qanastek/EMEA-V3 huggingface dataset:
Which measures are being taken to ensure the safe use of Fablyn?
X’ miżuri qed jittieħdu biex ikun żgurat l- użu sigur ta ’ Fablyn?
The company that makes Fablyn will make sure that an educational programme is available in all Member States for all healthcare workers who will prescribe Fablyn or order pelvic ultrasound scans for women taking the medicine.
Il- kumpanija li tagħmel Fablyn ser tassigura illi l- programm eduazzjonali huwa disponibbli fl- Istati Membri kollha għal ħaddiema tal- kura tas- saħħa kollha li ser jippreskrivu Fablyn jew jordnaw skens tat- tip ultrasound tal- pelvis għal nisa li jieħdu l- mediċina.
The programme will include information about the risk of venous thromboembolism, changes in the womb that may occur when taking the medicine, and the need to investigate unexplained bleeding from the womb.
Il- programm ser jinkludi informazzjoni dwar ir- riskju ta ’ tromboemboliżmu fil- vini, tibdil fil- ġuf li jista ’ jiġri meta tittieħed il- mediċina u l - ħtieġa li jiġu investigati tnixxijiet ta ’ demm mill- ġuf bla spjegazzjoni.
Other information about Fablyn:
Tagħrif ieħor dwar Fabyln:
The European Commission granted a marketing authorisation valid throughout the European Union for Fablyn to Pfizer Limited on 24 February 2009.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fis- suq valida madwar l- Unjoni Ewropea kollha għal Fabyln lil Pfizer Limited fis- 24 ta ’ Frar 2009.
The full EPAR for Fablyn can be found here.
L- EPAR sħiħ għal Fabyln jista ’ jinstab hawnhekk.
Route of EU number
Numru ta ’ Proċedura ta ’ l - EU
Oral use Oral use Oral use Oral use
Użu Orali Użu Orali Użu Orali Użu Orali
Blister (PV/ PVC/ alu) Blister (PV/ PVC/ alu) Blister (PV/ PVC/ alu) Bottle (HDPE)
Folja (PV/ PVC/ alu) Folja (PV/ PVC/ alu) Folja (PV/ PVC/ alu) Flixkun (HDPE)
7 tablets 28 tablets 30 tablets 90 tablets
7 pilloli 28 pilloli 30 pilloli 90 pilloli
FABLYN 500 microgram film-coated tablets.
FABLYN 500 mikrogramma pilloli miksija b’ rita.
Each film-coated tablet contains lasofoxifene tartrate, equivalent to 500 micrograms lasofoxifene.
Kull pillola miksija b’ rita fiha lasofoxifene tartrate, ekwivalenti għal 500 mikrogramma lasofoxifene.
Each film-coated tablet contains 71.34 mg lactose.
Kull pillola miksija b’ rita fiha 71. 34 mg lattosju.
Triangular, peach-coloured, film-coated tablets debossed with “ Pfizer” on one side and “ OPR 05” on the other side.
Pilloli miksija b’ rita li huma trijangulari, ta ’ kulur il- ħawħa, b ’ “ Pfizer ” immarkata fuq naħa waħda u “ OPR 05 ” fuq in- naħa l- oħra.
FABLYN is indicated for the treatment of osteoporosis in postmenopausal women at increased risk of fracture.
FABLYN huwa indikat għall- kura tal- osteoporożi f’ nisa li diġà għaddew mill- menopawsa li jkollhom riskju akbar ta ’ xi ksur.
A significant reduction in the incidence of vertebral and non-vertebral fractures but not hip fractures has been demonstrated (see section 5.1).
Ġie ppruvat tnaqqis sinifikanti fl- inċidenza ta ’ ksur vertebrali u dak mhux vertebrali, iżda mhux fl- inċidenza ta ’ ksur tal- ġenbejn (ara sezzjoni 5. 1).
When determining the choice of FABLYN or other therapies, including estrogens, for a postmenopausal woman, consideration should be given to menopausal symptoms, effects on uterine and breast tissues, and cardiovascular risks and benefits (see section 5.1).
Meta jkun qiegħed jiġi deċiż li mara li tkun għaddiet mill- menopawsa għandha tingħata FABLYN jew terapiji oħra, inklużi l- estroġeni, wieħed għandu jqis is- sintomi tal- menopawsa, l- effett fuq it- tessuti tal- utru u tas- sider, u riskji u benefiċċji kardjovaskulari (ara sezzjoni 5. 1).
Adult (postmenopausal women):
Adulti (nisa li jkunu diġà għaddew mill- menopawsa):
The recommended dose is one 500 microgram tablet daily.
Id- doża rrakkomandata hija ta ’ pillola waħda ta ’ 500 mikrogramma kuljum.
The tablet may be taken any time of day without regard to food and beverage intake.
Il- pillola tista ’ tittieħed fi kwalunkwe ħin tal- ġurnata u ma jaffetwax jekk din tittiħidx ma ’ l- ikel u max- xorb jew waħidha.
Supplemental calcium and/ or vitamin D should be added to the diet if daily intake is inadequate.
Jekk il- pazjenta ma tkunx qiegħda tieħu kalċju u vitamina D daqs kemm sippost tieħu f’ ġurnata, għandu jiżdied mad- dieta suppliment tal- kalċju u/ jew tal- vitamina D.
Postmenopausal women require an average of 1,500 mg/ day of elemental calcium.
Nisa li jkunu diġà għaddew mill- menopawsa għandhom bżonn medja ta ’ 1, 500 mg/ kuljum ta ’ kalċju elementari.
The recommended intake of vitamin D is 400-800 IU daily.
L- ammont irrakkomandat ta ’ vitamina D hu ta ’ 400- 800 IU kuljum.
Children and adolescents below 18 years of age:
2 Tfal u adoloxxenti ta ’ taħt it- 18- il sena:
There is no indication for FABLYN in children and adolescents below 18 years of age since the medicinal product is for use in postmenopausal women only.
FABLYN mhux indikat għall- ebda użu fit- tfal u l- adoloxxenti ta ’ taħt it- 18- il sena peress li dan il- prodott mediċinali huwa indikat biss għall- użu min- nisa li diġà għaddew mill- menopawsa.
Therefore safety and efficacy have not been studied (see section 5.2).
Għalhekk, is- sigurtà u l- effikaċja tiegħu ma ġewx studjati (ara sezzjoni 5. 2).
2 Elderly women (65 years and older):
Nisa anzjani (65 sena u akbar):
No dose adjustment is necessary in elderly female patients (see section 5.2).
M’ hemmx bżonn ta ’ aġġustament tad- doża fil- każ ta ’ pazjenti nisa li huma anzjani (ara sezzjoni 5. 2).
Hepatic insufficiency:
Insuffiċjenza tal- fwied:
No dose adjustment is required in patients with mild to moderate hepatic insufficiency (see section 5.2).
M’ hemmx bżonn ta ’ aġġustament tad- doża fil- każ ta ’ pazjenti li jbatu minn insuffiċjenza tal- fwied minn ħafifa sa moderata (ara sezzjoni 5. 2).
Safety and efficacy of lasofoxifene have not been evaluated in patients with hepatic insufficiency with liver function test > 1.5 ULN; therefore, FABLYN should be used with caution in these patients.
Is- sigurtà u l- effikaċja ta ’ lasofoxifene ma ġewx evalwati f’ pazjenti li jbatu minn insuffiċjenza tal- fwied li kellhom riżultati tat- test tal- funzjoni tal- fwied > 1. 5 ULN; għalhekk, FABLYN għandu jintuża b’ kawtela f’ dawn il- pazjenti.
No dose adjustment is necessary in patients with mild or moderate renal insufficiency (see section 5.2).
M’ hemmx bżonn ta ’ aġġustament tad- doża fil- każ ta ’ pazjenti li jbatu minn insuffiċjenza renali ħafifa jew moderata (ara sezzjoni 5. 2).
Safety and efficacy of lasofoxifene have not been evaluated in patients with severe renal insufficiency; therefore, FABLYN should be used with caution in these patients.
Is- sigurtà u l- effikaċja ta ’ lasofoxifene ma ġewx evalwati f’ pazjenti li jbatu minn insuffiċjenza renali severa; għalhekk, FABLYN għandu jintuża b’ kawtela f’ dawn il- pazjenti.
Due to the chronic nature of the disease process, FABLYN is intended for long-term use (see section 5.1).
Minħabba li l- proċess tal- marda huwa min- natura tiegħu kroniku, FABLYN huwa intenzjonat għal użu fit- tul (ara sezzjoni 5. 1).
Active or past history of venous thromboembolic events, including deep vein thrombosis, pulmonary embolism and retinal vein thrombosis.
Pazjenta tbati jew ġieli batiet fil- passat b’ każijiet ta ’ trombo- emboliżmu fil- vini, li jinkludu trombożi tal- vini l- fondi, emboliżmu pulmonari u trombożi tal- vina tar- retina.
Unexplained uterine bleeding.
Ħruġ ta ’ demm mill- utru li m’ hemmx spjegazzjoni għalih.
Pregnancy and lactation:
Tqala u treddigħ:
FABLYN is only for use in postmenopausal women.
FABLYN huwa indikat biss għall- użu min- nisa li diġà għaddew mill- menopawsa.
It must not be taken by women of child-bearing potential, pregnant women and lactating women (see section 4.6).
M’ għandux jittieħed min- nisa li għad jista ’ jkollhom it- tfal, min- nisa tqal jew li jkunu qegħdin ireddgħu (ara sezzjoni 4. 6).
4.4 Special warnings and precautions for use
3 4. 4 Twissijiet speċjali u prekawzjonijiet għall- użu
In clinical trials, FABLYN-treated women had an increased risk of venous thromboembolic events (deep vein thrombosis and pulmonary embolism) compared to placebo.
Fil- provi kliniċi, nisa kkurati b’ FABLYN kellhom riskju akbar ta ’ każijiet ta ’ trombo- emboliżmu fil- vini (trombożi tal- vini l- fondi u emboliżmu pulmonari) meta pparagunati mal- plaċebo.
Other venous thromboembolic events could also occur.
Jistgħu jseħħu wkoll tipi oħra ta ’ każijiet ta ’ trombo- emboliżmu fil- vini.
A less serious event, superficial thrombophlebitis, also has been reported more frequently with FABLYN compared to placebo.
It- tromboflebite superfiċjali, li hi każ inqas serju, ġiet irrappurtata b’ mod aktar frekwenti b’ FABLYN meta pparagunat mal- plaċebo.
The risk-benefit balance should be considered in patients at risk of venous thromboembolic events of any aetiology (see sections 4.3 and 4.8).
Għandu jiġi kkunsidrat il- bilanċ bejn ir- riskju u l- benefiċju fil- każ ta ’ pazjenti li huma f’ riskju li jkollhom każijiet ta ’ trombo- emboliżmu ta ’ kwalunkwe etjoloġija (ara sezzjoni 4. 3 u 4. 8).
Because immobilization increases the risk for venous thromboembolic events independent of therapy, FABLYN should be discontinued at least 3 weeks prior to and during prolonged immobilization (e. g., post-surgical recovery, prolonged bed rest), and therapy should be resumed only after the patient is fully ambulatory.
Minħabba li meta persuna ma tkunx tista ’ tiċċaqlaq, jiżdied ir- riskju ta ’ każijiet ta ’ trombo- emboliżmu, u dan indipendentement mit- terapija li tkun qiegħda tieħu, FABLYN għandu jitwaqqaf mill- inqas 3 ġimgħat qabel, u matul il- perjodu twil li fih persuna ma tkunx tista ’ tiċċaqlaq (eż., il- perjodu ta ’ wara operazzjoni li fih pazjenta tkun qiegħda tistrieħ biex terġa ’ tieħu saħħitha, perjodu twil li fih pazjenta jkollha toqgħod tistrieh fis- sodda minħabba raġunijiet ta ’ saħħa), u t- terapija għandha titkompla biss wara li l- pazjenta tkun terġa’ tista ’ timxi.
In addition, women taking FABLYN should be advised to move about periodically during prolonged travel.
Barra minn hekk, nisa li jkunu qegħdin jieħdu FABLYN għandhom jiġu avvżati biex jiċċaqalqu minn posthom u jippassiġġaw kull tant ħin meta jkunu qegħdin jivjaġġaw fit- tul.
Any unexplained vaginal bleeding should be investigated as clinically indicated.
Bħal ma hu klinikament indikat, kwalunkwe ħruġ ta ’ demm mill- vaġina li m’ hemmx spjegazzjoni għalih, għandu jiġi investigat.
FABLYN-treated and placebo-treated groups had similar incidences of endometrial hyperplasia and endometrial cancer (see section 5.1).
Gruppi li kienu qegħdin jingħataw FABLYN u gruppi li kienu qegħdin jingħataw il- plaċebo kellhom inċidenzi simili ta ’ iperplasija tal- endometriju u ta ’ kanċer fl- endometriju (ara sezzjoni 5. 1).
3 Lasofoxifene has been associated with benign endometrial effects.
Lasofoxifene ġie assoċjat ma ’ effetti beninni tal- endometriju.
These included, in some subjects, a small excess in the incidence of vaginal bleeding as well as endometrial cystic change viewed on ultrasound and histological benign cystic atrophy (a variant of atrophic endometrium).
F’ xi suġġetti, dawn kienu jinkludu inċidenza akbar ta ħruġ ta ’ demm żejjed mill- vaġina, kif ukoll bidla fiċ- ċesti tal- endometriju li dehret fl- eżami ultrasoniku u atrofija istoloġika beninna taċ- ċesti (varjant tal- atrofija tal- endometriju).
These cystic findings contributed to an approximate 1.5 mm increase in mean endometrial thickness.
Dawn iċ- ċesti misjuba kkaġunaw żieda fil- ħxuna medja tal- endometriju ta ’ bejn wieħed u ieħor 1. 5 mm.
As a consequence of these benign effects, more FABLYN-treated patients had a diagnostic uterine procedure compared to placebo-treated patients in the PEARL trial (see section 5.1).
B’ konsegwenza ta ’ dawn l- effetti beninni, kien hemm ammont akbar ta ’ pazjenti kkurati b ’ FABLYN li għaddew minn proċedura dijanjostika tal- utru meta pparagunati mal- pazjenti li kienu qegħdin jingħataw il- plaċebo fil- prova PEARL (ara sezzjoni 5. 1).
However, in clinical practice, these benign findings do not warrant further evaluation in women with no vaginal bleeding (in accordance with guidelines for postmenopausal women), as the risks of diagnostic uterine procedures in asymptomatic women outweigh any benefits.
Madanakollu, fil- prattika klinika (skont il- linji gwida għal nisa li diġà għaddew mill- menopawsa) dawn ir- riżultati beninni ma joħolqux il- ħtieġa ta ’ aktar evalwazzjoni f’ nisa li ma jkollhomx ħruġ ta ’ demm mill- vaġina, u dan peress li r- riskji tal- proċeduri dijanjostiċi tal- utru f’ nisa li ma jurux sintomi huma akbar mill- benefiċji li jista ’ jkun hemm.
Pathologists should be made aware of a history of lasofoxifene use when assessing endometrial histology, to ensure an accurate diagnosis of benign cystic atrophy when present.
Meta jkunu qegħdin jevalwaw l- istoloġija tal- endometriju, il- patologi għandhom jiġu mgħarrfa meta pazjenta tkun ħadet lasofoxifene fil- passat, u dan biex tiġi assigurata dijanjosi preċiża tal- atrofija beninna taċ- ċesti meta din il- kundizzjoni tkun preżenti.
The concurrent use of FABLYN and systemic estrogen or hormone therapy has not been studied and therefore concomitant use of FABLYN with systemic estrogens is not recommended.
L- użu flimkien ta ’ FABLYN u terapija sistemika bl- estroġen jew bl- ormoni ma ġiex studjat, u għalhekk l- użu ta ’ FABLYN u estroġeni sistemiċi fl- istess waqt mhuwiex irrakkomandat.
FABLYN has not been studied in women with a prior history of breast cancer.
FABLYN ma ġiex studjat f’ nisa li diġà kellhom kanċer tas- sider.
No data are available on its concomitant use with agents used in the treatment of early or advanced breast cancer.
M’ hemm l- ebda tagħrif dwar l- użu tiegħu flimkien ma ’ aġenti użati fil- kura tal- kanċer tas- sider meta jkun għadu fil- bidu tiegħu jew fi stadju avanzat.
Therefore, FABLYN should be used for the treatment of osteoporosis only after the treatment of breast cancer, including adjuvant therapy, has been completed.
Għalhekk, FABLYN għandu jintuża għall- kura tal- osteoporożi biss wara li tkun spiċċat tingħata l- kura għall- kanċer tas- sider, inkluża t- terapija awżiljari.
Any unexplained breast abnormality occurring during FABLYN therapy should be investigated.
Kwalunkwe anormalità fis- sider li sseħħ matul it- terapija b’ FABLYN għandha tiġi investigata.
FABLYN does not eliminate the risk of breast cancer (see section 5.1).
FABLYN ma jeliminax ir- riskju tal- kanċer tas- sider (ara sezzjoni 5. 1).
FABLYN may increase the incidence of hot flushes and is not effective in reducing hot flushes associated with estrogen deficiency.
FABLYN jista ’ jżid l- inċidenza tal- fwawar tal- menopawsa u mhuwiex effettiv fit- tnaqqis tal- fwawar tal- menopawsa assoċjati man- nuqqas tal- estroġenu.
In some asymptomatic patients, hot flushes may occur upon beginning therapy.
F’ xi pazjenti li ma jurux sintomi, il- fwawar tal- menopawsa jistgħu jibdew meta tinbeda t- terapija.
Limited clinical data suggest that in patients with a history of oral oestrogen-induced hypertriglyceridemia (> 5.6 mmol/ l), lasofoxifene may be associated with a marked increase in serum triglycerides.
4 Informazzjoni klinika limitata eżistenti tissuġġerixxi li lasofoxifene jista ’ jkun assoċjat ma ’ żieda kbira fit- trigliċeridi fis- serum f’ pazjenti li diġà kellhom ipertrigliċeridemija kkawżata mill- estroġenu mittieħed mill- ħalq (> 5. 6 mmol/ l).
Patients with this medical history should have serum triglycerides monitored when taking lasofoxifene.
Fil- każ ta ’ pazjenti li diġà kellhom din il- kundizzjoni fil- passat, il- livelli tagħom tat- trigliċeridi fis- serum għandhom jiġu monitorjati waqt li huma jkunu qegħdin jieħdu lasofoxifene
Lasofoxifene is highly protein bound, predominantly cleared by metabolism and is likely to undergo enterohepatic circulation (see section 5.2).
Lasofoxifene jeħel ħafna mal- proteini, jitneħħa fil- biċċa l- kbira tiegħu permezz tal- metaboliżmu u x’ aktarx li jiċċirkola mill- intestina għall- fwied u lura għall- intestina (ara sezzjoni 5. 2).
Safety and efficacy of FABLYN have not been evaluated in patients with liver function test > 1.5 ULN; therefore, FABLYN should be used with caution in these patients.
Is- sigurtà u l- effikaċja ta ’ FABLYN ma ġewx evalwati f’ pazjenti li kellhom riżultati tat- test tal- funzjoni tal- fwied > 1. 5 ULN; għalhekk, FABLYN għandu jintuża b’ kawtela f’ dawn il- pazjenti
Safety and efficacy of FABLYN have not been evaluated in patients with severe renal insufficiency; therefore, FABLYN should be used with caution in these patients (see section 4.2 and section 5.2).
Is- sigurtà u l- effikaċja ta ’ FABLYN ma ġewx evalwati f’ pazjenti li jbatu minn insuffiċjenza renali severa; għalhekk, FABLYN għandu jintuża b’ kawtela f’ dawn il- pazjenti (ara sezzjoni 4. 2 u sezzjoni 5. 2).
FABLYN contains lactose.
FABLYN fih il- lattosju.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Pazjenti li għandhom problemi ereditarji rari ta ’ nuqqas ta ’ tolleranza għall- galactose, nuqqas ta ’ Lapp lactase jew li l- musrana ż- żgħira tagħhom ma tassorbix kif sippost il- glukosju- galactose, m’ għandhomx jieħdu dan il- prodott mediċinali.
Based on the absence of clinically relevant effects of cholestyramine (anion exchange resin), fluconazole (CYP2C9 inhibitor), ketoconazole (CYP3A4/ 5 inhibitor) and paroxetine (CYP2D6 inhibitor) on lasofoxifene pharmacokinetics, other anion exchange resins and other inhibitors of these CYP isoforms are unlikely to produce clinically meaningful alterations in FABLYN exposure and no dose adjustments are required.
Minħabba n- nuqqas ta ’ effetti ta ’ rilevanza klinika ta ’ cholestyramine (anion exchange resin), fluconazole (impeditur tas- CYP2C9), ketoconazole (impeditur tas- CYP3A4/ 5) u paroxetine (impeditur tas- CYP2D6) fuq il- farmakokinetika ta ’ lasofoxifene, x’ aktarx li anion exchange resin oħra u impedituri oħra ta ’ dawn l- iżoformi CYP ma jipproduċux tibdil fl- esponiment ta ’ FABLYN li hu ta ’ rilevanza klinika, u m’ hemmx bżonn ta ’ aġġustament tad- doża.
Lasofoxifene clearance may be increased in patients chronically treated with inducers of CYP3A4 and UGTs (eg, phenytoin, carbamazepine, barbiturates and St John’ s Wort) resulting in reduced steady-state concentrations and may result in reduced efficacy.
It- tneħħija ta ’ lasofoxifene tista ’ tiżdied f’ pazjenti li jiġu kkurati kronikament b ’ indutturi ta ’ CYP3A4 u UGTs (eż, phenytoin, carbamazepine, barbiturati u l- fexfiex tar- raba ’ (St John’ s Wort)) u dan iwassal għal tnaqqis fil- konċentrazzjonijiet fissi u jista ’ jwassal għal tnaqqis fl- effikaċja.
4 Ketoconazole - The strong CYP3A4/ 5 inhibitor ketoconazole increased the systemic exposure of lasofoxifene by 20% which is not considered to be clinically meaningful.
Ketoconazole – Ketoconazole, l- impeditur qawwi ta ’ CYP3A4/ 5, żied l- esponiment sistemiku ta ’ lasofoxifene b’ 20%, li mhux meqjus bħala li hu klinikament rilevanti.
Paroxetine - The strong CYP2D6 inhibitor paroxetine increased the systemic exposure of lasofoxifene by 35% which is not considered to be clinically meaningful.
Paroxetine – Paoxetine, l- impeditur qawwi ta ’ CYP2D6, żied l- esponiment sistemiku ta ’ lasofoxifene b’ 35%, li mhux meqjus bħala li hu klinikament rilevanti.
Proton pump inhibitors – Data on the effect of concomitant administration of proton pump inhibitors (PPIs) with lasofoxifene is not available; thus, use of these agents with lasofoxifene should be considered with caution.
Impedituri tal- pompa tal- protoni – M’ hemmx informazzjoni dwar l- effett tal- għoti ta ’ impedituri tal- pompa tal- protoni (PPIs) flimkien ma ’ lasofoxifene; għalhekk, l- użu ta ’ dawn l- aġenti flimkien ma ’ lasofoxifene għandu jiġi kkunsidrat b’ kawtela.
In clinical studies, lasofoxifene did not alter the metabolism of dextromethorphan (CYP2D6 substrate) and chlorzoxazone (CYP2E1 substrate) or the pharmacokinetics of warfarin (CYP2C9 substrate), methylprednisolone (CYP3A4 substrate) or digoxin (MDR1 P-glycoprotein substrate).
Fi studji kliniċi, lasofoxifene ma biddilx il- metaboliżmu ta ’ dextromethorphan (substrat ta ’ CYP2D6) u chlorzoxazone (substrat ta ’ CYP2E1) jew il- farmakokinetika ta ’ warfarin (substrat ta ’ CYP2C9), methylprednisolone (substrat ta ’ CYP3A4) jew digoxin (substrat ta ’ glikoproteina P- MDR1).
Therefore FABLYN is unlikely to alter the pharmacokinetics of medicinal products that are cleared by metabolism via these CYP isoforms, or are transported by MDR1 P-glycoprotein.
Għalhekk, x’ aktarx li FABLYN ma jbiddilx il- farmakokinetika ta ’ prodotti mediċinali li jitneħħew mill- ġisem billi jiġu metaboliżżati permezz ta ’ dawn l- iżoformi CYP, jew billi jiġu trasportati permezz ta ’ glikoproteina P- MDR1.
Warfarin - Lasofoxifene had no effect on the pharmacokinetics of R- and S- warfarin.
Warfarin - Lasofoxifene ma kellux effett fuq il- farmakokinetika ta ’ R - u S - warfarin.
Mean international normalized ratio (INR) AUC and maximum value of INR after single-dose warfarin administration with lasofoxifene were approximately 8% and 16% lower, respectively, than after warfarin alone.
Il- medja tal- proporzjon normalizzat internazzjonali (INR) tal- AUC u l- valur massimu tal- INR wara li ngħatat doża waħda ta ’ warfarin flimkien ma ’ lasofoxifene, kienu ta ’ bejn wieħed u ieħor 8% u 16% inqas, rispettivament, milli kienu wara li ngħata warfarin waħdu.
These changes are not considered to be clinically meaningful.
Dawn il- bidliet mhumiex meqjusa bħala li għandhom rilevanza klinika.
4.6 Pregnancy and lactation
5 4. 6 Tqala u treddigħ
FABLYN must not be taken by women of child-bearing potential (see section 4.3).
FABLYN m’ għandux jittieħed min- nisa li jkun għad jista ’ jkollhom it- tfal (ara sezzjoni 4. 3).
There are no adequate data from the use of lasofoxifene in pregnant women.
M’ hemmx biżżejjed tagħrif mill- użu ta ’ lasofoxifene fuq nisa tqal.
Studies in animals have shown reproductive toxicity (see section 5.3).
Studji li saru fuq l- annimali urew tossiċità fis- sistema riproduttiva (ara sezzjoni 5. 3).
The potential risk for humans is unknown.
Ir- riskju potenzjali għall- bniedem għadu mhuwiex magħruf.
Lactation
Treddigħ
FABLYN must not be taken during lactation (see section 4.3).
FABLYN m’ għandux jittieħed waqt li mara tkun qiegħda tredda ’ (ara sezzjoni 4. 3).
It is not known whether lasofoxifene is excreted in human milk.
Għadu mhuwiex magħruf jekk lasofoxifene joħroġx mal- ħalib tas- sider tal- bniedem.
Animal studies have shown excretion of lasofoxifene in milk.
Studji fuq l- annimali urew li lasofoxifene joħroġ mal- ħalib tas- sider.
FABLYN has no known influence on the ability to drive and use machines.
FABLYN m’ għandu l- ebda effett magħruf fuq il- ħila li ssuq u tħaddem magni.
The safety of FABLYN in the treatment of osteoporosis was assessed in a large (8,556 patients) double-blind, randomized, placebo-controlled multinational Phase 3 fracture trial (the PEARL study).
Is- sigurtà ta ’ FABLYN fil- kura tal- osteoporożi ġiet evalwata fi prova klinika kbira (8, 556 pazjenta) multinazzjonali ta ’ Fażi 3 dwar il- ksur, li kienet double- blind, randomized, u kontrollata bil- plaċebo (l- istudju PEARL).
The duration of treatment in postmenopausal women was 60 months, 2,852 were randomized to FABLYN and 2,852 were randomized to placebo.
It- tul tal- kura f’ nisa li diġà għaddew mill- menopawsa kien ta ’ 60 xahar, 2, 852 pazjenta ġew randomized u ngħataw FABLYN u 2, 852 pazjenta ġew randomised u ngħataw il- plaċebo.
Within this study, 12.9% of FABLYN-treated women and 12.3% of placebo-treated women discontinued therapy due to adverse events.
F’ dan l- istudju, 12. 9% tan- nisa kkurati b ’ FABLYN u 12. 3% tan- nisa kkurati bil- plaċebo waqqfu t- trattament minħabba effetti avversi.
5 Venous Thromboembolic Events:
Każijiet ta ’ trombo- emboliżmu fil- vini:
The most serious adverse reaction related to FABLYN was VTE (deep venous thrombosis, pulmonary embolism, and retinal vein thrombosis).
L- aktar reazzjoni avversa serja relatata ma ’ FABLYN kienet il- VTE (trombożi tal- vini l- fondi, emboliżmu pulmonari, u trombożi tal- vina tar- retina).
Through 5 years of follow-up, 37 FABLYN-treated women (1.3%, or 2.90 per 1,000 patients years) had a VTE compared to 18 placebo-treated women (0.6%, or 1.41 per 1,000 patients years) and the hazard ratio was 2.06 (95% CI:
Matul 5 snin ta ’ osservazzjoni ta ’ wara l- kura, 37 mara li kienu kkurati f’ FABLYN (1. 3%, jew 2. 90 kull 1, 000 sena ta ’ pazjenta) kellhom VTE meta pparagunati ma ’ 18- il mara li kienu kkurati bil- plaċebo (0. 6%, jew 1. 41 kull 1, 000 sena ta ’ pazjenta), u l- proporzjon tal- periklu kien ta ’ 2. 06 (95% IK:
1.17, 3.61).
1. 17, 3. 61).
As observed with other Selective Estrogen Receptor Modulators (SERMs), slightly decreased (approximately 4%) platelet counts were observed in lasofoxifene-treated patients in PEARL.
Kif ġie osservat ukoll fil- każ ta ’ mediċini oħra, modulaturi selettivi tar- reċetturi tal- estroġenu (SERM) oħra, fl- istudju PEARL ġie osservat tnaqqis żgħir (ta ’ bejn wieħed u ieħor 4%) fl- għadd tal- pjastrini f’ pazjenti li kienu kkurati b’ lasofoxifene
Common adverse reactions considered to be related to FABLYN therapy were muscle spasms, hot flush and vaginal discharge.
Reazzjonijiet avversi komuni li kienu meqjusa bħala relatati mat- terapija b’ FABLYN kienu spażmi fil- muskoli, fwawar tal- menopawsa u tnixxija mill- vaġina.
Muscle spasms occurred in about one in 9 patients.
L- ispażmi fil- muskoli dehru f’ madwar pazjenta waħda minn 9 pazjenti.
Hot flush occurred in about one in 11 patients and was most commonly reported during the first 6 months of treatment.
Il- fwawar tal- menopawsa dehru f’ madwar pazjenta waħda minn 11- il pazjenta, u ġew irrappurtati l- aktar matul l- ewwel 6 xhur tal- kura.
Vaginal discharge occurred in about one in 26 patients.
It- tnixxija mill- vaġina dehret f’ madwar pazjenta waħda minn 26 pazjenta.
The safety of FABLYN in the treatment of osteoporosis was also assessed in a Phase 2 placebo-controlled trial in Japanese, Korean and Taiwanese women.
6 Is- sigurtà ta ’ FABLYN fil- kura tal- osteoporożi ġiet evalwata wkoll fi prova ta ’ Fażi 2 kontrollata bil- plaċebo fuq nisa Ġappuniżi, Koreani u Tajwaniżi.
The duration of treatment in postmenopausal women was 12 months, 124 were exposed to FABLYN and 125 were exposed to placebo.
It- tul tal- kura f’ nisa li diġà għaddew mill- menopawsa kien ta ’ 12- il xahar, 124 ġew esposti għal FABLYN u 125 ġew esposti għall- plaċebo.
Within this study, 3.2% of FABLYN-treated women and 8.0% of placebo-treated women discontinued therapy due to adverse events.
Fi 3. 2% tan- nisa li kienu kkurati b’ FABLYN u 8. 0% tan- nisa li kienu kkurati bil- plaċebo it- terapija twaqqfet minħabba effetti aversi li dehru.
Table 1 lists adverse reactions occurring in the two osteoporosis treatment clinical trials that occurred at an incidence greater than placebo.
Tabella 1 fiha lista ta ’ reazzjonijiet avversi li dehru fiż- żewġ provi kliniċi li saru fuq il- kura tal- osteoporożi, u li seħħew f’ inċidenza akbar mill- plaċebo.
Most of the adverse reactions occurring during the studies were mild and generally did not require discontinuation of therapy.
Ħafna mir- reazzjonijiet avversi li dehru matul l- istudji kienu ħfief, u b’ mod ġenerali ma wasslux għat- twaqqif tat- terapija.
Adverse reactions are listed by system organ class and frequency (very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10), uncommon (≥ 1/ 1,000 to < 1/ 100) and rare (≥ 1/ 10,000 to < 1/ 1,000)).
Ir- reazzjonijiet avversi huma mniżżla skont is- sistema tal- klassifikazzjoni tal- organi u l- frekwenza ((komuni ħafna (≥1/ 10), komuni (≥1/ 100 sa < 1/ 10), mhux komuni (≥1/ 1, 000 sa < 1/ 100) u rari (≥1/ 10, 000 sa < 1/ 1, 000)).
In each system organ class and frequency, adverse reactions are not presented in order of decreasing seriousness but in alphabetical order.
F’ kull sistema ta ’ klassifikazzjoni tal- organi u frekwenza, l- effetti avversi mhumiex imniżżla skont is- serjetà tagħhom iżda skont ordni alfabetika.
Adverse reactions observed in placebo-controlled osteoporosis treatment clinical trials in more FABLYN-treated women than in placebo-treated women
Reazzjonijiet avversi osservati fi provi kliniċi tal- kura tal- osteoporożi kontrollati bil- plaċebo aktar fin- nisa kkurati b’ FABLYN milli f’ dawk ikkurati bil- plaċebo
Urinary tract infection, vaginal candidiasis, vaginal infection, vulvovaginitis Arthritis infective, bronchitis, cellulitis, cervicitis, diverticulitis, fungal infection, furuncle, genital candidiasis, herpes simplex ophthalmic, impetigo, labyrinthitis, pyelonephritis, pyometra
Infezzjonijiet u infestazzjonijiet Candidiasis fil- vaġina, infezzjoni fil- vaġina, infezzjoni fis- sistema urinarja, Mhux komun: infjammazzjoni tal- vulva u tal- vaġina Artrite infettiva, bronkite, candidiasis fil- ġenitali, ċellulite, furunklu, herpes Rari: simplex fl- għajnejn, impetigo, infezzjoni tal- fungu, infjammazzjoni ta ’ l- għonq ta ’ l- utru, infjammazzjoni tad- divertikulu, labirintite, pajelonefrite, pajometra Neoplażmi beninni, malinni u dawk mhux speċifikati (inklużi ċesti u polipi) Fibroma, leiomyoma tal- utru Mhux komun:
Fibroma, uterine leiomyoma Benign breast neoplasm, breast fibroma, chronic lymphocytic leukaemia, endometrial neoplasm, female reproductive neoplasm, haemangioma, hepatic neoplasm malignant, leiomyoma, melanocytic naevus, multiple myeloma, neoplasm, parathyroid tumour benign
Emanġjoma, fibroma fis- sider, lewkimja limfoċitika kronika, lejomajoma, naevus Rari: melanoċitiku, neoplażma, neoplażma beninn tas- sider, neoplażma fis- sistema riproduttiva tan- nisa, neoplażma malinn tal- fwied, neoplażma tal- endometriju, tumur beninn fil- paratirojde, tumur multiplu malinn tal- mudullun tal- għadam Disturbi tad- demm u tas- sistema limfatika Anemija, makroċitosi, tromboċitopenija Mhux komuni:
Rare:
Anemija megaloblastika, ipokromasja Rari:
Immune system disorders Rare:
Disturbi fis- sistema immuni Allerġija marbuta ma ’ l- istaġuni Rari:
Hyperparathyroidism
Disturbi fis- sistema endokrinarja Iperparatirojdiżmu Rari:
Rare:
Disturbi fil- metaboliżmu u n- nutrizzjoni Dijabete mellitus Mhux komuni:
Diabetes mellitus Anorexia, decreased appetite, hypertriglyceridaemia, hypoalbuminaemia, hypophosphataemia, increased appetite, tetany, type 2 diabetes mellitus
Anoressija, dijabete mellitus tat- 2 tip, ipertrigliċeridemija, ipoalbuminemija, Rari: ipofosfatimija, tnaqqis fl- aptit, tetanja, żieda fl- aptit Disturbi psikjatriċi Cyclothymic disorder, ħolm anormali Rari:
Eye disorders
Disturbi fis- sistema nervuża Infart ċerebrali, senzazzjoni ta ’ ħruq, sindromu ta ’ nuqqas ta ’ kwiet fir- riġlejn, Mhux komuni: uġigħ ta ’ ras Amnesija, dimenzja tat- tip tal- marda Alzheimer, disgewsja, emigranja, emigranja Rari: b’ sintomi li wieħed iħosshom qabel attakk tal- epilessija, epilessija, idroċefalu, ipogewsja, kompressjoni tan- nervituri, marda tan- nerv tac- caqlieq, paresi,
Burning sensation, cerebral infarction, headache, restless legs syndrome Amnesia, dementia Alzheimer’ s type, dizziness postural, dysgeusia, epilepsy, hydrocephalus, hypogeusia, memory impairment, migraine, migraine with aura, motor neurone disease, nerve compression, paresis, presyncope, sciatica, vascular headache
7 presinkope, sturdament assocjat mal- pożizzjoni tal- ġisem, telf tal- memorja, uġiegħ ta ’ ras saskulari, xjatika Distrubi fl- għajnejn Għajnejn xotti Mhux komuni:
Dry eye Aphakia, chorioretinopathy, conjunctival haemorrhage, conjunctival hyperaemia, eye haemorrhage, eye pruritus, eyelid oedema, keratoconjunctivitis sicca, macular degeneration, ocular hyperaemia, pupils unequal, retinal detachment, retinal vascular disorder, retinopathy, visual acuity reduced, visual disturbance
Afakia, diġenerazzjoni tal- makula, disturbi fil- vista, disturbi vaskulari fir- retina, Rari: emorraġija fil- konġuntiva, emorraġija fl- għajnejn, ħakk fl- għajnejn, id- daqs tal- ħabba tal- għajnejn mhux l- istess, ikkawżata minn akkumulazzjoni ta ’ ilma, iperimija fl- għajnejn, iperimija tal- konġuntiva, korjoretinopatija, nefħa fl- għotjien tal- għajnejn kerato konġuntivite, retinopathy, tinqala ir- retina, tnaqqis fl- akutezza tal- vista Disturbi fil- widnejn u fis- sistema labirintika Disturbi fin- naħa ta ’ ġewwa tal- widna, skonfort fil- widnejn, vertigo kkawżat Rari: mill- pożizzjoni Disturbi fil- qalb Palpitazzjonijiet, takikardija Mhux komuni:
Palpitations, tachycardia Cardiac failure, cardiomegaly, cor pulmonale, sinus arrest, supraventricular extrasystoles, tricuspid valve incompetence
Attakk tal- qalb, cor pulmonale, ekstrasistoli supraventrikulari, inkompetenza Rari: tal- valvola tal- qalb magħmula minn tliet segmenti trijangulari, kardiomegalija, sinus arrest Disturbi vaskulari Fwawar tal- menopawsa Komuni:
Aortic aneurysm, arterial occlusive disease, capillary disorder, embolism, haematoma, haemorrhage, intermittent claudication, lymphostasis, thrombosis, vascular stenosis, venous thrombosis, venous thrombosis limb
Flebite, fwawar, tromboflebite, tromboflebite superfiċjali, trombożi tal- vini Mhux komuni: l- fondi, waqfien ta ’ ċirkolazzjoni fil- vini Anewriżma tal- aorta, disturbi fil- kapillari, ematoma, emboliżmu, emorraġija, Rari: ikkaġunat minn astruzzjoni fl- arterji, l- aktar fir- riġlejn, limfotasi, marda ta ’ sadd tal- arterji, stenosi vaskulari, trombożi, trombożi fil- vini, trombożi fil- vini tad- dirgħajn u tar- riġlejn, uġigħ li jieqaf u jerġa ’ jibda l- ħin kollu bħal ta ’ bugħawwieġ Disturbi respiratorji, toraċiċi u medjastinali Emboliżmu pulmonari, rinite allerġika, sogħla Mhux komuni:
Rare:
Granuloma pulmonari, mard kroniku ta ’ imblukkar fil- pulmun, rinite vasomotorja Rari:
Uncommon:
Disturbi gastro- intestinali Stitikezza Komuni:
Abdominal tenderness, anal fissure, anal spasm, cheilitis, cheilosis, colitis ulcerative, duodenal ulcer, duodenitis, dysphagia, gastric polyps, inguinal hernia, mouth ulceration, oesophagitis, oral pain, rectal polyp, rectal ulcer, stomach discomfort
Gass fl- istonku, gastrite, ħalq xott, sindromu tal- musrana sensittiva (IBS), uġigħ Mhux komuni: addominali, uġigħ fin- naħa ta ’ fuq taż- żaqq, uġigħ fin- naħa ta ’ isfel taż- żaqq Disfaġija, duwodenite, fissura anali, ftuq ingwinali, keilite, keilosi, kolite Rari: bl- ulċeri, osefaġite, polipa fir- rektum, polipi fl- istonku, sensittività addominali, skonfort fl- istonku, spażmu anali, tiġriħ fil- ħalq, uġigħ fil- ħalq, ulċera duwodenali, ulċera fir- rektum Disturbi fil- fwied u fil- marrara Kolelitiasi, stejatożi tal- fwied Mhux komuni:
Rare:
Disturbi fil- fwied, epatite, ġebla fil- marrara, koleċistite, suffejra Rari:
Rare:
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Iperidrosi Komuni:
Rare:
Alopeċja, eritema, ħakk, ħruġ ta ’ għaraq bil- lejl Mhux komuni:
Muscle spasms Back pain, neck pain, pain in extremity Arthropathy, bursitis, clubbing, coccydynia, costochondritis, dactylitis, exostosis, extremity contracture, haemarthrosis, joint stiffness, muscle contracture, muscle twitching, musculoskeletal discomfort, pain in jaw, periarthritis, rheumatoid arthritis, rotator cuff syndrome, tenosynovitis
Angjoedema, feriti fil- ġilda, disturbi fid- dwiefer, ġilda xotta, ħakk imxerred Rari: ma ’ partijiet differenti tal- ġisem, irritazzjoni fil- ġilda, mod mhux tas- soltu ta ’ kif jinħass ix- xagħar, nefħa fil- ġilda kkawżata minn akkumulazzjoni ta ’ ilma, onikoclasi, raxx li jqabbdek il- ħakk, pigmentazzjoni eċċessiva fil- ġilda, raxx maculo- papulari, reazzjoni ta ’ fotosensittività, rosacea, urtikarjaa Disturbi musko- skeltrali, tat- tessut konnettiv u disturbi tal- għadam
Rare:
8 Spażmi fil- muskoli Komuni ħafna:
Reproductive system and breast disorders Common:
Uġigħ fid- dahar, uġigħ fl- estremità, uġigħ fl- għonq Mhux komuni:
Adenomyosis, adnexa uteri cyst, adnexa uteri mass, breast discharge, breast engorgement, breast fibrosis, enlarged clitoris, fallopian tube cyst, nipple disorder, nipple pain, perineal laceration, pruritus genital, uterine cervical squamous metaplasia, uterine haemorrhage, uterine mass, vaginal erosion, vaginal inflammation, vaginal pain, vaginal wall congestion, varicose veins vulval, vulvar disorder
Artrite rewmatika, artropatija, bursite, caqliq involontarju fil- muskoli, clubbing, Rari: coccydynia, contracture fl- estremitajiet, dactylitis, ebusija tal- ġogi, eksostosi, emartrosi, kontrazzjoni tal- muskoli, kostokondrite, periartrite, sindromu rotator cuff, skonfort muskolu- skeltrali, tenosinovite, uġigħ fix- xedaq Disturbi fil- kliewi u fis- sistema urinarja Disturbi fl- uretra, għall- urinazzjoni, għamil tal- awrina frekwenti ħafna matul Mhux komuni: il- ġurnata, inkontinenza, qawmien bil- lejl, urinazzjoni b’ urġenza Bużżieqa tal- awrina ipertonika, disturbi fis- sistema urinarja, emorraġija fl- uretra, Rari: ħaġra fil- bużżieqa tal- awrina, iperkalċurja, polipi fil- bużżieqa tal- awrina, sklerosi tal- kliewi Disturbi fis- sistema riproduttiva u fis- sider Cystocele, disturbi fil- vaġina, disturbi fl- endometriju, ipertrofija tal- endometriju * Komuni (ħxuna sonografika tal- endometriju), qarnita fl- utru, tnixxija mill- vaġina Akkumulazzjoni ta ’ fluwidu fl- utru, colpocele, displasja ċervikali, disturbi Mhux komuni: fis- sider tan- nisa, disturbi fl- għonq tal- utru, ebusija fis- sider, emorraġija ġenitali, emorraġija ta ’ wara l- menopawsa, emorraġija vaġinali, erożjoni ċervikali tal- utru, ħakk fil- vulva u l- vaġina, iperplasija tal- endometriju ** (skont rapporti tal- investigazzjonijiet), l- utru joħroġ barra minn postu, polipi ċervikali, prolass vaġinali, rectocele, tnixxija anormali tad- demm mill- ġuf, tnixxija ġenitali, uġigħ fis- sider Adenomajosi, ċesti adnexa uteri, ċesti fit- tubu fallopjan, disturbi fil- bżieżel, Rari: disturbi fil- vulva, emorraġija fl- utru, fibrożi fiss- sider, ħakk fil- ġenitali, infjammazzjoni fil- vaġina, konġestjoni fil- ħajt tal- vaġina, mass fl- utru, massa adnexa uteri, metaplasija ċervikali skwamuża fl- utru, sider konġestjonat bid- demm, taħfir fil- vaġina, tiċrit fil- perinew, tkabbir tal- klitoride, tnixxija mis- sider, uġigħ fil- bżieżel, uġigħ fil- vaġina, vini varikużi fil- vulva Disturbi konġenitali, familjari u ġenetiċi Formazzjoni difettuża tal- vini Rari:
Investigations
Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata Rispons terapewtiku mhux mistenni Komuni:
Therapeutic response unexpected Chest pain, fatigue, feeling hot, oedema peripheral Chest discomfort, feeling drunk, hyperthermia, inflammation, mass, oedema, polyp
Għeja, nefħa qrib is- superfiċje tal- ġisem ikkawżata minn akkumulazzjoni ta ’ Mhux komuni: ilma, tħoss is- sħana, uġigħ fis- sider Infjammazzjoni, ipertermija, mass, nefħa fil- ġisem ikkawżata minn Rari: akkumulazzjoni ta ’ ilma, polipi, skonfort fis- sider, tħossok qisek fis- sakra Investigazzjonijiet Żieda fl- aspartate aminotransferase Komuni:
Aspartate aminotransferase increased Alanine aminotransferase increased, blood glucose increased, smear cervix abnormal, transaminases increased, weight increased
Smear tal- għonq ta ’ l- utru anormali, żieda fil- piż, żieda fit- transaminases, żieda Mhux komuni: fl- alanine aminotransferase, żieda tal- glukożju fid- demm Krejatinina fid- demm anormali, l- antiġen tal- wiċċ tal- epatite B pożittiv, mewġa Rari:
5′ nucleotidase increased, blood albumin decreased, blood creatinine abnormal, blood triglycerides increased, blood urine present, bone density decreased, chest X-ray abnormal, electrocardiogram T wave abnormal, gamma-glutamyltransferase increased, hepatitis B surface antigen positive, high density lipoprotein decreased, low density lipoprotein increased, pedal pulse decreased, platelet count decreased, ultrasound breast abnormal, ultrasound ovary abnormal
T tal- elettrokardjogramm anormali, preżenza tad- demm fl- awrina, riżultat tal- eżami ultrasoniku tal- ovarji anormali, riżultat tal- eżami ultrasoniku tas- sider anormali, tnaqqis fid- densità tal- għadam, tnaqqis fil- lipoproteina ta ’ densità għolja, tnaqqis fil- pedal pulse, tnaqqis fl- għadd tal- pjastrini fid- demm tnaqqis fl- albumina fid- demm, X- ray anormali tas- sider, żieda fil - 5 ′ nucleotidase, żieda fil- gamma- glutamyltransferase, żieda fil- lipoproteina ta ’ densità baxxa żieda fit- trigliċeridi fid- demm Korriment u avvelenament Rari:
Excoriation, genital injury, limb injury, skeletal injury, soft tissue injury, spinal fracture, thoracic vertebral fracture, tooth fracture
9 Korriment fid- dirgħajn u r- riġlejn, korriment fil- ġenitali, korriment fit- tessuti rotob, korriment skeletriku, ksur fl- ispina, ksur tas- snien, ksur vertebrali toraċiku, sliħ
* Endometrial hypertrophy is a MedDRA dictionary term that represents sonographic endometrial thickness findings.
* Ipertrofija tal- endometriju hija terminoloġija tad- dizzjunarju MedDRA li tirrappreżenta r- riżultati dwar il- ħxuna sonografika tal- endometriju
8 ** Endometrial hyperplasia events based on investigator reporting rather than histopathology findings and did not require histological confirmation.
** Effetti tal- iperplasija tal- endimetriju bbażati fuq rapporti tal- investigazzjonijiet mhux fuq ir- riżultati tal- istopatoloġija, u ma kinux jirrikjedu konferma istoloġika.
No case of FABLYN overdose has been reported.
L- ebda każ ta ’ doża eċċessiva b’ FABLYN ma ġie rrappurtat.
Lasofoxifene has been administered to postmenopausal women at single doses as high as 100 mg (200 times the recommended unit dose) and multiple doses as high as 10 mg/ day (20 times the recommended dose) for up to one year without dose-related serious adverse reactions.
Lasofoxifene ingħata lil nisa li diġà għaddew mill- menopawsa permezz ta ’ dożi singoli sa 100 mg (200 darba aktar mid- doża rrakkomandata) u permezz ta ’ dożi multipli sa 10 mg/ kuljum (20 darba aktar mid- doża rrakkomandata) għal massimu ta ’ sena mingħajr ma kien hemm reazzjonijiet avversi serji li huma relatati mad- dożaġġ.
There is no specific antidote for FABLYN.
M’ hemm l- ebda antidotu speċifiku għal FABLYN.
In the event of overdose, general supportive measures should be initiated based on the patient’ s signs and symptoms.
F’ każ ta ’ doża eċċessiva, għandhom jinbdew miżuri ġenerali ta ’ appoġġ skont is- sinjali u s- sintomi tal- pazjenta.
Selective Estrogen Receptor Modulator (SERM), ATC code:
Modulatur Selettiv tar- Riċetturi tal- Estroġenu (SERM), Kodiċi ATC:
Decreases in estrogen levels after menopause or oophorectomy lead to accelerated bone loss due to increased bone turnover, where bone resorption exceeds bone formation.
It- tnaqqis fil- livelli tal- estroġenu wara l- menopawsa jew wara operazzjoni fejn jitneħħa ovarju wieħed jew it- tnejn, iwasslu għal telf tal- għadam b’ ritmu mgħaġġel minħabba żieda fl- immudellar mill- ġdid tal- għadam, fejn l- assorbiment mill- ġdid jeċċedi l- formazzjoni tal- għadam.
The increased turnover causes accelerated bone loss because the compensatory increase in bone formation is not sufficient to offset increased bone resorption.
Iż- żieda fl- immudellar tal- għadam tikkawża tnaqqis fl- għadam b’ ritmu mgħaġġel minħabba l- fatt li ż- żieda fil- formazzjoni tal- għadam li ssir, biex tagħmel tajjeb għat- telf tal- għadam, ma tkunx biżżejjed biex toħloq bilanċ maż- żieda fl- assorbiment mill- ġdid tal- għadam.
In some women, these changes will eventually lead to decreased bone mass, osteoporosis, and increased risk for fractures, particularly of the spine, hip, and wrist.
F’ xi nisa, dawn il- bidliet eventwalment iwasslu għal tnaqqis fil- massa tal- għadam, għall- osteoporożi, u għal riskju akbar ta ’ ksur, speċjalment tal- ispina, il- ġenbejn u l- polz tal- idejn.
Vertebral fractures are the most common type of osteoporotic fracture in postmenopausal women.
Ksur vertebrali huwa l- aktar tip komuni ta ’ ksur ikkawżat mill- osteoporożi f’ nisa li diġà għaddew mill- menopawsa.
Lasofoxifene is a SERM whose biological actions are largely mediated through binding to estrogen receptors.
Lasofoxifene huwa SERM li l- azzjonijiet bijoloġiċi tiegħu huma fil- biċċa l- kbira medjati permezz tat- twaħħil mar- riċetturi tal- estroġenu.
This binding results in the activation of some estrogenic pathways and a blockade of others.
Dan it- twaħħil iwassal għall- attivazzjoni ta ’ xi passaġġi minn fejn jgħaddi l- estroġenu u għall- imblukkar ta ’ oħrajn.
Lasofoxifene produces tissue and cell-specific effects in estrogen-responsive tissues.
Lasofoxifene jipproduċi effetti fuq it- tessuti u effetti relatati maċ- ċelluli fuq it- tessuti li juru rispons għall- estroġenu.
Clinical data indicate that FABLYN has an estrogen-like agonist effect on bone as well as antagonistic effects on the breast.
It- tagħrif kliniku jindika li FABLYN għandu effett agonist li jixbaħ lil dak tal- estroġenu fuq l- għadam, kif ukoll effetti antagonistiċi fuq is- sider.
The effects of FABLYN on bone are manifested as reductions in the serum and urine levels of bone turnover markers, increases in bone mineral density (BMD), and decreases in incidence of fractures.
L- effetti ta ’ FABLYN fuq l- għadam jimmanifestaw ruħhom bħala tnaqqis fil- livelli fis- serum u fl- awrina tal- markaturi tal- immudellar mill- ġdid tal- għadam, żidiet fid- densità ta ’ minerali fl- għadam (BMD), u tnaqqis fl- inċidenza tal- ksur.
Skeletal effects:
Effetti skeltrali:
Bone turnover
L- immudellar tal- għadam mill- ġdid
In the osteoporosis treatment trials, FABLYN therapy resulted in consistent, statistically significant suppression of bone resorption and bone formation, as reflected by changes in serum and urine markers of bone turnover (e. g., C-telopeptide and markers of bone formation: osteocalcin, procollagen type 1 N-terminal propeptide, and bone-specific alkaline phosphatase).
C- telopeptide u markaturi tal- formazzjoni tal- għadam: osteocalcin, procollagen type 1 N- terminal propeptide, u alkaline phosphatase speċifikat għall- għadam).
The suppression of bone turnover markers was evident by 3 months and persisted throughout the 36-month observation period in a sub-study of the PEARL study.
Fi studju li jifforma parti mill- istudju PEARL, it- trażżin tal- markaturi tal- immudellar tal- għadam mill- ġdid beda jidher wara 3 xhur u baqa ’ matul il- perjodu ta ’ 36 xahar ta ’ osservazzjoni.
9 5-year results from large, multinational fracture trial (PEARL)
Riżultati ta ’ perjodu ta ’ 5 snin tal- prova l- kbira multinazzjonali dwar il ksurl (PEARL)
The effects of FABLYN on fracture incidence (table 2) were examined through 5 years; and BMD and bone biomarkers in postmenopausal women with osteoporosis were examined through 3 years in the PEARL study.
L- effetti ta ’ FABLYN fuq l- inċidenza tal- ksur (tabella 2) ġew eżaminati matul perjodu ta ’ 5 snin; u l- BMD u l- bijomarkaturi tal- għadam f’ nisa li diġà għaddew mill- menopawsa ġew eżaminati matul perjodu ta ’ 3 snin fl- istudju PEARL.
The study population consisted of 8,556 postmenopausal women with osteoporosis as defined by low BMD (vertebral or hip BMD at least 2.5 standard deviations below the mean value for healthy young women).
Il- populazzjoni li fuqha sar l- istudju kienet tikkonsisti fi 8556 mara li diġà għaddew mill- menopawsa li jbatu mill- osteoporożi kif jidher mill- BMD baxx tagħhom (il- BMD tas- sinsla tad- dahar jew tal- ġenbejn mill- inqas ikun 2. 5 devjazzjonijiet standard inqas mill- valur medju f’ nisa ta ’ età żgħira li jkunu f’ saħħithom).
Women enrolled in this study had a median age of 67 years (range 59 to 80) and a median time since menopause of 20 years.
In- nisa li kienu qegħdin jipparteċipaw f’ dan l- istudju kellhom età medja ta ’ 67 sena (medda minn 59 sa 80 sena) u medja ta ’ 20 sena minn meta kellhom il- menopawa.
All women in the study received calcium (1,000 mg/ day) and Vitamin D (400-800 IU/ day).
In- nisa kollha li kienu qegħdin jipparteċipaw fl- istudju ingħataw il- kalċju (1000 mg/ kuljum) u l- Vitamina D (400- 800 IU/ kuljum).
Fracture incidence in postmenopausal women over 5 years
Inċidenza ta ’ ksur fuq perjodu ta ’ 5 snin f’ nisa li diġà għaddew mill- menopawsa
reduction (95% CI) vs. placebo New radiographic vertebral fractures
Tnqqis relattiv tar- riskju (95% IK) vs. plaċebo
n=2,748
n=2, 748
n=2,744
n=2, 744
Percentage of patients with new fracture New radiographic vertebral fracture in patients with ≥ 1
ksur ġdid Ksur vertebrali radjografiku ġdid f’ pazjenti b’ linja bażi
5.6%
5. 6% n=778
9.3%
9. 3% n=774
Percentage of patients with new fracture New radiographic vertebral fracture in patients without any
tal- ksur ta ’ ≥ 1 Perċentwal ta ’ pazjenti bi ksur ġdid Ksur vertebrali radjografiku ġdid f’ pazjenti mingħajr ebda