qanastek/EMEA-V3 huggingface dataset:
alli capsules have a turquoise cap and body, with a dark blue band round the middle, imprinted with "alli".
Kapsuli alli huma ta ’ lewn turkważ, b’ għatu turkważ u faxxa blu skura fin- nofs, b ’ "alli" stampat fuqhom.
alli is available in pack sizes of 42, 60, 84 and 90 capsules.
alli huwa disponibbli f’ daqsijiet tal- pakkett ta ’ 42, 60, 84 u 90 kapsula.
Not all pack sizes may be available in all countries.
Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu disponibbli fil- pajjiżi kollha.
A blue carry case (Shuttle) is included in this pack for carrying your daily dose of alli.
29 Kontenitur blu biex iġġorr (Shuttle) huwa nkluż f’ dan il- pakkett biex iġġorr id- doża tiegħek ta ’ kuljum ta ’ alli.
28 Marketing authorisation holder and manufacturer
Id- Detentur ta ’ l- Awtorizzazzjoni għat- tqegħid fis- Suq u l- Manifattur
Glaxo Group Limited, Glaxo Wellcome House, Berkeley Avenue, Greenford, Middlesex UB6 0NN, United Kingdom.
Glaxo Group Limited, Glaxo Wellcome House, Berkeley Avenue, Greenford, Middlesex UB6 0NN, Ir- Renju Unit.
Famar, 190 11 Avlona, Greece Catalent UK Packaging Limited, Sedge Close, Headway, Great Oakley, Corby, Northamptonshire NN18 8HS, United Kingdom.
Famar, 190 11 Avlona, Il- Greċja Catalent UK Packaging Limited, Sedge Close, Headway, Great Oakley, Corby, Northamptonshire NN18 8HS, Ir- Renju Unit.
For any information about this medicinal product, contact the local representative of the Marketing Authorisation Holder:
Għal kull tagħrif dwar din il- mediċina, jekk jogħġbok ikkuntattja lir- rappreżentant lokali tad- Detentur ta ’ l- Awtorizzazzjoni għat- tqegħid fis- Suq:
You can also visit your country specific alli website for further information about the alli weight loss programme.
Għall- aktar tagħrif dwar il- programm ta ’ telf ta ’ piż alli, tista ’ iżżur il- website ta ’ alli speċifika għall - pajjiż tiegħek.
0043 (0) 512 / 390 11040 www.alliprogramm.at
0043 (0) 512 / 390 110- 40
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: http://www.emea.europa.eu/.
Informazzjoni dettaljata dwar din il- mediċina tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il - Mediċini (EMEA) http: // www. emea. europa. eu.
FURTHER HELPFUL INFORMATION
AKTAR TAGĦRIF TA ’ GĦAJNUNA
Being overweight will affect your health and increase your risk of developing serious health problems such as: • High blood pressure • Diabetes • Heart disease • Stroke • Certain forms of cancer • Osteoarthritis Talk to your doctor about your risk of developing these conditions.
Li jkollok piż żejjed ikollu effett fuq is- saħħa tiegħek u jżid ir- riskju tiegħek li tiżviluppa problemi serji tas- saħħa bħal: • Pressjoni tad- demm għolja • Dijabete • Mard tal- qalb • Puplesija • Ċerti forom ta ’ kanċer • Osteoartrite Tkellem mat- tabib tiegħek dwar ir- riskju tiegħek li tiżviluppa dawn il- kundizzjonijiet.
Importance of losing weight
Importanza li titlef il- piż
Losing weight and maintaining weight loss, for example by improving your diet and increasing your physical activity, can help reduce the risk of serious health problems and help improve your health.
Li titlef il- piż u żżomm dan it- telf fil- piż, eżempju billi ttejjeb id- dieta u żżid l- attività fiżika tiegħek, jista ’ jgħin biex inaqqas ir- riskju ta ’ problemi serji ta ’ saħħa u jgħin biex itejjeb is- saħħa tiegħek.
Helpful tips on your diet and your calorie and fat targets while taking alli
Punti ta ’ għajnuna dwar id- dieta tiegħek u l- miri tiegħek ta ’ kaloriji u xaħam waqt li qed tieħu alli
The capsules work by preventing some of the fat you eat from being absorbed but you can still eat foods from all the main food groups.
Il- kapsuli jaħdmu billi jwaqqfu xi ftit mix- xaħam li tiekol milli jiġi assorbit, iżda xorta tista ’ tiekol ikel mill- gruppi prinċipali kollha ta ’ ikel.
Although you should focus on the calories and fat that you eat, it is important to eat a balanced diet.
Għalkemm għandek tiffoka fuq il- kaloriji u x- xaħam li tiekol, huwa mportanti li tiekol dieta bilanċjata.
You should choose meals which contain a range of different nutrients and learn to eat healthily for the long term.
Għandek tagħżel ikliet li fihom firxa ta ’ nutrijenti differenti u titgħallem tiekol ikel tajjeb għas- saħħa għal tul ta ’ żmien.
Understanding the importance of calorie and fat targets
Spjegazzjoni ta ’ l- importanza tal- miri tal- kaloriji u x- xaħam
31 Calories are a measurement of the energy your body needs.
32 Kaloriji huma kejl ta ’ l- enerġija li ġismek għandu bżonn.
They are sometimes called kilocalories or kcal.
Dawn xi kultant jissejħu kilokaloriji jew kcal.
Energy may also be measured in kilojoules, which you may also see on food labels. • The calorie target is the maximum number of calories you’ll eat each day.
L- enerġija tista ’ tiġi mkejjla wkoll f’ kilojoules, li wkoll tista ’ tosserva fuq tikketti ta ’ l- ikel. • Il- mira ta ’ kaloriji hija n- numru massimu ta ’ kaloriji li se tiekol kuljum.
See the chart further on in this section. • Your fat gram target is the maximum number of grams of fat you’ll eat in each meal.
Ara t- tabella aktar l - isfel f’ din is- sessjoni. • Il- mira tiegħek ta ’ grammi ta ’ xaħam hija n- numru massimu ta ’ grammi ta ’ xaħam li se tiekol f’ kull ikla.
The fat gram target chart follows the information below on setting your calorie target. • Controlling your fat target is essential because of the way the capsules work.
It- tabella tal- mira ta ’ grammi ta ’ xaħam issegwi l- informazzjoni taħt dwar kif tistabilixxi l- mira tiegħek ta ’ kaloriji. • Li tikkontrolla l- mira tiegħek ta ’ xaħam huwa essenzjali minħabba l- mod ta ’ kif jaħdmu l - kapsuli.
Taking alli means your body will pass more fat through, and therefore may struggle to cope with eating as much fat as before.
Li tieħu alli jfisser li l- ġisem tiegħek se jgħaddi aktar xaħam, u għalhekk tista ’ ssibha diffiċli biex tlaħħaq ma ’ l- ammont ta ’ xaħam li kont tiekol qabel.
So by meeting your fat target, you’ll maximise weight loss results while minimising the risk of diet-related treatment effects. • You should aim to lose weight gradually and steadily.
Għalhekk billi tilħaq il- mira tiegħek ta ’ xaħam, se timmassimizza r- riżultati ta ’ telf ta ’ piż waqt li tnaqqas ir- riskju ta ’ effetti tal- kura relatati mad- dieta. • Inti għandek timmira li titlef il- piż b’ rata gradwali u kostanti.
Losing around 0.5 kg (1 lb) per week is ideal.
Telf ta ’ piż ta ’ madwar 0. 5 kg kull ġimgħa huwa ideali.
How to set your calorie target
Kif tistabilixxi il- mira tiegħek ta ’ kaloriji
The following table has been worked out so that it gives you a calorie target that’s about 500 calories fewer per day than your body needs to maintain your current weight.
It- tabella li ġejja nħadmet biex tagħtik mira ta ’ kaloriji li hija madwar 500 kalorija kuljum inqas minn dak li l- ġisem tiegħek jeħtieġ biex iżomm il- piż li għandek issa.
That adds up to 3500 fewer calories per week, about the number of calories in 0.5 kg (1 lb) of fat.
Dan ifisser 3500 inqas kull ġimgħa, madwar in- numru ta ’ kaloriji f’ 0. 5 kg ta ’ xaħam.
Your calorie target alone should allow you to lose weight at a gradual, steady pace of about 0.5 kg (1 lb) per week, without feeling frustrated or deprived.
Il- mira tiegħek ta ’ kaloriji waħedha għandha tgħinek titlef il- piż b’ rata gradwali u kostanti ta ’ madwar 0. 5 kg kull ġimgħa, mingħajr ma tħossok frustrat/ a jew nieqes/ nieqsa mill- ikel.
Eating fewer than 1200 calories per day is not recommended.
1200 kalorija
Women Low Activity
Baxxa Attività
Below 68.1 kg 68.1 kg to 74.7 kg 74.8 kg to 83.9 kg 84.0 kg and over
68. 1 kg sa 74. 7 kg 74. 8 kg sa 83. 9 kg 84. 0 kg u aktar Taħt 61. 2 kg
1200 calories 1400 calories 1600 calories 1800 calories
1400 kalorija 1600 kalorija 1800 kalorija 1400 kalorija
Moderate Activity
Moderata
Below 61.2 kg 61.3 kg to 65.7 kg 65.8 kg and over
61. 3 kg sa 65. 7 kg 65. 8 kg u aktar
1400 calories 1600 calories 1800 calories
1600 kalorija 1800 kalorija
Men
Irġiel
Low Activity
Attività
Below 65.7 kg 65.8 kg to 70.2 kg 70.3 kg and over
Taħt 65. 7 kg
Below 10 st 4 lb 10 st 5 lb to 11 st 11 st 1 lb and over
65. 8 kg sa 70. 2 kg 70. 3 kg u aktar
59.0 kg and over
59. 0 kg u aktar
How to set your fat target
Kif tistabilixxi il- mira tiegħek ta ’ xaħam
The following chart shows how to set your fat target based on the amount of calories you are allowed per day.
It- tabella li ġejja turi kif għandek tistabilixxi l- mira tiegħek ta ’ xaħam ibbażat fuq l- ammont ta ’ kaloriji li tista ’ tieħu kuljum.
You should plan to have three meals per day.
Għandek tippjana li tieħu tliet ikliet kuljum.
If you have set a target of 1400 calories per day, for example, the maximum amount of fat allowed per meal would be 15 g.
Biex ma
To stay within your daily allowance for fat, snacks should contain no more than 3 g of fat.
33 taqbisx il- mira tiegħek ta ’ xaħam ta ’ kuljum, ikliet ħfief (snacks) m’ għandhomx ikollhom aktar minn 3 g ta ’ xaħam.
Amount of calories you can eat per day
Ammont ta ’ kaloriji li tista ’ tiekol kuljum
Maximum amount of fat allowed per meal
Ammont massimu ta ’ xaħam li tista ’ tieħu f’ kull ikla
Maximum amount of fat allowed from snacks per day
Ammont massimu ta ’ xaħam li tista ’ tieħu minn ikliet ħfief (snacks) kuljum
Remember:
Ftakar:
• Stick to realistic calorie and fat targets as this is a good way of maintaining your weight loss achievements in the long-term. • Write down what you eat in a food diary, including the calorie and fat content. • Try to be more physically active before you start taking the capsules.
• Żomm miri ta ’ kaloriji u xaħam realistiċi għax dan huwa mod tajjeb biex iżżom il- piż li tkun tlift għal tul ta ’ żmien. • Ikteb dak li tiekol, inkluż il- kontenut ta ’ kaloriji u xaħam, fi djarju ta ’ l- ikel. • Qabel tibda tieħu l- kapsuli pprova kun aktar attiv/ a fiżikament.
Physical activity is an important part of a weight loss programme.
Attività fiżika hija parti mportanti ta ’ programm ta ’ telf ta ’ piż.
Remember to check with your doctor first if you have not exercised before. • Continue to be active while taking alli and after you stop taking it.
Ftakar biex l- ewwel tiċċekkja mat- tabib tiegħek jekk qatt m’ għamilt eżerċizzju qabel. • Ibqa ’ attiv waqt li tkun qed tieħu alli u wara li tieqaf tieħdu.
The alli weight loss programme combines the capsules with an eating plan and a wide range of resources to help you understand how to eat a reduced calorie, lower-fat diet and guidelines for becoming more active.
Il- programm ta ’ telf ta ’ piż alli jgħaqqad il- kapsuli ma ’ pjan ta ’ dak li tiekol u firxa wiesa ’ ta ’ riżorsi biex jgħinuk tifhem kif tiekol dieta b’ kaloriji mnaqqsa u b’ inqas xaħam u linji gwida biex issir aktar attiv/ a.
The alli website (please refer to your country specific website included in the list of local representatives above) provides you with a range of interactive tools, lower-fat recipes, physical activity tips and other useful information to help you lead a healthy life and to support you in meeting your weight loss goals, together with details of a weight loss programme which is individually tailored for you.
Il- website ta ’ alli (jekk jogħġbok irreferi għall- website speċifika għall- pajjiż tiegħek fil- lista ta ’ rappreżentanti lokali fuq) tipprovdilek firxa ta ’ għodod interattivi, riċetta b’ inqas xaħam, punti ta ’ għajnuna dwar attività fiżika u tagħrif utli ieħor biex jgħinuk tgħix ħajja b’ saħħtek u jtuk sapport biex tilħaq il- miri tiegħek ta ’ telf ta ’ piż, flimkien ma ’ dettalji ta ’ Programm għal telf ta ’ piż li huwa maħsub għalik individwalment.
Visit < www.xxx.xxx >
Żur www. alli. com. mt
Route of
Mnejn jingħata
administration
Daqs tal- Pakkett
250 micrograms
250 mikrogramma
Vial (glass)
Fjala (ħġieġ)
1 vial
1 Fjala
Aloxi 250 micrograms solution for injection.
Aloxi 250 mikrogramma soluzzjoni għall- injezzjoni.
One ml of solution contains 50 micrograms palonosetron (as hydrochloride).
1 ml ta ’ soluzzjoni fih 50 mikrogramma ta ’ palonosetron (bħala hydrochloride).
Each vial of 5 ml of solution contains 250 micrograms palonosetron (as hydrochloride).
Kull fjala ta ’ 5 ml ta ’ soluzzjoni fiha 250 mikrogramma ta ’ palonosetron (bħala hydrochloride).
Aloxi is indicated for: the prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy and the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy
Aloxi hu indikat għal: prevenzjoni ta ’ dardir u rimettar akut marbut ma ’ kemoterapija tal- kanċer li hi emetoġenika b’ mod qawwi u l- prevenzjoni ta ’ dardir u rimettar marbut ma ’ kemoterapija tal- kanċer li hi moderatament emetoġenika
250 micrograms palonosetron administered as a single intravenous bolus approximately 30 minutes before the start of chemotherapy.
250 mikrogramma ta ’ palonosetron mogħtija bħala bolus wieħed ġol- vina madwar 30 minuta qabel il - bidu tal- kemoterapija.
Aloxi should be injected over 30 seconds.
Aloxi għandu jkun injettat fuq perijodu ta ’ 30 sekonda.
The efficacy of Aloxi in the prevention of nausea and vomiting induced by highly emetogenic chemotherapy may be enhanced by the addition of a corticosteroid administered prior to chemotherapy.
L- effikaċja ta ’ Aloxi fil- prevenzjoni ta ’ dardir u rimettar ikkaġunati minn kemoterapija tal- kanċer li hi emetoġenika b’ mod qawwi tista ’ tittaffa biż- żieda ta ’ kortikosterojd li jingħata qabel il- kemoterapija.
Aloxi should be used only before chemotherapy administration.
Aloxi għandu jintuża biss qabel l- għoti tal- kimoterapija.
No dosage adjustment is necessary for the elderly.
L- ebda aġġustament fid- dożaġġ m’ hu meħtieġ għall- anzjani.
Aloxi is not recommended for use in children below age 18 due to insufficient data.
Aloxi mhuwiex irrakkomandat għall- użu fi tfal ta ’ taħt it- 18- il sena minħabba li m’ hemmx dejta biżżejjed.
Hepatic impaired patients
Patjenti b’ indeboliment tal- fwied
No dose adjustment is necessary for patients with impaired hepatic function.
L- ebda aġġustament fid- doża m’ hu meħtieġ għal pazjenti b’ indeboliment fil- funzjoni tal- fwied.
2 No dose adjustment is necessary for patients with impaired renal function.
2 Pazjenti b’ indeboliment tal- kliewi
No data are available for patients with end stage renal disease undergoing haemodialysis.
L- ebda informazzjoni m’ hi disponibbli għal pazjenti b’ mard tal- kliewi li jkun fl- aħħar stadju u li jkunu fuq l- emodijaliżi.
As palonosetron may increase large bowel transit time, patients with a history of constipation or signs of subacute intestinal obstruction should be monitored following administration.
Minħabba li palonosetron jista ’ jżid iż- żmien tal- mogħdija mill- musrana l- kbira, pazjenti bi storja medika ta ’ stitikezza jew b’ sinjali ta ’ ostruzzjoni intestinali sotto- akuta, għandhom ikunu mmonitorjati wara li jingħata.
Two cases of constipation with faecal impaction requiring hospitalisation have been reported in association with palonosetron 750 micrograms.
Żewġ każijiet ta ’ stitikezza b’ impatt fuq l- ippurgar u li kienu jeħtieġu li jiddaħħlu l - isptar kienu rrappurtati b’ rabta ma ’ palonosetron 750 mikrogramma.
At all dose levels tested, palonosetron did not induce clinically relevant prolongation of the QTc interval.
Fil- livelli kollha tad- doża li kienu ttestjati, palonosetron ma kkawżax żieda fl- intervall QTc li kien klinikament rilevanti.
A specific thorough QT/ QTc study was conducted in healthy volunteers for definitive data demonstrating the effect of palonosetron on QT/ QTc.
Studju speċifiku u ddettaljat dwar il- QT/ QTc sar f’ voluntiera b’ saħħithom għal dejta definittiva li turi l- effett ta ’ palonosetron fuq QT/ QTc.
Please refer to 5.1 Pharmacodynamics properties.
Jekk jogħġbok irreferi għal 5. 1 Tagħrif farmakodinamiku.
However, as for other 5-HT3 antagonists, caution should be exercised in the concomitant use of palonosetron with medicinal products that increase the QT interval or in patients who have or are likely to develop prolongation of the QT interval.
Madankollu, bħalma jiġri b’ antagonisti 5- HT3 oħrajn, għandha tingħata attenzjoni meta palonosetron jintuża flimkien ma ’ prodotti mediċinali li jżidu l- intervall QT jew f’ pazjenti li għandhom jew aktarx jiżviluppaw it- titwil ta ’ l- intervall QT.
Aloxi should not be used to prevent or treat nausea and vomiting in the days following chemotherapy if not associated with another chemotherapy administration.
Aloxi m’ għandux jintuża għall- prevenzjoni ta ’, jew għall- kura ta, ’ nawseja u rimettar fil- jiem ta ’ wara l- kimoterapija jekk ma jkunx assoċjat ma ’ għoti ta ’ kimoterapija oħra.
Based on in vitro studies, palonosetron does not inhibit or induce cytochrome P450 isoenzyme at clinically relevant concentrations.
Palonosetron hu primarjament immetabolizzat minn CYP2D6, b’ kontribuzzjoni żgħira mill- isoenzimi CYP3A4 u CYP1A2 Ibbażat fuq studji in vitro, palonosetron ma jinibixxix jew jikkaġuna l- isoenzim taċ- ċitokrom P450 f’ konċentrazzjonijiet li huma klinikament rilevanti.
Chemotherapeutic agents: in preclinical studies, palonosetron did not inhibit the antitumour activity of the five chemotherapeutic agents tested (cisplatin, cyclophosphamide, cytarabine, doxorubicin and mitomycin C).
Fi studji ta ’ qabel l- użu kliniku, palonosetron ma fixkelx attività kontra t - tumur tal- ħames sustanzi kemoterapewtiċi li kienu ttestjati (cisplatin, cyclophosphamide, cytarabine, doxorubicin u mitomycin C).
Metoclopramide: in a clinical study, no significant pharmacokinetic interaction was shown between a single intravenous dose of palonosetron and steady state concentration of oral metoclopramide, which is a CYP2D6 inhibitor.
Metoclopramide: fi studju kliniku, ma ntweriet l- ebda interazzjoni sinifikanti farmakokinetika bejn doża waħda ta ’ palonosetronom ġol- vina u konċentrazzjoni fl- istat fiss ta ’ metoclopramide orali, li hu inibitur ta ’ CYP2D6.
CYP2D6 inducers and inhibitors: in a population pharmacokinetic analysis, it has been shown that there was no significant effect on palonosetron clearance when co-administered with CYP2D6 inducers (dexamethasone and rifampicin) and inhibitors (including amiodarone, celecoxib, chlorpromazine, cimetidine, doxorubicin, fluoxetine, haloperidol, paroxetine, quinidine, ranitidine, ritonavir, sertraline or terbinafine).
Inducers u inibituri ta ’ CYP2D6: f’ analiżi farmakokinetika tal- popolazzjoni, intwera li ma kien hemm l- ebda effett sinifikanti fuq it- tneħħija ta ’ palonosetron meta jingħata flimkien ma ’ inducers CYP2D6 (dexamethasone u rifampicin) u inibituri (li jinkludu amiodarone, celecoxib, chlorpromazine, cimetidine, doxorubicin, fluoxetine, haloperidol, paroxetine, quinidine, ranitidine, ritonavir, sertraline jew terbinafine).
Corticosteroids: palonosetron has been administered safely with corticosteroids.
Kortikosterojdi: palonosetron ingħata b’ mod sigur ma ’ kortikosterojdi.
Other medicinal products: palonosetron has been administered safely with analgesics, antiemetic/ antinauseants, antispasmodics and anticholinergic medicinal products.
Prodotti mediċinali oħrajn: palonosetron ingħata b’ mod sigur ma ’ prodotti mediċinali analġesiċi, mediċini ta ’ kontra d- dardir u r- rimettar, mediċini antispażmodiċi u antikolinerġiċi.
For Palonosetron no clinical data on exposed pregnancies are available.
Għal Palonosetron m’ hemm l- ebda dejta klinika disponibbli dwar nisa esposti waqt it- tqala.
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/ foetal development, parturition or postnatal development.
Studji fuq l- annimali ma jurux effetti ħżiena diretti jew indiretti fuq it- tqala, fuq l- iżvilupp ta ’ l- embriju/ fetu, ħlas
3 There is no experience of palonosetron in human pregnancy so palonosetron should not be used in pregnant women unless it is considered essential by the physician.
Hemm biss informazzjoni limitata disponibbli mill- istudji fuq l- annimali dwar jekk jgħaddix mill- plaċenta (ara sezzjoni 5. 3).
As there are no data concerning palonosetron excretion in breast milk, breast-feeding should be discontinued during therapy.
Minħabba li m’ hemm l- ebda informazzjoni dwar it- tneħħija ta ’ palonosetron fil- ħalib tas- sider, it- treddigħ għandu jitwaqqaf matul it- terapija.
Since palonosetron may induce dizziness, somnolence or fatigue, patients should be cautioned when driving or operating machines.
Minħabba li palonosetron jista ’ jikkaġuna sturdament, ngħas jew għeja kbira, il- pazjenti għandhom jiġu mwissija biex joqogħdu attenti waqt is- sewqan jew it- tħaddim tal- magni.
In clinical studies at a dose of 250 micrograms (total 633 patients) the most frequently observed adverse reactions, at least possibly related to Aloxi, were headache (9%) and constipation (5%).
Fi studji kliniċi b’ doża ta ’ 250 mikrogramma (total ta ’ 633 pazjent), l- iktar reazzjonijiet avversi li kienu osservati b’ mod frekwenti, li kienu mill- inqas possibbilment relatati ma ’ Aloxi, kienu wġigħ ta ’ ras (9%) u stitikezza (5%).
In the clinical studies the following adverse reactions (ARs) were observed as possibly or probably related to Aloxi.
Fl- istudji kliniċi, ir- reazzjonijiet avversi (adverse reactions - ARs) li ġejjin kienu osservati bħala possibbilment jew probabbilment relatati ma ’ Aloxi.
These were classified as common (between 1% and 10%) or uncommon (between 0.1% and 1%).
Dawn kienu kklassifikati bħala komuni (bejn 1% u 10%) jew mhux komuni (bejn 0. 1% u 1%).
Common ARs
ARs Komuni
Uncommon ARs
ARs Mhux Komuni
(> 1/ 100 to < 1/ 10)
(> 1/ 100 sa < 1/ 10)
(> 1/ 1,000 to < 1/ 100)
(> 1/ 1, 000 sa < 1/ 100)
Hyperkalaemia, metabolic disorders, hypocalcaemia, hypokalaemia, anorexia, hyperglycaemia, appetite decreased
Iperkalemija, mard metaboliku, Disturbi fil- metaboliżmu u n- nutrizzjoni ipokalċimja, ipokalemija, anoreksja, ipergliċemija, nuqqas t’ aptit Ansjetà, burdata ewforika Disturbi psikjatriċi Disturbi fis- sistema nervuża
Psychiatric disorders
Uġigħ ta ’ ras
Anxiety, euphoric mood
Ngħas, nuqqas ta ’ rqad, parestesija,
Nervous system disorders
Disturbi fl- għajnejn Disturbi fil- widnejn u fis- sistema labirintika
Headache Dizziness
Sturdament
Eye disorders Ear and labyrinth disorders Cardiac disorders
irqad esaġerat, newropatija tas- sensi periferali Irritazzjoni fl- għajnejn, ambliopija Dardir waqt il- moviment/ ivvjaġġar, żanżin fil- widnejn
Eye irritation, amblyopia Motion sickness, tinnitus Tachycardia, bradycardia, extrasystoles, myocardial ischaemia, sinus tachycardia, sinus arrhythmia, supraventricular extrasystoles
Takikardija, bradikardija, extrasystoles, Disturbi fil- qalb iskemija mijokardjali, takikardija tas - sinus, arritmija tas- sinus, extrasystoles supraventrikulari Pressjoni tad- demm baxxa ħafna, Disturbi vaskulari pressjoni tad- demm għolja, tibdil fil - kulur tal- vini, vini minfuħin Disturbi respiratorji, toraċiċi u medjastinali
Vascular disorders
Sulluzzu
Hypotension, hypertension, vein discolouration, vein distended
Disturbi gastro- intestinali
Respiratory, thoracic and mediastinal disorders
Dispepsja, uġigħ ta ’ żaqq, uġigħ fin -
Hiccups
Dijarea
Gastrointestinal disorders Hepato-biliary disorders Skin and subcutaneous tissue disorders Musculoskeletal and connective tissue disorders
naħa ta ’ fuq taż- żaqq, ħalq xott, gass Iperbilirubinemja
Constipation Diarrhoea
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il - ġilda
Dyspepsia, abdominal pain, abdominal pain upper, dry mouth, flatulence Hyperbilirubinaemia Dermatitis allergic, pruritic rash Arthralgia
Dermatite allerġika, raxx bil- ħakk
Renal and urinary disorders General disorders and administration site conditions Investigations
Disturbi muskolu- skeltrali u tal - connective tissue Disturbi fil- kliewi u fis- sistema urinarja Disturbi ġenerali u kundizzjonijiet ta ’ mnejn jingħata Investigazzjonijiet
Urinary retention, glycosuria Asthenia, pyrexia, fatigue, feeling hot, influenza like illness Elevated transaminases,, electrocardiogram QT prolonged
Artralġja Żamma ta ’ l- awrina, glukosurja Astenja, deni, għeja kbira, tħoss is - sħana, mard qisu influwenza Transaminases għoljin, QT wiesa ’ fl - elettrokardjogramm
Very rare cases (< 1/ 10,000) of hypersensitivity reactions and injection site reactions (burning, induration, discomfort and pain) were reported from post-marketing experience.
Każijiet rari ħafna (< 1/ 10, 000) ta ’ reazzjonijiet ta ’ sensittività eċċessiva u reazzjonijiet fis- sit ta ’ l - injezzjoni (ħruq, ebusija, skonfort u uġigħ) kienu rrappurtati mill- esperjenza ta ’ wara l- bejgħ.
Doses of up to 6 mg have been used in clinical trials.
Dożi sa 6 mg intużaw fi provi kliniċi.
The highest dose group showed a similar incidence of adverse events compared to the other dose groups and no dose response effects were observed.
Il- grupp bl- ogħla doża wera inċidenza simili ta ’ avvenimenti avversi meta mqabbel ma ’ gruppi li ngħataw dożi oħrajn, u l- ebda effetti tar- rispons għad- doża ma kienu osservati.
In the unlikely event of overdose with Aloxi, this should be managed with supportive care.
Fil- każ mhux mistenni ta ’ doża eċċessiva b’ Aloxi, dan għandu jkun immaniġġjat b’ kura ta ’ appoġġ.
Dialysis studies have not been performed, however, due to the large volume of distribution, dialysis is unlikely to be an effective treatment for Aloxi overdose.
Ma sarux studji dwar id- dijaliżi, madankollu, minħabba l- volum kbir ta ’ distribuzzjoni, id- dijaliżi mhix mistennija li tkun kura effettiva għal doża eċċessiva b’ Aloxi.
5 PHARMACOLOGICAL PROPERTIES
5 5 TAGĦRIF FARMAKOLOĠIKU
Antiemetics and antinauseants, serotonin (5HT3) antagonists.
Antiemetiċi u kontra d- dardir, antagonisti ta ’ serotonin (5HT3).
5 Palonosetron is a selective high-affinity receptor antagonist of the 5HT3 receptor.
Palonosetron hu riċettur selettiv li għandu affinità qawwija u antagonist ta ’ ricettur 5HT3.
In two randomised, double-blind studies with a total of 1,132 patients receiving moderately emetogenic chemotherapy that included cisplatin ≤ 50 mg/ m2, carboplatin, cyclophosphamide ≤ 1,500 mg/ m2 and doxorubicin > 25 mg/ m2, palonosetron 250 micrograms and 750 micrograms were compared with ondansetron 32 mg (half-life 4 hours) or dolasetron 100 mg (half-life 7.3 hours) administered intravenously on Day 1, without dexamethasone.
F’ żewġ studji randomised, double- blind b’ total ta ’ 1, 132 pazjent li kienu qed jirċievu kemoterapija moderatament emetoġenika li kienet tinkludi cisplatin ≤ 50 mg/ m2, carboplatin, cyclophosphamide ≤ 1, 500 mg/ m2 u doxorubicin > 25 mg/ m2, palonosetron 250 mikrogramma u 750 mikrogramma, kienu mqabbla ma ’ ondansetron 32 mg (half- life ta ’ 4 sigħat) jew dolasetron 100 mg (half- life ta ’ 7. 3 sigħat) li ngħata minn ġol- vina f’ Jum 1, mingħajr dexamethasone.
In a randomised, double-blind study with a total of 667 patients receiving highly emetogenic chemotherapy that included cisplatin ≥ 60 mg/ m2, cyclophosphamide > 1,500 mg/ m2 and dacarbazine, palonosetron 250 micrograms and 750 micrograms were compared with ondansetron 32 mg administered intravenously on Day 1.
Fi studju randomised, double- blind b’ total ta ’ 667 pazjent li kienu qed jingħataw kemoterapija emetoġenika qawwija li kienet tinkludi cisplatin ≥ 60 mg/ m2, cyclophosphamide > 1, 500 mg/ m2 u dacarbazine, palonosetron 250 mikrogramma u 750 mikrogramma kienu mqabbla ma ’ ondansetron 32 mg mogħti minn ġol- vina f’ Jum 1.
Dexamethasone was administered prophylactically before chemotherapy in 67% of patients.
Dexamethasone ngħata b’ mod profilattiku qabel kemoterapija f’ 67% tal- pazjenti.
The pivotal studies were not designed to assess efficacy of palonosetron in delayed onset nausea and vomiting.
L- istudji importanti ħafna ma kienux maħsuba biex jevalwaw l- effikaċja ta ’ palonosetron fil- bidu li jittardja d- dardir u r- rimettar.
The antiemetic activity was observed during 0-24 hours, 24-120 hours and 0-120 hours.
L- attività tal- mediċini ta ’ kontra d- dardir u r- rimettar (antiemetiċi) kienet osservata matul perijodu ta ’ 0- 24 siegħa, 24- 120 siegħa u 0- 120 siegħa.
Results for the studies on moderately emetogenic chemotherapy and for the study on highly emetogenic chemotherapy are summarised in the following tables.
Ir- riżultati għall- istudji dwar kemoterapija moderatament emetoġenika u għall- istudju dwar il- kemoterapija emetoġenika qawwija huma elenkati fil- qosor fit- tabelli li ġejjin.
Palonosetron was non-inferior versus the comparators in the acute phase of emesis both in moderately and highly emetogenic setting.
Palonosetron ma kienx inferjuri mqabbel mal- komparaturi fil- fażi akuta ta ’ l- emesi, f’ ċirkustanzi ematoġeniċi kemm moderati u kemm qawwija.
Although comparative efficacy of palonosetron in multiple cycles has not been demonstrated in controlled clinical trials, 875 patients enrolled in the three phase 3 trials continued in an open label safety study and were treated with palonosetron 750 micrograms for up to 9 additional cycles of chemotherapy.
Għalkemm l- effikaċja komparattiva ta ’ palonosetron f’ ċikli multipli ma ntwerietx fi provi kliniċi kkontrollati, 875 pazjent rreġistrati fi tliet provi ta ’ fażi 3, komplew fi studju open label dwar is- sigurtà u kienu kkurati b’ 750 mikrogramma ta ’ palonosetron sa 9 ċikli addizzjonali ta ’ kemoterapija.
The overall safety was maintained during all cycles.
Is - sigurtà globali nżammet matul iċ- ċikli kollha.
Percentage of patients a responding by treatment group and phase in the Moderately Emetogenic Chemotherapy study versus ondansetron
6 Perċentwali ta ’ pazjenti a li jirrispondu skond il- grupp tal- kura u l- fażi fl- Istudju Tabella 1: dwar il- Kemoterapija Moderatament Emetoġenika mqabbla ma ’ ondansetron
Ondansetron
Ondansetron Aloxi 32 milligramma 250 mikrogramma (n= 185)
micrograms (n= 189)%
(n= 189)%%
Delta%
97. 5% CI b
Complete Response (No Emesis and No Rescue Medication)
Rispons Sħiħ (L- Ebda
97.5% CI b
Emesi u l- Ebda Mediċina tas- Salvataġġ)
0 – 24 hours
0 – 24 siegħa
81.0
81. 0
68.6
68. 6
[1.8%, 22.8%]
[1. 8%, 22. 8%]
24 – 120 hours 0 – 120 hours
24 – 120 siegħa 0 – 120 siegħa
74.1 69.3
74. 1 69. 3
55.1 50.3
55. 1 50. 3
19.0 19.0
19. 0 19. 0
[7.5%, 30.3%] [7.4%, 30.7%]
[7. 5%, 30. 3%] [7. 4%, 30. 7%] valur p c
Complete Control (Complete Response and No More Than Mild Nausea)
Kontroll Sħiħ (Rispons Sħiħ u b’ Forsi Dardir Ħafif)
p-value c
0 – 24 siegħa
0 – 24 hours 76.2 65.4 24 – 120 hours 66.7 50.3 0 – 120 hours 63.0 44.9 No Nausea (Likert Scale)
24 – 120 siegħa 0 – 120 siegħa
10.8 16.4 18.1
0. 001 0. 001
NS 0.001 0.001 p-value c
valur p c L- Ebda Dardir (Skala Likert)
0 – 24 hours 60.3 56.8 24 – 120 hours 51.9 39.5
0 – 24 siegħa
3.5 12.4
56. 8
0 – 120 hours Intent-to-treat cohort.
24 – 120 siegħa 0 – 120 siegħa
45.0
51. 9 45. 0
36.2
39. 5 36. 2
8.8
12. 4 8. 8
A lower bound greater than – 15% demonstrates non-inferiority between Aloxi and comparator. c Chi-square test.
Koorti bl- intenzjoni- li- tikkura. * (ITT) b L- istudju kien maħsub biex juri non- inferjorità. limitu ‘ l fuq minn – 15% turi non- inferjorità bejn Aloxi u l- komparatur. c Chi- square test.
Significance level at α =0.05.
Livell sinifikanti ta ’ α=0. 05.
Percentage of patients a responding by treatment group and phase in the Moderately Emetogenic Chemotherapy study versus dolasetron
7 Perċentwali ta ’ pazjenti a li jirrispondu skond il- grupp tal- kura u l- fażi fl- Istudju Tabella 2: dwar il- Kemoterapija Moderatament Emetoġenika kontra dolasetron
Dolasetron
Dolasetron Aloxi 100 milligramma 250 mikrogramma (n= 191)
63.0
63. 0
[-1.7%, 21.9%]
[- 1. 7%, 21. 9%]
54.0 46.0
54. 0 46. 0
38.7 34.0
38. 7 34. 0
15.3 12.0
15. 3 12. 0
[3.4%, 27.1%] [0.3%, 23.7%]
[3. 4%, 27. 1%] [0. 3%, 23. 7%] valur p c
Complete Control (Complete
Kontroll Sħiħ (Rispons Sħiħ u b’ Forsi Dardir Ħafif)
57.1
57. 1
48.1 41.8
48. 1 41. 8
36.1 30.9
36. 1 30. 9
12.0 10.9
12. 0 10. 9
0.018 0.027
0. 018 0. 027
No Nausea (Likert Scale)
valur p c L- Ebda Dardir (Skala Likert)
48.7
48. 7
41.4
41. 4
24 – 120 hours 0 – 120 hours
0 – 120 siegħa
41.8 33.9
33. 9
26.2 22.5
22. 5
15.6 11.4
11. 4
0.001 0.014
0. 014
Intent-to-treat cohort. b The study was designed to show non-inferiority.
Koorti bl- intenzjoni- li- tikkura. b L- istudju kien maħsub biex juri non- inferjorità.
A lower bound greater than – 15% demonstrates non-inferiority between Aloxi and comparator. c Chi-square test.
Lower bound ikbar minn – 15% turi non- inferjorità bejn Aloxi u l- komparatur. c Chi- square test.
Significance level at α =0.05.
Livell ta ’ importanza ta ’ α=0. 05.
Percentage of patients a responding by treatment group and phase in the Highly Emetogenic Chemotherapy study versus ondansetron
Perċentwali ta ’ pazjenti a li jirrispondu skond il- grupp tal- kura u l- fażi fl- Istudju dwar il- Kemoterapija Emetoġenika Qawwija kontra ondansetron
(n= 223)%
mikrogramma (n= 223)%
(n= 221)%
32 milligramma (n= 221)%
97.5% CI b
97. 5% CI b
0 – 24 hours 59.2 57.0 24 – 120 hours 45.3 38.9
0 – 24 siegħa
2.2 6.4
57. 0
[-8.8%, 13.1%] [-4.6%, 17.3%]
[- 8. 8%, 13. 1%]
0 – 120 hours
24 – 120 siegħa 0 – 120 siegħa
40.8
45. 3 40. 8
33.0
38. 9 33. 0
7.8
6. 4 7. 8
[-2.9%, 18.5%]
[- 4. 6%, 17. 3%] [- 2. 9%, 18. 5%] valur p c
Complete Control (Complete
Kontroll Sħiħ (Rispons Sħiħ u Ma Jkunx Hemm Dardir Ħlief Dardir Ħafif)
Response and No More
0 – 24 siegħa
Than Mild Nausea)
56. 5
p-value c
51. 6
0 – 24 hours 24 – 120 hours 0 – 120 hours No Nausea (Likert Scale)
24 – 120 siegħa 0 – 120 siegħa
56.5 40.8 37.7
40. 8 37. 7
51.6 35.3 29.0
35. 3 29. 0
4.9 5.5 8.7
5. 5 8. 7
0 – 24 hours 24 – 120 hours 0 – 120 hours a
0 – 24 siegħa
53.8 35.4 33.6
24 – 120 siegħa
49.3 32.1 32.1
0 – 120 siegħa
4.5 3.3 1.5
32. 1
7 The effect of palonosetron on blood pressure, heart rate, and ECG parameters including QTc were comparable to ondansetron and dolasetron in CINV clinical trials.
8 L- effett ta ’ palonosetron fuq il- pressjoni tad- demm, rata ta ’ taħbit tal- qalb, u l- parametri tal- ECG li jinkludu QTc, kienu komparabbli għal ondansetron u dolasetron fil- provi kliniċi CINV.
In non-clinical studies palonosetron possesses the ability to block ion channels involved in ventricular de- and re-polarisation and to prolong action potential duration.
Fi studji mhux kliniċi, palonosetron wera li għandu l- abbiltà li jimblokka l- kanali tal- joni involuti fid- di - u fir - ri- polarizzazzjoni ventrikulari u li jtawwal l- azzjoni potenzjali.
The effect of palonosetron on QTc interval was evaluated in a double blind, randomised, parallel, placebo and positive (moxifloxacin) controlled trial in adult men and women.
L- effett ta ’ palonosetron fuq l- intervall tal- QTc kien evalwat fi prova double blind, randomised, parallela, bil- plaċebo u positive (moxifloxacin) controlled f’ irġiel u nisa adulti.
The objective was to evaluate the ECG effects of IV administered palonosetron at single doses of 0.25, 0.75 or 2.25 mg in 221 healthy subjects.
L- għan kien li jiġu evalwati l- effetti tal- ECG ta ’ IV palonosetron mogħti f’ dożi waħidhom ta ’ 0. 25, 0. 75 jew 2. 25 mg f’ 221 persuna b’ saħħithom.
The study demonstrated no effect on QT/ QTc interval duration as well as any other ECG interval at doses up to 2.25 mg.
L- istudju ma wera l- ebda effett fuq it- tul tal- intervall QT/ QTc kif ukoll fuq kwalunkwe intervalli oħrajn tal- ECG f’ dożi sa 2. 25 mg.
No clinically significant changes were shown on heart rate, atrioventricular (AV) conduction and cardiac repolarization.
Ma ntwera l- ebda tibdil klinikament sinifikanti fuq ir- rata ta ’ taħbit tal- qalb, il- konduzzjoni atrijoventrikulari (AV) u r- ripolarizzazzjoni fil - qalb
Absorption Following intravenous administration, an initial decline in plasma concentrations is followed by slow elimination from the body with a mean terminal elimination half-life of approximately 40 hours.
Assorbiment Wara l- għoti ġol- vina, għall- ewwel il- konċentrazzjoni fil- plażma tonqos imbagħad ikun hemm eliminazzjoni bil- mod mill- ġisem b’ half- life tat- tneħħija terminali medja ta ’ madwar 40 siegħa.
Mean maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC0-∞) are generally dose-proportional over the dose range of 0.3– 90 μ g/ kg in healthy subjects and in cancer patients.
Il - medja tal- konċentrazzjoni massima tal- plażma (Cmax) u ż- żona taħt il- kurva ta ’ konċentrazzjoni- ħin (AUC0- ∞) huma ġeneralment proporzjonali għad- doża fuq il- firxa tad- doża ta ’ 0. 3– 90 μg/ kg f’ pazjenti b’ saħħithom u f’ pazjenti bil- kanċer.
Following intravenous administration of palonosetron 0.25 mg once every other day for 3 doses in 11 testicular cancer patients, the mean (± SD) increase in plasma concentration from Day 1 to Day 5 was 42 ± 34%.
Wara l- għoti ġol- vina ta ’ palonosetron 0. 25 mg darba kull jumejn għal tlett ijiem fi 11- il pazjent b’ kanċer testikulari, il- medja (± SD) taż- żieda tal- konċentrazzjoni fil- plażma minn Jum 1 sa Jum 5 kienet ta ’ 42 ± 34%.
After intravenous administration of palonosetron 0.25 mg once daily for 3 days in 12 healthy subjects, the mean (± SD) increase in plasma palonosetron concentration from Day 1 to Day 3 was 110 ± 45%.
Wara l- għoti ġol- vina ta ’ palonosetron 0. 25 mg darba kuljum għal tlett ijiem fi 12- il persuna b’ saħħithom, il- medja (± SD) taż- żieda tal- konċentrazzjoni ta ’ palonosetron fil- plażma minn Jum 1 sa Jum 5 kienet ta ’ 110 ± 45%.
Pharmacokinetic simulations indicate that the overall exposure (AUC0-∞) of 0.25 mg intravenous palonosetron administered once daily for 3 consecutive days was similar to a single intravenous dose of 0.75 mg, although Cmax of the 0.75 mg single dose was higher.
Simulazzjonijiet farmakokinetiċi jindikaw li l- espożizzjoni totali (AUC0- ∞) ta ’ 0. 25 mg ta ’ palonosetron mogħti fil- vina darba kuljum għal tlitt ijiem konsekuttivi kienet simili għal doża waħda ta ’ 0. 75 mg ġol- vina, għalkemm is- Cmax wara doża waħda ta ’ 0. 75 mg kienet ogħla.
Distribution Palonosetron at the recommended dose is widely distributed in the body with a volume of distribution of approximately 6.9 to 7.9 l/ kg.
Distribuzzjoni Palonosetron, fid- doża rrakkomandata, hu ddistribwit ħafna fil- ġisem b’ volum tad- distribuzzjoni ta ’ madwar 6. 9 sa 7. 9 l/ kg.
Approximately 62% of palonosetron is bound to plasma proteins.
Madwar 62% ta ’ palonosetron jintrabat mal- proteini tal- plażma.
Metabolism Palonosetron is eliminated by dual route, about 40% eliminated through the kidney and with approximately 50% metabolised to form two primary metabolites, which have less than 1% of the 5HT3 receptor antagonist activity of palonosetron.
Metaboliżmu Palonosetron jitneħħa permezz ta ’ rotta doppja: madwar 40% jitneħħa mill- kliewi u madwar 50% ikun metabolizzat biex jifforma żewġ metaboliti primarji, li għandhom inqas minn 1% ta ’ l- attività ta ’ l - antagonist tar- riċettur 5HT3 ta ’ palonosetron.
In vitro metabolism studies have shown that CYP2D6 and to a lesser extent, CYP3A4 and CYP1A2 isoenzymes are involved in the metabolism of palonosetron.
Studji dwar il- metaboliżmu in vitro urew li CYP2D6 u, fi grad inqas, l- isoenżimi ta ’ CYP3A4 u CYP1A2, jieħdu parti fil- metaboliżmu ta ’ palonosetron.
However, clinical pharmacokinetic parameters are not significantly different between poor and extensive metabolisers of CYP2D6 substrates.
Madankollu, il- parametri farmakokinetiċi kliniċi mhumiex differenti b’ mod sinifikanti bejn metabolisers batuti u estensivi tas- sottostrati ta ’ CYP2D6.
Palonosetron does not inhibit or induce cytochrome P450 isoenzymes at clinically relevant concentrations.
Palonosetron ma jinibixxix jew jikkaġuna isoenżimi taċ- ċitokrom P450 f’ konċentrazzjonijiet li huma klinikament relevanti.
Elimination After a single intravenous dose of 10 micrograms/ kg [14C]-palonosetron, approximately 80% of the dose was recovered within 144 hours in the urine with palonosetron representing approximately 40% of the administered dose, as unchanged active substance.
Eliminazzjoni Wara doża waħda ta ’ 10 mikrogrammi/ kg ta ’ [14C] - palonosetron fil- vina, madwar 80% tad- doża kienet eliminata fl- awrina bħala sustanza attiva mhux mibdula fi żmien 144 siegħa, li jirrappreżenta madwar 40% tad- doża mogħtija.
After a single intravenous bolus administration in healthy subjects the total body clearance of palonosetron was 173 ± 73 ml/ min and renal clearance was 53 ± 29 ml/ min.
Wara l- għoti ta ’ doża bolus waħda ġol- vina f’ persuni b’ saħħithom, it- tneħħija totali ta ’ palonosetron mill- ġisem kienet ta ’ 173 ± 73 ml/ min u t- tneħħija mill- kliewi kienet ta ’ 53 ± 29 ml/ min.
The low total body clearance and large volume of distribution resulted in a terminal elimination half-life in plasma of approximately 40 hours.
It- tneħħija baxxa totali mill- ġisem u l- volum baxx tad- distribuzzjoni rriżultat f’ half - life ta ’ l- eliminazzjoni terminali fil- plażma ta ’ madwar 40 siegħa.
Ten percent of patients have a mean terminal elimination half-life greater than 100 hours.
Għaxra fil- mija tal- pazjenti jkollhom medja tal- half- life ta ’ l- eliminazzjoni terminali akbar minn 100 siegħa.
Pharmacokinetics in special populations
9 Farmakokinetika f’ popolazzjonijiet specjali
Elderly: age does not affect the pharmacokinetics of palonosetron.
Anzjani: l- età ma taffettwax il- farmakokinetika ta ’ palonosetron.
No dosage adjustment is necessary in elderly patients.
L- ebda aġġustament fid- dożaġġ mhu meħtieġ f’ pazjenti anzjani.
8 Gender: gender does not affect the pharmacokinetics of palonosetron.
Sess: is- sess tal- persuna ma jaffettwax il- farmakokinetika ta ’ palonosetron.
No dosage adjustment is necessary based on gender.
L- ebda aġġustament fid - dożaġġ mhu meħtieġ skond is- sess tal- persuna.
Paediatric patients: no pharmacokinetic data are available in patients below 18 years of age.
L- ebda informazzjoni farmakokinetika mhi disponibbli f’ pazjenti li għandhom inqas minn 18- il sena.
Renal impairment: mild to moderate renal impairment does not significantly affect palonosetron pharmacokinetic parameters.
Indeboliment tal- kliewi: indeboliment tal- kliewi li jkun minn ħafif sa moderat ma jaffettwax b’ mod sinifikanti l- parametri farmakokinetiċi ta ’ palonosetron.
Severe renal impairment reduces renal clearance, however total body clearance in these patients is similar to healthy subjects.
Indeboliment sever tal- kliewi jnaqqas it - tneħħija mill- kliewi, madankollu it- tneħħija totali mill- ġisem f’ dawn il- pazjenti hi simili għal dik f’ pazjenti b’ saħħithom.
No dosage adjustment is necessary in patients with renal insufficiency.
L- ebda aġġustament fid- dożaġġ mhu meħtieġ f’ pazjenti b’ insuffiċjenza tal - kliewi.
No pharmacokinetic data in haemodialysis patients are available.
L- ebda informazzjoni farmakokinetika f’ pazjenti li qegħdin fuq l- emodijaliżi mhi disponibbli.
Hepatic impairment: hepatic impairment does not significantly affect total body clearance of palonosetron compared to the healthy subjects.
Indeboliment tal- fwied: l- indeboliment tal- fwied ma jaffettwax b’ mod sinifikanti t- tneħħija totali ta ’ palonosetron mill- ġisem meta mqabbla ma ’ dik ta ’ persuni b’ saħħithom.
While the terminal elimination half-life and mean systemic exposure of palonosetron is increased in the subjects with severe hepatic impairment, this does not warrant dose reduction.
Waqt li l- half- life ta ’ l - eliminazzjoni terminali u l- medja ta ’ l- espożizzjoni sistemika ta ’ palonosetron jiżdiedu f’ pazjenti b’ indeboliment serju tal- fwied, dan ma jiġġustifikax tnaqqis fid- doża.
Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.
Effetti fi studji mhux kliniċi kienu osservati biss f’ espożizzjonijiet li huma kkunsidrati li fil- prattika huma ħafna aktar mill- espożizzjoni massima fil- bniedem.
Nonclinical studies indicate that palonosetron, only at very high concentrations, may block ion channels involved in ventricular de- and re-polarisation and prolong action potential duration.
Studji mhux kliniċi jindikaw li palonosetron, f’ konċentrazzjonijiet qawwija ħafna biss, jista ’ jimblokka l- kanali ta ’ l- ijoni involuti fid- de - u fir- re- polarizzazzjoni ventrikulari u jtawlu kemm iddum l- azzjoni potenzjali.
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/ foetal development, parturition or postnatal development.
Studji fuq l- annimali ma jurux effetti ħżiena diretti jew indiretti fuq it- tqala, fuq l- iżvilupp ta ’ l - embriju/ fetu, ħlas jew żvilupp ta ’ wara t- twelid.
Only limited data from animal studies are available regarding the placental transfer (see section 4.6).
Hemm informazzjoni disponibbli limitata mill- istudji fuq l- annimali dwar jekk palonosetron jgħaddix mill- plaċenta (ara sezzjoni 4. 6).
Palonosetron is not mutagenic.
Palonosetron mhuwiex mutaġeniku.
High doses of palonosetron (each dose causing at least 30 times the human therapeutic exposure) applied daily for two years caused an increased rate of liver tumours, endocrine neoplasms (in thyroid, pituitary, pancreas, adrenal medulla) and skin tumours in rats but not in mice.
Dożi qawwija ta ’ palonosetron (kull doża li tikkawża mill- inqas 30 darba dak li jintuża fil- bnedmin) mogħtija kuljum għal sentejn, ikkawżat rata miżjuda ta ’ tumuri tal- fwied, neoplażmi endokrinali (fit- tirojde, pitwitarji, fil- pankreas, fil- medulla adrenali) u tumuri tal - ġilda fil- firien iżda mhux fil- ġrieden.
The underlying mechanisms are not fully understood, but because of the high doses employed and since Aloxi is intended for single application in humans, these findings are not considered relevant for clinical use.
Il- mekkaniżmi bażiċi mhumiex mifhuma kompletament, iżda minħabba d- dożi qawwija li jintużaw u minħabba li Aloxi hu intenzjonat għal applikazzjoni waħda fil - bnedmin, dawn is- sejbiet mhumiex ikkunsidrati li huma rilevanti għall- użu kliniku.
Mannitol Disodium edetate Sodium citrate Citric acid monohydrate Water for injections Sodium hydroxide solution Hydrochloric acid solution
Mannitol Disodium edetate Sodium citrate Citric acid monohydrate Ilma għall- injezzjonijiet Soluzzjoni ta ’ sodium hydroxide Soluzzjoni ta ’ hydrochloric acid
Upon opening of the vial, any unused solution should be discarded.
X’ ħin tiftaħ il- fjala, kwalunkwe soluzzjoni mhux użata għandha tintrema.
6.4 Special precautions for storage
10 6. 4 Prekawzjonijiet speċjali għall- ħażna
This medicinal product does not require any special storage conditions
Dan il- prodott mediċinali ma jeħtieġ l- ebda kundizzjonijiet speċjali tal- ħażna
Type I glass vial with chlorobutyl siliconised rubber stopper and aluminium cap.
Fjala tal- ħġieġ tat- Tip I b’ tapp tal- lastku siliconised tal- chlorobutyl u għatu ta ’ l- aluminju.
9 Available in packs of 1 vial containing 5 ml of solution.
Disponibbli f’ pakketti ta ’ fjala waħda li jkun fiha soluzzjoni ta ’ 5 ml.
6.6 Special Precautions for disposal
6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema
Single use only, any unused solution should be discarded.
Jintuża darba biss; kwalunkwe soluzzjoni mhux użata għandha tintrema.
MARKETING AUTHORISATION HOLDER
SID TA ’ L- AWTORIZZAZZJONI GĦALL- KUMMERĊ 7.
Damastown Mulhuddart Dublin 15 Republic of Ireland
Damastown Mulhuddart Dublin 15 Repubblika ta ’ l- Irlanda
MARKETING AUTHORISATION NUMBER
NUMRU( I) TA ’ L- AWTORIZZAZZJONI GĦALL- KUMMERĊ 8.
22 March 2005
22 ta ’ Marzu, 2005
11 A MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE
11 ANNESS II
Name and address of the manufacturer responsible for batch release
KUNDIZZJONIJIET TA ’ L- AWTORIZZAZZJONI GĦALL - KUMMERĊ
Damastown, Mulhuddart, Dublin 15 Republic of Ireland
Damastown, Mulhuddart, Dublin 15 Repubblika ta ’ l- Irlanda
B CONDITIONS OF THE MARKETING AUTHORISATION
B KUNDIZZJONIJIET TA ’ L- AWTORIZZAZZJONI GĦALL- KUMMERĊ
The holder of this marketing authorisation must inform the European Commission about the marketing plans for the medicinal product authorised by this decision.
Is- sid ta ’ din l- awtorizzazzjoni għall- kummerċ għandu jagħti tagħrif lill- Kummissjoni Ewropea dwar il- pjanijiet kummerċjali tal- prodott mediċinali awtorizzat b’ din id- deċiżjoni.
14 PARTICULARS TO APPEAR ON THE OUTER PACKAGING:
TIKKETTA
Aloxi 250 micrograms solution for injection Palonosetron (as hydrochloride)
Aloxi 250 mikrogramma soluzzjoni għall- injezzjoni Palonosetron (bħala hydrochloride)
One vial of 5 ml contains 250 micrograms of palonosetron 50 micrograms/ ml (as hydrochloride)
Fjala waħda ta ’ 5 ml fiha 250 mikrogramma ta ’ palonosetron 50 mikrogramma/ ml (bħala hydrochloride)