Zoledronic Acid Normon 4 mg/100 ml Solution for Infusion

Introduction

Package Leaflet: Information for the User

Zoledronic AcidNormon4 mg/100 ml solution for infusion EFG

Read all of this leaflet carefully before you start taking 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 or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

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

The active substance of this medicine 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:

??Preventbone complications, e.g. fractures, in adult patients with bone metastases (spread of cancer from the original 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 bone. This condition is known as tumor-induced hypercalcemia (TIH).

2. What you need to know before you take Zoledronic Acid Normon

Follow carefully all instructions given by your doctor.

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

Zoledronic Acid Normon must not be given to you

??if you are breast-feeding.

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

Warnings and precautions

Tell your doctor before Zoledronic Acid Normon is given to you:

??if you have or have had a kidney problem.

??if you have or have had 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 Normon.

??if you are receiving dental treatmentor are going to undergo dental surgery, inform your dentist that you are being treated with Zoledronic Acid Normon and inform your doctor about your dental treatment.

While being treated with Zoledronic Acid Normon, 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, 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 greater risk of developing osteonecrosis of the jaw.

Reduced levels of calcium in the blood (hypocalcemia) have been described, sometimes manifesting as 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 reported. In some cases, hypocalcemia may be 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. You will be given adequate calcium and vitamin D supplements.

Patients aged 65 and over

Zoledronic acid can be given to people aged 65 and over. There is no evidence to suggest that extra precautions are needed.

Children and adolescents

The use of this medicine is not recommended in adolescents and children under 18 years.

Other medicines and Zoledronic Acid Normon

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 may reduce calcium levels in the blood too much.

??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 Normon are unknown.

??Anti-angiogenic medicines (used to treat cancer), as the combination of these medicines with zoledronic acid has been associated with a higher risk of osteonecrosis of the jaw (ONJ).

Pregnancy and breast-feeding

Zoledronic acid must not be given to you if you are pregnant. Tell your doctor if you are or think you may be pregnant.

Zoledronic acid 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 Normon contains sodium

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

3. How to take Zoledronic Acid Normon

??This medicine should only be given 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, pharmacist, or nurse.

How much Zoledronic Acid Normon is given

??The usual single dose given 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 is Zoledronic Acid Normon 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 one zoledronic acid infusion.

How Zoledronic Acid Normon is given

??The medicine is given as a drip (infusion) in a vein that should last at least 15 minutes and should be given 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 Normon 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 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, it may be necessary to give you 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 period of 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 Normon or after stopping treatment.

??Irregular heart rhythm (atrial fibrillation) has been observed in patients treated with zoledronic acid for postmenopausal osteoporosis. It is not known 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, particularly of the face and throat.

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

??As a result of 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):

??As a result of low calcium levels: seizures, numbness, and tetany (secondary to hypocalcemia).

• Tell your doctor if you have ear pain, discharge from the ear, or an ear infection. These could be symptoms of damage to the bones of the ear.
• Very rare cases of osteonecrosis have also been reported in bones other than the jaw, especially in the hip or thigh. Tell your doctor immediately if you have symptoms such as new or increasing pain, swelling, or stiffness while being treated with Zoledronic Acid Normon 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 (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 the 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 disorders, 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 this and take any necessary measures.

??Weight gain.

??Increased sweating.

??Drowsiness.

??Blurred vision, tearing, sensitivity of the eyes to light.

??Sudden drop in blood pressure 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 thigh bone (femur) 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 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 the bones, joints, and/or muscles, occasionally debilitating.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is not listed in this leaflet. You can also report side effects directly via the Spanish Medicines Monitoring System for Human Use: 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 Normon

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

After opening the bag, the product should be used immediately to avoid microbial contamination. If not used immediately, the storage time and conditions before use are the responsibility of the handler and should not exceed 24 hours at 2°C - 8°C. Allow the refrigerated solution to reach room temperature before administration.

6. Container Contents and Additional Information

Zoledronic Acid Composition Normon

The active ingredient is zoledronic acid. One bag contains 4 mg of zoledronic acid, equivalent to 4.26 mg of zoledronic acid monohydrate.

The other components are mannitol (E-421), sodium citrate (E-331), and water for injectable preparations.

Product Appearance and Container Contents

Zoledronic Acid Normon is supplied as a clear and colorless solution. It is presented in 100 ml bags prepared for use in perfusion.

Zoledronic Acid Normon is supplied in containers containing one bag as a single unit.

Marketing Authorization Holder and Manufacturer

LABORATORIOS NORMON, S.A.

Ronda de Valdecarrizo, 6 – 28760 Tres Cantos – Madrid (SPAIN)

Date of Last Revision of this Leaflet: May 2025

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

INFORMATION FOR HEALTHCARE PROFESSIONALS

This information is intended only for healthcare professionals:

How to Prepare and Administer Zoledronic Acid Normon

Zoledronic Acid Normon 4 mg/100 ml solution for perfusion contains 4 mg of zoledronic acid in 100 ml of solution for perfusion for immediate use in patients with normal renal function.

For single use only. 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 perfusion preparation.

From a microbiological point of view, the solution for perfusion should be used immediately after the first opening. If not used immediately, the storage time and conditions before administration are the responsibility of the user and should not exceed 24 hours at 2°C - 8°C under normal conditions, unless the dilution is performed under controlled and validated aseptic conditions. The refrigerated solution should reach room temperature before administration.

The solution containing zoledronic acid should not be diluted or mixed with other perfusion solutions. It is administered as a single intravenous perfusion over 15 minutes in a separate perfusion line. Before and after the administration of Zoledronic Acid Normon, the patient's hydration status should be assessed to ensure they are adequately hydrated.

Zoledronic Acid Normon 4 mg/100 ml solution for perfusion can be used immediately without requiring additional dilution in patients with normal renal function. In patients with mild to moderate renal impairment, reduced doses should be prepared as detailed below.

To prepare reduced doses for patients with a baseline CLcr ≤ 60 ml/min, refer to Table 1 below. Extract the indicated volume of Zoledronic Acid Normon solution from the bag before administration.

Table 1:Preparation of Reduced Doses of Zoledronic Acid Normon 4 mg/100 ml Solution for Perfusion

*The doses have been calculated assuming a target AUC of 0.66 (mg•hr/l) (CLcr = 75 ml/min). It is expected that the reduced doses for patients with renal impairment will achieve the same AUC as that observed in patients with creatinine clearance of 75 ml/min.

Studies conducted with different polyvinyl chloride, polyethylene, and polypropylene perfusion lines did not reveal any incompatibility with zoledronic acid.

Since there are no data available on the compatibility of zoledronic acid with other substances administered intravenously, Zoledronic Acid Normon should not be mixed with other medications/substances and should always be administered through a separate perfusion line.

How to Store Zoledronic Acid Normon

• Keep this medication out of sight and reach of children.
• Do not use this medication after the expiration date stated on the container after CAD.
• The unopened bag does not require any special storage conditions. Store in the original container.
• After opening the bag, the product should be used immediately to avoid microbial contamination. If not used immediately, the storage times and conditions before use are the responsibility of the user and should not normally exceed 24 hours at 2°C - 8°C. The solution, if refrigerated, should reach room temperature before administration.