Zoledronic Acid Altan 4 mg/100 ml Solution for Infusion

2. What you need to know before you are given Zoledronic Acid Altan

Follow carefully all instructions given 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.

Zoledronic Acid Altan 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 Altan belongs), or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Tell your doctoror pharmacistbeforeyou are givenZoledronic Acid Altan:

• 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.
• if you are receiving dental treatmentor 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 this medicine, 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 not 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. An 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 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 necessary.

Children and adolescents

The use of zoledronic acid is not recommended in adolescents and children under 18 years of age.

Other medicines and Zoledronic Acid Altan

Tell your doctor 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.
• Talidomide (a medicine used to treat a type of blood cancer that affects the bone) or any other medicine that may harm the kidneys.
• Aclasta (a medicine that also contains zoledronic acid and is 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 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, drowsiness and somnolence 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

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

3. How Zoledronic Acid Altan is given

• Zoledronic acid should only be administered 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 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 Altan infusion every 3 to 4 weeks.
• If you are being treated to reduce the amount of calcium in the blood, you will normally only be given a single Zoledronic Acid Altan infusion.

How Zoledronic Acid Altan is given

• Zoledronic Acid Altan 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 Altan than you should

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

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, telephone 91 562 04 20.

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 calcium levels 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 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 tell 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 change in 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, discharge from the ear, or 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. Tell your doctor immediately if you have 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:

• Kidney inflammation (tubulointerstitial nephritis): signs and symptoms may include reduced urine output, 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 phosphate levels in the blood.

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

• Headache and flu-like symptoms consisting of fever, fatigue, weakness, somnolence, 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 red blood cell count (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 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.
• Numbness.
• Blurred vision, tearing, 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 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 bones, joints, and/or muscles, occasionally incapacitating.

Reporting of side effects

If you experience any side effects, tell your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Monitoring System for Human Use (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

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

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

Do not use this medicine after the expiry date that appears on the bag. The expiry date is the last day of the month indicated.

Do not store above 30°C

6. Container Contents and Additional Information

Composition of Zoledronic Acid Altan

• The active ingredient is zoledronic acid. Each 100 ml bag of solution contains 4 mg of zoledronic acid, equivalent to 4.265 mg of zoledronic acid monohydrate.
• One ml of solution contains 0.04 mg of zoledronic acid.
• The other components are: mannitol (E421), sodium citrate (E331), water for injectable preparations, hydrochloric acid and/or sodium hydroxide (for pH adjustment).

Appearance of the Product and Container Contents

Clear and colorless solution packaged in a clear and colorless bag.

It is presented as a single-unit container containing one bag or as multiple containers formed by 4 or 5 bags.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

ALTAN PHARMACEUTICALS, S.A.

C/Cólquide, No. 6, Portal 2, 1st Floor,

Office F, Prisma Building, Las Rozas,

28230 Madrid

Spain

Manufacturer

ALTAN PHARMACEUTICALS, S.A.

Polígono Industrial de Bernedo, s/n

01118 Bernedo (Álava)

Spain

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

Germany: Zoledronsäure Altan 4 mg/100 ml Infusionslösung

Belgium: Zoledroninezuur Altan 4 mg/100 ml oplossing voor infusie

Spain: Ácido Zoledrónico Altan 4 mg/100 ml solución para perfusión EFG

France: ACIDE ZOLEDRONIQUE ALTAN 4 mg/100 mL, solution pour perfusion

Italy: Acido zoledronico Altan Pharma 4 mg/100 ml soluzione per infusion

Portugal: Ácido Zoledrónico Altan 4 mg/100 ml Solução para perfusão

United Kingdom: Zoledronic Acid Altan 4 mg/100 ml solution for infusion

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

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

INFORMATION FOR THE HEALTHCARE PROFESSIONAL

How to Prepare and Administer Zoledronic Acid Altan

• Zoledronic Acid Altan contains 4 mg of zoledronic acid in 100 ml of solution for infusion for immediate use in patients with normal renal function.
• For single use. Any unused part 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 solution for infusion 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 infusion solutions. It is administered as a single intravenous infusion over 15 minutes in a separate infusion line. Before and after the administration of zoledronic acid, the patient's hydration status should be assessed to ensure they are adequately hydrated.
• This medicinal product 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 creatinine clearance ≤ 60 ml/min, see Table 1 below. Extract the indicated volume of zoledronic acid solution and replace it with an equal volume of sterile 9 mg/ml (0.9%) sodium chloride injection solution or 5% glucose injection solution.

Table 1: Preparation of Reduced Doses of Zoledronic Acid Altan

*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 a creatinine clearance of 75 ml/min.

• Studies conducted with different polyvinyl chloride, polyethylene, and polypropylene infusion lines did not reveal any incompatibility with Zoledronic Acid Altan.
• Since there are no data available on the compatibility of zoledronic acid with other substances administered intravenously, this medicinal product should not be mixed with other medicinal products/substances and should always be administered through a separate infusion line.

How to Store Zoledronic Acid Altan

• Keep this medicinal product out of the sight and reach of children.
• Do not use this medicinal product after the expiry date stated on the container.
• Do not store above 30°C.
• After opening the bag, the product should be used immediately to avoid microbial contamination.