Package leaflet: Information for the user

STEOZOL 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 STEOZOL is and what it is used for

2.    What you need to know before you are given STEOZOL

3.    How STEOZOL is used

4.    Possible side effects

5.    How to store STEOZOL

6.    Contents of the pack and other information

1.    What STEOZOL is and what    it used    for

The active substance in STEOZOL 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 adults 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 STEOZOL Follow carefully all instructions given to you by your doctor.

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

You should not be given STEOZOL:

•    if you are breast-feeding.

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

Warnings and precautions

Talk to your doctor, pharmacist or nurse before you are given STEOZOL:

•    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 STEOZOL.

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

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

Children and adolescent

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

Other medicines and STEOZOL

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.

•    Medicines containing zoledronic acid or any other bisphosphonate, since the combined effects of these medicines taken together with STEOZOL 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

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

You must not be given STEOZOL 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.

STEOZOL contains less than 1 mmol (23 mg) of sodium per ml of solution, which means it is essentially sodium free (that is, salt free).

3. How STEOZOL is used

•    STEOZOL 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.

Always use this medicine exactly your doctor has told you. Check with your doctor if you are not sure. How much STEOZOL 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 STEOZOL is given

•    If you are being treated for the prevention of bone complications, due to bone metastases, you will be given one infusion of STEOZOL 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 STEOZOL.

How STEOZOL is given

•    STEOZOL 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 STEOZOL 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 additional 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 at: 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 STEOZOL

Your doctor, pharmacist or nurse knows how to store STEOZOL properly (see section 6 “Information for the healthcare professional”).

6.    Contents of the pack and other information

What STEOZOL contains

-    The active substance of Steozol is zoledronic acid.

One prefilled syringe with 5 ml concentrate contains 4 mg zoledronic acid as zoledronic acid hemipentahydrate 4.66 mg.

1 ml of concentrate contains 0.8 mg zoledronic acid.

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

What STEOZOL looks like and contents of the pack

STEOZOL is supplied as a concentrate for solution for infusion. The solution is clear.

The syringes are made of crystal clear polymer (polycycloolefin) barrel with plastic tip cap and crystal clear polymer (styrene-butadiene) rubber stopper.

Each pack contains 1, 3, 4 or 10 prefilled syringe of 5 ml with 1, 3, 4 or 10 needles for the reconstitution of the solution.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

To be completed nationally

Manufacturer

Italfarmaco S.p.A.

Viale F. Testi, 330 20126 Milano - IT

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

IT    Steozol 4 mg/5 ml concentrato per soluzione per infusione

AT    Steozol

CZ    Steozol 4    mg/5 ml    koncentrat pro infuzni roztok

DK    Steozol

FI    Steozol 4 mg/5 ml infuusiokonsentraatti, liuosta varten

HU    Steozol 4 mg/5 ml koncentratum oldatos infuziohoz

NO    Steozol 4    mg/5 ml    konsentrat til infusjonsv^ske

SK STEOZOL 4 mg/5 ml koncentrat na pripravu infuzneho roztoku SE    Steozol

UK    Steozol 4 mg/5 ml    concentrate for solution for infusion

BG    Steozol 4 mg/5 ml    concentrate for solution for infusion

RO    Steozol 4 mg/5 ml    concentrat pentru solutie perfuzabila

DE    Steozol 4 mg/5 ml    Konzentrat zur Herstellung einer Infusionslosung

ES    STEOZOL 4 mg/5 ml concentrado para solucion para perfusion

FR    STEOZOL 4 mg/5 ml solution a diluer pour perfusion

EL    STEOZOL 4 mg/5 tcukvo Sia^upa yia napaoKeup Sia^upaxog npog sy%uop

This leaflet was last approved in 05/2014

INFORMATION FOR THE HEALTHCARE PROFESSIONAL

How to prepare and administer STEOZOL

-    Turn the syringe upside down, keeping the plunger down. Tap the syringe gently to let any air bubbles rise to the top. Push the plunger rod slowly until all air bubbles are gone. Steozol is now ready to inject into the solution for diultion. In case you only need part of the entire dose, use the scale on the syringe to see how much concentrate you withdraw.

-    To prepare an infusion solution containing 4 mg STEOZOL, further dilute the STEOZOL concentrate (5.0 ml) with 100 ml of 0.9 g/100 ml sodium chloride solution or 5 g/100 ml glucose solution. If a lower dose of STEOZOL 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 g/100 ml sodium chloride or 5 g/100 ml glucose solution.

Do not mix STEOZOL concentrate with calcium-containing or other divalent cationcontaining solutions such as lactated Ringer’s solution.

Instructions for preparing reduced doses of STEOZOL:

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

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

-    From a microbiological point of view, the diluted solution for infusion should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C - 8°C or at 25°C. The refrigerated solution should then be equilibrated to room temperature prior to administration.

-    The total time between dilution, storage in the refrigerator or at 25°C and end of administration must not exceed 24 hours.

-    The solution containing STEOZOL is given as a single 15-minute intravenous infusion in a separate infusion line. The hydration status of patients must be assessed prior to and following administration of STEOZOL 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 g/100 ml sodium chloride solution or 5 g/100 ml glucose solution) showed no incompatibility with STEOZOL.

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

How to store STEOZOL

-    Keep STEOZOL out of the sight and reach of children.

-    Do not use STEOZOL after the expiry date which is stated on the pack after “EXP”. The expiry date refers to the last day of that month.

-    This medicine does not require any special storage conditions

-    The diluted STEOZOL infusion solution should be used immediately in order to avoid microbial

contamination.

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