Fablyn

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

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1. NAME OF THE MEDICINAL PRODUCT 
 
FABLYN 500 microgram film-coated tablets. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains lasofoxifene tartrate, equivalent to 500 micrograms lasofoxifene. 
 
Excipient: Each film-coated tablet contains 71.34 mg lactose. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
 
Triangular, peach-coloured, film-coated tablets debossed with “Pfizer” on one side and “OPR 05” on 
the other side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
FABLYN is indicated for the treatment of osteoporosis in postmenopausal women at increased risk of 
fracture. A significant reduction in the incidence of vertebral and non-vertebral fractures but not hip 
fractures has been demonstrated (see section 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). 
 
4.2 Posology and method of administration 
 
Adult (postmenopausal women): 
 
The recommended dose is one 500 microgram tablet daily. 
 
The tablet may be taken any time of day without regard to food and beverage intake. 
 
Supplemental calcium and/or vitamin D should be added to the diet if daily intake is inadequate. 
Postmenopausal women require an average of 1,500 mg/day of elemental calcium. The recommended 
intake of vitamin D is 400-800 IU daily. 
 
Children and adolescents below 18 years of age: 
 
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. Therefore safety and efficacy have not been studied (see 
section 5.2). 
 
Elderly women (65 years and older): 
 
No dose adjustment is necessary in elderly female patients (see section 5.2). 
 

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Hepatic insufficiency: 
 
No dose adjustment is required in patients with mild to moderate hepatic insufficiency (see section 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. 
 
Renal insufficiency: 
 
No dose adjustment is necessary in patients with mild or moderate renal insufficiency (see section 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. 
 
Due to the chronic nature of the disease process, FABLYN is intended for long-term use (see section 5.1). 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients. 
 
Active or past history of venous thromboembolic events, including deep vein thrombosis, pulmonary 
embolism and retinal vein thrombosis. 
 
Unexplained uterine bleeding. 
 
Pregnancy and lactation: FABLYN is only for use in postmenopausal women. It must not be taken by 
women of child-bearing potential, pregnant women and lactating women (see section 4.6). 
 
4.4 Special warnings and precautions for use 
 
In clinical trials, FABLYN-treated women had an increased risk of venous thromboembolic events (deep 
vein thrombosis and pulmonary embolism) compared to placebo. Other venous thromboembolic events 
could also occur. A less serious event, superficial thrombophlebitis, also has been reported more frequently 
with FABLYN compared to placebo. 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). 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. In addition, 
women taking FABLYN should be advised to move about periodically during prolonged travel. 
 
Any unexplained vaginal bleeding should be investigated as clinically indicated. FABLYN-treated and 
placebo-treated groups had similar incidences of endometrial hyperplasia and endometrial cancer (see 
section 5.1). 
 
Lasofoxifene has been associated with benign endometrial effects. 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). These cystic 
findings contributed to an approximate 1.5 mm increase in mean endometrial thickness. 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). 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. 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. 
 
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. 
 

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FABLYN has not been studied in women with a prior history of breast cancer. No data are available on its 
concomitant use with agents used in the treatment of early or advanced breast cancer. Therefore, FABLYN 
should be used for the treatment of osteoporosis only after the treatment of breast cancer, including 
adjuvant therapy, has been completed. 
 
Any unexplained breast abnormality occurring during FABLYN therapy should be investigated. FABLYN 
does not eliminate the risk of breast cancer (see section 5.1). 
 
FABLYN may increase the incidence of hot flushes and is not effective in reducing hot flushes associated 
with estrogen deficiency. In some asymptomatic patients, hot flushes may occur upon beginning therapy. 
 
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. Patients with 
this medical history should have serum triglycerides monitored when taking lasofoxifene. 
 
Lasofoxifene is highly protein bound, predominantly cleared by metabolism and is likely to undergo 
enterohepatic circulation (see section 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. 
 
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). 
 
FABLYN contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase 
deficiency or glucose-galactose malabsorption should not take this medicinal product. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
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. 
 
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. 
 
Ketoconazole - The strong CYP3A4/5 inhibitor ketoconazole increased the systemic exposure of 
lasofoxifene by 20% which is not considered to be clinically meaningful. 
 
Paroxetine - The strong CYP2D6 inhibitor paroxetine increased the systemic exposure of lasofoxifene 
by 35% which is not considered to be clinically meaningful. 
 
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. 
 
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). 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. 
 
Warfarin - Lasofoxifene had no effect on the pharmacokinetics of R- and S- warfarin. Mean 
international normalized ratio (INR) AUC and maximum value of INR after single-dose warfarin 

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administration with lasofoxifene were approximately 8% and 16% lower, respectively, than after 
warfarin alone. These changes are not considered to be clinically meaningful. 
 
4.6 Pregnancy and lactation 
 
Pregnancy 
 
FABLYN is only for use in postmenopausal women. FABLYN must not be taken by women of child-
bearing potential (see section 4.3). There are no adequate data from the use of lasofoxifene in pregnant 
women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for 
humans is unknown.  
 
Lactation 
 
FABLYN is only for use in postmenopausal women. FABLYN must not be taken during lactation (see 
section 4.3). It is not known whether lasofoxifene is excreted in human milk. Animal studies have shown 
excretion of lasofoxifene in milk. 
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects on the ability to drive and use machines have been performed. 
 
FABLYN has no known influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
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). 
The duration of treatment in postmenopausal women was 60 months, 2,852 were randomized to 
FABLYN and 2,852 were randomized to placebo. 
 
Within this study, 12.9% of FABLYN-treated women and 12.3% of placebo-treated women 
discontinued therapy due to adverse events. 
 
Venous Thromboembolic Events: The most serious adverse reaction related to FABLYN was VTE 
(deep venous thrombosis, pulmonary embolism, and retinal vein thrombosis). 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: 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. 
 
Common adverse reactions considered to be related to FABLYN therapy were muscle spasms, hot 
flush and vaginal discharge. Muscle spasms occurred in about one in 9 patients . Hot flush occurred in 
about one in 11 patients and was most commonly reported during the first 6 months of treatment. 
Vaginal discharge occurred in about one in 26 patients. 
 
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. The duration of treatment in 
postmenopausal women was 12 months, 124 were exposed to FABLYN and 125 were exposed to 
placebo. Within this study, 3.2% of FABLYN-treated women and 8.0% of placebo-treated women 
discontinued therapy due to adverse events. 
 
Table 1 lists adverse reactions occurring in the two osteoporosis treatment clinical trials that occurred 
at an incidence greater than placebo. 

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Most of the adverse reactions occurring during the studies were mild and generally did not require 
discontinuation of therapy. 
 
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)). In each system 
organ class and frequency, adverse reactions are not presented in order of decreasing seriousness but 
in alphabetical order. 
 
Table 1: Adverse reactions observed in placebo-controlled osteoporosis treatment clinical trials 
in more FABLYN-treated women than in placebo-treated women 
 
Infections and infestations 
Uncommon: Urinary tract infection, vaginal candidiasis, vaginal infection, vulvovaginitis 
Rare: Arthritis infective, bronchitis, cellulitis, cervicitis, diverticulitis, fungal infection, 

furuncle, genital candidiasis, herpes simplex ophthalmic, impetigo, labyrinthitis, 
pyelonephritis, pyometra 

Neoplasms benign, malignant and unspecified (including cysts and polyps) 
Uncommon: Fibroma, uterine leiomyoma 
Rare: 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 

Blood and lymphatic system disorders 
Uncommon: Anaemia, macrocytosis, thrombocytopenia 
Rare: Anaemia megaloblastic, hypochromasia 
Immune system disorders 
Rare: Seasonal allergy 
Endocrine disorders 
Rare: Hyperparathyroidism 
Metabolism and nutrition disorders 
Uncommon: Diabetes mellitus 
Rare: Anorexia, decreased appetite, hypertriglyceridaemia, hypoalbuminaemia, 

hypophosphataemia, increased appetite, tetany, type 2 diabetes mellitus 
Psychiatric disorders 
Rare: Abnormal dreams, cyclothymic disorder 
Nervous system disorders 
Uncommon: Burning sensation, cerebral infarction, headache, restless legs syndrome 
Rare: 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 

Eye disorders 
Uncommon: Dry eye 
Rare: 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 

Ear and labyrinth disorders 
Rare: Ear discomfort, inner ear disorder, vertigo positional 
Cardiac disorders 
Uncommon: Palpitations, tachycardia 

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Rare: Cardiac failure, cardiomegaly, cor pulmonale, sinus arrest, supraventricular extrasystoles, 
tricuspid valve incompetence  

Vascular disorders 
Common: Hot flush 
Uncommon: Deep vein thrombosis, flushing, phlebitis, thrombophlebitis, thrombophlebitis superficial, 

venous stasis 
Rare: Aortic aneurysm, arterial occlusive disease, capillary disorder, embolism, haematoma, 

haemorrhage, intermittent claudication, lymphostasis, thrombosis, vascular stenosis, 
venous thrombosis, venous thrombosis limb 

Respiratory, thoracic and mediastinal disorders 
Uncommon: Cough, pulmonary embolism, rhinitis allergic 
Rare: Chronic obstructive pulmonary disease, pulmonary granuloma, vasomotor rhinitis 
Gastrointestinal disorders 
Common: Constipation 
Uncommon: Abdominal pain, abdominal pain lower, abdominal pain upper, dry mouth, flatulence, 

gastritis, irritable bowel syndrome 
Rare: 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 

Hepatobiliary disorders 
Uncommon: Cholelithiasis, hepatic steatosis 
Rare: Bile duct stone, cholecystitis, hepatitis, jaundice, liver disorder 
Skin and subcutaneous tissue disorders 
Common Hyperhidrosis 
Uncommon: Alopecia, erythema, night sweats, pruritus 
Rare: Angioedema, dry skin, hair texture abnormal, nail disorder, onychoclasis, 

photosensitivity reaction, pruritus generalized, rash maculo-papular, rash pruritic, 
rosacea, skin irritation, skin lesion, skin hyperpigmentation, skin oedema, urticaria 

Musculoskeletal, connective tissue and bone disorders 
Very 
common: 

Muscle spasms 

Uncommon: Back pain, neck pain, pain in extremity 
Rare: 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 

Renal and urinary disorders 
Uncommon: Micturition urgency, nocturia, pollakiuria, urethral disorder, urinary incontinence 
Rare: Calculus bladder, hypercalciuria, hypertonic bladder, nephrosclerosis, urethral 

haemorrhage, urinary bladder polyp, urinary tract disorder 
Reproductive system and breast disorders 
Common: Cystocele, endometrial disorder, endometrial hypertrophy* (sonographic endometrial 

thickness), uterine polyp, vaginal discharge, vaginal disorder 
Uncommon: Breast disorder female, breast induration, breast pain, cervix disorder, cervical dysplasia, 

cervical polyp, colpocele, endometrial hyperplasia** (based on investigator reporting), 
genital discharge, genital haemorrhage, hydrometra, metrorrhagia, postmenopausal 
haemorrhage, rectocele, uterine cervical erosion, uterine prolapse, vaginal haemorrhage, 
vaginal prolapse, vulvovaginal pruritus  

Rare: Adenomyosis, adnexa uteri cyst, adnexa uteri mass, breast discharge, breast 
engorgement, breast fibrosis, enlarged clitoris, fallopian tube cyst, nipple disorder, nipple 

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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 

Congenital, familial and genetic disorders 
Rare: Malformation venous 
General disorders and administration site conditions 
Common: Therapeutic response unexpected 
Uncommon: Chest pain, fatigue, feeling hot, oedema peripheral 
Rare: Chest discomfort, feeling drunk, hyperthermia, inflammation, mass, oedema, polyp 
Investigations 
Common: Aspartate aminotransferase increased 
Uncommon: Alanine aminotransferase increased, blood glucose increased, smear cervix abnormal, 

transaminases increased, weight increased 
Rare: 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 

Injury and poisoning 
Rare: Excoriation, genital injury, limb injury, skeletal injury, soft tissue injury, spinal fracture, 

thoracic vertebral fracture, tooth fracture 
 
* Endometrial hypertrophy is a MedDRA dictionary term that represents sonographic endometrial 
thickness findings. 
 
** Endometrial hyperplasia events based on investigator reporting rather than histopathology findings 
and did not require histological confirmation. 
 
4.9 Overdose 
 
No case of FABLYN overdose has been reported. 
 
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. 
 
There is no specific antidote for FABLYN. In the event of overdose, general supportive measures 
should be initiated based on the patient’s signs and symptoms. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Selective Estrogen Receptor Modulator (SERM), ATC code: {not yet 
assigned}  
 
Decreases in estrogen levels after menopause or oophorectomy lead to accelerated bone loss due to 
increased bone turnover, where bone resorption exceeds bone formation. The increased turnover 
causes accelerated bone loss because the compensatory increase in bone formation is not sufficient to 
offset increased bone resorption. In some women, these changes will eventually lead to decreased 

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bone mass, osteoporosis, and increased risk for fractures, particularly of the spine, hip, and wrist. 
Vertebral fractures are the most common type of osteoporotic fracture in postmenopausal women. 
 
Lasofoxifene is a SERM whose biological actions are largely mediated through binding to estrogen 
receptors. This binding results in the activation of some estrogenic pathways and a blockade of others. 
Lasofoxifene produces tissue and cell-specific effects in estrogen-responsive tissues. 
 
Clinical data indicate that FABLYN has an estrogen-like agonist effect on bone as well as antagonistic 
effects on the breast. 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. 
 
Skeletal effects: 
 
Bone turnover 
 
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). 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. 
 
5-year results from large, multinational fracture trial (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. 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). 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. All women in the study received calcium (1,000 
mg/day) and Vitamin D (400-800 IU/day). 
 
Table 2: Fracture incidence in postmenopausal women over 5 years 
 
 FABLYN Placebo Relative risk reduction (95% 

CI) vs. placebo 
New radiographic vertebral fractures 
Percentage of patients with new fracture 

n=2,748
5.6% 

n=2,744
9.3% 

41%a 
(28%, 52%) 

New radiographic vertebral fracture in patients with ≥ 
1 baseline fracture 
Percentage of patients with new fracture 

n=778
8.7% 

n=774
14.2%

42%b 
(21%, 57%) 

New radiographic vertebral fracture in patients 
without any prevalent fracture at baseline 
Percentage of patients with new fracture 

n=1,970
4.4% 

n=1,970
7.4% 

41%c 
(23%, 55%) 

Non-vertebral fractures 
Percentage of patients with non-vertebral fracture 

n=2,852
8.1% 

n=2,852
10.4%

24%d 
(9%, 36%) 

All clinical fractures 
Percentage of patients with clinical fracture 

n=2,852
9.3% 

n=2,852
12.1%

25%e 
(12%, 36%) 

Abbreviations: n= number of patients; CI = Confidence Intervals 
a p < 0.0001; b p = 0.0004; c p = 0.0002; d p = 0.0020; e p = 0.0004 
 
 
-Radiographic vertebral fractures 

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FABLYN significantly decreased the incidence of new radiographic vertebral fractures (excluding 
worsening of previous fractures) from 9.3% for placebo to 5.6% for FABLYN (relative risk reduction 
= 41%, p < 0.0001). This decrease was observed through the first year and was maintained through 5 
years. 
 
In women with a prevalent vertebral fracture at baseline, FABLYN significantly reduced the incidence 
of new vertebral radiographic fractures from 14.2% for placebo to 8.7% for FABLYN (relative risk 
reduction = 42%, p = 0.0004). In women without any prevalent vertebral fractures at baseline, the 
incidence of new radiographic vertebral fractures was significantly reduced from 7.4% for placebo to 
4.4% for FABLYN (relative risk reduction = 41%, p = 0.0002). 
 
Significantly fewer women experienced multiple radiographic vertebral fractures in the FABLYN 
treatment group versus the placebo group throughout 5 years of dosing (p < 0.0001). 
 
Significantly fewer women treated with FABLYN experienced moderate or severe vertebral fractures 
(as determined by the Genant scale) compared to women treated with placebo (5.2% placebo-treated 
women versus 3.3% FABLYN-treated women; p = 0.0006). 
 
-Non-vertebral fractures 
 
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). This decrease was observed through 
the first year and was maintained through 5 years. 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). 
 
-All clinical fractures 
 
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). This decrease was observed through 
the first year and maintained through 5 years. 
 
-Bone mineral density 
 
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 also 
significantly increased whole body bone mineral content (BMC), compared to placebo, at 3 years. 
Significant increases in BMD were observed as early as 3 months for lumbar spine and total hip. 
 
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. These referrals were significantly less frequent in the FABLYN group (0.9%) 
than in the placebo group (3.3%). 
 
Results from one-year trial in Asian subjects 
 
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. The study population consisted of 497 women with osteoporosis as 
defined by low vertebral BMD (T-score ≤ 2.5). Women in this study had a median age of 63 years 
(range 44 to 79) and a median time since menopause of 13 years. All women in the study received 
calcium (600-1200 mg/day) and Vitamin D (400-800 IU/day). 

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In this study, FABLYN significantly increased spine and hip (total hip and all subcomponents of the 
hip) BMD by 2 to 4%. It also reduced markers of bone turnover. 
 
Bone histomorphometry 
 
Bone formed during two years’ administration of lasofoxifene is of normal quality. To assess bone 
quality, bone biopsies were obtained from 71 postmenopausal women enrolled in BMD trials after 2 
years of treatment. There was no evidence of osteomalacia, marrow fibrosis, cellular toxicity, woven 
bone or other abnormalities affecting the quality of the bone following lasofoxifene treatment. 
 
Effects on the endometrium: 
 
The following results of the effects of FABLYN on the endometrium through 5 years of exposure are 
reported from the PEARL study. 
 
There was no difference between FABLYN- and placebo-treated women in the incidences of 
endometrial carcinoma and endometrial hyperplasia. 
 
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. 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). 
 
The incidence of endometrial cystic change and endometrial thickness was analyzed in a subset of the 
study population (298 patients) with an annual transvaginal ultrasound (TVU) through 3 years. 
Placebo-treated women had a 1.9% incidence in cystic change over 3 years, whereas the FABLYN-
treated women had a 20.4% incidence. All histology findings were benign. 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. The increase was observed at 12 months, and 
did not significantly increase through 3 years. In some cases, these findings were observed to resolve 
spontaneously on treatment. 
 
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. 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. 
 
The overall incidence of vaginal bleeding was low (≤ 2.6% in all treatment groups). Vaginal bleeding 
was reported in 74 (2.6%) FABLYN-treated women versus 37 (1.3%) placebo-treated women. The 
number of subjects discontinuing treatment as a result of vaginal bleeding was low [FABLYN: 4 
(0.1%), placebo: 0]. 
 
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. 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). More FABLYN-treated patients (7.0%) had a diagnostic procedure 
compared to placebo-treated patients (2.7%). 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). 
 
Effects on breast: 

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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: 3 (0.1%); 
HR 0.15 (CI 0.04, 0.50)), the risk of all breast cancer by 79% (placebo: 24 (0.9%), FABLYN: 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: 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: 4 (0.1%); HR 0.19 (CI 
0.07, 0.56)). FABLYN has no effect on the risk of ER negative breast cancer or ER negative invasive 
breast cancers. These observations support the conclusion that lasofoxifene has no intrinsic estrogen 
agonist activity in breast tissue. 
  
Effects on lipid metabolism and cardiovascular risk: 
 
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. 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. 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). 
 
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. 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). 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. 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). 
 
Effects on vulvar and vaginal atrophy (VVA): 
 
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). 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. Similar results for vaginal pH and MI were observed in the PEARL study. 
 
5.2 Pharmacokinetic properties 
 
The disposition of lasofoxifene was evaluated in 758 subjects in conventional clinical pharmacology 
studies. Pharmacokinetic data from over 2,000 postmenopausal women including patients in selected 
osteoporosis clinical trials contributed to a population pharmacokinetic analysis. 
 
Absorption: 
 
Lasofoxifene is slowly absorbed from the gastrointestinal tract with maximal plasma concentrations 
attained on average by approximately 6 hours after dosing. Ingestion of a high fat meal does not 
change the oral bioavailability of lasofoxifene. FABLYN may be administered any time of day 
without regard to food or beverage intake. 
 
Distribution: 
 

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The apparent volume of distribution (V/F) of lasofoxifene in postmenopausal women is approximately 
1,350 l. 
 
Lasofoxifene is highly bound to proteins in human plasma (>99%). Lasofoxifene binds to both 
albumin and α1-acid glycoprotein; however, it does not affect the binding of either warfarin or 
propranolol. 
 
Metabolism: 
 
Biotransformation and disposition of lasofoxifene in humans have been determined following oral 
administration of 14C-labeled lasofoxifene. Lasofoxifene is extensively metabolized in humans. 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. Three metabolites of lasofoxifene were detected in plasma: the direct glucuronide 
conjugate, the glucuronide of a hydroxylated metabolite, and the methylated catechol. 
 
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. 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. The apparent oral clearance (CL/F) of lasofoxifene in postmenopausal women is 
approximately 6.6 l/hr. 
 
Elimination: 
 
Lasofoxifene has a half-life of approximately 6 days. Lasofoxifene and its metabolites are primarily 
excreted in feces, with a minor component of urinary excretion of active substance-related material. 
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). Less 
than 2% of the administered dose was recovered in the urine as unchanged lasofoxifene. 
 
Linearity/non-linearity: 
 
Lasofoxifene exhibits linear pharmacokinetics over a wide dose range following single-dose (up to 
100 mg) and multiple-dose (up to 20 mg once daily) administration. Steady-state pharmacokinetics of 
lasofoxifene are consistent with expectations from its single-dose pharmacokinetics. 
 
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. 
 
Paediatric: 
 
The pharmacokinetics of lasofoxifene have not been evaluated in a paediatric population. 
 
Elderly: 
 
No clinically meaningful differences in lasofoxifene pharmacokinetic were observed over the age 
range of 40 to 80 years of age based on the results of a population pharmacokinetic analysis. No dose 
adjustment for FABLYN is necessary in elderly patients. 
 
Race: 
 
In a population pharmacokinetic analysis, no discernible difference in lasofoxifene pharmacokinetics 
was detected in different racial groups. This analysis included 2,049 postmenopausal women 

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consisting of 85.5% Caucasian, 8.6% Hispanic, 3.4% Asian, and 1.9% African American. 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. 
 
Gender: 
 
Since FABLYN is indicated for use only in postmenopausal women, no assessment of the effect of 
gender on lasofoxifene pharmacokinetics has been made. 
 
Hepatically impaired patients: 
 
Lasofoxifene was studied, as a single 0.25 mg dose, in healthy subjects and subjects with mild or 
moderate hepatic impairment. 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. These differences are not considered to be clinically meaningful. No dose adjustment 
for FABLYN is necessary for patients with mild or moderate hepatic insufficiency. Subjects with 
severe hepatic impairment have not been studied (see section 4.4). 
 
Renally impaired patients: 
 
Since less than 2% of lasofoxifene is recovered in urine as unchanged active substance, a study in 
subjects with renal insufficiency was not conducted. 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. No dose adjustment for FABLYN is necessary for patients with mild or moderate renal 
insufficiency (see section 4.4). 
 
5.3 Preclinical safety data 
 
Lasofoxifene was not genotoxic in any of the battery of tests applied. 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. 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. 
Although all of these tumours are believed to be the result of rodent-specific hormonal mechanisms, 
their relevance for humans is currently unknown. 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. 
 
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). 
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. 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. Reduced fertility, and an increase in pre- and post-implantation 
loss leading to reduced litter size and prolonged gestation were observed in females treated at ≥0.01 
mg/kg/day (below the level of systemic exposure in humans). In a prenatal and postnatal study in rats, 
at ≥0.01 mg/kg/day lasofoxifene delayed and/or disrupted parturition, increased pup mortality at birth, 
altered the achievement of developmental milestones, and reduced growth. Overall, the reproductive 
and developmental effects observed in animals are consistent with the SERM class of compounds. 
 

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6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core: 
 
Lactose anhydrous 
 
Microcrystalline cellulose 
 
Croscarmellose sodium 
 
Silica, colloidal anhydrous 
 
Magnesium stearate 
 
Tablet coating: 
 
Sunset yellow FCF aluminium lake (E110) 
 
Hypromellose 
 
Lactose monohydrate 
 
Titanium dioxide (E171) 
 
Triacetin 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
4 years 
 
6.4 Special precautions for storage 
 
This medicine does not require any special storage conditions. 
 
6.5 Nature and contents of container 
 
FABLYN film-coated tablets are supplied in PVC blisters with aluminum foil backing or HDPE 
bottles with polyethylene/aluminum foil lined polypropylene child-resistant closures. 
 
Blister packs of 7, 28 or 30 tablets and bottles of 90 tablets. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
No special requirements. 
 
7. MARKETING AUTHORISATION HOLDER 
 

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Dr. Friedrich Eberth Arzneimittel GmbH 
Am Bahnhof 2 
92289 Ursensollen 
Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/08/500/001 
 
EU/1/08/500/002 
 
EU/1/08/500/003 
 
EU/1/08/500/004 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
24 February 2009 
 
 
10. DATE OF REVISION OF THE TEXT 
 
<{MM/YYYY}> 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency (EMEA) http://www.emea.europa.eu/. 
 

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http://www.emea.europa.eu/�


 17

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE 
SUBSTANCE AND MANUFACTURING AUTHORISATION 
HOLDER RESPONSIBLE FOR BATCH RELEASE 

 
B. CONDITIONS OF THE MARKETING AUTHORISATION 

 
 

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A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH 
RELEASE 

 
Name and address of the manufacturer of the biological active substance  
 
Not applicable 
 
Name and address of the manufacturer responsible for batch release  
 
Pfizer Manufacturing Deutschland GmbH 
 
Heinrich Mack Strasse 35 
 
D-89257 Illertissen 
 
Germany 
 
 
B. CONDITIONS OF THE MARKETING AUTHORISATION 
 
 CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON THE 

MARKETING AUTHORISATION HOLDER 
 
Medicinal product subject to medical prescription. 
 
 CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 

USE OF THE MEDICINAL PRODUCT 
 
The Marketing Authorisation Holder (MAH) shall ensure that, prior to launch, all healthcare 
professionals who are expected to prescribe FABLYN or order gynaecological ultrasound of patients 
treated with FABLYN, are provided with access to risk minimisation educational programme. 
 
The programme shall have both electronic and printed form, which are identical in terms of content. 
 
The programme materials shall be provided via the following means: 
 
 Web-based  
 On CD  
 Printed on paper 
 
The programme shall convey the following key messages: 
 
 FABLYN increases risk of venous thromboembolism (VTE).  
 The approaches recommended for mitigation of risk of venous thromboembolism based on the 

SmPC, including contraindication of FABLYN in patients with active or past history of VTE.  
 FABLYN causes morphologic changes, particularly the cystic atrophy of endometrium. It 

results in increased mean endometrial thickness.  
 Based on the clinical trials, the morphologic changes caused by FABLYN are benign and do 

not require further investigation unless vaginal bleeding occurs.  
 References to authoritative international guidelines relevant for uterine surveillance.  
 The need to stop treatment with FABLYN and investigate when unexplained uterine bleeding 

occurs. 
 
The programme shall include the full text of the SmPC. 
 

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The MAH shall also provide access to educational programme for pathologists. This programme 
should focus on interpretation of endometrial biopsy of women treated with FABLYN. It must be in 
line with authoritative international guidelines and supported by evidence published in peer reviewed 
medical journals. 
 
 
 OTHER CONDITIONS 
 
Pharmacovigilance system 
 
The MAH must ensure that the system of pharmacovigilance, presented in Module 1.8.1. of the 
Marketing Authorisation, is in place and functioning before and whilst the product is on the market. 
 
Risk Management Plan 
 
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in 
the Pharmacovigilance Plan, as agreed in version 1.4 of the Risk Management Plan (RMP) presented 
in Module 1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP 
agreed by the CHMP. 
 
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the 
updated RMP should be submitted at the same time as the next Periodic Safety Update Report 
(PSUR). 
 
In addition, an updated RMP should be submitted 
 
 When new information is received that may impact on the current Safety Specification, 

Pharmacovigilance Plan or risk minimisation activities  
 Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being 

reached  
 At the request of the EMEA 
 

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ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 

 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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A. LABELLING 
 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR BLISTER PACK (30 film-coated tablets) 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
FABLYN 500 microgram film-coated tablets 
 
lasofoxifene 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains lasofoxifene tartrate, equivalent to 500 microgram lasofoxifene. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose 
 
See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For oral use. 
 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Sealed pack. 
 
Do not use if box has been opened. 
 
 
8. EXPIRY DATE 
 
EXP: 
 
 

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9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Dr. Friedrich Eberth Arzneimittel GmbH 
Am Bahnhof 2 
92289 Ursensollen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER 
 
EU/1/08/500/001 
 
EU/1/08/500/002 
 
EU/1/08/500/003 
 
EU/1/08/500/004 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
FABLYN 
 
 
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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR BLISTER PACK (7 film-coated tablets) 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
FABLYN 500 microgram film-coated tablets 
 
lasofoxifene 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains lasofoxifene tartrate, equivalent to 500 microgram lasofoxifene. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose 
 
See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
7 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For oral use. 
 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Sealed pack. 
 
Do not use if box has been opened. 
 
 
8. EXPIRY DATE 
 
EXP: 
 
 

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9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Dr. Friedrich Eberth Arzneimittel GmbH 
Am Bahnhof 2 
92289 Ursensollen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER 
 
EU/1/08/500/001 
 
EU/1/08/500/002 
 
EU/1/08/500/003 
 
EU/1/08/500/004 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR BOTTLE PACK (90 film-coated tablets) 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
FABLYN 500 microgram film-coated tablets 
 
lasofoxifene 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains lasofoxifene tartrate, equivalent to 500 microgram lasofoxifene. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose 
 
See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
90 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For oral use. 
 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Sealed pack. 
 
Do not use if box has been opened. 
 
 
8. EXPIRY DATE 
 
EXP: 
 
 

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9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Dr. Friedrich Eberth Arzneimittel GmbH 
Am Bahnhof 2 
92289 Ursensollen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER 
 
EU/1/08/500/001 
 
EU/1/08/500/002 
 
EU/1/08/500/003 
 
EU/1/08/500/004 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR BLISTER PACK (28 film-coated tablets) 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
FABLYN 500 microgram film-coated tablets 
 
lasofoxifene 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains lasofoxifene tartrate, equivalent to 500 microgram lasofoxifene. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose 
 
See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For oral use. 
 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Sealed pack. 
 
Do not use if box has been opened. 
 
 
8. EXPIRY DATE 
 
EXP: 
 
 

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9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Dr. Friedrich Eberth Arzneimittel GmbH 
Am Bahnhof 2 
92289 Ursensollen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER 
 
EU/1/08/500/001 
 
EU/1/08/500/002 
 
EU/1/08/500/003 
 
EU/1/08/500/004 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
BOTTLE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
FABLYN 500 microgram film-coated tablets 
 
lasofoxifene 
 
For oral use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER 
 
LOT: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
90 film-coated tablets 
 
 
6. OTHER 
 
 
 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER 7 tablets 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
FABLYN 500 microgram film-coated tablets 
 
lasofoxifene 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Eberth 
 
 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER 
 
LOT: 
 
 
5. OTHER 
 
Mon 
 
Tue 
 
Wed 
 
Thu 
 
Fri 
 
Sat 
 
Sun 
 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER 30 tablets 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
FABLYN 500 microgram film-coated tablets 
 
lasofoxifene 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Eberth 
 
 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER 
 
LOT: 
 
 
5. OTHER 
 
 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER 28 tablets 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
FABLYN 500 microgram film-coated tablets 
 
lasofoxifene 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Eberth 
 
 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER 
 
LOT: 
 
 
5. OTHER 
 
Mon 
 
Tue 
 
Wed 
 
Thu 
 
Fri 
 
Sat 
 
Sun 
 

 
 

 
 
 
 
 
 
 
 
 
 

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B. PACKAGE LEAFLET 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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PACKAGE LEAFLET: INFORMATION FOR THE USER 

 
FABLYN 500 microgram film-coated tablets  

lasofoxifene  
 
 
Read all of this leaflet carefully before you start taking this medicine.  
 Keep this leaflet. You may need to read it again.  
 If you have any further questions, ask your doctor or pharmacist.  
 This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours.  
 If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist.  
 
 
What is in this leaflet 
 
1. What FABLYN is and what it is used for  
2. Before you take FABLYN 
3. How to FABLYN  
4. Possible side effects  
5. How to store FABLYN 
6. Further information 
 
 
1. WHAT FABLYN IS AND WHAT IT IS USED FOR 
 
FABLYN is used to treat osteoporosis in women after the menopause (postmenopausal osteoporosis) 
who are likely to break bones, especially in the spine, hips and wrists. It belongs to a group of 
medicines called Selective Estrogen Receptor Modulators (SERM). 
 
In women with postmenopausal osteoporosis, FABLYN reduces the risk of both fractures of the spine 
(vertebral fractures) and non-spine fractures (non-vertebral fractures), but not hip fractures. 
 
 
2. BEFORE YOU TAKE FABLYN 
 
Do not take FABLYN 
 
 if you are allergic (hypersensitive) to lasofoxifene or any of the other ingredients of FABLYN.  
 if you currently have or previously had blood clots, for example in your veins, lungs or eyes 

(deep vein thrombosis, pulmonary embolism or retinal vein thrombosis).  
 if you have any vaginal bleeding. This must be investigated by your doctor before starting 

treatment.  
 if you could still become pregnant.  
 if you are pregnant or breast-feeding. 
 
 

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Take special care with FABLYN 
 if you are immobile for some time, such as, needing to be admitted to a hospital or having to 

stay in bed while recovering from an operation or an illness, as these may increase your risk of 
blood clots (deep vein thrombosis, pulmonary embolism or retinal vein thrombosis). Your 
doctor may recommend that you stop treatment at least 3 weeks prior to this time. 
Treatment with FABLYN can be restarted as soon as you regain your mobility and in 
consultation with your doctor. 

 
 if you are taking FABLYN, you should walk around or exercise your legs and feet at regular 

intervals when traveling long distances. This is because sitting for a long time in the same 
position may prevent good blood circulation and may increase your risk of blood clots. 

 
It is unlikely that FABLYN will cause vaginal bleeding. So any vaginal bleeding while you take 
FABLYN is unexpected. You should have this investigated by your doctor. 
 
The following are reasons why this medicine may not be suitable for you. You should talk to your 
doctor before starting to take FABLYN: 
 
 if you have or have had breast cancer.  
 if you experience any unexplained breast abnormality.  
 if you have severe liver disease.  
 if you have severe kidney disease. 
 
Taking other medicines 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 
including medicines obtained without a prescription. If you are taking estrogen replacement therapy (ERT) 
or hormone replacement therapy (HRT), FABLYN may not be suitable for you. 
 
Taking FABLYN with food and drink 
 
FABLYN can be taken with or without food and drink. 
 
Pregnancy and breast-feeding 
 
FABLYN is only for women after the menopause and must not be taken by women who can still 
become pregnant. 
 
Do not take FABLYN if you are pregnant or breast-feeding as it might be excreted in mother’s milk. 
 
Driving and using machines 
 
No studies on the effects on the ability to drive and use machines have been performed. 
 
FABLYN has no known influence on the ability to drive and use machines. 
 
Important information about some of the ingredients of FABLYN  
 
FABLYN contains lactose. If you have been told by your doctor that you have an intolerance to some 
sugars, contact your doctor before taking this medicine. 
 
 
3. HOW TO TAKE FABLYN 
 
Always take FABLYN exactly as your doctor has told you. You should check with your doctor or 
pharmacist if you are not sure. The usual dose is one tablet each day. 

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Swallow the tablet whole. You may take it with or without food. 
 
If you wish, you may take it with water or another beverage of choice. 
 
Your doctor may also advise you to take Calcium and Vitamin D supplements while you are treated 
with FABLYN if your daily intakes are not considered sufficient. 
 
If you take more FABLYN than you should 
 
If you take more tablets than you should, tell your doctor or pharmacist. 
 
If you forget to take FABLYN  
 
Do not take a double dose to make up for a forgotten tablet. Take your next tablet and continue as 
before. 
 
If you stop taking FABLYN  
 
You should talk to your doctor before stopping FABLYN. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, FABLYN can cause side effects, although not everybody gets them. 
 
Most of the side effects that occurred during studies were mild. 
 
These side effects may occur with certain frequencies, which are defined as follows: 
  
 Very common: affects more than 1 user in 10  
 Common: affects 1 to 10 users in 100  
 Uncommon: affects 1 to 10 users in 1,000  
 Rare: affects 1 to 10 users in 10,000  
 Very rare: affects less than 1 user in 10,000  
 Not known: frequency cannot be estimated from the available data 
 
Very common side effects: 
 
 Muscle cramps 
 
Common side effects: 
 
 Hot flush  
 Constipation  
 Pressure in the lower abdomen  
 Vaginal discharge  
 Excessive sweating 
 
Uncommon side effects: 
 
 Urinary tract infection, burning on urination, urgent need to urinate, urinary incontinence  
 Abdominal pain or pressure, pain in the back, neck, joints or chest  

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 Tiredness, abnormal or excessive bleeding commonly from the nose  
 Diabetes (typical symptoms are excessive thirst, frequent urination)  
 Burning sensation, dizziness, numbness, memory impairment, impaired or partial loss of 

movement of a limb, headache, restless legs syndrome (an irresistible urge to move legs to stop 
an uncomfortable or odd sensations)  

 Abnormal or irregular beating of the heart, increased heart rate  
 Swelling of hands, arms, feet or legs, limb pain  
 Cough, difficulty breathing, stuffy nose, runny nose  
 Dry mouth, flatulence (excessive amount of air or gases in the stomach or the intestine), 

stomach ache  
 Dry eye, hair loss, skin rash, night sweats, itching, feeling hot, weight gain  
 Breast stiffening, breast pain, vaginal bleeding, genital itching 
 
Rare side effects: 
 
 Infection in the ear, eye, respiratory tract or skin, diarrhea, blood in stools  
 Change in appetite  
 Abnormal dreams, mood swings  
 Dizziness, altered sense of taste, seizures, migraine, weakness of arms or legs, sciatica (pain felt 

in the lower back, buttock, and/or various parts of the leg and foot; typically on one side of the 
body)  

 Impaired vision, pain in eyes, itchy eyes, swollen eyelids, redness of the eyes, ear pain  
 Lip lesions, change of bowel habits, difficulty swallowing, mouth ulcer, heart burn, mouth pain, 

anal pain  
 Jaundice (yellowing of the skin and eyes), changes in blood tests of liver function  
 Dry skin, unusual hair texture, nail disorder, skin rash, skin darkening, altered shape of fingers, 

skin lesion  
 Painful urination, blood in urine  
 Breast discharge, breast lump, vaginal pain, varicose vein  
 Decreased pulse in feet, bruising 
 
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please 
tell your doctor or pharmacist. 
 
 
5. HOW TO STORE FABLYN 
 
Keep out of the reach and sight of children. 
 
Do not use FABLYN after the expiry date which is stated on the blister or bottle label and on the 
carton after “EXP:”. The expiry date refers to the last day of that month.  
 
This medicine does not require any special storage conditions. 
 
 
6. FURTHER INFORMATION 
 
What FABLYN contains  
 
 The active substance is lasofoxifene. Each film-coated tablet contains lasofoxifene tartrate, 

equivalent to 500 micrograms of lasofoxifene. 
 
 The other ingredients are lactose anhydrous; microcrystalline cellulose; croscarmellose sodium; 

silica, colloidal anhydrous; magnesium stearate; sunset yellow FCF aluminium lake (E110); 
hypromellose; lactose monohydrate; titanium dioxide (E171) and triacetin. 

 

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What FABLYN looks like and contents of the pack 
 
FABLYN tablets are triangular, peach coloured, film-coated tablets marked with “Pfizer” on one side 
and “OPR 05” on the other. 
 
The tablets are provided in blister packs containing 7, 28 or 30 tablets, and in bottle packs containing 
90 tablets. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
 
The Marketing Authorisation Holder is Dr. Friedrich Eberth Arzneimittel GmbH, Am Bahnhof 2,  
92289 Ursensollen, Germany. 
 
The Manufacturer is Pfizer Manufacturing Deutschland GmbH, Heinrich Mack Strasse 35, 89257 
Illertissen, Germany. 
 
This leaflet was last approved in {MM/YYYY}. 
 
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web 
site: http://www.emea.europa.eu/. 
 
 

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http://www.emea.europa.eu/�

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OF THE MARKETING AUTHORISATION
	A. LABELLING
	B. PACKAGE LEAFLET