Zoledronic Acid Accord

Leaflet accompanying the packaging: patient information

Zoledronic acid Accord 4 mg/100 mL, 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 any side effects occur, including any possible side effects not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

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

1. What is Zoledronic acid Accord and what is it used for

The active substance in Zoledronic acid Accord 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 bone complications,e.g. fractures in adult patients with bone metastases (spread of cancer from the original site to the bone);
• to reduce calcium levelsin the blood of 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 tumor-induced hypercalcemia (TIH).

2. Important information before using Zoledronic acid Accord

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

When not to use Zoledronic acid Accord:

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

Warnings and precautions

Before starting Zoledronic acid Accord, discuss with your doctor, pharmacist, or nurse:

• –if the patient has or has had kidney problems;
• –if the patient has or has had pain, swelling, or numbnessof the jaw, a feeling of heaviness in the jaw, or loosening of the teeth. The doctor may recommend that the patient undergo a dental examination before starting treatment with Zoledronic acid Accord.
• –if the patient is undergoing dental treatmentor plans to undergo jaw surgery; the patient should inform the dentist about the use of Zoledronic acid Accord and inform the doctor about the dental treatment.

During treatment with Zoledronic acid Accord, maintain good oral hygiene (including regular toothbrushing) and attend regular check-ups. If the patient experiences any symptoms in the mouth or teeth, such as tooth loosening, pain, or swelling, non-healing ulcers, or discharge, they should immediately contact their doctor and dentist, as these may be symptoms of a condition called jaw bone necrosis. Patients 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 previously taken bisphosphonates (for the treatment or prevention of bone disorders) may have a higher risk of developing jaw bone necrosis. In patients receiving zoledronic acid, decreased calcium levels in the blood (hypocalcemia) have been reported, sometimes causing muscle cramps, dry skin, and a feeling of burning. There have been reports of irregular heartbeats (arrhythmias), seizures, and muscle spasms and tremors (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 previously had hypocalcemia, it should be corrected before taking the first dose of Zoledronic acid Accord. The patient will receive appropriate calcium and vitamin D supplements.

Patient over 65 years old

Zoledronic acid Accord can be used in patients over 65 years old. There is no data on additional warnings required in this patient group.

Children and adolescents

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

Zoledronic acid Accord and other medicines

Tell your doctor or pharmacist about all medicines you are taking or have recently taken, as well as any medicines you plan to take. It is especially important to inform your doctor about the use of:

• antibiotics from the aminoglycoside group (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 their use 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 medicines that also contain zoledronic acid and are used to treat osteoporosis and other non-cancerous bone diseases or other bisphosphonates, as the combined effects of these medicines taken with Zoledronic acid Accord are not known;
• anti-angiogenic medicines (used to treat cancer), as their concurrent use with zoledronic acid has been associated with an increased risk of jaw bone necrosis (ONJ).

Pregnancy and breastfeeding

Zoledronic acid Accord should not be used during pregnancy. Inform your doctor if you are pregnant or think you may be pregnant. Zoledronic acid Accord should not be used in breastfeeding women. If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

There have been very rare cases of drowsiness associated with the use of Zoledronic acid Accord. Therefore, caution should be exercised when driving, operating machinery, and performing other activities that require focused attention.

Zoledronic acid Accord contains sodium

This medicine contains 342.9 mg of sodium (a major component of common salt) per vial. This is equivalent to 17.5% of the recommended maximum daily intake of sodium for an adult. However, if a 0.9% sodium chloride solution is used to dilute the medicinal product Zoledronic acid Accord before administration, the resulting sodium intake will be higher.

3. How to use Zoledronic acid Accord

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

What dose of Zoledronic acid Accord is used

• The single dose is 4 mg of zoledronic acid.
• If the patient has kidney function disorders, the doctor will administer a lower dose of the medicine, depending on the severity of the kidney disease.

How often is Zoledronic acid Accord used

• In the case of preventing bone complications caused by bone metastases, one infusion of Zoledronic acid Accord 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 Accord is used.

How to use Zoledronic acid Accord

• Zoledronic acid Accord 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 Accord than recommended

Patient who have been administered higher doses of Zoledronic acid Accord 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 function disorders. Patients with low calcium levels may require administration of a supplementary calcium infusion.

4. Possible side effects

Like all medicines, Zoledronic acid Accord can cause side effects, although not everybody gets them. The most common side effects are usually mild and will probably go away on their own in a short time.

Inform your doctor immediately if you experience any of the following side effects:

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

• Severe kidney function disorders (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, toothache, and/or jaw pain, swelling, or non-healing ulcers in the mouth or jaw, discharge, numbness, or a feeling of heaviness in the jaw, or loosening of the teeth. These may be symptoms of jaw bone damage (osteonecrosis). If such symptoms occur, inform your doctor or dentist immediately during or after treatment with Zoledronic acid Accord.
• In patients with postmenopausal osteoporosis treated with zoledronic acid, irregular heartbeats (atrial fibrillation) have been observed. It is not known whether zoledronic acid causes irregular heartbeats, but inform your doctor if you experience such symptoms 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 heartbeats (arrhythmias; secondary to hypocalcemia).
• Kidney function disorder 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 tetany (secondary to hypocalcemia).
• If the patient experiences ear pain, discharge from the ear, and/or ear infection, they should inform their doctor. These may be symptoms of bone tissue damage in the ear.
• Very rarely, bone necrosis of bones other than the jaw, especially the hip and thigh, has been observed. Inform your doctor immediately if you experience symptoms such as pain, weakness, or discomfort in the thigh, hip, or groin area, as this may already indicate a risk of thigh bone fracture.

Inform your doctor as soon as possible 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 bones, joints, and/or muscles. In most cases, no special treatment is required, and symptoms go away on their own after 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, shortness of breath, dizziness, anxiety, sleep disturbances, taste disturbances, tremors, numbness and tingling 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, sensitivity to light;
• Sudden feeling of cold with fainting, weakness, or collapse;
• Difficulty breathing, 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 long-term for osteoporosis. Inform your doctor if you experience symptoms such as pain, weakness, or discomfort 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 inflammation and joint swelling;
• Painful redness and/or swelling of the eye.

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

• Fainting caused by low blood pressure;
• Severe pain in bones, joints, and/or muscles, sometimes causing immobilization;

Frequency not known (cannot be estimated from the available data):

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

Reporting side effects

If you experience any side effects, including any possible side effects not listed in this leaflet, inform your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring 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, website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Zoledronic acid Accord

Your doctor, pharmacist, or nurse is informed about how to store Zoledronic acid Accord (see section 6). Store the medicine out of sight and reach of children. It is recommended to use Zoledronic acid Accord solution for infusion immediately after opening. If the solution is not used immediately, it should be stored in the refrigerator at a temperature of 2-8°C. Before administration, the cooled solution should reach room temperature.

6. Contents of the packaging and other information

What Zoledronic acid Accord contains

• -The active substance is zoledronic acid. One plastic bag contains 4 mg of zoledronic acid.
• -The other ingredients are: mannitol, sodium citrate dihydrate, sodium chloride, and water for injections.

What Zoledronic acid Accord looks like and contents of the pack

Zoledronic acid Accord is supplied in transparent, colorless, plastic, polyolefin bags with two ports made of PP, closed with elastomeric rubber stoppers, sealed with PP caps, placed in a protective bag (HDPE/LLDPE/PP). One bag contains 100 mL of solution. Zoledronic acid Accord is supplied in single packs containing 1, 4, or 10 plastic bags. Not all pack sizes may be marketed.

Marketing authorization holder

Accord Healthcare Polska Sp. z o.o., ul. Taśmowa 7, 02-677 Warsaw, Tel: +48 22 577 28 00

Manufacturer

Industria Farmaceutica Galenica Senese S.r.l., Via Cassia Nord 351, 53014 Monteroni d’Arbia, Italy

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

Date of last revision of the leaflet: September 2024

The following information is intended for healthcare professionals only:

Preparation and administration of Zoledronic acid Accord

• -Zoledronic acid Accord 4 mg/100 mL, solution for infusion contains 4 mg of zoledronic acid in 100 mL of ready-to-use solution for patients with normal kidney function.
• 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 rules should be followed.
• -From a microbiological point of view, the solution for infusion should be administered immediately after opening. If the medicine is not used immediately, the responsibility for the storage time and conditions before use lies with the user and should not exceed 24 hours at a temperature of 2°C – 8°C, unless the dilution was performed under aseptic conditions. Then, before administration, the cooled solution should reach room temperature.
• The solution containing zoledronic acid should not be diluted or mixed with other solutions for infusion. The solution is administered in a 15-minute intravenous infusion through a separate infusion line. The patient's hydration status should be assessed before each administration of Zoledronic acid Accord to ensure adequate hydration.
• The solution of zoledronic acid is administered in a 15-minute intravenous infusion through a separate infusion line. The patient's hydration status should be assessed before each administration of Zoledronic acid Accord to ensure adequate hydration.
• In patients with normal kidney function, Zoledronic acid Accord 4 mg/100 mL solution for infusion can be used without additional dilution. In patients with mild or moderate kidney function disorders, reduced doses of zoledronic acid are recommended according to the instructions below.

In order to prepare reduced doses for patients with a baseline CLcr ≤ 60 mL/min, use the data from Table 1 below. Withdraw the indicated volume of Zoledronic acid Accord solution and replace it with the same amount of sterile sodium chloride 9 mg/mL (0.9%) solution for injection or 5% glucose solution for injection.
Table 1: Preparation of reduced doses of Zoledronic acid Accord, 4 mg/100 mL, solution for infusion

• No incompatibilities of Zoledronic acid Accord with various infusion sets made of polyvinyl chloride, polyethylene, and polypropylene have been observed in studies.
• Since there is no data on the compatibility of Zoledronic acid Accord with other intravenously administered medicines, it should not be mixed with other preparations. The solution of Zoledronic acid Accord should always be administered in a separate infusion set.

Storage of Zoledronic acid Accord

• Store the medicine out of sight and reach of children.
• Do not use Zoledronic acid Accord after the expiry date stated on the packaging.
• -There are no special storage instructions.
• After opening the bag, Zoledronic acid Accord should be used immediately to avoid microbiological contamination.