qanastek/EMEA-V3 huggingface dataset:
Given that there are studies demonstrating negative effects of combined HRT on the risk of breast cancer and cardiovascular complications, the general recommendation for HRT is to only treat women with severe symptoms, negatively affecting their quality of life.
Meta wieħed iqis li hemm studji li juru effetti negattivi tal- HRT kombinat dwar ir- riskju tal- kanċer tas- sider u l- kumplikazzjonijiet kardjovaskulari, ir- rakkomandazzjoni ġenerali għall- HRT hi li jiġu ttrattati biss nisa b’ sintomi severi, li jkunu qed jaffettwaw il- kwalità tal- ħajja b’ mod negattiv.
The majority of the CHMP considered that the applicant/ MAH had adequately justified why an endometrial biopsy study on the exact dose was not performed, unlike with Activelle 0,5mg/ 0,1mg.
Il- maġġoranza tas- CHMP qiesu li l- applikant/ MAH kien iġġustifika adegwatament il- għala ma kienx sar studju fuq il- bijopsija endometrijali fuq id- doża eżatta, b’ differenza għal Activelle 0, 5mg/ 0, 1mg.
Based on several other studies of various doses of 1) unopposed oestrogens, 2) oestrogen-progestogen sequential combinations and 3) oestrogen-progestogen continuous combinations, the CHMP considered it reasonable and scientifically acceptable to extrapolate that this low dose continuous oestrogen-progestogen combination would result in a considerably lower rate of endometrial hyperplasia than seen with a combination containing twice the oestrogen dose.
Abbażi ta ’ diversi studji oħrajn ta ’ diversi dożi ta ’ 1) estroġeni mhux opponuti, 2) kombinazzjonijiet sekwenzjali ta ’ estroġenu- proġestoġen u 3) kombinazzjonijiet kontinwi ta ’ estroġenu- proġestoġen, is- CHMP qies li kien raġonevoli u xjentifikament aċċettabbli li jestrapola li din id- doża baxxa ta ’ kombinazzjoni kontinwa ta ’ estroġenu- proġestoġen kienet se tirriżulta f’ rata konsiderevolment iktar baxxa ta ’ iperplażja endometrijali minn dik li dehret f’ kombinazzjoni li fiha d- doppju tad- doża ta ’ l- estroġenu.
In a systematic review of 30 randomized controlled trials, unopposed moderate or high dose oestrogen therapy, when compared to placebo, was associated with a significant increase in rates of endometrial hyperplasia with increasing rates at longer duration of treatment (Lethaby et al.
Cochrane database of
Cochrane database of systematic reviews 2004; 3).
9 systematic reviews 2004; 3).
In this review, progestogen addition as continuous therapy was more effective than sequential therapy in reducing the risk of endometrial hyperplasia at longer duration of treatment.
F’ din l- analiżi, iż- żieda ta ’ proġestoġen bħala terapija kontinwa kienet iktar effettiva mit- terapija sekwenzjali fit- tnaqqis tar- riskju ta ’ l- iperplażja enodmetrijali aktar ma jdum it- trattament.
There was evidence of a higher incidence of hyperplasia when the progestogen was given every three months compared to when the progestogen was given sequentially every month.
Kien hemm evidenza ta ’ inċidenza ogħla ta ’ iperplażja meta l - proġestoġen ingħata kull tliet xhur meta mqabbel ma ’ meta l- proġestoġen ingħata sekwenzjalment kull xahar.
There was no significant difference in the rate of endometrial hyperplasia of continuous oestrogen- progestogen combinations in comparison with placebo after 12 and 24 months.
Ma kienx hemm differenza sinnifikanti fir- rata ta ’ iperplażja endometrijali ta ’ kombinazzjonijiet kontinwi ta ’ estroġenu- proġestoġen meta mqabbla mal - plaċebo wara 12 u 24 xahar.
This systematic review therefore supports that a continuous combined low dose regimen, as in Activelle 0,5mg/ 0,1mg, would provide sufficient endometrial protection.
Għalhekk, din l- analiżi sistematika tappoġġja l- idea li terapija b’ doża baxxa kombinata kontinwa, bħal f’ Activelle 0, 5mg/ 0, 1mg, tipprovdi protezzjoni enodometrijali suffiċjenti.
8 Additional data on effects of continuous oestrogen – progestogen combined products on emdometrial hyperplasia.
Dejta addizzjonali fuq l- effetti ta ’ prodotti b’ kombinazzjonijiet kontinwi ta ’ estroġenu – proġestoġen fuq l- iperplażja kombinata.
The applicant was asked to provide any additional data, from clinical and observational studies, of relevance for the effects of continuous oestrogen-progestogen combined products on endometrial hyperplasia or endometrial cancer.
L- applikant intalab jipprovdi dejta addizzjonali, minn studji kliniċi u ta ’ osservazzjoni, ta ’ relevanza għall- effetti fuq prodotti b’ kombinazzjonijiet kontinwi ta ’ estroġenu- proġestoġen fuq l - iperplażja endometrijali jew il- kanċer endometrijali.
Summary of CHMP’ s Opinion The CHMP noted that the applicant had provided the following arguments to support the endometrial safety of Activelle 0.5 mg/ 0.1 mg: a. the proliferative effect of unopposed oestrogens on the endometrium is dose-dependant, b. this proliferative effect of unopposed oestrogens is time-dependant, especially for high oestrogen doses, c. continuous combined therapy over long duration is more protective that sequential therapy in the prevention of endometrial hyperplasia or carcinoma.
Sommarju ta ’ l- Opinjoni tas- CHMP Is- CHMP innota li l- applikant kien ipprovda dawn l- argumenti biex jappoġġja s- sigurta endometrijali ta ’ Activelle 0. 5 mg/ 0. 1 mg: a. l- effett proliferattiv ta ’ l- estroġeni mhux opponuti fuq l- endometriju jiddependi mid- doża, b. dan l- effett proliferattiv ta ’ l- estroġeni mhux opponuti fuq l- endometriju jiddependi mill- ħin, speċjalment għal dożi għoljin ta ’ estroġenu, c. terapija kombinata kontinwa li ddum ħafna hija iktar protettiva minn terapija sekwenzjali fil - prevenzjoni ta ’ l- iperplażja jew karċinoma endometrijali.
Dose-dependency of the proliferative effect of unopposed oestrogens
Id- dipendenza fuq id- doża ta ’ l- effett proliferattiv ta ’ l- estroġeni mhux opponuti
The dose-dependency of the proliferative effect of unopposed oestrogens on the endometrium was sustained by data from the KLIM/ PD/ 11/ USA trial for E2 (0.5 mg and 1 mg) and from Pickar et al for conjugated equine oestrogens (CEE, 0.3 to 0.625 mg).
Id- dipendenza fuq id- doża ta ’ l- effett proliferativ ta ’ l- estroġeni mhux opponuti fuq l- endometriju issaħħet b’ dejta mill- prova KLIM/ PD/ 11/ USA għal E2 (0. 5 mg u 1 mg) u minn Pickar et al għal estroġeni ta ’ ekwini konġugati (CEE, minn 0. 3 sa 0. 625 mg).
- KLIM/ PD/ 11/ USA study:
- L- istudju KLIM/ PD/ 11/ USA:
This study focused on prevention of osteoporosis but endometrial safety of unopposed E2 0.5 mg or 1 mg during 2 years was also assessed.
Dan l- istudju ffoka fuq il- prevenzjoni ta ’ l- ostejoporożi, iżda s- sigurtà endometrijali ta ’ E2 0. 5 mg jew 1 mg mhux opponuti matul sentejn ġiet ivvalutata wkoll.
It should be noted that sample size was very small (22 to 29 women), and no 95% confidence intervals for the incidence of hyperplasia are stated.
Għandu jiġi nnutat li d- daqs tal- kampjun kien żgħir (bejn 22 u 29 mara), u ma ssemmew l- ebda intervalli ta ’ kunfidenza ta ’ 95% għall- inċidenza ta ’ l- iperplażja.
It can also be noticed that the monitoring of the endometrial thickness by pelvic ultrasound showed a significant increase, even with 0.5 mg E2, which was not reported in the placebo group.
Wieħed jista ’ jinnota wkoll li s - sorveljanza tal- ħxuna endometrijali permezz ta ’ ultrasound pelviku wriet żieda sinjifikanti, anke b’ 0. 5 mg E2, li ma ġietx irrapportata fil- grupp tal- plaċebo.
Thus, in spite of the dose-related increase in incidence of hyperplasia, data could be considered insufficient to draw definite conclusions regarding endometrial safety of E2 0.5 mg.
Għalhekk, minkejja żieda relatata mad- doża fl- inċidenza ta ’ l- iperplażja, id- dejta setgħet titqies insuffiċjenti biex wieħed jasal għal konklużjonijiet definiti dwar is- sigurtà endometrijali ta ’ E2 0. 5 mg.
The objective of this study was to determine the endometrial safety of 2 years of treatment with low CEE doses (0.3, 0.45 and 0.625 mg).
L- objettiv ta ’ dan l- istudju kien li jiddetermina s- sigurtà endometrijali ta ’ sentejn trattament b’ dożi baxxi ta ’ CEE (0. 3, 0. 45 u 0. 625 mg).
Data suggest a dose-response relationship between unopposed-CEE and risk of hyperplasia.
Id- dejta tissuġġerixxi li hemm relazzjoni dipendenti fuq id- doża bejn is- CEE mhux opponut u r- riskju ta ’ l- iperplażja.
As for the KLIM/ PD/ 11/ USA trial, sample size may be considered too low to draw definite conclusion with regard to endometrial safety.
Rigward il - prova KLIM/ PD/ 11/ USA, id- daqs tal- kampjun jista ’ jitqies żgħir wisq biex iwassal għal konklużjoni definita dwar is- sigurtà endometrijali.
In conclusion, the CHMP agreed that the proliferative effect of unopposed oestrogens on endometrium is dependent on the dose of oestrogens.
10 Bħala konklużjoni, is- CHMP qabel li l- effetti proliferattivi ta ’ l- estroġeni mhux opponuti fuq l - endometriju huma dipendenti mid- doża ta ’ l- estroġeni.
However, some CHMP members considered that even if the observed hyperplasia incidence with the new dose E2 0.5 mg/ NETA 0.1 mg should be lower than that observed with the E2 1mg/ NETA 0.1mg combination, it is not unequivocally demonstrated that it will be in an acceptable range regarding the European guideline.
Madankollu, xi membri tal- CHMP qiesu li anke jekk l- inċidenza osservata ta ’ l- iperplażja mad- doża ġdida ta ’ E2 0. 5 mg/ NETA 0. 1 mg għandha tkun inqas minn dik osservata b’ kombinazzjoni ta ’ E2 1mg/ NETA 0. 1mg, ma ntweriex inekwivokalment li se tkun fil- limiti aċċettabbli skond il- linja gwida Ewropea.
Duration-dependency of the proliferative effect of unopposed oestrogens
Id- dipendenza fuq id- doża ta ’ l- effett proliferattiv ta ’ l- estroġeni mhux opponuti
It is well established that the use of unopposed oestrogens in women with an intact uterus is associated with a gradually increasing incidence of hyperplasia with duration of treatment.
Huwa stabbilit sew li l- użu ta ’ estroġeni mhux opponuti fin- nisa b’ utru intatt huwa assoċjat ma ’ żieda gradwali fl- inċidenza ta ’ l- iperplażja fin- nisa waqt it- trattament.
However, some CHMP members were of the opinion that the data provided are insufficient to support that it is not the case with 0.5 mg E2.
Madankollu, xi membri tas- CHMP kienu tal- fehma li d- dejta pprovduta mhijiex biżżejjed biex tappoġġja l- ħsieb li dan mhuwiex il- każ bi 0. 5 mg E2.
The sample size of the KLIM/ PD/ 11/ USA study may be considered too small to draw any definite conclusion regarding endometrial safety of E2 0,5 mg, even for 2 year- treatment.
Id- daqs tal- kampjun ta ’ l- istudju KLIM/ PD/ 11/ USA jista ’ jitqies żgħir wisq biex iwassal għal xi konklużjoni definita dwar is- sigurtà endometrijali ta ’ E2 0. 5 mg, anke għal trattament li jdum sentejn.
In Pickar J. H. et al, the relationship between treatment duration and incidence of hyperplasia was also observed with the low dose of 0.3 mg CEE.
Fl- istudju ta ’ Pickar J. H. et al, ir- relazzjoni bejn id- dewmien tat- trattament u l- inċidenza ta ’ l- iperplażja ġew osservati wkoll bid- doża baxxa ta ’ 0. 3 mg CEE.
Continuous combined therapy versus sequential therapy in the prevention of endometrial hyperplasia or carcinoma
Terapija kontinwa kombinata mqabbla ma ’ terapija sekwenzjali fil- prevenzjoni ta ’ l - iperplażja jew karċinoma endometrijali
The Cochrane review (Lethaby et al 2004) and analysis of available observational data (Anderson 2003, Beresford 97, Jain 2000, Hill 2000, Hully 98, MWS 2005, Newcomb 2003, Pike 97, Pukkala 2001, Weiderpass 99) suggest that addition of progestogen for at least 12 days per cycle reduces, but may not completely eliminate, the increased incidence of endometrial cancer caused by unopposed oestrogens; and that combined continuous HRT does not increase the risk of endometrial cancer.
L- analiżi Cochrane (Lethaby et al 2004) u l- analiżi ta ’ dejta minn osservazzjonijiet disponibbli (Anderson 2003, Beresford 97, Jain 2000, Hill 2000, Hully 98, MWS 2005, Newcomb 2003, Pike 97, Pukkala 2001, Weiderpass 99) jissuġġerixxu li ż- żieda ta ’ proġestoġen għal ta ’ l- anqas 12- il jum f’ kull ċiklu tnaqqas, iżda tista ’ ma teliminax kompletament iż- żieda fl- inċidenza tal- kanċer endometrijali ikkawżat minn estroġeni mhux opponuti, u li HRT ikkombinat kontinwu ma jżidx ir- riskju ta ’ kanċer endometrijli.
However, the CHMP noted that the strengths studied did not include E2 0.5 mg/ NETA 0.1 mg.
Madankollu, is- CHMP innota li l- qawwiet studjati ma kinux jinkludu E2 0. 5 mg/ NETA 0. 1 mg.
The only trial that studied the 0.1 mg NETA dose was the Novo Nordisk study KLIM/ PD/ 7/ USA, which some CHMP members considered to be inconclusive.
L- unika prova li studjat id- doża ta ’ 0. 1 mg NETA kien l - istudju ta ’ Novo Nordisk KLIM/ PD/ 7/ USA, li xi membri tas- CHMP qiesu bħala wieħed inkonklussiv.
Therefore, data from higher dose of NETA or other progestogens may not be extrapolated to the NETA 0.1 mg dose.
Għalhekk, id- dejta minn doża ogħla ta ’ NETA jew proġestoġeni oħra ma tistax tiġi estrapolata għad- doża ta ’ 0. 1 mg NETA.
Taking the above arguments on board, the majority of CHMP members were of the opinion that the data presented demonstrate the importance of types of oestrogen-progestogen regimens for the association with endometrial cancer risk.
Meta qiesu dawn l- argumenti, il- maġġoranza tal- membri tas- CHMP kienu tal- fehma li d- dejta ppreżentata turi l- importanza ta ’ tipi ta ’ reġimens b’ estroġenu- proġestoġen għall- assoċjazzjoni mar- riskju tal- kanċer endometrijali.
These data, along with data on effects on endometrial hyperplasia, convincingly support the assumption that a continuous combined regimen protects the endometrium from both hyperplasia and neoplasia, a protective effect that seems to be both relative and absolute (i. e. conferring a lower risk than for untreated women) and that seems to increase with duration of intake.
Din id- dejta, flimkien ma ’ dejta dwar l- effetti fuq l- iperplażja endometrijali, tagħti appoġġ konvinċenti għas- suppożizzjoni li trattament kombinat kontinwu jipproteġi l- endometriju kemm mill- iperplażja kif ukoll min- neoplasja, effett protettiv li jidher li hu kemm relattiv kif ukoll assolut (jiġifieri jqiegħed lin- nisa trattati f’ riskju iżgħar min- nisa mhux ittrattati) u dan jidher li jiżdied iktar ma jdum it- trattament.
This observation is also consistent with the known pharmacodynamic effects of added progestogens on the endometrium, e. g. down regulation of oestrogen receptor (ER) levels and endometrial atrophy.
Din l- osservazzjoni hija konsistenti wkoll ma ’ l- effetti farmakodinamiċi magħrufa ta ’ proġestoġeni miżjuda fuq l- endometriju, eż. ir - regolazzjoni ’ l isfel tal- livelli tar- riċetturi ta ’ l- estroġenu (ER) u l- atrofija endometrijali.
On the basis of all these data, the majority of the CHMP was of the opinion that Activelle 0.5 mg estradiol/ 0.1 mg NETA is safe in terms of endometrial hyperplasia and neoplasia risk and that it offers a needed low-dose hormone replacement alternative with a positive benefit-risk.
Abbażi ta ’ din id- dejta kollha, il- maġġoranza tas- CHMP kienet tal- fehma li Activelle 0. 5 mg estradiol/ 0. 1 mg NETA huwa sigur f’ termini tar- riskju ta ’ l- iperplażja endometrijali u tan- neoplasja u joffri alternattiva meħtieġa għar- rimpjazzament ta ’ doża baxxa ta ’ ormoni b’ bilanċ pożittiv bejn il - benefiċċju u r- riskju.
10 GROUNDS
11 RAĠUNIJIET
Whereas
Billi
- the endometrial safety of Activelle 0.5mg estradiol/ 0.1mg NETA product is sufficiently supported
- is- sigurtà endometrijali tal- prodott Activelle 0. 5mg estradiol/ 0. 1mg NETA hija appoġġjata
from the submitted data.
b’ mod suffiċjenti bid- dejta sottomessa.
- on the level of endometrial hyperplasia, the trial on the 1 mg estradiol/ 0.1 mg NETA product
- fil- livell ta ’ l- iperplażja endometrijali, il- prova fuq il- prodott b’ 1 mg estradiol/ 0. 1 mg NETA
indicates an adequate protective effect, albeit with an upper confidence limit of the hyperplasia rate estimate exceeding recommendation in the guideline.
tindika effett protettiv adegwat, għalkemm b’ limitu ta ’ kunfidenza ta ’ fuq ta ’ l- istima tar- rata ta ’ l- iperplażja li jaqbeż ir- rakkomandazzjoni fil- linja gwida.
- the risk of hyperplasia in Activelle 0.5 mg estradiol/ 0.1 mg NETA is lower than for the 1 mg
- ir- riskju ta ’ l- iperplażja f’ Activelle 0. 5 mg estradiol/ 0. 1 mg NETA huwa iktar baxx milli għall -
estradiol/ 0.1 mg NETA product, containing one half of the dose as compared with the commercially available HRT product.
prodott NETA 1 mg estradiol/ 0. 1 mg, li fih nofs id- doża meta mqabbel ma ’ prodott HRT kummerċjalment disponibbli.
- the addition of a progestogen for 12 days of a monthly treatment cycle is considered sufficient to
- iż- żieda ta ’ proġestoġen għal 12- il jum f’ ċiklu ta ’ trattament ta ’ kull xahar hi meqjusa suffiċjenti
protect the endometrium from an excess risk of hyperplasia (and ultimately endometrial cancer), and even longer periods, and a continuous combination will confer increasing protective effects.
biex tipproteġi l- endometriju minn riskju eċċessiv ta ’ iperplażja (u finalment kanċer endometrijali), u anke perjodi itwal, u kombinazzjoni kontinwa twassal għal iktar effetti protettivi.
the CHMP has recommended the granting of the Marketing Authorisation(s) for which the Summary of Product Characteristics, labelling and package leaflet are set out in Annex III for Activelle and associated names (see Annex I).
Is- CHMP irrakkomanda l- għoti ta ’ l- Awtorizzazzjoni( jiet) għat- Tqegħid fis- Suq li għalihom, is - Sommarju tal- Karatteristiċi tal- Prodott, it- tikketta u l- fuljett ta ’ tagħrif huma stabbiliti fl- Anness III għal Activelle u ismijiet assoċjati (ara l- Anness I).
12 SUMMARY OF PRODUCT CHARACTERISTICS
12 ANNESS III
13 1.
13 SOMMARJU TAL- KARATTERISTIĊI TAL- PRODOTT
Activelle and associated names (see Annex I) 0.5 mg/ 0.1 mg film-coated tablets [See Annex I – To be completed nationally]
Activelle u ismijiet assoċjati miegħu (ara Anness I) 0. 5 mg/ 0. 1 mg pilloli miksijin b' rita [Ara Anness I – Biex timtela mill- pajjiż partikolari]
Each film-coated tablet contains:
Kull pillola miksija b' rita fiha:
Estradiol 0.5 mg (as hemihydrate) and norethisterone acetate 0.1 mg.
Estradiol 0. 5 mg (bħala hemihydrate) u norethisterone acetate 0. 1 mg.
Each film-coated tablet contains lactose monohydrate 37.5 mg.
Għal- lista kompleta ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1.
White, round, biconvex tablets with a diameter of 6 mm.
Pilloli bojod, tondi, konvessi b' dijametru ta '6 mm.
The tablets are engraved with “ NOVO 291” on one side and the “ APIS” on the other side.
Il- pilloli għandhom imnaqqax “ NOVO 291 ” fuq naħa u “ APIS ” fuq in- naħa l- oħra.
Hormone Replacement Therapy (HRT) for oestrogen deficiency symptoms in women more than one year after menopause.
Terapija Ormonali Sostitwita (HRT) għal nisa b' sintomi ta 'nuqqas ta' estroġenu wara aktar minn sena mill- menopawsa.
The experience of treating women older than 65 years is limited.
L- esperjenza ta 'kura fin- nisa ta' aktar minn 65 sena hija limitata.
Activelle is a continuous combined hormone replacement therapy intended for use in women with an intact uterus.
Activelle huwa terapija ormonali sostitwita, ikkombinata u kontinwa maħsub għall- użu f' nisa bl - utru intatt.
One tablet should be taken orally once a day without interruption, preferably at the same time every day.
Għandha tittieħed pillola waħda darba kuljum mill- ħalq mingħajr waqfien, preferibbilment fl- istess ħin kuljum.
For initiation and continuation of treatment of postmenopausal symptoms, the lowest effective dose for the shortest duration (see also section 4.4) should be used.
Fil- bidu u fit- tkomplija tal- kura ta 'sintomi ta' wara l- menopawsa, għandha tintuża l- inqas doża effettiva fl- iqsar żmien (ara wkoll sezzjoni 4. 4).
A switch to a higher dose product, e. g.
Bidla għal prodott b' doża ikbar, eż.
Activelle 1 mg/ 0.5 mg tablets, should be considered if the response after three months is insufficient for satisfactory symptom relief.
Activelle pilloli ta '1 mg/ 0. 5 mg, għandha tiġi kkunsidrata jekk ir- rispons wara tliet xhur ma jkunx biżżejjed għal serħan sodisfaċenti mis- sintomi.
In women with amenorrhea and not taking HRT or women transferring from another continuous combined HRT product, treatment with Activelle may be started on any convenient day.
F' nisa b' amenorreja u li ma jieħdux HRT jew nisa li jaqilbu minn prodott tal- HRT ikkombinat u kontinwu ieħor, kura b' Activelle tista 'tinbeda f' kwalunkwe ġurnata konvenjenti.
In women transferring from sequential HRT regimens, treatment should start right after their withdrawal bleeding has ended.
F' nisa li jaqilbu minn trattament sekwenzjali ta 'HRT, il- kura trid tinbeda hekk kif tispiċċa l- mestrwazzjoni fl - intervall tal- kura.
If the patient has forgotten to take a tablet, the tablet should be taken as soon as possible within the next twelve hours.
15 Jekk il- pazjenta tinsa tieħu pillola, il- pillola għandha tittieħed kemm jista 'jkun malajr fi żmien tnax- il siegħa.
Forgetting a dose may increase the likelihood of breakthrough bleeding and spotting.
Doża li ma tittiħidx tista 'żżid il- probabbiltà ta' mestrwazzjoni riżultat ta 'intervalli fil- kura u taqtir ħafif ta' demm waqt il- kura.
Active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction) Acute liver disease, or a history of liver disease as long as liver function tests have failed to return to normal
Sensittività eċċessiva għas- sustanzi attivi jew għal xi sustanzi mhux attivi • Kanċer tas- sider magħruf, fil- passat jew suspettat • Tumuri malinni magħrufa jew suspettati, dipendenti fuq estroġenu (eż. kanċer ta 'l - • endometriju) Demm mill- ġenitali li ma jinstabx waqt dijanjosi • Iperplejżja ta' l- endometriju mhux ikkurata • Trombo- emboliżmu tal- vini idjopatika preċedenti jew attwali (trombożi tal- vini fondi, • emboliżmu pulmonari) Mard trombo- emboliku arterjali attiv jew riċenti (eż. anġina, infart mijokardijaku) • Mard tal- fwied akut, jew passat ta 'mard tal- fwied sakemm it- testijiet tal- funzjoni tal - • fwied ma ġewx għan- normal Porfirja •
For the treatment of postmenopausal symptoms, HRT should only be initiated for symptoms that adversely affect quality of life.
Għall- kura ta 'sintomi ta' wara l- menopawsa, l- HRT għandu jinbeda biss għal sintomi li jaffettwaw il- kwalità tal- ħajja b' mod negattiv.
In all cases, a careful appraisal of the risks and benefits should be undertaken at least annually and HRT should only be continued as long as the benefit outweighs the risk.
F' kull każ, għandhom jiġu stmati bir- reqqa r- riskji u l- benefiċċji ta 'l- inqas kull sena u l- HRT għandu jitkompla sakemm il- benefiċċji jkunu akbar bil- qabda mir- riskji.
Medical examination/follow-up Before initiating or reinstituting HRT, a complete personal and family medical history should be taken.
Eżami mediku/ eżami ta 'wara l- kura Qabel ma jinbeda jew jerġa' jiġi istitwit l- HRT, għandha tittieħed l- istorja medika kompleta personali u tal- familja.
Physical (including pelvic and breast) examination should be guided by this and, by the contraindications and warnings for use.
L- eżami fiżiku (inkluż dak pelviku u tas- sider) għandu jiġi ggwidat minn dan u mill- kontra- indikazzjonijiet u twissijiet għall- użu.
During treatment periodic check-ups are recommended of a frequency and nature adapted to the individual woman.
Matul il- kura huma rrakkomandati eżamijiet mediċi perjodiċi ta 'frekwenza u ta' natura adattati għall- mara individwali.
Women should be advised what changes in their breasts should be reported to their doctor or nurse (see section below “Breast cancer”).
In- nisa għandhom jingħataw parir liema bidliet f' sidirhom għandhom jiġu rrappurtati lit- tabib jew lill - infermiera tagħhom (ara s- sezzjoni ta 'hawn taħt "Kanċer tas- sider").
Investigations, including mammography, should be carried out in accordance with currently accepted screening practices, modified to the clinical needs of the individual.
Għandhom jiġu mwettqa investigazzjonjiet, inkluża l- mammografija, skond il- prattiċi attwali aċċettati ta 'eżaminazzjoni, immodifikati għall- ħtiġijiet kliniċi ta' l- individwa.
Conditions which need supervision If any of the following conditions are present, have occurred previously, and/or have been aggravated during pregnancy or previous hormone treatment, the patient should be closely supervised.
Kundizzjonijiet li jeħtieġu superviżżjoni Jekk kwalunkwe mill- kundizzjonijiet li ġejjin huma preżenti, seħħew fil- passat, u/ jew iggravaw waqt it- tqala jew kura ormonali preċedenti, il- pazjenta għandha tiġi kkontrollata mill- viċin.
It should be taken into account that these conditions may recur or be aggravated during treatment with Activelle in particular:
Għandu jiġi kkunsidrat li dawn il- kundizzjonijiet jistgħu jerġgħu jitfaċċaw jew jiggravaw waqt il - kura b' Activelle b' mod partikolari:
Leiomyoma (uterine fibroids) or endometriosis
Leijomijoma (fibrojdi fl- utru) jew endometrijosi •
A history of, or risk factors for, thromboembolic disorders (see below)
Passat ta ', jew fatturi ta' riskju ta ', mard trombo- emboliku (ara hawn taħt) •
1st degree heredity for breast cancer
Fatturi ta 'riskju ta' tumuri dipendenti fuq estroġenu, eż. eredità ta 'l- ewwel grad għall - • kanċer tas- sider
Hypertension
Pressjoni għolja •
Liver disorders (e.g. liver adenoma)
Mard tal- fwied (eż. adenoma fil- fwied) •
Diabetes mellitus with or without vascular involvement
16 Dijabete mellitus b' involviment vaskulari jew mingħajru •
Cholelithiasis
Kolelitijasi •
Migraine or (severe) headache
Emigranja jew uġigħ ta 'ras (qawwi) •
Systemic lupus erythematosus
Lupus eritematosu sistemiku •
A history of endometrial hyperplasia (see below)
Passat ta 'Iperplejżja ta' l- endometriju (ara hawn taħt) •
Epilepsy
Epilessija •
Asthma
Ażma •
Otosclerosis
Otosklerosi •
15 Reasons for immediate withdrawal of therapy Therapy should be discontinued in case a contra-indication (see section 4.3) is discovered and in the following situations: • Jaundice or deterioration in liver function
Suffejra jew deterjorament fil- funzjoni tal- fwied •
• Significant increase in blood pressure
Żieda sinifikanti fil- pressjoni tad- demm •
• New onset of migraine-type headache
L- ewwel attakk qawwi ta 'wġigħ ta' ras tat- tip ta 'emigranja •
Endometrial hyperplasia The risk of endometrial hyperplasia and carcinoma is increased when oestrogens are administered alone for prolonged periods (see section 4.8).
Iperplejżja ta 'l- endometriju Ir- riskju ta' iperplejżja ta 'l- endometriju u karċinoma jiżdied meta estroġeni jingħataw waħidhom għal perjodi twal (ara sezzjoni 4. 8).
The addition of a progestagen for at least 12 days per cycle in non-hysterectomised women greatly reduces this risk.
Iż- żieda ta 'proġestoġenu għal mill- inqas 12- il jum kull ċiklu f' nisa li ma saritilhomx isterektomija tnaqqas dan ir- riskju bil- kbir.
Breakthrough bleeding and spotting may occur during the first months of treatment.
Fl- ewwel xhur tal- kura jistgħu jseħħu l- mestrwazzjoni riżultat ta 'intervalli fil- kura u taqtir ħafif ta' demm waqt il- kura.
If breakthrough bleeding or spotting appears after some time on therapy, or continues after treatment has been discontinued, the reason should be investigated, which may include endometrial biopsy to exclude endometrial malignancy.
Jekk il- mestrwazzjoni riżultat ta 'intervalli fill- kura jew taqtir ħafif ta' demm waqt il- kura jitfaċċaw wara xi żmien fuq it- terapija, jew ikomplu wara li l- kura tkun ġiet sospiża, għandha tiġi investigata r- raġuni, li tista 'tinkludi bijopsija ta' l- endometriju sabiex jiġi eskluż tumur malinn fl- endometriju.
Breast cancer A randomised placebo-controlled trial, the Women’s Health Initiative study (WHI), and epidemiological studies, including the Million Women Study (MWS), have reported an increased risk of breast cancer in women taking oestrogens, oestrogen-progestagen combinations or tibolone for HRT for several years (see section 4.8).
Kanċer tas- sider Prova klinika tat- tip randomised ikkontrollata bil- plaċebo, l- Inizjattiva għal- Saħħet in- Nisa (WHI), u studji epidemjoloġiċi, fosthom l- Istudju ta 'Miljun Mara (MWS), irrapportaw żieda ta' kanċer tas- sider f' nisa li jieħdu estroġeni, kombinazzjonijiet ta 'estroġeni- proġestoġeni jew tibolone għall - HRT għal ħafna snin (ara sezzjoni 4. 8).
For all HRT, an excess risk becomes apparent within a few years of use and increases with duration of intake but returns to baseline within a few (at most five) years after stopping treatment.
Għall- HRT kollha, riskju eċċessiv isir evidenti wara ftit snin ta 'użu u jiżdied tul iż- żmien tat- teħid iżda jerġa' lura għal- linja bażi fi ftit (l- aktar ħames) snin wara t- twaqqif tal- kura.
In the MWS, the relative risk of breast cancer with conjugated equine oestrogens (CEE) or estradiol (E2) was greater when a progestagen was added, either sequentially or continuously, and regardless of type of progestagen.
Fil- MWS, ir- riskju relattiv ta 'kanċer tas- sider b' estroġeni ekwini kkonjugati (CEE) jew estradiol (E2) kien ikbar meta proġestoġenu ġie miżjud, kemm b' mod sekwenzjali jew kontinwu, minkejja t- tip ta' proġestoġenu.
There was no evidence of a difference in risk between the different routes of administration.
Ma kien hemm l- ebda evidenza ta 'riskji differenti bejn ir- rotot differenti ta' mnejn jingħataw.
In the WHI study, the continuous combined conjugated equine oestrogen and medroxyprogesterone acetate (CEE + MPA) product used was associated with breast cancers that were slightly larger in size and more frequently had local lymph node metastases compared to placebo.
Fl- istudju WHI, il- prodott ikkombinat ta 'estroġeni ekwini kkonjugati kontinwi ma medroxyprogesterone acetate (CEE + MPA) użat ġie assoċjat ma' kanċers tas- sider li kienu
HRT, especially oestrogen-progestagen combined treatment, may increase the density of mammographic images which may adversely affect the radiological detection of breast cancer.
L- HRT, speċjalment il- kura kkombinata b 'estroġenu- proġestoġenu, tista' żżid id- densità tar - ritratti mammografiċi li jistgħu jaffettwaw b' mod negattiv l- osservazzjoni radjoloġika tal- kanċer tas- sider.
Venous thromboembolism HRT is associated with a higher relative risk of developing venous thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism.
Trombo- emboliżmu tal- vini L- HRT huwa assoċjat ma 'riskju relattiv ogħla ta' żvilupp ta 'trombo- emboliżmu tal- vini (VTE), jiġifieri trombożi tal- vini fondi jew emboliżmu pulmonari.
One randomised controlled trial and epidemiological studies found a two- to threefold higher risk for users compared with non-users.
Prova waħda klinika kkontrollata tat - tip randomised u studji epidemjoloġiċi sabu riskju minn darbtejn sa tliet darbiet akbar għal min uża HRT meta mqabbel ma 'min ma użax HRT.
For non-users it is estimated that the number of cases of VTE that will occur over a 5 year period is about 3 per 1000 women aged 50-59 years and 8 per 1000 women aged between 60-69 years.
Għal min ma użax HRT huwa stmat lin- numru ta 'każi ta' VTE li jseħħu fuq perjodu ta '5 snin huwa ta' madwar 3 f' kull 1000 mara bejn 50- 59 sena u 8 f' kull 1000 mara bejn 60- 69 sena.
It is estimated that in healthy women who use HRT for 5 years, the number of additional cases of VTE over a 5 year period will be between 2 and 6 (best estimate =4) per 1000 women aged 50-59 years and between 5 and 15 (best estimate =9) per 1000 women aged 60-69 years.
Huwa stmat li f' nisa b' saħħithom li jużaw HRT għal 5 snin, in- numru ta 'każi addizzjonali ta' VTE fuq perjodu ta '5 snin ikun bejn 2 u 6 (l- aħjar stima =4) f' kull 1000 mara bejn 50- 59 sena u bejn 5 u 15 (l- aħjar stima =9) f' kull 1000 mara bejn 60- 69 sena.
The occurrence of such an event is more likely in the first year of HRT than later.
L- okkorrenza li jseħħ dan huwa aktar probabbli fl- ewwel sena ta 'HRT milli wara.
Generally recognised risk factors for VTE include a personal history or family history, severe obesity (Body Mass Index > 30 kg/m2) and systemic lupus erythematosus (SLE).
Fatturi ta 'riskju in- ġenerali rikonoxxuti ta' VTE jinkludu l- istorja personali jew l- istorja tal - familja, obeżità severa (Indiċi tal- Massa tal- Ġisem > 30 kg/ m2) u lupus eritematosu sistemiku (SLE).
There is no consensus about the possible role of varicose veins in VTE.
M' hemmx qbil dwar ir- rwol possibbli tal- vini varikużi fil- VTE.
16 Patients with a history of VTE or known thrombophilic states have an increased risk of VTE.
Pazjenti b' passat ta 'VTE jew stati trombofiliċi magħrufa għandhom riskju ikbar ta' VTE.
HRT may add to this risk.
L- HRT jista 'jżid ma' dan ir- riskju.
Personal or strong family history of thromboembolism, or recurrent spontaneous abortion, should be investigated in order to exclude a thrombophilic predisposition.
Storja personali jew storja b' saħħitha tal- familja ta 'trombo - emboliżmu, jew abort spontanju rikorrenti, għandha tiġi investigata sabiex tiġi eskluża predispożizzjoni trombofilika.
Until a thorough evaluation of thrombophilic factors has been made or anticoagulant treatment initiated, use of HRT in such patients should be viewed as contraindicated.
Sakemm issir evalwazzjoni bir- reqqa tal- fatturi trombofiliċi jew tinbeda kura kontra l- koagulazzjoni tad- demm, l- użu tal- HRT f' dawn il- pazjenti għandha titqies bħala kontra- indikata.
Those women already on anticoagulant treatment require careful consideration of the benefit-risk of use of HRT.
Dawk in- nisa li diġa jieħdu kura kontra l- koagulazzjoni tad- demm jinħtieġu konsiderazzjoni attenta tar- riskju- benifiċċju ta 'l- użu tal- HRT.
The risk of VTE may be temporarily increased with prolonged immobilisation, major trauma or major surgery.
Ir- riskju ta 'VTE jista' jiżdied temporanjament b' immobilizzazzjoni fit- tul, trawma maġġuri jew kirurġija maġġuri.
As in all postoperative patients, scrupulous attention should be given to prophylactic measures to prevent VTE following surgery.
Bħal fil- pazjenti kollha wara operazzjoni, għandha tingħata attenzjoni metikoluża għall- miżuri profilattiċi sabiex tiġi evitata l- VTE wara kirurġija.
Where prolonged immobilisation is liable to follow elective surgery, particularly abdominal or orthopaedic surgery to the lower limbs, consideration should be given to temporarily stopping HRT four to six weeks earlier, if possible.
Fejn huwa probabbli li immobilizzazzjoni fit- tul issegwi kirurġija elettiva, partikolarment kirurġija addominali jew ortopedika fir- riġlejn, għandu jiġi kkunsidrat li jitwaqqaf temporanjament l- HRT minn erba 'sa sitt ġimgħat qabel, jekk ikun possibbli.
Treatment should not be restarted until the woman is completely mobilised.
Il- kura m' għandiex terġa 'tinbeda sakemm il- mara ma tkunx mobilizzata kompletament.
If VTE develops after initiating therapy, the drug should be discontinued.
Jekk tiżviluppa l- VTE wara li tinbeda t- terapija, il- mediċina għandha titwaqqaf.
Patients should be told to contact their doctors immediately when they are aware of a potential thromboembolic symptom (e.g. painful swelling of a leg, sudden pain in the chest, dyspnea).
Il- pazjenti għandhom ikunu infurmati li jkellmu t- tobba tagħhom minnufih meta jindunaw b' xi sintomu trombo- emboliku potenzjali (eż. sieq minfuħa muġugħa, uġigħ fis- sider għalgħarrieda, qtugħ ta 'nifs).
Coronary artery disease (CAD) There is no evidence from randomised controlled trials of cardiovascular benefit with continuous combined conjugated oestrogens and medroxyprogesterone acetate (MPA).
Mard fl- arterji koronarji (CAD) Minn provi kliniċi kkontrollati tat- tip randomised m' hemmx evidenza ta 'benefiċċji kardjovaskulari b' estroġeni kkonjugati, ikkombinati u kontinwi u medroxyprogesterone acetate (MPA).
For other HRT products there are only limited data from randomised controlled trials examining effects in cardiovascular morbidity or mortality.
Żewġ provi kliniċi kbar (WHI u HERS jiġifieri Studju tal- Qalb u Estroġenu / proġestin Sostitwit) urew żieda possibbli fir- riskju ta 'morbożità kardjovaskulari fl- ewwel sena ta' użu u l - ebda benefiċċju in ġenerali. Għall- prodotti oħra ta 'HRT hemm biss dejta limitat minn provi kliniċi kkontrollati tat- tip randomised li eżaminaw l- effetti fil- morbożità jew mortalità kardjovaskulari.
Therefore, it is uncertain whether these findings also extend to other HRT products.
Għaldaqstant, m' hemmx ċertezza jekk dawn is- sejbiet jistgħux jiġu estiżi wkoll għall- prodotti l- oħra ta 'HRT.
Stroke One large randomised clinical trial (WHI-trial) found, as a secondary outcome, an increased risk of ischaemic stroke in healthy women during treatment with continuous combined conjugated oestrogens and MPA.
18 Puplesija Prova klinika kbira tat- tip randomised (prova- WHI) sabet, bħala konsegwenza sekondarja, riskju akbar ta 'puplesija iskemika f' nisa b' saħħithom waqt kura b' estroġeni kkonjugati, ikkombinati u kontinwi u MPA.
For women who do not use HRT, it is estimated that the number of cases of stroke that will occur over a 5 year period is about 3 per 1000 women aged 50-59 years and 11 per 1000 women aged 60-69 years.
Għal nisa li ma jużawx HRT, huwa stmat lin- numru ta 'każi ta' puplesija li jseħħu fuq perjodu ta '5 snin huwa ta' madwar 3 f' kull 1000 mara bejn 50- 59 sena u 11 f' kull 1000 mara bejn 60- 69 sena.
It is estimated that for women who use conjugated oestrogens and MPA for 5 years, the number of additional cases will be between 0 and 3 (best estimate = 1) per 1000 users aged 50-59 years and between 1 and 9 (best estimate = 4) per 1000 users aged 60-69 years.
Huwa stmat li f' nisa li jużaw estroġeni kkonjugati u MPA għal 5 snin, in - numru ta 'każi addizzjonali jkun bejn 0 u 3 (l- aħjar stima =1) f' kull 1000 mara bejn 50- 59 sena u bejn 1 u 9 (l- aħjar stima =4) f' kull 1000 mara bejn 60- 69 sena.
It is unknown whether the increased risk also extends to other HRT products.
Mhux magħruf jekk iż- żieda fir - riskju jistax jiġi estiż ukoll għall- prodotti l- oħra ta 'HRT.
Ovarian cancer Long-term (at least 5-10 years) use of oestrogen-only HRT products in hysterectomised women has been associated with an increased risk of ovarian cancer in some epidemiological studies.
Kanċer ta 'l- ovarji L- użu fit- tul (mill- inqas 5- 10 snin) ta' prodotti tal- HRT b 'estroġenu biss f' nisa li kellhom isterektomija ġie assoċjat ma' żieda fir- riskju ta 'kanċer ta' l- ovarji f' xi studji epidemjoloġiċi.
It is uncertain whether long-term use of combined HRTs confers to a different risk than oestrogen-only products.
M' hemmx ċertezza jekk l- użu fit- tul tal- HRT ikkombinat għandux riskju differenti mill- prodotti b' estroġenu biss.
Other conditions Oestrogens may cause fluid retention, and therefore patients with cardiac or renal dysfunction should be carefully observed.
Kundizzjonijiet oħra L- estroġeni jistgħu jikkawżaw ir- retenzjoni ta 'fluwidu, u għaldaqstant pazjenti b' disfunzjoni kardijaka jew renali għandhom jiġu osservati bir- reqqa.
Patients with terminal renal insufficiency should be closely observed, since it is expected that the level of circulating active ingredients in Activelle will increase.
Pazjenti b' insuffiċjenza renali terminali għandhom jiġu osservati mill- qrib, billi huwa mistenni li jiżdied il- livell tas- sustanzi attivi f' Activelle fiċ- ċirkulazzjoni.
Women with pre-existing hypertriglyceridemia should be followed closely during oestrogen replacement or hormone replacement therapy, since rare cases of large increases of plasma triglycerides leading to pancreatitis have been reported with oestrogen therapy in this condition.
Nisa b' ipertrigliċeridimija diġà eżistenti għandhom jiġu investigati mill- qrib waqt terapija ta 'estroġenu sostitwit jew terapija ormonali sostitwita, billi każi rari ta' żidiet kbar ta 'trigliċeridi fil - plażma li wasslu għal pankreatite ġew irrapportati b' terapija ta' estroġeni f' din il- kundizzjoni.
Oestrogens increase thyroid binding globulin (TBG), leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 levels (by column or by radio- immunoassay) or T3 levels (by radio-immunoassay).
L- estroġeni jżidu l- globulina li teħel mat- tirojde (TBG), li twassal għal żieda ta 'l- ormon tat - tirojde totali fiċ- ċirkulazzjoni, kif imkejjel bil- jodju imwaħħal mal- proteini (PBI), bil- livelli ta' T4 (permezz ta 'analiżi b' kolonna jew radju- immunassaġġ) jew bil- livelli ta' T3 (permezz ta 'radju - immunassaġġ).
T3 resin uptake is decreased, reflecting the
L- assorbiment tar- reżina T3 jitnaqqas, u dan jirrifletti livell elevat ta 'TBG.
Free T4 and free T3 concentrations are unaltered.
Konċentrazzjonijiet ta 'T4 ħieles u T3 ħieles jibqgħu mhux mibdulin.
Other binding proteins may be elevated in serum, i.e. corticoid binding globulin (CBG), sex-hormone-binding globulin (SHBG) leading to increased circulating corticosteroids and sex steroids, respectively.
Proteini li jeħlu oħra jistgħu jkunu elevati fis- serum, jiġifieri l- globulina li teħel mal- kortikojde (CBG), il- globulina li teħel ma 'l- ormon tas- sess (SHBG) li twassal għal żieda ta' kortikosterojdi u sterojdi tas- sess fiċ - ċirkulazzjoni, rispettivament.
Free or biological active hormone concentrations are unchanged.
Konċentrazzjonijiet ta 'ormon attiv ħieles jew bijoloġiku jibqgħu mhux mibdulin.
Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-I-antitrypsin, and ceruloplasmin).
Proteini oħra fil- plażma jistgħu jiżdiedu (subtrat ta 'angiotensinogen/ renin, alpha - I- antitrypsin, u ceruloplasmin).
There is no conclusive evidence for improvement of cognitive function.
M' hemmx evidenza konklużiva ta 'titjib fil- funzjoni konoxxittiva.
There is some evidence from the WHI trial of increased risk of probable dementia in women who start using continuous combined CEE and MPA after the age of 65.
Hemm ftit evidenza mill- prova ta 'WHI ta' żieda fir- riskju ta 'dimenzja probabbli f' nisa li jibdew jużaw CEE kontinwi u kkombinati u MPA wara l- età ta' 65 sena.
It is unknown whether the findings apply to younger post- menopausal women or other HRT products.
Mhux magħruf jekk is- sejbiet japplikawx għal nisa wara l- menopawsa li jkunu iżgħar fl- età jew prodotti oħra ta 'HRT.
Activelle contains lactose monohydrate.
Activelle fih lactose monohydrate.
Patients with any of the following rare hereditary diseases should not take this medicine: galactose intolerance, lactase deficiency or glucose-galactose malabsorption.
Pazjenti li għandhom xi waħda mill- mard ereditarji rari li ġejjin m' għandhomx jieħdu din il- mediċina: intolleranza għal galactose, nuqqas ta 'lactase jew assorbiment ħażin ta' glucose- galactose.
4.5 Interaction with other medicinal products and other forms of interaction
Il- metaboliżmu ta 'l- estroġeni u l- proġestoġeni jista' jiżdied bl- użu fl- istess waqt ta 'sustanzi magħrufa li jistimolaw enżimi li jimmetabolizzaw il- mediċina, b' mod speċifiku enżimi ta'
The metabolism of oestrogens and progestagens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes such as anticonvulsants (e.g. phenobarbital, phenytoin, carbamazepin) and anti-infectives (e.g. rifampicin, rifabutin, nevirapine, efavirenz).
19 cytochrome P450 bħal mediċini kontra l- konvulżjonijiet (eż. phenobarbital, phenytoin, carbamazepin) u mediċini kontra l- infettar (eż. rifampicin, rifabutin, nevirapine, efavirenz).
Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones.
Ritonavir u nelfinavir, għalkemm magħrufin bħala inibituri qawwija, b' kuntrast juru karatteristiċi li jistimolaw meta jiġu użati ma 'ormoni sterojdi.
Herbal preparations containing St John’s Wort (Hypericum perforatum) may induce the metabolism of oestrogens and progestagens.
Preparazzjonijiet mill- ħxejjex li fihom St John’ s Wort (Hypericum perforatum) jistgħu jistimolaw il- metaboliżmu ta 'l- estroġeni u tal - proġestoġeni.
Clinically, an increased metabolism of oestrogens and progestagens may lead to decreased effect and changes in the uterine bleeding profile.
B' mod kliniku, żieda fil- metaboliżmu ta 'l- estroġeni u proġestoġeni tista' twassal għal tnaqqis fl - effett u tibdil fil- profil ta 'tnixxija ta' demm mill- utru.
Active substances that inhibit the activity of hepatic microsomal drug metabolizing enzymes e.g. ketoconazole, may increase circulating levels of the active substances in Activelle.
Sustanzi attivi li jinibixxu l- attività ta 'l- enżimi mikrosomali epatiċi li jimmetabolizzaw il - mediċina eż. ketaconazole, jistgħu jżidu l- livelli tas- sustanzi attivi f' Activelle fiċ- ċirkulazzjoni.
Activelle is not indicated during pregnancy.
Activelle mhux indikat fit- tqala.
If pregnancy occurs during medication with Activelle, treatment should be withdrawn immediately.
Jekk isseħħ it- tqala waqt il- kura b' Activelle, il- kura għandha titwaqqaf minnufih.
Data on a limited number of exposed pregnancies indicate adverse effects of norethisterone on the foetus.
Dejta fuq numru limitat ta 'tqalat esposti jindikaw effetti avversi ta' norethisterone fuq il- fetu.
At doses higher than normally used in OC and HRT formulations masculinisation of female foetuses was observed.
F' dożi ogħla minn dawk normalment użati f' formulazzjonijiet ta 'OC u HRT ġie osservat il - formazzjoni ta' karatteristiċi maskili f' feti femminili.
The results of most epidemiological studies to date relevant to inadvertent foetal exposure to combinations of oestrogens and progestagens indicate no teratogenic or foetotoxic effect.
Ir- riżultati tal- biċċa l- kbira tal- istudji epidemjoloġiċi sa llum relevanti għall- espożizzjoni aċċidentali tal- fetu għal kombinazzjonijiet ta 'estroġeni u proġestoġeni ma indikaw l- ebda effett teratoġeniku jew fetotossiku.
Lactation Activelle is not indicated during lactation
Treddigħ Activelle mhux indikat fit- treddigħ.
The most frequently reported adverse reaction in the clinical trial with Activelle was vaginal bleeding.
Ir- reazzjoni avversa li ġiet irrapportata b' mod l- aktar frekwenti fil- prova klinika b' Activelle kienet il- ħruġ ta 'demm mill- vaġina.
11% of women at month 1, 15% of women at month 4 and 11% of women at the end of the 6 month trial reported bleeding or spotting.
11% tan- nisa fl- ewwel xahar, 15% tan- nisa fir- raba 'xahar u 11% tan- nisa fi tmiem tal- prova klinika ta' sitt xhur irrapportaw ħruġ ta 'demm jew taqtir ħafif ta' demm.
All adverse reactions observed with a higher frequency in patients treated with Activelle compared to placebo and which on an overall judgement are possible related to treatment are presented below.
Ir- reazzjonijiet avversi kollha osservati li kellhom frekwenza ogħla f' pazjenti kkurati b' Activelle kkomparati mal- plaċebo u li b' fehma ġenerali huma possibbilment relatati mal- kura huma ppreżentati hawn taħt.
18 System organ class Infections and infestations
20 Sistema tal - klassifika ta 'l - organi Infezzjonijiet u infestazzjonijiet Disturbi fis - sistema immuni Disturbi fil - metaboliżmu u n - nutrizzjoni Disturbi psikjatriċi
Very common ≥1/10
Komuni ħafna ≥1/ 10
Common ≥1/100; < 1/10 Vulvovaginal mycotic infection, see also “Reproductive system and breast disorders
Komuni ≥1/ 100; < 1/ 10 Infezzjoni mikotika vulvo- vaġinali, ara wkoll "Disturbi fis - sistema riproduttiva u fis- sider"
Uncommon ≥1/1,000; < 1/100
Mhux komuni ≥1/ 1, 000; < 1/ 100 Sensittività eċċessiva, ara wkoll "Disturbi fil- ġilda u fit - tessuti ta 'taħt il - ġilda" Retenzjoni tal - fluwidu, ara wkoll "Disturbi ġenerali u kondizzjonijiet ta' mnejn jingħata" Depressjoni jew depressjoni ggravata Nervożità
Rare ≥1/10,000; < 1/1,000
Rari ≥1/ 10, 000; < 1/ 1, 000
Immune system disorders
Disturbi fis - sistema nervuża
Hypersensitivity, see also “Skin and subcutaneous tissue disorders
Uġigħ ta 'ras
Metabolism and nutrition disorders
Emigranja Sturdament
Fluid retention, see also “General disorders and administration site conditions
Disturbi gastro - intestinali Disturbi fil- ġilda u fit- tessuti ta 'taħt il- ġilda
Psychiatric disorders
Uġigħ addominali Tqalligħ
Depression or depression aggravated Nervousness
Nefħa addominali Dispepsja Ħakk jew urtikarja Alopeċja Akne
Nervous system disorders
Disturbi
Headache
Uġigħ fid -
Migraine Dizziness
Bugħawwieġ fis -
Gastrointestinal disorders Skin and subcutaneous tissue disorders
muskolu - skeletrali u tat - tessut konnettiv
Abdominal distension Dyspepsia Pruritus or urticaria Alopecia Acne
dahar Uġigħ fl- għonq Uġigħ fl - estremità
Back pain
saqajn
tissue disorders
21 Sistema tal - klassifika ta 'l - organi Disturbi fis -
Neck pain Pain in extremity
Komuni ħafna ≥1/ 10 Emorraġija
Reproductive system and breast disorders
Komuni ≥1/ 100; < 1/ 10 Jeħxien l -