Zoledronic acid Galenica Senese

Patient Information Leaflet

Zoledronic Acid Galenica Senese 4 mg/100 ml infusion solution

Zoledronic Acid
Generic Medicine
Please read all of this leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

1. What Zoledronic Acid Galenica Senese is and what it is used for
2. What you need to know before using Zoledronic Acid Galenica Senese
3. How to use Zoledronic Acid Galenica Senese
4. Possible side effects
5. How to store Zoledronic Acid Galenica Senese
6. Contents of the pack and other information

1. What Acido zoledronico Galenica Senese is and what it is used for

The active substance of Acido zoledronico Galenica Senese is zoledronic acid, belonging to a group of
substances called bisphosphonates. Zoledronic acid works by binding to bone and slowing down its rate of
turnover. It is used:

• To prevent bone complications, such as fractures, in adult patients with bone metastases (spread of the tumour from the primary tumour site to the bones).
• To reduce the level of calcium in the blood in adult patients in whom it is too high due to the presence of tumour. Tumours can accelerate normal bone turnover so that the release of calcium from bone is increased. This condition is known as tumour-induced hypercalcaemia (TIH).

2. What you need to know before using Zoledronic Acid Galenica Senese

Zoledronic Acid Galenica Senese must not be administered to you if:

• you are allergic to zoledronic acid, to any other bisphosphonate (the group of substances to which Zoledronic Acid Galenica Senese belongs), or to any of the other ingredients of this medicine (listed in section 6);
• you are breastfeeding.

Warnings and precautions
Talk to your doctor or nurse before you are given Zoledronic Acid Galenica Senese:

• if you have or have had kidney problems;
• if you have or have had pain, swelling or numbness in the jaw, a feeling of heaviness in the jaw, or tooth loss. Your doctor may recommend that you undergo a dental examination before starting treatment with zoledronic acid;
• if you are currently undergoing dental treatments or need to undergo dental surgery, inform your dentist that you are being treated with zoledronic acid and inform your doctor about your dental treatments.

During treatment with Zoledronic Acid Galenica Senese, you must maintain good oral hygiene (including regular tooth cleaning) and undergo regular dental check-ups.
Immediately inform your doctor and dentist if you experience any problems in your mouth or teeth, such as tooth loss, pain, swelling, failure of wounds 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 steroids, those undergoing dental surgery, those not receiving routine dental care, those with gum disease, smokers, or those previously treated with bisphosphonates (used to treat or prevent bone disorders) have a higher risk of developing osteonecrosis of the jaw.
In patients treated with zoledronic acid, reduced levels of calcium in the blood (hypocalcemia) have been reported, which may sometimes cause muscle cramps, dry skin, or a burning sensation. Cases of irregular heartbeat (cardiac arrhythmia), seizures, and muscle spasms or contractions (tetany) secondary to severe hypocalcemia have also been reported. In some cases, hypocalcemia may be life-threatening. If any of these conditions apply to you, inform your doctor immediately. If you have pre-existing hypocalcemia, it must be corrected before starting the first dose of zoledronic acid. You will be given appropriate calcium and vitamin D supplements.
Carefully follow all instructions provided by your doctor.
Before starting treatment with Zoledronic Acid Galenica Senese, your doctor will perform blood tests and will monitor your response to treatment at regular intervals.
This medicine contains 342.9 mg of sodium (a main component of table salt) per bag. This corresponds to 17.15% of the recommended daily sodium intake for an adult.

Elderly
Zoledronic Acid Galenica Senese can be administered to individuals aged 65 years and older.
There is no evidence that additional precautions are required.

Children and adolescents
Zoledronic Acid Galenica Senese is not recommended for use in adolescents and children under 18 years of age.

Other medicines and Zoledronic Acid Galenica Senese
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
It is particularly important that you inform your doctor if you are also taking:

• Aminoglycosides (medicines used to treat serious infections), calcitonin (a medicine used to treat postmenopausal osteoporosis and hypercalcemia), diuretics (medicines used to treat high blood pressure or edema), or other medicines that lower calcium levels, as combining these with bisphosphonates may cause an excessive decrease in blood calcium concentration.
• Thalidomide (a medicine used to treat certain types of bone-involving blood cancers) or any other medicine that may harm the kidneys.
• Aclasta (a medicine containing zoledronic acid used for the treatment of osteoporosis and other non-oncological bone disorders), or any other bisphosphonate, since the combined effects of these medicines when taken together with Zoledronic Acid Galenica Senese are unknown.
• Anti-angiogenic medicines (used to treat cancer), as their combination with Zoledronic Acid Galenica Senese has been associated with an increased risk of osteonecrosis of the jaw (ONJ).

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or nurse before receiving this medicine.
Zoledronic Acid Galenica Senese must not be administered if you are pregnant or breastfeeding.

Driving and use of machines
Drowsiness has been reported very rarely with the use of zoledronic acid. Therefore, you should exercise maximum caution when driving, operating machinery, or performing other activities requiring full attention.

3. How to use Zoledronic Acid Galenica Senese

• Zoledronic Acid Galenica Senese must be administered only by healthcare personnel trained in the intravenous administration of bisphosphonates, i.e. through a vein. If you have any doubts, consult your doctor or nurse.
• Your doctor will recommend that you drink sufficient water before each treatment to help prevent dehydration.
• Carefully follow all other instructions given by your doctor or nurse.

How much Zoledronic Acid Galenica Senese is administered

• The recommended single dose is 4 mg.
• If you have kidney problems, your doctor will administer a reduced dose based on the severity of your renal impairment.

How often Zoledronic Acid Galenica Senese is administered

• If you are being treated to prevent bone complications due to bone metastases, you will receive an infusion of Zoledronic Acid Galenica Senese every three or four weeks.
• If you are being treated to reduce the amount of calcium in your blood, normally only a single infusion of Zoledronic Acid Galenica Senese will be administered.

How Zoledronic Acid Galenica Senese is administered

• Zoledronic Acid Galenica Senese is administered by intravenous infusion (drip) over a period of at least 15 minutes and must be given as a single intravenous solution through a separate infusion line.

Patients who have blood calcium levels that are not too high may also be prescribed daily calcium and vitamin D supplements.

If you have been given more Zoledronic Acid Galenica Senese than you should have

If you have received doses higher than those recommended, you must be closely monitored by your doctor. This is because you may develop serum electrolyte abnormalities (e.g. abnormal levels of calcium, phosphate, and magnesium) and/or changes in renal function, including severe kidney impairment. If calcium levels drop too low, you may need to be given an intravenous calcium supplement.

If you have any doubts about how to use this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them. The most common side effects are usually mild and may disappear within a short time.
Contact your doctor immediately if you experience any of the following serious side effects:
Common (may affect up to 1 in 10 people):

• Severe kidney damage (this will be assessed by your doctor through specific blood tests);
• Low blood calcium levels.

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

• Pain in the mouth, teeth and/or jaw, swelling or failure of sores to heal in the mouth or jaw/mandible, discharge, numbness or a feeling of heaviness in the jaw, or tooth loss. These may be signs of bone damage in the jaw/mandible (osteonecrosis). If you experience any of these symptoms during or after stopping treatment with Zoledronic Acid Galenica Senese, inform your doctor and dentist immediately.
• In patients treated with zoledronic acid for postmenopausal osteoporosis, an irregular heart rhythm (atrial fibrillation) has been observed. It is currently unknown whether zoledronic acid causes this irregular heart rhythm, but you should report any such symptoms to your doctor after receiving zoledronic acid.
• Severe allergic reaction: shortness of breath, swelling, particularly 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).
• A kidney function disorder called Fanconi syndrome (this is usually diagnosed by your doctor through certain 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).
• Contact your doctor if you experience ear pain, ear discharge, and/or ear infection. These events could be signs of bone damage in the ear.
• Osteonecrosis has very rarely occurred in other bones besides the jaw/mandible, particularly in the hip or thigh. If you experience symptoms such as onset or worsening of pain, pain or stiffness during or after stopping treatment with Zoledronic Acid Galenica Senese, inform your doctor immediately.

Contact your doctor as soon as possible if any of the following side effects occur:
Very common (may affect more than 1 in 10 people):

• Low levels of phosphate in the blood.

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

• Headache and flu-like syndrome with 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 reactions, such as nausea and vomiting, as well as loss of appetite.
• Conjunctivitis.
• Reduction in 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, anxiety, sleep disorders, taste disturbances, tremor, tingling or numbness in the hands or feet, diarrhea, constipation, abdominal pain, dry mouth.
• Low white blood cell and platelet counts in the blood.
• Low levels of magnesium and potassium in the blood. Your doctor will monitor these and take necessary measures.
• Weight gain.
• Increased sweating.
• Drowsiness.
• Blurred vision, eye lesions, light sensitivity.
• Sudden cold sensation with fainting, weakness, or collapse.
• Breathing difficulty with wheezing or cough.
• Hives.

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

• Slow heart rate.
• Confusion.
• Rarely, an unusual femur fracture may occur, particularly in patients receiving long-term treatment for osteoporosis. Contact your doctor if you experience pain, weakness, or discomfort in the thigh, hip, or groin, as this may be an early sign of a possible femur fracture.
• Interstitial lung disease (inflammation of the tissue around the air sacs in the lungs).
• Influenza-like symptoms including arthritis and joint swelling.
• Painful redness and/or swelling of the eyes.

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

• Fainting due to low blood pressure.
• Severe bone, joint, and/or muscle pain, occasionally disabling.

Not known (frequency cannot be estimated from the available data):
Inflammation of the kidney (tubulointerstitial nephritis): signs and symptoms may include reduced urine volume, blood in the urine, nausea, and a general feeling of malaise.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national reporting system at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Zoledronic Acid Galenica Senese

Your doctor or nurse knows how to store Zoledronic Acid Galenica Senese appropriately.
This medicinal product must not be used after the expiry date stated on the packaging. The expiry date refers to the last day of that month.
After first opening, Zoledronic Acid Galenica Senese solution for infusion should preferably be used immediately. If not used immediately, it must be stored in a refrigerator at a temperature of 2°C – 8°C.
Your doctor or nurse knows how to appropriately dispose of unused medicines.

6. Package contents and other information

What Acido zoledronico Galenica Senese contains

• The active substance is zoledronic acid. One bag contains 4 mg of zoledronic acid, equivalent to 4.26 mg of zoledronic acid monohydrate.
• The other components are: mannitol, sodium citrate dihydrate, sodium chloride, water for injections.

Description of the appearance of Acido zoledronico Galenica Senese and package contents
Acido zoledronico Galenica Senese infusion solution is a clear, colourless solution free from visible particles.
Acido zoledronico Galenica Senese is available in packages containing one 100 ml polyolefin bag.

Marketing Authorisation Holder and Manufacturer
Industria Farmaceutica Galenica Senese S.r.l.
Via Cassia Nord, 351
53014 Monteroni d'Arbia (SI)
Italy

INFORMATION FOR HEALTHCARE PROFESSIONALS
Acido zoledronico Galenica Senese 4 mg/100 ml infusion solution
Zoledronic Acid
Equivalent medicinal product

How to prepare and administer Acido zoledronico Galenica Senese

• Acido zoledronico Galenica Senese infusion solution contains 4 mg of zoledronic acid in 100 ml of solution for immediate use in patients with normal renal function.
• For single use only. Any unused solution must be discarded. Only use solutions that are free from visible particles, colourless and clear. Aseptic techniques must be followed during the preparation of the infusion.
• From a microbiological standpoint, the infusion solution should be used immediately after first opening. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at 2°C - 8°C, unless dilution has occurred under controlled and validated aseptic conditions. Refrigerated solution must 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 infusion through a separate infusion line. The patient's hydration status should be assessed before and after administration of zoledronic acid to ensure adequate hydration.
• Acido zoledronico Galenica Senese 4 mg/100 ml infusion solution can be used immediately, without further preparation, in patients with normal renal function. In patients with mild to moderate renal impairment, reduced doses must be prepared according to the instructions below.

To prepare reduced doses for patients with baseline CLcr ≤ 60 ml/min, refer to Table 1 below. Remove the volume of Acido zoledronico Galenica Senese solution indicated from the bag and replace it with an equal volume of sterile sodium chloride 9 mg/ml (0.9%) injection solution or 5% glucose injection solution.

Table 1: Preparation of reduced doses of Acido zoledronico Galenica Senese 4 mg/100 ml infusion solution

* The doses were calculated assuming a target AUC of 0.66 (mg•hr/l) (CLcr = 75 ml/min). Administration of the reduced dose in patients with renal impairment is expected to achieve an AUC value equal to that observed in patients with a creatinine clearance of 75 ml/min.

• Studies with various types of infusion lines made of polyvinyl chloride, polyethylene, and polypropylene have shown no incompatibility with zoledronic acid.
• Since there are no data available on the compatibility of zoledronic acid with other substances administered intravenously, Acido zoledronico Galenica Senese must not be mixed with other medicinal products/substances and must always be administered using a separate infusion line.

How to store Acido zoledronico Galenica Senese

• Keep this medicine out of the sight and reach of children.
• Do not use Acido zoledronico Galenica Senese after the expiry date stated on the packaging. The expiry date refers to the last day of the month.
• This medicinal product does not require any special storage conditions.
• After first opening or after preparation of reduced doses of zoledronic acid (as described above), from a microbiological standpoint, the infusion solution should be used immediately. If not used immediately, the duration and conditions of storage prior to use are under the responsibility of the user and generally should not exceed 24 hours between 2°C and 8°C. If refrigerated, the solution must reach room temperature before administration.
• Do not dispose of the medicine via wastewater. This will help protect the environment.