Product Information for the Patient

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

Zoledronic Acid

Read this entire product information carefully before you receive this medication, as it contains important information for you.

???????Keep this product information, as you may need to read it again.

?If you have any questions, consult your doctor, pharmacist, or nurse.

?If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this product information. See section 4.

1. What is Zoledronic Acid Tillomed and how is it used

2. What you need to know before receiving Zoledronic Acid Tillomed

3. How to use Zoledronic Acid Tillomed

4. Possible adverse effects

5. Storage of Zoledronic Acid Tillomed

6. Contents of the package and additional information

The active ingredient ofZoledronic Acid Tillomedis 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, e.g. fractures, in adult patients with bone metastases (spread of cancer from the primary site to the bone)
• Reducing 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 in such a way that the release of calcium from the bone is increased. 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 Tillomed and will monitor your response to treatment at regular intervals.

Zoledronic Acid Tillomed should not be administered:

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

Warnings and precautions

Consult your doctor before Zoledronic Acid Tillomed is administered:

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 if a tooth has moved. Your doctor may recommend that you undergo a dental examination before starting treatment with Zoledronic Acid Tillomed.

if you are receiving dental treatment or are about to undergo dental surgery, inform your dentist that you are being treated with Zoledronic Acid Tillomed and inform your doctor about your dental treatment.

While being treated with Zoledronic Acid Tillomed, 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), which may manifest with muscle cramps, dry skin, and a burning sensation in patients who have received Zoledronic Acid Tillomed, have been described. Severe hypocalcemia has been associated with irregular heart rhythm (cardiac arrhythmia), convulsions, spasms, and involuntary muscle contractions (tetany). In some cases, hypocalcemia may be potentially fatal. If you have any of the conditions described, inform your doctor immediately. If you have a pre-existing hypocalcemia, it should be corrected before receiving the first dose of Zoledronic Acid Tillomed. You will be provided with adequate calcium and vitamin D supplements.

Patients 65 years and older

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

Children and adolescents

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

Use of Zoledronic Acid Tillomed with other medications

Inform your doctor if you are using, have used recently, or may need to use 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 decrease 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.

Aclasta (a medication that also contains zoledronic acid and is used to treat osteoporosis and other non-cancerous bone disorders), or any other bisphosphonate, as the combined effects of these medications administered with Zoledronic Acid Tillomed are unknown.

Anti-angiogenic medications (used to treat cancer), as the combination of these medications with Zoledronic Acid Tillomed has been associated with a higher risk of osteonecrosis of the jaw (ONJ).

Pregnancy and lactation

Zoledronic Acid Tillomed should not be administered if you are pregnant or breastfeeding. If you are pregnant or breastfeeding, or if you think you may be pregnant or plan to become pregnant, consult your doctor before receiving this medication.

Driving and operating machinery

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

Zoledronic Acid Tillomed contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per 5 ml of Zoledronic Acid Tillomed, i.e., it is essentially "sodium-free". If your doctor uses a saline solution to dilute Zoledronic Acid Tillomed, the sodium dose you receive would be higher.

Zoledronic Acid Tillomedshould only be administered by experienced healthcare professionals in the administration of intravenous bisphosphonates, i.e., administered through 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, pharmacist, or nurse carefully.

What dose of Zoledronic Acid Tillomed is administered

??The usual single dose administered is 4 mg.

?If you have a kidney problem, your doctor will give you a lower dose based on the severity of your kidney problem.

How often is Zoledronic Acid Tillomed administered

??If you are being treated for the prevention of bone complications due to bone metastases, you will be administered a perfusion of Zoledronic Acid Tillomed every three to four weeks.

?If you are being treated to reduce the amount of calcium in the blood, you will usually only be administered a perfusion of Zoledronic Acid Tillomed.

How is Zoledronic Acid Tillomed administered

??Zoledronic Acid Tillomed is administered as an infusion (perfusion) through a vein that must last at least 15 minutes and must be administered as a single intravenous solution in a separate infusion line.

Patients who do not have excessively high levels of calcium in the blood will also be prescribed calcium and vitamin D supplements to take every day.

If more Zoledronic Acid Tillomed is administered than recommended

If you have received doses higher than recommended, you must be closely monitored by your doctor. This is because you may develop abnormal serum electrolyte levels (e.g., abnormal levels of calcium, phosphorus, and magnesium in the blood) and/or changes in kidney function, including severe renal insufficiency. If the calcium level becomes too low, you may need to be administered a calcium supplement through an infusion.

In case of overdose or accidental ingestion, consult the Toxicology Service, phone: (91) 5620420, indicating the medication and the amount ingested.

Carry the medication packaging with you.

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

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 (may affect up to 1 in 10 patients):

?Severe kidney impairment (usually determined by your doctor with a specific blood test).

?Low calcium levels in the blood.

Less frequent (may affect up to 1 in 100 patients):

?Pain in the mouth, teeth, and/or jaw, swelling or difficulty healing of 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 Tillomed 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, especially of the face and throat.

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

?As a consequence of low calcium levels: irregular heart rhythm (cardiac arrhythmia; secondary to hypocalcemia).

?A kidney function alteration 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).

?Consult your doctor if you have ear pain, discharge from the ear, or a ear infection. These may be signs of bone damage in the ear.

??Osteonecrosis has also been observed in rare cases in other bones, such as 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 or after stopping treatment.

Frequency unknown: cannot be estimated from available data

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

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

Very frequent (may affect more than 1 in 10 patients):

?Low phosphate levels in the blood.

Frequent (may affect up to 1 in 10 patients):

?Headache and flu-like syndrome consisting of fever, fatigue, weakness, drowsiness, chills, and bone, joint, and/or muscle pain. In most cases, no specific treatment is required, and symptoms 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.

?Anemia (low red blood cell count in the blood).

Less frequent (may affect up to 1 in 100 patients):

?Hypersensitivity reactions.

?Low blood pressure.

?Chest pain.

?Skin reactions (redness and swelling) at the injection 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 levels of magnesium and potassium in the blood. Your doctor will monitor and take any necessary measures.

?Weight gain.

?Increased sweating.

?Numbness.

?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 femoral fractures, which may occur in rare cases, especially in patients receiving 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 femoral fracture.

?Pulmonary interstitial disease (inflammation of the tissue surrounding the air sacs of the lungs).

?Symptoms similar to the flu, including arthritis and joint swelling.

?Red, painful eye and/or swelling.

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

?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, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Vigilance of Medicines for Human Use:https://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 conserve Zoledronic Acid Tillomed properly (see section 6). Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging/container after "CAD". The expiration date is the last day of that month.

After dilution: chemical and physical stability has been demonstrated for use over 24 hours between 2°C - 8°C and at room temperature (20 -25°C).

From a microbiological point of view, the diluted solution for infusion should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and should not exceed 24 hours at 2°C - 8°C. The refrigerated solution should reach room temperature before administration.

Composition of Zoledronic Acid Tillomed

• The active ingredient is zoledronic acid. A vial contains 4 mg of zoledronic acid, equivalent to 4.264 mg of zoledronic acid monohydrate. One ml of concentrate contains zoledronic acid (as monohydrate of zoledronic acid 0.8 mg (anhydrous)
• The other components are: mannitol (E421), sodium citrate (E331), water for injectable preparations.

Aspect of the product and content of the packaging

Zoledronic acid Tillomed issupplied as a liquid concentrate in a vial. A vial contains 4 mg of zoledronic acid.

Each package contains the ampoule with the concentrate. Zoledronic acid is supplied in packages that contain 1, 4 or 10 vials. It may not be all commercialized.

Holder of the marketing authorization and responsible for the manufacture

Holder of the marketing authorization

Responsible for the manufacture1

MIAS Pharma Limited

Suite 2, Stafford House, Strand Road

Portmarnock, Co. Dublin

Ireland

SGS Pharma Magyarorszag Kft.

Derkovits Gyula Utca 53,

Budapest XIX, 1193,

Hungary

Tillomed Malta Limited

Malta Life Sciences Park

LS2.01.06 Industrial Estate,

San Gwann, SGN 3000, Malta

[1]Only the center that actually performs the release will be indicated in the commercialized product.

This medicinal product is authorized in the Member States of the European Economic Area with the following names:

Last review date of this leaflet: October 2024

INFORMATION FOR THE HEALTHCARE PROFESSIONAL

The information is intended solely for doctors or healthcare professionals (see section 3):

How to prepare and administer Zoledronic Acid Tillomed

??To prepare the infusion solution containing 4 mg of zoledronic acid, you must diluteZoledronic Acid Tillomedconcentrate (5.0 ml) with 100 ml of infusion solution free of calcium or other divalent cations.If a lower dose ofZoledronic Acid Tillomedis required, remove the appropriate volume first as indicated below and dilute it subsequently 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.

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

Instructions for preparing lower doses of Zoledronic Acid Tillomed:

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

-After dilution:stability has been demonstratedchemically and physically in usefor 24 hours between 2°C - 8°C and at room temperature (20 -25°C).

• From a microbiological point of view, the diluted infusion solution must be used immediately. If not used immediately, the time and storage conditions during its use before administration are the responsibility of the user and should not exceed 24 hours at 2°C – 8°C. The refrigerated solution must reach room temperature before administration.

• The solution containing zoledronic acid is administered as a single intravenous infusion over 15 minutes through a separate infusion line. Before and after administration of Zoledronic Acid Tillomed, the hydration status of patients should be evaluated to ensure they are adequately hydrated.

• Since there are no data available on the compatibility ofZoledronic Acid Tillomedwith other substances administered intravenously,Zoledronic Acid Tillomedshould not be mixed with other medications/substances and should be administered always through a separate infusion line.

How to store Zoledronic Acid Tillomed

• KeepZoledronic Acid Tillomedout of the reach and sight of children.
• Do not useZoledronic Acid Tillomedafter the expiry date appearing on the packaging.
• The unopened vial does not require special storage conditions.

The diluted infusion solution ofZoledronic Acid Tillomedshould be used immediately to avoid microbial contamination.