Zoledronic acid noridem

Package leaflet: Information for the user

Zoledronic Acid Noridem; 4 mg/5 mL, concentrate for solution for infusion
acidum zoledronicum
Please read all of this leaflet carefully before this medicine is administered because it
contains important information for you.

• Keep this leaflet as you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

The name of this medicine is Zoledronic Acid Noridem.
In the remainder of this leaflet, Zoledronic Acid Noridem 4 mg/5 mL concentrate for
infusion solution will be referred to as Zoledronic Acid.
Leaflet contents:

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

1. What Zoledronic Acid is and what it is 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 turnover. It is used:

• to prevent skeletal complications, such as fractures in adult patients with bone metastases (spread of cancer from its original site to the bones);
• to reduce calcium levels in the blood of adult patients when the calcium level is elevated due to cancer. Tumours may accelerate bone turnover, causing increased release of calcium from bone. This condition is known as tumour-induced hypercalcaemia (TIH).

2. Important information before using Zoledronic Acid

Follow all your doctor's instructions carefully.
Your doctor will order blood tests before starting treatment with Zoledronic Acid and will monitor your response to treatment at regular intervals.

Do not use Zoledronic Acid:

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

Warnings and precautions

Talk to your doctor before using Zoledronic Acid:

• 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 loose teeth; your doctor may recommend that you see a dentist before starting treatment with Zoledronic Acid;
• if you are currently undergoing dental treatment or are planning to have jaw surgery; in such cases, inform your dentist that you are taking Zoledronic Acid and inform your doctor about any dental treatment.

While being treated with Zoledronic Acid, maintain proper oral hygiene (including regular tooth brushing) and attend routine dental check-ups.
Contact your doctor and dentist immediately if you experience any symptoms in the mouth or teeth, such as loose teeth, pain or swelling, failure of a wound to heal, or discharge, as these may be signs of a condition called osteonecrosis of the jaw.
Patients undergoing chemotherapy and/or radiotherapy, those taking corticosteroids, those undergoing dental surgery, those who do not receive routine dental care, those with gum disease, those who use tobacco, or those who have previously taken bisphosphonates (for the treatment or prevention of bone disorders) may have an increased risk of developing osteonecrosis of the jaw.

Low blood calcium levels (hypocalcemia) have been reported in patients receiving Zoledronic Acid, which may sometimes cause muscle spasms, dry skin, and a burning sensation. Cases of irregular heartbeat (cardiac arrhythmia), seizures, muscle cramps, and muscle twitching (tetany) due to severe hypocalcemia have been reported. In some cases, hypocalcemia may be life-threatening. If any of these conditions apply to you, inform your doctor immediately. If you have hypocalcemia, it must be corrected before the first dose of Zoledronic Acid is administered. You will be given appropriate calcium and vitamin D supplements.

Patients aged 65 years and older
Zoledronic Acid can be used in patients aged 65 years and older. There are no data indicating additional warnings required for this patient group.

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

Zoledronic Acid and other medicines
Tell your doctor about all medicines you are currently taking, have recently taken, or plan to take. It is especially important to inform your doctor if you are taking:

• aminoglycoside antibiotics (medicines used to treat serious infections), calcitonin (a medicine used to treat postmenopausal osteoporosis and hypercalcemia), loop diuretics (medicines used to treat high blood pressure and edema), or other medicines that reduce calcium levels, as using them together with bisphosphonates may cause excessive reduction in blood calcium levels;
• 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 when taken together with Zoledronic Acid are unknown;
• anti-angiogenic medicines (used in cancer treatment), as concomitant administration with Zoledronic Acid has been associated with an increased risk of osteonecrosis of the jaw (ONJ).

Pregnancy and breastfeeding
Do not use Zoledronic Acid during pregnancy. Inform your doctor if you are pregnant or suspect you may be pregnant.
Do not use Zoledronic Acid if you are breastfeeding.
Before taking any medicine, consult your doctor if you are pregnant or breastfeeding.

Driving and operating machinery
Very rare cases of drowsiness have been reported with Zoledronic Acid. Therefore, exercise caution when driving, operating machinery, or performing other tasks requiring concentration.

Zoledronic Acid contains sodium
One mL of 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, meaning the medicine is considered "sodium-free".

3. How to use Zoledronic Acid

• Zoledronic Acid must be administered only by healthcare professionals trained in the intravenous administration of bisphosphonates (i.e. administration of bisphosphonates into a vein).
• Your doctor will recommend drinking an adequate amount of water before each dose to prevent dehydration.
• You must carefully follow all other instructions given by your doctor, pharmacist, or nurse.

What dose of Zoledronic Acid should be used

• The single dose of Zoledronic Acid is 4 mg.
• If the patient has impaired kidney function, the treating physician will administer a reduced dose depending on the severity of kidney disease.

How often should Zoledronic Acid be used

• For the prevention of skeletal complications due to bone metastases, one infusion of Zoledronic Acid should be given every three to four weeks.
• For the treatment of elevated blood calcium levels, usually only one infusion of Zoledronic Acid is administered.

How to use Zoledronic Acid

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

Patients whose blood calcium levels are not too high may be prescribed calcium and vitamin D for daily intake.
Overdose of Zoledronic Acid
Patients who have received higher than recommended doses of Zoledronic Acid should be closely monitored. This is necessary due to the risk of abnormal serum electrolyte levels (e.g. calcium, phosphate, and magnesium) and/or kidney function changes, including severe kidney impairment. Patients with low calcium levels may require supplemental calcium infusion.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will
experience them. The most common ones are usually mild and likely to resolve in a short
time.
You should immediately inform your doctor if any of the following adverse reactions
occur:
Common (may affect less than 1 in 10 people):

• Severe kidney function disorders (usually detected by the treating physician based on specific blood tests).
• Low calcium levels in the blood.

Uncommon (may affect less than 1 in 100 people):

• Oral pain, tooth and/or jaw pain, swelling or non-healing ulcers in the mouth or jaw, presence of discharge, numbness or heaviness in the jaw, or loose teeth. These may be symptoms of jaw bone damage (osteonecrosis). If such symptoms occur, you should immediately inform your doctor or dentist during or after treatment with Zoledronic Acid Noridem or after treatment.
• In postmenopausal women with osteoporosis treated with zoledronic acid, irregular heartbeat (atrial fibrillation) has been observed. It is not known whether zoledronic acid causes irregular heartbeat, but you should inform your doctor if such symptoms occur after receiving zoledronic acid.
• Severe allergic reactions: shortness of breath, swelling mainly of the face and throat.

Rare (may affect less than 1 in 1,000 people):

• As a consequence of low calcium levels: irregular heartbeat (cardiac arrhythmia; secondary to hypocalcemia).
• Kidney dysfunction known as Fanconi syndrome (confirmed by a physician after performing specific urine tests).

Very rare (may affect less than 1 in 10,000 people):

• As a consequence of low calcium levels: seizures, numbness, and tetany (secondary to hypocalcemia).
• If a patient experiences ear pain, ear discharge, and/or ear infection, this should be reported to the doctor. These may be symptoms of bone tissue damage in the ear.
• Very rarely, osteonecrosis of bones other than the jaw, especially in the hip and femur, has been observed. You should immediately inform your doctor if symptoms such as new or worsening pain, pain, or stiffness occur during or after treatment with Zoledronic Acid.

Unknown (frequency cannot be estimated from available data):

• Kidney inflammation (tubulointerstitial nephritis): objective and subjective symptoms may include reduced urine volume, presence of blood in urine, nausea, general malaise.

You should inform your doctor as soon as possible about the following adverse
reactions:
Very common (may affect more than 1 in 10 people):

• Low phosphate levels in the blood.

Common (may affect less than 1 in 10 people):

• Headache and flu-like symptoms including fever, fatigue, weakness, drowsiness, chills, and bone, joint, and/or muscle pain. In most cases, no specific treatment is required, and symptoms resolve within a short time (a few hours or days);
• Gastrointestinal symptoms such as nausea, vomiting, and loss of appetite;
• Conjunctivitis;
• Low number of red blood cells (anemia).

Uncommon (may affect less than 1 in 100 people):

• Hypersensitivity reactions;
• Low blood pressure;
• Chest pain;
• Skin reactions at the injection site (redness and swelling), rash, itching;
• High blood pressure, shallow breathing, dizziness, restlessness, sleep disturbances, taste disturbances, tremor, tingling and numbness of hands or feet, diarrhea, constipation, abdominal pain, dry mouth;
• Low number of white blood cells and platelets;
• Low magnesium and potassium levels in the blood. Your doctor will monitor this and order necessary tests;
• Increased body weight;
• Excessive sweating;
• Drowsiness;
• Blurred vision, tearing eyes, light sensitivity;
• Sudden feeling of coldness with fainting, flaccidity, or collapse;
• Difficulty breathing, with wheezing and coughing;
• Urticaria.

Rare (may affect less than 1 in 1,000 people):

• Slow heartbeat;
• Confusion;
• In rare cases, atypical femoral fractures may occur, particularly in patients treated long-term for osteoporosis. You should consult your doctor if you experience pain, weakness, or discomfort in the thigh, hip, or groin area, as this may be an early sign of a possible femoral fracture.
• Interstitial lung disease (inflammation of the tissue surrounding the lung alveoli).
• Flu-like symptoms, including joint inflammation and joint swelling;
• Painful redness and/or swelling of the eye.

Very rare (may affect less than 1 in 10,000 people):

• Fainting due to low blood pressure;
• Severe bone, joint, and/or muscle pain, sometimes leading to immobility;
• Partial redness (without pain) of the white part of the eye.

Reporting of adverse reactions
If any adverse symptoms occur, including any possible adverse reactions not listed in this
leaflet, you should inform your doctor, pharmacist, or nurse.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug
Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products,
Al. Jerozolimskie 181C
02-222 Warsaw
Tel: +48 22 49 21 301
Fax: +48 22 49 21 309
Email: [email protected]. Reporting adverse reactions helps to gather more information on
the safety of the medicine.

5. How to store Zoledronic Acid

The physician, pharmacist, or nurse is 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 millilitre corresponds to 1.13 mg of sodium.
• The other ingredients are: mannitol (E421), sodium citrate (E331) and water for injections.

What Zoledronic Acid looks like and contents of the pack
Zoledronic Acid is a clear, colourless solution free from visible particles.
One plastic or glass vial with 5 mL of concentrate contains 4 mg of zoledronic acid (anhydrous).
One millilitre of concentrate for infusion solution contains 1.13 mg of sodium in the form of sodium citrate.
Each pack contains one plastic or glass vial with concentrate. Zoledronic Acid Noridem is supplied in packs containing 1, 4 or 10 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation 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 authorised in the European Economic Area countries 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

Information intended exclusively for healthcare professionals

Preparation and administration of Zoledronic Acid Noridem

• To prepare an infusion solution containing 4 mg of zoledronic acid, the concentrate of Zoledronic Acid Noridem (5.0 mL) should be diluted in 100 mL of infusion solution free of calcium or other divalent cations. If a lower dose is required, the appropriate volume of the concentrate should first be withdrawn as recommended below, then diluted in 100 mL of infusion solution. To avoid potential incompatibilities, only 0.9% m/v sodium chloride solution or 5% m/v glucose solution should be used for dilution.

Do not mix the Zoledronic Acid Noridem solution with solutions containing calcium or
other divalent cations, e.g. Ringer's lactate solution.
Method for preparing reduced doses of Zoledronic Acid Noridem:
Withdraw the appropriate volume of concentrate according to the prescribed dose:

• 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 must be discarded. Only clear solutions without particles or discoloration should be used. Aseptic techniques must be observed during preparation of the infusion.
• From a microbiological standpoint, the diluted infusion solution should be administered immediately. If the medicinal product is not used immediately, the responsibility for storage conditions and duration prior to use lies with the user. The diluted solution is stable for no longer than 24 hours at 2°C–8°C. Before administration, refrigerated solution should be warmed to room temperature.
• The zoledronic acid solution should be administered as a 15-minute intravenous infusion via a separate infusion line. The patient's hydration status should be assessed prior to each administration of Zoledronic Acid Noridem to ensure adequate hydration.
• Studies using glass bottles and infusion bags and sets made of polyvinyl chloride, polyethylene, and polypropylene have shown no incompatibility with Zoledronic Acid Noridem.
• Since there are no data on compatibility with other intravenous medicinal products, Zoledronic Acid Noridem must not be mixed with other drugs. The Zoledronic Acid Noridem solution should always be administered using a separate infusion set.

Storage of Zoledronic Acid Noridem

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