Package leaflet: Information for the user Zoledronic acid Helm 4 mg/5 ml concentrate for 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.

What is in this leaflet

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

2.    Before you are given Zoledronic acid Helm

3.    How to use Zoledronic acid Helm

4.    Possible side effects

5.    How to store Zoledronic acid Helm

6.    Contents of the pack and other information

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

The active substance in Zoledronic acid Helm 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 in cases 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.    Before you are given Zoledronic acid Helm

Follow carefully all instructions given to you by your doctor.

Your doctor will carry out blood tests before you start treatment with Zoledronic acid Helm and will

check your response to treatment at regular intervals.

You should not be given Zoledronic acid Helm:

-    if you are breast-feeding.

-    if you are allergic (hypersensitive) to zoledronic acid, another bisphosphonate (the group of substances to which Zoledronic acid Helm belongs) or any of the other ingredients of Zoledronic acid Helm.

Before you are given Zoledronic acid Helm, 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 Helm.

Other medicines and Zoledronic acid Helm

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.

-    Aclasta (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 Helm are unknown.

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

Patients aged 65 years and over

Zoledronic acid Helm 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 Helm 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 Helm if you are pregnant. Tell your doctor if you are or think that you may be pregnant.

You must not be given Zoledronic acid Helm 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 Helm. You should therefore be careful when driving, using machinery or performing other tasks that need full attention.

Zoledronic acid Helm contains sodium

This medicinal product contains 45.39 mmol (or 905.6 mg) sodium per usual single infusion, when diluted with 100 ml 0.9% w/v (9 mg/ml) sodium chloride. To be taken into consideration by patients on a controlled sodium diet.

If you will receive a lower dose of zoledronic acid, ask your doctor for data on the sodium content.

When diluted in 5% w/v (50 mg/ml) glucose solution, the medicinal product contains less than 1 mmol sodium (23 mg) per infusion, i.e. essentially ‘sodium- free’.

3. How Zoledronic acid Helm is used

-    Zoledronic acid Helm 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 Helm 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 Helm 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 Helm 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 Helm.

How Zoledronic acid Helm is given

-    Zoledronic acid Helm 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 Helm than you should

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.

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 serious 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 any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please

tell your doctor, nurse or pharmacist.

5. How to store Zoledronic acid Helm

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

6. Contents of the pack and other information What Zoledronic acid Helm contains

-    The active substance of Zoledronic acid Helm is zoledronic acid.

-    One vial with 5 ml concentrate of Zoledronic acid Helm contains 4 mg of zoledronic acid and 5.6 mg sodium.

-    One ml concentrate contains 0.8 mg zoledronic acid and 1.12 mg sodium.

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

What Zoledronic acid Helm looks like and contents of the pack

Zoledronic acid Helm 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 Helm is supplied as packs containing 1 or 4 vials.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Helm AG Nordkanalstr. 28 20097 Hamburg Germany

This medicinal product is authorised in the Member States of the EEA under the following names:

Germany	Zoledronsaure Helm 4mg/5ml - Konzentrat zur Herstellung einer Infusionslosung
Greece	Zoledronic acid Helm 4mg/5ml - tcukvo Sra^upa yra napaaKeuq Sra^upaxog npog syxuaq
Spain	Acido zoledronico Helm 4mg/5ml - concentrado para solucion para perfusion
Finland	Tsoledronihappoa Helm 4mg/5ml - infuusiokonsentraatti, liuosta varten
France	Acide zoledronique Helm 4mg/5ml - solution a diluer pour perfusion
Italy	Acido zoledronico Helm 4mg/5ml - concentrato per soluzione per infusione
Norway	Zoledronsyre Helm 4mg/5ml - konsentrat til infusjonsv^ske, opplosning
Portugal	Acido zoledronico Helm 4mg/5ml - concentrado para soluqao para perfusao
Sweden	Zoledronsyra 4mg/5ml - koncentrat till infusionsvatska, losning
United Kingdom	Zoledronic acid Helm 4mg/5ml - concentrate for solution for infusion

This leaflet was last revised in 09/2012.

The following information is intended for healthcare professionals only:

INFORMATION FOR THE HEALTHCARE PROFESSIONAL How to prepare and administer Zoledronic acid Helm

- To prepare an infusion solution containing 4 mg Zoledronic acid Helm, further dilute the

Zoledronic acid Helm concentrate (5.0 ml) with 100 ml of calcium-free or other divalent cation-free infusion solution. If a lower dose of Zoledronic acid Helm is required, first withdraw the appropriate volume as indicated below and then dilute it further with 100 ml of infusion solution. To avoid potential incompatibilities, the infusion solution used for dilution must be either 0.9% w/v sodium chloride or 5% w/v glucose solution.

Do not mix Zoledronic acid Helm concentrate with calcium-containing or other divalent cation-containing solutions such as lactated Ringer’s solution.

Instructions for preparing reduced doses of Zoledronic acid Helm:

Withdraw the appropriate volume of the liquid concentrate, as follows:

■    4.4    ml    for 3.5 mg dose

■    4.1    ml    for 3.3 mg dose

■    3.8    ml    for 3.0 mg dose

-    After preparation, Zoledronic acid Helm infusion solution should preferably be used immediately. If the solution is not used immediately, storage prior to use is the responsibility of the care provider and should be in a refrigerator at 2°C - 8°C. Allow the refrigerated solution to reach room temperature before administration.

-    The total time between dilution, storage in the refrigerator and end of administration must not exceed 24 hours.

-    The solution containing Zoledronic acid Helm is given as a single 15-minute intravenous infusion. The hydration status of patients must be assessed prior to and following administration of Zoledronic acid Helm to ensure that they are adequately hydrated.

-    Studies with glass bottles, several types of infusion bags and infusion lines made from polyvinylchloride, polyethylene and polypropylene (prefilled with 0.9% w/v sodium chloride solution or 5% w/v glucose solution) showed no incompatibility with Zoledronic acid Helm.

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

How to store Zoledronic acid Helm

-    Keep Zoledronic acid Helm out of the reach and sight of children.

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

-    The unopened vial does not require any specific storage conditions.

-    The diluted Zoledronic acid Helm infusion solution should be used immediately in order to avoid microbial contamination.

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