qanastek/EMEA-V3 huggingface dataset:
The most common side effects in patients receiving Avastin with or without chemotherapy (seen in more than 1 patient in 10) are leucopenia (low levels of leucocytes, a type of white blood cell), thrombocytopenia (low levels of platelets in the blood), neutropenia (low levels of neutrophils, a type of white blood cell), peripheral sensory neuropathy (damage to nerves in the extremities, such as the hands and feet), hypertension (high blood pressure), diarrhoea, nausea (feeling sick), vomiting, asthenia (weakness), fatigue (tiredness), anorexia (loss of appetite), dysgeusia (taste disturbances), headache, eye disorders, dyspnoea (difficulty breathing), epistaxis (nosebleeds), rhinitis (blocked nose), constipation, stomatitis (inflammation of the lining of the mouth), rectal haemorrhage (bleeding from the rectum), exfoliative dermatitis (flaky skin), dry skin, skin discoloration, proteinuria (protein in the urine), pyrexia (fever) and pain.
L- aktar effetti sekondarji komuni f’ pazjenti li qed jirċievu Avastin bi jew mingħajr kemjoterapija (dehru f’ aktar minn pazjent 1 f’ 10) huma lewkopenija (livelli baxxi ta ’ lewkoċiti, tip ta ’ ċellola bajda tad- demm), tromboċitopenja (livelli baxxi ta ’ platelets fid- demm), newtropenija (livelli baxxi ta ’ newtrofili, tip ta ’ ċellola bajda tad- demm), newropatija periferika sensorjali (ħsara lin- nervituri fl - estremitajiet, bħal ma huma l- idejn u s- saqajn), ipertensjoni (pressjoni għolja fid- demm), dijarrea, nawżea (dardir), remettar, astenija (dgħjufija), għejja kbira, anoressija (telf ta ’ aptit), disgewsja (disturbi fit- togħma), uġigħ ta ’ ras, disturbi ta ’ l- għajnejn, dispnea (diffikultà fit- teħid tan- nifs), epistassi (tifriġ mill- imnieħer), rinite (imnieħer imblukkat), stitikezza, stomatite (infjammazzjoni tal - kisi tal- ħalq), emorraġija rettali (fsada mir- rektum), dermatite esfoljattiva (ġilda titqaxxar), ġilda xotta, ġilda li titlef il- kulur, proteinurja (proteina fl- awrina), piressija (deni) u uġigħ.
The most serious side effects are gastrointestinal perforations (holes in the gut), fistulae (abnormal tube-like connections between organs), haemorrhage (bleeding), and arterial thromboembolism (blood clots in the arteries).
L- aktar effetti sekondarji serji huma perforazzjonijiet gastrointestinali (toqob fil- musrana), fistuli (konnessjonijiet anormali f’ għamla ta ’ tubi bejn l- organi), emorraġija (fsada), u tromboemboliżmu arterjuż (ċapep ta ’ demm fl- arterji).
For the full list of all side effects reported with Avastin, see the Package Leaflet.
Għal- lista sħiħa ta ’ l- effetti sekondarji kollha irrapportati b’ Avastin, ara l- Fuljett ta ’ Tagħrif.
Avastin should not be used in people who may be hypersensitive (allergic) to bevacizumab or any of the other ingredients.
Avastin m’ għandux jintuża f’ nies li jistgħu jkunu ipersensittivi (allerġiċi) għal bevacizumab jew għal xi sustanzi oħra tiegħu.
Avastin should not be used in patients who are hypersensitive to Chinese hamster ovary cell products or other recombinant antibodies.
Avastin m’ għandux jintuża f’ pazjenti li huma sensittivi żżejjed għal prodotti miċ- ċelloli ta ’ l- ovarji tal- ħamster Ċiniż jew antikorpi rekombinanti oħra.
It should also not be given to pregnant women or to anyone who has untreated central nervous system metastases (secondary cancers in the brain or spinal cord).
Huwa m’ għandux jingħata 2/ 3 lil nisa tqal jew lil xi ħadd li għandu metastażijiet tas- sistema nervuża ċentrali mhux ittrattati (kanċers sekondarji fil- moħħ jew fis- sinsla).
Why has Avastin been approved?
Għaliex ġie approvat Avastin?
The Committee for Medicinal Products for Human Use (CHMP) decided that, in combination with other anticancer medicines, Avastin’ s benefits are greater than its risks for the treatment of metastatic 2/ 3 cancer of colon or rectum, and the first-line treatment of metastatic breast cancer, unresectable advanced, metastatic or recurrent non-small cell lung cancer with other than predominantly squamous cell histology, and advanced and/ or metastatic renal cell cancer.
Il- Kumitat għal Prodotti Mediċinali għal Użu mill- Bniedem (CHMP) iddeċieda li, f’ kumbinazzjoni ma ’ mediċini kontra l- kanċer oħra, il- benefiċċji ta ’ Avastin huma akbar mir- riskji tiegħu għat - trattament tal- kanċer metastatiku tal- kolon jew tar- rektum, u t- trattament primarju (‘ first- line treatment ’) tal- kanċer tas- sider metastatiku, u tal- kanċer tal- pulmun mhux ta ’ ċellola żgħira avvanzat, metastatiku jew rikorrenti li ma jistax jitneħħa bil- kirurġija waħedha f’ pazjenti li ċ- ċelloli tagħhom mhumiex tat- tip ‘ skwamuża ’ u kanċer taċ- ċelluli renali avvanzati u/ jew metastatiċi.
The Committee recommended that Avastin be given marketing authorisation.
Il- Kumitat irrakkomanda li Avastin jingħata awtorizzazzjoni għat- tqegħid fis- suq.
Other information about Avastin:
Tagħrif ieħor dwar Avastin:
The European Commission granted a marketing authorisation valid throughout the European Union for Avastin to Roche Registration Limited on 12 January 2005.
Il- Kummissjoni Ewropea tat l- awtorizzazzjoni għat- tqegħid fis- suq għal Avastin valida fl- Unjoni Ewropea kollha lil Roche Registration Limited fit- 12 ta ’ Jannar 2005.
The full EPAR for Avastin is available here.
L- EPAR sħiħ għal Avastin huwa disponibbli minn hawn.
EU-Number
Numru ta ’ l- EU
Concentrate for solution Intravenous use for infusion
Konċentrat għal soluzzjoni għall - infużjoni
Avastin 25 mg/ ml concentrate for solution for infusion.
Avastin 25 mg/ ml konċentrat għal soluzzjoni għall- infużjoni
Bevacizumab 25 mg per ml.
Bevacizumab 25 mg kull ml.
Each vial contains 100 mg of bevacizumab in 4 ml and 400 mg in 16 ml respectively.
Kull kunjett fih 100 mg ta ’ bevacizumab f’ 4 ml u 400 mg f’ 16 ml rispettivament.
Bevacizumab is a recombinant humanised monoclonal antibody produced by DNA technology in Chinese Hamster ovary cells.
Bevacizumab huwa antikorp monoklonali rikombinant umanizzat, prodott permezz ta ’ teknoloġija ta ’ DNA f’ ċelluli ovarji tal- ħamster Ċiniż.
Clear to slightly opalescent, colourless to pale brown liquid.
Likwidu ċar għal kemm xejn ikanġi, bla kulur għal kannella ċar.
Avastin (bevacizumab) in combination with fluoropyrimidine-based chemotherapy is indicated for treatment of patients with metastatic carcinoma of the colon or rectum.
Avastin (bevacizumab) f’ taħlita flimkien ma ’ kimoterapija bbażata fuq fluoropyrimidine huwa indikat għall- kura ta ’ pazjenti b’ karċinoma tal- kolon jew tar- rektum li mmetastatizzat.
Avastin in combination with paclitaxel is indicated for first-line treatment of patients with metastatic breast cancer.
Avastin flimkien ma ’ paclitaxel huwa ndikat għall- kura primarja ta ’ pazjenti b’ kanċer tas- sider li mmetastatizza.
Avastin, in addition to platinum-based chemotherapy, is indicated for first-line treatment of patients with unresectable advanced, metastatic or recurrent non-small cell lung cancer other than predominantly squamous cell histology.
Avastin, flimkien ma ’ kimoterapija ibbażata fuq platinum, huwa ndikat għall- kura primarja ta ’ pazjenti b’ kanċer fil- pulmun taċ- ċelluli mhux żgħar, li ma jistgħax jitneħħa, avvanzat, li mmetastatizza jew rikorrenti, minbarra istolġija taċ- ċellula fil- biċċa l- kbira skwamuża.
Avastin in combination with interferon alfa-2a is indicated for first line treatment of patients with advanced and/ or metastatic renal cell cancer.
Avastin flimkien ma ’ interferon alfa- 2a huwa indikat għall- kura primarja ta ’ pazjenti b’ kanċer taċ - ċelluli renali avvanzat u/ jew metastatiku.
Avastin must be administered under the supervision of a physician experienced in the use of antineoplastic medicinal products.
Avastin għandu jingħata taħt sorveljanza ta ’ tabib b’ esperjenza fl- użu ta ’ prodotti mediċinali antinejoplastiċi.
It is recommended that treatment be continued until progression of the underlying disease.
Huwa rakkomandat li l- kura titkompla sal- progressjoni tal- marda li hemm.
The initial dose should be delivered over 90 minutes as an intravenous infusion.
Id- doża tal- bidu għandha tingħata bħala infużjoni ġol- vini fuq perijodu ta ’ 90 minuta.
If the first infusion is well tolerated, the second infusion may be administered over 60 minutes.
Jekk l- ewwel infużjoni tkun ittollerata tajjeb, it- tieni infużjoni tista ’ tingħata fuq perijodu ta ’ 60 minuta.
If the 60-minute infusion is well tolerated, all subsequent infusions may be administered over 30-minutes.
Jekk l - infużjoni ta ’ 60 minuta tkun ittollerata tajjeb, kull infużjoni ta ’ wara tista ’ tingħata fuq perijodu ta ’ 30 minuta.
Do not administer as an intravenous push or bolus.
Tagħtix bħala injezzjoni push jew bolus ġol- vini.
Instructions for the preparation of Avastin infusions are described in section 6.6.
2 Istruzzjonijiet għall- preparazzjoni ta ’ infużjonijiet ta ’ Avastin huma deskritti f’ sezzjoni 6. 6.
Avastin infusions should not be administered or mixed with glucose solutions (see section 6.2).
Infużjonjiet ta ’ Avastin m’ għandhomx jingħataw jew jitħaltu ma ’ soluzzjonijiet tal- glukosju (ara sezzjoni 6. 2).
2 Metastatic carcinoma of the colon or rectum (mCRC)
Karċinoma tal- kolon jew tar- rektum li mmetastatizzat (mCRC)
The recommended dose of Avastin, administered as an intravenous infusion, is either 5 mg/ kg or 10 mg/ kg of body weight given once every 2 weeks or 7.5 mg/ kg or 15 mg/ kg of body weight given once every 3 weeks.
Id- doża rakkomandata ta ’ Avastin, mogħtija bħala infużjoni fil- vini, hija 5 mg/ kg jew 10 mg/ kg ta ’ piż tal- ġisem mogħtija darba kull ġimagħtejn jew 7. 5 mg/ kg jew 15 mg/ kg ta ’ piż tal- ġisem mogħtija darba kull 3 ġimgħat.
Dose reduction for adverse events is not recommended.
Mhux rakkomandat tnaqqis fid- doża minħabba episodji avversi.
If indicated, therapy should either be permanently discontinued or temporarily suspended as described in section 4.4.
Jekk meħtieġ, it- terapija għandha titwaqqaf għal kollox jew titwaqqaf temporanjament kik deskritt f’ sezzjoni 4. 4.
Metastatic breast cancer (mBC)
Kanċer tas- sider li mmetastatizza (mBC)
The recommended dose of Avastin is 10 mg/ kg of body weight given once every 2 weeks or 15 mg/ kg of body weight given once every 3 weeks as an intravenous infusion.
Id- doża rakkomandata ta ’ Avastin hija 10 mg/ kg ta ’ piż tal- ġisem mogħtija darba kull ġimagħtejn jew 15 mg/ kg ta ’ piż tal- ġisem mogħtija darba kull 3 ġimgħat bħala infużjoni fil- vini.
Non-small cell lung cancer (NSCLC)
Kanċer fil- pulmun taċ- ċelluli mhux żgħar (NSCLC)
Avastin is administered in addition to platinum-based chemotherapy for up to 6 cycles of treatment followed by Avastin as a single agent until disease progression.
Avastin jingħata flimkien ma ’ kimoterapija bbażata fuq platinum sa 6 ċikli ta ’ kura segwit minn Avastin bħala sustanża waħedha sal- progressjoni tal- marda.
The recommended dose of Avastin is 7.5 mg/ kg or 15 mg/ kg of body weight given once every 3 weeks as an intravenous infusion.
Id- doża rrakkomandata ta ’ Avastin hija 7. 5 mg/ kg jew 15 mg/ kg ta ’ piż tal- ġisem mogħtija darba kull 3 ġimgħat bħala infużjoni ġol- vini.
Clinical benefit in NSCLC patients has been demonstrated with both 7.5 mg/ kg and 15 mg/ kg doses.
Benefiċċju kliniku f’ pazjenti b’ NSCLC intwera kemm b’ doża ta ’ 7. 5 mg/ kg kif ukoll b’ 15 mg/ kg.
For details refer to section 5.1 Pharmacodynamic Properties, Non-small cell lung cancer (NSCLC).
Għad- dettalji rreferi għal sezzjoni 5. 1 Tagħrif farmakodinamiku, Kanċer fil- pulmun taċ- ċelluli mhux żgħar (NSCLC).
Advanced and/ or metastatic Renal Cell Cancer (mRCC)
Kanċer taċ- Ċelluli Renali avvanzat u/ jew matastatiku (mRCC)
The recommended dose of Avastin is 10 mg/ kg of body weight given once every 2 weeks as an intravenous infusion.
Id- doża rakkomandata ta ’ Avastin hija 10 mg/ kg ta ’ piż tal- ġisem mogħti darba kull ġimagħtejn bħala infużjoni ġol- vini.
Children and Adolescents:
Tfal u adoloxxenti:
The safety and efficacy in children and adolescents have not been established.
Is- sigurtà u l- effikaċja fit- tfal u l- adoloxxenti ma ġewx stabbiliti.
Avastin is not recommended for use in children and adolescents due to a lack of data on safety and efficacy (see section 5.3).
Avastin mhux rakkomandat għall- użu fit- tfal u adoloxxenti minħabba nuqqas ta ’ tagħrif dwar is- sigurtà u l- effikaċja (ara sezzjoni 5. 3).
No dose adjustment is required in the elderly.
M’ hemmx bżonn ta ’ aġġustament tad- doża fl- anzjani.
The safety and efficacy have not been studied in patients with renal impairment.
Is- sigurtà u l- effikaċja f’ pazjenti b’ indeboliment renali ma ġewx studjati.
The safety and efficacy have not been studied in patients with hepatic impairment.
Is- sigurtà u l- effikaċja f’ pazjenti b’ indeboliment tal- fwied ma ġewx studjati.
• Hypersensitivity to the active substance or to any of the excipients. • Hypersensitivity to Chinese hamster ovary (CHO) cell products or other recombinant human or humanised antibodies. • Pregnancy (see section 4.6). • Avastin is contraindicated in patients with untreated CNS metastases (see sections 4.4 and 4.8).
• Sensittività eċċessiva għas- sustanza attiva jew għal xi sustanzi mhux attivi. • Sensittività eċċessiva għall- prodotti taċ- ċelluli ta ’ l- ovarji tal- ħamster Ċiniż (CHO) jew għall - antikorpi oħra umani rikombinanti jew umanizzati. • Tqala (ara sezzjoni 4. 6) • Avastin huwa kontra- indikat f’ pazjenti b’ metastasi fis- CNS mhux ikkurati (ara sezzjoni 4. 4 u 4. 8).
Gastrointestinal perforations (see section 4.8) Patients may be at an increased risk for the development of gastrointestinal perforation when treated with Avastin.
Perforazzjonijiet gastro- intestinali (ara sezzjoni 4. 8) Il- pazjenti jistgħu jkunu f’ risku akbar li jiżviluppaw perforazzjoni gastro- intestinali meta kkurati b’ Avastin.
Intra-abdominal inflammatory process may be a risk factor for gastrointestinal perforations in patients with metastatic carcinoma of the colon or rectum, therefore, caution should be
Proċess ta ’ infjammazzjoni intra- addominali jista ’ jkun fattur ta ’ riskju għall- perforazzjoni gastro- intestinali f’ pazjenti b’ karċinoma tal- kolon jew tar- rektum li mmetastatizzat, għalhekk, irid ikun hemm kawtela meta dawn il- pazjenti jiġu kkurati.
Therapy should be permanently discontinued in patients who develop gastrointestinal perforation.
Il- kura trid titwaqqaf għal kollox f’ pazjenti li żviluppaw perforazzjoni gastro- intestinali.
Fistulae (see section 4.8) Patients may be at increased risk for the development of fistulae when treated with Avastin.
Fistuli (ara sezzjoni 4. 8) Pazjenti jistgħu jkunu f’ riskju akbar għall- iżvilupp ta ’ fistuli meta kkurati b’ Avastin.
Permanently discontinue Avastin in patients with TE (tracheoesophageal) fistula or any grade 4 fistula.
Waqqaf Avastin b’ mod permanenti f’ pazjenti b’ fistula TE (trakeoesofagali) jew kull fistula ta ’ grad 4.
Limited information is available on the continued use of Avastin in patients with other fistulae.
Hemm tagħrif limitat dwar it- tkomplija ta ’ l- użu ta ’ Avastin f’ pazjenti b’ fistuli oħra.
In cases of internal fistula not arising in the GI tract, discontinuation of Avastin should be considered
F’ każijiet ta ’ fistuli fil- ġewwieni b’ oriġini mhux fl- apparat tal- GI, għandu jiġi kkunsidrat il- waqfien ta ’ Avastin.
Wound Healing Complications (see section 4.8) Avastin may adversely affect the wound healing process.
Komplikazzjonijiet fil- Fejqan tal- Feriti (ara sezzjoni 4. 8) Avastin jista ’ jaffettwa b’ mod avvers il- proċess ta ’ fejqan tal- feriti.
Therapy should not be initiated for at least 28 days following major surgery or until the surgical wound is fully healed.
Terapija m’ għandiex tinbeda qabel ta ’ l- inqas 28 ġurnata wara operazzjoni maġġura jew qabel il- ferita ta ’ l- operazzjoni tfieq għal kollox.
In patients who experienced wound healing complications during therapy, treatment should be withheld until the wound is fully healed.
F’ pazjenti li kellhom komplikazzjonijiet fil- fejqan tal- ferita waqt terapija, il- kura għandha titwaqqaf sakemm il- ferita tfieq għal kollox.
Therapy should be withheld for elective surgery.
It- terapija għandha titwaqqaf għall- operazzjoni meħtieġa.
Hypertension (see section 4.8) An increased incidence of hypertension was observed in Avastin-treated patients.
Pressjoni għolja (ara sezzjoni 4. 8) Ġiet osservata żjieda fl- inċidenza ta ’ pressjoni għolja f’ pazjenti kkurati b’ Avastin.
Clinical safety data suggest that the incidence of hypertension is likely to be dose-dependent.
Tagħrif kliniku ta ’ sigurtà jissuġġerixxi li l- inċidenża ta ’ pressjoni għolja probabbli hija dipendenti mid- doża.
Pre existing hypertension should be adequately controlled before starting Avastin treatment.
Pressjoni għolja eżistenti minn qabel għandha tiġi kkontrollata b’ mod xieraq qabel tinbeda kura b’ Avastin.
There is no information on the effect of Avastin in patients with uncontrolled hypertension at the time of initiating therapy.
M’ hemmx tagħrif dwar l- effett ta ’ Avastin f’ pazjenti bi pressjoni għolja mhux kontrollata fil- bidu tal - kura.
Monitoring of blood pressure is generally recommended during therapy.
Sorveljanza tal- pressjoni tad- demm ġeneralment hija rakkomandata waqt il- kura.
In most cases hypertension was controlled adequately using standard antihypertensive treatment appropriate for the individual situation of the affected patient.
Fil- biċċa l- kbira tal- każijiet, il- pressjoni għolja kienet ikkontrollata b’ mod adegwat permezz ta ’ kura anti- ipertensiva stàndard, xierqa għas- sitwazzjoni individwali tal- pazjent involut.
The use of diuretics to manage hypertension is not advised in patients who receive a cisplatin-based chemotherapy regimen.
L- użu ta ’ dijuretiċi għall- immaniġġjar ta ’ pressjoni għolja mhux rakkomandat f’ pazjenti li qed jirċievu kors ta ’ kimoterapija bbażata fuq cisplatin.
Avastin should be permanently discontinued, if medically significant hypertension cannot be adequately controlled with antihypertensive therapy, or if the patient develops hypertensive crisis or hypertensive encephalopathy.
Avastin għandu jitwaqqaf għal kollox, jekk pressjoni għolja ta ’ sinifikanza medika ma tistax tiġi kkontrollata b’ mod adegwat b’ terapija anti- ipertensiva, jew jekk il - pazjent jiżviluppa kriżi ipertensiva jew enċefalopatija ipertensiva.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS) (see section 4.8) There have been rare reports of Avastin-treated patients developing signs and symptoms that are consistent with Reversible Posterior Leukoencephalopathy Syndrome (RPLS), a rare neurologic disorder, which can present with the following signs and symptoms among others: seizures, headache, altered mental status, visual disturbance, or cortical blindness, with or without associated hypertension.
Sindromu ta ’ Lewkoenċefalopatija Posterjuri Riversibbli (RPLS) (ara sezzjoni 4. 8) Kien hemm rapporti rari ta ’ pazjenti kkurati b’ Avastin li żviluppaw sinjali u sintomi li huma konsistenti mas- Sindromu ta ’ Lewkoenċefalopatija Posterjuri Riversibbli (RPLS), marda newroloġika rari, li tista ’ tippreżenta ruħa bis- sinjali u s- sintomi li ġejjin, fost oħrajn: eċċessjonijiet, uġigħ ta ’ ras, stat mentali alterat, problemi tal- vista, jew telf tal- vista kortikali, bi jew bla pressjoni għolja assoċjata.
A diagnosis of RPLS requires confirmation by brain imaging.
Dijanjożi ta ’ RPLS tinħtieġ li tiġi kkonfermata permezz ta ’ immaġini tal- moħħ.
In patients developing RPLS, treatment of specific symptoms including control of hypertension is recommended along with discontinuation of Avastin.
F’ pazjenti li qed jiżviluppaw RPLS, il- kura ta ’ sintomi speċifiċi inkluż il- kontroll ta ’ pressjoni għolja huwa rakkomandat flimkien mal- waqfien ta ’ Avastin.
The safety of reinitiating Avastin therapy in patients previously experiencing RPLS is not known.
Is- sigurtà ta ’ bidu mill- ġdid ta ’ kura b’ Avastin f’ pazjenti li qabel żviluppaw RPLS, mhix magħrufa.
Proteinuria (see section 4.8) Patients with a history of hypertension may be at increased risk for the development of proteinuria when treated with Avastin.
Proteina fl- awrina (ara sezzjoni 4. 8) Pazjenti b’ passat ta ’ pressjoni għolja jistgħu jkunu f’ riskju akbar li jiżviluppaw proteina fl- awrina meta kkurati b’ Avastin.
There is evidence suggesting that Grade 1 [US National Cancer Institute- Common Toxicity Criteria (NCI-CTC) version 2.0] proteinuria may be related to the dose.
Hemm evidenza li tissuġġerixxi li proteina fl- awrina ta ’ Grad 1 [US National Cancer Institute- Common Toxicity Criteria (NCI- CTC) verżjoni 2. 0] tista ’ tkun relatata mad- doża.
Monitoring of proteinuria by dipstick urinalysis is recommended prior to starting and during therapy.
Is - sorveljanza ta ’ proteina fl- awrina permezz ta ’ analiżi bl- istikka tal- pipi hija rakkomandata li ssir qabel ma tinbeda u waqt il- kura.
Therapy should be permanently discontinued in patients who develop Grade 4 proteinuria (nephrotic syndrome).
Il- kura għandha titwaqqf għal kollox f’ pazjenti li żviluppaw proteina fl - awrina ta ’ Grad 4 (sindromu nefrotiku).
Arterial Thromboembolism (see section 4.8) In five randomised clinical trials, the incidence of arterial thromboembolic events including cerebrovascular accidents (CVAs), transient ischaemic attacks (TIAs) and myocardial infarctions (MIs) was higher in patients receiving Avastin in combination with chemotherapy compared to those who received chemotherapy alone.
Trombo- emboliżmu Arterjali (ara sezzjoni 4. 8) F’ ħames provi kliniċi randomised, l- inċidenza ta ’ episodji trombo- embolitiċi arterjali, inkluż aċċidenti ċerebrovaskulari (CVAs), attakki iskemiċi temporanji (TIAs) u infarti mijokardiċi (MIs), kienet għola
Patients, receiving Avastin plus chemotherapy, with a history of arterial thromboembolism or age greater than 65 years have an increased risk of developing arterial thromboembolic events during therapy.
Pazjenti li qed jirċievu Avastin flimkien ma ’ kimoterapija, b’ passat ta ’ trombo- emboliżmu arterjali jew età aktar minn 65 sena għandhom riskju akbar ta ’ żvilupp ta ’ episodji trombo- embolitiċi arterjali waqt il- kura.
Caution should be taken when treating these patients with Avastin.
Għandu jkun hemm kawtela fil- kura ta ’ dawn il- pazjenti b’ Avastin.
Therapy should be permanently discontinued in patients who develop arterial thromboembolic events.
Il- kura għandha titwaqqaf għal kollox f’ pazjenti li jiżviluppaw episodji trombo- embolitiċi arterjali.
4 Venous Thromboembolism (see section 4.8) Patients may be at risk of developing venous thromboembolic events, including pulmonary embolism under Avastin treatment.
Tromboemboliżmu fil- Vini (ara sezzjoni 4. 8) Waqt kura b’ Avastin, il- pazjenti jistgħu jkunu f’ riskju li jiżviluppaw episodji ta ’ tromboembolżmu fil - vini, inkluż emboliżmu pulmonari.
Avastin should be discontinued in patients with life-threatening (Grade 4) pulmonary embolism, patients with ≤ Grade 3 need to be closely monitored.
Avastin għandu jitwaqqaf f’ pazjenti b’ emboliżmu pulmonari li huwa ta ’ periklu għall- ħajja (Grad 4), pazjenti b ’ ≤ Grad 3 għandhom jiġu sorveljati mill- viċin.
Haemorrhage The risk of CNS haemorrhage in patients with CNS metastases receiving Avastin could not be fully evaluated, as these patients were excluded from clinical trials.
Emorraġija Ir- riskju ta ’ emorraġija fis- CNS f’ pazjenti b’ metastasi fis- CNS li qed jieħdu Avastin ma tistax tiġi evalwata kompletament, għax dawn il- pazjenti kienu eskużi mil- istudji kliniċi.
Thus, Avastin should not be used in these patients (see sections 4.3 and 4.8).
Għalhekk Avastin m’ għandux jintuża f’ dawn il- pazjenti (ara sezzjoni 4. 3 u 4. 8).
Patients treated with Avastin have an increased risk of haemorrhage, especially tumour-associated haemorrhage.
Pazjenti kkurati b’ Avastin għandhom riskju akbar li jiżviluppaw emorraġija, speċjalment emorraġija assoċjata mat- tumur.
Avastin should be discontinued permanently in patients who experience Grade 3 or 4 bleeding during Avastin therapy (see section 4.8).
Avastin għandu jitwaqqaf għal kollox f’ pazjenti li jkollhom esperjenza ta ’ fsada ta ’ Grad 3 jew 4 waqt kura b’ Avastin (ara sezzjoni 4. 8).
There is no information on the safety profile of Avastin in patients with congenital bleeding diathesis, acquired coagulopathy or in patients receiving full dose of anticoagulants for the treatment of thromboembolism prior to starting Avastin treatment, as such patients were excluded from clinical trials.
M’ hemmx tagħrif dwar il- profil ta ’ sigurtà ta ’ Avastin f’ pazjenti b’ diathesis bi fsada konġenitali, b’ marda akkwistata tal- koagulazzjoni, jew f’ pazjenti li rċievew doża sħiħa ta ’ antikoagulanti għall - kura ta ’ trombo- emboliżmu qabel ma mbdiet l- kura b’ Avastin, minħabba li dawn il- pazjenti kienu esklużi mil- istudji kliniċi.
Therefore, caution should be exercised before initiating therapy in these patients.
Għalhekk, f’ dawn il- pazjenti, irid ikun hemm kawtela qabel ma tinbeda l - kura.
However, patients who developed venous thrombosis while receiving therapy did not appear to have an increased rate of grade 3 or above bleeding when treated with a full dose of warfarin and Avastin concomitantly.
Iżda, pazjenti li żviluppaw trombożi venuża waqt li qed jingħataw il- kura, ma dehrux li kellhom rata għola ta ’ fsada ta ’ grad 3 jew aktar meta kkurati b’ doża sħiħa ta ’ warfarin u Avastin flimkien.
Pulmonary Haemorrhage/ Haemoptysis Patients with non-small cell lung cancer treated with Avastin may be at risk of serious, and in some cases fatal, pulmonary haemorrhage/ haemoptysis.
Emorraġija fil- pulmun/ Emoptisi Pazjenti b’ kanċer taċ- ċelluli mhux żgħar tal- pulmun ikkurati b’ Avastin jistġħu jkunu f’ riskju ta ’ emorraġija fil- pulmun/ emoptisi serja u f’ xi każijiet fatali.
Patients with recent pulmonary haemorrhage/ haemoptysis (> 2.5 ml of red blood) should not be treated with Avastin.
Pazjenti b’ emorraġija fil- pulmun/ emoptisi reċenti (> 2. 5 ml ta ’ demm aħmar) m’ għandhomx jiġu kkurati b’ Avastin.
Congestive Heart Failure (CHF) (see section 4.8) Events consistent with CHF were reported in clinical trials.
Insuffiċjenza tal- Qalb Konġestiva (CHF) (ara sezzjoni 4. 8) Fi provi kliniċi kienu rrappurtati avvennimenti konsistenti ma ’ CHF.
The symptoms ranged from asymptomatic declines in left ventricular ejection fraction to symptomatic CHF, requiring treatment or hospitalisation.
Is- sintomi varjaw minn tnaqqis mingħajr sintomi tal- porzjon ta ’ tfigħ tal- ventriklu tax- xellug, għal CHF bis- sintomi li kienet teħtieġ kura jew li l- pazjent jiddaħħal l- isptar.
Most of the patients who experienced CHF had metastatic breast cancer and had received previous treatment with anthracyclines, prior radiotherapy to the left chest wall or other risk factors for CHF, such as pre-existing coronary heart disease or concomitant cardiotoxic therapy.
Il- biċċa l- kbira tal- pazjenti li kellhom esperjenza ta ’ CHF kellhom kanċer tas- sider li mmetastatizza u kienu rċievew kura b’ anthracyclines minn qabel, radjuterapija minn qabel lill- parti tax- xellug tas- sider jew fatturi ta ’ riskju oħra għal CHF, bħal mard koronarju tal- qalb eżistenti minn qabel jew terapija kardjotossika fl- istess ħin.
Caution should be exercised when treating patients with clinically significant cardiovascular disease or pre-existing congestive heart failure with Avastin.
Għandu jkun hemm kawtela meta pazjenti b’ marda kardjovaskulari ta ’ sinifikanza klinika jew insuffiċjenza tal- qalb konġestiva eżistenti minn qabel jiġu kkurati b’ Avastin.
Neutropenia (see section 4.8) Increased rates of severe neutropenia, febrile neutropenia, or infection with severe neutropenia (including some fatalities) have been observed in patients treated with some myelotoxic chemotherapy regimens plus Avastin in comparison to chemotherapy alone.
Newtropenja (ara sezzjoni 4. 8) Kienu osservati żiediet fir- rati ta ’ newtropenja severa, newtropenja bid- deni, jew infezzjoni b’ newtropenja severa (inkluż xi fatalitajiet) f’ pazjenti kkurati b’ xi programmi ta ’ kimoterapija majelotossika flimkien ma ’ Avastin meta mqabbla ma ’ kimoterapija waħedha.
Effect of antineoplastic agents on bevacizumab pharmacokinetics
Effett ta ’ sustanzi antineoplastiċi fuq il- farmakokinetika ta ’ bevacizumab
No clinically relevant pharmacokinetic interaction of co-administered chemotherapy on Avastin disposition has been observed based on the results of a population PK analysis.
Ibbażat fuq ir- riżultati ta ’ analiżi PK tal- popolazzjoni, ma kienet osservata l- ebda interazzjoni farmakokinetika ta ’ rilevanza klinika ta ’ l- għoti flimkien ta ’ kimoterapija fuq id- dispożizzjoni ta ’ Avastin.
There was no difference in clearance of Avastin in patients treated with single-agent Avastin compared to patients receiving Avastin in combination with the bolus-IFL regimen.
Ma kien hemm l- ebda differenza fit- tneħħija ta ’ Avastin f’ pazjenti kkurati b’ Avastin bħala sustanza waħedha meta mqabbel ma ’ pazjenti li rċievew Avastin flimkien mal- kors bolus- IFL.
The effect of other co-administered chemotherapies on Avastin clearance is considered not clinically significant.
L- effett ta ’ kimoterapiji oħra mogħtija flimkien fuq it- tneħħija ta ’ Avastin huwa kkunsidrat li mhux ta ’ rilevanza klinika.
Effect of bevacizumab on the pharmacokinetics of other antineoplastic agents
Effett ta ’ bevacizumab fuq il- farmakokinetika ta ’ sustanzi antineoplastiċi oħra
Results from a dedicated drug-drug interaction study, demonstrated no significant effect of bevacizumab on the pharmacokinetics of irinotecan and its active metabolite SN38.
Riżultati minn studju dedikat ta ’ interazzjoni bejn mediċina u oħra, ma wrew l- ebda effett sinifikanti ta ’ bevacizumab fuq il- farmakokinetika ta ’ irinotecan u l- metabolit attiv tiegħu SN38.
5 Results from one study in metastatic colorectal cancer patients demonstrated no significant effect of bevacizumab on the pharmacokinetic of capecitabine and its metabolites, and on the pharmacokinetics of oxaliplatin, as determined by measurement of free and total platinum.
Riżultati minn studju wieħed f’ pazjenti b’ kanċer metastatiku tal- kolorektum, ma wrew l- ebda effett sinifikanti ta ’ bevacizumab fuq il- farmakokinetika ta ’ capecitabine u l- metaboliti tiegħu, u fuq il - farmakokinetika ta ’ oxaliplatin, kif determinat mill- kejl ta ’ platinum ħieles u totali.
Results from one study in renal cancer patients demonstrated no significant effect of bevacizumab on the pharmacokinetics of interferon alfa-2a.
Riżultati minn studju wieħed f’ pazjenti b’ kanċer renali ma wrew l- ebda effett sinifikanti ta ’ bevacizumab fuq il- farmakokinetika ta ’ interferon alfa- 2a.
The potential effect of bevacizumab on the pharmacokinetics of cisplatin and gemcitabine was investigated in non-squamous NSCLC patients.
L- effett potenzjali ta ’ bevacizumab fuq il- farmakokinetika ta ’ cisplatin u gemcitabine kienet investigata f’ pazjenti b’ NSCLC mhux skwamuż.
Study results demonstrated no significant effect of bevacizumab on the pharmacokinetics of cisplatin.
Riżultati ta ’ l- istudju ma wrew l- ebda effett sinifikanti ta ’ bevacizumab fuq il- farmakokinetika ta ’ cisplatin.
Due to high inter-patient variability and limited sampling, the results from that study do not allow firm conclusions to be drawn on the impact of bevacizumab on gemcitabine pharmacokinetics.
Minħabba l- varjabilità għolja ta ’ bejn il- pazjenti u teħid limitat ta ’ kampjuni, ir- riżultati minn dak l- istudju ma jippermettux li jsiru konklużjonijiet ċerti dwar l- impatt ta ’ bevacizumab fuq il- farmakokinetika ta ’ gemcitabine.
Combination of bevacizumab and sunitinib malate
Taħlita ta ’ bevacizumab u sunitinib malate
In two clinical studies of metastatic renal cell carcinoma, microangiopathic haemolytic anaemia (MAHA) was reported in 7 of 19 patients treated with bevacizumab (10 mg/ kg every two weeks) and sunitinib malate (50 mg daily) combination.
F’ żewġ studji kliniċi ta ’ karċinoma metastatika taċ- ċellula renali, kienet irrapportata anemija emolitika mikroanġjopatika (MAHA), f’ 7 minn 19- il pazjent ikkurati bit- taħlita ta ’ bevacizumab (10 mg/ kg kull ġimagħtejn) u sunitinib malate (50 mg kuljum).
MAHA is a haemolytic disorder which can present with red cell fragmentation, anaemia, and thrombocytopenia.
MAHA hija disturb emolitiku li tista ’ tidher bi frammentazzjoni taċ- ċelluli l- ħomor, anemija u tromboċitopenja.
In addition, hypertension (including hypertensive crisis), elevated creatinine, and neurological symptoms were observed in some of these patients.
Barra dan, f’ xi wħud minn dawn il- pazjenti kienu osservati pressjoni għolja (inkluż kriżi ipertensiva), krejatinina għolja, u sintomi newroloġiċi.
All of these findings were reversible upon discontinuation of bevacizumab and sunitinib malate (see Hypertension, Proteinuria, RPLS in section 4.4 Special warnings and precautions for use).
Dawn is- sejbiet kollha kienu riversibli mal- waqfien ta ’ bevacizumab u sunitinib malate (ara Pressjoni għolja, Proteina fl- awrina, RPLS f’ sezzjoni 4. 4, Twissijiet speċjali u prekawzjonijiet għall- użu).
Radiotherapy
Radjuterapija
The safety and efficacy of concomitant administration of radiotherapy and Avastin has not been established.
Is- sigurtà u l- effikaċja ta ’ l- għotja fl- istess ħin ta ’ radjuterapija u Avastin ma ġewx stabbiliti.
Pregnancy There are no data on the use of Avastin in pregnant women.
Tqala M’ hemmx tagħrif dwar l- użu ta ’ Avastin f’ nisa tqal.
Studies in animals have shown reproductive toxicity including malformations (see section 5.3).
Studji fl- annimali wrew tossiċità riproduttiva, inkluż malformazzjonijiet (ara sezzjoni 5. 3).
IgGs are known to cross the placenta, and Avastin is anticipated to inhibit angiogenesis in the foetus, and thus is suspected to cause serious birth defects when administered during pregnancy.
IgGs huma magħrufa li jgħaddu mil- plaċenta, u Avastin huwa mistenni li jimpedixxi anġjoġenesi fil- fetu, u għalhekk hu maħsub li jikkawża difetti serji tat - twelid meta jingħata waqt it- tqala.
Avastin is contraindicated (see section 4.3) in pregnancy.
Avastin huwa kontra- indikat (ara sezzjoni 4. 3) fit- tqala.
Women of childbearing potential have to use effective contraception during (and up to 6 months after treatment).
Nisa li jista ’ jkollhom it- tfal iridu jużaw kontraċezzjoni effettiva waqt il- kura (u sa 6 xhur wara l- kura).
Lactation It is not known whether bevacizumab is excreted in human milk.
6 Treddigħ Mhux magħruf jekk bevacizumab jitneħħix fil- ħalib uman.
As maternal IgG is excreted in milk and bevacizumab could harm infant growth and development (see section 5.3), women must discontinue breast-feeding during therapy and not breast feed for at least six months following the last dose of Avastin.
Minħabba li IgG ta ’ l- omm jitneħħa fil - ħalib u bevacizumab jista ’ jagħmel ħsara lit- tkabbir u l- iżvilupp tat- tarbija (ara sezzjoni 5. 3), nisa jridu jwaqqfu t- treddigħ waqt il- kura u ma jreddgħux għal ta ’ l- inqas sitt xhur wara l- aħħar doża ta ’ Avastin.
No studies on the effects on the ability to drive and use machines have been performed.
Ma sarux studji dwar l- effett fuq il- ħila biex issuq jew tħaddem magni.
However, there is no evidence that Avastin treatment results in an increase in adverse events that might lead to impairment of the ability to drive or operate machinery or impairment of mental ability.
Iżda, m’ hemm l- ebda evidenza li kura b’ Avastin twassal għal żjieda fl- effetti avversi li jistgħu jwasslu għal tnaqqis fil- ħila biex issuq jew tħaddem magni jew tnaqqis fl- abilità mentali.
The overall safety profile of Avastin is based on data from over 3,500 patients with various malignancies, predominantly treated with Avastin in combination with chemotherapy in clinical trials.
Il- profil globali ta ’ sigurtà ta ’ Avastin huwa bbażat fuq tagħrif minn aktar minn 3, 500 pazjent b’ diversi tumuri malinni kkurati primarjament b’ Avastin flimkien ma ’ kimoterapija fi provi kliniċi.
6 The most serious adverse drug reactions were:
L- aktar reazzjonijiet avversi serji tal- mediċina kienu:
• Gastrointestinal perforations (see section 4.4). • Haemorrhage, including pulmonary haemorrhage/ haemoptysis, which is more common in non- small cell lung cancer patients (see section 4.4). • Arterial thromboembolism (see section 4.4).
• Perforazzjoni gastro- intestinali (ara sezzjoni 4. 4). • Emorraġija, inkluż emorraġija fil- pulmun/ emoptisi li hija aktar komuni f’ pazjenti b’ kanċer taċ - ċelluli mhux żgħar tal- pulmun (ara sezzjoni 4. 4). • Trombo- emboliżmu Arterjali (ara sezzjoni 4. 4).
The most frequently observed adverse drug reactions across clinical trials in patients receiving Avastin were hypertension, fatigue or asthenia, diarrhoea and abdominal pain.
L- aktar reazzjonijiet avversi tal- mediċina osservati tul il- provi kliniċi f’ pazjenti li qed jirċievu Avastin kienu pressjoni għoja, għejja jew astenja, dijarea, u uġigħ addominali.
Analyses of the clinical safety data suggest that the occurrence of hypertension and proteinuria with Avastin therapy are likely to be dose-dependent.
Analiżi ta ’ tagħrif kliniku ta ’ sigurtà jissuġġerixxi li l- okkorrenza ta ’ pressjoni għolja u proteina fl - awrina fil- kura b’ Avastin huma wisq probabbli dipendenti fuq id- doża.
Table 1 lists adverse drug reactions associated with the use of Avastin in combination with different chemotherapy regimens in multiple indications.
Tabella 1 tniżżel ir- reazzjonijiet avversi tal- mediċina assoċjati ma ’ l- użu ta ’ Avastin f’ taħlita ma ’ programmi ta ’ kimoterapija differenti f’ indikazzjonijiet multipli.
These reactions had occurred either with at least a 2% difference compared to the control arm (NCI-CTC grade 3-5 reactions) or with at least a 10% difference compared to the control arm (NCI-CTC grade 1-5 reactions), in at least one of the major clinical trials.
Dawn ir- reazzjonijiet seħħew jew b’ differenza ta ’ mill- anqas 2% meta mqabbla mal- grupp ta ’ kontroll (reazzjonijiet ta ’ Grad NCI- CTC 3- 5) jew b’ differenza ta ’ mill- anqas 10% meta mqabbla mal- grupp ta ’ kontroll (reazzjonijiet ta ’ Grad NCI- CTC 1- 5), f’ ta ’ l- anqas wieħed mill- provi kliniċi maġġuri.
The adverse drug reactions listed in this table fall into the following categories:
Ir- reazzjonijiet avversi tal- mediċina mniżżla f’ din it- tabella jaqgħu taħt il- kategoriji li ġejjin:
Very Common (≥ 10%) and Common (≥ 1% - < 10%).
Komuni Ħafna( ≥ 10%) u Komuni (≥ 1% - < 10%).
Adverse drug reactions are added to the appropriate category in the table below according to the highest incidence seen in any of the major clinical trials.
F’ kull sezzjoni ta ’ frekwenza, r- reazzjonijiet avversi għandhom jitniżżlu skond is- serjeta ’ tagħhom.
Within each frequency grouping adverse drug reactions are presented in the order of decreasing seriousness.
Ir- reazzjonijiet li huma l- aktar serji għandhom jitniżżlu l- ewwel, segwiti minn dawk anqas serji.
Some of the adverse drug reactions are reactions commonly seen with chemotherapy, (e. g. palmar-plantar erythrodysaesthesia syndrome with capecitabine and peripheral sensory neuropathy with paclitaxel or oxaliplatin); however, an exacerbation by Avastin therapy can not be excluded.
Xi wħud mir- reazzjonijiet avversi tal- mediċina huma reazzjonijiet osservati b’ mod komuni ma ’ kimoterapija (e. ż. sindrome ta ’ eritrodisasteżija palmari- plantari b’ capecitabine u newropatija sensorjali periferali b’ paclitaxel jew oxaliplatin); iżda żjieda minħabba kura b’ Avastin ma tistax tiġi eskluża.
Very Common and Common Adverse Drug Reactions
Reazzjonijiet ta ’ kull
NCI-CTC Grade 3-5 Reactions (≥ 2% difference between the study arms in at
(Differenza ta ’ ≥ 2% bejn il- gruppi studjati f’ minn ta ’ l- anqas prova klinika waħda)
All Grade Reactions (≥ 10% difference
Grad (Differenza ta ’ ≥ 10% bejn il- gruppi
System Organ Class (SOC)
Sistema tal- Klassifika tal- Organi (SOC)
between the study arms in at least one clinical trial)
studjati f’ minn ta ’ l- anqas prova klinika waħda)
Very Common
Reazzjonijiet ta ’ kull
Infections and infestations
Grad (Differenza ta ’ ≥ 10% bejn il- gruppi
Sepsis Abscess Infection
Sistema tal- Klassifika tal- Organi (SOC)
Blood and the
studjati f’ minn ta ’ l- anqas prova klinika waħda)
Leucopenia
Komuni ħafna Komuni
Febrile neutropenia
Komuni ħafna
lymphatic systems disorders
Disturbi tad- demm u
Thrombocytopenia Neutropenia
Tromboċitopenja Newtropenja
Peripheral sensory neuropathy
Newropatija sensorjali
Cerebrovascular accident Syncope Somnolence Headache
Inċident
Dysgeusia Headache
Disġewżja
Eye disorder
periferali
Cardiac disorders
ċerebrovaskulari Sinkope Ngħas Uġigħ ta ’ ras
Cardiac failure congestive
Uġigħ ta ’ ras
Supraventricular tachycardia
Disturbi fl- għajnejn Disturbi fl- għajnejn
7
Insuffiċjenza tal- qalb Disturbi fil- qalb konġestiva Takikardja supraventrikulari
NCI-CTC Grade 3-5 Reactions
Disturbi vaskulari
All Grade Reactions
Pressjoni għolja
(≥ 2% difference between the study arms in at
Trombo- emboliżmu (fl- arterji) *
(≥ 10% difference
Pressjoni għolja
System Organ Class (SOC)
Trombożi fil- vini l- kbar Emorraġija Disturbi Respiratorji,
least one clinical trial)
Emboliżmu pulmonari
between the study arms in at least one clinical trial)
Qtugħ ta ’ nifs
Very common
Toraċiċi u Medjastinali
Common
Qtugħ ta ’ nifs
Very Common
Epistassi
Vascular disorders
Ipoxja Epistassi
Hypertension
Rinite
Thromboembolism (arterial)*
Disturbi gastro -
Hypertension
Dijarea
Pulmonary embolism Dyspnoea Hypoxia Epistaxis
Perforazzjoni intestinali
Dyspnoea Epistaxis Rhinitis
Stitikezza
Gastrointestinal disorders
intestinali
Diarrhoea Nausea
Tqalligħ
Constipation Stomatitis
Stomatite
Intestinal obstruction Abdominal pain Gastrointestinal disorder
Sadd intestinali
Rectal haemorrhage
Emorraġija mir- rektum
Skin and subcutaneous
Uġigħ addominali Disturbi gastro - intestinali Disturbi fil- ġilda u fit -
Palmar-plantar
Sindromu ta ’
Exfoliative dermatitis
Dermatite bil- qxur
tissue disorders
tessuti ta ’ taħt il- ġilda
erythrodysaesthesia syndrome
eritrodisasteżija
Dry skin discolouration
Ġilda xotta
Musculoskeletal,
palmari- plantari
Muscular weakness
Tibdil fil- kulur tal- ġilda
connective tissue and bone disorders
Debbulizza tal- muskoli Disturbi muskolu - skeltrali, tal- connective tissue u tal- għadam
Proteinuria
Proteina fl- awrina
Urinary Tract Infection
Infezzjoni fil- passaġġ sistema urinarja urinarju
administration site conditions
kondizzjonijiet ta ’ mnejn jingħata
Lethargy
Letarġija
Asthenia Pain
Astenja Uġigħ
* Pooled arterial thromboembolic events including cerebrovascular accident, myocardial infarction, transient ischaemic attack and other arterial thromboembolic events.
* Avvenimenti trombo- embolitiċi arterjali miġbura, inkluż aċċident ċerebrovaskulari, infart mijokardijaku, attackk iskemiku li jgħaddi u avvenimenti trombo- embolitiċi arterjali oħrajn.
Data are unadjusted for the differential time on treatment.
It- tagħrif mhux aġġustat għall- ħin differenzjali ta ’ kura.
Further information on selected serious adverse drug reactions:
8 Aktar informazzjoni dwar reazzjonijiet avversi serji magħżula tal- mediċina:
Gastrointestinal perforations (see section 4.4):
Perforazzjonijiet gastro- intestinali (ara sezzjoni 4. 4):
Avastin has been associated with serious cases of gastrointestinal perforation or fistulae (see also under heading Fistulae).
Avastin kien assoċjat ma ’ każijiet serji ta ’ perforazzjoni gastro- intestinali jew fistuli (ara wkoll taħt it - titlu Fistuli).
Gastrointestinal perforation have been reported in clinical trials with an incidence of less than 1% in patients with metastatic breast cancer or non-squamous non-small cell lung cancer, and in up to 2.0% in metastatic colorectal cancer patients.
Fi studji kliniċi, perforazzjoni gastro- intestinali kienet irrappurtata b’ inċidenza ta ’ anqas minn 1% f’ pazjenti b’ kanċer tas- sider li mmetastatizza jew kanċer taċ- ċelluli mhux żgħar, mhux skwamuż tal - pulmun, u sa 2. 0% tal- pazjenti b’ kanċer li mmetastatizza tal- kolorektum.
Fatal outcome was reported in approximately a third of serious cases of gastrointestinal perforations, which represents between 0.2%-1% of all Avastin treated patients.
Riżultat fatali kien irrappurtat f’ madwar terz tal- każijiet serji ta ’ perforazzjoni gastro- intestinali, li jirrappreżenta bejn 0. 2% - 1% tal- pazjenti kollha kkurati b’ Avastin.
The presentation of these events varied in type and severity, ranging from free air seen on the plain abdominal X-ray, which resolved without treatment, to intestinal perforation with abdominal abscess and fatal outcome.
Il- preżentazzjoni ta ’ dawn l- episodji varjaw fit- tip u s- severità, minn dehra ta ’ arja ħielsa f’ X- ray sempliċi ta ’ l- addome, li ġiet imfejqa mingħajr kura, għal perforazzjoni intestinali b’ axxess addominali u mewt.
In some cases underlying intra-abdominal inflammation was present, either from gastric ulcer disease, tumour necrosis, diverticulitis, or chemotherapy-associated colitis.
F’ xi każijiet kien hemm infjammazzjoni intra- addominali minn qabel, jew minn marda ta ’ ulċera gastrika, nekrożi mit- tumur, divertikulitis, jew kolité assoċjata ma ’ kimoterapija.
8 Fistulae (see section 4.4):
Fistuli (ara sezzjoni 4. 4):
Avastin use has been associated with serious cases of fistulae including events resulting in death.
L- użu ta ’ Avastin kien assoċjat ma ’ każijiet serji ta ’ fistuli inkluż avvenimenti li rriżultaw f’ mewt.
In clinical trials, gastrointestinal fistulae have been reported with an incidence of up to 2% in patients with metastatic colorectal cancer, but were also reported less commonly in patients with other types of cancers.
Fi provi kliniċi, fistuli gastro- intestinali kienu rrappurtati b’ inċidenza sa 2% f’ pazjenti b’ kanċer metastatiku tal- kolorektum, iżda kienu rrappurtati wkoll bi frekwnza anqas komuni f’ pazjenti b’ tipi oħra ta ’ kanċers.
Uncommon (≥ 0.1% to < 1%) reports of other types of fistulae that involve areas of the body other than the gastrointestinal tract (e. g. bronchopleural, urogenital and biliary fistulae) were observed across various indications.
Rapporti mhux komuni (≥ 0. 1% sa < 1%) ta ’ tipi oħra ta ’ fistuli li jinvolvu partijiet oħra tal- ġisem minbarra l- apparat gastro- intestinali (e. ż. bronkoplewra, urogenitali u fistuli biljari) kienu osservati tul diversi ndikazzjonijiet.
Fistulae have also been reported in post-marketing experience.
Fistuli kienu rrappurtati wkoll fl- esperjenza ta ’ wara t - tqegħid fis- suq.
Events were reported at various time points during treatment ranging from one week to greater than 1 year from initiation of Avastin, with most events occurring within the first 6 months of therapy.
Avvenimenti kienu rrappurtati f’ diversi ħinijiet waqt il- kura b’ firxa minn ġimgħa sa aktar minn sena mill- bidu ta ’ Avastin, bil- biċċa l- kbira tal- avvenimenti jseħħu fl- ewwel 6 xhur ta ’ terapija.
Wound healing (see section 4.4):
Fejqan tal- feriti (ara sezzjoni 4. 4):
As Avastin may adversely impact wound healing, patients who had major surgery within the last 28 days were excluded from participation in phase III clinical trials.
Minħabba li Avastin jista ’ jaffettwa ħażin il- fejqan tal- feriti, pazjenti li kellhom operazzjoni maġġuri f’ dawn l- aħħar 28 ġurnata kienu esklużi milli jipparteċipaw fil- provi kliniċi ta ’ fażi III.
In clinical trials of metastatic carcinoma of the colon or rectum, there was no increased risk of post- operative bleeding or wound healing complications observed in patients who underwent major surgery 28-60 days prior to starting Avastin.
Fi provi klinċi dwar karċinoma metastatika tal- kolon jew rektum, ma kienux osservati l- ebda żjieda fir- riskju ta ’ fsada wara l- operazzjoni jew komplikazzjonijiet fil- fejqan ta ’ feriti f’ pazjenti li kellhom operazzjoni maġġuri 28- 60 ġurnata qabel ma ’ nbeda Avastin.
An increased incidence of post-operative bleeding or wound healing complication occurring within 60 days of major surgery was observed if the patient was being treated with Avastin at the time of surgery.
Żjieda fl- inċidenza ta ’ fsada ta ’ wara operazzjoni jew komplikazzjoni fil- fejqan tal- ferita li seħħew sa 60 ġurnata wara kirurġija maġġuri kienet osservata jekk il- pazjent kien ikkurat b’ Avastin fil- ħin tal- kirurġija.
The incidence varied between 10% (4/ 40) and 20% (3/ 15).
L- inċidenza varjat bejn 10% (4/ 40) u 20% (3/ 15).