Ibandronic acid noridem

Package leaflet: Information for the patient

Ibandronic Acid Noridem 6mg/6 mL, concentrate for solution for infusion
ibandronic acid
Please read this leaflet carefully before using this medicine, as it contains important information
for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please consult your doctor, pharmacist, or nurse.
• If you experience any side effects, including any not listed in this leaflet, please inform your doctor, pharmacist, or nurse. See section 4.

Table of contents

1. What Ibandronic Acid Noridem is and what it is used for
2. Important information before using Ibandronic Acid Noridem
3. How to use Ibandronic Acid Noridem
4. Possible side effects
5. How to store Ibandronic Acid Noridem
6. Contents of the pack and other information

1. What Ibandronic Acid Noridem is and what it is used for
Ibandronic Acid Noridem contains the active substance ibandronic acid. It belongs to a group of medicines called bisphosphonates.
Ibandronic Acid Noridem is used in adults who have been diagnosed with breast cancer that has spread to the bones (known as "bone metastases").

• It helps prevent bone fractures
• It helps prevent bone complications requiring surgical treatment or radiotherapy

Ibandronic Acid Noridem may also be prescribed in cases of elevated calcium levels in the blood caused by tumours.
The action of Ibandronic Acid Noridem is to inhibit the increased loss of calcium from bones. This helps prevent weakening of the bones.

2. Important information before using Ibandronic Acid Noridem

When not to use Ibandronic Acid Noridem

• if you are allergic to ibandronic acid or to any of the other ingredients of this medicine (listed in section 6)
• if you currently have or have previously had low levels of calcium in the blood serum

Do not take this medicine if any of the above conditions apply to you. If in doubt, please consult your doctor or pharmacist before using Ibandronic Acid Noridem.
Warnings and precautions
A rare but serious side effect called osteonecrosis of the jaw and (or) mandible (damage to the jaw and (or) mandible bone) has been reported very rarely in patients receiving Ibandronic Acid Noridem for cancer-related conditions after its market authorization. Osteonecrosis of the jaw and (or) mandible may also occur after treatment has ended.
It is important to take preventive measures against developing osteonecrosis of the jaw and (or) mandible, as it can be a painful and difficult-to-treat condition. To reduce the risk of osteonecrosis of the jaw and (or) mandible, appropriate precautions should be taken.
Before starting treatment with Ibandronic Acid Noridem, please discuss with your doctor or nurse:

• if you have any oral or dental conditions, such as poor dental health, gum disease, or planned tooth extraction
• if you do not receive routine dental care or have not had a dental check-up for a long time
• if you smoke (this may increase the risk of dental problems)
• if you have previously been treated with a bisphosphonate (used in the treatment or prevention of bone diseases)
• if you are taking medicines called corticosteroids (e.g. prednisolone or dexamethasone)
• if you have a diagnosis of cancer

Your doctor may recommend that you have a dental examination before starting treatment with Ibandronic Acid Noridem.
During treatment, you should maintain proper oral hygiene (including regular tooth brushing) and attend routine dental check-ups. If you wear dentures, ensure they are properly fitted. Patients undergoing dental treatment or those scheduled for dental procedures (e.g. tooth extraction) should inform their treating doctor and dentist that they are taking Ibandronic Acid Noridem.
If you experience any symptoms in your mouth or teeth, such as loose teeth, pain, swelling, non-healing ulcers, or discharge, contact your doctor and dentist immediately, as these may be signs of osteonecrosis of the jaw and (or) mandible.
Talk to your doctor, pharmacist, or nurse before taking Ibandronic Acid Noridem:

• if you are allergic to other bisphosphonates
• if you have high or low levels of vitamin D, calcium, or any other mineral metabolism disorder
• if you have kidney disease
• if you have heart conditions and your doctor has advised you to limit fluid intake

Serious, sometimes fatal, allergic reactions have been reported in patients treated with intravenous ibandronic acid.
If you experience any of the following symptoms: shortness of breath/difficulty breathing, tightness in the throat, swelling of the tongue, dizziness, feeling faint, redness or swelling of the face, skin rash, nausea, or vomiting, inform your doctor or nurse immediately (see section 4).
Children and adolescents
Ibandronic Acid Noridem must not be used in children and adolescents under 18 years of age.
Ibandronic Acid Noridem and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take. Ibandronic Acid Noridem may affect the action of other medicines. Likewise, other medicines may alter the effect of Ibandronic Acid Noridem.
In particular, inform your doctor or pharmacist if you are taking an antibiotic from the 'aminoglycoside' group, such as gentamicin. Caution is advised when aminoglycosides are used concomitantly with Ibandronic Acid Noridem, as they may cause decreased serum calcium levels.
Pregnancy and breastfeeding
Do not use Ibandronic Acid Noridem if you are pregnant or planning to become pregnant, or if you are breastfeeding.
Consult your doctor or pharmacist before using this medicine.
Driving and using machines
You may drive and operate machinery, as Ibandronic Acid Noridem has no effect or negligible effect on the ability to drive and use mechanical devices.
Inform your doctor if you intend to drive or operate machinery or equipment in motion.
Ibandronic Acid Noridem contains sodium
The sodium content of Ibandronic Acid Noridem is less than 1 mmol (23 mg) per dose, which is practically considered sodium-free.
3. How to use Ibandronic Acid Noridem
Administration of the medicine

• Ibandronic Acid Noridem is administered by a doctor or medical personnel experienced in cancer treatment
• Ibandronic Acid Noridem is given as an intravenous infusion
  Your doctor may order regular blood tests during treatment with Ibandronic Acid Noridem. These tests are performed to ensure that the dose of Ibandronic Acid Noridem is appropriate.

Dosage
Your doctor will determine the amount of Ibandronic Acid Noridem you will receive based on your condition.
If you have breast cancer with bone metastases, the recommended dose is 1 vial (6 mg) every 3–4 weeks, administered as an intravenous infusion lasting at least 15 minutes.
If you have elevated calcium levels in the blood due to tumour disease, the recommended dose is a single administration of 2 mg or 4 mg, depending on the severity of the condition. The medicine should be administered as an intravenous infusion lasting more than two hours. Re-administration may be considered in case of insufficient treatment response or disease recurrence.
If you have kidney disease, your doctor may adjust the dose and duration of the infusion.
If you have any further questions about the use of this medicine, please consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everybody gets them.
You should inform your doctor or nurse immediately if you notice any of the following serious adverse
reactions – immediate treatment with medicines may be required:
Rare (may affect up to 1 in 1,000 people):

• chronic pain and inflammation of the eye
• new pain, weakness or discomfort in the hip, thigh or groin area. These may be early signs of possible atypical fractures of the femur.

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

• pain or ulceration in the mouth or jaw and (or) mandible. These may be early signs of serious problems affecting the jaw or mandible (osteonecrosis (dead bone tissue) in the jawbone and (or) mandible).
• if the patient develops ear pain, ear discharge and (or) ear infection, inform the doctor. These may be symptoms of damage to the bone tissue in the ear.
• itching, swelling of the face, lips, tongue and throat, together with difficulty breathing. This may indicate a potentially life-threatening allergic reaction (see section 2)
• severe skin reactions Frequency unknown (frequency cannot be estimated from the available data):
• asthma attack

Other possible adverse effects
Common (may affect up to 1 in 10 people)

• flu-like symptoms including fever, chills and shivering, feeling unwell, fatigue, bone pain and muscle and joint aches. These symptoms usually resolve within a few hours or days. Speak to your nurse or doctor if any of these symptoms become troublesome or last longer than a few days.
• increased body temperature
• stomach ache or abdominal pain, indigestion, nausea, vomiting or diarrhoea (loose stools)
• low levels of calcium or phosphate in the blood
• changes in blood test results such as gamma-glutamyl transferase or creatinine
• heart rhythm disorders: bundle branch block
• bone or muscle pain
• headache, dizziness or feeling weak
• feeling thirsty, sore throat, taste disturbances
• swelling of legs or feet
• joint pain, arthritis or other joint problems
• parathyroid gland disorders
• bruising
• infections
• vision disorders known as cataracts
• skin disorders
• dental disorders

Uncommon (may affect less than 1 in 100 patients)

• chills, shivering
• low body temperature (hypothermia)
• disorders of cerebral blood vessels (cerebrovascular disorders – stroke or brain haemorrhage)
• cardiovascular disorders (including palpitations, heart attack, hypertension, varicose veins)
• changes in blood test results (anaemia)
• increased alkaline phosphatase levels in the blood
• fluid retention and swelling (lymphoedema)
• fluid in the lungs
• stomach problems such as gastritis and enteritis or gastritis
• gallstones
• inability to pass urine, bladder inflammation
• migraine
• neuralgia, nerve root disorders
• deafness
• increased sensitivity to sound, changes in taste, smell
• difficulty swallowing
• mouth ulceration, lip swelling (“cheilitis”), oral candidiasis
• itching or numbness around the mouth
• pelvic pain, vaginal discharge, itching or pain in the vagina
• benign skin overgrowth
• memory loss
• sleep disorders, anxiety, emotional lability, mood changes
• skin rash
• hair loss
• pain at the injection site
• weight loss
• renal cyst (fluid-filled sac in the kidney)

Reporting of adverse effects
If you experience any adverse effects, including any not listed in this leaflet,
tell your doctor, pharmacist or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, PL-02 222 Warsaw, Tel.: + 48 22 49 21 301, Fax: + 48 22 49 21 309, e-mail: [email protected]. By reporting adverse effects, additional information on the safety of the medicine can be collected.

5. How to store Ibandronic Acid Noridem

• Keep the medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the label and the carton indicated as (EXP). The expiry date refers to the last day of the stated month.
• After dilution, the infusion solution is stable for 24 hours at a temperature of 2°C - 8°C (in the refrigerator).
• Do not use this medicine if you notice that the solution is not clear or contains particles. Medicines should not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Ibandronic Acid Noridem contains

• The active substance is ibandronic acid.
• Other ingredients: Sodium chloride, Glacial acetic acid, Sodium acetate trihydrate, Water for injections.

What Ibandronic Acid Noridem looks like and contents of the pack
Ibandronic Acid Noridem is available as a liquid concentrate in a vial. One vial contains 6 mg of ibandronic acid.
Each pack contains vials of concentrate. Ibandronic Acid Noridem is supplied in packs containing 1, 5, and 10 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder:
Noridem Enterprises Ltd
Evagorou & Makariou,
Mitsi Building 3
Office 115, CY-1065 Nicosia, Cyprus

Manufacturer:
DEMO S.A.,
21 km National Road Athens-Lamia,
GR-14568 Krioneri,
Attica, Greece

This medicinal product is authorised in the European Economic Area under the following names:
United Kingdom: Ibandronic Acid 6 mg Concentrate for Solution for Infusion
Ireland: Ibandronic Acid 6 mg Concentrate for Solution for Infusion
Austria: Ibandronsäure Noridem 6 mg Konzentrat zur Herstellung einer Infusionslösung
Germany: Ibandronsäure Noridem 6 mg Konzentrat zur Herstellung einer Infusionslösung
Spain: Ácido Ibandrónico KERN PHARMA 6 mg concentrado para solución para perfusión EFG
Poland: Ibandronic Acid Noridem; 6mg/6 mL, concentrate for infusion solution
Greece: IBONDEM 6 mg/6ml πυκνό διάλυμα για παρασκευή διαλύματος προς έγχυση

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Information intended for healthcare professionals only:

Dosage: Prevention of skeletal-related events in patients with breast cancer and bone metastases
The recommended dose for preventing skeletal-related events in patients with breast cancer and bone metastases is 6 mg administered intravenously every 3–4 weeks. The dose should be given as an infusion over no less than 15 minutes.

Patients with renal impairment
Dose adjustment is not required in patients with mild renal impairment (CLcr ≥50 and <80 mL/min). In patients with moderate renal impairment (CLcr ≥30 and <50 mL/min) or severe renal impairment (CLcr <30 mL/min), treatment for the prevention of skeletal events in breast cancer with bone metastases should be administered according to the dosing recommendations below:

| Creatinine clearance (mL/min) | Dose | Dilution volume and infusion time | |-------------------------------|------|-----------------------------------| | 50 ≤ CLcr < 80 | 6 mg (6 mL concentrate diluted to 100 mL) | 100 mL / 15 minutes | | 30 ≤ CLcr < 50 | 4 mg (4 mL concentrate diluted to 500 mL) | 500 mL / 1 hour | | < 30 | 2 mg (2 mL concentrate diluted to 500 mL) | 500 mL / 1 hour |

Diluent: 0.9% sodium chloride solution or 5% glucose solution
Administration: every 3 to 4 weeks

The 15-minute infusion has not been studied in cancer patients with CLcr < 50 mL/min.

Dosage: Treatment of tumour-induced hypercalcaemia
Ibandronic Acid Noridem concentrate for infusion solution is usually administered in a hospital setting. The dose is determined by the physician, taking into account the following factors.

Prior to initiating treatment with Ibandronic Acid Noridem, the patient should be adequately hydrated with 0.9% sodium chloride solution (9 mg/mL). Both the severity of hypercalcaemia and the type of tumour should be considered. In most patients with marked hypercalcaemia (albumin-corrected serum calcium* ≥ 3 mmol/L or ≥ 12 mg/dL), a single dose of 4 mg is sufficient. In patients with moderate hypercalcaemia (albumin-corrected serum calcium < 3 mmol/L or < 12 mg/dL), an effective dose is 2 mg. The highest dose used in clinical trials was 6 mg; however, administration of this dose does not increase treatment efficacy.

*Note: Albumin-corrected serum calcium concentration is calculated as follows:

Albumin-corrected serum calcium (mmol/L) = Serum calcium (mmol/L) – [0.02 × Albumin (g/L)] + 0.8

or

Albumin-corrected serum calcium (mg/dL) = Serum calcium (mg/dL) + 0.8 × [4 – Albumin (g/dL)]

To convert albumin-corrected serum calcium concentration from mmol/L to mg/dL, multiply the value in mmol/L by 4.

In most cases, elevated serum calcium levels can be reduced to normal within 7 days. The median time to recurrence of hypercalcaemia (re-elevation of albumin-corrected serum calcium above 3 mmol/L) after administration of 2 mg and 4 mg doses was 18–19 days. After administration of a 6 mg dose, the median time to recurrence was 26 days.

Method and route of administration
Ibandronic Acid Noridem concentrate for infusion solution must be administered as an intravenous infusion.
The vial contents should be prepared as follows:

• Prevention of skeletal-related events in patients with breast cancer and bone metastases: Dilute in 100 mL of isotonic sodium chloride solution or 100 mL of 5% glucose solution; administer the resulting solution over at least 15 minutes. See dosage recommendations above for patients with renal impairment.

• Treatment of tumour-induced hypercalcaemia: Dilute in 500 mL of isotonic sodium chloride solution or 500 mL of 5% glucose solution and administer over 2 hours.

For single use only. The product must be diluted before use. After reconstitution: Store at 2–8°C (in a refrigerator). The diluted product has been shown to be chemically and physically stable for 24 hours when stored in the refrigerator or at 25°C, after dilution with 0.9% sodium chloride solution or 5% glucose solution to a final concentration of 0.012 mg/mL.

Note:
To avoid potential incompatibilities, Ibandronic Acid Noridem concentrate for infusion solution should only be mixed with isotonic sodium chloride solution or 5% glucose solution. Solutions containing calcium should not be mixed with Ibandronic Acid Noridem concentrate for infusion solution.
Diluted solutions are for single use only. Only clear, particle-free solutions should be used.
It is recommended that the product be used immediately after dilution (see section 5 of this leaflet, "How to store Ibandronic Acid Noridem").
Ibandronic Acid Noridem concentrate for infusion solution must always be administered as an intravenous infusion. Care must always be taken to ensure that Ibandronic Acid Noridem concentrate for infusion solution is not administered intra-arterially or extravascularly, as this may lead to tissue damage.

Frequency of administration
For the treatment of tumour-induced hypercalcaemia, Ibandronic Acid Noridem concentrate for infusion solution is usually administered as a single infusion.
For the prevention of skeletal-related events in patients with breast cancer and bone metastases, infusions of Ibandronic Acid Noridem are repeated every 3–4 weeks.

Duration of treatment
A second infusion has been administered in a limited number of patients (50 patients) due to recurrent hypercalcaemia. Re-treatment may be considered in cases of recurrent hypercalcaemia or inadequate response to prior treatment.
In patients with breast cancer and bone metastases, Ibandronic Acid Noridem infusions should be administered every 3–4 weeks. In clinical trials, treatment was continued for up to 96 weeks.

Overdose
There is currently no experience with acute poisoning with Ibandronic Acid Noridem concentrate for infusion solution. In preclinical studies using high doses, the kidneys and liver were identified as organs particularly susceptible to toxic effects; therefore, renal and hepatic function should be monitored.
In the event of clinically significant hypocalcaemia (very low serum calcium levels), correction should be performed by intravenous administration of calcium gluconate.