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

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

Follow carefully 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 breast-feeding.
• if you are allergic (hypersensitive) to zoledronic acid, another bisphosphonate (the group of substances to which zoledronic acid belongs), or any of the other ingredients of Zoledronic Acid Kern Pharma.

Warnings and precautions

Consult your doctor before you are given Zoledronic Acid Kern Pharma:

• if you have or have had a kidney problem.
• if you have or have had pain, swelling, or numbnessof the jaw, or a feeling of heaviness in the jaw or a tooth is loose. Your doctor may recommend that you undergo a dental examination before starting treatment with Zoledronic Acid Kern Pharma.
• if you are receiving dental 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 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 healing of ulcers or discharge, as these may be signs of a condition called osteonecrosis of the jaw. Patients who are receiving chemotherapy and/or radiotherapy, who are taking corticosteroids, who are undergoing dental surgery, who do not receive routine care, who have gum disease, who are smokers, or who have received prior treatment with a bisphosphonate (used to treat or prevent bone disorders) may be at 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 of age.

Use of Zoledronic Acid Kern Pharma with other medicines

Tell your doctor if you are using, have recently used, or might use 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 severe infections), as the combination of these with bisphosphonates can significantly decrease blood calcium levels.
• Thalidomide (a medicine used to treat a type of blood cancer that affects the bone) or any other medicine that may harm the kidneys.
• Other medicines that also contain zoledronic acid or any other bisphosphonate, as the combined effects of these medicines administered with Zoledronic Acid Kern Pharma are unknown.
• Anti-angiogenic medicines (used to treat cancer), as the combination of these medicines with zoledronic acid has been associated with reports of jaw osteonecrosis (JON).

Patient over 65 years

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

Pregnancy and breast-feeding

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

You should not be given Zoledronic Acid Kern Pharma if you are breast-feeding.

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

Driving and using machines

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

Zoledronic Acid Kern Pharma contains sodium

Patients on low-sodium diets should note 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 in a vein.

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

Follow carefully 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 be given a Zoledronic Acid Kern Pharma infusion every 3 to 4 weeks.

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

How Zoledronic Acid Kern Pharma is administered

Zoledronic Acid Kern Pharma is administered as a drip (infusion) in a vein that should last at least 20 minutes and should be administered as a single intravenous solution in a separate infusion line.

Patient who do not have high levels of calcium in the 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 higher doses than recommended, you should be closely monitored by your doctor. This is because you may develop changes in serum electrolytes (e.g., abnormal levels of calcium, phosphorus, and magnesium in the blood) and/or changes in kidney function, including severe kidney failure. If the level of calcium becomes too low, it may be necessary to administer a calcium supplement by infusion.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The most common are usually mild and will probably disappear after a short period of time.

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

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

• Severe kidney impairment (usually determined by your doctor with a specific blood test).
• Low level of calcium in the blood.

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

• Pain in the mouth, teeth, and/or jaw, swelling or difficulty healing of ulcers within 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 jawbone (osteonecrosis). Tell your doctor and dentist immediately if you experience these symptoms while being treated with Zoledronic Acid Kern Pharma or after stopping treatment.
• An irregular heartbeat (atrial fibrillation) has been observed in patients treated with zoledronic acid for postmenopausal osteoporosis. It is currently unknown whether zoledronic acid causes this irregular heartbeat, 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 the available data)

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

Tell your doctor as soon as possible about any of the following side effects:

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

• Low level of phosphates in the blood.

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

• Headache and flu-like syndrome consisting of fever, fatigue, weakness, drowsiness, chills, and pain in the bones, joints, and/or muscles. In most cases, no specific treatment is required, and the 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.
• Low level of red blood cells in the blood (anemia).

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

• Allergic reactions.
• Low blood pressure.
• Chest pain.
• Skin reactions (redness and swelling) at the infusion site, rash, itching.
• High blood pressure, difficulty breathing, dizziness, sleep disorders, tingling or numbness of the hands or feet, diarrhea.
• Decreased number of white blood cells and platelets.
• Low level of magnesium and potassium in the blood. Your doctor will monitor and take any necessary measures.
• Numbness.
• Tearing of the eyes, 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 to 1 in 1,000 people):

• Decreased heart rate.
• Confusion.
• Atypical fractures of the femur (thigh bone) that can occur rarely, especially in patients on prolonged treatment for osteoporosis. Tell your doctor if you notice pain, weakness, or discomfort in the thigh, hip, or groin, as these may be early signs of a possible fracture of the femur.
• A kidney function disorder called Fanconi syndrome (usually detected by your doctor with a urine test).

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

• Fainting due to low blood pressure.
• Severe pain in the bones, joints, and/or muscles, occasionally incapacitating.
• Painful redness of the eye and/or swelling.

If you experience any side effects,tell your doctor, nurse, or pharmacist. This includes any possible side effects not listed in this leaflet.

Other side effects:

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

• Tell your doctor if you have ear pain, your ear is discharging, or you have an ear infection. These could be symptoms of damage to the bones of the ear.
• There have also been rare cases of osteonecrosis in bones other than the jaw, especially in the hip or thigh. Tell your doctor immediately if you have symptoms such as the onset or worsening of discomfort, pain, or stiffness while you are receiving treatment with zoledronic acid or after stopping treatment.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible that they are not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Agency's website (www.notificaRAM.es). By reporting side 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 store Zoledronic Acid Kern Pharma properly (see section 6). Keep out of sight and reach of children.

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

Medicines should not be disposed of via wastewater or household waste. Dispose of the packaging and any unused medicine in the pharmacy's SIGRE collection point. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Container Content and Additional Information

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 Container Content

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

Zoledronic Acid Kern Pharma is supplied as a single-unit container that contains 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’Arabia (Siena)

Italy

Date of Last Revision of this Leaflet: October 2024

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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 solution for infusion for immediate use in patients with normal renal function.
• For single use. Any unused part of the solution must be discarded. Only clear solutions free of particles and discoloration should be used. Aseptic techniques should be used during infusion preparation.
• From a microbiological point of view, the solution for infusion should be used immediately after the first opening. If not used immediately, the time and storage conditions during use before administration are the responsibility of the user and should not exceed 24 hours at 2°C – 8°C under normal conditions, unless the dilution is performed under 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 in a separate infusion line. Before and after the administration of Zoledronic Acid Kern Pharma, the patient's hydration status should be assessed 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 impairment, 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. Remove the indicated 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 a target AUC of 0.66 (mg•hr/l) (CLcr = 75 ml/min). The reduced doses for patients with renal impairment are expected to achieve the same AUC as observed in patients with creatinine clearance of 75 ml/min.

• Studies conducted with different polyvinyl chloride, polyethylene, and polypropylene infusion lines did not reveal any incompatibility with zoledronic acid solutions.
• Since there are no data available 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 always be administered through a separate infusion line.

How to Store Zoledronic Acid Kern Pharma

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

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/