BONDRONAT 2 mg CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the Patient

Bondronat 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 experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the package leaflet:

1. What is Bondronat and what is it used for
2. What you need to know before you start receiving Bondronat
3. How to receive Bondronat
4. Possible side effects
5. Storage of Bondronat
6. Contents of the pack and further information

1. What is Bondronat and what is it used for

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

Bondronat is used in adults and has been prescribed to you if you have breast cancer that has spread to the bones (called bone metastases).

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

You may also be given Bondronat if you have high levels of calcium in your blood due to a tumor.

Bondronat works by reducing the amount of calcium that is lost from your bones. This helps to prevent your bones from becoming weaker.

2. What you need to know before you start receiving Bondronat

Do not receive Bondronat:

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

Do not take this medicine if any of the above applies to you. If you are not sure, talk to your doctor or pharmacist before receiving Bondronat.

Warnings and precautions

A rare adverse reaction called osteonecrosis of the jaw (ONJ) (bone damage in the jaw) has been reported during post-marketing experience in patients treated with Bondronat for cancer-related disorders. ONJ can also occur after stopping treatment.

It is important to try to prevent the development of ONJ as it is a painful condition that can be difficult to treat. To reduce the risk of developing osteonecrosis of the jaw, certain precautions should be taken.

Before receiving treatment, inform your doctor/nurse (healthcare professional) if:

• you have dental problems or are planning to undergo dental surgery
• you do not receive regular dental care or have not had a dental check-up for a long time
• you are a smoker (as this can increase the risk of dental problems)
• you have been previously 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 have a dental examination before starting treatment with Bondronat.

While you are being treated, you should maintain good oral hygiene (including regular tooth brushing) and have regular dental check-ups. If you wear dentures, you should ensure they fit properly. If you are undergoing dental treatment or are going to have dental surgery (e.g. tooth extraction), inform your doctor about your dental treatment and inform your dentist that you are being treated with Bondronat.

Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth, such as tooth loss, pain, or swelling, or difficulty healing of ulcers or discharge, as these may be signs of osteonecrosis of the jaw.

Atypical fractures of long bones, such as the forearm (ulna) and shin (tibia), have also been reported in patients receiving long-term treatment with ibandronate. These fractures occur after minimal or no trauma and some patients experience pain in the area of the fracture before a complete fracture occurs.

Talk to your doctor, pharmacist, or nurse before taking Bondronat:

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

Severe, sometimes fatal, allergic reactions have been observed in patients treated with intravenous ibandronic acid.

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

Children and adolescents

Bondronat should not be used in children and adolescents under 18 years of age.

Using Bondronat with other medicines

Tell your doctor or pharmacist if you are using or have recently used or might use any other medicines. This is because Bondronat may affect the way other medicines work. Other medicines may also affect the way Bondronat works.

In particular, tell your doctor or pharmacistif you are receiving a type of injected antibiotic called an aminoglycoside such as gentamicin. This is because both aminoglycosides and Bondronat can lower the level of calcium in your blood.

Pregnancy and breastfeeding

Do not receive Bondronat if you are pregnant, planning to become pregnant, or if you are breastfeeding.

Talk to your doctor or pharmacist before using this medicine

Driving and using machines

You can drive and use machines as Bondronat is not expected to have a significant effect on your ability to drive and use machines. However, talk to your doctor first if you want to drive, use machines, or tools.

Bondronat contains less than 1 mmol of sodium (23 mg) per vial; this is essentially sodium-free

3. How to receive Bondronat

Administration of this medicine

• Bondronat is normally administered by a doctor or other healthcare professional with experience in the treatment of cancer
• it is given by infusion into a vein.

Your doctor may perform regular blood tests while you are receiving Bondronat. This is to check that you are receiving the correct amount of this medicine.

Dose that you will receive

Your doctor will decide the dose of Bondronat that you will be given, depending on your illness.

If you have breast cancer that has spread to the bones, the recommended dose is 3 vials (6 mg) every 3-4 weeks, given by infusion into a vein over at least 15 minutes.

If you have high levels of calcium in your blood due to a tumor, the recommended dose is a single administration of 1 vial (2 mg) or 2 vials (4 mg), depending on the severity of your illness. The medicine should be given by infusion into a vein over 2 hours. A further dose may be considered if you do not respond or if your illness returns.

If you have kidney problems, your doctor will adjust the dose and duration of the infusion.

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

4. Possible side effects

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

Tell your doctor or nurse immediately if you notice any of the following serious side effects, as you may need urgent medical treatment:

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

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

• Pain or sensation of pain in the mouth or jaw. These can be early symptoms of serious jaw problems [necrosis (death of bone tissue) of the jawbone]
• Talk to your doctor if you have ear pain, discharge from the ear, or an ear infection. These could be symptoms of damage to the bones of the ear
• Itching, swelling of the face, lips, tongue, and throat, with difficulty breathing. You may be having a severe allergic reaction that can be life-threatening (see section 2)
• Severe skin reactions

Frequency not known(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, chills, and flushing, feeling of discomfort, fatigue, bone or muscle and joint pain. These symptoms usually disappear within a couple of hours or days. Talk to your nurse or doctor if any effect becomes troublesome or lasts more than a couple of days
• Increased body temperature
• Stomach and bowel pain, indigestion, nausea, vomiting, or diarrhea (intestinal loss)
• Decreased levels of calcium or phosphorus in the blood
• Changes in blood test results such as Gamma GT or creatinine
• A heart problem called "branch block"
• Muscle or bone pain
• Headache, feeling of dizziness or weakness
• Thirst, sore throat, changes in taste
• Swelling of the legs or feet
• Pain in the joints, arthritis, or other joint problems
• Problems with the parathyroid gland
• Bruising
• Infections
• An eye problem called cataracts
• Skin changes
• Dental changes

Uncommon(may affect up to 1 in 100 people)

• Shivering or shaking
• Excessive decrease in body temperature (hypothermia)
• A disease that affects the blood vessels in the brain called "cerebrovascular disorder" (stroke or cerebral hemorrhage)
• Cardiovascular changes (including palpitations, heart attack, hypertension, varicose veins)
• Changes in blood cells (anemia)
• Increased level of alkaline phosphatase in the blood
• Fluid accumulation and swelling (lymphedema)
• Fluid in the lungs
• Stomach problems such as gastroenteritis or gastritis
• Gallstones
• Urination problems (urinary retention), cystitis (bladder inflammation)
• Migraine
• Nerve pain, nerve root damage
• Deafness
• Increased sensitivity to sound, taste, touch, or smell changes
• Difficulty swallowing
• Ulcers in the mouth, swollen lips (cheilitis), oral thrush
• Itching or tingling sensation on the skin around the mouth
• Pelvic pain, discharge, itching, or vaginal pain
• Skin growth called (benign skin neoplasia)
• Memory loss
• Sleep changes, anxiety, mood changes, or emotional instability
• Skin rash
• Hair loss
• Pain or damage at the injection site
• Weight loss
• Kidney cyst (fluid-filled sac in the kidney)

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Bondronat

• Keep this medicine out of the sight and reach of children
• Do not use this medicine after the expiry date which is stated on the carton and label after EXP. The expiry date is the last day of the month stated
• After dilution, the infusion solution is stable for 24 hours between 2°C and 8°C (in a refrigerator)
• Do not use this medicine if you notice that the solution is not clear or contains particles.

6. Contents of the pack and further information

Composition of Bondronat

• The active substance is ibandronic acid. One vial with 2 ml of concentrate for solution for infusion contains 2 mg of ibandronic acid (as sodium monohydrate)
• The other ingredients are: sodium chloride, acetic acid, sodium acetate, water for injections.

Appearance of the product and pack contents

Bondronat is a clear and colorless solution. Bondronat is available in packs containing 1 vial (2 ml glass vial type I with a bromobutyl rubber stopper).

Marketing authorization holder and manufacturer

Marketing authorization holder

Atnahs Pharma Netherlands B.V.

Copenhagen Towers,

Ørestads Boulevard 108, 5.tv

DK-2300 København S

Denmark

Manufacturer

Atnahs Pharma Denmark ApS

Copenhagen Towers,

Ørestads Boulevard 108, 5.tv

DK-2300 København S

Denmark

or

Universal Farma, S.L.

C/ El Tejido

2 Azuqueca de Henares

19200 Guadalajara

Spain

Date of the last revision of this prospectus MM/YYYY}

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

The following information is intended only for healthcare professionals

Dosage: Prevention of Bone Events in Patients with Breast Cancer and Bone Metastases

The recommended dose for the prevention of bone events in patients with breast cancer and bone metastases is 6 mg by intravenous infusion every 3-4 weeks. The dose should be infused over at least 15 minutes.

Patients with renal insufficiency.

No dose adjustment is required for patients with mild renal insufficiency (CLcr ≥ 80 ml/min). Patients with moderate renal insufficiency (CLcr ≥ 50 ml/min) or severe renal insufficiency (CLcr <30 ml min), who also have breast cancer and bone metastatic disease are being treated for the prevention of events, should follow following dosing recommendations:< p>

1. Sodium chloride 0.9% solution or glucose 5% solution
2. Administration every 3-4 weeks

A 15-minute infusion time has not been studied in cancer patients with a CLcr <50 ml min.< p>

Dosage: Treatment of Tumor-Induced Hypercalcemia

Bondronat is administered in a hospital setting. The dose will be determined by the doctor, taking into account the following factors:

Prior to treatment with Bondronat, the patient should be adequately rehydrated with 9 mg/ml of sodium chloride (0.9%). Both the severity of hypercalcemia and the type of tumor should be taken into account. In most patients with severe hypercalcemia (albumin-corrected serum calcium* ≥ 3 mmol/l or ≥ 12 mg/dl), 4 mg is an adequate single dose. In patients with moderate hypercalcemia (albumin-corrected serum calcium <3 mmol l or < 12 mg dl), 2 is an effective dose. the maximum dose used in clinical trials was 6 mg, but this does not provide any additional benefit terms of efficacy.< p>

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

Albumin-corrected serum calcium (mmol/l) = serum calcium (mmol/l) - [0.02 x albumin (g/l)] + 0.8

Albumin-corrected serum calcium (mg/dl) = serum calcium (mg/dl) + 0.8 x [4 - albumin (g/dl)]

To convert the albumin-corrected serum calcium value from mmol/l to mg/dl, multiply by 4.

In most cases, an elevated serum calcium level can be reduced to normal levels within 7 days. The median time to relapse (new increase above 3 mmol/l of albumin-corrected serum calcium) was 18-19 days for the 2 mg and 4 mg doses. The median time to relapse was 26 days with the 6 mg dose.

Method and route of administration

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

To do this, the contents of the vial should be used as follows:

• Prevention of bone events in patients with breast cancer and bone metastases - add to 100 ml of isotonic sodium chloride solution or 100 ml of 5% dextrose solution and infuse over at least 15 minutes. See the dosing section above for patients with renal insufficiency
• Treatment of tumor-induced hypercalcemia - add to 500 ml of isotonic sodium chloride solution or 500 ml of 5% dextrose solution and infuse over 2 hours.

Note:

To avoid possible incompatibilities, Bondronat concentrate for solution for infusion should only be mixed with isotonic sodium chloride solution or 5% dextrose solution. It should not be mixed with solutions containing calcium.

Diluted solutions are for single use only. Only clear and particle-free solutions should be administered.

It is recommended that the product be used immediately after dilution (see point 5 of this prospectus: Storage of Bondronat).

Bondronat concentrate for solution for infusion should be administered by intravenous infusion. Care should be taken not to administer Bondronat concentrate for solution for infusion by intra-arterial or venous extravasation, as this could cause tissue damage.

Frequency of administration

For the treatment of tumor-induced hypercalcemia, Bondronat concentrate for solution for infusion is generally administered as a single infusion.

For the prevention of bone events in patients with breast cancer and bone metastases, Bondronat infusions are repeated at intervals of 3-4 weeks.

Duration of treatment

A limited number of patients (50 patients) received a second infusion for hypercalcemia. In cases of recurrent hypercalcemia or insufficient efficacy, the possibility of repeating treatment may be considered.

For patients with breast cancer and bone metastases, Bondronat infusions should be administered every 3-4 weeks. In clinical trials, treatment was maintained for up to 96 weeks.

Overdose:

There is currently no experience with acute intoxication with Bondronat concentrate for solution for infusion. Given that in preclinical studies at high doses, both the kidney and liver were found to be target organs for toxicity, renal and hepatic function should be monitored.

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