Zoledronic acid Seacross

Package leaflet: Information for the user

ZOLEDRONIC ACID SEACROSS 5 mg/100 mL solution for infusion

zoledronic acid
Equivalent 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, pharmacist or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

What is in this leaflet

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

1. What ACIDO ZOLEDRONICO SEACROSS is and what it is used for

ACIDO ZOLEDRONICO SEACROSS contains the active substance acido zoledronico (zoledronic acid). It belongs to a group of medicines called bisphosphonates and is used to treat postmenopausal women and adult men with osteoporosis or steroid-induced osteoporosis (caused by corticosteroid treatment used to manage inflammation), as well as for the treatment of Paget’s disease of bone in adults.

Osteoporosis
Osteoporosis is a disease that causes thinning and weakening of the bones. It is common in women after menopause, but can also occur in men. At menopause, the ovaries stop producing the female hormone estrogen, which helps maintain bone health. After menopause, bone loss occurs, bones become weaker and are more likely to break. Osteoporosis can also develop in both men and women due to long-term use of steroids, which may affect bone strength. Many patients with osteoporosis have no symptoms, but are still at risk of bone fractures because osteoporosis has made their bones more fragile. Reduced levels of circulating sex hormones, primarily estrogens converted from androgens, also play a role in the gradual bone loss observed in men. In both women and men, ACIDO ZOLEDRONICO SEACROSS strengthens the bones and reduces the risk of fractures.

ACIDO ZOLEDRONICO SEACROSS is also used in patients who have recently experienced a hip fracture due to minor trauma, such as a fall, and are therefore at increased risk of further bone fractures.

Paget’s disease of bone
It is normal for old bone to be removed and replaced by new bone tissue. This process is called bone remodeling. In Paget’s disease, bone remodeling occurs too rapidly, and the new bone forms in a disorganized way, making it weaker than normal. If left untreated, bones may become deformed, painful, and more likely to fracture. ACIDO ZOLEDRONICO SEACROSS works by normalizing the bone remodeling process, promoting normal bone formation and thereby restoring bone strength.

2. What you need to know before using ACIDO ZOLEDRONICO SEACROSS

Follow carefully all instructions given to you by your doctor, pharmacist, or nurse before ACIDO ZOLEDRONICO SEACROSS is administered.

ACIDO ZOLEDRONICO SEACROSS must not be given to you

• if you are allergic to zoledronic acid, other bisphosphonates, or any of the excipients of this medicine (listed in section 6).
• if you have hypocalcemia (i.e. if your blood calcium levels are too low).
• if you have severe kidney problems.
• if you are pregnant.
• if you are breastfeeding.

Warnings and precautions

Talk to your doctor before you are given ACIDO ZOLEDRONICO SEACROSS:

• if you are being treated with any medicine containing zoledronic acid, which is also the active substance in ACIDO ZOLEDRONICO SEACROSS (zoledronic acid is used in adult patients with certain types of cancer to prevent bone complications or to reduce calcium levels).
• if you have kidney problems or have had them in the past.
• if you cannot take a daily calcium supplement.
• if you have had part or all of your parathyroid glands surgically removed from your neck.
• if sections of your intestine have been removed.

An adverse effect called osteonecrosis of the jaw/mandible (bone damage of the jaw/mandible) has been reported in post-marketing experience in patients treated with zoledronic acid for the treatment of osteoporosis. Osteonecrosis of the jaw/mandible may even occur after discontinuation of treatment.

It is important to try to prevent the onset of osteonecrosis of the jaw/mandible, as it is a painful condition that may be difficult to treat. To reduce the risk of developing osteonecrosis of the jaw/mandible, there are certain precautions you should take.

Before receiving treatment with ACIDO ZOLEDRONICO SEACROSS, talk to your doctor, pharmacist, or nurse if:

• you have any mouth or dental problems such as poor dental health, gum disease, or if you have planned a dental extraction;
• you do not receive routine dental care or have not had a dental check-up for a long time;
• you are a smoker (as this may increase the risk of dental problems);
• you have previously been treated with a bisphosphonate (used to treat or prevent bone disorders);
• you are taking medicines called corticosteroids (such as prednisolone or dexamethasone);
• you have cancer.

Your doctor may ask you to have a dental examination before starting treatment with ACIDO ZOLEDRONICO SEACROSS.

During treatment with ACIDO ZOLEDRONICO SEACROSS, you must maintain good oral hygiene (including regular tooth cleaning) and receive routine dental check-ups. If you wear dentures, make sure they are properly fitted. If you are undergoing dental treatment or need to have dental surgery (e.g. tooth extractions), inform your doctor and tell your dentist that you are being treated with ACIDO ZOLEDRONICO SEACROSS. Immediately inform your doctor and dentist if you experience any mouth or dental problems such as tooth loss, pain, swelling, failure of wounds to heal, or discharge, as these may be signs of osteonecrosis of the jaw/mandible.

Monitoring tests

Your doctor must take a blood sample to check your kidney function (creatinine levels) before each infusion of ACIDO ZOLEDRONICO SEACROSS. It is important that you drink at least two glasses of fluid (for example, water) within a few hours before treatment with ACIDO ZOLEDRONICO SEACROSS, as instructed by your healthcare provider.

Children and adolescents

ACIDO ZOLEDRONICO SEACROSS is not recommended for use in individuals under 18 years of age.

Other medicines and ACIDO ZOLEDRONICO SEACROSS

Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.

It is important for your doctor to know about all medicines you are taking, especially if you are already taking other medicines that may potentially harm the kidneys (e.g. aminoglycosides) or diuretics (“water tablets”) that may cause dehydration.

Pregnancy and breastfeeding

If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, ACIDO ZOLEDRONICO SEACROSS must not be administered to you.

Ask your doctor, pharmacist, or nurse for advice before taking this medicine.

Driving and using machines

If you feel dizzy while taking ACIDO ZOLEDRONICO SEACROSS, do not drive or operate machinery until you feel better.

ACIDO ZOLEDRONICO SEACROSS contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 100 mL vial of ACIDO ZOLEDRONICO SEACROSS, i.e. essentially “sodium-free”.

3. How to use ACIDO ZOLEDRONICO SEACROSS

Follow carefully all instructions given to you by your doctor or nurse. If you have any doubts, consult your
doctor or nurse.
Osteoporosis
The usual dose is 5 mg, administered by your doctor or nurse as a single intravenous infusion once a year.
The infusion will last at least 15 minutes.
In case of a recent hip fracture, administration of ACIDO ZOLEDRONICO SEACROSS is recommended
two or more weeks after surgical repair of the hip fracture.
It is important to take calcium and vitamin D supplements (e.g. tablets) as instructed by your doctor.
For osteoporosis, ACIDO ZOLEDRONICO SEACROSS acts for one year. Your doctor will inform you
when to return for the next dose.
Paget’s disease
For the treatment of Paget’s disease, ACIDO ZOLEDRONICO SEACROSS should only be prescribed
by physicians experienced in the management of bone Paget’s disease.
The usual dose is 5 mg, administered by your doctor or nurse as an initial intravenous infusion.
The infusion will last at least 15 minutes. ACIDO ZOLEDRONICO SEACROSS may be effective for
more than one year, and your doctor will inform you whether further treatment is needed.
Your doctor may recommend taking calcium and vitamin D supplements (e.g. tablets) for at least the first
ten days following administration of ACIDO ZOLEDRONICO SEACROSS.
It is important that you follow this advice carefully to prevent low calcium levels in the blood in the period
following the infusion. Your doctor will inform you about possible symptoms associated with hypocalcemia.
ACIDO ZOLEDRONICO SEACROSS with food and drink
Make sure you drink enough fluids (at least one or two glasses) before and after treatment with
ACIDO ZOLEDRONICO SEACROSS, as directed by your doctor. This will help prevent dehydration.
On the day of treatment with ACIDO ZOLEDRONICO SEACROSS, you may eat normally. This is
particularly important for patients taking diuretics (water pills) and for elderly patients (65 years of age or older).
If you forget a dose of ACIDO ZOLEDRONICO SEACROSS
Contact your doctor or hospital as soon as possible to schedule a new appointment.
Before stopping treatment with ACIDO ZOLEDRONICO SEACROSS
If you are considering stopping treatment with ACIDO ZOLEDRONICO SEACROSS, attend your next
scheduled appointment and discuss this with your doctor. Your doctor can advise you and decide for how
long treatment should continue.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Side effects related to the first infusion are very common (occur in more than 30% of patients) but become less common after subsequent infusions. Most side effects, such as fever and chills, muscle or joint pain, and headache, occur within the first three days following administration of zoledronic acid. Symptoms are usually mild to moderate and resolve within three days. Your doctor may recommend a mild pain reliever such as ibuprofen or paracetamol to reduce these side effects. The likelihood of experiencing side effects decreases with subsequent doses of ACIDO ZOLEDRONICO SEACROSS.
Some side effects may be serious
Common (may affect up to 1 in 10 people)
In patients treated with zoledronic acid for postmenopausal osteoporosis, irregular heart rhythm (atrial fibrillation) has been observed. It is currently unclear whether zoledronic acid is the cause of this irregular heart rhythm, but you must inform your doctor if you experience such symptoms after receiving zoledronic acid.
Uncommon (may affect up to 1 in 100 people)
Swelling, redness, pain, and itching of the eyes or sensitivity of the eyes to light.
Very rare (may affect up to 1 in 10,000 people)
Contact your doctor if you experience ear pain, ear discharge, and/or ear infection. These episodes could be signs of bone damage in the ear.
Not known (frequency cannot be estimated from available data)
Pain in the mouth and/or jaw, swelling or sores in the mouth or jaw that do not heal, discharge, numbness, or a feeling of heaviness in the jaw, or tooth loss; these could be signs of severe deterioration of the jawbone/mandible (osteonecrosis). Immediately inform your doctor and dentist if such symptoms occur while you are being treated with zoledronic acid or after stopping treatment.
Kidney problems (e.g., reduced urine output) may occur. Your doctor should perform a blood test to check your kidney function before each infusion of zoledronic acid. It is important to drink at least one or two glasses of fluid (e.g., water) within a few hours before treatment with zoledronic acid, as advised by your healthcare provider.
If you experience any of these side effects, inform your doctor immediately.
Zoledronic acid may also cause other side effects
Very common (may affect more than 1 in 10 people)
Fever
Common (may affect up to 1 in 10 people)
Headache, dizziness, malaise, vomiting, diarrhea, muscle pain, bone and/or joint pain, back, arm, or leg pain, flu-like symptoms (e.g., fatigue, chills, joint and muscle pain), chills, feeling of tiredness and lack of interest, weakness, pain, feeling unwell, swelling and/or pain at the infusion site.
In patients with Paget’s disease, symptoms due to low blood calcium levels have been reported, such as muscle spasms, or numbness or tingling, particularly around the mouth.
Uncommon (may affect up to 1 in 100 people)
Influenza, upper respiratory tract infections, decreased red blood cell count, loss of appetite, insomnia, drowsiness which may include reduced alertness and consciousness, sensation of tingling or numbness, extreme fatigue, tremor, temporary loss of consciousness, eye infection or irritation or inflammation with pain and redness, dizziness, increased blood pressure, hot flushes, cough, shortness of breath, stomach ache, abdominal pain, constipation, dry mouth, heartburn, rash, excessive sweating, itching, skin redness, neck pain, muscle, bone, and/or joint stiffness, joint swelling, muscle spasms, shoulder pain, chest muscle and rib cage pain, joint inflammation, muscle weakness, abnormal kidney function tests, frequent abnormal urge to urinate, swelling of hands, ankles or feet, thirst, toothache, altered taste.
Rare (may affect up to 1 in 1,000 people)
Rarely, particularly in patients receiving long-term treatment for osteoporosis, an unusual fracture of the femur may occur. Contact your doctor if you experience pain, weakness, or discomfort in your thigh, hip, or groin, as this could be an early sign of a possible femur fracture. Low levels of phosphate in the blood.
Not known (frequency cannot be estimated from available data)
Severe allergic reactions including dizziness and difficulty breathing, swelling mainly of the face and throat, low blood pressure, dehydration secondary to acute phase reactions (symptoms following infusion such as fever, vomiting, and diarrhea).
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . Reporting side effects can help provide more information on the safety of this medicine.

5. How to store ACIDO ZOLEDRONICO SEACROSS

Your doctor, pharmacist or nurse will know how to store ACIDO ZOLEDRONICO SEACROSS appropriately.

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton and on the vial after "Exp".
• The unopened vial does not require any special storage conditions.
• After opening: Chemical and physical in-use stability has been demonstrated for 24 hours at 2 - 8°C or below 25°C.
• After opening the vial, the product should be used immediately to avoid microbial contamination. If not used immediately, the times and conditions of storage prior to use are the responsibility of the user and should normally not exceed 24 hours at 2°C - 8°C. Allow the solution taken from the refrigerator to reach room temperature before use.
• Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What ACIDO ZOLEDRONICO SEACROSS contains

• The active substance is zoledronic acid. Each 100 mL vial of solution contains 5 mg of zoledronic acid (as monohydrate).
• One mL of solution contains 0.05 mg of zoledronic acid (as monohydrate).
• The other components are mannitol (E421), sodium citrate (E331), and water for injections.

Description of the appearance of ACIDO ZOLEDRONICO SEACROSS and contents of the pack
ACIDO ZOLEDRONICO SEACROSS is a clear, colourless solution. The 100 mL solution is
packaged in transparent glass vials made of soda-lime silicate glass of type II, closed with chlorobutyl rubber stoppers of type I and sealed with aluminium flip-off caps with polypropylene seals.
ACIDO ZOLEDRONICO SEACROSS 5 mg/100 mL solution for infusion is supplied in:
1 vial
Marketing Authorisation Holder and Manufacturer
Seacross Pharma (Europe) Limited
POD 13, The Old Station House
15A Main Street, Blackrock
Dublin, A94 T8P8
Ireland
This medicinal product is authorised in the Member States of the European Economic Area under the following names:

INFORMATION FOR HEALTHCARE PROFESSIONALS
The following information is intended exclusively for healthcare professionals (see section 3):
How to prepare and administer ZOLEDRONIC ACID SEACROSS

• ZOLEDRONIC ACID SEACROSS 5 mg/100 mL infusion solution is ready for use.

For single use only. Any unused solution must be discarded. The solution should
only be used if it is clear, free from particles, and shows no discoloration. ZOLEDRONIC ACID SEACROSS must not be mixed or administered intravenously with other
medicinal products and must be administered through a separate infusion line with a vented membrane at a constant infusion rate. The infusion time must not be less than 15 minutes.
ZOLEDRONIC ACID SEACROSS must not come into contact with calcium-containing solutions. If
stored in a refrigerator, allow the solution to reach room temperature before administration.
Aseptic techniques must be followed during the preparation of the infusion.
The infusion must be administered in accordance with standard medical practice.
How to store ZOLEDRONIC ACID SEACROSS

• Keep ZOLEDRONIC ACID SEACROSS out of the sight and reach of children.
• Do not use this medicinal product after the expiry date stated on the carton and vial after "Exp".
• The unopened vial does not require any special storage conditions.
• After opening the vial, the product must be used immediately to avoid microbial contamination. If not used immediately, the in-use 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. Allow refrigerated solution to reach room temperature before administration.