qanastek/EMEA-V3 huggingface dataset:
For Section 4.3, the MAH proposal retained only two of the existing 8 contraindications (relating to hypersensitivity and breast feeding) and removed 6 (hepatic or renal impairment, cisplatin for patients with severe renal failure, pregnancy and lactation, combination with yellow fever, usage in children and concomitant administration of gemcitabine and radiotherapy).
Għal Sezzjoni 4. 3, il- proposta tal- MAH żammet biss tnejn mit- 8 kontraindikazzjonijiet eżistenti (li għandhom x’ jaqsmu mas- sensittività eċċessiva u t- treddigħ) u neħħiet 6 (indeboliment epatiku jew renali, cisplatin għal pazjenti b’ falliment renali sever, tqala u treddigħ, kumbinazzjoni mad- deni isfar, użu fit- tfal u għoti konkomitanti ta ’ gemcitabine u radjuterapija).
The CHMP was of the opinion that the MAH proposal was acceptable, but considered that interactions and conditions relevant for all cytotoxics are expected for gemcitabine and that adequate warning should therefore be provided in section 4.4 and 4.5.
Il- CHMP kien ta ’ l- opinjoni li l- proposta tal- MAH kienet aċċettabbli, iżda kkunsidra li l- interazzjonijiet u l- kundizzjonijiet relevanti għaċ- ċitotossiċi kollha huma mistennijin għal gemcitabine u li għaldaqstant twissija adegwata għandha tkun ipprovduta f’ sezzjoni 4. 4 u 4. 5.
Because no studies have been made in patients with renal or hepatic impaired, the CHMP did not consider there to be a need for an absolute contraindication, nor did it consider radiotherapy to be an absolute contra-indication.
Peress li ma sar l- ebda studju f’ pazjenti b’ indeboliment renali jew epatiku, il- CHMP ma kkunsidrax li hemm ħtieġa għall- kontraindikazzjoni assoluta, lanqas ma kkunsidra r- radjuterapija li hija kontra- indikazzjoni assoluta.
For Section 4.4, the MAH addressed impaired renal and hepatic function, paediatric recommendations and concomitant administration of gemcitabine and radiotherapy.
Għal Sezzjoni 4. 4, il- MAH indirizza funzjoni renali u epatika indebolita, rakkomandazzjonijiet pedjatriċi u għoti konkomittanti ta ’ gemcitabine u radjuterapija.
In general, the CHMP considered 13 the proposed wording to be adequate, but implemented a number of revisions, including sections on impaired bone-marrow function, combination with carboplatin and cisplatin, live attenuated vaccines and Pharmacovigilance reports on cardiovascular events and viral hepatitis reactivation.
B’ mod ġenerali, il- CHMP ikkunsidra li l- kitba proposta hija adegwata, iżda implimenta numru ta ’ reviżjonijiet, inklużi sezzjonijiet fuq funzjoni indebolita tal- mudullun, kombinazzjoni ma ’ carboplatin u cisplatin, vaċċini ħajjin attenwati u rapporti ta ’ Farmakoviġilanza fuq episodji kardjovaskulari u attivazzjoni mill- ġdid ta ’ epatite virali.
Sections 4.5, 4.6, 4.7, 4.8 and 4.9 were also harmonised.
Sezzjonijiet 4. 5, 4. 6, 4. 7, 4. 8 u 4. 9 ġew ukoll armonizzati.
For Section 4.8, the CHMP requested the clarification of the presentation of the post-marketing spontaneous report and also proposed a list of revised terms to be used in all the tables of adverse event in combination use in this section.
Għal Sezzjoni 4. 8, il- CHMP talab il - kjarifikazzjoni tal- preżentazzjoni tar- rapport spontanju ta ’ wara t- tqegħid fis- suq u ppropona wkoll lista ta ’ termini rreveduti li jintużaw fit- tabelli kollha ta ’ episodji avversi wżati f’ din is- sezzjoni.
Finally, a number of additional minor comments, including comments to remaining sections of the SPC, were made by the CHMP and implemented directly in the SPC text.
Finalment, saru numru ta ’ kummenti minuri addizjonali mill- CHMP, inklużi kummenti għas- sezzjonijiet tal- SPC li baqgħu u ġew implimentati direttament fit- test tal- SPC.
Other sections of the SPC:
Sezzjonijiet oħrajn tal- SPC:
While the full harmonisation of the quality dossier was not part of the scope of the referral, the sections of the SPC (in particular sections 2 and 6) and the corresponding Package Leaflet sections relating to Quality were assessed and harmonised.
Filwaqt li l - armonizzazzjoni sħiħa tar- rapport ta ’ kwalità ma kienx parti mill- iskop tar- referenza, is- sezzjonijiet tal - SPC (b’ mod partikolari sezzjonijiet 2 u 6) u s- sezzjonijiet tal- Fuljett ta ’ Tagħrif korrespondenti relatati mal- kwalità kienu vvalutati u armonizzati.
The CHMP considers that the divergences identified at the start of the referral have been resolved and that all issues raised in the List of Questions and in the List of Outstanding Issues have been properly addressed and answered satisfactorily.
Il- CHMP ikkunsidra li d- diverġenzi kollha identifikati fil- bidu tar- referenza ġew solvuti u li l- argumenti kollha mqajjmin fil- Lista ta ’ mistoqsijiet u l- Lista ta ’ Argumenti Pendenti ġew indirizzati bix- xieraq u mwieġbin b’ mod sodisfaċenti.
The proposed revisions to the Product Information were fully implemented.
Ir- reviżjonijiet proposti għat- Tagħrif tal- Prodott ġew implimentati b’ mod sħiħ.
In summary the MAH has deleted the indication for intravesical use and for 5-FU- refractory pancreatic cancer while the indication in ovarian cancer has been justified.
Fil- qosor, il- MAH neħħa l- indikazzjoni għall- użu intravesikali u għal kanċer tal- frixa refrattorju għal 5- FU waqt li l- indikazzjoni f’ kanċer ta ’ l- ovarju ġiet iġġustifikata.
Also, the use of Gemcitabine as a single agent in NSCLC was justified in specific situations.
L- użu ta ’ Gemcitabine bħala sustanza waħidha f’ NSCLC ukoll kien iġġustifikat f’ sitwazzjonijiet speċifiċi.
The CHMP therefore adopted the remaining five indications for Gemzar, as worded in the revised SPC.
Għaldaqstant, Il- CHMP adotta l - ħames indikazzjonijiet l- oħrajn għal Gemzar, kif miktubin fl- SPC rivedut.
14 GROUNDS FOR AMENDMENT OF THE SUMMARIES OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET
RAĠUNIJIET GĦALL- EMENDA TAS- SOMMARJU TAL- KARATTERISTIĊI TAL- PRODOTT, TIKKETTA U FULJETT TA ’ TAGĦRIF
- the scope of the referral was the harmonisation of the Summaries of Products Characteristics,
- l- iskop tar- referenza kien l- armonizzazzjoni tas- Sommarju tal- Karatteristiċi tal- Prodott, tikketta u fuljett
labelling and package leaflet.
ta ’ tagħrif.
- the Summaries of Products Characteristic, labelling and package leaflet proposed by the Marketing
- is- Sommarji tal- Karatteristiċi tal- Prodott, tikketta u fuljett ta ’ tagħrif proposti mid- Detenturi ta ’ l -
Authorisation Holders have been assessed based on the documentation submitted and the scientific discussion within the Committee,
Awtorizzazzjoni għat- Tqegħid fis- Suq ġew ivvalutati abbażi tad- dokumentazzjoni sottomessa u tad - diskussjoni xjentifika fi ħdan il- Kumitat,
the CHMP has recommended the amendment of the Marketing Authorisations for which the Summary of Product Characteristics, labelling and package leaflet are set out in Annex III for Gemzar.
il- CHMP irrakkomanda l- emenda ta ’ l- Awtorizzazzjonijiet għat- Tqegħid fis- Suq li għalihom, is - Sommarju tal- Karatteristiċi tal- Prodott, tikketta u fuljett ta ’ tagħrif huma stabbiliti fl- Anness III għal Gemzar.
15 ANNEX III
15 SOMMARJU TAL- KARATTERISTIĊI TAL- PRODOTT
Gemzar 1000 mg powder for solution for infusion
Gemzar 1000 mg trab għal soluzzjoni għall- infużjoni
One vial contains gemcitabine hydrochloride equivalent to 200 mg gemcitabine.
Kunjett fih gemcitabine hydrochloride ekwivalenti għal 200 mg gemcitabine.
One vial contains gemcitabine hydrochloride equivalent to 1000 mg gemcitabine.
Kunjett fih gemcitabine hydrochloride ekwivalenti għal 1000 mg gemcitabine.
After reconstitution, the solution contains 38 mg/ml of gemcitabine.
Wara r- rikostituzzjoni, is- soluzzjoni fiha 38 mg/ ml ta ’ gemcitabine.
Excipients Each 200 mg vial contains 3.5 mg (< 1 mmol) sodium.
Sustanzi mhux attivi Kull kunjett ta ’ 200 mg fih 3. 5 mg (< 1 mmol) sodium.
Each 1000 mg vial contains 17.5 mg (< 1 mmol) sodium.
Kull kunjett ta '1000 mg fih 17. 5 mg (< 1 mmol) sodium.
White to off-white plug or powder.
Trab għal soluzzjoni għall- infużjoni Trab jew plakka bajda tagħti fl- offwajt.
Gemcitabine is indicated for the treatment of locally advanced or metastatic bladder cancer in combination with cisplatin.
Gemcitabine huwa indikat għall- kura tal- kanċer tal- bużżieqa ta 'l- awrina lokalment avvanzat jew metastatiku flimkien ma ’ cisplatin.
Gemcitabine is indicated for treatment of patients with locally advanced or metastatic adenocarcinoma of the pancreas.
Gemcitabine huwa indikat għall- kura f’ pazjenti b’ adenokarċinoma tal- frixa lokalment avvanzat jew metastatiku.
Gemcitabine, in combination with c isplatin is indicated as first line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC).
Gemcitabine, flimkien ma ’ cisplatin huwa indikat bħala kura ta ’ l- ewwel għażla f’ pazjenti b’ kanċer tal - pulmun mhux ta 'ċelloli żgħar (NSCLC) lokalment avvanzat jew metastatiku.
Gemcitabine monotherapy can be considered in elderly patients or those with performance status 2.
Il- monoterapija b’ Gemcitabine tista ’ tiġi kkunsidrata f’ pazjenti anzjani jew f’ dawk b’ performance status 2.
Gemcitabine is indicated for the treatment of patients with locally advanced or metastatic epithelial ovarian carcinoma, in combination with carboplatin, in patients with relapsed disease following a recurrence-free interval of at least 6 months after platinum-based, first-line therapy.
Gemcitabine huwa indikat għall- kura ta 'pazjenti b’ karċinoma ta ’ l- epitelju ta ’ l- ovarji lokalment avvanzat jew metastatiku, flimkien ma ’ carboplatin, f’ pazjenti li reġgħu rkadew wara intervall ta ’ mill- inqas 6 xhur mingħajr rikorrenza wara terapija ta ’ l- ewwel għażla bbażata fuq platinum.
Gemcitabine, in combination with paclitaxel, is indicated for the treatment of patients with unresectable, locally recurrent or metastatic breast cancer who have relapsed following adjuvant/neoadjuvant chemotherapy.
17 Gemcitabine, flimkien ma ’ paclitaxel, huwa indikat għall- kura ta ’ pazjenti b’ kanċer tas- sider lokalment avvanzat jew metastatiku li ma jistax jitneħħa, li reġgħu rkadew wara kimoterapija supplimentari/ neo - supplimentari.
Prior chemotherapy should have included an anthracycline unless clinically contraindicated.
Kimoterapija preċedenti kellha tinkludi anthracycline sakemm mhux klinikament kontra - indikat.
18 4.2 Posology and method of administration
4. 2 Pożoloġija u metodu ta ’ kif għandu jingħata
Gemcitabine should only be prescribed by a physician qualified in the use of anti-cancer chemotherapy.
Gemcitabine għandu jiġi ordnat biss minn tabib ikkwalifikat fl- użu tal- kimoterapija kontra l- kanċer.
Recommended posology
Pożoloġija rrakkomandata
Bladder cancer Combination use The recommended dose for gemcitabine is 1000 mg/m2, given by 30-minute infusion.
Kanċer fil- bużżieqa ta 'l- awrina Użu kkombinat Id- doża rrakkomandat ta' gemcitabine hija ta '1000 mg/ m2, li tingħata b' infużjoni ta' 30 minuta.
The dose should be given on Days 1, 8 and 15 of each 28-day cycle in combination with cisplatin.
Id- doża għandha tingħata fl- ewwel, fit- tmien u fil- ħmistax- il jum ta 'kull ċiklu ta' 28 jum flimkien ma 'cisplatin.
Cisplatin is given at a recommended dose of 70 mg/m2 on Day 1 following gemcitabine or day 2 of each 28-day cycle.
Cisplatin jingħata f' doża rrakkomandata ta '70 mg/ m2 fl- ewwel jum wara gemcitabine jew fit- tieni jum ta' kull ċiklu ta '28 jum.
This 4-week cycle is then repeated.
Dan iċ- ċiklu ta 'erba' gimgħat imbagħad jiġi rrepetut.
Dosage reduction with each cycle or within a cycle may be applied based upon the grade of toxicity experienced by the patient.
Jista 'jiġi applikat it- tnaqqis fid - doża ma' kull ċiklu jew fiċ- ċiklu skond il- grad ta 'tossiċità milħuq fil- pazjent.
Pancreatic cancer The recommended dose of gemcitabine is 1000 mg/m2, given by 30-minute intravenous infusion.
Kanċer tal- frixa Id- doża rrakkomandat ta 'gemcitabine hija ta' 1000 mg/ m2, li tingħata b' infużjoni fil- vini ta '30 minuta.
This should be repeated once weekly for up to 7 weeks followed by a week of rest.
Din għandha tiġi rrepetuta darba fil- ġimgħa sa mhux aktar minn 7 ġimgħat u tiġi segwita b' ġimgħa ta 'mistrieħ.
Subsequent cycles should consist of injections once weekly for 3 consecutive weeks out of every 4 weeks.
Ċikli ta 'wara għandhom jikkonsistu f' injezzjonijiet darba fil- ġimgħa għal 3 ġimgħat konsekuttivi minn kull erba' ġimgħat.
Dosage reduction with each cycle or within a cycle may be applied based upon the grade of toxicity experienced by the patient.
Jista 'jiġi applikat it- tnaqqis fid- doża ma' kull ċiklu jew fiċ- ċiklu skond il- grad ta 'tossiċità milħuq fil- pazjent.
Non small Cell lung cancer Monotherapy The recommended dose of gemcitabine is 1000 mg/m2, given by 30-minute intravenous infusion.
Kanċer tal- pulmun mhux ta 'ċelloli żgħar Monoterapija Id- doża rrakkomandat ta' gemcitabine hija ta '1000 mg/ m2, li tingħata b' infużjoni fil- vini ta' 30 minuta.
This should be repeated once weekly for 3 weeks, followed by a 1-week rest period.
Din għandha tiġi rrepetuta darba fil- ġimgħa għal 3 ġimgħat u tiġi segwita b' ġimgħa ta 'mistrieħ.
This 4-week cycle is then repeated.
Dan iċ- ċiklu ta 'erba' ġimgħat imbagħad jiġi rrepetut.
Combination use The recommended dose for gemcitabine is 1250 mg/m2 body surface area given as a 30-minute intravenous infusion on Day 1 and 8 of the treatment cycle (21 days).
Użu kkombinat Id- doża rrakkomandat ta 'gemcitabine hija ta' 1250 mg/ m2 ta 'l- erja tas- superfiċje tal- ġisem li tingħata b' infużjoni fil- vini ta' 30 minuta fl- ewwel u fit- tmien jum taċ- ċiklu tal- kura (21 jum).
Dosage reduction with each cycle or within a cycle may be applied based upon the grade of toxicity experienced by the patient.
Jista 'jiġi applikat it - tnaqqis fid- doża ma' kull ċiklu jew fiċ- ċiklu skond il- grad ta 'tossiċità fil- pazjent.
Cisplatin has been used at doses between 75-100 mg/m2 once every 3 weeks.
Cisplatin intuża f' dożi bejn 75- 100 mg/ m2 darba kull 3 ġimgħat.
Breast cancer Combination use Gemcitabine in combination with paclitaxel is recommended using paclitaxel (175 mg/m2) administered on Day 1 over approximately 3-hours as an intravenous infusion, followed by gemcitabine (1250 mg/m2) as a 30-minute intravenous infusion on Days 1 and 8 of each 21-day cycle.
Kanċer tas- sider Użu kkombinat Gemcitabine flimkien ma 'paclitaxel huwa rrakkomandat b' paclitaxel (175 mg/ m2) jingħata fl- ewwel jum bħala infużjoni fil- vini ta' madwar 3 sigħat, u wara jingħata gemcitabine (1250 mg/ m2) bħala infużjoni fil - vini ta '30 minuta fl- ewwel u t- tmien jum ta' kull ċiklu ta '21 jum.
Dose reduction with each cycle or within a cycle may be applied based upon the grade of toxicity experienced by the patient.
Jista 'jiġi applikat it- tnaqqis fid- doża ma' kull ċiklu jew fiċ- ċiklu skond il- grad ta 'tossiċità fil- pazjent.
Patients should have an absolute granulocyte count of at least 1,500 (x 106/l) prior to initiation of gemcitabine + paclitaxel combination.
Il- pazjenti għandhom ikollhom għadd assolut ta 'granuloċiti ta' mill- inqas 1, 500 (x 106/ l) qabel tinbeda l- kombinazzjoni ta 'gemcitabine + paclitaxel.
Ovarian cancer Combination use Gemcitabine in combination with carboplatin is recommended using gemcitabine 1000 mg/m2 administered on Days 1 and 8 of each 21-day cycle as a 30-minute intravenous infusion.
Kanċer ta 'l- ovarji Użu kkombinat Gemcitabine flimkien ma' carboplatin huwa rrakkomandat b' gemcitabine 1000 mg/ m2 jingħata fl- ewwel u
After gemcitabine, carboplatin will be given on Day 1 consistent with a target Area under curve (AUC) of 4.0 mg/ml·min.
Wara gemcitabine, jingħata carboplatin fl- ewwel jum konsistenti ma 'mira ta' l- Erja taħt il- kurva (AUC) ta '4. 0 mg/ ml· min.
Dosage reduction with each cycle or within a cycle may be applied based upon the grade of toxicity experienced by the patient.
Jista 'jiġi applikat it- tnaqqis fid- doża ma' kull ċiklu jew fiċ- ċiklu skond il- grad ta 'tossiċità fil- pazjent.
Monitoring for toxicity and dose modification due to toxicity
Iċċekkjar għat- tossiċità u aġġustament fid- doża minħabba t- tossiċità
Dose modification due to non haematological toxicity Periodic physical examination and checks of renal and hepatic function should be made to detect non- 19 haematological toxicity.
Aġġustament fid- doża minħabba tossiċità li m’ hijiex ematoloġika Kull tant żmien għandu jsir eżami fiżiku u testijiet tal- funzjoni renali u epatika sabiex tara jekk hemmx xi tossiċità li m’ hijiex ematoloġika.
In general, for severe (Grade 3 or 4) non- haematological toxicity, except nausea/vomiting, therapy with gemcitabine should be withheld or decreased depending on the judgement of the treating physician.
Ġeneralment, għal tossiċità severa (Grad 3 jew 4) li m’ hijiex ematoloġika, ħlief għat- tqalligħ/ rimettar, it- terapija b’ gemcitabine għandha tinżamm jew titnaqqas skond kif jaħseb it - tabib li jkun qed jieħu ħsieb il- kura.
Doses should be withheld until toxicity has resolved in the opinion of the physician.
Id- dożi għandhom jinżammu sakemm skond l- opinjoni tat- tabib it - tossiċità ma tkunx baqgħet problema.
For cisplatin, carboplatin, and paclitaxel dosage adjustment in combination therapy, please refer to the corresponding Summary of Product Characteristics.
Għall- aġġustamenti fid- dożi ta ’ cisplatin, carboplatin u paclitaxel f’ terapija kkombinata, jekk jogħġbok irreferi għas- Sommarju tal- Karatteristiċi tal- Prodott korrispondenti.
Dose modification due to haematological toxicity Initiation of a cycle For all indications, the patient must be monitored before each dose for platelet and granulocyte counts.
Aġġustament fid- doża minħabba tossiċità ematoloġika Fil- bidu ta ’ ċiklu Għall- indikazzjonijiet kollha, qabel kull doża l- pazjent għandu jiġi eżaminat għall- għadd ta ’ pletjlits u granuloċiti.
Patients should have an absolute granulocyte count of at least 1,500 (x 106/l) and platelet account of 100,000 (x 106/l) prior to the initiation of a cycle.
Qabel ma jinbeda ċiklu, il- pazjenti għandhom ikollhom għadd assolut ta ’ granuloċiti ta ’ għallinqas 1, 500 (x 106/ l) u ammont ta ’ plejtlits ta ’ 100, 000 (x 106/ l)
Within a cycle Dose modifications of gemcitabine within a cycle should be performed according to the following tables:
Waqt ċiklu Waqt ċiklu, l- aġġustamenti fid- doża ta ’ gemcitabine għandhom isiru skond dawn it- tabelli li ġejjin:
Dose modification of gemcitabine within a cycle for bladder cancer, NSCLC and pancreatic cancer, given in monotherapy or in combination with cisplatin
Aġġustament fid- doża ta ’ gemcitabine waqt ċiklu għal kanċer tal- bużżieqa ta ’ l- awrina, NSCLC u kanċer tal- frixa, mogħti f’ monoterapija jew flimkien ma ’ cisplatin
Absolute granulocyte count (x 106/l)
Għadd assolut ta ’ granuloċiti
Percentage of st andard dose of Gemzar (%)
normali ta ’ Gemzar (%)
> 1,000
> 1, 000
> 100,000
> 100, 000
500-1,000
500- 1, 000
50,000-100,000
50, 000- 100, 000
< 50,000
< 50, 000
Omit dose *
Tagħtix id- doża *
*Treatment omitted will not be re-instated within a cycle before the absolute granulocyte count reaches at least 500 (x106/l) and the platelet count reaches 50,000 (x106/l).
* Il- kura li ma ngħatatx ma terġax tiddaħħal fiċ- ċiklu qabel ma l- għadd assolut tal- granuloċiti ma jilħaqx għallinqas 500 (x106/ l) u l- għadd tal- plejtlits jilħaq 50, 000 (x106/ l).
Dose modification of gemcitabine within a cycle for breast cancer, given in combination with paclitaxel
Aġġustament fid- doża ta ’ gemcitabine waqt ċiklu għal kanċer tas- sider, mogħti flimkien ma ’ paclitaxel
≥ 1,200
≥ 1, 200
> 75,000
> 75, 000
1,000- < 1,200 700- < 1,000
1, 000 - < 1, 200 700 - < 1, 000
or and
jew u
50,000-75,000 ≥ 50,000
50, 000- 75, 000 ≥ 50, 000
Omit dose*
Tagħtix id- doża *
*Treatment omitted will not be re-instated within a cycle.
* Il- kura li ma ngħatatx ma terġax tiddaħħal fiċ- ċiklu.
Treatment will start on day 1 of the next cycle once the absolute granulocyte count reaches at least 1,500 (x106/l) and the platelet count reaches 100,000 (x106/l).
Il- kura tiba fl- 1 ġurnata taċ- ċiklu li jmiss ladarba l - għadd assolut tal- ġranuloċiti jkun laħaq għallinqas 1, 500 (x106/ l) u l- għadd tal- plejtlits ikun laħaq 100, 000 (x106/ l).
Dose modification of gemcitabine within a cycle for ovarian cancer, given in combination with carboplatin
19 Aġġustament fid- doża ta ’ gemcitabine waqt ċiklu għal kanċer fl- ovarji, mogħti flimkien ma ’ carboplatin
Absolute granulocyte count (x 106/l)
Għadd assolut ta ’ granuloċiti (x 106/ l)
Platelet count (x 106/l)
(x 10 / l)
≥ 100,000
≥ 100, 000
1000-1,500
1000- 1, 500
75,000-100,000
75, 000- 100, 000
< 75,000
< 75, 000
20 Dose modifications due to haematological toxicity in subsequent cycles, for all indications The gemcitabine dose should be reduced to 75% of the original cycle initiation dose, in the case of the following haematological toxicities:
Fil- każijiet ta ’ dawn it- tossiċitajiet ematoloġiċi li ġejjin, id- doża ta ’ gemcitabine għandha titnaqqas sa 75% tad- doża inizjali taċ- ċiklu oriġinali:
• Absolute granulocyte count < 500 x 106/l for more than 5 days • Absolute granulocyte count < 100 x 106/l for more than 3 days • Febrile neutropaenia • Platelets < 25,000 x 106/l • Cycle delay of more than 1 week due to toxicity
Għadd assolut tal- granuloċiti < 500 x106/ l għal iżjed minn 5 ġranet • Għadd assolut tal- granuloċiti < 100 x 106/ l għal iżjed minn 3 ġranet • • Newtropenija febrili Plejtlits < 25, 000 x 106/ l • • Iċ- ċiklu jiġi pospost għal iżjed minn ġimgħa minħabba t- tossiċità
If extravasation occurs, generally the infusion must be stopped immediately and started again in another blood vessel.
Gemzar huwa tollerat tajjeb waqt l- infużjoni u jista ’ jingħata anki bil- pazjent mhux fis- sodda. Jekk ikun hemm estravażjoni, ġeneralment l- infużjoni għandha titwaqqaf immedjatament u terġa ’ tinbeda f’ vina/ arterja oħra.
The patient should be monitored carefully after the administration.
Il- pazjent għandu jiġi segwit b’ attenzjoni wara li jingħata d- doża.
For instructions on reconstitution, see section 6.6
Għall- istruzzjonijiet dwar ir- rikostituzzjoni, ara sezzjoni 6. 6
Patients with renal or hepatic impairment Gemcitabine should be used with caution in patients with hepatic or renal insufficiency as there is insufficient information from clinical studies to allow for clear dose recommendations for these patient populations (see sections 4.4 and 5.2).
Pazjenti b’ indeboliment renali jew epatiku Gemcitabine għandu jintuża b’ kawtela f’ pazjenti b’ insuffiċjenza epatika jew renali, peress li għal dawn il - popolazzjonijiet ta ’ pazjenti l- informazzjoni minn studji kliniċi m’ hijiex biżżejjed biex tagħtik rakkomandazzjonijiet ċari dwar id- doża (ara sezzjonijiet 4. 4 u 5. 2).
Elderly population( > 65 years) Gemcitabine has been well tolerated in patients over the age of 65.
Popolazzjoni anzjana (> 65 sena) Gemcitabine huwa tollerat tajjeb minn pazjenti li għandhom iżjed minn 65 sena.
There is no evidence to suggest that dose adjustments, other than those already recommended for all patients, are necessary in the elderly (see section 5.2).
M’ hemm ebda evidenza li tissuġġerixxi li fl- anzjani hemm bżonn ta ’ aġġustament fid- doża, ħlief għal dawk li huma diġà rrakkomandati għal pazjenti kollha (ara sezzjoni 5. 2)
Paediatric population (< 18 years) Gemcitabine is not recommended for use in children under 18 years of age due to insufficient data on safety and efficacy.
Popolazzjoni pedjatrika (< 18- il sena) Gemcitabine mhux rakkomandat għall- użu fit- tfal taħt it- 18- il sena minħabba li m’ hemmx informazzjoni biżżejjed dwar is- sigurtà u l- effikaċja.
Breast-feeding (see section 4.6).
Treddigħ (ara sezzjoni 4. 6)
Prolongation of the infusion time and increased dosing frequency have been shown to increase toxicity.
20 4. 4 Twissijiet speċjali u prekawzjonijiet għall- użu Ġie muri li żieda fil- ħin ta ’ l- infużjoni u żieda fil- frekwenza tad- dożaġġ iżidu it- tossiċità.
Haematological toxicity Gemcitabine can suppress bone marrow function as manifested by leucopaenia, thrombocytopaenia and anaemia.
Tossiċità ematoloġika Gemcitabine jista ’ jrażżan il- funzjoni tal- mudullun li jirriżulta f’ lewkopenja, tromboċitopenja u anemija.
Patients receiving gemcitabine should be monitored prior to each dose for platelet, leucocyte and granulocyte counts.
Qabel kull doża, pazjenti li jirċievu gemcitabine għandhom jiġu ċċekkjati għall- għadd ta ’ plejtlits, lewkoċiti u granuloċiti.
Suspension or modification of therapy should be considered when drug-induced bone marrow depression is detected (see section 4.2).
Jekk jinstab li hemm tnaqqis fil- funzjoni tal- mudullun kawża tal- mediċina, għnadha tiġi kkunsidrata s- sospensjoni jew l- aġġustament fit- terapija (ara sezzjoni 4. 2).
However, myelosuppression is short lived and usually does not result in dose reduction and rarely in discontinuation.
Madankollu, il - majelosuppressjoni tkun għal żmien qasir u ħafna drabi ma jkunx hemm bżonn ta ’ tnaqqis fid- doża u rarament ikun hemm bżonn li titwaqqaf il- kura.
Peripheral blood counts may continue to deteriorate after gemcitabine administration has been stopped.
L- għadd taċ- ċelluli tad- demm periferali jista ’ jkompli jiħżien wara li jkun waqaf l- għoti ta ’ gemcitabine.
In patients with impaired bone marrow function, the treatment should be started with caution.
Il- kura għandha tinbeda b’ kawtela f’ pazjenti b’ disfunzjoni fil- mudullun.
As with other cytotoxic treatments, the risk of cumulative bone-marrow suppression must be considered when gemcitabine treatment is given together with other chemotherapy
Bħal ma jiġri f’ kuri ċitotossiċi oħra, trid tikkonsidra r- riskju ta ’ suppressjoni tal- mudullun kumulattiv meta gemcitabine jingħata flimkien ma ’ kimoterapija oħra.
21 Hepatic insufficiency Administration of gemcitabine in patients with concurrent liver metastases or a pre-existing medical history of hepatitis, alcoholism or liver cirrhosis may lead to exacerbation of the underlying hepatic insufficiency.
Insuffiċjenza epatika F’ pazjenti li fl- istess waqt għandhom metastasi fil- fwied jew diġà għandhom passat mediku ta ’ epatite, alkoħoliżmu jew ċirrożi tal- fwied, l- għoti ta ’ gemcitabine jista ’ jwassal biex iżid l- insuffiċjenza epatika li diġà hemm.
Laboratory evaluation of renal and hepatic function (including virological tests) should be performed periodically.
Kull tant żmien għandu jsir evalwazzjoni fil- laboratorju tal- funzjoni renali u epatiku (inklużi t- testijiet viroloġiċi).
Gemcitabine should be used with caution in patients with hepatic insufficiency or with impaired renal function as there is insufficient information from clinical studies to allow clear dose recommendation for this patient population (see section 4.2).
Gemcitabine għandu jintuża b’ kawtela f’ pazjenti b’ insuffiċjenza epatika jew b’ indeboliment fil- funzjoni renali, peress li minn studji kliniċi m’ hemmx biżżejjed informazzjoni biex jagħtu rakkomandazzjoni ċara dwar id- dożaġġ f’ din il- popolazzjoni ta ’ pazjenti (ara sezzjoni 4. 2).
Concomitant radiotherapy Concomitant radiotherapy (given together or ≤7 days apart):
Radjoterapija fl- istess żmien Radjoterapija fl- istess żmien (mogħtija flimkien jew ≤7 tijiem minn xulxin):
Toxicity has been reported (see section 4.5 for details and recommendations for use).
Ġiet irrapportata t- tossiċità (ara sezzjoni 4. 5 għal dettalji u rakkomandazzjonijiet dwar l- użu)
Live vaccinations Yellow fever vaccine and other live attenuated vaccines are not recommended in patients treated with gemcitabine (see section 4.5).
Tilqim b’ viruses ħajjin Il- vaċċin tal- yellow fever u vaċċini oħra b’ viruses ħajjin iżda attenwati, m’ humiex rakkomandati f’ pazjenti kkurati b’ gemcitabine (ara sezzjoni 4. 5).
Cardiovascular Due to the risk of cardiac and/or vascular disorders with gemcitabine, particular caution must be exercised with patients presenting a history of cardiovascular events.
Kardjovaskulari Minħabba r- riskju ta ’ disturbi kardijaċi u/ jew vaskulari b’ gemcitabine, għandha tingħata attenzjoni partikolari f’ pazjenti b’ passat mediku ta ’ avvenimenti kardjovaskulari.
Pulmonary Pulmonary effects, sometimes severe (such as pulmonary oedema, interstitial pneumonitis or adult respiratory distress syndrome (ARDS)) have been reported in association with gemcitabine therapy.
Pulmonarju Ġew irrapportati effetti pulmonarji xi kultant severi (bħal edima pulmonari, pnewmonite interstizjali jew sindromu ta ’ diffikultà respiratorja ta ’ l- adulti (ARDS)) b’ rabta mat- terapija ta ’ gemcitabine.
The aetiology of these effects is unknown.
Il- kawża ta ’ dawn l- effetti m’ hijiex magħrufa.
If such effects develop, consideration should be made to discontinuing gemcitabine therapy.
Jekk jiżviluppaw dawn l- effetti għandu jiġi kkunsidrat it- twaqqif tat - terapija b’ gemcitabine.
Early use of supportive care measure may help ameliorate the condition.
L- użu mill- bidunett ta ’ miżuri ta ’ kura ta ’ sosteniment jistgħu jgħinu biex titjieb il - kundizzjoni.
Renal Clinical findings consistent with the haemolytic uraemic syndrome (HUS) were rarely reported in patients receiving gemcitabine (see section 4.8).
Renali Sejbiet kliniċi li jindikaw is- sidromu uremiku emolitiku (HUS), ġew irrapportati rarament f’ pazjenti li qed jirċievu gemcitabine (ara sezzjoni 4. 8).
Gemcitabine should be discontinued at the first signs of any evidence of microangiopathic haemolytic anaemia, such as rapidly falling haemoglobin with concomitant thrombocytopaenia, elevation of serum bilirubin, serum creatinine, blood urea nitrogen, or LDH.
Gemcitabine għandu jitwaqqaf ma ’ l- ewwel sinjali ta ’ evidenza ta ’ anemija emolitika mikroanġjopatika, bħal livell ta ’ emoglobina li jibda jinżel b’ mod mgħaġġel flimkien mat- tromboċitopenja, livelli għoljin tal - bilirubin fis- serum, tal- krejatinina fis- serum, tal- urea nitrogen fid -
Renal failure may not be reversible with discontinuation of therapy and dialysis may be required.
Anki bit- twaqqif tat- terapija, l- insuffiċjenza renali tista ’ ma tkunx riversibbli u jista ’ jkun hemm bżonn ta ’ dijaliżi.
Fertility In fertility studies gemcitabine caused hypospermatogenesis in male mice (see section 5.3).
Fertilità Fi studji ta ’ fertilità, gemcitabine ikkawża ipospermatoġeneżi fi ġrieden maskili (ara sezzjoni 5. 3).
Therefore, men being treated with gemcitabine are advised not to father a child during and up to 6 months after treatment and to seek further advice regarding cryoconservation of sperm prior to treatment because of the possibility of infertility due to therapy with gemcitabine (see section 4.6).
Għalhekk, irġiel taħt kura b’ gemcitabine huma mitluba li ma jkollhomx tfal waqt u sa 6 xhur wara l- kura u sabiex ifittxu parir dwar il- ħażna ta ’ l- isperma taħt kesħa kbira qabel il- kura minħabba l- possibbiltà ta ’ infertilità kawża tat- terapija b’ gemcitabine (ara sezzjoni 4. 6).
Sodium Gemzar 200 mg contains 3.5 mg (< 1 mmol) sodium per vial.
Sodium Kull kunjett ta ’ Gemzar 200 mg fih 3. 5 mg (< 1 mmol) ta ’ sodium.
This should be taken into consideration by patients on a controlled sodium diet.
Trid iżżomm dan f’ moħħok f’ pazjenti li qegħdin fuq dieta kkontrollata ta ’ sodium.
Gemzar 1000 mg contains 17.5 mg (< 1 mmol) sodium per vial.
Kull kunjett ta ’ Gemzar 1000 mg fih 17. 5 mg (< 1 mmol) ta ’ sodium.
22 4.5 Interaction with other medicinal products and other forms of interaction
4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l - effett farmaċewtiku tal- prodott
No specific interaction studies have been performed (see section 5.2)
Ma sarux studji dwar l- effett ta ’ mediċini jew ta ’ affarijiet oħra fuq l- effett farmaċewtiku tal- prodott (ara sezzjoni 5. 2).
Radiotherapy Concurrent (given together or ≤ 7 days apart) - Toxicity associated with this multimodality therapy is dependent on many different factors, including dose of gemcitabine, frequency of gemcitabine administration, dose of radiation, radiotherapy planning technique, the target tissue, and target volume.
Radjoterapija Fl- istess ħin (mogħtija flimkien jew ≤ 7 tijiem minn xulxin) – It- tossiċità assoċjata ma ’ din it- terapija b’ modalitajiet differenti tiddependi minn ħafna fatturi differenti li jinkludu d- doża ta ’ gemcitabine, kemm - il darba jingħata, id- doża ta ’ radjazzjoni, it- teknika ta ’ ippjanar tar- radjoterapija, it- tessut li se jiġi milqut u l- volum ta ’ dan it- tessut.
Pre-clinical and clinical studies have shown that gemcitabine has radiosensitising activity.
Studji kliniċi u ta ’ qabel l- użu kliniku wrew li gemcitabine għandu attività radjosensittizzanti.
In a single trial, where gemcitabine at a dose of 1,000 mg/m2 was administered concurrently for up to 6 consecutive weeks with therapeutic thoracic radiation to patients with non-small cell lung cancer, significant toxicity in the form of severe, and potentially life threatening mucositis, especially oesophagitis, and pneumonitis was observed, particularly in patients receiving large volumes of radiotherapy [median treatment volumes 4,795 cm3].
Ġiet murija tossiċità sinifikanti fil- forma ta ’ mukosite severa u potenzjalment fatali speċjalment esofaġite u pnewmonite, l- aktar f’ pazjenti li rċevew volumi kbar ta ’ radjazzjoni [volumi ta ’ kura medjani 4, 795cm3] fi studju wieħed fejn gemcitabine ġie mogħti għal massimu ta ’ 6 ġimgħat konsekuttivi f’ doża ta ’ 1, 000 mg/ m2 flimkien ma ’ dożi terapewtiċi ta ’ radjazzjoni toraċika f’ pazjenti b’ kanċer tal- pulmun mhux b’ ċelluli żgħar.
The optimum regimen for safe administration of gemcitabine with therapeutic doses of radiation has not yet been determined in all tumour types.
Studji magħmula sussegwentement jindikaw li huwa possibbli li tagħti dożi aktar baxxi ta ’ gemcitabine fl- istess ħin mar- radjoterapija b’ tossiċità li tkun tista ’ tobsorha, bħal fi studju ta ’ fażi II f’ kanċer tal- pulmun mhux b’ ċelluli żgħar, fejn dożi ta ’ radjazzjoni toraċika ta ’ 66 Gy ġew mogħtija flimkien ma ’ gemcitabine (600 mg / m2, erba ’ darbiet) u cisplatin (80 mg/ m2 darbtejn) għal 6 ġimgħat. L- aħjar skeda ta ’ dożaġġ għall- għoti bla periklu ta ’ gemcitabine flimkien ma ’ dożi terapewtiċi ta ’ radjazzjoni għada ma ġietx iddeterminata għat- tipi kollha ta ’ tumur.
Non-concurrent (given > 7 days apart)- Analysis of the data does not indicate any enhanced toxicity when gemcitabine is administered more than 7 days before or after radiation, other than radiation recall.
Meta mhux fl- istess żmien (mogħtija > 7 tijiem minn xulxin) - Analiżi tad- dejta ma tindikax żieda fit - tossiċità meta gemcitabine jingħata iżjed minn 7 tijiem qabel jew wara r- radjazzjoni, ħlief għall- effetti li jerġgħu jidhru ta ’ radjazzjoni li tkun ngħatat qabel.
Data suggest that gemcitabine can be started after the acute effects of radiation have resolved or at least one week after radiation.
Id- dejta tissuġġerixxi li gemcitabine jista ’ jinbeda wara li l- effetti akuti tar- radjazzjoni ikunu spiċċaw jew għallinqas ġimgħa wara r- radjazzjoni.
Radiation injury has been reported on targeted tissues (e.g. oesophagitis, colitis, and pneumonitis) in association with both concurrent and non-concurrent use of gemcitabine.
Ġew irrapportati feriti ta ’ radjazzjoni fuq it- tessuti fil- mira tal- kura (eż. esofaġite. kolite u pnewmonite) f’ assoċjazzjoni kemm ma ’ l- użu fl- istess ħin ta ’ gemcitabine u kemm meta mhux fl- istess ħin.
Others Yellow fever and other live attenuated vaccines are not recommended due to the risk of systemic, possibly fatal, disease, particularly in immunosuppressed patients.
Oħrajn Il- vaċċin tal- yellow fever u vaċċini oħrajn b’ viruses ħajjin iżda attenwati m’ humiex rakkomandati, speċjalment f’ pazjenti immunosoppressi, minħabba r- riskju ta ’ mard sistemiku li jista ’ jkun fatali.
4.6 Pregnancy and lactation
22 4. 6 Tqala u treddigħ
Pregnancy There are no adequate data from the use of gemcitabine in pregnant women.
Tqala M’ hemmx tagħrif biżżejjed dwar l- użu ta ’ gemcitabine fin- nisa tqal.
Studies in animals have shown reproductive toxicity (see section 5.3).
Studji fuq bhejjem urew tossiċità fis - sistema riproduttiva (ara sezzjoni 5. 3).
Based on results from animal studies and the mechanism of action of gemcitabine, this substance should not be used during pregnancy unless clearly necessary.
Minħabba r- riżultati ta ’ l- istudji fuq il- bhejjem u l- mod kif jaħdem gemcitabine, din is- sustanza m’ għandhiex tintuża fit- tqala sakemm mhux verament neċessarju.
Women should be advised not to become pregnant during treatment with gemcitabine and to warn their attending physician immediately, should this occur after all.
In- nisa għandhom jiġu mwissija biex ma joħorġux tqal waqt il- kura b’ gemcitabine u biex javżaw mall- ewwel lit - tabib li qed jieħu ħsiebhom jekk wara kollox dan iseħħ.
Breast-feeding It is not known whether gemcitabine is excreted in human milk and adverse effects on the suckling child cannot be excluded.
Treddigħ Mhux magħruf jekk gemcitabine jinstabx fil- ħalib uman u ma jistgħux jiġu esklużi effetti avversi fuq it - tarbija li qeda tredda ’.
Breast-feeding must be discontinued during gemcitabine therapy.
It- treddigħ għandu jieqaf waqt il- kura b’ gemcitabine.
Therefore, men being treated with gemcitabine are advised not to father a child during and up to 6 months after treatment and to seek further advice regarding cryoconservation of sperm prior to treatment because of the possibility of infertility due to therapy with gemcitabine.
Għalhekk, irġiel taħt kura b’ gemcitabine huma mitluba li ma jkollhomx tfal waqt u sa 6 xhur wara l- kura u sabiex ifittxu parir dwar il- ħażna ta ’ l- isperma taħt kesħa kbira qabel il- kura minħabba l- possibbiltà ta ’ infertilità kawża tat- terapija b’ gemcitabine.
However, gemcitabine has been reported to cause mild to moderate somnolence, especially in combination with 23 alcohol consumption.
Ma sarux studji dwar l- effetti fuq il- ħila biex issuq jew tħaddem magni. Madankollu, ġie rrapportat li gemcitabine jikkawża ħedla tan- ngħas ħafifa għal moderata speċjalment meta jittieħed flimkien ma ’ l - alkoħol.
Patients should be cautioned against driving or operating machinery until it is established that they do not become somnolent.
Il- pazjenti għandhom ikunu avżati biex ma jsuqux jew jħaddmu magni sakemm jiġi stabbilit li ma jkunux imħeddlin bin- ngħas.
The most commonly reported adverse drug reactions associated with Gemzar treatment include: nausea with or without vomiting, raised liver transaminases (AST/ALT) and alkaline phosphatase, reported in approximately 60% of patients; proteinuria and haematuria reported in approximately 50% patients; dyspnoea reported in 10-40% of patients (highest incidence in lung cancer patients); allergic skin rashes occur in approximately 25% of patients and are associated with itching in 10% of patients.
4. 8 Effetti mhux mixtieqa L- aktar reazzjonijiet avversi tal- mediċina irrapportati b’ mod komuni assoċjati mal- kura b’ Gemzar jinkludu: tqalligħ bir- rimettar jew mingħajr rimettar, livelli għoljin tat- transaminases t[ U1] al- fwied (AST/ ALT) u alkaline phosphatase li ġew irrapportati f’ madwar 60% tal- pazjenti; proteina u demm fl - awrina rrapportati f’ madwar 50% tal- pazjenti; diffikultà biex tieħu n- nifs irrapportata f’ 10- 40% tal - pazjenti (l- ogħla inċidenza f’ pazjenti b’ kanċer tal- pulmun); raxxijiet allerġiċi fuq il- ġilda jseħħu f’ madwar 25% tal- pazjenti u f’ 10% tal- pazjenti huma assoċjati ma ’ ħakk.
The frequency and severity of the adverse reactions are affected by the dose, infusion rate and intervals between doses (see section 4.4).
Id- doża, ir- rata ta ’ infużjoni u l- ħin li jgħaddi bejn doża u oħra jaffettwaw l- frekwenza u s- severità tar - reazzjonijiet avversi (ara sezzjoni 4. 4).
Dose-limiting adverse reactions are reductions in thrombocyte, leucocyte and granulocyte counts (see section 4.2).
Reazzjonijiet avversi li jillimitaw id- doża huma tnaqqis fl- għadd ta ’ tromboċiti, lewkoċiti u granuloċiti (ara sezzjoni 4. 2).
Clinical trial data Frequencies are defined as:
Tagħrif minn studji kliniċi Il- frekwenzi huma mfissra hekk:
Very common (≥1/10), Common (≥1/100 to < 1/10), Uncommon (≥1/1000 to < 1/100), Rare (≥1/10,000 to < 1/1000), Very Rare (< 1/10,000).
Komuni ħafna (≥1/ 10), Komuni (≥1/ 100 sa < 1/ 10), Mhux komuni (≥1/ 1000 sa < 1/ 100), Rari (≥1/ 10, 000 sa < 1/ 1000), Rari ħafna (< 1/ 10, 000).
The following table of undesirable effects and frequencies is based on data from clinical trials.
It- tabella li ġejja ta ’ l- effetti mhux mixtieqa u tal- frekwenzi hi bbażata fuq tagħrif minn studji kliniċi F’ kull sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa għandhom jitniżżlu skond is- serjetà tagħhom.
System Organ Class Blood and lymphatic system disorders
Sistema tal- klassifika ta ’ l- organi Disturbi tad- demm u tas- sistema limfatika
Frequency grouping Very common • Leucopaenia (Neutropaenia Grade 3 = 19.3%; Grade 4 = 6%).
Grupp ta ’ frekwenza Komuni ħafna • Lewkopenja (Newtropenja Grad 3 = 19. 3%; Grad 4 = 6%).
Bone-marrow suppression is usually mild to moderate and mostly affects the granulocyte count (see section 4.2) • Thrombocytopaenia • Anaemia
Ħafna drabi s- soppressjoni tal- mudullun tkun ħafifa għal moderata u l- aktar li taffettwa
Common • Febrile neutropaenia Very rare • Thrombocytosis
Grupp ta ’ frekwenza huwa l- għadd tal- granuloċiti (ara sezzjoni 4. 2) • Tromboċitopenja • Anemija
Immune system disorders
Komuni • Newtropenja bid- deni Rari ħafna • Tromboċitożi Disturbi fis- sistema immuni
Very Rare • Anaphylactoid reaction
Rari ħafna • Reazzjoni anafilattika
Common • Anorexia
Komuni • Anoressija
Common • Headache • Insomnia • Somnolence
Komuni • Uġigħ ta ’ ras • Insomnja • Ħedla tan- ngħas
Rare • Myocardial infarct
Rari • Infart mijokardiku
Rare • Hypotension
Rari • Pressjoni baxxa
24 System Organ Class Respiratory, thoracic and mediastinal disorders
Disturbi respiratorji, toraċiċi u medjastinali
Frequency grouping Very common • Dyspnoea –usually mild and passes rapidly without treatment
Komuni ħafna • Diffikultà biex tieħu n- nifs – ħafna drabi tkun ħafifa u tgħaddi mingħajr ebda kura
Common • Cough • Rhinitis
Komuni • Sogħla • Rinite
Uncommon • Interstitial pneumonitis (see section 4.4) • Bronchospasm –usually mild and transient but may require parenteral treatment Gastrointestinal disorders
Mhux komuni • Pnewmonite interstitzjali (ara sezzjoni 4. 4) • Spażmu fil- bronki – ħafna drabi ħafif u tranżitorju iżda jista ’ jkun hemm il - bżonn ta ’ kura parenterali Disturbi gastro- intestinali
Very common • Vomiting • Nausea
Komuni ħafna • Rimettar • Tqalligħ
Common • Diarrhoea • Stomatitis and ulceration of the mouth • Constipation
Komuni • Dijarea • Stomatite u ulċeri fil- ħalq • Stitikezza
Very common • Elevation of liver transaminases (AST and ALT) and alkaline phosphatase
Komuni ħafna • Livelli għoljin tat- transaminases tal - fwied (AST and ALT) u alkaline phosphatase
Common • Increased bilirubin
Komuni
Rare
24 Sistema tal- klassifika ta ’ l- organi
•
Grupp ta ’ frekwenza • Żieda fil- livell ta ’ bilirubin
Increased gamma-glutamyl transferase (GGT)
Rari • Żieda fil- livell ta ’ gamma- glutamyl transferase (GGT)
Very common • Allergic skin rash frequently associated with pruritus • Alopecia
Komuni ħafna • Raxx allerġika tal- ġilda ħafna drabi assoċjata ma ’ prurite • Alopeċja
Common • Itching • Sweating
Komuni • Ħakk • Għaraq
Ulceration Vesicle and sore formation Scaling
Ulċerazzjoni Ikollok il- formazzjoni ta ’ nfafet u ta ’ pjagi
Very rare • Severe skin reactions, including desquamation and bullous skin eruptions Musculoskeletal and connective tissue disorders
Rari ħafna • Reazzjonijiet severi fuq il- ġilda li jinkludu deskwamazzjoni u eruzzjonijiet bullożi fuq il- ġilda Disturbi muskolu- skeltrali u tal- connective tissue
Common • Back pain • Myalgia
Komuni • Uġigħ tad- dahar • Mijalġja
System Organ Class Renal and urinary disorders
Disturbi fil- kliewi u fis- sistema urinarja
Frequency grouping Very Common • Haematuria • Mild proteinuria
Komuni ħafna • Ematurja • Proteinurja ħafifa
Very common • Influenza-like symptoms - the most common symptoms are fever, headache, chills, myalgia, asthenia and anorexia.
Komuni ħafna • Sintomi bħal dawk ta ’ l- influwenza – l- aktar sintomi komuni huma deni, uġugħ ta ’ ras, tregħid, mijalġja, astenja u anoressija.
Cough, rhinitis, malaise, perspiration and sleeping difficulties have also been reported. • Oedema/peripheral oedema- including facial oedema.
Ġew irrapportati wkoll sogħla, rinite, telqa ġenerali, għaraq eċċessiv u diffikultà biex torqod. • Edima/ edima periferali- li tinkludi edima fil- wiċċ.
Oedema is usually reversible after stopping treatment
Normalment l- edima hija riversibbli wara li twaqqaf il - kura.
Common • Fever • Asthenia • Chills
Komuni • Deni • Astenja • Tregħid
Injection site reactions-mainly mild in nature
Reazzjonijiet fis- sit ta ’ l- injezzjoni - li
Injury, poisoning, and procedural Complications
25 Sistema tal- klassifika ta ’ l- organi Feriti, avvelenament u komplikazzjonijiet fil - proċedura
Radiation toxicity (see section 4.5).
Grupp ta ’ frekwenza ħafna drabi jkunu ħfief Tossiċità mir- radjazzjoni (ara sezzjoni 4. 5).
Postmarketing experience (spontaneous reports) frequency not known (can’t be estimated from the available data)
Esperjenza ta ’ wara li l- prodott tqiegħed fis- suq (rapporti spontanji) frekwenza mhux magħrufa (ma tistax tittieħed stima mid- dejta disponibbli)
Nervous system disorders Cerebrovascular accident
Disturbi fis- sistema nervuża Inċident ċerebrovaskulari
Cardiac disorders Arrythmias, predominantly supraventricular in nature Heart failure
Disturbi fil- qalb Arritmjas, l- iżjed tat- tip supraventrikulari Insuffiċjenza tal- qalb
Vascular disorders Clinical signs of peripheral vasculitis and gangrene
Disturbi vaskulari Sinjali kliniċi ta ’ vaskulite periferali u kankrena
Respiratory, thoracic and mediastinal disorders Pulmonary oedema Adult respiratory distress syndrome (see section 4.4)
Disturbi repiratorji, toraċiċi u medjastinali Edima pulmonarja Sindromu ta ’ diffikultà respiratorja fl- adulti (ara sezzjoni 4. 4)
Gastrointestinal disorders Ischaemic colitis
Disturbi gastro- intestinali Kolite iskemika
Hepatobiliary disorders Serious hepatotoxicity, including liver failure and death
Disturbi fil- fwied u fil- marrara Epatotossiċità serja li tinkludi insuffiċjenza tal- fwied u mewt
Skin and subcutaneous tissue disorders Severe skin reactions, including desquamation and bullous skin eruptions, Lyell’s Syndrome, Steven- Johnson Syndrome
Disturbi fil- ġilda u fit- tessut ta ’ taħt il- ġilda Reazzjoni severi fil- ġilda li jinkludi d- deskwamazzjoni u eruzzjonijiet bullożi fuq il- ġilda, Sindromu ta ’ Lyell, Sindromu Steven- Johnson
26 Renal and urinary disorders Renal failure (see section 4.4) Haemolytic uraemic syndrome (see section 4.4)
Disturbi fil- kliewi u fis- sistema urinarja Insuffiċjenza renali (ara sezzjoni 4. 4) Sindromu uremiku emolitiku (ara sezzjoni 4. 4)
Injury, poisoning and procedural complications Radiation recall
Feriti, avvelenament u komplikazzjonijiet fil- proċedura Jerġgħu joħorġu l- effetti tar- radjazzjoni li tkun ingħatat qabel
Combination use in breast cancer The frequency of grade 3 and 4 haematological toxicities, particularly neutropaenia, increases when gemcitabine is used in combination with paclitaxel.
Użu kkombinat fil- kanċer tas- sider Il- frekwenza tat- tossiċitajiet ematoloġiċi ta ’ grad 3 u 4, speċjalment in- newtropenja, jiżdiedu meta gemcitabine jintuża flimkien ma ’ paclitaxel.
However, the increase in these adverse reactions is not associated with an increased incidence of infections or haemorrhagic events.
Madankollu, iż- żieda f’ dawn ir- reazzjonijiet avversi m’ hijiex assoċjata ma ’ żieda fl- inċidenza ta ’ infezzjonijiet jew avvenimenti emorraġiċi.
Fatigue and febrile neutropaenia occur more frequently when gemcitabine is used in combination with paclitaxel.
Għeja u newtropenja bid - deni iseħħu b’ mod aktar frekwenti meta gemcitabine jintuża flimkien ma ’ paclitaxel.
Fatigue, which is not associated with anaemia, usually resolves after the first cycle.
L- għeja li mhix assoċjata ma ’ l- anemija, ħafna drabi tirrisolvi ruħha wara l- ewwel ċiklu.
Grade 3 and 4 Adverse Events Paclitaxel versus gemcitabine plus paclitaxel
Grad 3 Grad 4
Number (%) of Patients
Grad 3 Grad 4
Paclitaxel arm
5 (1. 9) 1 (0. 4) 0 0 11 (4. 2) 17 (6. 6) *
Gemcitabine plus
3 (1. 2) 0 3 (1. 2) 1 (0. 4) 5 (1. 9) 0 2( 0. 8) 0 9( 3. 5) 0
(N=259)
Numru (%) ta ’ Pazjenti
Paclitaxel arm (N=262)
doxorubicin u cisplatin) (N=196)
Laboratory
Laboratorju
3 (1.1) 1 (0.4)
Grad 3
Neutropaenia
Grad 4
11 (4.2)
Anemija
17 (6.6)*
30( 16)
82 (31.3)
4( 2) 47( 24)
45 (17.2)*
7( 4)
Non-laboratory
Tromboċitopenja
Febrile neutropaenia
15( 8)
3 (1.2)
25( 13)
12 (4.6)
57( 29)
1(0.4)
57( 29)
Fatigue Diarrhoea
Mhux ta ’ laboratorju