Zerlinda

Package leaflet: Information for the user

Zerlinda, 4 mg/100 ml, infusion solution
acidum zoledronicum
Please read all of this leaflet carefully before this medicine is used, as it contains
important information for the patient.

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

Leaflet contents

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

1. What Zerlinda is and what it is used for

The active substance in Zerlinda 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 remodelling. 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 bone).
• To reduce calcium levels in the blood of adult patients when the level is elevated due to the presence of cancer. Tumours can accelerate bone remodelling, causing increased release of calcium from bone. This condition is known as tumour-induced hypercalcaemia (TIH).

2. Important information before using Zerlinda

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

When not to use Zerlinda

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

Warnings and precautions
Before starting Zerlinda, discuss with your doctor

• if the patient has or has had kidney problems.
• if the patient has or has had pain, swelling or numbness in the jaw, a feeling of heaviness in the jaw, or loose teeth. Your doctor may recommend that the patient have a dental examination before starting treatment with Zerlinda.
• if the patient is currently undergoing dental treatment or is planning to have dental surgery; in such cases, the patient should inform their dentist about taking Zerlinda and inform their doctor about any dental treatment.

During treatment with Zerlinda, proper oral hygiene (including regular tooth brushing) should be maintained, and routine dental check-ups should be attended.
The patient should contact their doctor and dentist immediately if they experience any symptoms in the mouth or teeth, such as loose teeth, pain or swelling, non-healing sores, or discharge, as these may be signs of a condition called osteonecrosis of the jaw.
Patients who are receiving chemotherapy and/or radiotherapy, who are taking steroids, who are undergoing dental surgical procedures, who do not receive routine dental care, who have gum disease, who smoke, or who have previously taken bisphosphonates (used to treat or prevent bone diseases) may have an increased risk of developing osteonecrosis of the jaw.
Low blood calcium levels (hypocalcemia) have been reported in patients receiving Zerlinda, which may sometimes cause muscle cramps, dry skin, and a burning sensation.
Cases of irregular heartbeat (cardiac arrhythmia), seizures, muscle spasms, and twitching (tetany) due to severe hypocalcemia have also been reported. In some cases, hypocalcemia may be life-threatening. If any of these situations apply to the patient, they should inform their doctor immediately. If the patient has hypocalcemia, it must be corrected before the first dose of Zerlinda is administered. The patient will be given appropriate calcium and vitamin D supplements.

Patients aged 65 years and older
Zerlinda 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
Zerlinda is not recommended for use in children and adolescents under 18 years of age.

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

• Antibiotics of the aminoglycoside group (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), and other medicines that may 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 medicines containing zoledronic acid or other bisphosphonates, since the combined effects of these medicines taken together with Zerlinda are unknown.
• Anti-angiogenic medicines (used in cancer treatment), as using these together with Zerlinda is associated with an increased risk of osteonecrosis of the jaw.

Pregnancy and breastfeeding
Zerlinda must not be used during pregnancy. Inform your doctor if the patient is pregnant or suspects she may be pregnant.
Zerlinda must not be used in women who are breastfeeding.
If the patient is pregnant or breastfeeding, she should consult her doctor before using any medicine.

Driving and operating machinery
Very rare cases of drowsiness have been reported with the use of zoledronic acid.
Therefore, caution should be exercised when driving, operating machinery, or performing other activities requiring concentration.

Zerlinda contains sodium
This medicine contains 356 mg of sodium (the main component of table salt) in each 100 ml bag. This corresponds to 17.8% of the maximum recommended daily dietary sodium intake for adults.

3. How to use Zerlinda

• Zerlinda must be administered only by healthcare professionals trained 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 dose to prevent dehydration.
• All other instructions from the doctor, pharmacist, or nurse must be carefully followed.

What dose of Zerlinda is used

• The usual single dose 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 is Zerlinda used

• For prevention of skeletal complications due to bone metastases, one infusion of Zerlinda is given every three to four weeks.
• For treatment aimed at reducing elevated calcium levels in the blood, usually only one infusion of Zerlinda is administered.

How Zerlinda is administered

• Zerlinda is given as an intravenous infusion (drip) lasting at least 15 minutes and must be administered as a separate intravenous solution through a dedicated infusion line.

Patients who have low blood calcium levels may be prescribed calcium and vitamin D for daily use.
Overdose of Zerlinda
Patients who have received higher than recommended doses of Zerlinda should be closely monitored.
This is necessary due to the risk of abnormal serum electrolyte levels (e.g. abnormal calcium, phosphate, and magnesium levels) and (or) renal function changes, including severe kidney impairment. Patients with low calcium levels may require supplemental calcium infusion.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although they do not occur in everyone.
The most common ones are usually mild and likely to resolve within a short period of time.
You should immediately inform your doctor if any of the following adverse reactions occur:

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

• Pain in the mouth, tooth 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 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 Zerlinda.
• 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 up to 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 the physician after specific urine tests).

Very rare (may affect up to 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, 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, particularly 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 occur during or after treatment with Zerlinda.

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, and 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 up to 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 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, 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 levels of magnesium and potassium 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 cold with fainting, body collapse, or collapse.
• Difficulty breathing with wheezing and coughing.
• Urticaria (hives).

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

• Slow heartbeat.
• Confusion.
• Atypical femoral fractures may rarely 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 area, as this may be an early sign indicating a potential 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 up to 1 in 10,000 people):

• Fainting due to low blood pressure.
• Severe bone, joint, and/or muscle pain, sometimes leading to immobility.

Reporting of adverse reactions
If any adverse symptoms occur, including any 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 Reactions of Medicinal Products, 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 reactions can also be reported to the marketing authorization holder. Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Zerlinda

Your physician, pharmacist, or nurse has been informed about the proper way to store Zerlinda.
After first opening, Zerlinda should be used immediately. If the solution is not used immediately, it should be stored in a refrigerator at 2°C - 8°C.

6. Contents of the pack and other information

What Zerlinda contains

• The active substance in Zerlinda is zoledronic acid. Each 100 ml bag of solution contains 4 mg of zoledronic acid (as monohydrate).
• The other ingredients are: sodium chloride, mannitol, disodium citrate dihydrate, water for injections.

What Zerlinda looks like and contents of the pack
Zerlinda is a clear, colourless solution free from visible particles, supplied in a plastic bag made of a five-layer M312A polyolefin-based material, PVC, without plasticizer. The bag has two puncture ports with PP caps, each with a PP injection point and a breakable PP cap. The bag is further enclosed in a polyester Alox/PP overwrap and then placed in a cardboard box.
Pack sizes:
1 bag of 100 ml
10 bags of 100 ml
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Actavis Group PTC ehf.
Dalshraun 1
220 Hafnarfjörður
Iceland
Importer
S.C. Infomed Fluids S.R.L.
Str. Theodor Pallady nr.50
Sector 3, 032266 Bucharest
Romania
For further information about this medicinal product and its names in the European Economic Area countries, please contact the representative of the Marketing Authorisation Holder:
Teva Pharmaceuticals Polska Sp. z o.o., ul. Emilii Plater 53, 00-113 Warsaw, tel. (22) 345 93 00.

The following information is intended for healthcare professionals only:
INFORMATION FOR HEALTHCARE PROFESSIONALS
Preparation and administration of Zerlinda

• The infusion solution Zerlinda contains 4 mg of zoledronic acid in 100 ml of infusion solution intended for immediate administration to patients with normal renal function.
• For single use only. Any unused portion of the solution must be discarded. Only clear solutions free from particles and discoloration should be used. Aseptic techniques must be followed during preparation of the infusion.
• After first opening: the chemical and physical stability of the medicinal product has been demonstrated for 24 hours at 2°C - 8°C. From a microbiological standpoint, the infusion solution should be used immediately. If the product is not used immediately, the user is responsible for the storage conditions and duration prior to use, and the solution remains stable for no longer than 24 hours at 2°C - 8°C. The solution stored in the refrigerator should be brought to room temperature before administration.
• The solution containing zoledronic acid must not be further diluted or mixed with other infusion solutions. The medicine should be administered as an intravenous infusion lasting no less than 15 minutes through a separate infusion line. Before each administration of Zerlinda, the patient's hydration status should be assessed to ensure it is adequate.
• The infusion solution Zerlinda can be administered immediately to patients with normal renal function without further preparation. For patients with mild to moderate renal impairment, reduced doses should be prepared according to the instructions below.

To prepare reduced doses for patients with CL ≤60 ml/min, refer to Table 1 below. The specified volume of Zerlinda solution should be withdrawn from the bag and replaced with an equal volume of sterile 9 mg/ml (0.9%) sodium chloride injection solution or 5% glucose injection solution.
Table 1: Method for preparing reduced doses of Zerlinda 4 mg/100 ml, infusion solution

*Doses were calculated assuming target AUC values of 0.66 (mg•h/L) (CL = 75 mL/min). Administering lower doses to patients with renal impairment is considered to achieve equivalent AUC values as in patients with a creatinine clearance of 75 mL/min.
There are no available data regarding the compatibility of Zerlinda with other intravenously administered drugs. Zerlinda must not be mixed with other medicines/substances and should always be administered using a separate infusion set.
How to store Zerlinda

• Keep the medicine out of sight and reach of children.
• Do not use Zerlinda after the expiry date stated on the label and outer carton after "EXP". The expiry date refers to the last day of the specified month.
• There are no special storage requirements for this medicinal product.
• After opening the bag, the product should be used immediately to avoid microbiological contamination.