IBANDRONIC 6 mg /6 Ml Concentrate

Contents of the leaflet

1. PATIENT INFORMATION LEAFLET
2. Leaflet accompanying the packaging: patient information
3. Ibandronic Acid Noridem 6mg/6 mL, concentrate for solution for infusion
   1. Table of contents of the leaflet
4. What is Ibandronic Acid Noridem and what is it used for
5. Important information before taking Ibandronic Acid Noridem
   1. When not to take Ibandronic Acid Noridem
   2. Warnings and precautions
   3. Children and adolescents
   4. Ibandronic Acid Noridem and other medicines
   5. Pregnancy and breastfeeding
   6. Driving and using machines
   7. Ibandronic Acid Noridem contains sodium
   8. The sodium content of Ibandronic Acid Noridem is less than 1 mmol (23 mg) per dose, which is essentially sodium-free.
6. How to take Ibandronic Acid Noridem
   1. Administration
   2. Dose
7. Possible side effects
   1. Inform your doctor or nurse immediately if you notice any of the following serious side effects - you may need to be given other medicines:
   2. Other possible side effects
   3. Reporting side effects
8. How to store Ibandronic Acid Noridem
9. Contents of the packaging and other information
   1. What Ibandronic Acid Noridem contains
   2. What Ibandronic Acid Noridem looks like and contents of the pack
   3. Marketing authorization holder and manufacturer
   4. Marketing authorization holder:
   5. Manufacturer:
   6. This medicinal product is authorized in the Member States of the European Economic Area under the following names:
   7. Date of last revision of the leaflet 27/01/2017.
   8. Dosing: Prevention of bone events in patients with breast cancer and bone metastases
   9. Dosing: Treatment of tumor-induced hypercalcemia
   10. Method and route of administration
   11. Frequency of administration
   12. Duration of treatment
   13. Overdose

PATIENT INFORMATION LEAFLET

Leaflet accompanying the packaging: patient information

Ibandronic Acid Noridem 6mg/6 mL, concentrate for solution for infusion

ibandronic acid
Read carefully the contents of this leaflet before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor, pharmacist, or nurse.
• If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor, pharmacist, or nurse. See section
• 4.

Table of contents of the leaflet

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

1. What is Ibandronic Acid Noridem and what is it 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 when breast cancer has spread to the bone (called "bone metastases").

• Helps prevent bone fractures
• Helps prevent bone complications that require surgery or radiation

Ibandronic Acid Noridem may also be prescribed when there is a high level of calcium in the blood caused by tumors.
The action of Ibandronic Acid Noridem is to inhibit the increased loss of calcium from bones. This prevents bone weakening.

2. Important information before taking Ibandronic Acid Noridem

When not to take Ibandronic Acid Noridem

• if the patient is allergic to ibandronic acid or any of the other ingredients of this medicine (listed in section 6)
• if the patient has low calcium levels in the blood

Do not take the medicine if any of the above symptoms occur. In case of doubts before taking Ibandronic Acid Noridem, consult a doctor or pharmacist.

Warnings and precautions

A side effect called jaw bone necrosis (death of bone tissue in the jaw) has been very rarely reported in patients taking Ibandronic Acid Noridem for cancer-related diseases after its introduction to the market. Jaw bone necrosis may also occur after treatment has stopped.
It is essential to take preventive measures to avoid the development of jaw bone necrosis, as it can be a painful and difficult-to-treat condition. To reduce the risk of jaw bone necrosis, appropriate precautions should be taken.
Before starting Ibandronic Acid Noridem, discuss with your doctor or nurse:

• if you have any oral or dental problems, such as poor dental condition, gum disease, or planned tooth extraction
• if you do not receive regular dental care or have not had dental check-ups for a long time
• if you smoke (which may increase the risk of dental problems)
• if you have been previously treated with bisphosphonates (used to treat or prevent bone diseases)
• if you are taking corticosteroids (e.g., prednisolone or dexamethasone)
• if you have been diagnosed with cancer.

Your doctor may recommend that you have a dental check-up before starting Ibandronic Acid Noridem.
During treatment, maintain good oral hygiene (including regular tooth brushing) and attend regular dental check-ups. If you wear dentures, ensure they fit properly. Patients undergoing dental treatment or patients before dental procedures (e.g., tooth extraction) should inform their doctor and dentist that they are taking Ibandronic Acid Noridem.
If you experience any oral or dental problems, such as loose teeth, pain, or swelling, non-healing ulcers, or discharge, contact your doctor and dentist immediately, as these may be symptoms of jaw bone necrosis.
Talk to your doctor, pharmacist, or nurse before taking Ibandronic Acid Noridem:

• if you are allergic to other bisphosphonates
• in case of high or low levels of vitamin D, calcium, or other mineral disorders
• in case of kidney disease
• if you have heart disease and your doctor has recommended that you limit fluid intake

Severe, sometimes fatal, allergic reactions have been reported in patients treated with ibandronic acid administered intravenously.
If you experience any of the following symptoms: shortness of breath, difficulty breathing, feeling of choking in the throat, swelling of the tongue, dizziness, feeling of loss of consciousness, redness or swelling of the face, rash on the body, nausea, and vomiting, inform your doctor or nurse immediately (see section 4).

Children and adolescents

Ibandronic Acid Noridem should 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 taking, have recently taken, or might take. Ibandronic Acid Noridem may affect the action of other medicines. Other medicines may also affect the action of Ibandronic Acid Noridem.
In particular, inform your doctor or pharmacistif you are taking an antibiotic from the 'aminoglycoside' group, e.g., gentamicin. Caution is recommended when using aminoglycosides and Ibandronic Acid Noridem together, as they may cause a decrease in calcium levels in the blood.

Pregnancy and breastfeeding

Ibandronic Acid Noridem should not be used in pregnant or breastfeeding women or women planning to become pregnant.
Consult your doctor or pharmacist before taking this medicine.

Driving and using machines

You can drive and use machines as Ibandronic Acid Noridem has no or negligible influence on the ability to drive and use machines.
Tell your doctor if you want to drive or use machines or equipment in traffic.

Ibandronic Acid Noridem contains sodium

The sodium content of Ibandronic Acid Noridem is less than 1 mmol (23 mg) per dose, which is essentially sodium-free.

3. How to take Ibandronic Acid Noridem

Administration

• Ibandronic Acid Noridem is administered by a doctor or medical staff experienced in cancer treatment
• Ibandronic Acid Noridem is administered 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 correct.

Dose

Your doctor will determine the amount of Ibandronic Acid Noridem you will receive, depending on your disease.
If you have breast cancer with bone metastases, the recommended dose is 1 vial (6 mg) every 3-4 weeks, as an intravenous infusion lasting at least 15 minutes.
If you have high levels of calcium in the blood due to cancer, the recommended dose is a single administration of 2 mg or 4 mg, depending on the severity of the disease. The medicine should be administered as an intravenous infusion lasting more than 2 hours. Repeated doses may be considered in case of insufficient efficacy or relapse of the disease.
In patients with kidney disease, your doctor may adjust the dose and infusion time.
In case of further doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Ibandronic Acid Noridem can cause side effects, although not everybody gets them.

Inform your doctor or nurse immediately if you notice any of the following serious side effects - you may need to be given other medicines:

Rare(may affect up to 1 in 100 people):

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

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

• mouth or jaw pain or swelling. These may be early signs of serious jaw or dental problems (necrosis of the jawbone).
• if you experience ear pain, discharge from the ear, and/or ear infection, tell your doctor. These may be symptoms of bone damage in the ear.
• itching, swelling of the face, lips, tongue, and throat, with difficulty breathing. This may be a sign of a life-threatening allergic reaction (see section 2)
• severe skin reactions Frequency not known(frequency cannot be estimated from the available data):
• asthma attack

Other possible side effects

Common(may affect up to 1 in 10 people)

• flu-like symptoms, including fever, chills, and flushing, discomfort, fatigue, bone pain, and muscle and joint pain. These symptoms usually resolve within a few hours or days. Talk to your nurse or doctor if any of these symptoms become troublesome or last longer than a few days.
• increased body temperature
• stomach pain or abdominal pain, nausea, vomiting, or diarrhea (loose stools)
• low levels of calcium or phosphate in the blood
• changes in blood test results, such as gamma-glutamyltransferase or creatinine
• heart rhythm disturbances: blockage of the bundle branch
• bone or muscle pain
• headache, dizziness, or feeling of weakness
• feeling thirsty, sore throat, changes in taste
• swelling of the legs or feet
• joint pain, arthritis, or other joint problems
• parathyroid gland disorders
• bruising
• infections
• eye problems called cataracts
• skin diseases
• dental problems

Uncommon(may affect up to 1 in 100 people)

• shaking, chills
• low body temperature (hypothermia)
• brain and blood vessel disorders (stroke or brain bleeding)
• heart and blood vessel disorders (including irregular heartbeat, heart attack, high blood pressure, varicose veins)
• changes in blood test results (anemia)
• increased levels of alkaline phosphatase in the blood
• fluid retention and swelling (lymphedema)
• fluid in the lungs
• stomach problems such as gastritis or stomach inflammation
• gallstones
• urinary problems such as urinary retention or cystitis
• migraine
• nerve pain, nerve root disorders
• deafness
• increased sensitivity to sound, changes in taste or smell
• difficulty swallowing
• mouth ulcers, lip swelling (cheilitis), thrush
• itching or numbness around the mouth
• pelvic pain, discharge, itching, or pain in the vagina
• mild skin thickening
• memory loss
• sleep disturbances, anxiety, emotional instability, mood changes
• skin rash
• hair loss
• pain at the injection site
• weight loss
• kidney cyst (fluid-filled sac in the kidney).

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring, Office of 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 side effects, you can help provide more information on the safety of this medicine.

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 carton (EXP). The expiry date refers to the last day of the month.
• After dilution, the infusion solution is stable for 24 hours at 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 wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the packaging 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 authorization holder and manufacturer

Marketing authorization 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 authorized in the Member States of 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, koncentrat do sporządzania roztworu do infuzji
Greece: IBONDEM 6 mg/6ml πυκνό διάλυμα για παρασκευή διαλύματος προς έγχυση

Date of last revision of the leaflet 27/01/2017.

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Information intended for healthcare professionals only:

Dosing: Prevention of bone events in patients with breast cancer and bone metastases

The recommended dose for the prevention of bone events in patients with breast cancer and bone metastases is 6 mg administered intravenously every 3-4 weeks. The dose should be administered over a period of not less than 15 minutes.
Patients with renal impairment
In patients with mild renal impairment (CLcr ≥50 and <80 ml min), no dose adjustment is necessary. in patients with moderate renal impairment (clcr ≥30 and <50 min) or severe <30 treatment for the prevention of bone events breast cancer metastases should be administered according to following dosing recommendations:
Dosing
Infusion volume and time
CLcr (mL/min)
50 ≤ CLcr <80
6 mg (6 mL concentrate for solution for infusion) / 100 mL / 15 minutes
30 ≤ CLcr <50
4 mg (4 mL concentrate for solution for infusion) / 500 mL / 1 hour
<30
2 mg (2 mL concentrate for solution for infusion) / 500 mL / 1 hour
0.9% sodium chloride solution or 5% glucose solution
Administer every 3 to 4 weeks
No studies have been conducted with a 15-minute infusion in patients with CLCr <50 ml min.< p>

Dosing: Treatment of tumor-induced hypercalcemia

Ibandronic Acid Noridem concentrate for solution for infusion is usually administered in a hospital setting. The dose of Ibandronic Acid Noridem is determined by your doctor, taking into account the following factors.
Before starting treatment with Ibandronic Acid Noridem, the patient should be adequately hydrated with a 9 mg/mL (0.9%) sodium chloride solution. Both the severity of hypercalcemia and the type of tumor should be taken into account. In most patients with severe hypercalcemia (corrected serum calcium ≥ 3 mmol/l or ≥ 12 mg/dl), a single dose of 4 mg is sufficient. In patients with moderate hypercalcemia (corrected serum calcium <3 mmol l or < 12 mg dl), the effective dose is 2 mg.
The maximum dose used in clinical trials was 6 mg, but the use of such a dose does not increase the efficacy of the treatment.
*Note that corrected serum calcium is calculated as follows:
Corrected serum calcium (mmol/l)
=
Serum calcium (mmol/l) - [0.02 x serum albumin (g/l)] + 0.8
or
Corrected serum calcium (mg/dl)
=
Serum calcium (mg/dl) + 0.8 x [4 - serum albumin (g/dl)]
To convert corrected serum calcium from mmol/l to mg/dl, multiply the value in mmol/l by 4.
In most cases, elevated serum calcium can be reduced to normal levels within 7 days. The median time to relapse of hypercalcemia (re-elevation of corrected serum calcium to > 3 mmol/l) after administration of 2 mg and 4 mg doses was 18-19 days. After administration of the 6 mg dose, the median time to relapse was 26 days.

Method and route of administration

Ibandronic Acid Noridem concentrate for solution for infusion should be administered as an intravenous infusion.
To prepare the contents of the vial, follow these steps:

• prevention of bone events in patients with breast cancer and bone metastases – add to 100 mL of isotonic sodium chloride solution or 100 mL of 5% glucose solution; administer the resulting solution over at least 15 minutes.
  See also the dosing recommendations for patients with renal impairment above.

hypercalcemia treatment - add to 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 should be diluted before use. After reconstitution: Store in a refrigerator (2-8°C). The chemical and physical stability of the prepared product has been demonstrated for 24 hours when stored in a refrigerator and at 25°C, after dilution of the product in 0.9% sodium chloride solution or 5% glucose solution to a concentration of 0.012 mg/mL.

Frequency of administration

For the treatment of tumor-induced hypercalcemia, Ibandronic Acid Noridem concentrate for solution for infusion is usually administered as a single infusion.
To prevent bone events in patients with breast cancer and bone metastases, Ibandronic Acid Noridem infusions are repeated every 3-4 weeks.

Duration of treatment

In a limited number of patients (50 patients), a second infusion of Ibandronic Acid Noridem was administered due to hypercalcemia. Re-treatment may be considered in case of relapse or insufficient efficacy of the 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 no experience with acute overdose of Ibandronic Acid Noridem concentrate for solution for infusion. Since in preclinical studies, high doses have shown that the kidneys and liver are particularly susceptible to the toxic effects of the medicine, kidney and liver function should be monitored.
In case of clinically significant hypocalcemia (very low calcium levels in the blood), it should be corrected by intravenous administration of calcium gluconate.