Osporil

Package Leaflet: Information for the User

Osporil, 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.

• You should 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 and other information

• 1. What Osporil is and what it is used for
• 2. Before you are given Osporil
• 3. How Osporil is given
• 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 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 that has spread to the bone, when the levels are high.

2. Before you are given Osporil

Follow all your doctor's instructions carefully. Your doctor will order blood tests before you start taking Osporil and will check your response to treatment at regular intervals.

When Osporil must not be given

• if you are breast-feeding;
• if you are allergic to zoledronic acid or any other bisphosphonate (a group of medicines that includes Osporil) or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Before you are given Osporil, tell your doctor:

• if you have or have had kidney problems;
• if you have or have had pain, swelling, or numbnessin the jaw, feeling of heaviness in the jaw, or loosening of a tooth. Your doctor may recommend a dental examination before starting Osporil;
• if you are having dental treatmentor are planning a dental surgery, inform your dentist that you are being treated with Osporil and inform your doctor about your dental treatment.

During treatment with Osporil, you should maintain good oral hygiene (regularly brush your teeth) and have regular dental check-ups. If you have any symptoms in your mouth such as loose teeth, pain, or swelling, or any non-healing sores or discharge, you should contact your doctor and dentist as these could be signs of a condition called jawbone necrosis (osteonecrosis of the jaw).

Patients receiving chemotherapy and/or radiation therapy, taking steroids, undergoing dental surgery, not maintaining good oral hygiene, suffering from gum disease, smoking, or previously treated with bisphosphonates (used to prevent or treat bone diseases) are at increased risk of developing jawbone necrosis.

Patients treated with Osporil have reported low levels of calcium in the blood (hypocalcemia), which can sometimes cause muscle cramps, dry skin, and a tingling sensation.

Reports have been made of irregular heartbeat (arrhythmia), seizures, muscle cramps, and twitching (tetany) due to severe hypocalcemia. In some cases, hypocalcemia can be life-threatening. If any of these situations apply to you, you should inform your doctor immediately. If you have had hypocalcemia before, it must be corrected before the first dose of Osporil is given. You will be given calcium and vitamin D supplements.

Patients over 65 years of age

Osporil can be used in patients over 65 years of age. There are no additional warnings required for this age group.

Children and adolescents

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

Other medicines and Osporil

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), as the combination of these antibiotics with bisphosphonates may cause a significant decrease in calcium levels 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, used to treat osteoporosis and other non-cancerous bone diseases, or other bisphosphonates, as the combined effects of these medicines with Osporil are not known;
• anti-angiogenic medicines (used to treat cancer), as the combination of these medicines with Osporil has been associated with an increased risk of jawbone necrosis (osteonecrosis of the jaw).

Pregnancy and breast-feeding

Osporil must not be used during pregnancy. If you are pregnant or think you may be pregnant, you must tell your doctor.

Osporil must not be used in women who are breast-feeding.

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, you must ask your doctor for advice before taking this medicine.

Driving and using machines

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

Osporil contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per 100 ml vial, which is essentially 'sodium-free'.

3. How Osporil is given

Osporil must be administered by a healthcare professional, who has the necessary experience in the intravenous administration of bisphosphonates.

Your doctor will advise you to drink a sufficient amount of water before each administration of Osporil to prevent dehydration.

Follow all other instructions given by your doctor, nurse, or pharmacist.

What dose of Osporil will you be given

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

How often will you be given Osporil

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

How Osporil is given

Osporil is given as a drip (infusion) into a vein. The infusion should last at least 15 minutes and should be given as a separate intravenous infusion through a separate infusion line.

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

What to do if you are given too much Osporil

Patients who have been given too much Osporil should be carefully monitored. This is necessary because of the risk of abnormal levels of electrolytes in the blood (such as 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 be given a calcium infusion.

4. Possible side effects

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

You must tell your doctor immediately if you notice 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, and/or jaw pain, swelling, or non-healing sores in the mouth or jaw, discharge, numbness, or feeling of heaviness in the jaw, or loosening of a tooth. These could be signs of jawbone damage (osteonecrosis of the jaw). If you get any of these symptoms while being treated with Osporil or after you have finished treatment, you should tell your doctor or dentist immediately.
• 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 of these 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), seizures, numbness, and muscle cramps (secondary to hypocalcemia).
• Kidney problems called Fanconi syndrome (usually 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 cramps (secondary to hypocalcemia).
• If you experience ear pain, discharge from the ear, and/or ear infection, you should tell your doctor. These could be signs of bone damage in the ear.
• Very rarely, bone damage in the hip and thigh has been reported. You should tell your doctor immediately if you experience symptoms such as new or increasing pain, or stiffness during or after treatment with Osporil.

Frequency 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, feeling unwell.

Tell your doctor immediately if you notice 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 go away after a short time (a few hours or days);
• Gastrointestinal symptoms such as nausea, vomiting, and loss of appetite;
• Conjunctivitis;
• Low red blood cell count (anemia).

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

• Hypersensitivity reactions;
• Low blood pressure;
• Chest pain;
• Skin reactions (redness and swelling) at the infusion site, rash, itching;
• High blood pressure, shortness of breath, dizziness, sleep disturbances, taste disturbances, tingling and numbness of the hands or feet, constipation, abdominal pain, dry mouth;
• Low levels of magnesium and potassium in the blood. Your doctor will monitor this and order any necessary tests;
• Weight gain;
• Increased sweating;
• Sleepiness;
• Blurred vision, tearing, sensitivity to light;
• Sudden feeling of cold 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;
• In rare cases, unusual fractures of the thigh bone, especially in patients treated for osteoporosis for a long time. You should tell your doctor if you experience pain, weakness, or discomfort in the thigh, hip, or groin, as this could 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 in the eye area.

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.

5. How to store Osporil

Your doctor, nurse, or pharmacist are informed about how to store Osporil (see section 6).

After opening, the infusion solution 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 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 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

Date of last revision of the leaflet: 12.08.2024

INFORMATION INTENDED FOR MEDICAL PROFESSIONALS ONLY

Preparation and administration of Osporil

• Osporil, 4 mg/100 ml, solution for infusion contains 4 mg of zoledronic acid in 100 ml of solution for infusion for direct use in patients with normal kidney function.
• For single use only. Unused solution should be discarded. Only clear solution without particles or discoloration should be used. During preparation of the infusion, aseptic techniques should be followed.
• 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 the next use lies with the user and is usually not more than 24 hours at 2°C-8°C, unless dilution has been made in controlled and validated aseptic conditions. The cooled 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. It is given as a single 15-minute intravenous infusion in a separate infusion line. Before and after administration of Osporil, the patient's hydration status should be assessed to ensure that the patient is adequately hydrated.
• In patients with normal kidney function, Osporil, 4 mg/100 ml, solution for infusion can be used directly without further preparation. In patients with mild or moderate kidney impairment, smaller doses should be prepared according to the following instructions.

In patients with bone metastases and mild to moderate kidney impairment (creatinine clearance 30–60 ml/min), a dose reduction is recommended. To prepare the infusion, see Table 1 below.

*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 kidney function should provide the same AUC values as those observed in patients with creatinine clearance of 75 ml/min.

• Studies with several types of infusion lines made of polyvinyl chloride, polyethylene, and polypropylene did not show any incompatibility with Osporil.
• As there are no data on the compatibility of Osporil with other intravenously administered substances, Osporil should not be mixed with other medicines/substances and should always be administered through a separate infusion line.

How to store Osporil

• Store in a place out of the sight and reach of children.
• Do not use Osporil after the expiry date stated on the packaging.
• The unopened vial does not require any special storage conditions.
• After opening, the product should be used immediately to avoid microbial contamination.