbira ta ’ 8. 6 g ta ’ sodium phenylbutyrate.
Please note that the re- constituted granules will normally produce a milky white suspension.
Meta l- pazjent jeħtieġ għotja permezz ta ’ tubu, hu possibbli li AMMONAPS jitħallat ma ’ l- ilma qabel jintuża (is- solubilità ta ’ sodium phenylbutyrate tilħaq il- 5g f’ 10 ml ta ’ ilma.).
Where AMMONAPS granules need to be added to food, liquid or water, it is important that it is taken immediately after mixing.
Jekk jogħġbok innota li l- granijiet imħallta ma ’ l- ilma jipproduċu suspensjoni ta ’ kulur abjad tal- ħalib.
Any unused product or waste material should be disposed of in accordance with local requirements.
Meta l- granijiet ta ’ AMMONAPS għandhom jittieħdu ma ’ l- ikel, likwidu jew ilma, hu importanti li dawn jittieħdu immedjatament wara li jitħalltu.
EU/ 1/ 99/ 120/ 003 (266 g granules) EU/ 1/ 99/ 120/ 004 (532 g granules)
EU/ 1/ 99/ 120/ 003 (266 g granijiet) EU/ 1/ 99/ 120/ 004 (532 g granijiet)
Bioglan AB, Borrgatan 31, SE-211 24 Malmö, Sweden
• Bioglan AB, Borrgatan 31, SE- 211 24 Malmö, L- Isvezja
19 PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE PACKAGING
19 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA U FUQ IL- PAKKETT LI JMISS MAL- PRODOTT