qanastek/EMEA-V3 huggingface dataset:
Nervous system adverse reactions, particularly dizziness, nausea and abnormal gait appear to be correlated with CSF exposure, though a definitive relationship has not been established.
Reazzjonijiet avversi tas- sistema nervuża, partikularment l- isturdament, it- tqallih u l- mixi anormali, jidhru li kienu korrelati ma ’ l- espożizzjoni tas- CSF, għalkemm relazzjoni definittiva ma kienitx stabbilita.
Low plasma exposure occurs during IT infusion due to the low recommended IT infusion rates and relatively rapid plasma clearance (see section 5.2).
Espożizzjoni baxxa tal- plażma sseħħ matul l- infużjoni IT minħabba r- rati baxxi rakkomandati ta ’ l - infużjoni IT, u minħabba t- tneħħija relattivament mgħaġġla tal- plażma (ara sezzjoni 5. 2).
Therefore, pharmacological effects related to systemic exposure should be minimal.
Għalhekk, l - effetti farmakoloġiċi relatati ma ’ l- espożizzjoni sistemika għandhom ikunu minimi.
The median dose at response is approximately 6.0 μ g/ day and approximately 75% of responsive patients require ≤ 9.6 μ g/ day.
Il- medjan tad- doża waqt ir- rispons hu ta ’ madwar 6. 0 μg/ kuljum, u madwar 75% tal- pazjenti li jirrispondu jeħtieġu ≤ 9. 6 μg/ kuljum.
To limit the occurrence of serious adverse drug reactions, a maximum dose of 21.6 μ g/ day is recommended.
Biex tillimita l- okkorrenza ta ’ reazzjonijiet avversi serji tal - mediċina, doża massima ta ’ 21. 6 μg/ kuljum hi rakkomandata.
However, in clinical trials it has been observed that patients who tolerate doses of 21.6 μ g/ day following slow titration over a 3 to 4-week period, generally tolerate higher doses up to 48.0 μ g/ day.
Madankollu, fi provi kliniċi, kien osservat li l- pazjenti li jittolleraw dożi ta ’ 21. 6 μg/ kuljum wara titrazzjoni bil- mod fuq perijodu ta ’ minn 3 sa 4 ġimgħat, ġeneralment jittolleraw dożi ogħla sa 48. 0 μg/ kuljum.
There is no evidence of the development of pharmacological tolerance to ziconotide in patients.
M’ hemm l- ebda evidenza ta ’ l- iżvilupp ta ’ tolleranza farmakoloġika għal ziconotide fil- pazjenti.
However, in view of limited data, the development of tolerance cannot be excluded.
Madankollu, minħabba l- informazzjoni limitata, l- iżvilupp tat- tolleranza ma tistax tiġi eskluża.
Examination of the patency of the intrathecal catheter should be considered if the required ziconotide dose continually increases and there is no benefit or increase in drug reactions.
L - eżami tal- ftuħ tal- kateter ġot- teka għandu jiġi kkunsidrat jekk id- doża meħtieġa ta ’ ziconotide tiżdied kontinwament u ma jkun hemm l- ebda benefiċċju jew żieda fir- reazzjonijiet tal- mediċina.
There were three placebo-controlled clinical trials of IT ziconotide.
Kien hemm tliet provi kliniċi ta ’ ziconotide IT ikkontrollati bil- plaċebo.
Two short-term studies, 95-001 (malignant pain) and 96-002 (non malignant pain), involving 366 patients, demonstrated the efficacy of IT ziconotide in severe chronic pain using the percent change in Visual Analog Scale of Pain Intensity (VASPI) as the primary efficacy measure.
Żewġ studji li damu ftit, 95- 001 (uġigħ malinn) u 96- 002 (uġigħ mhux malinn), li kienu jinvolvu 366 pazjent, urew l- effikaċja ta ’ ziconotide IT f’ uġigħ kroniku sever bl- użu tal- bidla perċentwali fil- Visual Analog Scale of Pain Intensity (VASPI) bħala l- kejl ta ’ l- effikaċja primarja.
These studies were of short duration, 5 and 6 days respectively, and used a more rapid dose escalation and higher doses than recommended in Section 4.2.
Dawn l- istudji damu ftit, 5 u 6 ijiem rispettivament, u użaw żieda fid- doża iktar mgħaġġla, u dożi ogħla minn dawk rakkomandati f’ Sezzjoni 4. 2.
8 Efficacy results from study 95-001
8 Riżultati ta ’ l- effikaċja minn studju 95- 001
Initial Treatment Assignment
Assenjazzjoni tal- Kura Inizjali
Placebo (n = 40)
Plaċebo (n = 40)
Mean VASPI score at baseline in mm (SD)
Medja tal- punteġġ VASPI fil - linja bażi f’ mm (SD)
74.1 (± 13.82)
74. 1 (± 13. 82)
77.9 (± 13.60)
77. 9 (± 13. 60)
Mean VASPI score at end of initial titration in mm (SD)
Medja tal- punteġġ VASPI fit - tmiem tat- titrazzjoni inizjali f’ mm (SD)
35.7 (± 33.27)
35. 7 (± 33. 27)
61.0 (± 22.91)
61. 0 (± 22. 91)
% improvement in VASPI score at end of initial titration (SD)
% titjib fil- punteġġ VASPI fit- tmiem tat- titrazzjoni inizjali f’ mm (SD)
51.4 (± 43.63)
51. 4 (± 43. 63)
18.1 (± 28.28)
18. 1 (± 28. 28)
Respondera n (%) Dose at end of titration (μ g/ hr)
Pazjenti li rrispondewa n (%) Doża fit- tmiem tat- titrazzjoni (μg/ siegħa)
34 (47.9%)
34 (47. 9%)
7 (17.5%)
7 (17. 5%)
Mean Median Range
Medja Medjan Medda
0.91 0.60 0.074 - 9.36
0. 91 0. 60 0. 074 - 9. 36
Responders were defined as those patients who 1) experienced a ≥ 30% drop in VASPI score compared to baseline; 2) had stable or decreased concomitant opioid analgesics; and 3) had opiate type unchanged from preinfusion if receiving opiates.
Dawk li rrispondew kienu definiti bħala dawk il- pazjenti li 1) kellhom tnaqqis ta ’ ≥ 30% fil- punteġġ VASPI meta mqabbel mal- linja bażi; 2) kellhom analġeżiċi opioid fl- istess ħin stabbli jew imnaqqsa; u 3) kellhom it- tip ta ’ opiate mhux mibdul minn dak ta ’ qabel l- infużjoni, jekk kienu qed jirċievu l - opiates.
SD – Standard Deviation.
SD = Standard Deviation - Devjazzjoni Standard
Efficacy results from study 96-002
Riżultati ta ’ l- effikaċja minn studju 96- 002
Initial Treatment Assignment
Assenjazzjoni tal- Kura Inizjali Ziconotide (n = 169) b
Placebo (n = 86)
Plaċebo (n = 86)
80.1 (± 15.10)
80. 1 (± 15. 10)
76.9 (± 14.58)
76. 9 (± 14. 58)
54.4 (± 29.30)
54. 4 (± 29. 30)
71.9 (± 30.93)
71. 9 (± 30. 93)
31.2 (± 38.69)
31. 2 (± 38. 69)
6.0 (± 42.84)
6. 0 (± 42. 84)
57 (33.7%)
57 (33. 7%)
11 (12.8%)
11 (12. 8%)
1.02 0.50 0.019 - 9.60
1. 02 0. 50 0. 019 - 9. 60
Responders were defined as those patients who 1) experienced a ≥ 30% drop in VASPI score compared to baseline; 2) had stable or decreased concomitant opioid analgesics; and 3) had opiate type unchanged from preinfusion if receiving opiates. b 164 patients provided VASPI scores for ziconotide at the end of titration.
Dawk li rrispondew kienu definiti bħala dawk il- pazjenti li 1) kellhom tnaqqis ta ’ ≥ 30% fil- punteġġ VASPI meta mqabbel mal- linja bażi; 2) kellhom analġeżiċi opioid fl- istess ħin stabbli jew imnaqqsa; u 3) kellhom it- tip ta ’ opiate mhux mibdul minn dak ta ’ qabel l- infużjoni, jekk kienu qed jirċievu l - opiates. b 164 tal- pazjenti pprovdew il- punteġġi VASPI għal ziconotide fit- tmiem tat- titrazzjoni.
The aetiologies of pain in studies 95-001 (malignant pain) and 96-002 (non-malignant pain) were varied and included bone pain (n = 38) mostly due to bone metastases (n = 34), myelopathy (n = 38), half of whom had spinal cord injury with paralysis (n = 19), neuropathy (n = 79), radiculopathy (n = 24), spinal pain (n = 91) mostly due to failed back surgery (n = 82), and other aetiologies (n = 82).
L- etjoloġiji ta ’ l- uġigħ fi studji 95- 001 (uġigħ malinn) u 96- 002 (uġigħ mhux malinn) kienu varji u inkludew uġigħ fl- għadam (n = 38) l- iktar minħabba metastasi ta ’ l- għadam (n = 34), mjelopatija (n = 38), li nofshom kellhom korriment tas- sinsla flimkien ma ’ paralisi (n = 19), newropatija (n = 79), radikolpatija (n = 24), uġigħ fil- kolonna vertebrali (n = 91) l- iktar minħabba operazzjoni fid- dahar li ma rnexxietx (n = 82), u etjoloġiji oħrajn (n = 82).
Some patients had more than one cause of pain.
Xi pazjenti kellhom iktar minn kawża waħda ta ’ uġigħ.
The efficacy of IT ziconotide was apparent in all groups.
L- effikaċja ta ’ ziconotide IT kienet apparenti fil- gruppi kollha.
Study 301 (n = 220) was of longer duration (21 days), involved more cautious up-titration and lower doses of IT ziconotide, and enrolled the most refractory population of patients studied in the three studies.
9 Studju 301 (n = 220) kien ta ’ żmien itwal (21 jum), involva titrazzjoni ‘ l fuq b’ iktar kawtela u dożi iktar baxxi ta ’ ziconotide IT, u rreġistra l- iktar popolazzjoni refrattarja ta ’ pazjenti studjati fit- tliet studji.
The
Il- pazjenti kollha fi studju 301 kellhom terapija IT li ma rnexxietx b’ kumbinazzjonijiet ta ’ analġeżiċi, u t- tobba tagħhom ikkunsidraw li 97% tal- pazjenti kienu refrattarji għall- kuri li huma disponibbli fil- preżent.
9 majority had spinal pain (n = 134), especially failed back surgery (n = 110); a lower proportion had neuropathy (n = 36).
Il- maġġoranza kellhom uġigħ fil- kolonna vertebrali (n = 134), speċjalment operazzjoni fid- dahar li ma rnexxietx (n = 110); proporzjon iktar baxx kellhom newropatija (n = 36).
Only five had malignant pain.
Ħamsa biss kellhom uġigħ malinn.
The primary endpoint was the percent change in VASPI score.
Ir- riżultat aħħari primarju kienet il- bidla perċentwali fil- punteġġ VASPI.
The efficacy of IT ziconotide in study 301 was lower than in the previous two, short-term studies.
L- effikaċja ta ’ ziconotide IT fi studju 301 kienet iktar baxxa miż- żewġ studji li saru qabel u li damu żmien qasir.
The frequency and severity of adverse events were also lower.
Il- frekwenza u s- severità ta ’ l- avvenimenti avversi kienu iktar baxxi wkoll.
Efficacy results from study 301
Riżultati ta ’ l- effikaċja minn studju 301
Placebo (n = 108)
Plaċebo (n = 108)
80.7 (± 14.98)
80. 7 (± 14. 98)
80.7 (± 14.91)
80. 7 (± 14. 91)
67.9 (± 22.89)
67. 9 (± 22. 89)
74.1 (± 21.28)
74. 1 (± 21. 28)
% improvement in VASPI score at end of initial titration (SD)
% titjib fil- punteġġ VASPI fit - tmiem tat- titrazzjoni inizjali (SD)
14.7 (± 27.71)
14. 7 (± 27. 71)
7.2 (± 24.98)
7. 2 (± 24. 98)
0.0360
0. 0360
18 (16.1%)
18 (16. 1%)
13 (12.0%)
13 (12. 0%)
0.390
0. 390
0.29 0.25 0.0 - 0.80
0. 29 0. 25 0. 0 - 0. 80
Responders were defined as those who experienced a ≥ 30% drop in VASPI score compared to baseline.
Dawk li rrispondew kienu definiti bħala dawk li kellhom tnaqqis ta ’ ≥ 30% fil- punteġġ VASPI meta mqabbel mal- linja bażi.
Combination studies with IT Morphine
Studji kkumbinati bil- Morphine IT
Clinical studies 201 and 202 indicate that the combination of IT ziconotide and IT morphine may effectively reduce pain and decrease systemic opioid use over a sustained period of time for patients whose pain was inadequately controlled with their maximum tolerated dose of IT ziconotide (median 8.7 μ g/ day, mean 25.7 μ g/ day – study 201) or with IT morphine (study 202) alone.
Studji kliniċi 201 u 202 jindikaw li l- kumbinazzjoni ta ’ ziconotide IT u morphine IT tista ’ tnaqqas l - uġigħ b’ mod effettiv u tnaqqas l- użu ta ’ l- opioid sistemiku fuq perijodu sostnut ta ’ żmien għall - pazjenti li l- uġigħ tagħhom ma kienx ikkontrollat b’ mod adegwat, bid- doża massima ttollerata tagħhom ta ’ ziconotide IT (medjan 8. 7 μg/ kuljum, medja 25. 7 μg/ kuljum – studju 201) jew b’ morphine IT (studju 202) waħdu.
When adding IT ziconotide to stable doses of IT morphine, as with the initiation of IT ziconotide monotherapy, the appearance of psychotic adverse events (e. g., hallucinations, paranoid reactions) or discontinuation due to increased adverse events may occur.
Meta żżid ziconotide IT ma ’ dożi stabbli ta ’ morphine IT, bħalma jiġri meta tinbeda monoterapija ta ’ ziconotide IT, id- dehra ta ’ avvenimenti psikotiċi avversi (eż., alluċinazzjonijiet, reazzjonijiet paranojde) jew twaqqif minħabba ż- żieda ta ’ avvenimenti avversi, tista ’ sseħħ.
The CSF pharmacokinetics of ziconotide have been studied following one-hour IT infusions of 1 - 10 μ g of ziconotide in patients with chronic pain.
Il- farmakokinetiċi tas- CSF ta ’ ziconotide kienu studjati wara infużjonijiet IT ta ’ siegħa ta ’ 1 - 10 μg ta ’ ziconotide f’ pazjenti b’ uġigħ kroniku.
The plasma pharmacokinetics following intravenous doses (0.3 – 10 μ g/ kg/ 24 hr) were also studied.
Il- farmakokinetiċi tal- plażma wara dożi fil- vina (0. 3 - 10 μg/ kg/ 24 siegħa) kienu studjati wkoll.
IT and intravenous pharmacokinetics data are summarised below.
Informazzjoni dwar il- farmakokinetiċi IT u fil- vina huma murija fil- qosor hawn taħt.
CSF and Plasma Pharmacokinetics of Ziconotide [mean ± SD (median)]
10 Il- Farmakokinetiċi ta ’ CSF u tal- Plażma ta ’ Ziconotide [medja ± SD (medjan)]
Route of
Kif
Fluid
Matriċi tal -
Number
Numru ta ’
CL (ml/ min)
CL
t½ (hr)
t½
matrix
fluwidu
patients Intrathecal
Għal ġot - teka
0.38 ± 0.56 (0.26)
0. 38 ± 0. 56 (0. 26)
4.6 ± 0.9 (4.5)
4. 6 ± 0. 9 (4. 5)
Intravenous
Fil- vina
Plasma
Plażma
270 ± 44 (260)
270 (2
30,460 ± 6,366 (29,320)
30, 460 ± 6, 36 6 (29, 320)
1.3 ± 0.3 (1.3)
1. 3 ± 0. 3 (1. 3)
CL = clearance; Vd = distribution volume; t½ = half life
CL = tneħħija; Vd = distribuzzjoni tal- volum; t½ = half life
Following one-hour IT administration (1 – 10 μ g), both cumulative exposure (AUC; range:
Wara l- għoti IT ta ’ siegħa (1 – 10 μg), kemm l- espożizzjoni kumulattiva (AUC; medda:
83.6 – 608 ng/ h/ ml) and peak exposure (Cmax; range:
83. 6 – 608 ng/ siegħa/ ml) kif ukoll l- espożizzjoni massima (Cmax; medda:
Plasma concentrations
16. 4 – 132 ng/ ml) il- valuri kienu varjabbli u jiddependu mid- doża, iżda dehru biss li kienu biss bejn wieħed u ieħor proporzjonali għad- doża.
10 following continuous (≥ 48 h) IT infusion (≤ 21.6 μ g/ day) appear to be relatively low and typically undetectable (i. e., about 80% of plasma samples collected from pain patients contain no quantifiable medicinal product; < 0.04 ng/ ml).
Il- konċentrazzjonijiet fil- plażma wara infużjoni IT kontinwa (≥ 48 sigħat) (≤ 21. 6 μg/ kuljum) jidhru li jkunu relattivament baxxi u tipikament ma jkunux jistgħu jiġu osservati (i. e., madwar 80% tal- kampjuni tal- plażma miġbura minn pazjenti li kellhom uġigħ ma fihom l- ebda prodott mediċinali li seta ’ jiġi kkwantifikat; < 0. 04 ng/ ml).
No accumulation of ziconotide in plasma following long-term IT administration (up to 9 months) has been observed.
Ma kienet osservata l- ebda akkumulazzjoni ta ’ ziconotide fil- plażma wara l- għoti IT fit- tul (sa 9 xhur).
Median ziconotide CSF volume of distribution (Vd:
Il- medjan tal- volum tad- distribuzzjoni tas- CSF ta ’ ziconotide (Vd:
99 ml) is between the spinal cord CSF volume (approximately 75 ml) and total CSF volume (approximately 130 ml).
99 ml) hu bejn il - volum tas- CSF fis- sinsla (ta ’ madwar 75 ml) u l- volum totali tas- CSF (madwar 130 ml).
Ziconotide appears to distribute mainly within the CSF until transferred to the systemic circulation.
Ziconotide jidher li jitqassam primarjament ġos- CSF sakemm ikun ittrasferit fiċ- ċirkolazzjoni sistemika.
Upon reaching the systemic circulation, ziconotide appears to be more extensively distributed, based on a plasma distribution volume of approximately 30 l and is only about 53% bound (non-specifically) to human plasma proteins.
Meta jilħaq iċ- ċirkolazzjoni sistemika, ziconotide jidher li jkun iddistribwit b’ mod iktar estensiv, ibbażat fuq il- volum tad- distribuzzjoni tal- plażma ta ’ madwar 30 l u hu mwaħħal biss b’ madwar 53% (b’ mod mhux speċifiku) mal- proteini tal- plażma umana.
Ziconotide is a peptide consisting of 25 naturally-occurring amino acids of the L-configuration, and does not appear to be appreciably metabolised in the CSF.
Ziconotide hu peptide li jikkonsisti minn 25 amino acids li jseħħu b’ mod naturali li għandhom konfigurazzjoni L, u ma jidhirx li hu metabolat b’ mod apprezzabbli fis- CSF.
Following passage into the systemic circulation, ziconotide is expected to be primarily susceptible to proteolytic cleavage by various ubiquitous peptidases/ proteases present in most organs (e. g., kidney, liver, lung, muscle, etc.), and thus degraded to peptide fragments and its individual constituent free amino acids.
Wara li jgħaddi għal ġoċ- ċirkolazzjoni sistemika, ziconotide hu mistenni li jkun primarjament suxxettibbli għal cleavage proteolitiku minn peptidases/ proteases varji li huma preżenti kullimkien fil- biċċa l- kbira ta ’ l- organi (eż., kliewi, fwied, pulmun, muskoli, eċċ.), u għaldaqstant iddegrada għal frak tal- peptides u l- amino acids liberi kostitwenti individwali tiegħu.
The generated free amino acids are expected to be taken up by cellular carrier systems and either subjected to normal intermediary metabolism or used as substrates for constitutive biosynthetic processes.
L- amino acids liberi ġġenerati huma mistennija li jittieħdu minn sistemi ċellulari li jġorru u jew ikunu suġġetti għal metaboliżmu intermedjarju normali, jew jintużaw bħala sotto- strati għal proċessi bijosintetiċi kostituttivi.
Due to the wide distribution of these peptidases it is not expected that hepatic or renal impairment would affect the systemic clearance of ziconotide.
Minħabba d- distribuzzjoni mifruxa ta ’ dawn il- peptidases, mhux mistenni li indeboliment tal- fwied jew tal- kliewi ser jaffettwa t - tneħħija sistemika ta ’ ziconotide.
The biological activity of the various expected proteolytic degradation products has not been assessed.
L- attività bijoloġika mistennija tal- prodotti proteolitiċi varji tad - degradazzjoni ma kienitx evalwata.
It is unlikely that the degradation products of ziconotide will have significant biological activity, as peptides consisting of the individual peptide loop structures have been found to have binding affinities for N-type voltage sensitive calcium channels that are several orders of magnitude lower than that of the parent (ziconotide) compound.
Mhux mistenni li l- prodotti tad- degradazzjoni ta ’ ziconotide ser ikollhom attività bijoloġika sinifikanti, għax instab li l- peptides li jikkonsistu minn strutturi loop peptide individwali, għandhom affinitajiet li jwaħħlu għal N- type voltage sensitive calcium channels, li huma ħafna drabi iktar baxxi minn dawk tal- kompost prinċipali (ziconotide).
Mean ziconotide CL (0.38 ml/ min) approximates adult human CSF turnover rate (0.3 - 0.4 ml/ min).
Il- medja ta ’ ziconotide CL (0. 38 ml/ min) toqrob ir- rata ta ’ l- ammont tas- CSF ta ’ bniedem adult (0. 3 - 0. 4 ml/ min).
Hence, ziconotide appears to be mainly eliminated from the CSF (mean t½ = 4.6 hr) by bulk flow of CSF out of the CNS through the arachnoid villi with subsequent transfer into the systemic circulation.
Ghalhekk, ziconotide jidher li jkun primarjament eliminat mis- CSF (medja t½ = 4. 6 siegħa) mill- fluss bulk ta ’ CSF ‘ il barra mis- CNS mill- arachnoid villi bi trasferiment sussegwenti fiċ- ċirkolazzjoni sistemika.
Very low circulating plasma concentrations of ziconotide may be observed following IT administration due to both the low IT infusion rate and relatively rapid plasma clearance.
Il- konċentrazzjonijiet baxxi ħafna fil- plażma ta ’ ziconotide li tkun qed tiċċirkola, jistgħu jkunu osservati wara l- għoti IT minħabba kemm ir- rata baxxa ta ’ infużjoni IT, kif ukoll it- tneħħija relattivament mgħaġġla tal- plażma.
The mean plasma elimination half-life (t½) is 1.3 hr.
Il- medja tal- half- life (t½) ta ’ l - eliminazzjoni tal- plażma hi ta ’ 1. 3 siegħa.
Ziconotide is a relatively small molecular weight peptide (MW = 2,639) and is filtered by the kidney glomerulus, but only minimal amounts of ziconotide (< 1%) are recovered in human urine following intravenous infusion.
Ziconotide hu peptide li għandu piż molekulari relattivament żgħir (MW = 2, 639) u hu ffiltrat mill- glomerulus tal- kliewi, iżda ammonti minimi biss ta ’ ziconotide (< 1%) huma rkuprati fl- awrina tal- bniedem wara infużjoni fil- vina.
This is because almost all of the filtered active substance is rapidly endocytosed and ultimately transported back to the systemic circulation.
Dan hu minħabba li kważi s- sustanza attiva kollha ffiltrata tkun endocytosed malajr u fl- aħħar mill- aħħar ittrasportata lura lejn iċ- ċirkolazzjoni sistemika.
Specific populations:
Popolazzjonijiet speċifiċi:
Although only limited data are available, there is no obvious effect of race, height, weight, gender or age on CSF ziconotide exposure after IT administration.
Għalkemm hemm biss informazzjoni limitata disponibbli, m’ hemm l- ebda effett ovvju tar- razza, tul, piż, sess jew ta ’ l- età fuq l- espożizzjoni ta ’ ziconotide CSF wara l- għoti IT.
No formal studies assessing the impact of renal or hepatic dysfunction have been conducted; however, given that peptidases are present in various body organs, it is not anticipated that renal or hepatic dysfunction will significantly impact systemic exposure of ziconotide.
11 Ma saru l- ebda studji formali biex jevalwaw l- impatt ta ’ disfunzjoni tal- kliewi jew tal- fwied; madankollu, billi l- peptidases huma preżenti f’ diversi organi tal- ġisem, mhux mistenni li disfunzjoni tal- kliewi jew tal- fwied ser ikollha impatt sinifikanti fuq l- espożizzjoni sistemika ta ’ ziconotide.
Preclinical toxic effects related to ziconotide administration were observed only at exposures considered sufficiently in excess of the human exposure to indicate little risk in clinical use.
L- effetti tossiċi ta ’ qabel l- użu kliniku relatati ma ’ l- għoti ta ’ ziconotide kienu osservati biss f’ espożizzjonijiet ikkunsidrati li huma biżżejjed ’ il fuq mill- espożizzjoni fil- bniedem biex jindikaw ftit riskju fl- użu kliniku.
In subchronic continuous intrathecal infusion studies in rats and dogs, behavioural effects were seen at doses ≥ 8-fold the maximum recommended clinical intrathecal infusion dose of 21.6 μ g/ day (on a mg/ kg basis).
Fi studji dwar l- infużjoni sotto- kronika kontinwa għal ġot- teka fil- firien u klieb, l- effetti fuq l- imġiba kienu osservati f’ dożi ta ’ ≥ 8 darbiet iktar mill- massimu rakkomandat tad- doża ta ’ l- infużjoni klinika għal ġot- teka ta ’ 21. 6 μg/ kuljum (fuq bażi ta ’ mg/ kg).
These effects were defined by exaggerated pharmacological actions of ziconotide and not by neurotoxic lesions or target organ toxicity.
Dawn l- effetti kienu definiti minn azzjonijiet farmakoloġiċi esaġerati ta ’ ziconotide u mhux minn leżjonijiet newrotossiċi jew tossiċità ta ’ l- organu fil- mira.
Observations included transient and reversible neurological effects consisting of tremors, uncoordinated movements and hyper- and hypoactivity.
L- osservazzjonijiet kienu jinkludu effetti newroloġiċi li jgħaddu malajr u riversibbli li jikkonsistu minn rogħda, movimenti mhux koordinati u attività eċċessiva u attività baxxa ħafna.
The long-term consequences to neuronal function of continuous N-type calcium-channel block have not been demonstrated in experimental animals.
Il- konsegwenzi fit- tul lill- funzjoni newronali ta ’ N- type calcium- channel block kontinwu ma ntwerewx f’ esperimenti fuq l- annimali.
Changes in neurological signalling have not been studied in experimental animals.
Bidliet fis- senjalazzjoni newroloġika ma kienux studjati f’ esperimenti fuq l- annimali.
Ziconotide did not induce bacterial gene mutation and was not
Ziconotide ma kkawżax mutazzjoni fil- ġeni batterjali u ma kienx ġenotossiku.
Chronic animal studies have not been performed to assess the carcinogenic potential of ziconotide.
Ma sarux studji kroniċi fuq l- annimali biex jevalwaw il- potenzjal karċinoġeniku ta ’ ziconotide.
However, ziconotide did not induce cell transformation in the in vitro Syrian hamster embryo (SHE) assay and did not increase cell proliferation (pre-neoplastic lesion formation) or apoptosis after subchronic intrathecal exposure in dogs.
Madankollu, ziconotide ma kkawżax it- trasformazzjoni taċ- ċelluli fl- assaġġ in vitro tas- Syrian hamster embryo (SHE) u ma żiedx il- proliferazzjoni taċ- ċelluli (formazzjoni tal- leżjoni pre- neoplastika) jew apoptosi wara espożizzjoni sotto- kronika ghal ġot- teka fil- klieb.
In rat fertility studies, there were no effects in males while reductions in corpora lutea; implantation sites and number of live embryos were observed in females.
Fi studji dwar il- fertilità fil- firien, ma kien hemm l- ebda effetti fil- firien irġiel filwaqt li tnaqqis fil - corpora lutea; siti ta ’ l- impjantazzjoni u n- numru ta ’ embriji ħajjin kienu osservati fil- firien nisa.
No adverse effects on female reproduction and post-natal development in rats were seen at systemic exposures up to 2,300 times human exposures at the maximum recommended intrathecal dose.
Ma kienu osservati l- ebda effetti avversi fuq ir- riproduzzjoni tan- nisa u fuq l- iżvilupp ta ’ wara t- twelid fil - firien, f’ espożizzjonijiet sistemiċi sa 2, 300 darba ta ’ l- espożizzjoni fil- bniedem fid- doża għal ġot- teka massima rakkomandata.
Ziconotide was not teratogenic in rats and rabbits at exposures < 100 times human plasma levels.
Ziconotide ma kienx teratoġeniku fil- firien u fil- fniek f’ espożizzjonijiet < 100 darba iktar mil- livelli tal- plażma fil- bniedem.
These results do not indicate a significant risk to humans due to the relatively high systemic exposures needed to elicit these effects in rats and rabbits.
Dawn ir- riżultati ma jindikawx riskju sinifikanti għall- bnedmin minħabba l- espożizzjonijiet sistemiċi relattivament għoljin meħtieġa biex jikkawżaw dawn l- effetti fil- firien u fil- fniek.
Methionine Sodium chloride Water for injections Hydrochloric acid (pH adjuster) Sodium hydroxide (pH adjuster)
Methionine Sodium chloride Ilma għall- injezzjonijiet Hydrochloric acid (pH adjuster) Sodium hydroxide (pH adjuster)
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
Chemical and physical in use stability has been demonstrated for 60 days at 37°C.
12 L- istabbiltà kimika u fisika waqt l- użu kienet murija għal 60 jum f’ temperatura ta ’ 37°C.
From a microbiological point of view, if the product is diluted it should be transferred to the infusion pump immediately.
Mill- aspett mikrobijoloġiku, jekk il- prodott ikun dilwit, dan għandu jkun ittrasferit immedjatament fil - pompa ta ’ l- infużjoni.
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C – 8°C, unless dilution has taken place in controlled and validated aseptic conditions.
Jekk ma jintużax immedjatament, iż- żmien tal- ħażna waqt l- użu u l - kundizzjonijiet ta ’ qabel l- użu huma r- responsabbiltà ta ’ l- utent, u normalment ma jkunux itwal minn 24 siegħa f’ temperatura ta ’ 2°C – 8°C, ħlief jekk dilwizzjoni ma tkunx saret f’ kundizzjonijiet asettiċi kkontrollati u vverifikati.
Keep the vial in the outer carton in order to protect from light.
Żomm il- kunjett fil- kartuna ta ’ barra sabiex tilqa ’ mid - dawl.
Single-use Type I glass vials with butyl rubber stoppers coated with fluorinated polymer.
Kunjetti singoli tal- ħġieġ ta ’ Tip I li jintużaw darba biss, b’ tappijiet tal- lastku tal- butyl miksija bil - fluorinated polymer.
Each vial contains 1, 2 or 5 ml solution for infusion.
Kull kunjett fih 1, 2 jew 5 ml soluzzjoni għall- infużjoni.
One vial per carton.
Kunjett wieħed f’ kull kaxxa tal- kartun.
12 Not all pack sizes may be marketed.
Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għal skop kummerċjali.
If dilution is required, Prialt must be diluted aseptically with preservative-free sodium chloride 9 mg/ ml (0.9%) solution for injection before use.
Jekk id- dilwizzjoni tkun meħtieġa, Prialt irid jiġi dilwit b’ mod asettiku bi preservative- free sodium chloride 9 mg/ ml (0. 9%) soluzzjoni għall- injezzjoni qabel l- użu.
The concentration of the solution used in the infusion pump must be no lower than 5 μ g/ ml ziconotide in an external pump and 25 μ g/ ml in an internal pump.
Il- konċentrazzjoni tas- soluzzjoni użata fil- pompa ta ’ l- infużjoni trid tkun ta ’ mhux inqas minn 5 μg/ ml ta ’ ziconotide f’ pompa esterna u ta ’ 25 μg/ ml f’ pompa interna.
Strict aseptic procedures must be used during the preparation and handling of the solution for infusion and refilling of the pump.
Proċeduri stretti asettiċi jridu jintużaw matul il- preparazzjoni u l- immaniġġjar tas- soluzzjoni għall - infużjoni u l- mili mill- ġdid tal- pompa.
The patient and health-care providers must be familiar with the handling of the external or internal infusion system and be aware of the need to guard against infection.
Il- pazjent u persuni li jipprovdu l- kura medika jridu jkunu familjari ma ’ l- immaniġġjar tas- sistema ta ’ l- infużjoni esterna jew interna u jkunu konxji tal- ħtieġa biex jilqgħu kontra l- infezzjoni.
Prialt has been shown to be chemically and physically compatible with the implantable Synchromed pump and the external CADD-Micro pump at the concentration levels indicated above.
Intwera li Prialt kien kimikament u fiżikament kompatibbli mal- pompa Synchromed li tista ’ tkun impjantata u l- CADD- Micro pump esterna fil- livelli ta ’ konċentrazzjoni indikati hawn fuq.
Chemical and physical in-use stability has been demonstrated for 14 days at 37ºC in the Synchromed pump when the pump has not previously been exposed to the medicinal product.
L- istabbiltà kimika u fiżika waqt l- użu intweriet għal 14- il jum f’ temperatura ta ’ 37ºC fil- pompa Synchromed, meta l- pompa ma kienitx esposta minn qabel għall- prodott mediċinali.
The initial fill must therefore be replaced after 14 days.
Għalhekk, il- mili inizjali jrid jinbidel wara 14- il jum.
Prialt was stable for 60 days at 37°C in the Synchromed pump previously exposed to the medicinal product.
Prialt kien stabbli għal 60 jum f’ temperatura ta ’ 37°C fil- pompa Synchromed li kienet esposta minn qabel għall- prodott mediċinali.
Stability has been demonstrated for 21 days at room temperature in the CADD-Micro pump.
L- istabbiltà ntweriet għal 21 jum fit- temperatura tal- kamra fil - CADD- Micro pump.
Specific instructions for using the pumps must be obtained from the manufacturer.
Struzzjonijiet speċifiċi għall- użu tal- pompi jridu jinkisbu mingħand il- manifattur.
CE marked pumps equivalent to the Synchromed and CADD-Micro pump should be used to deliver Prialt.
Pompi mmarkati CE, li huma ekwivalenti għal Synchromed u CADD- Micro pump, għandhom jintużaw biex ifornu Prialt.
Pumps previously used to deliver other medicinal products must be washed out three times with sodium chloride 9 mg/ ml (0.9%) solution for injection (preservative-free) before being filled with Prialt.
Pompi li qabel kienu ntużaw biex ifornu prodotti mediċinali oħrajn, iridu jinħaslu tliet darbiet bis- sodium chloride 9 mg/ ml (0. 9%) soluzzjoni għall- injezzjoni (preservative- free) qabel ma jimtlew bi Prialt.
The introduction of air into the pump reservoir or cartridge should be minimized, as oxygen can degrade ziconotide.
Id- dħul ta ’ l- arja ġol- ġibjun tal- pompa jew ġol- iskartoċċ għandu jkun imminimizzat, għax l - ossiġnu jista ’ jiddegrada ziconotide.
Prior to initiation of therapy, an internal pump must be rinsed three times with 2 ml of Prialt at 25 μ g/ ml.
Qabel il- bidu tat- terapija, pompa interna trid titlaħlaħ tliet darbiet b’ 2 ml ta ’ Prialt f’ 25 μg/ ml.
The concentration of Prialt in a naïve pump may be reduced due to adsorption onto the surfaces of the device, and/ or dilution by the residual space of the device.
Il - konċentrazzjoni ta ’ Prialt f’ pompa naïve tista ’ tkun imnaqqsa minħabba l- assorbiment fuq l- uċuħ tat - 13 tagħmir, u/ jew id- dilwizzjoni mill- ispazju residwu tat- tagħmir.
Because of this, after the first use of Prialt, the reservoir should be emptied and refilled after 14 days.
Minħabba dan, wara l- ewwel użu ta ’ Prialt, il- ġibjun għandu jitbattal u jimtela mill- ġdid wara 14- il jum.
Subsequently the pump should be emptied and refilled every 60 days.
Sussegwentement, il- pompa għandha titbattal u timtela mill- ġdid kull 60 jum.
Prialt is a clear and colourless solution.
Prialt hu soluzzjoni ċara u bla kulur.
It should be inspected visually for particulate matter and discolouration prior to administration.
Il- mediċina għandha tiġi eżaminata viżwalment għal materjal f’ sura ta ’ partikuli u tibdil fil- kulur qabel ma tingħata.
The solution should not be used if discoloured or cloudy or if particulate matter is observed.
Is- soluzzjoni m’ għandhiex tintuża jekk tkun bidlet il- kulur jew tkun imċajpra, jew jekk ikun osservat materjal f’ sura ta ’ partikuli.
Any unused solution should be discarded according to local regulations.
Kull fdal tas- soluzzjoni li ma jkunx intuża, għandu jintrema kif jitolbu l- liġijiet lokali.
Eisai Ltd., 3 Shortlands London W6 8EE United Kingdom
Eisai Ltd., 3 Shortlands London W6 8EE Ir- Renju Unit
EU/ 1/ 04/ 302/ 001 – 1 ml solution for infusion.
EU/ 1/ 04/ 302/ 001 – 1 ml soluzzjoni għall- infużjoni.
EU/ 1/ 04/ 302/ 002 – 2 ml solution for infusion.
EU/ 1/ 04/ 302/ 002 – 2 ml soluzzjoni għall- infużjoni.
EU/ 1/ 04/ 302/ 003 – 5 ml solution for infusion.
EU/ 1/ 04/ 302/ 003 – 5 ml soluzzjoni għall- infużjoni.
21 February 2005
21 ta ’ Frar, 2005
Detailed information on this product is available on the website of the European Medicines Agency (EMEA) www. emea. europa. eu
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropea dwar il - mediċini (EMEA) www. emea. europa. eu
Prialt 25 micrograms/ ml solution for infusion.
Prialt 25 mikrogramma/ ml soluzzjoni għall- infużjoni.
One ml solution contains 25 μ g ziconotide (as ziconotide acetate).
1 ml soluzzjoni fih 25 μg ta ’ ziconotide (bħala ziconotide acetate).
(See section 6.6).
(ara sezzjoni 6. 6.)
15 Use in paediatric patients (< 18 years of age)
15 L- użu f’ pazjenti pedjatriċi (< 18- il sena)
Lower catheter tip placement, e. g. at the lumbar level, may reduce the incidence of ziconotide-related neurological adverse reactions.
It- tqegħid tat- tarf tal- kateter iktar fil - baxx, eż. fil- livell tas- sinsla, jista ’ jnaqqas l- inċidenza ta ’ reazzjonijiet newroloġiċi avversi relatati ma ’ ziconotide.
Only a small number of patients have received systemic chemotherapy and IT ziconotide.
Numru żgħir biss ta ’ pazjenti rċivew kimoterapija sistemika u ziconotide IT.
Caution should be exercised when ziconotide is administered to patients who are receiving systemic chemotherapy (see section 4.5).
Għandha tingħata attenzjoni meta ziconotide jingħata lil pazjenti li jkunu qegħdin jirċievu kimoterapija sistemika (ara sezzjoni 4. 5).
Cognitive and neuropsychiatric adverse reactions, particularly confusion, are common in patients treated with ziconotide.
16 Reazzjonijiet avversi konjittivi u newropsikjatriċi, partikularment il- konfużjoni, huma komuni f’ pazjenti kkurati b’ ziconotide.
16 Episodes of acute psychiatric disturbances, such as hallucinations, paranoid reactions, hostility, delirium, psychosis and manic reactions have been reported in patients treated with ziconotide.
Episodji ta ’ disturbi psikjatriċi akuti, bħal alluċinazzjonijiet, reazzjonijiet paranojde, ostilità, delirju, psikosi u reazzjonijiet manijaċi kienu rrappurtati f’ pazjenti kkurati b’ ziconotide.
Caution should be exercised when ziconotide is administered to patients who are receiving systemic chemotherapy (see section 4.4).
Għandha tingħata attenzjoni meta ziconotide jingħata lil pazjenti li jkunu qegħdin jirċievu kimoterapija sistemika (ara sezzjoni 4. 4).
17 4.6 Pregnancy and lactation
17 M’ hemm l- ebda informazzjoni disponibbli dwar l- użu fl- istess ħin ta ’ użu ta ’ agonisti opjojdi parzjali (eż. buprenorphine) ma’ ziconotide.
Metabolism and nutrition disorders
Disturbi fil- metaboliżmu u man- nutrizzjoni
18 Nervous system disorders
18 Disturbi fis- sistema nervuża
Common: dysarthria, amnesia, dysgeusia, tremor, balance impaired, ataxia, aphasia, burning sensation, sedation, paraesthesia, hypoaesthesia, disturbance in attention, speech disorder, areflexia, coordination abnormal, dizziness postural, cognitive disorder, hyperaesthesia, hyporeflexia, ageusia, depressed level of consciousness, dysaesthesia, parosmia, mental impairment
Komuni: disartrija, amnesija, disġewżja, rogħda, indeboliment fil- bilanċ, atassja, afasja, sensazzjoni ta ’ ħruq, sedazzjoni, parestesija, ipoestesija, disturb fl- attenzjoni, taħwid fid- diskors, assenza ta ’ riflessi, koordinazzjoni anormali, sturdament li jiddependi mill- qagħda, mard konjittiv, iperestesija, hyporeflexia, telf tas- sens tat- togħma, livell baxx ta ’ koxjenza, disestesija, parosmija, indeboliment mentali
Common: diplopia, visual disturbance, photophobia
Komuni: diplopja, disturb tal- vista, fotofobia
19 Renal and urinary disorders
19 Mhux komuni: rabdomijolosi, mijosite, uġigħ fid- dahar, kontrazzjonijiet tal- muskoli, uġigħ fl- għonq
In intravenous infusion studies, healthy male volunteers received ziconotide at doses of up to 70,000 μ g/ day or 3,200 times the maximum recommended daily intrathecal infusion dose.
Fi studji dwar l- infużjoni fil- vina, voluntiera rġiel b’ saħħithom irċivew ziconotide f’ dożi sa 70, 000 μg/ kuljum jew 3, 200 darba tal- massimu rakkomandat tad- doża ta ’ infużjoni ta ’ kuljum għal ġot- teka.
The maximum recommended intrathecal dose is 21.6 μ g/ day.
Id- doża massima rakkomandata ġot- teka hi ta ’ 21. 6 μg/ kuljum.
In some patients who received intrathecal doses greater than the maximum recommended dose, exaggerated pharmacological effects, e. g., ataxia, nystagmus, dizziness, stupor, depressed level of consciousness, muscle spasms, confusional state, sedation, hypotension, aphasia, speech disorder, nausea and vomiting were observed.
F’ xi pazjenti li rċivew dożi ġot- teka akbar mid- doża massima rakkomandata, effetti farmakoloġiċi esaġerati, eż., atassja, nystagmus, sturdament, mejt, livell baxx ta ’ koxjenza, spażmi tal- muskoli, stat ta ’ konfużjoni, sedazzjoni, pressjoni tad- demm baxxa ħafna, afasja, taħwid fid- diskors, tqallih u rimettar kienu osservati.
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 din 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 l- informazzjoni l - ġdida kull sena u ser taġġorna dan is- Sommarju tal- Karatteristiċi tal- Prodott skond il- bżonn.
Ziconotide is a synthetic analogue of a ω -conopeptide, MVIIA, found in the venom of the Conus magus marine snail.
Ziconotide hu analogu sintetiku ta ’ ω- conopeptide, MVIIA, li jinsab fil- velenu ta ’ Conus magus, bebbuxu tal- baħar.
21 Efficacy results from study 95-001
21 Riżultati ta ’ l- effikaċja minn studju 95- 001
Study 301 (n = 220) was of longer duration (21 days), involved more cautious up-titration and lower doses of IT ziconotide, and enrolled the most refractory population of patients studied in the three studies.
22 Studju 301 (n = 220) kien ta ’ żmien itwal (21 jum), involva titrazzjoni ‘ l fuq b’ iktar kawtela u dożi iktar baxxi ta ’ ziconotide IT, u rreġistra l- iktar popolazzjoni refrattarja ta ’ pazjenti studjati fit- tliet studji.
22 majority had spinal pain (n = 134), especially failed back surgery (n = 110); a lower proportion had neuropathy (n = 36).
Il- maġġoranza kellhom uġigħ fil- kolonna vertebrali (n = 134), speċjalment operazzjoni fid- dahar li ma rnexxietx (n = 110); proporzjon iktar baxx kellhom newropatija (n = 36).
The plasma pharmacokinetics following intravenous doses (0.3 – 10 μ g/ kg/ 24 hr) were also studied.
Il- farmakokinetiċi tal- plażma wara dożi fil- vina (0. 3 – 10 μg/ kg/ 24 siegħa) kienu studjati wkoll.
CSF and Plasma Pharmacokinetics of Ziconotide [mean ± SD (median)]
23 Il- Farmakokinetiċi ta ’ CSF u tal- Plażma ta ’ Ziconotide [medja ± SD (medjan)]
Route of
Kif jingħata
Fluid
Matriċ i tal - fluwid u
Number
Numru ta ’ pazjenti
t½ (hr)
t½ (sigħat)
administration
Għal ġot- teka
23 following continuous (≥ 48 h) IT infusion (≤ 21.6 μ g/ day) appear to be relatively low and typically undetectable (i. e., about 80% of plasma samples collected from pain patients contain no quantifiable medicinal product; < 0.04 ng/ ml).
Il- konċentrazzjonijiet fil- plażma wara infużjoni IT kontinwa (≥ 48 sigħat) (≤ 21. 6 μg/ kuljum) jidhru li jkunu relattivament baxxi u tipikament ma jkunux jistgħu jiġu osservati (i. e., madwar 80% tal- kampjuni tal- plażma miġbura minn pazjenti li kellhom uġigħ ma fihom l- ebda prodott mediċinali li seta ’ jiġi kkwantifikat; < 0. 04 ng/ ml).
Specific populations:
24 Popolazzjonijiet speċifiċi:
No formal studies assessing the impact of renal or hepatic dysfunction have been conducted; however, given that peptidases are present in various body organs, it is not anticipated that renal or hepatic dysfunction will significantly impact systemic exposure of ziconotide.
Ma saru l- ebda studji formali biex jevalwaw l- impatt ta ’ disfunzjoni tal- kliewi jew tal- fwied; madankollu, billi l- peptidases huma preżenti f’ diversi organi tal- ġisem, mhux mistenni li disfunzjoni tal- kliewi jew tal- fwied ser ikollha impatt sinifikanti fuq l- espożizzjoni sistemika ta ’ ziconotide.
However, ziconotide did not induce cell transformation in the in vitro Syrian hamster embryo (SHE) assay and did not increase cell proliferation (pre-neoplastic lesion formation) or apoptosis after subchronic intrathecal exposure in dogs.
Madankollu, ziconotide ma kkawżax it- trasformazzjoni taċ- ċelluli fl- assaġġ in vitro tas- Syrian hamster embryo (SHE) u ma żiedx il- proliferazzjoni taċ- ċelluli (formazzjoni tal- leżjoni pre- neoplastika) jew apoptosi wara espożizzjoni sotto- kronika għal ġot- teka fil- klieb.
Chemical and physical in use stability has been demonstrated for 60 days at 37°C.
L- istabbiltà kimika u fisika waqt l- użu kienet murija għal 60 jum f’ temperatura ta ’ 37°C.
25 6.5 Nature and contents of container
6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
Each vial contains 20 ml solution for infusion.
Kull kunjett fih 20 ml ta ’ soluzzjoni għall- infużjoni.
One vial per carton.
1 kunjett f’ kull kaxxa tal- kartun.
Prior to initiation of therapy, an internal pump must be rinsed three times with 2 ml of Prialt at 25 μ g/ ml.
26 Qabel il- bidu tat- terapija, pompa interna trid titlaħlaħ tliet darbiet b’ 2 ml ta ’ Prialt f’ 25 μg/ ml.
The concentration of Prialt in a naïve pump may be reduced due to adsorption onto the surfaces of the device, and/ or dilution by the residual space of the device.
Il - konċentrazzjoni ta ’ Prialt f’ pompa naïve tista ’ tkun imnaqqsa minħabba l- assorbiment fuq l- uċuħ tat - tagħmir, u/ jew id- dilwizzjoni mill- ispazju residwu tat- tagħmir.
EU/ 1/ 04/ 302/ 004 – 20 ml solution for infusion
EU/ 1/ 04/ 302/ 004 – 20 ml soluzzjoni għall- infużjoni.
Detailed information on this product is available on the website of the European Medicines Agency (EMEA) www. emea. europa. eu
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropea dwar il - mediċini (EMEA) emea. europa. eu
CONDITIONS OF THE MARKETING AUTHORISATION
KUNDIZZJONIJIET TA ’ L- AWTORIZZAZZJONI GĦALT - TQEGĦID FIS- SUQ C.
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE
DETENTUR L- AWTORIZZAZZJONI TAL- MANIFATTURA RESPONSABBLI GĦALL- ĦRUĠ TAL- LOTT
Eisai Manufacturing Limited European Knowledge Centre Mosquito Way Hatfield Herts AL10 9SN United Kingdom
Eisai Manufacturing Limited European Knowledge Centre Mosquito Way Hatfield Herts AL10 9SN Ir- Renju Unit
Summary of Product Characteristics, section 4.2.)
Sommarju tal- Karatteristiċi tal - Prodott, sezzjoni 4. 2).
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 A post-marketing registry study (PRIME) – will be performed.
Aspetti kliniċi Studju dwar reġistru ta ’ wara t- tqegħid fis- suq (PRIME) – għandu jiġi mwettaq.
This will be an open-label registry, which will provide long-term efficacy and safety data for IT ziconotide given to patients experiencing severe, chronic malignant and non-malignant pain.
Dan għandu jkun reġistru b’ open label li għandu jipprovdi dejta dwar l- effikaċja u s- sigurtà fit- tul għal IT ziconotide li jingħata lil pazjenti b’ uġigħ malinn jew mhux malinn li hu sever u kroniku.
Analyses of patient outcomes by pain aetiology (malignant, non-malignant), pain mechanism (neuropathic, non- neuropathic), and pain severity (VASPI score above or below 50 mm at baseline) will be conducted.
Ser isiru wkoll analiżi dwar l- eżitu ta ’ pazjenti dwar l- aetoloġija ta ’ l- uġigħ (malinn, mhux malinn), mekkaniżmu tal- uġigħ (newropatiku, mhux newropatiku), u s- severità tal- uġigħ (punteġġ VASPI ’ l fuq jew ’ l isfel minn 50 mm fil- linja ta ’ riferiment bażi).
The registry will help to define the use of ziconotide in the clinical setting e. g. optimal dosing regimen, the possible development of tolerance.
Ir- reġistru ser jgħin jiddefinixxi l- użu ta ’ ziconotide fl- ambjent kliniku eż. l- aħjar programm tal- kors tad- dożaġġ, u l- iżvilupp possibbli tat- tolleranza.
The use of ziconotide in combination with morphine or baclofen, rescue medication, the evaluation of health related quality of life, and the analysis of adverse events will also be taken into account.
L- użu ta ’ ziconotide flimkien ma ’ morphine jew baclofen, mediċina tas- salvataġġ, l- evalwazzjoni tal- kwalità tal- ħajja relatata mas- saħħa, u l- analiżi ta ’ avvenimenti avversi, ser jiġu kkunsidrati wkoll.
Enrollment into the registry will continue until at least 150 patients have received Prialt.
Ir- reklutaġġ fir- reġistru ser jissokta sakemm mill- inqas 150 pazjent ikunu ħadu Prialt.
The MAH should provide annual updates of the enrollment of patients in the PRIME registry at the time of the annual re-assessment and interim analysis as well.
Id- Detentur ta ’ l- Awtorizzazzjoni għat- tqegħid fis- suq għandu jipprovdi aġġornamenti annwali tar- reklutaġġ ta ’ pazjenti fir- Reġistru PRIME fil- ħin ta ’ l- evalwazzjoni mill- ġdid li ssir kull sena u l- analiżi interim ukoll.
This study commenced in March 2008.
Dan l- istudju beda f’ Marzu 2008.
The MAH should submit the final study report to the CHMP and consider the need for a submission of a variation to the SPC for any significant results arising from this study.
Id- Detentur ta ’ l- Awtorizzazzjoni għat- tqegħid fis- Suq għandu jissottometti r - rapport finali ta ’ l- istudju lis- CHMP u jikkunsidra l- ħtieġa għal sottomissjoni ta ’ varjazzjoni għall- SmPC għal kwalunkwe riżultati sinifikanti li joriġinaw minn dan l- istudju.
Prialt 100 micrograms/ ml, solution for infusion, ziconotide
Prialt 100 mikrogramma/ ml soluzzjoni għall- infużjoni. ziconotide
Each ml contains 100 micrograms ziconotide (as ziconotide acetate), (100 micrograms per vial),
Kull 1 ml fih 100 mikrogramma ta ’ ziconotide (bħala ziconotide acetate), (100 mikrogramma f’ kull kunjett),
Each ml contains 100 micrograms ziconotide (as ziconotide acetate), (200 micrograms per vial),
Kull 1 ml fih 100 mikrogramma ta ’ ziconotide (bħala ziconotide acetate), (200 mikrogramma f’ kull kunjett),
Each ml contains 100 micrograms ziconotide (as ziconotide acetate), (500 micrograms per vial),
Kull 1 ml fih 100 mikrogramma ta ’ ziconotide (bħala ziconotide acetate), (500 mikrogramma f’ kull kunjett),
methionine, sodium chloride, water for injections, hydrochloric acid and sodium hydroxide.
methionine, sodium chloride, ilma ghall- injezzjonijiet, hydrochloric acid u sodium hydroxide.
1 ml (1 x 1 ml vial)
1 ml (1 x 1 ml kunjett)
2 ml (1 x 2 ml vial)
2 ml (1 x 2 ml kunjett)
5 ml (1 x 5 ml vial)
5 ml (1 x 5 ml kunjett)
For intrathecal use only
Użu għal ġot- teka biss
3 Shortlands London W6 8EE United Kingdom
3 Shortlands London W6 8EE Ir- Renju Unit
NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION
ISEM IL- PRODOTT MEDICINALI U MNEJN GĦANDU JINGHATA
Intrathecal infusion
Infużjoni għal ġot- teka
34 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
35 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA
Prialt 25 micrograms/ ml, solution for infusion, ziconotide
Prialt 25 mikrogramma/ ml soluzzjoni għall- infużjoni, ziconotide
Each ml contains 25 micrograms ziconotide (as ziconotide acetate), (500 micrograms per vial),
Kull 1 ml fih 25 mikrogramma ta ’ ziconotide (bħala ziconotide acetate), (500 mikrogramma f’ kull kunjett),
methionine, sodium chloride, water for injections, hydrochloric acid and sodium hydroxide.
methionine, sodium chloride, ilma għall- injezzjonijiet, hydrochloric acid u sodium hydroxide.
20 ml (1 x 20 ml vial)
20 ml (1 x 20 ml f’ kull kunjett)
36 MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
37 TAGĦRIF MINIMU LI GĦANDU JIDHER FUQ IL- PAKKETTI Ż- ŻGĦAR EWLENIN
Prialt 100 micrograms/ ml, solution for infusion.
Prialt 100 mikrogramma/ ml soluzzjoni għall- infużjoni.