qanastek/EMEA-V3 huggingface dataset:
Zerit dosage 30 mg twice daily (every 12 hours) 40 mg twice daily
Doża ta ’ Zerit 30 mg darbtejn kuljum (kull 12- il siegħa) 40 mg darbtejn kuljum
Adolescents, children and infants over the age of 3 months: the recommended dosage is:
Adoloxxenti, tfal u trabi ’ l fuq minn 3 xhur: id- doża rrikmandata hija:
Patient weight < 30 kg ≥ 30 kg
Piż tal- pazjent < 30 kg ≥ 30 kg
Zerit dosage 1 mg/ kg twice daily (every 12 hours) adult dosing
Doża ta ’ Zerit 1 mg/ kg darbtejn kuljum (kull 12il siegħa) Doża ta ’ l- adulti
For optimal absorption, Zerit should be taken on an empty stomach (i. e. at least 1 hour prior to meals) but, if this is not possible, it may be taken with a light meal.
Għall- aħjar assorbiment, Zerit għandu jittieħed fuq stonku vojt (jiġifieri mill- inqas siegħa qabel l- ikel), iżda, jekk dan mhux possibli, jista ’ jittieħed ma 'ikla ħafifa.
Zerit may also be administered by carefully opening the hard capsule and mixing the contents with food.
Zerit jista ’ wkoll jingħata bili tiftaħ il - kapsula iebsa bil- galbu u tħallat il- kontenut ma ’ l- ikel.
Infants under the age of 3 months: please refer to the Summary of Product Characteristics of the powder formulation.
Jekk jogħġbok irreferi għas- Sommarju tal- Karatterstiċi tal- Prodott tal - formulazzjoni tat- trab.
Zerit has not been specifically investigated in patients over the age of 65.
Zerit ma ġiex investigat speċifikament f’ pazjenti ’ l fuq minn 65 sena.
Dose adjustments
Aġġustar tad- doża
Peripheral neuropathy: if symptoms of peripheral neuropathy develop (usually characterised by persistent numbness, tingling, or pain in the feet and/ or hands) (see section 4.4) patients should be switched to an alternative treatment regimen, if appropriate.
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.
In the rare cases when this is
F' dawk il- każijiet rari meta dan ma
2 inappropriate, dose reduction of stavudine may be considered, while the symptoms of peripheral neuropathy are under close monitoring and satisfactory virological suppression is maintained.
2 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.
The possible benefits of a dose reduction should be balanced in each case against the risks - which may result from this measure (lower intracellular concentrations).
Il- benefiċċji possibbli ta 'tnaqqis fid- doża għandhom ikunu bbilanċjati f' kull każ kontra r- riskju - li jistgħu jirriżultaw minn din il- miżura (konċentrazzjonijiet intraċellulari aktar baxxi).
Hepatic impairment: no initial dosage adjustment is necessary.
Indeboliment fil- fwied: m’ hemm bżonn ta 'ebda aġġustament fid- doża tal- bidu.
Renal impairment: the following dosages are recommended:
Indeboliment renali: dawn huma d- dożi rrikmandati:
Zerit dosage (according to creatinine clearance)
Doża ta ’ Zerit (skond it- tneħħija ta ’ krejatinina)
Patient weight
Piż tal- pazjent
≤ 25 ml/ min (including dialysis dependence*)
≤ 25 ml/ min (tinkludi dawk dipendenti fuq id dijaliżi *)
15 mg twice daily 20 mg twice daily
20 mg darbtejn kuljum
15 mg every 24 hours 20 mg every 24 hours
20 mg kull 24 siegħa
* Patients on haemodialysis should take Zerit after the completion of haemodialysis, and at the same time on non-dialysis days.
* Pazjenti fuq emodijaliżi, għandhom jieħdu Zerit wara li jlestu mill- emodijaliżi u jżommu l- istess ħin fil- ġurnata meta ma jagħmlux emodijaliżi.
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 ukoll 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 tirrikmanda 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 rrikmandata fl - adulti.
Hypersensitivity to stavudine or to any of the excipients.
Sensittività eċċessiva għal stavudine jew għal xi sustanzi mhux attivi.
Peripheral neuropathy: patients with a history of peripheral neuropathy are at increased risk for development of neuropathy.
Newropatija periferali: pazjenti li għandhom passat ta ’ newropatija periferali għandhom riskju akbar li jiżviluppaw din in- newropatija.
If Zerit must be administered in this setting, careful clinical monitoring is essential.
Jekk wieħed għandu jagħti Zerit lil dawn il- pazjenti, huwa essenzjali li jsegwi lil dawn il- pazjenti bir- reqqa.
Symptoms of peripheral neuropathy are characterised by persistent numbness, tingling, or pain in the feet and/ or hands.
Sintomi tan- newropatija periferali jinkludu tnemnim persistenti, tagħrix, jew uġigħ fis- saqajn u/ jew fl- idejn.
Pancreatitis: patients with a history of pancreatitis had an incidence of approximately 5% on Zerit, as compared to approximately 2% in patients without such a history.
Infjammazzjon tal- frixa (Pankreatite): bejn wieħed u ieħor 5% tal- pazjenti b' passat ta ’ pankreatite li kienu qegħdin jieħdu Zerit kellhom din il- marda, meta mqabbla ma 'bejn wieħed u ieħor 2% tal - pazjenti li qatt ma bagħtew minn infjammazzjoni tal- frixa.
Patients with a high risk of pancreatitis or those receiving products known to be associated with pancreatitis should be closely followed for symptoms of this condition.
Pazjenti li għandhom riskju kbir ta ’ infjammazzjoni tal- frixa jew dawk il- pazjenti li qegħdin jieħdu mediċini li jistgħu jikkawżaw infjammazzjoni tal- frixa għandhom jiġu segwiti bir- reqqa għas- sintomi ta ’ din il- kundizzjoni.
Lactic acidosis: lactic acidosis, usually associated with hepatomegaly and hepatic steatosis has been reported with the use of nucleoside reverse transcriptase inhibitors (NRTIs).
Aċidożi lattika: aċidożi lattika, is- soltu assoċjata ma ’ tkabbir tal- fwied u xaħam fil- fwied, ġiet irrappurtata meta ntużaw in- nuklejosidi inibituri tar- reverse- transcriptase (NRTIs).
Early symptoms (symptomatic hyperlactatemia) include benign digestive symptoms (nausea, vomiting and abdominal pain), non-specific malaise, loss of appetite, weight loss, respiratory symptoms (rapid and/ or deep breathing) or neurological symptoms (including motor weakness).
Sintomi tal- bidu (iperlaktejtimja sintomatika) jinkludu sintomi mhux malinji tad- diġestjoni (dardir, remettar u wġigħ ta ’ żaqq), mard mhux speċifiku, nuqqas ta ’ aptit, tnaqqis fil- piż, sintomi tan- nifs (nifs mgħaġġel u/ jew fil - fond) jew tan- nervituri (jinkludu dgħufija tal- muskoli motorjali).
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, ħsara fil- fwied, falliment tal- kliewi jew paraliżi tal- muskoli motorjali.
Lactic acidosis generally occurred after a few or several months of treatment.
L- aċidożi lattika ġeneralment ġrat wara ftit jew ħafna xhur ta 'kura.
Treatment with NRTIs should be discontinued if there is symptomatic hyperlactatemia and metabolic/ lactic acidosis, progressive hepatomegaly, or rapidly elevating aminotransferase levels.
3 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.
Caution should be exercised when administering NRTIs to any patient (particularly obese women) with hepatomegaly, hepatitis or other known risk factors for liver disease and hepatic steatosis (including certain medicinal products and alcohol).
Wieħed għandu joqgħod attent meta jagħti NRTIs lil kwalunkwe pazjent (speċjalment nisa ħoxnin) b' epatomegalija, epatite jew fatturi oħrajn magħrufin li huma ta ’ riskju għal mard fil- fwied u xaħam fil- fwied (steatożi) (jinkludi mediċini oħrajn u alkoħol).
Patients co-infected with hepatitis C and treated with alpha interferon and ribavirin may constitute a special risk.
Pazjenti li għandhom ukoll infezzjoni bl - epatite C u qegħdin jieħdu alpha interferon u ribavirin għandhom l- akbar riskju.
Patients at increased risk should be followed closely (see also section 4.6).
Pazjenti li għandhom riskju li jkollhom din il- kundizzjoni għandhom jiġu segwiti bir- reqqa (ara wkoll sezzjoni 4. 6).
Liver disease: hepatitis or liver failure, which was fatal in some cases, has been reported.
Mard tal- fwied: ġew irrappurtati xi każi ta ’ epatite jew insuffiċjenza tal- fwied, li f’ xi każi wasslu għall- mewt.
The safety and efficacy of stavudine has not been established in patients with significant underlying liver
Is- sigurtà u l- effikaċja ta ’ stavudine għadhom ma ġewx stabbiliti f’ pazjenti li għandhom mard tal- fwied sinifikanti.
Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an increased risk of severe and potentially fatal hepatic adverse events.
Pazjenti b’ epatite kronika B jew C li qegħdin fuq terapija antiretrovirali kombinata għandhom riskju akbar ta ’ mard tal- fwied qawwi u li jista ’ jwassal għall- mewt.
In case of concomitant antiviral therapy for hepatitis B or C, please refer also to the relevant product information for these medicinal products.
F’ każi fejn qegħdin ukoll jittieħdu mediċini kontra l- virus ta ’ l- epatite B jew C, jekk jogħġbok irreferi wkoll għat - tagħrif tal- prodott għal dawn il- mediċini.
Patients with pre-existing liver dysfunction including chronic active hepatitis have an increased frequency of liver function abnormalities during combination antiretroviral therapy and should be monitored according to standard practice.
Pazjenti li diġà għandhom mard tal- fwied li jinkludi l- epatite kronika attiva għandhom rata akbar ta ’ tibdil fil- funzjoni tal- fwied waqt it- terapija antiretrovirali kombinata u għandhom jiġu segwiti kif isir normalment.
If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered.
Jekk jidher li l- funzjoni tal- fwied qegħda tmur għall- agħar f’ dawn il- pazjenti, wieħed għandu jikkonsidra li jwaqqaf jew jinterrompi t- trattament.
In the event of rapidly elevating transaminase levels (ALT/ AST, > 5 times upper limit of normal, ULN), discontinuation of Zerit and any potentially hepatotoxic medicinal products should be considered.
Jekk il- livelli tat- transaminases jogħlew malajr (ALT/ AST, > 5 darbiet in- normal ULN) għandu jiġi ikkonsidrat il- waqfien ta ’ Zerit u mediċini oħra li jistgħu jkunu epatotossiċi.
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 'reattivitazzjoni 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.
Typically, such reactions have been observed within the first few weeks or months of initiation of CART.
Tipikament, reazzjonijiet bħal dawn kienu osservati fl- ewwel ftit ġimgħat jew xhur minn meta tinbeda CART.
Relevant examples are cytomegalovirus retinitis, generalised and/ or focal mycobacterial infections, and Pneumocystis carinii pneumonia.
Eżempji relevanti huma cytomegalovirus retinitis, infezzjonijiet mikobatteritiċi ġeneralizzati u/ jew fokali, u pnewmonja Pneumocystis carinii.
Any inflammatory symptoms should be evaluated and treatment instituted when necessary.
Kull sintomu ta 'infjammazzjoni għandu jiġi mistħarreġ u għandha tingħata l - kura fejn ikun hemm il- ħtieġa.
Lipodystrophy and metabolic abnormalities: combination antiretroviral therapy has been associated with the redistribution of body fat (lipodystrophy) in HIV patients.
Lipodistrofija u tibdil fil- metaboliżmu: it- terapija antiretrovirali kombinata ġiet assoċjata ma ’ tibdil fid- distribuzzjoni tax- xaħam fil- ġisem (lipodistrofija) f’ pazjenti b’ HIV.
The long-term consequences of these events are currently unknown.
Il- konsegwenzi fit- tul ta ’ dan s’ issa għadhom mhux magħrufa.
Knowledge about the mechanism is incomplete.
It- tagħrif dwar il- mekkaniżmu li bih dan isir m’ huwiex komplet.
A connection between visceral lipomatosis and Protease Inhibitors and lipoatrophy and NRTIs has been hypothesised.
Ġiet proposta rabta bejn il- lipomatożi ta 'l- organi tal- ġisem u inibituri tal- Protease u l- lipoatrofija u l - NRTIs.
A higher risk of lipodystrophy has been associated with individual factors such as older age, and with drug related factors such as longer duration of antiretroviral treatment and associated metabolic disturbances.
Riskju ikbar ta 'lipodistrofija ġie marbut ma' fatturi bħalma huma l- anzjanità, u fatturi li għandhom x’ jaqsmu mal- mediċini bħal kura antiretrovirali li tieħu fit- tul u tibdil fil- metaboliżmu assoċjat ma ’ dan.
Clinical examination should include evaluation for physical signs of fat redistribution.
Il- pazjent għandu jkun eżaminat għal sinjali ta ’ tibdil fid- distribuzzjoni tax- xaħam.
Consideration should be given to the measurement of fasting serum lipids and blood glucose.
Wieħed għandu jikkonsidra li jkejjel il- livell tal- lipidi u tal- glucose fid- demm tal- pazjent sajjem.
Lipid disorders should be managed as clinically appropriate (see section 4.8).
It - tibdil fil- livell tal- lipidi għandu jiġi ttrattat kif inhu indikat klinikament (ara sezzjoni 4. 8).
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 'pazejnti bil- lipoatrofija li jużaw stavudine.
This should be taken into account when considering initiation of combination antiretroviral therapy with stavudine.
Wieħed għandu jqis dan meta tkun qegħda tiġi kkunsidrata li tinbeda terapija ta ’ kombinazzjoni antiretrovirali bi 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).
Osteonecrosis: 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 'osteonecrosis kienu rrapurtati b' mod partikulari f' pazjenti bil- marda ta' l- HIV avvanzata u/ jew b' espożizzjoni fuq medda twila għat- terapija ta ’ kombinazzjoni antiretrovirali (CART).
Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.
Il- pazjenti huma rrikmandati li jfittxu parir mediku jekk iħossu xi wġigħ fil- ġogi, ebusija fl- għekiesi jew diffikultà biex jiċċaqilqu.
Zerit has not been specifically investigated in patients over the age of 65.
Zerit għadu ma ġiex studjat speċifikament f’ pazjenti li għandhom aktar minn 65 sena.
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 4.8).
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. 8).
Special consideration should be given to the antiretroviral treatment history and the resistance profile of the HIV strain of the mother.
Konsiderazzjoni speċjali għandha tingħata għall- istorja tal- kura antiretrovirali u l- profil tar- reżistenza tat- tip ta ’ l- HIV ta ’ l- omm.
Mitochondrial dysfunction: nucleoside and nucleotide analogues have been demonstrated in vitro and in vivo to cause a variable degree of mitochondrial damage.
Kemm in vivo, kif ukoll in vitro, deher li l- analogi tan- nuklejosidi u tan - nukleotidi jikkaġunaw, gradi varjabbli ta ’ ħsara fil- mitokondrija.
There have been reports of mitochondrial dysfunction in HIV-negative infants exposed in utero and/ or post-natally to nucleoside analogues (see also section 4.8).
Kien hemm rapporti ta ’ disfunzjoni tal- mitonkondrija fi trabi li huma negattivi għall- HIV li kienu esposti in utero u/ jew wara t- twelid għall- analogi tan- nuklejosidi (ara wkoll sezzjoni 4. 8).
The main adverse events reported are haematological disorders (anaemia, neutropenia), metabolic disorders (hyperlactatemia, hyperlipasemia).
L- effetti avversi l- aktar komuni li kienu rrapurtati jinkludu mard ematoloġiku (anemija, newrotropenja), u mard metaboliku (iperlaktimja, iperlipejżemja).
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).
Whether the neurological disorders are transient or permanent is currently unknown.
Bħalissa għadu mhux magħruf jekk dan il - mard newroloġiku jgħaddix maż- żmien jew huwiex permanenti.
Any child exposed in utero to nucleoside and nucleotide analogues, even HIV-negative children, should
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 ir- 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 perifrali (gravi f' xi każijiet) ġew irrapurtati b' 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 ħsara fil- fwied li rriżultaw f' mewt ġew irrapurtati waqt is - sorveljanza ta 'wara l- bejgħ lil pazjenti infettati bl- HIV ikkurati b' mediċini antiretrovirali u hydroxyurea; każijiet fatali tal- fwied ġewirrapurtati kemm- il darba f' pazjenti kkurati bi stavudine, hydroxyurea u didanosine.
Hence, hydroxyurea should not be used in the treatment of HIV infection.
Għalhekk, hydroxyurea m' għandux jintuża fil- kura ta 'l- infezzjoni ta' l - HIV.
Lactose intolerance: the hard capsule contains lactose (120 mg).
Intolleranza għal- lactose: il- kapsula iebsa fiha lactose (120 mg).
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption, should not take this medicine.
Pazjenti li jbatu minn mard rari li jintiret ta ’ intolleranza għall- galactose, Lapp lactase deficiency, jew nuqqas fl- assorbiment tal- glucose - galactose, m’ għandhomx jieħdu din il- mediċina.
Interaction studies have only been performed in adults
Studji ta 'interazzjoni saru biss fuq adulti
Since stavudine is actively secreted by the renal tubules, interactions with other actively secreted medicinal products are possible, e. g. with trimethoprim.
Billi stavudine joħroġ b’ mod attiv mit- tubi renali, huwa possibbli li dan jirreaġixxi ma ’ mediċini oħrajn li joħorġu b’ mod attiv ukoll p. e. ma ’ - trimethoprim.
No clinically relevant pharmacokinetic interaction has, however, been seen with lamivudine.
Madanakollu ma dehret l- ebda interazzjoni farmakokinetika klinikament relevanti ma ’ lamivudine.
Zidovudine and stavudine are phosphorylated by the cellular enzyme (thymidine kinase), which preferentially phosphorylates zidovudine, thereby decreasing the phosphorylation of stavudine to its active triphosphate form.
Zidovudine u stavudine jiġu fosforilizzati bl- enżima ċellulari (thymidine kinase) li preferenzjalment jiffosforiliżża zidovudine, għalhekk inaqqas il- fosforilazzjoni ta ’ stavudine għall- forma attiva tiegħu triphosphate.
Zidovudine is therefore not recommended to be used in combination with stavudine.
Għalhekk zidovudine m’ huwiex irrikmandat li jintuża flimkien ma ’ stavudine.
In vitro studies indicate that the activation of stavudine is inhibited by doxorubicin and ribavirin but not by other medicinal products used in HIV infection which are similarly phosphorylated, (e. g. didanosine, zalcitabine, ganciclovir and foscarnet) therefore, coadministration of stavudine with either doxorubicin or ribavirin should be undertaken with caution.
Studji in vitro jindikaw li l- attivazzjoni ta ’ stavudine titwaqqaf minn doxorubicin u ribavirin iżda mhux b’ mediċini oħrajn li jintużaw fl- infezzjoni bl- HIV li jiġu fosforiliżżati b’ mod simili (p. e. didanosine, zalcitabine, ganciclovir u foscarnet) u għalhekk, it- tħalit ta 'stavudine ma' jew doxorubicin jew ribavirin għandu jsir b' attenzjoni.
Stavudine’ s influence on the phosphorylation kinetics of nucleoside analogues other than zidovudine has not been investigated.
Għadha ma ġietx investigata l- influwenza ta ’ stavudine fuq il - kinetiċi tal- fosforiliżżazzjoni ta ’ analogi oħra tan- nuklejosidi barra minn zidovudine.
Clinically significant interactions of stavudine or stavudine plus didanosine with nelfinavir have not been observed.
Interazzjoni klinikament sinifikanti ta ’ stavudine jew stavudine plus didanosine, ma ’ nelfinavir għadha ma ntwerietx.
Stavudine does not inhibit the major cytochrome P450 isoforms CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4; therefore, it is unlikely that clinically significant drug interactions will occur with drugs metabolised through these pathways.
Stavudine ma ’ jnaqqasx l- effett ta ’ l- iżoformi maġġuri taċ- ċitokromju P450 CYP1A2, CYP2C9, CYP2C19, CYP2D6 u CYP3A4; għalhekk, m’ huwiex probabbli li stavudine jirreaġixxi b’ mod klinikament sinifikanti ma ’ mediċini li jiġu metabolizzati b’ dawn il- metodi.
Because stavudine is not protein-bound, it is not expected to affect the pharmacokinetics of protein-bound drugs.
5 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.
Ma saru l- ebda studji formali dwar l- interazzjoni ma ’ mediċini oħra.
Zerit should not be used during pregnancy unless clearly necessary.
Zerit m' għandux jintuża waqt it- tqala sakemm mhux meħtieġ b' mod ċar.
Clinical experience in pregnant women is limited, but congenital anomalies and abortions have been reported.
L- esperjenza klinika f’ nisa tqal hija limitata, imma ġew irrappurtati anomaliji konġenitali u abort.
In study AI455-094, performed in South-Africa, 362 mother-infant pairs were included in a prevention of mother-to-child-transmission study.
Fl- istudy 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.
Antiretroviral prophylaxis,
Nisa tqal li qatt ma ħadu kura ġew miktuba fl - istudju fil- ġimgħat 34- 36 tat- tqala u ngħataw kura antiretrovirali sakemm ħelsu.
5 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 the stavudine containing arms, the neonates were treated for 6 weeks with stavudine 1 mg/ kg BID.
Fil- gruppi li ngħataw stavudine, it- trabi ngħataw stavudine 1 mg/ kg BID għal 6 ġimgħat.
The follow-up time was up to 24 weeks of age.
Iż- żmien li fih ġew segwiti kien sakemm it- trabi kellhom 24 ġimgħa.
The mother-infant pairs were randomised to receive either stavudine (N= 91), didanosine (N= 94), stavudine + didanosine (N= 88) or zidovudine (N= 89).
Il- pari omm- tarbija ġew magħżulin b' mod każwali biex jirċievu jew stavudine (N= 91), didanosine (N= 94), stavudine+didanosine (N= 88) jew zidovudine (N= 89).
95% Confidence intervals for the mother-to-child-transmission rates were 5.4-19.3% (stavudine), 5.2-18.7% (didanosine); 1.3-11.2% (stavudine + didanosine); and 1.9-12.6% for zidovudine.
Intervalli tal- kunfidenza ta '95% għar- rata ta' trasmissjoni tal- marda mill- omm għat- tarbija kienu ta '5. 4- 19. 3% (stavudine), 5. 2- 18. 7% (didanosine); 1. 3- 11. 2% (stavudine+didanosine); u 1. 9- 12. 6% għal zidovudine.
Preliminary safety data from this study (see also section 4.8), showed an increased infant mortality in the stavudine + didanosine (10%) treatment group compared to the stavudine (2%), didanosine (3%) or zidovudine (6%) groups, with a higher incidence of stillbirths in the stavudine + didanosine group.
Tagħrif preliminari tas- sigurtà minn dan l- istudju (ara wkoll sezzjoni 4. 8), wera rata ta ’ mewt tat- trabi ogħla fil- grupp tat- trattament bi stavudine+didanosine (10%) meta mqabbla mal- grupp ta ’ stavudine (2%), didanosine (3%) jew zidovudine (6%), b’ numru ikbar ta ’ trabi jitwieldu mejta fil- grupp stavudine+didanosine.
Data on lactic acid in serum were not collected in this study.
Tagħrif fuq l- aċidu lattiku fis- serum ma nġabarx f’ dan l- istudju.
However, lactic acidosis (see section 4.4), sometimes fatal, has been reported in pregnant women who received the combination of didanosine and stavudine with or without other anti-retroviral treatment.
Madanakollu, l- aċidożi lattika (ara sezzjoni 4. 4), li xi drabi twassal għall- mewt, ġiet irrappurtata f’ nisa tqal li ngħataw il- kombinazzjoni ta ’ didanosine u stavudine ma ’ jew mingħajr trattament antiretrovirali ieħor.
Embryo-foetal toxicities were seen only at high exposure levels in animals.
Effett tossiku fuq l- embriju- fetu deher biss f’ dożi għoljin fl- annimali.
Preclinical studies showed placental transfer of stavudine (see section 5.3).
Studji ta ’ qabel l- użu kliniku wrew trasferiment ta ’ stavudine mill- plaċenta (ara sezzjoni 5. 3).
Until additional data become available, Zerit should be given during pregnancy only after special consideration; there is insufficient information to recommend Zerit for prevention of mother-to-child transmission of HIV.
Sakemm ikun hemm iktar tagħrif, Zerit għandu jingħata waqt it- tqala biss wara konsiderazzjonijiet speċjali; m’ hemmx biżżejjed informazzjoni biex Zerit ikun irrikmandat għall- prevenzjoni tat- trasmissjoni tal- marda ta ’ l- HIV mill - omm għat- tarbija.
Furthermore, the combination of stavudine and didanosine should be used with caution during pregnancy and is recommended only if the potential benefit clearly outweighs the potential risk.
Aktar minn hekk, il- kombinazzjoni ta ’ stavudine u didanosine għandha tintuża b’ kawtela waqt it- tqala u hija rrikmandata biss jekk il- potenzjal tal- benefiċċju jkun akbar mill - potenzjal tar- riskju b’ mod ċar.
It is recommended that HIV infected women should not breast-feed under any circumstances in order to avoid transmission of HIV.
Huwa rrikmandat li nisa li huma nfettati bl- HIV m’ għandhom ireddgħu taħt l- ebda ċirkostanza biex ma tkomplix tinxtered il- marda ta ’ l- HIV.
The data available on stavudine excretion into human breast milk are insufficient to assess the risk to the infant.
It- tagħrif li hemm fuq it- trasferiment ta ’ stavudine fil- ħalib tal- bniedem m’ huwiex biżżejjed biex wieħed jista ’ jkejjel ir- riskju għat- tarbija.
Studies in lactating rats showed that stavudine is excreted in breast milk.
Studji fil- firien ireddgħu wrew li stavudine joħroġ fil- ħalib tas- sider.
Therefore, mothers should be instructed to discontinue breast-feeding prior to receiving Zerit.
Għalhekk, l- ommijiet għandhom jiġu mgħallma biex iwaqqfu t- treddigħ qabel ma jibdew jieħdu Zerit.
Based on the pharmacodynamic properties of stavudine it is unlikely that Zerit affects the ability to drive or operate machinery.
Mill- karatteristiċi farmakodinamiċi ta ’ stavudine mhux probabbli li Zerit għandu effett fuq il- ħila biex issuq jew tħaddem magni.
Adults: extensive safety experience is available for Zerit used as monotherapy and in combination regimens.
Esperjenza fuq is- sigurtà hija disponibbli għal- formulazzjonijiet ta ’ Zerit wżat waħdu jew f’ terapija ta ’ kombinazzjoni.
Many of the serious undesirable effects with stavudine were consistent with the course of HIV infection or with the side effects of concomitant therapies.
Ħafna mill- effetti mħux mixtieqa serji li ġraw bi stavudine kellhom x’ jaqsmu ma ’ l- andament ta ’ l- infezzjoni b’ HIV jew b’ effetti mhux mixtieqa ta ’ mediċini oħra li kienu qegħdin jingħataw fl- istess ħin.
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%.
6 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%.
Dose-related peripheral neuropathy occurred in monotherapy trials with Zerit (see sections 4.2 and 4.4).
Kien hemm każijiet ta 'newropatija perifrali li għandha x’ taqsam mad- doża fi provi bi Zerit użat waħdu (ara sezzjonijiet 4. 2 u 4. 4).
The patients usually experienced resolution of symptoms after dose reduction or interruption.
Il- pazjenti s- soltu ħassew li għaddewlhom is- sintomi wara li tnaqqset id- doża jew twaqqaf il- kors.
Pancreatitis: pancreatitis, occasionally fatal, has been reported in up to 2-3% of patients enrolled in monotherapy clinical studies (see section 4.4).
Infjammazzjoni tal- frixa: infjammazzjoni tal- frixa, li xi kultant wasslet għall- mewt, ġiet irrappurtata f’ sa 2- 3% tal- pazjenti li ġew miktuba fi studji kliniċi ta ’ pazjenti li ngħataw Zerit waħdu (ara sezzjoni 4. 4).
Pancreatitis was reported in < 1% of patients in combination therapy studies with Zerit.
Ġiet irrapportata pankreatite f '< 1% tal- pazjenti fi studji ta' terapija ta ’ kombinazzjoni bi Zerit.
Lactic acidosis: cases of lactic acidosis, sometimes fatal, usually associated with severe hepatomegaly and hepatic steatosis, have been reported with the use of nucleoside analogues (see section 4.4).
Aċidożi lattika: każi ta ’ aċidożi lattika, li xi kultant wasslet għall- mewt, is- soltu assoċjata ma ’ tkabbir gravi tal- fwied u xaħam fil- fwied ġew irrappurtati meta ntużaw l- analogi tan- nuklejosidi (ara sezzjoni 4. 4).
Hepatitis or liver failure, which was fatal in some cases, has been reported with the use of stavudine and with other nucleoside analogues (see section 4.4).
Epatite jew insuffiċjenza tal- fwied, li f’ xi każi wasslu għall- mewt, ġew irrappurtati meta ntuża stavudine u analogi tan- nuklejosidi oħrajn (ara sezzjoni 4. 4).
6 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).
Lipodystrophy and metabolic abnormalities: combination antiretroviral therapy has been associated with redistribution of body fat (lipodystrophy) in HIV patients including the loss of peripheral and facial subcutaneous fat, increased intra-abdominal and visceral fat, breast hypertrophy and dorsocervical fat accumulation (buffalo hump).
Lipodistrofija u tibdil fil- metaboliżmu: it- terapija ta ’ kombinazzjoni antiretrovirali ġiet assoċjata ma ’ tibdil fid- distribuzzjoni tax- xaħam fil- ġisem (lipodistrofija) f’ pazjenti b’ HIV, li jinkludi telf ta 'xaħam ta ’ taħt il- ġilda periferali u tal- wiċċ, żieda fix- xaħam ta ’ ġoż- żaqq u madwar l- organi, żvilupp żejjed tas- sider u żieda ta ’ xaħam wara l- għonq (buffalo hump).
Combination antiretroviral therapy has been associated with metabolic abnormalities such as hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperglycaemia and hyperlactataemia (see section 4.4).
It- terapija antiretrovirali f’ kombinazzjoni ġiet assoċjata ma ’ tibdil fil- metaboliżmu bħal żieda tat - trigliċeridi fid- demm, żieda tal- kolesterol fid- demm, reżistenza għall- insulina, żieda tal- glucose fid - demm u żieda ta ’ aċidu lattiku fid- demm (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).
Osteonecrosis: każijiet ta 'osteonecrosis ġew irrapurtati, 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).
The frequency of this is unknown (see section 4.4).
Mhix magħrufa l- frekwenza ta 'dan (ara sezzjoni 4. 4).
The frequency of adverse reactions listed below is defined using the following convention: very common (≥ 1/ 10); common (≥ 1/ 100, < 1/ 10); uncommon (≥ 1/ 1,000, < 1/ 100); rare (≥ 1/ 10,000, < 1/ 1,000); very rare (< 1/ 10,000).
Il- frekwenza ta ’ reazzjonijiet avversi fil- lista li jmiss ġiet definita b’ dan il- mod: komuni ħafna (≥ 1/ 10); komuni (≥ 1/ 100, < 1/ 10); mhux komuni (≥ 1/ 1, 000, < 1/ 100); rari (≥ 1/ 10, 000, < 1/ 1, 000); rari ħafna (< 1/ 10, 000).
Undesirable effects (moderate to severe) were reported from 467 patients treated with Zerit in combination with lamivudine and efavirenz in two randomised clinical trials and an ongoing long-term follow-up study (total follow-up: median 56 weeks ranging up to 119 weeks).
Effetti mhux mixtieqa (moderati sa gravi) ġew irrappurtati f’ 467 pazjent li ħadu Zerit fil- forma li jintreħa mill- ewwel f’ kombinazzjoni ma 'lamivudine u efavirenz f’ żewġ studji kliniċi li saru b' mod każwali u fi studju li għadu għaddej fejn il- pazjenti ġew segwiti fit- tul (b’ kollox, bħala medja, il - pazjenti ġew segwiti għal punt medjan ta ’ 56 ġimgħa u l- iktar sa 119- il ġimgħa).
The following undesirable effects considered possibly related to study regimen based on investigators’ attribution, have been identified:
Dawn l- effeti mhux mixtieqa ġew identifikati mill- investigaturi bħala dawk li possibilment għandhom x’ jaqsmu mal- kura waqt l- istudju:
Endocrine disorders:
7 Disturbi fis- sistema endokrinarja:
uncommon: gynaecomastia
mhux komuni: tkabbir tas- sider fl- irġiel
common: diarrhoea, abdominal pain, nausea, dyspepsia uncommon: pancreatitis, vomiting
komuni: dijarrea, uġigħ addominali, nawsja, ħruq ta ’ stonku mhux komuni: pankreatite, remettar
common: fatigue uncommon: asthenia
komuni: għejja khux komuni: telqa gravi (asthenia)
Hepatobiliary disorders:
Disturbi fil- kliewi u fis- sistema urinarja:
uncommon: hepatitis or jaundice
mhux komuni: epatite u suffejra
common: lipoatrophy, * lipodystrophy uncommon: lactic acidosis (in some cases involving motor weakness), anorexia
komuni: lipoatrofija, * lipodistrofija mhux komuni: aċidożi lattika (f’ xi każi tinvolvi wkoll dgħufija tal - muskoli), anoreksja
Musculoskeletal and connective tissue disorders:
Disturbi muskolu- skeltrali u tal - connective tissueu ta ’ l- għadam
uncommon: arthralgia, myalgia
mhux komuni: uġigħ fil- ġogi, uġigħ fil- muskoli
common: peripheral neurologic symptoms including peripheral neuropathy, paresthesia, and peripheral neuritis; dizziness; abnormal dreams; headache, insomnia; abnormal thinking; somnolence
komuni: sintomi tan- nervituri periferali li jinkludu newropatija, tnemnim u infjammazzjoni tan- nervituri; sturdament; ħolm mhux tas- soltu; uġigħ ta ’ ras; nuqqas ta ’ rqad; ħsieb mhux tas- soltu; rqad
common: depression uncommon: anxiety, emotional lability
komuni: dipressjoni mhux komuni: ansjetà, emozzjonijiet mhux tas- soltu
Skin and subcutaneous tissue disorders:
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
common: rash, pruritus uncommon: urticaria
komuni: raxx, ħakk mhux komuni: urtikarja
7 *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).
Discontinuation due to undesirable events was 7% for the patients treated with Zerit.
7% tal- pazjenti li ħadu Zerit li intreħa mill- ewwel waqqfu t- trattament minħabba effetti mhux mixtieqa.
Laboratory abnormalities reported in these two trials and an ongoing follow-up study included elevations of ALT (> 5 x ULN) in 3%, of AST (> 5 x ULN) in 3%, of lipase (≥ 2.1 ULN) in 3% of the patients in the Zerit group.
Riżultati anormali tat- testijiet fil- laboratorju ġew rrappurtati f’ dawn iż- żewġ studji u fi studju fit- tul li għadu għaddej u dan jinkludi livell ogħla ta ’ ALT (> 5 x l- ogħla livell normali) fi 3%, ta ’ AST (> 5 x l- ogħla livell normali) fi 3%, ta ’ lipase (≥ 2. 1 x l- ogħla livell normali).
Neutropenia (< 750 cells/ mm3) was reported in 5%, thrombocytopenia (platelets < 50,000/ mm3) in 2%, and low haemoglobin (< 8 g/ dl) in < 1% of patients receiving Zerit.
Newtropenja (< 750 ċelloli/ mm3) ġie rrappurtat f ’ 5%, tromboċitopenja (plejtlets] < 50, 000/ mm3) fi 2% u emoglobina baxxa (< 8 g/ dl) f’ 1% tal- pazjenti fuq Zerit.
Macrocytosis was not evaluated in these trials, but was found to be associated with Zerit in an earlier trial (MCV > 112 fl occurred in 30% of patients treated with Zerit).
Makroċitożi ma ġietx evalwata f’ dawn l- istudji, imma nstab li hi assoċjata ma ’ Zerit fi prova li saret aktar kmieni (MCV > 112 fl dehret fi 30% tal- pazjenti li ħadu Zerit.
Adolescents, children and infants: undesirable effects and serious laboratory abnormalities reported to occur in paediatric patients ranging in age from birth through adolescence who received stavudine in clinical studies were generally similar in type and frequency to those seen in adults.
Adolexxenti, tfal u trabi: effetti mhux mixtieqa u testijiet tal- laboratorju mhux normali serji ġew irrapportati f’ pazjenti tfal li kellhom età li tvarja mit- twelid sa l- adolexxenza li ħadu stavudine fi studji kliniċi u dawn ġeneralment kienu jixbħu lil dawk li seħħew fl- adulti kemm fil- kwalità kif ukoll fil - kwantità.
However, clinically significant peripheral neuropathy is less frequent.
Iżda n- newropatija periferali fuq skala klinikament sinifikanti hija inqas komuni.
These studies include ACTG 240, where 105 paediatric patients ages 3 months to 6 years received Zerit 2 mg/ kg/ day for a median of 6.4 months; a controlled clinical trial where 185 newborns received Zerit 2 mg/ kg/ day either alone or in combination with didanosine from birth through 6 weeks of age; and a clinical trial where 8 newborns received Zerit 2 mg/ kg/ day in combination with didanosine and nelfinavir from birth through 4 weeks of age.
Dawn l - istudji jinkludu ACTG 240, fejn 105 pazjenti pedjatriċi bl- età tvarja minn 3 xhur għal 6 snin ngħataw Zerit 2 mg/ kg/ jum għal medja ta ’ 6. 4 xhur; studju kliniku kkontrollat fejn 185 tarbija tat- twelid ingħataw Zerit 2 mg/ kg/ jum waħdu jew ma ’ didanosine mit- twelid sakemm kellhom 6 ġimgħat; u studju kliniku fejn 8 trabi tat- twelid ingħataw Zerit 2 mg/ kg/ jum b’ kombinazzjoni ma ’ didanosine u nelfinavir mit- twelid sakemm kellhom 4 ġimgħat.
In study AI455-094 (see also section 4.6), the safety follow-up period was restricted to only six months, which may be insufficient to capture long-term data on neurological adverse events and mitochondrial toxicity.
Fi studju AI455- 094 (ara wkoll sezzjoni 4. 6), iż- żmien li ġiet segwita s- sigurtà tal- mediċina kien biss ta ’ sitt xhur, li jista ’ ma jkunx biżżejjed biex wieħed jiġbor tagħrif fit- tul fuq effetti avversi newroloġiċi u fuq effett tossiku fuq il- mitokondrija.
Relevant grade 3-4 laboratory abnormalities in the 91 stavudine treated infants were low neutrophils in 7%, low hemoglobin in 1%, ALT increase in 1% and no lipase abnormality.
Tagħrif
Data on lactic acid in serum were not collected.
8 fuq l- aċidu lattiku fid- demm ma nġabarx.
No notable differences in the frequency of adverse drug reactions were seen between treatment groups.
Ma deher li kien hemm l- ebda differenza sinifikanti fl- effetti mhux mixtieqa bejn iż- żewġ gruppi tat- trattament.
There was, however, an increased infant mortality in the stavudine + didanosine (10%) treatment group compared to the stavudine (2%), didanosine (3%) or zidovudine (6%) groups, with a higher incidence of stillbirths in the stavudine + didanosine group.
Kien hemm rata ogħla ta 'mewt tat- trabi fil- grupp stavudine+didanosine (10%) meta mqabbla mal- gruppi ta ’ stavudine (2%), didanosine (3%), jew zidovudine (6%), b’ ammont ogħla ta ’ trabi jitwieldu mejta fil- grupp stavudine+didanosine.
Postmarketing
Studji ta ’ wara l- bejgħ
The following events have been reported spontaneously during postmarketing experience:
Dan il- mard ġie rrappurt spontanjament wara li l- prodott inħareġ għall- bejgħ:
Not known: thrombocytopenia
Mhux magħruf: tromboċitopenja
Metabolic and nutrition disorders:
Disturbi fil- metaboliżmu u n - nutrizzjoni:
Common: asymptomatic hyperlactatemia, Not known: lactic acidosis
Komuni: iperlaktejtimja mhuxsintomatika, Mhux magħruf: aċidożi lattika
Hepatobiliary disorders:
Distubi fil- fwied u fil- marrara:
Not known: liver failure, hepatitis and hepatic steatosis
Mhux magħruf: ħsara fil- fwied, epatite u xaħam fil- fwied
Not known: motor weakness (most often reported in the setting of symptomatic hyperlactatemia or lactic acidosis syndrome)
Mhux magħruf: dgħufija tal- muskoli motorjali (dan ħafna drabi ġie rrappurtat meta kien hemm iperlaktejtimja sintomatika jew aċidożi lattika)
Mitochondrial dysfunction: review of the postmarketing safety database shows that adverse events indicative of mitochondrial dysfunction have been reported in the neonate and infant population exposed to one or more nucleoside analogues (see also section 4.4).
Mitokondriji ma jaħdmux: ħarsa lejn l- infomazzjoni kollha fuq is- sigurtà tal- mediċina li nġabret wara l- bejgħ, turi li effetti avversi li juru li l- mitokondriji ma jaħdmux sew, ġew irrappurtati fi trabi tat- twelid u trabi taħt is- sentejn li ġew esposti għal wieħed jew ħafna analogi tan- nuklejosidi (ara wkoll sezzjoni 4. 4).
The HIV status for the newborns and infants ≤ 3 months of age was negative, for older infants it tended to be positive.
L- istat ta ’ l- HIV fit- trabi tat- twelid u trabi ≤ 3 xhur fl- età kien wieħed negattiv, għat- trabi akbar minn hekk l- istat kellu tendenza jkun pożittiv.
The profile of the adverse events for newborns and infants ≤ 3 months of age showed increases in lactic acid levels, neutropenia, anaemia, thrombocytopenia, hepatic transaminase increases and increased lipids, including hypertriglyceridaemia.
Il- profil ta ’ l- effetti avversi fit- trabi tat - twelid u trabi ≤ 3 xhur wera żieda fil- livell ta ’ l- aċidu lattiku, newtropenja, anemja, tromboċitopenja, livell ogħla tat- transaminases u żieda fil- livell tax- xaħam fid- demm, li jinkludi livell ogħla ta 'trigliċeridi.
The number of reports in older infants was too small to identify a pattern.
In- numru tar- rapporti fi trabi akbar kien żgħir wisq biex wieħed ikun jista ’ jidentifika stampa ċara.
Experience in adults treated with up to 12 times the recommended daily dosage revealed no acute toxicity.
L- esperjenza f’ adulti li ħadu sa 12- il darba d- doża rrikmandata ta ’ kuljum ma wriet l- ebda effett tossiku akut.
Complications of chronic overdosage could include peripheral neuropathy and hepatic dysfunction.
Kumplikazzjonijiet li jidhru meta doża eċċessiva tittieħed fit- tul jistgħu jinkludu newropatija periferali u fwied ma jaħdimx tajjeb.
The mean haemodialysis clearance of stavudine is 120 ml/ min.
Il- clearance medju ta ’ stavudine bl- emodijaliżi huwa ta ’ 120 ml/ min.
The contribution of this to the total elimination in an overdose situation is unknown.
L- ammont li dan jikkontribwixxi għall- eliminazzjoni kollha f’ sitwazzjoni fejn tittieħed doża eċċessiva mhux magħruf.
It is not known whether stavudine is removed by peritoneal dialysis.
Mhux magħruf jekk stavudine titneħħiex b ’ - dijaliżi tal- peritonew.
Nucleoside reverse transcriptase inhibitor, ATC code:
Inibitur nuklejosida tar- reverse transcriptase, Kodiċi ATC:
Stavudine, a thymidine analogue, is an antiviral agent with in vitro activity against HIV in human cells.
Stavudine, li huwa analogu tat- thymidine, huwa mediċina kontra l- virus b’ attività in vitro kontra l- HIV fiċ- ċelloli tal- bniedem.
It is phosphorylated by cellular kinases to stavudine triphosphate which inhibits HIV reverse transcriptase by competing with the natural substrate, thymidine triphosphate.
Jiġi fosforilizzat b’ kinasi taċ- ċelluli għal stavudine triphosphate li jwaqqaf ir - reverse transcriptase ta ’ HIV billi jikkompeti mal- molekula li jaħdem fuqha s- soltu, thymidine triphospate.
It also inhibits viral DNA synthesis by causing DNA chain termination due to a lack of the 3’ -hydroxyl group necessary for DNA elongation.
Jinibixxi wkoll is- sinteżi tad- DNA mill- virus billi jagħmel terminazzjoni tal- katina tad - DNA minħabba nuqqas tal- grupp 3 ’ - idroxil li hemm bżonn biex id- DNA jittawwal.
Cellular DNA polymerase γ is also sensitive to inhibition by stavudine triphosphate, while cellular polymerases α and β are inhibited at concentrations 4,000-fold and 40-fold higher, respectively, than that needed to inhibit HIV reverse transcriptase.
Il- polymerase γ tad- DNA fiċ- ċelloli jnaqqas l- attivitΰ tiegħu b’ stavudine triphospate, waqt li l- attivitΰ tal- polymerase α u β ta ’ ġoċ- ċelloli titnaqqas b’ konċentrazzjonijiet 4, 000 u 40 darba ogħla rispettivament minn dik li hi meħtieġa biex ttinaqqas l- attività tar- reverse - transcriptase ta ’ l- HIV.
Stavudine treatment can select for and/ or maintain mutations associated with zidovudine resistance.
Il- kura b’ stavudine jista ’ tagħżel u/ jew iżomm mutazzjonijiet li huma assoċjati ma ’ resistenza għal zidovudine.
Isolates containing these mutations remain sensitive to stavudine.
Ċelluli iżolati li għandhom dawn il- mutazzjonijiet jibqgħu sensittivi għal stavudine.
The clinical relevance of these findings is unknown.
L - importanza klinika ta ’ dan mhix magħrufa.
The activity of stavudine is affected by multi-drug resistance associated mutations such as Q151 M.
9 L- attività ta ’ stavudine tiġi affettwata b’ mutazzjonijiet li jikkawżaw reżistenza għal ħafna mediċini bħal Q151 M.