qanastek/EMEA-V3 huggingface dataset:
The active substance in Lysodren, mitotane, is thought to work by preventing cells in the adrenal gland from working properly, by damaging their mitochondria (the energy-producing components), reducing the production of some steroid hormones.
Is- sustanza attiva f’ Lysodren, mitotane, hija maħsuba li taħdem billi timpedixxi liċ- ċelloli fil- glandola adrenali milli jaħdmu sewwa, billi tagħmel ħsara lill- mitokondrija tagħhom (il- komponenti li jipproduċu l- enerġija), biex hekk tnaqqas il- produzzjoni ta ’ xi ormoni tal- isterojdi.
It may also alter the breakdown of these hormones.
Hija tista ’ tibdel ukoll it- tkissir ta ’ dawn l - ormoni.
Together, these effects reduce the levels of the hormones in the body, improving the symptoms of the disease.
Flimkien, dawn l- effetti jnaqqsu l- livelli tal- ormoni fil- ġisem, li jwassal għal titjib fis- sintomi tal- marda.
How has Lysodren been studied?
Kif ġie studjat Lysodren?
Since the active substance in Lysodren, mitotane, is a well-established medicine that has been used in the treatment of adrenal cortical carcinoma in Europe since 1959, the company presented information from the published literature to support its application for Lysodren.
Peress li s- sustanza attiva f’ Lysodren, mitotane, hija mediċina stabbilita sewwa li ilha tintuża fit - trattament ta ’ karċinoma tal- kortiċi adrenali fl- Ewropa mill- 1959, il- kumpanija ppreżentat informazzjoni mil- letteratura ppubblikata biex issostni l- applikazzjoni tagħha għal Lysodren.
It presented the results of 220 studies published since 1990 on the use of the medicine in unresectable, metastatic adrenal cortical carcinoma.
Hija ppreżentat ir- riżultati ta ’ 220 studju ppubblikati mill- 1990 ’ l hawn dwar l- użu ta ’ din il- mediċina f’ karċinoma metastatika, li ma tistax titneħħa b’ intervent kirurġiku, tal- kortiċi adrenali.
The studies included over 500 adults and children, who were treated for various lengths of time with mitotane, either alone or in combination with other anticancer medicines.
L- istudji kienu jinkludu ’ l fuq minn 500 adult u tfal, li ġew ikkurati għal diversi tulijiet ta ’ żmien b’ mitotane, jew waħdu jew flimkien ma ’ mediċini oħra kontra l- kanċer.
The main measures of effectiveness in the studies included survival time, the reduction in tumour size and the time spent free of the symptoms of the disease.
Il- kejl prinċipali tal- effikaċja fl- istudji kien jinkludi ż- żmien ta ’ sopravivenza, it- tnaqqis fid- daqs tat- tumur u ż- żmien mingħajr is- sintomi tal - marda.
What benefit has Lysodren shown during the studies?
X’ benefiċċju wera Lysodren waqt l- istudji?
Overall, the studies suggested that Lysodren could provide a benefit in patients with advanced adrenal cortical carcinoma, by increasing survival times (by over five years in a few cases) and causing shrinkage or stabilisation of tumour size in 20 to 30% of patients.
B’ mod ġenerali, l- istudji ssuġġerew li Lysodren seta ’ jipprovdi benefiċċju f’ pazjenti b’ karċinoma avanzata tal- kortiċi adrenali, billi żied iż- żminijiet ta ’ sopravivenza (b’ aktar minn ħames snin fi ftit każijiet) u billi kkawża t- tnixxif jew l- istabbilizzazzjoni tad- daqs tat- tumur f’ 20 sa 30% tal- pazjenti.
It also reduced the symptoms of the disease, particularly in patients whose cancer was producing high hormone levels.
Huwa naqqas ukoll is- sintomi tal- marda, b’ mod partikolari f’ pazjenti li l- kanċer tagħhom kien qed jipproduċi livelli għoljin ta ’ ormoni.
There was insufficient evidence to support its use as an add-on to other anticancer medicines.
Ma kienx hemm evidenza biżżejjed biex issostni l- użu tiegħu bħala żieda għal mediċini oħra kontra l- kanċer.
Limited information was available on the use of mitotane in children, but overall, the children remained disease free for an average of seven months when taking the medicine.
Kienet disponibbli informazzjoni limitata dwar l- użu ta ’ mitotane fit- tfal, iżda b’ mod globali, it- tfal baqgħu ħielsa mill- marda għal medja ta ’ seba ’ xhur meta ħadu l- mediċina.
What is the risk associated with Lysodren?
X’ inhu r- riskju assoċjat ma ’ Lysodren?
The most common side effects with Lysodren (seen in more than 1 patient in 10) are increased blood levels of liver enzymes, cholesterol and triglycerides (a type of fat), leucopenia (low white blood cell counts), prolonged bleeding time, ataxia (difficulty co-ordinating movements), paraesthesia (abnormal sensations like pins and needles), vertigo (a spinning sensation), sleepiness, mucositis (inflammation of the mucous membranes, such as the lining of the mouth), vomiting, diarrhoea, nausea (feeling sick), epigastric discomfort (discomfort around the stomach), skin rash, myasthenia (muscle weakness), adrenal insufficiency (reduced adrenal gland activity), anorexia (loss of appetite), asthenia (weakness), gynaecomastia (breast enlargement) and confusion.
L- aktar effetti sekondarji komuni b’ Lysodren (dehru f’ aktar minn 1 minn kull 10 pazjenti) huma żjieda fl- enzimi tal- fwied, kolesterol, u trigliċeridi (tip ta ’ xaħam) fid- demm, lewkopenija (livelli baxxi ta ’ ċelloli bojod tad- demm), ħin itwal ta ’ fsada, atassja (diffikultà biex tikkoordina l- movimenti), konfużjoni, mijastenja (dgħjufija fil- muskoli), parasteżija (sensazzjonijiet abnormali bħal tingiż), vertiġini (sens ta 'tidwir), ngħas, mukożite (infjammazzjoni tal- membrani mukużi, bħal tar- rita tal - ħalq), remettar, dijarrea, nawsja (sensazzjoni ta ’ dardir), skonfort epigastriku (diqa madwar l- istonku), raxx tal- ġilda, mijastenija (dgħjufija fil- muskoli), nuqqas ta ’ adrenalina (tnaqqis ta ’ attività tal - glandola tal- adrenalina), anorressija (telf tal- aptit), astenija (dgħufija), ġinekomastija (tkabbir tas- sider) u konfużjoni.
For the full list of all side effects reported with Lysodren, see the Package Leaflet.
Għal- lista kompleta tal- effetti sekondarji kollha rrappurtati b’ Lysodren, ara l- Fuljett ta ’ Tagħrif.
Lysodren should not be used in people who may be hypersensitive (allergic) to mitotane or any of the other ingredients.
Lysodren m’ għandux jintuża f’ nies li jistgħu jkunu sensittivi żżejjed (allerġiċi) għal mitotane jew għal xi sustanzi oħra.
It must not be used in patients who are breast-feeding or who are taking spironolactone (a diuretic or ‘ water tablet’).
M’ għandux jintuża f’ pazjenti li jkunu qegħdin ireddgħu jew li jkunu qegħdin jieħdu spironolactone (dijuretiku jew ‘ pillola tal- ilma ’).
Why has Lysodren been approved?
Għaliex ġie approvat Lysodren?
The Committee for Medicinal Products for Human Use (CHMP) decided that Lysodren’ s benefits are greater than its risks for the treatment of advanced adrenal cortical carcinoma, but noted that the effect of Lysodren has not been established in adrenal cortical carcinoma that is not producing high levels of steroid hormones.
Il- Kumitat għall- Prodotti Mediċinali għall- Użu mill- Bniedem (CHMP) iddeċieda li l- benefiċċji ta ’ Lysodren huma akbar mir- riskji tiegħu għat- trattament ta ’ karċinoma avanzata tal- kortiċi adrenali, iżda nnota li l- effett ta ’ Lysodren ma ġiex stabbilit f’ karċinoma tal- kortiċi adrenali li ma tkunx qiegħda
The Committee recommended that Lysodren be given marketing authorisation.
2/ 3 tipproduċi livelli għoljin ta ’ ormoni tal- isterojdi.
Other information about Lysodren:
Tagħrif ieħor dwar Lysodren:
The European Commission granted a marketing authorisation valid throughout the European Union for Lysodren to Laboratoire HRA Pharma on 28 April 2004.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fis- suq valida madwar l- Unjoni Ewropea kollha għal Lysodren lil Laboratoire HRA Pharma fil- 28 ta ’ April 2004.
The marketing authorisation was renewed on 28 April 2009.
L- awtorizzazzjoni għat - tqegħid fis- suq iġġeddet fit- 28 ta ’ April 2009.
2/ 3 The summary of opinion of the Committee for Orphan Medicinal Products for Lysodren is available here.
Is- sommarju tal- opinjoni tal- Kumitat dwar Prodotti Mediċinali Orfni għal Lysodren jista ’ jinstab hawn.
The full EPAR for Lysodren can be found here.
L- EPAR sħiħ għal Lysodren jista ’ jiġi kkonsultat hawn.
This summary was last updated in 04-2009.
Dan is- sommarju kien aġġornat l- aħħar f’ 04- 2009.
Lysodren 500 mg tablets
Lysodren 500 mg pillola
Each tablet contains 500 mg of mitotane.
Kull pillola fiha 500 mg ta ’ mitotane
White, biconvex, round, scored tablets.
Pilloli bojod, ibbuzzati fuq iż- żewġ naħat, tondi u b’ linja mnaqqxa fuqhom.
Symptomatic treatment of advanced (unresectable, metastatic or relapsed) adrenal cortical carcinoma.
Kura sintomatika ta ’ karċinoma avvanzata fil- kortiċi adrenali (li ma titneħħiex b’ intervent kirurġiku, metastatika jew meta reġgħet ħarġet il- marda).
The effect of Lysodren on non-functional adrenal cortical carcinoma is not established.
L- effett ta 'Lysodren fuq karċinoma fil- kortiċi adrenali li mhux qed taħdem ma huwiex stabbilit.
Treatment should be initiated and followed by a suitably experienced specialist.
Il- kura għandha tinbeda u tiġi segwita minn speċjalista b’ esperjenza adegwata.
Posology Treatment in adults should be started with 2 - 3 g mitotane per day and increased progressively (e. g. at two-week intervals) until mitotane plasma levels reach the therapeutic window 14 – 20 mg/ l.
Pożoloġija Il- kura fl- adulti għandha tinbeda minn 2 – 3 g mitotane kuljum u għandha tiżdied progressivament (eż. wara intervalli ta ’ ġimagħtejn) sakemm il- livelli tal- plażma ta ’ mitotane jilħqu l- livell terapewtiku 14 – 20 mg/ l.
If it is urgent to control Cushing’ s symptoms in highly symptomatic patients, higher starting doses between 4 - 6 g daily could be necessary and daily dose increased more rapidly (e. g. every week).
Jekk ikun urġenti li s- sintomi ta ’ Cushing jiġu kkontrollati f’ pazjenti b’ sintomi qawwijin, jista ’ jkun hemm bżonn ta ’ dożi tal- bidu ogħla ta ’ bejn 4 – 6 g kuljum u mbagħad id- doża ta ’ kuljum tiżdied b’ rata aktar mgħaġġla (eż. kull ġimgħa).
A starting dose higher than 6 g/ day is generally not recommended.
Ġeneralment, doża ogħla minn 6 g/ kuljum mhijiex rakkomandata.
Dose adjustments, monitoring and discontinuation Dose adjustment is aimed to reach a therapeutic window (mitotane plasma levels between 14 and 20 mg/ l) which ensures optimal use of Lysodren with acceptable safety.
Aġġustamenti fid- doża, monitoraġġ u waqfien L- aġġustament tad- doża huwa immirat sabiex jilħaq marġini terapewtika (livelli ta ’ plażma mitotane bejn 14 u 20 mg/ L) li jassigura l- użu ta ’ Lysodren b’ sigurtà aċċettabbli.
Indeed, neurologic toxicity has been associated with levels above 20 mg/ l and therefore this threshold should not be reached.
Tassew it- tossiċità newroloġikà ġiet assoċjata ma ’ livelli ’ l- fuq minn 20 mg/ l u għalhekk dan il- livell m’ għandux jiġi milħuq.
Weaker evidence has suggested that mitotane plasma levels above 14 mg/ l may result in enhanced efficacy.
Evidenza aktar dgħajfa implikat li livelli tal- plażma ta ’ mitotane il- fuq minn 14 mg/ l jista ’ jirriżulta f’ effikaċja aktar għolja.
Mitotane plasma levels higher than 20 mg/ l may be associated with severe undesirable effects and offer no further benefit in terms of efficacy.
Livelli tal- plażma ta ’ mitotane ogħla minn 20 mg/ l jistgħu jkunu assoċjati ma ’ effetti serji mhux mixtieqa u ma joffru ebda benefiċċju addizzjonali f’ termini ta ’ effikaċja.
Mitotane plasma levels should therefore be monitored in order to adjust the Lysodren dose and to avoid reaching toxic levels.
Il- livelli tal- plażma ta ’ Mitotane għandhom jiġu mmonitorjati biex id- doża ta ’ Lysodren tiġi aġġustata u biex ikun evitat li jintlaħqu livelli tossiċi.
Dosing should be individually adjusted based on mitotane plasma levels monitoring and clinical tolerance until mitotane plasma levels reach the therapeutic window 14 – 20 mg/ l.
2 Id- dożaġġ għandu jiġi aġġustat individwalment abbażi tal- monitoraġġ u t- tolleranza klinika tal- livelli tal- plażma ta ’ mitotane sakemm il- livelli tal- plażma ta ’ mitotane jilħqu l- marġni terapewtika 14 – 20 mg/ l.
The target plasma concentration is usually reached within a period of 3 to 5 months.
Il- konċentrazzjoni tal- plażma fil- mira normalment tintlaħaq fi żmien perjodu ta ’ 3 sa 5 xhur.
Mitotane plasma levels should be assessed after each dose adjustment and at frequent (e. g. every two weeks) intervals, until the optimal maintenance dose is reached.
Il- livelli tal- plażma ta ’ Mitotane għandhom jiġu vvalutati wara kull aġġustament fid- doża u f’ intervalli spissi (eż. kull ġimagħtejn) sakemm tintlaħaq l- aħjar doża ta ’ stabbilità.
Monitoring should be more frequent (e. g. every week) when a high starting dose has been used.
Il- monitoraġġ għandu jkun iktar spiss (eż. kull ġimgħa) meta tkun intużat doża tal- bidu li tkun għolja.
It should be taken into account that dose adjustments do not produce immediate changes in plasma levels of mitotane (section 4.4).
Għandu jitqies il- fatt li l - aġġustamenti fid- doża ma jipproduċux kambjamenti immedjati fil- livelli tal- plażma ta ’ mitotane (sezzjoni 4. 4).
In addition, because of tissue accumulation, mitotane plasma levels should be monitored regularly (e. g. monthly)
Barra dan, minħabba akkumulazzjoni ta ’ tessut, il- livelli tal- plażma ta ’ mitotane għandhom jiġu mmonitorjati regolarment (eż kull xahar), ladarba tkun intlaħqet id- doża tal - manteniment.
Regular monitoring (e. g. every two months) of mitotane plasma levels is also necessary after interruption of treatment.
Monitoraġġ regolari (eż. kull xahrejn) tal- livelli tal- plażma ta ’ mitotane huwa wkoll necessarju wara twaqqif tal- kura.
Treatment can be resumed when mitotane plasma levels will be ranged between 14 - 20 mg/ l.
It- trattament jista ’ jerġa ’ jinbeda meta l- livelli tal- plażma ta ’ mitotane jkunu bejn 14 u 20 mg/ l.
Due to the prolonged half-life, significant serum concentrations may persist for weeks after cessation of therapy.
Minħabba lil ’ half- life ’ tiegħu hu mtawwal, konċentrazzjonijiet sinifikanti ta ’ serum jistgħu jippersistu għal ġimgħat wara t- twaqqif tat- terapija.
If serious adverse reactions occur, such as neurotoxicity, treatment with mitotane may need to be transiently interrupted.
Jekk iseħħu reazzjonijiet avversi serji, bħal newrotossiċità, jista ’ jkun hemm bżonn li l- kura b’ mitotane titwaqqaf temporanjament.
In case of mild toxicity, the dose should be reduced until the maximum tolerated dose is attained.
Fil- każ taż tossiċità ħafifa, id- doża għandha titnaqqas sakemm tintlaħaq id- doża massima tollerata.
Treatment with Lysodren should be continued as long as clinical benefits are observed.
Il- kura b’ Lysodren għandha titkompla sakemm jibqgħu jiġu osservati benefiċċji kliniċi.
If no clinical benefits are observed after 3 months at optimal dose, treatment should be permanently discontinued.
Jekk l- ebda benefiċċju kliniku ma jiġi osservat wara 3 xhur bl- aħjar doża, it- trattament għandu jitwaqqaf b’ mod permanenti.
Special populations Paediatric patients The experience in children is limited.
Popolazzjonijiet speċjali Pazjenti pedjatriċi L- esperjenza dwar l- użu fit- tfal hija limitata.
The paediatric posology of mitotane has not been well characterised but appears equivalent to that of adults after correction for body surface.
Il- pożoloġija pedjatrika ta 'mitotane għadha ma ġietx stabbilita sewwa imma tidher li hija ekwivalenti għal dik ta ’ l- adulti wara korrezzjoni għas- superfiċje tal- ġisem.
Treatment should be initiated at 1.5 to 3.5 g/ m2/ day in children and adolescents with the objective of reaching 4 g/ m2/ day.
Il- kura għandha tinbeda f’ doża ta ’ 1. 5 sa 3. 5 g/ m2/ ġurnata fit- tfal u l- adolexxenti bil- għan li tintlaħaq 4 g/ m2/ kuljum.
Mitotane plasma levels should be monitored as for adults, with particular attention when plasma levels reach 10 mg/ l as a quick increase in plasma levels may be observed.
Il- livelli tal- plażma ta ’ Mitotane għandhom jiġu mmonitorjati bħal fil- każ tal- adulti, b’ attenzjoni partikolari meta l- livelli tal- plażma jilħqu 10 mg/ l.
Dose may be reduced after 2 or 3 months according to the mitotane plasma levels or in case of serious toxicity.
Id- doża tista ’ titnaqqas wara xahrejn jew 3 xhur skont il- livelli tal- plażma ta 'mitotane jew f’ każ ta ’ tossiċità serja.
Hepatic impairment Since mitotane is mainly metabolised through the liver, mitotane plasma levels are expected to increase if liver function is impaired.
Indeboliment tal- fwied Minħabba li mitotane jiġi metaboliżżat prinċipalment fil- fwied, il- livelli tal- plażma ta ’ mitotane huma mistennija li jiżdiedu jekk ikun hemm indeboliment fil- funzjoni tal- fwied.
There is no experience in the use of mitotane in patients with hepatic impairment, so data are insufficient to give a dose recommendation in this group.
M’ hemmx esperjenza dwar l- użu ta ’ mitotane f’ pazjenti b’ indeboliment fil- fwied, u għalhekk m’ hemmx informazzjoni suffiċjenti biex tingħata rakkomandazzjoni ta ’ doża f’ dan il- grupp.
The use of mitotane in patients with severe hepatic impairment is not recommended.
L- użu ta ’ mitotane f’ pazjenti b’ indeboliment serju tal- fwied ma huwiex irrakkomandat.
In patients with mild or moderate hepatic impairment, caution should be exercised and monitoring of liver biochemistry should be performed.
F’ pazjenti b’ indeboliment tal- fwied minn ħafif sa moderat, wieħed għandu joqgħod attent u għandha ssir osservazzjoni tal- bijokimika tal- fwied.
Monitoring of mitotane plasma levels is specially recommended in these patients (see section 4.4).
L- osservazzjoni tal- livelli tal- plażma ta ’ mitotane hija rrakkomandata speċjalment f’ dawn il- pazjenti (ara sezzjoni 4. 4).
Renal impairment There is no experience in the use of mitotane in patients with renal impairment, so data are insufficient to give a dose recommendation in this group.
Indeboliment tal- kliewi M’ hemm l- ebda esperjenza dwar l- użu ta 'mitotane f’ pazjenti b’ indeboliment renali, u għalhekk m’ hemmx informazzjoni suffiċjenti biex tingħata rakkomandazzjoni ta ’ doża f’ dan il- grupp.
The use of mitotane in patients with severe renal impairment is not recommended and, in cases of mild to moderate renal impairment, caution should be exercised.
L- użu ta ’ mitotane f’ pazjenti b’ indeboliment serju renali mhuwiex rakkomandat u, f’ każi ta ’ indeboliment renali minn ħafif sa moderat, wieħed għandu joqgħod attent.
Monitoring of mitotane plasma levels is specially recommended in these patients (see section 4.4).
L- osservazzjoni tal- livelli tal- plażma ta ’ mitotane hija rrakkomandat speċjalment f’ dawn il- pazjenti (ara sezzjoni 4. 4).
Elderly patients (≥ 65 years old) There is no experience on the use of mitotane in elderly patients, so data are insufficient to give a dose recommendation in this group.
Wieħed għandu
Caution should be exercised and frequent monitoring of mitotane plasma levels is highly recommended.
3 joqgħod attent u huwa rrakkomandat ħafna li ssir osservazzjoni frekwenti tal- livelli tal- plażma ta ’ mitotane.
Method of administration The total daily dose may be divided in two or three doses according to patient’ s convenience.
Metodu ta ’ amministrazzjoni Id- doża totali ta ’ kuljum tista ’ tinqasam f’ żewġ jew tliet dożi skont il- konvenjenza tal- pazjent.
Tablets should be taken with water during meals containing fat-rich food (see section 4.5).
Il - pilloli għandhom jittieħdu mal- ilma matul ikliet li fihom ikel b’ ħafna xaħam (ara sezzjoni 4. 5).
Patients should be advised not to use any tablets showing signs of deterioration, and caregivers to wear disposable gloves when handling the tablets.
Il - pazjenti huma rrakkomandati li ma jużawx pilloli li juru xi sinjal ta ’ deterjorazzjoni, u dawk li jagħtu l- kura għandhom jilbsu ingwanti li jintremew wara l- użu meta jmissu l- pilloli.
Hypersensitivity to the active substance or to any of the excipients
Sensittività eċċessiva għas- sustanza attiva jew għal xi sustanzi mhux attivi.
2 Lactation (see section 4.6)
Treddigħ (ara sezzjoni 4. 6).
Concomitant use with spironolactone (see section 4.5)
Użu fl- istess ħin ma ’ spironalactone (ara sezzjoni 4. 5).
Before the initiation of the treatment:
Qabel ma tinbeda l- kura:
Large metastatic masses should be surgically removed as far as possible before starting mitotane treatment, in order to minimise the risk of infarction and haemorrhage in the tumour due to a rapid cytotoxic effect of mitotane.
Mases metastatiċi kbar għandhom jitneħħew b’ kirurġija kemm jista ’ jkun qabel ma tinbeda kura b' mitotane biex titnaqqas il- possibilità ta ’ infart u emorraġija fit- tumur kkawżati mill- effett ċitotossiku mgħaġġel ta 'mitotane.
Risk of adrenal insufficiency:
Riskju ta ’ indeboliment Adrenali:
All patients with non functional tumour and 75% of patients with functional tumour show signs of adrenal insufficiency.
Il- pazjenti kollha b’ tumuri mhux funzjonali u 75% tal- pazjenti b’ tumur funzjonali juru sinjali ta ’ indeboliment adrenali.
Therefore, steroid replacement may be necessary in these patients.
Għaldaqstant, jista ’ jkun hemm bżonn ta ’ sostituzzjoni ta ’ sterojdi f’ dawn il- pazjenti.
Since mitotane increases plasma levels of steroid binding proteins, free cortisol and corticotropin (ACTH) determinations are necessary for optimal dosing of steroid substitution (see section 4.8).
Minħabba li Mitotane jżid il- livelli tal- plażma ta ’ proteini li jeħlu ma ’ sterojdi, hemm bżonn ta ’ determinazzjonijiet ta ’ cortisol u corticotropin liberi (ACTH) għal aħjar dożaġġ ta ’ sostituzzjoni ta ’ sterjodi (ara sezzjoni 4. 8).
Shock, severe trauma or infection:
Xokk, trawma severa jew infezzjoni:
Mitotane should be temporarily discontinued immediately following shock, severe trauma or infection, since adrenal suppression is its prime action.
Mitotane għandu jitwaqqaf għal perijodu temporanju immedjatament wara xokk, trawma severa jew infezzjoni, minħabba li l- azzjoni primarja tiegħu hija trażżin adrenali.
Exogenous steroids should be administered in such circumstances, since the depressed adrenal gland may not immediately start to secrete steroids.
Sterojdi exoġeni għandhom jingħataw f’ dawn iċ- ċirkostanzi, minħabba li l- glandola adrenali mrażżna tista ’ ma tibdiex tipproduċi sterojdi immedjatament.
Because of an increased risk of acute adrenocortical insufficiency, patients should be instructed to contact their physician immediately if injury, infection, or any other concomitant illness occurs.
Minħabba riskju akbar ta ’ insuffiċjenza adrenokortikali akuta, il- pazjenti għandhom jiġu infurmati biex jikkuntattajaw lit- tabib tagħhom immedjatament f’ każ li jweġġgħu, li jkollhom xi infezzjoni, jew xi mard ieħor konkomittanti.
Patients should carry with them the Lysodren Patient Card provided with the package leaflet indicating that they are prone to adrenal insufficiency and that, in case of emergency care, adequate precautionary measures should be taken.
Il- pazjenti għandhom iġorru magħhom il- Kartuna tal- Pazjent Li Qed Jieħu Lysodren li tiġi pprovduta mal- fuljett ta ’ tagħrif li tindika li huma jbatu minn insuffiċjenza adrenali u li f’ każ ta ’ emerġenza, għandhom jittieħdu miżuri adegwati ta ’ prekawzjoni.
Monitoring of plasma levels:
Osservazzjoni tal- livelli fil- plażma:
Mitotane plasma levels should be monitored in order to adjust the mitotane dose, particularly if high starting doses are considered necessary.
Il- livelli tal- plażma ta ’ mitotane għandhom ikunu osservati sabiex id- doża ta ’ Lysodren tkun aġġustata, b’ mod partikolari jekk dożi tal- bidu għoljin ikunu meqjusin neċessarji.
Dose adjustments may be necessary to achieve the desired therapeutic levels in the window between 14 and 20 mg/ l and avoid specific adverse reactions (see section 4.2).
Jista ’ jkun hemm bżonn ta ’ aġġustamenti fid- doża sabiex jintlaħqu l- livelli terapewtiċi korretti fil- firxa ta ’ bejn 14 u 20 mg/ l u jiġu evitati reazzjonijiet avversi speċifiċi (ara sezzjoni 4. 2).
Hepatic or renal impairment:
Indeboliment tal- fwied jew tal- kliewi:
There are insufficient data to support the use of mitotane in patients with severe hepatic or renal impairment.
M’ hemmx biżżejjed informazzjoni sabiex tappoġġja l- użu ta ’ mitotane f’ pazjenti b’ indeboliment serju tal- fwied jew tal- kliewi.
In patients with mild or moderate hepatic or renal impairment, caution should be exercised and monitoring of mitotane plasma levels is particularly recommended (see section 4.2).
F’ pazjenti b’ indeboliment tal- fwied jew tal- kliewi ħafif għal moderat, għandha tingħata kawtela u l- monitoraġġ ta ’ livelli tal- plażma ta ’ mitotane huwa partikolarment rakkomandat (ara sezzjoni 4. 2).
Mitotane tissue accumulation:
Akkumulazzjoni tat- tessut mitotane:
Fat tissue can act as a reservoir for mitotane, resulting in a prolonged half-life and potential accumulation of mitotane.
It- tessut tax- xaħam jista ’ jaġixxi bħala post ta ’ ġbir għal mitotane f ’ ‘ half- life ’ mtawwal u akkumulazzjoni potenzjali ta ’ mitotane.
Consequently, despite a constant dose, mitotane levels may increase.
Konsegwentement, minkejja d- doża kostanti, il- livelli tal- mitotane jistgħu jiżdiedu.
Therefore, monitoring of mitotane plasma levels (e. g. every two months) is also necessary after interruption of treatment, as prolonged release of mitotane can occur.
Għalhekk, l- osservazzjoni tal- livelli tal- plażma ta ’ mitotane (eż kull xahrejn) huwa wkoll neċessarju wara interuzzjoni tat- trattament għax jista ’ jkun li mitotane jintreħa bil- mod.
Caution and close monitoring of mitotane plasma levels are highly recommended when treating overweight patients.
Kawtela u osservazzjoni mill- qrib tal- livelli tal- plażma ta ’ mitotane huma rakkomandati ferm meta jiġu ttrattati pazjenti b’ piż eċċessiv.
Central nervous system disorders:
4 Disturbi fis- sistema nervuża ċentrali:
Long-term continuous administration of high doses of mitotane may lead to reversible brain damage and impairment of function.
Teħid kontinwu fit- tul ta ’ dożi għolja ta ’ mitotane jista ’ jwassal għal ħsara riversibbli fil- moħħ u indeboliment fil- funzjoni tiegħu.
Behavioural and neurological assessments should be made at regular intervals, especially when mitotane plasma levels exceed 20 mg/ l (see section 4.8).
Għandha ssir osservazzjoni ta ’ l - imġieba u osservazzjoni newroliġika f’ perijodi regolari speċjalment meta l- livelli tal- plażma ta ’ mitotane jkunu ogħla minn 20 mg/ l (ara sezzjoni 4. 8).
Bleeding time:
Ħin ta ’ fsada:
Prolonged bleeding time has been reported in patients treated with mitotane and this should be taken into account when surgery is considered (see section 4.8).
Fsada fit- tul ġiet rrappurtata f’ pazjenti li kienu qed jieħdu mitotane u dan għandu jingħata importanza meta tkun qed tiġi kkunsidrata l- kirurġija (ara sezzjoni 4. 8).
Warfarin and coumarin-like anticoagulants:
Warfarin u sustanzi kontra l- koagulazzjoni bħal coumarin:
Physicians should closely monitor patients for a change in anticoagulant dose requirements when administering mitotane to patients on coumarin-like anticoagulants (see section 4.5).
It- tobba għandhom isegwu mill- qrib lill - pazjenti għal tibdil fir- rekwiżiti tad- doża kontra l- koagulazzjoni bħall- coumarin meta jagħtu Mitotane lil pazjenti li jkunu fuq sustanzi kontra l- koagulazzjoni simili għal coumarin (ara sezzjoni 4. 5).
Substances metabolised through cytochrome P450:
Sustanzi metabolizzati permezz ta ’ cytochrome P450:
Mitotane is a hepatic enzyme inducer and it should be used with caution in case of concomitant use of medicinal products influenced by hepatic enzyme
Mitotane jinduċi l- enżimi tal- fwied u għandu jittieħed b’ kawtela f’ każi meta jintuża fl- istess ħin ma ’ prodotti mediċinali li jiġu nfluwenzati bl - induzzjoni ta ’ enżimi tal- fwied (ara sezzjoni 4. 5).
Women of childbearing potential:
Nisa f’ età fertili:
Women of childbearing potential must use effective contraception during treatment with mitotane (see section 4.6).
Nisa f’ età fertili għandhom jużaw kontraċezzjoni effettiva matul kura b’ mitotane (ara sezzjoni 4. 6).
In children and adolescents, neuro-psychological retardation can be observed during mitotane treatment.
Fit- tfal u l- adoloxxenti, jista ’ jiġi osservat nuqqas ta 'żvilupp newro- psikoloġiku matul il- kura b' mitotane.
In such cases, thyroid function should be investigated in order to identify a possible thyroid impairment linked to mitotane treatment.
F’ dawn il- każijiet, il- funzjoni tat- tirojde għandha tiġi eżaminata biex wieħed jara jekk hemmx indeboliment tat- tirojde assoċjata ma ’ kura b' mitotane.
Spironolactone:
Spironalactone:
Mitotane must not be given in combination with spironolactone, since this active substance may block the action of mitotane (see section 4.3).
Mitotane m’ għandux jingħata flimkien ma ’ spironalactone minħabba li din is - sustanza attiva tista ’ twaqqaf l- azzjoni ta 'mitotane (ara sezzjoni 4. 3).
Mitotane has been reported to accelerate the metabolism of warfarin through hepatic microsomal enzyme induction, leading to an increase in dose requirements for warfarin.
Mitotane ġie rrappurtat li jgħaġġel il - metaboliżmu ta 'warfarina permezz ta ’ l- induzzjoni ta ’ l- enżimi mikrożomiċi tal- fwied, u dan iwassal għal żieda fir- rekwiżiti tad- doża għal warfarin.
Therefore, physicians should closely monitor patients for a change in anticoagulant dose requirements when administering mitotane to patients on coumarin-like anticoagulants.
Għalhekk, it- tobba għandhom isegwu l- pazjenti mill - qrib biex jaraw jekk ikunx hemm bżonn ta 'tibdil fid- doża tas- sustanzi kontra l- koagulazzjoni meta jagħtu mitotane lill- pazjenti li qed jieħdu sustanzi kontra l- koagulazzjoni bħal coumarin.
Mitotane has been shown to have an inductive effect on cytochrome P450 enzymes.
Mitotane wera li għandu effett ta 'induzzjoni fuq l- enżimi ta ’ cytochrome P450.
Therefore, the plasma concentrations of the substances metabolised via cytochrome P450 may be modified.
Għalhekk il- konċentrazzjonijiet fil- plażma tas- sustanzi metabolizzati permezz ta ’ cytochrome P450 jistgħu jiġu modifikati.
In the absence of information on the specific P450 isoenzymes involved, caution should be taken when co-prescribing active substances metabolised by this route such as, among others, anticonvulsants, rifabutin, rifampicin, griseofulvin and St.
Fl- assenza ta ’ informazzjoni dwar l- isoenżimi P450 speċifiċi involuti, wieħed għandu joqgħod attent meta jiġu preskritti flimkien sustanzi attivi li jiġu metabolizzati b’ dan il- mod bħal, fost oħrajn, antikonvulsanti, rifabutin, rifampicin, griseofulvin u St.
Medicinal products active on central nervous system:
Prodotti mediċinali attivi fuq is- sistema nervuża ċentrali:
Mitotane can cause central nervous system undesirable effects at high concentrations (see section 4.8).
Mitotane jista ’ jikkawża effetti mhux mixtieqa fuq is- sistema nervuża ċentrali meta jingħataw konċentrazzjonijiet għoljin (ara sezzjoni 4. 8).
Although no specific information on pharmacodynamic interactions in the central nervous system is available, this should be borne in mind when co-prescribing medicinal products with central nervous system depressant action.
Għalkemm ma 'hemm l- ebda informazzjoni speċifika dwar interazzjonijiet farmakodinamiċi fis - sistema nervuża ċentrali, dawn għandhom jittieħdu in konsiderazzjoni meta jiġu ko- preskritti prodotti mediċinali b’ azzjoni dipressanti fuq is- sistema nervuża ċentrali.
Fat-rich food:
Ikel u żjut:
Data with various mitotane formulations suggest that administration with fat-rich food enhances absorption of mitotane.
Informazzjoni dwar formulazzjonijiet varji ta ’ mitotane tissuġġerixxi li teħid ma ’ ikel b’ ħafna xaħam iżid l- assorbiment ta ’ mitotane (ara sezzjoni 5. 2).
Hormone binding protein:
Proteina li jingħaqdu mal- ormoni:
Mitotane has been shown to increase plasma levels of hormone binding proteins (e. g. sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG)).
Intwera li mitotane iżid il- livelli ta ’ proteini li jingħaqdu ma ’ l - ormoni tal- plażma (eż. globulina li tingħaqad mal- ormoni tas- sess (SHBG) u globulina li tingħaqad mal- kortikosteroji (CBG)).
This should be taken into account when interpreting the results of hormonal assays and may result in gynaecomastia.
Dan għandu jittieħed in konsiderazzjoni meta jiġu nterpretati r- riżultati tat - testijiet ta ’ l- ormoni u jista ’ jirriżulta f’ gajnekomastija.
Pregnancy Data on a limited number of exposed pregnancies indicate abnormalities on the adrenals of the foetus after exposure to mitotane.
5 Tqala Informazzjoni dwar numru limitat ta ’ każijiet ta 'tqala esposti tindika anormalitajiet fuq l- adrenali tal - fetu wara espożizzjoni għal mitotane.
Animal reproduction studies have not been conducted with mitotane.
Studji fl- annimali dwar l- effett ta 'mitotane fuq ir- riproduzzjoni għadhom ma sarux.
Animal studies with similar substances have shown reproductive toxicity (see section 5.3).
Studji fuq l- annimali b’ sustanzi simili wrew tossiċità fuq ir- riproduzzjoni (ara sezzjoni 5. 3).
Lysodren should be given to a pregnant woman only if clearly needed and if the clinical benefit clearly outweighs any potential risk to the foetus.
Lysodren għandu jingħata lill- mara tqila biss fejn hemm ħtieġa ċara għalih u jekk il - benefiċċju kliniku huwa wisq akbar minn kull riskju potenzjali għall- fetu.
Women of childbearing potential must use effective contraception during treatment and after discontinuation of treatment as long as mitotane plasma levels are detectable.
Nisa li jistgħu joħorġu tqal għandhom jużaw kontraċezzjoni effettiva matul il- kura u wara l- waqfien tal- kura sakemm il- livelli tal- plażma ta ’ mitotane ikunu traċċabbli.
The prolonged elimination of mitotane from the body after discontinuation of Lysodren should be considered.
Il- fatt li mitotane jiġi eliminat bil - mod mill- ġisem wara li jitwaqqaf Lysodren għandu jiġi kkunsidrat.
Lactation Due to the lipophilic nature of mitotane, it is likely to be excreted in breast milk.
Treddigħ Minħabba n- natura lipofilika ta ’ mitotane, huwa probabbli li joħroġ fil- ħalib tas- sider.
Breast-feeding is contraindicated while taking mitotane (see section 4.3) and after treatment discontinuation as long as mitotane plasma levels are detectable.
It- treddigħ huwa kontra- indikat waqt li jkun qed jingħata mitotane (ara sezzjoni 4. 3) u wara li titwaqqaf il- kura diment li l- livelli tal- plażma ta ’ mitotane ikunu traċċabbli.
Lysodren has a major influence on the ability to drive and use machines.
Lysodren għandu influwenza qawwija fuq il- ħila ta ’ sewqan u l- użu ta ’ magni.
Ambulatory patients should be warned not to drive or use machines.
Pazjenti li jkunu qegħdin jieħdu l- kura għandhom jiġu avżati biex ma jsuqux u ma jużawx magni.
Safety data are based on literature (mainly retrospective studies).
It- tagħrif dwar is- sigurtà huwa bbażat fuq il- letteratura (b’ mod ewlieni studji retrospettivi).
More than 80% of patients treated with mitotane have shown at least one type of undesirable effect.
Aktar minn 80% tal- pazjenti kkurati b’ mitotane wrew għallinqas tip wieħed ta ’ effett mhux mixtieq.
Adverse reactions listed below are classified according to frequency and system organ class.
Ir - reazzjonijiet avversi elenkati hawn taħt huma kklassifikati skont is- sistema ta ’ klassifika tal- organi u l - frekwenza.
Frequency groupings are defined according to the following convention:
Il- gruppi tal- frekwenza huma definiti skont il- konvenzjoni li ġejja:
Very common (≥ 1/ 10), Common (≥ 1/ 100 to < 1/ 10), Uncommon (≥ 1/ 1,000 to < 1/ 100), Rare (≥ 1/ 10,000 to < 1/ 1,000), Very rare (< 1/ 10,000), Not known (cannot be estimated from the available data).
Komuni ħafna (≥1/ 10), Komuni (≥1/ 100 sa < 1/ 10), Mhux komuni (≥1/ 1, 000 sa < 1/ 100), Rari (≥1/ 10, 000 sa < 1/ 1, 000), Rari ħafna (< 1/ 10, 000), mhux magħruf (ma tistax tittieħed stima mid- data disponibbli).
Frequency of adverse reactions identified from literature data Adverse reaction
Frekwenza ta ’ reazzjonijiet mhux mixtieqa identifikati mid- dejta tal- letteratura Reazzjoni avversa Sistema tal- Klassifika tal- Organi
Common
Mhux Magħruf
Not Known
Tnaqqis
Blood uric acid decreased
tal- uric acid fid -
Blood and lymphatic system disorders
Livell għoli ta ’ enzimi Investigazzjonijiet demm tal- fwied Żieda fil- kolesterol tal - plażma Żieda fit- trigliċeridi tal - plażma Anemija Disturbi fid- demm u fis - Lewkopenja Tromboċitopenja Ħin itwal ta ’ fsada sistema limfatika
Leucopoenia Bleeding time prolonged
Indeboliment mentali fis- sistema Atassja Disturbi Polinewropatija Parasteżija nervuża Disturbi fil- moviment Vertigo Sturdament Ħedla Uġigħ ta ’ ras Makulopatija Disturbi fl- għajnejn Tossiċità retinali Viżta doppja Opaċità tal- lenti Disturbi fil- viżta Viżta mċajpra
Nervous system disorders
6 Ipersekrezzjoni tas- saliva Mukosite Disturbi Remettar gastrointestinali Dijarrea Tqalligħ Skumdità epigastrika
Mental impairment Polyneuropathy Movement disorder Dizziness Headache
Ċistite emorraġika Disturbi fil- kliewi u fis - Ematurja sistema urinarja Protenurja Raxx tal- ġilda Disturbi fil- ġilda u fit - tessut ta ’ taħt il- ġilda Mijastenja Disturbi
Eye disorders
muskolu -
Maculopathy Retinal toxicity Diplopia Lens opacity Visual impairment Vision blurred
skeltrali
Mucositis Vomiting Diarrhoea Nausea Epigastric discomfort
tal -
Salivary hypersecretion
connective tissue Disturbi endokrinarja
Renal and urinary disorders
fis- sistema
Haemorrhagic cystitis Haematuria Proteinuria
Indeboliment adrenali Anoressija
Skin and subcutaneous tissue disorders
Indeboliment tat- tirojde Ipojuriċimja
Skin rash
Distrubi
Muscoloskeletal and connective tissue disorders
fil -
Myasthenia
Iperkolesterolimja
Endocrine disorders Metabolism and nutrition disorders
metaboliżmu u fin - Ipertrigliċeridimja nutrizzjoni Mikożi opportunistika Infezzjonijiet infestazzjonijiet Disturbi vaskulari
Adrenal insufficiency Anorexia Hypercholesterolemia Hypertriglyceridaemia
u
Thyroid impairment Hypouricaemia
Pressjoni għolja Pressjoni ortostatika baxxa Fwawar
5 Infections and infestations
Disturbi ġenerali u Astenja kondizzjonijiet ta 'mnejn jingħata
Opportunistic mycosis
Iperpireksja Uġigħ ġeneralizzat
Vascular disorders
Disturbi fil- fwied u fil -
Hyperpyrexia Generalised aching
Epatite awto- immuni
Hepatobiliary disorders Reproductive system Gynaecomastia and breast disorders Psychiatric disorders Confusion
Ħsara
Autoimmune hepatitis
fil- fwied
Liver damage (hepatocellular/ cholestatic / mixed)
(epatoċellulari/ kolestatika/ im marrara ħallta) fis- sistema Ġinekomastija Disturbi riproduttiva u fis- sider Konfużjoni Disturbi psikjatriċi
Gastrointestinal disorders are the most frequently reported (10 to 100% of patients) and are reversible when the dose is reduced.
Disturbi gastrointestinali huma l- effetti li jiġu rrappurtat bl- akbar frekwenza (10 sa 100% tal- pazjenti) u huwa riversibbli meta d- doża tiġi mnaqqsa.
Some of these effects (anorexia) may constitute the hallmark of initial central nervous system impairment.
Xi wħud minn dawn l- effetti (anoreksja) jistgħu jindikaw l- bidu ta ’ indeboliment fis- sistema nervuża ċentrali.
Nervous system undesirable effects occur in approximately 40% of patients.
Effetti mhux mixtieqa fuq is- sistema nervuża jseħħu bejn wieħed u ieħor f’ 40% tal- pazjenti.
Other undesirable central nervous effects have been reported in literature such as memory defects, aggressiveness, central vestibular syndrome, dysarthria, or Parkinson syndrome.
Effetti oħra mhux mixtieqa tas- sistema nervuża ġew rrrappurtati fil- litteratura bħal difetti fil- memorja, aggressività, sindromu vestibulari ċentrali, diżartrija, jew sindromu tal- Parkinsons.
Serious undesirable effects appear linked to the cumulative exposure to mitotane and are most likely to occur when mitotane plasma levels are at 20 mg/ l or above.
Effetti mhux mixtieqa serji jidhru li huma marbuta ma ’ l- esposizzjoni kumulattiva ta ’ mitotane u x’ aktarx li jseħħu l- aktar meta l- livelli tal- plażma ta ’ mitotane jkunu 20 mg/ l jew aktar.
At high doses and after prolonged utilization, brain function impairment can occur.
F’ dożi għolja u wara użu fit- tul, jista ’ jseħħ indeboliment fil- funzjoni tal- moħħ.
Nervous system undesirable effects appear reversible after cessation of mitotane treatment and decrease in plasma levels (see section 4.4).
Effetti mhux mixtieqa fis- sistema nervuża jidhru li huma riversibbli wara l- waqfien tal- kura b' mitotane u tnaqqis fil- livelli tal- plażma (ara sezzjoni 4. 4).
Skin rashes which have been reported in 5 to 25% of patients do not seem to be dose related.
Raxx fil- ġilda li ġie rrapportat f’ 5 sa 25% tal- pazjenti ma jidhirx li huwa relatat mad- doża.
Leucopoenia has been reported in 8 to 12% of patients.
Lewkopenja ġiet rappurtata fi 8 sa 12% tal- pazjenti.
Prolonged bleeding time appears a frequent finding (90%): although the exact mechanism of such an effect is unknown and its relation with mitotane or with the underlying disease is uncertain, it should be taken into account when surgery is considered.
Ħin itwal ta ’ fsada jidher li hu effett frekwenti (90% tal- każijiet): għalkemm il- mekkaniżmu eżatt ta ’ effett bħal dan mhux magħruf u r- relazzjoni tiegħu ma 'mitotane jew mal- marda mhix ċerta, dan għandu jittieħed in konsiderazzjoni meta tiġi kkunsidrata l- kirurġija.
The activity of liver enzymes (gamma-GT, aminotransferase, alkaline phosphatase) is commonly increased.
L- attività ta ’ l- enżimi tal- fwied (gamma- GT, aminotransferase, alkaline phosphatase) normalment tiżdied.
Autoimmune hepatitis has been reported in 7% of patients with no other information on mechanism.
7 tiġi mnaqqsa.
A case of cholestatic hepatitis has been reported.
Każ ta ’ epatite kolestatiku ġie irrapurtat.
Therefore, the possibility of mitotane-induced liver damage cannot be excluded.
Għalhekk, il- possibilità ta ’ ħsara fil- fwied ikkaġunata mill- mitotane ma tistax tiġi eskluża.
Paediatric patients Neuro-psychological retardation may be observed during mitotane treatment.
Pazjenti pedjatriċi Nuqqas ta ’ żvilupp newro- psikoloġiku jista ’ jiġi osservat matul il- kura b' mitotane.
In such cases, thyroid function should be investigated in order to identify a possible thyroid impairment linked to mitotane treatment.
F’ dawn il- każijiet, il- funzjoni tat- tirojde għandha tiġi eżaminata biex wieħed jara jekk hemmx indeboliment fit- tirojde assoċjata mal- kura b' mitotane.
Hypothyroidism and growth retardation may be also observed.
L- ipotirojdiżmu u dewmien ta ’ żvilupp fid- daqs jistgħu jiġu osservati wkoll.
Mitotane overdose may lead to central nervous system impairment especially if mitotane plasma levels are above 20 mg/ l.
Doża eċċessiva ta ’ mitotane tista ’ twassal għal disturbi fis- sistema nervuża ċentrali speċjalment jekk il- livelli tal- plażma ta ’ mitotane huma ogħla minn 20 mg/ l.
No proven antidotes have been established for mitotane overdose.
L- ebda antidoti għadhom ma ġew stabbiliti għal doża eċċessiva ta 'mitotane.
The patient should be followed closely, taking into account that impairment is reversible, but given the long half-life and the lipophilic nature of mitotane, it may take weeks to return to normal.
Il- pazjent għandu jiġi osservat mill- qrib, u wieħed għandu jżomm f' moħħu li dawn id- disturbi huma riversibbli iżda jridu jgħaddu ġimgħat biex kollox jerġa ’ għan - normal minħabba li mitotane għandu half- life twila u natura lipofilika.
Other effects should be treated symptomatically.
Effetti oħra għandhom jiġu trattati sintomatikalment.
Because of its lipophilic nature, mitotane is not likely to be dialysable.
Minħabba n- natura lipofilika tiegħu, mitotane x’ aktarx ma jistax jiġi msaffi b’ dijaliżi.
It is recommended to increase frequency of mitotane plasma level monitoring (e. g. every two weeks) in patients at risk of overdose (e. g. in case of renal or hepatic impairment, obese patients or patients with a recent weight loss).
Hu rrakkomandat li żżid il- frekwenza ta ’ l- osservazzjoni tal- livell tal- plażma ta ’ mitotane (eż kull ġimagħtejn) fil- pazjenti b’ riskju ta ’ doża eċċessiva (eż. fil- każ ta ’ indeboliment renali jew epatiku, pazjenti b’ piż żejjed jew pazjenti bi tnaqqis ta ’ piż reċenti).
Other antineoplastic agents, ATC code:
Kodiċi ATC:
Mechanism of action Mitotane is an adrenal cytotoxic active substance, although it can apparently also cause adrenal inhibition without cellular destruction.
Mekkaniżmu ta ’ azzjoni Mitotane huwa sustanza attiva ċitotossika adrenali, għalkemm tista ’ apparentament tikkawża wkoll inibizzjoni adrenali, mingħajr distruzzjoni ċellulari.
Its biochemical mechanism of action is unknown.
Il- mekkaniżmu biokimiku ta ’ l- azzjoni tiegħu mhux magħruf.
Available data suggest that mitotane modifies the peripheral metabolism of steroids and that it also directly suppresses the adrenal cortex.
L- informazzjoni disponibbli tissuġġerixxi li mitotane jimmodifika l- metaboliżmu periferali ta ’ l- isterojdi kif ukoll irażżan direttament il- kortiċi adrenali.
The administration of mitotane alters the extra-adrenal metabolism of cortisol in humans, leading to a reduction in measurable 17-hydroxy corticosteroids, even though plasma levels of corticosteroids do not fall.
It- teħid ta 'mitotane ibiddel il - metaboliżmu estra- adrenali tal- cortisol fil- bniedem, u jwassal għal tnaqqis fl- ammont ta' 17- hydroxy corticosteroids li jista 'jitkejjel, anke jekk il- livelli ta ’ kortikosterojdi fil- plażma ma jitbaxxewx.
Mitotane apparently causes increased formation of 6-beta- hydroxy cholesterol.
Mitotane apparentement jikkawża żieda fil- formazzjoni ta '6- beta- hydroxy cholesterol.
Clinical efficacy Mitotane has not been studied in a comprehensive clinical development program.
Effikaċja klinika Mitotane għadu ma ġiex studjat fi programm ta ’ żvilupp kliniku komprensiv.
Available clinical information comes mainly from published data in patients with inoperable or metastatic adrenal carcinoma.
L- informazzjoni klinika disponibbli ġejja prinċipalment mill- informazzjoni ppublikata dwar pazjenti b’ karċinoma adrenali inoperabbli jew metastatika.
In terms of overall survival, four studies conclude that mitotane treatment does not increase the survival rate whereas five find an increase in the survival rate.
F’ termini ta ’ sopravivenza in ġenerali, erba ’ studji jikkonkludu li l- kura b' mitotane ma żżidx ir- rata ta ’ sopravivenza filwaqt li ħames studji jsibu li kien hemm żieda fir- rata ta ’ sopravivenza.
Among the latter, three studies find such an increase only in patients in whom mitotane plasma is above 14 mg/ l.
Fost dawn ta ’ l- aħħar, tliet studji jsibu din iż- żieda biss f’ pazjenti li għandhom livell tal - plażma ta ’ mitotane ogħla minn 14 mg/ l.
In terms of total or partial tumour and/ or metastasis regression, eleven studies have shown some degree of improvement and sometimes occasional prolonged remissions.
F’ termini ta ’ rigressjoni totali jew parzjali ta ’ tumur u/ jew tal- metastasi, ħdax- il studju wrew xi ftit tat- titjib u ġieli perijodi twal ta ’ remissjoni.
However, in several studies, the objective criteria for evaluating tumour response are missing or not reported.
Madankollu, f’ diversi studji, il- kriterji għall- evalwazzjoni tar- rispons tat- tumur huma nieqsa jew ma ġewx rrappurtati.
There are nevertheless some studies which provide accurate information on tumour regression or disappearance and demonstrate that the threshold of 14 mg/ l appears necessary to induce an objective tumour regression.
Madankollu hemm ukoll xi studji li jipprovdu informazzjoni eżatta dwar ir- rigressjoni tat - tumur jew fejn it- tumur ma baqax jidher u juru li l- limitu ta ’ 14 mg/ l jidher li hu meħtieġ biex jikkawża rigressjoni oġġettiva tat- tumur.
In addition, mitotane induces a state of adrenal insufficiency which leads to the disappearance of Cushing syndrome in patients with secreting adrenal carcinoma and necessitates substitution hormonotherapy.
Mitotane jikkawża wkoll stat ta ’ insuffiċjenza adrenali li twassal biex ma jidhirx aktar is- sindromu Cushing f’ pazjenti b’ karċinoma adrenali li tnixxi u li tirrikjedi terapija ta ’ sostituzzjoni bl- ormoni.
Paediatric patients Clinical information comes mainly from a prospective trial (n= 24 patients) in children and adolescents aged at diagnosis from 5 months to 16 years (median age:
Pazjenti pedjatriċi L- informazzjoni klinika tiġi prinċipalment minn prova prospettiva (n=24 pazjenti) fit- tfal u adoloxxenti ta ’ età fid- dijanjożi minn 5 xhur sa 16- il sena (età medjana, 4 snin) li kellhom tumur