Osporil

Package leaflet: Information for the user

Osporil, 4 mg /100 ml, infusion solution
Acidum zoledronicum
Please read the entire leaflet carefully before use, as it contains
important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents:

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

1. What Osporil is and what it is used for

The active substance in Osporil 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 remodeling. It is used:

• to prevent bone 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 the increase is due to malignancy. Tumors may accelerate bone turnover, causing excessive release of calcium from the bones. This condition is known as tumor-induced hypercalcemia (TIH).

2. Important information before using Osporil

You must strictly follow all your doctor's instructions.
Your doctor will recommend blood tests before starting treatment with Osporil and will monitor your response to treatment at regular intervals.

When not to use Osporil

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

Warnings and precautions
Before using Osporil, 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. The treating physician may recommend a dental examination before starting treatment with Osporil;
• if the patient is currently undergoing dental treatment or plans to have jaw surgery, the patient should inform their dentist about taking Osporil and inform their physician about any dental procedures.

During treatment with Osporil, the patient should maintain proper oral hygiene (brush teeth regularly) and attend regular preventive check-ups.
If any oral problems occur, such as loose teeth, pain or swelling, non-healing sores, or discharge, the patient should contact their doctor and dentist immediately, as these may be symptoms of a condition called osteonecrosis of the jaw.
Patients receiving chemotherapy and/or radiotherapy, taking steroids, undergoing jaw surgery, not maintaining proper oral hygiene, suffering from gum disease, smokers, or patients previously treated with bisphosphonates (used to prevent or treat bone diseases) are at increased risk of developing osteonecrosis of the jaw.
Decreased calcium levels in the blood (hypocalcemia) have been reported in patients receiving Osporil, which may sometimes cause muscle cramps, dry skin, and tingling sensations.
Cases of irregular heartbeat (cardiac arrhythmia), seizures, muscle spasms, and tetany have been reported due to severe hypocalcemia. In some cases, hypocalcemia may be life-threatening. If any of these situations apply to the patient, the doctor should be informed immediately. Any pre-existing hypocalcemia must be corrected before administering the first dose of Osporil. The patient will receive appropriate calcium and vitamin D supplements.

Patients aged 65 years and older
Osporil may be used in patients aged 65 years and older. There are no data indicating additional warnings required in this patient group.

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

Osporil and other medicines
Inform 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 the use of:

• aminoglycoside antibiotics (medicines used to treat serious infections), because their concomitant use with bisphosphonates may cause excessive reduction in blood calcium levels;
• thalidomide (a medicine used in the treatment of certain blood cancers with bone involvement) or other medicines that may harm the kidneys;
• other medicines containing zoledronic acid used in the treatment of osteoporosis and other non-malignant bone diseases, or other bisphosphonates, because the combined effects of these medicines taken together with Osporil are unknown;
• anti-angiogenic medicines (used in cancer treatment), because concomitant use of these medicines with Osporil has been associated with an increased risk of osteonecrosis of the jaw (ONJ).

Pregnancy and breastfeeding
Osporil must not be used during pregnancy. If the patient is pregnant or suspects she may be pregnant, she should inform her doctor.
Osporil must not be used in breastfeeding women.
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor before using this medicine.

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

Osporil contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 100 ml vial, meaning the medicine is considered "sodium-free".

3. How to use Osporil

Osporil must be administered only by healthcare professionals
who have appropriate training 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.
Carefully follow all other instructions given by your doctor, nurse, or pharmacist.

What dose of Osporil should be used

• The recommended 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 should Osporil be used

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

How Osporil is administered
Osporil is given as an intravenous infusion (drip 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.
For patients whose calcium levels in the blood are not too high, the doctor will prescribe calcium and vitamin D for daily intake.

Overdose of Osporil
Patients who have received higher than recommended doses of Osporil should be closely monitored. This is necessary due to the possible occurrence of abnormal serum electrolyte levels (e.g. calcium, phosphate, and magnesium) 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 adverse reactions are usually mild in nature and are 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 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 up to 1 in 100 patients):

• Oral pain, toothache and (or) jaw pain, swelling or non-healing oral sores or on the jaw, discharge, numbness or sensation of heaviness in the jaw, or loose teeth. These may be symptoms of jaw bone damage (osteonecrosis). If such symptoms occur during treatment with Osporil or after its discontinuation, you should immediately inform your doctor or dentist.
• 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 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 patients):

• As a consequence of low calcium levels: irregular heartbeat (cardiac arrhythmia; secondary to hypocalcemia), seizures, numbness and tetany (secondary to hypocalcemia).
• Kidney dysfunction known as Fanconi syndrome (usually confirmed by the treating physician after specific urine tests).

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

• As a consequence of low calcium levels: convulsions, numbness and tetany (secondary to hypocalcemia).
• If a patient develops ear pain, ear discharge and (or) ear infection, the patient should inform the doctor. These may be symptoms of bone tissue damage in the ear.
• Osteonecrosis of bones other than the jaw, especially in the hip and thigh, has been very rarely observed. You should immediately inform your doctor if symptoms such as new or worsening pain, pain or stiffness during or after completion of treatment with the medicinal product Osporil occur.

Frequency not known: frequency cannot be estimated from the available data

• Kidney inflammation (tubulointerstitial nephritis): objective and subjective symptoms may include decreased urine volume, presence of blood in 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 up to 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 (anaemia).

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

• Hypersensitivity reactions;
• Low blood pressure;
• Chest pain;
• Skin reactions at the injection site such as redness and swelling, rash, itching;
• High blood pressure, shallow breathing, dizziness, sleep disturbances, taste disturbances, tingling and numbness in hands or feet, 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;
• Increased body weight;
• Increased sweating;
• Drowsiness;
• Blurred vision, watery eyes, light sensitivity;
• Sudden feeling of cold with fainting, body collapse or collapse;
• Breathing difficulties, with wheezing and coughing;
• Urticaria.

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

• Slow heart rate;
• 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 area, as this may be an early sign of 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 around the eyes.

Very rare (may affect up to 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 symptoms occur, including any adverse symptoms 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.
By reporting adverse reactions, more information on the safety of the medicine can be collected.

5. How to store Osporil

The physician in charge, nurse or pharmacist are informed about how to store the medicinal product
Osporil (see section 6).
After opening, the infusion solution should ideally 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 package and other information

What the medicine Osporil contains

• The active substance is zoledronic acid. One vial contains 4 mg of zoledronic acid (as zoledronic acid monohydrate).
• The other ingredients are: mannitol (E421), sodium citrate, water for injections and nitrogen.

What Osporil looks like and contents of the pack
Osporil is supplied as a solution in a glass vial. One vial contains 100 ml of solution.
Pack sizes:
1 vial of 100 ml
10 vials of 100 ml
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Egis Pharmaceuticals PLC
Keresztúri út 30-38
1106 Budapest
Hungary
Manufacturer:
SM Farmaceutici SRL
Zona Industriale
85050 Tito (PZ)
Italy
EGIS Pharmaceuticals PLC
Bökényföldi út 118-120
H-1165 Budapest
Hungary
This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Iceland Osporil 4mg/100ml innrennslislyf, lausn
Hungary Osporil 4mg/100ml oldatos infúzió
Slovakia Osporil 4mg/100ml
Poland Osporil
INFORMATION INTENDED ONLY FOR MEDICAL PROFESSIONALS
Preparation and administration of Osporil

• Osporil 4 mg/100 ml infusion solution contains 4 mg of zoledronic acid in 100 ml of infusion solution for direct administration in patients with normal renal function.
• For single use only. Any unused solution should be discarded. Only clear, colourless solution free from particulate matter or discolouration should be used. Aseptic techniques must be observed during preparation of the infusion.
• From a microbiological standpoint, the infusion solution should be administered immediately after first opening of the container. If not used immediately, the responsibility for storage conditions and duration prior to use rests with the user and should generally not exceed 24 hours at 2°C–8°C, unless dilution has been carried out under controlled and validated aseptic conditions. The cooled solution should be brought to room temperature before administration.
• The solution containing zoledronic acid must not be further diluted or mixed with other infusion solutions. It is administered as a single 15-minute intravenous infusion through a separate infusion line. Before and after administration of Osporil, the patient's hydration status should be assessed to ensure adequate hydration.
• In patients with normal renal function, Osporil 4 mg/100 ml infusion solution can be used directly without further preparation. In patients with mild to moderate renal impairment, reduced doses should be prepared according to the instructions below.

In patients with bone metastases and mild to moderate renal impairment prior to starting treatment (CLcr 30–60 ml/min), dose reduction is recommended. To prepare the infusion, see Table 1 below.
Remove the specified volume of Osporil solution from the vial and replace it with an equal volume of sterile 9 mg/ml (0.9%) sodium chloride solution for injection or 5% glucose solution for injection.
Table 1.: Preparation of reduced doses of Osporil 4 mg/100 ml infusion solution

* Doses were calculated assuming a target area under the concentration-time curve (AUC) of 0.66 (mg•h/L) (creatinine clearance = 75 mL/min). Reduced doses in patients with impaired renal function should provide the same AUC values as those observed in patients with a creatinine clearance of 75 mL/min.

• Studies with several types of infusion lines made of polyvinyl chloride, polyethylene, and polypropylene showed no incompatibility with Osporil.
• Since there are no data on the compatibility of Osporil with other intravenously administered substances, Osporil must not be mixed with other medicinal products/substances and should always be administered through a separate infusion line.

How to store Osporil

• Keep the medicine out of the sight and reach of children.
• Do not use Osporil after the expiry date stated on the container.
• The unopened vial does not require special storage conditions.
• After opening, the product should be used immediately to avoid microbiological contamination.