Leaflet: Information for the user

Zoledronic acid Kabi 4 mg/5 ml concentrate for solution for infusion EFG

Read this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist or nurse.
• If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

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

2.What you need to know before starting to use Zoledronic acid Kabi

3.How to use Zoledronic acid Kabi

4.Possible side effects

1. Storage of Zoledronic acid Kabi

6.Contents of the pack and additional information

The active ingredient ofZoledronic Acid Kabiis zoledronic acid, which belongs to a group of substances called bisphosphonates. Zoledronic acid acts by binding to bones and reducing the rate of bone remodeling. It is used:

• For preventing bone complications,such as fractures, in adult patients with bone metastases (spread of cancer 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 remodeling, leading to increased release of calcium from the bone. This condition is known as tumor-induced hypercalcemia (TIH).

Follow carefully all the instructions given by your doctor.

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

Zoledronic acid Kabi should not be administered

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

Warnings and precautions

Consult your doctor before starting to use Zoledronic acid Kabi

• if you have or have had a kidney problem
• if you have or have had jaw pain, swelling, or numbness, or a feeling of heaviness in the jaw or a tooth that moves. Your doctor may recommend that you undergo a dental examination before starting treatment with Zoledronic acid Kabi.
• if you are receiving dental treatment or are about 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 brushing of your teeth) 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 in healing ulcers or discharge, as these may be signs of a condition called osteonecrosis of the jaw.

Patients receiving chemotherapy and/or radiation therapy, taking corticosteroids, undergoing dental surgery, not receiving regular dental care, having gum disease, being smokers, or having received previous 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, which sometimes manifest with muscle cramps, dry skin, and a burning sensation in patients who have received zoledronic acid. Severe hypocalcemia has been associated with irregular heart rhythm (cardiac arrhythmia), convulsions, spasms, and involuntary muscle contractions (tetany). In some cases, hypocalcemia can be potentially fatal. If you experience any of these conditions, inform your doctor immediately. If you have a pre-existing hypocalcemia, it should be corrected before receiving the first dose of Zoledronic acid Kabi. You will be provided with adequate calcium and vitamin D supplements.

Patients aged 65 years and older

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

Children and adolescents

Zoledronic acid Kabi is not recommended for use in children and adolescents under 18 years.

Use of Zoledronic acid Kabi with other medications

Inform your doctor if you are taking, have taken recently, or may need to take any other medication. It is especially important to inform your doctor if you are also taking:

• Aminoglycosides(medications used to treat severe infections), calcitonin (a type of medication used to treat postmenopausal osteoporosis and hypercalcemia), diuretics (a type of medication for the treatment of high blood pressure or edema) or other medications that lower calcium levels, as the combination of these with bisphosphonates may significantly decrease blood calcium levels.
• Talidomide(a medication used to treat a type of blood cancer that affects the bone) or any other medication that may harm the kidneys.
• Othermedications containing zoledronic acidused to treat osteoporosis and other non-cancerous bone disorders, or any other bisphosphonate, as the combined effects of these medications administered with zoledronic acid are unknown.
• Anti-angiogenic medications(used to treat cancer), as the combination of these medications with zoledronic acid has been associated with an increased risk of osteonecrosis of the jaw (ONJ).

Pregnancy and lactation

Zoledronic acid Kabi should not be administered if you are pregnant. Inform your doctor if you are pregnant or think you may be pregnant.

Zoledronic acid Kabi should not be administered if you are breastfeeding.

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor before using this medication.

Driving and operating machinery

In rare cases, drowsiness and dizziness have been observed with the use of zoledronic acid. Therefore, you should exercise caution when driving, operating machinery, or performing other activities that require a lot of attention.

Zoledronic acid Kabi contains sodium

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

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

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

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

What amount of Ácido zoledrónico Kabi is administered

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

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

Frequent (affect 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.

Occasional (affect less than 1 in 100 patients)

• Pain in the mouth, teeth, and/or jaw, swelling, or difficulty healing sores inside the mouth or jaw, discharge, numbness, or heaviness in the jaw, or tooth loss. These may be signs of jaw bone damage (osteonecrosis). Inform your doctor and dentist immediately if you experience these symptoms while being treated with Zoledronic Acid Kabi or after completing treatment.
• Irregular heart rhythm (atrial fibrillation) has been observed in patients treated with zoledronic acid for postmenopausal osteoporosis. The current cause of this irregular heart rhythm is unknown, but you should inform 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 result of low calcium levels: irregular heartbeat (cardiac arrhythmia, secondary to hypocalcemia).

-A kidney function alteration known as Fanconi syndrome (usually detected by your doctor with a urine test).

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

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

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

Frequent (affect less than 1 in 10 patients)

• Low phosphate levels in the blood.

Occasional (affect 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 will 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.
• Conjunctivitis.
• Low red blood cell count in the blood (anemia).

Occasional (affect less than 1 in 100 patients)

• Hypersensitivity reactions.
• Low blood pressure.
• Chest pain.
• Reactions on the skin (redness and swelling) at the infusion site, rash, itching.
• High blood pressure, difficulty breathing, dizziness, anxiety, sleep disturbances, taste alterations, tremors, numbness or tingling in 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, watery eyes, sensitivity to light.
• Sudden cooling with fainting, weakness, or collapse.
• Difficulty breathing with wheezing or coughing.
• Urticaria.

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

• Decreased heart rate
• Confusion
• Atypical fractures of the femur (thigh bone) that may occur in rare cases, especially in patients undergoing prolonged treatment for osteoporosis. Inform your doctor if you experience pain, weakness, or discomfort in the thigh, hip, or groin, as these may be early signs of a possible femur fracture.
• Pulmonary interstitial disease (inflammation of the tissue surrounding the lung air sacs).
• Symptoms similar to the flu, including arthritis and joint swelling.
• Red, painful, and/or swollen eye.

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

• Loss of consciousness due to low blood pressure.
• Intense pain in the bones, joints, and/or muscles, occasionally incapacitating.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use, website:www.notificaRAM.es

By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Your doctor, pharmacist, or nurse knows how to storeZoledronic Acid Kabiproperly (see section 6).

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

• The active substance 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 injection.

Appearance of the product and contents of the pack

Zoledronic Acid Kabi is supplied as a solution in a transparent and colourless 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 authorisation holder and manufacturer responsible

Marketing authorisation holder

Fresenius Kabi España S.A.U

C/ Marina 16-18,

08005-BARCELONA

Manufacturer responsible

Fresenius Kabi Austria GmbH

Hafnerstrasse, 36,A-8055Graz

Austria

This medicinal product is authorised in the Member States of the EEA with the following names

Last update of the summary of product characteristics:August 2017

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

-----------------------------------------------------------------------------------------------------------------------

This information is intended solely for medical professionals or healthcare professionals:

How to prepare and administer Zoledronic Acid Kabi

• To prepare the infusion solution containing 4 mg of zoledronic acid, the concentrate of Zoledronic Acid Kabi (5.0 ml) must 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 must be removed first as indicated below and then diluted with 100 ml of infusion solution. To avoid possible incompatibilities, the infusion solution used for dilution must be sodium chloride 0.9% w/v or glucose 5% w/v solution.

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

Instructions for preparing lower doses of Zoledronic Acid Kabi:

Remove the appropriate volume from 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 only. Any unused portion of the solution must be discarded. Only transparent, particle-free and colourless solutions should be used. During the preparation of the infusion, aseptic techniques must be used.

• Shelf life after dilution:chemical and physical stability has been demonstrated in use for 24 hours between 2°C and 8°C.From a microbiological point of view, the diluted infusion solution must be used immediately. If not used immediately, the time and conditions of storage during use before administration are the responsibility of the user and should not exceed 24 hours at 2°C–8°C. The solution stored in the refrigerator must 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 must be evaluated to ensure they are adequately hydrated.

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

• Since there are no available data on the compatibility of Zoledronic Acid Kabi with other substances administered intravenously, Zoledronic Acid Kabi must not be mixed with other medicinal products/substances and must 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 shown on the container.
• The unopened vial does not require special storage conditions.
• For storage conditions after dilution, see “Shelf life after dilution”.