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

Introduction

Package Leaflet: Information for the User

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

Read all of 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 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 pack

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

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

The active substance in Zoledronic Acid Altan 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, e.g. fractures, in adult patients with bone metastases (cancer spread from the primary site to the bone).
• 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 are given Zoledronic Acid Altan

Follow carefully all instructions given to you by your doctor.

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

Do not use Zoledronic Acid Altan:

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

Warnings and precautions

Before using this medicine, talk to your doctor:

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

While being treated with zoledronic acid, 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 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. 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 receiving the first dose of zoledronic acid. You will be given adequate calcium and vitamin D supplements.

People over 65 years

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

Use in children and adolescents

Zoledronic Acid Altan is not recommended for use in adolescents and children under 18 years.

Other medicines and Zoledronic Acid Altan

Tell your doctor or pharmacist if you are using, have recently used, or might use 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.
• Other medicines that also contain zoledronic acid and are used to treat osteoporosis and other non-cancerous bone diseases, or any other bisphosphonate, as the combined effects of these medicines given with zoledronic acid are unknown.
• Anti-angiogenic medicines (used to treat cancer), as the combination of these medicines with Zometa has been associated with a higher risk of osteonecrosis of the jaw (ONJ).

Pregnancy and breast-feeding

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

Zoledronic Acid Altan must not be given to you if you are breast-feeding.

Ask your doctor or pharmacist for advice before taking any medicine if you are pregnant or breast-feeding.

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 Altan contains sodium (as sodium citrate).

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

3. How Zoledronic Acid Altan is given.

• This medicine should only be administered by healthcare professionals experienced in the administration of intravenous bisphosphonates, i.e., administered into 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 to you by your doctor, pharmacist, or nurse.

How much Zoledronic Acid Altan is given

• The usual single dose administered is 4 mg.
• If you have a kidney problem, your doctor will give you a lower dose depending on the severity of your kidney problem.

How often Zoledronic Acid Altan is given

• If you are being treated to prevent bone complications due to bone metastases, you will be given a zoledronic acid infusion every 3 to 4 weeks.
• If you are being treated to reduce the amount of calcium in the blood, you will usually only be given a single zoledronic acid infusion.

How Zoledronic Acid Altan is given

• This medicine is given as a drip (infusion) into a vein that should last at least 15 minutes and should be administered as a single intravenous infusion 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 Altan than you should

If you have received more than the recommended dose, you should be closely monitored by your doctor. This is because you may develop changes in the levels of certain substances in the blood (e.g., abnormal levels of calcium, phosphorus, and magnesium) and/or changes in kidney function, including severe kidney failure. If the level of calcium becomes too low, you may need to be given a calcium supplement by infusion.

4. Possible side effects

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

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

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

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

Uncommon (may affect up to 1 in 100 people):

• 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 Altan 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 inform your doctor if you experience these symptoms after receiving zoledronic acid.
• Severe allergic reaction: difficulty breathing, swelling, especially of the face and throat.

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

• Due to low calcium levels: irregular heart rhythm (cardiac arrhythmia; secondary to hypocalcemia).

• A condition affecting kidney function called Fanconi syndrome (usually detected by your doctor with a urine test).

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

• Due to low calcium levels: seizures, numbness, and tetany (secondary to hypocalcemia).
• Tell your doctor if you have ear pain, ear discharge, or suffer from an ear infection. These could be symptoms of damage to the bones of the ear.
• Osteonecrosis has also been rarely observed in other bones besides the jaw, especially in the hip or thigh. Inform your doctor immediately if you experience symptoms such as new or worsening pain, pain, or stiffness while receiving treatment with zoledronic acid or after stopping treatment.

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

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Tell your doctor as soon as possible if you experience any of the following side effects:

Very common (may affect more than 1 in 10 people):

• Low level of phosphates in the blood.

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

• Headache and flu-like symptoms 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 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 level of red blood cells in the blood (anemia).

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, difficulty breathing, dizziness, anxiety, sleep disturbances, taste disturbances, tremors, tingling, or numbness of the hands or feet, diarrhea, constipation, abdominal pain, dry mouth.
• Decreased number of white blood cells and platelets.
• Low level of magnesium and potassium in the blood. Your doctor will monitor and take any necessary measures.
• Weight gain
• Increased sweating
• Numbness.
• Blurred vision, tearing of the eyes, sensitivity of the eyes to light.
• Sudden cooling with fainting, weakness, or collapse.
• Difficulty breathing with wheezing or coughing.
• Hives.

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

• Decreased heart rate.
• Confusion.
• Atypical fractures of the femur (thigh bone) that can occur rarely, especially in patients on prolonged treatment for osteoporosis. Inform 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 of the eye and/or swelling.

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

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

Reporting of suspected adverse reactions:

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Spanish Pharmacovigilance System for human use medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Zoledronic Acid Altan.

Keep this medicine out of the sight and reach of children.

Your doctor, nurse, or pharmacist knows how to store this medicine properly (see section 6).

6. Container Content and Additional Information

Composition of Zoledronic Acid Altan

• The active ingredient is zoledronic acid. One vial contains 4 mg of zoledronic acid equivalent to 4.264 mg of zoledronic acid monohydrate
• The other components are: mannitol (E-421), sodium citrate (E-331), water for injectable preparations.

Appearance of Zoledronic Acid Altan and Container Content

It is supplied as a clear and colorless liquid concentrate in a vial. One vial contains 4 mg of zoledronic acid.

Each container contains the vial of concentrate. Zoledronic Acid Altan is supplied in containers that contain 1 vial.

Marketing Authorization Holder and Manufacturer

Marketing authorization holder:

Altan Pharmaceuticals, S.A.

C/Cólquide Nº 6, Portal 2, 1ª Planta – Oficina F, Edificio Prisma

28230 Las Rozas (Madrid)

Spain

Manufacturer

Altan Pharmaceuticals, S.A.

Polígono Industrial de Bernedo, s/n

01118 Bernedo (Álava)

Spain

Altan Pharmaceuticals, S.A.

Avda. de la Constitución, 198-199,

Polígono Industrial Monte Boyal,

Casarrubios del Monte, 45950 Toledo

Date of the last revision of this prospectus: 09/2024

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

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INFORMATION FOR THE HEALTHCARE PROFESSIONAL

How to Prepare and Administer Zoledronic Acid Altan

• To prepare the infusion solution containing 4 mg of zoledronic acid, Zoledronic Acid Altan 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 is required, the appropriate volume should be withdrawn as indicated below and then diluted with 100 ml of infusion solution. To avoid possible 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 Altan concentrate with solutions containing calcium or other divalent cations, such as lactated Ringer's solution.

Instructions for preparing lower doses of zoledronic acid:

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.
• From a microbiological point of view, the diluted infusion solution should 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 under normal conditions. The refrigerated solution should reach room temperature before administration.
• The solution containing zoledronic acid is administered as a single intravenous infusion over 15 minutes. Before and after the administration of zoledronic acid, the patient's hydration status should be assessed to ensure they are adequately hydrated.
• Studies with various types of infusion lines made of polyvinyl chloride, polyethylene, and polypropylene did not show incompatibility with zoledronic acid.
• Since there are no data available on the compatibility of zoledronic acid with other substances administered intravenously, Zoledronic Acid should not be mixed with other medications/substances and should always be administered through a separate infusion line.

How to Store Zoledronic Acid Altan

Keep this medication out of the reach and sight of children.

• Do not use this medication after the expiration date stated on the container after CAD.
• The unopened vial does not require special storage conditions.
• The diluted infusion solution of zoledronic acid should be used immediately to avoid microbial contamination.