ZOMETA 4 MG POWDER AND SOLVENT FOR SOLUTION FOR INFUSION - patient leaflet, side effects, dosage

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 Zometa is and what it is used for

• 2. What you need to know before you are given Zometa

• 3. How Zometa is used

• 4. Possible side effects

• 5. How to store Zometa

• 6. Contents of the pack and other information

1. what zometa is and what it is used for

The active substance in Zometa 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 are given zometa

Follow carefully all instructions given to you by your doctor.

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

You should not be given Zometa:

• – if you are breast-feeding.

• – if you are allergic to zoledronic acid, another bisphosphonate (the group of substances to which

Zometa belongs), or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

– 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. Your doctor may recommend a dental examination before you start treatment with Zometa.

• – if you are having dental treatment or are due to undergo dental surgery, tell your dentist that

you are being treated with Zometa and inform your doctor about your dental treatment.

While being treated with Zometa, you should maintain good oral hygiene (including regular teeth brushing) and receive routine dental check-ups.

Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth such as loose teeth, pain or swelling, or non-healing of sores or discharge, as these could be signs of a condition called osteonecrosis of the jaw.

Patients who are undergoing chemotherapy and/or radiotherapy, who are taking steroids, who are undergoing dental surgery, who do not receive routine dental care, who have gum disease, who are smokers, or who were previously treated with a bisphosphonate (used to treat or prevent bone disorders) may have a higher risk of developing osteonecrosis of the jaw.

Reduced levels of calcium in the blood (hypocalcaemia), sometimes leading to muscle cramps, dry skin, burning sensation, have been reported in patients treated with Zometa. 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 Zometa. You will be given adequate calcium and vitamin D supplements.

Patients aged 65 years and over

Zometa 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

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

Other medicines and Zometa

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 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 Zometa are unknown.

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

Pregnancy and breast-feeding

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

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

Zometa contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium free”. If your doctor uses a solution of common salt to dilute Zometa, the dose of sodium received would be larger.

3. How Zometa is used

• – Zometa 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 Zometa 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 Zometa is given

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

How Zometa is given

• – Zometa 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 Zometa 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:

– 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 non-healing sores inside the mouth or jaw, discharge, 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 while being treated with Zometa or after stopping treatment.

• – 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).

• – A kidney function disorder called Fanconi syndrome (will normally be determined by your doctor with certain urine tests).

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).

• – Talk to your doctor if you have ear pain, discharge from the ear, and/or an ear infection. These

could be signs of bone damage in the ear.

• – Osteonecrosis has also very rarely been seen occurring with other bones than the jaw, especially the hip or thigh. Tell your doctor immediately if you experience symptoms such as new onset or worsening of aches, pain or stiffness while being treated with Zometa or after stopping treatment.

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

– 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, anxiety, sleep disturbances, taste disturbances, trembling, tingling or numbness of the hands or feet, diarrhoea, constipation, abdominal pain, dry mouth.

• – 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.

• – Weight increase.

• – Increased sweating.

• – Sleepiness.

• – Blurred vision, 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.

• – Painful redness and/or swelling of the eye.

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.

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 national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. how to store zometa

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

6. contents of the pack and other information- the active substance of zometa is zoledronic acid. one vial contains 4 mg zoledronic acid, corresponding to 4.264 mg zoledronic acid monohydrate.

• – The other ingredients are mannitol, sodium citrate.

What Zometa looks like and contents of the pack

Zometa is supplied as a powder in a vial. One vial contains 4 mg of zoledronic acid.

Each pack contains the vial with powder, together with an ampoule of 5 ml water for injections, which is used to dissolve the powder.

Zometa is supplied as unit packs containing 1 or 4 vials and 1 or 4 ampoules, respectively, and as multi-packs containing 10 (10× 1+1) vials and ampoules. Not all pack sizes may be marketed.

Marketing Authorisation Holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Manufacturer

Novartis Pharma GmbH

Roonstrasse 25

D-90429 Nuremberg

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Sverige

Novartis Sverige AB

Tel: +46 8 732 32 00

United Kingdom

Novartis Pharmaceuticals UK Ltd.

Tel: +44 1276 698370

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:

INFORMATION FOR THE HEALTHCARE PROFESSIONAL

How to prepare and administer Zometa

• – To prepare an infusion solution containing 4 mg zoledronic acid, add 5 ml of water for injections from the ampoule supplied in the pack to the vial containing the Zometa powder under aseptic conditions. Shake the vial gently to dissolve the powder.

• – Further dilute the Zometa reconstituted solution (5 ml) with 100 ml of calcium-free or other divalent cation-free infusion solution. If a lower dose of Zometa is required, first withdraw the appropriate volume of the reconstituted solution (4 mg/5 ml) 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 Zometa reconstituted solution with calcium-containing or other divalent cation-containing solutions such as lactated Ringer’s solution.

Instructions for preparing reduced doses of Zometa:

Withdraw the appropriate volume of the reconstituted solution (4 mg/5 ml), 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 and discolouration should be used. Aseptic techniques must be followed during the preparation of the infusion.

• – From a microbiological point of view, the reconstituted and 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. The refrigerated solution should then be equilibrated to room temperature prior to administration.

• – The solution containing zoledronic acid 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 Zometa to assure that they are adequately hydrated.

• – Studies with several types of infusion lines made from polyvinylchloride, polyethylene and polypropylene showed no incompatibility with Zometa.

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

How to store Zometa

• – Keep Zometa out of the reach and sight of children.

• – Do not use Zometa after the expiry date stated on the pack.

• – The unopened vial does not require any specific storage conditions.

• – The diluted Zometa infusion solution should be used immediately in order to avoid microbial contamination.