qanastek/EMEA-V3 huggingface dataset:
Breakthrough pain Studies have shown that almost all patients, despite treatment with a fentanyl patch, require supplemental treatment with potent rapid-release medicinal products to arrest breakthrough pain.
48 Minkejja kura b’ garza ta ’ fentanyl, stħarriġ wera li kważi l- pazjenti kollha jkollhom bżonn ta ’ mediċini qawwija u li jaħdmu fil- pront sabiex jilqgħu immedjatament kontra l- ħruġ ta ’ uġigħ mhux mistenni.
48 Respiratory depression As with all potent opioids some patients may experience respiratory depression with Fentanyl- ratiopharm, and patients must be observed for this effect.
Dipressjoni respiratorja L- istess kif jiġri bl- użu tal- opjojdi qawwijin kollha, xi pażjenti jistgħu jbatu minn dipressjoni repiratorja meta jużaw Fentanyl- ratiopharm u l- pazjenti jridu jiġu sorveljati sewwa li ma ’ jkollhomx dan l- effett.
49 Due to limited experience in children under 12 years of age, Fentanyl-ratiopharm should be used in this age group only after careful consideration has been given to the benefit versus risk ratio.
Pazjenti pedjatriċi Minħabba l- użu limitat fit- tfal taħt it- 12- il sena, Fentanyl- ratiopharm għandu jintuża f’ din il - kategorija ta ’ pazjenti biss wara li jiġi stabbilit sewwa jekk il- benefiċċju potenzjali jiġġustifikax ir - riskju potenzjali assoċjat mal- użu.
50 4.6 Pregnancy and lactation
4. 6 Tqala u effetti fuq il- ħalib tas- sider
51 Very common: sweating, pruritus.
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Komuni ħafna: żieda fl- għaraq, ħakk.
53 Long-term carcinogenicity studies have not been performed.
Studji fit- tul dwar attivita 'karċinoġenika ma twettqux.
62 [10 transdermal patches:]
62 [10 garża transdermali:]
SPECIAL STORAGE CONDITIONS 65 Do not store above 25 °C.
65 Taħżinx f’ temperatura ’ l fuq minn 25°C
WHAT Fentanyl-ratiopharm IS AND WHAT IT IS USED FOR
X’ INHU FENTANYL- RATIOPHARM U GĦALXIEX JINTUŻA
BEFORE YOU USE Fentanyl-ratiopharm
QABEL MA TUŻA FENTANYL- RATIOPHARM
How to apply Fentanyl-ratiopharm
80 Kif tapplika l- Fentanyl- ratiopharm
- Find a flat part of your upper body (trunk) or upper arm, where the skin is without hair, cuts,
- Sib post ċatt fuq il- parti ta ’ fuq ta ’ ġismek (il- fuq mil- qadd) (jew il- parti ta ’ fuq ta ’ dirgħajk
spots or other skin blemishes.
fejn m’ hemmx pil, qsim, ponot jew xi difett ieħor.
The body part must not have been irradiated in connection with radiation therapy.
Il- parti tal- ġisem ma tridx tkun irritata minħabba trattament bir- raġġi.
81 Like all medicines, Fentanyl-ratiopharm can cause side effects, although not everybody gets them.
Bħal kull mediċina oħra, Fentanyl- ratiopharm jista ’ jkollu effetti sekondarji, għalkemm jistgħu ma ’ jidhrux f’ kulħadd.
82 Do not use Fentanyl-ratiopharm after the expiry date which is stated on the package.
Tużax Fentanyl- ratiopharm wara d- data ta ’ skadenza li tidher fuq il- pakett.
3 89143 Blaubeuren Germany This medicinal product is authorised in the Member States of the EEA under the following names:
3 89143 Blaubeuren Il- Ġermanja
Austria Germany Spain France The Netherlands United Kingdom
< DE/ H/ 0740/ 01/ MR > L- Awstrija Il- Ġermanja Spanja Franza L- Olanda Ir- Renju Unit
83 This leaflet was last approved in {MM/ YYYY}.
Dan il- fuljett kien approvat l- aħħar f ’ {XX/ SSSS}
How to apply Fentanyl-ratiopharm
87 Kif tapplika l- Fentanyl- ratiopharm
88 Like all medicines, Fentanyl-ratiopharm can cause side effects, although not everybody gets them.
Bħal kull mediċina oħra, Fentanyl- ratiopharm jista ’ jkollu effetti sekondarji, għalkemm jistgħu ma ’ jidhrux f’ kulħadd.
89 Do not use Fentanyl-ratiopharm after the expiry date which is stated on the package.
Tużax Fentanyl- ratiopharm wara d- data ta ’ skadenza li tidher fuq il- pakett.
{Name and address} {tel} {fax} {e-mail}
90 {telefon} {fax} {e- mail}
Austria Germany Spain France The Netherlands United Kingdom
< DE/ H/ 0740/ 02/ MR > L- Awstrija Il- Ġermanja Spanja Franza L- Olanda Ir- Renju Unit
90 This leaflet was last approved in {MM/ YYYY}.
Dan il- fuljett kien approvat l- aħħar f ’ {XX/ SSSS}
How to apply Fentanyl-ratiopharm
94 Kif tapplika l- Fentanyl- ratiopharm
95 Like all medicines, Fentanyl-ratiopharm can cause side effects, although not everybody gets them.
Bħal kull mediċina oħra, Fentanyl- ratiopharm jista ’ jkollu effetti sekondarji, għalkemm jistgħu ma ’ jidhrux f’ kulħadd.
96 Do not use Fentanyl-ratiopharm after the expiry date which is stated on the package.
Tużax Fentanyl- ratiopharm wara d- data ta ’ skadenza li tidher fuq il- pakett.
{Name and address} {tel} {fax} {e-mail}
97 {telefon} {fax} {e- mail}
Austria Germany Spain France The Netherlands United Kingdom
< DE/ H/ 0740/ 03/ MR > L- Awstrija Il- Ġermanja Spanja Franza L- Olanda Ir- Renju Unit
97 This leaflet was last approved in {MM/ YYYY}.
Dan il- fuljett kien approvat l- aħħar f ’ {XX/ SSSS}
How to apply Fentanyl-ratiopharm
101 Kif tapplika l- Fentanyl- ratiopharm
102 Like all medicines, Fentanyl-ratiopharm can cause side effects, although not everybody gets them.
Bħal kull mediċina oħra, Fentanyl- ratiopharm jista ’ jkollu effetti sekondarji, għalkemm jistgħu ma ’ jidhrux f’ kulħadd.
103 Do not use Fentanyl-ratiopharm after the expiry date which is stated on the package.
Tużax Fentanyl- ratiopharm wara d- data ta ’ skadenza li tidher fuq il- pakett.
{Name and address} {tel} {fax} {e-mail}
104 {telefon} {fax} {e- mail}
Austria Germany Spain France The Netherlands United Kingdom
< DE/ H/ 0740/ 04/ MR > L- Awstrija Il- Ġermanja Spanja Franza L- Olanda Ir- Renju Unit
104 This leaflet was last approved in {MM/ YYYY}.
Dan il- fuljett kien approvat l- aħħar f ’ {XX/ SSSS}
London, 23 October 2007 EMEA/ 331678/ 2007
Londra, it- 23 ta 'Ottubru 2007 EMEA/ 331678/ 2007
OPINION FOLLOWING AN ARTICLE 29(4)1 REFERRAL FOR Fentanyl-ratiopharm 25/ 50/ 75/ 100 µg/ h TTS and associated names
OPINJONI LI SSEGWI L- ARTIKOLU 29( 4) 1 RERERENZA GĦAL Fentanyl- ratiopharm 25/ 50/ 75/ 100 µg/ h TTS u assoċjati
Fentanyl-ratiopharm 25/ 50/ 75/ 100 µg/ h TTS and associated names, is an opioid analgesic which is indicated in severe chronic pain which can be adequately managed only with opioid analgesics.
Fentanyl- ratiopharm 25/ 50/ 75/ 100 µg/ h TTS u ismijiet assoċjati, hu analġesiku opioid li hu indikat għal uġigħ kroniku sever li jkun jista 'jiġi ġestit adegwatament biss b' analġesiċi opioid.
Ratiopharm GmbH submitted applications for mutual recognition of Fentanyl-ratiopharm 25/ 50/ 75/ 100 µg/ h TTS and associated names, transdermal patch on the basis of the marketing authorisation granted by Germany 04 April 2006.
Ratiopharm GmbH ippreżentat applikazzjonijiet għal għarfien reċiproku għal Fentanyl- ratiopharm 25/ 50/ 75/ 100 µg/ h TTS u ismijiet assoċjati, stikka transdermali skond l- awtorizzazzjoni għat- tqegħid fis- suq mogħtija mill- Ġermanja fl- 4 ta 'April ta' l- 2006.
These Member States were not able to reach an agreement in respect of the Mutual Recognition of the Marketing Authorisation granted by the Reference Member State.
Dawn l- Istati Membri ma setgħux jaqblu dwar l- Għarfien Reċiproku ta 'l- Awtorizzazzjoni għat- Tqegħid fis- Suq mogħtija mill- Istat Membru ta' Referenza.
During their July 2007 meeting, the CHMP, in the light of the overall data submitted and the scientific discussion within the Committee, was of the opinion that the benefit/ risk ratio is favourable for Fentanyl- ratiopharm 25/ 50/ 75/ 100 µg/ h TTS and associated names, that the objections raised by France should not prevent the granting of a Marketing Authorisation and that the Summary of Product Characteristics, labelling and package leaflet of the Reference Member State should be amended.
Waqt il- laqgħa tagħhom ta 'Lulju ta' l- 2007, is- CHMP, fid- dawl tad- dejta globali ppreżentata u d- diskussjoni xjentifika fi ħdan il- Kumitat, kien tal- fehma li l- bilanċ bejn il- benefiċċju u r- riskju kien favorevoli għal Fentanyl- ratiopharm 25/ 50/ 75/ 100 µg/ h TTS u ismijiet assoċjati, li l- objezzjonijiet imqajma minn Franza m' għandhomx jipprevjenu l- għoti ta 'l- Awtorizzazzjoni għat- Tqegħid fis- Suq u li s- Sommarju tal - Karatteristiċi tal- Prodott, it- tikketta u l- fuljett ta' tagħrif ta 'l- Istat Membru ta' Referenza għandhom jiġu emendati.
Ref. :EMEA/ 508212/ 2007
Ref.: EMEA/ 508221/ 2007
COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE OPINION FOLLOWING AN ARTICLE 36(1) REFERRAL
IL- KUMITAT GĦALL- PRODOTTI MEDIĊINALI GĦAL UŻU MILL- BNIEDEM OPINJONI WARA RIFERIMENT SKOND L- ARTIKOLU 36( 1)
Gadograf/ Gadovist International Non-Proprietary Name (INN):
Gadograf/ Gadovist Isem Internazzjonali Mhux Patentat (INN):
BACKGROUND INFORMATION* Gadovist/ Gadograf 1.0 mmol/ ml contains gadobutrol, a neutral macrocyclic gadolinium (Gd) complex with contrast-enhancing properties, which is used for magnetic resonance imaging (MRI).
TAGĦRIF TA 'SFOND * Gadovist/ Gadograf 1. 0 mmol/ ml fih gadobutrol, kumpless newtrali makroċikliku ta' gadolinju (Gd) b' karatteristiċi li jsaħħu l- kuntrast, użat għall- ħruġ ta 'immaġni bir- reżonanza manjetika (MRI).
MRI is a widely used technique for the evaluation and detection of diffuse liver disease as well as for further characterisation of focal liver disease.
L- MRI hi teknika użata ħafna għall- evalwazzjoni u s- sejbien ta 'mard diffuż tal- fwied kif ukoll għal studju iktar dettaljat ta' mard fokali tal- fwied.
Gd-based contrast agents are frequently administered prior to contrast-enhanced dynamic liver MRI and may improve both detection and classification of focal liver lesions.
Aġenti tal- kuntrast b' bażi ta 'Gd jingħataw sikwit qabel MRI dinamiku tal- fwied imsaħħaħ bil- kuntrast u jistgħu jtejbu kemm is- sejbien kif ukoll il- klassifikazzjoni ta' leżjonijiet fokali tal- fwied.
Gadovist/ Gadograf was approved for “ Contrast enhancement in cranial and spinal magnetic resonance imaging” in Germany in January 2000 and subsequently in June 2000 in the EU and Norway via the mutual recognition procedure (MRP).
Gadovist/ Gadograf kien approvat għal "Tisħiħ tal- kuntrast fl- immaġini bir- reżonanza manjetika (MRI) tal- kranju u tas- sinsla ” fil- Ġermanja f' Jannar 2000 u sussegwetament f' Ġunju 2000 fl- UE u fin- Norveġja permezz tal- proċedura ta 'rikonoxximent reċiproku (MRP).
A label extension to the indication “ Contrast-enhanced Magnetic resonance angiography” (CE-MRA) followed in November 2003.
Wara dan kien hemm estensjoni tat- tikketta għall- indikazzjoni “ Anġografija bir - reżonanza Manjetika imsaħħa bil- kuntrast ” (CE- MRA) f' Novembru.
In June 2005, a MR procedure started for a type II variation to add the indication of “ Contrast enhanced MRI of other body regions: liver, kidneys” and the following posology and method of administration/ dosage: “ CE-MRI of other body regions:
F' Ġunju ta 'l- 2005, inbdiet proċedura ta' rikonoxximent reċiproku għal varjazzjoni tat- tieni tip biex tiżdied l- indikazzjoni ta '“ MRI imsaħħaħ bil- kuntrast għal partijiet oħra tal- ġisem: il - fwied, il- kliewi ” u l- pożoloġija u l- metodu ta' amministrazzjoni/ doża li ġejjin: “ CE- MRI ta 'partijiet oħra tal- ġisem:
The recommended dose for adults is 0.1 mmol per kilogram body weight (mmol/ kg BW).
Id- doża rakkomandata għall- adulti hi 0. 1 mmol għal kull kilogramma li jiżen il- pazjent (mmol/ kg BW).
This is equivalent to 0.1 ml/ kg BW of the 1.0 M solution”.
Dan hu ekwivalenti għal 0. 1 ml/ kg BW tas - soluzzjoni tal- 1. 0 M ”.
After finalisation of the procedure the Spanish Agency for Medicines and Health Products initiated a referral for arbitration to the CHMP under article 36.1 of Directive 2001/ 83/ EC.
Wara t- tmiem tal- proċedura l- Aġenzija Spanjola għall- Mediċini u għall- Prodotti tas- Saħħa bdiet riferiment għal arbitraġġ lis- CHMP skond l- Artikolu 36. 1 tad - Direttiva 2001/ 83/ KE.
Having considered the grounds for the referral triggered by Spain, the CHMP, during its May 2006 plenary meeting, adopted a List of Questions and a TT for a referral procedure under Article 36.
Wara li kkunsidra r- raġunijiet għar- riferiment imressaq minn Spanja is- CHMP, waqt il- laqgħa plenarja tiegħu ta 'Mejju ta' l- 2006 adotta Lista ta 'Mistoqsijiet u TT għall- proċedura tar - riferiment skond l- Artikolu 36.
The CHMP appointed Dr.
Is- CHMP ħatar lil Dr.
Broich (DE) as Rapporteur and Dr.
Broich (DE) bħala Rapporteur u lil Dr.
Prieto (ES) as Co- Rapporteur.
Prieto (ES) bħala Ko- Rapporteur.
The questions identified pertained to insufficient data on the evaluation of disseminated liver disease that could justify an extrapolation to the general population undergoing examinations of liver and kidney.
Il- kwistjonijiet identifikati kellhom x' jaqsmu ma 'dejta insuffiċjenti fuq l- evalwazzjoni ta' mard tal- fwied disseminat li jista 'jiġġustifika estrapolazzjoni għall- popolazzjoni ġenerali li jkunu qed isirulha eżamijiet tal- fwied u tal- kliewi.
Concerns were further raised with regards to the Paediatric Indication and the use of the comparator Magnevist.
Tqajjem tħassib ukoll dwar l- Indikazzjoni Pedjatrika u dwar l- użu tal- komparatur Magnevist.
Magnevist is not approved "to classify focal lesions [of liver or kidney] as benign or malignant" throughout the EU and it was questioned whether it would support the granting of an indication for which Magnevist has not been approved.
Magnevist mhux approvat biex "jikklassifika l- leżjonijiet fokali [tal- fwied jew tal- kliewi] bħala beninji jew malinji" madwar l- UE u saret mistoqsija lill- UE jekk hija kinitx se tappoġġja l- għoti ta 'indikazzjoni fl- UE kollha li għaliha Magnevist ma kienx ġie approvat.
The Applicant was asked to justify the choice of this comparator and the clinical utility of Gadovist/ Gadograf with respect to diagnostic thinking, therapeutic management and clinical outcome.
L- Applikant intalab jiġġustifika l- għażla ta 'dan il- komparatur u l- utilità klinika ta' Gadovist/ Gadograf fir- rigward tal- ħsieb dijanjostiku, tal- ġestjoni terapewtika u tar- riżultat kliniku.
A Request for Supplementary Information was adopted on 16 November 2006.
Fis- 16 ta 'Novembru ta' l- 2006 ġiet addottata Talba għal Tagħrif Supplementari.
The company responded to these points on 30 November 2006.
Il- kumpanija intalbet tirrispondi għal dawn il - punti fit- 30 ta 'Novembru ta' l- 2006.
7 Westferry Circus, Canary Wharf, London, E14 4HB, UK Tel.
Fit- tweġiba tiegħu, l- Applikant indirizza l- kwistjoni ta 'l - utilità klinika billi qabbel MRI imsaħħaħ b' Gadovist ma' MRI imsaħħaħ b' Magnevist u saħaq 7 Westferry Circus, Canary Wharf, London, E14 4HB, UK Tel.
(44-20) 74 18 84 00 Fax (44-20) 74 18 86 68 E-mail: mail@emea. europa. eu http: / /www. emea. europa. eu ©. EMEA 2007 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged “ Contrast enhanced MRI of liver or kidneys in patients with high suspicion or evidence of having focal lesions to classify these lesions as benign or malignant”.
Taqsima 4. 1 (Indikazzjoni):
Section 4.2 (Posology): “ Paediatric patients Gadograf is not recommended for use in population below age 18 due to a lack of data on efficacy and safety.
Taqsima 4. 2 (Pożoloġija): “ Pazjenti pedjatriċi Gadograf mhux rakkomandat għall- użu f' pazjenti ta 'taħt it- 18- il sena minħabba nuqqas ta' dejta fuq l- effikaċja u s- sigurtà.
The CHMP opinion was converted into a Decision by the European Commission on 13 April 2007.
L- opinjoni tas- CHMP inbidlet f' Deċiżjoni mill- Kummissjoni Ewropea fit- 13 ta 'April ta' l - 2007.
The list of product names concerned is given in Annex I.
Il- lista ta 'ismijiet tal- prodotti konċernati qed tingħata fl- Anness I.
The scientific conclusions are provided in Annex II and the amended Summary of Product Characteristics in Annex III.
Il- konklużjonijiet xjentifiċi qed jingħataw fl- Anness II u s- Sommarju tal- Karatteristiċi tal- Prodott emendat fl- Anness III.
Notes:
Noti:
The information given in this document and Annexes reflect only the CHMP Opinion dated 14 December 2006.
It- tagħrif mogħti f' dan id- dokument u fl- Annessi jirrifletti biss l- Opinjoni tas- CHMP datata l - 14 ta 'Diċembru ta' l- 2006.
The Member States competent authorities will continue to keep the product under regular review.
L- awtoritajiet kompetenti ta 'l- Istati Membri se jkomplu janalizzaw il- prodott b’ mod regolari.
ANNEX I
ANNES I
LIST OF THE NAMES, PHARMACEUTICAL FORMS, STRENGTHS OF THE MEDICINAL PRODUCTS, ROUTE OF ADMINISTRATION, MARKETING AUTHORISATION HOLDERS IN THE MEMBER STATES
LISTA TA` L- ISMIJIET, GĦAMLIET FARMAĊEWTIĊI, QAWWIET TAL- PRODOTTI MEDIĊINALI, MNEJN JINGĦATA, L- APPLIKANTI U D- DETENTURI TA 'L - AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ FL- ISTATI MEMBRI
(Invented) Name
Isem Ivvintat
Austria
jingħata
Powder for solution for infusion
Trab għal soluzzjoni għall -
Intravenous use
Għall- użu minn
Austria
ġol- vini
Eli Lilly Ges. m. b. H Kölblgasse 8-10 1030 Wien Austria
Eli Lilly Ges. m. b. H Kölblgasse 8- 10 1030 Wien L- Awstrija
Intravenous use
Għall- użu minn ġol- vini
Belgium
Rue De L' Etuve 52 B- 1000 Brussels Il- Belġju
Eli Lilly Nederland B. V., Grootslag 1-5, 3991 RA Houten The Netherlands
Eli Lilly Nederland B. V., Grootslag 1- 5, 3991 RA Houten L- Olanda
intravenous use
Għall- użu minn ġol- vini
Eli Lilly Č R, s. r. o, Pobř ež ní 1A, 186 00 Praha 8 Czech Republic
Eli Lilly ČR, s. r. o, Pobřežní 1A, 186 00 Praha 8 Ir- Repubblika Ċeka
Eli Lilly Č R, s. r. o, Pobř ež ní 1A,, 186 00 Praha 8 Czech Republic
Eli Lilly ČR, s. r. o, Pobřežní 1A,, 186 00 Praha 8 Ir- Repubblika Ċeka
2 Cyprus
2 Ċipru
PHADISCO LTD 185 Giannou Kranidioti Avenue CY-2234 Latsia Cyprus
PHADISCO LTD 185 Giannou Kranidioti Avenue CY- 2234 Latsia Ċipru
Eli Lilly Danmark A/ S, Nybrovej 110, DK-2800 Kongens Lyngby Denmark
Eli Lilly Danmark A/ S, Nybrovej 110, DK- 2800 Kongens Lyngby Id- Danimarka
200 mg powder for
200 mg trab għal
Kingsclere Road, Basingstoke, Hampshire, RG21 6XA United Kingdom
Kingsclere Road, Basingstoke, Hampshire RG21 6AX Ir- Renju Unit
solution for infusion
soluzzjoni għall -
Eli Lilly Holdings Linited, Kingsclere Road, Basingstoke, Hampshire, RG21 6XA United Kingdom
Eli Lilly Holdings Limited Kingsclere Road, Basingstoke, Hampshire RG21 6AX Ir- Renju Unit
Gemzar 1 g powder for solution 1g for infusion
Gemzar 1 g trab għal soluzzjoni 1g għall- infużjoni
Oy Eli Lilly Finland, Ab Rajatorpantie 41 C, PL 16, 01641 Vantaa Finland
Oy Eli Lilly Finland, Ab Rajatorpantie 41 C, PL 16, 01641 Vantaa Il- Finlandja
Gemzar 200 mg powder for 200 mg solution for infusion
Gemzar 200 mg trab għal 200 mg soluzzjoni għall- infużjoni
Gemzar 1 g powder for solution 1 g for infusion
Gemzar 1 g trab għal soluzzjoni 1 g għall- infużjoni
3 France
3 Franza
13, rue Pagès 92158 Suresnes Cedex France
13, rue Pagès 92158 Suresnes Cedex Franza
LILLY France SAS 13, rue Pagès 92158 Suresnes Cedex France
LILLY France SAS 13, rue Pagès 92158 Suresnes Cedex Franza
Lilly Deutschland GmbH Teichweg 3 35396 Gießen Germany
Lilly Deutschland GmbH Teichweg 3 35396 Gießen Il- Ġermanja
FARMASERVE LILLY S. A. Cl 15 Km National Road Athens-Lamia Kifissia, 14564 Greece
FARMASERVE LILLY S. A. Cl 15 Km National Road Athens- Lamia Kifissia, 14564 Il- Greċja
FARMASERVE LILLY S.A.Cl 15 Km National Road Athens-Lamia Kifissia, 14564 Greece
FARMASERVE LILLY S. A. Cl 15 Km National Road Athens- Lamia Kifissia, 14564 Il- Greċja
Eli Lilly Nederland BV PO Box 379 3990 GD Houten The Netherlands
Eli Lilly Nederland BV PO Box 379 3990 GD Houten L- Olanda
1g
1g trab għall- injezzjoni 1g
Powder for Injection
Trab għall- Injezzjoni
200 mg
200 mg trab għall - 200 mg
4 Ireland
4 L- Irlanda
Eli Lilly and Company Limited Lilly House, Priestley Road, Basingstoke, Hampshire RG24 9NL United Kingdom
Ir- Renju Unit
Gemzar 200 mg powder for solution for infusion
Gemzar 200 mg trab għal soluzzjoni għall- infużjoni
Gemzar 1 g powder for solution 1g for infusion
Gemzar 1 g trab għal soluzzjoni għall- infużjoni
Eli Lilly Denmark, Nybrovej 110, 2800 Lyngby Denmark
Eli Lilly Denmark, Nybrovej 110, 2800 Lyngby Id- Danimarka
Via Gramsci 731/733 - 50019 Sesto Fiorentino, Florence Italy
Via Gramsci 731/ 733 - 50019 Sesto Fiorentino, Florence L- Italja
GEMZAR 200 mg powder for 200 mg solution for infusion and intravesical instillation
GEMZAR 200 mg trab għal soluzzjoni għall- infużjoni u instillazzjoni intravessikali
Powder for solution for infusion and intravesical instillation
Trab għal soluzzjoni għall - infużjoni u instillazzjoni intrvessikali
Intravenous use and intravesical use
Għall- użu minn ġol- vini u għall- użu intrvessikali
GEMZAR 1 g powder for 1g solution for infusion and intravesical instillation
GEMZAR 1 g trab għal soluzzjoni għall- infużjoni u instillazzjoni intravessikali
Eli Lilly Holdings Limited, Kingsclere Road, Basingstoke, Hampshire, RG 216XA5 United Kingdom
Eli Lilly Holdings Limited, Kingsclere Road, Basingstoke, Hampshire, RG 216XA5 Ir- Renju Unit
5 Latvia
5 Il- Latvja
Eli Lilly Holdings Limited Kingsclere Road, Basingstoke, Hampshire RG21 6XA United Kingdom
Eli Lilly Holdings Limited Kingsclere Road, Basingstoke, Hampshire RG21 6XA Ir- Renju Unit
Luxembourg
Il - Lussumburgu
52, rue de l'Etuve B-1000 Bruxelles Belgium
52, rue de l' Etuve B- 1000 Bruxelles Il- Belġju
6 The Netherlands
L- Olanda
Eli Lilly Nederland BV Grootslag 1-5 3991 RA Houten The Netherlands
Eli Lilly Nederland BV Grootslag 1- 5 3991 RA Houten L- Olanda
Eli Lilly Netherlands BV Grootslag 1-5 3991 RA Houten The Netherlands
Eli Lilly Netherlands BV Grootslag 1- 5 3991 RA Houten L- Olanda
Eli Lilly Norge AS, Postboks 6090 Etterstad, N-0601 Oslo Norway
Eli Lilly Norge AS, Postboks 6090 Etterstad, N- 0601 Oslo In- Norveġja
2 rue du colonel Lilly 67642 Fegersheim France
2 rue du colonel Lilly 67642 Fegersheim Franza
Portugal
7 Il- Portugall
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António Loureiro Borges, 1 - Piso 1 - Arquiparque - Miraflores 1499 - 016 Algés Il- Portugall
7 Portugal
Il- Portugall
Lilly France S.A.S 2 Rue du Colonel Lilly 6740 Fegersheim France
Lilly France S. A. S 2 Rue du Colonel Lilly 6740 Fegersheim France
Lilly France S.A.S 2 Rue du Colonel Lilly 6740 Fegersheim France
Lilly France S. A. S 2 Rue du Colonel Lilly 6740 Fegersheim Franza
Eli Lilly ČR, s.r.o., Pobřežní 1a, 186 00 Praha 8 Czech Republic
Eli Lilly ČR, s. r. o., Pobřežní 1a, 186 00 Praha 8 Ir- Repubblika Ċeka
Slovenia
L- Islovenja
Dunajska 156 1000 Ljubljana Slovenia
Dunajska 156 1000 Ljubljana L- Islovenja
Slovenia
ġol- vini
Lilly, S.A., Avenida de la Industria, 30 28108 Alcobendas Madrid Spain
Lilly, S. A., Avenida de la Industria, 30 28108 Alcobendas Madrid Spanja
GEMZAR 1 g Powder for 1g solution for injection
GEMZAR 1 g Trab għal soluzzjoni għall- infużjoni
Powder for solution for injection
Trab għal soluzzjoni għall - infużjoni
GEMZAR 200 mg Powder for 200 mg solution for injection
GEMZAR 200 mg Trab għal soluzzjoni għall- infużjoni
8 Sweden
L- Isvezja
Eli Lilly Sweden AB Box 721 169 27 Solna Sweden
Eli Lilly Sweden AB Box 721 169 27 Solna L- Isvezja
Eli Lilly and Company Limited Lilly House, Priestley Road, Basingstoke, Hampshire RG24 9NL United Kingdom
Eli Lilly and Company Limited Lilly House, Priestley Road, Basingstoke, Hampshire RG24 9NL Ir- Renju Unit
Gemzar 200 mg Powder for Solution for Infusion
Gemzar 200 mg Trab għal soluzzjoni għall- infużjoni
Gemzar 1g Powder for Solution 1g for Infusion
Gemzar 1g Trab għal soluzzjoni għall- infużjoni
SCIENTIFIC CONCLUSIONS AND GROUNDS FOR AMENDMENT OF THE SUMMARIES OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET PRESENTED BY THE EMEA
KONKLUŻJONIJIET XJENTIFIĊI U RAĠUNIJIET GĦALL- EMENDA TAS- SOMMARJU TAL- KARATTERISTIĊI TAL- PRODOTT, TIKKETTA U FULJETT TA ’ TAGĦRIF IPPREŻENTATI MILL- EMEA
OVERALL SUMMARY OF THE SCIENTIFIC EVALUATION OF GEMZAR
SOMMARJU ĠENERALI TA ’ L- EVALWAZZJONI XJENTIFIKA TA ’ GEMZAR
Gemzar was included in the list of products for SPC harmonisation, in accordance with Article 30(2) of Directive 2001/83/EC, as amended because of the divergences existing amongst the nationally authorised SPCs due to the divergent national decisions taken by Member States.
Gemzar kien inkluż fil- lista ta ’ prodotti għall- armonizzazzjoni tal- SPC, b’ mod konformi ma ’ l- Artikolu 30( 2) tad- Direttiva 2001/ 83/ KE, kif emendat minħabba d- diverġenzi li jeżistu fost l- SPC awtorizzati fuq livell nazzjonali minħabba d- deċiżjonijiet nazzjonali diverġenti meħudin mill- Istati Membri.
Gemzar (gemcitabine) is a pyrimidine antagonist (an antimetabolite) that is metabolised intracellularly to active diphosphate and triphosphate nucleosides which inhibit DNA synthesis.
Gemzar (gemcitabine) huwa antagonista ta ’ pyrimidine (antimetabolit) li huwa metabolizzat ġewwa ċ- ċelloli għal nukleosidi difosfati u trifosfati attivi li jimpedixxu s- sinteżi ta ’ DNA.
It is primarily active against cells in the S phase and is given in the management of solid tumours.
Huwa primarjament attiv kontra ċelloli fil- fażi S u jingħata fil- ġestjoni ta ’ tumuri solidi.
Gemcitabine (difluoro- deoxy-cytidine (dFdC)) is a cytotoxic anti-cancer agent, which exhibits cell phase specificity, primarily killing cells undergoing DNA synthesis (S-phase) and under certain conditions blocking the progression of cells through the G 1/S phase boundary.
Gemcitabine (difluoro- deoxy- cytidine (dFdC)) hija mediċina ċitotossika kontra l- kanċer, li tesibixxi speċifiċità tal- fażi ta ’ ċellola, billi primarjament toqtol ċelloli li qegħdin iġarrbu sinteżi tad- DNA (fażi- S) u taħt ċerti kundizzjonijiet jimblokka l - progressjoni ta ’ ċelloli minn ġewwa l- konfini tal- fażi G1/ S.
The following indications are currently approved for Gemzar and were assessed by the CHMP:
L- indikazzjonijiet li ġejjin huma fil- preżent approvati għal Gemzar u kienu evalwati mill- CHMP:
1) Bladder cancer, 2) Advanced Non- small cell lung cancer, 3) Advanced pancreatic cancer, 4) Breast cancer and 5) Ovarian cancer.
1) Kanċer tal- bużżieqa ta ’ l- awrina, 2) Kanċer ta ’ ċelloli tal- pulmun mhux żgħir avvanzat, 3) Kanċer pankrejatiku avvanzat, 4) Kanċer tas- sider 5) Kanċer ta ’ l- ovarju.
The CHMP assessed the SPC wording proposed by the MAH and the submitted rationales for the proposal.
Il- CHMP ivvaluta l- kitba tal- SPC proposta mill- MAH u r- raġunijiet fundamentali sottomessi għall- proposta.
Particular attention was given to the therapeutic indications of Gemzar.
Ingħatat attenzjoni partikolari għall- indikazzjonijiet terapewtiċi ta ’ Gemzar.
Critical Evaluation
Evalwazzjoni Kritika
For the indication in bladder cancer, the MAH provided data from two Phase 2 studies and from a pivotal Phase 3, showing that gemcitabine chemotherapy is active, tolerable, displays manageable toxicity and superiority to MVAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy in the treatment of patients with advanced or metastatic transitional cell carcinoma of the urothelium.
Għall- indikazzjoni f’ kanċer tal- bużżieqa ta ’ l- awrina, il- MAH ipprovda dejta minn żewġ studji ta ’ Fażi 2 u minn wieħed ewlieni ta ’ Fażi 3, li juri li l- kimoterapija gemcitabine hija attiva, tollerabbli, turi tossiċità u superjorità maniġjevoli għal kimoterapija MVAC (methotrexate, vinblastine, adriamycin u cisplatin) fil - kura ta ’ pazjenti b’ karċinoma ta ’ ċellola transizzjonali avvanzata jew metastatika tal- jurotiljum.
The MAH also defended the use of gemcitabine by intravesical administration, based on the proven activity in advanced bladder cancer, on the pharmacokinetic attributes of gemcitabine and on its high total body clearance.
Il- MAH iddefenda wkoll l- użu ta ’ gemcitabine permezz ta ’ għoti intravesikali, ibbażat fuq l- attività murija bi prova f’ kanċer tal- bużżieqa ta ’ l- awrina avvanzat, fuq il- karatteristiċi farmakokinetiċi ta ’ gemcitabine u fuq l - eliminazzjoni korporali totali għolja tiegħu.
The CHMP considered the data submitted in support of the bladder cancer indication and noted that all the submitted studies were conducted in patients with locally advanced or metastatic bladder cancer.
Il- CHMP ikkunsidra t- tagħrif ippreżentat bħala appoġġ għall- indikazzjoni ta ’ kanċer tal- bużżieqa ta ’ l - awrina u nnota li l- istudji kollha sottomessi saru f’ pazjenti b’ kanċer tal- bużżieqa ta ’ l- awrina lokalment avvanzat jew metastatiku.
Promising data in advanced bladder cancer and the need for other treatments for superficial bladder cancer led to the study of gemcitabine by intravesical administration in superficial bladder cancer but although the CHMP acknowledged that gemcitabine has shown activity in non-muscle invasive bladder cancer in intermediate and high risk patients, no actual data from Phase III trials has been submitted.
Tagħrif promettenti f’ kanċer tal- bużżieqa ta ’ l- awrina avvanzat u l- ħtieġa għal kuri oħrajn għal kanċer tal- bużżieqa ta ’ l- awrina superfiċjali wasslu għall- istudju ta ’ gemcitabine permezz ta ’ għoti intravesikali f’ kanċer tal- bużżieqa ta ’ l- awrina superfiċjali iżda għalkemm il- CHMP irrikkonoxxa li gemcitabine wriet attività f’ kanċer tal- bużżieqa ta ’ l- awrina mhux tal- muskolu f’ pazjenti ta ’ riskju għoli jew intermedjat, ma ġie sottomess l- ebda tagħrif effettiv minn provi ta ’ Fażi III.
Therefore the CHMP considers that the proposed broad indication “bladder cancer” is not justified, as the data provided was not sufficient to support the indication in superficial bladder cancer.
Għaldaqstant il- CHMP ikkunsidra li l- indikazzjoni wiesa ’ proposta “ kanċer tal- bużżieqa ta ’ l- awrina ” mhijiex iġġustifikata, peress li d- dejta pprovduta ma kinitx biżżejjed biex tappoġġja l- indikazzjoni f’ kanċer tal- bużżieqa ta ’ l - awrina superfiċjali.
The CHMP required the MAH to reflect the target population (patients with advanced/metastatic bladder cancer) and the combination treatment with cisplatin in the harmonized indication.
Il- CHMP ħtieġ lill- MAH li jirrifletti l- popolazzjoni fil- mira (pazjenti b’ kanċer tal - bużżieqa ta ’ l- awrina avvanzat/ metastatiku) u l- kura ta ’ kombinazzjoni b’ cisplatin fl- indikazzjoni armonizzata.
The MAH agreed to delete the indication in superficial bladder cancer and the CHMP accordingly proposed the following revised wording:
Il- MAH qabel li jneħħi l- indikazzjoni f’ kanċer tal- bużżieqa ta ’ l- awrina superfiċjali u l - CHMP għalhekk ippropona l- kitba rreveduta li ġejja:
“Gemcitabine is indicated in the treatment of locally advance or metastatic bladder cancer in combination with cisplatin.”.
“ Gemcitabine hija indikata fil- kura ta ’ kanċer tal- bużżieqa ta ’ l- awrina lokalment avvanzat jew metastatiku f’ kombinazzjoni ma ’ cisplatin ”.
The indication in pancreatic cancer is based on data from the pivotal Phase 3 study JHAY and the supporting study JHAZ.
L- indikazzjoni f’ kanċer tal- frixa hija bbażata fuq tagħrif mill- istudju ewlieni ta ’ Fażi 3 JHAY u l- istudju ta ’ appoġġ JHAZ.
Intravenous gemcitabine has become widely accepted as the standard of chemotherapy care for advanced pancreatic cancer but has yielded disappointing results as combination treatment in patients with locally advanced (nonresectable) or metastatic pancreatic cancer and the MAH considered that gemcitabine monotherapy remains the standard of chemotherapy care for advanced/metastatic, nonresectable pancreatic adenocarcinoma.
Gemcitabine intravenuża ġiet aċċettata b’ mod komuni bħala l- istandard ta ’ kura b’ kimoterapija għall- kanċer tal- frixa avvanzat iżda ta riżultati diżappuntanti bħala kura ta ’ kombinazzjoni f’ pazjenti b’ kanċer tal- frixa lokalment avvanzat (li ma jistax jitneħħa bil- kirurġija) jew metastatiku u l - MAH ikkunsidra li monoterapija b’ gemcitabine tibqa ’ l- istandard ta ’ kura ta ’ kimoterapija għall - adenokarċinoma pankreatika avvanzata/ metastatika, li ma tistax titneħħa bil- kirurġija.
Therefore the CHMP agreed with the proposal but asked the MAH to justify the proposed wording regarding 5-FU refractory patients.
11 Għaldaqstant il- CHMP qabel mal- proposta iżda talab lill- MAH jiġġustifika l- kitba proposta rigward pazjenti refrattorji għal 5- FU.
The MAH agreed that the indication is redundant because the first line treatment of pancreatic treatment with gemcitabine is standard of care and agreed to remove it.
Il- MAH qabel li l- indikazzjoni hija superfluwa għaliex il- kura ta ’ l- ewwel linja b’ gemcitabine hija standard ta ’ kura u qabel li jneħħiha.
The CHMP also deleted the mention of performance status and adopted the following wording:
Il- CHMP ħassar ukoll l- aċċenn ta ’ stejtus ta ’ prestazzjoni u adotta l- kitba li ġejja:
11 “Gemcitabine is indicated for the treatment of patients with locally advanced or metastatic adenocarcinoma of the pancreas”.
“ Gemcitabine hija indikata għall- kura ta ’ pazjenti b’ adenokarċinoma tal- frixa lokalment avvanzata jew metastatika ”.
The indication in non-small cell lung cancer is based on data from Phase II and Phase III trials and indicated that gemcitabine has been shown to be active in the treatment of non-small cell lung cancer (NSCLC) and that in addition to gemcitabine single-agent activity, a preponderance of data supports the activity and safety of its combination with cisplatin in the treatment of NSCLC, irrespective of the different doses and schedules.
L- indikazzjoni f’ kanċer ta ’ ċelloli tal- pulmun mhux żgħir hija bbażata fuq tagħrif minn provi ta ’ Fażi II u Fażi III u indikat li gemcitabine intwera li huwa attiv fil- kura ta ’ kanċer ta ’ ċelloli tal- pulmun mhux żgħir (NSCLC) u li flimkien ma ’ attività tas- sustanza singola gemcitabine, tgħarbil minn qabel tat- tagħrif jappoġġja l- attività u s- sigurtà tal- kombinazzjoni tiegħu ma ’ cisplatin fil- kura ta ’ NSCLC, irrispettivament mid- dożi u l- iskedi differenti.
The MAH therefore considered the positive benefit-risk ratio to be established for the use of gemcitabine/cisplatin in the treatment of NSCLC.
Għaldaqstant, il- MAH ikkunsidra l- proporzjon benefiċċju- riskju bħala wieħed pożittiv biex ikun stabbilit għall- użu ta ’ gemcitabine/ cisplatin fil- kura ta ’ NSCLC.
The CHMP agreed that gemcitabine used as single agent has shown activity against NSCLC but considered that the combination treatment with gemcitabine + cisplatin is the first line of treatment in patients with advanced/metastatic NSCLC and therefore asked the MAH to further justify the indication of Gemzar as combination treatment and as single agent in NSCLC, bearing in mind that single-agent therapy will usually be restricted to patients with a borderline performance status, elderly patients or pretreated patients.
Il- CHMP qabel li gemcitabine użat bħala sustanza waħidha wera attività kontra NSCLC iżda ikkunsidra li kura ta ’ kumbinazzjoni b’ gemcitabine + cisplatin hija l- ewwel linja ta ’ kura f’ pazjenti b ’ NSCLC avvanzata/ metstatika u għalhekk talab lill- MAH biex jiġġustifika iktar l- indikazzjoni ta ’ Gemzar bħala kura ta ’ kombinazzjoni u bħala mediċina waħidha f’ NSCLC, filwaqt li qies li terapija ta ’ mediċina waħidha ġeneralment tkun ristretta għal pazjenti bi stejtus ta ’ eżekuzzjoni fil- limitu, pazjenti anzjani jew pazjenti diġà ikkurati.
The MAH agreed that platinum-based combination therapies are the standard of care but defended the use of gemcitabine monotherapy in the treatment of elderly patients and patients with a Performance Status of 2, as these groups are at higher risk for chemotherapy-related morbidities or in cases where platinum-based combinations cannot be tolerated.
Il- MAH qabel li kuri ta ’ kombinazzjoni bbażati fuq il- platinju huma l- istandard ta ’ kura iżda ddefenda l - użu ta ’ monoterapija b’ gemcitabine fil- kura ta ’ pazjenti anzjani u pazjenti bi Stejtus ta ’ Prestazzjoni 2, peress li dawn il- gruppi huma f’ riskju iktar għoli għall- morbiditajiet relatati mal- kimoterapija jew f’ każijiet fejn kombinazzjonijiet ibbażati fuq platinju ma jistgħux ikunu ttollerati.
The MAH supported its position by providing guidelines from major oncology societies and review of the literature and proposed a new wording for the single agent in NSCLC indication.
Il- MAH appoġġja l - pożizzjoni tiegħu billi pprovda linji gwida minn soċjetajiet ta ’ l- onkoloġija maġġuri u minn studju tal - letteratura u ppropona kitba ġdida għal sustanza waħidha fl- indikazzjoni NSCLC.
The CHMP reviewed the MAH responses and agreed that as a single agent, gemcitabine has a specific role in patients with a borderline performance status and elderly patients and that gemcitabine is an option between other treatments, although no specific agent has been identified to be better than others.
Il- CHMP irreveda r - reazzjonijiet tal- MAH u qabel li bħala sustanza waħidha, gemcitabine għandha rwol speċifiku f’ pazjenti bi stejtus ta ’ prestazzjoni fil- limitu u f’ pazjenti anzjani u li gemcitabine hija għażla fost kuri oħrajn, għalkemm l- ebda mediċina speċifika ma ġiet identifikata li hija aħjar mill- oħrajn.
The CHMP adopted the proposed revised wording:
Il- CHMP adotta l- kitba rreveduta proposta:
“Gemcitabine, in combination with cisplatin is indicated as first line treatment of patients with locally advanced or metastatic non small cell lung cancer.
“ Gemcitabine, f’ kombinazzjoni ma ’ cisplatin hija indikata bħala kura ta ’ l- ewwel linja għal pazjenti b’ kanċer ta ’ ċelloli tal- pulmun mhux żgħir lokalment avvanzat jew metastatiku.
Gemcitabine monotherapy can be considered in elderly patients or those with performance status 2.”
Monoterapija b ’ gemcitabine tista ’ tkun ikkunsidrata f’ pazjenti anzjani jew f’ dawk bi stejtus ta ’ prestazzjoni 2. ”
Regarding breast cancer, the MAH only proposed combination use for inclusion in the harmonised SPC, although a Phase 3 study showed the activity of single-agent gemcitabine for the treatment of metastatic breast cancer (MBC). The indication was supported by a clinical expert report and efficacy data from Phase 2 and 3 single-agent studies of Gemzar in the treatment of breast cancer, including studies conducted by the MAH and results from the published literature.
L- indikazzjoni kienet appoġġjata permezz ta ’ rapport kliniku ta ’ espert u dejta ta ’ effikaċja minn studji ta ’ Fażi 2 u 3 ta ’ Gemzar b’ sustanza waħidha fil- kura ta ’ kanċer tas - sider, inklużi studji magħmulin mill- MAH u riżultati mill- letteratura ppubblikata.
Overall, the MAH therefore considered gemcitabine plus paclitaxel combination chemotherapy to be an effective regimen in patients with metastatic breast cancer, with an expected and manageable toxicity and a favourable risk-benefit profile.
Għaldaqstant, kollox ma ’ kollox, il- MAH ikkunsidra li l- kombinazzjoni ta ’ gemcitabine flimkien ma ’ paclitaxel hija effettiva f’ pazjenti b’ kanċer tas- sider metastatiku, b’ tossiċità mistennija u maneġjevoli u bi profil ta ’ riskju - benefiċċju favorevoli.
The CHMP was of the opinion that gemcitabine has shown activity as single agent in MBC but the lack of Phase III trials in this setting makes it difficult to give a specific recommendation about the precise place of gemcitabine in the treatment of advance breast cancer.
Il- CHMP kien ta ’ l- opinjoni li gemcitabine wera attività bħala sustanza waħda f’ MBC iżda n- nuqqas ta ’ provi ta ’ Fażi III f’ dan l- ambjent jagħmluha diffiċli biex tingħata rakkomandazzjoni speċifika dwar il- post preċiż ta ’ gemcitabine fil- kura ta ’ kanċer tas- sider avvanzat.
The CHMP therefore considered that the greatest benefit from gemcitabine is achieved when it is administered in the first and second line setting in combination with taxanes and adopted the following wording:
Għaldaqstant, il- CHMP ikkunsidra li l- ikbar benefiċċju minn gemcitabine jinkiseb meta jingħata fl- ambjent ta ’ l- ewwel u t- tieni linja f’ kombinazzjoni ma ’ taxanes u adotta l- kitba l- ġejja:
Gemcitabine, in combination with paclitaxel, is indicated for the treatment of patients with unresectable, locally recurrent or metastatic breast cancer who have relapsed following adjuvant/neoadjuvant chemotherapy.
12 Gemcitabine, f’ kombinazzjoni ma ’ paclitaxel, huwa indikat għall- kura ta ’ pazjenti b’ kanċer tas- sider li ma jitneħħix bil- kirurġija, lokalment rikorrenti jew metastatiku li reġgħu rkadew wara kimoterapija aġġuvanti/ neoaġġuvanti.
Prior chemotherapy should have included an anthracycline unless clinically contraindicated.”
Il- kimoterapija ta ’ qabel kellha tinkludi anthracycline sakemm dan ma kienx klinikament kontraindikat. ”
Regarding ovarian cancer, the MAH proposed a wording for combination use in this indication, although activity is shown by gemcitabine as a single agent, and provided a clinical expert report and supplementary information to support the indication.
Rigward il- kanċer ta ’ l- ovarji, il- MAH ippropona kitba għall- użu ta ’ kombinazzjoni f’ din l- indikazzjoni, għalkemm attività tidher permezz ta ’ gemcitabine bħala sustanza waħidha, u pprovda rapport kliniku ta ’ espert u tagħrif supplimentari biex jappoġġja l- indikazzjoni.
The MAH focused the discussion on the pivotal randomized Phase 3 Study JHQJ, and the main supportive single-arm Phase 2 Study JHRW.
Il- MAH iffoka d- diskussjoni fuq Studju ewlieni randomizzat ta ’ Fażi 3 JHQJ, u l- fergħa waħda ta ’ appoġġ ewlenija ta ’ Fażi 2 ta ’ Studju JHRW.
The MAH concluded that the studies demonstrated that gemcitabine plus carboplatin is superior to 12 carboplatin in terms of time to disease progression (TtDP) and response rate in patients with platinum- sensitive recurrent ovarian cancer.
Il - MAH ikkonkluda li l- istudji wrew li gemcitabine flimkien ma ’ carboplatin huwa superjuri għal carboplatin f’ termini ta ’ żmien għall- progressjoni tal- marda (TtDP) u rata ta ’ reazzjoni f’ pazjenti b’ kanċer ta ’ l- ovarju rikorrenti sensittivi għal platinju.
This improvement in PFS and response rate is only associated with some additional, readily manageable toxicity, resulting in a favourable risk benefit profile.
Dan it- titjib f’ PFS u r- rata ta ’ reazzjoni huma assoċjati biss b’ xi tossiċità faċilment maniġevoli, addizjonali, li tirriżulta fi profil ta ’ riskju benefiċċju favorevoli.
The CHMP noted the pivotal study JHQJ was powered to detect differences in TtDP in overall survival and that the pivotal study for the ovarian cancer had a specific population consisting of platinum sensitive patients with a very poor prognosis and the CHMP was of the opinion that the proposed wording was in accordance with the submitted study for the marketing authorisation in this indication.
Il- CHMP innota li l- istudju ewlieni JHQJ ingħata l- abbilità biex isib id- differenzi f’ TtDP f’ sopravivenza totali u l- istudju ewlieni tal- kanċer ta ’ l- ovarji kellu popolazzjoni speċifika li tikkonsisti minn pazjenti sensittivi għal platinju bi pronjożi tassew ħażina u l- CHMP kien ta ’ l- opinjoni li l- kitba proposta kienet f’ konformità ma ’ l- istudju sottomess għall- awtorizzazzjoni għat- tqegħid fis- suq għal din l- indikazzjoni.
As no studies were available to support the use of gemcitabine as single agent neither in first or second line, the CHMP requested the MAH to further discuss the indication of Gemzar in ovarian cancer.
Peress li ma kien hemm l- ebda studju biex jappoġġja l- użu ta ’ gemcitabine bħala sustanza waħidha la fl - ewwel u lanqas fit- tieni linja, il- CHMP talab lill- MAH biex jiddiskuti iktar l- indikazzjoni ta ’ Gemzar f’ kanċer ta ’ l- ovarji.
The MAH defended the use of gemcitabine for the ovarian cancer indication based on a number of guidelines, considering that based on the demonstrated significant benefits of gemcitabine in combination with carboplatin, the acceptable toxicity profile and the tolerability of the treatment, this combination presents a favourable risk/benefit relationship in the treatment of recurrent ovarian cancer patients.
Il- MAH iddefenda l- użu ta ’ gemcitabine għall- indikazzjoni ta ’ kanċer ta ’ l- ovarji abbażi ta ’ għadd ta ’ linji gwidi, u kkunsidra li abbażi ta ’ benefiċċji sinjifikanti murijin ta ’ gemcitabine f’ kombinazzjoni ma ’ carboplatin, il- profil ta ’ tossiċità aċċettabbli u t- tollerabbilità tal- kura, din il- kombinazzjoni tippreżenta relazzjoni ta ’ riskju/ benefiċċju favorevoli fil- kura ta ’ pazjenti b’ kanċer ta ’ l- ovarji rikorrenti.
In addition, the use of gemcitabine for the treatment of recurrent ovarian cancer has been widely recognized and the MAH therefore believes that carboplatin plus gemcitabine represents a valuable option for treating patients with recurrent ovarian cancer.
Barra minn hekk, l- użu ta ’ gemcitabine għall- kura ta ’ kanċer ta ’ l- ovarju rikorrenti kien rikonoxxut f’ bosta nħawi u l - MAH għaldaqstant jemmen li carboplatin flimkien ma ’ gemcitabin jirrappreżenta għażla prezzjuża għall - kura ta ’ pazjenti b’ kanċer ta ’ l- ovarju rikorrenti.
The CHMP reviewed the information regarding the use of Gemcitabine in ovarian cancer and was of the opinion that the combination gemcitabine/carboplatin is an option in second line therapy in patients with sensitive platinum disease and an alternative in patients with previous paclitaxel/carboplatin toxicity (Therefore the CHMP retained the indication in ovarian cancer in the harmonised SPC, with the wording:
Il- CHMP irreveda t- tagħrif rigward l- użu ta ’ Gemcitabine f’ kanċer ta ’ l- ovarji u kien ta ’ l- opinjoni li l- kombinazzjoni gemcitabine/ carboplatin hija għażla fit- terapija tat- tieni linja f’ pazjenti b’ mard sensittiv għal platinju u alternattiva f’ pazjenti b’ tossiċità ta ’ qabel b’ paclitaxel/ carboplatin (Għaldaqstant il- CHMP żamm l- indikazzjoni f’ kanċer ta ’ l- ovarju fl- SPC armonizzat, bil- kitba:
“Gemcitabine is indicated in locally advanced or metastatic epithelial ovarian carcinoma, in combination with carboplatin, in patients with relapsed disease following a recurrence free interval of at least 6 months after-platinum based, first-line therapy”
“ Gemcitabine hija indikata f’ karċinoma epiteljali ta ’ l- ovarji lokalment avvanzata jew metastatika, f’ kombinazzjoni ma ’ carboplatin, f’ pazjenti b’ rikaduta tal- marda wara intervall ħieles minn rikaduta ta ’ mill- inqas 6 xhur wara terapija ta ’ l- ewwel linja bbażata fuq il- platinju ”
For Section 4.2, the MAH proposed a harmonised wording, addressing in particular the sections about dosage adjustment, about impaired renal function and on precautions in administration.
Għal Sezzjoni 4. 2, il- MAH ippropona kitba armonizzata, li tindirizza b’ mod partikolari s- sezzjonijiet dwar aġġustament fid- dożaġġ, dwar indeboliment tal- funzjoni renali u dwar prekawzjonijiet fl- għoti.
The CHMP requested clarifications on treatment continuation and more details specific to the individual indications, in particular breast cancer and ovarian cancer.
Il- CHMP talab kjarifikazzjonijiet fuq il- kontinwazzjoni tal- kura u iktar dettalji speċifiċi għall- indikazzjonijiet individwali, b’ mod partikolari kanċer tas- sider u kanċer ta ’ l- ovarji.
The CHMP retained the conservative age of 18 and also noted that information regarding hepatic impairment was included and therefore requested the MAH to further discuss patients with renal or hepatic impairment and whether severe impairment had significant effect on gemcitabine pharmacokinetics.
Il- CHMP żamm l- età konservattiva ta ’ 18 u innota wkoll li tagħrif rigward indeboliment epatiku kien inkluż u għaldaqstant talab lill- MAH biex jiddiskuti iktar il- pazjenti b’ indeboliment renali jew epatiku u jekk indeboliment sever kellux effett sinjifikanti fuq il- farmakokinetiċi ta ’ gemcitabine.
The MAH provided an updated posology taking into account the CHMP comments.
Il- MAH ipprovda pożoloġija aġġornata li tqis il- kummenti tal- CHMP.
No specific studies were performed in severely renally or hepatically impaired patients but based on published literature, the MAH considered that there was no indication that these patients differ significantly from the mild to moderate renally impaired group, in terms of Cmax or clearance.
Ma sar l- ebda studju speċifiku f’ pazjenti b’ indeboliment renali jew epatiku sever iżda abbażi ta ’ letteratura ppublikata, il- MAH ikkunsidra li ma hemm l- ebda indikazzjoni li dawn il- pazjenti huma ferm differenti mill- grupp b’ indeboliment renali ħafif għal moderat, f’ termini ta ’ Cmax jew eliminazzjoni.
The MAH also considered that the limited data available does not permit any dose modifications to be suggested in the SPC for patients with renal or hepatic impairment and that the precautions already adequately reflect the information available.
Il- MAH ikkunsidra wkoll li t- tagħrif limitata disponibbli ma jippermettix modifikazzjonijiet fid- doża li jridu jkunu ssuġġeriti fl- SPC
Based on the responses, the CHMP revised the text in section 4.2.
Il- CHMP irreveda t- test f’ sezzjoni 4. 2, abbażi ta ’ dawn ir- reazzjonijiet.