natgillin/translations-raw huggingface dataset:
Fablyn nedsatte signifikant forekomsten af non- vertebrale frakturer fra 10, 4% for placebo til 8, 1% for Fablyn (relativ reduktion af risiko = 24%, p = 0, 0020).
FABLYN significantly decreased the incidence of non-vertebral fractures from 10.4% for placebo to 8.1% for FABLYN (relative risk reduction = 24%, p = 0.0020).
Reduktionen i forekomsten af non- vertebrale frakturer blev også set hos postmenopausale kvinder med svær osteoporose (defineret som baseline lænderygsøjle- BMD T- score ≤ - 2, 5 + prævalent fraktur eller BMD T- score ≤ - 3) (p = 0, 0183).
The reduction in the incidence of non-vertebral fractures was also observed in postmenopausal women with severe osteoporosis (defined as a baseline lumbar spine BMD T-score ≤ -2.5 + prevalent fracture or BMD T-score ≤ -3) (p = 0.0183).
- Alle kliniske frakturer
-All clinical fractures
Fablyn nedsatte signifikant forekomsten af alle kliniske frakturer fra 12, 1% for placebo til 9, 3% for Fablyn (relativ reduktion af risiko = 25%, p = 0, 0004).
FABLYN significantly decreased the incidence of all clinical fractures from 12.1% for placebo to 9.3% for FABLYN (relative risk reduction = 25%, p = 0.0004).
- Knogle mineraldensitet (BMD)
-Bone mineral density
I et 3- års substudie under PEARL- studiet (n=760) forøgede Fablyn signifikant BMD (sammenlignet med placebo) i lænderygsøjle (3, 3%), total hofte (3, 0%), lårbenshals (3, 3%), trochanter major (3, 6%), intertrochantær- område (2, 6%), Wards trekant (5, 9%) og underarm (1, 8%) efter 3 år.
In a 3-year substudy of the PEARL study (n=760), FABLYN significantly increased BMD (compared to placebo) at lumbar spine (3.3%), total hip (3.0%), femoral neck (3.3%), greater trochanter (3.6%), intertrochanteric area (2.6%), Ward’ s triangle (5.9%) and forearm (1.8%) at 3 years.
Fablyn øgede også signifikant helkrops- knoglemineralindholdet (BMC) sammenlignet med placebo efter 3 år.
FABLYN also significantly increased whole body bone mineral content (BMC), compared to placebo, at 3 years.
Der blev foretaget en analyse af de patienter, der blev henvist til egen læge med henblik på eventuelt præparatskifte efter observation af et af følgende fund: a) ≥7% BMD- tab i lænderygsøjle eller ≥10% BMD- tab i lårbenshals efter 12 måneder; b) ≥11% BMD- tab i lænderygsøjle eller ≥14% BMD- tab i lårbenshals efter 24 måneder; c) ≥2 on- study radiografisk verificerede rygsøjlefrakturer efter 24 måneder.
An analysis was conducted of the subjects who were referred to their physician for consideration of treatment with an alternative osteoporosis medicinal product if one of the following was observed: a) ≥ 7% BMD loss at LS or ≥ 10% BMD loss at femoral neck at Month 12; b) ≥ 11% BMD loss at lumbar spine (LS) or ≥ 14% BMD loss at femoral neck at Month 24; c) ≥ 2 on-study radiographic vertebral fractures by Month 24.
Der var signifikant færre af disse henvisninger i Fablyn- gruppen (0, 9%) end i placebogruppen (3, 3%).
These referrals were significantly less frequent in the FABLYN group (0.9%) than in the placebo group (3.3%).
Resultater fra 1- års- studie med asiatiske patienter
Results from one-year trial in Asian subjects
Fablyns virkning på BMD hos postmenopausale japanske, koreanske og taiwanesiske kvinder med osteoporose blev også undersøgt i et 1- års randomiseret, placebokontrolleret, dobbelblindt osteoporose- studie.
The effects of FABLYN on BMD in postmenopausal Japanese, Korean and Taiwanese women with osteoporosis were also examined in a one-year, randomized, placebo-controlled, double-blind osteoporosis treatment trial.
Studiepopulationen bestod af 497 kvinder med osteoporose, defineret ved lav rygsøjle- BMD (T- score ≤ 2, 5).
The study population consisted of 497 women with osteoporosis as defined by low vertebral BMD (T-score ≤ 2.5).
Alle kvinder i studiet fik calcium (600- 1200 mg dagligt) og vitamin D (400- 800 IU dagligt).
All women in the study received calcium (600-1200 mg/ day) and Vitamin D (400-800 IU/ day).
I dette studie øgede Fablyn signifikant rygsøjle - og hofte- BMD (total hofte og alle subkomponenter af hoften) med 2 til 4%.
In this study, FABLYN significantly increased spine and hip (total hip and all subcomponents of the hip) BMD by 2 to 4%.
Behandlingen nedsatte også knogleomsætnings- markører.
It also reduced markers of bone turnover.
Der var ingen tegn på osteomalaci, knoglemarvsfibrose, cellulær toksicitet, woven bone eller andre abnormiteter, som kunne påvirke knoglekvaliteten efter lasofoxifen- behandling.
There was no evidence of osteomalacia, marrow fibrosis, cellular toxicity, woven bone or other abnormalities affecting the quality of the bone following lasofoxifene treatment.
Følgende information om Fablyns virkning på endometriet gennem 5 års eksponering kommer fra PEARL- studiet.
The following results of the effects of FABLYN on the endometrium through 5 years of exposure are reported from the PEARL study.
Der var ingen forskel i forekomsten af endometriekarcinom og endometriehyperplasi mellem Fablyn - og placebobehandlede kvinder.
There was no difference between FABLYN- and placebo-treated women in the incidences of endometrial carcinoma and endometrial hyperplasia.
1, 5 mm.
11 Lasofoxifene may be associated with benign endometrial effects: endometrial cystic change viewed on ultrasound and histological benign cystic atrophy (a variant of atrophic endometrium), contributing to approximately 1.5 mm increase in mean endometrial thickness.
4. 4).
In clinical practice, these benign findings do not warrant further evaluation in women with no vaginal bleeding, in accordance with guidelines for postmenopausal women (see section 4.4).
Placebobehandlede kvinder havde en forekomst af cystiske forandringer på 1, 9% over 3 år, mens Fablyn- behandlede kvinder havde en forekomst på 20, 4%.
Placebo-treated women had a 1.9% incidence in cystic change over 3 years, whereas the FABLYN-treated women had a 20.4% incidence.
Placebobehandlede kvinder havde et fald i den gennemsnitlige endometrietykkelse på 0, 7 mm fra baseline over 3 år, mens Fablyn- behandlede kvinder havde en gennemsnitlig stigning på 1, 4 mm.
Placebo-treated women had a 0.7 mm mean decrease from baseline in endometrial thickness over 3 years, whereas the FABLYN-treated women had a 1.4 mm mean increase.
Hos kvinder med en uterus ved baseline blev der fundet histologisk benigne endometriepolypper hos 34 af 2302 (1, 5%) Fablyn- behandlede kvinder versus 18 af 2309 (0, 8%) placebobehandlede kvinder.
In all women with a uterus at baseline, histologically benign endometrial polyps were reported in 34 of 2,302 (1.5%) FABLYN-treated women versus 18 of 2,309 (0.8%) placebo-treated women.
I en undergruppe af studiepopulationen, designet til at undersøge endometriehistologi (1080 patienter) ved en TVU efter 3 år, blev der fundet histologisk benigne endometriepolypper hos 20 af 366 (5, 5%) Fablyn- behandlede kvinder og hos 12 af 360 (3, 3%) placebobehandlede kvinder.
In a subset of the study population designed to look at endometrial histology (1,080 patients) with a TVU at 3 years, histologically benign endometrial polyps were reported in 20 of 366 (5.5%) FABLYN-treated women and 12 of 360 (3.3%) placebo-treated women.
Den totale forekomst af vaginalblødning var lav (≤ 2, 6% i alle behandlingsgrupper).
The overall incidence of vaginal bleeding was low (≤ 2.6% in all treatment groups).
Vaginalblødning blev set hos 74 (2, 6%) Fablyn- behandlede kvinder versus 37 (1, 3%) placebobehandlede kvinder.
Vaginal bleeding was reported in 74 (2.6%) FABLYN-treated women versus 37 (1.3%) placebo-treated women.
Antallet af patienter, der fik seponeret behandlingen på grund af vaginalblødning, var lavt [Fablyn:
The number of subjects discontinuing treatment as a result of vaginal bleeding was low [FABLYN:
Antallet af hysterektomier i Fablyn- gruppen (27/ 2302 patienter, 1, 2%) og i placebogruppen (24/ 2309 patienter, 1, 0%) var ens.
The number of hysterectomies in the FABLYN-treated group (27/ 2,302 patients, 1.2%) and the placebo-treated group (24/ 2,309 patients, 1.0%) were similar.
For at vurdere virkningen af Fablyn på diagnostiske uterine procedurer (dvs. hysteroskopi, sonohysterografi med saltvandsindsprøjtning, endometriebiopsi, polypektomi eller dilatation og curettage) blev der udført en undersøgelse af kvinder uden planlagt TVU- overvågning (4055 patienter).
To assess the effect of FABLYN on diagnostic uterine procedures (i. e., hysteroscopy, saline infused sonohysterogram, endometrial biopsy, polypectomy or dilation and curettage), an analysis was conducted on women without planned TVU surveillance (4,055 patients).
Flere Fablyn- behandlede patienter (7, 0%) end placebobehandlede patienter (2, 7%) fik foretaget en diagnostisk procedure.
More FABLYN-treated patients (7.0%) had a diagnostic procedure compared to placebo-treated patients (2.7%).
Der blev udført flere diagnostiske uterine procedurer på Fablyn- behandlede patienter som følge af vaginal blødning (som beskrevet i protokollen) og asymptomatiske endometriefund (f. eks. mistanke om uteruspolypper, endometrietykkelse).
Diagnostic uterine procedures were performed in a greater number of FABLYN-treated patients as a result of vaginal bleeding (as mandated by the protocol) and asymptomatic endometrial findings (e. g., suspected uterine polyps, endometrial thickness).
Sammenlignet med placebo nedsatte Fablyn- behandling risikoen for invasiv mammacancer med 85% (placebo:
Over the 5 years of the PEARL study (involving 8,556 patients), FABLYN treatment compared to placebo reduced the risk of invasive breast cancer by 85% (placebo:
20 (0, 7%), Fablyn:
20 (0.7%), FABLYN:
3 (0, 1%); HR 0, 15 (CI 0, 04; 0, 50)), risikoen for alle typer af mammacancer med 79% (placebo:
3 (0.1%); HR 0.15 (CI 0.04, 0.50)), the risk of all breast cancer by 79% (placebo:
24 (0, 9%), Fablyn:
24 (0.9%), FABLYN:
5 (0, 2%); HR 0, 21 (CI 0, 08; 0, 55)), risikoen for østrogenreceptor- positiv invasiv mammacancer med 83% (placebo:
5 (0.2%); HR 0.21 (CI 0.08, 0.55)), the risk of estrogen receptor (ER) positive invasive breast cancer by 83% (placebo:
18 (0, 7%), Fablyn:
18 (0.7%), FABLYN:
3 (0, 1%); HR 0, 17 (CI 0, 05; 0, 57)) og risikoen for østrogenreceptor- positiv mammacancer med 81% (placebo:
3 (0.1%); HR 0.17 (CI 0.05, 0.57)) and the risk of estrogen receptor (ER) positive breast cancer by 81% (placebo:
21 (0, 8%), Fablyn:
21 (0.8%), FABLYN:
4 (0, 1%); HR 0, 19 (CI 0, 07; 0, 56)).
4 (0.1%); HR 0.19 (CI 0.07, 0.56)).
Fablyn påvirker ikke risikoen for østrogenreceptor- negativ mammacancer eller østrogenreceptor- negativ invasiv mammacancer.
FABLYN has no effect on the risk of ER negative breast cancer or ER negative invasive breast cancers.
12 Virkninger på lipidmetabolisme og kardiovaskulær risiko:
12 Effects on lipid metabolism and cardiovascular risk:
Fablyns virkning på lipidprofilen blev undersøgt i et 3- års substudie under PEARL- studiet; substudiet involverede 1014 postmenopausale kvinder.
The effect of FABLYN on the lipid profile was evaluated in a 3-year substudy of the PEARL study; the substudy enrolled 1,014 postmenopausal women.
I forhold til placebo nedsatte Fablyn signifikant totalkolesterol, LDL- kolesterol, LDL- associeret apolipoprotein B- 100 og high- sensitivity C- reaktivt protein (gennemsnitlige ændringer henholdsvis - 10, 4%, - 15, 8%, - 11, 8%, - 12, 5%); Der blev ikke set signifikante ændringer af HDL- kolesterol eller VLDL- kolesterol.
Relative to placebo, FABLYN significantly decreased total cholesterol, LDL cholesterol, LDL-associated apolipoprotein B-100, and high sensitivity C-reactive protein (median changes -10.4%, -15.8%, -11.8%, -12.5%, respectively); no significant changes versus placebo were seen for HDL cholesterol or VLDL cholesterol.
Der blev set statistisk signifikante stigninger i apolipoprotein A- 1, som er associeret med HDL- kolesterol, og i serumtriglycerider (gennemsnitlig ændring vs. placebo henholdsvis 6, 1% og 4, 9%).
Statistically significant increases were seen for apolipoprotein A-1, which is associated with HDL cholesterol, and serum triglycerides (median changes vs. placebo 6.1% and 4.9%, respectively).
For hele studiepopulationen (N=8556) var der efter 5 år signifikant lavere forekomst af alvorlige koronare hændelser, herunder koronardød, ikke- fatal myokardieinfarkt, ny iskæmisk hjertesygdom, hospitalisering på grund af ustabil angina pectoris og revaskulariseringsprocedurer.
At 5 years in the overall study population (N=8,556), the incidence of major coronary events, including coronary death, non-fatal myocardial infarction, new ischemic heart disease, hospitalization for unstable angina, and revascularisation procedures, was significantly lower.
Der var 0, 51 hændelser/ 100 patientår hos Fablyn- behandlede patienter sammenlignet med 0, 75 hændelser/ 100 patientår hos placebobehandlede patienter (HR 0, 68; 95% CI 0, 50; 0, 93, p= 0, 016).
There were 0.51 events/ 100 patient-years for FABLYN-treated patients compared to 0.75 events/ 100 patient-years in placebo-treated patients (HR 0.68; 95% CI 0.50, 0.93, p= 0.016).
I det samme studie var der efter 5 år ingen stigning i risikoen for apopleksi, herunder hæmoragisk, iskæmisk, embolisk apopleksi, ikke- specificeret apopleksi og transitorisk iskæmisk hændelse hos Fablyn- behandlede patienter.
In the same study at 5 years, there was no increase in the risk of stroke including hemorrhagic, ischemic, embolic stroke, stroke type unspecified and transient ischemic attacks in FABLYN-treated patients.
Der var 0, 48 hændelser/ 100 patientår i placebo- gruppen og 0, 36 hændelser/ 100 patientår blandt Fablyn- behandlede patienter (HR = 0, 75; 95% CI 0, 51; 1, 10 p = 0, 140).
There were 0.48 events/ 100 patient years in the placebo group and 0.36 events/ 100 patient years among FABLYN-treated patients (HR = 0.75; 95% CI 0.51, 1.10, p = 0.140).
Fablyns virkning i behandlingen af VVA blev undersøgt i to 12- ugers fase 3- studier med postmenopausale kvinder med moderate eller alvorlige tegn og symptomer på VVA, uafhængigt af osteoporose- status (889 patienter).
The efficacy of FABLYN in the treatment of VVA was investigated in two 12-week Phase 3 studies in postmenopausal women with moderate or severe signs and symptoms of VVA, regardless of osteoporosis status (involving 889 patients).
I begge studier nedsatte behandlingen sværhedsgraden af patienternes mest generende baseline VVA- symptom, nedsatte vaginalt pH, nedsatte procentdelen af vaginale parabasale celler fra maturation index (MI) og øgede procentdelen af vaginale overfladeceller fra MI.
In both studies, it decreased the severity of the subject’ s most bothersome baseline VVA symptom, decreased vaginal pH, decreased the percentage of vaginal parabasal cells from the maturation index (MI) and increased the percentage of vaginal superficial cells from the MI.
Lignende resultater for vaginalt pH og MI sås i PEARL- studiet.
Similar results for vaginal pH and MI were observed in the PEARL study.
Farmakokinetiske data fra mere end 2000 postmenopausale kvinder, inklusive patienter i udvalgte osteoporose- studier, har dannet grundlag for en populationsfarmakokinetisk analyse.
Pharmacokinetic data from over 2,000 postmenopausal women including patients in selected osteoporosis clinical trials contributed to a population pharmacokinetic analysis.
Lasofoxifen absorberes langsomt fra mave- tarm- kanalen og maksimale plasmakoncentrationer opnås gennemsnitligt 6 timer efter dosering.
Lasofoxifene is slowly absorbed from the gastrointestinal tract with maximal plasma concentrations attained on average by approximately 6 hours after dosing.
1350 l.
The apparent volume of distribution (V/ F) of lasofoxifene in postmenopausal women is approximately 1,350 l.
Lasofoxifen er i høj grad bundet til proteiner i humant plasma (> 99%).
Lasofoxifene is highly bound to proteins in human plasma (> 99%).
Lasofoxifen bindes til både albumin og α1- acid glycoprotein, men påvirker ikke bindingen af hverken warfarin eller propranolol.
Lasofoxifene binds to both albumin and α 1-acid glycoprotein; however, it does not affect the binding of either warfarin or propranolol.
13 Metabolisme:
13 Metabolism:
Der er identificeret fem metaboliske pathways for lasofoxifen: direkte glucuronidation; direkte sulfonering; hydroxylering af phenyltetralin- delen (med efterfølgende konjugerende metabolisme af catechol- intermediaterne ved metylering og glucuronidation); oxidering af pyrrolidinringen; og phenylhydroxylering.
Five metabolic pathways of lasofoxifene have been identified: direct glucuronidation; direct sulfation; hydroxylation at the phenyl tetraline moiety (with subsequent conjugative metabolism of the catechol intermediates by methylation and glucuronidation); oxidation at the pyrrolidine ring; and phenyl hydroxylation.
Dette indikerer, at disse metabolitter sandsynligvis ikke bidrager til lasofoxifens farmakologiske aktivitet.
The binding affinities of the major circulating metabolites of lasofoxifene were at least 31-fold and 18-fold less than those of lasofoxifene for the estrogen receptor alpha and the estrogen receptor beta, respectively, indicating that these metabolites are unlikely to contribute to the pharmacologic activity of lasofoxifene.
Lasofoxifens 2 primære eliminationsveje er oxidering af en række cytochrome P450- systemer, herunder CYP 2D6 og 3A4/ 5, samt konjugering af lasofoxifen.
Oxidation, by multiple cytochrome P450s including CYPs 2D6 and 3A4/ 5, and conjugation of lasofoxifene are the two primary mechanisms of elimination of lasofoxifene from the systemic circulation.
6, 6 l/ time.
The apparent oral clearance (CL/ F) of lasofoxifene in postmenopausal women is approximately 6.6 l/ hr.
6 dage.
Lasofoxifene has a half-life of approximately 6 days.
Lasofoxifen og dets metabolitter udskilles primært i fæces med kun en mindre del af det lasofoxifen- relaterede materiale udskilt i urinen.
Lasofoxifene and its metabolites are primarily excreted in feces, with a minor component of urinary excretion of active substance-related material.
66% i fæces og 6% i urin).
Following oral administration of 14C-labeled lasofoxifene in solution to humans, approximately 72% of the radioactive dose was recovered by day 24 (approximately 66% in feces and 6% in urine).
Mindre end 2% af den administrerede dosis blev genfundet i urinen som uomdannet lasofoxifen.
Less than 2% of the administered dose was recovered in the urine as unchanged lasofoxifene.
Lasofoxifens steady state- farmakokinetik stemmer overens med, hvad der kunne forventes ud fra enkeltdosis- farmakokinetikken.
Steady-state pharmacokinetics of lasofoxifene are consistent with expectations from its single-dose pharmacokinetics.
6 dage ved steady state, hvilket giver små koncentrationsudsving over doseringsintervallet på 24 timer.
At steady state, the half-life of lasofoxifene in postmenopausal women is approximately 6 days, resulting in small fluctuations in concentrations over the 24-hour dosing interval.
Denne analyse inkluderede 2049 postmenopausale kvinder, bestående af 85, 5% kaukasiske, 8, 6% latin- amerikanske, 3, 4% asiatiske og 1, 9% afro- amerikanske kvinder.
This analysis included 2,049 postmenopausal women consisting of 85.5% Caucasian, 8.6% Hispanic, 3.4% Asian, and 1.9% African American.
Resultaterne fra et fase 1- studie hos japanske og kaukasiske kvinder stemmer overens med den populationsfarmakokinetiske analyse og viser ingen forskelle i lasofoxifens farmakokinetik mellem disse 2 populationer.
The results of a phase 1 study in Japanese and Caucasian women was consistent with the population pharmacokinetic analysis and showed no discernible difference in lasofoxifene pharmacokinetics in these two populations.
14 Køn:
14 Gender:
Lasofoxifen blev undersøgt som en enkeltdosis på 0, 25 mg hos raske frivillige og frivillige med mild eller moderat leverinsufficiens.
Lasofoxifene was studied, as a single 0.25 mg dose, in healthy subjects and subjects with mild or moderate hepatic impairment.
Plasmaindholdet af lasofoxifen var omtrent det samme hos raske frivillige som hos frivillige med mild leverinsufficiens (Child- Pugh Class A) og moderat øget (38%) hos frivillige med moderat leverinsufficiens (Child- Pugh Class B) sammenlignet med raske frivillige.
Plasma lasofoxifene exposure was approximately the same in healthy subjects as in subjects with mild hepatic impairment (Child-Pugh Class A) and was modestly increased (38%) in subjects with moderate hepatic impairment (Child-Pugh Class B) compared to healthy subjects.
4. 4).
Subjects with severe hepatic impairment have not been studied (see section 4.4).
Da mindre end 2% af lasofoxifen genfindes i urinen som uomdannet substans, er der ikke foretaget undersøgelser på personer med nyreinsufficiens.
Since less than 2% of lasofoxifene is recovered in urine as unchanged active substance, a study in subjects with renal insufficiency was not conducted.
I en populationsfarmakokinetisk analyse ses der ingen klinisk relevante forskelle i lasofoxifens farmakokinetik mellem postmenopausale kvinder med estimeret creatininclearance så lav som 32 ml/ min og kvinder med normal creatininclearance.
In a population pharmacokinetic analysis, there were no clinically meaningful differences in lasofoxifene pharmacokinetics between postmenopausal women with estimated creatinine clearance as low as 32 ml/ min and those with normal creatinine clearance.
4. 4).
No dose adjustment for FABLYN is necessary for patients with mild or moderate renal insufficiency (see section 4.4).
I 2- års carcinogenicitets- undersøgelser på rotter (≥1 mg/ kg/ dag; 7 gange den systemiske eksponering efter en human dosis på 0, 5 mg/ dag, baseret på plasma- AUC) sås en øget forekomst af renale tubulære adenomer og carcinomer hos hanner og granulosacelletumorer i ovarierne hos hunner.
In two-year carcinogenicity studies conducted in rats (≥ 1 mg/ kg/ day; 7 times systemic exposure following a human dose of 0.5 mg/ day based on plasma AUC) an increased incidence of renal tubular adenoma and carcinoma in males and granulosa cell tumours of the ovary in females was noted.
I den tilsvarende 2- års undersøgelse på mus (≥2 mg/ kg/ dag; mindre end den systemiske eksponering efter en human dosis på 0, 5 mg/ dag baseret på plasma- AUC) sås en øget forekomst af adrenokorticale adenomer og carcinomer, interstitielle celletumorer i testes, benigne og maligne ovarietumorer og benigne uterine glandulære polypper.
In the corresponding 2-year study in mice (≥ 2 mg/ kg/ day; less than systemic exposure following a human dose of 0.5 mg/ day based on plasma AUC), there was an increased incidence of adrenal cortical adenoma and carcinoma, interstitial cell tumors of the testis, benign and malignant ovarian tumors and benign uterine glandular polyps.
Selvom alle disse tumorer anses for at være forårsaget af en gnaver- specifik hormonel mekanisme, er relevansen for mennesker ukendt.
Although all of these tumours are believed to be the result of rodent-specific hormonal mechanisms, their relevance for humans is currently unknown.
Baseret på 3 - og 5- års humane data fra de kliniske studier var forekomsten af cancer under behandlingen med lasofoxifen ikke højere end for placebo.
Based on 3- and 5-year human data in the clinical trials, the incidence of cancer during treatment with lasofoxifene was not higher than for placebo.
53 gange AUC hos mennesker) eller kaniner op til en dosis på 3 mg/ kg (under niveauet for systemisk eksponering hos mennesker).
Lasofoxifene was not teratogenic in rats up to a dose of 10mg/ kg (approximately 53 times the AUC in humans) or rabbits up to a dose of 3 mg/ kg (below the level of systemic exposure in humans).
400 gange AUC hos mennesker), og var forbundet med en øget embryo- føtal letalitet og generel mistrivsel.
Increased incidence of imperforate anus, hypoplastic tail, edema and limb flexures noted in fetuses of pregnant rats dosed at 100 mg/ kg (approximately 400 times the AUC in humans) were associated with increased embryo-fetal lethality and generalized failure to thrive.
42 gange AUC hos mennesker), hvilket kom til udtryk i en nedsættelse af parringsindeks, implantationssteder og fostre.
In fertility studies conducted in rats with lasofoxifene, slight effects on male reproductive performance occurred at ≥ 10 mg/ kg/ day (approximately 42 times the AUC in humans) as evidenced by decreases in copulation index, implantation sites, and fetuses sired.