PACKAGE LEAFLET: INFORMATION FOR THE USER

Zoledronic acid 4 mg/5 ml concentrate for solution for infusion

Zoledronic acid

Read all of this leaflet carefully before you are given Zoledronic acid 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, nurse or pharmacist.

If you get any of the side effects talk to your doctor, nurse or pharmacist. This includes any possible side effects not listed in this leaflet.

In this leaflet

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

2.    What you need to know before you use Zoledronic acid

3.    How to use Zoledronic acid

4.    Possible side effects

5.    How to store Zoledronic acid

Contents of the pack and other information

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

The active substance in Zoledronic acid concentrate 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, e g. 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 use 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 (hypersensitive) to zoledronic acid, another bisphosphonate (the group of substances to which Zoledronic acid belongs), or any of the other ingredients in this medicine (listed in section 6).

Warnings and precautions

Before you are given Zoledronic acid, tell your doctor:

•    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.

Other medicines and Zoledronic acid

Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. 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

• A medicine that also contains zoledronic acid and is 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.

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.

Use in children and adolescents

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

Pregnancy and breast-feeding

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 concentrate contains sodium

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

3. How to use Zoledronic acid

•    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, nurse or pharmacist.

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 r 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, Zoledronic acid can cause side effects, although not everybody gets them.

The most common ones are usually mild and will probably disappear after a short time.

The frequency of possible side effects listed below is defined using the following convention:

•    very common: affects more than 1 user in 10

•    common: affects 1 to 10 users in 100

•    uncommon: affects 1 to 10 users in 1,000

•    rare: affects 1 to 10 users in 10,000

•    very rare: affects less than 1 user in 10,000

•    not known: frequency cannot be estimated from the available data.

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

Common:

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

•    Low level of calcium in the blood.

Uncommon:

•    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.

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

Very common:

•    Low level of phosphate in the blood.

Common:

•    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:

•    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:

•    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.

Very rare:

•    Fainting due to low blood pressure.

•    Severe bone, joint and/or muscle pain, occasionally incapacitating.

•    Painful redness and/or swelling of the eye.

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

pharmacist. This includes any side effects not listed

in this leaflet.

5. How to store Zoledronic acid

Your doctor, nurse or pharmacist knows how to store

Zoledronic acid properly (see section 6).

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

•    Do not use Zoledronic acid after the expiry date which is stated on the carton and bottle after EXP.

Storage of the bottle:

•    The unopened bottle does not require any special storage conditions.

Storage after aseptic dilution:

•    After aseptic dilution, it is preferable to use the diluted product immediately. If not used immediately, the duration and conditions of storage prior to use are the user’s responsibility. The total time between dilution, storage in a refrigerator at 2°C - 8°C and end of administration must not exceed 24 hours.

6. Contents of the pack and other information

What Zoledronic acid concentrate contains

•    The active substance of Zoledronic acid concentrate is zoledronic acid. One vial with 5 ml concentrate contains 4 mg zoledronic acid (anhydrous). One ml concentrate contains zoledronic acid (as monohydrate) corresponding to 0.8 mg zoledronic acid (anhydrous).

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

What Zoledronic acid looks like and contents of the pack

Zoledronic acid is supplied as a liquid concentrate in a vial. One vial contains 4 mg of zoledronic acid.

Each pack contains the vial with concentrate.

Zoledronic acid is supplied as packs containing 1,4,5 or 10 vials. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Dr. Reddy’s Laboratories (UK) Ltd., 6 Riverview Road, Beverley, HU17 OLD, United Kingdom

This leaflet was last revised in 08/2012