PATIENT INFORMATION LEAFLET

Zoledronic Acid Kern Pharma 4 mg/100 ml Solution for Infusion EFG

Read this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4

1.What is Zoledronic Acid Kern Pharma and what it is used for

2.What you need to know before you are given Zoledronic Acid Kern Pharma

3.How to use Zoledronic Acid Kern Pharma

4.Possible side effects

5Storage of Zoledronic Acid Kern Pharma

6.Contents of the pack and additional information

The active ingredient of Ácido Zoledrónico Kern Pharma is zoledronic acid, which belongs to a group of substances called bisphosphonates. Zoledronic acid acts by binding to bones and reducing the rate of bone remodeling.It is used for:

• Preventing bone complications, e.g. fractures, in adult patients with bone metastases (spread of cancer from the primary site to the bone).

Reducing the amount of calciumin the blood in adult patients where it is too high due to the presence of a tumor. Tumors can accelerate normal bone remodeling, resulting in increased release of calcium from the bone. This condition is known as tumor-induced hypercalcemia (TIH).

Follow all the instructions given by your doctor carefully.

Your doctor will perform blood tests before starting treatment with Zoledronic Acid Kern Pharma and will monitor your response to treatment at regular intervals.

Do not use Zoledronic Acid Kern Pharma

• if you are breastfeeding.
• if you are allergic (hypersensitive) to zoledronic acid, another bisphosphonate (a group of substances to which zoledronic acid belongs), or to any of the other components of Zoledronic Acid Kern Pharma.

Warnings and precautions

Consult your doctor before Zoledronic Acid Kern Pharma is administered to you:

• if you have or have had akidney problem.
• if you have or have hadjaw pain, swelling, or numbness, or a feeling of heaviness in the jaw or a tooth that moves. Your doctor may recommend that you undergo a dental examination before starting treatment with Zoledronic Acid Kern Pharma.
• if you are receivingdental treatmentor are going to undergo dental surgery, inform your dentist that you are being treated with Zoledronic Acid Kern Pharma and inform your doctor about your dental treatment.

While being treated with Zoledronic Acid Kern Pharma, you must maintain good oral hygiene (including regular brushing of your teeth) and undergo routine dental check-ups.

Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth, such as tooth loss, pain, or swelling, or difficulty in healing ulcers or discharge, as these may be signs of a condition called osteonecrosis of the jaw. Patients receiving chemotherapy and/or radiation therapy, taking corticosteroids, undergoing dental surgery, not receiving regular care, having gum disease, being smokers, or having received previous treatment with a bisphosphonate (used to treat or prevent bone disorders) may be at a higher risk of developing osteonecrosis of the jaw.

Use in children and adolescents

Zoledronic Acid Kern Pharma is not recommended for use in adolescents and children under 18 years old.

Use of Zoledronic Acid Kern Pharma with other medications

Inform your doctor if you are using, have used recently, or may take any other medication, including those purchased without a prescription. It is especially important to inform your doctor if you are also taking:

• Aminoglycosides (medications used to treat severe infections), as the combination of these with bisphosphonates may significantly decrease blood calcium levels.
• Talidomide (a medication used to treat a type of blood cancer that affects the bone) or any other medication that may harm the kidneys.
• Other medications that also contain zoledronic acid, or any other bisphosphonate, as the combined effects of these medications administered with Zoledronic Acid Kern Pharma are unknown.
• Anti-angiogenic medications (used to treat cancer), as the combination of these medications with zoledronic acid has been associated with reports of osteonecrosis of the jaw (ONJ).

Patients 65 years and older

Zoledronic Acid Kern Pharma can be administered to people 65 years and older. There is no evidence to suggest that additional precautions are necessary.

Pregnancy and lactation

Do not administer Zoledronic Acid Kern Pharma if you are pregnant. Inform your doctor if you are or think you may be pregnant.

Do not administer Zoledronic Acid Kern Pharma if you are breastfeeding.

Consult your doctor before using this medication if you are pregnant or during lactation, think you may be pregnant, or are planning to become pregnant.

Driving and operating machinery

In very rare cases, drowsiness and numbness have been observed with the use of Zoledronic Acid Kern Pharma. Therefore, you should be careful when driving, operating machinery, or performing other activities that require a lot of attention.

Zoledronic Acid Kern Pharma contains Sodium

Patients with low-sodium diets should note that this medication contains 342.9 mg (14.9 mmol) of sodium in 100 ml.

Zoledronic Acid Kern Pharma should only be administered by experienced healthcare professionals in the administration of intravenous bisphosphonates, i.e., administered through a vein.

Your doctor will recommend that you drink a sufficient amount of water before each treatment to help prevent dehydration.

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

What amount of Zoledronic Acid Kern Pharma is administered

The usual single dose administered is 4 mg.

If you have a kidney problem, your doctor will give you a lower dose based on the severity of your kidney problem.

How often Zoledronic Acid Kern Pharma is administered

If you are being treated for the prevention of bone complications due to bone metastases, you will be given an infusion of Zoledronic Acid Kern Pharma every three to four weeks.

If you are being treated to reduce the amount of calcium in your blood, you will usually only be given one infusion of Zoledronic Acid Kern Pharma.

How Zoledronic Acid Kern Pharma is administered

Zoledronic Acid Kern Pharma is administered as an intravenous infusion that must last at least 20 minutes and must be administered as a single solution through a separate infusion line.

Patients who do not have high levels of calcium in their blood will also be prescribed calcium and vitamin D supplements to take every day.

If you are given more Zoledronic Acid Kern Pharma than you should

If you have received doses higher than recommended, you should be closely monitored by your doctor. This is because you may develop abnormal serum electrolyte levels (e.g., abnormal levels of calcium, phosphorus, and magnesium in the blood) and/or changes in kidney function, including severe renal insufficiency. If your calcium level becomes too low, you may need to be given a calcium supplement through an infusion.

Like all medicines,this medicinecan cause side effects, although not everyone will experience them. The most common ones are generally mild and will probably disappear after a short interval of time.

Inform your doctor immediately if you experience any of the following side effects:

Common side effects(may affectup to1 in 10 patients):

• Severe kidney impairment (your doctor will normally determine this with a specific blood test).
• Low calcium levels in the blood.

Uncommon side effects(may affect up to1 in 100 patients):

• Pain in the mouth, teeth, and/or jaw, swelling or difficulty in healing of sores inside the mouth or jaw, discharge, numbness or heaviness in the jaw, or tooth loss. These may be signs of jaw bone damage (osteonecrosis). Inform your doctor and dentist immediately if you experience these symptoms while being treated with Zoledronic Acid Kern Pharma or after completing treatment.
• Irregular heart rhythm (atrial fibrillation) has been observed in patients treated with zoledronic acid for postmenopausal osteoporosis. The current cause of this irregular heart rhythm is unknown, but you should inform your doctor if you experience these symptoms after receiving zoledronic acid.
• Severe allergic reaction: difficulty breathing, swelling mainly of the face and throat.

Frequency not known (cannot be estimated from available data)

• Tubulointerstitial nephritis: symptoms and signs may include reduced urine volume, blood in the urine, nausea, general feeling of discomfort.

Inform your doctor as soon as possible if you experience any of the following side effects:

Very common side effects(may affect more than 1 in 10 patients):

• Low phosphate levels in the blood.

Common side effects(may affect up to1 in 10 patients):

• Headache and flu-like syndrome consisting of fever, fatigue, weakness, drowsiness, chills, and bone, joint, and/or muscle pain. In most cases, no specific treatment is required, and symptoms disappear after a short period of time (a few hours or days).
• Gastrointestinal reactions such as nausea and vomiting, as well as loss of appetite.
• Conjunctivitis.
• Anemia (low red blood cell count in the blood).

Uncommon side effects(may affect up to1 in 100 patients):

• Hypersensitivity reactions.
• Low blood pressure.
• Chest pain.
• Reactions on the skin (redness and swelling) at the infusion site, rash, itching.
• High blood pressure, difficulty breathing, dizziness, sleep disturbances, tingling or numbness in the hands or feet, diarrhea.
• Decreased white blood cell and platelet count.
• Low levels of magnesium and potassium in the blood. Your doctor will monitor this and take any necessary measures.
• Numbness.
• Excessive tearing, sensitivity of the eyes to light.
• Sudden cooling with fainting, weakness, or collapse.
• Difficulty breathing with wheezing or coughing.
• Hives.

Rare side effects(may affect up to1 in 1,000 patients):

• Decreased heart rate.
• Confusion.
• Atypical fractures of the femur (thigh bone) that may occur in rare cases, especially in patients undergoing prolonged treatment for osteoporosis. Inform your doctor if you experience pain, weakness, or discomfort in the thigh, hip, or groin, as these may be early signs of a possible femur fracture.
• A kidney function disorder known as Fanconi syndrome (your doctor will normally detect this with a urine test).

Very rare side effects(may affect up to1 in 10,000 patients):

• Fainting due to low blood pressure.
• Intense pain in the bones, joints, and/or muscles, occasionally incapacitating.
• Red, painful eye and/or swelling.

If you experience any side effect,inform your doctor, nurse, or pharmacist. This includes any side effect not mentioned in this leaflet.

Other side effects:

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

• Consult your doctor if you have ear pain, discharge from the ear, or ear infection. These may be signs of bone damage in the ear.
• Other rare cases of osteonecrosis have been observed in bones other than the jaw, especially in the hip or thigh. Inform your doctor immediately if you experience symptoms such as the onset or worsening of pain, discomfort, or stiffness while receiving treatment with zoledronic acid or after stopping treatment.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect not appearing in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use (Website:www.notificaRAM.es). By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Your doctor, nurse, or pharmacist knows how to conserve Zoledronic Acid Kern Pharma properly (see section 6). Keep out of sight and reach of children.

After the first opening, preferablyZoledronic Acid Kern Pharmainfusion solution should be used immediately. If not used immediately, it should be stored in a refrigerator at 2°C – 8°C.

Medicines should not be thrown down the drains or in the trash. Dispose of the containers and medicines you no longer need at the SIGRE collection pointof the pharmacy.In case of doubt, ask your pharmacist how to dispose of the containers and medicines you no longer need. This way, you will help protect the environment.

Composition of Zoledronic Acid Kern Pharma

• The active ingredient is zoledronic acid. Each plastic bag contains 4 mg of zoledronic acid.
• The other components are: mannitol (E421), sodium citrate (E331), sodium chloride, and water for injectable preparations.

Appearance of Zoledronic Acid Kern Pharma and contents of the package

Zoledronic Acid Kern Pharma is supplied as a clear and colorless solution in an incolor and transparent plastic bag. A plastic bag contains 100 ml of solution.

Zoledronic Acid Kern Pharma is supplied as a single unit package containing a plastic bag.

Holder of the Marketing Authorization

Kern Pharma, S.L.

Venus, 72 - Pol. Ind. Colón II

08228 Terrassa (Barcelona)

Spain

Responsible for manufacturing

Industria Farmaceutica Galenica Senese s.r.l.

Via Cassia Nord, 351

53014 Monteroni d’Arabia (Siena)

Italy

Last review date of this leaflet: October 2024

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INFORMATION FOR THE HEALTHCARE PROFESSIONAL

How to prepare and administer Zoledronic Acid Kern Pharma

• Zoledronic Acid Kern Pharma 4 mg/100 ml solution for infusion, contains 4 mg of zoledronic acid in 100 ml of solution for infusion for immediate use in patients with normal renal function.
• For single use. Any unused portion of the solution must be discarded. Only transparent, particle-free, and colorless solutions should be used. During the preparation of the infusion, aseptic techniques should be used.
• From a microbiological point of view, the infusion solution should be used immediately after the first opening. If not used immediately, the time and storage conditions during its use before administration are the responsibility of the user and should not exceed 24 hours at 2°C – 8°C, except that the dilution should be performed in controlled and validated aseptic conditions. The refrigerated solution should reach room temperature before administration.
• The solution containing zoledronic acid should not be diluted or mixed with other infusion solutions. It is administered as a single intravenous infusion over 20 minutes through a separate infusion line. Before and after administration of Zoledronic Acid Kern Pharma, the hydration status of the patients should be evaluated to ensure they are adequately hydrated.
• Zoledronic Acid Kern Pharma 4 mg/100 ml solution for infusion can be used immediately without requiring additional dilution in patients with normal renal function. In patients with mild to moderate renal insufficiency, reduced doses should be prepared as detailed below.

To prepare reduced doses for patients with a baseline CLcr ≤ 60 ml/min, see Table 1 below. Extract the indicated volume of Zoledronic Acid Kern Pharma solution from the bag and replace it with an equal volume of sterile sodium chloride 9 mg/ml (0.9%) or sterile glucose 5% injection solution.

Table 1: Preparation of reduced doses of Zoledronic Acid Kern Pharma 4 mg/100 ml solution for infusion

* The doses have been calculated assuming an AUC of 0.66 (mg•hr/l) (CLcr = 75 ml/min). It is expected that the reduced doses for patients with renal insufficiency will achieve the same AUC as observed in patients with a creatinine clearance of 75 ml/min.

• Studies conducted with different types of infusion lines (chloroprene, polyethylene, and polypropylene) did not reveal any incompatibility with zoledronic acid solutions.
• Since there are no available data on the compatibility of zoledronic acid solutions with other substances administered intravenously, Zoledronic Acid Kern Pharma should not be mixed with other medications/substances and should be administered through a separate infusion line.

How to store Zoledronic Acid Kern Pharma

• Keep Zoledronic Acid Kern Pharma out of the sight and reach of children.
• Do not use Zoledronic Acid Kern Pharma after the expiration date appearing on the package.
• The unopened container does not require special storage conditions.
• After opening the container, the product should be used immediately to avoid microbial contamination.

The detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/