qanastek/EMEA-V3 huggingface dataset:
G-CSF (or GM-CSF) may be given as concomitant therapy to support the blood count when the ANC count is < 1,000/ mm3 in subsequent cycles.
Il- G- CSF (jew GM- CSF) jista ’ jingħata bħala terapija konkomitanti biex jinżamm l- għadd taċ- ċelluli fid- demm meta l- għadd ta 'l- ANC < 1, 000/ mm3 fiċ- ċikli sussegwenti.
The haematological toxicity for ovarian cancer patients is less severe than in the AIDS-KS setting (see section for ovarian cancer patients above).
It- tossiċità ematoloġika f' pazjenti b' kanċer ta ’ l- ovarji hija anqas gravi milli f' dawk bl- AIDS- KS (ara t- taqsima dwar pazjenti b' kanċer ta ’ l- ovarji hawn fuq).
Respiratory undesirable effects commonly occurred in clinical studies of Caelyx and may be related to opportunistic infections in the AIDS population.
Fl- istudji kliniċi dwar Caelyx, effetti mhux mixtieqa respiratorji seħħew b’ mod komuni u jistgħu jkunu relatati ma ’ infezzjonijiet opportunistiċi (OI’ s) fil- popolazzjoni ta ’ pazjenti bl- AIDS.
Opportunistic infections (OI’ s) are observed in KS patients after administration with Caelyx, and are frequently observed in patients with HIV-induced immunodeficiency.
Infezzjonijiet opportunistiċi (OI’ s) jkunu osservati f’ pazjenti b’ KS wara li jingħata Caelyx, u ta ’ spiss jidhru f’ pazjenti li jsofru minn nuqqas fis- sistema immunitarja minħabba HIV.
The most frequently observed OI’ s in clinical studies were candidiasis, cytomegalovirus, herpes simplex, Pneumocystis carinii pneumonia, and mycobacterium avium complex.
L- iżjed OI’ s frekwenti fl- istudji kliniċi kienu; kandidijażi, ċitomegalovirus, Herpes simplex, pulmonite b’ Pneumocystis carinii u mycobacterium avium complex.
Undesirable effects observed in patients with AIDS-KS according to CIOMS III frequency categories (Very common (> 1/ 10); Common (> 1/ 100 ,< 1/10); Uncommon (> 1/1 ,000, < 1/100)) were as follows:
Effwtti mhux mixtieqa li dehru f’ pazjenti b’ AIDS- KS skond kategoriji tal- frekwenza CIOMS III (Komuni ħafna (> 1/ 10); Komuni (> 1/ 100, < 1/ 10); Mhux komuni (> 1/ 1, 000, < 1/ 100)) kienu hekk kif imiss:
Uncommon: confusion
Infezzjonijiet u infestazzjonijiet Komuni: monilijażi orali
Common: dizziness Uncommon: paresthesia
Disturbi tad- demm u tas- sistema limfatika Komuni ħafna: newtropinja, anemija, lewkopinja Komuni: tromboċitopenja
Common: retinitis
Disturbi fil- metaboliżmu u n- nutrizzjoni Komuni: anoressja
Vascular disorders:
Disturbi psikjatriċi
18 Common: vasodilatation
18 Mhux komuni: konfużjoni.
Respiratory, thoracic and mediastinal disorders:
Disturbi fis- sistema nervuża Komuni: sturdament Mhux komuni: parasteżija
Common: dyspnoea
Disturbi fl- għajnejn Komuni: renite
Gastrointestinal disorders:
Disturbi vaskulari Komuni: vażodilatazzjoni
Very common: nausea Common: diarrhoea, stomatitis, vomiting, mouth ulceration, abdominal pain, glossitis, constipation, nausea and vomiting
Disturbi gastro- intestinali Komuni ħafna: tqallih Komuni: dijarrea, stomatite, rimettar, ulċeri fil- ħalq, uġigħ addominali, glossite, stitikezza, tqallih u rimettar
Common: alopecia, rash Uncommon: palmar-plantar erythrodysesthesia (PPE)
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Komuni: alopeċja, raxx Mhux komuni: palmar- plantar erythrodysesthesia (PPE)
Common: asthenia, fever, infusion-associated acute reactions
Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata Komuni: astenja, deni, reazzjonijiet akuti ta ’ l- infużjoni
Common: weight loss.
Investigazzjonijiet Komuni: tnaqqis fil- piż tal- ġisem
Other less frequently (< 5%) observed undesirable effects included hypersensitivity reactions including anaphylactic reactions.
Effetti mhux mixtieqa oħrajn li kienu innutati b’ mod anqas frekwenti (< 5%) kienu jinkludu reazzjonijiet ta ’ sensittività eċċessiva inklużi reazzjonijiet anafilattiċi.
Following marketing, bullous eruption has been reported rarely in this population.
Wara li tqiegħed fuq is- suq, f’ din il- popolazzjoni kienu rappurtat każijiet rari ta ’ bżieżaq bil- materja fil- ġilda.
Clinically significant laboratory abnormalities frequently (≥ 5%) occurred including increases in alkaline phosphatase; AST and bilirubin which were believed to be related to the underlying disease and not Caelyx.
Anormalitajiet frekwenti tal- laboratorju klinikament sinifikanti (≥ 5%) li seħħew kienu jinkludu żidiet f’ alkaline phosphatase; AST u bilirubin li kienu meqjusa relatati mal- marda primarja u mhux ma ’ Caelyx.
Reduction in haemoglobin and platelets were less frequently (< 5%) reported.
Tnaqqis ta ’ l- emoglobulina u plejtlets kien rappurtat b' mod anqas frekwenti (< 5%).
Sepsis related to leukopaenia was rarely (< 1%) observed.
Sepsis relatata mal- lewkopenija ġiet innutata rarament (< 1%).
Some of these abnormalities may have been related to the underlying HIV infection and not Caelyx.
X' uħud minn dawn l- abnormalitajiet setgħu kienu relatati ma 'l- infezzjoni HIV primarja u mhux ma’ Caelyx.
All patients:
Il- pazjenti kollha:
100 out of 929 patients (10.8%) with solid tumours were described as having an infusion-associated reaction during treatment with Caelyx as defined by the following Costart terms: allergic reaction, anaphylactoid reaction, asthma, face oedema, hypotension, vasodilatation, urticaria, back pain, chest pain, chills, fever, hypertension, tachycardia, dyspepsia, nausea, dizziness, dyspnoea, pharyngitis, rash, pruritus, sweating, injection site reaction and medicinal product interaction.
100 mid- 929 pazjent (10. 8%) b' tumuri solidi ġew deskritti bħala li kellhom reazzjonijiet assoċjati ma 'l- infużjoni waqt it- trattament b’ Caelyx skond it- terminoloġija Costart li ġejja: reazzjoni allerġika, reazzjoni anafilattojdika, ażżma, edima fil- wiċċ, pressjoni baxxa, vażodilatazzjoni, urtikarja, uġigħ fid- dahar, uġigħ fis- sider, dehxiet, deni, pressjoni għolja, takikardja, dispepsja, tqallih, sturdament, qtugħ ta ’ nifs, farinġite, raxx, ħakk, għaraq, reazzjoni fil- post mnejn tingħata l- injezzjoni u nuqqas ta ’ qbil ma ’ prodotti mediċinali.
Permanent treatment discontinuation was infrequently reported at 2%.
Waqfien permanenti tat- trattament ġie rrappurtat b' mod rari b' rata ta '2%.
A similar incidence of infusion reactions (12.4%) and treatment discontinuation (1.5%) was observed in the breast cancer program.
Inċidenza simili ta 'reazzjonijiet għall- infużjoni (12. 4%) u waqfien tat- trattament (1. 5%) kienu nnotati fil- programm ta' kanċer tas- sider.
In patients with multiple myeloma receiving Caelyx plus bortezomib, infusion-associated reactions have been reported at a rate of 3%.
F’ pazjenti b’ majeloma multipla li kienu qed jirċievu Caelyx ma ’ bortezomib, reazzjonijiet assoċjati ma ’ l- infużjoni kienu rrappurtati b’ rata ta ’ 3%.
In patients with AIDS-KS, infusion-associated reactions, were characterised by flushing, shortness of breath, facial oedema, headache, chills, back pain, tightness in the chest and throat and/ or hypotension and can be expected at the rate of 5% to 10%.
F' pazjenti bl- AIDS- KS, ir- reazzjonijiet marbuta ma 'l- infużjoni kienu kkaratterizzati minn fawriet, qtugħ ta' nifs, edima fil- wiċċ, uġigħ ta 'ras, dehxiet, uġigħ fid- dahar, tagħfis fis- sider u l - griżmejn u/ jew pressjoni baxxa u wieħed jista' jistenna li jseħħu b' rata ta 'bejn 5% u 10%.
Very rarely, convulsions have been observed in relation to infusion reactions.
Rari ħafna, konvulżjonijiet kienu osservati b’ mod li kienu relatati mar- reazzjonijiet għall- infużjoni.
In all patients, infusion associated reactions occurred primarily during the first infusion.
Fil- pazjenti kollha, dawn seħħew primarjament waqt l- ewwel infużjoni.
Temporarily stopping the infusion usually resolves these symptoms without further therapy.
Il- waqfien temporanju ta 'l- infużjoni s - soltu jsib tarf ta' dawn is- sintomi mingħajr terapija oħra.
In nearly all patients, Caelyx treatment can be resumed after all symptoms have resolved without recurrence.
F' kważi l- pazjenti kollha, it- trattament b’ Caelyx jista 'jerġa jitkompla wara li jkunu għebu s- sintomi kollha mingħajr ma jerġgħu jseħħu.
Infusion reactions rarely recur after the first treatment cycle with Caelyx (see section 4.2).
Ir - reazzjonijiet għall- infużjoni rari li jseħħu wara l- ewwel ċiklu ta 'trattament b’ Caelyx (ara sezzjoni 4. 2).
Myelosuppression associated with anaemia, thrombocytopaenia, leukopaenia, and rarely febrile neutropaenia, has been reported in Caelyx -treated patients.
19 Majelosoppressjoni assoċjata ma ’ anemija, tromboċitopenja, lewkopenja, u rarament, newtropenja bid - deni, kienu rappurtati f’ pazjenti trattati b’ Caelyx.
Stomatitis has been reported in patients receiving continuous infusions of conventional doxorubicin hydrochloride and was frequently reported in patients receiving Caelyx.
Stomatite ġiet irrapurtata f' pazjenti li kienu qed jieħdu trattament kontinwu b’ doxorubicin hydrochloride konvenzjonali u ġiet rappurtata spiss f' pazjenti li kienu qed jieħdu Caelyx.
It did not interfere with patients completing therapy and no dosage adjustments are generally required, unless stomatitis is affecting a patient’ s ability to eat.
Dan ma fixkilx lill- pazjenti li spiċċaw it- terapija u l- ebda tibdil fid- dożaġġ ma jkun meħtieġ ġeneralment, sakemm l- istomatite ma tkunx qed taffettwa l- kapaċità tal- pazjent li jiekol.
In this case, the dose interval may be extended by 1 - 2 weeks or the dose reduced (see section 4.2).
F' dan il- każ, l- intervall bejn id- dożi jista 'jittawwal b' 1- 2 ġimgħat jew id- doża titnaqqas (ara sezzjoni 4. 2).
19 An increased incidence of congestive heart failure is associated with doxorubicin therapy at cumulative lifetime doses > 450 mg/ m2 or at lower doses for patients with cardiac risk factors.
Inċidenza ogħla ta 'insuffiċjenza tal- qalb konġestiva hi marbuta mat- terapija b’ doxorubicin f' dożi kumulattivi tul il- ħajja ta '> 450 mg/ m2 jew f' dożi aktar baxxi f' pazjenti b' fatturi ta' riskju kardijaku.
Endomyocardial biopsies on nine of ten AIDS-KS patients receiving cumulative doses of Caelyx greater than 460 mg/ m2 indicate no evidence of anthracycline-induced cardiomyopathy.
Bijopsiji endomijokardiċi f’ disa 'minn għaxar pazjenti li kienu qegħdin jieħdu dożi kumulattivi ta' Caelyx akbar minn 460 mg/ m2 ma juru l- ebda prova ta 'kardjomijopatija minħabba anthracycline.
The recommended dose of Caelyx for AIDS-KS patients is 20 mg/ m2 every two-to-three weeks.
Id - doża rakkomandata ta 'Caelyx għal pazjenti bl- AIDS- KS hi ta' 20 mg/ m2 kull ħmistax jew tlett ġimgħat.
The cumulative dose at which cardiotoxicity would become a concern for these AIDS-KS patients (> 400 mg/ m2) would require more than 20 courses of Caelyx therapy over 40 to 60 weeks.
Id- doża kumulattiva li biha l- kardjotossiċità ssir problema għal dawn il- pazjenti bl- AIDS- KS (> 400 mg/ m2) tkun teħtieġ 20 kors ta 'terapija b’ Caelyx fuq iżjed minn 40 sa 60 ġimgħa.
In addition, endomyocardial biopsies were performed in 8 solid tumour patients with cumulative anthracycline doses of 509 mg/ m2 – 1,680 mg/ m2.
Barra minn dan saru bijopsiji endomijokardijaċi f' 8 pazjenti b' tumuri solidi b' dożi kumulattivi ta 'anthracycline ta' 509 mg/ m2 – 1, 680 mg/ m2.
The range of Billingham cardiotoxicity scores was grades 0 - 1.5.
Il- medda ta 'livelli ta' kardjotossiċità Billingham kienu ta ’ gradi 0 - 1. 5.
These grading scores are consistent with no or mild cardiac toxicity.
Dawn ir- riżultati fil- gradazzjoni huma konsistenti ma ’ nuqqas ta 'tossiċità kardijaka jew tossiċità kardijaka ħafifa.
In the pivotal phase III trial versus doxorubicin, 58/ 509 (11.4%) randomized subjects (10 treated with Caelyx at a dose of 50 mg/ m2/ every 4 weeks versus 48 treated with doxorubicin at a dose of 60 mg/ m2/ every 3 weeks) met the protocol-defined criteria for cardiac toxicity during treatment and/ or follow-up.
Fil- provi pivotali tal- fażi III versus doxorubicin, 58/ 509 (11. 4%) suġġetti randomized (10 ttrattati b’ Caelyx b' doża ta '50 mg/ m2/ kull 4 ġimgħat versus 48 ittrattati b’ doxorubicin b' doża ta' 60 mg/ m2/ kull 3 ġimgħat) laħqu l- kriterji skond il- protokoll għall- kardjotossiċità waqt it- trattament u/ jew wara t- trattament.
Cardiac toxicity was defined as a decrease of 20 points or greater from baseline if the resting LVEF remained in the normal range or a decrease of 10 points or greater if the LVEF became abnormal (less than the lower limit for normal).
Il- kardjotossiċità ġiet deskritta bħala tnaqqis ta '20 punt jew iżjed mill- linja bażika jekk l - LVEF jibqa' fil- medda normali jew tnaqqis ta '10 punti jew aktar jekk l- LVEF sar anormali (anqas mill- limitu l- iżjed baxx tan- normali).
None of the 10 Caelyx subjects who had cardiac toxicity by LVEF criteria developed signs and symptoms of CHF.
L- ebda wieħed mill- 10 pazjenti ttrattati b’ Caelyx li kellhom kardjotossiċità skond il- kriterji LVEF ma żviluppa sinjali jew sintomi ta 'CHF.
In contrast, 10 of 48 doxorubicin subjects who had cardiac toxicity by LVEF criteria also developed signs and symptoms of CHF.
B' kuntrast ma 'dan, 10 mit- 48 suġġett b’ doxorubicin li kellhom kardjotossiċità skond il- kriterji LVEF żviluppaw ukoll sinjali u sintomi ta' CHF.
In patients with solid tumours, including a subset of patients with breast and ovarian cancers, treated at a dose of 50 mg/ m2/ cycle with lifetime cumulative anthracycline doses up to 1,532 mg/ m2, the incidence of clinically significant cardiac dysfunction was low.
F' pazjenti b' tumuri solidi, fosthom sottogrupp ta 'pazjenti b' kanċer tas- sider jew ta ’ l- ovarji, ittrattati b' doża ta' 50 mg/ m2/ ċiklu b' dożi ta 'anthracycline kumulattivi għall- ħajjithom sa 1, 532 mg/ m2, l - inċidenza ta' disfunzjoni kardijaka klinikament sinifikanti kienet baxxa.
Of the 418 patients treated with Caelyx 50 mg/ m2/ cycle, and having a baseline measurement of left ventricular ejection fraction (LVEF) and at least one follow-up measurement assessed by MUGA scan, 88 patients had a cumulative anthracycline dose of > 400 mg/ m2, an exposure level associated with an increased risk of cardiovascular toxicity with conventional doxorubicin.
Mill- 418 pazjent ittrattati b’ Caelyx 50 mg/ m2/ ċiklu u li kellhom kejl ta 'linja bażika ta' frazzjoni tal- ħruġ ventrikolari tax- xellug (LVEF) u għalmenu kejl wieħed ta 'wara l- kura mkejjel b' skan MUGA, 88 pazjent kellhom doża kumulattiva ta' anthracycline ta '> 400 mg/ m2, livell ta' esponiment assoċjat ma 'riskju akbar ta' tossiċità kardjovaskolari b’ doxorubicin konvenzjonali.
Only 13 of these 88 patients (15%) had at least one clinically significant change in their LVEF, defined as an LVEF value less than 45% or a decrease of at least 20 points from baseline.
13 biss minn dawn it- 88 pazjent (15%) kellhom mill- anqas tibdil wieħed klinikament sinifikanti fil- valur ta ’ l- LVEF tagħhom, definit bħala valur LVEF anqas minn 45% jew tnaqqis ta 'mill- anqas 20 punt mill- linja bażika.
Furthermore, only 1 patient (cumulative anthracycline dose of 944 mg/ m2), discontinued study treatment because of clinical symptoms of congestive heart failure.
Barra minn dan pazjent 1 biss (doża kumulattiva ta 'anthracycline ta' 944 mg/ m2), waqqaf it- trattament minħabba sintomi kliniċi ta 'insuffiċjenza tal- qalb konġestiva.
As with other DNA-damaging antineoplastic agents, secondary acute myeloid leukemias and myelodysplasias have been reported in patients having received combined treatment with doxorubicin.
Bħalma jiġri b' sustanzi antinejoplastiċi oħra li jagħmlu ħsara lid- DNA, ġew irrappurtati lewċemiji majelojdiċi sekondarji akuti u majelojdisplażiji f' pazjenti li kienu ngħataw trattament kombinat b’ doxorubicin.
Therefore, any patient treated with doxorubicin should be kept under haematological supervision.
Għalhekk kwalunkwe pazjent ittrattat b’ doxorubicin għandu jinżamm taħt superviżjoni ematoloġika.
Although local necrosis following extravasation has been reported very rarely, Caelyx is considered to be an irritant.
Għalkemm in- nekrożi wara fsada f’ xi tessut ġiet irrappurtat rarament ħafna, Caelyx jitqies bħala irritanti.
Animal studies indicate that administration of doxorubicin hydrochloride as a liposomal formulation reduces the potential for extravasation injury.
Studji fl- annimali juru illi l- għoti ta 'doxorubicin hydrochloride bħala formulazzjoni liposomali jnaqqas il- potenzjal għal dannu minn fsada f’ xi tessut.
If any signs or symptoms of extravasation occur (e. g., stinging, erythema) terminate the infusion immediately and restart in another vein.
Jekk iseħħu xi sinjali jew sintomi ta 'fsada f’ xi tessut (eż. tingiż, ħmura) waqqaf l- infużjoni immedjatament u erġa' ibda ġo vina oħra.
The application of ice over the site of extravasation for approximately 30 minutes may be helpful in alleviating the local reaction.
It - tqegħid ta 'silġ fil- post tal- fsada fit- tessut għal madwar 30 minuta jista' jgħin biex itaffi r- reazzjoni fil - post.
Caelyx must not be given by the intramuscular or subcutaneous route.
Caelyx m' għandux jingħata b' rotta intramuskolari jew taħt it- tessuti tal- ġilda.
Recall of skin reaction due to prior radiotherapy has rarely occurred with Caelyx administration.
20 Tiġdid ta 'reazzjoni fil- ġilda minħabba radjoterapija preċedenti rari seħħet bl- użu ta’ Caelyx.
Following the marketing of Caelyx, serious skin conditions including erythema multiforme, Stevens Johnson syndrome and toxic epidermal necrolysis have been reported very rarely.
Wara it- tqegħid fis- suq ta ’ Caelyx, kondizzjoni serja tal- ġilda inkluża erythema multiforme, sindrome Stevens Johnsons u nekroliżi tossika tal- ġilda kienu rappurtati rari ħafna.
In patients treated with Caelyx, cases of venous thromboembolism, including thrombophlebitis, venous thrombosis and pulmonary embolism have been seen uncommonly.
F’ pazjenti kkurati b’ Caelyx, każijiet ta ’ tromboemboliżmu fil- vini, inklużi tromboflebite, trombożi fil - vini u emboliżmu fil- pulmun deheru b’ mod mhux komuni.
However, because patients with cancer are at increased risk for thromboembolic disease, a causal relationship cannot be determined.
Madankollu, peress li pazjenti b’ tumur għandhom riskju akbar ta ’ mard trombo- emboliku, ma jistax ikun stabbilit x’ kienet il- kawża.
20 Acute overdosing with doxorubicin hydrochloride worsens the toxic effects of mucositis, leukopaenia and thrombocytopaenia.
Doża eċċessiva akuta b’ doxorubicin hydrochloride żżid l- effetti tossiċi ta ’ mukożite, lewkopenija u tromboċitopenja.
Treatment of acute overdose of the severely myelosuppressed patient consists of hospitalisation, antibiotics, platelet and granulocyte transfusions and symptomatic treatment of mucositis.
It- trattament ta 'doża eċċessiva akuta ta' pazjent gravement majelosoppress tikkonsisti fit- teħid l- isptar, antibijotiċi, trasfużjonijiet ta 'plejtlets u granuloċiti u trattament sintomatiku tal- mukożite.
Cytotoxic agents (anthracyclines and related substances), ATC code:
Sustanzi ċitotossiċi (anthracyclines u sustanzi relatati) Kodiċi ATC:
The active ingredient of Caelyx is doxorubicin hydrochloride, a cytotoxic anthracycline antibiotic obtained from Streptomyces peucetius var. caesius.
Is- sustanza attiva ta’ Caelyx hija doxorubicin hydrochloride, antibijotiku anthracycline ċitotossiku li jiġi minn Streptomyces peucetius var. caesius.
The exact mechanism of the antitumour activity of doxorubicin is not known.
Il- mekkaniżmu preċiż ta 'l- attività anti- tumurali ta ’ doxorubicin mhux magħruf.
It is generally believed that inhibition of DNA, RNA and protein synthesis is responsible for the majority of the cytotoxic effects.
B’ mod ġenerali huwa maħsub illi l- impediment tad- DNA, RNA u tas - sinteżi proteinika huma responsabbli għall- biċċa l- kbira ta 'l- effetti ċitotossiċi.
This is probably the result of intercalation of the anthracycline between adjacent base pairs of the DNA double helix thus preventing their unwinding for replication.
Dan probabliment huwa ir- riżultat ta 'l- interkalar ta' anthracycline bejn il- pari ta ’ bażijiet ħdejn xulxin ta 'l- elika doppja tad - DNA u b' hekk iżommu milli tissepara biex titkattar.
A phase III randomized study of Caelyx versus doxorubicin in patients with metastatic breast cancer was completed in 509 patients.
Studju randomized tal- fażi III ta ’ Caelyx versus doxorubicin f' pazjenti b' kanċer tas- sider metastatiku tlesta f' 509 pazjent.
The protocol-specified objective of demonstrating non-inferiority between Caelyx and doxorubicin was met, the hazard ratio (HR) for progression-free survival (PFS) was 1.00 (95% CI for HR=0.82 - 1.22).
Il- mira stabbilita skond il- protokoll biex jintwera li Caelyx mhux inferjuri għal doxorubicin ntlaħqet, il- proporzjon ta 'riskju (HR) għal sopravivenza minn progressjoni tal- marda (PFS) kien 1. 00 (95% CI għal HR=0. 82 - 1. 22).
The treatment HR for PFS when adjusted for prognostic variables was consistent with PFS for the ITT population.
It- trattament HR għall- PFS meta rranġata għall - varjanti mbassra kien konsistenti ma 'PFS għall- popolazzjoni ITT.
The primary analysis of cardiac toxicity showed the risk of developing a cardiac event as a function of cumulative anthracycline dose was significantly lower with Caelyx than with doxorubicin (HR=3.16, p < 0.001).
L- analiżi primarja ta 'kardjotossiċità wriet li r- riskju li jiiżviluppa avveniment kardijaku f' relazzjoni mad- doża kumulattiva ta' anthracycline kien iżjed baxx b' mod sinifikanti meta jintuża Caelyx milli doxorubicin (PR=3. 16, p < 0. 001).
At cumulative doses greater than 450 mg/ m2 there were no cardiac events with Caelyx.
F' dożi kumulattivi ogħla minn 450 mg/ m2 ma seħħewx avvenimenti kardijaċi b’ Caelyx.
A phase III comparative study of Caelyx versus topotecan in patients with epithelial ovarian cancer following the failure of first-line, platinum based chemotherapy was completed in 474 patients.
Studju komparattiv ta ’ fażi III ta ’ Caelyx versus topotecan f' pazjenti b' kanċer ta ’ l- ovarji epitiljali wara li kienet falliet il- kura preferita b’ kemoterapija ta 'platinum, tlesta f' 474 pazjent.
There was a benefit in overall survival (OS) for Caelyx-treated patients over topotecan-treated patients as indicated by a hazard ratio (HR) of 1.216 (95% CI; 1.000, 1.478), p=0.050.
Kien hemm benefiċċju fis- sopravivenza ġenerali (OS) għall- pazjenti trattati b’ Caelyx fuq dawk b’ topotecan kif jidher mill- proporzjon ta ’ periklu (HR) ta ’ 1. 216 (95% CI; 1. 000, 1. 478), p=0. 050.
The survival rates at 1, 2 and 3 years were 56.3%, 34.7% and 20.2% respectively on Caelyx, compared to 54.0%, 23.6% and 13.2% on topotecan.
Ir- rati ta ’ sopravivenza f’ etajiet ta ’ sena, 2 u 3 snin kienu 56. 3%, 34. 7% u 20. 2% rispettivament fuq Caelyx, imqabbla ma ’ 54. 0%, 23. 6% u 13. 2% fuq topotecan.
For the sub-group of patients with platinum-sensitive disease the difference was greater:
Għas- sottogrupp ta ’ pazjenti li kellhom marda sensittiva għall- platinum, id- differenza kienet akbar:
HR of 1.432 (95% CI; 1.066, 1.923), p=0.017.
HR ta ’ 1. 432 (95% CI; 1. 066, 1. 923), p=0. 017.
The survival rates at 1, 2 and 3 years were 74.1%, 51.2% and 28.4% respectively on Caelyx, compared to 66.2%, 31.0% and 17.5% on topotecan.
Ir- rati ta ’ sopravivenza f’ etajiet ta ’ sena, 2 u 3 snin kienu 74. 1%, 51. 2% u 28. 4% rispettivament fuq Caelyx, imqabbla ma ’ 66. 2%, 31. 0% u 17. 5% fuq topotecan.
The treatments were similar in the sub-group of patients with platinum refractory disease:
It- trattamenti kienu simili fis- sottogrupp ta ’ pazjenti b’ marda refrattorja tal- platinum:
HR of 1.069 (95% CI; 0.823, 1.387), p=0.618.
HR ta ’ 1. 069 (95% CI; 0. 823, 1. 387), p=0. 618.
The survival rates at 1, 2 and 3 years were 41.5%, 21.1% and 13.8% respectively on Caelyx, compared to 43.2%, 17.2% and 9.5% on topotecan.
Ir- rati ta ’ sopravivenza f’ etajiet ta ’ sena, 2 u 3 snin kienu ta ’ 41. 5%, 21. 1% u 13. 8% rispettivament b’ Caelyx, imqabbla ma ’ 43. 2%, 17. 2% u 9. 5% fuq topotecan.
A phase III randomized, parallel-group, open-label, multicentre study comparing the safety and efficacy of Caelyx plus bortezomib combination therapy with bortezomib monotherapy in patients with multiple myeloma who have received at least 1 prior therapy and who did not progress while receiving anthracycline-based therapy, was conducted in 646 patients.
21 Studju multiċentriku, open- label, bi gruppi paralleli, randomized ta ’ fażi III li kien iqabbel is- sigurtà u l- effikaċja tat- terapija kombinata b’ Caelyx u bortezomib ma ’ monoterapija b’ bortezomib f’ pazjenti b’ majeloma multipla li rċevew mill- anqas terapija 1 minn qabel u li ma avvanzawx filwaqt li kienu qed jirċievu terapija bbażata fuq anthracycline, sar f’ 646 pazjenti.
There was a significant improvement in the primary endpoint of time to progression (TTP) for patients treated with combination therapy of Caelyx plus bortezomib compared to patients treated with bortezomib monotherapy as indicated by a risk reduction (RR) of 35% (95% CI; 21-47%), p < 0.0001, based on 407 TTP events.
Kien hemm titjib sinifikanti fil- fini ewlieni għaż- żmien biex avvanza (TTP) għall- pazjenti kkurati bit- terapija kombinata b’ Caelyx u bortezomib meta mqabbla ma ’ pazjenti kkurati b’ monoterapija b’ bortezomib hekk kif indikat b’ nuqqas fir- riskju (RR) ta ’ 35% (95% CI; 21- 47%), p < 0. 0001, ibbażat fuq 407 każ ta ’ TTP.
The median TTP was 6.9 months for the bortezomib monotherapy patients compared with 8.9 months for the Caelyx plus bortezomib combination therapy patients.
Il - medjan tat- TTP kien 6. 9 xhur għall- pazjenti fuq monoterapija b’ bortezomib meta mqabbel ma ’ 8. 9 xhur għall- pazjenti fuq terapija kombinata b’ Caelyx u bortezomib.
A protocol-defined interim analysis (based on 249 TTP events) triggered early study termination for efficacy.
Analiżi interim definita mill - protokol (ibbażata fuq 294 każ ta ’ TTP) ikkawżat waqfien kmieni ta ’ l- istudju għall- effikaċja.
This interim analysis showed a TTP risk reduction of 45% (95% CI; 29-57%), p < 0.0001.
Din l - analiżi interim uriet tnaqqis fir- riskju TTP ta ’ 45% (95% CI; 29- 57%), p < 0. 0001.
The median TTP was 6.5 months for the bortezomib monotherapy patients compared with 9.3 months for the Caelyx plus
It- TTP medjan kien 6. 5 xhur għall- pazjenti fuq monoterapija b’ bortezomib meta mqabbel ma ’ 9. 3 xhur għall- pazjenti fuq terapija kombinata b’ Caelyx u bortezomib.
These results, though not mature, constituted the protocol defined final analysis.
Dawn ir- riżultati, għalkemm mhux maturi, ikkonstitwixxew l- analiżi finali definita mill- protokol.
Caelyx is a long-circulating pegylated liposomal formulation of doxorubicin hydrochloride.
Caelyx huwa formulazzjoni pegilata liposomali li ddum tiċċirkola ta 'doxorubicin hydrochloride.
Pegylated liposomes contain surface-grafted segments of the hydrophilic polymer methoxypolyethylene glycol (MPEG).
Il - liposomi pegilati fihom segmenti mlaqqma fil- wiċċ tal- hydrophilic polymer methoxypolyethylene glycol (MPEG).
These linear MPEG groups extend from the liposome surface creating a protective coating that reduces interactions between the lipid bilayer membrane and the plasma components.
Dawn il- kategoriji ta 'MPEG linejari joħorġu mill- wiċċ tal- liposoma biex joħolqu kisja protettiva li tnaqqas l- interazzjonijiet bejn il- membrana b’ żewġ saffi ta ’ lipidi u l- komponenti tal - plażma.
This allows the Caelyx liposomes to circulate for prolonged periods in the blood stream.
Dan jippermetti lill- liposomi ta’ Caelyx li jiċċirkolaw għal perijodi twal fid- demm.
Pegylated liposomes are small enough (average diameter of approximately 100 nm) to pass intact (extravasate) through defective blood vessels supplying tumours.
Il- liposomi pegilati huma żgħar biżżejjed (dijametru medju madwar 100 nm) biex jgħaddu sħaħ (barra mill- vini) minn vini tad- demm difettużi li jkunu jissupplixxu lit- tumuri.
Evidence of penetration of pegylated liposomes from blood vessels and their entry and accumulation in tumours has been seen in mice with C-26 colon carcinoma tumours and in transgenic mice with KS-like lesions.
Ix- xhieda ta 'penetrazzjoni ta' liposomi pegilati mill- vini tad- demm u d- dħul tagħhom u akkumulu fit- tumuri intwerew fil- ġrieden b' tumuri C- 26 karċinoma tal- kolon u fi ġrieden transġeniċi b' leżjonijiet bħall- KS.
The pegylated liposomes also have a low permeability lipid matrix and internal aqueous buffer system that combine to keep doxorubicin hydrochloride encapsulated during liposome residence time in circulation.
Il- liposomi pegilati għandhom ukoll matriċi lipida ta 'permejabilità baxxa u sistema interna ta' baffer akweju li jaħdmu flimkien biex iżommu doxorubicin hydrochloride enkapsulat fil- ħin ta 'residenza tal- liposoma fiċ - ċirkolazzjoni.
The plasma pharmacokinetics of Caelyx in humans differ significantly from those reported in the literature for standard doxorubicin hydrochloride preparations.
Il- famakokinetika tal- plażma fil- bniedem ta’ Caelyx hija differenti b' mod sinifikanti minn dik rappurtata fil- litteratura għall- preparati ta’ doxorubicin hydrochloride standard.
At lower doses (10 mg/ m2 – 20 mg/ m2) Caelyx displayed linear pharmacokinetics.
F' dożi iżjed baxxi (10 mg/ m2 – 20 mg/ m2) Caelyx wera farmakokinetika linejari.
Over the dose range of 10 mg/ m2 – 60 mg/ m2 Caelyx displayed non-linear pharmacokinetics.
Il- medda ta 'dożaġġ ta' 10 mg/ m2 – 60 mg/ m2 Caelyx wera farmakokinetiċi mhux- linejari.
Standard doxorubicin hydrochloride displays extensive tissue distribution (volume of distribution:
Doxorubicin hydrochloride standard wera distribuzzjoni estensiva fit- tessut (volum ta 'distribuzzjoni:
700 to 1,100 l/ m2) and a rapid elimination clearance (24 to 73 l/ h/ m2).
700 sa 1, 000 l/ m2) u tneħħija mgħaġġla mill- ġisem (24 sa 73 l/ h/ m2).
In contrast, the pharmacokinetic profile of Caelyx indicates that Caelyx is confined mostly to the vascular fluid volume and that the clearance of doxorubicin from the blood is dependent upon the liposomal carrier.
B' kuntrast ma 'dan, il- profil farmakokinetiku ta’ Caelyx juri li Caelyx jinżamm prinċipalment fil- volum ta' fluwidu vaskolari u l- clearance ta ’ doxorubicin mid- demm tiddependi mill- vettura tal- liposoma.
Doxorubicin becomes available after the liposomes are extravasated and enter the tissue compartment.
Doxorubicin ikun disponibbli wara li l- liposomi joħorġu mill - vini u jidħlu fil- kompartiment tat- tessut.
At equivalent doses, the plasma concentration and AUC values of Caelyx which represent mostly pegylated liposomal doxorubicin hydrochloride (containing 90% to 95% of the measured doxorubicin) are significantly higher than those achieved with standard doxorubicin hydrochloride preparations.
F' dożi ekwivalenti, il- konċentrazzjoni ta 'plażma u valuri AUC ta ’ Caelyx li jirrappreżentaw prinċipalment doxorubicin hydrochloride liposomali pegilat (fihom 90% sa 95% ta ’ doxorubicin imkejjel) huma ogħla b' mod sinifikanti minn dawk li jintlaħqu bil- preparazzjonijiet doxorubicin hydrochloride standard.
Caelyx should not be used interchangeably with other formulations of doxorubicin hydrochloride.
Caelyx m' għandux jinbidel bħala ekwivalenti ma 'formulazzjonijiet oħra ta' doxorubicin hydrochloride.
Population pharmacokinetics The pharmacokinetics of Caelyx was evaluated in 120 patients from 10 different clinical trials using the population pharmacokinetic approach.
Farmakokinetiċi tal- popolazzjoni Il- farmakokinetiċi ta’ Caelyx ġew evalwati f' 120 pazjent minn 10 provi kliniċi differenti bl- użu ta 'l - approċċ tal- farmakokinetika tal- popolazzjoni.
The pharmacokinetics of Caelyx over the dose range of 10 mg/ m2 to 60 mg/ m2 was best described by a two compartment non-linear model with zero order input and Michaelis-Menten elimination.
Il- farmakokinetika ta’ Caelyx fuq medda ta 'dożaġġ ta' 10 mg/ m2 – 60 mg/ m2 ġiet deskritta l- aħjar permezz ta 'mudell mhux linejari ta' żewġ kumpartimenti b' input ta 'ordni zero u eliminazzjoni Michaelis- Menten.
The mean intrinsic clearance of Caelyx was 0.030 l/ h/ m2 (range 0.008 to 0.152 l/ h/ m2) and the mean central volume of distribution was 1.93 l/ m2 (range 0.96 – 3.85 l/ m2) approximating the plasma volume.
Il- clearance medja intrinsika ta’ Caelyx kienet ta '0. 030 l/ h/ m2 (medda 0. 008 sa 0. 152 l/ h/ m2) u l- volum ta' distribuzzjoni ċentrali medju kien ta '
The apparent half-life ranged from 24 – 231 hours, with a mean of 73.9 hours.
Il- half- life apparenti kien ta 'bejn 24 – 231 siegħa, b' medja ta' 73. 9 siegħa.
Breast cancer patients The pharmacokinetics of Caelyx determined in 18 patients with breast carcinoma were similar to the pharmacokinetics determined in the larger population of 120 patients with various cancers.
Pazjenti B' Kanċer Tas- Sider Il- farmakokinetiċi ta ’ Caelyx stabbiliti f' 18- il pazjent b' karċinoma tas- sider kienu jixbhu lil dawk il - farmakokinetiċi stabbiliti f' popolazzjoni akbar ta '120 pazjent b' diversi tipi ta' kanċer.
The mean intrinsic clearance was 0.016 l/ h/ m2 (range 0.008 - 0.027 l/ h/ m2), the mean central volume of distribution was 1.46 l/ m2 (range 1.10 - 1.64 l/ m2).
It- tneħħija medja intrinsika kienet ta '0. 016 l/ h/ m2 (medda 0. 008 - 0. 027 l/ h/ m2), il- volum ċentrali medju ta' distribuzzjoni kien ta '1. 46 l/ m2 (medda 1. 10 - 1. 64 l/ m2).
The mean apparent half-life was 71.5 hours (range 45.2 - 98.5 hours).
Il- medja tal- half- life apparenti kienet ta '71. 5 siegħa (medda 45. 2 - 98. 5 siegħa).
Ovarian cancer patients The pharmacokinetics of Caelyx determined in 11 patients with ovarian carcinoma were similar to the pharmacokinetics determined in the larger population of 120 patients with various cancers.
Pazjenti B' Kanċer Ovarju Il- farmakokinetiċi ta ’ Caelyx stabbiliti fi 11- il pazjent b' karċinoma ovarja kienu jixbhu il - farmakokinetiċi stabbiliti f' popolazzjoni akbar ta '120 pazjent b' diversi tipi ta' kanċer.
The mean intrinsic clearance was 0.021 l/ h/ m2 (range 0.009 – 0.041 l/ h/ m2), the mean central volume of distribution was 1.95 l/ m2 (range 1.67 – 2.40 l/ m2).
Il- clearance medja intrinsika kienet ta '0. 021 l/ h/ m2 (medda 0. 009 - 0. 041 l/ h/ m2), il- volum ċentrali medju ta' distribuzzjoni kien ta '1. 95 l/ m2 (medda 1. 67 - 2. 40 l/ m2).
The mean apparent half-life was 75.0 hours (range 36.1 – 125 hours).
Il- medja tal- half- life apparenti kienet ta '75 siegħa (medda 36. 1 - 125 siegħa).
22 AIDS-KS patients The plasma pharmacokinetics of Caelyx were evaluated in 23 patients with KS who received single doses of 20 mg/ m2 administered by a 30-minute infusion.
Pazjenti Bl- AIDS- KS Il- farmakokinetiċi tal- plażma ta’ Caelyx ġew evalwati f' 23 pazjent bis- SK li ngħataw dożi ta ’ darba ta '20 mg/ m2 mogħtija b' infużjoni ta' 30 minuta.
The pharmacokinetic parameters of Caelyx (primarily representing pegylated liposomal doxorubicin hydrochloride and low levels of unencapsulated doxorubicin hydrochloride) observed after the 20 mg/ m2 doses are presented in Table 8.
Il- parametri farmakokinetiċi ta ’ Caelyx (primarjament jirrappreżentaw doxorubicin hydrochlorinated liposomali pegilat u livelli baxxi ta 'doxorubicin hydrochlorinated mhux enkapsulati) li ġew innotati wara l- użu ta' dożi ta '20 mg/ m2 qed jiġu ppreżentati f' Tabella 8.
Pharmacokinetic Parameters in Caelyx-Treated AIDS-KS
Parametri farmakokinetiċi f' pazjenti bl- AIDS- KS ttrattati b’ Caelyx
Mean + Standard Error
Medja + Żball Standard
Maximum Plasma Concentration* (µg/ ml)
8. 34 ± 0. 49 Konċentrament ta 'Plażma Massimu * (µg/ ml)
Plasma Clearance (l/ h/ m2) Volume of Distribution (l/ m2) AUC (µg/ ml⋅ h) λ 1 half-life (hours) λ 2 half-life (hours) *Measured at the end of a 30-minute infusion
Clearance mill- Plażma (l/ h/ m2) Volum ta 'Distribuzzjoni (l/ m2) AUC (µg/ ml⋅h) λ1 half- life (sigħat) λ2 half- life( sigħat) * Imkejjel fl- aħħar ta' infużjoni ta '30 minuta
0.041 ± 0.004 2.72 ± 0.120 590.00 ± 58.7 5.2 ± 1.4 55.0 ± 4.8
0. 041 ± 0. 004 2. 72 ± 0. 120 590. 00 ± 58. 7 5. 2 ± 1. 4 55. 0 ± 4. 8
In repeat dose studies conducted in animals, the toxicity profile of Caelyx appears very similar to that reported in humans who receive long-term infusions of standard doxorubicin hydrochloride.
Fi studji ta 'dożi ripetuti li saru fuq annimali, il- profil ta' tossiċità ta ’ Caelyx jidher li jixbah lil dak rappurtat fil- bniedem f' pazjenti li jingħataw infużjonijiet ta 'doxorubicin hydrochloride standard fit- tul.
With Caelyx, the encapsulation of doxorubicin hydrochloride in pegylated liposomes results in these effects having a differing strength, as follows.
Fil- każ ta ’ Caelyx, l- enkapsular ta ’ doxorubicin hydrochloride f' liposomi pegilati jwassal biex dawn l - effetti jkollhom qawwiet differenti kif ġej:
Cardiotoxicity:
Kardjotossiċità:
Studies in rabbits have shown that the cardiotoxicity of Caelyx is reduced compared with conventional doxorubicin hydrochloride preparations.
Studji fil- fniek urew illi l- kardjotossiċità ta’ Caelyx hi mnaqqsa meta mqabbla ma 'preparati konvenzjonali ta' doxorubicin hydrochloride.
Dermal toxicity:
Tossiċità fil- ġilda:
In studies performed after the repeated administration of Caelyx to rats and dogs, serious dermal inflammations and ulcer formations were observed at clinically relevant dosages.
F' studji li saru wara li ngħataw dożi ripetuti lil firien u lill- klieb, ġew innutati f' dożaġġ klinikament rilevanti, infjammazzjonijiet serji fil- ġilda u formazzjoni ta 'ulċeri.
In the study in dogs, the occurrence and severity of these lesions was reduced by lowering the dose or prolonging the intervals between doses.
Fl- istudju fil - klieb l- okkorrenza u l- gravità ta 'dawn il- leżjonijiet tnaqqset billi tbaxxiet id- doża jew billi ttawlu l - intervalli bejn id- dożi.
Similar dermal lesions, which are described as palmar-plantar erythrodysesthesia were also observed in patients after long-term intravenous infusion (see section 4.8).
Leżjonijiet fil- ġilda bħal dawn, li huma deskritti bħala palmar- plantar erythrodysesthesia ġew innutati wkoll f' pazjenti wara infużjonijiet fil- vina fit- tul (ara sezzjoni 4. 8).
Anaphylactoid response:
23 Rispons anafilattojdiku:
During repeat dose toxicology studies in dogs, an acute response characterised by hypotension, pale mucous membranes, salivation, emesis and periods of hyperactivity followed by hypoactivity and lethargy was observed following administration of pegylated liposomes (placebo).
Waqt studji ta 'tossikoloġija ta' dożi ripetuti fil- klieb, ripons akut ikkaratteriżat minn pressjoni baxxa, membrani tal- mukożi pallidi, salivazzjoni, emeżi u perijodi ta 'iperattività segwiti minn attività mnaqqsa u letarġija ġew innutati wara l- użu ta ’ liposomi pegilati (plaċebo).
A similar, but less severe response was also noted in dogs treated with Caelyx and standard doxorubicin.
Rispons simili iżda anqas gravi ġiet innutata wkoll fi klieb ittrattati b’ Caelyx u doxorubicin standard.
The hypotensive response was reduced in magnitude by pretreatment with antihistamines.
Ir- rispons ta 'pressjoni baxxa kien anqas fid- daqs meta ngħata trattament qabel bl- anti- istaminiċi.
However, the response was not life-threatening and the dogs recovered quickly upon discontinuation of treatment.
Madankollu r- rispons ma kienx ta ’ theddida għall- ħajja u l- klieb irkupraw malajr wara li twaqqaf it - trattament.
Local toxicity:
Tossiċità ta ’ mnejn jingħata:
Subcutaneous tolerance studies indicate that Caelyx, as against standard doxorubicin hydrochloride, causes slighter local irritation or damage to the tissue after a possible extravasation.
Studji ta 'tolleranza fit- tessuti ta ’ taħt il- ġilda juru li Caelyx, kuntrarjament għal doxorubicin hydrochloride standard, jikkawża irritazzjoni mnejn jingħata iżjed ħafifa jew ħsara fit- tessut aktar ħafifa wara possibilità li jkun ħareġ mill- vini.
Mutagenicity and carcinogenicity:
Mutaġeniċità u karċinoġeniċità:
Although no studies have been conducted with Caelyx, doxorubicin hydrochloride, the pharmacologically active ingredient of Caelyx, is mutagenic and carcinogenic.
Għalkemm ma sarux studji b’ Caelyx, doxorubicin hydrochloride, is - sustanza farmakoloġikament attiva f’ Caelyx, hi mutaġenika u karċinoġenika.
Pegylated placebo liposomes are neither mutagenic nor genotoxic.
Liposomi plaċebo pegilati mhumiex mutaġeniċi u lanqas karċinoġeniċi.
23 Reproductive toxicity:
Tossiċità tas- sistema riproduttiva:
Caelyx resulted in mild to moderate ovarian and testicular atrophy in mice after a single dose of 36 mg/ kg.
Caelyx wassal għal atrofija ħafifa jew moderata ta ’ l- ovarja u tat - testikoli fil- ġrieden wara doża waħda ta '36 mg/ kg.
Decreased testicular weights and hypospermia were present in rats after repeat doses ≥ 0.25 mg/ kg/ day and diffuse degeneration of the seminiferous tubules and a marked decrease in spermatogenesis were observed in dogs after repeat doses of 1 mg/ kg/ day (see section 4.6).
Tnaqqis ta 'piż testikolari u tnaqqis fil- produzzjoni ta' sperma seħħew fil- firien wara dożi ripetuti ≥ 0. 25 mg/ kg/ jum u deġenerazzjoni tat- tubi li jġorri l - isperma u tnaqqis sostanzjali fil- produzzjoni ta 'sperma ġew innutati fil- klieb wara dożi ripetuti ta' 1 mg/ kg/ jum (ara sezzjoni 4. 6).
Nephrotoxicity:
Nefrotossiċità:
A study has shown that Caelyx at a single intravenous dose of over twice the clinical dose produces renal toxicity in monkeys.
Studju wera li Caelyx mogħti bħala doża ta ’ darba minn ġol vina ta ’ ‘ l fuq mid- doppju tad- doża klinika jwassal għal tossiċità renali ta ’ xadini.
Renal toxicity has been observed with even lower single doses of doxorubicin HCl in rats and rabbits.
Tossiċità renali intweriet anki b’ dożi aktar baxxi mogħtija f’ darba ta ’ doxorubicin HCl f’ firien u fniek.
Since an evaluation of the post-marketing safety database for Caelyx in patients has not suggested a significant nephrotoxicity liability of Caelyx, these findings in monkeys may not have relevance to patient risk assessment.
Peress li evalwazzjoni tad- dejtabejż ta ’ sigurtà ta ’ wara t- tqegħid fis- suq għal Caelyx f’ pazjenti ma weriex nefrotossiċità sinifikanti attribwita għal Caelyx, dawn is- sejbiet fix- xadini jista ’ jkun li ma jkollhomx rilevanza għall- istima tar- riskju fil - pazjenti.
α -(2-[1,2-distearoyl-sn-glycero(3)phosphooxy]ethylcarbamoyl)-ω -methoxypoly(oxyethylen)- 40 sodium salt (MPEG-DSPE) fully hydrogenated soy phosphatidylcholine (HSPC) cholesterol ammonium sulphate sucrose histidine water for injections hydrochloric acid sodium hydroxide
α - (2 - [1, 2- distearoyl - sn- glycero (3) phosphooxy] ethylcarbamoyl) - ω- methoxypoly (oxyethylen) - 40 sodium salt (MPEG- DSPE) fully hydrogenated soy phosphatidylcholine (HSPC) cholesterol ammonium sulphate sucrose histidine ilma għall- injezzjonijiet hydrochloric acid sodium hydroxide.
6.2 Incompatibilities
6. 2 Inkompatabilitajiet
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
Dan il- prodott mediċinali m' għandux jitħallat ma 'prodotti mediċinali oħrajn ħlief dawk imsemmija f' sezzjoni 6. 6.
20 months
20 xahar
After dilution:
Wara li jiġi dilwit:
- Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C to 8°C.
24
- From a microbiological point of view, the product should be used immediately.
- Mill- lat mikrobijoloġiku, il- prodott għandu jintuża minnufih.
If not used
Jekk ma jintużax minnufih, il -
immediately, in-use storage times and conditions prior to use are the responsibility of the user and should not be longer than 24 hours at 2°C to 8°C.
kundizzjonijiet u ż- żmien tal- ħażna waqt l- użu, huma responsabbiltà ta 'min jużah u m' għandhomx ikunu iżjed minn 24 siegħa f' 2°C sa 8°C.
- Partially used vials must be discarded.
- Kunjetti mhux użati għall- kollox għandhom jintremew.
Store in a refrigerator (2°C - 8°C).
Aħżen fil- friġġ (2°C sa 8°C).
Type I glass vials, each with a siliconised grey bromobutyl stopper, and an aluminium seal, with a deliverable volume of 10 ml (20 mg) or 25 ml (50 mg).
Kunjetti tal- ħġieġ Tip I, kull waħda b' tapp tal- bromobutyl griż silikonizzat u siġill ta 'l- aluminium, b' volum li jista' jintuża ta '10 ml (20 mg) jew 25 ml (50 mg).
Caelyx is supplied as a single pack or packs of ten vials.
Caelyx jinbiegħ bħala pakkett ta 'kunjett wieħed jew ta' għaxar kunjetti.
24 6.6 Special precautions for disposal
6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema
Do not use material that shows evidence of precipitation or any other particulate matter.
Tużax materjal li juri ħjiel ta 'preċipitazzjoni jew partikolat ieħor.
Caution must be exercised in handling Caelyx solution.
Wieħed irid joqgħod attent hu u juża s- soluzzjoni ta ’ Caelyx.
The use of gloves is required.
L- użu ta 'l- ingwanti hu meħtieġ.
If Caelyx comes into contact with skin or mucosa, wash immediately and thoroughly with soap and water.
Jekk Caelyx imiss il- ġilda jew il- mukoża, aħsel minnufih bl- ilma u s- sapun.
Caelyx must be handled and disposed of in a manner consistent with that of other anticancer medicinal products in accordance with local requirements.
Caelyx għandu jintuża u jintrema skond il- mod kif isir bil- prodotti mediċinali kontra l- kanċer l- oħrajn skond il- ħtiġiet lokali.
Determine the dose of Caelyx to be administered (based upon the recommended dose and the patient’ s body surface area).
Stabilixxi d- doża ta 'Caelyx li għandha tingħata (bbażata fuq id- doża rakkomandata u l- erja tas - superfiċje tal- ġisem tal- pazjent).
Take the appropriate volume of Caelyx up into a sterile syringe.
Iġbed il- volum xieraq ta 'Caelyx f' siringa sterili.
Aseptic technique must be strictly observed since no preservative or bacteriostatic agent is present in Caelyx.
Għandha tintuża teknika asettika bl- iżjed mod strett peress illi f’ Caelyx m’ hemmx sustanzi preżervattivi jew batterjostatiċi.
The appropriate dose of Caelyx must be diluted in 5% (50 mg/ ml) glucose solution for infusion prior to administration.
Id- doża appropjata ta 'Caelyx għandha tiġi dilwita f' 5% (50 mg/ ml) soluzzjoni glucose għall- infużjoni qabel ma tingħata.
For doses < 90 mg, dilute Caelyx in 250 ml, and for doses ≥ 90 mg, dilute Caelyx in 500 ml.
Għal dożi < 90 mg iddilwixxi Caelyx f' 250 ml u għal dożi ≥ 90 mg, iddilwixxi Caelyx f' 500 ml.
This can be infused over 60 or 90 minutes as detailed in 4.2.
Dan jista 'jiġi infuż fuq medda ta' 60 jew 90 minuta kif spjegat f '4. 2.
The use of any diluent other than 5% (50 mg/ ml) glucose solution for infusion, or the presence of any bacteriostatic agent such as benzyl alcohol may cause precipitation of Caelyx.
L- użu ta 'dilwent ieħor minflok 5% (50 mg/ ml) soluzzjoni glucose għall- infużjoni jew il- preżenza ta' sustanzi batterjostatiċi bħalma hu benzyl alcohol jista 'jwassal għall- preċipitazzjoni ta’ Caelyx.
It is recommended that the Caelyx infusion line be connected through the side port of an intravenous infusion of 5% (50 mg/ ml) glucose.
Huwa rrakkomandat li l- linja ta 'infużjoni ta’ Caelyx titqabbad mill- port tal- ġenb ta' l- infużjoni għal ġol vina ta '5% (50 mg/ ml) glucose.
Infusion may be given through a peripheral vein.
L- infużjoni tista 'ssir minn vina periferali.
Do not use with in-line filters.
Tużahx b’ filtri tal- pajp tad- dripp.
SP Europe Rue de Stalle 73 B – 1180 Bruxelles Belgium
SP Europe Rue de Stalle 73 B - 1180 Bruxelles Il- Belġju
EU/ 1/ 96/ 011/ 001 EU/ 1/ 96/ 011/ 002 EU/ 1/ 96/ 011/ 003 EU/ 1/ 96/ 011/ 004
EU/ 1/ 96/ 011/ 001 EU/ 1/ 96/ 011/ 002 EU/ 1/ 96/ 011/ 003
Date of first authorization:
Data ta ’ l- ewwel awtorizzazzjoni:
21 June 1996 Date of last renewal:
21 ta 'Ġunju 1996 Data ta ’ l- aħħar tiġdid:
19 May 2006
19 ta ’ Mejju 2006
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il - Mediċini (EMEA) http: // www. emea. europa. eu /
26 A.
26 ANNESS II
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE
DETENTUR TA ’ L- AWTORIZZAZZJONI TAL- MANIFATTURA RESPONSABBLI GĦALL- HRUĠ TAL- LOTT
SP Labo N. V., Industriepark 30, 2220, Heist-op-den-Berg, Belgium
SP Labo N. V., Industriepark 30, 2220, Heist- op- den- Berg, Il- Belġju
Pharmacovigilance system The MAH must ensure that the system of Pharmacovigilance, as described in version dated June 2007 presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and whilst the product is on the Market.
Sistema ta ’ Farmakoviilanza L- MAH għandu jaċċerta ruħu li s- sistema ta ’ Farmakoviilanza, hekk kif deskritta fil- verżjoni datata Ġunju 2007 preżentata f’ Modulu 1. 8. 1 ta ’ L- Applikazzjoni Għat- Tqegħid fis- Suq, tkun f’ lokha u taħdem qabel u waqt li l- prodott ikun fis- Suq.