Zoledronic acid Teva

Package leaflet: Information for the user

Zoledronic Acid Teva 4 mg/5 ml concentrate for solution for infusion

zoledronic acid
Read 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 questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet

1. What Zoledronic Acid Teva is and what it is used for
2. What you need to know before you are given Zoledronic Acid Teva
3. How Zoledronic Acid Teva is given
4. Possible side effects
5. How to store Zoledronic Acid Teva
6. Contents of the pack and other information

1. What Acido Zoledronico Teva is and what it is used for

The active substance of this medicine is zoledronic acid, which belongs to a group of substances called bisphosphonates. Zoledronic acid works by binding to bone and slowing down its rate of metabolism. It is used:

• To prevent bone complications, such as fractures, in adult patients with bone metastases (spread of tumour from the primary tumour site to the bones).
• To reduce the amount of calcium in the blood in adult patients in whom it is too high due to the presence of a tumour. Tumours can accelerate normal bone metabolism so that the release of calcium from bone is increased. This condition is known as tumour-induced hypercalcaemia (TIH).

2. What you should know before being given Acido Zoledronico Teva

Follow carefully all instructions given to you by your doctor.
Before starting treatment with Acido Zoledronico Teva, your doctor will carry out blood tests and will monitor your response to treatment at regular intervals.
Acido Zoledronico Teva must not be given to you:

• if you are breastfeeding.
• if you are allergic to zoledronic acid, to 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
Talk to your doctor before being given Acido Zoledronico Teva:

• if you have or have had kidney problems.
• if you have or have had pain, swelling or numbness in the jaw/mandible, a feeling of heaviness in the jaw/mandible, or tooth loss. Your doctor may recommend that you undergo a dental examination before starting treatment with Acido Zoledronico Teva.
• if you are currently undergoing dental treatments or need to undergo dental surgery, inform your dentist that you are being treated with Acido Zoledronico Teva and inform your doctor about your dental treatments.

During treatment with Acido Zoledronico Teva, you must maintain good oral hygiene (including regular tooth cleaning) and have routine dental check-ups.
Immediately inform your doctor and dentist if you experience any problems with your mouth or teeth such as tooth loss, pain, swelling, failure of sores to heal, or discharge, as these may be signs of a condition called osteonecrosis of the jaw/mandible.
Patients receiving chemotherapy and/or radiotherapy, those taking steroids, those undergoing dental surgery, those not receiving routine dental care, those with gum disease, smokers, or those previously treated with bisphosphonates (used to treat or prevent bone disorders) have a higher risk of developing osteonecrosis of the jaw/mandible.
Low levels of calcium in the blood (hypocalcaemia) have been reported in patients treated with Acido Zoledronico Teva, which may sometimes cause muscle cramps, dry skin, or a burning sensation. Cases of irregular heartbeat (cardiac arrhythmia), seizures, and muscle spasms and contractions (tetany) secondary to severe hypocalcaemia have been reported. In some circumstances, hypocalcaemia may be life-threatening. If any of these conditions apply to you, inform your doctor immediately.
If you have pre-existing hypocalcaemia, it must be treated before starting the first dose of Acido Zoledronico Teva. You will be given adequate calcium and vitamin D supplementation.
Patients aged 65 years and older
Acido Zoledronico Teva can be administered to patients aged 65 years and older. There is no evidence that additional precautions are required.
Children and adolescents
Acido Zoledronico Teva is not recommended for use in adolescents and children under 18 years of age.
Other medicines and Acido Zoledronico Teva
Inform your doctor if you are taking, have recently taken, or might take any other medicines. It is particularly important that you inform 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 combining these with bisphosphonates may cause a marked decrease in blood calcium concentration.
• Thalidomide (a medicine used to treat certain types of blood cancers involving bones) or any other medicine that may be harmful to the kidneys.
• Other medicines containing zoledronic acid used to treat osteoporosis and other non-oncological bone disorders, or any other bisphosphonate, since the combined effects of these medicines when taken together with Acido Zoledronico Teva are unknown.
• Anti-angiogenic medicines (used to treat cancer), as the combination with zoledronic acid has been associated with an increased risk of jaw osteonecrosis.

Pregnancy and breastfeeding
Acido Zoledronico Teva must not be given to you if you are pregnant. Inform your doctor if you are pregnant or suspect you may be pregnant.
Acido Zoledronico Teva must not be given to you if you are breastfeeding.
Ask your doctor for advice before taking any medicine during pregnancy or while breastfeeding.
Driving and use of machines
Drowsiness and numbness have very rarely occurred with the use of Acido Zoledronico Teva. Therefore, you should exercise maximum caution when driving, operating machinery, or performing other activities requiring full attention.
Acido Zoledronico Teva contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per vial, i.e. it is essentially ‘sodium-free’.

3. How Acido Zoledronico Teva is administered

• Acido Zoledronico Teva must be administered only by healthcare professionals trained in the use of intravenous bisphosphonates, i.e. through a vein.
• Your doctor will recommend that you drink sufficient water before each treatment to help prevent dehydration.
• Carefully follow all other instructions given by your doctor, pharmacist or nurse.

What dose you will be given

• The usual single dose is 4 mg.
• If you have kidney problems, your doctor will administer a reduced dose based on the severity of your renal impairment.

How often Acido Zoledronico Teva is administered

• If you are being treated to prevent bone complications due to bone metastases, you will receive an infusion of Acido Zoledronico Teva every three or four weeks.
• If you are being treated to reduce the level of calcium in your blood, you will normally receive a single infusion of Acido Zoledronico Teva.

How Acido Zoledronico Teva is administered

• Acido Zoledronico Teva is administered intravenously as an infusion lasting at least 15 minutes and must be given as a single intravenous solution through a separate infusion line.

Patients with not excessively high blood calcium levels may also be prescribed daily calcium and vitamin D supplements.
If you have been given more Acido Zoledronico Teva than you should have
If you have received doses higher than those recommended, you must be closely monitored by your doctor. This is because you may develop serum electrolyte abnormalities (e.g. abnormal levels of calcium, phosphate and magnesium) and/or changes in renal function, including severe kidney impairment. If your calcium levels drop too low, you may need to be given calcium supplementation by infusion.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will get them. The most common ones are usually mild and may disappear in a short time.
Contact your doctor immediately if you experience any of the following
side effects:
Common (may affect up to 1 in 10 people):

• Severe kidney failure (this will be confirmed by your doctor through specific blood tests).
• 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 failure of healing of sores in the mouth or jaw, discharge, numbness or a feeling of heaviness in the jaw, or tooth loss. These may be signs of jaw damage (osteonecrosis). If you experience such symptoms during or after stopping treatment with Zoledronic Acid Teva, inform your doctor and dentist immediately.
• In patients being treated with zoledronic acid for postmenopausal osteoporosis, an irregular heartbeat (atrial fibrillation) has been observed. It is currently unknown whether zoledronic acid causes this irregular heartbeat, but you must inform your doctor if you develop such symptoms after receiving zoledronic acid.
• Severe allergic reactions: difficulty breathing, swelling, particularly of the face and throat.

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

• As a consequence of low calcium levels: irregular heartbeat (cardiac arrhythmia secondary to hypocalcaemia).
• A kidney function disorder called Fanconi syndrome (usually diagnosed by your doctor through urine tests).

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

• As a consequence of low calcium levels: seizures, numbness and tetany (secondary to hypocalcaemia).
• Contact your doctor if you experience ear pain, ear discharge, and/or ear infection. These episodes could be signs of bone damage in the ear.
• Osteonecrosis has very rarely occurred in other bones besides the jaw, particularly in the hip or thigh. If you experience symptoms such as onset or worsening of pain, or pain or stiffness during or after stopping treatment with Zoledronic Acid Teva, inform your doctor immediately.

Not known: frequency cannot be estimated from the available data

• Inflammation of the kidney (tubulointerstitial nephritis): signs and symptoms may include decreased urine volume, blood in the urine, nausea, and a general feeling of being unwell.

Contact your doctor as soon as possible if any of the following side effects occur:
Very common (may affect more than 1 in 10 people):

• Low levels of phosphate in the blood.

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

• Headache and a flu-like syndrome with fever, fatigue, weakness, drowsiness, chills, and bone, joint, and/or muscle pain. In most cases, no specific treatment is required and symptoms resolve within a short 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, tremor, tingling or numbness in the hands or feet, diarrhoea, constipation, abdominal pain, dry mouth.
• Low levels of white blood cells and platelets in the blood.
• Low levels of magnesium and potassium in the blood. Your doctor will monitor these and take necessary measures.
• Weight gain.
• Increased sweating.
• Drowsiness.
• Blurred vision, eye lesions, light sensitivity.
• Sudden chills with fainting, weakness or collapse.
• Breathing difficulties with wheezing or coughing.
• Hives.

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

• Slow heartbeat.
• Confusion.
• Rarely, an unusual femur fracture may occur, particularly in patients receiving long-term treatment for osteoporosis. Contact your doctor if you experience pain, weakness or discomfort in the thigh, hip or groin, as this could be an early sign of a possible femur fracture.
• Interstitial lung disease (inflammation of lung tissue).
• Flu-like symptoms including arthritis and joint swelling.
• Painful redness and/or swelling of the eyes.

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 disabling.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 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 on the label of the
vial after Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
After dilution, it is preferable to use the diluted medicine immediately. If not used
immediately, the times and conditions of storage prior to use are the responsibility
of the user. The total time between dilution, storage in a refrigerator at 2°C – 8°C, and completion
of administration must not exceed 24 hours.
Do not use this medicine if you notice particles or any change in colour or appearance of the solution.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Acido Zoledronico Teva contains

• The active substance is zoledronic acid. Each vial contains 4 mg of zoledronic acid (as monohydrate).
• The other components are: mannitol, sodium citrate, water for injections.

Description of the appearance of Acido Zoledronico Teva and contents of the pack
Acido Zoledronico Teva is supplied as a concentrate for solution for infusion. Each plastic or clear glass vial contains 5 ml of a clear, colourless concentrate.
Acido Zoledronico Teva is available in packs containing 1, 4 or 10 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Teva B.V.
Swensweg 5
2031 GA Haarlem
The Netherlands

Manufacturer
Pharmachemie B.V.
Swensweg 5
2031 GA Haarlem
The Netherlands
PLIVA Croatia Ltd
Prilaz baruna Filipovića 25
10 000 Zagreb
Croatia

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

België/Belgique/Belgien Lietuva
Teva Pharma Belgium N.V./S.A./AG UAB Teva Baltics
Tél/Tel: +32 38207373 Tel: +370 52660203

България Luxembourg/Luxemburg
Тева Фарма ЕАД Teva Pharma Belgium N.V./S.A./AG
Тел.: +359 24899585 Belgique/Belgien
Tél/Tel: +32 38207373

Česká republika Magyarország
Teva Pharmaceuticals CR, s.r.o. Teva Gyógyszergyár Zrt.
Tel: +420 251007111 Tel.: +36 12886400

Danmark Malta
Teva Denmark A/S TEVA HELLAS Α.Ε.
Tlf.: +45 44985511 il-Greċja
Tel: +30 2118805000

Deutschland Nederland
TEVA GmbH Teva Nederland B.V.
Tel: +49 73140208 Tel: +31 8000228400

Eesti Norge
UAB Teva Baltics Eesti filiaal Teva Norway AS
Tel: +372 6610801 Tlf: +47 66775590

Ελλάδα Österreich
TEVA HELLAS A.E. ratiopharm Arzneimittel Vertriebs-GmbH
Τηλ: +30 2118805000 Tel: +43 1970070

España Polska
Teva Pharma, S.L.U. Teva Pharmaceuticals Polska Sp. z o.o.
Tel: +34 915359180 Tel.: +48 223459300

France Portugal
Teva Santé Teva Pharma - Produtos Farmacêuticos,
Tél: +33 155917800 Lda.
Tel: +351 214767550

Hrvatska România
Pliva Hrvatska d.o.o. Teva Pharmaceuticals S.R.L.
Tel: +385 13720000 Tel: +40 212306524

Ireland Slovenija
Teva Pharmaceuticals Ireland Pliva Ljubljana d.o.o.
Tel: +44 2075407117 Tel: +386 15890390

Ísland Slovenská republika
Teva Pharma Iceland ehf. TEVA Pharmaceuticals Slovakia s.r.o.
Sími: +354 5503300 Tel: +421 257267911

Italia Suomi/Finland
Teva Italia S.r.l. Teva Finland Oy
Tel: +39 028917981 Puh/Tel: +358 201805900

Κύπρος Sverige
TEVA HELLAS A.E. Teva Sweden AB
Ελλάδα Tel: +46 42121100
Τηλ: +30 2118805000

Latvija
UAB Teva Baltics filiāle Latvijā
Tel: +371 67323666

Other sources of information
More detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu

The following information is intended exclusively for healthcare professionals:

How to prepare and administer Zoledronic Acid Teva

• To prepare an infusion solution containing 4 mg of zoledronic acid, further dilute Zoledronic Acid Teva concentrate (5 mL) with 100 mL of an infusion solution free of calcium or other bivalent cations. If a reduced dose of zoledronic acid is required,
  withdraw initially the appropriate volume as indicated below and then further dilute it in
  100 mL of infusion solution. To avoid potential incompatibilities, the infusion solution used for dilution must be either 0.9% w/v sodium chloride solution or 5% w/v glucose solution.
  Zoledronic Acid Teva concentrate must not be mixed with solutions containing calcium or
  other bivalent cations such as lactated Ringer's solution.
  Instructions for preparing reduced doses of Zoledronic Acid Teva:
  Withdraw the appropriate volume of concentrate as follows:

• 4.4 mL for the 3.5 mg dose

• 4.1 mL for the 3.3 mg dose

• 3.8 mL for the 3.0 mg dose

• For single use only. Any unused solution residue must be discarded. Only use clear, particle-free, colourless solution. Aseptic techniques must be followed during preparation of the infusion.

• From a microbiological standpoint, the diluted infusion solution should be used immediately. See below for maximum storage times during use.

• The solution containing zoledronic acid must be administered as a single 15-minute infusion through a separate infusion line. The hydration status of patients must be assessed before and after administration of Zoledronic Acid Teva to ensure adequate hydration.

• Studies performed using infusion lines made of polyvinyl chloride, polyethylene, and polypropylene have shown no incompatibility with zoledronic acid.

• Since compatibility data with other intravenously administered substances are not available, zoledronic acid must not be mixed with other medicinal products and/or substances and must always be administered through a separate infusion line.

How to store Zoledronic Acid Teva
Unopened vial

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

Diluted solution

• The freshly prepared infusion solution of Zoledronic Acid Teva should preferably be used immediately. If the solution is not used immediately, storage prior to use is the responsibility of the user and must be carried out under refrigerated conditions at 2°C - 8°C.
• The total time between dilution, refrigerated storage, and completion of administration must not exceed 24 hours.