Package Leaflet: Information for the User Zoledronic acid 4 mg/100 ml Solution For Infusion

Zoledronic acid

Read all of this leaflet carefully before you are given 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 Zoledronic acid is and what it is used for

2.    What you need to know before you are given Zoledronic acid

3.    How Zoledronic acid is used

4.    Possible side effects

5.    How to store Zoledronic acid

6.    Contents of the pack and other information

1. What Zoledronic acid is and what it is used for

The active substance in Zoledronic acid solution is zoledronic acid, which belongs to a group of substances called bisphosphonates. Zoledronic acid works by attaching itself to the bone and slowing down the rate of bone change. It is used:

•    To prevent bone complications, eg. fractures, in adult patients with bone metastases (spread of cancer from primary site to the bone)

•    To reduce the amount of calcium in the blood in adult patients where it is too high due to the presence of a tumour. Tumours can accelerate normal bone change in such a way that the release of calcium from bone is increased. This condition is known as tumour-induced hypercalcaemia (TIH).

2. What you need to know before you are given Zoledronic acid

Follow carefully all instructions given to you by your doctor.

Your doctor will carry out blood tests before you start treatment with Zoledronic acid and will check your response to treatment at regular intervals.

You should not be given Zoledronic acid:

•    if you are breast-feeding

•    if you are allergic to zoledronic acid, another bisphosphonate (the group of substances to which Zoledronic acid belongs), or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor before you are given

Zoledronic acid:

•    if you have or have had a kidney problem

•    if you have or have had pain, swelling or numbness of the jaw, a feeling of heaviness in the jaw or loosening of a tooth

•    if you are having dental treatment or are due to undergo dental surgery, tell your dentist that you are being treated with Zoledronic acid.

Reduced levels of calcium in the blood (hypocalcaemia), sometimes leading to muscle cramps, dry skin, burning sensation, have been reported in patients treated with zoledronic acid. Irregular heart beat (cardiac arrhythmia), seizures, spasm and twitching (tetany) have been reported as secondary to severe hypocalcaemia. In some instances the hypocalcaemia may be life-threatening. If any of these apply to you, tell your doctor straight away.

Patients aged 65 years and over

Zoledronic acid can be given to people aged 65 years and over. There is no evidence to suggest that any extra precautions are needed.

Children and adolescents

Zoledronic acid is not recommended for use in adolescents and children below the age of 18 years.

Other medicines and Zoledronic acid

Tell your doctor if you are taking, have recently taken or might take any other medicines. It is especially important that you tell your doctor if you are also taking:

•    Aminoglycosides (medicines used to treat severe infections), since the combination of these with bisphosphonates may cause the calcium level in the blood to become too low

•    Thalidomide (a medicine used to treat a certain type of blood cancer involving the bone) or any other medicines which may harm your kidneys

•    Other medicines that also contain zoledronic acid and are used to treat osteoporosis and other non-cancer diseases of the bone or any other bisphosphonate, since the combined effects of these medicines taken together with Zoledronic acid are unknown

•    Anti-angiogenic medicines (used to treat cancer), since the combination of these with zoledronic acid has been associated with an increased risk of osteonecrosis of the jaw (ONJ).

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

You should not be given Zoledronic acid if you are pregnant. Tell your doctor if you are or think that you may be pregnant.

You must not be given Zoledronic acid if you are breast-feeding.

Ask your doctor for advice before taking any medicine while you are pregnant or breast-feeding.

Driving and using machines

There have been very rare cases of drowsiness and sleepiness with the use of Zoledronic acid. You should therefore be careful when driving, using machinery or performing other tasks that need full attention.

Zoledronic acid solution contains sodium

This medicinal product contains less than 1 mmol (23 mg) sodium per dose, i.e. essentially ‘sodium-free'.

3. How Zoledronic acid is used

•    Zoledronic acid must only be given by healthcare professionals trained in administering bisphosphonates intravenously, i.e. through a vein.

•    Your doctor will recommend that you drink enough water before each treatment to help prevent dehydration.

•    Carefully follow all the other instructions given to you by your doctor, pharmacist or nurse.

How much Zoledronic acid is given

•    The usual single dose given is 4 mg.

•    If you have a kidney problem, your doctor will give you a lower dose depending on the severity of your kidney problem.

How often Zoledronic acid is given

•    If you are being treated for the prevention of bone complications due to bone metastases, you will be given one infusion of Zoledronic acid every three to four weeks.

•    If you are being treated to reduce the amount of calcium in your blood, you will normally only be given one infusion of Zoledronic acid.

How Zoledronic acid is given

• Zoledronic acid is given as a drip (infusion) into a vein which should take at least 15 minutes and should be administered as a single intravenous solution in a separate infusion line.

Patients whose blood calcium levels are not too high will also be prescribed calcium and vitamin D supplements to be taken each day.

If you are given more Zoledronic acid than you should be

If you have received doses higher than those recommended, you must be carefully monitored by your doctor. This is because you may develop serum electrolyte abnormalities (e.g. abnormal levels of calcium, phosphorus and magnesium) and/or changes in kidney function, including severe kidney impairment. If your level of calcium falls too low, you may have to be given supplemental calcium by infusion.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The most common ones are usually mild and will probably disappear after a short time.

Tell your doctor about any of the following serious side effects straight away:

Common (may affect up to 1 in 10 people)

•    severe kidney impairment (will normally be determined by your doctor with certain specific blood tests)

•    low level of calcium in the blood

Uncommon (may affect up to 1 in 100 people)

•    pain in the mouth, teeth and/or jaw, swelling or sores inside the mouth, numbness or a feeling of heaviness in the jaw, or loosening of a tooth. These could be signs of bone damage in the jaw (osteonecrosis). Tell your doctor and dentist immediately if you experience such symptoms

•    irregular heart rhythm (atrial fibrillation) has been seen in patients receiving zoledronic acid for postmenopausal osteoporosis. It is currently unclear whether zoledronic acid causes this irregular heart rhythm but you should report it to your doctor if you experience such symptoms after you have received zoledronic acid

•    severe allergic reaction: shortness of breath, swelling mainly of the face and throat

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

•    as a consequence of low calcium values: irregular heart beat (cardiac arrhythmia; secondary to hypocalcaemia), seizures, numbness and tetany (secondary to hypocalcaemia)

Tell your doctor about any of the following side effects as soon as possible:

Very common (may affect more than 1 in 10 people)

•    low level of phosphate in the blood

Common (may affect up to 1 in 10 people)

•    headache and a flu-like syndrome consisting of fever, fatigue, weakness, drowsiness, chills and bone, joint and/or muscle ache. In most cases no specific treatment is required and the symptoms disappear after a short time (couple of hours or days)

•    gastrointestinal reactions such as nausea and vomiting as well as loss of appetite

•    conjunctivitis

•    low level of red blood cells (anaemia)

Uncommon (may affect up to 1 in 100 people)

•    hypersensitivity reactions

•    low blood pressure

•    chest pain

•    skin reactions (redness and swelling) at the infusion site, rash, itching

•    high blood pressure, shortness of breath, dizziness, sleep disturbances, tingling or numbness of the hands or feet, diarrhoea

•    low counts of white blood cells and blood platelets

•    low level of magnesium and potassium in the blood. Your doctor will monitor this and take any necessary measures

•    sleepiness

•    tearing of the eye, eye sensitivity to light

•    sudden coldness with fainting, limpness or collapse

•    difficulty in breathing with wheezing or coughing

•    urticaria

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

•    slow heart beat

•    confusion

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

•    interstitial lung disease (inflammation of the tissue around the air sacks of the lungs)

•    flu-like symptoms including arthritis and joint swelling

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

•    fainting due to low blood pressure

•    severe bone, joint and/or muscle pain, occasionally incapacitating

•    painful redness and/or swelling of the eye

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 Yellow Card Scheme, website www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Zoledronic acid

Your doctor, pharmacist or nurse knows how to store Zoledronic acid properly (see section 6).

After first opening, Zoledronic acid solution for infusion should preferably be used immediately. If the solution is not used immediately, it should be stored in a refrigerator at 2°C-8°C.

For further information please refer also to the information for the healthcare professional at the end of this leaflet.

6. Contents of the pack and other information

What Zoledronic acid solution contains

•    The active substance is zoledronic acid. One bottle contains 4 mg zoledronic acid, corresponding to 4.264 mg zoledronic acid monohydrate.

•    The other ingredients are mannitol, sodium citrate and water for injections.

What Zoledronic acid solution looks like and contents of the pack

Zoledronic acid solution is a clear and colourless solution for infusion in a clear tubular glass vial. One vial contains 100 ml solution.

Zoledronic acid is supplied in packs containing 1, 4 or 5 vials. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Dr. Reddy's Laboratories (UK) Ltd., 6 Riverview Road, Beverley, East Yorkshire, HU17 0LD, United Kingdom

This leaflet was last revised in 03/2014