qanastek/EMEA-V3 huggingface dataset:
Grade 3= severe pain requiring analgesics (or narcotic analgesics for ≤ 72 hours) and/ or limiting usual activities; Grade 4= severe pain requiring hospitalisation or prolongation of hospitalisation, resulting in death, or persistent or significant disability/ incapacity, or life- threatening, or medically significant. c Grade 3= ≥ 50 mm but < 85 mm average diameter; Grade 4= ≥ 85 mm average diameter. d Grade 3= ≥ 25 mm but< 50 mm average diameter; Grade 4= ≥ 50 mm average diameter. e Grade 3= ≥ 3 cm; Grade 4= If draining. f Grade 3= refractory to topical treatment or requiring oral or parenteral treatment; Grade 4= not defined. g Grade 3= > 3 cm but ≤ 5 cm; Grade 4= > 5 cm.
Grad 3= uġigħ qawwi bi bżonn ta ’ analġeżiċi (jew analġeżiċi narkotiċi għal ≤ 72 siegħa) u/ jew bi tfixkil fl- attivitajiet ta 'kuljum; Grad 4= uġigħ qawwi bi bżonn li l- pazjent jinżàmm l- isptar jew idum iktar l- isptar, li jwassal għall- mewt, jew diżabilità/ inkapaċità persistenti jew sinifikanti, jew b’ periklu għall- ħajja, jew ta ’ sinifikanza medika. c Grad 3= ≥ 50 mm iżda < 85 mm dijametru medju; Grad 4= ≥ 85 mm dijametru medju d Grad 3= ≥ 25 mm iżda < 50 mm dijametru medju; Grad 4= ≥ 50 mm dijametru medju e Grad 3= ≥ 3 cm; Grad 4= Jekk qed tnixxi. f Grad 3= kura refrattorja jew topika jew bżonn ta ’ kura orali jew parenterali; Grad 4= mhux imfissra. g Grad 3= > 3 cm iżda ≤ 5 cm; Grad 4= > 5 cm.
Other adverse reactions
Reazzjonijiet avversi oħrajn
The addition of Fuzeon to background antiretroviral therapy generally did not increase the frequency or severity of most adverse reactions.
Ġeneralment iż- żieda ta ’ Fuzeon ma ’ terapija antiretrovirali minn qabel ma żidiedtx il- frekwenza jew is- severità tal- biċċa l- kbira tar- reazzjonijiet avversi.
The most frequently reported events occurring in the TORO 1 and TORO 2 studies were diarrhoea (38 versus 73 patients with event per 100 patient years for Fuzeon + OB versus OB) and nausea (27 versus 50 patients with event per 100 patient years for Fuzeon + OB versus OB).
L- aktar episodji rrapportati b’ mod frekwenti li seħħew fl- istuji TORO 1 u TORO 2 kienu dijarea (38 kontra 73 pazjent b’ episodju kull 100 sena ta 'pazjent għal Fuzeon + OB kontra OB) u tqalligħ (27 kontra 50 pazjent b’ episodju kull 100 sena ta' pazjent għal Fuzeon + OB kontra OB).
The following list presents events seen at a higher rate among patients receiving Fuzeon+OB regimen than among patients on the OB alone regimen with an exposure adjusted increase of at least 2 patients with event per 100 patient-years.
5 Il- lista li ġejja tirrappreżenta l- episodji li dehru b’ rata ogħla fost pazjenti li ingħataw il- programm ta ’ kura Fuzeon+ OB meta mqabbla ma ’ pazjenti li ingħataw programm ta ’ kura b’ OB waħdu b’ żieda f’ espożizzjoni aġġustata ta ’ mill- inqas 2 pazjenti b’ episodju kull 100 sena ta ’ pazjent.
These events are then designated frequency estimation (“ very common” (≥ 1/ 10), or “ common” (≥ 1/ 100, < 1/ 10)).
Dawn l- episodji huma mbagħad mogħtija stima ta ’ frekwenza (“ komuni ħafna ” (≥1/ 10), jew “ komuni ” (≥1/ 100, < 1/ 10)).
A statistically significant increase was seen for pneumonia and lymphadenopathy.
Dehret żieda statistikament sinifikanti għall- pnewmonja u limfadenopatija.
Most adverse reactions were of mild or moderate intensity.
Il- maġġoranza tar - reazzjonijiet kienu ħfief għal moderati fl- intensità tagħhom.
Infections and Infestations Common: - sinusitis, skin papilloma, influenza, pneumonia, ear infection.
Infezzjonijiet u Infestazzjonijiet Komuni: - sinusite, papilloma tal- ġilda, influwenza, pnewmonja, infezzjoni tal- widnejn.
5 Blood and Lymphatic System Disorders Common: - lymphadenopathy.
Disturbi tad- Demm u tas- Sistema Limfatika Komuni: - limfadenopatija.
Metabolism and Nutrition Disorders Common: - appetite decreased, anorexia, hypertriglyceridaemia, diabetes mellitus.
Disturbi fil- Metaboliżmu u n- Nutrizzjoni Komuni: - tnaqqis fl- aptit, anoressija, ipertrigliċeridimja, dijabete mellitus.
Psychiatric Disorders Common: - anxiety, nightmare, irritability.
Disturbi Psikjatriċi Komuni: - ansjetà, inkubi, irritabilità.
Nervous System Disorders Very Common: - peripheral neuropathy.
Disturbi fis- Sistema Nervuża Komuni Ħafna: - newropatija periferali.
Common: -hypoaesthesia, disturbance in attention, tremor.
Komuni: - ipoestesija, disturbi fl- attenzjoni, tregħid.
Eye Disorders Common: - conjunctivitis.
Disturbi fl- Għajnejn Komuni: - konġuntivite.
Ear and Labyrinth disorders Common: - vertigo.
Disturbi fil- widnejn u fis- sistema Labirintika Komuni: - vertigo
Respiratory, Thoracic and Mediastinal Disorders Common: - nasal congestion.
Disturbi Respiratorji, Toraċiċi u Medjastinali Komuni: - konġestjoni fl- imnieħer.
Gastrointestinal Disorders Common: - pancreatitis, gastro-oesophageal reflux disease.
Disturbi Gastro- intestinali Komuni: - pankreatite, marda tar- rifluss gastro- esofaġali.
Skin and Subcutaneous Tissue Disorders Common: - dry skin, eczema seborrhoeic, erythema, acne.
Disturbi fil- Ġilda u fit- Tessut ta ’ taħt il- Ġilda Komuni: - ġilda xotta, ekżema seborrejika, eritema, akne.
Musculoskeletal, Connective Tissue and Bone Disorders Common: - myalgia.
Disturbi Muskolu- skeletrali, tal- Connective Tissue u tal- Għadam Komuni: - mijalġja
Renal and Urinary Disorders Common: - Calculus renal.
Disturbi fil- Kliewi u fis- Sistema Urinarja Komuni: - Kalkulus renali.
General Disorders and Administration Site Conditions Common: - influenza like illness, weakness.
Disturbi Ġenerali u Kondizzjonijiet ta ’ mnejn jingħata Komuni: - mard bħall- influwenza, debbulizza.
Investigations Very Common: - weight decreased Common: - blood triglycerides increased, haematuria present.
Investigazzjonijiet Komuni Ħafna: - tnaqqis fil- piż Komuni: - żieda ta ’ trigliċeridi fid- demm, preżenza ta ’ ematurja.
In addition there have been a small number of hypersensitivity reactions attributed to enfuvirtide and in some cases recurrence has occurred upon re-challenge.
Barra minn hekk kien hemm ukoll numru żgħir ta ’ reazzjonijiet ta ’ sensittività eċċessiva attribwiti għal enfuvirtide u f’ xi każijiet dawn reġgħu seħħu meta l- pazjenti reġgħu ingħataw il- prodott mediċinali.
(See section 4.4)
(Ara sezzjoni 4. 4)
In HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise (see section 4.4).
6 F’ pazjenti nfetti b’ HIV b’ defiċjenza immuni severa fil- ħin li tinbeda t- terapija antiretrovirali kombinata (CART), tista ’ sseħħ reazzjoni infjammatorja għall- infezzjonijiet mingħajr sintomi jew infezzjonijiet residwali opportunistiċi (ara sezzjoni 4. 4).
Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to CART.
Kienu rrappurtati każijiet ta ’ osteonekrożi, speċjalment f’ pazjenti b’ fatturi ta ’ riskju ġeneralment magħrufa, marda ta ’ l- HIV avvanzata jew esponiment fit- tul għal CART.
The frequency of this is unknown (see section 4.4).
Il- frekwenza ta ’ din mhix magħrufa (ara sezzjoni 4. 4).
Laboratory abnormalities
Anormalitajiet tal- Laboratorju
Through week 48, eosinophilia [greater than the Upper Limit
Il- biċċa l- kbira tal- pazjenti ma kellhomx tibdil fil- grad ta ’ tossiċità fl- ebda parametru tal- laboratorju waqt l- istudju ħlief dawk elenkati f’ Tabella 3.
6 of Normal of > 0.7 x 109/ l] occurred at a higher rate amongst patients in the Fuzeon containing group (12.4 patients with event per 100 patient-years) compared with OB alone regimen (5.6 patients with event per 100 patient-years).
Matul l- 48 ġimgħa, esinofilja [aktar mill- Ogħla Limitu tan- Normal ta ’ > 0. 7 x 109/ 1] seħħet b’ rata ogħla f’ pazjenti fil- grupp b’ Fuzeon (12. 4 pazjent b’ effett għal kull 100 sena ta ’ pazjent) meta mqabbla ma ’ programm ta ’ kura b’ OB waħdu (5. 6 pazjent b’ effett għal kull 100 sena ta ’ pazjent).
When using a higher threshold for eosinophilia (> 1.4 x 109/ l), the patient exposure adjusted rate of eosinophilia is equal in both groups (1.8 patients with event per 100 patient- years).
Meta jintuża limitu ogħla għal esinofilja (> 1. 4 x 109/ l), ir- rata aġġustata ta ’ l- espożizzjoni tal- pazjent ta ’ esinofilja huwa ugwali fiż- żewġ gruppi (1. 8 pazjent b’ episodju għal kull 100 sena ta ’ pazjent).
Exposure adjusted Grade 3 & 4 laboratory abnormalities among patients on Fuzeon+OB and OB alone regimens, reported at more than 2 patients with event per 100 patient years
Gradazzjoni tal- Parametri tal -
Laboratory Parameters
Programm ta ’ kura b ’
Fuzeon+OB regimen
Programm ta ’ kura b’ OB waħdu
OB alone regimen
Kull 100 sena ta ’ pazjent
Grading n (Total Exposure patient years) ALAT
n (Total ta ’ snin ta ’ Espożizzjoni ta ’ pazjent) ALAT
Per 100 patient years 663 (557.0)
663 (557. 0)
Per 100 patient years 334 (162.1)
334 (162. 1)
4.8 1.4
4. 8 1. 4
4.3 1.2
4. 3 1. 2
3 (6.5-7.9 g/ dL) Gr.
3 (6. 5- 7. 9 g/ dL) Gr.
4 (< 6.5 g/ dL) Creatinine phosphokinase
4 (< 6. 5 g/ dL) Creatinine phosphokinase
2.0 0.7
2. 0 0. 7
1.9 1.2
1. 9 1. 2
8.3 3.1
8. 3 3. 1
8.0 8.6
8. 0 8. 6
No case of overdose has been reported.
L- ebda każ ta ’ doza eċċessiva ma ġie rrappurtat.
The highest dose administered to 12 patients in a clinical trial was 180 mg as a single dose subcutaneously.
L- ogħla doża mogħtija lil 12- il pazjent fi prova klinika kienet ta ’ 180 mg bħala doża waħda minn taħt il- ġilda.
These patients did not experience any adverse reactions that were not seen with the recommended dose.
Dawn il- pazjenti ma wrewx reazzjonijiet avversi li ma deherux bid- doża rakkomandata.
In an Early Access Program study, one patient administered 180 mg of Fuzeon as a single dose on one occasion.
F’ studu ta ’ Program Bikri ta ’ Aċċess, pazjent wieħed kien amministrat 180 mg ta ’ Fuzeon bħala doża waħda fuq okkażżjoni waħda.
He did not experience an adverse reaction as a result.
Hu ma esperjenzax reazzjoni avversa bħala riżultat.
There is no specific antidote for overdose with enfuvirtide.
M’ hemmx antidotu speċifiku għal doża eċċessiva ta ’ enfuvirtide.
Treatment of overdose should consist of general supportive measures.
Il- kura ta ’ doża eċċessiva għandha tikkonsisti minn miżuri ġenerali ta ’ support.
Other antivirals, ATC code:
Antivirali oħrajn, Kodiċi ATC:
J05AX07
J05 A- X07
Mechanism of Action:
Mekkaniżmu ta ’ Azzjoni:
Enfuvirtide is a member of the therapeutic class called fusion inhibitors.
Enfuvirtide huwa membru tal- klassi terapewtika msejħa inibituri tal- fużjoni.
It is an inhibitor of the structural rearrangement of HIV-1 gp41 and functions by specifically binding to this virus protein extracellularly thereby blocking fusion between the viral cell membrane and the target cell membrane, preventing the viral RNA from entering into the target cell.
Huwa inibitur ta ’ l- arranġament strutturali mill- ġdid ta ’ gp41 ta ’ HIV- 1 u jaħdem billi jeħel
The susceptibility to enfuvirtide of 612 HIV recombinants containing the env genes from HIV RNA samples taken at baseline from patients in Phase III studies gave a geometric mean EC 50 of 0.259 μ g/ ml (geometric mean + 2SD = 1.96 μ g/ ml) in a recombinant phenotype HIV entry assay.
Is- suxxettibilità għal enfuvirtide ta ’ 612 rikombinanti ta ’ HIV li fihom il - ġeni env minn kampjuni ta ’ RNA ta ’ HIV meħuda fil- linja bażi minn pazjenti fi studji ta ’ Fażi III taw medja ġeometrika ta ’ EC50 ta ’ 0. 259 μg/ ml (medja ġeometrika + 2SD = 1. 96 μg/ ml) f' analiżi tad- dħul ta 'HIV b’ fenotip rikombinanti.
Enfuvirtide also inhibited HIV-1 envelope mediated cell-cell fusion.
Enfuvirtide waqqaf ukoll il- fużjoni bejn ċellula u oħra medjata mill - envelop ta ’ HIV- 1.
Combination studies of enfuvirtide with representative members of the various antiretroviral classes exhibited additive to synergistic antiviral activities and an absence of antagonism.
Studji ta ’ taħtita ta ’ enfuvirtide flimkien ma ’ membri rappreżentattivi tad- diversi klassijiet antiretrovirali wrew attivitajiet antivriali addittivi għal sinerġistiċi u nuqqas ta ’ antagoniżmu.
The relationship between the in vitro susceptibility of HIV-1 to enfuvirtide and inhibition of HIV-1 replication in humans has not been established.
Ir- relazzjoni bejn is- suxxettibiltà in vitro ta ’ l- HIV- 1 għal enfuvirtide u l- inibizzjoni ta ’ replikazzjoni ta ’ l- HIV- 1 fil- bnedmin ma ġietx stabbilita.
Antiretroviral drug resistance:
Reżistenza għall- mediċina antiretrovirali:
Incomplete viral suppression may lead to the development of drug resistance to one or more components of the regimen.
Soppressjoni virali mhux kompleta tista ’ twassal għall - iżvilupp ta ’ reżistenza għall- mediċini għal wieħed jew aktar mill- komponenti tal- programm ta ’ kura.
7 In Vitro resistance to enfuvirtide:
Reżistenza In Vitro għal enfuvirtide:
HIV-1 isolates with reduced susceptibility to enfuvirtide have been selected in vitro which harbour substitutions in amino acids (aa) 36-38 of the gp41 ectodomain.
Iżolati ta ’ HIV- 1 b’ suxxettibiltà mnaqqsa għal enfuvirtide ntagħżlu in vitro li għandhom sostituzzjonijiet f’ aċidi amminiċi (aa) 36- 38 ta ’ gp41 ectodomain.
These substitutions were correlated with varying levels of reduced enfuvirtide susceptibility in HIV site- directed mutants.
Dawn is- sostituzzjonijiet kienu korrelatati ma ’ livelli varji ta ’ suxxettibiltà mnaqqsa għal enfuvirtide f’ mutanti ta ’ HIV mmirati lejn il- post.
In Vivo resistance to enfuvirtide:
Reżistenza In Vivo għal enfuvirtide:
In phase III clinical studies HIV recombinants containing the env genes from HIV RNA samples taken up to week 24 from 187 patients showed > 4 fold reduced susceptibility to enfuvirtide compared with the corresponding pre-treatment samples.
Fl- istudji kliniċi ta ’ Fażi III rikombinanti ta ’ HIV li fihom il- ġeni ta ’ env minn kampjuni ta ’ RNA ta ’ HIV meħuda sa ġimgħa 24 minn 187 pazjent urew tnaqqis ta ’ > 4 darbiet fis- suxxettibiltà għal enfuvirtide meta mqabbla mal- kampjuni korrispondenti ta ’ qabel il- kura.
Of these, 185 (98.9%) env genes carried specific substitutions in region of aa 36 - 45 of gp41.
Minn dawn, 185 (98. 9%) ġeni ta ’ env kellhom sostituzzjonijiet speċifiċi ta ’ aa 36 – 45 ta ’ gp 41.
The substitutions observed in decreasing frequency were at aa positions 38, 43, 36, 40, 42 and 45.
Is - sostituzzjonijiet osservati bl- akbar frekwenza mniżżla l- ewwel kienu f’ pożizzjonijiet aa 38, 43, 36, 40, 42 u 45.
Specific single substitutions at these residues in gp41 each resulted in a range of decreases from baseline in recombinant viral susceptibility to enfuvirtide.
Kull sostituzzjoni singola speċifika f’ dawn ir- reżidwi f’ gp41 wasslet għal firxa ta ’ tnaqqis fis - suxxettibiltà rikombinanti virali għal enfuvirtide mill- linja bażi.
The geometric mean changes ranged from 15.2 fold for V38M to 41.6 fold for V38A.
It- tibdil fil- medja ġeometrika varja minn 15. 2- il darba għal V38M għal 41. 6- il darba għal V38A.
There were insufficient examples of multiple substitutions to determine any consistent patterns of substitutions or their effect on viral susceptibility to enfuvirtide.
Ma kienx hemm biżżejjed eżempji ta ’ sostituzzjonijiet multipli sabiex xejriet konsistenti ta ’ sostituzzjonijiet jew l- effetti tagħhom fuq is - suxxettibiltà virali għal enfuvirtide jiġu stabbiliti.
The relationship of these substitutions to in vivo effectiveness of enfuvirtide has not been established.
Ir- relazzjoni ta ’ dawn is- sostituzzjonijiet għall - effettività in vivo ta ’ enfuvirtide ma ġietx stabbilita.
Decrease in viral sensitivity was correlated to the degree of pre-treatment resistance to background therapy.
Tnaqqis fis- sensittività virali ġie korrelatat mal - grad ta ’ reżistenza għall- terapija li diġa qed tintuża ta ’ qabel il- kura.
(See Table 5)
(Ara Tabella 5).
Cross-resistance:
Reżistenza Incroċjata:
Due to its novel viral target enfuvirtide is equally active in vitro against both wild- type laboratory and clinical isolates and those with resistance to 1, 2 or 3 other classes of antiretrovirals (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors).
Minħabba l- mira virali ġdida tiegħu, enfuvirtide għandu l- istess livell ta ’ attività in vitro kemm kontra iżolati kliniċi, kontra dawk tal- laboratorju tat- tip salvaġġ, kif ukoll kontra dawk b’ reżistenza għal 1, 2, jew 3 klassijiet oħrajn ta ’ antiretrovirali (impedituri nucleoside reverse transcriptase, impedituri non- nucleoside reverse transcriptase u impedituri protease).
Conversely, mutations in aa 36-45 of gp41 which give resistance to enfuvirtide would not be expected to give cross resistance to other classes of antiretrovirals.
Bil- maqlub, mutazzjonijiet f’ aa 36- 45 ta ’ gp41 li jagħtu reżistenza għal enfuvirtide mhux mistennija li jagħtu wkoll reżistenza incroċjata għal klassijiet oħrajn ta ’ antiretrovirali.
Clinical Pharmacodynamic data
Tagħrif Farmakodinamiku Kliniku
Studies in Antiretroviral Experienced Patients:
Studji f’ Pazjenti b’ Esperjenza Antiretrovirali:
The clinical activity of Fuzeon (in combination with other antiretroviral agents) on plasma HIV RNA levels and CD4 counts have been investigated in two randomised, multicentre, controlled studies (TORO 1 and TORO 2) of Fuzeon of 48 weeks duration.
L- attività klinika ta ’ Fuzeon (mogħti flimkien ma ’ aġenti antiretrovirali oħrajn) fuq livelli ta ’ RNA ta ’ l- HIV fil- plażma u l- għadd CD4 ġiet investigata f’ żewġ studji ta ’ 48 ġimgħa randomised, multiċentrali u kontrollati (TORO 1 u TORO 2) b’ Fuzeon.
995 patients comprised the intent-to-treat population.
Il - popolazzjoni b’ intenzjoni li tiġi kkurata kienet ta ’ 995 pazjent.
Patient demographics include a median baseline HIV-1 RNA of 5.2 log10 copies/ ml and 5.1 log10 copies/ ml and median baseline CD4 cell count of 88 cells/ mm3 and 97 cells/ mm3 for Fuzeon + OB and OB, respectively.
Id- demografika tal- pazjenti jinkludu linja bażi medjana ta ’ RNA ta ’ HIV- 1 ta ’ 5. 2 log10 kopji/ ml u 5. 1 log10 kopji/ ml u l- linja bażi medjana tal- għadd ta ’ ċelluli CD4 ta ’ 88 ċellula/ mm3 u 97 ċellula/ mm3 għal Fuzeon + OB u OB, rispettivament.
Patients had prior exposure to a median of 12 antiretrovirals for a median of 7 years.
Pazjenti kellhom espożizzjoni minn qabel għal medjan ta ’ 12- il antiretrovirali għal medjan ta ’ 7 snin.
All patients received an optimised background (OB) regimen consisting of 3 to 5 antiretroviral agents selected on the basis of the patient's prior treatment history, as well as baseline genotypic and phenotypic viral resistance measurements.
Il- pazjenti kollha rċevew programm ta ’ kura (OB) fl- sfond ottimizzat li kkonsista fi 3 sa 5 aġenti antiretrovirali magħżula fuq il- bażi ta ’ kura preċedenti tal- pazjent, kif ukoll fuq il- kejl ta ’ reżistenza virali ġenotipika u fenotipika fil- linja bażi.
The proportion of patients achieving viral load of < 400 copies/ ml at week 48 was 30.4% among patients on the Fuzeon+OB regimen compared to 12% among patients receiving OB regimen only.
Il- proporzjon ta ’ pazjenti li laħqu viral load ta ’ < 400 kopji/ ml f’ ġimgħa 48 kienu 30. 4% fost il - pazjenti fuq programm ta ’ kura b’ Fuzeon+OB meta mqabbel ma ’ 12% fost pazjenti fuq programm ta ’
The mean CD4 cell count increase was greater in patients on the Fuzeon + OB regimen than in patients on OB regimen only.
(ara Tabella 4)
(see Table 4)
Tabella 4
Outcomes of Randomised Treatment at Week 48 (Pooled Studies TORO 1 and TORO 2, ITT)
Riżultati ta ’ Kura Randomizzat f’ Ġimgħa 48 (Studji Kombinati ta ’ TORO 1 u TORO 2 ITT)
Outcomes
Riżultati
Treatment
Differenza
p-value
valur p
Difference Confidence Interval
Interval ta ’ Konfidenz a
HIV-1 RNA Log Change from baseline (log10 copies/ ml)*
RNA ta ’ HIV- 1 Log Bidla mill- linja bażi (log10 kopji/ ml) *
-1.48
- 1. 48
-0.63
- 0. 63
LSM -1.073, - < .0001 -0.85 0.628
LSM - 0. 85
CD4+ cell count Change from baseline (cells/ mm3)#
Għadd ta ’ ċelluli CD4+
LSM 25.1, 67.8 < .0001 46.4
25. 1, 67. 8 <. 0001
HIV RNA > 1 log below Baseline**
RNA ta ’ HIV > 1 log taħt Il- Linja Bażi **
247 (37.4%)
247 (37. 4%)
57 (17.1%)
57 (17. 1%)
Odds Ratio 2.16, 4.20 < .0001 3.02
Odds Ratio 2. 16, 4. 20 <. 0001 3. 02
HIV RNA < 400 copies/ ml**
RNA ta ’ HIV < 400 kopji/ ml **
40 (12.0%) Odds Ratio 2.36, 5.06 < .0001 3.45
40 (12. 0%) Odds Ratio 2. 36, 5. 06 <. 0001 3. 45
HIV RNA < 50 copies/ ml
RNA ta ’ HIV < 50 kopji/ ml **
26 (7.8%) Odds Ratio 1.76, 4.37 < .0001 2.77
26 (7. 8%) Odds Ratio 1. 76, 4. 37 <. 0001 2. 77
Discontinued due to adverse reactions/ intercurrent † illness/ labs
Twaqqfu minħabba reazzjonijiet avversi/ mard fl- istess waqt/ lab
Discontinued due to injection † site reactions
Twaqqfu minħabba reazzjonijiet † fil- post ta ’ l- injezzjoni
Discontinued due to other †φ § reasons
Twaqqfu minħabba raġunijiet † φ§ oħrajn
* Based on results from pooled data of TORO 1 and TORO 2 on ITT population, week 48 viral load for subjects who were lost to follow-up, discontinued therapy, or had virological failure replaced by their last observation (LOCF). # Last value carried forward. ** M-H test:
* Bbażat fuq riżultati minn tagħrif kombinat ta ’ TORO 1 u TORO 2 fuq popolazzjoni ITT, il- viral load f’ ġimgħa 48 għal persuni li waqfu wara l- vista ta’ wara, waqqfu t- terapija, jew kellhom insuffiċjenza viroloġika sostitwita bl- aħħar osservazzjoni tagħhom (LOCF). # L- aħħar valur miġjub ’ l quddiem. ** M- H test:
Discontinuations or virological failure considered as failures. † Percentages based on safety population Fuzeon+background (N=663) and background (N=334).
Waqfien jew insuffiċjenza viroloġika meqjusa bħala insuffiċjenzi. † Perċentwali bbażat fuq popolazzjoni ta ’ sigurtà Fuzeon+sfond (N=663) u sfond (N=334).
Denominator for non-switch patients:
Denominatur għal pazjenti li ma qalbux:
N=112. φ As per the judgment of the investigator. § Includes discontinuations from loss to follow-up, treatment refusal, and other reasons.
N=112. φ Skond id- deċiżjoni ta ’ l- investigatur. § Jinkludi waqfien wara l- vista ta’ wara, rifjut ta ’ kura, u raġunijiet oħrajn.
Fuzeon+OB therapy was associated with a higher proportion of patients reaching < 400 copies/ ml (or < 50 copies/ ml) across all subgroups based on baseline CD4, baseline HIV-1 RNA, number of prior antiretrovirals (ARVs) or number of active ARVs in the OB regimen.
Terapija ta ’ Fuzeon+OB kienet assoċjata ma 'proporzjon ogħla ta' pazjenti li laħħqu < 400 kopja/ ml (jew 50 kopja/ ml) tul is- sotto gruppi kollha bbażat fuq CD4 fil- linja bażi, RNA ta ’ HIV- 1 fil- linja bażi, n- numru ta ’ antiretrovirali ta ’ qabel (ARVs) jew in- numru ta ’ ARVs attivi fil- programm ta ’ kura OB.
However, subjects with baseline CD4 > 100 cells/ mm3, baseline HIV-1 RNA < 5.0 log10 copies/ ml, ≤ 10 prior ARVs, and/ or other active ARVs in their OB regimen were more likely to achieve a HIV-1 RNA of < 400 copies/ ml (or < 50 copies/ ml) on either treatment.
Iżda, persuni b’ linja bażi ta ’ CD4 > 100 ċellula/ mm3, linja bażi ta ’ RNA ta ’ HIV- 1 < 5. 0 log10 kopji/ ml, u/ jew ARVs attivi oħra, fil- programm ta ’ kura ta ’ OB tagħhom kienu aktar probabbli li jiksbu RNA ta ’ HIV- 1 ta ’ < 400 kopja/ ml (jew < 50 kopja/ ml) fuq kwalunkwe kura.
(see Table 5)
(Ara Tabella 5)
9 Table 5
9 Tabella 5 Proporzjon ta ’ pazjenti li laħqu < 400 kopja/ ml u < 50 kopja/ ml f’ Ġimgħa 48 skond is- sottogrupp (TORO 1 u TORO 2 miġbura flimkien, ITT) Sottogrupp
Proportion of Patients achieving < 400 copies/ ml and < 50 copies/ ml at Week 48 by subgroup (pooled TORO 1 and TORO 2, ITT)
RNA ta ’ HIV- 1 < 400
Subgroups
kopja/ ml
HIV-1 RNA < 400 copies/ ml HIV-1 RNA < 50 copies/ ml
RNA ta ’ HIV- 1 < 50 kopja/ ml
BL HIV-1 RNA < 5.0 log101 copies/ ml BL HIV-1 RNA ≥ 5.0 log101 copies/ ml
BL RNA ta ’ HIV- 1 < 5. 0 log101 kopji/ ml BL RNA ta ’ HIV- 1 ≥ 5. 0 log101 kopji/ ml
118/ 269 (43.9%) 83/ 392 (21.2%)
118/ 269 (43. 9%) 83/ 392 (21. 2%)
26/ 144 77/ 269 (18.1%) (28.6%) 14/ 190 44/ 392 (7.4%) (11.2%)
26/ 144 77/ 269 (18. 1%) (28. 6%) 14/ 190 44/ 392 (7. 4%) (11. 2%)
18/ 144 (12.5%) 8/ 190 (4.2%)
18/ 144 (12. 5%) 8/ 190 (4. 2%)
Total prior ARVs ≤ 101 Total prior ARVs > 101
Total ta ’ ARVs qabel ≤ 101 Total ta ’ ARVs qabel > 101
100/ 215 (46.5%) 101/ 446 (22.6%)
100/ 215 (46. 5%) 101/ 446 (22. 6%)
29/ 120 64/ 215 (24.2%) (29.8%) 11/ 214 57/ 446 (5.1%) (12.8%)
29/ 120 64/ 215 (24. 2%) (29. 8%) 11/ 214 57/ 446 (5. 1%) (12. 8%)
19/ 120 (15.8%) 7/ 214 (3.3%)
19/ 120 (15. 8%) 7/ 214 (3. 3%)
0 Active ARVs in
0 ARVs attivi fl -
background1,2 1 Active ARV in
isfond1, 2 ARV 1 fl- isfond1, 2
(8.0%) 56/ 194
(8. 0%) 56/ 194
(3.5%) 34/ 194
(3. 5%) 34/ 194
background1,2 ≥ 2 Active ARVs in
≥2 ARVs fl- isfond1, 2
background1,2 1
1
(37.8%)
(37. 8%)
(17.5%)
(17. 5%)
(22.4%)
(22. 4%)
(12.0%)
(12. 0%)
Discontinuations or virological failures considered as failures.
Waqfien jew insuffiċjenzi viroloġiċi meqjusa bħala insuffiċjenzi.
2 Based on GSS score.
2 Ibbażat fuq il- punteġġ GSS.
The pharmacokinetic properties of enfuvirtide have been evaluated in HIV-1-infected adult and paediatric patients.
It- tagħrif farmakokinetiku ta ’ enfuvirtide ġie evalwat f’ pazjenti adulti u pedjatriċi infettati bl- HIV- 1.
The absolute bioavailability after subcutaneous administration of enfuvirtide 90 mg in the abdomen was 84.3 ± 15.5%.
Il- biodisponibiltà assoluta wara għotja minn taħt il- ġilda ta ’ enfuvirtide 90 mg fl - addome kienet ta ’ 84. 3 ± 15. 5%.
Mean (± SD) Cmax was 4.59 ± 1.5 μ g/ ml, AUC was 55.8 ± 12.1 μ g*hr/ ml The subcutaneous absorption of enfuvirtide is proportional to the administered dose over the 45 to 180 mg dose range.
L- assorbiment minn taħt il- ġilda ta ’ enfuvirtide huwa proporzjonali mad- doża mogħtija fuq il- medda ta ’ dożi minn 45 sa ’ 180 mg.
Subcutaneous absorption at the 90 mg dose is comparable when injected into abdomen, thigh or arm.
L- assorbiment minn taħt il- ġilda ta ’ doża ta ’ 90 mg huwa simili meta injettata fl- addome, fil- koxxa jew fid- driegħ.
In four separate studies (N = 9 to 12) the mean steady state trough plasma concentration ranged from 2.6 to 3.4 μ g/ ml.
F’ erba ’ studji separati (N=9 sa ’ 12) il- medja ta ’ konċentrazzjoni l- aktar baxxa fi stat fiss fil- plażma varjat minn 2. 6 sa ’ 3. 4 μg/ ml.
The steady state volume of distribution with intravenous administration of a 90 mg dose of enfuvirtide was 5.5 ± 1.1 l.
Il- volum ta ’ distribuzzjoni fi istat fiss b’ għotja minn taħt il- ġilda ta ’ doża ta ’ 90 mg enfuvirtide kien ta ’ 5. 5 ± 1. 11.
Enfuvirtide is 92% bound to plasma proteins in HIV infected plasma over a plasma concentration range of 2 to 10 μ g/ ml.
Enfuvirtide huwa 92% marbut ma ’ proteini tal- plażma fi plażma infettata bl- HIV fuq medda ta ’ konċentrazzjonijiet fil- plażma bejn 2 sa ’ 10 μg/ ml.
It is bound predominantly to albumin and to a lower extent to α -1 acid glycoprotein.
Huwa marbut l - aktar ma ’ albumin u fi grad anqas ma ’ α- 1 acid glycoprotein.
In in vitro studies, enfuvirtide was not displaced from its binding sites by other medicinal products, nor did enfuvirtide displace other medicinal products from their binding sites.
Fi istudji in vitro, enfuvirtide ma tneħħiex mill- postijiet ta ’ rbit tiegħu minn prodotti mediċinali oħrajn, u enfuvirtide ma neħħiex prodotti mediċinali oħrajn mill- postijiet ta ’ rbit tagħhom.
In HIV patients, enfuvirtide levels in the cerebrospinal fluid have been reported to be negligible.
F’ pazjenti bl- HIV, livelli ta 'enfuvirtide fil - fluwidu ċerebrospinali kien irrappurtat bħala negliġibli.
As a peptide, enfuvirtide is expected to undergo catabolism to its constituent amino acids, with subsequent recycling of the amino acids in the body pool.
Bħala peptide, enfuvirtide huwa mistenni li jgħaddi minn kataboliżmu għal l- aċidi amminiċi li minnhom huwa magħmul, biex imbagħad l- aċidi aminiċi jiġu rriċiklati ġol- ġisem.
In vitro human microsomal studies and in in vivo studies indicate that enfuvirtide is not an inhibitor of CYP450 enzymes.
Studji mikrosomali umani in vitro u studji in vivo jindikaw li enfivirtide m’ huwiex impeditur ta ’ l- enżimi CYP450.
In in vitro human microsomal and hepatocyte studies, hydrolysis of the amide group of the C-terminus amino acid, phenylalanine results in a deamidated metabolite and the formation of this metabolite is not NADPH dependent.
Fi studji b’ epatoċiti u mikrosomi umani in vitro, l- idrolisi tal- grupp amide ta ’ l- aċidu aminu fit- terminu C, phenylalanine twassal għal metabolita deamidat u l- formazzjoni ta ’ dan il- metabolta m’ huwiex dipendenti minn NADPH.
This metabolite is detected in human plasma following administration of enfuvirtide, with an AUC ranging from 2.4 to 15% of the enfuvirtide AUC.
Dan il - metabolita jista ’ jinstab fil- plażma umana wara l- għotja ta ’ enfuvirtid, b’ AUC li tvarja minn 2. 4 sa ’ 15% ta 'l- AUC ta ’ enfuvirtide.
Clearance of enfuvirtide after intravenous administration 90 mg was 1.4 ± 0.28 l/ h and the elimination half-life was 3.2 ± 0.42 h.
It- tneħħija ta ’ enfuvirtide wara għotja ta ’ 90 mg minn ġol- vini kienet ta ’ 1. 4 ± 0. 28 l/ h u l- half- life kienet ta ’ 3. 2 ± 0. 42 h.
Following a 90 mg subcutaneous dose of enfuvirtide the
Wara doża ta ’ 90 mg enfuvirtide minn taħt il- ġilda l- half life ta ’
10 half-life of enfuvirtide is 3.8 ± 0.6 h.
10 enfuvirtide kienet ta ’ 3. 8 ± 0. 6 h.
Mass balance studies to determine elimination pathway(s) of enfuvirtide have not been performed in humans.
Ma sarux studji tal- bilanċ tal- massa fil- bnedmin sabiex jinstab( u) l - mezz( i) ta ’ eliminazzjoni ta ’ enfuvirtide.
Hepatic Insufficiency:
Insuffiċjenza Epatika:
The pharmacokinetics of enfuvirtide have not been studied in patients with hepatic impairment.
Il- farmakokinetika ta ’ enfuvirtide ma ġietx studjata f’ pazjenti b’ indeboliment epatiku.
Analysis of plasma concentration data from patients in clinical trials indicated that the clearance of enfuvirtide is not affected to any clinically relevant extent in patients with mild to moderate renal impairment.
Analiżi ta ’ riżultati ta ’ konċentrazzjoni fil- plażma minn pazjenti fi provi kliniċi indikat li t- tneħħija ta ’ enfuvirtide m’ hijiex affettwata b’ mod klinikament rilevanti f’ pazjenti b’ indeboliment renali ħafif għal moderat.
In a renal impairment study AUC of enfuvirtide was increased on average by 43-62% in patients with severe or end stage renal disease compared to patients with normal renal function.
Fi studju dwar indeboliment renali, l- AUC ta ’ enfuvirtide żdiedet b’ medja ta ’ 43- 62% f’ pazjenti b’ indeboliment renali sever jew b’ marda renali ta ’ l- aħħar stadju, meta mqabbel ma ’ pazjenti b’ funzjoni renali normali.
Hemodialysis did not significantly alter enfuvirtide clearance.
Emodijalisi ma biddlitx it- tneħħija ta ’ enfuvirtide b’ mod sinifikanti.
Less than 13% of the dose was removed during hemodialysis.
Inqas minn 13% tad- doża tneħħiet waqt l- emodijalisi.
No dose adjustment is required for patients with impaired renal function.
M’ hemmx bżonn ta ’ aġġustament fid- doża għall- pazjenti b’ indeboliment fil- funzjoni renali.
The pharmacokinetics of enfuvirtide have not been formally studied in elderly patients over 65 years of age.
Il- farmakokinetika ta ’ enfuvirtide ma ġietx studjati formalment f’ pazjenti anzjani b’ età 'l fuq minn 65 sena.
Gender and Weight:
Sess u Piż:
Analysis of plasma concentration data from patients in clinical trials indicated that the clearance of enfuvirtide is 20% lower in females than males irrespective of weight and is increased with increased body weight irrespective of gender (20% higher in a 100 kg and 20% lower in a 40 kg body weight patient relative to a 70 kg reference patient).
L- analiżi ta ’ tagħrif dwar il- konċentrazzjoni fil- plażma minn pazjenti fi provi kliniċi indikat li t- tneħħija ta ’ enfuvirtide hija 20% inqas fin- nisa milli fl- irġiel irrispettivament mill- piż, u tiżdied mal- piż irrispettivament mis- sess ta ’ l- individwu (20% ogħla f’ pazjent li jiżen 100 kg u 20% anqas f’ pazjent li jiżen 40 kg meta mqabbla ma 'pazjent li jiżen 70 kg).
However, these changes are not clinically significant and no dose adjustment is required.
Iżda dawn it- tibdiliet m’ humiex klinikament sinifikanti u m’ hemm bżonn ta 'l- ebda tibdil fid- doża.
Analysis of plasma concentration data from patients in clinical trials indicated that the clearance of enfuvirtide was not different in Afro-Americans compared to Caucasians.
L- analiżi ta ’ tagħrif dwar il- konċentrazzjoni fil- plażma minn pazjenti fi provi kliniċi ndikat li t - tneħħija ta ’ enfuvirtide ma kienetx differenti f’ Afro- Amerikani meta mqabbla mal- Kawkasi.
Other PK studies suggest no difference between Asians and Caucasians after adjusting exposure for body weight.
Studji tal - PK oħrajn ma jurux differenzi bejn l- Ażjatiċi u l- Kawkasi wara l- aġġustar ta ’ l- espożizzjoni minħabba l- piż.
Paediatric Patients:
Pazjenti Pedjatriċi:
The pharmacokinetics of enfuvirtide have been studied in 37 paediatric patients.
Il- farmakokinetika ta ’ enfuvirtide ġiet studjata f’ 37 pazjent pedjatriku.
A dose of 2 mg/ kg bid (maximum 90 mg bid) provided enfuvirtide plasma concentrations similar to those obtained in adult patients receiving 90 mg bid dosage.
Doża ta ’ 2 mg/ kg (massimu ta ’ 90 mg) tat konċentrazzjonijiet ta ’ enfuvirtide fil- plażma simili għal dawk f’ pazjenti adulti li rċivew dożaġġ ta ’ 90 mg bid.
In 25 paediatric patients ranging in age from 5 to 16 years and receiving the 2 mg/ kg bid dose into the upper arm, anterior thigh or abdomen, the mean steady-state AUC was 54.3 ± 23.5 μ g*h/ ml, Cmax was 6.14 ± 2.48 μ g/ ml, and Ctrough was 2.93 ± 1.55 μ g/ ml.
F’ 25 pazjent pedjatriku ta ’ etajiet bejn il- 5 u s- 16- il sena li rċevew doża ta ’ 2 mg/ kg bid fin- naħa ta ’ fuq tad- driegħ, fin- naħa ta ’ quddiem tal- koxxa jew fl - addome, l- AUC fi istat fiss medju kienet ta ’ 54. 3 ± 23. 5 μg* h/ ml, is- Cmax kienet ta ’ 6. 14 ± 2. 48 μg/ ml, u s- Ctrough kienet ta ’ 2. 93 ± 1. 55 μg/ ml.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and late embryonal development.
Informazzjoni li mhiex klinika, magħmula fuq studji konvenzjonali ta ’ sigurtà farmakoloġika, effett tossiku minn dożi ripetuti, effett tossiku fuq il- ġeni, u dewmien fl- iżvilupp ta ’ l- embriju ma ’ turi l - ebda periklu speċjali għall- bnedmin.
Long-term animal carcinogenicity studies have not been performed.
Ma sarux studji dwar l- effetti karċinoġeniċi għal żmien twil fuq l - annimali.
Studies in guinea pigs indicated a potential for enfuvirtide to produce delayed contact hypersensitivity.
Studji fuq il- fniek ta ’ l- Indi jindikaw potenzjal li enfuvirtide jipproduċi sensittività eċċessiva ttardjata għal kuntatt.
In a rat model on the resistance to influenza infection, an impairment of IFN-γ production was observed.
F’ mudell fil- far dwar ir- reżistenza għall- infezzjoni ta ’ l- influwenza, kienet osservata tnaqqis fil- produzzjoni ta ’ IFN- γ.
The resistance to influenza and streptococcal infection in rats was only weakly compromised.
Ir- reżistenza għall- infezzjoni u nfezzjonijiet kkawżati minn streptococci fil- firien, kienet kompromessa biss b’ mod ħafif.
The clinical relevance of these findings is unknown.
L- importanza klinika ta ’ dawn is- sejbiet m’ hijiex magħrufa.
Powder Sodium carbonate Mannitol Sodium hydroxide Hydrochloric Acid
Trab Sodium carbonate Mannitol Sodium hydroxide Hydrochloric Acid
11 Solvent Water for Injections
Solvent Ilma għall- injezzjonijiet
Powder 3 years
Trab 3 snin
Solvent 3 years
Solvent 3 snin
Shelf life after reconstitution After reconstitution:
Żmien kemm idum tajjeb wara r- rikostituzzjoni Wara r- rikostituzzjoni:
Chemical and physical in-use stability has been demonstrated for 48 hours at 5°C when protected from light.
Meta mħares mid- dawl, l- istabbilità kimika u fiżika waqt l- użu ntweriet għal 48 siegħa f’ temperatura ta '5oC.
From a microbiological point of view, the product should be used immediately.
Mill- aspett mikrobijoloġiku, il- prodott għandu jintuża minnufih.
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 to 8°C, unless reconstitution has taken place in controlled and validated aseptic conditions.
Jekk ma jintużax minnufih, il- perjodu u l- kundizzjonijiet tal- ħażna qabel l- użu huma r- responsabbiltà ta ’ min qed jagħmel użu minnu u normalment m’ humiex aktar minn 24 siegħa f’ temperatura ta ’ 2oC sa ’ 8oC, sakemm ir- rikostituzzjoni ma sseħħx taħt kundizzjonijiet asettiċi kontrollati u validati.
Powder Keep the vial in the outer carton in order to protect from light.
Trab Żomm il- kunjett fil- kartuna ta ’ barra sabiex tilqa ’ mid- dawl.
For storage conditions of the reconstituted medicinal product, see section 6.3.
Għall- kundizzjonijiet ta ’ ħażna għall - prodott mediċinali rikostitwit, ara sezzjoni 6. 3.
Solvent This medicinal product does not require any special storage conditions.
Solvent Dan il- prodott mediċinali m’ għandu bżonn ta ’ l- ebda kundizzjonijiet speċjali ta ’ ħażna.
Powder Vial:
Trab Kunjett:
3 ml vial, colourless glass type 1 Closure:
Għatu:
Seal:
Siġill:
lyophilisate stopper, rubber (latex free) aluminum seal with flip-off cap
kunjett ta ’ 3 ml, ħġieġ bla kulur tat- tip 1 tapp tal- lajofilizzazzjoni, gomma (mingħajr latex) siġill ta ’ l- aluminju b’ għatu flip- off
Vial:
Kunjett:
Seal:
Għatu Siġill:
2 ml vial, colourless glass type 1 rubber stopper (latex free) aluminum seal with flip-off cap
kunjett ta ’ 2ml, ħġieġ bla kulur tat- tip 1 tapp tal- gomma (mingħajr latex) siġill ta ’ l- alumniju b’ għatu flip- off
Pack sizes
12 Daqsijiet tal- pakkett
Pack 1 60 vials powder for solution for injection 60 vials solvent 60 3 ml syringes 60 1 ml syringes 180 alcohol swabs
Pakkett 1 60 kunjett bi trab għal soluzzjoni għall- injezzjoni 60 kunjett b’ solvent 60 siringa tat- 3 ml 60 siringa tal- 1 ml 180 msielaħ bl- alkoħol
12 Pack 2 60 vials powder for solution for injection 60 vials solvent
Pakkett 2 60 kunjett bi trab għal soluzzjoni għall- injezzjoni 60 kunjett b’ solvent
Any unused product should be disposed of in accordance with local requirements.
Kull fdal tal- prodott li ma jkunx intuża jew skart li jibqa wara l- użu tal- prodott għandu jintrema kif jitolbu l- liġijiet lokali.
Patients should be instructed on the use and administration of Fuzeon by a healthcare professional before using for the first time.
Qabel l- ewwel użu, il- pazjenti għandhom jiġu mgħarrfa minn professjonist fil- kura tas- saħħa dwar l - użu u l- amministrazzjoni ta ’ Fuzeon
Fuzeon must only be reconstituted with 1.1 ml of Water for Injections.
Fuzeon għandu jiġi rikostitwit b’ 1. 1 ml Ilma għall- Injezzjonijiet biss.
Patients must be instructed to add the water for injections and then gently tap the vial with their fingertip until the powder begins to dissolve.
Il- pazjenti għandhom jiġu mgħarrfa biex iżidu l- ilma għall- injezzjonijiet u mbagħad itektku l- kunjett bil- mod bil- ponta ta ’ subgħajhom sakemm it- trab jibda jinħall.
They must never shake the vial or turn it upside down to mix— this will cause excessive foaming.
Qatt m’ għandhom iħawwdu l- kunjett jew idawruh rasu 'l isfel biex iħalltu – dan jikkawża ragħwa eċċessiva.
After the powder begins to dissolve they can set the vial aside to allow it to completely dissolve.
Wara li t- trab jibda jinħall, jistgħu jħallu l - kunjett sabiex jinħall kompletament.
The powder may take up to 45 minutes to dissolve into solution.
It- trab jista ’ jieħu sa 45 minuta biex jinħall f’ soluzzjoni.
The patient can gently roll the vial between their hands after adding the water for injections until it is fully dissolved and this may reduce the time it takes for the powder to dissolve.
Il - pazjenti jistgħu jgerbu l- kunjett bil- mod bejn idejhom wara li jżidu l- ilma għall- injezzjonijiet sakemm jinħall għal kollox u dan jista ’ jnaqqas il- ħin meħtieġ għat- trab biex jinħall.
Before the solution is withdrawn for administration, the patient should inspect the vial visually to ensure that the contents are fully in solution, and that the solution is clear and without bubbles or particulate matter.
Qabel il- ġbid tas - soluzzjoni sabiex tittieħed, il- pazjent għandu jifli l- kunjett viżwalment sabiex jiżgura li l- kontenut huwa kollu f’ soluzzjoni, u li s- soluzzjoni hija ċara u mingħajr bżieżaq jew frak.
If there is evidence of particulate matter, the vial must not be used and should be discarded or returned to the pharmacy.
Jekk ikun hemm xi frak, il- kunjett m’ għandhiex tintuża u għandha tintrema jew tittieħed lura l- ispiżerija.
The solvent vials contain 2 ml Water for Injections, of which 1.1 ml must be withdrawn for the reconstitution of the powder.
Il- kunjetti bis- solvent fihom 2 ml Ilma għall- Injezzjonijiet, li minnhom 1. 1 ml għandu jinġibed għar - rikostituzzjoni tat- trab.
Patients should be instructed to discard the remaining volume in the solvent vials.
Il- pazjenti għandhom jiġu nformati biex jarmu l- volum li jifdal fil- kunjett tas - solvent.
Fuzeon contains no preservative.
Fuzeon ma fihx preservattivi.
Once reconstituted, the solution should be injected immediately.
Meta s- soluzzjoni tiġi rikostitwita, din trid tiġi injettata minnufih.
If the reconstituted solution cannot be injected immediately, it must be kept refrigerated until use and used within 24 hours.
Jekk is- soluzzjoni rikostitwita ma ’ tistax tiġi injettata minnufih, din għandha tinżamm fil- friġġ sakemm tintuża u għandha tintuża fi żmien 24 siegħa.
Refrigerated reconstituted solution should be brought to room temperature before injection.
Soluzzjoni rikostitwita li kienet fil- friġġ għandha tinġieb għal temperatura tal- kamra qabel l- injezzjoni.
1 ml of the reconstituted solution should be injected subcutaneously in the upper arm, abdomen or anterior thigh.
1 ml ta ’ soluzzjoni rikostitwita għandha tiġi injettata minn taħt il- ġilda fin- naħa ta ’ fuq tad- driegħ, fl - addome jew fin- naħa ta ’ quddiem tal- koxxa.
The injection should be given at a site different from the preceding injection site and where there is no current injection site reaction.
L- injezzjoni għandha tingħata f’ post differenti minn fejn ingħatat id- darba ta ’ qabel u f’ post fejn m’ hemmx reazzjoni għall- injezzjoni.
A vial is suitable for single use only; unused portions must be discarded.
Kunjett wieħed huwa tajjeb għall- użu ta 'darba biss; porzjonijiet li ma jintużawx għandhom jintremew.
MARKETING AUTHORISATION HOLDER
SID TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ
Roche Registration Limited 6 Falcon Way Shire Park Welwyn Garden City AL7 1TW United Kingdom
Roche Registration Limited 6 Falcon Way Shire Park Welwyn Garden CIty AL7 1TWIr- Renju Unit
Date of last renewal:
Data ta ’ l- ewwel awtorizzazzjoni:
27 May 2003 DD-MM-YY
27 ta ’ Mejju 2003 Data ta ’ l- aħħar tiġdid:
Detailed information on this medicinal product is available on the web site of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il - Mediċini (EMEA) http: // www. emea. europa. eu /.
Fuzeon 90 mg/ ml powder for solution for injection
Fuzeon 90 mg/ ml trab għal soluzzjoni għall- injezzjoni
Each ml of reconstituted solution contains 90 mg enfuvirtide.
Kull ml ta ’ soluzzjoni rikostituta fiha 90 mg enfuvirtide.
White to off-white lyophilised powder.
Trab għal soluzzjoni għall- injezzjoni Trab lajofilizzat, abjad jagħti fl- offwajt.
(see section 5.1).
(ara sezzjoni 5. 1)
In deciding on a new regimen for patients who have failed an antiretroviral regimen, careful consideration should be given treatment history of the individual patient and the patterns of mutations associated with different drugs.
Biex jiġi deċiż programm ta ’ kura ġdid għal pazjenti li ma rnexxewx bi programm ta ’ kura antiretrovirali, għandha tingħata konsiderazzjoni speċjali lill- kura li ngħatat fil- passat għal kull pazjent individwali, kif ukoll lit- tipi ta ’ mutazzjonijiet assoċjati ma ’ prodotti mediċinali differenti.
(See sections 4.4 and 5.1).
(Ara sezzjonijiet 4. 4 u 5. 1).
In clinical trials the dosage regimen in Table 1 below was used:
Fi provi kliniċi kien użat il- programm ta ’ dożaġġ kif jidher f’ Tabella 1 taħt.
No data are available to establish a dose recommendation for patients with hepatic impairment (See sections 4.4 and 5.2).
(Ara sezzjonijiet 4. 4 u 5. 2).
(See section 5.1)
(Ara sezzjoni 5. 1)
Hypersensitivity reactions have occasionally been associated with therapy with enfuvirtide and in rare cases hypersensitivity reactions have recurred on re-challenge.
Xi kultant reazzjonijiet ta ’ sensittività eċċessiva ġew assoċjati ma ’ terapija b’ enfuvirtide u f’ każijiet rari reazzjonijiet ta ’ sensittività eċċessiva reġgħu seħħew meta l- pazjenti reġgħu ingħataw il- prodott mediċinali.
16 antiretroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse events.
16 kliniċi ta ’ fażi III kien hemm ftit pazjenti li kienu ko- infettati bl- epatite B/ C.
Administration of Fuzeon to non-HIV-1 infected individuals may induce anti-enfuvirtide antibodies that cross-react with HIV gp-41.
L- għotja ta ’ Fuzeon lil individwi li m’ humiex infettati b’ HIV- 1 tista ’ twassal għal anti- korpi anti - enfuvirtide li jkollhom reazzjoni inkroċjata ma 'HIV gp- 41.
Data is limited in patients with moderate to severe renal impairment, and in patients maintained on dialysis.
Tagħrif huwa limitat f' pazjenti b’ indeboliment renali moderat għal serju u f’ pazjenti miżmuma fuq dijalisi.
(See sections 4.2 and 5.2).
(Ara sezzjonijiet 4. 2 u 5. 2)
In an in-vivo human metabolism study enfuviritide, at the recommended dose of 90 mg twice daily, did not inhibit the metabolism of substrates by CYP3A4 (dapsone), CYP2D6 (debrisoquine), CYP1A2 (caffeine), CYP2C19 (mephenytoin), and CYP2E1 (chlorzoxazone).
Fi studju in vivo tal- metaboliżmu uman, enfuviritide, fid- doża rakkomandata ta ’ 90 mg darbtejn kuljum, ma waqqafx il- metaboliżmu ta ’ substrati permezz ta ’ CYP3A4 (dapsone), CYP2D6 (debrisoquine), CYP1A2 (kaffeina), CYP2C19 (mephenytoin), u CYP2E1 (chlorzoxazone).
There are no adequate and well-controlled studies in pregnant women.
4. 6 Tqala u treddigħ M’ hemmx studji biżżejjed jew kontrollati sew dwar l- użu waqt it- tqala.
It is not known whether enfuvirtide is secreted in human milk.
Mhux magħruf jekk enfuvirtide jitneħħiex mal- ħalib tas- sider uman.
17 4.7 Effects on ability to drive and use machines
17 4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
There is no evidence that enfuviritide may alter the patient’ s ability to drive and use machines, however, the adverse event profile of enfuvirtide should be taken into account.
M’ hemmx evidenza li enfuviritide jista ’ jbiddel il- ħila tal- pazjent biex isuq jew iħaddem magni, iżda, wieħed għandu jikkunsidra il- profil ta ’ effetti avversi ta ’ enfuvirtide.
Safety results are expressed as the number of patients with an adverse reaction per 100 patient-years of exposure (except for injection site reactions).
Riżultati ta ’ sigurtà huma espressi bħala n- numru ta 'pazjenti b’ reazzjoni avversa kull 100 sena ta ’ pazjent ta ’ espożizzjoni (ħlief għal reazzjonijiet fil- post tal- injezzjoni)
Summary of individual signs/ symptoms characterising local injection site reactions in studies TORO 1 and TORO 2 combined (% of patients) n=663
Sommarju ta ’ sinjali/ sintomi ndividwali li jikkaratterizzaw reazzjonijiet lokali fil - post tal- injezzjoni fl- istudji TORO 1 u TORO 2 flimkien (% tal- pazjenti)
Withdrawal Rate due to ISRs
n=663 Rata ta ’ Rtirar minħabba ISRs
Backgrounda 96.1%
96. 1%
The following list presents events seen at a higher rate among patients receiving Fuzeon+OB regimen than among patients on the OB alone regimen with an exposure adjusted increase of at least 2 patients with event per 100 patient-years.
Dawn l- episodji
These events are then designated frequency estimation (“ very common” (≥ 1/ 10), or “ common” (≥ 1/ 100, < 1/ 10)).
18 huma mbagħad mogħtija stima ta ’ frekwenza (“ komuni ħafna ” (≥1/ 10), jew “ komuni ” (≥1/ 100, < 1/ 10)).
18 Blood and Lymphatic System Disorders Common: - lymphadenopathy.
Disturbi tad- Demm u tas- Sistema Limfatika Komuni: - limfadenopatija.
Common: - hypoaesthesia, disturbance in attention, tremor.
Komuni: - ipoestesija, disturbi fl- attenzjoni, tregħid.