Zerlinda

Package Leaflet: Information for the User

Zerlinda, 4 mg/100 ml, Solution for Infusion

Zoledronic acid

Read all of this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. 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, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

• 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 of 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 change. It is used:

• To prevent bone complications,e.g. fractures in adult patients with bone metastases from solid tumors (spread of cancer from the original site to the bone).
• To reduce high levels of calcium in the bloodin adult patients with cancer, when the levels are too high due to the presence of a tumor. Tumors can speed up bone breakdown, leading to high levels of calcium released from the bone. This condition is called tumor-induced hypercalcemia (TIH).

2. Important information before using Zerlinda

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

When not to use Zerlinda

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

Warnings and precautions

Before starting Zerlinda, discuss with your doctor

• –if you have or have had kidney problems.
• –if you have or have had pain, swelling, or numbnessin your jaw, a feeling of heaviness in your jaw, or a loose tooth. Your doctor may recommend that you have a dental check-up before starting Zerlinda.
• –if you are having or plan to have dental treatmentor surgery; you should inform your dentist that you are being treated with Zerlinda and inform your doctor about any dental treatment.

During treatment with Zerlinda, maintain good oral hygiene (including regular tooth brushing) and schedule routine dental check-ups. If you experience any problems with your mouth or teeth, such as loose teeth, pain, or swelling, or non-healing sores or discharge, tell your doctor and dentist immediately, as these could be signs of a condition called jawbone necrosis (death of jawbone tissue).

Patients who are receiving or have received chemotherapy, radiotherapy, or steroids, or who have had dental surgery, do not receive routine dental care, have gum disease, smoke, or have been taking bisphosphonates (used to treat or prevent bone diseases) may have a higher risk of developing jawbone necrosis.

Low levels of calcium in the blood (hypocalcemia) have been reported in patients receiving Zerlinda, sometimes leading to muscle cramps, dry skin, and a tingling sensation. Rare cases of irregular heartbeat (arrhythmia), seizures, and muscle spasms or twitching have been reported due to severe hypocalcemia. In some cases, hypocalcemia can be life-threatening. If any of these situations apply to you, tell your doctor immediately. If you have hypocalcemia, it should be corrected before you receive the first dose of Zerlinda. You will receive calcium and vitamin D supplements.

Patients aged 65 and over

Zerlinda can be used in patients aged 65 and over. There are no special warnings or precautions for this age group.

Children and adolescents

Zerlinda is not recommended for children and adolescents under 18 years of age.

Zerlinda and other medicines

Tell your doctor about all medicines you are taking or have recently taken, and about any medicines you plan to take. It is particularly important to tell your doctor if you are taking:

• Aminoglycoside antibiotics (used to treat severe infections), calcitonin (used to treat osteoporosis and hypercalcemia), loop diuretics (used to treat high blood pressure and swelling), and other medicines that lower calcium levels, as using them together with bisphosphonates may cause too low levels of calcium in the blood.
• Thalidomide (used to treat certain blood cancers with bone involvement) or other medicines that can harm the kidneys.
• Other medicines containing zoledronic acid or other bisphosphonates, as the combined effects of these medicines with Zerlinda are not known.
• Anti-angiogenic medicines (used to treat cancer), as using them together with Zerlinda may increase the risk of jawbone necrosis.

Pregnancy and breastfeeding

Zerlinda must not be used during pregnancy. If you are pregnant or think you may be pregnant, tell your doctor. Zerlinda must not be used in women who are breastfeeding. If you are pregnant or breastfeeding, ask your doctor for advice before taking any medicine.

Driving and using machines

There have been very rare reports of drowsiness in patients taking zoledronic acid. Therefore, you should be careful when driving, operating machinery, and performing other activities that require your full attention.

Zerlinda contains sodium

This medicine contains 356 mg of sodium (the main component of common salt) per 100 ml of solution, which is approximately 17.8% of the maximum recommended daily intake of sodium for adults.

3. How to use Zerlinda

• Zerlinda must be administered only by healthcare professionals who have the necessary training to administer bisphosphonates intravenously.
• Your doctor will advise you to drink plenty of water before each infusion to prevent dehydration.
• Follow all other instructions from your doctor, pharmacist, or nurse.

What dose of Zerlinda will you receive

• The usual single dose of Zerlinda is 4 mg.
• If you have kidney problems, your doctor will give you a lower dose of Zerlinda, depending on the severity of your kidney disease.

How often will you receive Zerlinda

• In the prevention of bone complications due to bone metastases, one infusion of Zerlinda is given every 3 to 4 weeks.
• In the treatment of high levels of calcium in the blood, one infusion of Zerlinda is usually given.

How will you receive Zerlinda

• Zerlinda is given as a drip (infusion) into a vein, which should last at least 15 minutes and should be given as a separate intravenous solution through a separate infusion line.

Patients with normal calcium levels in the blood will be prescribed calcium and vitamin D supplements to take every day.

What to do if you receive more Zerlinda than you should

Patients who receive more Zerlinda than they should will be closely monitored. This is necessary because of the risk of abnormal levels of electrolytes in the blood (e.g. abnormal levels of calcium, phosphorus, and magnesium) and/or changes in kidney function, including severe kidney problems. Patients with low levels of calcium in the blood may need to receive a calcium infusion.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

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

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

• Severe kidney problems (usually detected by your doctor through specific blood tests).
• Low levels of calcium in the blood.

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

• Pain in the mouth, toothache, or jaw pain, swelling, or non-healing sores in the mouth or jaw, discharge, numbness, or a feeling of heaviness in the jaw or loose teeth. These could be signs of jawbone necrosis. If you experience any of these symptoms, tell your doctor or dentist immediately, during or after treatment with Zerlinda.
• In patients with postmenopausal osteoporosis treated with zoledronic acid, there have been reports of irregular heartbeat (atrial fibrillation). It is not known whether zoledronic acid causes irregular heartbeat, but you should tell your doctor if you experience any symptoms after taking zoledronic acid.
• Severe allergic reactions: difficulty breathing, swelling mainly of the face and throat.

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

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

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

• As a result of low levels of calcium in the blood: seizures, numbness, and muscle spasms or twitching (secondary to hypocalcemia).
• If you experience ear pain, discharge from the ear, and/or ear infection, tell your doctor. These could be signs of bone damage in the ear.
• Very rarely, bone necrosis has been reported in bones other than the jaw, especially the hip and thigh. Tell your doctor immediately if you experience symptoms such as new or increasing pain, pain, or stiffness during or after treatment with Zerlinda.

Not known (frequency cannot be estimated from the available data):

• Kidney inflammation (interstitial nephritis): symptoms may include decreased urine output, blood in the urine, nausea, general feeling of being unwell.

Tell your doctor as soon as possible if you experience any of the following side effects:

Very common (may affect more than 1 in 10 people):

• Low levels of phosphorus in the blood.

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

• Headache and flu-like symptoms including fever, fatigue, weakness, sleepiness, chills, and pain in the bones, joints, and/or muscles. In most cases, no special treatment is needed, and the symptoms will go away 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):

• Allergic reactions.
• Low blood pressure.
• Chest pain.
• Skin reactions (redness and swelling) at the infusion site, rash, itching.
• High blood pressure, shallow breathing, dizziness, anxiety, sleep disturbances, taste disturbances, trembling, numbness, and tingling in the hands or feet, diarrhea, constipation, abdominal pain, dry mouth.
• Low white blood cell and platelet count.
• Low levels of magnesium and potassium in the blood. Your doctor will monitor this and order any 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.
• Rarely, atypical fractures of the thigh bone may occur, especially in patients treated long-term for osteoporosis. You should talk to your doctor if you experience pain, weakness, or discomfort in the thigh, hip, or groin, as this may be an early sign of a 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 due to low blood pressure.
• Severe pain in the bones, joints, and/or muscles, sometimes causing immobilization.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in the "Contact" section below. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Zerlinda

Your doctor, pharmacist, or nurse is informed about how to store Zerlinda properly.

After opening, Zerlinda should be used immediately. If the solution is not used immediately, it should be stored in the refrigerator at 2°C - 8°C.

6. Contents of the pack and other information

What Zerlinda contains

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

What Zerlinda looks like and contents of the pack

Zerlinda is a clear and colorless solution without visible particles, supplied in a plastic bag made of a five-layer material M312A, based on polyolefin, PVC, without a plasticizer. Two injection ports with a cap made of PP with a breaking point on the PP cap. The bag is additionally placed in a packaging made of Polyester Alox/PP, and then in a cardboard box.

Pack sizes:

1 bag of 100 ml

10 bags of 100 ml

Not all pack sizes may be marketed.

Marketing Authorization 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 more information about this medicine, please contact the Marketing Authorization Holder.

Teva Pharmaceuticals Polska Sp. z o.o., ul. Emilii Plater 53, 00-113 Warszawa, tel. (22) 345 93 00.

Date of last revision of the leaflet:August 2024

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The following information is intended for healthcare professionals only:

Information for Healthcare Professionals

Preparation and administration of Zerlinda

• The solution for infusion Zerlinda contains 4 mg of zoledronic acid in 100 ml of solution for infusion, ready for immediate use in patients with normal kidney function.
• For single use only. Any unused solution should be discarded. Only clear solutions without visible particles or discoloration should be used. When preparing the infusion, aseptic techniques should be followed.
• After opening: the chemical and physical stability of the medicinal product has been demonstrated for 24 hours at 2°C - 8°C. From a microbiological point of view, the solution for infusion should be used immediately. If not used immediately, the responsibility for the storage conditions and the storage time before use lies with the user, and the solution is stable for no longer than 24 hours at 2°C - 8°C. The solution should be brought to room temperature before administration.
• The solution containing zoledronic acid should not be further diluted or mixed with other solutions for infusion. Zerlinda should be given as an intravenous infusion over a period of not less than 15 minutes through a separate infusion line.
• Before each infusion of Zerlinda, the patient's hydration status should be assessed to ensure it is adequate.

Zerlinda solution for infusion can be administered to patients with normal kidney function without further preparation. For patients with mild to moderate kidney impairment, reduced doses of Zerlinda should be prepared according to the instructions below.

In order to prepare reduced doses for patients with CL ≤60 ml/min, use the data from the following Table 1. Withdraw the specified volume of Zerlinda solution from the bag and replace it with the same volume of sterile sodium chloride 9 mg/ml (0.9%) solution for injection or 5% glucose solution for injection.

*Doses were calculated assuming target AUC 0,66 (mg•h/l) (CL =75 ml/min). It is assumed that giving lower doses to patients with kidney impairment will achieve similar AUC values as in patients with creatinine clearance of 75 ml/min.

There are no data available on the compatibility of Zerlinda with other intravenous drugs. Zerlinda should not be mixed with other medicines or substances and should always be administered through a separate infusion set.

How to store Zerlinda

• Store in a place where children cannot see or reach it.
• Do not use Zerlinda after the expiry date stated on the label and carton after "EXP". The expiry date refers to the last day of that month.
• There are no special storage instructions for this medicinal product.
• After opening the bag, use immediately to avoid microbial contamination.