qanastek/EMEA-V3 huggingface dataset:
To minimise variability in the individual patient, administration of lapatinib should be standardised in relation to food intake, for example always be taken before a meal (see sections 4.5 and 5.2 for information on absorption).
Biex tiġi mnaqqsa il- varjabbilità bejn il- pazjent individwali, l - amministrazzjoni ta ’ lapatinib għandha tiġi standardizzata skond it- teħid ta ’ l- ikel, per eżempju dejjem tittieħed qabel l- ikel (ara sezzjonijiet 4. 5 u 5. 2 għal informazzjoni dwar l- assorbiment).
Missed doses should not be replaced and the dosing should resume with the next scheduled daily dose (see section 4.9).
Dożi li ma jittieħdux m’ għandhomx jiġu sostitwiti u d- dożaġġ għandu jitkompla bid- doża skedata ta ’ kuljum li jkun imiss (ara sezzjoni 4. 9).
The recommended dose of capecitabine is 2000 mg/ m2/ day taken in 2 doses 12 hours apart on days 1- 14 in a 21 day cycle (see section 5.1).
Id- doża rakkommandata ta ’ capecitabine hija ta ’ 2000 mg/ m2/ kuljum li tittieħed f’ 2 dożi imbegħdin 12 il - siegħa minn xulxin fil- ġranet 1- 14 f’ ċiklu ta ’ 21 ġurnata (ara sezzjoni 5. 1).
Capecitabine should be taken with food or within 30 minutes after food.
Capecitabine għandu jittieħed ma ’ l- ikel jew fi żmien 30 minuta wara l- ikel.
Dose delay and dose reduction
2 Posponimeni tad- doża u tnaqqis tad- doża
Cardiac events
Każi tal- qalb
2 Lapatinib should be discontinued in patients with symptoms associated with decreased left ventricular ejection fraction (LVEF) that are National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grade 3 or greater or if their LVEF drops below the institutions lower limit of normal (see section 4.4).
Lapatinib m’ għandux jibqa ’ jingħata lill- pazjenti b’ sintomi assoċjati ma ’ tnaqqis fil- porzjon imbuttat ’ il barra mill- ventrikulu tan- naħa tax- xellug (LVEF) li huma Kriteriji ta ’ Terminoloġija Komuni għal Reazzjonijiet Avversi ta ’ l- Istitut Nazzjonali tal- Kanċer (NCI CTCAE) ta ’ grad 3 jew akbar jew jekk l- LVEF tagħhom jonqos aktar mill- limitu l- aktar baxx tan- normal ta ’ l- istituzzjoni (ara sezzjoni 4. 4).
Lapatinib may be restarted at a reduced dose (1000 mg/ day) after a minimum of 2 weeks and if the LVEF recovers to normal and the patient is asymptomatic.
Lapatinib jista ’ jerġa ’ jinbeda f’ doża imnaqqsa (1000 mg/ ġurnata) wara minimu ta ’ ġimgħatejn u jekk l- LVEF jirkupra għan- normal u l- pazjent ma ’ jkollux sintomi.
Interstitial lung disease / pneumonitis
Mard ta ’ l- interstizju tal- pulmun / pulmonite
Lapatinib should be discontinued in patients who experience pulmonary symptoms which are NCI CTCAE grade 3 or greater (see section 4.4).
Lapatinib m’ għandux jibqa ’ jingħata lill- pazjenti li jesperjenzaw sintomi pulmonarji li huma ta ’ NCI CTCAE grad 3 jew aktar (ara sezzjoni 4. 4).
Other toxicities
Tossiċitajiet oħra
Discontinuation or interruption of dosing with lapatinib may be considered when a patient develops toxicity greater than or equal to grade 2 on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).
Sospensjoni jew interruzzjoni tad- dożaġġ b’ lapatinib għandu jiġi kkunsidrat meta pazjent jiżviluppa tossiċità aktar minn jew ekwivalenti għal grad 2 skond il- Kriteriji ta ’ Terminoloġija Komuni għal Reazzjonijiet Avversi ta ’ l- Istitut Nazzjonali tal- Kanċer (NCI CTCAE).
Dosing can be restarted at 1250 mg/ day when the toxicity improves to grade 1 or less.
Id- dożaġġ jista ’ jerġa ’ jinbeda b’ 1250mg/ ġurnata meta t- tossiċità titjieb għal grad 1 jew anqas.
If the toxicity recurs, then lapatinib should be restarted at a lower dose (1000 mg/ day).
Jekk it- tossiċità terġa ’ titfaċċa, lapatinib imbagħad għandu jinbeda f’ doża aktar baxxa (1000mg/ ġurnata).
The prescribing information for capecitabine must be consulted for guidance on dose delay and dose reduction recommendations for capecitabine.
Informazzjoni dwar il- preskrizzjoni ta ’ capecitabine għandha tiġi kkonsultata għall- gwida dwar rakkomandazzjonijiet għall- posponiment tad- doża u tnaqqis tad- doża ta ’ capecitabine.
Caution is advised in patients with severe renal impairment as there is no experience of lapatinib in this population (see section 5.2),
Attenzjoni hija rrikmandata f’ pazjenti b’ indeboliment renali serju minħabba li m’ hemmx esperjenza ta ’ lapatinib f’ din il- popolazzjoni (ara sezzjoni 5. 2).
Lapatinib should be discontinued if changes in liver function are severe and patients should not be retreated (see section 4.4).
Lapatinib għandu jitwaqqaf jekk il- bidla fil- funzjoni tal- fwied hija severa u l- pazjenti m’ għandhomx jingħataw il- kura darb’ oħra (ara sezzjoni 4. 4).
Administration of lapatinib to patients with moderate to severe hepatic impairment should be undertaken with caution due to increased exposure to the medicinal product.
L- amminsitrazzjoni ta ’ lapatinib lill- pazjenti b’ indeboliment epatiku moderat sa serju fil- bidu tal- kura għandha ssir b’ attenzjoni minħabba żieda fl- esponiment għall- prodott mediċinali.
Insufficient data are available in patients with hepatic impairment to provide a dose adjustment recommendation (see section 5.2).
Id- dejta disponibbli f’ pazjenti b’ indeboliment epatiku hija nsuffiċjenti biex tipprovdi rakkommandazzjoni għal aġġustament tad - doża (ara sezzjoni 5. 2).
Paediatrics
Tfal
Tyverb is not recommended for use in paediatrics due to insufficient data on safety and efficacy.
Tyverb mhux irrakkommandat għall- użu fit- tfal minħabba dejta insuffiċjenti dwar sigurtà u effikaċja.
There are limited data of the use of lapatinib in patients aged 65 years and older.
Hemm dejta limitata dwar l- użu ta ’ lapatinib f’ pazjenti li għandom minn 65 sena ‘ l fuq.
Please refer to the capecitabine prescribing information for relevant contraindications and safety information when administering lapatinib in combination with capecitabine.
3 Jekk jogħġbok irreferi għall- informazzjoni dwar il- preskrizzjoni ta ’ capecitabine għall- kontra - indikazzjonijiet rilevanti u informazzjoni ta ’ sigurtà meta qed tamministra lapatinib flimkien ma ’ capecitabine.
4.4 Special warnings and precautions for use
4. 4 Twissijet speċjali u prekawzjonjiet għall- użu
3 Lapatinib has been associated with reports of decreases in left ventricular ejection fraction (LVEF) (see section 4.8).
Lapatinib ġie assoċjat ma ’ rapporti ta ’ tnaqqis fil- porzjon imbuttat ’ il barra mill- ventrikulu tan- naħa tax - xellug (LVEF) (ara sezzjoni 4. 8).
Caution should be taken if lapatinib is to be administered to patients with conditions that could impair left ventricular function.
Għandu jkun hemm attenzjoni jekk lapatinib ikun se jiġi amministrat lill - pazjenti b’ kundizzjonijiet li jistgħu jgħarrqu l- funzjoni tal- ventrikulu tan- naħa tax- xellug.
LVEF should be evaluated in all patients prior to initiation of treatment with lapatinib to ensure that the patient has a baseline LVEF that is within the institutions normal limits.
L- LVEF għandu jiġi evalwat fil- pazjenti kollha qabel ma ’ tinbeda l- kura b’ lapatinib biex ikun żgurat li l- pazjent għandu linja bażi ta ’ LVEF li qegħda fil- limiti tan- normal ta ’ l- istituzzjoni.
LVEF should continue to be evaluated during treatment with lapatinib to ensure that LVEF does not decline to an unacceptable level (see section 4.2).
L- LVEF għandu jkomli jiġi evalwat waqt il - kura b’ lapatinib biex ikun żgurat li l- LVEF ma jonqosx għal- livell mhux aċċettabbli (ara sezzjoni 4. 2).
Lapatinib has been associated with reports of pulmonary toxicity including interstitial lung disease and pneumonitis (see section 4.8).
Lapatinib ġie assoċjat ma ’ rapporti ta ’ tossiċità pulmonari inkluż mard ta ’ l- interstizju tal- pulmun u pulmonite (ara sezzjoni 4. 8).
Patients should be monitored for symptoms of pulmonary toxicity (see section 4.2).
Il- pazjenti għandhom jiġu osservati l- ħin kollu għal sintomi ta ’ tossiċità pulmonari (ara sezzjoni 4. 2).
Hepatotoxicity has occurred with lapatinib use and may in rare cases be fatal.
Kien hemm tossiċita ’ tal- fwied bl- użu ta ’ lapatinib u f’ każi rari tista ’ tkun fatali.
Liver function (transaminases, bilirubin and alkaline phosphatase) should be monitored before initiation of treatment and monthly thereafter, or as clinically indicated.
Għandu jkun osservat il - funzjoni tal- fwied (transaminases, bilirubin u alkaline phosphatase) qabel tibda ’ l- kura u kull xahar wara, jew kif indikat klinikament.
Lapatinib dosing should be discontinued if changes in liver function are severe and patients should not be retreated.
Għandu jitwaqqaf id- dożaġġ b’ lapatinib jekk ikun hemm xi bdil sever fil - funzjoni tal- fwied u l- pazjenti m’ għandhomx jerġgħu jingħataw il- kura.
Caution is warranted if lapatinib is prescribed to patients with moderate or severe hepatic impairment (see sections 4.2 and 5.2).
Hija meħtieġa attenzjoni jekk lapatinib jiġi preskritt lill- pazjenti b’ indeboliment epatiku moderat jew serju (ara sezzjonijiet 4. 2 u 5. 2).
Caution is advised if lapatinib is prescribed to patients with severe renal impairment (see sections 4.2 and 5.2).
Hija rrikkmandata attenzjoni jekk lapatinib jiġi preskritt lill- pazjenti b’ indeboliment serju tal- kliewi (ara sezzjonijiet 4. 2 u 5. 2).
Diarrhoea, including severe diarrhoea, has been reported with lapatinib treatment (see section 4.8).
Dijarea, inkluż dijarea serja kienet irrappurtata f’ kura b’ lapatinib (ara sezzjoni 4. 8).
Proactive management of diarrhoea with anti-diarrhoeal agents is important.
Immaniġġar proattiv tad - dijarea b’ aġenti kontra d- dijarea huwa importanti.
Severe cases of diarrhoea may require administration of oral or intravenous electrolytes and fluids, and interruption or discontinuation of lapatinib therapy (see section 4.2 – dose delay and dose reduction – other toxicities).
Każi serji ta ’ dijarea jista ’ jkollhom bżonn amministrazzjoni ta ’ fluwidi u elettroliti orali jew ġol- vini u interruzzjoni jew sospensjoni ta ’ terapija b’ lapatinib (ara sezzjoni 4. 2 – posponiment tad- doża jew tnaqqis tad- doża – tossiċitajiet oħra).
Concomitant treatment with inducers of CYP3A4 should be avoided due to risk of decreased exposure to lapatinib (see section 4.5).
Kura konkomitanti b’ indutturi ta ’ CYP3A4 għandha tiġi evitata minħabba riskju ta ’ tnaqqis fl- esponiment għal lapatinib (ara sezzjoni 4. 5).
Concomitant treatment with strong inhibitors of CYP3A4 should be avoided due to risk of increased exposure to lapatinib (see section 4.5).
Kura konkomitanti b’ impedituri qawwija ta ’ CYP3A4 għandha tiġi evitata minħabba riskju ta ’ żieda fl - esponiment għal lapatinib (ara sezzjoni 4. 5).
Grapefruit juice should be avoided during treatment with lapatinib (see section 4.5).
Meraq tal- grejpfrut għandu jiġi evitat waqt kura b’ lapatinib (ara sezzjoni 4. 5).
Coadministration of lapatinib with medicinal product with narrow therapeutic windows that are substrates of CYP3A4 or CYP2C8 should be avoided (see section 4.5).
L- amministrazzjoni ta ’ lapatinib flimkien ma ’ prodotti mediċinali li għandhom indiċi terapewtiċi dojoq u li huma sustrati ta ’ CYP3A4 jew CYP2C8 għandhom jiġu evitati (ara sezzjoni 4. 5).
Concomitant treatment with substances that increase gastric pH should be avoided, as lapatinib solubility and absorption may decrease (see section 4.5).
Kura konkomitanti b’ sustanzi li jżidu l- pH ta ’ l- istonku għandhom jiġu evitati minħabba li s- solubilità u l - assorbiment ta ’ lapatinib jistgħu jonqsu (ara sezzjoni 4. 5).
4.5 Interaction with other medicinal products and other forms of interaction
4. 5 Prodotti medicinali oħra li ma jaqblux ma ’ dan il- prodott u affarijiet oħra li jistgħu jibdlu l - effett farmaċewtiku tal- prodott
Effects of other medicinal products on lapatinib
Effetti ta ’ prodotti mediċinali oħra fuq lapatinib
Lapatinib is predominantly metabolised by CYP3A (see section 5.2).
Lapatinib huwa l- biċċa l- kbira mmetabolizzat permezz ta ’ CYP3A (ara sezzjoni 5. 2).
In healthy volunteers receiving ketoconazole, a strong CYP3A4 inhibitor, at 200 mg twice daily for 7 days, systemic exposure to lapatinib (100 mg daily) was increased approximately 3.6– fold, and half- life increased 1.7 – fold.
F’ voluntiera b’ saħħithom li kienu qed jirċievu ketoconazole, impeditur qawwi ta ’ CYP3A4, f’ doża ta ’ 200mg darbtejn kuljum għal 7 ijiem, esponiment sistemiku għal lapatinib (100 mg kuljum) żdied bejn
Coadministration of lapatinib with strong inhibitors of CYP3A4 (e. g. ritonavir, saquinavir, telithromycin, ketoconazole, itraconazole, voriconazole, posaconazole, nefazodone) should be avoided.
L- amministrazzjoni ta ’ lapatinib flimkien ma ’ impedituri qawwija ta ’ CYP3A4 (e. ż. ritonavir, saquinavir, telithromycin, ketoconazole, itraconazole, voriconazole, posaconazole, nefazodone) għandha tiġi evitata.
Coadministration of lapatinib with moderate inhibitors of CYP3A4 should proceed with caution and clinical adverse reactions should be carefully monitored.
L- amministrazzjoni ta ’ lapatinib flimkien ma ’ impedituri moderati ta ’ CYP3A4 għandha ssir b’ attenzjoni u għandu jkun hemm monitoraġġ b’ attenzjoni għal reazzjonijiet kliniċi avversi.
4 In healthy volunteers receiving carbamazepine, a CYP3A4 inducer, at 100 mg twice daily for 3 days and 200 mg twice daily for 17 days, systemic exposure to lapatinib was decreased approximately 72%.
F’ voluntiera b’ saħħithom li kienu qed jirċievu carbamazepine, induttur ta ’ CYP3A4, f’ doża ta ’ 100mg darbtejn kuljum għal 3 ijiem u 200mg darbtejn kuljum għal 17- il ġurnata, esponiment sistemiku għal lapatinib naqas bejn wieħed u ieħor 72%.
Coadministration of lapatinib with known inducers of CYP3A4 (e. g. rifampicin, rifabutin, carbamazepine, phenytoin or Hypericum perforatum [St John’ s wort]) should be avoided.
L- amministrazzjoni ta ’ lapatinib flimkien ma ’ indutturi magħrufa ta ’ CYP3A4 (e. ż. rifampicin, rifabutin, carbamazepine, phenytoin or Hypericum perforatum [St John’ s wort]) għandha tiġi evitata.
Lapatinib is a substrate for the transport proteins Pgp and BCRP.
Lapatinib huwa sustrat għal proteini ta ’ trasport Pgp u BCRP.
Inhibitors (ketoconazole, itraconazole, quinidine, verapamil, cyclosporine, erythromycin) and inducers (rifampin, St John’ s Wort) of these proteins may alter the exposure and/ or distribution of lapatinib (see section 5.2).
Impedituri (ketoconazole, itraconazole, quinidine, verapamil, cyclosporine, erythromycin) u indutturi (rifampin, St John’ s Wort) ta ’ dawn il- proteini jistgħu jibdlu l- esponiment u/ jew id- distribuzzjoni ta ’ lapatinib (ara sezzjoni 5. 2).
The solubility of lapatinib is pH-dependent.
Is- solubilità ta ’ lapatinib hija dipendenti mill- pH.
Concomitant treatment with substances that increase gastric pH should be avoided, as lapatinib solubility and absorption may decrease.
Kura konkomitanti b’ sustanzi li jżidu l- pH ta ’ l- istonku għandhom jiġu evitati minħabba li s- solubilità u l- assorbiment ta ’ lapatinib jista ’ jonqos.
Effects of lapatinib on other medicinal products
Effetti ta ’ lapatinib fuq prodotti mediċinali oħra
Lapatinib inhibits CYP3A4 and CYP2C8 in vitro at clinically relevant concentrations.
Lapatinib jimpedixxi CYP3A4 u CYP2C8 in vitro f’ konċentrazzjonijiet klinikament rilevanti.
Coadministration of lapatinib with medicines with narrow therapeutic windows that are substrates of CYP3A4 (e. g. cisapride, pimozide and quinidine) or CYP2C8 (e. g. repaglinide) should be avoided (see sections 4.4 and 5.2).
L - amministrazzjoni ta ’ lapatinib flimkien ma ’ mediċini b’ indiċi terapewtiċi dojoq li huma sustrati ta ’ CYP3A4 (e. ż. cisapride, pimozide and quinidine) jew CYP2C8 (e. ż. repaglinide) għandha tiġi evitata (ara sezzjonijiet 4. 4 u 5. 2).
If lapatinib is administered in combination with paclitaxel (175 mg/ m2 every three weeks), severe neutropenia may coincide with diarrhoea.
Jekk lapatinib jiġi amministrat flimkien ma paclitaxel (175mg/ m² kull tlett ġimgħat), newtropenja serja tista ’ tiġri fl- istess ħin ma ’ dijarea.
This warrants monitoring and early treatment of diarrhoea.
Dan jiġġustifika monitoraġġ u kura bikrija tad- dijarea.
Lapatinib inhibits the transport proteins Pgp, BCRP and OATP1B1 in vitro.
Lapatinib jimpedixxi l- proteini ta ’ transport Pgp, BCRP u OATP1B1 in vitro.
The clinical relevance of this effect has not been evaluated.
Ir- rilevanza klinika ta ’ dan l - effett ma ġietx evalwata.
It cannot be excluded that lapatinib will affect the pharmacokinetics of substrates of Pgp (e. g. digoxin), BCRP (e. g. topotecan) and OATP1B1 (e. g. rosuvastatin) (see section 5.2).
Ma jistax jiġi eskluż li lapatinib jaffettwa l- farmakokinetika tas- sustrati ta ’ Pgp (e. ż. digoxin), BCRP (e. ż. topotecan) u OATP1B1 (e. ż. rosuvastatin) (ara sezzjoni 5. 2).
Concomitant administration of lapatinib with capecitabine or trastuzumab did not meaningfully alter the pharmacokinetics of these agents (or the metabolites of capecitabine) or lapatinib.
L- amministrazzjoni konkomitanti ta ’ lapatinib ma ’ capecitabine u trastuzumab ma bidlitx b’ mod sinifikattiv il- farmakokinetika ta ’ dawn l- aġenti (jew il- metaboliti ta ’ capecitabine) jew ta ’ lapatinib.
Interactions with food and drink
Interazzjonijiet ma ’ l- ikel u max- xorb
The bioavailability of lapatinib is increased up to about 4 times by food, depending on e. g. the fat content in the meal (see sections 4.2 and 5.2).
Il- biodisponibiltà ta ’ lapatinib tiżdied madwar 4 darbiet permezz ta ’ l- ikel, skond e. ż. l- ammont ta ’ xaħam fl - ikla (ara sezzjonijiet 4. 2 u 5. 2).
Grapefruit juice may inhibit CYP3A4 in the gut wall and increase the bioavailability of lapatinib and should therefore be avoided during treatment with lapatinib.
Il- meraq tal- grejpfrut jista ’ jimpedixxi CYP3A4 fil- membrana tal- musrana u jżid il- biodisponibiltà ta ’ lapatinib u għalhekk għandu jiġi evitat waqt kura b’ lapatinib.
There are no adequate data from the use of lapatinib in pregnant women.
M’ hemmx tagħrif biżżejjed dwar l- użu ta ’ lapatinib waqt it- tqala.
Studies in animals have shown reproductive toxicity (see section 5.3).
Studji fuq annimali urew ħsara fuq is - sistema riproduttiva (ara sezzjoni 5. 3).
The potential risk for humans is not known.
Mhux magħruf ir- riskju potenzjali fuq in- nies.
Lapatinib should not be used during pregnancy unless clearly necessary.
Lapatinib m’ għandux jintuża waqt it- tqala jekk ma jkunx hemm ċertezza li hemm bżonnu.
Women of childbearing potential should be advised to use adequate contraception and avoid becoming pregnant while receiving treatment with lapatinib.
Nisa li jista ’ jkollhom it- tfal għandhom jiġu mwissija biex jużaw kontraċezzjoni adegwata u jevitaw li joħorġu tqal waqt li qed jirċievu kura b’ lapatinib.
The safe use of lapatinib during lactation has not been established.
Is- sigurtà ta ’ l- użu ta ’ lapatinib waqt it- treddigħ għadha ma ’ ġietx stabbilita.
It is not known whether lapatinib is excreted in human milk.
M’ huwiex magħruf jekk lapatinib jitneħħiex għal ġol- ħalib uman.
In rats, growth retardation was observed in pups which were exposed to lapatinib via breast milk.
Fil- firien, ġie osservat żvilupp tal- ġisem ritardat fil- frieħ li kienu esposti għal- lipatinib mill- ħalib tas- sider.
Breast feeding must be discontinued in women who are receiving therapy with lapatinib.
Treddigħ għandu jitwaqqaf f’ nisa li qed jirċievu kura b’ lapatinib.
The clinical status of
Effett li jista ’ jkun ta ’ ħsara fuq attivitajiet bħal dawn ma ’ jistax jiġi mbassar mill- farmakoloġija ta ’ lapatinib.
5 the patient and the adverse event profile of lapatinib should be borne in mind when considering the patient's ability to perform tasks that require judgement, motor or cognitive skills.
L- istat kliniku tal- pazjent u l - profil tal- ġrajjiet avversi ta ’ lapatinib għandu jinżamm fil- moħħ meta tiġi kkunsidrata l- abbiltà tal- pazjent li jagħmel biċċiet ta ’ xogħol li għalihom jinħtieġ ġudizzju u kapaċitajiet ta ’ ċaqlieq u konoxxottivi.
Safety of lapatinib has been evaluated as monotherapy or in combination with other chemotherapies for various cancers including patients who received lapatinib in combination with capecitabine (see section 5.1).
Is- sigurtà ta ’ lapatinib ġiet evalwata bħala monoterapija jew flimkien ma ’ kimoterapiji oħra għal diversi kankri inkluż f’ pazjenti li rċievew lapatinib flimkien ma ’ capecitabine (ara sezzjoni 5. 1).
The most common adverse reactions (> 25%) during therapy with lapatinib plus capecitabine were gastrointestinal (diarrhoea, nausea, and vomiting) or dermatologic (palmar-plantar erythrodysesthesia [PPE] and rash).
L- aktar reazzjonijiet avversi komuni (> 25%) waqt kura b’ lapatinib ma ’ capecitabine kienu gastro- intestinali (dijarea, dardir, u rimettar) jew dermatoloġiċi (eritrodisestesja fil- pala ta 'l- id u tas- sieq [PPE] u raxx).
The incidence of PPE was similar in both lapatinib plus capecitabine and capecitabine alone treatment arms.
L - inċidenza ta ’ PPE kienet tixtiebaħ kemm bil - fergħat ta ’ kura ta ’ lapatinib ma ’ capecitabine kif ukoll b’ capecitabine waħdu.
Diarrhoea was the most common adverse reaction resulting in discontinuation of treatment and this had a similar incidence in both treatment groups (lapatinib plus capecitabine:
Dijarea kienet l- aktar reazzjoni avversa komuni li wasslet għal waqfien mill- kura u din kellha inċidenza tixtiebaħ fiż- żewġ gruppi ta ’ kura (lapatinib ma ’ capacitabine:
The following convention has been utilised for the classification of frequency:
Il- konvenzjoni li ġejja ġiet utilizzata għall- klassifikazzjoni tal- frekwenza:
Very common ((≥ 1/ 10), Common (≥ 1/ 100 to < 1/ 10), Uncommon (≥ 1/ 1,000 to < 1/ 100), Rare (≥ 1/ 10,000 to < 1/ 1,000) and Very rare (< 1/ 10,000), not known (cannot be estimated from the available data).
Komuni ħafna (≥1/ 10), Komuni (≥1/ 100 sa < 1/ 10), Mhux komuni (≥1/ 1, 000 to < 1/ 100), Rari (≥1/ 10, 000 to < 1/ 1, 000), u Rari ħafna (< 1/ 10, 000), mhux magħrufa (ma tistax tiġi kkalkulata mid- data disponibbli).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
F’ kull grupp ta ’ frekwenza, l- effetti mhux mixtieqa għandhom jitniżżlu skond is- serjetà tagħhom.
The following adverse reactions have been reported to be associated with lapatinib:
Ir- reazzjonijiet avversi li ġejjin kienu rrappurtati li kienu assoċjati ma ’ lapatinib:
Cardiac disorders Common
Disturbi fil- qalb Komuni
Decreased left ventricular ejection fraction (see section 4.2 - dose reduction – cardiac events and section 4.4)
Tnaqqis fil- porzjon imbuttat ’ il barra mill- ventrikulu tan- naħa tax - xellug (ara sezzjoni 4. 2 – tnaqqis tad- doża – każi tal- qalb u sezzjoni 4. 4)
Interstitial lung disease/ pneumonitis
Mard ta ’ l- interstizju tal- pulmun/ pulmonite
Gastrointestinal disorders Very common
Disturbi gastro- intestinali Komuni ħafna
Diarrhoea, which may lead to dehydration (see section 4.2 - dose delay and dose reduction – other toxicities and section 4.4).
Dijarea, li tista ’ twassal għal deidrazzjoni (ara sezzjoni 4. 2 – posponiment tad- doża u tnaqqis tad- doża – tossiċitajiet oħra u sezzjoni 4. 4).
Nausea Vomiting
Dardir Rimettar
Skin and subcutaneous tissue disorders Very common
Disturbi fil- ġilda u Komuni ħafna
Rash (including dermatitis acneiform) (see section 4.2 - dose delay and dose reduction – other toxicities)
fit- tessuti ta ’ taħt il- ġilda Raxx (li jinkludi dermatite acneiform) (ara sezzjoni 4. 2 – posponiment tad- doża u tnaqqis tad- doża – tossiċitajiet)
Hepatobiliary disorders Common
Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata Komuni ħafna Disturbi fil- fwied u Komuni
Hyperbilirubinaemia, hepatotoxicity
Għeja fil- marrara Iperbilirubinimija, tossiċita ’ tal- fwied
The following additional adverse reactions have been reported to be associated with lapatinib in combination with capecitabine with a frequency difference of greater than 5% compared to capecitabine alone.
Ir- reazzjonijiet avversi addizzjonali li ġejjin ġew irrappurtati li kienu assoċjati ma ’ lapatinib mogħti flimkien ma ’ capecitabine b’ differenza fil- frekwenza ta ’ aktar minn 5% meta mqabbla ma ’ capecitabine waħdu.
Gastrointestinal disorders Very common Skin and subcutaneous Very common
6 Disturbi gastro- intestinali Komuni ħafna Disturbi fil- ġilda u Komuni ħafna
Dyspepsia tissue disorders Dry skin
Dispepsja fit- tessuti ta ’ taħt il- ġilda Ġilda xotta
6 In addition, the following adverse reactions were reported to be associated with lapatinib in combination with capecitabine but were seen at a similar frequency in the capecitabine alone arm.
Addizzjonalment, ir- reazzjonijiet avversi li ġejjin ġew irrappurtati li kienu assoċjati ma ’ lapatinib mogħti flimkien ma ’ capecitabine iżda kienu dehru fi frekwenza tixtiebaħ fil- fergħa ta ’ capecitabine waħdu.
Nervous system disorders Common
Disturbi fis- sistema nervuża Komuni
Gastrointestinal disorders Very common Skin and subcutaneous Very common
Disturbi gastro- intestinali Komuni ħafna Disturbi fil- ġilda u Komuni ħafna
Stomatitis, constipation, abdominal pain tissue disorders Palmar-plantar erythrodysaesthesia
Stomatite, stitikezza, uġigħ fl- addome fit- tessuti ta ’ taħt il- ġilda Eritrodisestesja fil- pala ta 'l- id u tas- sieq
Musculoskeletal and connective tissue disorders Very common General disorders and Very common Psychiatric disorders
Disturbi muskolu- skeletrali u tal- connective tissue Komuni ħafna
Pain in extremity, back pain administrative site conditions Mucosal inflammation
Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata Komuni ħafna Disturbi psikjatriċi
Decreased left ventricular ejection fraction Left ventricular ejection fraction (LVEF) decreases have been reported in approximately 1% of patients receiving lapatinib and were asymptomatic in more than 90% of cases.
Tnaqqis fil- porzjon imbuttat ’ il barra mill- ventrikulu tan- naħa tax- xellug Tnaqqis fil- porzjon imbuttat ’ il barra mill- ventrikulu tan- naħa tax- xellug (LVEF) kien irrappurtat f’ bejn wieħed u ieħor 1% tal- pazjenti li kienu qed jirċievu lapatinib u li ma kienux juru sintomi f’ aktar minn 90% tal- każi.
LVEF decreases resolved or improved in more than 60% of cases on discontinuation of treatment with lapatinib.
Tnaqqis fl- LVEF irrisolva kompletament jew mar għall- aħjar f’ aktar minn 60% tal- każijiet meta twaqqfet il- kura b’ lapatinib.
Symptomatic LVEF decreases were observed in approximately 0.1% of patients who received lapatinib monotherapy.
Tnaqqis fl- LVEF fejn intwerew sintomi kien osservat f’ bejn wieħed u ieħor 0. 1% tal- pazjenti li rċievew lapatinib waħdu.
Observed symptoms included dyspnoea, cardiac failure and palpitations.
Is- sintomi osservati kienu jinkludu dispneja, insuffiċjenza kardijaka u palpitazzjonijiet.
All events resolved promptly on discontinuation of lapatinib.
Il- każijiet kollha rrisolvew fil- pront malli twaqqaf lapatinib.
LVEF decreases were reported in 2.5% of patients who received lapatinib in combination with capecitabine, as compared to 1.0% with capecitabine alone.
Tnaqqis fl- LVEF kien irrappurtat f’ 2. 5% tal- pazjenti li rċievew lapatinib flimkien ma ’ capecitabine, meta mqabbla ma ’ 1. 0% b’ capacitabine waħdu.
Diarrhoea Diarrhoea occurred in approximately 65% of patients who received lapatinib in combination with capecitabine.
Dijarea Kien hemm dijarea f’ bejn wieħed u ieħor 65% tal- pazjenti li rċievew kura b’ lapatinib flimkien ma 'capecitabine.
Most cases of diarrhoea were grade 1 or 2 and did not result in discontinuation of treatment with lapatinib.
L- aktar każijiet ta ’ dijarea kienu ta ’ grad 1 jew 2 u ma wasslux għal waqfien mill- kura b’ lapatinib.
Diarrhoea responds well to proactive management (see section 4.4).
Id- dijarea irrispondiet tajjeb għall- immaniggar proattiv (ara sezzjoni 4. 4).
Rash Rash occurred in approximately 28% of patients who received lapatinib in combination with capecitabine.
Raxx Kien hemm raxx f’ bejn wieħed u ieħor 28% tal- pazjenti li rċievew kura b’ lapatinib flimkien ma ’ capecitabine.
Rash was generally low grade and did not result in discontinuation of treatment with lapatinib.
Ir- raxx kien il- biċċa l- kbira ta ’ grad baxx u ma wassalx għall- waqfien mill- kura b’ lapatinib.
There is no specific antidote for the inhibition of EGFR (ErbB1) and/ or ErbB2 (HER2) tyrosine phosphorylation.
M’ hemm l- ebda antidot speċifiku għall- impediment ta ’ l- introduzzjoni tal- grupp fosfat f’ tyrosine ta ’ EGFR (ErbB1) u/ jew ErbB2 (HER2).
The maximum oral dose of lapatinib that has been administered in clinical trials is 1800 mg once daily.
Id- doża orali massima ta ’ lapatinib li kienet amministrata fil- provi kliniċi hija ta ’ 1800mg darba kuljum.
There has been a report of one patient who took an overdose of 3000 mg of lapatinib for 10 days and suffered grade 3 diarrhoea and vomiting on day 10.
Kien hemm rapport ta ’ pazjent wieħed li ħa doża eċċessiva ta ’ 3000mg lapatinib għal 10 ijiem u sofra minn dijarea fi grad 3 u rimettar fl- 10 jum.
The symptoms resolved following intravenous hydration and interruption of treatment with lapatinib and letrozole.
Is- sintomi irrisolvew wara idratazzjoni fil- vini u waqfien mill- kura b’ lapatinib u letrozole.
Lapatinib is not significantly renally excreted and is highly bound to plasma proteins, therefore haemodialysis would not be expected to be an effective method to enhance the elimination of lapatinib.
Lapatinib ma jitneħħiex b’ mod sinifikanti mill- kliewi u jeħel ħafna mal- proteini fil- plażma, għalhekk id - dijalisi tad- demm ma tkunx mistennija li tkun metodu effettiv biex ittejjeb l- eliminazzjoni ta ’ lapatinib.
7 Pharmacotherapeutic group:
Kategorija farmakoterapewtika:
Protein kinase inhibitor, ATC code:
Impeditur tal- proteina kinase, Kodiċi ATC:
This medicinal product has been authorised under a so-called “ conditional approval” scheme.
Dan il- prodott mediċinali ġie awtoriżżat taħt dik li tissejjaħ skema ta ’ "approvazzjoni b’ kondizzjoni".
This means that furrther evidence on this medicinal product is awaited.
Dan ifisser li għada mistennija aktar evidenza fuq dan il- prodott mediċinali.
The European Medicines Agency (EMEA) will review new information on the product every year and this SPC will be updated as necessary.
L- Agenzija Ewropeja dwar il- Mediċini (EMEA) ser tirevedi l- informazzjoni ġdida fuq il- prodott kull sena u ser taġġorna dan l- SPC, skond il- bżonn.
Lapatinib a 4-anilinoquinazoline, is an inhibitor of the intracellular tyrosine kinase domains of both EGFR (ErbB1) and of ErbB2 (HER2) receptors (estimated Kiapp values of 3nM and 13nM, respectively) with a slow off-rate from these receptors (half-life greater than or equal to 300 minutes).
Lapatinib li huwa 4- anilinoquinazoline, huwa impeditur ta ’ l- unitajiet globulari kemm tar- riċetturi EGFR (ErbB1) kif ukoll ErbB2 (HER2) (valuri Kiapp stmati ta ’ 3nM u 13nM, rispettivament) ta ’ tyrosine kinase intraċellulari li jinħall bil- mod minn dawn ir- riċetturi (half- life aktar minn jew ta ’ 300 minuta).
Lapatinib inhibits ErbB-driven tumour cell growth in vitro and in various animal models.
Lapatinib jimpedixxi tkabbir ta ’ ċelluli ta ’ tumuri misjuqa minn ErbB in vitro u f’ diversi mudelli ta ’ annimali.
The growth inhibitory effects of lapatinib were evaluated in trastuzumab-conditioned cell lines.
L- effetti ta ’ lapatinib li jimpedixxu t- tkabbir kienu evalwati f’ razez ta ’ ċelluli kkundizzjonati b’ trastuzumab.
Lapatinib retained significant activity against breast cancer cell lines selected for long-term growth in trastuzumab-containing medium in vitro.
Lapatinib żamm attività sinifikanti kontra razez ta ’ ċelluli tal- kanċer tas- sider li kienu magħżula minħabba tkabbir għal tul ta ’ żmien f’ sustanza ta ’ tkabbir in vitro li kien fiha trastuzumab.
The efficacy and safety of lapatinib in combination with capecitabine in breast cancer patients with good performance status was evaluated in a randomized, phase III trial.
L- effikaċja u s- sigurtà ta ’ lapatinib flimkien ma ’ capecitabine f’ pazjenti b’ kanċer tas- sider li kienu fi stat tajjeb kienu ivvalutati fi prova tal- fażi III randomized.
Patients eligible for enrolment had ErbB2 (HER2)-over-expressing, locally advanced or metastatic breast cancer, progressing after prior treatment that included taxanes, anthracyclines and trastuzumab.
Pazjenti eliġibbli biex jiddaħlu fil- prova kellhom ErbB2 (HER2) qed tesprimi b’ mod żejjed, kanċer tas- sider lokalment avvanzat jew mifrux, li avvanza wara li kien diġà hemm kura li kienet tinkludi taxanes, anthracyclines u trastuzumab.
LVEF was evaluated in all patients (using echocardiogram or MUGA) prior to initiation of treatment with lapatinib to ensure baseline LVEF was within the institutions normal limits.
L- LVEF kien ivvalutat fil - pazjenti kollha (permezz ta ’ ekukardjugramm jew MUGA) qabel ma ’ nbdiet il- kura b’ lapatinib biex jiġi żgurat li l- linja bażi ta ’ LVEF kienet fil- limiti tan- normal ta ’ l- istituzzjoni.
In clinical trials LVEF was monitored at approximately eight week intervals during treatment with lapatinib to ensure it did not decline to below the institutions lower limit of normal.
Fil- provi kliniċi LVEF kien immonitorjat bejn wieħed u ieħor kull tmien ġimgħat waqt il- kura b’ lapatinib biex ikun żgurat li ma ’ niżlix fl- livell anqas mill- livell l- aktar baxx tan- normal ta ’ l- istituzzjoni.
The majority of LVEF decreases (greater than 60%) were observed during the first nine weeks of treatment, however limited data was available for long term exposure.
Il- biċċa l- kbira ta ’ tnaqqis fl- LVEF (aktar minn 60%) kien osservat fl- ewwel disa ’ ġimgħat tal- kura, madankollu d- dejta disponibbli għal- esponiment fit- tul kienet limitata.
Patients were randomized to receive either lapatinib 1250 mg once daily (continuously) plus capecitabine (2000 mg/ m2/ day on days 1-14 every 21 days), or to receive capecitabine alone (2500 mg/ m2/ day on days 1-14 every 21 days).
Il- pazjenti kienu randomized biex jew jirċievu lapatinib 1250mg darba kuljum (kontinwament) flimkien ma’ capecitabine (2000mg/ m2/ kuljum fil- ġranet 1- 14 kull 21 ġurnata), jew inkella biex jirċievu capacitabine waħdu (2500mg/ m2/ ġurnata fil- ġranet 1- 14 kull 21 ġurnata).
The primary endpoint was time to progression (TTP).
L- istadju aħħari ewlieni kien iż- żmien li jittieħed biex javvanza (TTP).
Assessments were undertaken by the study investigators and by an independent review panel, blinded to treatment.
Ittieħdu stimi mill- investigaturi u minn pànel ta ’ reviżjoni indipendenti, li kienu fl- għama dwar il- kura.
The study was halted based on the results of a pre-specified interim analysis that showed an improvement in TTP for patients receiving lapatinib plus capecitabine.
L- istudju twaqqaf skond ir- riżultati ta ’ analiżi temporanja speċifikata minn qabel li wriet titjib fit- TTP għal pazjenti li kienu qed jirċievu lapatinib flimkien ma ’ capecitabine.
An additional 75 patients were enrolled in the study between the time of the interim analysis and the end of the enrolment.
Fiż- żmien bejn l- analiżi temporanja u l- waqfien mis- sehem fl- istudju, 75 pazjent ieħor iddaħħlu fl- istudju.
Investigator analysis on data at the stop of enrolment is presented in the following table.
Aġġornament tat- TTP ibbażat fuq id- dejta fil- waqfien mis- sehem fl- istudju hija ppreżentata fit- tabella li ġejja.
Investigator assessment
8 Stima ta ’ investigatur
Lapatinib (1,250 mg/ day)+
Lapatinib (1, 250mg/ ġurnata) +
Capecitabine (2,500 mg/ m2/ day)
Capecitabine
capecitabine (2,000 mg/ m2/ day) Number of TTP events
(2, 500mg/ m2/ ġurnata) capecitabine (2000mg/ m2/ ġurnata) Numru ta ’ każi ta ’ TTP
= 198) 121
(N = 198) 121
Median TTP, weeks Hazard Ratio
Medjan ta ’ TTP, ġimgħat
23.9
23. 9
0.72
18. 3
18.3
0. 72
(95% CI) p value
(95% CI) Valur p
(0.56, 0.92) 0.008
(0. 56, 0. 92) 0. 008
The independent assessment of the data also demonstrated that lapatinib when given in combination with capecitabine significantly increased time to progression (Hazard Ratio 0.57 [95% Cl 0.43, 0.77] p=0.0001) compared to capecitabine alone.
Assessjar independenti tad- dejta wera wkoll li lapatinib meta ngħata flimkien ma ’ capecitabine, żied b’ mod sinifikanti iż- żmien sa l- avvanz (Proporzjon ta ’ periklu 0. 57 [95% CI 0. 43, 0. 77] p=0. 0001) meta mqabbel ma ’ capecitabine waħdu.
8 Results of an updated analysis of the overall survival data to 28 September 2007 are presented in the table below.
Riżultati ta’ analiżi aġġornata tad- dejta dwar sopravivenza totali sat- 28 ta ’ Settembru 2007 qed jiġu preżentati fit- tabella hawn taħt.
Lapatinib (1,250 mg/ day)+
Lapatinib (1, 250 mg/ ġurnata) + capecitabine (2, 000 mg/ m2/ ġurnata)
Capecitabine (2,500 mg/ m2/ day)
Capecitabine (2, 500 mg/ m2/ ġurnata
capecitabine (2,000 mg/ m2/ day) Number of subjects who died
(N = 207)
(N
(N = 201)
Median overall survival, weeks
Medja ta ’ sopravivenza fuq kollox, ġimgħat
74.0
74. 0
65.9
65. 9
Hazard Ratio
Proporzjon ta ’ periklu
(0.71, 1.12) 0.3
(0. 71, 1. 12) 0. 3
On the combination arm, there were 4 (2%) progressions in the central nervous system as compared with the 13 (6%) progressions on the capecitabine alone arm.
mqabbla ma ’ 13 (6%) - il każ ta ’ avvanz mill- fergħa ta ’ capecitabine waħdu.
The absolute bioavailability following oral administration of lapatinib is unknown, but it is incomplete and variable (approximately 70% coefficient of variation in AUC).
Il- biodisponibiltà assoluta wara amminstrazzjoni orali ta ’ lapatinib m’ hix magħrufa, iżda m’ hijiex kompluta u hija varjabbli (ko- effiċjent ta ’ varjazzjoni ta ’ bejn wieħed u ieħor 70% fl- AUC).
Serum concentrations appear after a median lag time of 0.25 hours (range 0 to 1.5 hours).
Konċentrazzjonijiet tas - serum jidhru wara interval ta ’ żmien medjan ta ’ 0. 25 siegħa (limiti bejn 0 sa 1. 5 sigħat).
Peak plasma concentrations (Cmax) of lapatinib are achieved approximately 4 hours after administration.
L- ogħla konċentrazzjonijiet ta ’ lapatinib fil- plażma (Cmax) jinkisbu bejn wieħed u ieħor 4 sigħat wara l - amministrazzjoni.
Daily dosing of 1250 mg produces steady state geometric mean (coefficient of variation) Cmax values of 2.43 (76%) µg/ ml and AUC values of 36.2 (79%) µg*hr/ ml.
Dożaġġ kuljum ta ’ 1250 mg jipproduċi valuri tal- medja ġeometrika (ko- effiċjent ta ’ varjazzjoni) Cmax fl- istat fiss ta ’ 2. 43 (76%) µg/ ml u valuri AUC ta ’ 36. 2 (79%) µg* siegħa/ ml.
Systemic exposure to lapatinib is increased when administered with food.
L- esponiment sistemiku għal lapatinib jiżdied meta jkun amministrat ma ’ l- ikel.
Lapatinib AUC values were approximately 3- and 4-fold higher (Cmax approximately 2.5 and 3– fold higher) when administered with a low fat (5% fat [500 calories]) or with a high fat (50% fat [1,000 calories]) meal, respectively.
Valuri ta ’ l- AUC ta ’ laptinib kienu bejn wieħed u ieħor 3 u 4 darbiet ogħla (Cmax bejn wieħed u ieħor 2. 5 sa 3 darbiet ogħla) meta ġie amministrat ma ’ ikel b’ kontenut baxx ta ’ xaħam (5% xaħam [500 kalorija]) jew ma ’ ikla b’ kontenut ogħli ta ’ xaħam (50% xaħam [1, 000 kalorija]), rispettivament.
Lapatinib is highly bound (greater than 99%) to albumin and alpha-1 acid glycoprotein.
Lapatinib jeħel ħafna (aktar minn 99%) ma ’ l- albumina u mal- glikoproteina alpha- 1 acid.
In vitro studies indicate that lapatinib is a substrate for the transporters BCRP (ABCG1) and p-glycoprotein (ABCB1).
Studji in vitro jindikaw li lapatinib huwa sustrat għat- trasportaturi BCRP (ABCG1) u l- glikoproteina p (ABCB1).
Lapatinib has also been shown in vitro to inhibit these efflux transporters, as well as the hepatic uptake transporter OATP 1B1, at clinically relevant concentrations (IC50 values were equal to 2.3 µg/ ml).
Lapatinib in vitro intwera wkoll li jimpedixxi dawn it- trasportaturi ta ’ l- effluss, kif ukoll it- trasportatur OATP 1B1 ta ’ l- assorbiment epatiku, f’ konċentrazzjonijiet klinikament rilevanti (valuri ta ’ IC50 kienu ta ’ 2. 3 µg/ ml).
The clinical significance of these effects on the pharmacokinetics of other medicinal products or the pharmacological activity of other anti-cancer agents is not known.
It - tifsira klinika ta ’ dawn l- effetti fuq il- farmakokinetika ta ’ prodotti mediċinali oħra jew l- attività farmakoloġika ta ’ aġenti oħra kontra l- kanċer m’ hix magħrufa.
Lapatinib undergoes extensive metabolism, primarily by CYP3A4 and CYP3A5, with minor contributions from CYP2C19 and CYP2C8 to a variety of oxidated metabolites, none of which account for more than 14% of the dose recovered in the faeces or 10% of lapatinib concentration in plasma.
9 Lapatinib jgħaddi minn metaboliżmu estensiv, primarjament permezz ta ’ CYP3A4 u CYP3A5, b’ kontribuzzjonijiet żgħar minn CYP2C19 u CYP2C8 li jwassal għal taħlita ta ’ sustanzi tal- metaboliżmu ossidati, li l- ebda waħda minnhom ma ’ tikkontribwixxi għal aktar minn 14% tad- doża li nkisbet lura mill - ippurgar jew 10% tal- konċentrazzjoni ta ’ lapatinib fil- plażma.
Lapatinib inhibits CYP3A (Ki 0.6 to 2.3 µg/ ml) and CYP2C8 (0.3 µg/ ml) in vitro at clinically relevant concentrations.
Lapatinib jimpedixxi CYP3A (Ki 0. 6 sa 2. 3 µg/ ml) u CYP2C8 (0. 3 µg/ ml) in vitro f’ konċentrazzjonijiet klinikament rilevanti.
Lapatinib did not significantly inhibit the following enzymes in human liver microsomes:
Lapatinib ma jimpedixxix b’ mod sinifikanti l- enzimi li ġejjin fil- mikrosomi tal- fwied uman:
CYP1A2, CYP2C9, CYP2C19, and CYP2D6 or UGT enzymes (in vitro IC50 values were greater than or equal to 6.9 µg/ ml).
CYP1A2, CYP2C9, CYP2C19, u CYP2D6 jew enzimi UGT (valuri IC50 in vitro kienu aktar minn jew ekwivalenti għal 6. 9 µg/ ml).
The half-life of lapatinib measured after single doses increases with increasing dose.
Il- half- life ta ’ lapatinib imkejla wara dożi waħdiet tiżdied ma ’ żieda fid- doża.
However, daily dosing of lapatinib results in achievement of steady state within 6 to 7 days, indicating an effective half-life of 24 hours.
Madankollu, dożaġġ kuljum b’ lapatinib iwassal biex jinkiseb stat fiss fi żmien 6 sa 7 ijiem, li jindika half- life attwali ta ’ 24 siegħa.
Lapatinib is predominantly eliminated through metabolism by CYP3A4/ 5.
Lapitinib huwa l- biċċa l- kbira eliminat permezz tal- metaboliżmu minn CYP3A4/ 5.
Biliary excretion may also contribute to the elimination.
Eskrezzjoni mill- marrara tista ’ wkoll tikkontribwixxi għall- eliminazzjoni.
The primary route of excretion for lapatinib and its metabolites is in faeces.
Ir- rotta ewlenija ta ’ eskrezzjoni għal laptinib u s- sustanzi tal- metaboliżmu tiegħu hija fl- ippurgar.
Recovery of unchanged lapatinib in faeces accounts for a median 27% (range 3 to 67%) of an oral dose.
Il- ġbir lura ta ’ lapatinib mhux mibdul fl- ippurgar jikkontribwixxi għall- medjan ta ’ 27% (limiti bejn 3 sa 67%) tad- doża orali.
Less than 2% of the administered oral dose (as lapatinib and metabolites) excreted in urine.
Anqas minn 2% tad- doża orali amministrata (bħala lapatinib u sustanzi tal- metaboliżmu) titneħħa fl- awrina.
9 Lapatinib pharmacokinetics have not been specifically studied in patients with renal impairment or in patients undergoing haemodialysis.
Il- farmakokinetika ta ’ lapatinib ma ġietx studjata speċifikament f’ pazjenti b’ indeboliment renali jew f’ pazjenti li qed jagħmlu d- dijalisi tad- demm.
Available data suggest that no dose adjustment is necessary in patients with mild to moderate renal impairment.
Dejta disponibbli tissuġġerixxi li m’ hemm bżonn l- ebda aġġustament tad- doża f’ pazjenti b’ indeboliment renali ħafif sa moderat.
The pharmacokinetics of lapatinib were examined in subjects with moderate (n = 8) or severe (n = 4) hepatic impairment (Child-Pugh scores of 7-9, or greater than 9, respectively) and in 8 healthy control subjects.
Il- farmakokinetika ta ’ lapatinib kienet eżaminata f’ individwi b’ indeboliment epatiku moderat (n = 8) jew serju (n = 4) (Punti Child- Pugh minn 7- 9, jew aktar minn 9, rispettivament) u fi 8 individwi b’ saħħithom bħala kontroll.
Systemic exposure (AUC) to lapatinib after a single oral 100 mg dose increased approximately 56% and 85% in subjects with moderate and severe hepatic impairment, respectively.
L- esponiment sistemiku (AUC) għal lapatinib wara doża orali waħda ta ’ 100mg żdied bejn wieħed u ieħor 56% u 85% f’ individwi b’ indeboliment epatiku moderat u serju, rispettivament.
Administration of lapatinib in patients with hepatic impairment should be undertaken with caution (see sections 4.2 and 4.4).
L - amministrazzjoni ta ’ lapatinib f’ pazjenti b’ indeboliment epatiku għandha ssir b’ attenzjoni (ara sezzjonijiet 4. 2 u 4. 4).
Lapatinib was studied in pregnant rats and rabbits given oral doses of 30, 60, and 120 mg/ kg/ day.
Lapainib kien studjat f’ firien u fniek tqal li ingħatawlhom dożi orali ta ’ 30, 60, u 120 mg/ kg/ kuljum.
There were no teratogenic effects; however, minor anomalies (left-sided umbilical artery, cervical rib and precocious ossification) occurred in rats at ≥ 60 mg/ kg/ day (4 times the expected human clinical exposure).
Ma kienx hemm effetti teratoġeniċi; madankollu seħħew anomaliji żgħar (arterja taż- żokra fuq in- naħa tax - xellug, kustilja ċervikali u ossifikazzjoni prekoċi) fil- firien f’ doża ta ’ ≥60 mg/ kg/ kuljum (4 darbiet aktar mill- esponiment kliniku uman mistenni).
In rabbits, lapatinib was associated with maternal toxicity at 60 and 120 mg/ kg/ day (8% and 23% of the expected human clinical exposure, respectively) and abortions at 120 mg/ kg/ day.
Fil- fniek, lapatinib kien assoċjat ma ’ tossiċità ta l- omm f’ doża ta ’ 60 u 120 mg/ kg/ kuljum (8% u 23% ta ’ l- esponiment kliniku uman mistenni, rispettivament) u aborti f’ doża ta ’ 120 mg/ kg/ kuljum.
At ≥ 60 mg/ kg/ day there were decreased foetal body weights, and minor skeletal variations.
F’ doża ta ’ ≥60 mg/ kg/ kuljum kien hemm tnaqqis fil- piż tal- fetu u varjazzjonijiet skelettrali żgħar.
In the rat pre- and postnatal development study, a decrease in pup survival occurred between birth and postnatal day 21 at doses of 60 mg/ kg/ day or higher (5 times the expected human clinical exposure).
Fl- istudju ta ’ l- iżvilupp tal- far qabel u wara t- twelid, kien hemm tnaqqis fis- sopravivenza tal- frieħ bejn it- twelid u l- 21 ġurnata wara t- twelid f’ dożi ta ’ 60mg/ kg/ kuljum jew aktar (5 darbiet aktar mill - esponiment kliniku uman mistenni).
The highest no- effect dose for this study was 20 mg/ kg/ day.
L- ogħla doża li ma kelliex effett għal dan l- istudju kienet 20mg/ kg/ kuljum.
There were no effects on male or female rat gonadal function, mating, or fertility at doses up to 120 mg/ kg/ day (females) and up to 180 mg/ kg/ day (males) (8 and 3 times the expected human clinical exposure, respectively).
Ma kienx hemm effetti fuq il- funzjoni gonadali tal- far raġel jew mara, tgħammir jew fertilità f’ dożi sa 120mg/ kg/ kuljum (nisa) u sa 180mg/ kg/ kuljum (irġiel) (8 u 3 darbiet aktar mill- esponiment kliniku uman mistenni, rispettivament).
The effect on human fertility is unknown.
L- effett fuq il- fertilità umana mhux magħruf.
Lapatinib was not clastogenic or mutagenic in a battery of assays including the Chinese hamster chromosome aberration assay, the Ames assay, human lymphocyte chromosome aberration assay and an in vivo rat bone marrow chromosome aberration assay.
Lapatinib ma kienx klastoġeniku jew mutaġeniku f’ għadd kbir ta ’ analiżi inkluż l- analiżi ta ’ l- aberrazzjoni tal- kromosoma tal- ħamster Ċiniż, l- analiżi Ames, l- analiżi ta ’ l- aberrazzjoni tal- kromosoma limfoċita umana u analiżi in vitro ta ’ l- aberrazzjoni tal- kromosoma tal- mudullun ta ’ l- għadam tal- far.
6.1 List of excipients
6. 1 Lista ta ’ susanzi mhux attivi
Tablet core Microcrystalline cellulose Povidone (K30) Sodium starch glycolate (Type A) Magnesium stearate
Qalba tal- pillola Microcrystalline cellulose Povidone (K30) Sodium starch glycolate (Tip A) Magnesium stearate
Tablet coating Hypromellose Titanium dioxide (E171) Macrogol 400 Polysorbate 80 Iron oxide yellow (E172) Iron oxide red (E172)
Kisja tal- pillola Hypromellose Titanium dioxide (E171) Macrogol 400 Polysorbate 80 Iron oxide yellow (E172) Iron oxide red (E172)
Each pack of Tyverb contains 70 tablets in foil blisters (polyamide / aluminium / polyvinyl chloride / aluminium) of 10 tablets each.
Kull pakkett ta ’ Tyverb fih 70 pillola f’ folji (polyamide / aluminium / polyvinyl chloride / aluminium) ta ’ 10 pilloli l- waħda.
Each foil has a perforation down the middle to allow the blisters to be separated into a daily dose of 5 tablets.
Kull folja fiha toqob minn naħa s’ oħra biex il- folja tkun tista ’ tinqata’ f’ doża ta ’ kuljum ta ’ 5 pilloli.
Multipacks contain 140 film-coated tablets consisting of 2 x 70 tablet packs in a large outer carton.
Pakketti multipli fihom 140 pillola miksija b’ rita li jikkonsistu f’ 2 pakketti b’ 70 pillola l- wieħed f’ pakkett ta ’ barra tal- kartun kbir.