Conbriza

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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1. NAME OF THE MEDICINAL PRODUCT

CONBRIZA 20 mg film-coated tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains bazedoxifene acetate equivalent to 20 mg bazedoxifene.

Excipient with known effect:

Each film-coated tablet contains 142.8 mg lactose (as monohydrate).

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Film-coated tablet.

White to off-white, capsule-shaped, film-coated tablet debossed on one side with “WY20”.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications 

CONBRIZA is indicated for the treatment of postmenopausal osteoporosis in women at increased risk 
of fracture. A significant reduction in the incidence of vertebral fractures has been demonstrated; 
efficacy on hip fractures has not been established.

When determining the choice of CONBRIZA or other therapies, including oestrogens, for an 
individual 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

Posology

The recommended dose of CONBRIZA is one tablet once daily, at any time of day, with or without 
food (see section 5.2).

Doses higher than 20 mg are not recommended because there is no demonstrable increased efficacy 
and higher doses may be associated with additional risk (see section 5.1).

Supplemental calcium and/or vitamin D should be added to the diet if daily intake is inadequate.

Special Populations

Patients with renal impairment
Bazedoxifene has not been sufficiently evaluated in patients with severe renal impairment; caution 
should be used in this population (see sections 4.4 and 5.2).

No dose adjustment is required for mild or moderate renally impaired patients.



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Patients with hepatic impairment
Safety and efficacy of bazedoxifene have not been evaluated in patients with hepatic impairment; use 
in this population is not recommended (see sections 4.4 and 5.2).

Elderly patients
No dose adjustment is necessary based on age (see section 5.2).

Paediatric population 
There is no relevant use of bazedoxifene in the paediatric population.

Method of administration

Oral use.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Active or past history of venous thromboembolic events, including deep vein thrombosis, pulmonary 
embolism, and retinal vein thrombosis.

CONBRIZA is only indicated for use in postmenopausal women. Bazedoxifene must not be taken by 
women of child-bearing potential (see sections 4.6 and 5.3).

Unexplained uterine bleeding.

Patients with signs or symptoms of endometrial cancer; safety in this patient group has not been 
adequately studied.

4.4 Special warnings and precautions for use

Use of CONBRIZA is not recommended in women at an increased risk for venous thromboembolic 
events. CONBRIZA is associated with an increased risk of venous thromboembolism (VTE). In 
clinical trials, the highest rate of VTE was observed during the first year of treatment, with a relative 
risk of 2.69 compared to placebo. After 3 years the relative risk was 1.63 and after a 5 year study 
period the relative risk was 1.50; after 7 years the relative risk was 1.51 (see sections 4.8 and 5.1). The 
risk factors associated with VTE cases in clinical trials included: advanced age, obesity, 
immobilisation, surgery, major trauma and malignancy. CONBRIZA should be discontinued prior to 
and during prolonged immobilisation (e.g., post-surgical recovery, prolonged bed rest), and therapy 
should be resumed only after the patient is fully ambulatory. In addition, women taking CONBRIZA
should be advised to move about periodically during prolonged travel.

Bazedoxifene has not been studied in premenopausal women. Its safety in premenopausal women has 
not been established, and its use is not recommended in this population.

There is no evidence of endometrial proliferation. Any uterine bleeding during CONBRIZA therapy is 
unexpected and should be fully investigated.

Bazedoxifene has not been studied in women with triglyceride levels 300 mg/dl (3.4 mmol/litre). It 
may increase serum triglyceride levels; therefore, caution should be exercised in patients with known 
hypertriglyceridaemia (see section 5.1).

The safety of CONBRIZA in patients with breast cancer has not been studied. No data are available on 
the concomitant use with agents used in the treatment of early or advanced breast cancer. Therefore, 
bazedoxifene is not recommended for treatment or prevention of breast cancer.



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Bazedoxifene has not been sufficiently evaluated in patients with severe renal impairment; caution 
should be used in this population.

Patients with hepatic impairment showed a 4.3-fold increase in area under the curve (AUC) [on 
average] compared with controls. Use in this population is not recommended (see sections 4.2
and 5.2).

CONBRIZA 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

In a 30-day study, bazedoxifene increased hormone-binding globulin concentrations, including 
corticosteroid-binding globulin (CBG), sex hormone-binding globulin (SHBG) and thyroxine-binding 
globulin (TBG).

Bazedoxifene undergoes metabolism by uridine diphosphate glucuronosyltransferase (UGT) enzymes 
in the intestinal tract and liver (see section 5.2). The metabolism of bazedoxifene may be increased by 
concomitant use of substances known to induce UGTs, such as rifampicin, phenobarbital, 
carbamazepine, and phenytoin, potentially leading to decreased systemic concentrations of 
bazedoxifene.

Bazedoxifene undergoes little or no cytochrome P450 (CYP)-mediated metabolism. Bazedoxifene 
does not induce or inhibit the activities of major CYP isoenzymes. In vitro data suggest that 
bazedoxifene is unlikely to interact with co-administered medicinal products via CYP-mediated 
metabolism.

There were no significant pharmacokinetic interactions between bazedoxifene and the following 
medicinal products: ibuprofen, atorvastatin, azithromycin, or an antacid containing aluminium and
magnesium hydroxide. Based on in vitro bazedoxifene plasma protein binding characteristics, drug 
interactions with warfarin, digoxin and diazepam are unlikely.

4.6 Fertility, pregnancy and lactation

Pregnancy

CONBRIZA is only for use in postmenopausal women. It is contraindicated in women of 
child-bearing potential (see section 4.3). There are no data from the use of bazedoxifene in pregnant 
women. Studies in rabbits have shown reproductive toxicity (see section 5.3). The potential risk for 
humans is unknown.

Breast-feeding

It is not known whether bazedoxifene is excreted in human milk. CONBRIZA is only indicated for use 
in postmenopausal women (see section 4.3) and should not be used during breast-feeding.

Fertility

Studies in rats have shown adverse effects on fertility (see section 5.3). The potential risk for humans 
is unknown. 

4.7 Effects on ability to drive and use machines

CONBRIZA has minor influence on the ability to drive and use machines.

In clinical trials, somnolence was reported as an adverse reaction, and patients should be advised on 
the potential effect on driving and using machines.



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Patients may experience visual symptoms such as visual acuity disturbance or blurred vision. If such 
symptoms occur, patients should avoid driving or use of machines that requires accurate visual 
perception until symptoms have resolved, or until they have received medical advice that it is safe to 
do so.

4.8 Undesirable effects

Summary of the safety profile

The safety of CONBRIZA has been evaluated in two multicentre, double-blind, randomised, placebo-
and active-control, Phase 3 trials: 7,492 evaluable postmenopausal women in a three-year osteoporosis 
treatment trial (1,886 women received bazedoxifene 20 mg; 1,872 women received bazedoxifene 
40 mg; 1,849 women received raloxifene; 1,885 women received placebo) and 1,583 evaluable 
postmenopausal women in a 2-year osteoporosis prevention trial (321 women received bazedoxifene 
10 mg; 322 women received bazedoxifene 20 mg; 319 women received bazedoxifene 40 mg; 
311 women received raloxifene; 310 women received placebo).

The majority of adverse reactions occurring during the clinical trials were mild to moderate in severity 
and did not lead to discontinuation of therapy.
The most frequent drug-related adverse reactions in double-blind, randomised studies were hot flushes 
and muscle spasms (includes leg cramps).

Tabulated list of adverse reactions

The safety data in the following table are derived from both clinical trials and spontaneous 
post-marketing reporting.

Adverse reactions are categorized according to the following frequencies: very common ( 1/10); 
common ( 1/100 to  1/10); uncommon ( 1/1,000 to  1/100); rare ( 1/10,000 to  1/1,000); not 
known (cannot be estimated from the available data). Within each frequency grouping, adverse 
reactions are presented in order of decreasing seriousness.

System organ 
class

Very 
common

Common Uncommon Frequency not 
known (cannot 

be estimated 
from available 

data)
Immune system 
disorders

Hypersensitivity

Nervous system 
disorders

Somnolence

Eye disorders Retinal vein 
thrombosis*

Vision 
disorders/Ocular 
events#

Cardiac disorders Palpitations

Vascular 
disorders

Hot flush Deep vein 
thrombosis*,
thrombophlebitis 
superficial

Respiratory, 
thoracic and 
mediastinal 
disorders

Pulmonary 
embolism*

Gastrointestinal 
disorders

Dry mouth



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System organ 
class

Very 
common

Common Uncommon Frequency not 
known (cannot 
be estimated 

from available 
data)

Skin and 
subcutaneous 
tissue disorders

Urticaria, rash, 
pruritus

Musculoskeletal 
and connective 
tissue disorders

Muscle 
spasms 
(includes 
leg cramps)

General disorders 
and 
administration 
site conditions

Oedema 
peripheral

Investigations Blood 
triglycerides 
increased, alanine 
aminotransferase 
increased, 
aspartate 
aminotransferase 
increased.

Description of selected adverse reactions

*In the osteoporosis treatment trial in 7,492 evaluable subjects (mean age=66 years), the 
bazedoxifene-treated women had an increased risk of venous thromboembolism (deep vein 
thrombosis, pulmonary embolism and retinal vein thrombosis). The rate per 1,000 women-years 
through the 3-year study period was 2.86 in the bazedoxifene 20 mg group and 1.76 in the placebo
group, and through the 5-year study period was 2.34 in the bazedoxifene 20 mg group and 1.56 in the
placebo group. The rate per 1,000 women-years through the 7 year study period was 2.06 in the 
bazedoxifene 20 mg group and 1.36 in the placebo group. The rate of VTE was highest in the first year
with a relative risk of 2.69. After 3 years the relative risk was 1.63 and after a 5 year study period the 
relative risk was 1.50. After 7 year study period the relative risk was 1.51 (see section 5.1). Other 
venous thromboembolic events could also occur.

#There have been post-marketing reports of ocular events other than retinal vein thrombosis. These 
reports include visual acuity reduced, blurred vision, photopsia, visual field defect, visual impairment, 
dry eye, eyelid oedema, blepharospasm, eye pain and eye swelling. The underlying nature of these 
events is uncertain. If ocular symptoms occur, patients should be advised to seek medical attention.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

In the case of overdose, there is no specific antidote, and treatment should be symptomatic.



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5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Selective estrogen receptor modulator, ATC code: G03XC02.

Mechanism of action

Bazedoxifene belongs to a class of compounds known as selective estrogen receptor modulators 
(SERMs). Bazedoxifene acts as both an oestrogen-receptor agonist and/or antagonist, depending upon 
the cell and tissue type and target genes. Bazedoxifene decreases bone resorption and reduces 
biochemical markers of bone turnover to the premenopausal range. These effects on bone remodeling 
lead to an increase in bone mineral density (BMD), which in turn contributes to a reduction in the risk 
of fractures. Bazedoxifene functions primarily as an oestrogen-receptor antagonist in uterine and 
breast tissues.

Clinical efficacy

The efficacy of bazedoxifene was established in two multicentre, double-blind, randomised, placebo-
and active-control, Phase 3 trials: 3-year osteoporosis treatment trial and a 2-year osteoporosis 
prevention trial.

Osteoporosis treatment trial
In the osteoporosis treatment study, 7,492 postmenopausal women (mean age of 66 years; range 50 to 
85 years and a mean time of 19.5 years since menopause) received bazedoxifene (20 or 40 mg daily), 
raloxifene (60 mg daily), or placebo to evaluate the incidence of new vertebral fractures over 3 years 
(3-year core study). The 3-year core study was extended twice, with two 2-year double-blind, placebo-
controlled extensions, resulting in a total treatment duration of up to 7 years (7-year study). A total of 
3,146 subjects continued into the first 2-year extension (bazedoxifene 20 mg: n=1,047, bazedoxifene
40/20 mg: n=1,041, placebo: n=1,058). The bazedoxifene 40 mg dose was decreased to a 20 mg dose 
after approximately 4 years. The raloxifene group was discontinued during the first 2-year extension.
A total of 1,732 subjects continued into the second 2-year extension (bazedoxifene 20 mg: n=560, 
bazedoxifene 40/20 mg: n=582, and placebo: n=590). All subjects were to receive 1,200 mg of 
elemental calcium and 400 IU of vitamin D daily.

This study included mostly Caucasian (87.3%) subjects who were either osteoporotic without baseline 
vertebral fracture (BMD T-score at lumbar spine [LS] or femoral neck [FN] between -2.5 and -4.0) or 
osteoporotic, with at least 1 mild baseline vertebral fracture. The mean LS and FN T-scores at baseline 
were -2.4 and -1.7, respectively.

There was a significant reduction in the incidence of new vertebral fractures after 3 years of treatment 
with bazedoxifene 20 mg (42%), bazedoxifene 40 mg (37%) and raloxifene 60 mg (42%) compared to 
placebo. The reduction in the incidence of vertebral fracture was similar among bazedoxifene and 
raloxifene treatment groups. The treatment effect was similar among those with and without prevalent
vertebral fractures (Table 1).



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Table 1: Effect of bazedoxifene on risk of vertebral fractures after 3 years of treatment

Number of subjects Absolute 
risk 

reduction

Relative risk 
reduction 
(95% CI)

Bazedoxifene 
20 mg

Placebo

Total number of subjects n=1,724 n=1,741

Number (%)a of subjects with 
new vertebral fracture

35 (2.34%) 59 (4.07%) 1.73% 42%b

(11%, 62%)
Subjects with no baseline fracture n=757 n=760

Number (%)a of subjects with ≥1 
new vertebral fracture

13 (1.98%) 20 (3.13%) 1.15% 35%c

Subjects with 1 baseline fracture n=967 n=981

Number (%)a of subjects with ≥1 
new vertebral fracture

22 (2.63%) 39 (4.80%) 2.17% 45%d

(6%, 68%)
a Kaplan-Meier rate estimates
b p-value=0.015
c p-value=0.22
d p-value=0.035

After 5 years of treatment, the incidence of new vertebral fractures remained lower in the 
bazedoxifene 20 mg group (4.49%) compared to placebo (6.82%) with a relative risk reduction of 36% 
(p=0.014).

After 7 years of treatment, the incidence of new vertebral fractures remained lower in the 
bazedoxifene 20 mg group (7.64%) compared to placebo (9.90%) with a relative risk reduction of 30% 
(p=0.022).

The incidence of non-vertebral osteoporosis-related fractures was similar among bazedoxifene 20 mg 
(5.68%), raloxifene 60 mg (5.87%), and placebo (6.26%) groups. In a post-hoc analysis, the 10-year 
fracture probability as an index of baseline fracture risk was determined. The mean 10-year fracture 
probability of a major osteoporotic fracture for the entire study population was 11%. In subjects 
treated with bazedoxifene, the incidence of fractures was related to the baseline fracture risk: the 
higher the fracture risk, the greater the benefit with bazedoxifene treatment. In subjects with 10-year 
fracture probabilities at or above 16%, bazedoxifene was associated with a significant decrease in the 
risk of all clinical fractures.

In a post-hoc analysis, the relative risk of non-vertebral fractures in bazedoxifene-treated subjects 
decreased with increased fracture probability. In subjects with a fracture probability of 20% or greater 
(n = 618), the risk of non-vertebral fractures in bazedoxifene-treated subjects was decreased by 55% 
(95% CI: 18-76) compared to placebo-treated subjects.

The increase in LS BMD compared with placebo with bazedoxifene 20 mg and raloxifene 60 mg was 
significant at 6 months (1.02% and 1.29%, respectively) and was maintained through 3 years (1.32% 
and 2.08%, respectively). The effect of bazedoxifene on BMD at other skeletal sites was similar. The 
increases in BMD relative to placebo remained statistically significant at all skeletal sites throughout 
the 5 years of treatment with bazedoxifene. After 7 years of treatment with bazedoxifene the increases 
in BMD relative to placebo remained statistically significant at the femoral neck, femoral trochanter, 
and total hip. The increase from baseline in lumbar spine BMD at 7 years in the bazedoxifene 20 mg 
group was not statistically greater than in the placebo group.

Discontinuation from the study was required when excessive bone loss or incident vertebral fractures 
occurred. Such discontinuation was statistically significant more frequently in the placebo group 
(4.0%) than in the bazedoxifene 20 mg (2.8%) or raloxifene 60 mg (2.1%) groups.



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Osteoporosis prevention trial
The prevention study (1,583 subjects; mean age, 58 years; mean years since menopause, 11) compared 
BMD effects of bazedoxifene (10, 20, or 40 mg daily), raloxifene (60 mg daily), and placebo. All 
subjects received calcium supplementation daily; most received 600 mg calcium (e.g., Caltrate) 
daily, while some received up to 1,200 mg daily. This study included subjects who had a LS or FN 
neck BMD T-score no less than -2.5. The median T-score ranged from -0.6 to -1.4, depending on the 
skeletal site.

BMD was preserved in bazedoxifene 20 mg and raloxifene 60 mg-treated subjects, while significant 
loss in BMD was observed in patients receiving placebo. The increase in LS BMD with bazedoxifene 
20 mg and raloxifene 60 mg, compared with placebo, was significant at 6 months (1.14% and 1.26%, 
respectively) and was maintained through 2 years (1.41% and 1.49%, respectively). The effect of 
bazedoxifene on BMD at other skeletal sites was similar.

Clinical safety

Assessment of bone histomorphometry and bone turnover
In the osteoporosis treatment study in 7,492 postmenopausal women (mean age = 66 years), 121 bone 
biopsies were obtained from iliac crest after the administration of fluorochrome label from the subjects 
in bazedoxifene, raloxifene and placebo groups (bazedoxifene 20 mg = 28; bazedoxifene 40 mg = 29, 
raloxifene 60 mg = 32, placebo = 32) after approximately 2 or 3 years of treatment. Histological 
assessment of bone biopsies from all treatment groups revealed formation of normal lamellar bone in 
all treated subjects. There was no evidence of osteomalacia, peritrabecular or marrow fibrosis, cellular 
toxicity or woven bone in any of the bone-biopsy specimens in any of the treatment groups. 
Histomorphometric assessment revealed normal mineralisation, as evidenced by the presence of 
normal osteoid thickness, normal mineralisation lag time, and mineral apposition rate.

In the osteoporosis treatment study, bazedoxifene 20 mg and raloxifene 60 mg therapy resulted in a 
significant reduction of serum markers of bone resorption (C-telopeptide) and bone formation 
(osteocalcin), when compared to placebo, indicating a reduction in bone turnover. Median reductions 
from baseline over 25% for C-telopeptide and osteocalcin were observed with bazedoxifene therapy. 
Similar reductions in the rate of bone turnover have been observed in the osteoporosis prevention 
study.

Effects on lipid metabolism and cardiovascular system
In the osteoporosis treatment study after 3 years of treatment, bazedoxifene 20 mg and raloxifene 
60 mg exhibited significant reductions in serum total cholesterol, low-density lipoprotein (LDL) 
cholesterol and a significant increase in high-density lipoprotein (HDL) cholesterol compared to 
placebo. The median percent change from baseline of total cholesterol, LDL cholesterol and HDL 
cholesterol with bazedoxifene 20 mg were –3.75%, –5.36% and 5.10%, respectively, and were similar 
to that observed with raloxifene 60 mg. The effect on triglycerides in the bazedoxifene 20 mg and 
raloxifene 60 mg groups was similar to placebo. This lipid profile was maintained throughout the 
7 years of treatment. The treatment effect on lipids was similar in the osteoporosis prevention study. 
The clinical relevance of these changes has not been established.

In the osteoporosis treatment trial in 7,492 subjects (mean age = 66 years), the bazedoxifene-treated 
women had an increased risk of VTE (deep vein thrombosis, pulmonary embolism and retinal vein 
thrombosis) (see section 4.8). The highest rate of VTE per 1,000 women-years of follow up was 
observed during the first year: 4.64 in the bazedoxifene 20 mg group and 1.73 in the placebo group 
(relative risk 2.69).The rate per 1,000 women-years at 3 years was 2.86 in the bazedoxifene 20 mg 
group and 1.76 in the placebo group (relative risk 1.63). The rate per 1,000 women-years at 5 years 
was 2.34 in the bazedoxifene 20 mg group and 1.56 in the placebo group (relative risk 1.50). After 
7 years the rate per 1,000 women-years was 2.06 in the bazedoxifene 20 mg group and 1.36 in the 
placebo group (relative risk 1.51).



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Cerebrovascular effects 
In the 3 year core study the rate per 1,000 women-years for ischaemic strokes was similar between the 
20 mg bazedoxifene (1.98) and placebo (2.2) groups and higher in the 40 mg bazedoxifene (2.72) 
group. The rate per 1,000 women years for transient ischaemic attacks (TIA) was similar between the 
20 mg bazedoxifene (1.1) and placebo (0.88) groups and higher in the 40 mg bazedoxifene (1.59) 
group. 

After 5 years of treatment the rate per 1,000 women-years for ischaemic strokes was similar between 
the 20 mg bazedoxifene (1.87) and the placebo (2.02) groups. The rate per 1,000 women years for TIA 
was higher for the 20 mg bazedoxifene group (0.94) compared to placebo (0.62).

After 7 years of treatment, the rate per 1,000 women-years for ischaemic strokes was the same for the 
20 mg bazedoxifene (1.78) and the placebo (1.78) groups. The rate per 1,000 women years for TIA 
was higher for the bazedoxifene 20 mg group (0.96) compared to placebo (0.55).

Effects on the uterus
In the osteoporosis treatment study, transvaginal ultrasonography (TVU) showed minimal changes in 
endometrial thickness in placebo (-0.08 mm, n=131), bazedoxifene 20 mg (-0.07 mm, n=129), and 
raloxifene 60 mg (0.16 mm, n=110) treated groups after 2 years. At 3 years, there were no cases of 
endometrial cancer and 1 case (0.1%) of endometrial hyperplasia in the bazedoxifene 20 mg-treated 
subjects. There was 1 case (0.1%) of endometrial cancer, 1 case of sarcoma (0.1%), and 1 case (0.1%) 
of endometrial hyperplasia in the raloxifene 60 mg-treated subjects. There were 3 cases (0.2%) of 
endometrial cancer and 1 case (0.1%) of endometrial hyperplasia in the placebo group. Endometrial 
polyps were diagnosed in 10 subjects in the bazedoxifene 20 mg, 17 subjects in the raloxifene 60 mg, 
and 11 subjects in the placebo treatment groups through month 36.

After 5 years of treatment, the endometrial thickness in the bazedoxifene 20 mg group did not change 
and remained similar to placebo; there were no cases of endometrial cancer in the bazedoxifene 20 mg 
group compared to 6 cases in the placebo group (p<0.05).

After 7 years of treatment, the endometrial thickness in the bazedoxifene 20 mg group did not change 
and remained similar to placebo; there were no cases of endometrial cancer in the bazedoxifene 20 mg 
group compared to 7 cases in the placebo group (p<0.008).

In the osteoporosis prevention study, TVU showed minimal changes from baseline in endometrial 
thickness in placebo (-0.24 mm, n=154), bazedoxifene 20 mg (-0.06 mm, n=158) and raloxifene 60 mg 
(0.01 mm, n=154) treated groups after 2 years. No cases of hyperplasia or endometrial malignancy 
were identified in any bazedoxifene- or raloxifene-treated subjects.

Effects on the breast
In the osteoporosis treatment study, the incidence of breast-related adverse events in the bazedoxifene 
group was similar to placebo at 3 years. There were 5 cases of breast cancer per 4,591 person-years of 
follow-up in the bazedoxifene 20 mg group (1.09 per 1,000), 7 cases of breast cancer per 4,526 
person-years of follow-up in the raloxifene 60 mg group (1.55 per 1,000), and 8 cases of breast cancer 
per 4,604 person-years of follow-up in the placebo group (1.74 per 1,000). After 5 years of treatment, 
there were 9 cases of breast cancer in the bazedoxifene 20 mg group (1.40 per 1,000 women-years) 
and 10 cases in the placebo group (1.56 per 1,000 women-years). After 7 years of treatment, there 
were 13 cases of breast cancer in the bazedoxifene 20 mg group (1.78 per 1,000 women-years) and 
11 cases in the placebo group (1.50 per 1,000 women-years).

In the osteoporosis prevention study, the incidence of breast-related adverse events (breast tenderness, 
pain, breast cancer, benign breast neoplasm) in the bazedoxifene 20 mg and raloxifene 60 mg groups 
was similar to placebo.

In the breast-density study, an ancillary study of the osteoporosis treatment study, 444 postmenopausal 
women (mean age = 59 years) with osteoporosis from all 4 treatment groups, were evaluated for 
mammographic breast density changes at 24 months. Mean changes in mammographic breast density 



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in the bazedoxifene 20 mg group were significantly reduced from baseline (-1.45 percentage points, 
p<0.05) while no changes were observed in the placebo group (-0.15 percentage points). 

Effects on thyroid and ovarian malignancies
In the osteoporosis treatment study in 7,492 postmenopausal women (mean age, 66 years), among 
1,886 subjects treated with bazedoxifene (20 mg), there were 5 cases of thyroid cancer (0.69 per 
1,000) and among 1,885 subjects treated with placebo, there was 1 case of thyroid cancer (0.14 per 
1,000) after 7 years of treatment. There were no cases on thyroid cancer in the 40 mg treatment group 
up to 5 years.

In the osteoporosis treatment study in 7,492 postmenopausal women (mean age, 66 years), among 
1,886 subjects treated with bazedoxifene (20 mg), there were 5 cases of ovarian cancer (0.69 per 
1,000) and among 1,885 subjects treated with placebo, there were 0 cases of ovarian cancer after 
7 years of treatment. There was one case of ovarian cancer in the 40 mg treatment group up to 5 years.

5.2 Pharmacokinetic properties

The mean pharmacokinetic parameters of bazedoxifene after multiple doses in healthy 
postmenopausal ambulatory women who were naturally postmenopausal or who had undergone 
bilateral oophorectomy are summarized in Table 2.

Table 2. Mean ± SD pharmacokinetic parameters of bazedoxifene (n=23)
Cmax

(ng/ml)
tmax
(h)

t½
(h)

AUC
(ngh/ml)

Cl/F
(l/h/kg)

Multiple dose
20 mg/day 6.2 ± 2.2 1.7 ± 1.8 28 ± 11 82 ± 37 4.1 ± 1.7

Absorption

Bazedoxifene is rapidly absorbed with a tmax of approximately 2 hours and exhibits a linear increase in 
plasma concentrations for single doses from 0.5 mg up to 120 mg and multiple daily doses from 1 mg 
to 80 mg. The absolute bioavailability of bazedoxifene is approximately 6%.

When single doses of 20 mg bazedoxifene were administered with a high-fat meal, Cmax and AUC 
increased by 28% and 22%, respectively. An additional study evaluating the effects of a standardized 
medium-fat meal on the pharmacokinetics of bazedoxifene at steady-state showed a 42% and 35% 
increase in Cmax and AUC, respectively, when 20 mg bazedoxifene was administered with food. 
Because these changes are not considered clinically relevant, bazedoxifene can be administered 
without regard to meals.

Distribution

Following intravenous administration of a 3 mg dose of bazedoxifene, the volume of distribution is 
14.7 ± 3.9 l/kg. Bazedoxifene is highly bound (98% - 99%) to plasma proteins in vitro.

Biotransformation

The metabolic disposition of bazedoxifene in postmenopausal women has been determined following 
oral administration of 20 mg of radio-labelled bazedoxifene. Bazedoxifene is extensively metabolised 
in women. Glucuronidation is the major metabolic pathway. Little or no cytochrome P450-mediated 
metabolism is evident. Bazedoxifene-5-glucuronide is the major circulating metabolite. The 
concentrations of this glucuronide are approximately 10-fold higher than those of unchanged active 
substance in plasma.

Elimination

Bazedoxifene is eliminated with a half-life of approximately 30 hours. Steady-state concentrations are 
achieved by the second week of once-daily administration. The apparent oral clearance of 



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bazedoxifene is approximately 4 to 5 l/h/kg. The major route of excretion of radio-labelled 
bazedoxifene is the faeces, and less than 1% of the dose is eliminated in urine.

Special populations

Hepatic impairment
The disposition of a single 20 mg dose of bazedoxifene was compared in patients with hepatic 
impairment [Child-Pugh Class A (n=6), B (n=6), and C (n=6)] and subjects with normal hepatic 
function (n=18). On average, patients with hepatic impairment showed a 4.3-fold increase in AUC 
compared with controls. Safety and efficacy have not been evaluated further in patients with hepatic 
insufficiency. Use in this patient population is not recommended (see sections 4.2 and 4.4).

Renal impairment
Limited clinical data (n=5) are available in subjects with moderate renal impairment 
(CrCl  50 ml/min). A single 20 mg dose of bazedoxifene was administered to these subjects. 
Negligible amounts of bazedoxifene were eliminated in urine. Impaired renal function showed little or 
no influence on bazedoxifene pharmacokinetics, and no dosing adjustment is required.

Elderly patients
The pharmacokinetics of a 20 mg single-dose of bazedoxifene were evaluated in a study in 26 healthy 
postmenopausal women. On average, compared to women 51 to 64 years of age (n=8), women 65 to 
74 years of age (n=8) showed a 1.5-fold increase in AUC, and women 75 years of age (n=8) showed 
a 2.3-fold increase in AUC. This increase was most likely attributed to age-related changes in hepatic 
function. No dose adjustment is necessary based on age.

Paediatric population
The pharmacokinetics of bazedoxifene have not been studied in the paediatric population.

Race
No pharmacokinetic differences based on ethnic group were observed.

5.3 Preclinical safety data

In rabbit studies, abortion and an increased incidence of heart (ventricular septal defect) and skeletal 
system (ossification delays, misshapen or misaligned bones, primarily of the spine and skull) 
anomalies in the foetuses were present at maternally toxic doses of 0.5 mg/kg/day (1.5 times the 
human exposure). Treatment of rats at maternally toxic doses 1 mg/kg/day (0.3 times the human 
exposure) resulted in reduced numbers of live foetuses and/or reductions in foetal body weights. No 
foetal developmental anomalies were observed.

Female rats were administered daily doses of 0.3 to 30 mg/kg (0.03 to 8 times the human exposure) 
prior to and during mating with untreated males. Oestrous cycles and fertility were adversely affected 
in all bazedoxifene-treated female groups.

The effects of bazedoxifene treatment on bone, uterus, and mammary gland were assessed in 
ovariectomized rats (0.15 to 1.5 mg/kg/day) and non-human primates [Cynomolgus macaques] (0.2 to 
25.0 mg/kg/day). In rats, treatment with bazedoxifene for approximately one year partially prevented 
the effects of ovariectomy on numerous skeletal parameters (bone mineral content, bone mineral 
density, and architecture). Additionally, uterine wet weights were reduced compared with untreated 
animals and histologic evaluation demonstrated little to no difference from the untreated controls. In 
monkeys, treatment with bazedoxifene for 18 months resulted in the partial preservation of cortical 
and cancellous bone mass as determined by BMD measurements. The partial preservation of bone 
mass was achieved by reductions in the ovariectomy-induced increases in bone turnover, evaluated by 
biochemical markers of bone turnover and histomorphometric indices measured in cancellous and 
cortical bone. Importantly, in both species, the administration of bazedoxifene had no deleterious 
effects on bone quality. Like the rodent results, bazedoxifene treatment in non-human primates 



13

resulted in uterine and mammary gland atrophy without other histological differentiation from 
untreated animals.

Repeated-dose studies in normally cycling rodents and cynomolgus monkeys revealed a marked 
stimulation of ovarian follicle growth without ovulation, leading to partly haemorrhagic-ovarian cysts 
and markedly elevated estradiol levels. This pharmacological effect of bazedoxifene can also be 
expected in pre-menopausal women, but is considered clinically irrelevant in post-menopausal 
women.

In 6-month carcinogenicity studies in transgenic mice, there was an increased incidence of benign, 
ovarian granulosa-cell tumours in female mice given 150 or 500 mg/kg/day. Systemic exposure 
(AUC) to bazedoxifene in these groups was 35 and 69 times that in postmenopausal women 
administered 20 mg/day for 14 days.

In a 2-year carcinogenicity study in rats, an increased incidence of benign, ovarian granulosa-cell 
tumours was observed in female rats at dietary concentrations of 0.03 and 0.1%. Systemic exposure 
(AUC) of bazedoxifene in these groups was 2.6 and 6.6 times that observed in postmenopausal women 
administered 20 mg/day for 14 days.

The observation of benign, ovarian granulosa-cell tumours in female mice and rats administered 
bazedoxifene is a class effect of SERMs, related to its pharmacology in rodents when treated during 
their reproductive lives, when their ovaries are functional and responsive to hormonal stimulation.

Bazedoxifene was not genotoxic or mutagenic in a battery of tests, including in vitro bacterial reverse 
mutation assay, in vitro mammalian cell forward mutation assay at the thymidine kinase (TK±) locus 
in L5178Y mouse lymphoma cells, in vitro chromosome aberration assay in Chinese hamster ovary 
(CHO) cells, and in vivo mouse micronucleus assay.

Bazedoxifene caused corticomedullar nephrocalcinosis and enhanced spontaneous chronic progressive 
nephropathy (CPN) in male rats. Urine parameters were pathologically changed. In long-term studies 
renal tumours (adenomas and carcinomas) were observed at all doses tested, most likely as a 
consequence of this chronic renal damage. In the 2-year carcinogenicity study, bazedoxifene, 
administered orally in the diet to rats at dosages of 0, 0.003%, 0.01%, 0.03%, or 0.1%, resulted in 
exposures, based on surface area (mg/m2) of approximately 0.6 to 23 times and 0.9 to 31 times in 
males and females, respectively, the clinical dose of 20 mg. Since chronic progressive nephropathy 
and corticomedullar nephrocalcinosis are most likely rat-specific nephropathies, these findings are 
presumably not relevant for humans.

In an 18-month bone efficacy study in aged ovariectomized cynomolgus monkeys, bazedoxifene, 
administered orally to monkeys at dosages of 0, 0.2, 0.5, 1, 5, or 25 mg/kg/day, resulted in exposures, 
based on surface area (mg/m2) of approximately 0.2 to 24 times the clinical dose of 20 mg. Renal cell 
carcinomas were observed in this study. These tumours are considered as spontaneous renal cell 
carcinomas that are known to occur in nonhuman primates and are unlikely to be relevant to humans.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core:
Lactose monohydrate
Microcrystalline cellulose
Pregelatinised starch (maize)
Sodium starch glycolate
Sodium lauryl sulfate



14

Colloidal anhydrous silica
Magnesium stearate
Ascorbic acid

Film coating:
Hypromellose
Titanium dioxide (E171)
Macrogol 400

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

18 months.

6.4 Special precautions for storage

Do not store above 25C.

6.5 Nature and contents of container

PVC/Aclar blister packs of 7, 28, 30, 84, and 90 film-coated tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal 

No special requirements. 

7. MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/09/511/001
EU/1/09/511/002
EU/1/09/511/003
EU/1/09/511/004
EU/1/09/511/005

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 17 April 2009

Date of latest renewal: 17 April 2014

10. DATE OF REVISION OF THE TEXT



15

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu/.



16

ANNEX II

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE
MARKETING AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 
THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT



17

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer responsible for batch release

Pfizer Ireland Pharmaceuticals
Little Connell
Newbridge
County Kildare
Ireland

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to medical prescription. 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

 Periodic Safety Update Reports

The marketing authorisation holder shall submit periodic safety update reports for this product 
in accordance with the requirements set out in the list of Union reference dates (EURD list) 
provided for under Article 107c(7) of Directive 2001/83/EC and published on the European 
medicines web-portal.

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT

 Risk Management Plan (RMP)

The MAH shall perform the required pharmacovigilance activities and interventions detailed in 
the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed 
subsequent updates of the RMP.

An updated RMP should be submitted:
 At the request of the European Medicines Agency;
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached.

If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the 
same time.



18

ANNEX III

LABELLING AND PACKAGE LEAFLET



19

A. LABELLING



20

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON TEXT

1. NAME OF THE MEDICINAL PRODUCT

CONBRIZA 20 mg film-coated tablets
Bazedoxifene 

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each film-coated tablet contains bazedoxifene acetate equivalent to 20 mg bazedoxifene.

3. LIST OF EXCIPIENTS

Also contains lactose.
See leaflet for further information. 

4. PHARMACEUTICAL FORM AND CONTENTS

7 film-coated tablets
28 film-coated tablets
30 film-coated tablets
84 film-coated tablets
90 film-coated tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Oral use.
Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Do not store above 25ºC.



21

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

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/09/511/001 28 tablets
EU/1/09/511/002 30 tablets
EU/1/09/511/003 84 tablets
EU/1/09/511/004 90 tablets
EU/1/09/511/005   7 tablets

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

CONBRIZA

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC:
SN: 
NN: 



22

MINIMUM PARTICULARS TO APPEAR ON BLISTERS AND STRIPS

BLISTER

1. NAME OF THE MEDICINAL PRODUCT

CONBRIZA 20 mg film-coated tablets

Bazedoxifene

2. NAME OF THE MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



23

B. PACKAGE LEAFLET



24

Package Leaflet: Information for the patient

CONBRIZA 20 mg film-coated tablets
Bazedoxifene

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you.
 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 only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
 If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4.

What is in this leaflet:

1. What CONBRIZA is and what it is used for
2. What you need to know before you take CONBRIZA
3. How to take CONBRIZA
4. Possible side effects
5. How to store CONBRIZA
6. Contents of the pack and other information

1. What CONBRIZA is and what it is used for

CONBRIZA contains the active substance bazedoxifene, and is a medicine that belongs to a group of 
non-hormonal medicines called Selective Estrogen Receptor Modulators (SERMs). It is used for the 
treatment of osteoporosis in women after they have reached menopause, when they are at an increased 
risk of fractures. It works by slowing or stopping the thinning of bone in these women. This medicine
should not be used for the treatment of osteoporosis in men.

2. What you need to know before you take CONBRIZA

Do not take CONBRIZA

 if you are allergic to bazedoxifene or any of the other ingredients of this medicine (listed in
section 6).

 if you have or have had a blood clot (for example, in the blood vessels in your legs, lungs, or 
eyes).

 if you are pregnant or could still become pregnant. This medicine may cause harm to your 
unborn child if taken during pregnancy.

 if you have any unexplained vaginal bleeding. This must be investigated by your doctor.
 if you have active uterine cancer.

Warnings and precautions

Talk to your doctor or pharmacist before taking CONBRIZA

 as it may increase your risk of getting blood clots. While very infrequent, these clots can cause 
serious medical problems, disability or death. Speak with your doctor to see if you are at 
increased risk for blood clots.

 if you are immobile (unable to move) for some time, such as being wheel-chair bound, sitting for 
a prolonged period of time or having to stay in bed while recovering from an operation or 



25

illness. If you are traveling on long trips, you should walk around or exercise your legs and feet 
at regular intervals. 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. If you need to remain 
immobile for an extended period of time or are scheduled to have surgery, it is important for 
you to talk to your doctor about ways you can reduce the risk of blood clots.

 if you are pre-menopausal. CONBRIZA has only been studied in women who have reached 
menopause, and therefore is not recommended.

 if you have had increased levels of triglycerides (a type of fat found in your blood) in the past.
 if you have liver or severe kidney problems.
 if you have any vaginal bleeding while you take CONBRIZA, you should speak with your 

doctor.
 if you are suffering from breast cancer, as there is insufficient experience with this medicine use 

in women with this disease.

The above are some reasons why this product may not be suitable for you. If any of them apply to you, 
talk to your doctor before you take the medicine.

Other medicines and CONBRIZA

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines.

Pregnancy and breast-feeding

CONBRIZA is for use only by postmenopausal women. It must not be taken by women who are 
pregnant or who could still have a baby. Do not take this medicine if you are breast-feeding, because it 
is not known whether it is excreted in mother's milk.

Driving and using machines

If you feel drowsy after taking this medicine, you should avoid driving or operating machines. 

You may notice problems with your eyesight such as blurred vision while taking this medicine. If this 
happens, you should avoid driving or operating machines until your doctor tells you that it is safe to do 
so.

CONBRIZA contains lactose

This medicine contains lactose (a type of sugar). If you have been told by your doctor that you have an 
intolerance to some sugars, contact your doctor before taking this medicinal product.

3. How to take CONBRIZA

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. You should continue taking this medicine as long as your doctor tells 
you to. In order for this medicine to treat osteoporosis, it must be taken daily.

 The recommended dose is one tablet by mouth daily. Taking more than one tablet daily is not 
more effective and may carry additional risks.

 You can take the tablet at any time of the day, with or without food.
 This medicine should be taken with an adequate amount of calcium and vitamin D. Consult your 

doctor to see if your dietary calcium and vitamin D intake is adequate and whether you need 
calcium and vitamin D supplementation. If you take supplemental calcium and/or vitamin D, it 
may be taken at the same time as this medicine.



26

If you take more CONBRIZA than you should

Tell your doctor or pharmacist if you accidentally take more CONBRIZA than you should.

If you forget to take CONBRIZA

If you forget to take a tablet, take it as soon as you remember. However, if it is almost time to take 
your next dose of this medicine, skip the dose you missed and only take your next scheduled dose. Do 
not take a double dose to make up for a forgotten tablet.

If you stop taking CONBRIZA

If you decide to stop taking this medicine before finishing the prescribed course of treatment, you 
should talk to your doctor first.

If you have any further questions on the use or stopping the use of this medicine, ask your doctor or 
pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects – Stop taking CONBRIZA and see a doctor immediately

Uncommon (may affect up to 1 in 100 people):

 If you have signs of a blood clot in the legs or lungs, such as painful swelling and redness of the 
legs, sudden chest pain, or difficulty in breathing;

 If you have signs of a blood clot in the eye (retinal vein), such as one sided visual disturbance or 
visual impairment or blurring or loss of vision in one eye.

 If you get any of the problems listed under ‘Do not take CONBRIZA’

Not known (frequency cannot be estimated from the available data):
 If you have other events affecting the eye and/or vision (seeing sparks or flashes of light, 

narrowing of visual field, and swelling of eye or eyelid)

Other side effects

Some patients have experienced the following side effects while taking CONBRIZA:

Very common (may affect more than 1 in 10 people):

 Muscle spasms (includes leg cramps)
 Hot flushes
 Swelling of the hands, feet and legs (peripheral oedema)

Common (may affect up to 1 in 10 people):

 Allergic reaction (including hypersensitivity and urticaria)
 Rash, itching
 Dry mouth
 Increase in blood triglycerides (fat found in your blood)
 Increase in liver enzymes
 Drowsiness



27

Not known (frequency cannot be estimated from the available data):

 Palpitations (awareness of your heart beat)
 Dry eye, eye pain, visual acuity reduced, visual impairment, blepharospasm (abnormal, 

involuntary blinking or spasm of the eyelids).

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine.

5. How to store CONBRIZA

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and blister after EXP. The 
expiry date refers to the last date of that month.

Do not store above 25C.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What CONBRIZA contains

 The active substance is bazedoxifene. Each film-coated tablet contains bazedoxifene acetate 
equivalent to 20 mg bazedoxifene.

 The other ingredients are lactose monohydrate (see section 2 “CONBRIZA contains lactose”), 
microcrystalline cellulose, pre-gelatinised starch (maize), sodium starch glycolate, sodium 
lauryl sulfate, colloidal anhydrous silica, magnesium stearate, ascorbic acid, hypromellose, 
titanium dioxide (E171) and macrogol 400.

What CONBRIZA looks like and contents of the pack

CONBRIZA is supplied as a white to off-white, capsule-shaped, film-coated tablet marked with 
“WY20”. They are packed in PVC/Aclar blisters and are available in packs of 7, 28, 30, 84 or 90 
tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder: 
Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium.

Manufacturer: 
Pfizer Ireland Pharmaceuticals, Little Connell, Newbridge, County Kildare, Ireland.



28

For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder:

België/Belgique/Belgien
Luxembourg/Luxemburg
Pfizer S.A./N.V.
Tél/Tel: +32 (0)2 554 62 11

Latvijā
Pfizer Luxembourg SARL filiāle Latvijā
Tel.: + 371 670 35 775

България 
Пфайзер Люксембург САРЛ, 
Клон България 
Тел.: +359 2 970 4333

Lietuva
Pfizer Luxembourg SARL filialas Lietuvoje
Tel. + 370 52 51 4000

Česká Republika
Pfizer s.r.o. 
Tel: +420-283-004-111

Magyarország
Pfizer Kft
Tel: +36 1 488 3700

Danmark
Pfizer ApS 
Tlf: +45 44 201 100 

Malta
Vivian Corporation Ltd.
Tel: +35621 344610

Deutschland
Pfizer Pharma PFE GmbH
Tel: +49 (0) 800 8535555

Nederland
Pfizer BV
Tel: +31 (0)10 406 43 01

Eesti
Pfizer Luxembourg SARL Eesti filiaal
Tel.: +372 666 7500

Norge
Pfizer AS
Tlf: +47 67 526 100 

Ελλάδα
Pfizer Hellas A.E.
Τηλ.: +30 210 6785 800

Österreich
Pfizer Corporation Austria Ges.m.b.H.
Tel: +43 (0)1 521 15-0

España
Pfizer, S.L.
Tel: +34 91 490 99 00

Polska
Pfizer Polska Sp. z o.o. 
Tel:+48 22 335 61 00 

France
Pfizer
Tél: +33 (0)1 58 07 34 40 

Portugal
Pfizer Biofarmacêutica, Sociedade Unipessoal Lda
Tel: +351 21 423 5500

Hrvatska
Pfizer Croatia d.o.o.
Tel: + 385 1 3908 777

România
Pfizer Romania S.R.L
Tel: +40 (0) 21 207 28 00

Ireland
Pfizer Healthcare Ireland
Tel: 1800 633 363 (toll free)
+44 (0)1304 616161

Slovenija
Pfizer Luxembourg SARL
Pfizer, podružnica za svetovanje s področja
farmacevtske dejavnosti, Ljubljana
Tel.: + 386 (0) 1 52 11 400

Ísland
Icepharma hf
Simi: +354 540 8000

Slovenská Republika
Pfizer Luxembourg SARL, 
organizačná zložka 
Tel: + 421 2 3355 5500



29

Italia
Pfizer S.r.l. 
Tel: +39 06 33 18 21

Suomi/Finland
Pfizer Oy 
Puh/Tel: +358 (0)9 430 040

Kύπρος
Pfizer Hellas (Cyprus Branch) A.E. 
Τηλ: +357 22 817690

Sverige 
Pfizer AB 
Tel:+46 (0)8 550 520 00 

United Kingdom
Pfizer Limited,
Tel: +44 (0) 1304 616161

This leaflet was last revised in {MM/YYYY}.

Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/.


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO SAFE ANDEFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET