Fosavance

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS

 



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1. NAME OF THE MEDICINAL PRODUCT

FOSAVANCE 70 mg/2,800 IU tablets
FOSAVANCE 70 mg/5,600 IU tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

FOSAVANCE 70 mg/2,800 IU tablets
Each tablet contains 70 mg alendronic acid (as sodium trihydrate) and 70 micrograms (2,800 IU) 
colecalciferol (vitamin D3).

Excipients with known effect
Each tablet contains 62 mg lactose (as lactose anhydrous) and 8 mg sucrose.

FOSAVANCE 70 mg/5,600 IU tablets
Each tablet contains 70 mg alendronic acid (as sodium trihydrate) and 140 micrograms (5,600 IU) 
colecalciferol (vitamin D3).

Excipients with known effect
Each tablet contains 63 mg lactose (as lactose anhydrous) and 16 mg sucrose.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Tablet
FOSAVANCE 70 mg/2,800 IU tablets
Modified capsule-shaped, white to off-white tablets, marked with an outline of a bone image on one 
side, and '710' on the other.

FOSAVANCE 70 mg/5,600 IU tablets
Modified rectangle-shaped, white to off-white tablets, marked with an outline of a bone image on one 
side, and '270' on the other.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

FOSAVANCE is indicated for the treatment of postmenopausal osteoporosis in women at risk of 
vitamin D insufficiency. It reduces the risk of vertebral and hip fractures.

4.2 Posology and method of administration

Posology

The recommended dose is one tablet once weekly.

Patients should be instructed that if they miss a dose of FOSAVANCE they should take one tablet on 
the morning after they remember. They should not take two tablets on the same day but should return 
to taking one tablet once a week, as originally scheduled on their chosen day.

Due to the nature of the disease process in osteoporosis, FOSAVANCE is intended for long-term use.

 



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The optimal duration of bisphosphonate treatment for osteoporosis has not been established. The need 
for continued treatment should be re-evaluated periodically based on the benefits and potential risks of 
FOSAVANCE on an individual patient basis, particularly after 5 or more years of use.

Patients should receive supplemental calcium if intake from diet is inadequate (see section 4.4). 
Additional supplementation with vitamin D should be considered on an individual basis taking into 
account any vitamin D intake from vitamins and dietary supplements. 

FOSAVANCE 70 mg/2,800 IU tablets
The equivalence of intake of 2,800 IU of vitamin D3 weekly in FOSAVANCE to daily dosing of 
vitamin D 400 IU has not been studied.

FOSAVANCE 70 mg/5,600 IU tablets
The equivalence of intake of 5,600 IU of vitamin D3 weekly in FOSAVANCE to daily dosing of 
vitamin D 800 IU has not been studied.

Elderly
In clinical studies there was no age-related difference in the efficacy or safety profiles of alendronate. 
Therefore no dose adjustment is necessary for the elderly.

Renal impairment
FOSAVANCE is not recommended for patients with renal impairment where creatinine clearance is 
less than 35 ml/min, due to lack of experience. No dose adjustment is necessary for patients with a 
creatinine clearance greater than 35 ml/min. 

Paediatric population
The safety and efficacy of FOSAVANCE in children less than 18 years of age have not been 
established. This medicinal product should not be used in children less than 18 years of age because no 
data are available for the alendronic acid/colecalciferol combination. Currently available data for 
alendronic acid in the paediatric population is described in section 5.1.

Method of administration

Oral use.

To permit adequate absorption of alendronate:

FOSAVANCE must be taken with water only (not mineral water) at least 30 minutes before the first 
food, beverage, or medicinal product (including antacids, calcium supplements and vitamins) of the 
day. Other beverages (including mineral water), food and some medicinal products are likely to reduce 
the absorption of alendronate (see section 4.5 and section 4.8).

The following instructions should be followed exactly in order to minimise the risk of oesophageal 
irritation and related adverse reactions (see section 4.4):

 FOSAVANCE should only be swallowed after getting up for the day with a full glass of water 
(not less than 200 ml).

 Patients should only swallow FOSAVANCE whole. Patients should not crush or chew the tablet 
or allow the tablet to dissolve in their mouths because of a potential for oropharyngeal 
ulceration.

 Patients should not lie down for at least 30 minutes after taking FOSAVANCE and until after 
the first food of the day.

 FOSAVANCE should not be taken at bedtime or before arising for the day.

 



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4.3 Contraindications

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

- Abnormalities of the oesophagus and other factors which delay oesophageal emptying such as 
stricture or achalasia.

- Inability to stand or sit upright for at least 30 minutes.

- Hypocalcaemia.

4.4 Special warnings and precautions for use

Alendronate 

Upper gastrointestinal adverse reactions
Alendronate can cause local irritation of the upper gastrointestinal mucosa. Because there is a potential 
for worsening of the underlying disease, caution should be used when alendronate is given to patients 
with active upper gastrointestinal problems, such as dysphagia, oesophageal disease, gastritis, 
duodenitis, ulcers, or with a recent history (within the previous year) of major gastrointestinal disease 
such as peptic ulcer, or active gastrointestinal bleeding, or surgery of the upper gastrointestinal tract 
other than pyloroplasty (see section 4.3). In patients with known Barrett's oesophagus, prescribers 
should consider the benefits and potential risks of alendronate on an individual patient basis.

Oesophageal reactions (sometimes severe and requiring hospitalisation), such as oesophagitis, 
oesophageal ulcers and oesophageal erosions, rarely followed by oesophageal stricture, have been 
reported in patients receiving alendronate. Physicians should therefore be alert to any signs or 
symptoms signalling a possible oesophageal reaction and patients should be instructed to discontinue 
alendronate and seek medical attention if they develop symptoms of oesophageal irritation such as 
dysphagia, pain on swallowing or retrosternal pain or new or worsening heartburn (see section 4.8).

The risk of severe oesophageal adverse reactions appears to be greater in patients who fail to take 
alendronate properly and/or who continue to take alendronate after developing symptoms suggestive 
of oesophageal irritation. It is very important that the full dosing instructions are provided to, and are
understood by the patient (see section 4.2). Patients should be informed that failure to follow these 
instructions may increase their risk of oesophageal problems.

While no increased risk was observed in extensive clinical trials with alendronate, there have been rare 
(post-marketing) reports of gastric and duodenal ulcers, some of which were severe and with 
complications (see section 4.8).

Osteonecrosis of the jaw
Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including 
osteomyelitis), has been reported in patients with cancer who are receiving treatment regimens 
including primarily intravenously administered bisphosphonates. Many of these patients were also 
receiving chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in 
patients with osteoporosis receiving oral bisphosphonates. 

The following risk factors should be considered when evaluating an individual’s risk of developing 
osteonecrosis of the jaw:
 potency of the bisphosphonate (highest for zoledronic acid), route of administration (see above)

and cumulative dose
 cancer, chemotherapy, radiotherapy, corticosteroids, angiogenesis inhibitors, smoking
 a history of dental disease, poor oral hygiene, periodontal disease, invasive dental procedures 

and poorly fitting dentures

 



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A dental examination with appropriate preventive dentistry should be considered prior to treatment 
with oral bisphosphonates in patients with poor dental status.

While on treatment, these patients should avoid invasive dental procedures if possible. For patients 
who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate 
the condition. For patients requiring dental procedures, there are no data available to suggest whether 
discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. Clinical 
judgement of the treating physician should guide the management plan of each patient based on 
individual benefit/risk assessment.

During bisphosphonate treatment, all patients should be encouraged to maintain good oral hygiene, 
receive routine dental check-ups, and report any oral symptoms such as dental mobility, pain, or 
swelling.

Osteonecrosis of the external auditory canal
Osteonecrosis of the external auditory canal has been reported with bisphosphonates, mainly in 
association with long-term therapy. Possible risk factors for osteonecrosis of the external auditory 
canal include steroid use and chemotherapy and/or local risk factors such as infection or trauma. The 
possibility of osteonecrosis of the external auditory canal should be considered in patients receiving 
bisphosphonates who present with ear symptoms such as pain or discharge, or chronic ear infections.

Musculoskeletal pain
Bone, joint, and/or muscle pain has been reported in patients taking bisphosphonates. In 
post-marketing experience, these symptoms have rarely been severe and/or incapacitating (see 
section 4.8). The time to onset of symptoms varied from one day to several months after starting 
treatment. Most patients had relief of symptoms after stopping treatment. A subset had recurrence of 
symptoms when rechallenged with the same medicinal product or another bisphosphonate.

Atypical fractures of the femur
Atypical subtrochanteric and diaphyseal femoral fractures have been reported with bisphosphonate 
therapy, primarily in patients receiving long-term treatment for osteoporosis. These transverse or short 
oblique, fractures can occur anywhere along the femur from just below the lesser trochanter to just 
above the supracondylar flare. These fractures occur after minimal or no trauma and some patients 
experience thigh or groin pain, often associated with imaging features of stress fractures, weeks to 
months before presenting with a completed femoral fracture. Fractures are often bilateral; therefore the 
contralateral femur should be examined in bisphosphonate-treated patients who have sustained a 
femoral shaft fracture. Poor healing of these fractures has also been reported. Discontinuation of 
bisphosphonate therapy in patients suspected to have an atypical femur fracture should be considered 
pending evaluation of the patient, based on an individual benefit risk assessment.
During bisphosphonate treatment patients should be advised to report any thigh, hip or groin pain and 
any patient presenting with such symptoms should be evaluated for an incomplete femur fracture.

Renal impairment
FOSAVANCE is not recommended for patients with renal impairment where creatinine clearance is 
less than 35 ml/min (see section 4.2).

Bone and mineral metabolism
Causes of osteoporosis other than oestrogen deficiency and ageing should be considered.

Hypocalcaemia must be corrected before initiating therapy with FOSAVANCE (see section 4.3). 
Other disorders affecting mineral metabolism (such as vitamin D deficiency and hypoparathyroidism) 
should also be effectively treated before starting this medicinal product. The content of vitamin D in 
FOSAVANCE is not suitable for correction of vitamin D deficiency. In patients with these conditions, 
serum calcium and symptoms of hypocalcaemia should be monitored during therapy with 
FOSAVANCE.

 



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Due to the positive effects of alendronate in increasing bone mineral, decreases in serum calcium and 
phosphate may occur especially in patients taking glucocorticoids in whom calcium absorption may be 
decreased. These are usually small and asymptomatic. However, there have been rare reports of 
symptomatic hypocalcaemia, which have occasionally been severe and often occurred in patients with 
predisposing conditions (e.g. hypoparathyroidism, vitamin D deficiency and calcium malabsorption) 
(see section 4.8).

Colecalciferol
Vitamin D3 may increase the magnitude of hypercalcaemia and/or hypercalciuria when administered to 
patients with disease associated with unregulated overproduction of calcitriol (e.g. leukaemia, 
lymphoma, sarcoidosis). Urine and serum calcium should be monitored in these patients.

Patients with malabsorption may not adequately absorb vitamin D3.

Excipients
This medicinal product contains lactose and sucrose. Patients with rare hereditary problems of fructose 
intolerance, galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption or 
sucrase-isomaltase insufficiency should not take this medicinal product.

4.5 Interaction with other medicinal products and other forms of interaction

Alendronate 
If taken at the same time, it is likely that food and beverages (including mineral water), calcium 
supplements, antacids, and some oral medicinal products will interfere with absorption of alendronate. 
Therefore, patients must wait at least 30 minutes after taking alendronate before taking any other oral 
medicinal product (see sections 4.2 and 5.2).

Since Non Steroidal Anti-Inflammatory Drug (NSAID) use is associated with gastrointestinal 
irritation, caution should be used during concomitant use with alendronate.

Colecalciferol
Olestra, mineral oils, orlistat, and bile acid sequestrants (e.g. cholestyramine, colestipol) may impair 
the absorption of vitamin D. Anticonvulsants, cimetidine and thiazides may increase the catabolism of 
vitamin D. Additional vitamin D supplements may be considered on an individual basis.

4.6 Fertility, pregnancy and lactation

FOSAVANCE is only intended for use in postmenopausal women and therefore it should not be used 
during pregnancy or in breast-feeding women.

Pregnancy
There are no or limited amount of data from the use of alendronate in pregnant women. Studies in 
animals have shown reproductive toxicity. Alendronate given during pregnancy in rats caused dystocia 
related to hypocalcaemia (see section 5.3). Studies in animals have shown hypercalcaemia and 
reproductive toxicity with high doses of vitamin D (see section 5.3). FOSAVANCE should not be 
used during pregnancy.

Breast-feeding
It is unknown whether alendronate/metabolites are excreted in human milk. A risk to the 
newborns/infants cannot be excluded. Colecalciferol and some of its active metabolites pass into 
breast milk. FOSAVANCE should not be used during breast-feeding.

Fertility
Bisphosphonates are incorporated into the bone matrix, from which they are gradually released over a 
period of years. The amount of bisphosphonate incorporated into adult bone, and hence, the amount 
available for release back into the systemic circulation, is directly related to the dose and duration of 
bisphosphonate use (see section 5.2). There are no data on foetal risk in humans. However, there is a 

 



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theoretical risk of foetal harm, predominantly skeletal, if a woman becomes pregnant after completing 
a course of bisphosphonate therapy. The impact of variables such as time between cessation of 
bisphosphonate therapy to conception, the particular bisphosphonate used, and the route of 
administration (intravenous versus oral) on the risk has not been studied.

4.7 Effects on ability to drive and use machines

FOSAVANCE has no or negligible direct influence on the ability to drive and use machines. Patients 
may experience certain adverse reactions (for example, blurred vision, dizziness and severe bone 
muscle or joint pain (see section 4.8)) that may influence the ability to drive and use machines. 

4.8 Undesirable effects

Summary of the safety profile
The most commonly reported adverse reactions are upper gastrointestinal adverse reactions including 
abdominal pain, dyspepsia, oesophageal ulcer, dysphagia, abdominal distension and acid regurgitation
(> 1 %).

Tabulated list of adverse reactions
The following adverse reactions have been reported during clinical studies and/or post-marketing use 
with alendronate.

No additional adverse reactions have been identified for the combination of alendronate and 
colecalciferol.

 



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Frequencies are defined as: 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), very rare (< 1/10,000)

System organ class Frequency Adverse reactions
Immune system disorders Rare hypersensitivity reactions including urticaria and 

angioedema
Metabolism and nutrition 
disorders

Rare symptomatic hypocalcaemia, often in association 
with predisposing conditions.§

Nervous system disorders Common headache, dizziness†

Uncommon dysgeusia†

Eye disorders Uncommon eye inflammation (uveitis, scleritis, or episcleritis)
Ear and labyrinth 
disorders

Common vertigo†

Very rare osteonecrosis of the external auditory canal 
(bisphosphonate class adverse reaction)

Gastrointestinal disorders Common abdominal pain, dyspepsia, constipation, diarrhoea, 
flatulence, oesophageal ulcer*, dysphagia*, 
abdominal distension, acid regurgitation

Uncommon nausea, vomiting, gastritis, oesophagitis*, 
oesophageal erosions*, melena†

Rare oesophageal stricture*, oropharyngeal ulceration*, 
upper gastrointestinal PUBs (perforation, ulcers, 
bleeding)§

Skin and subcutaneous 
tissue disorders

Common alopecia†, pruritus†

Uncommon rash, erythema
Rare rash with photosensitivity, severe skin reactions 

including Stevens-Johnson syndrome and toxic 
epidermal necrolysis‡

Musculoskeletal and 
connective tissue disorders

Very common musculoskeletal (bone, muscle or joint) pain which is 
sometimes severe†§

Common joint swelling†

Rare osteonecrosis of the jaw‡§; atypical subtrochanteric 
and diaphyseal femoral fractures (bisphosphonate 
class adverse reaction)

General disorders and 
administration site 
conditions

Common asthenia†, peripheral oedema†

Uncommon transient symptoms as in an acute-phase response 
(myalgia, malaise and rarely, fever), typically in 
association with initiation of treatment†

§See section 4.4
†Frequency in Clinical Trials was similar in the medicinal product and placebo group.
*See sections 4.2 and 4.4
‡This adverse reaction was identified through post-marketing surveillance. The frequency of rare was 
estimated based on relevant clinical trials.

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

Alendronate 
Symptoms
Hypocalcaemia, hypophosphataemia and upper gastrointestinal adverse reactions, such as upset 
stomach, heartburn, oesophagitis, gastritis, or ulcer, may result from oral overdose.

 

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Management
No specific information is available on the treatment of overdose with alendronate. In case of overdose 
with FOSAVANCE, milk or antacids should be given to bind alendronate. Owing to the risk of 
oesophageal irritation, vomiting should not be induced and the patient should remain fully upright.

Colecalciferol
Vitamin D toxicity has not been documented during chronic therapy in generally healthy adults at a 
dose less than 10,000 IU/day. In a clinical study of healthy adults a 4,000 IU daily dose of vitamin D3
for up to five months was not associated with hypercalciuria or hypercalcaemia.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Drugs for treatment of bone diseases, Bisphosphonates, combinations,
ATC code: M05BB03 

Mechanism of action

Alendronate 
Alendronate sodium is a bisphosphonate that inhibits osteoclastic bone resorption with no direct effect 
on bone formation. Preclinical studies have shown preferential localisation of alendronate to sites of 
active resorption. Activity of osteoclasts is inhibited, but recruitment or attachment of osteoclasts is 
not affected. The bone formed during treatment with alendronate is of normal quality.

Colecalciferol (vitamin D3)
Vitamin D3 is produced in the skin by conversion of 7-dehydrocholesterol to vitamin D3 by ultraviolet 
light. In the absence of adequate sunlight exposure, vitamin D3 is an essential dietary nutrient. 
Vitamin D3 is converted to 25-hydroxyvitamin D3 in the liver, and stored until needed. Conversion to 
the active calcium-mobilizing hormone 1,25-dihydroxyvitamin D3 (calcitriol) in the kidney is tightly 
regulated. The principal action of 1,25-dihydroxyvitamin D3 is to increase intestinal absorption of both 
calcium and phosphate as well as regulate serum calcium, renal calcium and phosphate excretion, bone 
formation and bone resorption.

Vitamin D3 is required for normal bone formation. Vitamin D insufficiency develops when both 
sunlight exposure and dietary intake are inadequate. Insufficiency is associated with negative calcium 
balance, bone loss, and increased risk of skeletal fracture. In severe cases, deficiency results in 
secondary hyperparathyroidism, hypophosphataemia, proximal muscle weakness and osteomalacia, 
further increasing the risk of falls and fractures in osteoporotic individuals. Supplemental vitamin D 
reduces these risks and their consequences.

Osteoporosis is defined as bone mineral density (BMD) of the spine or hip 2.5 standard deviations 
(SD) below the mean value of a normal young population or as a previous fragility fracture, 
irrespective of BMD.

Clinical efficacy and safety

FOSAVANCE studies
The effect of the lower dose of FOSAVANCE (alendronate 70 mg/vitamin D3 2,800 IU) on vitamin D 
status was demonstrated in a 15-week, multinational study that enrolled 682 osteoporotic 
post-menopausal women (serum 25-hydroxyvitamin D at baseline: mean, 56 nmol/l [22.3 ng/ml]; 
range, 22.5-225 nmol/l [9-90 ng/ml]). Patients received the lower strength (70 mg/2,800 IU) of 
FOSAVANCE (n=350) or FOSAMAX (alendronate) 70 mg (n=332) once a week; additional 
vitamin D supplements were prohibited. After 15 weeks of treatment, the mean serum 
25-hydroxyvitamin D levels were significantly higher (26 %) in the FOSAVANCE (70 mg/2,800 IU) 
group (56 nmol/l [23 ng/ml]) than in the alendronate-only group (46 nmol/l [18.2 ng/ml]). The 

 



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percentage of patients with vitamin D insufficiency (serum 25-hydroxyvitamin D < 37.5 nmol/l
[< 15 ng/ml]) was significantly reduced by 62.5 % with FOSAVANCE (70 mg/2,800 IU) vs. 
alendronate-only (12 % vs. 32 %, respectively), through week 15. The percentage of patients with 
vitamin D deficiency (serum 25-hydroxyvitamin D  22.5 nmol/l [ 9 ng/ml]) was significantly 
reduced by 92 % with FOSAVANCE (70 mg/2,800 IU) vs. alendronate-only (1 % vs 13 %, 
respectively). In this study, mean 25-hydroxyvitamin D levels in patients with vitamin D insufficiency 
at baseline (25-hydroxyvitamin D, 22.5 to 37.5 nmol/l [9 to < 15 ng/ml]) increased from 30 nmol/l
(12.1 ng/ml) to 40 nmol/l (15.9 ng/ml) at week 15 in the FOSAVANCE (70 mg/2,800 IU) group 
(n=75) and decreased from 30 nmol/l (12.0 ng/ml) at baseline to 26 nmol/l (10.4 ng/ml) at week 15 in 
the alendronate-only group (n=70). There were no differences in mean serum calcium, phosphate, or 
24-hour urine calcium between treatment groups.

The effect of the lower dose of FOSAVANCE (alendronate 70 mg/vitamin D3 2,800 IU) plus an 
additional 2,800 IU Vitamin D3 for a total of 5,600 IU (the amount of vitamin D3 in the higher dose of 
FOSAVANCE) once weekly was demonstrated in a 24-week, extension study that enrolled 
619 osteoporotic post-menopausal women. Patients in the Vitamin D3 2,800 group received 
FOSAVANCE (70 mg/2,800 IU) (n=299) and patients in the Vitamin D3 5,600 group received 
FOSAVANCE (70 mg/2,800 IU) plus an additional 2,800 IU vitamin D3 (n=309) once a week; 
additional vitamin D supplements were allowed. After 24-weeks of treatment, the mean serum 
25-hydroxyvitamin D levels were significantly higher in the Vitamin D3 5,600 group (69 nmol/l 
[27.6 ng/ml]) than in the Vitamin D3 2,800 group (64 nmol/l [25.5 ng/ml]). The percentage of patients 
with vitamin D insufficiency was 5.4 % in the Vitamin D3 2,800 group vs. 3.2 % in the Vitamin D3
5,600 group through the 24-week extension. The percentage of patients with vitamin D deficiency was 
0.3 % in the Vitamin D3 2,800 group vs. zero in the Vitamin D3 5,600 group. There were no 
differences in mean serum calcium, phosphate, or 24-hour urine calcium between treatment groups. 
The percentage of patients with hypercalciuria at the end of the 24-week extension was not statistically 
different between treatment groups.

Alendronate studies
The therapeutic equivalence of alendronate once weekly 70 mg (n=519) and alendronate 10 mg daily 
(n=370) was demonstrated in a one-year multicentre study of post-menopausal women with 
osteoporosis. The mean increases from baseline in lumbar spine BMD at one year were 5.1 % (95 % 
CI: 4.8, 5.4 %) in the 70 mg once-weekly group and 5.4 % (95 % CI: 5.0, 5.8 %) in the 10 mg daily 
group. The mean BMD increases were 2.3 % and 2.9 % at the femoral neck and 2.9 % and 3.1 % at the 
total hip in the 70 mg once weekly and 10 mg daily groups, respectively. The two treatment groups 
were also similar with regard to BMD increases at other skeletal sites.

The effects of alendronate on bone mass and fracture incidence in post-menopausal women were 
examined in two initial efficacy studies of identical design (n=994) as well as in the Fracture 
Intervention Trial (FIT: n=6,459).

In the initial efficacy studies, the mean BMD increases with alendronate 10 mg/day relative to placebo 
at three years were 8.8 %, 5.9 % and 7.8 % at the spine, femoral neck and trochanter, respectively. 
Total body BMD also increased significantly. There was a 48 % reduction (alendronate 3.2 % vs 
placebo 6.2 %) in the proportion of patients treated with alendronate experiencing one or more 
vertebral fractures relative to those treated with placebo. In the two-year extension of these studies 
BMD at the spine and trochanter continued to increase and BMD at the femoral neck and total body 
were maintained.

FIT consisted of two placebo-controlled studies using alendronate daily (5 mg daily for two years and 
10 mg daily for either one or two additional years):

 FIT 1: A three-year study of 2,027 patients who had at least one baseline vertebral 
(compression) fracture. In this study alendronate daily reduced the incidence of  1 new 
vertebral fracture by 47 % (alendronate 7.9 % vs. placebo 15.0 %). In addition, a statistically 
significant reduction was found in the incidence of hip fractures (1.1 % vs. 2.2 %, a reduction of 
51 %).

 



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 FIT 2: A four-year study of 4,432 patients with low bone mass but without a baseline vertebral 
fracture. In this study, a significant difference was observed in the analysis of the subgroup of 
osteoporotic women (37 % of the global population who correspond with the above definition of 
osteoporosis) in the incidence of hip fractures (alendronate 1.0 % vs. placebo 2.2 %, a reduction 
of 56 %) and in the incidence of  1 vertebral fracture (2.9 % vs. 5.8 %, a reduction of 50 %).

Laboratory test findings
In clinical studies, asymptomatic, mild and transient decreases in serum calcium and phosphate were 
observed in approximately 18 % and 10 %, respectively, of patients taking alendronate 10 mg/day 
versus approximately 12 % and 3 % of those taking placebo. However, the incidences of decreases in 
serum calcium to < 8.0 mg/dl (2.0 mmol/l) and serum phosphate to  2.0 mg/dl (0.65 mmol/l) were 
similar in both treatment groups.

Paediatric population
Alendronate sodium has been studied in a small number of patients with osteogenesis imperfecta 
under the age of 18 years. Results are insufficient to support the use of alendronate sodium in 
paediatric patients with osteogenesis imperfecta.

5.2. Pharmacokinetic properties

Alendronate 

Absorption
Relative to an intravenous reference dose, the oral mean bioavailability of alendronate in women was 
0.64 % for doses ranging from 5 to 70 mg when administered after an overnight fast and two hours 
before a standardised breakfast. Bioavailability was decreased similarly to an estimated 0.46 % and 
0.39 % when alendronate was administered one hour or half an hour before a standardised breakfast. 
In osteoporosis studies, alendronate was effective when administered at least 30 minutes before the 
first food or beverage of the day.

The alendronate component in the FOSAVANCE (70 mg/2,800 IU) combination tablet and the
FOSAVANCE (70 mg/5,600 IU) combination tablet is bioequivalent to the alendronate 70 mg tablet.

Bioavailability was negligible whether alendronate was administered with, or up to two hours after, a 
standardised breakfast. Concomitant administration of alendronate with coffee or orange juice reduced 
bioavailability by approximately 60 %.

In healthy subjects, oral prednisone (20 mg three times daily for five days) did not produce a clinically 
meaningful change in oral bioavailability of alendronate (a mean increase ranging from 20 % to 44 %).

Distribution
Studies in rats show that alendronate transiently distributes to soft tissues following 1 mg/kg 
intravenous administration but is then rapidly redistributed to bone or excreted in the urine. The mean 
steady-state volume of distribution, exclusive of bone, is at least 28 litres in humans. Concentrations of 
alendronate in plasma following therapeutic oral doses are too low for analytical detection (< 5 ng/ml). 
Protein binding in human plasma is approximately 78 %.

Biotransformation
There is no evidence that alendronate is metabolised in animals or humans.

Elimination
Following a single intravenous dose of [14C]alendronate, approximately 50 % of the radioactivity was 
excreted in the urine within 72 hours and little or no radioactivity was recovered in the faeces. 
Following a single 10 mg intravenous dose, the renal clearance of alendronate was 71 ml/min, and 
systemic clearance did not exceed 200 ml/min. Plasma concentrations fell by more than 95 % within 
six hours following intravenous administration. The terminal half-life in humans is estimated to 

 



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exceed ten years, reflecting release of alendronate from the skeleton. Alendronate is not excreted 
through the acidic or basic transport systems of the kidney in rats, and thus it is not anticipated to 
interfere with the excretion of other medicinal products by those systems in humans.

Colecalciferol

Absorption
In healthy adult subjects (males and females), following administration of FOSAVANCE 
70 mg/2,800 IU tablets after an overnight fast and two hours before a meal, the mean area under the 
serum-concentration-time curve (AUC0-120 hrs) for vitamin D3 (unadjusted for endogenous vitamin D3
levels) was 296.4 nghr/ml. The mean maximal serum concentration (Cmax) of vitamin D3 was 
5.9 ng/ml, and the median time to maximal serum concentration (Tmax) was 12 hours. The 
bioavailability of the 2,800 IU vitamin D3 in FOSAVANCE is similar to 2,800 IU vitamin D3
administered alone.

In healthy adult subjects (males and females), following administration of FOSAVANCE 
70 mg/5,600 IU after an overnight fast and two hours before a meal, the mean area under the serum-
concentration-time curve (AUC0-80 hrs) for vitamin D3 (unadjusted for endogenous vitamin D3 levels) 
was 490.2 nghr/ml. The mean maximal serum concentration (Cmax) of vitamin D3 was 12.2 ng/ml and 
the median time to maximal serum concentration (Tmax) was 10.6 hours. The bioavailability of the 
5,600 IU vitamin D3 in FOSAVANCE is similar to 5,600 IU vitamin D3 administered alone.

Distribution
Following absorption, vitamin D3 enters the blood as part of chylomicrons. Vitamin D3 is rapidly 
distributed mostly to the liver where it undergoes metabolism to 25-hydroxyvitamin D3, the major 
storage form. Lesser amounts are distributed to adipose and muscle tissue and stored as vitamin D3 at 
these sites for later release into the circulation. Circulating vitamin D3 is bound to vitamin D-binding 
protein.

Biotransformation
Vitamin D3 is rapidly metabolized by hydroxylation in the liver to 25-hydroxyvitamin D3, and 
subsequently metabolized in the kidney to 1,25-dihydroxyvitamin D3, which represents the 
biologically active form. Further hydroxylation occurs prior to elimination. A small percentage of 
vitamin D3 undergoes glucuronidation prior to elimination.

Elimination
When radioactive vitamin D3 was administered to healthy subjects, the mean urinary excretion of 
radioactivity after 48 hours was 2.4 %, and the mean faecal excretion of radioactivity after 4 days was 
4.9 %. In both cases, the excreted radioactivity was almost exclusively as metabolites of the parent. 
The mean half-life of vitamin D3 in the serum following an oral dose of FOSAVANCE
(70 mg/2,800 IU) is approximately 24 hours.

Renal impairment
Preclinical studies show that alendronate that is not deposited in bone is rapidly excreted in the urine. 
No evidence of saturation of bone uptake was found after chronic dosing with cumulative intravenous 
doses up to 35 mg/kg in animals. Although no clinical information is available, it is likely that, as in 
animals, elimination of alendronate via the kidney will be reduced in patients with impaired renal 
function. Therefore, somewhat greater accumulation of alendronate in bone might be expected in 
patients with impaired renal function (see section 4.2).

5.3 Preclinical safety data

Non-clinical studies with the combination of alendronate and colecalciferol have not been conducted.

Alendronate
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential. Studies in rats have 

 



13

shown that treatment with alendronate during pregnancy was associated with dystocia in dams during 
parturition which was related to hypocalcaemia. In studies, rats given high doses showed an increased 
incidence of incomplete foetal ossification. The relevance to humans is unknown.

Colecalciferol
At doses far higher than the human therapeutic range, reproductive toxicity has been observed in 
animal studies. 

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Microcrystalline cellulose (E460)
Lactose anhydrous
Medium chain triglycerides
Gelatin
Croscarmellose sodium
Sucrose
Colloidal silicon dioxide
Magnesium stearate (E572)
Butylhydroxytoluene (E321)
Modified starch (maize)
Sodium aluminium silicate (E554)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

18 months.

6.4 Special precautions for storage

Store in the original blister in order to protect from moisture and light.

6.5 Nature and contents of container

FOSAVANCE 70 mg/2,800 IU tablets
Aluminium/aluminium blisters, in cartons containing 2, 4, 6 or 12 tablets.

FOSAVANCE 70 mg/5,600 IU tablets
Aluminium/aluminium blisters, in cartons containing 2, 4 or 12 tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7. MARKETING AUTHORISATION HOLDER(S)

Merck Sharp & Dohme B.V.
Waarderweg 39

 



14

2031 BN Haarlem
The Netherlands

8. MARKETING AUTHORISATION NUMBER(S)

FOSAVANCE 70 mg/2,800 IU tablets
EU/1/05/310/001 – 2 tablets
EU/1/05/310/002 – 4 tablets
EU/1/05/310/003 – 6 tablets
EU/1/05/310/004 – 12 tablets

FOSAVANCE 70 mg/5,600 IU tablets
EU/1/05/310/006 – 2 tablets
EU/1/05/310/007 – 4 tablets
EU/1/05/310/008 – 12 tablets

9. DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION

Date of first authorisation: 24 August 2005
Date of latest renewal: 24 April 2015

10. DATE OF REVISION OF THE TEXT

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

 



15

ANNEX II

A. MANUACTURER(S) 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

 



16

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer(s) responsible for batch release

Merck Sharp & Dohme BV
Waarderweg 39
2031 BN, Haarlem
The Netherlands

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 requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal.

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE 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.

 



17

ANNEX III

LABELLING AND PACKAGE LEAFLET

 



18

A. LABELLING

 



19

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
CARTON FOR FOSAVANCE 70 mg/2,800 IU

1. NAME OF THE MEDICINAL PRODUCT

FOSAVANCE 70 mg/2,800 IU tablets
alendronic acid /colecalciferol

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 70 mg alendronic acid (as sodium trihydrate) and 70 micrograms (2,800 IU) 
colecalciferol (vitamin D3.).

3. LIST OF EXCIPIENTS

Also contains: lactose and sucrose. See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

2 tablets
4 tablets
6 tablets
12 tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Once weekly.
For oral use. 

Take one tablet once a week

Mark the day of the week that best fits your schedule:
MON
TUE
WED
THU
FRI
SAT
SUN

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.

 



20

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original blister in order to protect from moisture and light.

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

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/05/310/001 (2 tablets)
EU/1/05/310/002 (4 tablets)
EU/1/05/310/003 (6 tablets)
EU/1/05/310/004 (12 tablets)

13. BATCH NUMBER

Batch

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

FOSAVANCE
70 mg
2,800 IU

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

 



21

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC:
SN:
NN:

 



22

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER FOR FOSAVANCE 70 mg/2,800 IU

1. NAME OF THE MEDICINAL PRODUCT

FOSAVANCE
70 mg/2,800 IU
tablets
alendronic acid/colecalciferol

2. NAME OF THE MARKETING AUTHORISATION HOLDER

MSD

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

 



23

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
CARTON FOR FOSAVANCE 70 mg/5,600 IU

1. NAME OF THE MEDICINAL PRODUCT

FOSAVANCE 70 mg/5,600 IU tablets
alendronic acid /colecalciferol 

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 70 mg alendronic acid (as sodium trihydrate) and 140 micrograms (5,600 IU) 
colecalciferol (vitamin D3.).

3. LIST OF EXCIPIENTS

Also contains: lactose and sucrose. See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

2 tablets
4 tablets
12 tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Once weekly.
For oral use. 

Take one tablet once a week

Mark the day of the week that best fits your schedule:
MON
TUE
WED
THU
FRI
SAT
SUN

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.

 



24

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original blister in order to protect from moisture and light.

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

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/05/310/006 (2 tablets)
EU/1/05/310/007 (4 tablets)
EU/1/05/310/008 (12 tablets)

13. BATCH NUMBER

Batch

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

FOSAVANCE 
70 mg
5,600 IU

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

 



25

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC:
SN:
NN:

 



26

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER FOR FOSAVANCE 70 mg/5,600 IU

1. NAME OF THE MEDICINAL PRODUCT

FOSAVANCE
70 mg/5,600 IU
tablets
alendronic acid/colecalciferol

2. NAME OF THE MARKETING AUTHORISATION HOLDER

MSD

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

 



27

PARTICULARS TO APPEAR WITHIN THE OUTER PACKAGING (CARTON)

Instruction Card

Important information

How to take FOSAVANCE tablets

1. Take one tablet once a week.
2. Choose the day of the week that best fits your schedule. When you get out of bed on the day 

you have chosen, and before taking your first food, drink or other medicines, swallow (do not 
crush or chew the tablet or allow it to dissolve in your mouth) one FOSAVANCE tablet with a 
full glass of water (not mineral water).

3. Continue your morning activities. You can sit, stand or walk – just stay fully upright. Don’t 
lie down, eat, drink or take other medicines for at least 30 minutes. Do not lie down until after 
your first food of the day.

4. Remember, take FOSAVANCE once each week on that same day for as long as your doctor 
prescribes it.

If you miss a dose, take only one FOSAVANCE tablet on the morning after you remember. Do not 
take two tablets on the same day. Return to taking one tablet once a week, as originally scheduled on 
your chosen day.

There is important additional information about how to take FOSAVANCE in the package leaflet. 
Please read it carefully.

 



28

B. PACKAGE LEAFLET

 



29

Package Leaflet: Information for the user

FOSAVANCE 70 mg/2,800 IU tablets
FOSAVANCE 70 mg/5,600 IU tablets

Alendronic acid /colecalciferol

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.
- It is particularly important to understand the information in section 3 before taking this 

medicine.

What is in this leaflet

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

1. What FOSAVANCE is and what it is used for

What is FOSAVANCE?
FOSAVANCE is a tablet containing the two active substances, alendronic acid (commonly called 
alendronate) and colecalciferol known as vitamin D3.

What is alendronate?
Alendronate belongs to a group of non-hormonal medicines called bisphosphonates. Alendronate 
prevents the loss of bone that occurs in women after they have been through the menopause, and helps 
to rebuild bone. It reduces the risk of spine and hip fractures. 

What is vitamin D?
Vitamin D is an essential nutrient, required for calcium absorption and healthy bones. The body can 
only absorb calcium properly from our food if it has enough vitamin D. Very few foods contain 
vitamin D. The main source is through exposure to summer sunlight, which makes vitamin D in our 
skin. As we get older our skin makes less vitamin D. Too little vitamin D may lead to bone loss and 
osteoporosis. Severe vitamin D deficiency may cause muscle weakness which can lead to falls and a 
greater risk of fractures.

What is FOSAVANCE used for?
Your doctor has prescribed FOSAVANCE to treat your osteoporosis and because you are at risk of 
vitamin D insufficiency. It reduces the risk of spine and hip fractures in women after menopause.

What is osteoporosis?
Osteoporosis is a thinning and weakening of the bones. It is common in women after the menopause. 
At the menopause, the ovaries stop producing the female hormone, oestrogen, which helps to keep a 
woman’s skeleton healthy. As a result, bone loss occurs and bones become weaker. The earlier a 
woman reaches the menopause, the greater the risk of osteoporosis. 

 



30

Early on, osteoporosis usually has no symptoms. If left untreated, however, it can result in broken 
bones. Although these usually hurt, breaks in the bones of the spine may go unnoticed until they cause 
height loss. Broken bones can happen during normal, everyday activity, such as lifting, or from minor 
injury that would not generally break normal bone. Broken bones usually occur at the hip, spine, or 
wrist and can lead not only to pain but also to considerable problems like stooped posture (‘dowager’s 
hump’) and loss of mobility.

How can osteoporosis be treated?
As well as your treatment with FOSAVANCE, your doctor may suggest you make changes to your 
lifestyle to help your condition, such as:

Stopping smoking Smoking appears to increase the rate at which you lose bone and, therefore, 
may increase your risk of broken bones.

Exercise Like muscles, bones need exercise to stay strong and healthy. Consult your 
doctor before you begin any exercise programme.

Eating a balanced diet Your doctor can advise you about your diet or whether you should take any 
dietary supplements.

2. What you need to know before you take FOSAVANCE

Do not take FOSAVANCE
 if you are allergic to alendronic acid, colecalciferol or any of the other ingredients of this 

medicine (listed in section 6),
 if you have certain problems with your gullet (oesophagus - the tube that connects your mouth 

with your stomach) such as narrowing or difficulty swallowing,
 if you cannot stand or sit upright for at least 30 minutes,
 if your doctor has told you that you have low blood calcium.

If you think any of these apply to you, do not take the tablets. Talk to your doctor first and follow the 
advice given.

Warnings and precautions
Talk to your doctor or pharmacist before taking FOSAVANCE if:
 you suffer from kidney problems,
 you have, or have recently had, any swallowing or digestive problems,
 your doctor has told you that you have Barrett's oesophagus (a condition associated with 

changes in the cells that line the lower oesophagus),
 you have been told you have trouble absorbing minerals in your stomach or intestines 

(malabsorption syndrome),
 you have poor dental health, gum disease, a planned dental extraction or you don’t receive 

routine dental care,
 you have cancer,
 you are undergoing chemotherapy or radiotherapy,
 you are taking angiogenesis inhibitors (such as bevacizumab, or thalidomide) which are used in 

the treatment of cancer,
 you are taking corticosteroids (such as prednisone or dexamethasone) which are used in the 

treatment of such conditions as asthma, rheumatoid arthritis, and severe allergies,
 you are or have been a smoker (as this may increase the risk of dental problems).

You may be advised to have a dental check-up before starting treatment with FOSAVANCE.

 



31

It is important to maintain good oral hygiene when being treated with FOSAVANCE. You should 
have routine dental check-ups throughout your treatment and you should contact your doctor or dentist 
if you experience any problems with your mouth or teeth such as loose teeth, pain or swelling.

Irritation, inflammation or ulceration of the gullet (oesophagus – the tube that connects your mouth 
with your stomach) often with symptoms of chest pain, heartburn, or difficulty or pain upon 
swallowing may occur, especially if patients do not drink a full glass of water and/or if they lie down 
less than 30 minutes after taking FOSAVANCE. These side effects may worsen if patients continue to 
take FOSAVANCE after developing these symptoms.

Children and adolescents
FOSAVANCE should not be given to children and adolescents less than 18 years of age.

Other medicines and FOSAVANCE
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.

It is likely that calcium supplements, antacids, and some oral medicines will interfere with the 
absorption of FOSAVANCE if taken at the same time. Therefore, it is important that you follow the 
advice given in section 3 and wait at least 30 minutes before taking any other oral medicines or 
supplements.

Certain medicines for rheumatism or long-term pain called NSAIDs (e.g. acetylsalicylic acid or 
ibuprofen) might cause digestive problems. Therefore, caution should be used when these medicines 
are taken at the same time as FOSAVANCE.

It is likely that certain medicines or food additives may prevent the vitamin D in FOSAVANCE from 
getting into your body, including artificial fat substitutes, mineral oils, the weight loss medicine, 
orlistat, and the cholesterol-lowering medicines, cholestyramine and colestipol. Medicines for fits 
(seizures) (like phenytoin or phenobarbital) may decrease the effectiveness of vitamin D. Additional 
vitamin D supplements may be considered on an individual basis.

FOSAVANCE with food and drink
It is likely that food and beverages (including mineral water) will make FOSAVANCE less effective if 
taken at the same time. Therefore, it is important that you follow the advice given in section 3. You 
must wait at least 30 minutes before taking any food and beverages except water.

Pregnancy and breast-feeding
FOSAVANCE is only intended for use in postmenopausal women. You should not take 
FOSAVANCE if you are or think you may be pregnant, or if you are breast-feeding.

Driving and using machines
There have been side effects (for example, blurred vision, dizziness and severe bone, muscle or joint 
pain) reported with FOSAVANCE that may affect your ability to drive or operate machinery (see
section 4). If you experience any of these side effects you should not drive until you feel better.

FOSAVANCE contains lactose and sucrose. 
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 FOSAVANCE

Always take FOSAVANCE exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.

Take one FOSAVANCE tablet once a week.

 



32

Follow these instructions carefully.

1) Choose the day of the week that best fits your schedule. Every week, take one FOSAVANCE 
tablet on your chosen day.

It is very important to follow instructions 2), 3), 4) and 5) to help the FOSAVANCE tablet reach your 
stomach quickly and help reduce the chance of irritating your gullet (oesophagus - the tube that 
connects your mouth with your stomach).

2) After getting up for the day and before taking any food, drink, or other medicine, swallow your 
FOSAVANCE tablet whole with a full glass of water only (not mineral water) (not less than 
200 ml), so that FOSAVANCE is adequately absorbed.

 Do not take with mineral water (still or sparkling).
 Do not take with coffee or tea.
 Do not take with juice or milk.

Do not crush or chew the tablet or allow it to dissolve in your mouth because of the possibility of 
mouth ulceration.

3) Do not lie down — stay fully upright (sitting, standing or walking) — for at least 30 minutes 
after swallowing the tablet. Do not lie down until after your first food of the day.

4) Do not take FOSAVANCE at bedtime or before getting up for the day.

5) If you develop difficulty or pain upon swallowing, chest pain, or new or worsening heartburn, 
stop taking FOSAVANCE and contact your doctor.

6) After swallowing your FOSAVANCE tablet, wait at least 30 minutes before taking your first 
food, drink, or other medicine of the day, including antacids, calcium supplements and vitamins. 
FOSAVANCE is effective only if taken when your stomach is empty.

If you take more FOSAVANCE than you should
If you take too many tablets by mistake, drink a full glass of milk and contact your doctor 
immediately. Do not make yourself vomit, and do not lie down.

If you forget to take FOSAVANCE
If you miss a dose, just take one tablet on the morning after you remember. Do not take two tablets on 
the same day. Return to taking one tablet once a week, as originally scheduled on your chosen day.

If you stop taking FOSAVANCE
It is important that you take FOSAVANCE for as long as your doctor prescribes the medicine. Since it 
is not known how long you should take FOSAVANCE, you should discuss the need to stay on this 
medicine with your doctor periodically to determine if FOSAVANCE is still right for you.

An Instruction Card is included in the carton for FOSAVANCE. It contains important information 
reminding you how to take FOSAVANCE properly.

If you have any further questions on 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. 

 



33

See your doctor immediately if you notice any of the following side effects, which may be serious, 
and for which you may need urgent medical treatment:
Common (may affect up to 1 in 10 people):
 heartburn; difficulty swallowing; pain upon swallowing; ulceration of the gullet (oesophagus -

the tube that connects your mouth with your stomach) which can cause chest pain, heartburn or 
difficulty or pain upon swallowing.

Rare (may affect up to 1 in 1,000 people):
 allergic reactions such as hives; swelling of the face, lips, tongue and/or throat, possibly causing 

difficulty breathing or swallowing; severe skin reactions,
 pain in the mouth, and/or jaw, swelling or sores inside the mouth, numbness or a feeling of 

heaviness in the jaw, or loosening of a tooth. These could be signs of bone damage in the jaw 
(osteonecrosis) generally associated with delayed healing and infection, often following tooth 
extraction. Contact your doctor and dentist if you experience such symptoms,

 unusual fracture of the thigh bone particularly in patients on long-term treatment for 
osteoporosis may occur rarely. Contact your doctor if you experience pain, weakness or 
discomfort in your thigh, hip or groin as this may be an early indication of a possible fracture of 
the thigh bone,

 bone, muscle and/or joint pain which is severe.

Other side effects include
Very common (may affect more than 1 in 10 people):
 bone, muscle and/or joint pain which is sometimes severe.

Common (may affect up to 1 in 10 people): 
 joint swelling,
 abdominal pain; uncomfortable feeling in the stomach or belching after eating; constipation; full 

or bloated feeling in the stomach; diarrhoea; flatulence, 
 hair loss; itching,
 headache; dizziness,
 tiredness; swelling in the hands or legs.

Uncommon (may affect up to 1 in 100 people): 
 nausea; vomiting, 
 irritation or inflammation of the gullet (oesophagus – the tube that connects your mouth with 

your stomach) or stomach, 
 black or tar-like stools, 
 blurred vision; pain or redness in the eye,
 rash; redness of the skin,
 transient flu-like symptoms, such as aching muscles, generally feeling unwell and sometimes 

with fever usually at the start of treatment,
 taste disturbance. 

Rare (may affect up to 1 in 1,000 people): 
 symptoms of low blood calcium levels including muscle cramps or spasms and/or tingling 

sensation in the fingers or around the mouth, 
 stomach or peptic ulcers (sometimes severe or with bleeding), 
 narrowing of the gullet (oesophagus – the tube that connects your mouth with your stomach), 
 rash made worse by sunlight;
 mouth ulcers.

Very rare (may affect up to 1 in 10,000 people): 
 talk to your doctor if you have ear pain, discharge from the ear, and/or an ear infection. These 

could be signs of bone damage in the ear.

 



34

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 FOSAVANCE

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 the blister after EXP. 
The expiry date refers to the last day of that month.

Store in the original blister in order to protect from moisture and light.

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 FOSAVANCE contains

The active substances are alendronic acid and colecalciferol (vitamin D3). Each FOSAVANCE 70 
mg/2,800 IU tablet contains 70 mg alendronic acid (as sodium trihydrate) and 70 micrograms 
(2,800 IU) colecalciferol (vitamin D3). Each FOSAVANCE 70 mg/5,600 IU tablet contains 70 mg 
alendronic acid (as sodium trihydrate) and 140 micrograms (5,600 IU) colecalciferol (vitamin D3).

The other ingredients are microcrystalline cellulose (E460), lactose anhydrous (see section 2), medium 
chain triglycerides, gelatin, croscarmellose sodium, sucrose (see section 2), colloidal silicon dioxide, 
magnesium stearate (E572), butylhydroxytoluene (E321), modified starch (maize), and sodium 
aluminium silicate (E554).

What FOSAVANCE looks like and contents of the pack

FOSAVANCE 70 mg/2,800 IU tablets are available as modified capsule-shaped, white to off-white 
tablets marked with an outline of a bone image on one side and ‘710’ on the other. FOSAVANCE 
70 mg/2,800 IU tablets are available in packs containing 2, 4, 6 or 12 tablets.

FOSAVANCE 70 mg/5,600 IU tablets are available as modified rectangle-shaped, white to off-white 
tablets marked with an outline of a bone image on one side and ‘270’ on the other. FOSAVANCE
70 mg/5,600 IU tablets are available in packs containing 2, 4 or 12 tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder.

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


35

Belgique/België/Belgien
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Lietuva
UAB Merck Sharp & Dohme
Tel.: +370 5 278 02 47
msd_lietuva@merck.com

България
Мерк Шарп и Доум България ЕООД
Тел.: +359 2 819 3737
info-msdbg@merck.com

Luxembourg/Luxemburg
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Česká republika
Merck Sharp & Dohme s.r.o. 
Tel.: +420 233 010 111
dpoc_czechslovak@merck.com

Magyarország
MSD Pharma Hungary Kft.
Tel.: +36 1 888 53 00
hungary_msd@merck.com

Danmark
MSD Danmark ApS
Tlf: +45 44824000
dkmail@merck.com

Malta
Merck Sharp & Dohme Cyprus Limited
Tel: 8007 4433 (+356 99917558)
malta_info@merck.com

Deutschland
MSD SHARP & DOHME GMBH
Tel: 0800 673 673 673
(+49 (0) 89 4561 2612)
e-mail@msd.de

Nederland 
Merck Sharp & Dohme BV
Tel.: 0800 9999000 (+31 23 5153153)
medicalinfo.nl@merck.com

Eesti
Merck Sharp & Dohme OÜ
Tel.: +372 6144 200
msdeesti@merck.com

Norge
MSD (Norge) AS
Tlf: +47 32 20 73 00
msdnorge@msd.no

Eλλάδα
BIANEΞ Α.Ε
Τηλ: +30 210 80091 11
Mailbox@vianex.gr

Österreich
Merck Sharp & Dohme Ges.m.b.H.
Tel: +43 (0) 1 26 044
msd-medizin@merck.com

España
Merck Sharp & Dohme de España, S.A.
Tel: +34 91 321 06 00
msd_info@merck.com

Polska
MSD Polska Sp.z o.o. 
Tel.: +48 22 549 51 00
msdpolska@merck.com

France
MSD France
Tél: + 33 (0) 1 80 46 40 40

Portugal
Merck Sharp & Dohme, Lda
Tel: + 351 214 465700
inform_pt@merck.com

Hrvatska
Merck Sharp & Dohme d.o.o.
Tel: + 385 1 6611 333
croatia_info@merck.com

România
Merck Sharp & Dohme Romania S.R.L.
Tel: + 4021 529 29 00
msdromania@merck.com

Ireland
Merck Sharp & Dohme Ireland (Human Health) 
Limited
Tel: +353 (0)1 2998700
medinfo_ireland@merck.com

Slovenija
Merck Sharp & Dohme, inovativna zdravila 
d.o.o.
Tel: + 386 1 5204201
msd_slovenia@merck.com

 

mailto:msd_info@merck.com
mailto:e-mail@msd.de
mailto:hungary_msd@merck.com
mailto:dpoc_belux@merck.com
mailto:dpoc_belux@merck.com


36

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Merck Sharp & Dohme, s. r. o.
Tel.: +421 2 58282010
dpoc_czechslovak@merck.com

Ιtalia
MSD Italia S.r.l.
Tel: +39 06 361911
medicalinformation.it@merck.com

Suomi/Finland
MSD Finland Oy
Puh/Tel: +358 (0) 9 804650
info@msd.fi

Κύπρος
Merck Sharp & Dohme Cyprus Limited
Τηλ: 80000 673 (+357 22866700)
cyprus_info@merck.com

Sverige
Merck Sharp & Dohme (Sweden) AB
Tel: +46 77 5700488
medicinskinfo@merck.com

Latvija
SIA Merck Sharp & Dohme Latvija
Tel: +371 67364 224
msd_lv@merck.com

United Kingdom
Merck Sharp & Dohme Limited
Tel: +44 (0) 1992 467272
medicalinformationuk@merck.com

This leaflet was last revised in <{MM/YYYY}>

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

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) 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
	A. LABELLING
	B. PACKAGE LEAFLET