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

Introduction

Package Leaflet: Information for the User

Zoledronic Acid Kabi 4 mg/5 ml Concentrate for Solution for Infusion EFG

Read all of this leaflet carefully before you start using 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 experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the Package Leaflet

1. What is Zoledronic Acid Kabi and what is it used for
2. What you need to know before you start using Zoledronic Acid Kabi
3. How to use Zoledronic Acid Kabi
4. Possible side effects
   1. Storage of Zoledronic Acid Kabi

1. Contents of the pack and further information

1. What is Zoledronic Acid Kabi and what is it used for

The active substance of Zoledronic Acid Kabi is zoledronic acid, which belongs to a group of substances called bisphosphonates. Zoledronic acid works by binding to bone and reducing the rate of bone turnover. It is used:

• To prevent bone complications,such as fractures, in adult patients with bone metastases (cancer spread from the primary site to the bone)
• To reduce the amount of calciumin the blood in adult patients where it is too high due to the presence of a tumor. Tumors can accelerate normal bone turnover, resulting in increased release of calcium from the bone. This condition is known as tumor-induced hypercalcemia (TIH).

2. What you need to know before you start taking Zoledronic Acid Kabi

Follow carefully all instructions given by your doctor.

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

Zoledronic Acid Kabi must not be administered

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

Warnings and precautions

Talk to your doctor before you start using Zoledronic Acid Kabi

• if you have or have had a kidney problem
• if you suffer or have suffered from pain, swelling, or numbnessof the jaw, or a feeling of heaviness in the jaw or a tooth becomes loose. Your doctor may recommend that you undergo a dental examination before starting treatment with Zoledronic Acid Kabi.
• if you are receiving dental treatmentor are going to undergo dental surgery, inform your dentist that you are being treated with Zoledronic Acid Kabi and inform your doctor about your dental treatment.

While being treated with Zoledronic Acid Kabi, you must maintain good oral hygiene (including regular tooth brushing) and undergo routine dental check-ups.

Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth, such as tooth loss, pain or swelling, or difficulty healing of ulcers or discharge, as these may be signs of a condition called osteonecrosis of the jaw.

Patients who are receiving chemotherapy and/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 received prior treatment with a bisphosphonate (used to treat or prevent bone disorders) may be at a higher risk of developing osteonecrosis of the jaw.

Reduced levels of calcium in the blood (hypocalcemia) have been described, sometimes manifesting with muscle cramps, dry skin, and a burning sensation in patients who have received zoledronic acid. An irregular heart rhythm (cardiac arrhythmia), seizures, spasms, and involuntary muscle contractions (tetany) secondary to severe hypocalcemia have been described. In some cases, hypocalcemia can be potentially life-threatening. If you experience any of these conditions, inform your doctor immediately. If you have pre-existing hypocalcemia, it should be corrected before you receive the first dose of Zoledronic Acid Kabi. You will be given adequate calcium and vitamin D supplements.

Patients aged 65 and over

Zoledronic Acid Kabi can be administered to people aged 65 and over. There is no evidence to suggest that additional precautions are necessary.

Children and adolescents

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

Using Zoledronic Acid Kabi with other medicines

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 postmenopausal osteoporosis and hypercalcemia), loop diuretics (a type of medicine used to treat high blood pressure or edema), or other medicines that lower calcium levels, as the combination of these with bisphosphonates can significantly lower blood calcium levels.
• Thalidomide(a medicine used to treat a type of blood cancer that affects the bone) or any other medicine that may harm the kidneys.
• Othersmedicines containing zoledronic acidused to treat osteoporosis and other non-cancerous bone diseases, or any other bisphosphonate, as the combined effects of these medicines administered with zoledronic acid are unknown.
• Anti-angiogenic medicines(used to treat cancer), as the combination of these medicines with zoledronic acid has been associated with an increased risk of osteonecrosis of the jaw (ONJ).

Pregnancy and breast-feeding

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

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

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before using this medicine.

Driving and using machines

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

Zoledronic Acid Kabi contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose, so it is essentially "sodium-free".

3. How to use Zoledronic Acid Kabi

Zoledronic Acid Kabi should only be administered by healthcare professionals experienced in the administration of intravenous bisphosphonates, i.e., administered in a vein.

Your doctor will recommend that you drink a sufficient amount of water before each treatment to help prevent dehydration.

Follow carefully all other instructions given by your doctor, nurse, or pharmacist.

How much Zoledronic Acid Kabi is administered

• The recommended single dose administered is 4 mg.

• If you have kidney problems, your doctor will administer a lower dose depending on the severity of your kidney problem.

How often is Zoledronic Acid Kabi administered

• If you are being treated to prevent bone complications due to bone metastases, you will be given an infusion of Zoledronic Acid Kabi every 3 or 4 weeks.

• If you are being treated to reduce the amount of calcium in the blood, you will normally only be given one infusion of Zoledronic Acid Kabi.

How Zoledronic Acid Kabi is administered

Zoledronic Acid Kabi is administered as a drip (infusion) in a vein that should last at least 20 minutes and should be administered as a single intravenous solution 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 more Zoledronic Acid Kabi than you should

If you have received doses higher than recommended, you should be closely monitored by your doctor. This is because you may develop changes in serum electrolytes (e.g., abnormal calcium, phosphorus, and magnesium levels in the blood) and/or changes in kidney function, including severe kidney failure. If the calcium level becomes too low, it may be necessary to administer a calcium supplement by infusion.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The most common are usually mild and will probably disappear after a short period of time.

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

Common (affects less than 1 in 10 patients)

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

Uncommon (affects less than 1 in 100 patients)

• Pain in the mouth, teeth, and/or jaw, swelling, or difficulty healing of ulcers within the mouth or jaw, discharge, numbness, or a feeling of heaviness in the jaw or tooth loss. These may be signs of damage to the jawbone (osteonecrosis). Tell your doctor and dentist immediately if you experience these symptoms while being treated with Zoledronic Acid Kabi or after stopping treatment.
• An irregular heart rhythm (atrial fibrillation) has been observed in patients treated with zoledronic acid for postmenopausal osteoporosis. It is currently unknown whether zoledronic acid causes this irregular heart rhythm, but you should tell your doctor if you experience these symptoms after receiving zoledronic acid.
• Severe allergic reaction: difficulty breathing, swelling, mainly of the face and throat.

Rare (may affect up to 1 in 1,000 patients)

• As a consequence of low calcium levels: irregular heartbeat (cardiac arrhythmia, secondary to hypocalcemia).
• A change in kidney function called Fanconi syndrome (usually detected by your doctor with a urine test).

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

• As a consequence of low calcium levels: seizures, numbness, and tetany (secondary to hypocalcemia).
• Tell your doctor if you have ear pain, ear discharge, and/or suffer from an ear infection. These could be signs of damage to the bones in the ear.
• Osteonecrosis has also been rarely observed in other bones apart from the jaw, especially in the hip or thigh. Tell your doctor immediately if you have symptoms such as the onset or worsening of discomfort, pain, or stiffness while receiving treatment with Zoledronic Acid Kabi or after stopping treatment.

Frequency not known: cannot be estimated from the available data.

• Kidney inflammation (tubulointerstitial nephritis): signs and symptoms may include reduced urine volume, blood in the urine, nausea, feeling unwell.

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

Very common (affects less than 1 in 10 patients)

• Low phosphate levels in the blood.

Common (affects less than 1 in 10 patients)

• Headache and flu-like syndrome consisting of fever, fatigue, weakness, drowsiness, chills, and pain in the bones, joints, and/or muscles. In most cases, no specific treatment is required, and symptoms disappear after a short period (a few hours or days).
• Gastrointestinal reactions such as nausea and vomiting, as well as loss of appetite.
• Conjunctivitis.
• Low red blood cell count (anemia).

Uncommon (affects less than 1 in 100 patients)

• Hypersensitivity reactions.
• Low blood pressure.
• Chest pain.
• Skin reactions (redness and swelling) at the infusion site, rash, itching.
• High blood pressure, difficulty breathing, dizziness, anxiety, sleep disorders, taste disturbances, tremors, tingling or numbness of the hands or feet, diarrhea, constipation, abdominal pain, dry mouth.
• Decreased white blood cell and platelet count.
• Low magnesium and potassium levels in the blood. Your doctor will monitor and take any necessary measures.
• Weight gain.
• Increased sweating.
• Drowsiness.
• Blurred vision, tearing, sensitivity of the eyes to light.
• Sudden cooling with fainting, weakness, or collapse.
• Difficulty breathing with wheezing or coughing.
• Hives.

Rare (affects less than 1 in 1,000 patients)

• Decreased heart rate
• Confusion
• Atypical fractures of the femur (thigh bone) that can occur rarely, especially in patients on long-term treatment for osteoporosis. Tell your doctor if you notice 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 surrounding the air sacs in the lungs).
• Symptoms similar to flu, including arthritis and swelling of the joints.
• Painful redness and/or swelling of the eye.

Very rare (affects less than 1 in 10,000 patients)

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

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You can also report side effects directly to the Spanish Medicines Agency, website: www.notificaRAM.es

By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Zoledronic Acid Kabi

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

6. Container contents and additional information

Composition of Zoledronic Acid Kabi 4 mg/5 ml concentrate for solution for infusion

• The active ingredient is zoledronic acid. One vial contains 4 mg of zoledronic acid (as monohydrate).
• The other components are: mannitol (E421), sodium citrate (E331), and water for injectable preparations.

Appearance of the product and container contents

Zoledronic Acid Kabi is supplied as a solution in a transparent and colorless plastic vial.

The 5 ml vial of Zoledronic Acid Kabi is supplied in packs of 1, 4, or 10 vials.

Only some pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Fresenius Kabi España S.A.U

C/ Marina 16-18,

08005-BARCELONA

Manufacturer

Fresenius Kabi Austria GmbH

Hafnerstrasse, 36, A-8055 Graz

Austria

This medicinal product is authorized in the Member States of the EEA under the following names

Date of last revision of this leaflet:August 2024

Detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.

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This information is intended for healthcare professionals only:

How to prepare and administer Zoledronic Acid Kabi

• To prepare the infusion solution containing 4 mg of zoledronic acid, the Zoledronic Acid Kabi concentrate (5.0 ml) should be diluted with 100 ml of calcium-free infusion solution or other divalent cation-free solution. If a lower dose of Zoledronic Acid Kabi is required, the appropriate volume should be withdrawn as indicated below and then diluted with 100 ml of infusion solution. To avoid potential incompatibilities, the infusion solution used for dilution should be 0.9% w/v sodium chloride or 5% w/v glucose solution.

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

Instructions for preparing lower doses of Zoledronic Acid Kabi:

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 of particles and discoloration should be used. Aseptic techniques should be used during the preparation of the infusion.

• Validity period after dilution: chemical and physical stability has been demonstrated for 24 hours at 2°C to 8°C. From a microbiological point of view, the diluted infusion solution should be used immediately. If not used immediately, the storage time and conditions are the responsibility of the user and should not exceed 24 hours at 2°C to 8°C under normal conditions. The refrigerated solution should reach room temperature before administration.

• The solution containing Zoledronic Acid Kabi is administered as a single intravenous infusion over 20 minutes in a separate infusion line. Before and after administration of Zoledronic Acid Kabi, the patient's hydration status should be assessed to ensure they are adequately hydrated.

• Studies with glass vials, as well as various types of polyvinyl chloride, polyethylene, and polypropylene containers (pre-filled with 0.9% w/v sodium chloride solution or 5% w/v glucose solution), did not show any incompatibility with Zoledronic Acid Kabi.

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

How to store Zoledronic Acid Kabi

• Keep this medicinal product out of the sight and reach of children.
• Do not use this medicinal product after the expiry date stated on the packaging.
• The unopened vial does not require special storage conditions.
• For storage conditions after dilution, see "Validity period after dilution".