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

Package leaflet: Information for the user

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 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.

Leaflet contents

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

2. What you need to know before you use Zoledronic Acid Kabi

3. How to use Zoledronic Acid Kabi

4. Possible side effects

5. How to store Zoledronic Acid Kabi

6. Contents of the pack and other information

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

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

• To prevent bone complications, such as fractures, in adult patients with bone metastases (spread of cancer from its original site to the bone)
• To reduce the level of calcium in the blood in adult patients when it is too high due to the presence of a tumour. Tumours can accelerate normal bone remodelling, leading to increased release of calcium from bone. This condition is known as tumour-induced hypercalcaemia (TIH).

2. What you need to know before starting to take Zoledronic Acid Kabi

Carefully follow all instructions given to you 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 must not be given if you:

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

Warnings and precautions

Talk to your doctor before starting to use Zoledronic Acid Kabi if:

• you have or have had a kidney problem
• you have or have had pain, swelling or numbness in the jaw, a feeling of heaviness in the jaw, or loose teeth. Your doctor may recommend that you have a dental examination before starting treatment with Zoledronic Acid Kabi.
• you are receiving dental treatment or are scheduled 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 should 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, taking corticosteroids, undergoing dental surgery, not receiving routine dental care, have gum disease, are smokers, or have previously received treatment with a bisphosphonate (used to treat or prevent bone disorders) may have an increased risk of developing osteonecrosis of the jaw.

Reduced levels of calcium in the blood (hypocalcemia) have been reported, which sometimes present as muscle cramps, dry skin, and a burning sensation in patients treated with zoledronic acid. Irregular heart rhythm (cardiac arrhythmia), seizures, and involuntary muscle spasms and contractions (tetany) secondary to severe hypocalcemia have also been reported. In some cases, hypocalcemia may be potentially life-threatening. If you experience any of these conditions, inform your doctor immediately. If you have a history of hypocalcemia, it must be corrected before receiving the first dose of Zoledronic Acid Kabi. You will be provided with appropriate calcium and vitamin D supplements.

Patients aged 65 years and older

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

Children and adolescents

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

Use of Zoledronic Acid Kabi with other medicines

Inform your doctor if you are taking, have recently taken, or might need to take any other medicines. It is especially important to 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 or edema), or other medicines that lower calcium levels, as combining these with bisphosphonates may markedly reduce blood calcium concentration.
• Thalidomide (a medicine used to treat a type of bone cancer), or any other medicine that may harm the kidneys.
• Other medicines containing zoledronic acid used to treat osteoporosis and other non-cancerous bone diseases, or any other bisphosphonate, as the combined effects of these medicines when administered together with zoledronic acid are unknown.
• Antiangiogenic 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 breastfeeding

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

You must not be given Zoledronic Acid Kabi if you are breastfeeding.

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

Driving and use of machines

Somnolence and numbness have been observed very rarely with the use of zoledronic acid. Therefore, you should be cautious when driving, operating machinery, or performing other activities requiring high attention.

Zoledronic Acid Kabi contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose, and is therefore considered essentially “sodium-free”.

3. How to use Zoledronic Acid Kabi

Zoledronic Acid Kabi must only be administered by healthcare professionals experienced in the administration of intravenous bisphosphonates, that is, administered into the vein.

Your doctor will advise you to drink an adequate amount of water before each treatment to help prevent dehydration.

Carefully follow all other instructions given by your doctor, nurse, or pharmacist.

What dose of Zoledronic Acid Kabi is administered

• The recommended single dose is 4 mg.

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

How often Zoledronic Acid Kabi is administered

• If you are being treated to prevent bone complications due to bone metastases, you will receive a Zoledronic Acid Kabi infusion every three or four weeks.

• If you are being treated to reduce high levels of calcium in the blood, you will usually receive only one Zoledronic Acid Kabi infusion.

How Zoledronic Acid Kabi is administered

Zoledronic Acid Kabi is administered as an intravenous drip (infusion) lasting at least 20 minutes and must be given as a single intravenous solution through a separate infusion line.

Patients who do not have excessively high blood calcium levels will also be prescribed daily calcium and vitamin D supplements to take.

If you are given more Zoledronic Acid Kabi than you should

If you have received doses higher than recommended, you must be closely monitored by your doctor. This is because you may develop serum electrolyte disturbances (e.g. abnormal levels of calcium, phosphate, and magnesium in the blood) and/or changes in kidney function, including severe renal failure. If calcium levels become too low, you may require calcium supplementation administered by infusion.

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

4. Possible adverse effects

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

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

Frequent (affect less than 1 in 10 patients)

• Severe kidney impairment (this is usually detected by your doctor through a specific blood test).
• Low blood calcium levels.

Uncommon (affect less than 1 in 100 patients)

• Pain in the mouth, teeth and/or jaw, swelling or difficulty healing sores in 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 jaw bone (osteonecrosis). Inform your doctor and dentist immediately if you experience these symptoms while being treated with Zoledronic Acid Kabi or after treatment has ended.
• 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 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 consequence of low calcium levels: irregular heartbeat (cardiac arrhythmia, secondary to hypocalcemia).
• A kidney function disorder called Fanconi syndrome (this is usually detected by your doctor through 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).
• Inform your doctor if you have ear pain, ear discharge, and/or an ear infection. These could be signs of bone damage in the ear.
• Rare cases of osteonecrosis in bones other than the jaw, particularly in the hip or thigh, have also been reported. Inform your doctor immediately if you experience symptoms such as new or worsening 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, and a general feeling of discomfort.

Inform your doctor as soon as possible if you experience any of the following adverse effects:

Very common (affects less than 1 in 10 patients)

• Low levels of phosphate 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 bones, joints, and/or muscles. In most cases, no specific treatment is required, and symptoms resolve after a short period (a few hours or days).
• Gastrointestinal reactions such as nausea and vomiting, as well as loss of appetite.
• Conjunctivitis.
• Low levels of red blood cells in the blood (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 in the hands or feet, diarrhea, constipation, abdominal pain, dry mouth.
• Decrease in the number of white blood cells and platelets.
• Low levels of magnesium and potassium in the blood. Your doctor will monitor this and take any necessary measures.
• Weight gain.
• Increased sweating.
• Drowsiness.
• Blurred vision, watery eyes, sensitivity of the eyes to light.
• Sudden cooling with fainting, weakness, or collapse.
• Breathing difficulty with wheezing or cough.
• Urticaria.

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

• Decreased heart rate.
• Confusion.
• Atypical femoral fractures (thigh bone) which may rarely occur, especially in patients undergoing long-term treatment for osteoporosis. Inform your doctor if you notice pain, weakness, or discomfort in the thigh, hip, or groin, as these may be early symptoms indicating a possible femoral fracture.
• Interstitial lung disease (inflammation of the tissue surrounding the air sacs in the lungs).
• Flu-like symptoms including arthritis and joint swelling.
• 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 bones, joints and/or muscles, occasionally disabling.

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor or pharmacist, even if it is a possible adverse reaction not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines at: www.notificaRAM.es

By reporting adverse reactions, 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 properly store Zoledronic Acid Kabi (see section 6).

6. Contents of the pack and other information

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 injections.

Appearance of the product and pack contents

Zoledronic Acid Kabi is supplied as a solution in a clear, colourless plastic vial.

Zoledronic Acid Kabi 5 ml vials are available in pack sizes 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 EEA Member States under the following names

Date of the most recent review of this summary: August 2024

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/.

This information is intended solely for 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) should be diluted with 100 ml of an infusion solution free of calcium or other divalent cations. If a lower dose of Zoledronic Acid Kabi is required, first withdraw the appropriate volume as indicated below and then dilute it with 100 ml of infusion solution. To avoid potential incompatibilities, the infusion solution used for dilution must be either 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 from the liquid concentrate as follows:

• 4.4 ml for a 3.5 mg dose

• 4.1 ml for a 3.3 mg dose

• 3.8 ml for a 3.0 mg dose

• For single use only. Any unused portion of the solution must be discarded. Only clear, particle-free, and colorless solutions should be used. Aseptic techniques must be used during the preparation of the infusion.

• Shelf life after dilution: Chemical and physical in-use stability has been demonstrated for 24 hours between 2°C and 8°C. From a microbiological standpoint, the diluted infusion solution should be used immediately. If not used immediately, the time and conditions of storage prior to administration are the responsibility of the user and, under normal circumstances, 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 20-minute intravenous infusion through a separate infusion line. Before and after administration of Zoledronic Acid Kabi, the patient's hydration status should be assessed to ensure adequate hydration.

• Studies using glass vials, as well as various types of containers made of polyvinyl chloride, polyethylene, and polypropylene (pre-filled with 0.9% w/v sodium chloride solution or 5% w/v glucose solution), showed no 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 always be administered through a separate infusion line.

How to store Zoledronic Acid 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 special storage conditions.
• For storage conditions after dilution, see “Shelf life after dilution”.