qanastek/EMEA-V3 huggingface dataset:
BEFORE YOU TAKE [INVENTED NAME] 400 MG FILM-COATED TABLETS
QABEL MA TIEĦU [ISEM IVVINTAT] 400MG PILLOLI MIKSIJA B’ RITA
Contact your doctor if you are not sure if you belong to a patient group described below.
Kellem lit- tabib tiegħek jekk m’ intix ċert jekk tagħmilx parti minn grupp ta ’ pazjenti deskritt isfel.
Do not take [Invented name] 400 mg film-coated tablets
Tieħux [Isem Ivvintat] 400mg pilloli miksija b’ rita:
- If you are allergic (hypersensitive) to the active ingredient moxifloxacin, any other quinolone
- Jekk inti allerġiku/ a (tbagħti minn sensittività eċċessiva) għas- sustanza attiva moxifloxacin,
antibiotics or any of the other ingredients (see section 6.
anti- bijotiċi quinolones oħra jew għal xi sustanzi oħra (ara sezzjoni 6.
Further information) of [Invented name] 400 mg film-coated tablets.
Aktar tagħrif) ta ’ [Isem Ivvintat] 400mg pilloli miksija b’ rita.
- If you are pregnant or breast-feeding.
- Jekk inti tqila jew qed tredda ’.
- If you are under 18 years of age.
- Jekk għandek età taħt 18- il sena.
- If you have a history of tendon disease or disorder which was related to treatment with
- Jekk għandek passat ta ’ marda tat- tendon jew marda li kienet relata ma ’ kura b’ anti- bijotiċi
quinolone antibiotics (see sections Take special care... and 4.
quinolone (ara sezzjonijiet Oqgħod attent ħafna... u 4.
- If you were born with or have had any condition with certain abnormal electrocardiogram
- Jekk inti twelidt bi jew kellek kull kundizzjoni b’ ċerti bidliet mhux normali fl -
(ECG, electrical recording of the heart) changes, have salt imbalance in the blood, especially low concentrations of potassium in the blood (hypokalaemia) which are currently not corrected by treatment, have a very slow heart rate (bradycardia), have a weak heart (heart failure), have a history of abnormal heart rhythms (arrhythmias), or you are taking other medicines that result in certain abnormal ECG changes (see section Taking other medicines).
elettrokardjogramm (ECG, irrekordjar ta ’ l- elettriku tal- qalb), għadek żbilanċ tal- melħ fid- demm, speċjalment konċentrazzjonijiet baxxi ta ’ potassju fid- demm (ipokalimja) li bħalissa mhux ikkoreġuti b’ kura, għandek rata tal- qalb baxxa ħafna (bradikardija), għandek qalb dgħajjfa (insuffiċjenza tal- qalb), għandek passat ta ’ ritmu tal- qalb mhux normali (arritmija), jew qed tieħu mediċini oħra li jwasslu għal ċerti bidliet mhux normali fl- ECG (ara sezzjoni Meta tieħu mediċini oħra).
This is because [Invented name] can cause a certain change on the ECG, that is a prolongation of the QT-interval i. e delayed conduction of electrical signals.
Dan minħabba li [Isem Ivvintat] jista ’ jikkawża ċertu bidla fuq l- ECG, jiġifieri titwil ta ’ l - intervall QT i. e. ittardjar fit- trasmissjoni tas- sinjali elettriċi.
- If you have a severe liver disease or increased liver enzymes (transaminases) higher than 5 times
- Jekk għandek marda tal- fwied severa jew żjieda fl- enżimi tal- fwied (transaminases) ogħla minn
the upper normal limit.
5 darbiet il- limitu normali ta ’ fuq.
Take special care with [Invented name] 400 mg film-coated tablets
Oqgħod attent ħafna b ’ [Isem Ivvintat] 400mg pilloli miksija b’ rita
Before taking [Invented name] 400 mg film-coated tablets
Qabel tieħu [Isem Ivvintat] 400mg pilloli miksija b’ rita
- [Invented name] can change your heart’ s ECG.
- [Isem Ivvintat] jista ’ jbiddel l- ECG ta ’ qalbek.
If you are currently taking any medicine that
Jekk bħalissa qed tieħu xi mediċina li tnaqqas il -
decrease your blood potassium levels, consult your doctor before taking [Invented name].
livelli ta ’ potassju fid- demm tiegħek, kellem lit- tabib tiegħek qabel tieħu [Isem Ivvintat].
If you experience palpitations or irregular heart beat during the period of treatment, you should inform your doctor immediately.
Jekk tħoss palpitazzjonijiet jew taħbit tal- qalb irregolari waqt il- perijodu ta ’ kura, għandek tinforma lit- tabib tiegħek minnufiħ.
He/ she may wish to perform an ECG to measure your heart rhythm.
Għandu/ a mnejn ikun jixtieq jagħmel ECG biex ikejjel ir- ritmu ta ’ qalbek.
- If you suffer from epilepsy or a condition which makes you likely to have convulsions, consult
- Jekk issofri minn epilessija jew minn kundizzjoni li tagħmlek probabbli li jkollok
your doctor before taking [Invented name].
konvulżjonijiet, kellem lit- tabib tiegħek qabel tieħu [Isem Ivvintat].
- If you or any member of your family have glucose-6-phosphate dehydrogenase deficiency (a
- Jekk inti jew xi membru tal- familja tiegħek għandhom nuqqas ta ’ glucose- 6- phosphate
rare hereditary disease), inform your doctor, who will advise whether [Invented name] is suitable for you.
dehydrogenase (marda ereditarja rari), għarraf lit- tabib tiegħek, li jtik parir jekk [Isem Ivvintat] huwiex adattat għalik.
- If you have a complicated infection of the female upper genital tract (e. g. associated with an
- Jekk għandek infezzjoni kumplikata ta ’ l- apparat ġenitali ta ’ fuq tal- mara (e. ż. assoċjat ma ’
abscess of the fallopian tubes and ovaries or of the pelvis), for which your doctor considers an intravenous treatment necessary, treatment with [Invented name] tablets is not appropriate.
axxess tat- tubi fallopjani u ta ’ l- ovarji jew tal- pelvi), li għalija t- tabib tiegħek jikkunsidra kura minn ġol- vini bħala neċessarja, kura b’ pilloli [Isem Ivvintat] mhux adattata.
- For the treatment of mild to moderate infections of the female upper genital tract your doctor
- Għall- kura ta ’ infezzjonijiet ħfief sa moderati ta ’ l- apparat ġenitali ta ’ fuq tal- mara t- tabib
should prescribe another antibiotic in addition to [Invented name].
tiegħek jista ’ jippreskrivi wkoll anti- bijotiku ieħor flimkien ma ’ [Isem Ivvintat].
If there is no improvement in symptoms after 3 days of treatment, please consult your doctor.
Jekk m’ hemmx titjib fis- sintomi wara 3 ġranet ta ’ kura, jekk jogħġbok kellem lit- tabib tiegħek.
When taking [Invented name] 400 mg film-coated tablets
Meta tieħu [Isem Ivvintat] 400mg pilloli miksija b’ rita
- The risk of cardiac abnormalities may increase with increase of the dose.
- Ir- riskju ta ’ anormalitajiet tal- qalb jista ’ jiżjied ma ’ żjieda fid- doża.
Therefore, you should
Għalhekk, għandek issegwi
adhere to the dosage.
d- dożaġġ.
- There is a rare chance that you may experience a severe, sudden allergic reaction (an
- Hemm possibbiltà rari li inti tista ’ taqbdek reazzjoni allerġika severa f’ daqqa (reazzjoni
anaphylactic reaction/ shock) even with the first dose, with the following symptoms: tightness in the chest, feeling dizzy, feeling sick or faint, or experience dizziness on standing.
anafilattika/ xokk) anki ma ’ l- ewwel doża, bis- sintomi li gejjin: tagħfis fis- sider, tħossok sturdut, tħossok ma tiflaħx jew b’ ħass ħażin, jew ikollok esperjenza ta ’ sturdament waqt li bilwieqfa.
If so, stop taking [Invented name] and seek medical advice immediately.
Jekk jaqbdek dan, waqqaf it- teħid ta ’ [Isem Ivvintat] u fittex parir mediku minnufih.
- [Invented name] may cause a rapid and severe inflammation of the liver which could lead to
- [Isem Ivvintat] jista ’ jikkawża infjammazzjoni rapida u severa tal- fwied li tista ’ twassal għall -
Possible side effects).
insuffiċjenza tal- fwied li hija ta ’ periklu għall- ħajja (ara sezzjoni 4. Effetti sekondarji li jista ’ jkollu).
Please contact your doctor before you continue the treatment if you develop signs such as rapidly feeling unwell and/ or being sick associated with yellowing of the whites of the eyes, dark urine, itching of the skin, a tendency to bleed or liver induced disease of the brain (symptoms of a reduced liver function or a rapid and severe inflammation of the liver).
Jekk jogħġbok ikkuntattja t- tabib tiegħek qabel tkompli l- kura jekk tiżviluppa sinjali inkluż li tħossok ma tiflaħx f’ daqqa u/ jew tirremetti assoċjata ma ’ sfurija ta ’ l- abjad ta ’ l - għajnejn, awrina skura, ħakk fil- ġilda, tendenza ta ’ fsada jew marda tal- moħħ ikkawżata mill - fwied (sintomi ta ’ funzjoni tal- fwied imnaqqsa jew infjammazzjoni rapida u severa tal- fwied).
- You may develop diarrhoea whilst taking, or after taking, antibiotics including [Invented name].
- Inti tista ’ tiżviluppa dijarea waqt li qed tieħu jew wara li ħadt, anti- bijotiċi inkluż [Isem
If this becomes severe or persistent or you notice that your stool contains blood or mucus you should stop taking [Invented name] immediately and consult your doctor.
Jekk din issir severa jew persistenti jew tinnota li l- purgar tiegħek fih demm jew mukus inti għandek tieqaf tieħu [Isem Ivvintat] minnufih u tkellem lit- tabib tiegħek.
In this situation, you should not take medicines that stop or slow down bowel movement.
F’ din is - sitwazzjoni, inti m’ għandekx tieħu mediċini li jwaqqfu jew inaqqsu l- moviment tal- musrana.
- [Invented name] may occasionally cause pain and inflammation of your tendons, particularly if
- [Isem Ivvintat] xi kultant jista ’ jikkawża uġigħ u infjammazzjoni fit- tendons tiegħek,
you are elderly or if you are currently being treated with corticosteroids.
speċjalment jekk inti anzjan jew jekk bħalissa qed tiġi kkurat b’ kortikosterojdi.
At the first sign of any pain or inflammation you should stop taking [Invented name], rest the affected limb and consult your doctor immediately.
Ma ’ l- ewwel sinjal ta ’ xi uġigħ jew infjammazzjoni għandek tieqaf tieħu [Isem Ivvintat], isserraħ id - driegħ/ riġel affettwat u tkellem lit- tabib tiegħek minnufih.
- If you are elderly with existing kidney problems take care that your fluid intake is sufficient
- Jekk inti anzjan bi problemi eżistenti tal- kliewi ħu ħsieb li t- teħid ta ’ fluwidi tiegħek huwa
because dehydration may increase the risk of kidney failure.
biżżejjed peress li deidratazzjoni tista ’ żżid ir- riskju ta ’ insuffċjenza tal- kliewi.
- If your eyesight becomes impaired or if you have any other eye disturbances whilst taking
- Jekk il- vista tiegħek tiġi mdgħajjfa jew jekk ikollok xi disturbi oħra fl- għajnejn waqt li qed tieħu
[Invented name], consult an eye specialist immediately.
[Isem Ivvintat], kellem speċjalista ta ’ l- għajnejn minnufih.
You
- Anti- bijotiċi quinolone jistgħu jagħmlu l- ġilda tiegħek aktar sensittivàgħad- dawl tax- xemx jew
should avoid prolonged exposure to sunlight or strong sunlight and should not use a sunbed or any other UV lamp while taking [Invented name].
Inti għandek tevita esponiment intawwal għad- dawl tax- xemx jew għad- dawl tax- xemx qawwi u m’ għandekx tuża sunbed jew xi lampa tal- UV oħra waqt li qed tieħu [Isem Ivvintat].
Taking other medicines Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines besides [Invented name], including medicines obtained without a prescription.
Jekk jogħġbok għid lit- tabib jew lill- ispiżjar tiegħek jekk qiegħed tieħu jew ħadt dan l- aħħar xi mediċini oħra minbarra [Isem Ivvintat], anki dawk mingħajr riċetta.
For [Invented name] be aware of the following:
Għal [Isem Ivvintat] għandek tkun taf dan li ġej:
- If you are taking [Invented name] and other medicines that affect your heart there is an
- Jekk qed tieħu [Isem Ivvintat] u mediċini oħra li jaffettwaw lill- qalbek hemm riskju akbar li it -
increased risk for altering your heartbeat.
taħbit ta ’ qalbek jinbidel.
Therefore, do not take [Invented name] together with the following medicines:
Għalhekk, tieħux [Isem Ivvintat] flimkien mal- mediċini li ġejjin:
Medicines that belong to the group of anti-arrhythmics (e. g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide), neuroleptics (e. g. phenothiazines, pimozide, sertindole, haloperidol, sultopride), tricyclic antidepressants, some antimicrobials (e. g. sparfloxacin, intravenous erythromycin, pentamidine, antimalarials particularly halofantrine), some antihistamines (e. g. terfenadine, astemizole, mizolastine), and other medicines (e. g. cisapride, intravenous vincamine, bepridil and diphemanil).
Mediċini li jagħmlu parti mill- grupp ta ’ anti- arritmijaċi (e. ż. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide), newrolettiċi (e. ż. phenothiazines, pimozide, sertindole, haloperidol, sultopride), antidepressanti triċikliċi, ċerti sustanzi kontra l - mikrobi (e. ż. sparfloxacin, erythromycin ġol- vini, pentamidine, mediċini kontra l- malarja speċjalment halofantrine), ċerti antistaminiċi (e. ż. terfenadine, astemizole, mizolastine), u mediċini oħra (e. ż. cisapride, vincamine ġol- vini, bepridil u diphemanil).
- Any medicine containing magnesium or aluminium such as antacids for indigestion, or any
- Kull mediċina li fiha manjesju jew aluminju bħal antaċidi għall- indiġestjoni, jew kull mediċina
medicine containing iron or zinc, medicine containing didanosine or medicine containing sucralfate to treat gastrointestinal disorders can reduce the action of [Invented name] tablets.
li fiha ħadid jew zingu, mediċini li fihom didanosine jew mediċini li fihom sucralfate għall- kura ta ’ disturbi gastro- intestinali jistgħu jnaqqsu l- azzjoni ta ’ pilloli ta ’ [Isem Ivvintat].
Therefore, take your [Invented name] tablet 6 hours before or after taking the other medicine.
Għalhekk, ħu l- pillola ta ’ [Isem Ivvintat] tiegħek 6 sigħat qabel jew wara li tieħu l- mediċina l- oħra.
- If you are currently taking oral anti-coagulants (e. g. warfarin), it may be necessary for your
- Teħid ta ’ faħam mediċinali orali fl- istess ħin ma ’ pilloli [Isem Ivvintat] inaqqas l- azzjoni ta ’
doctor to monitor your blood clotting times.
- Jekk bħalissa qed tieħu sustanzi kontra l- koagulazzjoni mill- ħalq (e. ż. warfarin), jista ’ jkun
Taking [Invented name] 400 mg film-coated tablets with food and drink The effect of [Invented name] is not influenced by food including dairy products.
neċessarju għat- tabib tiegħek li jissorvelja l- ħinijiet tat- taqgħid tad- demm tiegħek.
Pregnancy and breast-feeding Do not take [Invented name] if you are pregnant or breast-feeding.
Meta tieħu [Isem Ivvintat] 400mg pilloli miksija b’ rita ma ’ l- ikel u max- xorb:
Ask your doctor or pharmacist for advice before taking any medicine.
Tqala u Treddigħ Tieħux [Isem Ivvintat] jekk inti tqila jew qed tredda ’ Itlob il- parir tat- tabib jew ta ’ l- ispiżjar tiegħek qabel tieħu xi mediċina.
Driving and using machines [Invented name] may make you feel dizzy or light-headed.
[Isem Ivvintat] jista ’ jġagħlek tħossok sturdut jew mhux f’ siktek.
If you are affected in this way do not drive or operate machinery.
Jekk inti affettwat b’ dan il- mod, issuqx jew tħaddem magni.
Important information about some of the ingredients of [Invented name] 400 mg film-coated tablets [Invented name] tablets contain lactose.
Pilloli ta ’ [Isem Ivvintat] fihom lactose.
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking [Invented name].
Jekk it- tabib tiegħek qallek li għandek intolleranza għal xi zokkrijiet, ikkuntattja lit- tabib tiegħek qabel tieħu [Isem Ivvintat].
HOW TO TAKE [INVENTED NAME] 400 MG FILM-COATED TABLETS
KIF GĦANDEK TIEĦU [ISEM IVVINTAT] 400MG PILLOLI MIKSIJA B’ RITA
Always take [Invented name] exactly as your doctor has told you.
Dejjem għandek tieħu [Isem Ivvintat] skond il- parir tat- tabib.
You should check with your doctor or pharmacist if you are not sure how to take [Invented name].
Dejjem għandek taċċerta ruħek mat - tabib jew ma ’ l- ispiżjar tiegħek jekk ikollok xi dubju dwar kif għandek tieħu [Isem Ivvintat].
The usual dose for adults is one 400 mg film-coated tablet once daily.
Id- doża li ssoltu tingħata għall- adulti hija pillola waħda miksija b’ rita ta ’ 400mg darba kuljum.
[Invented name] tablets are for oral use.
Pilloli [Isem Ivvintat] huma għall- użu orali.
Swallow the tablet as a whole (to mask the bitter taste) and with plenty of liquid.
Ibla ’ l- pillola sħiħa (biex tgħatti t- togħma morra) ma ’ ħafna likwidu.
You can take [Invented name] with or without food.
Tista ’ tieħu [Isem Ivvintat] ma ’ l- ikel jew mingħajr ikel.
It is recommended that you take the tablet at approximately the same time each day.
Huwa rrakkomandat li inti tieħu l- pillola bejn wieħed u ieħor fl- istess ħin kuljum.
No adjustment of the dose is required in elderly patients, patients with a low bodyweight or in patients with kidney problems.
L- ebda aġġustment fid- doża ma huwa meħtieġ f’ pazjenti anzjani, pazjenti b’ piż tal- ġisem baxx jew f’ pazjenti bi problemi fil- kliewi.
The duration of treatment depends upon the type of infection.
It- tul tal- kura jiddependi mit- tip ta ’ infezzjoni.
Unless otherwise indicated by your doctor the recommended durations of use of [Invented name] are: -
Sakemm mhux indikat mod ieħor mit- tabib tiegħek it - tul ta ’ l- użu ta ’ [Isem Ivvintat] irrakkomandat huwa: -
Sudden worsening of chronic bronchitis (acute exacerbation of chronic bronchitis)
Irkadar f’ daqqa ta ’ bronkite kronika (irkadar akut ta ’ bronkite kronika)
10 days - days
5 - 10 ġranet
Infection of the lungs acquired (pneumonia) outside the hospital, except severe cases
- Infezzjoni tal- pulmuni (pnewmonja) miksuba minbarra l- isptar, minbarra każijiet severi
10
10 ġranet - -
Acute infection of the sinuses (acute bacterial sinusitis)
Infezzjoni akuta tas- sinusis (sinożite akuta mill- batterja) Infezzjonijiet ta ’ l- apparat ġenitali ta ’ fuq tal- mara ħfief sa moderati (marda infjammatorja tal- pelvi), inkluż infezzjoni tat- tubi fallopjani u infezzjoni
7
7 ġranet
Mild to moderate infections of the female upper genital tract (pelvic inflammatory disease), including infection of the fallopian tubes and infection of the uterus mucous membrane days
tal- membrana mukuża ta ’ l- utru
14
14- il ġurnata
It is important that you complete the course of treatment, even if you begin to feel better after a few days.
Huwa importanti li inti tkompli l- kors ta ’ kura kollu, anki jekk tibda tħossok aħjar wara ftit ġranet.
If you stop taking this medicine too soon your infection may not be completely cured, the infection may return or your condition may get worse, and you may also create a bacterial resistance to the antibiotic.
Jekk inti tieqaf tieħu din il- mediċina kmien wisq l- infezzjoni tiegħek tista ’ ma tkunx fieqet għal kollox, l- infezzjoni tista ’ terġa ’ titfaċċa jew il- kundizzjoni tiegħek tista ’ tmur għal agħar, u tista ’ wkoll toħloq reżistenza tal- batterja għall- anti- bijotiku.
The recommended dose and duration of treatment should not be exceeded (see section 2.
Id- doża rrakkomandata u t- tul ta ’ kura m’ għandhomx jinqabżu (ara sezzjoni 2.
Before you take [Invented name]..., Take special care...).
Qabel ma tieħu [Isem Ivvintat]..., Oqgħod attent ħafna...).
If you take more [Invented name] 400 mg film-coated tablets than you should
Jekk tieħu [Isem Ivvintat] 400mg pilloli miksija b’ rita aktar milli suppost:
21 If you take more than the prescribed one tablet a day, seek medical advice immediately and, if possible, take any remaining tablets, the packaging or this leaflet with you to show the doctor or pharmacist what you have taken.
21 Jekk tinsa tieħu [Isem Ivvintat] 400mg pilloli miksija b’ rita:
If you forget to take [Invented name] 400 mg film-coated tablets If you forget to take your tablet you should take it as soon as you remember on the same day.
Jekk tinsa tieħu l- pillola tiegħek għandek teħodha hekk kif tiftakar fl- istess ġurnata.
If you do not take your tablet on one day, take your normal dose (one tablet) on the next day.
Jekk ma tieħux il - pillola tiegħek f’ xi ġurnata, ħu d- doża normali (pillola waħda) l- ġurnata ta ’ wara.
Do not take a double dose to make up for a forgotten dose.
M’ għandekx tieħu doża doppja biex tpatti għal kull pillola li tkun insejt tieħu.
If you are unsure about what to do, consult your doctor or pharmacist.
Jekk m’ intix ċert dwar x’ għandek tagħmel, kellem lit- tabib jew lill- ispiżjar tiegħek.
If you stop taking [Invented name] 400 mg film-coated tablets If you stop taking this medicine too soon your infection may not be completely cured.
Jekk tieqaf tieħu din il- mediċina kmieni wisq l- infezzjoni tiegħek jista ’ ma tkunx fieqet għal kollox.
Consult your doctor if you wish to stop taking your tablets before the end of the course of treatment.
Kellem lit- tabib tiegħek jekk tixtieq tieqaf tieħu l- pilloli tiegħek qabel it- tmiem tal- kors ta ’ kura.
London, 14 August 2008 EMEA/ CHMP/ 524135/ 2008
Londra, 14 ta ’ Awwissu 2008 EMEA/ CHMP/ 364412/ 2008
COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) OPINION FOLLOWING AN ARTICLE 6 (12) REFERRAL
OPINJONI TAL- KUMITAT GĦAL PRODOTTI MEDIĊINALI GĦAL UŻU MILL - BNIEDEM (CHMP) WARA RIFERIMENT SKOND L- ARTIKOLU 6 (12)
Actira and associated names
Actira u ismijiet assoċjati
International non-proprietary name (INN): moxifloxacin
Denominazzjoni Komuni Internazzjonali (DKI): moxifloxacin
BACKGROUND INFORMATION *
INFORMAZZJONI TA ’ SFOND *
Actira film-coated tablets contain 400 mg moxifloxacin as hydrochloride.
Actira pilloli miksijin b’ rita fihom 400 mg moxifloxacin bħala hydrochloride.
It is approved for the treatment of the following bacterial infections if they are caused by bacteria susceptible to moxifloxacin: acute exacerbation of chronic bronchitis; community acquired pneumonia, except severe cases; acute bacterial sinusitis (adequately diagnosed).
Huwa approvat għall - kura tal- infezzjonijiet batteriċi li ġejjin jekk ikunu kkawżati minn batterji suxxettibbli għal moxifloxacin: taħrix akut tal- bronkite kronika; pnewmonja akkwistata mill- Komunità, għajr għal każijiet severi; sinusite batterjali akuta (dijanjostikata b’ mod adegwat).
The tablets have to be taken orally once daily for up to 10 days, depending on the indication.
Il- pilloli jeħtieġ li jittieħdu mill- ħalq darba kuljum għal mhux aktar minn 10 t’ ijiem, jiddependi fuq l - indikazzjoni.
In clinical trials the tablets have been studied for up to 14 days treatment.
Fil- provi kliniċi, il- pilloli ġew studjati għal kura ta ’ mhux aktar minn 14- il jum.
Actira was initially approved in June 1999.
Actira ġie approvat inizjalment f’ Ġunju 1999.
This Referral procedure relates to a request for arbitration concerning a type II variation for a new indication to include treatment of mild to moderate pelvic inflammatory disease (PID), i. e. infections of upper genital tract, including salpingitis and endometritis.
Din il- proċedura ta ’ Riferiment għandha x’ taqsam ma ’ talba għal arbitraġġ li tikkonċerna l- varjazzjoni ta ’ tip II għal indikazzjoni ġdida biex tinkludi l- kura ta ’ mard infjammatorju tal- pelvi ħafif għal moderat (PID), jiġifieri infezzjonijiet fil- parti ta ’ fuq tal- passaġġ ġenitali, inkluż salpinġite u endometrite.
At the end of the mutual recognition procedure there was a discrepancy between different EU Member States regarding the wording of the indication that should adequately reflect the clinical data submitted by the company, and an official referral for arbitration according to Article 6(12) of Commission Regulation EC No 1084/ 2003, as amended, was notified by Belgium to the CHMP on 19 October 2007.
Fi tmiem il- proċedura ta ’ rikonoxximent reċiproku, kien hemm diskrepanza bejn l- Istati Membri differenti tal- UE fir- rigward tal- formolazzjoni tal- indikazzjoni li tirrifletti b’ mod adegwat id- dejta klinika ippreżentata mill- kumpanija, u riferiment uffiċjali għall- arbitraġġ skont l- Artikolu 6( 12) tar - Regolament tal- Kummissjoni KE Nru 1084/ 2003, kif emendat, ġie nnotifikat mill- Belġju lis- CHMP fid- 19 ta ’ Ottubru 2007.
The main unresolved areas of concern identified by Belgium were in terms of efficacy the emergence of moxifloxacin-resistant strains of N. gonorrhoeae and the feasibility of the treatment in the proposed indication in clinical practice.
L- oqsma ta ’ tħassib ewlenin mhux riżolti identifikati mill- Belġju kienu, f’ termini ta ’ effikaċja, il- feġġa ta ’ razez reżistenti għal moxifloxacin ta ’ N. gonorrhoeae u l- fattibbiltà tal- kura fl- indikazzjoni proposta fil- prattika klinika.
In terms of safety the longer treatment duration, the risk of effects on cartilage in young patients and the risk of QT-prolongation were of concern.
F’ termini ta ’ sigurtà fir- rigward ta ’ kura fit- tul, ir- riskju tal- effetti fuq il - kartilaġni (qarquċa tal- għadam) f’ żgħażagħ u r- riskju tal- prolongament- QT kienu ta ’ tħassib.
The arbitration procedure was discussed by the CHMP at its plenary meeting in November 2007 and a Rapporteur (Dr Harald Enzmann) and Co-Rapporteur (Dr.
Il- proċedura ta ’ arbitraġġ ġiet diskussa mis- CHMP fil- laqgħa plenarja tiegħu f’ Novembru 2007 u nħatru Rapporteur (Dr Harald Enzmann) u Ko- Rapporteur (Dr.
The Referral procedure was initiated on 15 November with the adoption of a CHMP List of Questions to be addressed by the MAHs.
Il- proċedura ta ’ Riferiment inbdiet fil- 15 ta ’ Novembru bl- adozzjoni ta ’ Lista ta ’ Mistoqsijiet tas- CHMP sabiex tiġi indirizzata mid- Detenturi ta ’ l- Awtorizzazzjoni g] at- Tqeg] id fis- Suq (MAHs).
Written explanations were provided by the Marketing Authorisation Holders (MAH) on 18 January 2008 and 27 February 2008.
Spjegi bil- miktub ġew ipprovduti mid- Detenturi tal- Awtorizzazzjonijiet għat- Tqegħid fis- Suq (MAH) nhar it- 18 ta ’ Jannar 2008 u s- 27 ta ’ Frar 2008.
The CHMP considered that moxifloxacin cannot be used in the setting of PID in empirical monotherapy due to the increasing incidence of fluoroquinolone-resistant N. gonorrhoeae, unless a resistant strain can be excluded.
Is- CHMP qies li moxifloxacin ma jistax jintuża fl- istabbiliment tal- PID f’ monoterapija empirika dovuta għal inċidenza miżjuda ta ’ fluoroquinolone- resistant N. gonorrhoeae, sakemm razza reżistenti tista ’ tiġi eskluża.
Moxifloxacin should therefore be given in combination with another appropriate antibacterial agent (e. g. a cephalosporin) for the treatment of mild to moderate PID, unless moxifloxacin-resistant N. gonorrhoeae can be excluded.
Għaldaqstant, Moxifloxacin għandu jingħata f’ kombinazzjoni ma ’ sustanza anti batterjali xierqa oħra (eż. cephalosporin) għall- kura ta ’ PID ħafifa għal moderata, sakemm N. gonorrhoeae reżistenti għal moxifloxacin tkun tista ’ tiġi eskluża.
The Committee further considered that the benefit/ risk balance concerning the use of moxifloxacin up to 14 days in the PID indication remains positive, and that information and recommendations on the use of moxifloxacin, and the measures that should be taken before it is prescribed, are adequately addressed in the ‘ contraindications’ and ‘ special warnings and precautions for use’ sections of the EU SPC.
Il- Kumitat ikkunsidra wkoll li l- bilanċ bejn il- benefiċċju/ riskju dwar l- użu ta ’ moxifloxacin sa 14- il jum fl- indikazzjoni PID jibqa ’ pożittiv, u li l- informazzjoni u r- rakkomandazzjonijiet dwar l- użu ta ’ moxifloxacin, u l- miżuri li għandhom jittieħdu qabel ma jingħata, huma indirizzati adegwatament fis - sezzjonijiet ‘ kontraindikazzjonijiet ’ u ‘ twissijiet speċjali u prekwazjonijiet għall- użu ’ tal- SPC tal- UE.
In view of the data provided on efficacy and safety, the benefit/ risk of the proposed extended indication “ mild to moderate pelvic inflammatory disease” was therefore considered to be positive by the CHMP as the initially proposed wording was adequately revised to reflect the current knowledge.
Minħabba d- dejta pprovduta dwar l- effikaċja u s- sigurtà, il- benefiċċju/ riskju tal- indikazzjoni estiża proposta “ mard infjammatorju ħafif għal moderat tal- pelvi ” għaldaqstant tqies bħala wieħed pożittiv mis- CHMP minħabba li l- formolazzjoni proposta inizjalment ġiet riveduta adegwatament sabiex tirrifletti l- għarfien attwali.
On 19 March 2008, the CHMP recommended the variation to the Marketing Authorisations to include this indication.
Fid- 19 ta ’ Marzu 2008, is- CHMP irrakkomanda l- varjazzjoni tal- Awtorizzazzjonijiet għat- Tqegħid fis - Suq sabiex jinkludu din l- indikazzjoni.
The list of product names concerned is given in Annex I.
Il- lista tal- ismijiet tal- prodotti konċernati hija mogħtija fl- Anness I.
The scientific conclusions are provided in Annex II, together with the amended product information in Annex III.
Il- konklużjonijiet xjentifiċi huma mogħtija fl- Anness II, flimkien mal- informazzjoni dwar il- prodott emendata fl- Anness III.
The final opinion was converted into a Decision by the European Commission on 14 July 2008.
L- opinjoni finali inqelbet f’ Deċiżjoni mill- Kummissjoni Ewropea fl- 14 ta ’ Lulju 2008.
∗ Notes: the information given in this document and its annexes reflects only the CHMP opinion dated 19 March 2008.
∗ Noti: l- informazzjoni mogħtija f’ dan id- dokument u l- annessi tiegħu jirriflettu biss l- opinjoni tas- CHMP datata d- 19 ta ’ Marzu 2008.
The Member States’ competent authorities will continue to keep the product under regular review.
L- awtoritajiet kompetenti tal- Istati Membri sejrin jibqgħu jżommu l- prodott taħt reviżjoni regolari.
LIST OF THE NAMES, PHARMACEUTICAL FORM, STRENGTH OF THE MEDICINAL PRODUCTS, ROUTE OF ADMINISTRATION, APPLICANTS / MARKETING AUTHORISATION HOLDER IN THE MEMBER STATES
LISTA TA` L- ISMIJIET, GĦAMLA FARMAĊEWTIKA, QAWWA TAL- PRODOTTI MEDIĊINALI, MNEJN JINGĦATA, L- APPLIKANTI, ID- DETENTURI TA` L - AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ FL- ISTATI MEMBRI
Marketing Authorisation Holder
Id- Detentur ta ’ l - L- Applikant Awtorizzazzjoni għat - tqegħid fis- suq
(Invented) Name
Isem (Ivvintat)
Austria
L- Awstrija
Novo Nordisk Pharma GmbH Opernring 3-5 A-1010 Vienna Austria
Novo Nordisk Pharma GmbH Opernring 3- 5 A- 1010 Vienna L- Awstrija
Estradiol (as hemihydrate) 0.5 mg Film-coated tablets Oral use + Norethisterone acetate 0.1 mg
Estradiol (bħala hemihydrate) 0. 5 mg + Norethisterone acetate 0. 1 mg
Belgium
Pilloli miksijin b’ rita
Novo Nordisk Pharma
Użu orali
Activelle minor
Il- Belġju
N. V Boulevard International 55/ 6, B-1070 Brussel Belgium
Novo Nordisk Pharma N. V Boulevard International 55/ 6, B- 1070 Brussel Il- Belġju
+ Norethisterone acetate 0.1 mg
Estradiol (bħala hemihydrate) 0. 5 mg + Norethisterone acetate 0. 1 mg
Bulgaria
Użu orali
Czech Republic
Ir- Repubblika Ċeka
Denmark
Użu orali
Estradiol (as hemihydrate) 0.5 mg Film-coated tablets Oral use + Norethisterone acetate 0.1 mg
Estradiol (bħala hemihydrate) 0. 5 mg + Norethisterone
Estonia
Użu orali
Novo Nordisk A/ S Novo Allé DK-2880 Bagsværd Denmark
Id- Danimarka
Activelle
L- Estonja
Finland
Użu orali
Novo Nordisk A/ S Novo Allé DK-2880 Bagsværd
Novo Nordisk A/ S Novo Allé DK- 2880 Bagsværd Id- Danimarka
2 Member State
Pilloli miksijin b’ rita
Marketing Authorisation Holder
Użu orali
Applicant
Franza
(Invented) Name
Novo Nordisk
Pharmaceutical Form
Estradiol (bħala
Route of administration
Pilloli miksijin
Denmark France
Użu orali
30 Rue De Valmy FR-92936 Paris La Defence Cedex France
Pharmaceutique mg/ 0, 1 mg S. A. comprimé 30 Rue De Valmy pelliculé FR- 92936 Paris La Defence Cedex Franza
Activelle 0,5 mg/ 0,1 Estradiol (as hemihydrate) 0.5 mg Film-coated tablets Oral use mg comprimé pelliculé + Norethisterone acetate 0.1 mg
hemihydrate) 0. 5 mg + Norethisterone acetate 0. 1 mg
Germany
b’ rita
Novo Nordisk A/ S Novo Allé DK-2880 Bagsværd Denmark
Novo Nordisk A/ S Noviana Novo Allé DK- 2880 Bagsværd Id- Danimarka
Noviana Estradiol (as hemihydrate) 0.5 mg Film-coated tablets Oral use + Norethisterone acetate 0.1 mg
Estradiol (bħala hemihydrate) 0. 5 mg + Norethisterone acetate 0. 1 mg
Hungary
Użu orali
Novo Nordisk A/ S Novo Allé DK-2880 Bagsværd Denmark
Novo Nordisk A/ S Noviana Novo Allé filmtabletta DK- 2880 Bagsværd Id- Danimarka
Noviana filmtabletta Estradiol (as hemihydrate) 0.5 mg Film-coated tablets Oral use + Norethisterone acetate 0.1 mg
Estradiol (bħala hemihydrate) 0. 5 mg + Norethisterone acetate 0. 1 mg
Iceland
Użu orali
Activelle low 0.5 Estradiol (as hemihydrate) 0.5 mg Film-coated tablets Oral use mg/ 0.1 mg tablets + Norethisterone acetate 0.1 mg filmuhúðaðar töflur
Estradiol (bħala hemihydrate) 0. 5 mg + Norethisterone acetate 0. 1 mg
Ireland
L- Irlanda
Novo Nordisk A/ S Novo Allé DK-2880 Bagsværd Denmark
Novo Nordisk A/ S Activelle Tablets Novo Allé DK- 2880 Bagsværd Id- Danimarka
Activelle Tablets Estradiol (as hemihydrate) 0.5 mg Film-coated tablets Oral use + Norethisterone acetate 0.1 mg
Estradiol (bħala hemihydrate) 0. 5 mg + Norethisterone acetate 0. 1 mg
Italy
L- Italja
Novo Nordisk A/ S Novo Allé DK-2880 Bagsværd Denmark
Novo Nordisk A/ S Activelle 0, 5 Novo Allé mg/ 0, 1 mg DK- 2880 compresse film - Bagsværd rivestite Id- Danimarka
Activelle 0,5 mg/ 0,1 Estradiol (as hemihydrate) 0.5 mg Film-coated tablets Oral use mg compresse film- + Norethisterone acetate 0.1 mg rivestite
Estradiol (bħala hemihydrate) 0. 5 mg + Norethisterone acetate 0. 1 mg
Latvia
Il- Latvja
Noviana 0,5 mg/ 0,1 Estradiol (as hemihydrate) 0.5 mg Film-coated tablets Oral use mg apvalkotā s tabletes + Norethisterone acetate 0.1 mg
Estradiol (bħala hemihydrate) 0. 5 mg + Norethisterone acetate 0. 1 mg
3 Member State
Pilloli miksijin b’ rita
Applicant
Il- Litwanja
(Invented) Name
Novo Nordisk A/ S Activelle Novo Allé DK- 2880 Bagsværd Id- Danimarka
Strength
Estradiol (bħala hemihydrate) 0. 5 mg + Norethisterone acetate 0. 1 mg
Pharmaceutical Form
Pilloli miksijin b’ rita
Route of administration
Użu orali
Lithuania
Il- Lussumburgu
Novo Nordisk A/ S Novo Allé DK-2880 Bagsværd Denmark
Novo Nordisk Activelle Pharma N. V comprimés Riverside pelliculés
Estradiol (as hemihydrate) 0.5 mg Film-coated tablets Oral use + Norethisterone acetate 0.1 mg
Estradiol (bħala hemihydrate) 0. 5 mg +
Luxembourg
Użu orali
Novo Nordisk Pharma N. V Riverside Business Park Boulevard International BE-1070 Brussels Belgium
Business Park Boulevard International BE- 1070 Brussels Il- Belġju
Estradiol (as hemihydrate) 0.5 mg Film-coated tablets Oral use + Norethisterone acetate 0.1 mg
Norethisterone acetate 0. 1 mg
Netherlands
L- Olanda
Flemingweg 18 NL-2408 AV Alphen a/ d Rijn Netherlands
Flemingweg 18 NL- 2408 AV Alphen a/ d Rijn l- Olanda
Norway
Użu orali
Novo Nordisk A/ S
Novo Nordisk A/ S Novo Allé DK- 2880 Bagsværd Id- Danimarka
Noviana 0,5 mg/ 0,1
Noviana 0, 5 mg/ 0, 1 mg tablett filmdrbħalajert
Estradiol (as hemihydrate) 0.5 mg Film-coated tablets Oral use
Estradiol (bħala hemihydrate) 0. 5 mg + Norethisterone acetate 0. 1 mg
Novo Allé DK-2880 Bagsværd Denmark
Pilloli miksijin b’ rita
mg tablett filmdrasjert + Norethisterone acetate 0.1 mg
Użu orali
Portugal
Il- Portugall
Novo Nordisk, A/ S DNK Novo Allé, DK-2880 Bagsvaerd Denmark
Novo Nordisk, A/ S DNK Novo Allé, DK- 2880 Bagsvaerd Id- Danimarka
Activelle Estradiol (as hemihydrate) 0.5 mg Film-coated tablets Oral use + Norethisterone acetate 0.1 mg
Estradiol (bħala hemihydrate) 0. 5 mg + Norethisterone acetate 0. 1 mg
Romania
Użu orali
Noviana comprimate Estradiol (as hemihydrate) 0.5 mg Film-coated tablets Oral use filmate + Norethisterone acetate 0.1 mg
Estradiol (bħala hemihydrate) 0. 5 mg + Norethisterone acetate 0. 1 mg
Slovak Republic
Is- Slovakkja
Novo Nordisk A/ S Novo Allé DK-2880 Bagsværd Denmark
Novo Nordisk A/ S Noviana Novo Allé DK- 2880 Bagsværd
Noviana Estradiol (as hemihydrate) 0.5 mg Film-coated tablets Oral use + Norethisterone acetate 0.1 mg
Estradiol (bħala hemihydrate) 0. 5 mg + Norethisterone
Marketing Authorisation Holder
Pilloli miksijin b’ rita
Applicant
Użu orali
(Invented) Name
5
Strength
Id- Danimarka
Pharmaceutical Form
acetate 0. 1 mg
Slovenia
Is- Slovenja
Estradiol (as hemihydrate) 0.5 mg Film-coated tablets Oral use + Norethisterone acetate 0.1 mg
Estradiol (bħal hemihydrate) 0. 5 mg + Norethisterone acetate 0. 1 mg
Novo Nordisk A/ S Novo Allé
Novo Nordisk A/ S Novo Allé DK- 2880 Bagsværd Id- Danimarka
DK-2880 Bagsværd Denmark
Pilloli miksijin b’ rita
recubiertos de película
Użu orali
Sweden
L- Isvezja
Activelle Estradiol (as hemihydrate) 0.5 mg Film-coated tablets Oral use + Norethisterone acetate 0.1 mg
Estradiol (bħal hemihydrate) 0. 5 mg + Norethisterone acetate 0. 1 mg
Novo Nordisk Pharma Ltd Broadfield Park Brighton Road UK- RH11 9RT Crawley West Sussex United Kingdom
Novo Nordisk Pharma Ltd Broadfield Park Brighton Road UK - RH11 9RT Crawley West Sussex Ir- Renju Unit
Noviana film-coated Estradiol (as hemihydrate) 0.5 mg Film-coated tablets Oral use tablets + Norethisterone acetate 0.1 mg
Estradiol (bħal hemihydrate) 0. 5 mg + Norethisterone acetate 0. 1 mg
5 ANNEX II
Pilloli miksijin b’ rita
SCIENTIFIC CONCLUSIONS AND GROUNDS PRESENTED BY THE EMEA
Użu orali
6 SCIENTIFIC CONCLUSIONS
6 ANNESS II
OVERALL SUMMARY OF THE SCIENTIFIC EVALUATION OF ACTIVELLE AND ASSOCIATED NAMES (SEE ANNEX I)
SOMMARJU ĠENERALI U EVALWAZZJONI XJENTIFIKA TA ’ ACTIVELLE U L - ISMIJIET ASSOĊJATI (ARA L- ANNESS I)
Activelle 0.5 mg/ 0.1 mg is a continuous combined hormone replacement therapy (HRT) product containing 0.5 mg estradiol (E2) and 0.1 mg norethisterone acetate (NETA).
Activelle 0. 5 mg/ 0. 1 mg huwa prodott tat- terapija tar- rimpjazzament ta ’ l- ormoni kombinata kontinwa (HRT) li fih 0. 5 mg estradiol (E2) u 0. 1 mg norethisterone acetate (NETA).
It is intended for once daily administration to postmenopausal women with an intact uterus.
Huwa maħsub sabiex jingħata darba kuljum lil nisa ta ’ wara l- menopawża b’ utru intatt.
It is a lower strength with a lower oestrogen/ progestogen ratio than the currently approved Activelle, which contains 1 mg E2 and 0.5 mg NETA.
Huwa inqas qawwi b’ bilanċ ta ’ l- estroġenu/ proġestoġen iktar baxx mill- prodott Activelle li huwa attwalment approvat u li fih 1 mg E2 u 0. 5 mg NETA.
The referral under article 29(4) of directive 2001/ 83/ EC was notified to the CHMP on March 3rd, 2008 as Germany and France did not consider the application acceptable.
Ir- riferiment skond l- Artikolu 29( 4) tad- Direttiva 2001/ 83/ KE kien innotifikat lis- CHMP fit- 3 ta ’ Marzu, 2008 billi l- Ġermanja u Franza ma qisux l- applikazzjoni bħala waħda aċċettabbli.
Both considered the endometrial safety of Activelle 0.5 mg/ 0.1 mg to be insufficiently demonstrated according to the CHMP guideline for HRT products (EMEA/ CHMP/ 021/ 97 rev 1).
It- tnejn li huma qiesu li s- sigurtà endometrijali ta ’ Activelle 0. 5 mg/ 0. 1 mg ma kinitx intweriet b’ mod suffiċjenti skond il- linja gwida tas- CHMP għall- prodotti tal- HRT (EMEA/ CHMP/ 021/ 97 rev 1).
A list of questions highlighting the issues to be discussed during this procedure was finalised on the 19th of March, 2008.
Fid- 19 ta ’ Marzu, 2008 ġiet iffinalizzata lista ta ’ mistoqsijiet li tissottolineja l- kwistjonijiet li kellhom jiġu diskussi waqt din il- proċedura.
The two issues discussed were as follows:
Iż- żewġ kwistjonijiet diskussi kienu kif ġej:
Endometrial Safety The applicant/ MAH was asked to demonstrate the endometrial safety of Activelle 0.5mg/ 0.1mg for the following reasons:
Sigurtà Endometrijali L- applikant / MAH intalab juri s- sigurtà endometrijali ta ’ Activelle 0. 5mg/ 0. 1mg għar- raġunijiet li ġejjin:
- The endometrial safety data is not in accordance with the European guideline on clinical
- Id- dejta tas- sigurtà endometrijali mhix konformi mal- linja gwida Ewropea dwar l -
investigation of medicinal products for hormone replacement therapy of oestrogen deficiency symptoms in post menopausal women (EMEA/ CHMP/ 021/ 97 rev1).
investigazzjoni klinika ta ’ prodotti mediċinali għat- terapija tar- rimpjazzament ta ’ l- ormoni għas - sintomi tad- defiċjenza ta ’ l- estroġenu f’ nisa ta ’ wara l- menopawża (EMEA/ CHMP/ 021/ 97 rev1).
- The endometrial safety data was extrapolated from another combination containing 1.0 mg estradiol
- Id- dejta dwar is- sigurtà endometrijali ġiet estrapolata minn kombinazzjoni oħra li kien fiha 1. 0
and 0.1mg norethisterone acetate (NETA).
mg estradiol u 0. 1mg norethisterone acetate (NETA).
In this study, the upper limit of the two-sided 95% CI of the incidence of endometrial hyperplasia was higher than the upper limit of 2%, and is therefore not considered acceptable. -The endometrial safety of the combination of oestrogen and progestogen for the new ratio of 0.5mg/ 0.1mg cannot be extrapolated from the already licensed dose of Activelle, which contains 1mg estradiol and 0.5mg NETA.
F’ dan l- istudju, il- limitu ta ’ fuq ta ’ CI ta ’ 95% b’ żewġ naħat ta ’ l- inċidenza ta ’ l- iperplażja endometrijali kien ikbar mil- limitu massimu ta ’ 2%, u għalhekk mhuwiex meqjus aċċettabbli.
In the already licensed dose of Activelle, the ratio between NETA and E2 is 1:2, while this ratio is 1:5 in the new strength of Activelle.
Fid- doża diġà mogħtija liċenzja ta ’ Activelle, il- proporzjon bejn NETA u E2 huwa 1: 2, waqt li dan il- bilanċ huwa 1: 5 fid- doża l- ġdida ta ’ Activelle.
Summary of CHMP Opinion
Sommarju ta ’ l- Opinjoni tas- CHMP
Activelle 0.5 mg/ 0.1 mg is a continuous combined HRT that contains the half dose of estradiol (E2) and the fifth of the dose of norethisterone acetate (NETA) that in the known fixed combination Activelle (E2 1 mg/ NETA 0.5 mg).
Activelle 0. 5 mg/ 0. 1 mg huwa HRT kontinwu kombinat li fih in- nofs doża ta ’ estradiol (E2) u 1/ 5 tad- doża ta ’ norethisterone acetate (NETA) fil- kombinazzjoni fissa magħrufa ta ’ Activelle (E2 1 mg/ NETA 0. 5 mg).
This means that the doses of E2 and NETA are decreased by 50% and 80%, respectively.
Dan ifisser li d- dożi ta ’ E2 u NETA jitnaqqsu b’ 50% u 80%, rispettivament.
Therefore, this new product contains a known progestogen at a lower dose than the known marketed dose, and a new ratio oestrogen/ progestogen (1:5 instead of 1:2).
Għalhekk, dan il- prodott ġdid fih proġestoġen magħruf f’ doża iktar baxxa mid - doża magħrufa mqiegħda fis- suq, u bilanċ ġdid ta ’ l- estroġenu/ proġestoġen (1: 5 minflok 1: 2).
According to the guideline on clinical investigation of medicinal products for hormone replacement therapy of oestrogen deficiency symptoms in postmenopausal women (EMEA/ CHMP/ 021/ 97 Rev.
Skond il- linja gwida ta ’ l- investigazzjoni klinika tal- prodotti mediċinali għat- terapija tar - rimpjazzament ta ’ l- ormoni tas- sintomi tad- defiċjenza tal- estroġenu f’ nisa ta ’ wara l- menopawża (EMEA/ CHMP/ 021/ 97 Rev.
1) endometrial safety has to be demonstrated unequivocally before approval.
1), is- sigurtà endometrijali trid tintwera b’ mod inekwivokabbli qabel l- approvazzjoni.
It states that “ for a new combination of oestrogen/ progestogen (e. g. new administration scheme or new strength) or a new progestogen in a fixed combination, endometrial data are required, except for a known progestogen, with the same administration route and the same progestogen dose as in known fixed combination with oestrogen, where data on endometrial safety can be extrapolated from the fixed combination if exposure to the oestrogen is similar or lower”.
Din il- linja gwida tgħid li “ għal kombinazzjoni ta ’ estroġenu/ proġestoġen (eż. skema ġdida ta ’ amministrazzjoni jew qawwa ġdida) jew proġestoġen ġdid f’ kombinazzjoni fissa, hi meħtieġa dejta endometrijali, ħlief għal proġestoġen magħruf, bl- istess mod ta ’ amministrazzjoni u l- istess doża ta ’ proġestoġen bħal f’ kombinazzjoni fissa magħrufa bl - estroġenu, fejn id- dejta fuq is- sigurtà endometrijali tista ’ tiġi estrapolata minn kombinazzjoni fissa jekk l- estroġenu jkun preżenti f’ livelli simili jew iktar baxxi ”.
According to this recommendation, the applicant provided data from a trial (KLIM/ PD/ 7/ USA) which studied endometrial safety of the combination of E2 1 mg and NETA 0.1 mg.
8 Skond din ir- rakkomandazzjoni, l- applikant ipprovda dejta minn prova (KLIM/ PD/ 7/ USA) li studjat is- sigurtà endometrijali tal- kombinazzjoni ta ’ 1 mg E2 u 0. 1 mg NETA 0. 1 mg.
However, the some members of the CHMP noted that this trial failed to demonstrate the endometrial safety of the combination of E2 1 mg and NETA 0.1 mg, as the upper limit of the two-sided 95% confidence
Madankollu, l- istess membri tas- CHMP innotaw li din il- prova naqset milli turi s- sigurtà endometrijali tal- kombinazzjoni ta ’ 1 mg E2 u 0. 1 mg NETA, billi l- limitu massimu ta ’ l- intervall tal- kunfidenza ta ’ 95% b’ żewġ naħat tal- frekwenza osservata ta ’ l- iperplażja endometrijali kien 2. 90% u għalhekk qabeż il- livell aċċettabbli ta ’ 2%.
7 interval of the observed frequency of endometrial hyperplasia was 2.90% and then exceeded the acceptable limit of 2%.
Id- dejta miġmugħa minn bosta kombinazzjonijiet tal- HRT bl- estroġenu/ proġestin
combinations in Europe show that the incidence of hyperplasia or more serious adverse endometrial outcomes was approximately 0.26% during the first year of treatment, that is well under the observed hyperplasia incidence of 0.8% in the KLIM/ PD/ 7/ USA trial.
sekwenzjali u kontinwi awtorizzati riċentement turi li l- inċidenza ta ’ l- iperplażja jew konsegwenzi endometrijali iktar serji kienu bejn wieħed u ieħor 0. 26% matul l- ewwel sena ta ’ trattament, jiġifieri ferm inqas mill- inċidenza osservata ta ’ l- iperplażja ta ’ 0. 8% fil- prova KLIM/ PD/ 7/ USA.
A new combination should not induce a higher frequency of hyperplasia as compared to the recently authorised combinations.
Kombinazzjoni ġdida m’ għandhiex tinduċi frekwenza ogħla ta ’ iperplażja meta mqabbla ma ’ kombinazzjonijiet awtorizzati riċentament.
- The proportion of proliferative endometrium (71%) was higher, on the contrary the proportion of
Il- proporzjon ta ’ endometriju proliferattiv (71%) kien ogħla; għall- kuntrarju, il- proporzjon
atrophic endometrium was lower (19%) than expected for a continuous combination.
ta ’ endometriju atrofiku kien inqas (19%) milli mistenni mill- kombinazzjoni kontinwa.
Moreover, one endometrial sample from a woman who received the E2 1 mg/ NETA 0.1 mg combination was evaluated as “ disordered proliferative” state.
Madankollu, kampjun endometrijali minn mara li kienet ingħatat kombinazzjoni ta ’ E2 1 mg/ NETA 0. 1 mg ġie evalwat bħala fi stat “ proliferattiv diżordnat ”.
According to the European guideline, the endometrial biopsies should be classified, according to standardized criteria into the general classes of atrophic, proliferative, secretory, hyperplasia without atypia, hyperplasia with atypia, cancer and others.
Skont il- linja gwida Ewropea, il- bijopsiji endometrijali għandhom jiġu klassifikati, skond kriterji standardizzati fi klassijiet ġenerali bħala atrofiċi, proliferattivi, sekretorji, iperplażja mingħajr atipja, iperplażja bl- atipja, kanċer u oħrajn.
The class “ disordered proliferative” used in study KLIM/ PD/ 7/ USA is not well defined and not usually recognized.
Il- klassi “ proliferattiva diżordnata ” użata fl- istudju KLIM/ PD/ 7/ USA mhijiex definita sew u normalment mhijiex rikonoxxuta.
It corresponds to abnormal endometrium and distinction from hyperplasia is not so clear.
Tikkorrispondi għal endometriju anormali u d- distinzjoni mill- iperplażja mhijiex daqshekk ċara.
- For the calculation of the incidence rate of endometrial hyperplasia and the two-sided 95%
Għall- kalkolu tar- rata ta ’ l- inċidenza ta ’ l- iperplażja endometrijali u l- intervall ta ’ konfidenza
confidence interval, in case of insufficient tissue obtained by biopsy and endometrial thickness ≥  5 mm, the biopsy should be repeated or patient excluded from the calculation.
ta ’ 95% b’ żewġ naħat, jekk minn bijopsija jinkiseb ammont insuffiċjenti ta ’ tessut jew ikun hemm ħxuna endometrijali ≥ 5 mm, il- bijopsija għandha terġa ’ ssir jew inkella l- pazjent  jitneħħa mill- kalkolu.
In the present study, 7 samples had insufficient tissue and endometrial thickness > 4mm (the cut-off point for endometrial thickness was 4 mm).
Fl- istudju attwali, seba ’ kampjuni kellhom tessut insuffiċjenti u ħxuna endometrijali > 4mm (il- punt kruċjali għall- ħxuna endometrijali kien 4 mm).
Consequently, these 7 samples should have been excluded from the final calculation.
Konsegwentament, dawn is- seba ’ kampjuni kellhom jiġu esklużi mill- kalkolu finali.
Taking into account the points above, the some CHMP were of the opinion that endometrial safety of Activelle 0.5 mg/ 0.1 mg could not be supported by the KLIM/ PD/ 7/ USA trial.
Meta qies il- punti ta ’ hawn fuq, l- istess CHMP kien tal- fehma li s- sigurtà endometrijali ta ’ Activelle 0. 5 mg/ 0. 1 mg ma setgħetx tiġi appoġġjata mill- prova ta ’ KLIM/ PD/ 7/ USA.
However, a majority of CHMP members endorsed the applicant/ MAH’ s approach to provide a very low dose alternative of combined continuous HRT.
Madankollu, l- maġġoranza tal- membri tas- CHMP approvaw l- approċċ ta ’ l- applikant/ MAH li jipprovdi alternattiva b’ doża baxxa ta ’ HRT kontinwu kombinat.