Zoledronic acid Altan 4 mg/100 ml solution for infusion EFG

Package Leaflet: Information for the User

Introduction

Package leaflet: information for the patient

Zoledronic Acid Altan 4 mg/100 ml solution for infusion EFG

Read the entire 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 questions, ask your doctor, pharmacist, or nurse.
• If you experience any adverse reactions, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.

Leaflet Contents

1. What Zoledronic Acid Altan is and what it is used for
2. What you need to know before using Zoledronic Acid Altan
3. How to use Zoledronic Acid Altan
4. Possible side effects
5. How to store 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 of this medicine is zoledronic acid, which belongs to a group of substances called bisphosphonates. Zoledronic acid works by binding to bones and slowing down bone turnover. It is used for:

• Preventing bone complications, e.g. fractures, in adult patients with bone metastases (spread of cancer from the primary site to bone)

• Reducing the amount of calcium in the blood in adult patients in whom it is too high due to the presence of a tumour. Tumours can accelerate normal bone turnover so that release of calcium from bone is increased. This condition is known as tumour-induced hypercalcaemia (TIH).

2. What you need to know before using Zoledronic Acid Altan

Carefully follow all instructions given to you by your doctor.

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

Do not use Zoledronic Acid Altan:

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

Warnings and precautions

Talk to your doctor or pharmacist before using Zoledronic Acid Altan:

• if you have or have had a kidney problem.

• if you have or have had pain, swelling, or numbness in the jaw, a feeling of heaviness in the jaw, or if your teeth become loose. Your doctor may recommend that you undergo a dental examination before starting treatment with zoledronic acid.

• if you are receiving dental treatment or are scheduled 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 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 receiving chemotherapy and/or radiotherapy, those taking corticosteroids, those undergoing dental surgery, those who do not receive routine dental care, those with gum disease, smokers, or those who have not previously received treatment with a bisphosphonate (used to treat or prevent bone disorders) may have an increased risk of developing osteonecrosis of the jaw.

Reduced levels of calcium in the blood (hypocalcemia) have been reported, which may sometimes manifest as muscle cramps, dry skin, and a burning sensation in patients treated with zoledronic acid. Irregular heart rhythm (cardiac arrhythmia), seizures, and involuntary muscle spasms and contractions (tetany) secondary to severe hypocalcemia have also been reported. In some cases, hypocalcemia may be potentially life-threatening. If you have any of the conditions described, inform your doctor immediately. If you have a history of hypocalcemia, it must be corrected before receiving the first dose of zoledronic acid. You will be given appropriate calcium and vitamin D supplements.

Patients aged 65 years and older

Zoledronic acid can be administered to individuals aged 65 years and older. There is no evidence suggesting that additional precautions are required.

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

Inform your doctor if you are taking, have recently taken, or might need to take any other medicines. It is especially important that you inform your doctor if you are also taking:

• Aminoglycosides (medicines used to treat serious 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 combining these with bisphosphonates may markedly reduce blood calcium concentration.
• Thalidomide (a medicine used to treat a type of bone-affecting blood cancer) 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, since the combined effects of these medicines when administered with zoledronic acid are unknown.
• Antiangiogenic medicines (used to treat cancer), as the combination of these medicines with zoledronic acid has been associated with an increased risk of osteonecrosis of the jaw (ONJ).

Pregnancy and breastfeeding

You must not be given zoledronic acid if you are pregnant. Inform your doctor if you are or think you might be pregnant.

You must not be given zoledronic acid if you are breastfeeding.

Consult your doctor before using any medicine if you are pregnant or breastfeeding.

Driving and using machines

Very rarely, drowsiness and numbness have been observed with the use of zoledronic acid. Therefore, you should exercise caution when driving, operating machinery, or performing other activities requiring full attention.

Zoledronic Acid Altan contains sodium

This medicine contains less than 23 mg (1 mmol) of sodium per dose and is therefore considered essentially “sodium-free.”

3. How to use Zoledronic Acid Altan

• Zoledronic acid should only be administered by healthcare professionals experienced in the administration of intravenous bisphosphonates, i.e., drugs given into a vein.
• Your doctor will recommend that you drink an adequate amount of water before each treatment to help prevent dehydration.
• Carefully follow all other instructions given by your doctor, pharmacist, or nurse.

How much 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 depending on the severity of your kidney problem.

How often Zoledronic Acid Altan is administered

• If you are being treated to prevent bone complications due to bone metastases, you will receive a Zoledronic Acid Altan infusion every three to four weeks.
• If you are being treated to reduce high levels of calcium in the blood, you will usually receive only one infusion of Zoledronic Acid Altan.

How Zoledronic Acid Altan is administered

• Zoledronic Acid Altan is administered as an intravenous drip (infusion) lasting at least 15 minutes and must be given as a single intravenous solution through a separate infusion line.

Patients who do not have high blood calcium levels will also be prescribed daily calcium and vitamin D supplements to take.

If you are given 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 serum electrolyte disturbances (e.g., abnormal levels of calcium, phosphate, and magnesium in the blood) and/or changes in kidney function, including severe renal failure. If calcium levels become too low, you may need to receive calcium supplementation via infusion.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them. The most common ones are generally mild and may disappear after a short period of time.

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

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

• Severe kidney problems (usually detected by your doctor through a specific blood test).
• Low calcium levels in the blood.

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

• Pain in the mouth, teeth and/or jaw, swelling or difficulty healing sores in the mouth or jaw, discharge, numbness or a sensation of heaviness in the jaw, or tooth loss. These may be signs of damage to the jaw bone (osteonecrosis). Inform your doctor and dentist immediately if you experience these symptoms while being treated with zoledronic acid or after stopping treatment.
• 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 such 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 disorder known as Fanconi syndrome (usually detected by your doctor through 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, ear discharge, or an ear infection. These could be symptoms of damage to the ear bones.
• Rare cases of osteonecrosis in bones other than the jaw, especially in the hip or thigh, have also been reported. Inform your doctor immediately if you experience symptoms such as new or worsening discomfort, pain, or stiffness while receiving zoledronic acid treatment or after stopping treatment.

Frequency not known: cannot be estimated from available data:

• Kidney inflammation (tubulointerstitial nephritis): signs and symptoms may include reduced urine volume, blood in the urine, nausea, and general malaise.

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

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

• Low levels of phosphate in the blood.

Common (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 resolve 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 patients):

• Hypersensitivity reactions.
• Low blood pressure.
• Chest pain.
• Reactions at the infusion site (redness and swelling), rash, itching.
• High blood pressure, difficulty breathing, dizziness, anxiety, sleep disorders, taste disturbances, tremors, tingling or numbness in hands or feet, diarrhea, constipation, abdominal pain, dry mouth.
• Decreased number of white blood cells and platelets.
• Low levels of magnesium and potassium in the blood. Your doctor will monitor this and take any necessary measures.
• Weight gain.
• Increased sweating.
• Numbness.
• Blurred vision, watery eyes, sensitivity of the eyes to light.
• Sudden collapse with fainting, weakness, or collapse.
• Difficulty breathing with wheezing or coughing.
• Hives.

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

• Slowed heart rate.
• Confusion.
• Atypical femoral fractures (thigh bone fractures) which may occur rarely, especially in patients on long-term 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 indicating a possible femoral fracture.
• Interstitial lung disease (inflammation of the tissue surrounding the air sacs in the lungs).
• Flu-like symptoms including arthritis and joint swelling.
• 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 disabling.

Reporting of adverse effects

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines (www.notificaRAM.es). By reporting adverse 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 properly store this medicine (see section 6).

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

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

Do not store above 30°C.

6. Package contents and other information

Composition of Zoledronic Acid Altan

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

Appearance of the product and contents of the pack

Clear, colourless solution contained in a transparent, colourless bag.

It is available as a single pack containing one bag or as multiple packs containing 4 or 5 bags.

Only certain pack 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. Edificio Prisma, 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 European Economic Area member states 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 most recent revision of this leaflet: 09/2024

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

INFORMATION FOR HEALTHCARE PROFESSIONALS

How to prepare and administer Zoledronic Acid Altan

• Zoledronic Acid Altan contains 4 mg of zoledronic acid in 100 ml of ready-to-use infusion solution for patients with normal renal function.
• For single use only. Any unused portion of the solution must be discarded. Only solutions that are clear, particle-free, and colourless should be used. Aseptic techniques must be used during the preparation of the infusion.
• From a microbiological standpoint, the infusion solution should be used immediately after first opening. If not used immediately, the time and storage conditions prior to administration are the user's responsibility and, under normal conditions, should not exceed 24 hours at 2°C – 8°C, unless dilution is performed under controlled and validated aseptic conditions. The refrigerated solution must reach room temperature before administration.
• The solution containing zoledronic acid must not be diluted or mixed with other infusion solutions. It is administered as a single intravenous infusion over 15 minutes via a separate infusion line. Before and after administration of zoledronic acid, the patient's hydration status should be assessed to ensure adequate hydration.
• This medicine can be used immediately without requiring additional dilution in patients with normal renal function. In patients with mild to moderate renal impairment, reduced doses must be prepared as detailed below.

To prepare reduced doses for patients with a baseline CrCl ≤ 60 ml/min, refer to Table 1 below. Remove 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

| Baseline CrCl (ml/min) | Volume of Zoledronic Acid Solution to be removed (ml) | Replacement Volume (ml) of 0.9% Sodium Chloride or 5% Glucose Solution | Final Volume (ml) | Final Concentration of Zoledronic Acid (mg/100 ml) | |------------------------|--------------------------------------------------------|------------------------------------------------------------------------|-------------------|--------------------------------------------------| | 40 – 60 | 25 | 25 | 100 | 3 | | 35 – <40 | 38 | 38 | 100 | 2.5 | | 30 – <35 | 50 | 50 | 100 | 2 | | 25 – <30 | 63 | 63 | 100 | 1.5 | | 20 – <25 | 75 | 75 | 100 | 1 |

*Doses have been calculated assuming an AUC target of 0.66 (mg•hr/L) (CLcr = 75 ml/min). Reduced doses for patients with renal impairment are expected to achieve the same AUC as that observed in patients with a creatinine clearance of 75 ml/min.

• Studies conducted using different infusion lines made of polyvinyl chloride, polyethylene, and polypropylene showed no incompatibility with Zoledronic Acid Altan.
• Since compatibility data of zoledronic acid with other intravenously administered substances are not available, this medicinal product must not be mixed with other medicines/substances and should always be administered through a separate infusion line.

How to store Zoledronic Acid Altan

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine 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.