Zoledronic acid Fresenius Kabi

Package Leaflet: Information for the User

Zoledronic Acid Fresenius Kabi 4 mg/5 ml

concentrate for solution for infusion
Generic medicine
Please read this leaflet carefully before you are given this
medicine as it contains important information.

• 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 possible side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

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

1. What Acido Zoledronico Fresenius Kabi is and what it is used for

The active substance of Acido Zoledronico Fresenius Kabi is zoledronic acid,
a member of a class 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 cancer 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 cancer. Tumours can accelerate normal bone metabolism, resulting in increased release of calcium from bone. This condition is known as tumour-induced hypercalcaemia (TIH).

2. What you should know before being given Zoledronic Acid

Fresenius Kabi
Carefully follow all instructions given to you by your doctor.
Before starting treatment with Zoledronic Acid Fresenius Kabi, your doctor will perform blood tests and will monitor your response to treatment at regular intervals.
Zoledronic Acid Fresenius Kabi must not be given to you:

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

Warnings and precautions
Talk to your doctor before being given Zoledronic Acid Fresenius Kabi

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

During treatment with Zoledronic Acid Fresenius Kabi, you should maintain good oral hygiene (including regular tooth cleaning) and should receive routine dental check-ups.
Immediately inform your doctor and dentist if you experience any problems in your mouth or with your teeth such as tooth loss, pain, swelling, failure of wounds to heal, or discharge, as these may be signs of a condition called osteonecrosis of the jaw.
Patients receiving chemotherapy and/or radiotherapy, those taking steroids, those undergoing dental surgery, those who do not receive 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.
In patients treated with zoledronic acid, reduced levels of calcium in the blood (hypocalcemia) have been reported, which may sometimes cause muscle cramps, dry skin, or a burning sensation. Cases of irregular heartbeat (cardiac arrhythmia), seizures, muscle spasms, and contractions (tetany) secondary to severe hypocalcemia have also been reported. In some circumstances, hypocalcemia can be life-threatening. If any of these conditions apply to you, inform your doctor immediately. If you have pre-existing hypocalcemia, it must be treated before the first dose of Zoledronic Acid Fresenius Kabi is administered. You will be given adequate calcium and vitamin D supplementation.

Patients aged 65 years and older
Zoledronic Acid Fresenius Kabi can be administered to individuals aged 65 years and older. There is no evidence that additional precautions are required.

Children and adolescents
Zoledronic Acid Fresenius Kabi is not recommended for use in children and adolescents under 18 years of age.

Other medicines and Zoledronic Acid Fresenius Kabi
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 hypercalcemia), loop diuretics (a type of medicine used to treat high blood pressure and edema), 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 the bones) or any other medicine that may be harmful to the kidneys.
• Medicines containing zoledronic acid used for the treatment of osteoporosis and other non-oncological bone disorders, or any other bisphosphonate, since the combined effects of these medicines when taken together with zoledronic acid are unknown.
• Anti-angiogenic medicines (used in cancer treatment), as their combination with zoledronic acid has been associated with an increased risk of osteonecrosis of the jaw.

Pregnancy and breastfeeding
Zoledronic Acid Fresenius Kabi must not be given to you if you are pregnant.
Inform your doctor if you are pregnant or think you may be pregnant.
Zoledronic Acid Fresenius Kabi must not be given to you if you are breastfeeding.
Ask your doctor for advice before taking any medicine during pregnancy or breastfeeding.

Driving or using machinery
Drowsiness and numbness have very rarely occurred with the use of Zoledronic Acid. You should therefore exercise maximum caution when driving, operating machinery, or performing other activities requiring full attention.

Zoledronic Acid Fresenius Kabi contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e. is essentially “sodium-free”.

3. How Acido Zoledronico Fresenius Kabi is used

Acido Zoledronico Fresenius Kabi must be administered only by healthcare personnel 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 provided by your doctor, nurse, or pharmacist.

How much Acido Zoledronico Fresenius Kabi is administered

• The usual single dose administered 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 Fresenius Kabi is administered

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

How Acido Zoledronico Fresenius Kabi is administered
Acido Zoledronico Fresenius Kabi is administered intravenously as an infusion lasting at least 20 minutes and must be given as a single intravenous solution through a separate infusion line.
Patients with not excessively elevated blood calcium levels may also be prescribed daily calcium and vitamin D supplements.

If you have been given more Acido Zoledronico Fresenius Kabi than you should have
If doses higher than recommended have been administered, 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 calcium levels become too low, you may need to be given an intravenous calcium supplement.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them. The most common side effects are usually mild and may disappear within a short time.
Contact your doctor immediately if you experience any of the following serious side effects:

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

• Severe kidney impairment (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 mouth or jaw sores to heal, discharge, numbness or heaviness sensation in the jaw, or tooth loss. These may be signs of jaw bone damage (osteonecrosis). If you experience any of these symptoms during or after stopping treatment with Acido Zoledronico Fresenius Kabi, inform your doctor and dentist immediately.
• In patients treated with zoledronic acid for postmenopausal osteoporosis, irregular heart rhythm (atrial fibrillation) has been observed. It is currently unclear whether zoledronic acid causes this irregular heart rhythm, but you should report to your doctor if you develop such symptoms after receiving zoledronic acid.
• Severe allergic reactions: shortness of breath, 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 hypocalcemia).
• A kidney function disorder called Fanconi syndrome (this is usually diagnosed by your doctor through certain 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 hypocalcemia).
• Contact your doctor if you experience ear pain, ear discharge, and/or ear infection. These episodes could be symptoms 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 stiffness during or after stopping treatment with Acido Zoledronico Fresenius Kabi, contact your doctor immediately.

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

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 flu-like syndrome with fever, tiredness, weakness, drowsiness, chills, and bone, joint, and/or muscle pain. In most cases, no specific treatment is required and symptoms disappear within a short time (a few hours or days).
• Gastrointestinal reactions such as nausea, vomiting, and loss of appetite.
• Conjunctivitis.
• Low levels of red blood cells in the blood (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, skin rash, itching.
• High blood pressure.
• Shortness of breath.
• Dizziness.
• Anxiety.
• Sleep disturbances.
• 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 tearing, light sensitivity.
• Sudden chills with fainting, weakness, or collapse.
• Breathing difficulties with wheezing or cough.
• Hives.

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

• Slow heart rate.
• Confusion.
• Rarely, an unusual femur fracture may occur, particularly in patients on 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 the tissue around the air sacs in the lungs).
• Influenza-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 effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Acido Zoledronico Fresenius Kabi

Your doctor, pharmacist or nurse knows how to store Acido Zoledronico Fresenius Kabi appropriately (see section 6).

6. Package contents and other information

What Acido Zoledronico Fresenius Kabi contains

• The active substance of Acido Zoledronico Fresenius Kabi is zoledronic acid. One vial contains 4 mg of zoledronic acid (as monohydrate).
• The excipients are: mannitol, sodium citrate, water for injections.

Description of the appearance of Acido Zoledronico Fresenius Kabi and contents of the
package
Acido Zoledronico Fresenius Kabi is supplied as a solution in a clear, colourless plastic vial.
Acido Zoledronico Fresenius Kabi is available in pack sizes containing 1, 4 or 10 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Fresenius Kabi Italia S.r.l.
Via Camagre, 41
37063 Isola della Scala, Verona
Italy

Manufacturer
Fresenius Kabi Austria GmbH
Hafnerstrasse 36
A-8055 Graz, Austria

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

The following information is intended for healthcare professionals only
How to prepare and administer Zoledronic Acid Fresenius Kabi

• To prepare an infusion solution containing 4 mg of zoledronic acid, further dilute Zoledronic Acid Fresenius Kabi concentrate (5 ml) with 100 ml of an infusion solution free of calcium or other bivalent cations. If a reduced dose of Zoledronic Acid Fresenius Kabi is required, first withdraw the appropriate volume as follows, 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.

Do not mix Zoledronic Acid Fresenius Kabi with solutions containing calcium or
other bivalent cations such as lactated Ringer's solution.
Instructions for preparing reduced doses of Zoledronic Acid Fresenius Kabi:
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 remaining must be discarded. Only clear, particle-free, colourless solution should be used. Aseptic techniques must be followed during the preparation of the infusion.

o Stability after dilution: Chemical and physical in-use stability has been demonstrated for 24 hours at 2–8°C. From a microbiological standpoint, the diluted infusion solution should be used immediately. If not used immediately, storage time and conditions prior to use are under the responsibility of the user and normally should not exceed 24 hours between 2°C and 8°C. The refrigerated solution must be brought to room temperature before administration.
o The solution containing Zoledronic Acid Fresenius Kabi must be administered as a single infusion lasting 20 minutes via a separate infusion line. The patient's hydration status should be assessed before and after administration of Zoledronic Acid Fresenius Kabi to ensure adequate hydration.
o Studies using glass vials, as well as various types of containers made of polyvinyl chloride, polyethylene, and polypropylene (pre-filled with either 0.9% w/v sodium chloride solution or 5% w/v glucose solution), have not shown any incompatibility with Zoledronic Acid Fresenius Kabi.
o Since compatibility data with other medicinal products administered intravenously are not available, Zoledronic Acid Fresenius Kabi 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 Fresenius Kabi

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the packaging.
• The unopened vial does not require any special storage conditions.
• For storage conditions after dilution, see “stability after dilution”.