Zoledronic acid Kern Pharma 4 mg/100 ml solution for infusion EFG

Package leaflet: Information for the user

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE PATIENT

Zoledronic Acid Kern Pharma 4 mg/100 ml solution for infusion EFG

Read the entire 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, consult your doctor or pharmacist.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are effects not listed in this leaflet. See section 4.

Leaflet contents:

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

1. What Ácido Zoledrónico Kern Pharma is and what it is used for

The active substance in Ácido Zoledrónico Kern Pharma is zoledronic acid, which belongs to a group of substances called bisphosphonates. Zoledronic acid works by binding to bone and slowing down bone turnover. It is used for:

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

• Reducing the level of calcium in the blood in adult patients in whom it is too high due to the presence of a tumour. Tumours can accelerate normal bone remodelling, leading to increased release of calcium from bone. This condition is known as tumour-induced hypercalcaemia (TIH).

2. What you need to know before being administered Zoledronic Acid Kern Pharma

Carefully follow all instructions given by your doctor.

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, to any other bisphosphonate (a group of substances to which zoledronic acid belongs), or to any of the other ingredients of Zoledronic Acid Kern Pharma.

Warnings and precautions

Consult your doctor before being administered Zoledronic Acid Kern Pharma:

• if you have or have had a kidney problem.
• if you have or have had pain, swelling, or numbness in the jaw, a feeling of heaviness in the jaw, or loose teeth. Your doctor may recommend that you undergo a dental examination before starting treatment with Zoledronic Acid Kern Pharma.
• if you are receiving dental treatment or are scheduled for 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 should maintain good oral hygiene (including regular tooth brushing) 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 healing of ulcers or discharge, as these may be signs of a condition called osteonecrosis of the jaw. Patients undergoing chemotherapy and/or radiotherapy, those taking corticosteroids, those undergoing dental surgery, those not receiving routine dental care, those with gum disease, smokers, or those who have previously received treatment with a bisphosphonate (used to treat or prevent bone disorders) may have an increased risk of developing osteonecrosis of the jaw.

Use in children and adolescents

The use of Zoledronic Acid Kern Pharma is not recommended in adolescents and children under 18 years of age.

Use of Zoledronic Acid Kern Pharma with other medicines

Inform your doctor if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription. It is especially important that you inform your doctor if you are also taking:

• Aminoglycosides (medicines used to treat serious infections), as combining these with bisphosphonates may markedly reduce blood calcium levels.
• Thalidomide (a medicine used to treat a type of blood cancer affecting bone) or any other medicine that may harm the kidneys.
• Other medicines containing zoledronic acid or any other bisphosphonate, since the combined effects of these medicines administered together with Zoledronic Acid Kern Pharma are unknown.
• Antiangiogenic medicines (used to treat cancer), as the combination of these medicines with zoledronic acid has been associated with reports of osteonecrosis of the jaw (ONJ).

Patients aged 65 years and older

Zoledronic Acid Kern Pharma may be administered to patients aged 65 years and older. There is no evidence suggesting that additional precautions are required.

Pregnancy and breastfeeding

You must not be given Zoledronic Acid Kern Pharma if you are pregnant. Inform your doctor if you are or think you may be pregnant.

You must not be given Zoledronic Acid Kern Pharma if you are breastfeeding.

Consult your doctor before using this medicine if you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby.

Driving and use of machines

Very rarely, drowsiness and numbness have been observed with the use of Zoledronic Acid Kern Pharma. Therefore, you should exercise caution when driving, operating machinery, or performing other activities requiring high concentration.

Zoledronic Acid Kern Pharma contains Sodium

Patients on sodium-restricted diets should be aware that this medicine contains 342.9 mg (14.9 mmol) of sodium in 100 ml.

3. How to use Zoledronic Acid Kern Pharma

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

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

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

How much 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 depending on the severity of your kidney problem.

How often Zoledronic Acid Kern Pharma is administered

If you are being treated to prevent bone complications due to bone metastases, you will receive a Zoledronic Acid Kern Pharma infusion every three to four weeks.

If you are being treated to reduce the level of calcium in the blood, you will usually receive only one infusion of Zoledronic Acid Kern Pharma.

How Zoledronic Acid Kern Pharma is administered

Zoledronic Acid Kern Pharma is administered as an intravenous drip (infusion) lasting at least 20 minutes and must be given as a single intravenous solution through a separate infusion line.

Patients who do not have excessively high blood calcium levels will also be prescribed daily calcium and vitamin D supplements.

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

If you have received doses higher than recommended, you must be closely monitored by your doctor. This is because you may develop disturbances in serum electrolytes (e.g., abnormal levels of calcium, phosphate, and magnesium in the blood) and/or changes in kidney function, including severe renal failure. If calcium levels become too low, you may require calcium supplementation administered by infusion.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them. The most common ones are usually mild and may disappear after a short period of time.

Tell your doctor immediately if you experience any of the following adverse effects:

Frequent adverse effects (may affect up to 1 in 10 patients):

• Severe kidney impairment (this will normally be detected by your doctor through a specific blood test).
• Low calcium levels in the blood.

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

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

Frequency not known (cannot be estimated from available data)

• Kidney inflammation (tubulointerstitial nephritis): signs and symptoms may include reduced urine volume, blood in the urine, nausea, and general feeling of discomfort.

Tell your doctor as soon as possible if you experience any of the following adverse effects:

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

• Low phosphate levels in the blood.

Frequent adverse effects (may affect up to 1 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 resolve after a short period (a few hours or days).
• Gastrointestinal reactions such as nausea and vomiting, as well as loss of appetite.
• Conjunctivitis.
• Low red blood cell count (anemia).

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

• Hypersensitivity reactions.
• Low blood pressure.
• Chest pain.
• Reactions at the infusion site (redness and swelling), skin rash, itching.
• High blood pressure, difficulty breathing, dizziness, sleep disorders, tingling or numbness in the hands or feet, diarrhea.
• Decreased number of white blood cells and platelets.
• Low magnesium and potassium levels in the blood. Your doctor will monitor this and take any necessary measures.
• Numbness.
• Tearing of the eyes, sensitivity of the eyes to light.
• Sudden onset of coldness with fainting, weakness, or collapse.
• Wheezing or coughing with difficulty breathing.
• Hives (urticaria).

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

• Slowed heart rate.
• Confusion.
• Atypical femoral fractures (thigh bone), which may rarely occur, especially in patients on long-term treatment for osteoporosis. Inform your doctor if you notice pain, weakness, or discomfort in the thigh, hip, or groin, as these may be early symptoms indicating a possible femoral fracture.
• A kidney function disorder called Fanconi syndrome (this will normally be detected by your doctor through a urine test).

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

• Fainting due to low blood pressure.
• Severe bone, joint, and/or muscle pain, occasionally disabling.
• Painful redness of the eye and/or swelling.

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

Other adverse effects:

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

• Consult your doctor if you have ear pain, discharge from the ear, or an ear infection. These could be symptoms of damage to the ear bones.
• Rare cases of osteonecrosis in bones other than the jaw, particularly in the hip or thigh, have also been reported. Inform your doctor immediately if you experience symptoms such as new or worsening pain, discomfort, or stiffness while receiving treatment with zoledronic acid or after stopping treatment.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines (Website: www.notificaRAM.es). By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Zoledronic Acid Kern Pharma

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

After first opening, Zoledronic Acid Kern Pharma infusion solution should preferably be used immediately. If not used immediately, it must be stored in a refrigerator at 2°C – 8°C.

Medicines must not be disposed of via wastewater or household waste. Dispose of unused medicines and their containers at the SIGRE Point at your pharmacy. If in doubt, ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the container and other information

Composition of Zoledronic Acid Kern Pharma

• The active substance 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 injections.

Appearance of Zoledronic Acid Kern Pharma and contents of the container

Zoledronic Acid Kern Pharma is supplied as a clear, colourless solution in a colourless, transparent plastic bag. One plastic bag contains 100 ml of solution.

Zoledronic Acid Kern Pharma is supplied as a single-unit pack containing one plastic bag.

Marketing Authorization Holder

Kern Pharma, S.L.
Venus, 72 - Pol. Ind. Colón II
08228 Terrassa (Barcelona)
Spain

Manufacturer

Industria Farmaceutica Galenica Senese s.r.l.
Via Cassia Nord, 351
53014 Monteroni d’Arbia (Siena)
Italy

Date of the most recent revision of this leaflet: October 2024

INFORMATION FOR HEALTHCARE PROFESSIONALS

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 ready-to-use solution for infusion in patients with normal renal function.
• For single use only. Any unused portion of the solution must be discarded. Only solutions that are clear, particle-free, and colourless should be used. Aseptic techniques must be used 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 time and conditions prior to administration are the user's responsibility and, under normal conditions, must not exceed 24 hours at 2°C – 8°C, unless the dilution is performed under controlled and validated aseptic conditions. The solution stored in the refrigerator must be brought to room temperature before administration.
• The solution containing zoledronic acid must not be diluted or mixed with other infusion solutions. It is administered as a single intravenous infusion over 20 minutes via a separate infusion line. Before and after administration of Zoledronic Acid Kern Pharma, the patient's hydration status should be assessed to ensure adequate hydration.
• Zoledronic Acid Kern Pharma 4 mg/100 ml solution for infusion can be used immediately without further dilution in patients with normal renal function. In patients with mild to moderate renal impairment, reduced doses must be prepared as detailed below.

To prepare reduced doses for patients with a baseline creatinine clearance (CLcr) ≤ 60 ml/min, refer to Table 1 below. Remove the specified volume of Zoledronic Acid Kern Pharma solution from the bag and replace it with an equal volume of sterile 9 mg/ml (0.9%) sodium chloride injection solution or 5% glucose 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 target of 0.66 (mg•hr/l) (CLcr = 75 ml/min). Reduced doses for patients with renal impairment are expected to achieve the same AUC as that observed in patients with a creatinine clearance of 75 ml/min.

• Studies conducted using different infusion lines made of polyvinyl chloride, polyethylene, and polypropylene showed no 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 must not be mixed with other medicinal products/substances and should always be administered via 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 expiry date stated on the container.
• The unopened vial does not require special storage conditions.
• After opening the vial, the product should be used immediately to avoid microbial contamination.

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/