ALENDRONIC ACID ONCE WEEKLY

Ireland - English - HPRA (Health Products Regulatory Authority)

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Active ingredient:
ALENDRONIC ACID
Available from:
Accord Healthcare Limited
ATC code:
M05BA04
INN (International Name):
ALENDRONIC ACID
Dosage:
70 Milligram
Pharmaceutical form:
Tablets
Prescription type:
Product subject to prescription which may be renewed (B)
Therapeutic area:
alendronic acid
Authorization status:
Marketed
Authorization number:
PA1390/035/002
Authorization date:
2011-02-18

Package leaflet: Information for the user

Alendronic Acid Once weekly 70 mg Tablets

(Alendronic Acid)

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

symptoms 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. How to take Alendronic acid, before taking

this medicine.

What is in this leaflet

1. What Alendronic Acid Tablets are and what they are used for

2. What you need to know before you take Alendronic Acid Tablets

3. How to take Alendronic Acid Tablets

4. Possible side effects

5. How to store Alendronic Acid Tablets

6. Contents of the pack and other information

1. What Alendronic Acid Tablets are and what they are used for

What is Alendronic acid?

Alendronic acid tablet is a tablet containing the active substance alendronic acid (commonly called alendronate) and belongs

to a group of non-hormonal medicines called bisphosphonates. Alendronic acid 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 are Alendronic Acid Tablets used for?

Your doctor has prescribed alendronic acid tablets to treat your osteoporosis. Alendronic acid reduces the risk of spine and

hip fractures.

Alendronic acid is a once weekly treatment.

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.

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 Alendronic acid Tablet, 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

(especially calcium and Vitamin D).

2. What you need to know before you take Alendronic Acid Tablets

Do not take Alendronic Acid Tablets

if you are allergic to alendronic acid 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 Alendronic acid

It is important to tell your doctor before taking Alendronic Acid Tablets if

you suffer from kidney problems

you have 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 low blood calcium

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)

You are taking corticosteroids (such as prednisone or dexamethasone)

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 Alendronic acid Tablets.

It is important to maintain good oral hygiene when being treated with Alendronic Acid Tablets. 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 Alendronic Acid Tablets. These side effects

may worsen if patients continue to take Alendronic Acid Tablets after developing these symptoms.

Children and adolescents

Alendronic acid Tablets should not be given to children and adolescents.

Other medicines and Alendronic acid Tablets

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 Alendronic acid

Tablets if taken at the same time. Therefore, it is important that you follow the advice given in section 3 How to take

Alendronic acid Tablets.

Certain medicines for rheumatism or long-term pain called NSAIDs (e.g acetylsalicyclic acid or ibuprofen) might cause

digestive problems. Therefore, caution should be used when these medicines are taken at the same time as Alendronic acid

Tablets.

Alendronic Acid Tablets with food and drink

It is likely that food and beverages (including mineral water) will make Alendronic acid Tablets less effective if taken at the

same time. Therefore, it is important that you follow the advice given in section 3 How to take Alendronic Acid Tablets.

Pregnancy, breast-feeding and fertility

Alendronic acid tablet is only intended for use in postmenopausal women. If you are pregnant or breast-feeding, think you

may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

There have been side effects (including blurred vision, dizziness and severe bone, muscle or joint pain) reported with

alendronic acid tablets that may affect your ability to drive or operate machinery. Individual responses to alendronic acid

tablets may vary (See section 4.)

Alendronic Acid Tablets contains lactose

If you have been told by your doctor that you have intolerance to some sugars, contact your doctor before taking this

medicine.

3. How to take Alendronic Acid Tablets

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you

are not sure.

Take one Alendronic Acid Tablet once a week.

Follow these instructions carefully to make sure you will benefit from alendronic acid.

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

It is very important to follow instructions 2), 3), 4) and 5) to help the alendronic acid 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 alendronic acid tablet

with a full glass of water only (not mineral water) (not less than 200 ml).

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.

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 alendronic acid 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 alendronic acid

and contact your doctor.

6) After swallowing your alendronic acid tablet, wait at least 30 minutes before taking your first food, drink, or other

medicine of the day, including antacids, calcium supplements and vitamins. Alendronic Acid is effective only if taken when

your stomach is empty.

If you take more Alendronic Acid Tablets 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 Alendronic Acid Tablets

If you miss a dose, just take one Alendronic Acid Tablets 70 mg on the morning after you remember. Do not take a double

dose to make up for a forgotten dose. Return to taking one tablet once a week, as originally scheduled on your chosen day.

If you stop taking Alendronic Acid Tablets

It is important that you continue taking Alendronic Acid Tablets for as long as your doctor prescribes the medicine. Since it

is not known how long you should take Alendronic Acid Tablets, you should discuss the need to stay on this medicine with

your doctor periodically to determine if Alendronic acid tablets are still right for you.

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.

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;

headache; dissiness,

hair loss; itching

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

rash; redness of the skin

blurred vision; pain or redness in the eye,

transient flu-like symptoms, such as aching muscles, generally feeling unwell and sometimes with fever usually at

the start of tratment,

taste disturbance.

Rare side (may affect up to 1 in 1000 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 when the tablets have been chewed or sucked

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.

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. By reporting side effects, you can help provide more information on the safety of this medicine.

For IE- You can also report side effects directly 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.

5. How to store Alendronic Acid Tablets

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

This medicinal product does not require any special storage conditions

Do not take 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.

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 Alendronic Acid Tablets contain

The active substance is alendronic acid (as sodium alendronate).

Each tablet contains 70mg alendronic acid (as alendronate sodium)

The other ingredients are lactose anhydrous, cellulose microcrystalline (E460), croscarmellose sodium and magnesium

stearate.

What Alendronic Acid Tablets look like and content of the pack:

Alendronic Acid 70 mg Tablets are available as white to off-white, oval, biconvex tablet debossed with ‘AHI’ on one side

and plain on other side.

Alendronic Acid 70 mg Tablets are available in OPA-Al-PVC/Al blister packs containing 4 tablets or 12* tablets.

Not all pack sizes may be marketed

* Not for UK market

Marketing Authorisation Holder and Manufacturer

Accord Healthcare Limited

Sage House , 319 Pinner Road,

North Harrow, Middlesex

HA1 4HF,

United Kingdom

The leaflet was last approved in 10/2016.

Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Alendronic Acid Once Weekly 70 mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 70mg alendronic acid (as alendronate sodium)

Excipients: Each tablet contains 272.070 mg of Lactose Anhydrous

For a full list of excipients see section 6.1

3 PHARMACEUTICAL FORM

Tablet

White to off- white, oval, biconvex, tablet, debossed with ‘AHI’ on one side and plain on other side.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Treatment of post-menopausal osteoporosis. Alendronic acid reduces the risk of vertebral and hip fractures.

4.2 Posology and method of administration

Posology

The recommended dosage is one 70 mg tablet

once weekly.

The optimal

duration of bisphosphonate treatment

osteoporosis has not been established.

The need for continued treatment should be re-evaluated periodically based on

the benefits and potential risks of Alendronic acid Once Weekly 70 mg on an individual patient basis, particularly after

5 or more years of use.

Elderly

In clinical studies there was no age-related difference in the efficacy or safety profiles of alendronic acid. Therefore no

dosage adjustment is necessary for the elderly.

Renal impairment

No dosage adjustment

is necessary for

patients with GFR greater

than 35 ml/min.

Alendronic acid Tablet is not

recommended for patients with renal impairment where GFR is less than 35 ml/min, due to lack of experience.

Paediatric population

Alendronate Sodium is not recommended for use in children under the age of 18 years due to insufficient data on safety

and efficacy in conditions associated with paediatric osteoporosis (See also section 5.1).

Alendronic acid Once Weekly 70 mg has not been investigated in the treatment of glucocorticoid-induced osteoporosis.

Method of administration

Oral use.

To permit adequate absorption of alendrnic acid:

Alendronic acid Tablet must be taken at least 30 minutes before the first food,

beverage,

or medicinal product of the

day with plain water only. Other beverages (including mineral water), food and some medicinal products are likely to

reduce the absorption of alendronic acid (see section 4.5).

To facilitate delivery to the stomach and thus reduce the potential for local and oesophageal irritation/adverse

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experiences (see section 4.4):

Alendronic acid Tablet should only be swallowed upon arising for the day with a full glass of water (not less than

200 ml or 7 fluid ounce).

Patients should not chew or crush the tablet or allow the tablet to dissolve in their mouths because of a potential

for oropharyngeal ulceration.

Patients should not lie down until after their first food of the day which should be at least 30 minutes after taking

the tablet.

Patients should not lie down for at least 30 minutes after taking Alendronic acid.

Alendronic acid Tablet should not be taken at bedtime or before arising for the day.

Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate (see section 4.4).

4.3 Contraindications

Alendronic acid is contraindicated in:

Hypersensitivity to the active substance 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

Upper gastrointestinal adverse reactions

Alendronic acid can cause local

irritation of

the upper

gastro-intestinal

mucosa.

Because there is a potential

worsening of the underlying disease, caution should be used when alendronic acid tablet is given to patients with active

upper gastro-intestinal problems, such as dysphagia,

oesophageal disease,

gastritis,

duodenitis,

ulcers or with a recent

history (within the previous year) of major gastro-intestinal

disease such as peptic ulcer,

or active gastro-intestinal

bleeding,

or surgery of the upper gastro-intestinal

tract

other thank pyloroplasty (see section 4.5).

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 or perforation, have been reported in patients receiving

alendronic acid. Physicians should therefore be alert to any signs or symptoms signalling a possible oesophageal

reaction and patients should be instructed to discontinue alendronic acid tablet and seek medical attention if they

develop symptoms of oesophageal irritation such as dysphagia, pain on swallowing or retrosternal pain, new or

worsening heartburn.

The risk of severe oesophageal adverse experiences appears to be greater in patients who fail to take alendronic acid

properly and/or who continue to take alendronic acid tablet

after developing symptoms suggestive of oesophageal

irritation. It is very important that the full dosing instructions are provided to, and 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, there have been rare (post-marketing) reports of

gastric and duodenal ulcers, some severe and with complications.

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

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

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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, smoking

a history of dental disease, poor oral hygiene, periodontal disease, invasive dental procedures and poorly fitting

dentures.

A dental

examination

with

appropriate

preventive

dentistry

should

considered

prior

treatment

with

bisphosphonates in patients with poor dental status.

While on treatment,

these patients should avoid invasive dental

procedures if

possible.

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,

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 including

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. A subset

had recurrence of symptoms when rechallenged with the same drug 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

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.

Skin reactions

In post-marketing experience, there have been rare reports of severe skin reactions including Stevens Johnson

syndrome and toxic epidermal necrolysis.

Missed dose

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Patients should be instructed that if they miss a dose of Alendronic acid once weekly tablet, 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.

Renal impairment

Alendronic acid tablet is not recommended for patients with renal impairment where GFR is less than 35 ml/min, (see

section 4.2).

Bone and mineral metabolism

Causes of osteoporosis other than oestrogen deficiency, ageing and glucocorticoid use should be considered.

Hypocalcaemia must

be corrected before initiating therapy with alendronic acid (see section 4.3).

Other

disorders

affecting mineral metabolism (such as vitamin D deficiency and hypoparathyroidism) should also be effectively treated.

In patients with these conditions, serum calcium and symptoms of hypocalcaemia should be monitored during therapy

with alendronic acid.

Due to the positive effects of alendronic acid 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).

Ensuring adequate calcium and vitamin D intake is particularly important in patients receiving glucocorticoids.

Excipients

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

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 alendronic acid. Therefore, patients must wait at

least 30 minutes after taking alendronic acid before taking any other oral medicinal product (see sections 4.2 and 5.2).

No other interactions with medicinal

products of clinical

significance are anticipated.

A number of patients in the

clinical

trials

received oestrogen (intravaginal,

transdermal,

oral)

while

taking alendronic

acid.

No adverse

experiences attributable to their concomitant use were identified.

Since NSAID use is associated with gastrointestinal irritation, caution should be used during concomitant use with

alendronate.

Although specific interaction studies were not performed, in clinical studies alendronic acid was used concomitantly

with a wide range of commonly prescribed medicinal products without evidence of clinical adverse interactions.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no 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 hypocalcemia (see section

5.3).

Alendronic acid should not be used during pregnancy.

Breast-feeding

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It is not known whether alendronic acid is excreted into human breast milk. Given the indication, alendronic acid tablet

should not be used by breast-feeding women.

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 theoretical risk of foetal harm,

predominantly skeletal,

if a women

becomes pregnant

after

completing a course of

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

No studies on the effects on the ability to drive and use machines have been performed. However, certain adverse

reactions that have been operated with 'alendronic acid'

may affect some patients'

ability to drive or operate machinery.

Individual responses to 'alendronic acid'

may vary (see section 4.8).

4.8 Undesirable effects

In a one-year study in post-menopausal women with osteoporosis the overall safety profiles of Alendronic acid tablet

70 mg (n=519) and alendronic acid tablet 10 mg/day (n=370) were similar.

In two three-year studies of virtually identical design, in post-menopausal women (alendronic acid tablet 10 mg: n=196,

placebo: n=397) the overall safety profiles of alendronic acid tablet 10 mg/day and placebo were similar.

Adverse experiences reported by the investigators as possibly, probably or definitely drug-related are presented below

if they occurred in

1% in either treatment group in the one-year study, or in

1% of patients treated with alendronic

acid tablet 10 mg/day and at a greater incidence than in patients given placebo in the three-year studies

One-Year Study

Three-Year Studies

Alendronic

Acid

Once Weekly

70 mg

(n = 519)

Alendronic

Acid

10 mg/day

(n = 370) %

Alendronic

Acid

10 mg/day

(n = 196)

Placebo

(n = 397)%

Gastro-intestinal

abdominal pain

dyspepsia

acid

regurgitation

nausea

abdominal

distention

constipation

diarrhoea

dysphagia

flatulence

gastritis

gastric ulcer

oesophageal

ulcer

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Tabulated list of adverse reactions

The following adverse experiences have also been reported during clinical studies and/or post-marketing use:

Frequencies are defined as:

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 including isolated cases)

Musculoskeletal

musculoskeletal

(bone, muscle or

joint) pain

muscle cramp

Neurological

headache

System Organ Class

Frequency

Adverse Experience Term

Immune

system

disorders:

Rare

hypersensitivity

reactions

including

urticaria and angioedema

Metabolism

and

nutrition disorders:

Rare

symptomatic

hypocalcaemia,

often

association with predisposing conditions

Nervous

system

disorders:

Common

headache, dizziness

Uncommon

dysgeusia

Eye disorders:

Uncommon

eye inflammation (uveitis, scleritis,

episcleritis)

Ear

and

labyrinth

disorders:

Common

Vertigo

Very rare

Osteonecrosis

external

auditory

canal

(bisphosphonate

class

adverse

reaction)

Gastro-intestinal

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

gastro-intestinal

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

joint)

pain which is sometimes severe

†§

Common:

joint swelling

Rare:

Osteonecrosis

‡§

atypical

subtrochanteric

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

rarely,

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Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization 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

Symptoms

Hypocalcaemia, hypophosphataemia and upper gastro-intestinal adverse events, such as upset stomach, heartburn,

oesophagitis, gastritis, or ulcer, may result from oral overdosage.

Management

No specific information is available on the treatment of overdosage with alendronic acid.

Milk or antacids should be

given to bind alendronic acid tablet. Owing to the risk of oesophageal irritation, vomiting should not be induced and the

patient should remain fully upright.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group:.

Drugs affecting bone structure and mineralisation, bisphosphonates.

ATC Code: M05B A04

Mechanism of action

The active ingredient

of 'Alendronic acid Tablets',

alendronate sodium,

is a bisphosphonate that

inhibits osteoclastic

bone resorption with no direct

effect

on bone formation.

Preclinical

studies have shown preferential

localisation of

alendronic acid to sites of

active resorption.

Activity of

osteoclasts is inhibited,

recruitment

attachment

osteoclasts is not affected. The bone formed during treatment with alendronic acid is of normal quality.

Clinical efficacy and safety

Treatment of post-menopausal osteoporosis

Osteoporosis is defined as BMD of the spine or hip 2.5 SD below the mean value of a normal young population or as a

previous fragility fracture, irrespective of BMD.

The therapeutic equivalence of 'Alendronic acid Tablets'

70 mg (n=519) and alendronic acid 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

fever),

typically

association

with

initiation of treatment†.

See section 4.4

†Frequency in Clinical Trials was similar in the drug 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.

Identified in postmarketing experience.

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groups were also similar with regard to BMD increases at other skeletal sites.

The effects of alendronic acid tablet 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 bone mineral density (BMD) increases with alendronic acid 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 (alendronic acid 3.2% vs placebo 6.2%) in the

proportion of patients treated with alendronic acid 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 alendronic acid 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.

this study alendronic acid daily reduced the incidence of

1 new vertebral fracture by 47% (alendronic

acid 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%).

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 (alendronic acid 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 LESS-THAN OR EQUAL TO (8804)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

Absorption

Relative to an intravenous reference dose, the oral mean bioavailability of alendronic acid tablet 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 alendronic acid tablet was

administered one hour or half an hour before a standardised breakfast. In osteoporosis studies, alendronic acid tablet

was effective when administered at least 30 minutes before the first food or beverage of the day.

Bioavailability was negligible whether alendronic acid was administered with, or up to two hours after, a standardised

breakfast. Concomitant administration of alendronic acid tablet 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 alendronic acid tablet (a mean increase ranging from 20% to 44%).

Distribution

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Studies in rats show that alendronic acid tablet 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 drug 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 alendronic acid is metabolised in animals or humans.

Elimination

Following a single intravenous dose of

alendronic acid tablet,

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 alendronic acid tablet

was 71 ml/min,

and systemic clearance did not

exceed

ml/min.

Plasma

concentrations

fell

more

than

95% within six

hours

following

intravenous

administration. The terminal half-life in humans is estimated to exceed ten years, reflecting release of alendronic acid

from the skeleton. Alendronic acid tablet 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.

Renal impairment

Preclinical studies show that the drug 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 alendronic acid via

the kidney will be reduced in patients with impaired renal function. Therefore, somewhat greater accumulation of

alendronic acid in bone might be expected in patients with impaired renal function (see section 4.2).

5.3 Preclinical safety data

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 shown that treatment with alendronic acid

tablet 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 fetal ossification. The relevance to

humans is unknown.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactose, anhydrous

Cellulose, microcrystalline (E460)

Croscarmellose sodium

Magnesium stearate

6.2 Incompatibilities

Not applicable

6.3 Shelf life

3 years

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions

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6.5 Nature and contents of container

OPA-AL-PVC/Al blister

Pack size: 4 tablets or 12* tablets

* Not for UK market

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Any unused product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

Accord Healthcare Limited

Sage House

319 Pinner Road

North Harrow

Middlesex HA1 4 HF

United Kingdom

8 MARKETING AUTHORISATION NUMBER

PA 1390/035/002

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 18

February 2011

Date of last renewal: 26

August 2013

10 DATE OF REVISION OF THE TEXT

May 2018

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