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PACKAGE LEAFLET: INFORMATION FOR THE USER    saraoooLrooo

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, nurse or pharmacist.

•    If you get any side effects, talk to your doctor, nurse or pharmacist. 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 given

4.    Possible side effects

5.    How to store Zoledronic acid

6.    Contents of the pack and other information

What Zoledronic acid is and what it is used for

The active substance in Zoledronic acid solution for infusion 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).

What you need to know 2 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 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).

•    if you are breast-feeding.

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. If you have pre-existing hypocalcaemia, it must be corrected before initiating the first dose of Zoledronic acid. You will be given adequate calcium and vitamin D supplements.

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 which 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 medicines with zoledronic acid has been associated with an increased risk of osteonecrosis of the jaw (ONJ).

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 solution for infusion contains sodium.

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

How Zoledronic acid is given

•    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 zoledronic acid.

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.

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 children and adolescents 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), calcitonin (a type of medicine used to treat post-menopausal osteoporosis and hypercalcaemia), loop diuretics (a type of medicine to treat high blood pressure or oedema) or other calcium lowering medicines, since the combination of these with bisphosphonates

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.

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INFORMATION FOR THE HEALTHCARE PROFESSIONAL

How to prepare and administer Zoledronic acid

•    Zoledronic acid 4 mg/ioo ml solution for infusion contains 4 mg zoledronic acid in loo ml of infusion solution for immediate use in patients with normal renal function.

•    For single use only. Any unused solution should be discarded. Only clear solution free from particles and discolouration should be used. Aseptic techniques must be followed during the preparation of the infusion.

-    The solution containing zoledronic acid must not be further diluted or mixed with other infusion solutions. It is given as a single intravenous infusion in a separate infusion line in no less than 15 minutes. The hydration status of patients must be assessed prior to and following administration of Zoledronic acid to ensure that they are adequately hydrated.

-    Zoledronic acid 4 mg/1oo ml solution for infusion can be used immediately without further preparation for patients with normal renal function. In patients with mild to moderate renal impairment, reduced doses should be prepared as instructed below.

•    To prepare reduced doses for patients with baseline CLcr < 6o ml/min, refer to Table 1 below. Remove the volume of Zoledronic acid solution indicated from the bottle and replace with an equal volume of sterile sodium chloride 9 mg/ml (o.9%) solution for injection, or 5% glucose solution for injection.

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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.

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

•    As a consequence of low calcium values: irregular heart beat (cardiac arrhythmia; secondary to hypocalcaemia).

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

•    As a consequence of low calcium values: 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, fainting due to low blood pressure.

•    Weakness.

•    Chest pain.

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

•    High blood pressure, shortness of breath, dizziness, anxiety, sleep disturbances, taste disturbances, tingling or numbness of the hands or feet, diarrhoea, constipation, abdominal pain, dry mouth, trembling.

•    Increased sweating.

•    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.

•    Blurred vision, tearing of the eye, eye sensitivity to light.

•    Sudden coldness with fainting, limpness or collapse.

•    Swelling of hands, ankles or feet.

•    Difficulty in breathing with wheezing or coughing.

•    Itchy rash (urticaria).

•    Indigestion, inflammation of the stomach,

•    Blood in urine

•    Increased or reduced sense of touch or sensation.

•    Muscle cramps.

•    Weight increase.

Rare (may affect up to 1 in 1,000

people):

•    Slow heartbeat

•    Confusion

•    High levels of potassium or sodium in the blood

•    Weakness, bruising and frequent infections due to lack of blood cells

•    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.

•    Painful redness and/or swelling of the eye.

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

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

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 (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

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

Your doctor, nurse or pharmacist knows how to store this medicine properly.

Do not use this medicine after the expiry date which is stated on the carton and on the bottle. The expiry date refers to the last days of that month.

This medicinal product does not require any special storage conditions.

After first opening, the product should be used immediately. Discard any unused contents.

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.

Contents of the pack and other information

What Zoledronic acid solution for infusion contains

The active substance is zoledronic acid. One bottle of 100 ml solution for infusion contains 4 mg zoledronic acid, corresponding to 4.264 mg zoledronic acid monohydrate.

1 ml solution contains 0.04 mg zoledronic acid.

The other ingredients are mannitol (E421), sodium citrate (E331) and water for injections.

What Zoledronic acid solution for infusion looks like and contents of the pack

The medicinal product is presented as a “ready-to-use” solution for infusion in a clear, colourless plastic bottle. The solution for infusion is clear, colourless.

Zoledronic acid solution for infusion is supplied as a unit pack containing 1 bottle or as multipacks comprising 3, 4 or 10 cartons, each containing 1 bottle of 100 ml solution for infusion.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Sandoz Ltd,

Frimley Business Park, Frimley, Camberley, Surrey, GU16 7SR, UK.

Manufacturer

Lek Pharmaceuticals d.d., Verovskova 57,

1526 Ljubljana,

Slovenia

or

Ebewe Pharma GmbH Nfg. KG, Mondseestrasse 11,

A-4866 Unterach,

Austria

or

Novartis Pharma GmbH, Roonstrasse 25 und Obere Turnstrasse 8; 90429,

Nurnberg,

Germany.

or

Lek S.A.

Podlipie 16

95-010 Strykow, Poland

This leaflet was last revised in 05/2015.

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Table 1: Preparation of reduced doses of Zoledronic acid 4 mg/100 ml solution for infusion

Doses have been calculated assuming target AUC of 0.66 (mg^hr/l)

(CLcr = 75 ml/min). The reduced doses for patients with renal impairment are expected to achieve the same AUC as that seen in patients with creatinine clearance of 75 ml/min.

-    Studies with several types of infusion lines made from polyvinylchloride, polyethylene and polypropylene showed no incompatibility with Zoledronic acid.

-    Since no data are available on the compatibility of Zoledronic acid with other intravenously administered substances, Zoledronic acid must not be mixed with other medications/substances and should always be given through a separate infusion line.

How to store Zoledronic acid

•    Keep Zoledronic acid out of the sight and reach of children.

•    Do not use Zoledronic acid after the expiry date stated on the pack.

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

•    After opening the bottle, the product should be used immediately in order to avoid microbial contamination.

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