Zomikos

PATIENT REMINDER CARD
The reminder card contains important safety information that should be known before and during treatment with zoledronic acid (Zomikos medicinal product) administered as an infusion, used in oncology indications.

Your doctor has prescribed zoledronic acid (Zomikos medicinal product) as an intravenous infusion to prevent bone complications (e.g. fractures) caused by bone metastases or malignant bone tumors, and to reduce elevated calcium levels in the blood of adult patients when this elevation is due to the presence of cancer. Tumors may accelerate bone turnover, leading to increased release of calcium from bones. This condition is known as tumor-induced hypercalcemia (TIH).

In patients receiving infusions of zoledronic acid (Zomikos medicinal product) in oncology indications, a rare adverse reaction called osteonecrosis of the jaw (ONJ) (damage to the jawbone) has been reported. ONJ may also occur after discontinuation of treatment.

To reduce the risk of developing osteonecrosis of the jaw, certain precautions should be followed:

Before starting treatment:

• Before beginning treatment, ask your doctor to inform you about ONJ.
• Ask your doctor whether a dental examination is recommended before starting treatment with zoledronic acid (Zomikos medicinal product).
• Inform your treating physician/nurse (healthcare professional) about any symptoms or problems in the mouth or teeth.

Patients undergoing dental surgery (e.g. tooth extraction), those who do not receive routine dental care, patients with gum disease, smokers, patients receiving other oncology treatments, or those previously treated with bisphosphonates (used in the treatment or prevention of bone diseases) may be at higher risk of developing ONJ.

During treatment:

• Maintain proper oral hygiene, ensure proper fit of dental prostheses, and attend regular dental check-ups.
• Patients undergoing dental treatment or prior to dental procedures (e.g. tooth extraction) should inform their treating physician and inform their dentist that they are receiving zoledronic acid (Zomikos medicinal product).
• Immediately contact your treating physician and dentist if you experience any symptoms in the mouth or teeth, such as loose teeth, pain or swelling, non-healing ulcers, or discharge, as these may be signs of osteonecrosis of the jaw.

Package leaflet: information for the patient

Zomikos, 4 mg/5 ml, concentrate for solution for infusion
Acidum zoledronicum
Please read this leaflet carefully before using the medicine, as it contains important information for you.

• Keep this leaflet for future reference.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not give it to others. This medicine may harm someone else, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

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

1. What Zomikos is and what it is used for

The active substance in Zomikos 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 (cancer spread from its original site to the bones);
to reduce elevated calcium levels in the blood of adult patients when this elevation is due to cancer. Tumors may accelerate bone turnover, causing increased release of calcium from bones. This condition is known as tumor-induced hypercalcemia (TIH).

2. Important information before using Zomikos

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

When not to use Zomikos:

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

Warnings and precautions
Before using Zomikos, discuss the following 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 you visit a dentist before starting treatment with Zomikos;
• if the patient is currently undergoing dental treatment or plans to have jaw surgery; in such cases, inform your dentist that you are receiving Zomikos and inform your doctor about any dental procedures.

While being treated with Zomikos, 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.
Patients undergoing chemotherapy and/or radiotherapy, those taking corticosteroids, those undergoing jaw 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 a burning sensation.
Cases of irregular heartbeat (cardiac arrhythmia), seizures, muscle spasms, and tetany have been reported due to severe hypocalcaemia. In some cases, hypocalcaemia may be life-threatening. If any of these apply to you, inform your doctor immediately. If the patient has hypocalcaemia, it must be corrected before the first dose of Zomikos is administered. The patient will receive appropriate calcium and vitamin D supplements.

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

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

Zomikos with other medicines
Tell your doctor about all medicines the patient is currently taking, has recently taken, or plans to take. It is especially important to inform your doctor if the patient is 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 using these together with bisphosphonates may cause excessive reduction in blood calcium;
• thalidomide (a medicine used to treat certain blood cancers with bone involvement) or other medicines that may harm the kidneys;
• Aclasta (a medicine also containing zoledronic acid, used to treat osteoporosis and other non-tumour bone diseases) or other bisphosphonates, as the combined effects of these medicines with Zomikos 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
Zomikos must not be used during pregnancy. Inform your doctor if you are pregnant or suspect you may be pregnant.
Zomikos must not be used in breastfeeding women.
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.

Zomikos contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) in 5 ml of concentrate, meaning the medicine is considered "sodium-free". However, if your doctor uses 0.9% w/v sodium chloride solution to dilute Zomikos, the resulting dose of sodium will be higher.

3. How to use Zomikos

• Zomikos must be administered only by healthcare professionals who are adequately trained in the intravenous administration of bisphosphonates.
• Your doctor will recommend drinking an adequate amount of water before each dose to prevent dehydration.
• You must carefully follow all other instructions provided by your doctor, pharmacist, or nurse.

What dose of Zomikos should be used
The single dose of Zomikos is 4 mg. If the patient has impaired kidney function, the treating physician will prescribe a lower dose depending on the severity of kidney disease.

How often should Zomikos be used
For the prevention of skeletal complications due to bone metastases, one infusion of Zomikos is administered every three to four weeks.
For the treatment of elevated calcium levels in the blood, usually only a single infusion of Zomikos is given.

How Zomikos is administered
Zomikos is administered as an intravenous infusion (drip infusion). The infusion must last at least 15 minutes and should be given as a separate intravenous solution through a dedicated infusion line.
For patients whose blood calcium levels are not too high, the doctor will prescribe daily calcium and vitamin D supplements.

Overdose of Zomikos
Patients who have received doses of Zomikos higher than recommended 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 all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The most common adverse reactions are usually mild and are likely to resolve within 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 patients):
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 patients):
pain in the mouth, tooth and/or jaw pain, swelling or non-healing ulcers in the mouth or jaw, presence of 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 Zomikos;
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 patients):
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 specific urine tests).

Very rare (may affect less than 1 in 10,000 patients):
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 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 the medicinal product Zomikos.

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 the 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 patients):
low phosphate levels in the blood.

Common (may affect less than 1 in 10 patients):
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 patients):
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 in 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;
weight gain;
excessive sweating;
drowsiness;
blurred vision, tearing of the eyes, light sensitivity;
sudden feeling of cold with fainting, collapse, or weakness;
difficulty breathing, with wheezing and coughing;
urticaria.

Rare (may affect less than 1 in 1,000 patients):
slow heart rate;
confusion;
in rare cases, atypical femoral fractures 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 area, as this may be an early sign indicating 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 patients):
fainting due to low blood pressure;
severe bone, joint, and/or muscle pain, sometimes leading to immobility.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, you should inform your doctor or pharmacist. 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
PL-02 222 Warsaw
Tel.: + 48 22 49 21 301
Faks: + 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 the medicine Zomikos

The prescribing doctor, nurse, or pharmacist is informed about how to store the medicine
Zomikos.
The medicine should be stored in a place inaccessible and out of sight of children.
Do not freeze.
Do not use this medicine after the expiry date stated on the carton after: Expiry date (EXP). The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via the sewage system or household waste bins. Ask a pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the packaging and other information

What Zomikos contains
The active substance in Zomikos is zoledronic acid. One 5 ml vial of concentrate contains 4 mg of zoledronic acid, equivalent to 4.264 mg of monohydrate zoledronic acid.
Other ingredients: mannitol, sodium citrate, water for injections.

What Zomikos looks like and contents of the pack
Zomikos is supplied as a liquid concentrate in a vial. Each vial contains 4 mg of zoledronic acid.
Each pack contains one vial of concentrate. Zomikos is available in packs containing 1, 4, or 10 vials in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Vipharm S.A.
ul. A. i F. Radziwiłłów 9
05-850 Ożarów Mazowiecki
Poland
e-mail: [email protected]
tel.: (+4822) 679 51 35

This medicinal product has been authorised in the EEA Member States under the following names:
Czech Republic: Zomikos 4mg/5ml
Germany: Zoledronsäure Vipharm 4mg/5ml Konzentrat zur Herstellung einer Infusionslösung
Poland: Zomikos
Slovakia: Zomikos 4mg/5ml
Hungary: Zoledronsav Vipharm 4mg/5ml koncentrátum oldatos infúzióhoz

INFORMATION FOR MEDICAL PERSONNEL

Preparation and administration of Zomikos
To prepare an infusion solution containing 4 mg of zoledronic acid, the Zomikos concentrate (5.0 ml) should be diluted in 100 ml of infusion solution that does not contain calcium or other divalent cations.
If a lower dose is required, the appropriate volume of the concentrate should first be withdrawn as recommended below, and 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 Zomikos solution with solutions containing calcium or other divalent cations, e.g. Ringer's lactate solution.

Method for preparing reduced doses of Zomikos:
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 portions must be discarded.
Only clear solutions free from particles and discoloration should be used.
Aseptic techniques must be followed during preparation of the infusion.
From a microbiological point of view, the diluted infusion solution should be used immediately. If not used immediately, the responsibility for storage conditions and duration prior to use lies with the user, and the solution is stable for no longer than 24 hours at 2°C – 8°C. Before administration, refrigerated solutions should be brought to room temperature.

The zoledronic acid solution should be administered as a 15-minute intravenous infusion via a separate infusion line. Patient hydration status should be assessed prior to each administration of Zomikos to ensure adequate hydration.

Studies have shown no incompatibility of Zomikos with various types of infusion sets made of polyvinyl chloride, polyethylene, and polypropylene.

Due to lack of data on compatibility with other intravenous medicinal products, Zomikos should not be mixed with other medicines. The Zomikos solution should always be administered using a separate infusion set.

Storage of Zomikos

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