qanastek/EMEA-V3 huggingface dataset:
A more than 10-fold reduced sensitivity to stavudine has been reported for some strains with reduced sensitivity to zidovudine and lamivudine.
Ġie rrappurtat tnaqqis ta ’ aktar minn 10 darbiet fis- sensitività għal stavudine f’ xi razez ta ’ ċelloli b’ sensittività inqas għal zidovudine u lamivudine.
No mutations associated with high degree resistance specifically to stavudine have been revealed in vivo.
Ma dehru l- ebda mutazzjonijiet assoċjati ma ’ reżistenza għolja b’ mod speċifiku għal stavudine in vivo.
Zerit has been studied in combination with other antiretroviral agents, e. g. didanosine, lamivudine, ritonavir, indinavir, saquinavir, efavirenz, and nelfinavir.
Zerit ġie studjat b’ kombinazzjoni ma ’ mediċini antiretrovirali oħra p. e. didanosine, lamivudine, ritonavir, indinavir, saquinavir, efavirenz u nelfinavir.
Study AI455-099 was a 48-week, randomised, double-blind study with Zerit (40 mg twice daily), in combination with lamivudine (150 mg twice daily) plus efavirenz (600 mg once daily), in 391 treatment-naive patients, with a median CD4 cell count of 272 cells/ mm3 (range 61 to 1,215 cells/ mm3) and a median plasma HIV-1 RNA of 4.80 log10 copies/ ml (range 2.6 to 5.9 log 10 copies/ ml) at baseline.
Studju AI455- 099 kien studju ta ’ 48 ġimgħa, b' kampjun magħżul kif jinzerta, double blind fejn Zerit (40 mg darbtejn kuljum) flimkien ma 'lamivudine (150 mg darbtejn kuljum) kif ukoll efavirenz (600 mg darba kuljum), fi 391 pazjent li qatt ma kienu ħadu trattament qabel, b’ għadd medju ta ’ ċelloli CD4 ta ’ 272 ċellolia/ mm3 (ammont ivarja bejn 61 u 1, 215 ċelloli/ mm3) u livell medju ta ’ plażma HIV- 1 RNA ta ’ 4. 80 log10 kopji/ ml (livell ivarja bejn 2. 6 sa 5. 9 log10 kopji/ ml) fil- linja bażi.
Patients were primarily males (70%) and non-white (58%) with a median age of 33 years (range 18 to 68 years).
Pazjenti kienu l- aktar rġiel (70%) u mhux bojod (58%) b’ età medja ta ’ 33 sena (età tvarja bejn 18 sa 68 sena).
Study AI455-096 was a 48-week, randomised, double-blind study with Zerit (40 mg twice daily), in combination with lamivudine (150 mg twice daily) plus efavirenz (600 mg once daily), in 76 treatment-naive patients, with a median CD4 cell count of 261 cells/ mm3 (range 63 to 962 cells/ mm3) and a median plasma HIV-1 RNA of 4.63 log10 copies/ ml (range 3.0 to 5.9 log10 copies/ ml) at baseline.
Studju AI455- 096 kien studju ta ’ 48 ġimgħa, b' kampjun magħżul kif jinzerta, double blind fejn Zerit (40 mg darbtejn kuljum) flimkien ma 'lamivudine (150 mg darbtejn kuljum) kif ukoll efavirenz (600 mg darba kuljum), f’ 76 pazjenti li qatt ma kienu ħadu trattament qabel, b’ għadd medju ta ’ ċelloli CD4 ta ’ 261 ċellolia/ mm3 (ammont ivarja bejn 63 u 962 ċelloli/ mm3) u livell medju ta ’ plażma HIV- 1 RNA ta ’ 4. 63 log10 kopji/ ml (livell ivarja bejn 3. 0 sa 5. 9 log10 kopji/ ml) fil- linja bażi.
Patients were primarily males (76%) and white (66%) with a median age of 34 years (range 22 to 67 years).
Pazjenti kienu l - aktar rġiel (76%) u bojod (66%) b’ età medja ta ’ 34 sena (età tvarja bejn 22 u 67 sena).
9 The results of AI455-099 and AI455-096 are presented in the table below:
Ir- riżultati ta ’ AI455- 099 u AI455- 096 jidhru fit- tabella hawn taħt:
Percent of Percent of
ta ’ l- HIV < 400 kopji/ ml
HIV RNA
ta ’ l- HIV < 50 kopji/ ml
CD4 Mean
bidu( log10
AI455-099 (48 weeks) b
AI455- 099 (48 ġimgħa) b
patients with HIV patients with HIV Mean Change RNA < 400 RNA < 50 from Baseline copies/ ml copies/ ml (log10 Treatment Treatment copies/ ml) response (%)a response (%)a
kura (%)
change from Baseline (cells/ mm3)
kura (%)
Zerit + lamivudine + efavirenz (n = 391) AI455-096 (48 weeks) b
Zerit + lamivudine + efavirenz (n = 391) AI455- 096 (48 ġimgħa) b
+182
- 2. 83 +182
+195
- 2. 64 +195
Percent of patients who have HIV RNA < 400 c/ ml or < 50 c/ ml and do not meet any criteria for treatment failure including the occurrence of a new AIDS-defining diagnosis. b These studies were designed to compare two formulations of Zerit.
Perċentwali ta ’ pazjenti li kellhom HIV RNA < 400c/ ml jew < 50c/ ml u ma jissodisfaw ebda kriterju għall- falliment tal- kura inkluż dijanjożi ġdida li tiddefinixxi l- AIDS. b Dawn l- istudji kienu maħsuba sabiex iqabblu żewġ formulazzjonijiet ta 'Zerit.
Only the data from the marketed formulation is presented.
Qed tiġi ppreżentat biss id- data mill- formulazzjoni li tinsab għall- bejgħ.
In adolescents, children and infants, use of stavudine is supported by evidence from adequate and well-controlled studies in adults with additional pharmacokinetic and safety data in paediatric patients (see also sections 4.8 and 5.2).
F’ adolexxenti, tfal u trabi, l- użu ta ’ stavudine huwa megħjun b’ tagħrif minn studji apposta u kkontrollati tajba f’ adulti b’ aktar tagħrif fuq is- sigurtà u l- farmakokinetika fil- pazjenti pedjatriċi (ara wkoll sezzjonijiet 4. 8 u 5. 2).
Absorption: the absolute bioavailability is 86±18%.
Assorbiment: il- bijodisponibilità assoluta hija ta ’ 86±18%.
After multiple oral administration of 0.5-0.67 mg/ kg doses, a Cmax value of 810±175 ng/ ml was obtained.
Wara li ngħataw ħafna dożi orali ta ’ 0. 5 - 0. 67 mg/ kg, kien hemm livell ta ’ Cmax ta ’ 810±175 ng/ ml.
Cmax and AUC increased proportionally with dose in the dose ranges, intravenous 0.0625-0.75 mg/ kg, and oral 0.033-4.0 mg/ kg.
Cmax u AUC wrew żieda proporzjonali mad - doża fil- livelli tad- doża mill- vini 0. 0625- 0. 75 mg/ kg u mill- ħalq 0. 033- 4. 0 mg/ kg.
In eight patients receiving 40 mg twice daily in the fasted state, steady-state AUC0-12h was 1284±227 ng⋅ h/ ml (18%) (mean ± SD [% CV]), Cmax was 536±146 ng/ ml (27%), and Cmin was 9±8 ng/ ml (89%).
Fi tmien pazjenti li ħadu 40 mg darbtejn kuljum waqt li kienu sajma, l- AUC0- 12h fi stat stabbli kien 1284±227 ng⋅h/ ml (18%) (medja ± SD [% CV]), Cmax kien 536±146 ng/ ml (27%), u Cmin kien 9±8 ng/ ml (89%).
A study in asymptomatic patients demonstrated that systemic exposure is similar while Cmax is lower and Tmax is prolonged when stavudine is administered with a standardised, high-fat meal compared with fasting conditions.
Studju f’ pazjenti li ma wrew l- ebda sintomi wera li l- livell ta ’ l- espożizzjoni tas - sistema jixxiebaħ filwaqt li Cmax huwa iktar baxx u Tmax jittawwal meta stavudine jingħata ma ikla
The clinical significance of this is unknown.
L - importanza klinika ta ’ dan għadha mhux magħrufa.
Distribution: the apparent volume of distribution at steady state is 46±21 l.
Distribuzzjoni: il- volum tad- distribuzzjoni apparenti li jidher fi stat stabbli huwa ta ’ 46±21 l.
It was not possible to detect stavudine in cerebrospinal fluid until at least 2 hours after oral administration.
Stavudine ma setax jitkejjel fil- fluwidu ċerebrospinali qabel mill- inqas 2 sigħat wara li ngħata mill - ħalq.
Four hours after administration, the CSF/ plasma ratio was 0.39±0.06.
Erba ’ sigħat wara li ngħata, il- livell CSF/ plażma kien ta ’ 0. 39±0. 06.
No significant accumulation of stavudine is observed with repeated administration every 6, 8, or 12 hours.
Ma dehret l- ebda akkumulazzjoni sinifikanti ta ’ stavudine meta dan ingħata kull 6, 8 jew 12- il- siegħa.
Binding of stavudine to serum proteins was negligible over the concentration range of 0.01 to 11.4 µg/ ml.
L- irbit ta ’ stavudine mal- proteini tas- serum kien negliġibbli fejn il- konċentrazzjoni kienet tvarja minn 0. 01 sa 11. 4 µg/ ml.
Stavudine distributes equally between red blood cells and plasma.
Stavudine jitqassam indaqs bejn iċ- ċelloli ħomor tad- demm u l- plażma.
Metabolism: the metabolism of stavudine has not been elucidated in humans.
Metaboliżmu: il- metaboliżmu ta ’ stavudine għadu mhux ċar fil- bniedem.
Studies in monkeys indicate that approximately 50% is excreted unchanged in the urine, most of the remainder is hydrolysed to thymine and sugar.
Studji fix- xadini wrew li bejn wieħed u ieħor 50% joħroġ fi stat mhux mibdul fl- awrina, il- biċċa l- kbira tal- bqija tiġi idrolizzata għal thymine u zokkor.
Elimination: the terminal elimination half-life is 1.3±0.2 hours after a single dose, and 1.4±0.2 hours after multiple doses, and is independent of dose.
Tindif: il- half life terminali hija ta ’ 1. 3±0. 2 siegħat wara doża waħda, u ta ’ 1. 4±0. 2 siegħat wara ħafna dożi, u mhux relatat mad- doża.
In vitro, stavudine triphosphate has an intracellular half-life of 3.5 hours in CEM T-cells (a human T-lymphoblastoid cell line) and peripheral blood mononuclear cells, supporting twice daily dosing.
In vitro, stavudine triphosphate għandu half- life intraċellulari ta ’ 3. 5 siegħa fiċ- ċelloli T CEM (razza ta ’ ċelloli ta ’ T- limfoblastojd tal- bniedem) u ċelloli tad- demm periferali li għandhom nukleju wieħed, li jsaħħaħ l- ideja li tingħata d- doża ta ’ darbtejn kuljum.
Total clearance of stavudine is 594±164 ml/ min, and renal clearance is 237±98 ml/ min, indicating active tubular secretion in addition to glomerular filtration.
Il- clearance totali ta ’ stavudine hija ta ’ 594±164 ml/ min, u l- clearance mill- kliewi hija ta ’ 237±98 ml/ min, li tindika li t- tubi ż- żgħar qegħdin jeliminaw s- sustanza b’ mod attiv, flmkien mal - filtrazzjoni fil- glomeruli.
After intravenous administration, 42±7% of dose is excreted unchanged in the urine.
Wara li tingħata mill- vini, 42±7% tad- doża titneħħa bla ma tinbidel fl - awrina.
The corresponding values after oral single and multiple dose administration are 34±5% and 40±12%, respectively.
Il- valuri korrispondenti għal doża waħda u ħafna dożi mill- ħalq huwa ta ’ 34±5% u 40±12%, rispettivament.
The remaining 60% of the drug is presumably eliminated by endogenous pathways.
Il- bqija tal- mediċina, 60%, x’ aktarx titneħħa b’ sistemi endoġeni.
The half-life of stavudine is approximately 2 hours.
Il- half- life ta ’ stavudine huwa bejn wieħed u ieħor ta ’ 2 sigħat.
Intra- and interindividual variation in
Il- farmakokinetiċi ta ’ stavudine kienu indipendenti mill- ħin, minħabba li l- proporzjon ta ’ AUC( ss) fi stat stabbli mqabbel ma ’ l - AUC( 0- t) wara l- ewwel doża kien bejn wieħed u ieħor ta ’ 1.
10 pharmacokinetic characteristics of stavudine is low, approximately 15% and 25%, respectively, after oral administration.
Il- varjazzjoni fl - istess individwu u bejn l- individwi tal- karatteristiċi farmakokinetiċi ta ’ stavudine kienet baxxa, bejn wieħed u ieħor 15% u 25%, rispettivament, wara amministrazzjoni orali.
Special Populations
Popolazzjonijiet speċjali
Adolescents, children and infants: total exposure to stavudine was comparable between adolescents, children and infants ≥ 14 days receiving the 2 mg/ kg/ day dose and adults receiving 1 mg/ kg/ day.
Adolexxenti, tfal u trabi: l- espożizzjoni totali għal stavudine kienet komparabbli bejn adolexxenti tfal u trabi ≥ 14- il ġurnata wara li ħadu d- doża ta ’ 2mg/ kg/ jum u adulti li ħadu 1 mg/ kg/ jum.
Apparent oral clearance was approximately 14 ml/ min/ kg for infants ages 5 weeks to 15 years, 12 ml/ min/ kg for infants ages 14 to 28 days, and 5 ml/ min/ kg for infants on the day of birth.
Il- clearance orali apparenti kienet ta ’ bejn wieħed u ieħor 14 ml/ min/ kg għal tfal ta ’ daqs bejn 5 ġimgħat u 15- il sena, 12 ml/ min/ kg għal trabi ta ’ bejn 14 u 28 ġurnata, u 5 ml/ min/ kg għal trabi fil- ġurnata li twieldu.
Two to three hours post-dose, CSF/ plasma ratios of stavudine ranged from 16% to 125% (mean of 59%±35%).
Sagħtejn jew tlett siegħat wara d- doża, il- proporzjon CSF/ plażma varja minn 16% sa 125% (medja ta ’ 59% ±35%).
Renal impairment: the clearance of stavudine decreases as creatinine clearance decreases; therefore, it is recommended that the dosage of Zerit be adjusted in patients with reduced renal function (see section 4.2).
Indeboliment tal- kliewi: it- tindif ta ’ stavudine jonqos kif jonqos it- tindif tal- krejatinina; għalhekk, hu irrikmandat li d- doża ta ’ Zerit tiġi mibdula f’ pazjenti li għandhom il- kliewi ma jaħdmux sew (ara sezzjoni 4. 2).
Hepatic impairment: stavudine pharmacokinetics in patients with hepatic impairment were similar to those in patients with normal hepatic function.
Indeboliment tal- fwied: il- farmakokinetiċi ta ’ stavudine f’ pazjenti b’ indeboliment tal- fwied kienu jixbħu lil dawk f’ pazjenti fejn il- fwied tagħhom kien jaħdem tajjeb.
Animal data showed embryo-foetal toxicity at very high exposure levels.
Tagħrif mill- annimali wrew effett tossiku fuq l- embrju u l- fetu meta ġew esposti għal livelli għoljin ħafna.
An ex vivo study using a term human placenta model demonstrated that stavudine reaches the foetal circulation by simple diffusion.
Studju ex vivo li sar b’ mudell tal- plaċenta tal- bniedem wera li stavudine jilħaq iċ- ċirkolazzjoni tal- fetu b' diffużjoni sempliċi.
A rat study also showed placental transfer of stavudine, with the foetal tissue concentration approximately 50% of the maternal plasma concentration.
Studju fil- firien ukoll wera trasferiment ta ’ stavudine mill- plaċenta, bil - konċentrazzjoni fil- fetu bejn wieħed u ieħor 50% ta ’ dak f’ demm l- omm.
Stavudine was genotoxic in in vitro tests in human lymphocytes possessing triphosphorylating activity (in which no no-effect level was established), in mouse fibroblasts, and in an in vivo test for chromosomal aberrations.
Stavudine wera ġenotossiċità fi studji in vitro fuq limfoċiti tal- bniedem li setgħu jagħmlu trifosforilizzazzjoni (fejn ġie stabbilit il- livell ta 'bla effett), f' ċelloli fibroblastiċi tal- ġrieden, u fi studju in vivo biex juri aberrazzjonijiet (aberrations) fil- kromożomi.
Similar effects have been observed with other nucleoside analogues.
Effetti jixxiebħu ntwerew b’ analogi oħra tan- nuklejosidi.
Stavudine was carcinogenic in mice (liver tumours) and rats (liver tumours: cholangiocellular, hepatocellular, mixed hepatocholangiocellular, and/ or vascular; and urinary bladder carcinomas) at very high exposure levels.
Stavudine kkawża kanċer fil- ġrieden (tumur tal- fwied) u firien (tumur tal- fwied: karċinomi taċ- ċelloli tat- tubi tal- marrara (cholangocellular), taċ- ċelloli tal- fwied, tat- tnejn f’ daqqa u/ jew vaskulari; u
No carcinogenicity was noted at doses of 400 mg/ kg/ day in mice and 600 mg/ kg/ day in rats, corresponding to exposures ~ 39 and 168 times the expected human exposure, respectively, suggesting an insignificant carcinogenic potential of stavudine in clinical therapy.
Ma deher l- ebda effett kanċeroġeniku f’ dożi ta 400 mg/ kg/ jum fil- ġrieden u 600 mg/ kg/ jum fil- firien, li jissarrfu f' espożizzjoni ta 'bejn wieħed u ieħor 39 u 168- il- darba akbar mill- espożizzjoni fil- bniedem, rispettivament, u dan jissuġġerixxi li l- potenzjal kanċeroġeniku ta ’ stavudine huwa insinifikanti.
Capsule contents:
Kontenuti tal- kapsula:
Lactose Magnesium stearate Microcrystalline cellulose Sodium starch glycolate
Lactose Magnesium stearate Microcrystalline cellulose Sodium starch glycolate
Gelatin Iron oxide colorant (E172) Silicon dioxide Sodium laurilsulphate Titanium dioxide (E171)
Gelatin Kulur iron oxide (E172) Silicon dioxide Sodium laurilsulphate Titanium dioxide (E171)
The capsule shells are marked using edible black printing ink containing:
Il- qoxra tal- kapsuli hija mmarkata b’ inka sewda li tista ’ tittiekel li fiha:
Shellac Propylene Glycol Purified Water
Shellac Propylene Glycol Ilma ppurifikat Potassium Hydroxide Iron Oxide (E172)
11 Potassium Hydroxide Iron Oxide (E172)
6. 2 Inkompatibilitajiet
Store in the original package.
Taħżinx f’ temperatura ’ l fuq minn 30°C Aħżen fil- pakkett oriġinali
High-density polyethylene (HDPE) bottles with child resistant screw cap (60 hard capsules per bottle), or
Fliexken tal- polyethylene ta ’ densità għolja (HDPE) b’ għatu tal- kamin li ma jinfetaħx mit- tfal (60 kapsula ibsin f’ kull flixkun), jew
aclar/ aluminum blisters with 14 hard capsules per card and 4 cards (56 hard capsules) per carton.
folji aclar/ aluminju b’ 14- il kapsula iebsa f’ kull kartuna u erba ’ kartun (56 kapsuli ibsin) f’ kull pakkett.
08 May 1996 Date of last renewal:
8 ta ’ Mejju 1996 Data ta ’ l- aħħar tiġdid:
08 June 2006
8 ta ’ Ġunju 2006
{month year}
{XX/ SSSS}
Detailed information on this product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/.
< Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta 'l- Aġenzija Ewropea dwar il - mediċini (EMEA) http: // www. emea. europa. eu /.
Zerit 20 mg hard capsule
Zerit 20 mg kapsula iebsa
Each hard capsule contains 20 mg of stavudine.
Kull kapsula iebsa fiha 20 mg ta ’ stavudine.
The hard capsule is brown, opaque and imprinted with “ BMS” over a BMS code “ 1965” on one side and “ 20” on the other side.
Il- kapsula iebsa hija kannella, opaka u għandha l- kliem “ BMS ” mixquxa fuq il- kodiċi BMS “ 1965 ” fuq naħa waħda u “ 20 ” fuq in- naħa l- oħra.
13 inappropriate, dose reduction of stavudine may be considered, while the symptoms of peripheral neuropathy are under close monitoring and satisfactory virological suppression is maintained.
14 jkunx adegwat, wieħed jista 'jikkunsidra tnaqqis fid- doża ta' stavudine, waqt li jkun hemm monitoraġġ mill- qrib tas- sintomi tan- newropatija periferali u jinżamm trażżin viroloġiku sodisfaċenti.
15 mg twice daily 20 mg twice daily
15 mg darbtejn kuljum
15 mg every 24 hours 20 mg every 24 hours
20 mg darbtejn kuljum
Treatment with NRTIs should be discontinued if there is symptomatic hyperlactatemia and metabolic/ lactic acidosis, progressive hepatomegaly, or rapidly elevating aminotransferase levels.
15 It- trattament bl- NRTIs għandu jitwaqqaf jekk ikun hemm iperlaktejtimja sintomatika u aċidożi metabolika/ lattika, fwied imkabbar, jew il- livelli ta ’ aminotransferase jogħlew bil- għaġġla.
Lactose intolerance: the hard capsule contains lactose (180 mg).
Intolleranza għal- lactose: il- kapsula iebsa fiha lactose (180 mg).
Because stavudine is not protein-bound, it is not expected to affect the pharmacokinetics of protein-bound drugs.
17 Minħabba li stavudine ma jorbotx mal- proteini, mhux mistenni li jaffetwa l- farmakokinetika tal - mediċini li jorbtu mal- proteini.
16 the same medications as given to the mother, was given to the new-born infant within 36 hours of delivery and continued for 6 weeks.
Profilassi antiretrovirali, l- istess mediċina li ngħatat lill- omm, ingħatat lit- tarbija tat- twelid mhux aktar tard minn 36 siegħa wara t- twelid u tkompliet għal 6 ġimgħat.
In combination studies of Zerit with lamivudine plus efavirenz, the frequency of peripheral neurologic symptoms was 19% (6% for moderate to severe) with a rate of discontinuation due to neuropathy of 2%.
18 Newropatija periferali: fi studji flimkien ta 'Zerit ma ’ lamivudine u efavirenz, il- frekwenza ta' sintomi ta 'newropatija periferali kienet 19% (6% kienu moderati sa gravi) b’ rata ta ’ twaqqif tat- trattament minħabba n- newropatija ta ’ 2%.
17 Immune reactivation syndrome: 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).
Sindromu ta 'reattivitazzjoni immunitarja: f' pazjenti infettati bl- HIV b' nuqqas gravi ta' immunità fiż - żmien ta 'meta tinbeda terapija ta ’ kombinazzjoni antiretrovirali (CART), jsita' jkun hemm reazzjoni ta 'infjammazzjoni fl- infezzjonijiet li ma jkunu wrew l- ebda sintomu jew li jkun għad baqa' (ara sezzjoni 4. 4).
Endocrine disorders:
19 Disturbi fis- sistema endokrinarja:
18 *Lipoatrophy was observed in a long-term follow-up study of stavudine in combination with lamivudine and efavirenz (total follow-up: median 148 weeks ranging up to 207 weeks).
* Il- lipoatrofija kienet osservata fi studju ta 'follow- up fuq medda twila ta' żmien ta 'stavudine flimkien ma' lamivudine u efavirenz (follow- up totali: minn medja 148 ġimgħa sa 207 ġimgħat).
Data on lactic acid in serum were not collected.
20 fuq l- aċidu lattiku fid- demm ma nġabarx.
The activity of stavudine is affected by multi-drug resistance associated mutations such as Q151 M.
21 L- attività ta ’ stavudine tiġi affettwata b’ mutazzjonijiet li jikkawżaw reżistenza għal ħafna mediċini bħal Q151 M.
20 The results of AI455-099 and AI455-096 are presented in the table below:
Ir- riżultati ta ’ AI455- 099 u AI455- 096 jidhru fit- tabella hawn taħt:
21 pharmacokinetic characteristics of stavudine is low, approximately 15% and 25%, respectively, after oral administration.
Il- varjazzjoni fl - istess individwu u bejn l- individwi tal- karatteristiċi farmakokinetiċi ta ’ stavudine kienet baxxa, bejn wieħed u ieħor 15% u 25%, rispettivament, wara amministrazzjoni orali.
22 Potassium Hydroxide Iron Oxide (E172)
6. 2 Inkompatibilitajiet
Zerit 30 mg hard capsule
Zerit 30 mg kapsula iebsa
Each hard capsule contains 30 mg of stavudine.
Kull kapsula iebsa fiha 30 mg ta ’ stavudine.
The hard capsule is light and dark orange, opaque and imprinted with “ BMS” over a BMS code “ 1966” on one side and “ 30” on the other side.
Il- kapsula iebsa hija oranġjo ċar u skur, opaka u għandha l- kliem “ BMS ” mixquxa fuq il- kodiċi BMS “ 1966 ” fuq naħa waħda u “ 30 ” fuq in- naħa l- oħra.
24 inappropriate, dose reduction of stavudine may be considered, while the symptoms of peripheral neuropathy are under close monitoring and satisfactory virological suppression is maintained.
26 jkunx adegwat, wieħed jista 'jikkunsidra tnaqqis fid- doża ta' stavudine, waqt li jkun hemm monitoraġġ mill- qrib tas- sintomi tan- newropatija periferali u jinżamm trażżin viroloġiku sodisfaċenti.
Treatment with NRTIs should be discontinued if there is symptomatic hyperlactatemia and metabolic/ lactic acidosis, progressive hepatomegaly, or rapidly elevating aminotransferase levels.
27 It- trattament bl- NRTIs għandu jitwaqqaf jekk ikun hemm iperlaktejtimja sintomatika u aċidożi metabolika/ lattika, fwied imkabbar, jew il- livelli ta ’ aminotransferase jogħlew bil- għaġġla.
Because stavudine is not protein-bound, it is not expected to affect the pharmacokinetics of protein-bound drugs.
29 Minħabba li stavudine ma jorbotx mal- proteini, mhux mistenni li jaffetwa l- farmakokinetika tal - mediċini li jorbtu mal- proteini.
27 the same medications as given to the mother, was given to the new-born infant within 36 hours of delivery and continued for 6 weeks.
Profilassi antiretrovirali, l- istess mediċina li ngħatat lill- omm, ingħatat lit- tarbija tat- twelid mhux aktar tard minn 36 siegħa wara t- twelid u tkompliet għal 6 ġimgħat.
In combination studies of Zerit with lamivudine plus efavirenz, the frequency of peripheral neurologic symptoms was 19% (6% for moderate to severe) with a rate of discontinuation due to neuropathy of 2%.
30 Newropatija periferali: fi studji flimkien ta 'Zerit ma ’ lamivudine u efavirenz, il- frekwenza ta' sintomi ta 'newropatija periferali kienet 19% (6% kienu moderati sa gravi) b’ rata ta ’ twaqqif tat- trattament minħabba n- newropatija ta ’ 2%.
28 Immune reactivation syndrome: 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).
Sindromu ta 'reattivitazzjoni immunitarja: f' pazjenti infettati bl- HIV b' nuqqas gravi ta' immunità fiż - żmien ta 'meta tinbeda terapija ta ’ kombinazzjoni antiretrovirali (CART), jsita' jkun hemm reazzjoni ta 'infjammazzjoni fl- infezzjonijiet li ma jkunu wrew l- ebda sintomu jew li jkun għad baqa' (ara sezzjoni 4. 4).
Endocrine disorders:
31 Disturbi fis- sistema endokrinarja:
29 *Lipoatrophy was observed in a long-term follow-up study of stavudine in combination with lamivudine and efavirenz (total follow-up: median 148 weeks ranging up to 207 weeks).
* Il- lipoatrofija kienet osservata fi studju ta 'follow- up fuq medda twila ta' żmien ta 'stavudine flimkien ma' lamivudine u efavirenz (follow- up totali: minn medja 148 ġimgħa sa 207 ġimgħat).
Data on lactic acid in serum were not collected.
32 fuq l- aċidu lattiku fid- demm ma nġabarx.
30 4.9 Overdose
4. 9 Doża eċċessiva
The activity of stavudine is affected by multi-drug resistance associated mutations such as Q151 M.
33 L- attività ta ’ stavudine tiġi affettwata b’ mutazzjonijiet li jikkawżaw reżistenza għal ħafna mediċini bħal Q151 M.
31 The results of AI455-099 and AI455-096 are presented in the table below:
Ir- riżultati ta ’ AI455- 099 u AI455- 096 jidhru fit- tabella hawn taħt:
32 pharmacokinetic characteristics of stavudine is low, approximately 15% and 25%, respectively, after oral administration.
Il- varjazzjoni fl - istess individwu u bejn l- individwi tal- karatteristiċi farmakokinetiċi ta ’ stavudine kienet baxxa, bejn wieħed u ieħor 15% u 25%, rispettivament, wara amministrazzjoni orali.
33 Potassium Hydroxide Iron Oxide (E172)
6. 2 Inkompatibilitajiet
Zerit 40 mg hard capsule
Zerit 40 mg kapsula iebsa
Each hard capsule contains 40 mg of stavudine.
Kull kapsula iebsa fiha 40 mg ta ’ stavudine.
The hard capsule is dark orange, opaque and imprinted with “ BMS” over a BMS code “ 1967” on one side and “ 40” on the other side.
Il- kapsula iebsa hija oranġjo skur, opaka u għandha l- kliem “ BMS ” mixquxa fuq il- kodiċi BMS “ 1967 ” fuq naħa waħda u “ 40 ” fuq in- naħa l- oħra.
35 inappropriate, dose reduction of stavudine may be considered, while the symptoms of peripheral neuropathy are under close monitoring and satisfactory virological suppression is maintained.
38 jkunx adegwat, wieħed jista 'jikkunsidra tnaqqis fid- doża ta' stavudine, waqt li jkun hemm monitoraġġ mill- qrib tas- sintomi tan- newropatija periferali u jinżamm trażżin viroloġiku sodisfaċenti.
Treatment with NRTIs should be discontinued if there is symptomatic hyperlactatemia and metabolic/ lactic acidosis, progressive hepatomegaly, or rapidly elevating aminotransferase levels.
39 It- trattament bl- NRTIs għandu jitwaqqaf jekk ikun hemm iperlaktejtimja sintomatika u aċidożi metabolika/ lattika, fwied imkabbar, jew il- livelli ta ’ aminotransferase jogħlew bil- għaġġla.
Lactose intolerance: the hard capsule contains lactose (240 mg).
Intolleranza għal- lactose: il- kapsula iebsa fiha lactose (240 mg).
Because stavudine is not protein-bound, it is not expected to affect the pharmacokinetics of protein-bound drugs.
41 Minħabba li stavudine ma jorbotx mal- proteini, mhux mistenni li jaffetwa l- farmakokinetika tal - mediċini li jorbtu mal- proteini.
38 the same medications as given to the mother, was given to the new-born infant within 36 hours of delivery and continued for 6 weeks.
Profilassi antiretrovirali, l- istess mediċina li ngħatat lill- omm, ingħatat lit- tarbija tat- twelid mhux aktar tard minn 36 siegħa wara t- twelid u tkompliet għal 6 ġimgħat.
In combination studies of Zerit with lamivudine plus efavirenz, the frequency of peripheral neurologic symptoms was 19% (6% for moderate to severe) with a rate of discontinuation due to neuropathy of 2%.
42 Newropatija periferali: fi studji flimkien ta 'Zerit ma ’ lamivudine u efavirenz, il- frekwenza ta' sintomi ta 'newropatija periferali kienet 19% (6% kienu moderati sa gravi) b’ rata ta ’ twaqqif tat- trattament minħabba n- newropatija ta ’ 2%.
39 Immune reactivation syndrome: 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).
Sindromu ta 'reattivitazzjoni immunitarja: f' pazjenti infettati bl- HIV b' nuqqas gravi ta' immunità fiż - żmien ta 'meta tinbeda terapija ta ’ kombinazzjoni antiretrovirali (CART), jsita' jkun hemm reazzjoni ta 'infjammazzjoni fl- infezzjonijiet li ma jkunu wrew l- ebda sintomu jew li jkun għad baqa' (ara sezzjoni 4. 4).
Endocrine disorders:
43 Disturbi fis- sistema endokrinarja:
40 *Lipoatrophy was observed in a long-term follow-up study of stavudine in combination with lamivudine and efavirenz (total follow-up: median 148 weeks ranging up to 207 weeks).
* Il- lipoatrofija kienet osservata fi studju ta 'follow- up fuq medda twila ta' żmien ta 'stavudine flimkien ma' lamivudine u efavirenz (follow- up totali: minn medja 148 ġimgħa sa 207 ġimgħat).
Data on lactic acid in serum were not collected.
44 fuq l- aċidu lattiku fid- demm ma nġabarx.
41 4.9 Overdose
4. 9 Doża eċċessiva
The activity of stavudine is affected by multi-drug resistance associated mutations such as Q151 M.
45 L- attività ta ’ stavudine tiġi affettwata b’ mutazzjonijiet li jikkawżaw reżistenza għal ħafna mediċini bħal Q151 M.
42 The results of AI455-099 and AI455-096 are presented in the table below:
Ir- riżultati ta ’ AI455- 099 u AI455- 096 jidhru fit- tabella hawn taħt:
43 pharmacokinetic characteristics of stavudine is low, approximately 15% and 25%, respectively, after oral administration.
Il- varjazzjoni fl - istess individwu u bejn l- individwi tal- karatteristiċi farmakokinetiċi ta ’ stavudine kienet baxxa, bejn wieħed u ieħor 15% u 25%, rispettivament, wara amministrazzjoni orali.
44 Potassium Hydroxide Iron Oxide (E172)
6. 2 Inkompatibilitajiet
Zerit 200 mg powder for oral solution
Zerit 200 mg trab għal soluzzjoni orali
The powder contains 200 mg of stavudine.
It- trab fih 200 mg ta ’ stavudine.
The reconstituted solution contains 1 mg of stavudine per ml.
Is- soluzzjoni rikostitwita fiha 1 mg ta 'stavudine kull ml.
Zerit powder appears as off-white to pale-pink, gritty powder.
Zerit trab li jidher bħala trab ramli, offwajt għal roża mitfi.
Zerit dosage 30 mg twice daily (every 12 hours) 40 mg twice daily (every 12 hours)
Doża ta ’ Zerit 30 mg darbtejn kuljum (kull 12- il siegħa) 40 mg darbtejn kuljum
Adolescents, children and infants: the recommended dosage is:
Adoloxxenti, tfal u trabi: id- doża rrikmandata hija:
Patient age and/ or weight From birth* to 13 days old
Età u piż tal- pazjent Minn età tat- twelid * sa 13– il ġurnata Għallinqas 14- il ġurnata u < 30 kg ≥ 30 kg
Zerit dosage 0.5 mg/ kg twice daily (every 12 hours)
Doża ta ’ Zerit 0. 5mg/ kg darbtejn kuljum (kull 12- il siegħa) 1 mg/ kg darbtejn kuljum (kull 12il siegħa) Doża ta ’ l- adulti
*The reduced posology in neonates from 0 to 13 days is based on average study data and may not correspond to invidual variation in kidney maturation.
* Id- doża inqas fit- trabi ta ’ età bejn 0 sa 13- il ġurnata hija bbażata fuq tagħrif medju minn studji u tista ’ ma tkunx taqbel ma 'varjazzjonijiet individwali fl- iżvilupp tal- kliewi.
Dosing recommendations are not available for neonates with a gestational age < 37 weeks.
M’ hemmx doża rrikmandata għal trabi għandhom jitwieldu ta ’ < 37 ġimgħa.
Zerit has not been specifically investigated in patients over the age of 65.
Zerit għadu ma ġiex studjat speċifikament f’ pazjenti fuq il- 65 sena.
Instructions for preparation, see section 6.6.
Struzzjonijiet għall- preparazzjoni, ara sezzjoni 6. 6.
In the rare cases when this is
50 Newropatija periferali: jekk jiżviluppaw is- sintomi tan- newropatija periferali (issoltu tintagħraf minn telf ta ’ sensazzjoni persistenti, tnemnim, jew uġigħ fis- saqajn u/ jew fl- idejn) (ara sezzjoni 4. 4), wieħed għandu jikkunsidra li jibdel il- kura tal- pazjent għal waħda oħra.
46 inappropriate, dose reduction of stavudine may be considered, while the symptoms of peripheral neuropathy are under close monitoring and satisfactory virological suppression is maintained.
F' dawk il- każijiet rari meta dan ma jkunx adegwat, wieħed jista 'jikkunsidra tnaqqis fid- doża ta' stavudine, waqt li jkun hemm monitoraġġ mill- qrib tas- sintomi tan- newropatija periferali u jinżamm trażżin viroloġiku sodisfaċenti.
15 mg twice daily 20 mg twice daily
15 mg darbtejn kuljum 20 mg darbtejn kuljum
15 mg every 24 hours 20 mg every 24 hours
15 mg kull 24 siegħa 20 mg kull 24 siegħa
Since urinary excretion is also a major route of elimination of stavudine in paediatric patients, the clearance of stavudine may be altered in paediatric patients with renal impairment.
Minħabba l- fatt li t - tneħħija ma ’ l- urina hija wkoll mezz prinċipali ta ’ eliminazzjoni ta ’ stavudine f’ pazjenti pedjatriċi, it- tneħħija ta ’ stavudine tista ’ tinbidel f’ pazjenti pedjatriċi li għandhom indeboliment tal- kliewi.
Although there are insufficient data to recommend a specific dosage adjustment of Zerit in this patient population, a reduction in the dose and/ or an increase in the interval between doses proportional to the reduction for adults should be considered.
Għalkemm m’ hemmx tagħrif biżżejjed biex jiġi rrikmandat aġġustament speċifiku ta ’ doża ta ’ Zerit f’ din il- popolazzjoni ta ’ pazjenti, wieħed għandu jikkonsidra li jnaqqas id - doża u/ jew itawwal l- intervall ta ’ bejn id- dożi proporzjonalment mat- tnaqqis fid- doża rrikmandat fl - adulti.
Lactic acidosis has a high mortality and may be associated with pancreatitis, liver failure, renal failure, or motor paralysis.
L- aċidożi lattika għandha rata ta 'mewt għolja u tista ’ tidher ukoll ma ’ l- infjammazzjoni tal- frixa, falliment tal- fwied, falliment tal - kliewi jew paraliżi tal- muskoli motorjali.
Treatment with NRTIs should be discontinued if there is symptomatic hyperlactatemia and metabolic/ lactic acidosis, progressive hepatomegaly, or rapidly elevating aminotransferase levels.
51 It- trattament bl- NRTIs għandu jitwaqqaf jekk ikun hemm iperlaktejtimja sintomatika u aċidożi metabolika/ lattika, fwied imkabbar, jew il- livelli ta ’ aminotransferase jogħlew bil- għaġġla.
Immune reactivation syndrome: in HIV-infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms.
Sindromu ta 'riattivitazzjoni immunitarja f' pazjenti infettati bl- HIV b' nuqqas gravi ta' immunità fiż - żmien ta 'meta tingħata t- terapija ta ’ kombinazzjoni antiretrovirali (CART), jista' jkun hemm reazzjoni ta 'infjammazzjoni mill- patoġeni opportunisti li ma jkunu wrew l- ebda sintomu jew residwi u jikkawżaw kundizzjonijiet kliniċi serji, jew aggravar tas- sintomi.
There is evidence that mitochondrial DNA toxicity may be associated with specific features of lipoatrophy in patients using stavudine.
Hemm evidenza li tossiċità mitokondrijali tad- DNA tista 'tkun assoċjata ma' karatteristiċi speċifiċi ta 'pazjenti bil- lipoatrofija li jużaw stavudine.
Osteonecrosis: although the etiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV-disease and/ or long-term exposure to combination antiretroviral therapy (CART).
Osteonekrożi: għalkemm l- etjoloġija hi kkunsidrata li għandha ħafna fatturi (inklużi l- użu ta 'sterojdi tal- kortiċi, konsum ta' alkoħol, trażżin gravi ta 'l- immunità, indiċi ta' massa tal- ġisem ogħla), każi ta 'osteonekrożi kienu rrappurtati b' mod partikulari f' pazjenti bil- marda ta' l- HIV avvanzata u/ jew b' espożizzjoni fuq medda twila għat- terapija ta ’ kombinazzjoni antiretrovirali (CART).
Diabetic patients: the reconstituted powder for oral solution contains 50 mg sucrose per ml of reconstituted solution.
Pazjenti dijabetiċi: it- trab għal soluzzjoni orali fih 50 mg sucrose kull ml tas- soluzzjoni rikostitwita.
Infants under the age of 3 months: safety data is available from clinical trials up to 6 weeks of treatment in 179 newborns and infants < 3 months of age (see section 4.6).
Tagħrif dwar is- sigurtà minn provi kliniċi fuq trattament li ħa sa 6 ġimgħat f' 179 tarbija tat- twelid u trabi < 3 xhur huwa disponibbli (ara sezzjoni 4. 6).
The main adverse events reported are haematological disorders (anaemia, neutropenia), metabolic disorders (hyperlactatemia, hyperlipasemia).
L- effetti avversi l- aktar komuni li kienu rrappurtati jinkludu mard ematoloġiku (anemija, newrotropenja), u mard metaboliku (iperlaktimja, iperlipejżemja).
48 Some late-onset neurological disorders have been reported (hypertonia, convulsion, abnormal behaviour).
Xi mard newroloġiku li deher iktar tard ġie irrappurtat (ipertonja, aċċessjoni, imġiba mhux normali).
Any child exposed in utero to nucleoside and nucleotide analogues, even HIV-negative children, should have clinical and laboratory follow-up and should be fully investigated for possible mitochondrial dysfunction in case of relevant signs or symptoms.
Kull tarbija esposta in utero għall - analogi tan- nuklejosidi u tan- nukleotidi, anke trabi li huma negattivi għall- HIV, għandhom jiġu segwiti klinikament u f’ testijiet tal- laboratorju u jridu jiġu investigati kompletament għall- possibiltà ta ’ disfunzjoni tal- mitokondrija f’ każ ta ’ sinjali jew sintomi relevanti.
These findings do not affect current national recommendations to use antiretroviral therapy in pregnant women to prevent vertical transmission of HIV.
Dan it- tagħrif m’ għandux jaffetwa r- rakkomandazzjonijiet nazzjonali kurrenti għall- użu tat- terapija antiretrovirali f’ nisa tqal għall- prevenzjoni tat- tixrid vertikali tal- marda ta ’ l- HIV.
Not recommended combinations: pancreatitis (fatal and nonfatal) and peripheral neuropathy (severe in some cases) have been reported in HIV infected patients receiving stavudine in association with hydroxyurea and didanosine.
Kombinazzjonijiet mhux rakkommandati: pankreatite (fatali u mhux fatali) u newropatija periferali (gravi f' xi każijiet) ġew irrappurtati f' xi pazjenti infettati bl- HIV li jieħdu stavudine flimkien ma 'hydroxyurea u didanosine.
Hepatotoxicity and hepatic failure resulting in death were reported during postmarketing surveillance in HIV infected patients treated with antiretroviral agents and hydroxyurea; fatal hepatic events were reported most often in patients treated with stavudine, hydroxyurea and didanosine.
Epatotossiċità u falliment tal- fwied li rriżultaw f' mewt ġew irrappurtati waqt is- sorveljanza ta 'wara l- bejgħ f' pazjenti infettati bl- HIV ikkurati b' mediċini antiretrovirali u hydroxyurea; każijiet fatali tal- fwied ġew irrappurtati kemm- il darba f' pazjenti kkurati bi stavudine, hydroxyurea u didanosine.
Because stavudine is not protein-bound, it is not expected to affect the pharmacokinetics of protein-bound drugs.
Minħabba li stavudine ma jorbotx mal- proteini, mhux mistenni li jaffetwa l- farmakokinetika tal - mediċini li jorbtu mal- proteini.
There have been no formal interaction studies with other medicinal products.
53 Ma saru l- ebda studji formali dwar l- interazzjoni ma ’ mediċini oħra.
In study AI455-094, performed in South-Africa, 362 mother-infant pairs were included in a prevention of mother-to-child-transmission study.
Fl- istudju AI455- 094, li sar fl- Afrika t' Isfel, 362 par ta 'ommijiet u wliedhom kienu inklużi fi studju ta' prevenzjoni ta 'trasmissjoni mill- omm għat- tarbija.
Treatment naive pregnant women were enrolled into the study at gestation week 34-36 and given antiretroviral treatment until delivery.
Nisa tqal li qatt ma ħadu kura ġew miktuba fl - istudju fil- ġimgħat 34- 36 tat- tqala u ngħataw kura antiretrovirali sakemm ħelsu.
Antiretroviral prophylaxis, the same medications as given to the mother, was given to the new-born infant within 36 hours of
Profilassi antiretrovirali, l- istess mediċina li ngħatat lill- omm, ingħatat lit- tarbija tat- twelid mhux aktar tard minn 36 siegħa wara t- twelid u tkompliet għal 6 ġimgħat.
In combination studies of Zerit with lamivudine plus efavirenz, the frequency of peripheral neurologic symptoms was 19% (6% for moderate to severe) with a rate of discontinuation due to neuropathy of 2%.
Fi studji ta 'kombinazzjoni ta' Zerit ma ’ lamivudine u efavirenz, il- frekwenza ta 'sintomi ta' newropatija periferali kienet 19% (6% kienu moderati sa gravi) b’ rata ta ’ twaqqif tat -
Dose-related peripheral neuropathy occurred in monotherapy trials with Zerit (see sections 4.2 and 4.4).
Kien hemm każijiet ta 'newropatija periferali relatata mad - doża fi provi bi Zerit użat waħdu (ara sezzjonijiet 4. 2 u 4. 4).
50 Immune reactivation syndrome: 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).
Sindromu ta 'riattivitazzjoni immunitarja: f' pazjenti infettati bl- HIV b' nuqqas gravi ta' immunità fiż - żmien ta 'meta tinbeda terapija ta ’ kombinazzjoni antiretrovirali (CART), jista' jkun hemm reazzjoni ta 'infjammazzjoni għal infezzjonijiet opportunistiċi li ma jkunu wrew l- ebda sintomu jew residwi (ara sezzjoni 4. 4).
Osteonecrosis: cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to combination antiretroviral therapy (CART).
Osteonekrożi: każijiet ta 'Osteonekrożi ġew irrappurtati, b' mod partikulari f' pazjenti b' fatturi ġeneralment magħrufin li huma ta ’ riskju, marda ta' l- HIV jew espożizzjoni fuq medda twila għat - terapija ta ’ kombinazzjoni antiretrovirali (CART).
Endocrine disorders:
55 Disturbi fis- sistema endokrinarja:
common: fatigue uncommon: asthenia
komuni: għejja mhux komuni: telqa gravi (asthenia)
51 *Lipoatrophy was observed in a long-term follow-up study of stavudine in combination with lamivudine and efavirenz (total follow-up: median 148 weeks ranging up to 207 weeks).
* Il- lipoatrofija kienet osservata fi studju ta 'follow- up fuq medda twila ta' żmien ta 'stavudine flimkien ma' lamivudine u efavirenz (follow- up totali: minn medja 148 ġimgħa sa 207 ġimgħat).
Data on lactic acid in serum were not collected.
56 fuq l- aċidu lattiku fid- demm ma nġabarx.
The following events have been reported spontaneously during postmarketing experience:
Dan il- mard ġie rrappurtat spontanjament wara li l- prodott inħareġ għall- bejgħ:
Not known: liver failure, hepatitis and hepatic steatosis
Mhux magħruf: falliment tal- fwied, epatite u xaħam fil- fwied
52 4.9 Overdose
4. 9 Doża eċċessiva
The activity of stavudine is affected by multi-drug resistance associated mutations such as Q151 M.
57 L- attività ta ’ stavudine tiġi affettwata b’ mutazzjonijiet li jikkawżaw reżistenza għal ħafna mediċini bħal Q151 M.
Study AI455-099 was a 48-week, randomised, double-blind study withZerit (40 mg twice daily), in combination with lamivudine (150 mg twice daily) plus efavirenz (600 mg once daily), in 391 treatment-naive patients, with a median CD4 cell count of 272 cells/ mm3 (range 61 to 1,215 cells/ mm3) and a median plasma HIV-1 RNA of 4.80 log10 copies/ ml (range 2.6 to 5.9 log 10 copies/ ml) at baseline.
Studju AI455- 099 kien studju ta ’ 48 ġimgħa, b' kampjun magħżul kif jinzerta, double blind fejn Zerit (40 mg darbtejn kuljum) flimkien ma 'lamivudine (150 mg darbtejn kuljum) kif ukoll efavirenz (600 mg darba kuljum), fi 391 pazjent li qatt ma kienu ħadu trattament qabel, b’ għadd medju ta ’ ċelloli CD4 ta ’ 272 ċellolia/ mm3 (ammont ivarja bejn 61 u 1, 215 ċelloli/ mm3) u livell medju ta ’ plażma HIV- 1 RNA ta ’ 4. 80 log10 kopji/ ml (livell ivarja bejn 2. 6 sa 5. 9 log10 kopji/ ml) fil- linja bażi.
53 The results of AI455-099 and AI455-096 are presented in the table below:
Ir- riżultati ta ’ AI455- 099 u AI455- 096 jidhru fit- tabella hawn taħt:
Only the data from the marketed formulation is presented.
Qed tiġi ppreżentata biss id- data mill- formulazzjoni li tinsab għall- bejgħ.
Intra-and interindividual variation in
Il- farmakokinetiċi ta ’ stavudine kienu indipendenti mill- ħin, minħabba li l- proporzjon ta ’ AUC( ss) fi stat stabbli mqabbel ma ’ l - AUC( 0- t) wara l- ewwel doża kien bejn wieħed u ieħor ta ’ 1.
54 pharmacokinetic characteristics of stavudine is low, approximately 15% and 25%, respectively, after oral administration.
Il- varjazzjoni fl - istess individwu u bejn l- individwi tal- karatteristiċi farmakokinetiċi ta ’ stavudine kienet baxxa, bejn wieħed u ieħor 15% u 25%, rispettivament, wara amministrazzjoni orali.
Cherry flavour Methylhydroxybenzoate (E218) Propylhydroxybenzoate (E216) Silicon dioxide Simethicone Sodium carmellose Sorbic acid Stearate emulsifiers Sucrose
Togħma taċ- ċirasa Methylhydroxybenzoate (E218) Propylhydroxybenzoate (E216) Silicon dioxide Simethicone Sodium carmellose Sorbic acid Emulsifikanti stearate Sukrose
55 After reconstitution, the prepared oral solution is stable for 30 days in a refrigerator (2°C-8°C).
Wara rikostituzzjoni, is- soluzzjoni orali ppreparata tibqa 'stabbli għal 30 ġurnata fil- friġġ (2°C- 8°C).
Do not store the dry powder above 30°C.
Taħżinx it- trab f’ temperatura ‘ l fuq minn 30°C.
After reconstitution, store in a refrigerator (2°C-8°C).
Wara rikostituzzjoni, aħżen fi friġġ (2°C- 8°C).
Keep the bottle tightly closed.
Aħżen fil- pakkett oriġinali Żomm il- flixkun magħluq sew.
HDPE bottle with child resistant screw cap, fill mark (200 ml of solution after reconstitution) and measuring cup.
Flixkun (HDPE) b’ għatu tal- kamin li ma jinfetaħx mit- tfal, b' marka sa fejn jimtela ’ (200 ml ta ’ likwidu wara t- taħlita) u tazza tad- doża.
Instructions for preparation Reconstitute with water to a 200 ml deliverable volume solution (stavudine concentration of 1 mg/ ml): add 202 ml of water to the original bottle (when the patient makes up the solution, they should be instructed to fill to the mark).
Struzzjonijiet dwar il- preparazzjoni Ħallat bl- ilma sakemm ikun hemm volum ta ’ likwidu ta ’ 200 ml (konċentrazzjoni ta 'stavudine ta' 1 mg/ ml): żid 202 ml ta 'ilma fil- flixkun oriġinali (meta l- pazjent jagħmel is- soluzzjoni, għandu jimla sal- marka).
Replace the cap.
Erġa poġġi l- għatu f’ postu.
Shake the bottle well until the powder dissolves completely.
Ħallat il- flixkun sew sakemm it- trab jinħall kompletament.
The solution appears as a colourless to slightly pink, hazy solution.
Is- soluzzjoni tidher bħala soluzzjoni bla kulur għal kemmxejn roża u ftit imċajpra.
Dispense the solution with the measuring cup provided, or for doses less than 10 ml, dispense with a syringe.
Ipprepara it- taħlita fit- tazza tad- doża pprovduta, jew għal dożi ta ’ inqas minn 10 ml, agħti l- mediċina b’ siringa.
The patient should be instructed to shake the bottle well prior to measuring each dose.
Il- pazjent għandu jiġi mgħarraf biex iħallat il- flixkun tajjeb qabbel ma jkejjel kull doża.
Disposal Any unused product or waste material should be disposed of in accordance with local requirements.
Rimi Kull fdal tal- prodott li ma jkunx intuża jew skart li jibqa 'wara l- użu tal- prodott għandu jintrema kif jitolbu l- liġijiet lokali.
56 ANNEX II
61 ANNESS II
57 A MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE
62 A DETENTUR TA ’ L- AWTORIZZAZZJONI TAL- MANIFATTURA RESPONSABBLI GĦALL- ĦRUĠ TAL- LOTT
Bristol-Myers Squibb, Champ “ Lachaud”, La Goualle, 19250 Meymac, France
Bristol- Myers Squibb, Champ “ Lachaud ”, La Goualle, 19250 Meymac, Franza
The holder of this marketing authorisation must inform the European Commission about the marketing plans for the medicinal product authorised by this decision.
Id- detentur ta ’ l- awtorizzazzjoni għat- tqegħid fis- suq għandu jinforma lill- Kummissjoni Ewropea dwar il- pjani ta 'tqegħid fis- suq għall- prodott mediċinali awtorizzat b' din id- deċiżjoni.
Periodic Safety Update Reports (PSUR’ s):
Rapporti Perjodiċi dwar Aġġornamenti fuq is- Sigurtà (PSUR’ s):
The Marketing Authorisation Holder will submit yearly PSUR’ s
Id- Detentur ta 'l- Awtorizzazzjoni tal - Manifattura se jissottometti PSURs ta' kull sena
Pharmacovigilance system The MAH must ensure that the system of pharmacovigilance, as described in version 3.0 presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and whilst the product is on the market.
Sistema ta ’ farmakoviġilanza Id- detentur ta ’ l- awtorizzazzjoni għat- tqegħid fis- suq għandu jiżgura li s- sistema ta ’ farmakoviġilanza, kif deskritta fil- verżjoni 3. 0 ippreżentata fil- Modulu 1. 8. 1 ta ’ l- Applikazzjoni għall- Awtorizzazzjoni għat- Tqegħid fis- Suq, tkun fis- seħħ u li din tkun qegħda taħdem qabel u waqt li l- prodott ikun fis- suq.
58 ANNEX III
63 ANNESS III
OUTER CARTON TEXT (BLISTER)
KITBA FUQ IL- KARTUNA TA 'BARRA (FOLJA)
Zerit 15 mg hard capsules Stavudine
Zerit 15 mg kapsuli iebsin Stavudine
Each hard capsule contains 15 mg stavudine.
Kull kapsula iebsa fiha 15 mg ta ’ stavudine.
Lactose and colorants (E171, E172)
Lactose u sustanzi koloranti (E171, E172)
56 hard capsules
56 kapsula iebsa
Oral use Read the package leaflet before use.
Użu orali Aqra il- fuljett ta ’ tagħrif qabel l- użu.
62 MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS
67 TAGĦRIF MINIMU LI GĦANDU JIDHER FUQ L- ISTRIXXI JEW FUQ IL- FOLJI
BLISTER TEXT
KITBA STAMPATA FUQ IL- FOLJI
OTHERS
OĦRAJN