Zometa 4 mg powder and solvent for solution for infusion

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 treat bone metastases (spread of cancer from the primary cancer site to the bone) and to prevent associated/related bone complications, e.g. fractures.
• To reduce the amount of calcium in the blood 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).

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 (hypersensitive) to zoledronic acid, another bisphosphonate (the group of substances to which Zometa belongs), or any of the other ingredients of Zometa.

Before you are given Zometa, tell your doctor:

• if you have or have had a liver problem.
• if you have or have had a kidney problem.
• if you have or have had a heart 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 Zometa.

Using other medicines

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 or any other medicines which may harm your kidneys.

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.

Use in children

There have been 2 studies on the use of Zometa in children with severe osteogenesis imperfecta (a genetic disorder, also called ?brittle bone disease?). However, it has not been established whether these children will benefit from Zometa treatment.

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

The effects of Zometa on driving, using machines and performing other tasks that need your full attention have not been studied. However, there have been very rare cases of drowsiness with the use of Zometa. You should therefore be careful when driving, using machinery or performing other tasks that need full attention.

• 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 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 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.

How often you will be given Zometa

? If you are being treated for 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.

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.

Like all medicines, Zometa 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 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, as reported with other bisphosphonates (the group of substances to which Zometa belongs).
• Blood tests indicating changes in kidney function (higher levels of creatinine), including severe kidney impairment. Such changes are also known to occur with other medicinal products of this kind. In addition, some cases of kidney disease have been reported.
• Low level of red blood cells (anaemia).
• 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.
• 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.

Rare:

• Slow heart beat.
• Confusion.

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.

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.

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.

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

What Zometa contains

• The active substance of Zometa is zoledronic acid.
• 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 packs containing 1, 4 or 10 vials and 1, 4 or 10 ampoules, respectively. Not all pack sizes may be marketed.

Marketing Authorisation Holder

Novartis Europharm Limited
Wimblehurst Road
Horsham
West Sussex, RH12 5AB
United Kingdom

Manufacturer

Novartis Pharma GmbH
Roonstrasse 25
D-90429 Nuremberg
Germany

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

BelgiëBelgiqueBelgien Novartis Pharma N.V. TélTel 32 2 246 16 11 LuxembourgLuxemburg Novartis Pharma GmbH TélTel 49 911 273 0

Novartis Pharma Services Inc. . 359 2 489 98 28 Magyarország Novartis Hungária Kft. Pharma Tel. 36 1 457 65 00

eská republika Novartis s.r.o. Tel 420 225 775 111 Malta Novartis Pharma Services Inc. Tel 356 2298 3217

Danmark Novartis Healthcare AS Tlf 45 39 16 84 00 Nederland Novartis Pharma B.V. Tel 31 26 37 82 111

Deutschland Novartis Pharma GmbH Tel 49 911 273 0 Norge Novartis Norge AS Tlf 47 23 05 20 00

Eesti Novartis Pharma Services Inc. Tel 372 60 62 400 Österreich Novartis Pharma GmbH Tel 43 1 86 6570

Novartis Hellas A.E.B.E. 30 210 281 17 12 Polska Novartis Poland Sp. z o.o. Tel. 48 22 550 8888

España Novartis Farmacéutica, S.A. Tel 34 93 306 42 00 Portugal Novartis Farma - Produtos Farmacêuticos, S.A. Tel 351 21 000 8600

France Novartis Pharma S.A.S. Tél 33 1 55 47 66 00 România Novartis Pharma Services Inc. Tel 40 21 31299 01

Ireland Novartis Ireland Limited Tel 353 1 260 12 55 Slovenija Novartis Pharma Services Inc. Tel 386 1 300 75 77

Ísland Vistor hf. Sími 354 535 7000 Slovenská republika Novartis Slovakia s.r.o. Tel 421 2 5542 5439

Italia Novartis Farma S.p.A. Tel 39 02 96 54 1 SuomiFinland Novartis Finland Oy PuhTel 358 9 61 33 22 11

357 22 690 690 Sverige Novartis Sverige AB Tel 46 8 732 32 00

Latvija Novartis Pharma Services Inc. Tel 371 7 887 070 United Kingdom Novartis Pharmaceuticals UK Ltd. Tel 44 1276 698370

Lietuva
Novartis Pharma Services Inc.
Tel: +370 5 269 16 50

This leaflet was last approved in

INFORMATION FOR THE HEALTHCARE PROFESSIONAL

How to prepare and administer Zometa

• To prepare an infusion solution containing 4 mg Zometa, 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
• The Zometa 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 reconstitution, dilution, storage in the refrigerator and end of administration must not exceed 24 hours.
• The solution containing Zometa is given as a single 15-minute intravenous infusion. The hydration status of patients must be assessed prior to and following administration of Zometa to assure 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 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 Zometa infusion solution should preferably be used immediately. If the solution is not used immediately, storage prior to use is the responsibility of the user and should be in a refrigerator at 2°C ? 8°C.
• The total time between reconstitution, dilution, storage in the refrigerator and end of administration must not exceed 24 hours.