ZOLEDRONIC ACID TEVA 4 mg/5 ml CONCENTRATE FOR INFUSION SOLUTION

2. What you need to know before you are given Zoledronic Acid Teva

Follow carefully all instructions given to you by your doctor.

Your doctor will perform blood tests before you start treatment with Zoledronic Acid Teva and will monitor your response to treatment at regular intervals.

Zoledronic Acid Teva must not be given to you

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

Warnings and precautions

Tell your doctor before Zoledronic Acid Teva is given to you:

• if you have or have had any kidney problems.
• if you have or have had any pain, swelling or numbness of the jaw, or a feeling of heaviness in the jaw or loosening of a tooth. Your doctor may recommend that you have a dental check-up before starting treatment with Zoledronic Acid Teva.
• if you are receiving dental treatment or are about to undergo dental surgery, tell your dentist that you are being treated with Zoledronic Acid Teva and tell your doctor about your dental treatment.

While being treated with Zoledronic Acid Teva, you should maintain good oral hygiene (including regular tooth brushing) and receive routine dental check-ups. If you experience any problems with your mouth or teeth, such as loose teeth, pain or swelling, or non-healing of sores or discharge, tell your doctor and dentist immediately, as these may be signs of a condition called osteonecrosis of the jaw.

Patients who are receiving chemotherapy or radiotherapy, who are taking corticosteroids, who are undergoing dental surgery, who do not receive routine dental care, who have gum disease, who are smokers or who have been treated with a bisphosphonate (used to treat or prevent bone disorders) may be at a greater risk of developing osteonecrosis of the jaw.

Low levels of calcium in the blood (hypocalcaemia) have been observed in patients receiving Zoledronic Acid Teva, sometimes leading to muscle cramps, dry skin and a tingling sensation. Irregular heart rhythm (arrhythmia), convulsions, spasms and involuntary muscle contractions (tetany) secondary to severe hypocalcaemia have also been reported. In some cases, hypocalcaemia may be life-threatening. If you experience any of these conditions, tell your doctor immediately. If you have pre-existing hypocalcaemia, it must be corrected before you receive your first dose of Zoledronic Acid Teva. You will be given adequate calcium and vitamin D supplements.

Patients over 65 years

Zoledronic Acid Teva can be given to people over 65 years of age. There is no need for any special precautions.

Children and adolescents

Zoledronic Acid Teva is not recommended for use in adolescents and children under 18 years.

Other medicines and Zoledronic Acid Teva

Tell your doctor if you are taking, have recently taken or might take any other medicines. It is particularly important to tell your doctor if you are also taking:

• Aminoglycosides (medicines used to treat serious infections), calcitonin (a type of medicine used to treat postmenopausal osteoporosis and hypercalcaemia), loop diuretics (a type of medicine used to treat high blood pressure or oedema) or other medicines that lower calcium levels, as the combination of these with bisphosphonates may severely lower blood calcium levels.
• Talidomide (a medicine used to treat a type of blood cancer that affects the bone) or any other medicine that may harm your kidneys.
• Other medicines that also contain zoledronic acid and are used to treat osteoporosis and other non-cancerous bone diseases, or any other bisphosphonate, as the combined effects of these medicines given with Zoledronic Acid Teva are unknown.
• Anti-angiogenic medicines (used to treat cancer), as the combination of these medicines with Zoledronic Acid Teva has been associated with a higher risk of osteonecrosis of the jaw (ONJ).

Pregnancy and breast-feeding

You must not be given Zoledronic Acid Teva if you are pregnant. Tell your doctor if you are pregnant or think you might be pregnant.

You must not be given Zoledronic Acid Teva if you are breast-feeding.

Ask your doctor or pharmacist for advice before taking any medicine if you are pregnant or breast-feeding.

Driving and using machines

In rare cases, somnolence and fatigue have been observed with the use of zoledronic acid. Therefore, you should be careful when driving, using machines or performing other activities that require full attention.

Zoledronic Acid Teva contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per vial, i.e. essentially “sodium-free”.

3. How Zoledronic Acid Teva is given

• Zoledronic Acid Teva should only be given by healthcare professionals experienced in the administration of intravenous bisphosphonates.

• Your doctor will advise you to drink a sufficient amount of water before each treatment to help prevent dehydration.
• Follow carefully all other instructions given to you by your doctor, pharmacist or nurse.

How much Zoledronic Acid Teva is given

• The usual single dose given is 4 mg.
• If you have kidney problems, your doctor will give you a lower dose depending on the severity of your kidney problems.

How often Zoledronic Acid Teva is given

• If you are being treated to prevent bone complications due to bone metastases, you will be given a Zoledronic Acid Teva infusion every 3 to 4 weeks.
• If you are being treated to reduce the amount of calcium in the blood, you will usually only be given a single infusion of Zoledronic Acid Teva.

How Zoledronic Acid Teva is given

• Zoledronic Acid Teva is given as a drip (infusion) into a vein that should last at least 15 minutes and should be given as a single intravenous infusion in a separate infusion line.

Patient who do not have high levels of calcium in the blood will also be prescribed calcium and vitamin D supplements to take every day.

If you are given too much Zoledronic Acid Teva

If you have received more than the recommended dose, you will be closely monitored by your doctor. This is because you may develop changes in the levels of certain minerals in the blood (e.g. abnormal levels of calcium, phosphorus and magnesium) and/or changes in kidney function, including severe kidney failure. If your calcium level becomes too low, you may need to be given a calcium supplement 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 disappear after a short period of time.

Tell your doctor immediately if you experience any of the following side effects:

Common (may affect up to 1 in 10 people):

• Severe kidney impairment (usually determined by your doctor with a specific blood test).
• Low levels of calcium in the blood.

Uncommon (may affect up to 1 in 100 people):

• Pain in the mouth, teeth and/or jaw, swelling or difficulty healing of sores inside the mouth or jaw, discharge, numbness or a feeling of heaviness in the jaw, or tooth loss. These may be signs of bone damage in the jaw (osteonecrosis). Tell your doctor and dentist immediately if you experience these symptoms while being treated with Zoledronic Acid Teva or after stopping treatment.
• An irregular heart rhythm (atrial fibrillation) has been observed in patients treated with zoledronic acid for postmenopausal osteoporosis. It is not known whether zoledronic acid causes this irregular heart rhythm, but you should tell your doctor if you experience any symptoms after receiving zoledronic acid.
• Severe allergic reaction: shortness of breath, swelling, particularly of the face and throat.

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

• As a result of low calcium levels: irregular heart rhythm (arrhythmia; secondary to hypocalcaemia).
• A kidney problem called Fanconi syndrome (usually detected by your doctor with a urine test).

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

• As a result of low calcium levels: convulsions, numbness and tetany (secondary to hypocalcaemia).
• Tell your doctor if you have ear pain, discharge from the ear or an ear infection. These could be symptoms of damage to the bones of the ear.
• Osteonecrosis has also been rarely reported in other bones, especially the hip and thigh. Tell your doctor immediately if you experience symptoms such as new or increasing pain, swelling or stiffness while being treated with Zoledronic Acid Teva or after stopping treatment.

Tell your doctor as soon as possible if you experience any of the following side effects:

Very common (may affect more than 1 in 10 people):

• Low levels of phosphates in the blood.

Common (may affect up to 1 in 10 people):

• Headache and flu-like symptoms that include fever, fatigue, weakness, somnolence, chills and bone, joint and/or muscle pain. In most cases, no specific treatment is required and the symptoms disappear after a short period of time (a few hours or days).
• Gastrointestinal reactions such as nausea and vomiting, as well as loss of appetite.
• Low levels of red blood cells in the blood (anaemia).
• Conjunctivitis

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 disorders, taste disturbances, tremors, numbness or tingling of the hands or feet, diarrhoea, constipation, abdominal pain, dry mouth.
• Decreased white blood cell and platelet counts.
• Low levels of magnesium and potassium in the blood. Your doctor will monitor this and take any necessary action.
• Weight gain.
• Increased sweating
• Numbness.

• Blurred vision, tearing, sensitivity to light.

• Sudden drop in blood pressure with fainting, weakness or collapse
• Difficulty breathing with wheezing or coughing.
• Hives.

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

• Slow heart rate.
• Confusion.
• Atypical fractures of the thigh bone (femur) that can occur rarely, especially in patients on long-term treatment for osteoporosis. Tell your doctor if you experience pain, weakness or discomfort in the thigh, hip or groin, as these may be early signs of a possible fracture of the femur.
• Interstitial lung disease (inflammation of the tissue that surrounds the air sacs in the lungs).
• Flu-like symptoms that include arthritis and swelling of the joints.
• Painful redness and swelling of the eye and/or eyelid.

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

• Fainting due to low blood pressure.
• Severe pain in the bones, joints and/or muscles, occasionally debilitating.

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. Storage of Zoledronic Acid Teva

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

Do not use this medicine after the expiry date which is stated on the carton and vial label after EXP. The expiry date refers to the last day of the month shown.

This medicine does not require any special storage conditions.

The diluted solution for infusion of Zoledronic Acid Teva should be used immediately. If not used immediately, the storage times and conditions are the responsibility of the user.

The total time between reconstitution, storage in the refrigerator at 2-8°C and administration must not exceed 24 hours.

Do not use this medicine if you notice particles or discolouration of the solution.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Container contents and additional information

Composition of Zoledronic Acid Teva

• The active substance of Zoledronic Acid Teva is zoledronic acid. One vial contains 4 mg of zoledronic acid (as monohydrate).
• The other ingredients are: mannitol, sodium citrate, water for injections.

Appearance and container contents of the product

Zoledronic Acid Teva is supplied as a concentrate for solution for infusion. Each plastic or glass vial contains 5 ml of a clear and colorless concentrate.

Zoledronic Acid Teva is supplied in packs containing 1, 4 or 10 vials.

Only some pack sizes may be marketed.

Marketing authorisation holder

Teva B.V.

Swensweg 5

2031GA Haarlem

Netherlands

Manufacturer

Pharmachemie B.V.

Swensweg 5,

2031 GA Haarlem

Netherlands

PLIVA Croatia Ltd

Prilaz baruna Filipovica 25,

10 000 Zagreb

Croatia

For further information on this medicinal product, please contact the local representative of the marketing authorisation holder:

Date of last revision of this leaflet:MM/YYYY

Other sources of information

Detailed information on this medicinal product is available on the European Medicines Agency website http://www.ema.europa.eu

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This information is intended only for healthcare professionals:

How to prepare and administer Zoledronic Acid Teva

• To prepare the infusion solution containing 4 mg of zoledronic acid, Zoledronic Acid Teva concentrate (5 ml) should be diluted with 100 ml of calcium-free infusion solution or another divalent cation-free infusion solution. If a lower dose of Zoledronic Acid Teva is required, the appropriate volume should be withdrawn as indicated below and then diluted with 100 ml of infusion solution. To avoid possible incompatibilities, the infusion solution used for dilution should be sodium chloride 9 mg/ml (0.9%) or glucose 5% w/v solution.

Do not mix Zoledronic Acid Teva concentrate with solutions containing calcium or other divalent cations, such as Ringer's lactate solution.

Instructions for preparing lower doses of Zoledronic Acid Teva:

Withdraw the appropriate volume of the liquid concentrate as indicated below:

• 4.4 ml for a dose of 3.5 mg
• 4.1 ml for a dose of 3.3 mg
• 3.8 ml for a dose of 3.0 mg

• For single use. Any unused portion of the solution should be discarded. Only clear solutions free from particles and discoloration should be used. Aseptic techniques should be used during the preparation of the infusion.

• From a microbiological point of view, the diluted infusion solution should be used immediately. The maximum storage times are shown below.

• The solution containing zoledronic acid should be administered as a single intravenous infusion over 15 minutes in a separate infusion line. Before and after administration of Zoledronic Acid Teva, the patient's hydration status should be assessed to ensure they are adequately hydrated.

• Studies conducted with different types of polyvinyl chloride, polyethylene, and polypropylene infusion lines did not reveal any incompatibility with Zoledronic Acid Teva.

• Since there are no data available on the compatibility of Zoledronic Acid Teva with other substances administered intravenously, Zoledronic Acid Teva should not be mixed with other medicinal products/substances and should always be administered through a separate infusion line.

Storage of Zoledronic Acid Teva

Unopened vial

• Keep Zoledronic Acid Teva out of sight and reach of children.
• Do not use Zoledronic Acid Teva after the expiry date stated on the carton after EXP.

Diluted solution

• The diluted infusion solution of Zoledronic Acid Teva should be used preferably immediately. If not used immediately, the time and conditions of storage during use before administration are the responsibility of the user and should be stored in a refrigerator at 2°C to 8°C.
• The total time between dissolution, storage in the refrigerator, and the end of administration should not exceed 24 hours.