Zoledronic acid Altan 4 mg/5 ml concentrate for solution for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Zoledronic Acid Altan 4 mg/5 ml concentrate for solution for infusion EFG

Read all of this 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 get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What zoledronic acid Altan is and what it is used for

The active substance in Zoledronic Acid Altan is zoledronic acid, which belongs to a group of substances called bisphosphonates. Zoledronic acid works by binding to bone 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 level 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 calcium release 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 this medicine, to another bisphosphonate (a group of substances to which zoledronic acid belongs), or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Before using this medicine, consult your doctor:

• if you have or have had kidney problems.
• if you have or have had pain, swelling, or numbness in the jaw, a feeling of heaviness in the jaw, or if a tooth becomes loose. Your doctor may recommend a dental examination before starting treatment with zoledronic acid.
• if you are undergoing dental treatment or are scheduled for 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 zoledronic acid, 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 not receiving routine dental care, those with gum disease, smokers, or those previously treated 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 or contractions (tetany) secondary to severe hypocalcemia have also been reported. In some cases, hypocalcemia may be potentially life-threatening. If you experience any of these symptoms, inform your doctor immediately. If you have a history of hypocalcemia, it must be corrected before receiving your first dose of zoledronic acid. You will be provided with appropriate calcium and vitamin D supplements.

Patients aged 65 years and older

Zoledronic Acid Altan may be administered to patients aged 65 years and older. There is no evidence suggesting that additional precautions are required.

Use in children and adolescents

The use of Zoledronic Acid Altan is not recommended in adolescents and children under 18 years of age.

Other medicines and Zoledronic Acid Altan

Inform your doctor or pharmacist 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.
• Other medicines containing zoledronic acid used to treat osteoporosis and other non-cancerous bone diseases, or any other bisphosphonate, as the combined effects of these medicines when administered together with zoledronic acid are unknown.
• Antiangiogenic medicines (used to treat cancer), as the combination of these medicines with Zometa has been associated with an increased risk of osteonecrosis of the jaw (ONJ).

Pregnancy and breastfeeding

Zoledronic Acid Altan must not be given to you if you are pregnant. Inform your doctor if you are or think you may be pregnant.

Zoledronic Acid Altan must not be given to you 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 high concentration.

Zoledronic Acid Altan contains sodium (as sodium citrate).

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

3. How to use Zoledronic Acid Altan

• This medicine should only be administered by healthcare professionals experienced in the administration of intravenous bisphosphonates, i.e., medicines given directly into the vein.

• Your doctor will advise you to drink an adequate amount of fluid before each treatment to help prevent dehydration.

• Carefully follow all other instructions provided 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 impairment.

How often Zoledronic Acid Altan is given

• If you are being treated to prevent bone complications due to bone metastases, you will receive a zoledronic acid 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 zoledronic acid infusion.

How Zoledronic Acid Altan is given

• This medicine is administered as an intravenous infusion (drip) lasting no less than 15 minutes and must be given as a single intravenous solution through a separate infusion line.

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

If you are given more Zoledronic Acid Altan than you should have

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 require calcium supplementation administered by infusion.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them. The most common ones are usually 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 impairment (this will normally be 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 of sores in the mouth or jaw, discharge, numbness or a sensation of 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 Altan 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 (this will normally be 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.
• Osteonecrosis in bones other than the jaw has also been rarely observed, especially in the hip or thigh. Inform your doctor immediately if you experience symptoms such as new or worsening pain, discomfort, 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 volume, blood in the urine, nausea, and feeling generally unwell.

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

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

• Low levels of phosphate in the blood.

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

• 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 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 in the hands or feet, diarrhea, constipation, abdominal pain, dry mouth.
• Decrease in the 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, light sensitivity.
• Sudden cooling with fainting, weakness, or collapse.
• Difficulty breathing with wheezing or coughing.
• Urticaria (hives).

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

• 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 your thigh, hip, or groin, as these may be early symptoms indicating a possible femoral fracture.
• Interstitial lung disease (inflammation of the tissue surrounding the air sacs in the lungs).
• Flu-like symptoms including joint pain (arthritis) and joint swelling.
• Painful eye redness and/or swelling.

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

• Fainting due to low blood pressure.
• Severe bone, joint, and/or muscle pain, occasionally disabling.

Reporting suspected adverse reactions:

If you experience any type of adverse effect, please consult your doctor, pharmacist, or nurse, and report it through the Spanish Pharmacovigilance System for Human Medicinal Products: https://www.notificaram.es. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. Storage of Zoledronic Acid Altan.

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

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

6. Package contents and other information

Composition of Zoledronic Acid Altan

• The active substance is zoledronic acid. One vial contains 4 mg of zoledronic acid, equivalent to 4.264 mg of zoledronic acid monohydrate.
• The other components are: mannitol (E-421), sodium citrate (E-331), water for injections.

Appearance of Zoledronic Acid Altan and contents of the pack

Supplied as a clear, colourless liquid concentrate in a vial. One vial contains 4 mg of zoledronic acid.

Each pack contains one vial of concentrate. Zoledronic Acid Altan is supplied in packs containing 1 vial.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Altan Pharmaceuticals, S.A.
C/Cólquide No. 6, Portal 2, 1st Floor – Office F, Edificio Prisma
28231 Las Rozas (Madrid)
Spain

Manufacturer:

Altan Pharmaceuticals, S.A.
Polígono Industrial de Bernedo, s/n
01118 Bernedo (Álava)
Spain

Altan Pharmaceuticals, S.A.
Avda. de la Constitución, 198-199,
Polígono Industrial Monte Boyal,
Casarrubios del Monte, 45950 Toledo
Spain

Date of the most recent revision of this package leaflet: 09/2024

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

INFORMATION FOR HEALTHCARE PROFESSIONALS

How to prepare and administer Zoledronic Acid Altan

• To prepare an infusion solution containing 4 mg of zoledronic acid, dilute Zoledronic Acid Altan concentrate (5.0 ml) with 100 ml of infusion solution free of calcium or other divalent cations. If a lower dose of zoledronic acid is required, first withdraw the appropriate volume as indicated below and then dilute it with 100 ml of infusion solution. To avoid potential incompatibilities, the infusion solution used for dilution must be 0.9% w/v sodium chloride or 5% w/v glucose solution.

Do not mix Zoledronic Acid Altan concentrate with solutions containing calcium or other divalent cations, such as lactated Ringer's solution.

Instructions for preparing lower doses of zoledronic acid:

Withdraw the appropriate volume of liquid concentrate as follows:

• 4.4 ml for a 3.5 mg dose

• 4.1 ml for a 3.3 mg dose

• 3.8 ml for a 3.0 mg dose

• For single use only. Any unused portion of the solution must be discarded. Only use solutions that are clear, particle-free, and colourless. Aseptic techniques must be used during preparation of the infusion.

• From a microbiological standpoint, the diluted infusion solution should be used immediately. If not used immediately, the user is responsible for ensuring storage conditions and duration prior to administration, which under normal circumstances must 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 15-minute intravenous infusion. Before and after administration of zoledronic acid, the patient's hydration status should be assessed to ensure adequate hydration.

• Studies using various types of infusion sets made of polyvinyl chloride, polyethylene, and polypropylene showed no incompatibility with zoledronic acid.

• Since compatibility data with other intravenously administered substances are not available, Zoledronic Acid should not be mixed with other medicinal products/substances and must always be administered via 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 packaging after EXP.
• The unopened vial does not require special storage conditions.
• The diluted infusion solution of zoledronic acid should be used immediately to avoid microbial contamination.