qanastek/EMEA-V3 huggingface dataset:
Patients with abnormal echocardiogram findings or cardiovascular symptoms should be followed regularly with echocardiogram procedures.
3 b’ riżultati ta ’ ekokardjogramma abnormali jew sintomi kardjovaskulari għandhom jkunu segwiti regolarment bi proċeduri ta ’ ekokardjogramma.
Patients
Ipertrofija ta ’ tessut limfojdi (eż., tat- tunsilli) assoċjat ma ’ kumplikazzjonijiet, bħal ma huma nħir, apnija ta ’ waqt l- irqad, u effużjonijiet kroniċi fil- parti tan- nofs tal- widna ġew irrapportati bl- użu ta ’ INCRELEX.
3 should have examinations periodically and at the occurrence of clinical symptoms to rule out such potential complications or to initiate appropriate treatment.
Il- pazjenti għandhom jiġu eżaminati perijodikament u kif iseħħu sintomi kliniċi biex jeliminaw kumplikazzjonijiet potenzjali jew biex jibdew trattament xieraq.
Intracranial hypertension (IH) with papilloedema, visual changes, headache, nausea and/ or vomiting has been reported in patients treated with INCRELEX, as has been reported with therapeutic GH administration.
Pressjoni għolja fil- kranju (IH) b’ papilledima, tibdil viżwali, uġigħ ta ’ ras, nawsja u/ jew rimettar ġew irrapportati f’ pazjenti ttrattati b’ INCRELEX, kif ġew ukoll irrapportati b’ amministrazzjoni terapewtika ta ’ GH.
IH-associated signs and symptoms resolved after interruption of dosing.
Sinjali u sintomi assoċjati ma ’ IH irrisolvew wara t- twaqqif ta ’ l- iddożar.
Funduscopic examination is recommended at the initiation, periodically during the course of INCRELEX therapy and at the occurrence of clinical symptoms.
Eżami fundoskopiku huwa rrakkomandat fil- bidu, perijodikament waqt il- kors ta ’ terapija b’ INCRELEX u kif iseħħu sintomi kliniċi.
Slipped capital femoral epiphysis and progression of scoliosis can occur in patients who experience rapid growth.
Ċaqlieq ta ’ l- epifissi tar- ras tal- femora u progressjoni ta ’ skoljożi tista ’ iseħħ f’ pazjenti li jesperjenzaw żvilupp mgħaġġel.
These conditions and other symptoms and signs known to be associated with GH treatment in general should be monitored during INCRELEX treatment.
Dawn il- kundizzjonijiet u sintomi u sinjali oħra magħrufa li huma assoċjati ma ’ trattament b’ GH in ġenerali għandhom jiġu sorveljati waqt trattament b’ INCRELEX.
Any patient with the onset of a limp or complaint of hip or knee pain should be evaluated.
Kull pazjent li jibda jzappap jew li jilmenta minn uġigħ fil- ġenb jew fl- irkoppa għandu jiġi evalwat.
As with any exogenous protein administration, local or systemic allergic reactions may occur.
Reazzjonijiet allerġiċi lokali jew sistemiċi jistgħu jseħħu bħal bi kwalunkwe għoti ta ’ proteina eżoġena.
Parents and patients should be informed that such reactions are possible and that if an allergic reaction occurs, treatment should be interrupted and prompt medical attention should be sought.
Il- ġenituri u l- pazjenti għandhom jiġi mgħarrfa li reazzjonijiet bħal dawn jistgħu jkunu possibbli u li jekk iseħħ xi reazzjoni allerġika, it- trattament għandu jiġi mwaqqaf u għandhom ifittxu attenzjoni medika mill- aktar fis.
Treatment should be reconsidered if after a year patients remain non-responsive.
It- trattament għandu jiġi rikunsidrat mill- ġdid jekk wara sena l- pazjenti jibqgħu ma jirreaġġixux.
Persons who have allergic reactions to injected IGF-1, who have unexpectedly high blood values of IGF-1 after injection, or who fail to show a growth response may be having an antibody response to injected IGF-1.
Persuni li jkollhom reazzjonijiet allerġiċi għal IGF- 1 injettat, li għandhom valuri tad- demm mhux mistennija li jkunu għoljin ta ’ IGF- 1 wara l- injezzjoni, jew li jonqsu li juru rispons ta ’ żvilupp jista ’ jkun li jkollhom rispons antikorporali għal IGF- 1 injettat.
In such instances, follow the instructions for antibody testing.
F’ każijiet bħal dawn segwi l- istruzzjonijiet għal testijiet ta ’ antikorpi.
INCRELEX contains 9 mg/ ml benzyl alcohol as a preservative.
INCRELEX fih 9 mg/ ml benzyl alcohol bħala preservattiv.
Benzyl alcohol may cause toxic reactions and anaphylactoid reactions in infants and children up to 3 years old.
Benzyl alcohol jista ’ jikkaġuna reazzjonijiet tossiċi u reazzjonijiet anafilattojdifi fi trabi u tfal żgħar sa 3 snin t’ età.
No interaction studies have been performed.
Ma sarux studji dwar l- effett ta 'mediċini jew ta' affarijiet oħra fuq l- effett farmaċewtiku tal- prodott.
A negative pregnancy test and education about adequate contraception are recommended for all women of child bearing potential prior to treatment with INCRELEX.
Test negattiv tat- tqala u edukazzjoni dwar kontraċezzjoni adegwata huma rakkomandati għan- nisa li jista ’ jkollhom it- tfal qabel trattament b’ INCRELEX.
There are no adequate data for the use of mecasermin in pregnant women.
M’ hemmx tagħrif biżżejjed dwar l- użu ta ’ mecasermin waqt it- tqala.
Animal studies are insufficient with respect to pregnancy (see section 5.3).
Studji fuq bhejjem m’ humiex biżżejjed rigward l- effetti fuq it- tqala (ara sezzjoni 5. 3).
INCRELEX should not be used during pregnancy unless clearly necessary.
INCRELEX m’ għandux jintuża waqt it- tqala jekk m’ hemmx bżonn ċar.
Breast-feeding while taking INCRELEX is not recommended.
It- treddigħ waqt it- teħid ta 'INCRELEX mhux rakkomandat.
4 4.8 Undesirable effects
4 Ma sarux studji dwar l- effetti fuq il- ħila biex issuq jew tħaddem magni.
An integrated safety database from clinical studies contains 76 subjects with severe Primary IGFD treated for a mean duration of 4.4 years and representing 321 subject-years.
Dejtabejż integrata dwar is- sigurtà minn stħarriġ kliniku b' 76 suġġett li għandhom IGFD Primarja severa ttrattata għal żmien medju ta ’ 4. 4 snin u jirrapreżenta 321 suġġetti- snin.
Hypoglycaemia is the most frequently reported adverse drug reaction.
L- ipogliċemija hija l- aktar reazzjoni avversa tal- mediċina irrapportata ta ’ spiss.
The thirty-six subjects (47%) who had one or more episodes of hypoglycaemia included 4 subjects who had hypoglycaemic seizure on one or more occasion.
Is- sitta u tletin suġġetti (47%) li kellhom episodju wieħed jew aktar ta ’ ipogliċemija kienu jinkludu 4 suġġetti li kellhom aċċessjoni ta ’ l- ipogliċemija f’ waħda jew aktar okkażjonijiet.
Of the 36 subjects, 12 (33%) had a history of hypoglycaemia prior to beginning treatment.
Mis- 36 suġġetti, 12 (33%) kellhom storja ta ’ ipogliċemija qabel il- bidu tat- trattament.
The frequency of hypoglycaemia was highest in the first month of treatment, and episodes were more frequent in younger children.
Il- frekwenza ta ’ ipogliċemija kienet l- ogħla fl - ewwel xahar tat- trattament, u l- episodji kienu aktar frekwenti fi tfal iżgħar.
Symptomatic hypoglycaemia was generally avoided when a meal or snack was consumed either shortly before or after the administration of INCRELEX.
Ipogliċemija sintomatika kienet ġeneralment evitata meta ttieħdet ikla jew snekk kemm ftit qabel jew kemm wara l - amministrazzjoni ta ’ INCRELEX.
Injection site hypertrophy occurred in 24 subjects (32%).
Ipertrofija fis- sit ta ’ l- injezzjoni seħħet f’ 24 suġġetti (32%).
This reaction was generally associated with lack of proper rotation of injections.
Ir- reazzjoni kienet ġeneralment assoċjata ma ’ nuqqas ta ’ tidwir ta ’ l- injezzjonijiet kif suppost.
When injections were properly dispersed, the condition resolved.
Meta l- injezzjonijiet kienu mxerrda sewwa l- kundizzjoni rrisolviet ruħa.
Tonsillar hypertrophy was noted in 12 (16%) subjects, particularly in the first 1 to 2 years of therapy with lesser tonsillar growth in subsequent years.
Ipertrofija tat- tunsilli kienet innotata fi 12- il (16%) suġġett, partikolarment fi żmien bejn l- ewwel sena u sentejn ta ’ terapija bi tnaqqis fl- iżvilupp tat- tunsilli fis- snin segwenti.
Snoring, generally beginning in the first year of treatment, was reported in 17 subjects (22%).
Inħir, ġeneralment li jibda waqt l- ewwel sena tat- trattament, kien irrapportat fi 17- il suġġett (22%).
Hypoacusis was reported in 15 subjects (20%).
Tnaqqis fis- smigħ kien irrapportat fi 15- il suġġett (20%).
Intracranial hypertension occurred in three subjects (4%).
Pressjoni għolja ġol- kranju seħħet fi tliet suġġetti (4%).
In two subjects the events resolved without interruption of INCRELEX treatment.
F’ żewġ suġġetti r- reazzjonijiet irrisolvew rwieħhom mingħajr l- interuzzjoni ta ’ trattament b’ INCRELEX.
INCRELEX treatment was discontinued in the third subject and resumed later at a lower dose without recurrence.
It- trattament kien imwaqqaf fit- tielet suġġett u reġa ’ inbeda aktar tard mingħajr rikorrenza.
Fourteen subjects (18%) had headache considered related to study drug.
Erbatax- il suġġett (18%) kellhom uġigħ ta ’ ras ikkunsidrat relatat ma ’ l- istudju fuq il- mediċina.
As with all protein pharmaceuticals, some patients may develop antibodies to INCRELEX.
Xi wħud mill- pazjenti jistgħu jiżviluppaw antikorpi għal INCRELEX, kif jiġri bil- mediċini proteiniċi kollha.
Anti-IGF-1 antibodies were observed in 11 of 23 children with severe Primary IGFD tested during the first year of therapy.
Antikorpi anti- IGF- 1 kienu osservati fi 11 minn 23 tfal b’ IGFD primarja severa mistħarrġa waqt l- ewwel sena tat- terapija.
However, no clinical consequences of these antibodies were observed (e. g., allergic reactions or attenuation of growth).
Madankollu, l- ebda konsegwenzi kliniċi ta ’ dawn l- antikorpi ma kienu osservati (eż, reazzjonijiet allerġiċi jew tnaqqis fl- iżvilupp).
Table 1 contains very common (≥ 1/ 10) and common (≥ 1/ 100 to < 1/ 10) adverse reactions for which there is at least a reasonable suspicion of a causal relationship to INCRELEX treatment which occurred in clinical trials.
Tabella 1 fiha reazzjonijiet avversi komuni ħafna (≥ 1/ 10) u komuni (≥ 1/ 100 to < 1/ 10) li seħħew waqt provi kliniċi għal liema hemm ta ’ l- anqas suspett raġeonevoli ta ’ relazzjoni kawżali ma ’ trattament b’ INCRELEX.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
F’ kull ragruppament ta ’ frekwenzi, effetti mhux mixtieqa kienu ppreżentati fl- ordni ta ’ tnaqqis fis- serjetà.
Adverse Drug Reactions in Clinical Trials
Reazzjonijiet Avversi tal- Mediċina fil- Provi Kliniċi
Adverse Reaction System Organ Class
Reazzjoni Avversa Sistema tal- Klassifika ta 'l- Organi
Investigations
Stħarriġ
Cardiac murmur, abnormal tympanometry, abnormal echocardiogram, increased alanine aminotransferase*, increased aspartate aminotransferase*, increased weight
Mormuriju tal- qalb, timpanometrija abnormali, ekokardjogramm abnormali, żieda fl- alanine aminotransferase *, żieda fl- aspartate aminotransferase *, żieda fil- piż
Cardiomegaly, ventricular hypertrophy, atrial hypertrophy*, tachycardia, tachycardia paroxysmal*, mitral valve incompetence*, tricuspid valve incompetence*
Kardjomegalja, ipertrofija ventrikulari, ipertrofija atrijali *, takikardja, takikardja parossimali *, inkompetenza tal- valv mitrali *, inkompetenza tal- valv trikuspidu *
Congenital, Familial and Genetic Disorders
Disturbi konġenitali, familjali u ġenetiċi
Congenital jaw malformation, pigmented naevus*
Malformazzjoni tax- xedaq konġenitali, naevus pigmentat *
Blood and Lymphatic System Disorders
Disturbi tad- demm u fis- sistema limfatika
Thymus hypertrophy
Ipertrofija tat- tijmu
Nervous System Disorders
Disturbi fis- Sistema Nervuża
Headache
Uġigħ ta 'ras
Convulsions, febrile convulsion*, benign intracranial hypertension, loss of consciousness*, sleep apnoea syndrome, dizziness, tremor*, restless leg syndrome*
Aċċessjonijiet, deni bl- aċċessjonijiet *, pressjoni intrakranjali għolja beninn, jintilfu minn sensihom *, sindromu ta 'apneja fl- irqad, sturdament, rogħda *, sindromu tar- riġel irrekwiet *
Papilloedema, reduced visual acuity*, myopia*
Papilloedema, akutezza viżwali mnaqqsa *, mijopja *
Ear and Labyrinth Disorders
Disturbi fil- widnejn u fis- sistema labirintika
Hypoacusis
Ipoacusi
Otorrhoea, ear disorder*, middle ear disorder*, tympanic membrane disorder*, ear pain, ear congestion*, fluid in middle ear
Otorrhea, disturbi tal- widnejn *, disturb tal- widna tan- nofs *, disturbi tal- membrana timpanika *, uġigħ fil- widna, konġestjoni tal- widna *, fluwidu fil- widna tan- nofs
Respiratory, Thoracic and Mediastinal Disorders
Disturbi respiratorji, toraċiċi u medjastinali
Tonsillar hypertrophy, snoring
Ipertrofija tat- tunsilli, nħir
Adenoidal hypertrophy, nasal turbinate hypertrophy*, dyspnoea*, nasal mucosal disorder*, obstructive airway disorder*, abnormal respiration*, nasal congestion, mouth breathing
Ipertrofija adenojdali, ipertrofija turbinata nażali *, dispneja *, disturb mukosali ta 'l- imnieħer *, disturb ta' impediment tal- passaġġ tan - nifs *, respirazzjoni abnormali *, konġestjoni nażali, nifs mill- ħalq
6 Adverse Reaction System Organ Class
6 Reazzjoni Avversa Sistema tal- Klassifika ta 'l- Organi
Gastrointestinal Disorders
Disturbi fil- kliewi u fis- sistema urinarja
Nephrolithiasis*, hydronephrosis*, renal colic*
Nefrolitjasi *, idronefrosi *, kolika renali *
Skin and Subcutaneous Tissue Disorders
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il - ġilda
Skin hypertrophy, acrochordons*, abnormal hair texture*
Ipertrofija tal- ġilda, akrokordons *, it- tessut tax - xagħar abnormali *
Musculoskeletal and Connective Tissue Disorders
Disturbi muskolu- skeletrali, u tal - connective tissue
Arthralgia, pain in extremity, myalgia, scoliosis*, spinal deformity*, soft tissue disorder*, muscle cramp*, flank pain*, musculoskeletal stiffness*
Artralġja, uġigħ fl - estremitajiet, mijalgja, skoljosi *, sfigurazzjoni fl - ispina dorsali *, disturb tat - tessut artab *, bugħawwieġ *, uġigħ fil- ġnub *, ebusija muskolu- skeletrali *
Metabolism and Nutrition Disorders
Disturbi fil- metaboliżmu u n- nutrizzjoni
Hypoglycaemic seizure, hyperglycaemia, hyperlipidaemia*, obesity*
aċċessjoni ipogliċemika, ipergliċemija, iperlipidemija *, obesità *
Infections and Infestations
Infezzjonijiet u infestazzjonijiet
Febrile infection*, upper respiratory tract infection*, otitis media, otitis media serous, chronic otitis media serous *, otitis externa*, pharyngitis*, tonsillitis, ear infection, oral candidiasis*
Infezzjoni tad- deni *, infezzjoni fl- apparat respiratorju ta 'fuq *, otitis media, otitis media serous, otitis media serous chronic *, otitis externa *, farinġite *, tonsillite, infezzjoni fil- widnejn, kandidjasi orali *
Surgical and Medical Procedures
Proċeduri Kirurġiċi u Mediċi
Adenotonsillectomy*, adenoidectomy, ear tube insertion
Adenotonsilletomija *, adenojdetomija, inseriment fit- tubu tal- widna
General Disorders and Administration Injection site hypertrophy Site Conditions
Disturbi ġenerali u kundizzjonijiet ta 'mnejn jingħata
Mucosal membrane hyperplasia, hypertrophy, injection site pain, injection site bruising, injection site fibrosis*, injection site reaction*, injection site swelling*, injection site induration*, injection site pigmentation changes*, mucosal oedema*, asthenia*, lethargy*, chest discomfort*
Iperplasja fil- membrana mukosali, ipertrofija, uġigħ fis- sit ta 'l- injezzjoni, tbenġil fis- sit ta' l- injezzjoni, fibrosi fis- sit ta 'l- injezzjoni *, reazzjoni fis- sit ta' l- injezzjoni *, tinfiħ fis- sit ta 'l- injezzjoni *, twebbis fis- sit ta' l- injezzjoni *, bidliet fil - pigmentazzjoni tas- sit ta 'l- injezzjoni *, edema mukosali *, astenja *, letarġija *, skumdità fis- sider *
Reproductive System and Breast Disorders
Disturbi fis- Sistema Riproduttiva u fis- Sider Disturbi psikjatriċi
Depression*, sleep terror, nervousness, abnormal behaviour*, disorientation*
Ginaekomastja, ċista ta ’ l - ovarji * Depressjoni *, biża 'waqt l- irqad, nervożità, imġieba abnormali *, disorjentament *
* = occurred in only 1 subject (1%)
* = seħħ f' suġġett 1 biss (1%)
Acute overdose could lead to hypoglycaemia.
Doża eċċessiva akuta tista 'twassal għal ipogliċemija.
Long-term overdose may result in signs and symptoms of acromegaly or gigantism.
Teħid eċċessiv fuq tul ta ’ żmien jista ’ jirriżulta f’ sinjali u sintomi ta ’ akromegalija jew ġgantiżmu.
Treatment of acute overdose of mecasermin should be directed at alleviating any hypoglycaemic effects.
Trattament ta ’ teħid eċċessiv akut ta ’ mecasermin għandu jiġi dirett biex itaffi kwalunkwe effetti ta ’ ipogliċemija.
Oral glucose or food should be consumed.
Għandu jittieħed glukosju orali jew ma ’ l- ikel.
If the overdose results in loss of consciousness, intravenous glucose or parenteral glucagon may be required to reverse the hypoglycaemic effects.
Jekk it- teħid eċċessiv jirriżulta f’ telf mis- sensi, glukows ġol- vina jew glukagon parenterali jistgħu ikunu meħtieġa biex jirrevokaw ruħhom l- effetti ipogliċemiċi.
Somatropin and agonists, ATC code:
Kodiċi ATC:
authorised under “ Exceptional Circumstances”.
Dan il- prodott mediċinali kien 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 ma kienx possibbli li tinkiseb informazzjoni kompleta dwar 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 Ewropeja 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.
Mecasermin is a human insulin-like growth factor-1 (rhIGF-1) produced by recombinant DNA technology.
Mecasermin huwa fattur- 1 ta ’ l- iżvilupp li jixbaħ lill- insulina umana (rhIGF- 1) magħmul b’ teknoloġija rikombinanti tad- DNA.
IGF-1 consists of 70 amino acids in a single chain with three intramolecular disulfide bridges and a molecular weight of 7649 daltons.
IGF- 1 jikkonsisti minn 70 aċidu amminiku f’ katina waħda bi tlett pontijiet disulfide intramolekolari u piż molekolari ta ’ 7649 daltons.
The amino acid sequence of the product is identical to that of endogenous human IGF-1.
Is- sekwenza ta ’ aċidi amminiċi tal- prodott hija identika ma dik ta ’ IGF- 1 endoġenu uman.
The rhIGF-1 protein is synthesised in bacteria (E. coli) that have been modified by the addition of the gene for human IGF-1.
Il- proteina rhIGF- 1 hija sintetizzata fil- batterji (E. coli) li ġew immodifikati biż- żieda tal- ġene għal IGF- 1 uman.
Insulin-like growth factor-1 (IGF-1) is the principal hormonal mediator of statural growth.
Il- fattur- 1 ta ’ l- iżvilupp li jixbaħ lill- insulina (IGF- 1) huwa l- medjatur ormonali prinċipali ta ’ l - iżvilupp staturali.
Under normal circumstances, growth hormone (GH) binds to its receptor in the liver and other tissues, and stimulates the synthesis/ secretion of IGF-1.
Taħt cirkustanzi normali, l- ormon ta 'l- iżvilupp (GH) jintrabat mar- riċettur tiegħu fil- fwied u tessuti oħra, u jistimula t- tnixxija/ sintesi ta ’ IGF- 1.
In target tissues the Type 1 IGF-1 receptor, which is homologous to the insulin receptor, is activated by IGF-1, leading to intracellular signaling which stimulates multiple processes leading to statural growth.
Fit- tessuti bersalljati r- riċettur IGF- 1 Tip 1, li huwa omologu għar- riċettur ta ’ l- insulina, huwa attivat minn IGF- 1, u jwassal għal sinjalar intraċellolari li jistumula proċessi multipli li jwasslu għal żvilupp staturali.
The metabolic actions of IGF-1 are in part directed at stimulating the uptake of glucose, fatty acids, and amino acids so that metabolism supports growing tissues.
Parti mill- effetti metaboliċi ta ’ IGF- 1 huma diretti li jistumulaw it- teħid ta ’ glukows, aċidi grassi, u aċidi amminiċi sabiex il - metaboliżmu jsostni lit- tessuti li jkunu qegħdin jikbru.
The following actions have been demonstrated for endogenous human IGF-1:
Ir- reazzjonijiet li ġejjin ġew murija għal IGF- 1 endoġenu uman:
8 Tissue Growth
8 Żvilupp tat- Tessut
• Skeletal growth is accomplished at the epiphyseal plates at the ends of a growing bone.
• Żvilupp skeletriku huwa milħuq fil- platti epifissjali fit- trufijiet ta ’ l- għadma li tkun qiegħda tikber.
Growth and metabolism of epiphyseal plate cells are directly stimulated by GH and IGF-1. • Organ growth: treatment of IGF-1 deficient rats with rhIGF-1 results in whole body and organ growth. • Cell growth:
L- iżvilupp u l- metaboliżmu taċ- ċelloli tal- platti epifissjali huma stimulati direttament minn GH u IGF- 1. • Żvilupp ta ’ l- organi: trattament ta ’ firien defiċjenti minn IGF- 1 b’ rhIGF- 1 irriżulta fi żvilupp tal- ġisem kollu u ta ’ l- organi. • Żvilupp ta ’ ċelloli:
IGF-1 receptors are present on most types of cells and tissues.
Riċetturi IGF 1 qegħdin fuq il- parti l- kbira taċ- ċelloli u tessuti.
IGF-1 has mitogenic activity that leads to an increased number of cells in the body.
IGF- 1 għandu attività mitoġenika li twassal għal numru akbar ta ’ ċelloli fil- ġisem.
Carbohydrate Metabolism
Metaboliżmu tal- Karboidrati
IGF-1 suppresses hepatic glucose production, stimulates peripheral glucose utilization, and can reduce blood glucose and cause hypoglycaemia.
IGF 1 iwaqqaf il- produzzjoni ta ’ glukows epatiku, jistimula l- użu periferiku tal- glukows, u jista ’ jnaqqas il- glukows fid- demm u jikkaġuna ipogliċemija.
IGF-1 has inhibitory effects on insulin secretion.
IGF- 1 għandu effetti inibitorji fuq it- tnixxija ta ’ l- insulina.
Bone/ Mineral Metabolism
Metaboliżmu ta ’ l- Għadam/ Minerali
Circulating IGF-1 plays an important role in the acquisition and maintenance of bone mass.
IGF- 1 fiċ- ċirkulazzjoni jilgħab rwol importanti fil- kisba u l- manteniment tal- massa ta ’ l- għadam.
IGF-1 increases bone density.
IGF- 1 iżid id- densità ta ’ l- għadam.
Five clinical studies (4 open-label and 1 double-blind, placebo-controlled) were conducted with INCRELEX.
Ħames studji kliniċi (4 b’ tikketta tidher u 1 double- blind, ikkontrollat bi plaċebo) kienu magħmula b’ INCRELEX.
Subcutaneous doses of mecasermin, generally ranging from 60 to 120 μ g/ kg given twice daily (BID), were administered to 76 paediatric subjects with severe Primary IGFD.
Dożi ta ’ mecasermin mogħtija taħt il- ġilda, ġeneralment ivarjaw minn 60 sa 120 μg/ kg mogħtija darbtejn kuljum (BID), kienu mogħtija lil 76 suġġett pedjatriku b’ IGFD primarja severa.
Patients were enrolled in the studies on the basis of extreme short stature, slow growth rates, low IGF-1 serum concentrations, and normal GH secretion.
Pazjenti kienu reġistrati fl- istudju fuq bażi ta ’ statura qasira estrema, rati ta ’ żvilupp baxxi, konċentrazzjonijiet baxxi ta ’ IGF- 1 fis- serum, u tnixxija normali ta ’ GH.
Baseline characteristics for the patients evaluated in the primary and secondary efficacy analyses from the combined studies were (mean ± SD): chronological age (years):
Karatteristiċi fil- linja bażi ta 'riferiment għall- pazjenti evalwati fl- analiżi ta ’ l- effikaċja primarji u sekondarji minn stħarriġ ikkumbinati kienu (medja ± SD): età kronoloġika (snin):
6.8 ± 3.8; height (cm):
6. 8 ± 3. 8; tul (ċm):
85.0 ± 15.3; height standard deviation score (SDS): -6.7 ± 1.8; height velocity (cm/ yr):
85. 0 ± 15. 3; skor ta 'devjazzjoni standard tat- tul (SDS): - 6. 7 ± 1. 8; veloċità tat- tul (ċm/ sena):
2.8 ± 1.8; height velocity SDS: -3.3 ± 1.7; IGF-1 (ng/ ml):
2. 8 ± 1. 8; veloċità tat- tul SDS: - 3. 3 ± 1. 7; IGF- 1 (ng/ ml):
21.9 ± 24.8; IGF-1 SDS: -4.4 ± 2.0; and bone age (years):
21. 9 ± 24. 8; IGF- 1 SDS: - 4. 4 ± 2. 0; età ta ’ l- għadam (snin):
Sixty-two subjects had at least one year of treatment.
Tnejn u sittin suġġett ħadu trattament ta ’ l- anqas ta ’ sena.
Of these, 53 (85%) had Laron syndrome-like phenotype; 7 (11%) had GH gene deletion, and 1 (2%) had neutralizing antibodies to GH.
Minn dawn, 53 (85%) kellhom fenotip bħas - sindromu ta ’ Laron; 7 (11%) kellhom eliminazzjoni tal- ġene tal- GH, u 1 (2%) kellu antikorpi newtralizzanti għal GH.
Thirty-eight (61%) of the subjects were male; 49 (79%) were Caucasian.
Tmienja u tlettin (61%) mis- suġġetti rġiel; 49 (79%) kienu Kawkasi.
Fifty-six (90%) of the subjects were prepubertal at baseline.
Fil- linja bażi ta ’ riferiment sitta u ħamsin (90%) suġġett kienu fiż- żmien ta ’ qabel il- pubertà.
Annual results for height velocity, height velocity SDS, and height SDS are shown in Table 2.
Riżultati annwali għal veloċità tat- tul, SDS tal- veloċità tat- tul u SDS tat- tul jidhru fit- Tabella 2.
Pre- treatment height velocity data were available for 59 subjects.
Kien hemm dejta tal- veloċità tat- tul ta ’ qabel it- trattament għal 59 suġġett.
The height velocities at a given year of treatment were compared by paired t-tests to the pre-treatment height velocities of the same subjects completing that treatment year.
Il- veloċitajiet tat- tul f’ sena tat - trattament mogħtija kienu komparati permezz ta ’ testijiet- t pari mal- veloċitajiet tat- tul ta ’ qabel it- trattament ta ’ l- istess suġġetti li spiċċaw dik is- sena tat- trattament.
9 Table 2:
9 Tabella 2:
Annual Height Results by Number of Years Treated with INCRELEX
Riżultati Annwali ta 'Tul ma' l- Għadd ta 'Snin Trattati b' INCRELEX Veloċità ta' titwil (ċm/ sena)
Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year
Sena 1 Sena 2 Sena 3 Sena 4 Sena 5 Sena 6 Sena
7 Year 8
7 Sena 8
Mean (SD)
(SD) Medju
2.8 (1.8)
2. 8 (1. 8)
4.7 4.7
4. 7 4. 7
(2.2)
(2. 2)
(1.4)
(1. 4)
(1.9)
(1. 9)
(1.6)
(1. 6)
(1.5)
(1. 5)
(1.2)
(1. 2)
Mean (SD) for
(SD) Medju għal bidla qabel Tx
change from pre-Tx
+5. 2 (2. 6)
(2.6)
+3. 0 (2. 3)
(2.3) (2.3)
+2. 6 (2. 3)
(2.1)
+1. 6 (2. 1)
(1.8)
+1. 5 (1. 8)
(1.7)
+1. 5 (1. 7)
(2.1) (1.8) (1.7) (2.1)
+1. 0 (2. 1)
(2.4)
+0. 9 (2. 4)
P-value for change from pre-Tx [1] Height Velocity SDS
Valur- P għal bidla minn pre- Tx [1] Veloċità tat- tul SDS
< 0.0001 < 0.0001 < 0.0001 < 0.0001 0.0015
< 0. 0001 < 0. 0001 < 0. 0001 < 0. 0001 0. 0015
0.0009 0.0897 0.2135
0. 0009 0. 0897 0. 2135
-3.3 (1.7)
- 3. 3 (1. 7)
-0.2
- 0. 2
-0.3
- 0. 3
-0.4 -0.4
- 0. 4 - 0. 4
(2.9)
(2. 9)
(2.0)
(2. 0)
(2.1)
(2. 1)
(1.4) (1.9)
(1. 4) (1. 9)
(1.8)
(1. 8)
+2.7 +2.5
+5. 1 (3. 1)
(3.1)
+3. 2 (2. 2)
(2.2)
+3. 1 (2. 4)
(2.4)
+2. 5 (2. 1)
(2.1) (2.2)
+2. 5 (2. 2)
(2.2) (2.4) (2.1) (2.2)
+2. 7 +2. 5 (1. 7) (2. 1)
(1.7)
+2. 8 (2. 7)
P-value for change from pre-Tx [1] Height SDS
Valur- P għal bidla minn pre- Tx [1] Tul SDS
< 0.0001 < 0.0001 < 0.0001 < 0.0001 0.0001
< 0. 0001 < 0. 0001 < 0. 0001 < 0. 0001 0. 0001
0.0003 0.0041
0. 0003 0. 0041
-6.7 (1.8)
- 6. 7 (1. 8)
-5.9 (1.7)
- 5. 9 (1. 7)
-5.6 (1.8)
- 5. 6 (1. 8)
-5.3 -5.3 (1.8) (1.8)
- 5. 3 - 5. 3 (1. 8) (1. 8)
-5.5 (1.8)
- 5. 5 (1. 8)
-5.4 (1.8)
- 5. 4 (1. 8)
-5.2 (2.0)
- 5. 2 (2. 0)
-5.2 (1.9)
- 5. 2 (1. 9)
(SD) for
(SD) Medju għal
+0.8
+0. 8
+1.1
+1. 1
+1.4 +1.4
+1. 4 +1. 4 +1. 4 +1. 4 +1. 4
+1.6
+1. 6
change from pre-Tx
bidla minn qabel Tx
(0.5)
(0. 5)
(0.8)
(0. 8)
(1.0)
(1. 0)
(1.1)
(1. 1)
(1.3)
(1. 3)
(1.1) (1.3) (1.2) (1.1)
(1. 1) (1. 3) (1. 2) (1. 1)
P-value for change from pre-Tx [1]
Valur- P għal bidla minn pre- Tx [1]
< 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 0.0001 < 0.0001
< 0. 0001 < 0. 0001 < 0. 0001 < 0. 0001 < 0. 0001 < 0. 0001 0. 0001 < 0. 0001
Pre-Tx = Pre-treatment; SD = Standard Deviation; SDS = Standard Deviation Score [1] P-values for comparison versus pre-Tx values were computed using paired t-tests.
Pre- Tx = Qabel it- trattament; SD = Devjazzjoni Standard; SDS = Skor ta 'Devjazzjoni Standard [1] Valuri P għal paragun kontra valuri pre- Tx kienu maħduma permezz ta' testijiet- t pari.
Forty-seven subjects were included in an analysis of the effects of INCRELEX on bone age advancement.
Sebgħa u erbgħin suġġett kienu inklużi f’ analiżi ta ’ l- effetti ta ’ INCRELEX fuq żieda fl- età ta ’ l- għadam.
The mean ± SD change in chronological age was 5.1 ± 3.0 years and the mean ± SD change in bone age was 5.8 ± 2.9 years.
Il- medja ± bidla SD fl- età kronoloġika kienet 5. 1 ± 3. 0 snin u l- medja ± bidla SD fl- età ta ’ l- għadam kienet 5. 8 ± 2. 9 snin
Efficacy is dose dependent.
L- effikaċja hija dipendenti fuq id- doża.
For subjects receiving doses between 100 and 120 μ g/ kg BID, the mean first year height velocity was approximately 8.7 cm/ yr.
Għal suġġetti li qegħdin jingħataw dożi bejn 100 u 120 μg/ kg BID, il- veloċità tat- tul medja fl- ewwel sena kienet bejn wieħed u ieħor 8. 7 ċm/ sena.
5.2 Pharmacokinetic properties
5. 2 Tagħrif Farmakokinetiku
GENERAL CHARACTERISTICS
KARATTERISTIĊI ĠENERALI
The absolute subcutaneous bioavailability of mecasermin in severe Primary IGFD subjects has not been determined.
Il- bijodisponibiltà assoluta ta ’ mecasermin mogħti taħt il- ġilda f’ suġġetti b’ IGFD primarja severa ma ġietx determinata.
The bioavailability of mecasermin after subcutaneous administration in healthy subjects has been reported to be approximately 100%.
Il- bijodisponibilità ta ’ mecasermin wara għoti taħt il- ġilda f’ suġġetti f’ saħħithom ġiet rrapportata li hija bejn wieħed u ieħor 100%.
10 Distribution
Distribuzzjoni
In blood, IGF-1 is bound to six IGF binding proteins (IGFBPs), with ~80% bound as a complex with IGFBP-3 and an acid-labile subunit.
10 Fid- demm, IGF- 1 huwa marbut ma ’ sitt proteini ta ’ l- irbit ta ’ IGF, bi 80% marbut bħala kumpless ma ’ IGFBP- 3 u sottounità li hi acid- labile.
IGFBP-3 is reduced in subjects with severe Primary IGFD, resulting in increased clearance of IGF-1 in these subjects relative to healthy subjects.
IGFBP- 3 huwa baxx f’ suġġetti b’ IGFD primarja severa, li jirriżulta fi tneħħija akbar ta ’ IGF- 1 f’ dawn is- suġġetti relativament għal suġġetti f’ saħħithom.
The total IGF-1 volume of distribution (mean ± SD) after subcutaneous administration of INCRELEX in 12 subjects with severe Primary IGFD is estimated to be 0.257 (± 0.073) l/ kg at a mecasermin dose of 0.045 mg/ kg, and is estimated to increase as the dose of mecasermin increases.
Il- volum ta ’ distribuzzjoni ta ’ IGF totali (medja ± SD) fi 12- il suġġett b’ IGFD Primarja severa wara injezzjoni taħt il- ġilda ta ’ INCRELEX huwa kkalkulat li huwa 0. 257 (± 0. 073) l/ kg f’ doża ta ’ mecasermin ta ’ 0. 045 mg/ kg, u huwa kkalkulat li jiżdid hekk kif tiżdied id- doża ta ’ mecasermin.
Limited information is available on the concentration of unbound IGF-1 after the administration of INCRELEX.
Hemm tagħrif ristrett fuq il- konċentrazzjoni ta ’ IGF- 1 mhux marbut wara l- amministrazzjoni ta ’ INCRELEX.
Both the liver and the kidney have been shown to metabolise IGF-1.
Kemm il- fwied u l- kliewi ntwerew li jistgħu jimmetabolizzaw IGF- 1.
Excretion
Eskrezzjoni
The mean terminal t1/ 2 of total IGF-1 after single subcutaneous administration of 0.12 mg/ kg in three paediatric subjects with severe Primary IGFD is estimated to be 5.8 hours.
It- t1/ 2 terminali medju ta ’ IGF- 1 totali wara doża waħda ta ’ 0. 12 mg/ kg mogħtija taħt il- ġilda fi tliet suġġetti pedjatriċi b’ IGFD primarja severa hija kkalkulata li hija 5. 8 sigħat.
Clearance of total IGF-1 is inversely proportional to serum IGFBP-3 levels and total IGF-1 systemic clearance (CL/ F) is estimated to be 0.04 l/ hr/ kg at 3 mg/ l IGFBP-3 in 12 subjects.
Tneħħija ta ’ IGF- 1 totali hija proporzjonalment bil- maqlub ta ’ livelli ta ’ IGFBP- 3 fis- serum u tneħħija sistemika totali ta ’ IGF - 1 (CL/ F) hija kkalkulata li hija 0. 04 l/ hr/ kg at 3 mg/ l IGFBP- 3 fi 12- il suġġett.
CHARACTERISTICS IN SPECIAL POPULATIONS
KARATTERISTIĊI TA 'POPULAZZJONIJIET SPEĊJALI
Geriatric
Gerjatriku
The pharmacokinetics of INCRELEX have not been studied in subjects greater than 65 years of age.
Il- farmakokinetiċi ta 'INCRELEX ma ġewx studjati f' suġġetti li huma akbar minn 65 sena.
Children
Tfal
The pharmacokinetics of INCRELEX have not been studied in subjects younger than 12 years of age.
Il- farmakokinetiċi ta 'INCRELEX ma ġewx studjati f' suġġetti li huma iżgħar minn 12 sena.
Gender
Ġeneru
In children over 12 years old with Primary IGFD and in healthy adults there were no apparent differences between males and females in the pharmacokinetics of INCRELEX.
Fi tfal li għandhom aktar minn 12- il sena li għandhom IGFD primarja u f' adulti b' saħħithom ma dehrx li kien hemm differenzi fil- farmakokinetiċi ta 'INCRELEX bejn irġiel u nisa.
No information is available.
L- ebda informazzjoni disponibbli.
Renal insufficiency
Insuffiċjenza renali
No studies have been conducted in children with renal impairment.
L- ebda studju ma ġie mwettaq fi tfal li għandhom insuffiċjenza renali.
Hepatic insufficiency
Insuffiċjenza epatika
No studies have been conducted to determine the effect of hepatic impairment on the pharmacokinetics of mecasermin.
L- ebda studju ma 'ġie mwettaq biex jistabilixxi l- effett ta' indeboliment epatiku fuq il- farmakokinetiċi ta 'mecasermin.
11 5.3 Preclinical safety data
11 Tossiċità riproduttiva
In rats and rabbits reproductive toxicity was studied after intravenous but not after subcutaneous application (the normal clinical route).
Tossiċità riproduttiva fil- firien u fil- fniek kienu studjati wara applikazzjoni ġol- vina iżda mhux wara applikazzjoni taħt il- ġilda (ir- rotta klinika normali).
These studies did not indicate direct or indirect harmful effects with respect to fertility and pregnancy, but due to the different route of application the relevance of these findings is unclear.
Dawn l- istudji ma indikawx effetti ta ’ ħsara diretti jew indiretti fir- rigward ta ’ fertilità u tqala, iżda minħabba ir- rotot differenti ta ’ applikazzjoni r - rilevanza ta ’ dawn ir- riżultati mhix ċara.
Placental transfer of mecasermin was not studied.
Trasferiment ta ’ mecasermin mis- sekonda ma kienx mistħarreġ.
Carcinogenesis
Karċinoġenesi
Mecasermin was administered subcutaneously to Sprague Dawley rats at doses of 0, 0.25, 1, 4, and 10 mg/ kg/ day for up to 2 years.
Mecasermin kien mogħti taħt il- ġilda lill- firien Sprague Dawley f’ dożi ta ’ 0, 0. 25, 1, 4, u 10 mg/ kg kuljum sa żmien ta ’ sentejn.
An increased incidence of adrenal medullary hyperplasia and pheochromocytoma was observed in male rats at doses of 1 mg/ kg/ day and above (≥ 1 times the clinical exposure with the maximum recommended human dose [MRHD] based on AUC) and female rats at all dose levels (≥ 0.3 times the clinical exposure with the MRHD based on AUC).
Żieda fl- inċidenża ta ’ iperplażja tal- medulla adrenali u fejokromoċitoma kienet osservata fil- firien irgiel f’ dożi ta ’ 1mg/ kg/ kuljum u ogħla (≥ 1 darba l- esponiment kliniku bid- doża umana massima rakkomandata [MRHD] ibbażata fuq l- AUC) u fil- firien nisa fil- livelli tad- dożi kollha (≥ 0. 3 drabi l- esponiment kliniku bl- MHRD ibbażat fuq l- AUC).
An increased incidence of keratoacanthoma in the skin was observed in male rats at doses of 4 and 10 mg/ kg/ day (≥ 4 times the exposure with the MRHD based on AUC).
Żieda fl- inċidenża ta ’ keratoakantoma fil- gilda kienet osservata fil- firien irġiel f’ dożi ta ’ 4 u 10 mg/ kg/ kuljum (≥ 4 darbiet l- esponiment bl- MRHD ibbażat fuq l- AUC).
An increased incidence of mammary gland carcinoma in both male and female rats was observed in animals treated with 10 mg/ kg/ day (7 times the exposure with the MRHD based on AUC).
Żieda fl- inċidenża ta ’ karċinoma tal- glandoli mammarji kemm fil- firien irġiel u kemm fin- nisa kienet osservata fl- annimali ttrattati b’ 10 mg/ kg/ kuljum (7 darbiet l- esponiment bl- MRHD ibbażat fuq l- AUC).
Excess mortality secondary to IGF-1 induced hypoglycaemia was observed in the carcinogenesis studies.
Eċċess ta ’ mortalità sekondarja minn ipogliċemija ikkaġunata minn IGF- 1 kienet osservata fl- istharriġ tal- karċinoġenesi.
Benzyl alcohol Sodium chloride Polysorbate 20 Glacial acetic acid Sodium acetate Water for injections
Benzyl alcohol Sodium chloride Polysorbate 20 Glacial acetic acid Sodium acetate Ilma għall- injezzjonijiet
Chemical and physical in-use stability has been demonstrated for 30 days at 2°C to 8°C.
L- istabilità kimika u fiżika waqt l- użu ġiet murija għal 30 jum f' 2°C sa 8°C.
From a microbiological point of view, once opened, the product may be stored for a maximum of 30 days at 2°C to 8°C.
Mil- lat mikrobijoloġiku, la darba jkun miftuħ, il- prodott irid jiġi maħżun għal massimu ta '30 jum f' temperatura ta' 2°C sa 8°C.
Other in-use storage times and conditions are the responsibility of the user.
Ħinijiet u kundizzjonijiet ta 'ħażna waqt l- użu oħrajn huma r - responsabilità ta' l- utent.
Keep the vial in the outer carton in order to protect from light.
Żomm il- fjala fil- kartuna ta 'barra sabiex tilqa' mid- dawl.
4 ml of solution in a 5 ml vial (type I glass) closed with a latex-free stopper (bromobutyl/ isoprene polymer) and a seal (lacquered plastic).
12 4 ml ta 'soluzzjoni f’ kunjett ta' 5 ml (ħġieġ ta 'tip I) magħluq b' għatu li ma fihx latex (bromobutyl/ isoprene polymer) u siġill (plastik ivverniċċjat).
Pack size of 1 vial.
Daqs tal- pakkett ta 'kunjett 1.
INCRELEX is supplied as a sterile solution with preservative for multiple use.
INCRELEX jiġi bħala soluzzjoni sterili bi preservattiv għal użu multiplu.
The solution should be clear immediately after removal from the refrigerator.
Is- soluzzjoni għandha tkun ċara immedjatament kif tinħareġ minn ġol friġġ.
If the solution is cloudy, or contains particulate matter, it must not be injected.
Jekk is- soluzzjoni tkun mċajpra, jew fiha l- frak, m' għandhiex tiġi injettata.
Tercica Europe Limited Riverside One Sir John Rogerson’ s Quay Dublin 2 Republic of Ireland
Tercica Europe Limited Riverside One Sir John Rogerson’ s Quay Dublin 2 Ir- Repubblika Irlandiża
Date of first authorisation:
l- ewwel awtorità:
MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE
MANIFATTUR( I) TAS- SUSTANZA( I) BIJOLOĠIKA( ĊI) ATTIVA( I) U DETENTUR( I) TA ’ L- AWTORIZZAZZJONI TAL- MANIFATTURA RESPONSABBLI GĦALL- HRUĠ TAL- LOTT B.
CONDITIONS OF THE MARKETING AUTHORISATION
KUNDIZZJONIJIET TA 'L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ Ċ.
SPECIFIC OBLIGATIONS TO BE FULFILLED BY THE MARKETING AUTHORISATION HOLDER
OBBLIGAZZJONIJIET SPEĊIFIĊI — TAD- DETENTUR TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ
Name and address of the manufacturer(s) responsible for batch release
Isem u indirizz tal- manifattur responsabbli għall- ħruġ tal- lott.
Beaufour Ipsen Industrie Rue d'Ethe Virton 28100 Dreux France
Beaufour Ipsen Industrie Rue d' Ethe Virton 28100 Dreux Franza
The MAH must ensure that, at launch, all physicians who are expected to prescribe INCRELEX are provided with a “ physician information pack” containing the following:
L- MAH għandu jiżgura li, mal- illanċjar, it- tobba kollha li mistennija jippreskrivu INCRELEX jiġu provduti b ’ "pakkett ta ’ informazzjoni għat- tabib" li fih dan li ġej:
The physician information about INCRELEX should contain the following key elements:
It- tagħrif għat- tabib dwar INCRELEX għandu jikkonsisti mill- elementi ewlenin li ġejjin:
To educate parents on the signs, symptoms and treatment of hypoglycaemia, including injection of glucagon.
Li jeduka lil ġenituri dwar is- sinjali, sintomi u trattament ta ’ l- ipogliċemija, li jinkludi l- injezzjoni ta ’ glucagon.
That patients should have examinations of the ears, nose and throat periodically and at the occurrence of clinical symptoms to rule out such potential complications or to initiate appropriate treatment.
Li pazjenti għandu jkollhom eżamijiet fuq il- widnejn, l- imnieħer u l- griżmejn kull tant żmien u meta jseħħu xi sintomi kliniċi sabiex jiġu eliminati komplikazzjonijiet potenzjali jew sabiex jibda trattament xieraq.
To perform a routine funduscopic examination prior to beginning treatment and periodically during treatment or at the occurrence of clinical symptoms.
Sabiex isir eżami funduskopiku ta ’ rutina qabel ma jinbeda t- trattament u kull tant żmien waqt it- trattament jew kif iseħħu xi sintomi kliniċi.
INCRELEX is contraindicated in the presence of active or suspected neoplasia, and therapy should be discontinued if evidence of neoplasia develops.
INCRELEX huwa kontra- indikat fil- preżenza ta ’ neoplasja suspettuża jew attiva, u t - terapija għandha titwaqqaf jekk ikun hemm evidenza li tiżviluppa n- neoplasja.
Slipped capital femoral epiphysis and progression of scoliosis can occur in patients who experience rapid growth.
Ċaqlieq ta ’ l- epifissi tar- ras tal- femora u progressjoni ta ’ l- iskoljosi jistgħu jseħħu f’ pazjenti li jgħaddu minn tkabbir f’ daqqa.
These conditions should be monitored during INCRELEX treatment.
Dawn il- kundizzjonijiet għandhom jiġu monitorati waqt it- trattament b’ INCRELEX.
To inform parents and patients that allergic reactions are possible and that if this occurs treatment should be interrupted and prompt medical attention should be sought.
15 • Sabiex jinforma lil ġenituri u ‘ l pazjenti li reazzjonijiet allerġiċi huma possibbli u jekk dawn iseħħu t- trattament għandu jiġi interrot u attenzjoni medika fil- pront għandha tiġi mfittxija. • Tagħrif dwar kampjuni immunoġeniċi.
That INCRELEX should be administered shortly before or after a meal or snack because it has insulin-like hypoglycaemic effects.
• Li INCRELEX għandu jiġi mogħti ftit qabel jew wara xi ikla jew snekk peress li għandu effetti ipogliċimiċi bħal ta ’ l- insulina. • Is- sinjali u s- sintomi ta ’ ipogliċemija.
Instructions on the administration of glucagon should severe hypoglycaemia occur.
Li l- ġenituri u l- kuraturi għandhom dejjem jiżguraw li t- tfal dejjem għandhom sors ta ’ zokkor.
The dose of INCRELEX should not be doubled to make up for one or more omitted doses.
Struzzjonijiet dwar l- għoti ta ’ glukagon jekk ikun hemm ipogliċemija severa. • INCRELEX m’ għandux jingħata jekk il- pazjent mhux kapaċi jiekol għal kwalunkwe raġuni.
To avoid engaging in any high-risk activities (such as vigorous physical activity) within 2 - 3 hours after dosing, particularly at the initiation of INCRELEX treatment, until a well-tolerated dose of INCRELEX has been established.
Id- doża ta ’ INCRELEX m’ għandiex tiġi irdoppjata sabiex tpatti għal doża waħda jew aktar mitlufin. • Sabiex jiġi evitat li wieħed jagħmel attivitajiet ta ’ riskju għoli (bħal attività fiżika vigoruża) f’ 2- 3 sigħat wara li jingħata d- doża, b’ mod partikolari wara l- bidu tat- trattament b’ INCRELEX, sakemm tkun ġiet stabbilita doża ta ’ INCRELEX li tkun ittollerata tajjeb. • Struzzjonijiet biex tbiddel u tnewweb is- sit ta ’ l- injezzjoni għal kull injezzjoni sabiex tevita l- iżvilupp ta ’ lipoipertrofija. • Struzzjonijiet biex tirraporta l- bidu jew it- tiħżin ta ’ tinħir li jista ’ jindika żieda fit - tkabbir ta ’ tunsilli u/ jew adenojdi wara l- bidu tat- tratatment b’ INCRELEX. • Sabiex jiġi rraportat l- bidu ta ’ vista mċajpra b’ uġigħ ta ’ ras severa u nawsja assoċjata u rimettar lit- tabib tagħhom. • Sabiex jiġi rapportat il- bidu ta ’ zzappip jew ilment tal- ġenb jew uġigħ fl- irkoppa lit - tabib tagħhom sabiex jiġi evalwat.
In addition there will be a dosing guide, and a dose calculator, for use by physician and patients to include information on the individualised dose escalation to minimise the risk of medication errors and hypoglycaemia.
Barraminhekk ser ikun hemm gwida għad- dożaġġ, u kalkulatur tad- doża, għall- użu minn tabib u pazjenti sabiex tiġi inkluża informazzjoni fuq skala individwalizzata ta ’ dożi dejjem tikber sabiex wieħed jimminimizza r- riskju ta ’ erruri mediċi u l- ipogliċemija.
• OTHER CONDITIONS Pharmacovigilance system
• KUNDIZZJONIJIET OĦRA Sistema Farmakoviġilanza
The MAH must ensure that the system of pharmacovigilance, as described in version 3 dated 3 June 2008 presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and whilst the product is on the market.
L- MAH għandu jiżgura li s- sistema ta ’ farmakoviġilanza kif deskritta f’ verżjoni 3 data 03/ 06/ 2008 ippreżentata fil- Modulu 1. 8. 1 ta ’ l- Applikazzjoni ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq, hija f’ postha u qed taħdem qabel u waqt li l- prodott ikun fis- suq.
Risk Management plan The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan, as agreed in Version 2 of 1.9. of the Risk Management Plan (RMP) presented in Module 1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP agreed by the CHMP
Pjan dwar Ġestjoni ta ’ Riskju L- MAH jimpenja ruħu li jwettaq l- istudji dwar l- attivitajiet ta ’ farmakoviġilanza addizzjonali ddettaljata fil- Pjan ta ’ Farmakoviġilanza, kif miftehma f’ Verżjoni 2 ta ’ 1. 9 tal- Pjan dwar Ġestjoni ta ’ Riskju (RMP) ippreżentat fil- Modulu 1. 8. 2 ta ’ l- Applikazzjoni ta ’ l- Awtorizzazzjoni għat- Tqegħid fis - Suq u kull aġġornament ieħor ta ’ l- RMP miftiehem mis- CHMP.
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the updated RMP should be submitted at the same time as the next Periodic Safety Update Report (PSUR).
Skond il- Linja Gwida tas- CHMP dwar Sistemi dwar Ġestjoni ta ’ Riskju għal prodotti mediċinali għal użu mill- bniedem, l- RMP aġġornat għandu jiġi sottomess fl- istess żmien tar- Rapport Perijodiku Aġġornat dwar is- Sigurtà (PSUR).
In addition, an updated RMP should be submitted When new information is received that may impact on the current Safety Specification, Pharmacovigilance Plan or risk minimisation activities Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being reached At the request of the EMEA
Barraminhekk, RMP aġġornat għandu jiġi sottomess • Meta tasal informazzjoni ġdida li jista ’ jkollha impatt fuq l- ispeċifikazzjoni tas- sigurta ’ kurrenti, il- Pjan ta ’ Famakoviġilanza jew tirriskja l- attivitajiet li jiminimizzaw ir- riskju. • Fi żmien 60 jum ta ’ tragward importanti (farmakoviġilanza jew minimizzazzjoni tar- riskju) milħuq • Fuq talba ta ’ l- EMEA
C.
16 Ċ.
SPECIFIC OBLIGATIONS TO BE FULFILLED BY THE MARKETING AUTHORISATION HOLDER
OBBLIGAZZJONIJIET SPEĊIFIĊI TAD- DETENTUR TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ
16 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 li ġejjin fiż- żmien speċifikat, u r- riżultati ta' dawn l- istudji għandhom iservu ta 'bażi għall- istima tal- profil bejn il- benefiċċju/ riskju li ssir kull sena.
Clinical aspects
Aspetti kliniċi
• To develop and validate an immunogenicity assay for assessing anti-IGF-I antibodies.
• Sabiex tiżviluppa u tivvalida assaġġ ta ’ immunoġeniċità għall- analiżi ta ’ antikorpi ta ’ anti- IGF- I.
The final report shall be submitted by 31/03/2009.
Ir- rapport finali għandu jiġi sottomess sal- 31/ 03/ 2009
• To perform one long-term safety study where mecasermin treatment is initiated in early phase of childhood and continued to adulthood in order to investigate:
• Sabiex jitwettaq studju wieħed dwar is- sigurtà fuq perijodu ta ’ żmien twil meta it- trattament b’ mecasermin jinbeda f’ fażi bikrija ta ’ tfulija u jkompli fl- istat ta ’ adult biex jiġi mistħarreġ:
• Long-term toxicity in patients undergoing developmental changes • Possible occurrence of malignancies as well as other risks
Tossiċità fuq perijodu ta ’ żmien twil f’ pazjenti li jkun għaddejjin bidliet ta ’ żvilupp Il- possibilita li jseħħu malinni kif ukoll riskji oħra
The first interim report shall be submitted by 31/12/2008, and subsequent interim reports will be submitted every year until the final patient is followed for 5 years.
L- ewwel rapport interim għandu jiġi sottomess sal- 31/ 12/ 2008, u rapporti interim sussegwenti għandhom jiġu sottomessi kull sena sakemm l- aħħar pazjent jiġi segwit għal 5 snin.
LABELING AND PACKAGE LEAFLET
TIKKETTA U FULJETT TA ’ TAGĦRIF
INCRELEX 10 mg/ml solution for injection.
INCRELEX 10 mg/ ml soluzzjoni għall- injezzjoni.
One ml contains 10 mg of mecasermin.
Kull ml fih 10 mg ta 'mecasermin.
Each vial contains 40 mg of mecasermin.
Kull kunjett fiha 40 mg ta 'mecasermin.
Other ingredients: benzyl alcohol, sodium chloride, polysorbate 20, glacial acetic acid, sodium acetate and water for injections.
Sustanzi oħra: benzyl alcohol, sodium chloride, polysorbate 20, glacial acetic acid, sodium acetate u ilma għall- injezzjonijiet.
One multi-use vial of 4 ml.
Kunjett wieħed ta 'użu multiplu ta' 4 ml.
Subcutaneous use.
Użu taħt il- ġilda.
EXP After first opening, use within 30 days.
Wara li jinfetaħ l- ewwel darba, uża fi żmien 30 jum.
Keep vial in the outer carton in order to protect from light.
Żomm il- kunjett fil- kartuna ta 'barra sabiex tilqa' mid- dawl.
Tercica Europe Limited Riverside One Sir John Rogerson’s Quay Dublin 2 Republic of Ireland
Tercica Europe Limited Riverside One Sir John Rogerson’ s Quay Dublin 2 Ir- Repubblika Irlandiża
INCRELEX 10 mg/ml injection Mecasermin SC
INCRELEX 10 mg/ ml injezzjoni Mecasermin SC
23 PACKAGE LEAFLET:
23 FULJETT TA 'TAGĦRIF: