qanastek/EMEA-V3 huggingface dataset:
Frequencies are defined as common (≥ 1/ 100, < 1/ 10) or uncommon (≥ 1/ 1,000, < 1/ 100).
Il- frekwenzi huma definiti bħala komuni (≥1/ 100, < 1/ 10) jew mhux komuni (≥1/ 1, 000, < 1/ 100).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
L- effetti li huma l - aktar serji għandhom jitniżżlu l- ewwel, segwiti minn dawk anqas serji.
Blood and lymphatic system disorders Common: thrombocytopenia, leucopenia, granulocytopenia Uncommon: leukocytosis
Disturbi tad- demm u tas- sistema limfatika Komuni: tromboċitopenja, lewkopenja, granuloċitopenja Mhux Komuni: lewkoċitosi
Eye disorders Common: conjunctivitis, corneal opacity, keratitis, photophobia, eye pain Uncommon: blepharitis
Disturbi fl- għajnejn Komuni: konġuntivite, opaċità tal- kornea, keratite, fotofobia, uġigħ fl- għajnejn Mhux Komuni: blefarite
Skin and subcutaneous tissue disorders Uncommon: exfoliative dermatitis, erythematous rash, pruritus
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Mhux Komuni: exfoliative dermatitis, raxx eritematuż, ħakk
Nitisinone treatment is associated with elevated tyrosine levels.
Il- kura b’ nitisinone hi marbuta ma ’ livelli għoljin ta ’ tyrosine.
Elevated levels of tyrosine have been associated with corneal opacities and hyperkeratotic lesions.
Livelli għoljin ta ’ tyrosine kienu marbuta ma ’ opaċitajiet tal- kornea u leżjonijiet iperkeratotiċi.
Restriction of tyrosine and phenylalanine in the diet should limit the toxicity associated with this type of tyrosinemia (see section 4.4).
Ir- restrizzjoni ta ’ tyrosine u phenylalanine fid- dieta għandha tillimita t- tossiċità marbuta ma ’ dan it- tip ta ’ tirosinemia (ara sezzjoni 4. 4).
Accidental ingestion of nitisinone by individuals eating normal diets not restricted in tyrosine and phenylalanine will result in elevated tyrosine levels.
F’ każ li individwi li qegħdin fuq dieti normali, li mhumiex ristretti għal tyrosine u phenylalanine, jibilgħu nitisinone b’ mod aċċidentali, dan ser jirriżulta f’ livelli għoljin ta ’ tyrosine.
Elevated tyrosine levels have been associated with toxicity to eyes, skin, and the nervous system.
Livelli għoljin ta ’ tyrosine kienu assoċjati ma ’ tossiċità ta ’ l- għajnejn, tal- ġilda, u tas- sistema nervuża.
Restriction of tyrosine and phenylalanine in the diet should limit toxicity associated with this type of tyrosinemia.
Ir- restrizzjoni ta ’ tyrosine u phenylalanine fid- dieta għandha tillimita t- tossiċità marbuta ma ’ dan it- tip ta ’ tirosinemia.
No information about specific treatment of overdose is available.
L- ebda tagħrif dwar il- kura speċifika ta ’ doża eċċessiva mhu disponibbli.
Other alimentary and metabolism products.
Prodotti tal- metaboliżmu u prodotti oħrajn ta ’ l- ikel.
The biochemical defect in hereditary tyrosinemia type 1 (HT-1) is a deficiency of fumarylacetoacetate hydrolase, which is the final enzyme of the tyrosine catabolic pathway.
Id- difett bijokimiku fit- tirosinemia ereditarja ta ’ tip 1 (HT- 1) hu defiċjenza ta ’ fumarylacetoacetate hydrolase, li hu l- enzima finali tal- passaġġ kataboliku ta ’ tyrosine.
Nitisinone is a competitive inhibitor of 4-hydroxyphenylpyruvate dioxygenase, an enzyme which precedes fumarylacetoacetate hydrolase in the tyrosine catabolic pathway.
Nitisinone hu inibitur kompetittiv ta ’ 4- hydroxyphenylpyruvate dioxygenase, enzima li għandha preċedenza fuq fumarylacetoacetate hydrolase fil- passaġġ kataboliku ta ’ tyrosine.
By inhibiting the normal catabolism of tyrosine in patients with HT-1, nitisinone prevents the accumulation of the toxic intermediates maleylacetoacetate and fumarylacetoacetate.
Billi jinibixxi l- kataboliżmu normali ta ’ tyrosine f’ pazjenti b’ HT- 1, nitisinone jevita l- akkumulazzjoni ta ’ l- intermedji tossiċi maleylacetoacetate u fumarylacetoacetate.
In patients with HT-1, these intermediates are converted to the toxic metabolites succinylacetone and succinylacetoacetate.
F’ pazjenti b’ HT- 1, dawn l- intermedji jinbidlu għal metaboliti tossiċi succinylacetone u succinylacetoacetate.
Succinylacetone inhibits the porphyrin synthesis pathway leading to the accumulation of 5-aminolevulinate.
Succinylacetone jinibixxi s- sintesi tal- passaġġ ta ’ porphyrin li jwassal għall- akkumulazzjoni ta ’ 5- aminolevulinate.
Nitisinone treatment leads to normalised porphyrin metabolism with normal erythrocyte PBG- synthase activity and urine 5-ALA, decreased urinary excretion of succinylacetone, increased plasma tyrosine concentration and increased urinary excretion of phenolic acids.
4 Il- kura b’ nitisinone twassal għal metaboliżmu normalizzat ta ’ porphyrin bl- attività ta ’ erythrocyte PBG- synthase normali u 5- ALA fl- awrina, tnaqqis fit- tneħħija fl- awrina ta ’ succinylacetone, żieda fil - konċentrazzjoni ta ’ tyrosine fil- plażma u żieda fit- tneħħija fl- awrina tal- phenolic acids.
Available data from a clinical study indicates that in more than 90% of the patients urine succinylacetone was normalized during the first week of treatment.
Dejta disponibbli minn studju kliniku tindika li iktar minn 90% ta ’ succinylacetone fl- awrina tal- pazjenti kien normalizzat matul l- ewwel ġimgħa tal- kura.
Succinylacetone should not be detectable in urine or plasma when the nitisinone dose is properly adjusted.
Succinylacetone m’ għandux ikun osservat fl- awrina jew fil- plażma meta d- doża ta ’ nitisinone tkun aġġustata kif suppost.
4 Effects on overall survival When compared to data for historical controls, it can be seen that treatment with nitisinone together with dietary restriction results in a better survival probability in all HT-1 phenotypes.
Effetti fuq is- sopravivenza totali Meta mqabbel ma ’ l- informazzjoni għal kontrolli storiċi, jista ’ jiġi nnutat li l- kura b’ nitisinone flimkien ma ’ restrizzjoni tad- dieta, irriżultat fi probabbiltà aħjar tas- sopravivenza fil- fenotipi HT- 1 kollha.
This is seen in the following table:
Dan jintwera fit- tabella li ġejja:
Age at start of treatment
Età fil- bidu tal- kura jew
Survival probability
Probabbiltà tas- sopravivenza
or diagnosis
dijanjosi
Nitisinone treatment
Kura b’ nitisinone
Dietary control *
Kontroll tad- dieta *
5 years
10 snin 5 sni
5 years
5 snin 10 snin 5 snin
10 years
10 snin
< 2 months > 2-6 months > 6 months
< xahrejn > 2- 6 xhur > 6 xhur
* From Figure 1, Van Spronsen et al., 1994.
* Minn Figura 1, Van Spronsen et al., 1994.
Treatment with nitisinone was also found to result in reduced risk for the development of hepatocellular carcinoma (2.3 to 3.7-fold) compared to historical data on treatment with dietary restriction alone.
Instab ukoll li l- kura b’ nitisinone irriżultat f’ riskju mnaqqas għall- iżvilupp ta ’ karċinoma epatoċellulari (2. 3 sa 3. 7 darbiet) meta mqabbla ma ’ d- dejta storika dwar il- kura bir- restrizzjoni tad- dieta waħidha.
It was found that the early initiation of treatment resulted in a further reduced risk for the development of hepatocellular carcinoma (13.5-fold when initiated prior to the age of 12 months).
Instab li l- bidu bikri tal- kura rriżulta f’ riskju mnaqqas b’ mod addizzjonali għall- iżvilupp ta ’ karċinoma epatoċellulari (13. 5 darbiet meta tinbeda qabel l- età ta ’ 12- il xahar).
This medicinal product has been authorised under “ Exceptional Circumstances”.
Din il- mediċina kienet awtorizzata taħt ‘ ċirkustanzi ta ’ eċċezzjoni ’.
This means that due to the rarity of the disease it has not been possible to obtain complete information on this medicinal product.
Dan ifisser li minħabba li l- marda li qed tbati minnha hija rari, kien impossibbli li tinkiseb informazzjoni kompleta dwar il- benefiċċji u r- riskji ta ’ dan il- prodott mediċinali.
The European Medicines Agency (EMEA) will review any new information which may become available every year and this SPC will be updated as necessary.
L- Aġenzija Ewropea dwar il- Mediċini (EMEA) ser tirrevedi kull tip ta ’ informazzjoni ġdida li toħroġ kull sena u ser taġġorna dan is- Sommarju tal- Karatteristiċi tal- Prodott, skond il- bżonn.
Formal absorption, distribution, metabolism and elimination studies have not been performed with nitisinone.
Studji formali dwar l- assorbiment, id- distribuzzjoni, il- metaboliżmu u l- eliminazzjoni ma sarux b’ nitisinone.
In 10 healthy male volunteers, after administration of a single dose of nitisinone capsules (1 mg/ kg body weight) the terminal half-life (median) of nitisinone in plasma was 54 hours.
F’ 10 voluntiera rġiel b’ saħħithom, wara l- għoti ta ’ doża waħda ta ’ kapsuli ta ’ nitisinone (1 mg / kg ta ’ piż tal- ġisem) il- half- life terminali (medjan) ta ’ nitisinone fil- plażma kienet ta ’ 54 siegħa.
Population pharmacokinetic analysis has been conducted on a group of 207 HT-1 patients.
L- analiżi farmakokinetika tal- popolazzjoni twettqet fuq grupp ta ’ 207 pazjenti li kellhom l- HT- 1.
The clearance and half-life were determined to be 0.0956 l/ kg body weight/ day and 52.1 hours respectively.
It - tneħħija u l- half- life kienu ddeterminati li huma 0. 0956 litri / kg ta ’ piż tal- ġisem / kuljum u 52. 1 sigħat rispettivament.
In vitro studies using human liver microsomes and cDNA-expressed P450 enzymes have shown limited CYP 3A4-mediated metabolism.
Studji in vitro bl- użu ta ’ mikrosomi tal- fwied uman u enzimi cDNA- expressed P450 urew metaboliżmu limital medjat minn CYP 3A4.
Nitisinone has shown embryo-foetal toxicity in the mouse and rabbit at clinically relevant dose levels.
Nitisinone wera tossiċità embriju- fetali fil- ġrieden u fil- fniek f’ livelli tad- doża li kienu klinikament rilevanti.
In the rabbit, nitisinone induced a dose-related increase in malformations (umbilical hernia and gastroschisis) from a dose level of 2.5-fold higher than the maximum recommended human dose (2 mg/ kg/ day).
Fil- fniek, nitisinone ikkaġuna żieda fil- malformazzjonijiet relatati mad- doża (ernja umbilikali u gastroschisis) minn livell ta ’ doża ta ’ 2. 5 darbiet ogħla mill- massimu rakkomandat fil - bniedem (2 mg/ kg/ kuljum).
A pre and postnatal development study in the mouse showed statistically significant reduced pup survival and pup growth during the weaning period at dose levels of 125- and 25-fold, respectively, the maximum recommended human dose, with a trend effect on pup survival starting from the dose of 5 mg/ kg/ day.
Studju dwar l- iżvilupp ta ’ qabel u wara t- twelid fil- ġrieden wera sopravivenza u t- tkabbir tal- frieħ matul il- perjodu tal- ftim, li kienu mnaqqsa b’ mod statistikament sinifikanti f’ livelli ta ’ doża ta ’ 125 u 25 darba, rispettivament, tad- doża massima rakkomandata fil- bniedem, b’ effett ta ’ l- andament tas- sopravivenza tal- frieħ li jibda mid- doża ta ’ 5 mg/ kg/ kuljum.
In rats, exposure via milk resulted in reduced mean pup weight and corneal lesions.
Fil- firien, l- espożizzjoni permezz tal - ħalib irriżultat f’ medja mnaqqsa tal- piż tal- frieħ u leżjonijiet tal- kornea.
No mutagenic but a weak clastogenic activity was observed in in vitro studies.
5 L- ebda attività mutaġenika ma kienet osservata, iżda attività klastoġenika dgħajfa kienet osservata fi studji in vitro.
There was no evidence of in vivo genotoxicity (mouse micronucleus assay and mouse liver UDS assay).
Ma kien hemm l- ebda evidenza ta ’ ġenotossiċità in vivo (fl- assaġġ tal- mikronukleu tal - ġrieden u fl- assaġġ UDS tal- fwied tal- ġrieden).
Carcinogenicity studies have not been performed.
Ma sarux studji dwar il- karċinoġeneċità.
Capsule content pregelatinised starch (maize)
Kontenut tal- kapsula pregelatinised starch (maize)
Capsule shell gelatin titanium dioxide (E 171) imprint: black iron oxide (E 172), shellac, propylene glycol
Qoxra tal- kapsula gelatin titanium dioxide (E 171) stampar: black iron oxide (E 172), shellac, propylene glycol
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.
Matul iż- żmien kemm idum tajjeb il- prodott mediċinali, il- pazjent jista ’ jaħżen il- prodott finali għal perjodu wieħed ta ’ 3 xhur f’ temperatura ta ’ mhux iktar minn 25°C, u wara dan, il- prodott għandu jintrema.
High density polyethylene bottle with a tamper proof low density polyethylene cap, containing 60 capsules.
Flixkun tal- polyethylene b’ densità għolja, b’ għatu tal- polyethylene li jirreżisti l- ftuħ bi protezzjoni kontra t- tbagħbis, li fih 60 kapsula.
Swedish Orphan International AB Drottninggatan 98 SE-111 60 Stockholm Sweden
Swedish Orphan International AB Drottninggatan 98 SE- 111 60 Stockholm Svezja
Orfadin 5 mg hard capsules.
Orfadin 5 mg kapsuli iebsin
Each capsule contains 5 mg nitisinone.
Kull kapsula fiha 5 mg ta ’ nitisinone.
White, opaque capsules marked “ NTBC 5mg” on one side of the capsule.
Kapsuli bojod, opaki, immarkati b ’ “ NTBC 5 mg ” fuq naħa waħda tal- kapsula.
Nitisinone treatment should be initiated and supervised by a physician experienced in the treatment of HT-1 patients.
It- terapija b ’ b’ nitisinone deferiprone trid tinbeda u tiġi mmaniġġjata minn tabib li għandu esperjenza fil- kura ta ’ pazjenti bl- HT- 1.
Treatment of all genotypes of the disease should be initiated as early as possible to increase overall survival and avoid complications such as liver failure, liver cancer and renal disease.
Il- kura tal- ġenotipi kollha tal- marda għandhom jinbdew kmieni kemm jista ’ jkun biex iżidu s- sopravivenza totali u jevitaw komplikazzjonijiet bħal insufffiċjenza tal- fwied, kanċer tal- fwied u mard mard renali.
Adjunct to the nitisinone treatment, a diet deficient in phenylalanine and tyrosine is required and should be followed by monitoring of plasma amino acids (see sections 4.4 and 4.8).
Kura aġġuntiva għall- kura b’ nitisinone, dieta li hi defiċjenti f’ phenylalanine u tyrosine hi meħtieġa u għandha tiġi segwita minn monitoraġġ ta ’ l- amino acids tal - plażma (ara sezzjonijiet 4. 4 u 4. 8).
The recommended initial dose is 1 mg/ kg body weight/ day divided in 2 doses administered orally.
Id- doża tal- bidu rakkomandata hi ta ’ 1 mg għal kull kilogramm ta ’ piż tal- ġisem kuljum maqsuma f’ 2 dożi li jingħataw mill- ħalq.
The capsule may be opened and the content suspended in a small amount of water or formula diet immediately before intake.
Il- kapsula tista ’ tinfetaħ u l- kontenut jitħallat ma ’ ammont żgħir ta ’ ilma jew dieta tal- formula immedjatament qabel tittieħed.
A dose of 2 mg/ kg body weight/ day may be needed based on the evaluation of all biochemical parameters.
Doża ta ’ 2 mg għal kull/ kg ta’ piż tal- ġisem kuljum tista ’ tkun meħtieġa bbażata fuq l- evalwazzjoni tal- parametri bijokimiċi kollha.
However, in addition to the tests above, during the initiation of therapy or if there is a deterioration it may be necessary to follow more closely all available biochemical parameters (i. e. plasma succinylacetone, urine 5-aminolevulinate (ALA) and erythrocyte porphobilinogen (PBG)-synthase activity).
Madankollu, flimkien mat- testijiet t’ hawn fuq, matul il- bidu tat- terapija jew jekk ikun hemm deterjorament, jista ’ jkun meħtieġ li ssegwi iktar mill- qrib il- parametri bijokimiċi kollha disponibbli (i. e. succinylacetone fil- plażma, 5- aminolevulinate (ALA) fl- awrina u l- attività ta ’ erythrocyte porphobilinogen (PBG) - synthase).
7 4.3 Contraindications
8 4. 3 Kontra- indikazzjonijiet
Mothers receiving nitisinone should not breast-feed (see sections 4.6 and 5.3).
Ommijiet li jkunu qed jużaw nitisinone m’ għandhomx ireddgħu (ara sezzjonijiet 4. 6 u 5. 3).
Platelet and white blood cell (WBC) monitoring It is recommended that platelet and white cell counts are monitored regularly, as a few cases of reversible trombocytopenia and leucopenia were observed during clinical evaluation.
Monitoraġġ tal- plejtlits u taċ- ċelluli bojod tad- demm (white blood cell - WBC) Hu rakkomandat li l- għadd tal- plejtlits u taċ- ċelluli bojod tad- demm ikun immonitorjat regolarment, minħabba li xi ftit każijiet ta ’ tromboċitopenja u lewkopenja riversibbli kienu osservati matul l- evalwazzjoni klinika.
However, nitisinone has been co- administered with food during the generation of efficacy and safety data.
Madankollu, nitisinone ingħata flimkien ma ’ l- ikel matul produzzjoni ta ’ dejta ta ’ l- effikaċja u s- sigurtà.
The potential risk for humans is unknown.
Ir- riskju potenzjali ghall- bnedmin mhuwiex maghruf.
Lactation It is not known whether nitisinone is excreted in human breast milk.
9 Treddigħ Mhuwiex magħruf jekk nitisinone jitneħħiex fil- ħalib tas- sider uman.
Animal studies have shown adverse postnatal effects via exposure of nitisinone in milk.
Studji fuq l- annimali wrew effetti avversi wara t- twelid permezz ta ’ l- espożizzjoni ta ’ nitisinone fil- ħalib.
Therefore, mothers receiving nitisinone should not breast-feed, since a risk to the suckling child cannot be excluded (see sections 4.3 and 5.3).
Għalhekk, ommijiet li jkunu qed jieħdu nitisinone m’ għandhomx ireddgħu, għax ir- riskju lit- tarbija li tkun qed terda ’ ma jistax jiġi eskluż (ara sezzjonijiet 4. 3 u 5. 3).
8 4.7 Effects on ability to drive and use machines
4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
Blood and lymphatic system disorders Common: thrombocytopenia, leucopenia, granulocytopenia Uncommon: leucocytosis
Disturbi tad- demm u tas- sistema limfatika Komuni: tromboċitopenja, lewkopenja, granuloċitopenja Mhux Komuni: lewkoċitosi
In patients with HT-1, these intermediates are converted to the toxic metabolites succinylacetone and succinylacetoacetate.
10 succinylacetone u succinylacetoacetate.
Nitisinone treatment leads to normalised porphyrin metabolism with normal erythrocyte PBG- synthase activity and urine 5-ALA, decreased urinary excretion of succinylacetone, increased plasma tyrosine concentration and increased urinary excretion of phenolic acids.
Il- kura b’ nitisinone twassal għal metaboliżmu normalizzat ta ’ porphyrin bl- attività ta ’ erythrocyte PBG- synthase normali u 5- ALA fl- awrina, tnaqqis fit- tneħħija fl- awrina ta ’ succinylacetone, żieda fil - konċentrazzjoni ta ’ tyrosine fil- plażma u żieda fit- tneħħija fl- awrina tal- phenolic acids.
Available data from a clinical study indicates that in more than 90% of the patients urine succinylacetone was normalized during the
Informazzjoni disponibbli minn studju kliniku tindika li iktar minn 90% ta ’ succinylacetone fl- awrina tal- pazjenti kien normalizzat matul l- ewwel ġimgħa tal- kura.
Effects on overall survival When compared to data for historical controls, it can be seen that treatment with nitisinone together with dietary restriction results in a better survival probability in all HT-1 phenotypes.
Effetti fuq is- sopravivenza totali Meta mqabbel ma ’ l- informazzjoni għal kontrolli storiċi, jista ’ jiġi nnutat li l- kura b’ nitisinone flimkien ma ’ restrizzjoni tad- dieta, irriżultat fi probabbiltà aħjar tas- sopravivenza fil- fenotipi HT- 1 kollha.
5 years
10 snin 5 sn
*From Figure 1, Van Spronsen et al., 1994.
* Minn Figura 1, Van Spronsen et al., 1994.
This means that due to the rarity of the disease it has not been possible to obtain complete information on this medicinal product.
Dan ifisser li minħabba li l- marda li qed tbati minnha hija rari, kien impossibbli li tinkiseb informazzjoni kompleta dwar dwar il- benefiċċji u r- riskji ta ’ dan il- prodott mediċinali.
The clearance and half-life were determined to be 0.0956 l/ kg body weight/ day and 52.1 hours respectively.
It - tneħħija u l- half- life kienu ddeterminati li huma 0. 0956 l / kg ta ’ piż tal- ġisem kuljum u 52. 1 sigħat rispettivament.
A pre and postnatal development study in the mouse showed statistically significant reduced pup survival and pup growth during the weaning period at dose levels of 125- and 25-fold, respectively, the maximum recommended human dose, with a trend effect on pup survival starting from the dose of 5 mg/ kg/ day.
Studju dwar l- iżvilupp ta ’ qabel u wara t- twelid fil- ġrieden wera sopravivenza u t- tkabbir tal- frieħ matul il- perjodu tal- ftim, li kienu mnaqqsa b’ mod statistikament sinifikanti f’ livelli ta ’ doża ta ’ 125 u
In rats, exposure via milk resulted in reduced mean pup weight and corneal lesions.
11 25 darba, rispettivament, tad- doża massima rakkomandata fil- bniedem, b’ effett ta ’ l- andament tas - sopravivenza tal- frieħ li jibda mid- doża ta ’ 5 mg/ kg/ kuljum.
No mutagenic but a weak clastogenic activity was observed in in vitro studies.
L- ebda attività mutaġenika ma kienet osservata, iżda attività klastoġenika dgħajfa kienet osservata fi studji in vitro.
Orfadin 10 mg hard capsules.
Orfadin 10 mg kapsuli iebsin.
Each capsule contains 10 mg nitisinone.
Kull kapsula fiha 10 mg ta ’ nitisinone.
White, opaque capsules marked “ NTBC 10mg” on one side of the capsule.
Kapsuli bojod, opaki, immarkati b ’ “ NTBC 10mg ” fuq naħa waħda tal- kapsula.
Adjunct to the nitisinone treatment, a diet deficient in phenylalanine and tyrosine is required and should be followed by monitoring of plasma amino acids (see sections 4.4 and 4.8).
Kura aġġuntiva għall- kura b’ nitisinone il- kura, dieta li hi defiċjenti f’ phenylalanine u tyrosine hi meħtieġa u għandha tiġi segwita minn monitoraġġ ta ’ l- amino acids tal - plażma (ara sezzjonijiet 4. 4 u 4. 8).
The recommended initial dose is 1 mg/ kg body weight/ day divided in 2 doses administered orally.
Id- doża tal- bidu rakkomandata hi ta ’ 1 mg/ kg ta ’ piż tal- ġisem kuljum maqsuma f’ 2 dożi li jingħataw mill- ħalq.
If urine succinylacetone is still detectable one month after the start of nitisinone treatment, the nitisinone dose should be increased to 1.5 mg/ kg body weight/ day divided in 2 doses.
Jekk succinylacetone fl - awrina jkun jista ’ jiġi osservat wara xahar mill- bidu tal- kura b’ nitisinone, id- doża ta ’ nitisinone għandha tiżdied għal 1. 5 mg/ kg ta ’ piż tal- ġisem kuljum, maqsuma f’ 2 dożi.
12 4.3 Contraindications
14 4. 3 Kontra- indikazzjonijiet
Mothers receiving nitisinone should not breast-feed (see section 4.6 and 5.3).
Ommijiet li jkunu qed jużaw nitisinone m’ għandhomx ireddgħu (ara sezzjonijiet 4. 6 u 5. 3).
Platelet and white blood cell (WBC) monitoring It is recommended that platelet and white cell counts are monitored regularly, as a few cases of reversible trombocytopenia and leucopenia were observed during clinical evaluation.
Monitoraġġ tal - plejtlits u taċ- ċelluli bojod tad- demm (white blood cell - WBC) Hu rakkomandat li l- għadd tal - plejtlits u taċ- ċelluli bojod tad- demm ikun immonitorjat regolarment, minħabba li xi ftit każijiet ta ’ tromboċitopenja u lewkopenja riversibbli kienu osservati matul l- evalwazzjoni klinika.
Studies in animals have shown reproductive toxicity (see sections 5.3).
Studji fuq l- annimali wrew tossiċità riproduttiva (ara sezzjoni 5. 3).
Lactation It is not known whether nitisinone is excreted in human breast milk.
15 Treddigħ Mhuwiex magħruf jekk nitisinone jitneħħiex fil- ħalib tas- sider uman.
Skin and subcutaneous tissue disorders Uncommon: pruritus, exfoliative dermatitis, erythematous rash
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Mhux Komuni: exfoliative dermatitis, raxx eritematuż, ħakk
In patients with HT-1, these intermediates are converted to the toxic metabolites succinylacetone and succinylacetoacetate.
16 succinylacetone u succinylacetoacetate.
Available data from a clinical study indicates that in more than 90% of the patients urine succinylacetone was normalized during the
Dejta disponibbli minn studju kliniku tindika li iktar minn 90% ta ’ succinylacetone fl- awrina tal- pazjenti kien normalizzat matul l- ewwel ġimgħa tal- kura.
5 years
10 snin 5 s
In 10 healthy male volunteers, after administration of a single dose of nitisinone capsules (1 mg/ kg body weight) the terminal half-life (median) of nitisinone in plasma was 54 hours.
F’ 10 voluntiera rġiel b’ saħħithom, wara l- għoti ta ’ doża waħda ta ’ kapsuli ta ’ nitisinone (1 mg/ kg ta ’ piż tal- ġisem) il- half- life terminali (medjan) ta ’ nitisinone fil- plażma kienet ta ’ 54 siegħa.
The clearance and half-life were determined to be 0.0956 l/ kg body weight/ day and 52.1 hours respectively.
It - tneħħija u l- half- life kienu ddeterminati li huma 0. 0956 litri/ kg ta ’ piż tal- ġisem kuljum u 52. 1 sigħat rispettivament.
In rats, exposure via milk resulted in reduced mean pup weight and corneal lesions.
17 25 darba, rispettivament, tad- doża massima rakkomandata fil- bniedem, b’ effett ta ’ l- andament tas - sopravivenza tal- frieħ li jibda mid- doża ta ’ 5 mg/ kg/ kuljum.
16 ANNEX II
19 ANNESS II
Apoteket AB Produktion & Laboratorier Prismavägen 2 SE-141 75 Kungens Kurva Sweden
Apoteket AB Produktion & Laboratorier Prismavägen 2 SE- 141 75 Kungens Kurva Svezja
The Marketing Authorisation Holder shall complete the following programme of studies within the specified time frame, the results of which shall form the basis of the annual reassessment of the benefit/ risk profile.
Id- detentur ta ’ l- awtorizzazzjoni għat- tqegħid fis- suq għandu jtemm il- programm ta ’ studji fiż- żmien speċifikat, u r- riżultati ta ’ dawn l- istudji għandhom iservu ta ’ bażi għall- istima tal- profil bejn il - benefiċċju/ riskju li jsir kull sena.
Area1 Clinical
Deskrizzjoni
Description The company should establish a Post Marketing Surveillance Program (PMS) for the use of nitisinone in the treatment of Hypertyrosinaemia type 1, including liver, renal, haematological, neurological and ophthalmic status.
Il- kumpanija għandha tistabbilixxi Programm ta ’ Sorveljanza ta ’ Wara l- Bejgħ (Post Marketing Surveillance Program - PMS) għall- użu ta ’ nitisinone fil- kura ta ’ Ipertirosinemija tip 1, li tinkludi l- istat tal- fwied, tal- kliewi, l- istat ematoloġiku, newroloġiku u oftalmiku.
The PMS protocol has been developed and provided to the CHMP.
Il- protokoll PMS kien żviluppat u pprovdut lis- CHMP.
All relevant data gathered from this program will be summarized and included in the PSUR.
Ser isir sommarju ta ’ l- informazzjoni rilevanti kollha miġbura minn dan il- programm u dan ser ikun inkluż fil- PSUR.
Due date2 Available data will be provided in the PSUR according to the normal reporting schedule.
L - informazzjoni disponibbli ser tkun ipprovduta fil- PSUR skond l - iskeda normali tar - rappurtaġġ.
Areas:
Oqsma:
Quality, Non-clinical, Clinical, Pharmacovigilance 2.
Kwalità, Mhux Klinika, Klinika, Farmakoviġilanza 2.
Due date for the follow-up measure or for the first interim report if a precise date cannot be committed to.
Id- data ta ’ l- għeluq għall- miżura follow- up jew għall- ewwel rapport interim jekk ma jkunx hemm impenn għal data preċiża.
18 ANNEX III
21 ANNESS III
20 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
23 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA
OUTER PACKAGING/ CARTON
PAKKETT/ KARTUNA TA ’ BARRA
Orfadin 2 mg hard capsules Nitisinone
Orfadin 2 mg kapsuli iebsin Nitisinone
Each capsule contains 2 mg nitisinone
Kull kapsula fiha 2 mg ta ’ nitisinone
60 hard capsules
60 kapsula iebsin
SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCT OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE
PREKAWZJONIJIET SPEĊJALI GĦAR- RIMI TA ’ PRODOTTI MEDIĊINALI MHUX UŻATI JEW SKART MINN DAWN IL- PRODOTTI MEDIĊINALI, JEKK HEMM BŻONN
22 PARTICULARS TO APPEAR ON IMMEDIATE PACKAGING UNITS
25 TAGĦRIF MINIMU LI GĦANDU JIDHER FUQ IL- PAKKETTI Ż- ŻGĦAR EWLENIN
IMMEDIATE PACKAGING/ BOTTLE LABEL
PAKKETT EWLIENI/ TIKKETTA TAL- FLIXKUN
Orfadin 2 mg hard capsules Nitisinone Oral use
Orfadin 2 mg kapsuli iebsin Nitisinone Użu orali
EXP {MM/ YYYY)
EXP {XX/ SSSS}
Orfadin capsules can be stored for a single period of 3 months at a temperature not above 25°C, after which the product must be discarded.
Il- kapsuli Orfadin jistgħu jinħażnu għal perjodu wieħed ta ’ 3 xhur f’ temperatura ta ’ mhux iktar minn 25°C, u wara dan, il- prodott għandu jintrema.
CONTENTS BY UNIT
IL- KONTENUT SKOND IL- PIŻ, VOLUM, JEW PARTI INDIVIDWALI
23 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
26 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA
Orfadin 5 mg hard capsules Nitisinone
Orfadin 5 mg kapsuli iebsin Nitisinone
Each capsule contains 5 mg nitisinone
Kull kapsula fiha 5 mg ta ’ nitisinone
EXP{MM/ YYYY}
EXP {XX/ SSSS}
25 PARTICULARS TO APPEAR ON IMMEDIATE PACKAGING UNITS
28 TAGĦRIF MINIMU LI GĦANDU JIDHER FUQ IL- PAKKETTI Ż- ŻGĦAR EWLENIN
Orfadin 5 mg hard capsules Nitisinone Oral use
Orfadin 5 mg kapsuli iebsin Nitisinone Użu orali
EXP {MM/ YYYY
EXP {XX/ SSSS}
26 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
29 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA
Orfadin 10 mg hard capsules Nitisinone
Nitisinone
Each capsule contains 10 mg nitisinone
Kull kapsula fiha 10 mg ta ’ nitisinone.
28 PARTICULARS TO APPEAR ON IMMEDIATE PACKAGING UNITS
31 TAGĦRIF MINIMU LI GĦANDU JIDHER FUQ IL- PAKKETTI Ż- ŻGĦAR EWLENIN
Orfadin 10 mg hard capsules Nitisinone Oral use
Nitisinone Użu orali
EXP {MM/ YYYY
EXP{ XX/ SSSS}
30 PACKAGE LEAFLET:
33 FULJETT TA ’ TAGĦRIF:
Orfadin 2 mg hard capsules Orfadin 5 mg hard capsules Orfadin 10 mg hard capsules nitisinone
Orfadin 2 mg kapsuli iebsin Orfadin 5 mg kapsuli iebsin Orfadin 10 mg kapsuli iebsin. nitisinone
- This medicine has been prescribed for you.
- Din il- mediċina ġingħatat lilek.
What Orfadin is and what it is used for 2.
X’ inhu Orfadin u għalxiex jintuża 2.
Before you take Orfadin 3.
Qabel ma ’ tieħu Orfadin 3.
How to take Orfadin 4.
Kif għandek tieħu Orfadin 4.
Possible side effects 5 How to store Orfadin 6.
Effetti sekondarji li jista ’ jkollu 5 Kif taħżen Orfadin 6.
WHAT ORFADIN IS AND WHAT IT IS USED FOR
X’ INHU ORFADIN U GĦALXIEX JINTUŻA
Orfadin is used for treatment of a disease called hereditary tyrosinemia type I.
Orfadin jintuża għall- kura ta ’ marda msejħa tirosinemia ereditarja ta ’ tip 1.
In this disease the body is unable to completely break down the amino acid tyrosine.
F’ din il- marda l- ġisem ma jkunx kapaċi li jkisser kompletament l- amino acid tyrosine.
Harmful substances will be formed and accumulate in the body.
Sustanzi li jagħmlu l- ħsara ser jiffurmaw u jakkumulaw fil- ġisem.
Orfadin blocks the breakdown of tyrosine and by doing so the harmful substances are not formed.
Orfadin jimblokka t- tkissir ta ’ tyrosine, u minħabba f’ hekk is- sustanzi li jagħmlu l- ħsara ma jiffurmawx.
However, tyrosine will remain in the body and therefore a special diet (with low tyrosine and phenylalanine content) must be followed when taking Orfadin.
Madankollu, tyrosine ser jibqa ’ fil- ġisem u għalhekk dieta speċjali (b’ kontenut baxx ta ’ tyrosine u phenylalanine) trid tkun segwita meta jittieħed Orfadin.
BEFORE YOU TAKE ORFADIN
QABEL MA ’ TIEĦU ORFADIN
Do not take Orfadin:
Tieħux Orfadin:
- if you are allergic (hypersensitive) to nitisinone or any of the other ingredients of Orfadin.
- jekk inti allerġiku/ a (tbati minn sensittività eċċessiva) għal nitisinone jew sustanzi oħra ta ’
Take special care with Orfadin:
Oqgħod attent ħafna b’ Orfadin:
- if you get red eyes or any other signs of effects on the eyes.
- jekk ikollok għajnejk ħomor jew kwalunkwe sinjali oħrajn ta ’ effetti fuq l- għajnejn.
Contact your doctor immediately for
Ikkuntattja
an eye examination.
t- tabib tiegħek immedjatament għal eżami ta ’ l- għajnejn.
Eye problems could be a sign of inadequate dietary control.
Problemi ta ’ għajnejn jistgħu jkunu sinjal ta ’ kontroll inadegwat tad- dieta.
During the treatment, blood samples will be drawn in order for your doctor to check whether the treatment is adequate and to make sure that there are no possible side effects causing blood disorders.
Matul il- kura, ser jittieħdulek kampjuni tad- demm sabiex it- tabib tiegħek ikun jista ’ jiċċekkja jekk il - kura hix adegwata u biex jaċċerta ruħu li m’ hemm l- ebda effetti sekondarji possibbli li qed jikkawżaw disturbi tad- demm.
Your liver will be checked at regular intervals as the disease affects the liver.
Il- fwied tiegħek ser ikun iċċekkjat f’ intervalli regolari, għax il- marda taffettwa l- fwied.
Pregnancy The safety of Orfadin has not been studied in pregnant women.
34 Tqala Is- sigurtà ta ’ Orfadin ma ġietx studjata f’ nisa tqal.
Please contact your doctor if you plan to become pregnant.
Jekk jogħġbok ikkuntattja lit- tabib tiegħek jekk qed tippjana li toħroġ tqila.
If you become pregnant you should contact your doctor immediately.
Jekk toħroġ tqila, għandek ikkuntattja lit- tabib tiegħek immedjatament.
31 Breast-feeding The safety of Orfadin has not been studied in breast-feeding women and therefore you should not breast-feed while taking Orfadin.
Jekk qed tredda ’ Is- sigurtà ta ’ Orfadin ma kinitx studjata f’ nisa li qed ireddgħu, u għalhekk m’ għandekx tredda ’ waqt li tkun qed tieħdu Orfadin.
HOW TO TAKE ORFADIN
KIF GĦANDEK TIEĦU ORFADIN
Always take Orfadin exactly as your doctor has told you.
Dejjem għandek tieħu Orfadin skond il- parir tat- tabib.
The usual total daily dose is 1 mg/ kg body weight divided in morning and evening administrations.
Id- doża normali ta ’ kuljum hi ta ’ 1 mg / kg għal kull kilogramm ta ’ piż tal- ġisem maqsuma fit- teħid ta ’ filgħodu u ta ’ filgħaxija.
The capsules should be swallowed whole with water.
Il- kapsuli għandhom jinbelgħu sħaħ flimkien ma ’ l- ilma.
If you have problems with swallowing the capsules, they may be opened and the powder suspended into a small amount of water or formula diet just before intake.
Jekk ikollok problemi biex tibla ’ l- kapsuli, tista ’ tiftaħhom u tħoll it- trab ma ’ ammont żgħir ta ’ ilma jew dieta tal- formula immedjatament qabel tieħu l- mediċina.
If you have the impression that Orfadin is not working properly, talk to your doctor.
Jekk ikollok l- impressjoni li Orfadin mhux qed jaħdem kif suppost, kellem lit- tabib tiegħek.
Do not change the dose or stop the treatment without talking to your doctor.
Tibdilx id- doża jew twaqqaf il- kura mingħajr ma titkellem mat- tabib tiegħek.
If you take more Orfadin than you should:
Jekk tieħu Orfadin aktar milli suppost:
If you have taken more than you should, contact your doctor or pharmacist.
Jekk tieħu Orfadin aktar milli suppost, ikkuntattja lit- tabib jew lill- ispiżjar tiegħek.
If you forget to take Orfadin:
Jekk tinsa tieħu Orfadin:
Like all medicines, Orfadin can cause side effects, although not everybody gets them.
Bħal kull mediċina oħra, Orfadin jista ’ jkollu effetti sekondarji, għalkemm ma jidhrux fuq kulħadd.
The most common (more than 1 out of 100 patients and less than 1 out of 10 patients) side effects are: different eye symptoms (inflammation of the conjunctiva, opacity in the cornea, inflammation in the cornea, sensitivity to light, eye pain), reduced number of platelets and white blood cells, shortage of certain white blood cells (granulocytopenia).
L- iktar effetti sekondarji komuni (iktar minn 1 minn kull 100 pazjent u inqas minn 1 minn kull 10 pazjenti) huma: sintomi differenti ta ’ għajnejn (infjammazzjoni tal- konġuntiva, opaċità fil- kornea, infjammazzjoni fil- kornea, sensittività għad- dawl, uġigħ fl- għajnejn), tnaqqis fin- numru ta ’ plejtlets u ċelluli bojod tad- demm, nuqqas ta ’ ċerti ċelluli bojod tad- demm (granuloċitopenja).
Uncommon (more than 1 out of 1,000 patients and less than 1 out of 100 patients) side effects are: inflammation of the eyelid, increased number of white blood cells, itching, skin inflammation (exfoliative dermatitis), rash.
Effetti sekondarji mhux komuni (iktar minn 1 minn kull 1, 000 pazjent u inqas minn 1 minn kull 100 pazjent) huma: infjammazzjoni ta ’ tebqet il- għajn, żieda fin- numru ta ’ ċelluli bojod tad- demm, ħakk, infjammazzjoni tal- ġilda (exfoliative dermatitis), raxx.
If you notice any side effects relating to the eyes, you should contact your doctor immediately for an eye examination.
Jekk tinnota kwalunkwe effetti sekondarji relatati ma ’ l- għajnejn, għandek tikkuntattja lit- tabib tiegħek immedjatament għal eżami ta ’ l- għajnejn.
HOW TO STORE ORFADIN
KIF TAĦŻEN ORFADIN
Do not use Orfadin after the expiry date which is stated on the bottle and the carton after “ EXP”.
Tużax Orfadin wara d- data ta ’ skadenza, li tidher fuq il- flixkun u fuq il- kaxxa tal- kartun wara “ JIS ”.
32 Orfadin capsules can be removed from the refrigerator for one single period of maximum 3 months and stored at a temperature not above 25°C, after which the product must be discarded.
35 Il- kapsuli Orfadin jistgħu jitneħħew mill- friġġ għal perjodu wieħed ta ’ 3 xhur u jinħażnu f’ temperatura ta ’ mhux iktar minn 25°C, u wara dan, il- prodott għandu jintrema.
What Orfadin contains The active substance is nitisinone.
X’ fih Orfadin Is- sustanza attiva hi nitisinone.
Each capsule contains 2 mg, 5 mg or 10 mg nitisinone.
Kull kapsula fiha 2 mg, 5 mg jew 10 mg ta ’ nitisinone.
Other ingredients:
Is- sustanzi l- oħra huma:
Capsule content: pregelatinised starch (from maize) Capsule shell: gelatine and titanium dioxide (E 171) Printing ink: iron oxide (E 172), shellac and propylene glycol
Kontenut tal- kapsula: pregelatinised starch (mill- maize) Qoxra tal- kapsula: gelatine u titanium dioxide (E 171) Linka ta ’ l- istampar: iron oxide (E 172), shellac u propylene glycol
What Orfadin looks like and contents of the pack Orfadin capsules are white, opaque, hard gelatin capsules, imprinted with “ NTBC” and the strength “ 2 mg”, “ 5 mg” or “ 10 mg”, in black.
Id- Dehra ta ’ Orfadin u d- daqs tal- pakkett Il- kapsuli Orfadin huma bojod, opaki u magħmula minn ġelatina iebsa, bil- kliem “ NTBC ” u l- qawwa “ 2 mg ”, “ 5 mg ” jew “ 10 mg ”, stampat bl- iswed fuqhom.
The capsule contains a white to off-white powder.
Il- kapsula fiha trab abjad jew abjad jagħti fil - griż.
The capsules are packaged in plastic bottles with child resistant closures.
Il- kapsuli huma ppakkjati fi fliexken tal- plastik b’ għotjien li ma jistgħux jinfetħux mit- tfal.
Each bottle contains 60 capsules.
Kull flixkun fih 60 kapsula.
Marketing Authorisation Holder SWEDISH ORPHAN INTERNATIONAL AB Drottninggatan 98 SE-111 60 Stockholm Sweden
Id- Detentur ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq SWEDISH ORPHAN INTERNATIONAL AB Drottninggatan 98 SE- 111 60 Stockholm Svezja
Manufacturer Apoteket AB Produktion & Laboratorier Prismavägen 2 SE-141 75 Kungens Kurva Sweden
Manifattur Apoteket AB Produktion & Laboratorier Prismavägen 2 SE- 141 75 Kungens Kurva Svezja
This leaflet was last approved on
Dan il- fuljett kien approvat l- aħħar f
This medicine has been authorised under “ Exceptional Circumstances”.
Din il- mediċina kienet awtorizzata taħt “ Ċirkustanzi ta ’ eċċezzjoni ”.
This means that because of the rarity of this disease it has been impossible to get complete information on this medicine.
Dan ifisser li minħabba r- rarità tal- marda kien impossibbli li jinkiseb tagħrif sħiħ dwar din il- mediċina.
The European Medicines Agency (EMEA) will review any new information on the medicine every year and this leaflet will be updated as necessary.
L- Aġenzija Ewropeja dwar il - Mediċini (EMEA) ser tirrevedi kull tip ta ’ informazzjoni ġdida li toħroġ kull sena u dan il- fuljett ser jiġi aġġornat, skond il- bżonn.
Orgalutran 0.25 mg/ 0.5 ml solution for injection
Orgalutran 0. 25 mg/ 0. 5 ml soluzzjoni għal injezzjoni
Each pre-filled syringe contains 0.25 mg of ganirelix in 0.5 ml aqueous solution.
Kull siringa mimlija lesta ta ’ Orgalutran fiha s- sustanza attiva ganirelix, 0. 25 mg f’ soluzzjoni ta ’ 0. 5 ml ta ’ ilma.
The active substance ganirelix (INN) is a synthetic decapeptide with high antagonistic activity to the naturally occurring gonadotrophin releasing hormone (GnRH).
Is- sustanza attiva ganirelix (INN) hi decapeptide sintetiku, li għandu attività għolja antagonistika għal ormon li jinstab b' mod naturali, ormon li jeħles il- gonadotrophin (GnRH).
The amino acids at positions 1, 2, 3, 6, 8 and 10 of the natural GnRH decapeptide have been substituted resulting in N-Ac-D-Nal(2)1, D- -pClPhe2, D-Pal(3)3, D-hArg(Et2)6, L-hArg(Et2)8, D-Ala10]-GnRH with a molecular weight of 1570.4.
Il - piż molekulari huwa ta '1570. 4.
Clear and colourless aqueous solution.
Soluzzjoni ta ’ l- ilma li hi ċara u bla kulur.
The prevention of premature luteinising hormone (LH) surges in women undergoing controlled ovarian hyperstimulation (COH) for assisted reproduction techniques (ART).
Għall- prevenzzjoni ta 'żjieda primatura fil- livelli ta' l- ormon lutejnizzanti (LH) fin- nisa, li jingħataw terapija ta 'stimulazzjoni eċċessiva kkontrollata ta' l- ovarji (COH) għat- teknika ta 'riproduzzjoni assistita (ART).
In clinical trials Orgalutran was used with recombinant human follicle stimulating hormone (FSH).
Fi provi kliniċi, Orgalutran ntuża ma 'l- ormon rikombinanti li jistimula l- follikulu uman (FSH).
Orgalutran should only be prescribed by a specialist experienced in the treatment of infertility.
Orgalutran għandu jiġi ordnat biss minn speċjalisti li għandhom esperjenza fit- trattament ta 'l - infertilità.
Posology Orgalutran is used to prevent premature LH surges in patients undergoing COH.
Pożoloġija Orgalutran jingħata biex jiprevjeni żjidiet primaturi fil- livell ta ’ l- LH, f’ pazjenti li jkunu għaddejjin bit- trattament ta 'l - (COH).
Controlled ovarian hyperstimulation with FSH may start at day 2 or 3 of menses.
L- istimulazzjoni eċċessiva kkontrollata ta ’ l- ovarji permezz tal- FSH, tista ’ tibda fit- 2 jew 3 jum tal- mestrwu.
Orgalutran (0.25 mg) should be injected subcutaneously once daily, starting on day 6 of FSH administration.
Orgalutran (0. 25 mg) għandu jingħata b’ injezzjoni waħda kuljum taħt il- ġilda, u jiġi mibdi fis- 6 jum ta ’ l- għoti tal- FSH.
The start of Orgalutran may be delayed in absence of follicular growth, although clinical experience is based on starting Orgalutran on day 6 of FSH.
Għalkemm dak li hu magħruf klinikament huwa msejjes fuq il- bidu ta ’ Orgalutran fis- 6 jum minn meta jingħata l- FSH, l- użu ta ’ Orgalutran jista ’ jibda tard jekk ma jkunx hemm żvilupp follikulari.
Orgalutran and FSH should be administered approximately at the same time.
Orgalutran u FSH għandhom jingħataw bejn wieħed u ieħor fl- istess ħin.
However, the preparations should not be mixed and different injection sites are to be used.
Madankollu, il- preparazzjonijiet m’ għandhomx jitħalltu u l- injezzjonijiet għandhom isiru f’ siti differenti.
FSH dose adjustments should be based on the number and size of growing follicles, rather than on the amount of circulating oestradiol (see section 5.1).
L- aġġustamenti tad- doża ta ’ FSH għandhom jiddependu fuq in- numru u d- daqs tal- follikuli li jkunu qed jiżviluppaw, milli fuq il- livell ta ’ oestradiol li jiċċirkola (ara sezzjoni 5. 1).
Daily treatment with Orgalutran should be continued up to the day that sufficient follicles of adequate size are present.
Orgalutran għandu jingħata kuljum sa dak il- jum li jkun hemm numru xieraq ta ’ follikuli ta 'daqs suffiċjenti.
Final maturation of follicles can be induced by administering human chorionic gonadotrophin (hCG).
Il- maturazzjoni finali tal- follikuli tista ’ tiġi kkaġunata billi tingħata l- chorionic gonadotrophin tal- bniedem (hCG).
Because of the half- life of ganirelix, the time between two Orgalutran injections as well as the time between the last Orgalutran injection and the hCG injection should not exceed 30 hrs, as otherwise a premature LH surge may occur.
Minħabba l- half- life ta ’ ganirelix, iż- żmien bejn żewġ injezzjonijiet ta 'Orgalutran, kif ukoll iż- żmien bejn l- aħħar injezzjoni ta' Orgalutran u l- injezzjoni tal - hCG għandu jkun ta ’ mhux aktar minn 30 siegħa, inkella jista 'jkun hemm żjieda primatura fil- livell tal- LH.
Therefore, when injecting Orgalutran in the morning, treatment with Orgalutran should be continued throughout the gonadotrophin treatment period including the day of triggering ovulation.
Meta
When injecting Orgalutran in the afternoon the last Orgalutran injection should be given in the afternoon prior to the day of triggering ovulation.
2 tingħata l- injezzjoni ta 'Orgalutran wara nofsinhar, l- aħħar injezzjoni ta' Orgalutran għandha tingħata wara nofsinhar qabel l- jum ta ’ l- istimulazzjoni ta ’ l- ovulazzjoni.
Orgalutran has shown to be safe and effective in patients undergoing multiple treatment cycles.
Hemm x’ juri li Orgalutran ma jikkawża l- ebda periklu u hu effettiv f’ pazjenti li qed jirċievu ċikli multipliċi ta ’ trattament.
2 The need for luteal phase support in cycles using Orgalutran has not been studied.
Il- ħtieġa ta ’ sapport fil- fażi luteali f’ ċiklu meta jintuża Orgalutran ma kienx studjat.
In clinical trials, luteal phase support was given according to study centres’ practice.
Fi studji kliniċi, is- sapport fil- fażi luteali ngħata skond il- prattika taċ- ċentri ta ’ studju.
Subjects with renal or hepatic impairment:
Pazjenti b ’ indeboliment renali jew tal- fwied:
There is no experience of the use of Orgalutran in subjects with renal or hepatic impairment.
M’ hemmx esperjenza dwar l- użu ta ’ Orgalutran f’ pazjenti b' indeboliment renali jew tal- fwied.
Therefore, specific dose recommendations cannot be given (see section 4.3).
Għalhekk, ma jistgħux jingħataw rakkomandazzjonijiet speċifiki dwar id- doża (ara sezzjoni 4. 3).
Method of administration Orgalutran should be administered subcutaneously, preferably in the upper leg.
Metodu ta 'kif għandu jingħata Orgalutran għandu jingħata taħt il- ġilda, preferibbilment fin- naħa ta ’ fuq tar- riġlejn.
The injection site should be varied to prevent lipoatrophy.
Is- sit tat- tilqima għandu jinbidel biex ma jkunx hemm lipoatrofija.
The patient or her partner may perform the injections of Orgalutran themselves, provided that they are adequately instructed and have access to expert advice.
L- injezzjoni b 'Orgalutran tista ’ ssir mill- pazjenta nnifisha jew mis- sieħeb tagħha, kemm- il darba jkunu mħarrġa sew u jkollhom aċċess għal parir speċjalizzat.
− Hypersensitivity to the active substance or to any of the excipients. − Hypersensitivity to gonadotrophin-releasing hormone (GnRH) or any other GnRH analogue − Moderate or severe impairment of renal or hepatic function − Pregnancy or lactation.
− Sensittività eċċessiva għas- sustanza attiva jew għal xi sustanzi mhux attivi; − Sensittività eċċessiva għall- ormon li jeħles il- gonadotrophin (GnRH) jew sustanza li tixbah GnRH; − Indeboliment moderat jew serju fil- ħidma tal- kliewi jew tal- fwied. − Tqala jew waqt l- irdigħ.
Special care should be taken in women with signs and symptoms of active allergic conditions.
Irid ikun hemm attenzjoni speċjali f' nisa li jkollhom sinjali u sintomi tal- kondizzjonijiet allerġiċi attivi.
In the absence of clinical experience, Orgalutran treatment is not advised in women with severe allergic conditions.
Fin- nuqqas ta 'l- esperjenza klinika, trattament bl- Orgalutran mhuwiex rakkomandat f' nisa li jkollhom allerġiji serji.
Ovarian hyperstimulation syndrome (OHSS) may occur during or following ovarian stimulation.
Jista jkun hemm is- sindrome tas- sensittività eċċessiva ovarjana (OHSS), li tista 'sseħħ waqt jew wara l- kura ta ’ l- istimulazzjoni tal- ovarji.
OHSS must be considered an intrinsic risk of gonadotrophin stimulation.
OHSS għandha tiġi kkunsidrata bħala riskju intrinsiku għall - istimulazzjoni gonadotrophin.
OHSS should be treated symptomatically, e. g. with rest, intravenous infusion of electrolyte solutions or colloids and heparin.
L- OHSS għandha tiġi ttrattata skond is- sintomi tal- pazjent, eż. b’ serħan, infużjoni ġol- vina ta ’ soluzzjonijiet jew colloids ta ’ l- elettroliti u eparina.
Since infertile women undergoing assisted reproduction, and particularly IVF, often have tubal abnormalities the incidence of ectopic pregnancies might be increased.
Billi nisa infertili li jkunu qegħdin fuq programm ta ’ riproduzzjoni assistita, u partikolarment IVF, ta ’ spiss ikollhom anormalitajiet fit- tubi, l- inċidenza ta ’ tqalat ektopiċi tista ’ tiżdid.
Early ultrasound confirmation that a pregnancy is intrauterine is therefore important.
Għalhekk huwa importanti li wieħed jikkonferma kmieni permezz ta ’ l- ultrasound li t- tqala qegħda fil- ġuf.
The incidence of congenital malformations after Assisted Reproductive Technologies (ART) may be higher than after spontaneous conceptions.
L- inċidenza ta ’ malformazzjonijiet konġenitali, wara terapija permezz tat- Teknoloġiji tar - Riproduzzjoni Assistita (ART), tista ’ tkun ogħla minn meta jkun hemm tnissil naturali.
This is thought to be due to differences in parental characteristics (e. g. maternal age, sperm characteristics) and an increased incidence of multiple gestations.
Huwa maħsub li dan jiġri minħabba differenzi li ġejjin mill- ġenituri (eż. l- età ta ’ l- omm, karatteristiċi ta ’ l- isperma), kif ukoll minħabba inċidenza ogħla ta ’ ġestazzjonijiet multipli.