Zoledronic Acid Noridem

PATIENT INFORMATION LEAFLET

Leaflet attached to the packaging: information for the user

Zoledronic Acid Noridem; 4 mg/5 mL, concentrate for solution for infusion

zoledronic acid

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor, pharmacist, or nurse.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should inform their doctor, pharmacist, or nurse. See section 4.

The name of the medicine is Zoledronic Acid Noridem.

In the rest of this leaflet, Zoledronic Acid Noridem 4 mg/5 mL concentrate for solution for infusion is referred to as Zoledronic Acid.
Table of contents of the leaflet:

• 1. What is Zoledronic Acid and what is it used for
• 2. Important information before using Zoledronic Acid
• 3. How to use Zoledronic Acid
• 4. Possible side effects
• 5. How to store Zoledronic Acid
• 6. Contents of the pack and other information

1. What is Zoledronic Acid and what is it used for

The active substance in Zoledronic Acid is zoledronic acid, which belongs to a group of medicines called bisphosphonates. Zoledronic acid works by binding to bone tissue and slowing down the rate of bone change. It is used:

• to prevent bone complications,e.g. fractures in adult patients with bone metastases (cancer spread from the original site to the bone);
• to reduce calcium levels in the bloodof adult patients, in cases where the level is increased due to the presence of cancer. Cancers can accelerate bone turnover, causing increased release of calcium from bone. This condition is called cancer-related hypercalcemia.

2. Important information before using Zoledronic Acid

Follow all the doctor's instructions.
The doctor will prescribe blood tests before starting Zoledronic Acid and will check the response to treatment at regular intervals.

Do not use Zoledronic Acid:

• if the patient is breastfeeding;
• if the patient is allergic to zoledronic acid, other bisphosphonates (a group of medicines to which Zoledronic Acid belongs), or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Before using Zoledronic Acid, discuss with your doctor:

• if the patient has or has had kidney problems;
• if the patient has or has had mouth, tooth, or jaw pain, swelling or numbness,a feeling of heaviness in the jaw, or loosening of teeth; The doctor may recommend that the patient undergo a dental examination before starting treatment with Zoledronic Acid.
• if the patient is undergoing dental treatmentor is going to undergo jaw surgery; the patient should inform their dentist about taking Zoledronic Acid and inform their doctor about the dental treatment.

During treatment with Zoledronic Acid, maintain good oral hygiene (including regular toothbrushing) and attend regular check-ups.
Immediately consult the doctor and dentist if the patient experiences any mouth or tooth problems, such as loose teeth, pain or swelling, non-healing sores or discharge, as these may be signs of a condition called jawbone necrosis.
Patient who are undergoing chemotherapy and (or) radiotherapy, who are taking corticosteroids, who are undergoing jaw surgery, who do not receive regular dental care, who have gum disease, who smoke, or who have taken bisphosphonates (for the treatment or prevention of bone disorders) may have a higher risk of developing jawbone necrosis.
Patients receiving Zoledronic Acid have reported low calcium levels in the blood (hypocalcemia), sometimes causing muscle cramps, dry skin, and a burning sensation. There have been reports of irregular heartbeat (arrhythmia), seizures, and muscle spasms (tetany) due to severe hypocalcemia. In some cases, hypocalcemia can be life-threatening. If any of these situations apply to the patient, they should immediately inform their doctor. If the patient has hypocalcemia, it should be corrected before taking the first dose of Zoledronic Acid. The patient will receive appropriate calcium and vitamin D supplements.

Patient over 65 years of age

Zoledronic Acid can be used in patients over 65 years of age. There is no need for additional warnings in this patient group.

Children and adolescents

Zoledronic Acid should not be used in children and adolescents under 18 years of age.

Zoledronic Acid and other medicines

Tell the doctor about all medicines the patient is taking or has recently taken, as well as any medicines the patient plans to take. It is especially important to inform the doctor about taking:

• aminoglycoside antibiotics(medicines used to treat severe infections), calcitonin (a medicine used to treat postmenopausal osteoporosis and hypercalcemia), loop diuretics (medicines used to treat high blood pressure and swelling) and other medicines that lower calcium levels, as using them in combination with bisphosphonates may cause excessive lowering of calcium levels in the blood;
• thalidomide(a medicine used to treat certain blood cancers with bone involvement) or other medicines that may be harmful to the kidneys;
• other products containing zoledronic acid(sometimes used to treat osteoporosis and other non-cancerous bone diseases), or other bisphosphonates, as the combined effects of these medicines taken with Zoledronic Acid are not known;
• anti-angiogenic medicines (used to treat cancer), as taking them with Zoledronic Acid has been associated with an increased risk of jawbone necrosis (ONJ).

Pregnancy and breastfeeding

Zoledronic Acid should not be used during pregnancy. Inform the doctor if the patient is pregnant or suspects pregnancy.
Zoledronic Acid should not be used in breastfeeding women.
Before taking any medicine, consult a doctor if the patient is pregnant or breastfeeding.

Driving and using machines

Very rare cases of drowsiness have been reported with Zoledronic Acid. Therefore, caution should be exercised when driving, operating machinery, and performing other activities that require focused attention.

Zoledronic Acid contains sodium

One mL of the concentrate for solution for infusion contains 1.13 mg of sodium in the form of sodium citrate.
The medicine contains less than 1 mmol (23 mg) of sodium per vial, i.e. the medicine is considered "sodium-free".

3. How to use Zoledronic Acid

• Zoledronic Acid should only be administered by healthcare professionals with appropriate training in the intravenous administration of bisphosphonates (i.e. administration of bisphosphonates into a vein).
• The doctor will recommend drinking an adequate amount of water before each administration of Zoledronic Acid to prevent dehydration.
• Follow all other instructions from the doctor, pharmacist, or nurse.

What dose of Zoledronic Acid is used

• The single dose of Zoledronic Acid is 4 mg.
• If the patient has kidney problems, the doctor will prescribe a lower dose of Zoledronic Acid, depending on the severity of the kidney disease.

How often is Zoledronic Acid used

• In the case of preventing bone complications caused by bone metastases, one infusion of Zoledronic Acid is administered every three to four weeks.
• In the case of treatment aimed at reducing calcium levels in the blood, usually only one infusion of Zoledronic Acid is administered.

How to use Zoledronic Acid

• Zoledronic Acid is administered as a drip infusion (infusion) into a vein. The infusion should last at least 15 minutes and should be administered as a separate intravenous solution through a separate infusion line.

Patient with calcium levels in the blood that are not too high will be prescribed calcium and vitamin D by the doctor for daily intake.

Using a higher dose of Zoledronic Acid than recommended

Patient who have been given higher doses of Zoledronic Acid than recommended should be closely monitored. This is necessary due to the possibility of abnormal electrolyte levels in the serum (e.g. calcium, phosphorus, and magnesium) and/or changes in kidney function, including severe kidney problems. Patients with low calcium levels may require an additional calcium infusion.

4. Possible side effects

Like all medicines, Zoledronic Acid can cause side effects, although not everybody gets them. The most common side effects are usually mild and will probably disappear within a short time.

Immediately inform the doctor about the following side effects:

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

• Severe kidney problems (usually detected by the doctor based on specific blood tests).
• Low calcium levels in the blood.

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

• Mouth pain, tooth pain, or jaw pain, swelling or non-healing sores in the mouth or jaw, discharge, numbness or a feeling of heaviness in the jaw, or loosening of teeth. These may be symptoms of jawbone damage (necrosis). If such symptoms occur, immediately inform the doctor or dentist during or after treatment with Zoledronic Acid.
• In patients with postmenopausal osteoporosis treated with zoledronic acid, irregular heartbeat (atrial fibrillation) has been observed. It is not known whether zoledronic acid causes irregular heartbeat, but the doctor should be informed if such symptoms occur after taking zoledronic acid.
• Severe allergic reactions: shortness of breath, swelling mainly of the face and throat.

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

• As a result of low calcium levels: irregular heartbeat (arrhythmia; secondary to hypocalcemia).
• Kidney problems called Fanconi syndrome (confirmed by the doctor after performing specific urine tests).

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

• As a result of low calcium levels: seizures, numbness, and muscle spasms (tetany; secondary to hypocalcemia).
• If the patient experiences ear pain, ear discharge, and/or ear infection, they should inform their doctor. These may be symptoms of bone damage in the ear.
• Very rarely, necrosis of bones other than the jaw, especially the hip and thigh, has been observed. Immediately inform the doctor if symptoms such as pain or stiffness occur during or after treatment with Zoledronic Acid.

Unknown (frequency cannot be estimated from the available data):

• Kidney inflammation (interstitial nephritis): subjective and objective symptoms may include decreased urine output, blood in the urine, nausea, general malaise.

Immediately

inform
the doctor
about
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 including fever, fatigue, weakness, drowsiness, chills, and pain in the bones, joints, and/or muscles. In most cases, no special treatment is required, and the symptoms disappear within a short time (a few hours or days);
• Gastrointestinal symptoms such as nausea and vomiting, and 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 injection site, rash, itching;
• High blood pressure, shallow breathing, dizziness, anxiety, sleep disturbances, taste disorders, tremors, tingling, and numbness of hands or feet, diarrhea, constipation, abdominal pain, dry mouth;
• Low white blood cell and platelet count;
• Low magnesium and potassium levels in the blood. The doctor will monitor this and prescribe necessary tests
• Weight gain;
• Increased sweating;
• Drowsiness;
• Blurred vision, tearing, eye sensitivity to light;
• Sudden feeling of coldness with fainting, weakness, or collapse;
• Breathing difficulties, with wheezing and coughing;
• Hives.

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

• Slow heartbeat;
• Confusion;
• In rare cases, atypical fractures of the thigh bone, especially in patients treated for osteoporosis for a long time. The doctor should be consulted if pain, weakness, or discomfort occurs in the thigh, hip, or groin area, as this may already indicate a risk of thigh bone fracture.
• Interstitial lung disease (inflammation of the tissue surrounding the air sacs in the lungs).
• Flu-like symptoms, including joint and muscle pain
• Painful redness and/or swelling of the eye.

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

• Fainting due to low blood pressure;
• Severe pain in the bones, joints, and/or muscles, sometimes causing immobilization;
• Partial redness (without pain) of the white part of the eye.

Reporting side effects

If side effects occur, including any side effects not listed in the leaflet, inform the doctor, pharmacist, or nurse.
Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products,
Jerozolimskie Avenue 181C
02-222 Warsaw
tel.: + 48 22 49 21 301
fax: + 48 22 49 21 309
e-mail: ndl@urpl.gov.pl. By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Zoledronic Acid

The doctor, pharmacist, or nurse are informed about how to store Zoledronic Acid (see section 6).

6. Contents of the pack and other information

What Zoledronic Acid contains

• The active substance is zoledronic acid. One vial contains 4 mg of zoledronic acid, and each milliliter corresponds to 1.13 mg of sodium
• The other ingredients of the medicine are: mannitol (E421), sodium citrate (E331), and water for injections.

What Zoledronic Acid looks like and what the pack contains

Zoledronic Acid is a clear, colorless solution without visible particles.
One plastic or glass vial with 5 mL of concentrate contains 4 mg of zoledronic acid (anhydrous).
One milliliter of the concentrate for solution for infusion contains 1.13 mg of sodium in the form of sodium citrate.
Each pack contains a plastic or glass vial with concentrate. Zoledronic Acid is supplied in packs containing 1, 4, or 10 vials.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder:Noridem Enterprises Ltd., Evagorou & Makariou, Mitsi Building
3, Suite 115, CY-1065 Nicosia, Cyprus.
Manufacturer:DEMO S.A. Pharmaceutical Industry, 21 km National Road Athens-Lamia, GR-
145 68 Krioneri, Athens, Greece.

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

UK: Zoledronic Acid 4 mg/5 mL Concentrate for Solution for Infusion
IE: Zoledronic Acid 4 mg/5 mL Concentrate for Solution for Infusion
AT: Zoledronsäure Noridem 4 mg/5 mL Konzentrat zur Herstellung einer Infusionslösung
DE: Zoledronsäure Noridem 4 mg/5 mL Konzentrat zur Herstellung einer Infusionslösung
ES: Ácido Zoledrónico Kern Pharma 4 mg/5mL concentrado para solución para perfusión EFG
PL: Zoledronic Acid Noridem
EL: ZOXALON 4 mg/5 mL πυκνό διάλυμα για παρασκευή διαλύματος προς έγχυση

Date of last revision of the leaflet: 07/2024.

Information intended for healthcare professionals only

Preparation and administration of Zoledronic Acid

• To prepare a solution for infusion containing 4 mg of zoledronic acid, the Zoledronic Acid concentrate (5.0 mL) should be diluted in 100 mL of infusion solution without calcium or other solution without divalent cations. If a lower dose is required, the appropriate volume of the preparation should be withdrawn as instructed below and then diluted in 100 mL of infusion solution. To avoid potential incompatibilities, 0.9% m/v sodium chloride solution or 5% m/v glucose solution should be used for dilution.

Zoledronic Acid solution should not be mixed with solutions containing calcium or other divalent cations, e.g. Ringer's solution with lactate.

Method of preparation of reduced doses of Zoledronic Acid:
Withdraw the appropriate volume of concentrate, according to the prescribed dose:

• 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 solution should be discarded. Only clear solutions without precipitated particles and discoloration should be used. During preparation of the infusion, aseptic principles should be followed.
• From a microbiological point of view, the diluted infusion solution should be administered immediately. If the medicinal product is not used immediately, the responsibility for the storage conditions and duration before use lies with the user, and the solution is stable for no longer than 24 hours at 2°C - 8°C. Before administration, the refrigerated solution should be allowed to reach room temperature.
• The zoledronic acid solution is administered as a 15-minute intravenous infusion through a separate infusion line. The patient's hydration status should be assessed before each administration of Zoledronic Acid to ensure adequate hydration.
• Studies using glass bottles, several types of infusion bags, and infusion lines made of polyvinyl chloride, polyethylene, and polypropylene have not shown any incompatibility with Zoledronic Acid.
• Since there are no data on the compatibility of Zoledronic Acid with other intravenously administered medicines, it should not be mixed with other preparations. The Zoledronic Acid solution should always be administered in a separate infusion set.

Storage of Zoledronic Acid

• The medicine should be stored out of the reach and sight of children.
• Do not use Zoledronic Acid after the expiry date stated on the packaging.
• No special precautions for storage of unopened vials are necessary.
• The diluted Zoledronic Acid solution should be used immediately to avoid microbial contamination.