ACTONEL 5 Milligram Film Coated Tablet

Ireland - English - HPRA (Health Products Regulatory Authority)

Buy It Now

Active ingredient:
RISEDRONATE SODIUM
Available from:
Warner Chilcott UK Limited
ATC code:
M05BA07
INN (International Name):
RISEDRONATE SODIUM
Dosage:
5 Milligram
Pharmaceutical form:
Film Coated Tablet
Prescription type:
Product subject to prescription which may be renewed (B)
Therapeutic area:
Bisphosphonates
Authorization status:
Authorised
Authorization number:
PA1635/001/001
Authorization date:
2010-04-30

Package leaflet:

Information for the patient

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 Actonel is and what it is used for

2. What you need to know before you take Actonel

3. How to take Actonel

4. Possible side effects

5. How to store Actonel

6. Contents of the pack and other information

1. What Actonel is and what it is used

for

What Actonel is

Actonel belongs to a group of

non-hormonal medicines called

bisphosphonates which are used

to treat bone diseases. It works

directly on your bones to make

them stronger and therefore less

likely to break.

Bone is a living tissue. Old bone is constantly

removed from your skeleton and replaced with new

bone.

Postmenopausal osteoporosis is a condition

occurring in women after the menopause where the

bones become weaker, more fragile and more likely

to break after a fall or strain.

Osteoporosis is more likely to occur in women who

have reached the menopause early and also in

patients treated long-term with steroids.

The spine, hip and wrist are the most likely bones

to break, although this can happen to any bone in

your body. Osteoporosis – related fractures can also

cause back pain, height loss and a curved back.

Many patients with osteoporosis have no symptoms

and you may not even have known that you had it.

What Actonel is used for

The treatment of osteoporosis

in postmenopausal women

The prevention of osteoporosis

in women with an increased risk of osteoporosis

(including low bone mass, early menopause or a

family history of osteoporosis).

in postmenopausal women who have been on

high doses of steroid drugs for a long time. It

maintains or increases bone mass.

2.

What you need to know before you

take Actonel

Do not take Actonel

If you are allergic to risedronate sodium or any

of the other ingredients of this medicine (listed in

section 6).

If your doctor has told you that you have a

condition called hypocalcaemia (a low blood

calcium level).

If you may be pregnant, are pregnant or planning

to become pregnant.

If you are breast-feeding.

If you have severe kidney problems.

Warnings and precautions

Talk to your doctor or pharmacist before taking

Actonel

If you are unable to stay in an upright position

(sitting or standing) for at least 30 minutes.

If you have abnormal bone and mineral

metabolism (for example lack of vitamin D,

parathyroid hormone abnormalities, both leading

to a low blood calcium level).

If you have or have had problems in the past with

your oesophagus (the tube that connects your

mouth with your stomach). For instance you may

have or have had pain or difficulty in swallowing

food or you have previously been told that you

have Barrett’s oesophagus (a condition associated

with changes in the cells that line the lower

oesophagus).

If you have been told by your doctor that you have

an intolerance to some sugars (such as lactose).

If you have had or have pain, swelling or

numbness of the jaw or a “heavy jaw feeling” or

loosening of a tooth.

If you are under dental treatment or will undergo

dental surgery, tell your dentist that you are being

treated with Actonel.

Your doctor will advise you on what to do when

taking Actonel if you have any of the above.

Children and adolescents

Risedronate sodium is not recommended for use in

children below age 18 due to insufficient data on

safety and efficacy.

Other medicines and Actonel

Medicines containing one of the following lessen the

effect of Actonel if taken at the same time:

calcium

magnesium

aluminium (for example some indigestion mixtures)

iron.

Take these medicines at least 30 minutes after your

Actonel tablet.

Tell your doctor or pharmacist if you are taking,

have recently taken or might take any other

medicines.

Actonel with food and drink

It is very important that you do

NOT take your Actonel tablet with

food or drinks (other than plain

water) so that it can work properly.

In particular do not take this

medicine at the same time as dairy

products (such as milk) as they contain calcium (see

section 2, “Other medicines and Actonel”).

Take food and drinks (other than plain water) at least

30 minutes after your Actonel tablet.

Pregnancy and breast-feeding

Do NOT take Actonel if you may be pregnant, are

pregnant or planning to become pregnant (see

section 2, “Do not take Actonel”). The potential

risk associated with the use of risedronate sodium

(active substance in Actonel) in pregnant women is

unknown.

Do NOT take Actonel if you are breast-feeding (see

section 2, “Do not take Actonel”).

Driving and using machines

Actonel is not known to affect your ability to drive

and use machines.

Actonel contains a small amount of lactose

(see section 2, “Warnings and precautions”).

3. How to take Actonel

Always take this medicine exactly as your doctor or

pharmacist has told you. Check with your doctor or

pharmacist if you are not sure.

The recommended dose is ONE Actonel tablet

(5 mg of risedronate sodium) once a day.

For your convenience, the days of the week are

printed on the blister foil to help you remember to

take your medicine.

WHEN to take the Actonel tablet

IT IS BEST to take your Actonel tablet at least

30 minutes before the first food, drink (other than

plain water) or other medicine of the day.

If in particular instance you are unable to take your

Actonel tablet at this time, you may take it on an

empty stomach, at the same time every day, in one

of the following ways:

EITHER

Between meals: at least 2 hours after your last

food, drink (other than plain water) or other

medicine. Do not eat or drink (other than plain

water) for 2 hours after taking the tablet.

OR

In the evening: at least 2 hours after your last

food, drink (other than plain water) or other

medicine of the day. Actonel should be taken at

least 30 minutes before going to bed.

HOW to take the Actonel tablet

Take the tablet whilst you are in

an upright position (you may sit

or stand) to avoid heartburn.

Swallow it with at least one glass

(120 ml) of plain water.

Swallow it whole. Do not suck or

chew it.

Do not lie down for 30 minutes after taking your

tablet.

Your doctor will tell you if you need calcium and

vitamin supplements, if you are not taking enough

from your diet.

If you take more Actonel than you should

If you or somebody else has accidentally taken more

Actonel tablets than prescribed, drink one full glass

of milk and seek medical attention.

If you forget to take Actonel

If you have forgotten to take your

tablet at your regular time, you

can take it at the next possible time

according to the instruction above

(i.e. before breakfast, between

meals, or in the evening).

Do not take a double dose to make

up for a forgotten tablet.

If you stop taking Actonel

If you stop treatment you may begin to lose bone

mass. Please talk to your doctor before you consider

stopping treatment.

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.

Stop taking Actonel and contact a doctor

immediately if you experience any of the

following:

Symptoms of a severe allergic reaction such as:

– Swelling of the face, tongue or throat

– Difficulties in swallowing

– Hives and difficulties in breathing

Severe skin reactions that can include blistering of

the skin.

Tell your doctor promptly if you experience

the following

side effects:

Eye inflammation, usually with pain, redness and

light sensitivity.

Bone necrosis of the jaw (osteonecrosis)

associated with delayed healing and infection,

often following tooth extraction (see section 2,

“Warnings and precautions”).

Symptoms from oesophagus such as pain when

you swallow, difficulties in swallowing, chest pain

or new/worsened heartburn.

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.

Please turn over...

* Please note that only Artwork Studio is permitted to make changes to the above artwork.

No changes are permitted by any 3rd party other than added notes and mark ups for required changes.

approved for print/date

Proof Round

UK-Eire-Artwork-Support@Actavis.com

Technical

Approval

Non Printing Colours

Colours

Date sent:

Date received:

Item no:

Originator:

Origination Date:

Revision Date:

Revised By:

Dimensions:

Min Body Text Size:

Supplier:

Risedronic Acid (Actonel) 5mg Tablets PIL - UK/IE

Black

BBBA1004

S.Anson

23.06.17

06.07.17

S.Anson

190 x 600

10pt

Actavis Bulgaria

Dupnitsa

23.06.17

29.06.17

2

However in clinical studies the other side effects that

were observed were usually mild and did not cause

the patient to stop taking their tablets.

Common side effects (may affect up to 1 in 10

people)

Indigestion, feeling sick, stomach ache, stomach

cramps or discomfort, constipation, feelings of

fullness, bloating, diarrhoea.

Pain in your bones, muscles or joints.

Headache.

Uncommon side effects (may affect up to 1 in

100 people)

Inflammation or ulcer of the oesophagus (the

tube that connects your mouth with your stomach)

causing difficulty and pain in swallowing (see

also section 2, “Warnings and precautions”),

inflammation of the stomach and duodenum

(bowel draining the stomach).

Inflammation of the coloured part of the eye (iris)

(red painful eyes with a possible change in vision).

Rare side effects (may affect up to 1 in 1,000

people)

Inflammation of the tongue (red swollen, possibly

painful), narrowing of the oesophagus (the tube

that connects your mouth with your stomach).

Abnormal liver tests have been reported. These

can only be diagnosed from a blood test.

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.

During post-marketing experience, the following

have been reported (unknown frequency):

Hair loss

Liver disorders, some cases were severe

Rarely, at the beginning of treatment, a patient’s

blood calcium and phosphate levels may fall. These

changes are usually small and cause no symptoms.

Reporting of side effects

If you get any side effects, talk to your doctor,

pharmacist or nurse. This includes any possible side

effects not listed in this leaflet. You can also report

side effects directly via:

United Kingdom

Yellow Card Scheme at:

www.mhra.gov.uk/yellowcard

Ireland

HPRA Pharmacovigilance, Earlsfort Terrace,

IRL - Dublin 2;

Tel: +353 1 6764971; Fax: +353 1 6762517.

Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

By reporting side effects you can help provide more

information on the safety of this medicine.

5. How to store Actonel

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 day of that month.

This medicine does not require any special storage

conditions.

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 Actonel contains

The active substance is risedronate sodium. Each

tablet contains 5 mg risedronate sodium, equivalent

to 4.64 mg risedronic acid.

The other ingredients are:

Tablet core: lactose monohydrate (see section 2),

crospovidone, magnesium stearate and cellulose

microcrystalline.

Film coating: hypromellose, macrogol,

hydroxypropylcellulose, colloidal anhydrous silica,

titanium dioxide [E171], iron oxide yellow [E172].

What Actonel looks like and contents of

the pack

Actonel 5 mg film-coated tablets are oval yellow

tablets with the letters “RSN” on one side and

“5 mg” on the other side. The tablets are supplied

in blister packs of 14, 28 (2x14), 84 (6x14), 98

(7x14) tablets. Not all pack sizes may be marketed.

Marketing Authorisation Holder and

Manufacturer

Marketing Authorisation Holder

Warner Chilcott UK Limited,

Old Belfast Road,

Millbrook, Larne, County Antrim,

BT40 2SH, United Kingdom

Manufacturer:

Balkanpharma-Dupnitsa AD,

3, Samokovsko Shosse Str.,

2600 Dupnitsa, Bulgaria

This medicinal product is authorised in

the Member States of the EEA under the

following names:

Belgium:

Actonel 5 mg filmomhulde

tabletten,

Actonel 5 mg comprimé pelliculé,

Actonel 5 mg Filmtabletten

France:

Actonel 5 mg comprimé pelliculé

Germany:

Actonel 5 mg Filmtabletten

Ireland:

Actonel 5 mg film-coated tablets

Italy:

Actonel 5 mg compresse rivestite

con film

Luxembourg:

Actonel 5 mg comprimé pelliculé,

The Netherlands: Actonel 5 mg, filmomhulde

tabletten

Spain:

Actonel 5 mg comprimidos

recubiertos con película

Sweden:

Optinate 5 mg filmdragerade

tabletter

United Kingdom: Actonel 5 mg film-coated tablets

This leaflet was last revised in: June 2017

BBBA1004

* Please note that only Artwork Studio is permitted to make changes to the above artwork.

No changes are permitted by any 3rd party other than added notes and mark ups for required changes.

approved for print/date

Proof Round

UK-Eire-Artwork-Support@Actavis.com

Technical

Approval

Non Printing Colours

Colours

Date sent:

Date received:

Item no:

Originator:

Origination Date:

Revision Date:

Revised By:

Dimensions:

Min Body Text Size:

Supplier:

Risedronic Acid (Actonel) 5mg Tablets PIL - UK/IE

Black

BBBA1004

S.Anson

23.06.17

06.07.17

S.Anson

190 x 600

10pt

Actavis Bulgaria

Dupnitsa

23.06.17

29.06.17

2

Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Actonel 5 mg film coated tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains 5 mg risedronate sodium (equivalent to 4.64 mg risedronic acid).

Excipient with known effect:

Each film-coated tablet contains lactose.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Film-coated tablet.

Oval yellow film-coated tablet with RSN on one side and 5 mg on the other.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Treatment of postmenopausal osteoporosis, to reduce the risk of vertebral fractures. Treatment of established

postmenopausal osteoporosis, to reduce the risk of hip fractures. Prevention of osteoporosis in postmenopausal women

with increased risk of osteoporosis (see section 5.1)

To maintain or increase bone mass in postmenopausal women undergoing long

term (more than 3 months), systemic

corticosteroid treatment at doses

7.5 mg/day prednisone or equivalent.

4.2 Posology and method of administration

Posology

The recommended daily dose in adults is one 5 mg tablet orally.

Special populations

Elderly

No dosage adjustment is necessary since bioavailability, distribution and elimination were similar in elderly (>60 years of age)

compared to younger subjects.

Renal Impairment

No dosage adjustment is required for those patients with mild to moderate renal impairment. The use of risedronate sodium is

contraindicated in patients with severe renal impairment (creatinine clearance lower than 30 ml/min) (see sections 4.3 and 5.2).

Paediatric population

Risedronate sodium is not recommended for use in children below age 18 due to insufficient data on safety and efficacy

(see section 5.1).

Method of administration

The absorption of Actonel is affected by food, thus to ensure adequate absorption patients should take Actonel:

Before breakfast: At least 30 minutes before the first food, other medicinal product or drink (other than plain water) of the

day.

In the particular instance that before breakfast dosing is not practical, Actonel can be taken between meals or in the evening at the

same time everyday, with strict adherence to the following instructions, to ensure Actonel is taken on an empty stomach:

Between meals: Actonel should be taken at least 2 hours before and at least 2 hours after any food, medicinal product or

H

e

a

l

t

h

P

r

o

d

u

c

t

s

R

e

g

u

l

a

t

o

r

y

A

u

t

h

o

r

i

t

y

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

D

a

t

e

P

r

i

n

t

e

d

1

7

/

1

0

/

2

0

1

7

C

R

N

2

1

9

6

7

1

6

p

a

g

e

n

u

m

b

e

r

:

1

drink (other than plain water).

In the evening: Actonel should be taken at least 2 hours after the last food, medicinal product or drink (other than plain

water) of the day. Actonel should be taken at least 30 minutes before going to bed.

If an occasional dose is missed, Actonel can be taken before breakfast, between meals, or in the evening according to the

instructions above.

The tablets must be swallowed whole and not sucked or chewed. To aid delivery of the tablet to the stomach Actonel is to be taken

while in an upright position with a glass of plain water (>120 ml). Patients should not lie down for 30 minutes after taking the

tablet (see section 4.4).

Supplemental calcium and vitamin D should be considered if the dietary intake is inadequate.

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 risedronate on an individual patient basis,

particularly after 5 or more years of use.

4.3 Contraindications

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

Hypocalcaemia (see section 4.4).

Pregnancy and lactation.

Severe renal impairment (creatinine clearance <30 ml/min).

4.4 Special warnings and precautions for use

Foods, drinks (other than plain water) and medicinal products containing polyvalent cations (such as calcium,

magnesium, iron and aluminium) interfere with the absorption of bisphosphonates and should not be taken at the same

time as Actonel (see section 4.5). In order to achieve the intended efficacy, strict adherence to dosing recommendations

is necessary (see section 4.2).

Efficacy of bisphosphonates in the treatment of postmenopausal osteoporosis is related to the presence of low bone

mineral density (BMD T

score at hip or lumbar spine <

2.5 SD) and/or prevalent fracture.

High age or clinical risk factors for fracture alone are not reasons to initiate treatment of osteoporosis with a

bisphosphonate.

The evidence to support efficacy of bisphosphonates including Actonel in very elderly women (>80 years) is limited

(see section 5.1).

Bisphosphonates have been associated with oesophagitis, gastritis, oesophageal ulcerations and gastroduodenal

ulcerations. Thus caution should be used:

In patients who have a history of oesophageal disorders which delay oesophageal transit or emptying e.g. stricture or

achalasia.

In patients who are unable to stay in the upright position for at least 30 minutes after taking the tablet.

If risedronate is given to patients with active or recent oesophageal or upper gastrointestinal problems (including

known Barrett’s oesophagus).

Prescribers should emphasise to patients the importance of paying attention to the dosing instructions and be alert to

any signs or symptoms of possible oesophageal reaction. The patients should be instructed to seek timely medical

attention if they develop symptoms of oesophageal irritation such as dysphagia, pain on swallowing, retrosternal pain

or new/worsened heartburn.

Hypocalcaemia should be treated before starting Actonel therapy. Other disturbances of bone and mineral metabolism

(e.g. parathyroid dysfunction, hypovitaminosis D) should be treated at the time of starting Actonel therapy.

Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including osteomyelitis) has

been reported in patients with cancer receiving treatment regimens including primarily intravenously administered

bisphophonates. 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.

H

e

a

l

t

h

P

r

o

d

u

c

t

s

R

e

g

u

l

a

t

o

r

y

A

u

t

h

o

r

i

t

y

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

D

a

t

e

P

r

i

n

t

e

d

1

7

/

1

0

/

2

0

1

7

C

R

N

2

1

9

6

7

1

6

p

a

g

e

n

u

m

b

e

r

:

2

A dental examination with appropriate preventive dentistry should be considered prior to treatment with

bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, radiotherapy, corticosteroids,

poor oral hygiene).

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 judgment of the treating physician should guide the management plan of each patient based on individual

benefit/risk assessment.

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 including

chronic ear infections.

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.

This medicinal product 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

No formal interaction studies have been performed, however no clinically relevant interactions with other medicinal

products were found during clinical studies.

Concomitant ingestion of medications containing polyvalent cations (e.g. calcium, magnesium, iron and aluminium)

will interfere with the absorption of risedronate sodium (see section 4.4).

Risedronate sodium is not systemically metabolised, does not induce cytochrome P450 enzymes, and has low protein

binding.

In the risedronate sodium Phase III osteoporosis studies, acetyl salicylic acid or NSAID use was reported by 33% and

45% of patients respectively.

If considered appropriate risedronate sodium may be used concomitantly with oestrogen supplementation.

H

e

a

l

t

h

P

r

o

d

u

c

t

s

R

e

g

u

l

a

t

o

r

y

A

u

t

h

o

r

i

t

y

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

D

a

t

e

P

r

i

n

t

e

d

1

7

/

1

0

/

2

0

1

7

C

R

N

2

1

9

6

7

1

6

p

a

g

e

n

u

m

b

e

r

:

3

4.6 Fertility, pregnancy and lactation

There are no adequate data from the use of risedronate sodium in pregnant women. Studies in animals have shown

reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Studies in animal indicate that a

small amount of risedronate sodium pass into breast milk.

Risedronate sodium must not be used during pregnancy or by breast

feeding women.

4.7 Effects on ability to drive and use machines

Actonel has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

Risedronate sodium has been studied in phase III clinical studies involving more than 15,000 patients. The majority of

undesirable effects observed in clinical studies was mild to moderate in severity and usually did not require cessation of

therapy.

Adverse experiences reported in phase III clinical studies in postmenopausal women with osteoporosis treated for up to

36 months with risedronate 5 mg/day (n=5020) or placebo (n=5048) and considered possibly or probably related to

risedronate are listed below using the following convention (incidences versus placebo are shown in brackets): very

common (

1/10); common (

1/100; <1/10); uncommon (

1/1,000; <1/100); rare (

1/10,000; <1/1,000); very rare

(<1/10,000).

Nervous system disorders

Common: headache (1.8% vs. 1.4%)

Eye disorders

Uncommon: iritis*

Gastrointestinal disorders

Common: constipation (5.0% vs. 4.8%), dyspepsia (4.5% vs. 4.1%), nausea (4.3% vs. 4.0%), abdominal pain (3.5% vs.

3.3%), diarrhoea (3.0% vs. 2.7%)

Uncommon: gastritis (0.9% vs. 0.7%), oesophagitis (0.9% vs. 0.9%), dysphagia (0.4% vs. 0.2%), duodenitis (0.2% vs.

0.1%), oesophageal ulcer (0.2% vs. 0.2%)

Rare: glossitis (<0.1% vs. 0.1%), oesophageal stricture (<0.1% vs. 0.0%),

Musculoskeletal and connective tissues disorders

Common: musculoskeletal pain (2.1% vs. 1.9%)

Investigations

Rare: abnormal liver function tests*

* No relevant incidences from Phase III osteoporosis studies; frequency based on adverse event/laboratory/rechallenge

findings in earlier clinical studies.

Laboratory findings

Early, transient, asymptomatic and mild decreases in serum calcium and phosphate levels have been observed in some

patients.

The following additional adverse reactions have been reported during post

marketing use (frequency unknown):

Eye disorders

iritis, uveitis

H

e

a

l

t

h

P

r

o

d

u

c

t

s

R

e

g

u

l

a

t

o

r

y

A

u

t

h

o

r

i

t

y

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

D

a

t

e

P

r

i

n

t

e

d

1

7

/

1

0

/

2

0

1

7

C

R

N

2

1

9

6

7

1

6

p

a

g

e

n

u

m

b

e

r

:

4

Musculoskeletal and connective tissues disorders

osteonecrosis of the jaw

Skin and subcutaneous tissue disorders

hypersensitivity and skin reactions, including angioedema, generalised rash, urticaria and bullous skin reactions, some

severe including isolated reports of Stevens

Johnson syndrome toxic epidermal necrolysis and leukocytoclastic

vasculitis.

hair loss.

Immune system disorders

anaphylactic reaction

Hepatobiliary disorders

serious hepatic disorders. In most of the reported cases the patients were also treated with other products known to

cause hepatic disorders.

During post

marketing experience the following reactions have been reported:

Rare: Atypical subtrochanteric and diaphyseal femoral fractures (bisphosphonate class adverse reaction).

Very rare: Osteonecrosis of the external auditory canal (bisphosphonate class adverse reaction).

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

HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie;

E-mail: medsafety@hpra.ie.

4.9 Overdose

No specific information is available on the treatment of overdose with risedronate sodium.

Decreases in serum calcium following substantial overdose may be expected. Signs and symptoms of hypocalcaemia

may also occur in some of these patients.

Milk or antacids containing magnesium, calcium or aluminium should be given to bind risedronate and reduce

absorption of risedronate sodium. In cases of substantial overdose, gastric lavage may be considered to remove

unabsorbed risedronate sodium.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Bisphosphonates

ATC Code: M05 BA07

Mechanism of action

Risedronate sodium is a pyridinyl bisphosphonate that binds to bone hydroxyapatite and inhibits osteoclast

mediated

bone resorption. The bone turnover is reduced while the osteoblast activity and bone mineralisation is preserved.

Pharmacodynamic effects

In preclinical studies risedronate sodium demonstrated potent anti

osteoclast and antiresorptive activity, and dose

dependently increased bone mass and biomechanical skeletal strength. The activity of risedronate sodium was

confirmed by measuring biochemical markers for bone turnover during pharmacodynamic and clinical studies.

Decreases in biochemical markers of bone turnover were observed within 1 month and reached a maximum in 3

H

e

a

l

t

h

P

r

o

d

u

c

t

s

R

e

g

u

l

a

t

o

r

y

A

u

t

h

o

r

i

t

y

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

D

a

t

e

P

r

i

n

t

e

d

1

7

/

1

0

/

2

0

1

7

C

R

N

2

1

9

6

7

1

6

p

a

g

e

n

u

m

b

e

r

:

5

months.

Clinical efficacy and safety

Treatment and Prevention of Postmenopausal Osteoporosis

A number of risk factors are associated with postmenopausal osteoporosis including low bone mass, low bone mineral

density, early menopause, a history of smoking and a family history of osteoporosis. The clinical consequence of

osteoporosis is fractures. The risk of fractures is increased with the number of risk factors.

The clinical programme studied the effect of risedronate sodium on the risk of hip and vertebral fractures and contained

early and late postmenopausal women with and without fracture. Daily doses of 2.5 mg and 5 mg were studied and all

groups, including the control groups, received calcium and vitamin D (if baseline levels were low). The absolute and

relative risks of new vertebral and hip fractures were estimated by use of a time

first event analysis.

Two placebo

controlled studies (n=3,661) enrolled postmenopausal women under 85 years with vertebral

fractures at baseline. Risedronate sodium 5 mg daily given for 3 years reduced the risk of new vertebral fractures

relative to the control group. In women with respectively at least 2 or at least 1 vertebral fractures, the relative

risk reduction was 49% and 41% respectively (incidence of new vertebral fractures with risedronate sodium

18.1% and 11.3%, with placebo 29.0% and 16.3%, respectively). The effect of treatment was seen as early as the

end of the first year of treatment. Benefits were also demonstrated in women with multiple fractures at baseline.

Risedronate sodium 5 mg daily also reduced the yearly height loss compared to the control group.

Two further placebo controlled studies enrolled postmenopausal women above 70 years with or without vertebral

fractures at baseline. Women 70

79 years were enrolled with femoral neck BMD T

score <

3 SD

(manufacturer’s range, i.e.

2.5 SD using NHANES III(National Health and Nutrition Examination Survey)) and

at least one additional risk factor. Women >80 years could be enrolled on the basis of at least one non

skeletal

risk factor for hip fracture or low bone mineral density at the femoral neck. Statistical significance of the efficacy

of risedronate sodium versus placebo is only reached when the two treatment groups 2.5 mg and 5 mg are

pooled. The following results are only based on a

posteriori analysis of subgroups defined by clinical practise

and current definitions of osteoporosis:

In the subgroup of patients with femoral neck BMD T

score <

2.5 SD (NHANES III ) and at least one

vertebral fracture at baseline, risedronate sodium given for 3 years reduced the risk of hip fractures by 46%

relative to the control group (incidence of hip fractures in combined risedronate sodium 2.5 mg and 5 mg groups

3.8%, placebo 7.4%);

Data suggest that a more limited protection than this may be observed in the very elderly (>80 years). This may

be due to the increasing importance of non

skeletal factors for hip fracture with increasing age.

In these studies, data analysed as a secondary endpoint indicated a decrease in the risk of new vertebral

fractures in patients with low femoral neck BMD without vertebral fracture and in patients with low femoral neck

BMD with or without vertebral fracture.

Risedronate sodium 5 mg daily given for 3 years increased bone mineral density (BMD) relative to control at the

lumbar spine, femoral neck, trochanter and wrist and prevented bone loss at the mid

shaft radius.

In a one

year follow

up off therapy after three years treatment with risedronate sodium 5 mg daily there was

rapid reversibility of the suppressing effect of risedronate sodium on bone turnover rate.

In postmenopausal women taking oestrogen, risedronate sodium 5 mg daily increased bone mineral density

(BMD) at the femoral neck and mid

shaft radius only, compared to oestrogen alone.

Bone biopsy samples from postmenopausal women treated with risedronate sodium 5 mg daily for 2 to 3 years,

showed an expected moderate decrease in bone turnover. Bone formed during risedronate sodium treatment was

of normal lamellar structure and bone mineralisation. These data together with the decreased incidence of

osteoporosis related fractures at vertebral sites in women with osteoporosis appear to indicate no detrimental

effect on bone quality.

Endoscopic findings from a number of patients with a number of moderate to severe gastrointestinal complaints

in both risedronate sodium and control patients indicated no evidence of treatment related gastric, duodenal or

oesophageal ulcers in either group, although duodenitis was uncommonly observed in the risedronate sodium

H

e

a

l

t

h

P

r

o

d

u

c

t

s

R

e

g

u

l

a

t

o

r

y

A

u

t

h

o

r

i

t

y

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

D

a

t

e

P

r

i

n

t

e

d

1

7

/

1

0

/

2

0

1

7

C

R

N

2

1

9

6

7

1

6

p

a

g

e

n

u

m

b

e

r

:

6

group.

In a trial comparing before

breakfast dosing and dosing at other times of the day in women with postmenopausal

osteoporosis, lumbar spine BMD gains were statistically higher with before

breakfast dosing.

In osteopenic postmenopausal women, risedronate sodium has shown superiority to placebo in increasing lumbar

spine BMD at 12 and 24 months.

Corticosteroid Induced Osteoporosis

The clinical programme included patients initiating corticosteroid therapy (>7.5 mg/day prednisone or equivalent)

within the previous 3 months or patients who had been taking corticosteroids for more than 6 months. Results of these

studies demonstrate that:

Risedronate sodium 5 mg daily given for one year maintains or increases bone mineral density (BMD) relative to

control at the lumbar spine, femoral neck, and trochanter.

Risedronate sodium 5 mg daily reduced the incidence of vertebral fractures, monitored for safety, relative to control

at 1 year in pooled studies.

histological examination of bone biopsies from patients taking corticosteroids and risedronate sodium 5 mg daily did

not show signs of disturbed mineralisation process.

Paediatric population

The safety and efficacy of risedronate sodium has been investigated in a 3-year study (a randomized, double-blind,

placebo-controlled, multicenter, parallel group study of one year duration followed by 2 years of open-label treatment)

in paediatric patients aged 4 to less than 16 years with mild to moderate osteogenesis imperfecta. In this study, patients

weighing 10-30 kg received risedronate 2.5 mg daily and patients weighing more than 30 kg received risedronate 5 mg

daily.

After completion of its one-year randomized, double-blind, placebo-controlled phase, a statistically significant increase

in lumbar spine BMD in the risedronate group versus placebo group was demonstrated; however an increased number

of patients with at least 1 new morphometric (identified by x-ray) vertebral fracture was found in the risedronate group

compared to placebo. During the one-year double-blind period, the percentage of patients who reported clinical

fractures was 30.9% in the risedronate group and 49.0% in the placebo group. In the open-label period when all patients

received risedronate (month 12 to month 36), clinical fractures were reported by 65.3% of patients initially randomized

to the placebo group and by 52.9% of patients initially randomized to the risedronate group. Overall, results do not

support the use of risedronate sodium in paediatric patients with mild to moderate osteogenesis imperfecta.

5.2 Pharmacokinetic properties

Absorption

Absorption after an oral dose is relatively rapid (t

~1 hour) and is independent of dose over the range studied (2.5 to

30 mg). Mean oral bioavailability of the tablet is 0.63% and is decreased when risedronate sodium is administered with

food. Bioavailability was similar in men and women.

Distribution

The mean steady state volume of distribution is 6.3 L/kg in humans. Plasma protein binding is about 24%.

Biotransformation

There is no evidence of systemic metabolism of risedronate sodium.

Elimination

Approximately half of the absorbed dose is excreted in urine within 24 hours, and 85% of an intravenous dose is

recovered in the urine after 28 days. Mean renal clearance is 105 ml/min and mean total clearance is 122 ml/min, with

the difference probably attributed to clearance due to adsorption to bone. The renal clearance is not concentration

dependent, and there is a linear relationship between renal clearance and creatinine clearance. Unabsorbed risedronate

sodium is eliminated unchanged in faeces. After oral administration the concentration

time profile shows three

elimination phases with a terminal half

life of 480 hours.

Special Populations

H

e

a

l

t

h

P

r

o

d

u

c

t

s

R

e

g

u

l

a

t

o

r

y

A

u

t

h

o

r

i

t

y

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

D

a

t

e

P

r

i

n

t

e

d

1

7

/

1

0

/

2

0

1

7

C

R

N

2

1

9

6

7

1

6

p

a

g

e

n

u

m

b

e

r

:

7

Elderly

No dosage adjustment is necessary.

Acetyl salicylic acid/NSAID users

Among regular acetyl salicylic acid or NSAID users (3 or more days per week) the incidence of upper gastrointestinal

adverse events in risedronate sodium treated patients was similar to that in control patients.

5.3 Preclinical safety data

In toxicological studies in rat and dog dose dependent liver toxic effects of risedronate sodium were seen, primarily as

enzyme increases with histological changes in rat. The clinical relevance of these observations is unknown. Testicular

toxicity occurred in rat

and dog at

exposures considered in excess of the human therapeutic exposure.

Dose related

incidences of

upper

airway irritation were frequently noted in rodents.

Similar

effects have been seen with other

bisphosphonates. Lower respiratory tract effects were also seen in longer term studies in rodents, although the clinical

significance of

these findings is unclear.

In reproduction toxicity studies at

exposures close to clinical

exposure

ossification changes were seen in sternum and/or skull of foetuses from treated rats and hypocalcemia and mortality in

pregnant females allowed to deliver. There was no evidence of teratogenesis at 3.2mg/kg/day in rat and 10mg/kg/day in

rabbit,

although data are only available on a small

number of rabbits.

Maternal

toxicity prevented testing of higher

doses. Studies on genotoxicity and carcinogenesis did not show any particular risks for humans.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core:

Lactose monohydrate

Cellulose microcrystalline

Crospovidone

Magnesium stearate.

Film coating:

Iron oxide yellow E172

Hypromellose

Macrogol

Hyprolose

Colloidal anhydrous silica

Titanium dioxide E171.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

5 years.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Opaque PVC/aluminium foil blister cards of 14 tablets in a cardboard carton, tablet count 14, 28 (2 x 14), 84 (6 x 14),

98 (7 x 14) or 10 x 14 (hospital bundle).

2 x 10 count perforated blister strip (hospital unit dose)

H

e

a

l

t

h

P

r

o

d

u

c

t

s

R

e

g

u

l

a

t

o

r

y

A

u

t

h

o

r

i

t

y

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

D

a

t

e

P

r

i

n

t

e

d

1

7

/

1

0

/

2

0

1

7

C

R

N

2

1

9

6

7

1

6

p

a

g

e

n

u

m

b

e

r

:

8

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7 MARKETING AUTHORISATION HOLDER

Warner Chilcott UK Limited

Old Belfast Road

Millbrook

Larne

County Antrim

BT40 2SH

United Kingdom

8 MARKETING AUTHORISATION NUMBER

PA 1635/1/1

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 20

March 2000

Date of last renewal: 13

August 2009

10 DATE OF REVISION OF THE TEXT

February 2016

H

e

a

l

t

h

P

r

o

d

u

c

t

s

R

e

g

u

l

a

t

o

r

y

A

u

t

h

o

r

i

t

y

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

D

a

t

e

P

r

i

n

t

e

d

1

7

/

1

0

/

2

0

1

7

C

R

N

2

1

9

6

7

1

6

p

a

g

e

n

u

m

b

e

r

:

9

Similar products

Search alerts related to this product

View documents history

Share this information