qanastek/EMEA-V3 huggingface dataset:
Careful monitoring and prompt treatment interruption is recommended if the patient develops a grade 2, 3 or 4 adverse event during treatment and subsequent dose adjustment as outlined in Table 3 above.
Sorveljanza bir- reqqa u interruzzjoni fil- pront tal- kura huwa rakkomandat f’ każ li l- pazjent isofri minn episodju avvers ta ’ grad 2, 3 jew 4 waqt il- kura u d- dożi li jmissu għandhom jiġu aġġustati kif indikat f’ Tabella 3 aktar ’ l fuq.
If the calculated creatinine clearance decreases during treatment to a value below 30 ml/ min, Xeloda should be discontinued.
Jekk waqt il- kura t- tneħħija tal - krejatinina kkalkulata tonqos għall- valur ta ’ inqas minn 30 mL/ min, Xeloda għandu jitwaqqaf.
These dose adjustment recommendations for renal impairment apply both to monotherapy and combination use (see also section “ Elderly” below).
Dawn ir- rakkomandazzjonijiet dwar l- aġġustament tad- doża għall- indeboliment fil- kliewi japplikaw kemm għal kura li tittieħed waħidha u kif ukoll f’ użu flimkien ma ’ mediċini oħra (ara wkoll Sezzjoni “ Anzjani ” aktar ’ l isfel).
There is no experience in children (under 18 years).
M’ hemm l- ebda esperjenza fit- tfal (taħt it- 18- il sena).
During Xeloda monotherapy, no adjustment of the starting dose is needed.
Waqt monoterapija b’ Xeloda, mhux meħtieġ l- ebda aġġustament fid- doża tal- bidu.
However, grade 3 or 4 treatment-related adverse reactions were more frequent in patients ≥ 60 years of age compared to younger patients.
Madankollu, reazzjonijiet avversi ta ’ grad 3 jew 4 li huma relatati mal- kura kienu aktar frekwenti f’ pazjenti li għandhom ≥ 60 sena meta mqabbla ma ’ pazjenti iżgħar.
When Xeloda was used in combination with other agents, elderly patients (≥ 65 years) experienced more grade 3 and grade 4 adverse drug reactions, including those leading to discontinuation, compared to younger patients.
Meta Xeloda ntuża flimkien ma ’ sustanzi oħra, pazjenti anzjani (≥65 sena) kellhom esperjenza akbar ta ’ reazzjonijiet avversi għall- mediċina ta ’ grad 3 u grad 4, inkluż dawk li wasslu għat- twaqqif, meta mqabbel ma ’ pazjenti iżgħar.
Careful monitoring of patients ≥ 60 years of age is advisable.
Sorveljanza bir- reqqa ta ’ pazjenti li għandhom ≥ 60 sena huwa rakkomandat.
- In combination with docetaxel: an increased incidence of grade 3 or 4 treatment-related adverse
- Flimkien ma ’ docetaxel: inċidenza ogħla ta ’ reazzjonijiet avversi ta ’ grad 3 jew 4 li huma
reactions and treatment-related serious adverse reactions were observed in patients 60 years of age or more (see section 5.1).
relatati mal- kura u ta ’ reazzjonijiet avversi serji li huma relatati mal- kura ġew osservati f’ pazjenti li għandhom 60 sena jew aktar (ara sezzjoni 5. 1).
For patients 60 years of age or more, a starting dose reduction of Xeloda to 75% (950 mg/ m2 twice daily) is recommended.
Għall- pazjenti li għandhom 60 sena jew aktar, tnaqqis fid- doża tal- bidu ta ’ Xeloda għal 75% (950 mg/ m2 darbtejn kuljum) huwa rakkomandat.
If no toxicity is observed in patients ≥ 60 years of age treated with a reduced Xeloda starting dose in combination with docetaxel, the dose of Xeloda may be cautiously escalated to 1250 mg/ m2 twice daily.
Jekk l- ebda tossiċità ma tiġi osservata f’ pazjenti li għandhom ≥ 60 sena kkurati b’ doża tal- bidu ta ’ Xeloda mnaqqsa flimkien ma ’ docetaxel, id- doża ta ’ Xeloda tista ’ tiġi miżjuda b’ kawtela għal 1250 mg/ m2 darbtejn kuljum.
- In combination with irinotecan: for patients 65 years of age or more, a starting dose reduction of
- Flimkien ma ’ irinotecan: għall- pazjenti b’ età ta ’ 65 sena jew aktar, hija rakkomandata tnaqqis
Xeloda to 800 mg/ m2 twice daily is recommended.
fid- doża tal- bidu ta ’ Xeloda għal 800 mg/ m2 darbtejn kuljum.
• History of severe and unexpected reactions to fluoropyrimidine therapy, • Hypersensitivity to capecitabine or to any of the excipients or fluorouracil, • In patients with known dihydropyrimidine dehydrogenase (DPD) deficiency, • During pregnancy and lactation, • In patients with severe leucopenia, neutropenia, or thrombocytopenia, • In patients with severe hepatic impairment, • In patients with severe renal impairment (creatinine clearance below 30 ml/ min), • Treatment with sorivudine or its chemically related analogues, such as brivudine (see section 4.5), • If contraindications exist to any of the agents in the combination regimen, that agent should not be used.
• Passat mediku ta ’ reazzjonijiet serji u mhux mistennija għat- terapija bi fluoropyrimidine, • Sensitività eċċessiva għal capecitabine, jew għal xi sustanzi mhux attivi, jew għal fluorouracil, • F’ pazjenti b’ defiċjenza magħrufa ta ’ dihydropyrimidine dehydrogenase (DPD), • Waqt it- tqala u t- treddigħ, • F’ pazjenti b’ lewkopenja, newtropenja, jew tromboċitopenja severa, • F’ pazjenti b’ indeboliment sever tal- fwied, • F’ pazjenti b’ indeboliment sever tal- kliewi (tneħħija tal- krejatinina taħt 30 ml/ min), • Kura b’ sorivudine jew u bl- analogi relatati kimikament miegħu, bħal brivudine (ara sezzjoni 4. 5), • Jekk jeżistu kontra- indikazzjonijiet għal xi sustanzi fil- programm ta ’ taħlita, dik is- sustanza m’ għandiex tintuża.
6 4.4 Special warnings and precautions for use
6 4. 4 Twissijiet speċjali u prekawzjonijiet għall- użu
Dose limiting toxicities include diarrhoea, abdominal pain, nausea, stomatitis and hand-foot syndrome (hand-foot skin reaction, palmar-plantar erythrodysesthesia).
Tossiċitajiet li jillimitaw id- doża jinkludu dijarea, uġigħ addominali, tqalligħ, stomatite u s- sindrome ta ’ l- idejn u s- saqajn (reazzjoni tal- ġilda fl- idejn u fis- saqajn, eritrodisasteżija palmari- plantari).
Most adverse reactions are reversible and do not require permanent discontinuation of therapy, although doses may need to be withheld or reduced.
Il - biċċa l- kbira tar- reazzjonijiet avversi huma riversibbli u ma jeħtieġux interruzzjoni permanenti tat - terapija, għalkemm jista ’ jkun hemm bżonn li xi dożi jiġu miżmuma jew imnaqqsa.
Diarrhoea.
Dijarea.
Patients with severe diarrhoea should be carefully monitored and given fluid and electrolyte replacement if they become dehydrated.
Pazjenti b’ dijarea serja għandhom jiġu osservati b’ attenzjoni u mogħtija sostituzzjoni ta ’ fluwidu u elettroliti jekk jiġu deidratati.
Standard antidiarrhoeal treatments (e. g. loperamide) may be used.
Tista ’ tintuża kura stàndard kontra d- dijarea (eż. loperamide).
NCIC CTC grade 2 diarrhoea is defined as an increase of 4 to 6 stools/ day or nocturnal stools, grade 3 diarrhoea as an increase of 7 to 9 stools/ day or incontinence and malabsorption.
Dijarea ta ’ grad NCIC CTC 2 hija definita bħala żjieda ta ’ 4 sa 6 ħmieġ/ kuljum jew ħmieġ bil- lejl, dijarea ta ’ grad 3 bħala żjieda ta ’ 7 sa 9 ħmieġ/ kuljum jew inkontinenza u assorbiment imnaqqas.
Grade 4 diarrhoea is an increase of ≥ 10 stools/ day or grossly bloody diarrhoea or the need for parenteral support.
Dijarea ta ’ grad 4 hija żjieda ta ’ ≥10 ħmieġ/ kuljum jew dijarea b’ ħafna demm jew il- bżonn ta ’ appoġġ parenterali.
Dose reduction should be applied as necessary (see section 4.2).
Għandu jsir tnaqqis fid- doża skond il- bżonn (ara sezzjoni 4. 2).
Dehydration.
Deidrazzjoni:
Dehydration should be prevented or corrected at the onset.
Id- deidrazzjoni għandha tiġi evitata jew ikkoreġuta mill- bidu.
Patients with anorexia, asthenia, nausea, vomiting or diarrhoea may rapidly become dehydrated.
Pazjenti bl- anoreksja, astenja, tqalligħ, rimettar jew dijarea jistgħu jsiru deidratati malajr.
If Grade 2 (or higher) dehydration occurs, Xeloda treatment should be immediately interrupted and the dehydration corrected.
Jekk isseħħ deidrazzjoni ta ’ Grad 2 (jew ogħla), il- kura b’ Xeloda għandha titwaqqaf minnufih u d- deidrazzjoni kkoreġuta.
Treatment should not be restarted until the patient is rehydrated and any precipitating causes have been corrected or controlled.
Il- kura m’ għandhiex terġa tinbeda qabel il- pazjent jiġi idratat mill- ġdid u fatturi ta ’ kawża jiġu kkoreġuti jew ikkontrollati.
Dose modifications applied should be applied for the precipitating adverse event as necessary (see section 4.2).
Modifikazzjonijiet tad- doża applikati għandhom jiġu applikati għall- avvenniment avvers li kkawżha, skond il- ħtieġa (ara sezzjoni 4. 2).
Hand-foot syndrome (also known as hand-foot skin reaction or palmar-plantar erythrodysesthesia or chemotherapy induced acral erythema).
Sindrome ta ’ l- idejn u s- saqajn (magħruf ukoll bħala reazzjoni tal- ġilda ta ’ l- idejn u s- saqajn jew eritrodisasteżija palmari- plantari jew eritema akrali kkaġunata mill- kemjoterapija).
Grade 1 hand- foot syndrome is defined as numbness, dysesthesia/ paresthesia, tingling, painless swelling or erythema of the hands and/ or feet and/ or discomfort which does not disrupt the patient’ s normal activities.
Sindrome ta ’ l - idejn u s- saqajn ta ’ grad 1 huwa definit bħala tnemnim, disestesja/ parestesja, tingiż, nefħa mingħajr uġigħ jew eritema ta ’ l- idejn u/ jew tas- saqajn u/ jew skumdità li ma ttellifx l- attivitajiet normali tal - pazjent.
Grade 2 hand- foot syndrome is painful erythema and swelling of the hands and/ or feet and/ or discomfort affecting the patient’ s activities of daily living.
Sindrome ta ’ l- idejn u s- saqajn ta ’ Grad 2 huwa eritema bl- uġigħ u nefħa ta ’ l- idejn u/ jew tas- saqajn u/ jew skumdità li taffettwa l- attivitajiet tal- ħajja ta ’ kuljum tal- pazjent.
Grade 3 hand- foot syndrome is moist desquamation, ulceration, blistering and severe pain of the hands and/ or feet and/ or severe discomfort that causes the patient to be unable to work or perform activities of daily living.
Sindrome ta ’ l- idejn u s- saqajn ta ’ Grad 3 huwa tqaxxir mxarrab tal- ġilda, ulċerazzjoni, nfafet u uġigħ serju ta ’ l- idejn u/ jew tas- saqajn u/ jew skumdità serja li ġġiegħel il- pazjent li ma jibqax kapaċi jaħdem jew li jagħmel l- attivitajiet tal- ħajja ta ’ kuljum.
If grade 2 or 3 hand- foot syndrome occurs, administration of Xeloda should be interrupted until the event resolves or decreases in intensity to grade 1.
Jekk isseħħ sindrome ta ’ l- idejn u s- saqajn ta ’ grad 2 jew 3, l- għoti ta ’ Xeloda għandu jiġi interrott sakemm ir- reazzjoni tieqaf jew tnaqqas fl- intensità għal grad 1.
Following grade 3 hand- foot syndrome, subsequent doses of Xeloda should be decreased.
Wara sindrome ta ’ l- idejn u s- saqajn ta ’ grad 3, id- dożi ta ’ Xeloda li jmissu għandhom jiġu mnaqqsa.
When Xeloda and cisplatin are used in combination, the use of vitamin B6 (pyridoxine) is not advised for symptomatic or secondary prophylactic treatment of hand– foot syndrome, because of published reports that it may decrease the efficacy of cisplatin.
Meta Xeloda u cisplatin jintużaw flimkien, l- użu ta ’ vitamina B6 (pyridoxine) mhux rakkomandat għall- kura profilattika sintomatika jew sekondarja ts- sindrome ta ’ l- idejn u s- saqajn, minħabba rapporti ppublikati li hija tista ’ tnaqqas l- effikaċja ta ’ cisplatin.
Cardiotoxicity.
Kardjotossiċità.
Cardiotoxicity has been associated with fluoropyrimidine therapy, including myocardial infarction, angina, dysrhythmias, cardiogenic shock, sudden death and electrocardiographic changes.
Il- kardjotossiċità ġiet assoċjata mat- terapija b’ fluoropyrimidine, inkluż infart mijokardijaku, anġina, disritmija, xokk kardjoġeniku, mewt għal għarrieda u bidliet elettrokardjografiċi.
These adverse reactions may be more common in patients with a prior history of coronary artery disease.
Dawn ir- reazzjonijiet avversi jistgħu jkunu aktar komuni f’ pazjenti li għandhom passat ta ’ mard ta ’ l- arterji tal- koronarja.
Cardiac arrhythmias, angina pectoris, myocardial infarction, heart failure and cardiomyopathy have been reported in patients receiving Xeloda.
Arritmija kardijaka, anġina pectoris, infart mijokardijaku, insuffiċjenza tal- qalb u kardjomijopatija ġew irrapportati f’ pazjenti li qed jieħdu Xeloda.
Caution must be exercised in patients with history of significant cardiac disease, arrhythmias and angina pectoris (See section 4.8).
Trid tingħata attenzjoni lill- pazjenti li għandhom passat ta ’ mard kardijaku sinifikanti, arritmija u anġina pectoris (Ara sezzjoni 4. 8).
Hypo- or hypercalcaemia.
Ipo - jew iperkalċimja.
Hypo- or hypercalcaemia has been reported during Xeloda treatment.
Ipo - jew iperkalċimja ġew irrapportati waqt il- kura b’ Xeloda.
Caution must be exercised in patients with pre-existing hypo- or hypercalcaemia (see section 4.8).
Trid tingħata attenzjoni lill- pazjenti li diġa għandhom ipo - jew iperkalċimja (ara sezzjoni 4. 8).
Central or peripheral nervous system disease.
Mard tas- sistema nervuża ċentrali jew periferali.
Caution must be exercised in patients with central or peripheral nervous system disease, e. g. brain metastasis or neuropathy (see section 4.8).
Trid tingħata attenzjoni lill- pazjenti b’ mard fis - sistema nervuża ċentrali jew periferali eż. metastasi fil- moħħ jew newropatija (ara sezzjoni 4. 8).
Diabetes mellitus or electrolyte disturbances.
Dijabete mellitus jew disturbi fl- elettroliti.
Caution must be exercised in patients with diabetes mellitus or electrolyte disturbances, as these may be aggravated during Xeloda treatment.
Fi studju dwar l- interazzjoni tal- mediċina waqt l- għoti ta ’ doża waħda ta ’ warfarin, kien hemm żjieda sinifikattiva fil- medja ta ’ l- AUC (+57%) ta ’ S- warfarin.
7 Coumarin-derivative anticoagulation.
7 sistema ta ’ l- isoenżimi taċ- ċitokromju P450 2C9.
Patients receiving concomitant Xeloda and oral coumarin-derivative anticoagulant therapy should have their anticoagulant response (INR or prothrombin time) monitored closely and the anticoagulant dose adjusted accordingly (see section 4.5).
Pazjenti li qed jieħdu Xeloda u terapija ta ’ antikoagulazzjoni b’ derivattiv tal- coumarin mill- ħalq flimkien għandu jkollhom r- respons antikoagulanti tagħhom (INR jew ħin protrombin) osservat b’ attenzjoni kbira u d- doża antikoagulanti mibdula skond ir- riżultat (ara sezzjoni 4. 5).
Hepatic impairment.
Indeboliment tal- fwied.
In the absence of safety and efficacy data in patients with hepatic impairment, Xeloda use should be carefully monitored in patients with mild to moderate liver dysfunction, regardless of the presence or absence of liver metastasis.
Fin- nuqqas ta ’ informazzjoni dwar is- sigurtà u l- effikaċja f’ pazjenti b’ indeboliment tal- fwied, l- użu ta ’ Xeloda għandu jiġi osservat b’ attenzjoni f’ pazjenti li l- fwied tagħhom ma jaħdimx normali b’ mod ħafif għal moderat, mingħajr ma jingħata każ tal- preżenza jew in - nuqqas ta ’ metastasi tal- fwied.
Administration of Xeloda should be interrupted if treatment-related elevations in bilirubin of > 3.0 x ULN or treatment-related elevations in hepatic aminotransferases (ALT, AST) of > 2.5 x ULN occur.
L- għoti ta ’ Xeloda għandu jiġi interrott f’ każ li sseħħ żjieda fil- livelli ta ’ bilirubin ta ’ > 3. 0 x ULN relatata mal- kura jew żjieda fil- livell ta ’ aminotransferases tal- fwied (ALT, AST) ta ’ > 2. 5 x ULN relatata mal- kura.
Treatment with Xeloda monotherapy may be resumed when bilirubin decreases to ≤ 3.0 x ULN or hepatic aminotransferases decrease to ≤ 2.5 x ULN.
Il- kura b’ Xeloda li tittieħed waħidha tista ’ titkompla meta l- bilirubin jonqos għal ≤ 3. 0 x ULN jew l- aminotransferases epatiċi jitnaqqsu għal ≤ 2. 5 x ULN.
The incidence of grade 3 or 4 adverse reactions in patients with moderate renal impairment (creatinine clearance 30-50 ml/ min) is increased compared to the overall population (see section 4.2 and 4.3).
Reazzjonijiet avversi ta ’ grad 3 jew 4 f’ pazjenti b’ indeboliment moderat tal - kliewi (tneħħija tal- krejatinina 30- 50 ml/ min) iseħħu aktar ta ’ spiss meta mqabbla mal- popolazzjoni totali (ara sezzjonijiet 4. 2 u 4. 3).
As this medicinal product contains anhydrous lactose as an excipient, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Minħabba li dan il- prodott mediċinali fiħ anhydrous lactose bħala sustanza mhux attiva, pazjenti b’ problemi ereditarji rari ta ’ intolleranza għal galactose, nuqqas ta ’ Lapp lactase jew assorbiment ħażin ta ’ glucose- galactose m’ għandhomx jieħdu din il- mediċina.
Interaction with other medicinal products:
Interazzjonijiet ma ’ prodotti mediċinali oħra:
Coumarin-derivative anticoagulants: altered coagulation parameters and/ or bleeding have been reported in patients taking Xeloda concomitantly with coumarin-derivative anticoagulants such as warfarin and phenprocoumon.
Antikoagulanti derivattivi ta ’ coumarin: bdil fil- parametri tal- koagulazzjoni u/ jew fil- fsada ġew irrapportati f’ pazjenti li kienu qed jieħdu Xeloda waqt kura b’ antikoagulanti derivattivi ta ’ coumarin, bħal warfarin u phenprocoumon.
These reactions occurred within several days and up to several months after initiating Xeloda therapy and, in a few cases, within one month after stopping Xeloda.
Dawn ir- reazzjonijiet seħħew f’ temp ta ’ diversi ġranet u sa diversi xhur wara l- bidu tat- terapija b’ Xeloda u, fi ftit każijiet, fi żmien xahar wara li Xeloda twaqqaf.
In a clinical pharmacokinetic interaction study, after a single 20 mg dose of warfarin, Xeloda treatment increased the AUC of S-warfarin by 57% with a 91% increase in INR value.
Fi studju kliniku farmakokinetiku dwar l- interazzjonijiet, wara doża waħda ta ’ 20 mg ta ’ warfarin, il- kura b’ Xeloda żiedet l- AUC ta ’ S- warfarin b’ 57% b’ żjieda ta ’ 91% fil- valur ta ’ l- INR.
Since metabolism of R- warfarin was not affected, these results indicate that capecitabine down-regulates isozyme 2C9, but has no effect on isozymes 1A2 and 3A4.
Billi l- metaboliżmu ta ’ R- warfarin ma kienx affettwat, dawn ir- riżultati jindikaw li capecitabine jnaqqas l- attività ta ’ isoenżima 2C9, iżda m’ għandu l- ebda effect fuq l- isoenżimi 1A2 u 3A4.
Patients taking coumarin-derivative anticoagulants concomitantly with Xeloda should be monitored regularly for alterations in their coagulation parameters (PT or INR) and the anti-coagulant dose adjusted accordingly.
Pazjenti li qed jieħdu antikoagulanti derivattiv ta ’ coumarin flimkien ma ’ Xeloda, għandhom jiġu osservati regolarment għal tibdil fil- parametri tal- koagulazzjoni tagħhom (PT jew INR) u d- doża ta ’ l- antikoagulanti aġġustata kif suppost.
Phenytoin: increased phenytoin plasma concentrations resulting in symptoms of phenytoin intoxication in single cases have been reported during concomitant use of Xeloda with phenytoin.
Phenytoin: żjieda fil- konċentrazzjonijiet ta ’ phenytoin fil- plażma li tirriżulta f’ sintomi ta ’ intossikazzjoni ta ’ phenytoin f’ każijiet individwali, ġew irrapportati waqt l- użu ta ’ Xeloda flimkien ma ’ phenytoin.
Patients taking phenytoin concomitantly with Xeloda should be regularly monitored for increased phenytoin plasma concentrations.
Pazjenti li qed jieħdu phenytoin flimkien ma ’ Xeloda għandhom jiġu osservati regolarment għal żidiet fil- konċentrazzjonijiet ta’ phenytoin fil- plażma.
Folinic acid: a combination study with Xeloda and folinic acid indicated that folinic acid has no major effect on the pharmacokinetics of Xeloda and its metabolites.
Folinic acid: studju ta ’ taħlita b’ Xeloda u folinic acid indika li folinic acid m’ għandu l- ebda effett maġġuri fuq il- farmakokinetika ta ’ Xeloda u l- metaboliti tiegħu.
However, folinic acid has an effect on the pharmacodynamics of Xeloda and its toxicity may be enhanced by folinic acid: the maximum tolerated dose (MTD) of Xeloda alone using the intermittent regimen is 3000 mg/ m2 per day whereas it is only 2000 mg/ m2 per day when Xeloda was combined with folinic acid (30 mg orally bid).
Madankollu, folinic acid għandu effett fuq il- farmakodinamika ta ’ Xeloda u t- tossiċità tiegħu tista ’ tiġi msaħħa minn folinic acid: id - doża massima tollerata (MTD) ta ’ Xeloda waħdu bl- użu ta ’ kors intermittenti huwa ta ’ 3000 mg/ m2 kuljum filwaqt li l- MTD hija biss ta ’ 2000 mg / m2 kuljum meta Xeloda jittieħed flimkien ma ’ folinic acid (30 mg meħud mill- ħalq darbtejn kuljum).
8 Sorivudine and analogues: a clinically significant drug-drug interaction between sorivudine and 5-FU, resulting from the inhibition of dihydropyrimidine dehydrogenase by sorivudine, has been described.
Sorivudine u analogi: ġiet deskritta interazzjoni ta ’ sinifikanza klinika bejn sorivudine u 5- FU, li rriżultat mill- impedizzjoni ta ’ dihydropyrimidine dehydrogenase minn sorivudine.
This interaction, which leads to increased fluoropyrimidine toxicity, is potentially fatal.
Din l- interazzjoni, li twassal għal żjieda fit- tossiċità ta ’ fluoropyrimidine, hija potenzjalment fatali.
Therefore, Xeloda must not be administered concomitantly with sorivudine or its chemically related analogues, such as brivudine (see section 4.3).
Għalhekk, Xeloda ma jistax jingħata flimkien ma ’ sorivudine jew ma ’ l- analogi relatati kimikament miegħu, bħal brivudine
There must be at least a 4-week waiting period between end of treatment with sorivudine or its chemically related analogues such as brivudine and start of Xeloda therapy.
Għandu jkun hemm ta 'l- inqas perijodu ta' stennija ta '4 ġimgħat bejn it- tmiem tal - kura b’ sorivudine jew bl- analogi relatati b’ mod kimiku miegħu bħal brivudine u l- bidu tat- terapija ta ’ Xeloda.
Antacid: the effect of an aluminum hydroxide and magnesium hydroxide-containing antacid on the pharmacokinetics of capecitabine was investigated.
Antaċidi: l- effett ta ’ antaċidi li fihom aluminium hydroxide u magnesium hydroxide fuq il - farmakokinetika ta ’ capecitabine kien investigat.
There was a small increase in plasma concentrations of capecitabine and one metabolite (5’ -DFCR); there was no effect on the 3 major metabolites (5’ -DFUR, 5-FU and FBAL).
Kien hemma żjieda żgħira fil- konċentrazzjonijiet fil - plażma ta ’ capecitabine u metabolit wieħed (5 ’ - DFCR); ma kien hemm l- ebda effett fuq il- 3 metaboliti maġġuri (5 ’ - DFUR, 5- FU u FBAL).
Allopurinol: interactions with allopurinol have been observed for 5-FU; with possible decreased efficacy of 5-FU.
Allopurinol: interazzjonijiet ma ’ allopurinol ġew osservati għal 5- FU; bi tnaqqis possibbli ta ’ l - effikaċja ta ’ 5- FU.
Concomitant use of allopurinol with Xeloda should be avoided.
L- użu ta ’ allopurinol flimkien ma ’ Xeloda għandu jiġi evitat.
For potential interactions with isozymes 1A2, 2C9 and 3A4, see interactions with coumarin-derivative anticoagulation.
Interazzjoni maċ- ċitokromju P- 450: għall- interazzjonijiet potenzjali ma ’ isoenżimi 1A2, 2C9 u 3A4, ara l- interazzjonijiet ma ’ antikoagulanti derivattivi ta ’ coumarin.
Interferon alpha: the MTD of Xeloda was 2000 mg/ m2 per day when combined with interferon alpha- 2a (3 MIU/ m2 per day) compared to 3000 mg/ m2 per day when Xeloda was used alone.
Interferon alfa: l- MTD ta ’ Xeloda kienet ta ’ 2000 mg/ m2 kuljum meta meħud flimkien ma ’ interferon alfa- 2a (3 MIU/ m2 kuljum) imqabbla ma ’ 3000 mg/ m2 kuljum meta Xeloda jintuża waħdu.
Radiotherapy: the MTD of Xeloda alone using the intermittent regimen is 3000 mg/ m2 per day, whereas, when combined with radiotherapy for rectal cancer, the MTD of Xeloda is 2000 mg/ m2 per day using either a continuous schedule or given daily Monday through Friday during a 6-week course of radiotherapy.
Radjuterapija: l- MTD ta ’ Xeloda waħdu bl- użu ta ’ kors intermittenti hija ta ’ 3000 mg/ m2 kuljum, filwaqt, meta kkombinat ma ’ radjuterapija għall- kanċer fir- rektum, l- MTD ta ’ Xeloda hija 2000 mg/ m2 kuljum bl- użu ta ’ programm kontinwu jew mogħti kuljum mit- Tnejn sal- Ġimgħa waqt kors ta ’ sitt ġimgħat ta ’ radjuterapija.
Oxaliplatin: no clinically significant differences in exposure to capecitabine or its metabolites, free platinum or total platinum occurred when capecitabine was administered in combination with oxaliplatin or in combination with oxaliplatin and bevacizumab.
Oxaliplatin: l- ebda differenzi ta ’ sinifikanza klinika fl- espożizzjoni għal capecitabine jew għall - metaboliti tiegħu, platinum ħieles jew platinum totali ma dehru meta capecitabine ingħata f’ taħlita ma ’ oxaliplatin jew f’ taħlita ma ’ oxaliplatin u bevacizumab.
Bevacizumab: there was no clinically significant effect of bevacizumab on the pharmacokinetic parameters of capecitabine or its metabolites in the presence of oxaliplatin.
Bevacizumab: ma kien hemm l- ebda effett ta ’ sinifikanza klinika ta ’ bevacizumab fuq il- parametri farmakokinetiċi ta ’ capecitabine jew tal- metaboliti tiegħu fil- preżenza ta ’ oxaliplatin.
Food interaction:
Interazzjoni ma ’ l- ikel:
In all clinical trials, patients were instructed to administer Xeloda within 30 minutes after a meal.
Fil- provi kliniċi kollha, il- pazjenti kienu mitluba biex jieħdu Xeloda fi żmien 30 minuta wara l- ikel.
Since current safety and efficacy data are based upon administration with food, it is recommended that Xeloda be administered with food.
Billi t- tagħrif kurrenti dwar is- sigurtà u l- effikaċja hu bbażat fuq l- għoti ma ’ ikel, huwa rakkomandat li Xeloda jingħata ma ’ l- ikel.
Administration with food decreases the rate of capecitabine absorption (see section 5.2).
L- għoti ma ’ l- ikel inaqqas ir- rata ta ’ l - assorbiment ta ’ capecitabine (ara sezzjoni 5. 2).
There are no studies in pregnant women using Xeloda; however, it should be assumed that Xeloda may cause foetal harm if administered to pregnant women.
M’ hemmx studji dwar nisa tqal li qed jużaw Xeloda; madankollu, wieħed għandu jassumi li Xeloda jista ’ jikkawża ħsara lill- fetu jekk tingħata lil nisa tqal.
In reproductive toxicity studies in animals, Xeloda administration caused embryolethality and teratogenicity.
Fi studji dwar it- tossiċità riproduttiva fl - annimali, l- għoti ta ’ Xeloda kkawża mewt ta ’ l- embriju u teratoġeniċità.
These findings are expected effects of fluoropyrimidine derivatives.
Dawn is- sejbiet huma l- effetti mistennija tad- derivattivi ta ’ fluoropyrimidine.
Xeloda is contraindicated during pregnancy.
Xeloda m’ għandux jingħata waqt it- tqala.
Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with Xeloda.
Nisa li jista ’ jkollhom it- tfal għandhom jingħataw il- parir biex jevitaw li joħorġu tqal waqt li qed jirċievu l- kura b’ Xeloda.
If the patient becomes pregnant while receiving Xeloda, the potential hazard to the foetus must be explained.
Jekk il- pazjenta toħroġ tqila waqt li tkun qed tieħdu Xeloda, il - periklu potenzjali lill- fetu irid jiġi spjegat.
It is not known whether Xeloda is excreted in human breast milk.
Mhuwiex magħruf jekk Xeloda joħroġx fil- ħalib tas- sider uman.
In lactating mice, considerable amounts of capecitabine and its metabolites were found in milk.
Fi ġrieden li kienu qed jreddgħu, ammonti konsiderevoli ta ’ capecitabine u l- metaboliti tiegħu nstabu fil- ħalib.
Breast-feeding should be discontinued while receiving treatment with Xeloda.
It- treddigħ għandu jitwaqqaf waqt l- kura b’ Xeloda.
Xeloda has minor or moderate influence on the ability to drive and use machines.
Xeloda għandu effett żgħir jew moderat fuq il- ħila biex issuq u tħaddem maġni.
Xeloda may cause dizziness, fatigue and nausea.
Xeloda jista ’ jikkawża sturdament, għeja u tqalligħ.
9 4.8 Undesirable effects
9 4. 8 Effetti mhux mixtieqa
Summary of the safety profile
Sommarju tal- profil ta ’ sigurtà
The overall safety profile of Xeloda is based on data from over 3000 patients treated with Xeloda as monotherapy or Xeloda in combination with different chemotherapy regimens in multiple indications.
Il- profil globali ta ’ sigurtà ta ’ Xeloda huwa bbażat fuq tagħrif minn aktar minn 3000 pazjent ikkurati b’ Xeloda bħala monoterapija jew Xeloda f’ taħlita ma ’ korsijiet differenti ta ’ kimoterapija f’ indikazzjonijiet multipli.
The safety profiles of Xeloda monotherapy for the metastatic breast cancer, metastatic colorectal cancer and adjuvant colon cancer populations are comparable.
Il- profili ta ’ sigurtà ta ’ monoterapija ta ’ Xeloda għall- popolazzjonijiet ta ’ kanċer metastatiku tas- sider, kanċer metastatiku tal- kolon u tar- rektum u ta ’ kura awżiljarja f’ kanċer tal- kolon huma komparabbli.
See section 5.1 for details of major studies, including study designs and major efficacy results.
Ara sezzjoni 5. 1 għad- dettalji ta ’ l- istudji maġġuri, inkluż id- disinji ta ’ l - istudju u r- riżultati maġġuri ta ’ l- effikaċja.
The most commonly reported and/ or clinically relevant treatment-related adverse drug reactions (ADRs) were gastrointestinal disorders (especially diarrhoea, nausea, vomiting, abdominal pain, stomatitis), hand-foot syndrome (palmar-plantar erythrodysesthesia), fatigue, asthenia, anorexia, cardiotoxicity, increased renal dysfunction on those with preexisting compromised renal function, and thrombosis/ embolism.
L- aktar reazzjonijiet avversi tal- mediċina (ADRs) relatati mal- kura rrapportati b’ mod frekwenti u/ jew ta ’ rilevanza klinika kienu disturbi gastro- intestinali (speċjalment dijarea, tqalligħ, rimettar, uġigħ addominali, stomatite), s- sindrome ta ’ l- idejn u s- saqajn (eritrodisasteżija palmari- plantari), għeja, astenja, anoreksja, kardjotossiċità, disfunzjoni renali miżjuda f’ dawk b’ funzjoni renali kompromessa minn qabel, u trombożi/ emboliżmu.
Tabulated summary of adverse reactions
Sommarju f’ tabella tar- reazzjonijiet avversi
ADRs considered by the investigator to be possibly, probably, or remotely related to the administration of Xeloda are listed in Table 4 for Xeloda given as a single agent and in Table 5 for Xeloda given in combination with different chemotherapy regimens in multiple indications.
ADRs ikkunsidrati mill- investigatur bħala possibbilment, probabbilment jew remotament relatati ma ’ l- għoti ta ’ Xeloda huma mniżżla f’ Tabella 4 għal Xeloda mogħti bħala sustanza waħedha u f’ Tabella 5 għal Xeloda mogħti flimkien ma ’ korsijiet ta ’ kimoterapija differenti f’ indikazzjonijiet multipli.
The following headings are used to rank the ADRs by frequency: very common (≥ 1/ 10), common (≥ 1/ 100, < 1/ 10) and uncommon (≥ 1/ 1,000, < 1/ 100).
Il - kategoriji li ġejjin huma wżati biex jikklassifikaw l- ADRs skond il- frekwenza: komuni ħafna (≥1/ 10), komuni (≥1/ 100, < 1/ 10) u mhux komuni (≥1/ 1, 000, < 1/ 100).
Within each frequency grouping, ADRs are presented in order of decreasing seriousness.
F’ kull sezzjoni ta ’ frekwenza, l- ADRs għandhom jitniżżlu skond is- serjetà tagħhom.
Xeloda Monotherapy:
Monoterapija b’ Xeloda:
Table 4 lists ADRs associated with the use of Xeloda monotherapy based on a pooled analysis of safety data from three major studies including over 1900 patients (studies M66001, SO14695, and SO14796).
Tabella 4 telenka l- ADRs assoċjati ma ’ l- użu ta ’ Xeloda bħala monoterapija ibbażati fuq analiżi globali ta ’ tagħrif dwar is- sigurtà minn tliet studji maġġuri li kienu jinkludu aktar minn 1900 pazjent (studji M66001, SO14695, u SO14796).
ADRs are added to the appropriate frequency grouping according to the overall incidence from the pooled analysis.
L- ADRs huma miżjuda mal- ġrupp ta ’ frekwenza xieraq skond l- inċidenza totali mill- analiżi globali.
Table 4 Summary of related ADRs reported in patients treated with Xeloda monotherapy
10 Tabella 4 Sommarju ta ’ l- ADRs relatati rrapportati f’ pazjenti kkurati b’ monoterapija ta ’ Xeloda Mhux Komuni Komuni
Uncommon
Kull grad
All grades All grades
Kull grad
Severe and/ or Life-
Severi u/ jew ta ’
threatening (grade 3-4) or considered medically relevant Infections and infestations
periklu għall- ħajja (grad 3- 4) jew ikkunsidrati rilevanti medikament Sepsis, Infezzjonijiet u infestazzjonijiet
Herpes viral infection, Nasopharyngitis, Lower respiratory tract infection
Infezzjoni virali ta ’ l - Herpes, Nasofarinġite, Infezzjoni fl- apparat respiratorju t’ isfel
Sepsis, Urinary tract infection, Cellulitis, Tonsillitis, Pharyngitis, Oral candidiasis, Influenza, Gastroenteritis, Fungal infection, Infection, Tooth abscess
Infezzjoni fl- apparat ta ’ l- awrina, Ċellulite, Tonsillite, Farinġite, Kandidajasi orali, Influwenza, Gastroenterite, Infezzjoni mill- moffa, Infezzjoni, Axxess f’ sinna
Neoplasm benign, malignant and unspecified
Neoplażmi beninni, malinni u dawk mhux speċifikati (inklużi ċesti u polipi)
Neutropenia, Anaemia
Newtropenija,
Body System
Newtropenija bid- deni,
Common
tas- sistema limfatika
Uncommon
Anemija
All grades All grades
Panċitopenija, Granuloċitopenija, Tromboċitopenija, Lewkopenija, Anemija emolitika, Proporzjon Normalizzat Internazzjonali (INR) miżjud/ Ħin ta ’ Prothrombin imtawwal
threatening (grade 3-4) or considered medically relevant Immune system disorders
Disturbi fis- sistema immuni
Hypersensitivity
Sensittività eċċessiva Dijabete,
Dehydration, Decreased appetite, Weight decreased
Deidratazzjoni, Tnaqqis fl- aptit, Tnaqqis fil- piż
Diabetes, Hypokalaemia, Appetite disorder, Malnutrition, Hypertriglyceridaemia,
Ipokalimja, Disturbi fl- aptit, Nutrizzjoni ħażina, Ipertrigliċeridemija
Insomnia, Depression
Stat ta ’ konfużjoni,
Confusional state, Panic attack, Depressed mood, Libido decreased
Attakk ta ’ paniku, Burdata depressa, Tnaqqis fil- libido Afasja,
Headache, Lethargy Dizziness, Parasthesia Dysgeusia
Uġigħ ta ’ ras, Letarġija, Sturdament, Parasteżija, Disgewsja
Aphasia, Memory impairment, Ataxia, Syncope, Balance disorder, Sensory disorder, Neuropathy peripheral
Nuqqas tal- memorja, Ataxja, Sinkope, Disturbi fil- bilanċ, Disturbi fis- sensi, Newropatija periferali Tnaqqis fl- akutezza tal -
Lacrimation increased, Conjunctivitis, Eye irritation
Żjieda fid- dmugħ, Konġuntivite, Irritazzjoni fl- għajnejn
Visual acuity reduced, Diplopia
vista, Diplopja
Ear and labyrinth disorders
Sistema tal- Ġisem
Vertigo, Ear pain
Vertigo, Uġigħ fil- widnejn
Angina unstable, Angina pectoris, Myocardial ischaemia, Atrial fibrillation, Arrhythmia, Tachycardia, Sinus tachycardia, Palpitations
Anġina instabbli, Anġina pectoris, Iskemija mijokardjali, Fibrillazzjoni atrijali, Arritmija, Takikardija, Takikardija tas- sinus, Palpitazzjonijiet
Deep vein thrombosis, Hypertension, Petechiae, Hypotension, Hot flush, Peripheral coldness
Trombożi fil- vini l - kbar, Ipertensjoni, Petekje, Fwawar, Kesħa fil- periferi Emboliżmu pulmonari,
Dyspnoea, Epistaxis, Cough, Rhinorrhea
Qtugħ ta ’ nifs, Epistassi, Sogħla, Rinorreja
Pulmonary embolism, Pneumothorax, Haemoptysis, Asthma, Dyspnoea exertional
Pnewmotorax, Emoptisi, Ażżma, Qtugħ ta ’ nifs ma ’ l - eżerċizzju
Diarrhoea, Vomiting, Nausea, Stomatitis, Abdominal pain
Dijarea, Rimettar, Tqalligħ, Stomatite,
Gastrointestinal haemorrhage, Constipation, Upper abdominal pain, Dyspepsia, Flatulence, Dry mouth
Fsada gastro- intestinali, Stitikezza, Uġigħ fil- parti ta ’ fuq ta ’ l- addome,
Intestinal obstruction, Ascites, Enteritis, Gastritis, Dysphagia, Abdominal pain lower, Oesophagitis, Abdominal discomfort, Gastrooesophageal reflux disease, Colitis, Blood in stool
Uġigħ fil- parti t’ isfel ta ’ l- addome, Osofaġite, Skumdità addominali, Marda ta ’ rifluss gastro- osofaġali, Kolite, Demm fl- ippurgar
Hepatobiliary Disorders
Disturbi fil- fwied u fil - marrara
Hyperbilirubinemia, Liver function test abnormalities
Iperbilirubinemija, Anormalitajiet fit- test tal- funzjoni tal- fwied
11
12 Mhux Komuni
Rash, Alopecia, Erythema, Dry skin, Pruritus, Skin hyper- pigmentation, Rash macular, Skin desquamation, Dermatitis, Pigmentation disorder, Nail disorder
Kull grad periklu għall- ħajja (grad 3- 4) jew ikkunsidrati rilevanti medikament Ulċeri fil- ġilda, Raxx, Sindrome ta ’ Disturbi fil- ġilda u fit - Raxx, Alopeċja, eritrodisasteżija tessuti ta ’ taħt il- ġilda Uritkarja, Eritema, palmari- plantari Reazzjoni ta ’ Ġilda xotta, fotosensittività, Ħakk, Eritema ta ’ l- idejn, Iperpigmentazzjoni tal - Nefħa fil- wiċċ, ġilda, Purpura Raxx makulari, Tqaxxir tal- ġilda, Dermatite, Disturbi fil - pigmentazzjoni, Disturbi fid- dwiefer Nefħa fil- ġogi, Disturbi muskolu - skeletrali u tal - connective tissue
Pain in extremity, Back pain, Arthralgia
Uġigħ fl- estremitajiet, Uġigħ fid- dahar, Artralġja
Joint swelling, Bone pain, Facial pain, Musculoskeletal stiffness, Muscular weakness
Uġigħ fl- għadam, Uġigħ fil- wiċċ, Egħbusija muskolu - skeletrali, Dgħjufija muskolari
Hydronephrosis, Urinary incontinence, Haematuria, Nocturia, Blood creatinine increased
Idronefrożi, Inkontinenza ta ’ l - awrina, Ematurja, Nokturja, Żjieda tal- krejatinina fid- demm
Vaginal haemorrhage
Emorraġija fil- vaġina Edima,
Fatigue, Asthenia
kondizzjonijiet ta 'mnejn jingħata
Pyrexia, Lethargy, Oedema peripheral, Malaise, Chest pain
Letarġija, Edima periferali, Tħossok ma tiflaħx, Uġigħ fis- sider
Oedema, Chills, Influenza like illness, Rigors, Body temperature increased
Marda bħal l - influwenza, Rogħda, Żjieda tat- temperatura tal- ġisem
Blister, Overdose
Nuffata, Doża eċċessiva
Xeloda in combination therapy:
13 Xeloda f’ terapija ta ’ taħlita:
Table 5 lists ADRs associated with the use of Xeloda in combination with different chemotherapy regimens in multiple indications based on safety data from over 1400 patients.
Tabella 5 telenka l- ADRs assoċjati ma ’ l- użu ta ’ Xeloda f’ taħlita ma ’ korsijiet ta ’ kimoterapija differenti f’ indikazzjonijiet multipli ibbażati fuq tagħrif dwar is- sigurtà minn akar minn 1400 pazjent.
ADRs are added to the appropriate frequency grouping (Very common or Common) according to the highest incidence seen in any of the major clinical trials and are only added when they were seen in addition to those seen with Xeloda monotherapy or seen at a higher frequency grouping compared to Xeloda monotherapy (see Table 4).
L- ADRs huma miżjuda mal- grupp ta ’ frekwenza xieraq (Komuni ħafna jew Komuni) skond l- ogħla inċidenza osservata f’ xi wieħed mill- provi kliniċi maġġuri u huma miżjuda biss meta huma kienu osservati minbarra dawk li dehru b’ monoterapija ta ’ Xeloda jew li dehru fi grupp ta ’ frekwenza aktar għolja meta mqabbel ma ’ monoterapija ta ’ Xeloda (ara Tabella 4).
Uncommon ADRs reported for Xeloda in combination therapy are consistent with the ADRs reported for Xeloda monotherapy or reported for monotherapy with the combination agent (in literature and/ or respective summary of product characteristics).
ADRs mhux komuni rrapportati għal Xeloda f’ terapija kombinata huma konsistenti ma ’ l- ADRs irrapportati għall - monterapija b’ Xeloda jew irrapportati għall- monoterapija bis- sustanza kombinata (fil- letteratura u/ jew sommarju tal- karatterisitiċi tal- prodott rispettiv).
Some of the ADRs are reactions commonly seen with the combination agent (e. g. peripheral sensory neuropathy with docetaxel or oxaliplatin, hypertension seen with bevacizumab); however an exacerbation by Xeloda therapy can not be excluded.
Xi ADRs huma reazzjonijiet osservati b’ mod komuni bis- sustanza kombinata (e. ż. newropatija periferali tas- sensi ma ’ docetaxel jew oxaliplatin, pressjoni għolja osservata ma ’ bevacizumab); iżda rkadar ikkawżat minn terapija ta ’ Xeloda ma jistax jiġi eskluż.
Table 5 Summary of related ADRs reported in patients treated with Xeloda in combination treatment in addition to those seen with Xeloda monotherapy or seen at a higher frequency grouping compared to Xeloda monotherapy Body System
Sommarju ta ’ l- ADRs relatati rrapportati f’ pazjenti kkurati b’ Xeloda f’ kura ta ’ taħlita li kienu osservati minbarra dawk li dehru b’ monoterapija ta ’ Xeloda jew li dehru fi grupp ta ’ frekwenza aktar għolja meta mqabbel ma ’ monoterapija ta ’ Xeloda
All grades
Kull grad
Infections and infestations
Infezzjonijiet u infestazzjonijiet Disturbi tad- demm u
Herpes zoster, Urinary tract infection, Oral candidiasis, Upper respiratory tract infection, Rhinitis, Influenza, +Infection
Herpes zoster, Infezzjoni fl- apparat ta ’ l - awrina, Kandidajasi orali, Infezzjoni fl- apparat repiratorju ta ’ fuq, Rinite, Influwenza, + Infezzjoni Depressjoni tal- mudullun, +Newtropenija bid -
Body System
Lewkopenija, Anemija, +Deni
Very common
deni
Common
newtropeniku, Tromboċitopenija Disturbi fis- sistema immuni
All grades
Sensittività eċċessiva
All grades
Tnaqqis fl- aptit
Blood and lymphatic system
Disturbi psikjatriċi Disturbi fis- sistema nervuża
+
Disturbi fl- irqad, Ansjetà Newrotossiċità, Tregħid, Nevralġija, Reazzjoni ta ’ sensittività eċċessiva
Neutropenia, +Leucopenia,
Disturbi fl- għajnejn
Bone marrow depression, +Febrile
Żjieda fid- dmugħ
disorders
Disturbi fil- vista, Għajn tinħass xotta
Anaemia, +Neutropenic fever,
Tinnitus, Ipoakusis
Neutropenia
Disturbi fil- qalb
Thrombocytopenia Immune system disorders Metabolism and nutrition disorders
Fibrillazzjoni atrijali, Iskemija/ infart kardijaku
- Appetite decreased
Disturbi vaskulari
Hypersensitivity Hypokalaemia, Hyponatremia, Hypomagnesaemia, Hypocalcaemia, Hyperglycaemia
Edima fir- riġlejn, Pressjoni għolja, + Emboliżmu u trombożi
Psychiatric disorders Nervous system disorders
Fwawar, Pressjoni baxxa, Kriżi ipertensiva
- Taste disturbance, Paraesthesia and dysaesthesia, Peripheral neuropathy, Dysgeusia, Headache
Disturbi respiratorji, toraċiċi u medjastinali
Sleep disorder, Anxiety Neurotoxicity, Tremor, Neuralgia, Hypersensitivity reaction
Uġigħ fil- griżmejn, Disasteżija tal- farinġi
Eye disorders Ear and labyrinth disorders Cardiac disorders
Sulluzzu, Uġigħ faringolarinġali, Disfonija
Lacrimation increased - -
Disturbi gastro - intestinali
Visual disorders, Dry eye Tinnitus, Hypoacusis Atrial fibrillation, Cardiac ischemia/ infarction
Emorraġija fl- apparat gastro- intestinali ta ’ fuq, Ulċerazzjoni fil- ħalq, Gastrite, Distensjoni addominali, marda tar- rifluss gastro- osofagali, Uġigħ fil- ħalq, Disfaġija, Emorraġija mir - rektum, Uġigħ fil- parti t’ isfel ta ’ l- addome
Lower limb oedema, Hypertension, +Embolism and thrombosis
Funzjoni epatika mhux normali
Flushing, Hypotension, Hypertensive crisis
Disturbi fil- ġilda u fit -
Respiratory, thoracic and mediastinal system disorders Gastrointestinal disorders
Iperidrosi, Raxx b’ eritema, Urtikarja, Tgħereq
Sore throat, Dysaesthesia pharynx Constipation, Dyspepsia
tessuti ta ’ taħt il- ġilda
Hiccups, Pharyngolaryngeal pain, Dysphonia Upper gastrointestinal haemorrhage, Mouth ulceration, Gastritis, Abdominal distension, Gastroesophageal reflux disease, Oral pain, Dysphagia, Rectal haemorrhage, Abdominal pain lower
dwiefer
Hepatobiliary disorders Skin and subcutaneous tissue disorders
ħafna matul il- lejl
- Alopecia, Nail disorder
Disturbi muskolu -
Hepatic function abnormal Hyperhidrosis, Rash erythematous, Urticaria, Night sweats
Uġigħ fix- xedaq, Spażmi fil- muskoli, Trismus,
Musculoskeletal and connective tissue disorders Renal and urinary disorder
skeletrali u tal - connective tissue
Myalgia, Arthralgia, Pain in extremity -
Uġigħ fl- estremitajiet
Pain in jaw, Muscle spasms, Trismus, Muscular weakness Haematuria, Proteinuria, Creatinine renal clearance decreased
Ematurja, Proteina fl- awrina, Tnaqqis fit - tneħħija tal- krejatinina mill- kliewi
General disorders and administration site conditions
Infjammazzjoni fil- mukoża, Uġigħ fid -
Pyrexia, Weakness, +Lethargy
kondizzjonijiet ta 'mnejn jingħata
Mucosal inflammation, Pain in limb, Pain, Temperature intolerance, Chills, Chest pain, Influenza-like illness, +Fever
dirgħajn jew/ u fir- riġlejn, Uġigħ, Intolleranza għat- temperatura, Rogħda ta ’ bard, Uġigħ fis - sider, Marda bħall- infulwenza, +Deni
Injury, poisoning and procedural complications +
Korriment, avvelenament u komplikazzjonijiet ta ’ xi proċedura
For each term, the frequency count was based on ADRs of all grades.
+ Għal kull terminu, l- għadd tal- frekwenza kien ibbażat fuq ADRs ta ’ kull grad.
For terms marked with a “ +”, the frequency count was based on grade 3-4 ADRs.
Għal termini mmarkati b ’ “ + ”, l- għadd tal- frekwenza kien ibbażat fuq ADRs ta ’ grad 3- 4.
ADRs are added according to the highest incidence seen in any of the major combination trials.
L- ADRs huma miżjuda skond l - ogħla inċidenza osservata f’ wieħed mill- provi ta ’ taħlita maġġuri.
13 Post-Marketing Experience:
Esperjenza ta ’ Wara t- Tqegħid fis- Suq:
The following additional serious adverse reactions have been identified during post-marketing exposure:
Ir- reazzjonijiet avversi serji oħra li ġejjin ġew identifikati waqt espożizzjoni ta ’ wara t- tqegħid fis- suq:
- Very rare: lacrimal duct stenosis
- Rari ħafna: stenosi tal- passaġġ tad- dmugħ
- Very rare: hepatic failure and cholestatic hepatitis have been reported during clinical trials and
- Rari ħafna: insuffiċjenza epatika u epatite kolestatika kienu rrappurtati waqt il- provi kliniċi u
post-marketing exposure
waqt espożizzjoni ta ’ wara t- tqegħid fis- suq
Description of selected adverse reactions
Deskrizzjoni ta ’ reazzjonijiet avversi magħżula
Hand-foot syndrome (see section 4.4):
Sindrome ta ’ l- idejn u s- saqajn (ara sezzjoni 4. 4):
For the capecitabine dose of 1250 mg/ m2 twice daily on days 1 to 14 every 3 weeks, a frequency of 53% to 60% of all-grades HFS was observed in capecitabine monotherapy trials (comprising studies in adjuvant therapy in colon cancer, treatment of metastatic colorectal cancer, and treatment of breast cancer) and a frequency of 63% was observed in the capecitabine/ docetaxel arm for the treatment of metastatic breast cancer.
Għad- doża ta ’ 1250 mg/ m2 capecitabine darbtejn kuljum fi ġranet 1 sa 14 kull 3 ġimgħat, kienet osservata frekwenza ta ’ HFS ta ’ kull grad ta ’ 53% sa 60% fil- provi ta ’ monoterapija b’ capecitabine (inkluż studji b’ terapija awżiljarja f’ kanċer tal- kolon, kura ta ’ kanċer metastatiku tal- kolorektum, u kura tal- kanċer tas- sider) u kienet osservata frekwenza ta ’ 63% fil- grupp ta ’ capecitabine/ docetaxel għall- kura ta ’ kanċer metastatiku tas- sider.
For the capecitabine dose of 1000 mg/ m2 twice daily on days 1 to 14 every 3 weeks, a frequency of 22% to 30% of all-grade HFS was observed in capecitabine combination therapy
Għad- doża ta ’ 1000 mg/ m2 capecitabine darbtejn kuljum fi ġranet 1 sa 14 kull 3 ġimgħat, kienet osservata frekwenza ta ’ HFS ta ’ kull grad ta ’ 22% sa 30% f’ terapija kombinata ta ’ capecitabine.
A meta-analysis of 13 clinical trials with data from over 3800 patients treated with capecitabine monotherapy or capecitabine in combination with different chemotherapy regimens in multiple indications (colon, colorectal, gastric and breast cancer) showed that HFS (all grades) occurred in 1788 (47%) patients after a median time of 155 [95% CI 135, 187] days after starting treatment with capecitabine.
Meta- analiżi ta ’ 13- il prova klinika b’ tagħrif minn aktar minn 3800 pazjent kkurati b’ capecitabine bħala monoterapija jew capecitabine flimkien ma ’ korsijiet ta ’ kimoterapiji differenti f’ indikazzjonijiet multipli (kanċer tal- kolon, tal- kolorektum, ta ’ l- istonku u tas- sider) wriet li HFS (kull grad) seħħet f’ 1788 (47%) pazjent wara ħin medjan ta ’ 155 [95% CI 135, 187] ġurnata wara l- bidu tal- kura b’ capecitabine.
In all studies combined, the following covariates were statistically significantly associated with an increased risk of developing HFS: increasing capecitabine starting dose (gram), decreasing cumulative capecitabine dose (0.1*kg), increasing relative dose intensity in the first six weeks, increasing duration of study treatment (weeks), increasing age (by 10 year increments), female gender, and good ECOG performance status at baseline (0 versus ≥ 1).
Fl- istudji kollha kombinati, l- kovarjanti li ġejjin kienu assoċjati b’ mod statistikament sinifikanti ma ’ żjieda fir- riskju ta ’ żvilupp ta ’ HFS: żjieda fid- doża (grammi) tal- bidu ta ’ capecitabine, tnaqqis fid- doża kumulattiva ta ’ capecitabine (0. 1* kg), żjieda fl- intensità tad- doża relattiva fl- ewwel sitt ġimgħat, żjieda fit- tul ta ’ kura taħt studju (ġimgħat), żjieda fl- età (b’ żjidiet ta ’ 10 snin), sess femminili, u ECOG performance status fil- linja bażi tajjeb (0 kontra ≥1).
Diarrhoea (see section 4.4):
Dijarea (ara sezzjoni 4. 4):
Xeloda can induce the occurrence of diarrhoea, which has been observed in up to 50% of patients.
Xeloda jista ’ jinduċi l- okkorrenza ta ’ dijarea, li kienet osservata f’ sa 50% tal- pazjenti.