Zoledronic acid accord

Package leaflet: Information for the patient

Zoledronic Acid Accord 4 mg/100 mL, infusion solution
Acidum zoledronicum
Please read all of this leaflet carefully before use, as it contains important information for the patient.

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

Table of contents

1. What Zoledronic Acid Accord is and what it is 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 pack and other information

1. What Zoledronic Acid Accord is and what it is 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 skeletal complications, such as fractures in adult patients with bone metastases (spread of cancer from its original site to the bones);
• to reduce elevated calcium levels in the blood of adult patients when high calcium is caused by cancer. Tumours can accelerate bone turnover, leading to increased release of calcium from bones. This condition is known as tumour-induced hypercalcaemia (TIH).

2. Important information before using Zoledronic Acid Accord

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

Do not use Zoledronic Acid Accord:

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

Warnings and precautions
Before starting treatment with Zoledronic Acid Accord, discuss with your doctor,
pharmacist, or nurse:

• 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 a dental examination before starting treatment with Zoledronic Acid Accord.
• if you are currently undergoing dental treatment or plan to have dental surgery; in such cases, inform your dentist that you are taking Zoledronic Acid Accord and inform your doctor about any dental procedures.

During treatment with Zoledronic Acid Accord, maintain good 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 (ONJ).
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 who have previously taken bisphosphonates (to treat or prevent bone disorders) may have an increased risk of developing osteonecrosis of the jaw.

Hypocalcaemia (low blood calcium levels) has been reported in patients receiving zoledronic acid, sometimes causing muscle cramps, dry skin, and burning sensations. Severe hypocalcaemia has been associated with irregular heartbeat (cardiac arrhythmia), seizures, muscle spasms, and tetany. In some cases, hypocalcaemia may be life-threatening. If any of these apply to you, inform your doctor immediately. If you have previously had hypocalcaemia, it should be corrected before your first dose of Zoledronic Acid Accord. You will be given appropriate calcium and vitamin D supplements.

Patients aged 65 years and older
Zoledronic Acid Accord may be used in patients aged 65 years and older. There are no additional warnings required specifically for this patient group.

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

Zoledronic Acid Accord and other medicines
Tell your doctor or pharmacist 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 hypercalcaemia), loop diuretics (medicines used to treat high blood pressure and oedema), or other medicines that lower calcium levels, as their use in combination with bisphosphonates may lead to excessive reduction in blood calcium;
• thalidomide (a medicine used to treat certain blood cancers with bone involvement) or other medicines that may be harmful to the kidneys;
• other medicines containing zoledronic acid used to treat osteoporosis and other non-malignant bone diseases, or other bisphosphonates, as the combined effects of these medicines with Zoledronic Acid Accord are unknown;
• anti-angiogenic medicines (used in cancer treatment), as their concomitant use with zoledronic acid has been associated with an increased risk of osteonecrosis of the jaw (ONJ).

Pregnancy and breastfeeding
Zoledronic Acid Accord must not be used during pregnancy. Inform your doctor if you are pregnant or suspect you may be pregnant.
Zoledronic Acid Accord must not be used in women who are breastfeeding.
If you are pregnant, breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor or pharmacist before using this medicine.

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

Zoledronic Acid Accord contains sodium
This medicine contains 342.9 mg of sodium (the main component of table salt) per bag. This is equivalent to 17.5% of the maximum recommended daily intake of sodium for an adult. However, if the medicinal product Zoledronic Acid Accord is diluted using 0.9% w/v sodium chloride solution (saline), the resulting sodium dose will be higher.

3. How to use Zoledronic Acid Accord

• Zoledronic Acid Accord must only be administered by healthcare professionals trained in the intravenous administration of bisphosphonates (i.e. administration of bisphosphonates into a vein).
• Your doctor will advise you to drink 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 Accord should be used

• The single dose is 4 mg of zoledronic acid.
• If you have kidney function impairment, your doctor will give you a lower dose depending on the severity of kidney disease.

How often Zoledronic Acid Accord should be used

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

How Zoledronic Acid Accord is administered

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

For patients whose blood calcium levels are not too high, the doctor will prescribe calcium and vitamin D for daily intake.
Overdose of Zoledronic Acid Accord
Patients who have received higher than recommended doses of Zoledronic Acid Accord should be closely monitored. This is necessary due to the possibility of developing 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 side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
The most commonly occurring side effects are usually mild and are likely to
resolve within a short period of time.
You should immediately inform your doctor if any of the following side effects 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):

• Mouth pain, tooth and/or jaw pain, swelling or non-healing sores in the mouth or jaw, 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 Accord.
• 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 hypocalcaemia).
• Kidney dysfunction known as Fanconi syndrome (confirmed by the doctor after performing specific urine tests).

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

• As a consequence of low calcium levels: seizures, tetany, and numbness (secondary to hypocalcaemia).
• If a patient experiences ear pain, ear discharge, and/or ear infection, they should inform their 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 thigh, has been observed. You should immediately inform your doctor if symptoms such as new or worsening pain, pain or stiffness during or after treatment with Zoledronic Acid Accord occur.

You should 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 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 red blood cell count (anaemia).

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, shortness of breath, dizziness, restlessness, sleep disturbances, taste disturbances, tremor, tingling and numbness in hands or feet, diarrhoea, constipation, abdominal pain, dry mouth;
• Low white blood cell and platelet count;
• Low magnesium and potassium levels in the blood. Your doctor will monitor this and order necessary tests;
• Weight gain;
• Excessive sweating;
• Drowsiness;
• Blurred vision, watery eyes, light sensitivity;
• Sudden feeling of cold with fainting, collapse, or weakness;
• Difficulty breathing, with wheezing and coughing;
• Urticaria (hives).

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

• Slow heartbeat;
• Confusion;
• In rare cases, atypical fractures of the femur may occur, particularly in patients receiving long-term treatment for osteoporosis. You should consult your doctor if you experience pain, weakness, or discomfort in the thigh, hip, or groin, 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;

Frequency not known (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.

Reporting of side effects
If any adverse effects occur, including any adverse effects not listed
in this leaflet, you should inform your doctor or pharmacist. Adverse effects 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
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the responsible entity.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Zoledronic Acid Accord

The prescribing physician, pharmacist, or nurse is informed about how to store Zoledronic Acid Accord (see section 6).
Keep the medicine out of the sight and reach of children.
It is recommended that Zoledronic Acid Accord infusion solution be used immediately after first opening. If the solution is not used immediately after opening, it should be stored in a refrigerator at 2-8°C.

6. Contents of the pack 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, disodium 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, colourless, plastic, polyolefin bags with two PP ports, closed with elastomeric rubber stoppers and sealed with PP caps, placed in a protective bag (HDPE/LLDPE/PP).
Each bag contains 100 mL of solution.
Zoledronic Acid Accord is supplied in unit packs containing 1, 4 or 10 plastic bags.
Not all pack sizes may be marketed.
Marketing Authorisation 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 authorised in the European Economic Area member states under the following names:

The following information is intended for medical personnel 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 renal function.
• For single use only. Any unused portions must be discarded. Only clear solutions free from particulate matter and discoloration should be used. Aseptic techniques must be followed during infusion preparation.
• From a microbiological standpoint, the infusion solution should be administered immediately after opening. If not used immediately, the user is responsible for storage conditions and duration prior to use, which should not exceed 24 hours at 2°C–8°C, unless dilution has been carried out under aseptic conditions. Prior to administration, refrigerated solution should be allowed to reach room temperature.
• The solution containing zoledronic acid must not be diluted or mixed with other infusion solutions. The solution should be 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 Accord to ensure adequate hydration.
• The zoledronic acid solution should be 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 Accord to ensure adequate hydration.
• In patients with normal renal function, Zoledronic Acid Accord 4 mg/100 mL solution for infusion may be used without further dilution. In patients with mild to moderate renal impairment, reduced doses of zoledronic acid are recommended according to the instructions below.

To prepare reduced doses for patients with baseline CLcr ≤ 60 mL/min,
refer to the data in Table 1 below. Remove the specified volume of Zoledronic Acid
Accord solution and replace it with an equal volume of sterile sodium chloride 9 mg/mL (0.9%)
injection solution or 5% glucose injection solution.
Table 1: Preparation of reduced doses of Zoledronic Acid Accord
4 mg/100 mL, solution for infusion

• Clinical studies have shown no incompatibility of Zoledronic Acid Accord with various infusion sets made of polyvinyl chloride, polyethylene, and polypropylene.
• Since there are no data available on the compatibility of Zoledronic Acid Accord with other intravenous medicinal products, it should not be mixed with other preparations. The Zoledronic Acid Accord solution must always be administered using a separate infusion set.

Storage of Zoledronic Acid Accord

• Keep the medicine out of the sight and reach of children.
• Do not use Zoledronic Acid Accord after the expiry date stated on the packaging.
• No special storage conditions required.
• After opening the bag, Zoledronic Acid Accord should be used immediately to avoid microbiological contamination.