B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Iasibon 1 mg concentrate for solution for infusion ibandronic acid

Read all of this leaflet carefully before you start using 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, pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4

What is in this leaflet :

• 1. What Iasibon is and what it is used for

• 2. What you need to know before you receive Iasibon

• 3. How to receive Iasibon

• 4. Possible side effects

• 5. How to store Iasibon

• 6. Contents of the pack and other information

1. What Iasibon is and what it is used for

Iasibon contains the active substance ibandronic acid. This belongs to a group of medicines called bisphosphonates.

Iasibon is used in adults and prescribed to you if you have breast cancer that has spread to your bones (called ‘bone metastases’).

• It helps to prevent your bones from breaking (fractures)
• It helps to prevent other bone problems that may need surgery or radiotherapy

Iasibon can also be prescribed if you have a raised calcium level in your blood due to a tumour.

Iasibon works by reducing the amount of calcium that is lost from your bones. This helps to stop your bones from getting weaker.

2. What you need to know before you receive Iasibon

Do not receive Iasibon

• if you are allergic to ibandronic acid or any of the other ingredients of this medicine that are listed in section 6
• if you have, or have ever had low levels of calcium in your blood.

Do not receive this medicine if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before having Iasibon.

Warnings and precautions

A side effect called osteonecrosis of the jaw (ONJ) (bone damage in the jaw) has been reported very rarely in the post marketing setting in patients receiving ibandronate for cancer-related conditions. ONJ can also occur after stopping treatment.

It is important to try and prevent ONJ developing as it is a painful condition that can be difficult to treat. In order to reduce the risk of developing osteonecrosis of the jaw, there are some precautions you should take.

Before receiving treatment, tell your doctor/nurse (health care professional) if:

• you have any problems with your mouth or teeth such as poor dental health, gum disease, or a planned tooth extraction
• you don’t receive routine dental care or have not had a dental check up for a long time
• you are a smoker (as this may increase the risk of dental problems)
• you have previously been treated with a bisphosphonate (used to treat or prevent bone disorders)
• you are taking medicines called corticosteroids (such as prednisolone or dexamethasone)
• you have cancer.

Your doctor may ask you to undergo a dental examination before starting treatment with Iasibon.

While being treated, you should maintain good oral hygiene (including regular teeth brushing) and receive routine dental check-ups. If you wear dentures you should make sure these fit properly. If you are under dental treatment or will undergo dental surgery (e.g. tooth extractions), inform your doctor about your dental treatment and tell your dentist that you are being treated with Iasibon.

Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth such as loose teeth, pain or swelling, non-healing of sores or discharge, as these could be signs of osteonecrosis of the jaw.

Talk to your doctor, pharmacist or nurse before receiving Iasibon:

• if you are allergic to any other bisphosphonates
• if you have high or low levels of vitamin D, calcium or any other minerals
• if you have kidney problems
• if you have heart problems and the doctor recommended to limit your daily fluid intake

Cases of serious, sometimes fatal allergic reaction have been reported in patients treated with intravenous ibandronic acid.

If you experience one of the following symptoms, such as shortness of breath/difficulty breathing, tight feeling in throat, swelling of tongue, dizziness, feeling of loss of consciousness, redness or swelling of face, body rash, nausea and vomiting, you should immediately alert your doctor or nurse (see section 4).

Children and adolescents

Iasibon should not be used in children and adolescents below the age of 18 years.

Other medicines and Iasibon

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This is because Iasibon can affect the way some other medicines work. Also, some other medicines can affect the way Iasibon works.

In particular, tell your doctor or pharmacist if you are receiving a type of antibiotic injection called ‘aminoglycoside’ such as gentamicin. This is because aminoglycosides and Iasibon can both lower the amount of calcium in your blood.

Pregnancy and breast-feeding

Do not receive Iasibon if you are pregnant, planning to get pregnant or if you are breast-feeding. Ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

You can drive and use machines as it’s expected that Iasibon has no or negligible effect on your ability to drive and use machines. Talk to your doctor first if you want to drive, use machines or tools.

Iasibon contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium-free”.

• 3. How to receive Iasibon

Receiving this medicine

• Iasibon is normally given by a doctor or other medical staff who have experience with the treatment of cancer.
• it is given as an infusion into your vein

Your doctor may do regular blood tests while you are receiving Iasibon. This is to check that you are being given the right amount of this medicine.

How much to receive

Your doctor will work out how much Iasibon you will be given depending on your illness.

If you have breast cancer that has spread to your bones, then the recommended dose is 6 ampoules (6 mg) every 3–4 weeks, as an infusion in your vein over at least 15 minutes.

If you have a raised calcium level in your blood due to a tumour then the recommended dose is a single administration of 2 ampoules (2 mg) or 4 ampoules (4 mg), depending on the severity of your illness. The medicine should be administered as an infusion in your vein over two hours. A repeated dose may be considered in case of insufficient response or if your illness reappears.

Your doctor may adjust your dose and duration of intravenous infusion if you have kidney problems.

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.

Talk to a nurse or a doctor straight away if you notice any of the following serious side effects -you may need urgent medical treatment:

Rare (may affect up to 1 in 1,000 people)

• persistent eye pain and inflammation
• new pain, weakness or discomfort in your thigh, hip or groin. You may have early signs of a possible unusual fracture of the thigh bone.

Very rare (may affect up to 1 in 10,000 people)

• pain or sore in your mouth or jaw, You may have early signs of severe jaw problems (necrosis (dead bone tissue) in the jaw bone.
• itching, swelling of your face, lips, tongue and throat, with difficulty breathing. You may be having a serious, potentially life threatening allergic reaction (see section 2).
• severe adverse skin reactions
• ear pain, discharge from the ear, and/or an ear infection. These could be signs of bone damage in the ear.

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

• asthma attack

Other possible side effects

Common (may affect up to 1 in 10 people)

• rise in body temperature.
• flu-like symptoms, including fever, shaking and shivering, feeling of discomfort, fatigue, bone

pain and aching muscles and joints. These symptoms usually disappear within a couple of hours or days. Talk to a nurse or doctor if any effects become troublesome or last more than a couple of days

• stomach and tummy pain, indigestion, being sick vomiting or having diarrhoea (loose bowels)
• low calcium or phosphate levels in your blood
• changes in blood test results such as Gamma GT or creatinine
• a heart rhythm problem called ‘bundle branch block’
• pain in your bone or muscles
• headache, feeling dizzy or feeling weak
• feeling thirsty, sore throat, changes in taste
• swollen legs or feet
• aching joints, arthritis, or other joint problems
• problems with your parathyroid gland
• bruising
• infections
• a problem with your eyes called ‘cataracts’
• skin problems
• tooth problems.

Uncommon (may affect less than 1 in 100 people)

• shaking or shivering
• your body temperature getting too low (‘hypothermia’)
• a condition affecting the blood vessels in your brain called ‘cerebrovascular disorder’ (stroke or brain bleeding)
• heart and circulatory problems (including palpitations, heart attack, hypertension (high blood pressure) and varicose veins)
• changes in your blood cells (‘anaemia’)
• a high level of alkaline phosphatase in your blood
• fluid build up and swelling (‘lymphoedema’)
• fluid in your lungs
• stomach problems such as ‘gastroenteritis’ or ‘gastritis’
• gallstones
• being unable to pass water (urine), cystitis (bladder inflammation)

migraine

pain in your nerves, damaged nerve root

deafness

increased sensitivity of sound, taste or touch or changes in smell

difficulty swallowing

mouth ulcers, swollen lips (‘cheilitis’), oral thrush

itching or tingling skin around your mouth

pelvic pain, discharge, itching or pain in the vagina

a skin growth called a ‘benign skin neoplasm’

memory loss

sleep problems, feeling anxious, emotional instability, or mood swings skin rash

hair loss

injury or pain at the injection site

weight loss

kidney cyst (fluid-filled sac in the kidney)

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 the national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Iasibon

• 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 folding box and on the label after EXP. The expiry date refers to the last day of that month
• After dilution the infusion solution is stable for 24 hours at 2–8 °C (in a refrigerator)
• Do not use this medicine if you notice that the solution is not clear or contains particles

• 6. Content of the pack and other information

What Iasibon contains

• The active substance is ibandronic acid. One ampoule with 1 mL of a concentrate for solution for infusion contains 1 mg ibandronic acid (as sodium monohydrate)
• The other ingredients are sodium chloride, glacial acetic acid, sodium acetate trihydrate and water for injections

What Iasibon looks like and contents of the pack

Iasibon is a colourless, clear solution. Iasibon 1 mg is supplied as pack containing 1 ampoule (2 mL

type I glass ampoule).

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Pharmathen S.A.

Dervenakion 6

Pallini 15351

Attiki

Greece

Manufacturer

Pharmathen S.A.

Dervenakion 6

Pallini 15351

Attiki

Greece

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

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site: -------------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only

Dose: Prevention of skeletal events in patients with breast cancer and bone metastases

The recommended dose for prevention of skeletal events in patients with breast cancer and bone metastases is 6 mg intravenously given every 3–4 weeks. The dose should be infused over at least 15 minutes.

Patients with renal impairment

For patients with mild renal impairment (CLcr >50 and <80 mL/min) no dosage adjustment is necessary. For patients with moderate renal impairment (CLcr >30 and <50 mL/min) or severe renal impairment (CLcr <30 mL/min) being treated for the prevention of skeletal events in patients with breast cancer and metastatic bone disease the following dosing recommendations should be followed:

1 0.9% sodium chloride solution or 5% glucose solution

2 Administration every 3 to 4 week

A 15 minute infusion time has not been studied in cancer patients with CLCr <50 mL/min.

Dose: Treatment of tumour-induced hypercalcaemia

Iasibon is usually administered in a hospital setting. The dose is determined by the doctor considering the following factors.

Prior to treatment with Iasibon the patient should be adequately rehydrated with 9 mg/mL (0.9%) sodium chloride. Consideration should be given to the severity of the hypercalcaemia as well as the tumour type. In most patients with severe hypercalcaemia (albumin-corrected serum calcium* >3 mmol/L or >12 mg/dL) 4 mg is an adequate single dosage. In patients with moderate hypercalcaemia (albumin-corrected serum calcium <3 mmol/L or <12 mg/dL) 2 mg is an effective dose. The highest dose used in clinical trials was 6 mg but this dose does not add any further benefit in terms of efficacy.

• * Note albumin-corrected serum calcium concentrations are calculated as follows:

Albumin-corrected = Serum calcium (mmol/L) – [0.02 x albumin (g/L)] +

Serum calcium 0.8

(mmol/L)

or

Albumin-corrected = Serum calcium (mg/dL) + 0.8 x [4 – albumin (g/dL)]

Serum calcium (mg/dL)

To convert the albumin-corrected serum calcium in mmol/L value to mg/dL, multiply by 4.

In most cases a raised serum calcium level can be reduced to the normal range within 7 days. The median time to relapse (re-increase of serum albumin-corrected serum calcium above 3 mmol/L) was 18–19 days for the 2 mg and 4 mg doses. The median time to relapse was 26 days with a dose of 6 mg.

Method and route of administration

Iasibon concentrate for solution for infusion should be administered as an intravenous infusion.

For this purpose the contents of the vial are to be used as follows:

• Prevention of Skeletal Events in patients with breast cancer and bone metastases – added to 100 mL isotonic sodium chloride solution or 100 mL 5% dextrose solution and infused over at least 15 minutes. See also dosage section above for patients with renal impairment
• Treatment of tumour-induced hypercalcaemia – added to 500 mL isotonic sodium chloride solution or 500 mL 5% dextrose solution and infused over 2 hours

Note:

In order to avoid potential incompatibilities Iasibon concentrate for solution for infusion should only be diluted with isotonic sodium chloride solution or 5% dextrose solution. Calcium containing solutions should not be mixed with Iasibon concentrate for solution for infusion.

Diluted solutions are for single use. Only clear solutions without particles should be used.

It is recommended that the product once diluted be used immediately (see point 5 of this leaflet “How to store Iasibon”).

Iasibon concentrate for solution for infusion should be administered as an intravenous infusion.

Care must be taken not to administer Iasibon concentrate for solution for infusion via intra-arterial or paravenous administration, as this could lead to tissue damage.

Frequency of administration

For treatment of tumour induced hypercalcaemia, Iasibon concentrate for solution for infusion is generally given as a single infusion.

For the prevention of skeletal events in patients with breast cancer and bone metastases, the Iasibon infusion is repeated at 3–4 week intervals.

Duration of treatment

A limited number of patients (50 patients) have received a second infusion for hypercalcaemia.

Repeated treatment may be considered in case of recurrent hypercalcaemia or insufficient efficacy.

For patients with breast cancer and bone metastases, Iasibon infusion should be administered every 3–4 weeks. In clinical trials, therapy has continued for up to 96 weeks.

Overdose

Up to now there is no experience of acute poisoning with Iasibon concentrate for solution for infusion. Since both the kidney and the liver were found to be target organs for toxicity in preclinical studies with high doses, kidney and liver function should be monitored.

Clinically relevant hypocalcaemia (very low serum calcium levels) should be corrected by intravenous administration of calcium gluconate.

Package leaflet: Information for the patient

Iasibon 2 mg concentrate for solution for infusion ibandronic acid

Read all of this leaflet carefully before you start using 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, pharmacist or nurse
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4

What is in this leaflet :

• 1. What Iasibon is and what it is used for

• 2. What you need to know before you receive Iasibon

• 3. How to receive Iasibon

• 4. Possible side effects

• 5. How to store Iasibon

• 6. Contents of the pack and other information

1. What Iasibon is and what it is used for

Iasibon contains the active substance ibandronic acid. This belongs to a group of medicines called bisphosphonates.

Iasibon is used in adults and prescribed to you if you have breast cancer that has spread to your bones (called ‘bone metastases’).

• It helps to prevent your bones from breaking (fractures)
• It helps to prevent other bone problems that may need surgery or radiotherapy

Iasibon can also be prescribed if you have a raised calcium level in your blood due to a tumour.

Iasibon works by reducing the amount of calcium that is lost from your bones. This helps to stop your bones from getting weaker.

2. What you need to know before you receive Iasibon

Do not receive Iasibon

• if you are allergic to ibandronic acid or any of the other ingredients of this medicine that are listed in section 6
• if you have, or have ever had low levels of calcium in your blood

Do not receive this medicine if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before having Iasibon.

Warnings and precautions

A side effect called osteonecrosis of the jaw (ONJ) (bone damage in the jaw) has been reported very rarely in the post marketing setting in patients receiving ibandronate for cancer-related conditions. ONJ can also occur after stopping treatment.

It is important to try and prevent ONJ developing as it is a painful condition that can be difficult to treat. In order to reduce the risk of developing osteonecrosis of the jaw, there are some precautions you should take.

Before receiving treatment, tell your doctor/nurse (health care professional) if:

• you have any problems with your mouth or teeth such as poor dental health, gum disease, or a planned tooth extraction
• you don’t receive routine dental care or have not had a dental check up for a long time
• you are a smoker (as this may increase the risk of dental problems)
• you have previously been treated with a bisphosphonate (used to treat or prevent bone disorders)
• you are taking medicines called corticosteroids (such as prednisolone or dexamethasone)
• you have cancer.

Your doctor may ask you to undergo a dental examination before starting treatment with Iasibon.

While being treated, you should maintain good oral hygiene (including regular teeth brushing) and receive routine dental check-ups. If you wear dentures you should make sure these fit properly. If you are under dental treatment or will undergo dental surgery (e.g. tooth extractions), inform your doctor about your dental treatment and tell your dentist that you are being treated with Iasibon.

Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth such as loose teeth, pain or swelling, non-healing of sores or discharge, as these could be signs of osteonecrosis of the jaw.

Talk to your doctor, pharmacist or nurse before receiving Iasibon:

• if you are allergic to any other bisphosphonates
• if you have high or low levels of vitamin D, calcium or any other minerals
• if you have kidney problems.
• if you have heart problems and the doctor recommended to limit your daily fluid intake

Cases of serious, sometimes fatal allergic reaction have been reported in patients treated with intravenous ibandronic acid.

If you experience one of the following symptoms, such as shortness of breath/difficulty breathing, tight feeling in throat, swelling of tongue, dizziness, feeling of loss of consciousness, redness or swelling of face, body rash, nausea and vomiting, you should immediately alert your doctor or nurse (see section 4).

Children and adolescents

Iasibon should not be used in children and adolescents below the age of 18 years.

Other medicines and Iasibon

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This is because Iasibon can affect the way some other medicines work. Also, some other medicines can affect the way Iasibon works.

In particular, tell your doctor or pharmacist if you are receiving a type of antibiotic injection called ‘aminoglycoside’ such as gentamicin. This is because aminoglycosides and Iasibon can both lower the amount of calcium in your blood.

Pregnancy and breast-feeding

Do not receive Iasibon if you are pregnant, planning to get pregnant or if you are breast-feeding. Ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

You can drive and use machines as it’s expected that Iasibon has no or negligible effect on your ability to drive and use machines. Talk to your doctor first if you want to drive, use machines or tools.

Iasibon contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium-free”.

Receiving this medicine

• Iasibon is normally given by a doctor or other medical staff who have experience with the treatment of cancer.
• it is given as an infusion into your vein

Your doctor may do regular blood tests while you are receiving Iasibon. This is to check that you are being given the right amount of this medicine.

How much to receive

Your doctor will work out how much Iasibon you will be given depending on your illness.

If you have breast cancer that has spread to your bones, then the recommended dose is 3 ampoules (6 mg) every 3–4 weeks, as an infusion in your vein over at least 15 minutes.

If you have a raised calcium level in your blood due to a tumour then the recommended dose is a single administration of 1 ampoule (2 mg) or 2 ampoules (4 mg), depending on the severity of your illness. The medicine should be administered as an infusion in your vein over two hours. A repeated dose may be considered in case of insufficient response or if your illness reappears.

Your doctor may adjust your dose and duration of intravenous infusion if you have kidney problems.

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.

Talk to a nurse or a doctor straight away if you notice any of the following serious side effects -you may need urgent medical treatment:

Rare (may affect up to 1 in 1,000 people)

• persistent eye pain and inflammation
• new pain, weakness or discomfort in your thigh, hip or groin. You may have early signs of a possible unusual fracture of the thigh bone.

Very rare (may affect up to 1 in 10,000 people)

• pain or sore in your mouth or jaw You may have early signs of severe jaw problems (necrosis (dead bone tissue) in the jaw bone).
• itching, swelling of your face, lips, tongue and throat, with difficulty breathing. You may be having a serious, potentially life threatening allergic reaction (see section 2)
• severe adverse skin reactions
• ear pain, discharge from the ear, and/or an ear infection. These could be signs of bone damage in the ear.

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

• asthma attack

Other possible side effects

Common (may affect up to 1 in 10 people)

• flu-like symptoms, including fever, shaking and shivering, feeling of discomfort, fatigue, bone

pain and aching muscles and joints. These symptoms usually disappear within a couple of hours or days. Talk to a nurse or doctor if any effects become troublesome or last more than a couple of days

• rise in body temperature.
• stomach and tummy pain, indigestion, being sick vomiting or having diarrhoea (loose bowels)
• low calcium or phosphate levels in your blood
• changes in blood test results such as Gamma GT or creatinine
• a heart rhythm problem called ‘bundle branch block’
• pain in your bone or muscles
• headache, feeling dizzy or feeling weak
• feeling thirsty, sore throat, changes in taste
• swollen legs or feet
• aching joints, arthritis, or other joint problems
• problems with your parathyroid gland
• bruising
• infections
• a problem with your eyes called ‘cataracts’
• skin problems
• tooth problems.

Uncommon (may affect less than 1 in 100 people)

• shaking or shivering
• your body temperature getting too low (‘hypothermia’)
• a condition affecting the blood vessels in your brain called ‘cerebrovascular disorder’ (stroke or brain bleeding)
• heart and circulatory problems (including palpitations, heart attack, hypertension (high blood pressure) and varicose veins)
• changes in your blood cells (‘anaemia’)
• a high level of alkaline phosphatase in your blood
• fluid build up and swelling (‘lymphoedema’)
• fluid in your lungs
• stomach problems such as ‘gastroenteritis’ or ‘gastritis’
• gallstones
• being unable to pass water (urine), cystitis (bladder inflammation)
• migraine
• pain in your nerves, damaged nerve root
• deafness
• increased sensitivity of sound, taste or touch or changes in smell
• difficulty swallowing
• mouth ulcers, swollen lips (‘cheilitis’), oral thrush
• itching or tingling skin around your mouth
• pelvic pain, discharge, itching or pain in the vagina
• a skin growth called a ‘benign skin neoplasm’
• memory loss
• sleep problems, feeling anxious, emotional instability, or mood swings
• skin rash
• hair loss
• injury or pain at the injection site
• weight loss
• kidney cyst (fluid-filled sac in the kidney)

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.Y ou can also report side effects directly via the national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

How to store Iasibon

• 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 folding box and on the label after EXP. The expiry date refers to the last day of that month.
• After dilution the infusion solution is stable for 24 hours at 2–8 °C (in a refrigerator).
• Do not use this medicine if you notice that the solution is not clear or contains particles.

• 6. Content of the pack and other information

What Iasibon contains

• The active substance is ibandronic acid. One ampoule with 2 mL of a concentrate for solution for infusion contains 2 mg ibandronic acid (as sodium monohydrate)
• The other ingredients are sodium chloride, glacial acetic acid, sodium acetate trihydrate and water for injections

What Iasibon looks like and contents of the pack

Iasibon is a colourless, clear solution. Iasibon 2mg is supplied as pack containing 1 ampoule (4 mL type

I glass ampoule).

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Pharmathen S.A.

Dervenakion 6

Pallini 15351

Attiki

Greece

Manufacturer

Pharmathen S.A.

Dervenakion 6

Pallini 15351

Attiki

Greece

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

This leaflet was last revised in {MM/YYYY}

Detailed information on this medicine is available on the European Medicines Agency web site: -------------------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only

Dose: Prevention of skeletal events in patients with breast cancer and bone metastases

The recommended dose for prevention of skeletal events in patients with breast cancer and bone metastases is 6 mg intravenously given every 3–4 weeks. The dose should be infused over at least 15 minutes.

Patients with renal impairment

For patients with mild renal impairment (CLcr >50 and <80 mL/min) no dosage adjustment is necessary. For patients with moderate renal impairment (CLcr >30 and <50 mL/min) or severe renal impairment (CLcr <30 mL/min) being treated for the prevention of skeletal events in patients with breast cancer and metastatic bone disease the following dosing recommendations should be followed:

A 15 minute infusion time has not been studied in cancer patients with CLCr <50 mL/min.

Dose: Treatment of tumour-induced hypercalcaemia

Iasibon is usually administered in a hospital setting. The dose is determined by the doctor considering the following factors.

Prior to treatment with Iasibon the patient should be adequately rehydrated with 9 mg/mL (0.9%) sodium chloride. Consideration should be given to the severity of the hypercalcaemia as well as the tumour type. In most patients with severe hypercalcaemia (albumin-corrected serum calcium* >3 mmol/L or >12 mg/dL) 4 mg is an adequate single dosage. In patients with moderate hypercalcaemia (albumin-corrected serum calcium <3 mmol/L or <12 mg/dL) 2 mg is an effective dose. The highest dose used in clinical trials was 6 mg but this dose does not add any further benefit in terms of efficacy.

• * Note albumin-corrected serum calcium concentrations are calculated as follows:

Albumin-corrected = Serum calcium (mmol/L) – [0.02 x albumin (g/L)] +

Serum calcium 0.8

(mmol/L)

or

Albumin-corrected = Serum calcium (mg/dL) + 0.8 x [4 – albumin (g/dL)]

Serum calcium (mg/dL)

To convert the albumin-corrected serum calcium in mmol/L value to mg/dL, multiply by 4.

In most cases a raised serum calcium level can be reduced to the normal range within 7 days. The median time to relapse (re-increase of serum albumin-corrected serum calcium above 3 mmol/l) was 1819 days for the 2 mg and 4 mg doses. The median time to relapse was 26 days with a dose of 6 mg.

Method and route of administration

Iasibon concentrate for solution for infusion should be administered as an intravenous infusion.

For this purpose the contents of the vial are to be used as follows:

• Prevention of Skeletal Events in patients with breast cancer and bone metastases – added to 100 mL isotonic sodium chloride solution or 100 mL 5% dextrose solution and infused over at least 15 minutes. See also dosage section above for patients with renal impairment
• Treatment of tumour-induced hypercalcaemia – added to 500 mL isotonic sodium chloride solution or 500 mL 5% dextrose solution and infused over 2 hours

Note:

In order to avoid potential incompatibilities Iasibon concentrate for solution for infusion should only be diluted with isotonic sodium chloride solution or 5% dextrose solution. Calcium containing solutions should not be mixed with Iasibon concentrate for solution for infusion.

Diluted solutions are for single use. Only clear solutions without particles should be used.

It is recommended that the product once diluted be used immediately (see point 5 of this leaflet “How to store Iasibon”).

Iasibon concentrate for solution for infusion should be administered as an intravenous infusion.

Care must be taken not to administer Iasibon concentrate for solution for infusion via intra-arterial or paravenous administration, as this could lead to tissue damage.

Frequency of administration

For treatment of tumour induced hypercalcaemia, Iasibon concentrate for solution for infusion is generally given as a single infusion.

For the prevention of skeletal events in patients with breast cancer and bone metastases, the Iasibon infusion is repeated at 3–4 week intervals.

Duration of treatment

A limited number of patients (50 patients) have received a second infusion for hypercalcaemia.

Repeated treatment may be considered in case of recurrent hypercalcaemia or insufficient efficacy.

For patients with breast cancer and bone metastases, Iasibon infusion should be administered every 3–4 weeks. In clinical trials, therapy has continued for up to 96 weeks.

Overdose

Up to now there is no experience of acute poisoning with Iasibon concentrate for solution for infusion. Since both the kidney and the liver were found to be target organs for toxicity in preclinical studies with high doses, kidney and liver function should be monitored.

Clinically relevant hypocalcaemia (very low serum calcium levels) should be corrected by intravenous administration of calcium gluconate.

Package leaflet: Information for the patient

Iasibon 6 mg concentrate for solution for infusion ibandronic acid

Read all of this leaflet carefully before you start using 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, pharmacist or nurse
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet :

• 1. What Iasibon is and what it is used for

• 2. What you need to know before you receive Iasibon

• 3. How to receive Iasibon

• 4. Possible side effects

• 5. How to store Iasibon

• 6. Contents of the pack and other information

1. What Iasibon is and what it is used for

Iasibon contains the active substance ibandronic acid. This belongs to a group of medicines called bisphosphonates.

Iasibon is used in adults and prescribed to you if you have breast cancer that has spread to your bones (called ‘bone metastases’)

• It helps to prevent your bones from breaking (fractures)
• It helps to prevent other bone problems that may need surgery or radiotherapy

Iasibon can also be prescribed if you have a raised calcium level in your blood due to a tumour.

Iasibon works by reducing the amount of calcium that is lost from your bones. This helps to stop your bones from getting weaker.

2. What you need to know before you receive Iasibon

Do not receive Iasibon

• if you are allergic to ibandronic acid or any of the other ingredients of this medicine that are listed in section 6
• if you have, or have ever had low levels of calcium in your blood.

Do not receive this medicine if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before having Iasibon.

Warnings and precautions

A side effect called osteonecrosis of the jaw (ONJ) (bone damage in the jaw) has been reported very rarely in the post marketing setting in patients receiving ibandronate for cancer-related conditions. ONJ can also occur after stopping treatment.

It is important to try and prevent ONJ developing as it is a painful condition that can be difficult to treat. In order to reduce the risk of developing osteonecrosis of the jaw, there are some precautions you should take.

Before receiving treatment, tell your doctor/nurse (health care professional) if:

• you have any problems with your mouth or teeth such as poor dental health, gum disease, or a planned tooth extraction
• you don’t receive routine dental care or have not had a dental check up for a long time
• you are a smoker (as this may increase the risk of dental problems)
• you have previously been treated with a bisphosphonate (used to treat or prevent bone disorders)
• you are taking medicines called corticosteroids (such as prednisolone or dexamethasone)
• you have cancer.

Your doctor may ask you to undergo a dental examination before starting treatment with Iasibon.

While being treated, you should maintain good oral hygiene (including regular teeth brushing) and receive routine dental check-ups. If you wear dentures you should make sure these fit properly. If you are under dental treatment or will undergo dental surgery (e.g. tooth extractions), inform your doctor about your dental treatment and tell your dentist that you are being treated with Iasibon.

Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth such as loose teeth, pain or swelling, non-healing of sores or discharge, as these could be signs of osteonecrosis of the jaw.

Talk to your doctor, pharmacist or nurse before receiving Iasibon:

• if you are allergic to any other bisphosphonates
• if you have high or low levels of vitamin D, calcium or any other minerals
• if you have kidney problems.
• If you have heart problems and the doctor recommended to limit your daily fluid intake

Cases of serious, sometimes fatal allergic reaction have been reported in patients treated with intravenous ibandronic acid.

If you experience one of the following symptoms, such as shortness of breath/difficulty breathing, tight feeling in throat, swelling of tongue, dizziness, feeling of loss of consciousness, redness or swelling of face, body rash, nausea and vomiting, you should immediately alert your doctor or nurse (see section 4).

Children and adolescents

Iasibon should not be used in children and adolescents below the age of 18 years.

Other medicines and Iasibon

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This is because Iasibon can affect the way some other medicines work. Also, some other medicines can affect the way Iasibon works.

In particular, tell your doctor or pharmacist if you are receiving a type of antibiotic injection called ‘aminoglycoside’ such as gentamicin. This is because aminoglycosides and Iasibon can both lower the amount of calcium in your blood.

Pregnancy and breast-feeding

Do not receive Iasibon if you are pregnant, planning to get pregnant or if you are breast-feeding. Ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines:

You can drive and use machines as it’s expected that Iasibon has no or negligible effect on your ability to drive and use machines. Talk to your doctor first if you want to drive, use machines or tools.

Iasibon contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium-free”.

• 3. How to receive Iasibon

Receiving this medicine

• Iasibon is normally given by a doctor or other medical staff who have experience with the treatment of cancer.
• It is given as an infusion into your vein

Your doctor may do regular blood tests while you are receiving Iasibon. This is to check that you are being given the right amount of this medicine.

How much to receive

Your doctor will work out how much Iasibon you will be given depending on your illness.

If you have breast cancer that has spread to your bones, then the recommended dose is 1 vial (6 mg) every 3–4 weeks, as an infusion in your vein over at least 15 minutes.

If you have a raised calcium level in your blood due to a tumour, then the recommended dose is a single administration of 2 mg or 4 mg, depending on the severity of your illness. The medicine should be administered as an infusion in your vein over two hours. A repeated dose may be considered in case of insufficient response or if your illness reappears.

Your doctor may adjust your dose and duration of intravenous infusion if you have kidney problems.

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.

Talk to a nurse or a doctor straight away if you notice any of the following serious side effects -you may need urgent medical treatment:

Rare (may affect up to 1 in 1,000 people)

• persistent eye pain and inflammation
• new pain, weakness or discomfort in your thigh, hip or groin. You may have early signs of a possible unusual fracture of the thigh bone

Very rare (may affect up to 1 in 10,000 people)

• pain or sore in your mouth or jaw. You may have early signs of severe jaw problems (necrosis (dead bone tissue) in the jaw bone).
• itching, swelling of your face, lips, tongue and throat, with difficulty breathing. You may be having a serious, potentially life threatening allergic reaction (see section 2)
• severe adverse skin reactions
• ear pain, discharge from the ear, and/or an ear infection. These could be signs of bone damage in the ear.

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

• asthma attack

Other possible side effects

Common (may affect up to 1 in 10 people)

• flu-like symptoms, including fever, shaking and shivering, feeling of discomfort, fatigue, bone pain and aching muscles and joints. These symptoms usually disappear within a couple of hours or days. Talk to a nurse or doctor if any effects become troublesome or last more than a couple of days
• rise in body temperature.
• stomach and tummy pain, indigestion, being sick vomiting or having diarrhoea (loose bowels)
• low calcium or phosphate levels in your blood
• changes in blood test results such as Gamma GT or creatinine
• a heart rhythm problem called ‘bundle branch block’
• pain in your bone or muscles
• headache, feeling dizzy or feeling weak
• feeling thirsty, sore throat, changes in taste
• swollen legs or feet
• aching joints, arthritis, or other joint problems
• problems with your parathyroid gland
• bruising
• infections
• a problem with your eyes called ‘cataracts’
• skin problems
• tooth problems.

Uncommon (may affect less than 1 in 100 people)

• shaking or shivering
• your body temperature getting too low (‘hypothermia’)
• a condition affecting the blood vessels in your brain called ‘cerebrovascular disorder’ (stroke or brain bleeding)
• heart and circulatory problems (including palpitations, heart attack, hypertension , high blood pressure and varicose veins)
• changes in your blood cells (‘anaemia’)
• a high level of alkaline phosphatase in your blood
• fluid build up and swelling (‘lymphoedema’)
• fluid in your lungs
• stomach problems such as ‘gastroenteritis’ or ‘gastritis’
• gallstones
• being unable to pass water (urine), cystitis (bladder inflammation)
• migraine
• pain in your nerves, damaged nerve root
• deafness
• increased sensitivity of sound, taste or touch or changes in smell
• difficulty swallowing
• mouth ulcers, swollen lips (‘cheilitis’), oral thrush
• itching or tingling skin around your mouth
• pelvic pain, discharge, itching or pain in the vagina
• a skin growth called a ‘benign skin neoplasm’
• memory loss
• sleep problems, feeling anxious, emotional instability, or mood swings
• skin rash
• hair loss
• injury or pain at the injection site
• weight loss

kidney cyst (fluid-filled sac in the kidney).

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. Y ou can also report side effects directly via the national reporting system listed inBy reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Iasibon

• 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 folding box and on the label after EXP. The expiry date refers to the last day of that month.
• After dilution the infusion solution is stable for 24 hours at 2–8 °C (in a refrigerator)
• Do not use this medicine if you notice that the solution is not clear or contains particles

• 6. Content of the pack and other information

What Iasibon contains

• The active substance is ibandronic acid. One vial with 6 mL of a concentrate for solution for infusion contains 6 mg ibandronic acid (as sodium monohydrate).
• The other ingredients are sodium chloride, glacial acetic acid, sodium acetate trihydrate and water for injections.

What Iasibon looks like and contents of the pack

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 Iasibon is and what it is used for.

• 2. What you need to know before you take Iasibon.

• 3. How to take Iasibon.

• 4. Possible side effects.

• 5. How to store Iasibon.

• 6. Contents of the pack and other information

1. What Iasibon is and what it is used for

Iasibon contains the active substance ibandronic acid. This belongs to a group of medicines called bisphosphonates.

Iasibon is used in adults and prescribed to you if you have breast cancer that has spread to your bones (called ‘bone metastases’).

• It helps to prevent your bones from breaking (fractures).
• It also helps to prevent other bone problems that may need surgery or radiotherapy.

Ibandronate works by reducing the amount of calcium that is lost from your bones. This helps to stop your bones from getting weaker.

2. What you need to know before you take Iasibon

Do not take Iasibon

• – if you are allergic to ibandronic acid or any of the other ingredients of this medicine that are listed in section 6

• – if you have problems with your food pipe /gullet (oesophagus) such as narrowing or difficulty swallowing

• – if you cannot stand or sit upright for at least one hour (60 minutes) at a time

• – if you have or ever had low calcium in your blood.

Do not take this medicine if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking Iasibon.

Warnings and precautions

A side effect called osteonecrosis of the jaw (ONJ) (bone damage in the jaw) has been reported very rarely in the post marketing setting in patients receiving ibandronate for cancer-related conditions. ONJ can also occur after stopping treatment.

It is important to try and prevent ONJ developing as it is a painful condition that can be difficult to treat. In order to reduce the risk of developing osteonecrosis of the jaw, there are some precautions you should take.

Before receiving treatment, tell your doctor/nurse (health care professional) if:

• you have any problems with your mouth or teeth such as poor dental health, gum disease, or a planned tooth extraction
• you don’t receive routine dental care or have not had a dental check up for a long time
• you are a smoker (as this may increase the risk of dental problems)
• you have previously been treated with a bisphosphonate (used to treat or prevent bone disorders)
• you are taking medicines called corticosteroids (such as prednisolone or dexamethasone)
• you have cancer.

Your doctor may ask you to undergo a dental examination before starting treatment with Iasibon.

While being treated, you should maintain good oral hygiene (including regular teeth brushing) and receive routine dental check-ups. If you wear dentures you should make sure these fit properly. If you are under dental treatment or will undergo dental surgery (e.g. tooth extractions), inform your doctor about your dental treatment and tell your dentist that you are being treated with Iasibon.

Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth such as loose teeth, pain or swelling, non-healing of sores or discharge, as these could be signs of osteonecrosis of the jaw.

Talk to your doctor or pharmacist before taking Iasibon:

• if you are allergic to any other bisphosphonates
• if you have any swallowing or digestion problems
• if you have high or low blood levels of vitamin D or any other minerals
• if you have kidney problems

Irritation, inflammation or ulceration of the gullet/food pipe (oesophagus) often with symptoms of severe pain in the chest, severe pain after swallowing food and/or drink, severe nausea, or vomiting may occur, especially if you do not drink a full glass of water and/or if you lie down within an hour of taking Iasibon. If you develop these symptoms, stop taking Iasibon and tell your doctor straight away (see sections 3 and 4).

Children and adolescents

Iasibon should not be used in children and adolescents below the age of 18 years.

Other medicines and Iasibon

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This is because Iasibon can affect the way some other medicines work. Also some other medicines can affect the way Iasibon works.

In particular, tell your doctor or pharmacist if you are taking any of the following medicines:

• supplements containing calcium, magnesium, iron or aluminium
• acetylsalicylic acid and non-steroidal anti-inflammatory medicines called “NSAIDs”, such as, ibuprofen or naproxen. This is because NSAIDs and Iasibon can both irritate your stomach and gut
• a type of antibiotic injection called “aminoglycoside” such as gentamicin. This is because aminoglycosides and Iasibon can both lower the amount of calcium in your blood

Taking medicines that reduce stomach acid such as cimetidine and ranitidine, may slightly increase the effects of Iasibon.

Iasibon with food and drink

Do not take Iasibon with food or any other drinks except plain water as Iasibon is less effective if it is taken with food or drink (see section 3).

Take Iasibon at least 6 hours after you had last had anything to eat, drink or any other medicines or supplements (e.g. products containing calcium (milk), aluminium, magnesium and iron) except water. After taking your tablet, wait at least 30 minutes. Then you can have your first food and drink, and take any medicines or supplements (see section 3).

Pregnancy and breast feeding

Do not take Iasibon if you are pregnant, planning to get pregnant or if you are breast-feeding.

Ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

You can drive and use machines as it’s expected that Iasibon has no or negligible effect on your ability to drive and use machines. Talk to your doctor first if you want to drive, use machine or tools.

Iasibon contains lactose.

If you have been told by your doctor that you cannot tolerate or digest some sugars, talk to your doctor before taking this medicine.

3. How to take Iasibon

Always take this medicine exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Take your tablet at least 6 hours after you had last had anything to eat, drink or any other medicines or supplements except water. Water with a high concentration of calcium should not be used. If there is concern regarding potentially high levels of calcium in the tap water (hard water), it is advised to use bottled water with a low mineral content.

Your doctor may do regular blood tests while you are taking Iasibon. This is to check that you are being given the right amount of medicine.

Taking this medicine

It is important that you take Iasibon at the right time and in the right way. This is because it can cause irritation, inflammation or ulcers in your food pipe/gullet (oesophagus).

You can help stop this happening by doing the following:

• Take your tablet as soon as you get up for the day before having your first food, drink, any medicine or supplements
• Take your tablet with a full glass of water only (about 200 mL). Do not take your tablet with any drink other than water
• Swallow the tablet whole. Do not chew, suck or crush the tablet. Do not let the tablet dissolve in your mouth
• After taking your tablet, wait at least 30 minutes. Then you can have your first food and drink and take any medicines or supplements
• Stay upright (sitting or standing) while taking your tablet and for the next hour (60 minutes). Otherwise, some of the medicine could leak back into your food pipe/gullet (oesophagus)

How much to take

The usual dose of Iasibon is one tablet each day. If you have moderate kidney problems, your doctor may reduce your dose to one tablet every other day. If you have severe kidney problems, your doctor may reduce your dose to one tablet each week.

If you take more Iasibon than you should

If you take too many tablets talk to a doctor or go to hospital straight away. Drink a full glass of milk before you go. Do not make yourself sick. Do not lie down.

If you forget to take Iasibon

Do not take a double dose to make up for a forgotten dose. If you are taking a tablet each day, skip the missed dose completely. Then carry on as usual the next day. If you are taking a tablet every other day or once a week, ask your doctor or pharmacist for advice.

If you stop taking Iasibon

Keep taking Iasibon for as long as your doctor tells you. This is because the medicine will only work if it is taken all the time.

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.

Talk to a nurse or a doctor straight away if you notice any of the following serious side effects, you may need urgent medical treatment:

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

• feeling sick, heartburn and discomfort in swallowing (inflammation of your gullet/ food pipe)

Uncommon (may affect less than 1 in 100 people):

• severe stomach pain. This could be a sign of an ulcer of the first section of the bowel (duodenum) that is bleeding, or that your stomach is inflamed (gastritis)

Rare (may affect up to 1 in 1,000 people)

• persistent eye pain and inflammation
• new pain, weakness or discomfort in your thigh, hip or groin. You may have early signs of a possible unusual fracture of the thigh bone

Very rare (may affect up to 1 in 10,000 people)

• pain or sore in your mouth or jaw. You may have early signs of severe jaw problems (necrosis (dead bone tissue) in the jaw bone)
• itching, swelling of your face, lips, tongue and throat, with difficulty breathing. You may be having a serious, potentially life threatening allergic reaction
• severe adverse skin reactions
• ear pain, discharge from the ear, and/or an ear infection. These could be signs of bone damage in the ear.

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

• asthma attack

Other possible side effects

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

• tummy pain, indigestion
• low calcium levels in your blood
• weakness

Uncommon (may affect less than 1 in 100 people):

• chest pain
• itching or tingling skin (paraesthesia)
• flu-like symptoms, feeling generally unwell or in pain
• dry mouth, strange taste in your mouth or difficulty swallowing
• anaemia (bloodlessness)
• high levels of urea or high levels of parathyroid hormone in your blood.

Reporting of side effects

5. How to store Iasibon

• 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 blister and carton after EXP. The expiry date refers to the last day of that month
• Store in the original package in order to protect from moisture.
• 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 Iasibon contains

• The active substance is ibandronic acid. Each film-coated tablet contains 50 mg of ibandronic acid (as sodium monohydrate)

The other ingredients are:

• tablet core: povidone, microcrystalline cellulose, crospovidone, maize starch pregelatinised, glycerol dibehenate, colloidal anhydrous silica.
• tablet coat: titanium dioxide (E171), lactose monohydrate, hypromellose (E464), macrogol 4000

What Iasibon looks like and contents of the pack

Iasibon is a colourless, clear solution. Iasibon 1 mg is supplied as pack containing 1 ampoule (2 mL

type I glass ampoule).

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Pharmathen S.A.

Dervenakion 6

Pallini 15351

Attiki

Greece

Manufacturer

Pharmathen S.A.

Dervenakion 6

Pallini 15351

Attiki

Greece

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

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site: -------------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only

Dose: Prevention of skeletal events in patients with breast cancer and bone metastases

The recommended dose for prevention of skeletal events in patients with breast cancer and bone metastases is 6 mg intravenously given every 3–4 weeks. The dose should be infused over at least 15 minutes.

Patients with renal impairment

For patients with mild renal impairment (CLcr >50 and <80 mL/min) no dosage adjustment is necessary. For patients with moderate renal impairment (CLcr >30 and <50 mL/min) or severe renal impairment (CLcr <30 mL/min) being treated for the prevention of skeletal events in patients with breast cancer and metastatic bone disease the following dosing recommendations should be followed:

1 0.9% sodium chloride solution or 5% glucose solution

2 Administration every 3 to 4 week

A 15 minute infusion time has not been studied in cancer patients with CLCr <50 mL/min.

Dose: Treatment of tumour-induced hypercalcaemia

Iasibon is usually administered in a hospital setting. The dose is determined by the doctor considering the following factors.

Prior to treatment with Iasibon the patient should be adequately rehydrated with 9 mg/mL (0.9%) sodium chloride. Consideration should be given to the severity of the hypercalcaemia as well as the tumour type. In most patients with severe hypercalcaemia (albumin-corrected serum calcium* >3 mmol/L or >12 mg/dL) 4 mg is an adequate single dosage. In patients with moderate hypercalcaemia (albumin-corrected serum calcium <3 mmol/L or <12 mg/dL) 2 mg is an effective dose. The highest dose used in clinical trials was 6 mg but this dose does not add any further benefit in terms of efficacy.

• * Note albumin-corrected serum calcium concentrations are calculated as follows:

Albumin-corrected = Serum calcium (mmol/L) – [0.02 x albumin (g/L)] +

Serum calcium 0.8

(mmol/L)

or

Albumin-corrected = Serum calcium (mg/dL) + 0.8 x [4 – albumin (g/dL)]

Serum calcium (mg/dL)

To convert the albumin-corrected serum calcium in mmol/L value to mg/dL, multiply by 4.

In most cases a raised serum calcium level can be reduced to the normal range within 7 days. The median time to relapse (re-increase of serum albumin-corrected serum calcium above 3 mmol/L) was 18–19 days for the 2 mg and 4 mg doses. The median time to relapse was 26 days with a dose of 6 mg.

Method and route of administration

Iasibon concentrate for solution for infusion should be administered as an intravenous infusion.

For this purpose the contents of the vial are to be used as follows:

• Prevention of Skeletal Events in patients with breast cancer and bone metastases – added to 100 mL isotonic sodium chloride solution or 100 mL 5% dextrose solution and infused over at least 15 minutes. See also dosage section above for patients with renal impairment
• Treatment of tumour-induced hypercalcaemia – added to 500 mL isotonic sodium chloride solution or 500 mL 5% dextrose solution and infused over 2 hours

Note:

In order to avoid potential incompatibilities Iasibon concentrate for solution for infusion should only be diluted with isotonic sodium chloride solution or 5% dextrose solution. Calcium containing solutions should not be mixed with Iasibon concentrate for solution for infusion.

Diluted solutions are for single use. Only clear solutions without particles should be used.

It is recommended that the product once diluted be used immediately (see point 5 of this leaflet “How to store Iasibon”).

Iasibon concentrate for solution for infusion should be administered as an intravenous infusion.

Care must be taken not to administer Iasibon concentrate for solution for infusion via intra-arterial or paravenous administration, as this could lead to tissue damage.

Frequency of administration

For treatment of tumour induced hypercalcaemia, Iasibon concentrate for solution for infusion is generally given as a single infusion.

For the prevention of skeletal events in patients with breast cancer and bone metastases, the Iasibon infusion is repeated at 3–4 week intervals.

Duration of treatment

A limited number of patients (50 patients) have received a second infusion for hypercalcaemia.

Repeated treatment may be considered in case of recurrent hypercalcaemia or insufficient efficacy.

For patients with breast cancer and bone metastases, Iasibon infusion should be administered every 3–4 weeks. In clinical trials, therapy has continued for up to 96 weeks.

Overdose

Up to now there is no experience of acute poisoning with Iasibon concentrate for solution for infusion. Since both the kidney and the liver were found to be target organs for toxicity in preclinical studies with high doses, kidney and liver function should be monitored.

Clinically relevant hypocalcaemia (very low serum calcium levels) should be corrected by intravenous administration of calcium gluconate.

Package leaflet: Information for the patient

Iasibon 2 mg concentrate for solution for infusion ibandronic acid

Read all of this leaflet carefully before you start using 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, pharmacist or nurse
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4

What is in this leaflet :

• 1. What Iasibon is and what it is used for

• 2. What you need to know before you receive Iasibon

• 3. How to receive Iasibon

• 4. Possible side effects

• 5. How to store Iasibon

• 6. Contents of the pack and other information

1. What Iasibon is and what it is used for

Iasibon contains the active substance ibandronic acid. This belongs to a group of medicines called bisphosphonates.

Iasibon is used in adults and prescribed to you if you have breast cancer that has spread to your bones (called ‘bone metastases’).

• It helps to prevent your bones from breaking (fractures)
• It helps to prevent other bone problems that may need surgery or radiotherapy

Iasibon can also be prescribed if you have a raised calcium level in your blood due to a tumour.

Iasibon works by reducing the amount of calcium that is lost from your bones. This helps to stop your bones from getting weaker.

2. What you need to know before you receive Iasibon

Do not receive Iasibon

• if you are allergic to ibandronic acid or any of the other ingredients of this medicine that are listed in section 6
• if you have, or have ever had low levels of calcium in your blood

Do not receive this medicine if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before having Iasibon.

Warnings and precautions

A side effect called osteonecrosis of the jaw (ONJ) (bone damage in the jaw) has been reported very rarely in the post marketing setting in patients receiving ibandronate for cancer-related conditions. ONJ can also occur after stopping treatment.

It is important to try and prevent ONJ developing as it is a painful condition that can be difficult to treat. In order to reduce the risk of developing osteonecrosis of the jaw, there are some precautions you should take.

Before receiving treatment, tell your doctor/nurse (health care professional) if:

• you have any problems with your mouth or teeth such as poor dental health, gum disease, or a planned tooth extraction
• you don’t receive routine dental care or have not had a dental check up for a long time
• you are a smoker (as this may increase the risk of dental problems)
• you have previously been treated with a bisphosphonate (used to treat or prevent bone disorders)
• you are taking medicines called corticosteroids (such as prednisolone or dexamethasone)
• you have cancer.

Your doctor may ask you to undergo a dental examination before starting treatment with Iasibon.

While being treated, you should maintain good oral hygiene (including regular teeth brushing) and receive routine dental check-ups. If you wear dentures you should make sure these fit properly. If you are under dental treatment or will undergo dental surgery (e.g. tooth extractions), inform your doctor about your dental treatment and tell your dentist that you are being treated with Iasibon.

Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth such as loose teeth, pain or swelling, non-healing of sores or discharge, as these could be signs of osteonecrosis of the jaw.

Talk to your doctor, pharmacist or nurse before receiving Iasibon:

• if you are allergic to any other bisphosphonates
• if you have high or low levels of vitamin D, calcium or any other minerals
• if you have kidney problems.
• if you have heart problems and the doctor recommended to limit your daily fluid intake

Cases of serious, sometimes fatal allergic reaction have been reported in patients treated with intravenous ibandronic acid.

If you experience one of the following symptoms, such as shortness of breath/difficulty breathing, tight feeling in throat, swelling of tongue, dizziness, feeling of loss of consciousness, redness or swelling of face, body rash, nausea and vomiting, you should immediately alert your doctor or nurse (see section 4).

Children and adolescents

Iasibon should not be used in children and adolescents below the age of 18 years.

Other medicines and Iasibon

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This is because Iasibon can affect the way some other medicines work. Also, some other medicines can affect the way Iasibon works.

In particular, tell your doctor or pharmacist if you are receiving a type of antibiotic injection called ‘aminoglycoside’ such as gentamicin. This is because aminoglycosides and Iasibon can both lower the amount of calcium in your blood.

Pregnancy and breast-feeding

Do not receive Iasibon if you are pregnant, planning to get pregnant or if you are breast-feeding. Ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

You can drive and use machines as it’s expected that Iasibon has no or negligible effect on your ability to drive and use machines. Talk to your doctor first if you want to drive, use machines or tools.

Iasibon contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium-free”.

Receiving this medicine

• Iasibon is normally given by a doctor or other medical staff who have experience with the treatment of cancer.
• it is given as an infusion into your vein

Your doctor may do regular blood tests while you are receiving Iasibon. This is to check that you are being given the right amount of this medicine.

How much to receive

Your doctor will work out how much Iasibon you will be given depending on your illness.

If you have breast cancer that has spread to your bones, then the recommended dose is 3 ampoules (6 mg) every 3–4 weeks, as an infusion in your vein over at least 15 minutes.

If you have a raised calcium level in your blood due to a tumour then the recommended dose is a single administration of 1 ampoule (2 mg) or 2 ampoules (4 mg), depending on the severity of your illness. The medicine should be administered as an infusion in your vein over two hours. A repeated dose may be considered in case of insufficient response or if your illness reappears.

Your doctor may adjust your dose and duration of intravenous infusion if you have kidney problems.

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.

Talk to a nurse or a doctor straight away if you notice any of the following serious side effects -you may need urgent medical treatment:

Rare (may affect up to 1 in 1,000 people)

• persistent eye pain and inflammation
• new pain, weakness or discomfort in your thigh, hip or groin. You may have early signs of a possible unusual fracture of the thigh bone.

Very rare (may affect up to 1 in 10,000 people)

• pain or sore in your mouth or jaw You may have early signs of severe jaw problems (necrosis (dead bone tissue) in the jaw bone).
• itching, swelling of your face, lips, tongue and throat, with difficulty breathing. You may be having a serious, potentially life threatening allergic reaction (see section 2)
• severe adverse skin reactions
• ear pain, discharge from the ear, and/or an ear infection. These could be signs of bone damage in the ear.

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

• asthma attack

Other possible side effects

Common (may affect up to 1 in 10 people)

• flu-like symptoms, including fever, shaking and shivering, feeling of discomfort, fatigue, bone

pain and aching muscles and joints. These symptoms usually disappear within a couple of hours or days. Talk to a nurse or doctor if any effects become troublesome or last more than a couple of days

• rise in body temperature.
• stomach and tummy pain, indigestion, being sick vomiting or having diarrhoea (loose bowels)
• low calcium or phosphate levels in your blood
• changes in blood test results such as Gamma GT or creatinine
• a heart rhythm problem called ‘bundle branch block’
• pain in your bone or muscles
• headache, feeling dizzy or feeling weak
• feeling thirsty, sore throat, changes in taste
• swollen legs or feet
• aching joints, arthritis, or other joint problems
• problems with your parathyroid gland
• bruising
• infections
• a problem with your eyes called ‘cataracts’
• skin problems
• tooth problems.

Uncommon (may affect less than 1 in 100 people)

• shaking or shivering
• your body temperature getting too low (‘hypothermia’)
• a condition affecting the blood vessels in your brain called ‘cerebrovascular disorder’ (stroke or brain bleeding)
• heart and circulatory problems (including palpitations, heart attack, hypertension (high blood pressure) and varicose veins)
• changes in your blood cells (‘anaemia’)
• a high level of alkaline phosphatase in your blood
• fluid build up and swelling (‘lymphoedema’)
• fluid in your lungs
• stomach problems such as ‘gastroenteritis’ or ‘gastritis’
• gallstones
• being unable to pass water (urine), cystitis (bladder inflammation)
• migraine
• pain in your nerves, damaged nerve root
• deafness
• increased sensitivity of sound, taste or touch or changes in smell
• difficulty swallowing
• mouth ulcers, swollen lips (‘cheilitis’), oral thrush
• itching or tingling skin around your mouth
• pelvic pain, discharge, itching or pain in the vagina
• a skin growth called a ‘benign skin neoplasm’
• memory loss
• sleep problems, feeling anxious, emotional instability, or mood swings
• skin rash
• hair loss
• injury or pain at the injection site
• weight loss
• kidney cyst (fluid-filled sac in the kidney)

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.Y ou can also report side effects directly via the national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

• 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 folding box and on the label after EXP. The expiry date refers to the last day of that month.
• After dilution the infusion solution is stable for 24 hours at 2–8 °C (in a refrigerator).
• Do not use this medicine if you notice that the solution is not clear or contains particles.

• 6. Content of the pack and other information

What Iasibon contains

• The active substance is ibandronic acid. One ampoule with 2 mL of a concentrate for solution for infusion contains 2 mg ibandronic acid (as sodium monohydrate)
• The other ingredients are sodium chloride, glacial acetic acid, sodium acetate trihydrate and water for injections

What Iasibon looks like and contents of the pack

Iasibon is a colourless, clear solution. Iasibon 2mg is supplied as pack containing 1 ampoule (4 mL type

I glass ampoule).

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Pharmathen S.A.

Dervenakion 6

Pallini 15351

Attiki

Greece

Manufacturer

Pharmathen S.A.

Dervenakion 6

Pallini 15351

Attiki

Greece

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

This leaflet was last revised in {MM/YYYY}

Detailed information on this medicine is available on the European Medicines Agency web site: -------------------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only

Dose: Prevention of skeletal events in patients with breast cancer and bone metastases

The recommended dose for prevention of skeletal events in patients with breast cancer and bone metastases is 6 mg intravenously given every 3–4 weeks. The dose should be infused over at least 15 minutes.

Patients with renal impairment

For patients with mild renal impairment (CLcr >50 and <80 mL/min) no dosage adjustment is necessary. For patients with moderate renal impairment (CLcr >30 and <50 mL/min) or severe renal impairment (CLcr <30 mL/min) being treated for the prevention of skeletal events in patients with breast cancer and metastatic bone disease the following dosing recommendations should be followed:

A 15 minute infusion time has not been studied in cancer patients with CLCr <50 mL/min.

Dose: Treatment of tumour-induced hypercalcaemia

Iasibon is usually administered in a hospital setting. The dose is determined by the doctor considering the following factors.

Prior to treatment with Iasibon the patient should be adequately rehydrated with 9 mg/mL (0.9%) sodium chloride. Consideration should be given to the severity of the hypercalcaemia as well as the tumour type. In most patients with severe hypercalcaemia (albumin-corrected serum calcium* >3 mmol/L or >12 mg/dL) 4 mg is an adequate single dosage. In patients with moderate hypercalcaemia (albumin-corrected serum calcium <3 mmol/L or <12 mg/dL) 2 mg is an effective dose. The highest dose used in clinical trials was 6 mg but this dose does not add any further benefit in terms of efficacy.

• * Note albumin-corrected serum calcium concentrations are calculated as follows:

Albumin-corrected = Serum calcium (mmol/L) – [0.02 x albumin (g/L)] +

Serum calcium 0.8

(mmol/L)

or

Albumin-corrected = Serum calcium (mg/dL) + 0.8 x [4 – albumin (g/dL)]

Serum calcium (mg/dL)

To convert the albumin-corrected serum calcium in mmol/L value to mg/dL, multiply by 4.

In most cases a raised serum calcium level can be reduced to the normal range within 7 days. The median time to relapse (re-increase of serum albumin-corrected serum calcium above 3 mmol/l) was 1819 days for the 2 mg and 4 mg doses. The median time to relapse was 26 days with a dose of 6 mg.

Method and route of administration

Iasibon concentrate for solution for infusion should be administered as an intravenous infusion.

For this purpose the contents of the vial are to be used as follows:

• Prevention of Skeletal Events in patients with breast cancer and bone metastases – added to 100 mL isotonic sodium chloride solution or 100 mL 5% dextrose solution and infused over at least 15 minutes. See also dosage section above for patients with renal impairment
• Treatment of tumour-induced hypercalcaemia – added to 500 mL isotonic sodium chloride solution or 500 mL 5% dextrose solution and infused over 2 hours

Note:

In order to avoid potential incompatibilities Iasibon concentrate for solution for infusion should only be diluted with isotonic sodium chloride solution or 5% dextrose solution. Calcium containing solutions should not be mixed with Iasibon concentrate for solution for infusion.

Diluted solutions are for single use. Only clear solutions without particles should be used.

It is recommended that the product once diluted be used immediately (see point 5 of this leaflet “How to store Iasibon”).

Iasibon concentrate for solution for infusion should be administered as an intravenous infusion.

Care must be taken not to administer Iasibon concentrate for solution for infusion via intra-arterial or paravenous administration, as this could lead to tissue damage.

Frequency of administration

For treatment of tumour induced hypercalcaemia, Iasibon concentrate for solution for infusion is generally given as a single infusion.

For the prevention of skeletal events in patients with breast cancer and bone metastases, the Iasibon infusion is repeated at 3–4 week intervals.

Duration of treatment

A limited number of patients (50 patients) have received a second infusion for hypercalcaemia.

Repeated treatment may be considered in case of recurrent hypercalcaemia or insufficient efficacy.

For patients with breast cancer and bone metastases, Iasibon infusion should be administered every 3–4 weeks. In clinical trials, therapy has continued for up to 96 weeks.

Overdose

Up to now there is no experience of acute poisoning with Iasibon concentrate for solution for infusion. Since both the kidney and the liver were found to be target organs for toxicity in preclinical studies with high doses, kidney and liver function should be monitored.

Clinically relevant hypocalcaemia (very low serum calcium levels) should be corrected by intravenous administration of calcium gluconate.

Package leaflet: Information for the patient

Iasibon 6 mg concentrate for solution for infusion ibandronic acid

Read all of this leaflet carefully before you start using 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, pharmacist or nurse
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet :

• 1. What Iasibon is and what it is used for

• 2. What you need to know before you receive Iasibon

• 3. How to receive Iasibon

• 4. Possible side effects

• 5. How to store Iasibon

• 6. Contents of the pack and other information

1. What Iasibon is and what it is used for

Iasibon contains the active substance ibandronic acid. This belongs to a group of medicines called bisphosphonates.

Iasibon is used in adults and prescribed to you if you have breast cancer that has spread to your bones (called ‘bone metastases’)

• It helps to prevent your bones from breaking (fractures)
• It helps to prevent other bone problems that may need surgery or radiotherapy

Iasibon can also be prescribed if you have a raised calcium level in your blood due to a tumour.

Iasibon works by reducing the amount of calcium that is lost from your bones. This helps to stop your bones from getting weaker.

2. What you need to know before you receive Iasibon

Do not receive Iasibon

• if you are allergic to ibandronic acid or any of the other ingredients of this medicine that are listed in section 6
• if you have, or have ever had low levels of calcium in your blood.

Do not receive this medicine if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before having Iasibon.

Warnings and precautions

A side effect called osteonecrosis of the jaw (ONJ) (bone damage in the jaw) has been reported very rarely in the post marketing setting in patients receiving ibandronate for cancer-related conditions. ONJ can also occur after stopping treatment.

It is important to try and prevent ONJ developing as it is a painful condition that can be difficult to treat. In order to reduce the risk of developing osteonecrosis of the jaw, there are some precautions you should take.

Before receiving treatment, tell your doctor/nurse (health care professional) if:

• you have any problems with your mouth or teeth such as poor dental health, gum disease, or a planned tooth extraction
• you don’t receive routine dental care or have not had a dental check up for a long time
• you are a smoker (as this may increase the risk of dental problems)
• you have previously been treated with a bisphosphonate (used to treat or prevent bone disorders)
• you are taking medicines called corticosteroids (such as prednisolone or dexamethasone)
• you have cancer.

Your doctor may ask you to undergo a dental examination before starting treatment with Iasibon.

While being treated, you should maintain good oral hygiene (including regular teeth brushing) and receive routine dental check-ups. If you wear dentures you should make sure these fit properly. If you are under dental treatment or will undergo dental surgery (e.g. tooth extractions), inform your doctor about your dental treatment and tell your dentist that you are being treated with Iasibon.

Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth such as loose teeth, pain or swelling, non-healing of sores or discharge, as these could be signs of osteonecrosis of the jaw.

Talk to your doctor, pharmacist or nurse before receiving Iasibon:

• if you are allergic to any other bisphosphonates
• if you have high or low levels of vitamin D, calcium or any other minerals
• if you have kidney problems.
• If you have heart problems and the doctor recommended to limit your daily fluid intake

Cases of serious, sometimes fatal allergic reaction have been reported in patients treated with intravenous ibandronic acid.

If you experience one of the following symptoms, such as shortness of breath/difficulty breathing, tight feeling in throat, swelling of tongue, dizziness, feeling of loss of consciousness, redness or swelling of face, body rash, nausea and vomiting, you should immediately alert your doctor or nurse (see section 4).

Children and adolescents

Iasibon should not be used in children and adolescents below the age of 18 years.

Other medicines and Iasibon

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This is because Iasibon can affect the way some other medicines work. Also, some other medicines can affect the way Iasibon works.

In particular, tell your doctor or pharmacist if you are receiving a type of antibiotic injection called ‘aminoglycoside’ such as gentamicin. This is because aminoglycosides and Iasibon can both lower the amount of calcium in your blood.

Pregnancy and breast-feeding

Do not receive Iasibon if you are pregnant, planning to get pregnant or if you are breast-feeding. Ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines:

You can drive and use machines as it’s expected that Iasibon has no or negligible effect on your ability to drive and use machines. Talk to your doctor first if you want to drive, use machines or tools.

Iasibon contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium-free”.

• 3. How to receive Iasibon

Receiving this medicine

• Iasibon is normally given by a doctor or other medical staff who have experience with the treatment of cancer.
• It is given as an infusion into your vein

Your doctor may do regular blood tests while you are receiving Iasibon. This is to check that you are being given the right amount of this medicine.

How much to receive

Your doctor will work out how much Iasibon you will be given depending on your illness.

If you have breast cancer that has spread to your bones, then the recommended dose is 1 vial (6 mg) every 3–4 weeks, as an infusion in your vein over at least 15 minutes.

If you have a raised calcium level in your blood due to a tumour, then the recommended dose is a single administration of 2 mg or 4 mg, depending on the severity of your illness. The medicine should be administered as an infusion in your vein over two hours. A repeated dose may be considered in case of insufficient response or if your illness reappears.

Your doctor may adjust your dose and duration of intravenous infusion if you have kidney problems.

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.

Talk to a nurse or a doctor straight away if you notice any of the following serious side effects -you may need urgent medical treatment:

Rare (may affect up to 1 in 1,000 people)

• persistent eye pain and inflammation
• new pain, weakness or discomfort in your thigh, hip or groin. You may have early signs of a possible unusual fracture of the thigh bone

Very rare (may affect up to 1 in 10,000 people)

• pain or sore in your mouth or jaw. You may have early signs of severe jaw problems (necrosis (dead bone tissue) in the jaw bone).
• itching, swelling of your face, lips, tongue and throat, with difficulty breathing. You may be having a serious, potentially life threatening allergic reaction (see section 2)
• severe adverse skin reactions
• ear pain, discharge from the ear, and/or an ear infection. These could be signs of bone damage in the ear.

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

• asthma attack

Other possible side effects

Common (may affect up to 1 in 10 people)

• flu-like symptoms, including fever, shaking and shivering, feeling of discomfort, fatigue, bone pain and aching muscles and joints. These symptoms usually disappear within a couple of hours or days. Talk to a nurse or doctor if any effects become troublesome or last more than a couple of days
• rise in body temperature.
• stomach and tummy pain, indigestion, being sick vomiting or having diarrhoea (loose bowels)
• low calcium or phosphate levels in your blood
• changes in blood test results such as Gamma GT or creatinine
• a heart rhythm problem called ‘bundle branch block’
• pain in your bone or muscles
• headache, feeling dizzy or feeling weak
• feeling thirsty, sore throat, changes in taste
• swollen legs or feet
• aching joints, arthritis, or other joint problems
• problems with your parathyroid gland
• bruising
• infections
• a problem with your eyes called ‘cataracts’
• skin problems
• tooth problems.

Uncommon (may affect less than 1 in 100 people)

• shaking or shivering
• your body temperature getting too low (‘hypothermia’)
• a condition affecting the blood vessels in your brain called ‘cerebrovascular disorder’ (stroke or brain bleeding)
• heart and circulatory problems (including palpitations, heart attack, hypertension , high blood pressure and varicose veins)
• changes in your blood cells (‘anaemia’)
• a high level of alkaline phosphatase in your blood
• fluid build up and swelling (‘lymphoedema’)
• fluid in your lungs
• stomach problems such as ‘gastroenteritis’ or ‘gastritis’
• gallstones
• being unable to pass water (urine), cystitis (bladder inflammation)
• migraine
• pain in your nerves, damaged nerve root
• deafness
• increased sensitivity of sound, taste or touch or changes in smell
• difficulty swallowing
• mouth ulcers, swollen lips (‘cheilitis’), oral thrush
• itching or tingling skin around your mouth
• pelvic pain, discharge, itching or pain in the vagina
• a skin growth called a ‘benign skin neoplasm’
• memory loss
• sleep problems, feeling anxious, emotional instability, or mood swings
• skin rash
• hair loss
• injury or pain at the injection site
• weight loss

kidney cyst (fluid-filled sac in the kidney).

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. Y ou can also report side effects directly via the national reporting system listed inBy reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Iasibon

• 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 folding box and on the label after EXP. The expiry date refers to the last day of that month.
• After dilution the infusion solution is stable for 24 hours at 2–8 °C (in a refrigerator)
• Do not use this medicine if you notice that the solution is not clear or contains particles

• 6. Content of the pack and other information

What Iasibon contains

• The active substance is ibandronic acid. One vial with 6 mL of a concentrate for solution for infusion contains 6 mg ibandronic acid (as sodium monohydrate).
• The other ingredients are sodium chloride, glacial acetic acid, sodium acetate trihydrate and water for injections.

What Iasibon looks like and contents of the pack

Iasibon is a colourless, clear solution. Iasibon 6mg is supplied as packs containing 1, 5 and 10 vials (9 mL type I glass vial with a bromobutyl rubber stopper).

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Pharmathen S.A.

Dervenakion 6

Pallini 15351

Attiki

Greece

Manufacturer

Pharmathen S.A.

Dervenakion 6

Pallini 15351

Attiki

Greece

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

Belgie/Belgiqu­e/Belgien

Pharmathen S.A.

Tél/Tel: +30 210 66 04 300

Luxembourg/Lu­xemburg

This leaflet was last revised in { MM/YYYY}

Detailed information on this medicine is available on the European Medicines Agency web site:

The following information is intended for healthcare professionals only

Dose: Prevention of skeletal events in patients with breast cancer and bone metastases

The recommended dose for prevention of skeletal events in patients with breast cancer and bone metastases is 6 mg intravenously given every 3–4 weeks. The dose should be infused over at least 15 minutes.

Patients with renal impairment

For patients with mild renal impairment (CLcr >50 and <80 mL/min) no dosage adjustment is necessary. For patients with moderate renal impairment (CLcr >30 and <50 mL/min) or severe renal impairment (CLcr <30 mL/min) being treated for the prevention of skeletal events in patients with breast cancer and metastatic bone disease the following dosing recommendations should be followed:

1 0.9% sodium chloride solution or 5% glucose solution

2 Administration every 3 to 4 week

A 15 minute infusion time has not been studied in cancer patients with CLCr <50 mL/min.

Dose: Treatment of tumour-induced hypercalcaemia

Iasibon is usually administered in a hospital setting. The dose is determined by the doctor considering the following factors.

Prior to treatment with Iasibon the patient should be adequately rehydrated with 9 mg/mL (0.9%) sodium chloride. Consideration should be given to the severity of the hypercalcaemia as well as the tumour type. In most patients with severe hypercalcaemia (albumin-corrected serum calcium* >3 mmol/L or >12 mg/dL) 4 mg is an adequate single dosage. In patients with moderate hypercalcaemia (albumin-corrected serum calcium <3 mmol/L or <12 mg/dL) 2 mg is an effective dose. The highest dose used in clinical trials was 6 mg but this dose does not add any further benefit in terms of efficacy.

* Note albumin-corrected serum calcium concentrations are calculated as follows:

Serum calcium (mmol/L) – [0.02 x albumin (g/L)] + 0.8

or

Serum calcium (mg/dL) + 0.8 x [4 – albumin (g/dL)]

To convert the albumin-corrected serum calcium in mmol/L value to mg/dL, multiply by 4.

In most cases a raised serum calcium level can be reduced to the normal range within 7 days. The median time to relapse (re-increase of serum albumin-corrected serum calcium above 3 mmol/L) was 18–19 days for the 2 mg and 4 mg doses. The median time to relapse was 26 days with a dose of 6 mg.

Method and route of administration

Iasibon concentrate for solution for infusion should be administered as an intravenous infusion.

For this purpose the contents of the vial are to be used as follows:

• Prevention of Skeletal Events in patients with breast cancer and bone metastases – added to 100 mL isotonic sodium chloride solution or 100 mL 5% dextrose solution and infused over at least 15 minutes. See also dosage section above for patients with renal impairment
• Treatment of tumour-induced hypercalcaemia – added to 500 mL isotonic sodium chloride solution or 500 mL 5% dextrose solution and infused over 2 hours

Note:

In order to avoid potential incompatibilities Iasibon concentrate for solution for infusion should only be diluted with isotonic sodium chloride solution or 5% dextrose solution. Calcium containing solutions should not be mixed with Iasibon concentrate for solution for infusion.

Diluted solutions are for single use. Only clear solutions without particles should be used.

It is recommended that the product once diluted be used immediately (see point 5 of this leaflet ‘How to store Iasibon’).

Iasibon concentrate for solution for infusion should be administered as an intravenous infusion.

Care must be taken not to administer Iasibon concentrate for solution for infusion via intra-arterial or paravenous administration, as this could lead to tissue damage.

Frequency of administration

For treatment of tumour induced hypercalcaemia, Iasibon concentrate for solution for infusion is generally given as a single infusion.

For the prevention of skeletal events in patients with breast cancer and bone metastases, the Iasibon infusion is repeated at 3–4 week intervals.

Duration of treatment

A limited number of patients (50 patients) have received a second infusion for hypercalcaemia. Repeated treatment may be considered in case of recurrent hypercalcaemia or insufficient efficacy.

For patients with breast cancer and bone metastases, Iasibon infusion should be administered every 3–4 weeks. In clinical trials, therapy has continued for up to 96 weeks.

Overdose

Up to now there is no experience of acute poisoning with Iasibon concentrate for solution for infusion. Since both the kidney and the liver were found to be target organs for toxicity in preclinical studies with high doses, kidney and liver function should be monitored.

Clinically relevant hypocalcaemia (very low serum calcium levels) should be corrected by intravenous administration of calcium gluconate.

Package leaflet: Information for the patient

Iasibon 50 mg film-coated tablets ibandronic 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 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 Iasibon is and what it is used for.

• 2. What you need to know before you take Iasibon.

• 3. How to take Iasibon.

• 4. Possible side effects.

• 5. How to store Iasibon.

• 6. Contents of the pack and other information

1. What Iasibon is and what it is used for

Iasibon contains the active substance ibandronic acid. This belongs to a group of medicines called bisphosphonates.

Iasibon is used in adults and prescribed to you if you have breast cancer that has spread to your bones (called ‘bone metastases’).

• It helps to prevent your bones from breaking (fractures).
• It also helps to prevent other bone problems that may need surgery or radiotherapy.

Ibandronate works by reducing the amount of calcium that is lost from your bones. This helps to stop your bones from getting weaker.

2. What you need to know before you take Iasibon

Do not take Iasibon

• – if you are allergic to ibandronic acid or any of the other ingredients of this medicine that are listed in section 6

• – if you have problems with your food pipe /gullet (oesophagus) such as narrowing or difficulty swallowing

• – if you cannot stand or sit upright for at least one hour (60 minutes) at a time

• – if you have or ever had low calcium in your blood.

Do not take this medicine if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking Iasibon.

Warnings and precautions

A side effect called osteonecrosis of the jaw (ONJ) (bone damage in the jaw) has been reported very rarely in the post marketing setting in patients receiving ibandronate for cancer-related conditions. ONJ can also occur after stopping treatment.

It is important to try and prevent ONJ developing as it is a painful condition that can be difficult to treat. In order to reduce the risk of developing osteonecrosis of the jaw, there are some precautions you should take.

Before receiving treatment, tell your doctor/nurse (health care professional) if:

• you have any problems with your mouth or teeth such as poor dental health, gum disease, or a planned tooth extraction
• you don’t receive routine dental care or have not had a dental check up for a long time
• you are a smoker (as this may increase the risk of dental problems)
• you have previously been treated with a bisphosphonate (used to treat or prevent bone disorders)
• you are taking medicines called corticosteroids (such as prednisolone or dexamethasone)
• you have cancer.

Your doctor may ask you to undergo a dental examination before starting treatment with Iasibon.

While being treated, you should maintain good oral hygiene (including regular teeth brushing) and receive routine dental check-ups. If you wear dentures you should make sure these fit properly. If you are under dental treatment or will undergo dental surgery (e.g. tooth extractions), inform your doctor about your dental treatment and tell your dentist that you are being treated with Iasibon.

Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth such as loose teeth, pain or swelling, non-healing of sores or discharge, as these could be signs of osteonecrosis of the jaw.

Talk to your doctor or pharmacist before taking Iasibon:

• if you are allergic to any other bisphosphonates
• if you have any swallowing or digestion problems
• if you have high or low blood levels of vitamin D or any other minerals
• if you have kidney problems

Irritation, inflammation or ulceration of the gullet/food pipe (oesophagus) often with symptoms of severe pain in the chest, severe pain after swallowing food and/or drink, severe nausea, or vomiting may occur, especially if you do not drink a full glass of water and/or if you lie down within an hour of taking Iasibon. If you develop these symptoms, stop taking Iasibon and tell your doctor straight away (see sections 3 and 4).

Children and adolescents

Iasibon should not be used in children and adolescents below the age of 18 years.

Other medicines and Iasibon

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This is because Iasibon can affect the way some other medicines work. Also some other medicines can affect the way Iasibon works.

In particular, tell your doctor or pharmacist if you are taking any of the following medicines:

• supplements containing calcium, magnesium, iron or aluminium
• acetylsalicylic acid and non-steroidal anti-inflammatory medicines called “NSAIDs”, such as, ibuprofen or naproxen. This is because NSAIDs and Iasibon can both irritate your stomach and gut
• a type of antibiotic injection called “aminoglycoside” such as gentamicin. This is because aminoglycosides and Iasibon can both lower the amount of calcium in your blood

Taking medicines that reduce stomach acid such as cimetidine and ranitidine, may slightly increase the effects of Iasibon.

Iasibon with food and drink

Do not take Iasibon with food or any other drinks except plain water as Iasibon is less effective if it is taken with food or drink (see section 3).

Take Iasibon at least 6 hours after you had last had anything to eat, drink or any other medicines or supplements (e.g. products containing calcium (milk), aluminium, magnesium and iron) except water. After taking your tablet, wait at least 30 minutes. Then you can have your first food and drink, and take any medicines or supplements (see section 3).

Pregnancy and breast feeding

Do not take Iasibon if you are pregnant, planning to get pregnant or if you are breast-feeding.

Ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

You can drive and use machines as it’s expected that Iasibon has no or negligible effect on your ability to drive and use machines. Talk to your doctor first if you want to drive, use machine or tools.

Iasibon contains lactose.

If you have been told by your doctor that you cannot tolerate or digest some sugars, talk to your doctor before taking this medicine.

3. How to take Iasibon

Always take this medicine exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Take your tablet at least 6 hours after you had last had anything to eat, drink or any other medicines or supplements except water. Water with a high concentration of calcium should not be used. If there is concern regarding potentially high levels of calcium in the tap water (hard water), it is advised to use bottled water with a low mineral content.

Your doctor may do regular blood tests while you are taking Iasibon. This is to check that you are being given the right amount of medicine.

Taking this medicine

It is important that you take Iasibon at the right time and in the right way. This is because it can cause irritation, inflammation or ulcers in your food pipe/gullet (oesophagus).

You can help stop this happening by doing the following:

• Take your tablet as soon as you get up for the day before having your first food, drink, any medicine or supplements
• Take your tablet with a full glass of water only (about 200 mL). Do not take your tablet with any drink other than water
• Swallow the tablet whole. Do not chew, suck or crush the tablet. Do not let the tablet dissolve in your mouth
• After taking your tablet, wait at least 30 minutes. Then you can have your first food and drink and take any medicines or supplements
• Stay upright (sitting or standing) while taking your tablet and for the next hour (60 minutes). Otherwise, some of the medicine could leak back into your food pipe/gullet (oesophagus)

How much to take

The usual dose of Iasibon is one tablet each day. If you have moderate kidney problems, your doctor may reduce your dose to one tablet every other day. If you have severe kidney problems, your doctor may reduce your dose to one tablet each week.

If you take more Iasibon than you should

If you take too many tablets talk to a doctor or go to hospital straight away. Drink a full glass of milk before you go. Do not make yourself sick. Do not lie down.

If you forget to take Iasibon

Do not take a double dose to make up for a forgotten dose. If you are taking a tablet each day, skip the missed dose completely. Then carry on as usual the next day. If you are taking a tablet every other day or once a week, ask your doctor or pharmacist for advice.

If you stop taking Iasibon

Keep taking Iasibon for as long as your doctor tells you. This is because the medicine will only work if it is taken all the time.

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.

Talk to a nurse or a doctor straight away if you notice any of the following serious side effects, you may need urgent medical treatment:

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

• feeling sick, heartburn and discomfort in swallowing (inflammation of your gullet/ food pipe)

Uncommon (may affect less than 1 in 100 people):

• severe stomach pain. This could be a sign of an ulcer of the first section of the bowel (duodenum) that is bleeding, or that your stomach is inflamed (gastritis)

Rare (may affect up to 1 in 1,000 people)

• persistent eye pain and inflammation
• new pain, weakness or discomfort in your thigh, hip or groin. You may have early signs of a possible unusual fracture of the thigh bone

Very rare (may affect up to 1 in 10,000 people)

• pain or sore in your mouth or jaw. You may have early signs of severe jaw problems (necrosis (dead bone tissue) in the jaw bone)
• itching, swelling of your face, lips, tongue and throat, with difficulty breathing. You may be having a serious, potentially life threatening allergic reaction
• severe adverse skin reactions
• ear pain, discharge from the ear, and/or an ear infection. These could be signs of bone damage in the ear.

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

• asthma attack

Other possible side effects

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

• tummy pain, indigestion
• low calcium levels in your blood
• weakness

Uncommon (may affect less than 1 in 100 people):

• chest pain
• itching or tingling skin (paraesthesia)
• flu-like symptoms, feeling generally unwell or in pain
• dry mouth, strange taste in your mouth or difficulty swallowing
• anaemia (bloodlessness)
• high levels of urea or high levels of parathyroid hormone in your blood.

Reporting of side effects

5. How to store Iasibon

• 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 blister and carton after EXP. The expiry date refers to the last day of that month
• Store in the original package in order to protect from moisture.
• 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 Iasibon contains

• The active substance is ibandronic acid. Each film-coated tablet contains 50 mg of ibandronic acid (as sodium monohydrate)

The other ingredients are:

• tablet core: povidone, microcrystalline cellulose, crospovidone, maize starch pregelatinised, glycerol dibehenate, colloidal anhydrous silica.
• tablet coat: titanium dioxide (E171), lactose monohydrate, hypromellose (E464), macrogol 4000