Label: Information for the Patient

Zoledronic Acid Altan 4 mg/100 ml Solution for Infusion EFG

Read this label carefully before this medicine is administered to you, as it contains important information for you.

• Keep this label, 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 label. See section 4.

The active ingredient of this medication is 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 all the instructions given by your doctor carefully.

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

Zoledronic Acid Altan 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 Altan belongs), or to any of the other components of this medication (listed in section 6).

Warnings and precautions

Consult your doctoror pharmacistbeforestarting to useZoledronic Acid Altan:

• if you have or have had akidney problem.

• if you have or have hadjaw pain, swelling, or numbness, or a feeling of heaviness in the jaw or a loose tooth. Your doctor may recommend that you undergo a dental examination before starting treatment with zoledronic acid.
• if you are receivingdental treatmentor are about 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 medication, 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 not 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) have been described in patients who have received zoledronic acid, which may manifest as muscle cramps, dry skin, and a burning sensation. Severe hypocalcemia has been associated with irregular heart rhythm (arrhythmia), convulsions, spasms, and involuntary muscle contractions (tetany). In some cases, hypocalcemia may be potentially fatal. If you experience any of these conditions, inform your doctor immediately. If you have a pre-existing hypocalcemia, it should be corrected before receiving the first dose of zoledronic acid. You will be provided with adequate calcium and vitamin D supplements.

Patients 65 years and older

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

Other medications and Zoledronic Acid Altan

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

Pregnancy and lactation

Zoledronic acid should not be administered if you are pregnant. Inform your doctor if you are or think you may be pregnant.

Zoledronic acid should not be administered if you are breastfeeding.

Consult your doctor before using any medication if you are pregnant or during the lactation period.

Driving and operating machinery

In rare cases, drowsiness and dizziness have been observed with the use of zoledronic acid. Therefore, you should exercise caution when driving, operating machinery, or performing other activities that require close attention.

Zoledronic Acid Altan contains sodium

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

• Zoledronic acid should 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 amount of Zoledronic Acid Altan 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 Altan administered

• If you are being treated for the prevention of bone complications due to bone metastases, you will be administered a Zoledronic Acid Altan infusion 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 one infusion of Zoledronic Acid Altan.

How Zoledronic Acid Altan is administered

• Zoledronic Acid Altan is administered as an infusion (infusion) 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 high levels of calcium in the blood will also be prescribed calcium and vitamin D supplements to take every day.

If you are administered more Zoledronic Acid Altan 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 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 your doctor or pharmacist immediately or call the Toxicological Information Service, phone 91 562 04 20.

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.

Infrequent (may affect up to 1 in 100 patients):

• Pain in the mouth, teeth, and/or jaw, swelling or difficulty in healing of sores inside the mouth or jaw, secretion, 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 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 mainly 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 known as 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, the ear is discharging, or you have an ear infection. These could be signs of bone damage in the ear.
• Osteonecrosis has also been observed rarely in other bones apart from the jaw, especially in 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 not known: cannot be estimated from available data:

• Renal inflammation (tubulointerstitial nephritis): symptoms and signs may include reduced urine volume, blood in the urine, nausea, general feeling of discomfort.

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 will 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.
• Low red blood cell count in the blood (anemia).

Infrequent (may affect up to 1 in 100 patients):

• Hypersensitivity reactions.
• Low blood pressure.
• Chest pain.
• Reactions on the skin (redness and swelling) at the infusion 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 magnesium and potassium levels in the blood. Your doctor will monitor and take any necessary measures.
• Weight gain.
• Increased sweating.
• Numbness.
• Blurred vision, tearing in the 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 fractures of the femur (thigh bone) that may occur in rare cases, especially in patients undergoing 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 femur fracture.
• Pulmonary interstitial disease (inflammation of the tissue surrounding the lung air sacs).
• 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):

• Fainting 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 effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report them directly through the Spanish System for the Vigilance of Medicinal Products for Human Use (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 store this medication properly (see section 6).

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date that appears on the package. The expiration date is the last day of the month indicated.

Do not store above 86°F (30°C)

Composition of Zoledronic Acid Altan

• The active ingredient is zoledronic acid. Each 100 ml solution bag contains 4 mg of zoledronic acid, equivalent to 4.265 mg of zoledronic acid monohydrate.
• 1 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 contents of the package

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

It is presented as a single unit package containing a bag or as multiple packages consisting of 4 or 5 bags.

Only some package sizes may be commercially available.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

ALTAN PHARMACEUTICALS, S.A.

C/Cólquide, Nº 6, Portal 2, 1ª Planta,

Office F. Edificio Prisma, Las Rozas,

28230 Madrid

Spain

Responsible for manufacturing

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 with 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

Last review date of this leaflet:09/2024

The detailed information of this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (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 perfusion solution for immediate use in patients with normal renal function.
• 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.
• From a microbiological point of view, the perfusion solution should be used immediately after the first opening. 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, except that the dilution is performed in controlled and validated aseptic conditions. The solution stored in the refrigerator 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 through a separate infusion line. Before and after administration of zoledronic acid, the hydration status of patients should be evaluated 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 insufficiency, reduced doses should be prepared as detailed below.

To prepare reduced doses for patients with a baseline CLcr ≤ 60 ml/min, see Table 1 below. Extract the indicated volume of zoledronic acid solution and replace it with an equal volume of sterile 0.9% sodium chloride injection or 5% glucose injection.

Table 1: Preparation of reduced doses of Zoledronic Acid Altan

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

• Studies conducted with different types of infusion lines (chloroprene, polyethylene, and polypropylene) did not reveal any incompatibility with Zoledronic Acid Altan.
• Since there are no available data on the compatibility of zoledronic acid with other substances administered intravenously, this medicinal product should not be mixed with other medications/substances and should 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 expiration date appearing on the package.
• Do not store at a temperature above 30°C.
• After opening the bag, the product should be used immediately to avoid microbial contamination.