Patient leaflet - Ibandronic Acid 6 mg concentrate for solution for infusion
What this medicine is and what it is used for
This medicine contains the active substance ibandronic acid.
This belongs to a group of medicines called bisphosphonates.
This medicine is used in adults and prescribed to you if you
have breast cancer that has spread to your bones (called
‘bone metastases’).
•It helps to prevent your bones from breaking (fractures)
- It helps to prevent other bone problems that may need
surgery or radiotherapy
This medicine can also be prescribed if you have a raised
calcium level in your blood due to a tumour.
This medicine works by reducing the amount of calcium that
is lost from your bones. This helps to stop your bones from
getting weaker.
What you need to know before you receive this medicine
Do not receive this medicine
- if you are allergic to ibandronic acid or any of the other
ingredients of this medicine that are listed in section 6
- if you have, or have ever had, low levels of calcium in
your blood.
Do not receive this medicine if any of the above apply to you.
If you are not sure, talk to your doctor or pharmacist before
having this medicine.
Warnings and precautions
A side effect called osteonecrosis of the jaw (ONJ) (bone
damage in the jaw) has been reported very rarely in the
post marketing setting in patients receiving ibandronate for
cancer-related conditions. ONJ can also occur after
stopping treatment.
It is important to try and prevent ONJ developing as it is a
painful condition that can be difficult to treat. In order to
reduce the risk of developing osteonecrosis of the jaw, there
are some precautions you should take.
Before receiving treatment, tell your doctor/nurse (health care
professional) if:
- you have any problems with your mouth or teeth such as poor
dental health, gum disease, or a planned tooth extraction
- you don’t receive routine dental care or have not had a dental
check up for a long time
- you are a smoker (as this may increase the risk of
dental problems)
- you have previously been treated with a bisphosphonate
(used to treat or prevent bone disorders)
- you are taking medicines called corticosteroids (such as
prednisolone or dexamethasone)
•you have cancer.
Your doctor may ask you to undergo a dental examination
before starting treatment with ibandronic acid.
While being treated, you should maintain good oral hygiene
(including regular teeth brushing) and receive routine dental
check-ups. If you wear dentures you should make sure these
fit properly. If you are under dental treatment or will undergo
dental surgery (e.g. tooth extractions), inform your doctor
about your dental treatment and tell your dentist that you are
being treated with ibandronic acid.
Contact your doctor and dentist immediately if you experience
any problems with your mouth or teeth such as loose teeth,
pain or swelling, non-healing of sores or discharge, as these
could be signs of osteonecrosis of the jaw.
Package leaflet: Information for the patient
Ibandronic acid 1mg concentrate for solution for infusion Ibandronic acid 2mg concentrate for solution for infusion Ibandronic acid 6mg concentrate for solution for infusion
Talk to your doctor, pharmacist or nurse before receiving ibandronic acid:
•if you are allergic to any other bisphosphonates
- if you have high or low levels of vitamin D, calcium or any other minerals
•if you have kidney problems
- if you have heart problems and the doctor recommended to limit your daily fluid intake.
Cases of serious, sometimes fatal allergic reaction have been reported in patients treated with intravenous ibandronic acid. If you experience one of the following symptoms, such as shortness of breath / difficulty breathing, tight feeling in throat, swelling of tongue, dizziness, feeling of loss of consciousness, redness or swelling of face, body rash, nausea and vomiting, you should immediately alert your doctor or nurse (see section 4).
Children and adolescents
This medicine should not be used in children and adolescents below the age of 18 years.
Other medicines and Ibandronic acid
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This is because ibandronic acid can affect the way some other medicines work. Also, some other medicines can affect the way ibandronic acid works.
In particular, tell your doctor or pharmacist if you are receiving a type of antibiotic injection called ‘aminoglycoside’ such as gentamicin. This is because aminoglycosides and ibandronic acid can both lower the amount of calcium in your blood.
Pregnancy and breast-feeding
Do not receive this medicine if you are pregnant, planning to get pregnant or if you are breast-feeding. Ask your doctor or pharmacist for advice before taking this medicine.
Driving and using machines
You can drive and use machines as it’s expected that this medicine has no or negligible effect on your ability to drive and use machines. Talk to your doctor first if you want to drive, use machines or tools.
This medicine contains less than 1mmol sodium (23mg) per dose, that is to say essentially “sodium-free”.
How to receive this medicine
Receiving this medicine
- This medicine is normally given by a doctor or other medical staff who have experience with the treatment of cancer. •It is given as an infusion into your vein.
Your doctor may do regular blood tests while you are receiving Ibandronic acid. This is to check that you are being given the right amount of this medicine.
How much to receive
Your doctor will work out how much Ibandronic acid you will be given depending on your illness.
If you have breast cancer that has spread to your bones, then the recommended dose is 6mg every 3-4 weeks, as an infusion in your vein over at least 15 minutes.
If you have a raised calcium level in your blood due to a tumour then the recommended dose is a single administration of 2mg or 4mg, depending on the severity of your illness. The medicine should be administered as an infusion in your vein over two hours. A repeated dose may be considered in case of insufficient response or if your illness reappears. Your doctor may adjust your dose and duration of intravenous infusion if you have kidney problems.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Possible side effects
Like all medicines, this medicine can cause side effects although not everybody gets them.
Talk to a nurse or a doctor straight away if you notice any of the following serious side effects - you may need urgent medical treatment:
The following information is intended for healthcare professionals only
Dose: Prevention of skeletal events in patients with breast cancer and bone metastases The recommended dose for prevention of skeletal events in patients with breast cancer and bone metastases is 6mg intravenously given every 3-4 weeks. The dose should be infused over at least 15 minutes.
Patients with renal impairment
For patients with mild renal impairment (CLcr ≥50 and <80ml/min) no dosage adjustment is necessary. For patients with moderate renal impairment (CLcr ≥30 and <50ml/min) or severe renal impairment (CLcr <30ml/min) being treated for the prevention of skeletal events in patients with breast cancer and metastatic bone disease the following dosing recommendations should be followed:
1 0.9% sodium chloride solution or 5% glucose solution
2 Administration every 3 to 4 week
A 15 minute infusion time has not been studied in cancer patients with CLCr <50ml/min.
Dose: Treatment of tumour-induced hypercalcaemia
Ibandronic acid is usually administered in a hospital setting. The dose is determined by the doctor considering the following factors.
Prior to treatment with ibandronic acid the patient should be adequately rehydrated with 9mg/mL (0.9%) sodium chloride. Consideration should be given to the severity of the hypercalcaemia as well as the tumour type. In most patients with severe hypercalcaemia (albumin-corrected serum calcium* ≥3mmol/L or ≥12mg/dL) 4mg is an adequate single dosage. In patients with moderate hypercalcaemia (albumin-corrected serum calcium <3mmol/L or <12mg/dL) 2mg is an effective dose. The highest dose used in clinical trials was 6mg but this dose does not add any further benefit in terms of efficacy.
* Note albumin-corrected serum calcium concentrations are calculated as follows: Albumin-corrected Serum calcium (mmol/L) = Serum calcium (mmol/L) - [0.02 x albumin (g/L)] + 0.8 or
Albumin-corrected Serum calcium (mg/dL) = Serum calcium (mg/dL) + 0.8 x [4 - albumin (g/dL)]
To convert the albumin-corrected serum calcium in mmol/L value to mg/dL, multiply by 4.
(continued overleaf)
6
Rare (may affect up to 1 in 1,000 people)
•persistent eye pain and inflammation
- new pain, weakness or discomfort in your thigh, hip or groin.
You may have early signs of a possible unusual fracture of the
thigh bone.
Very rare (may affect up to 1 in 10,000 people)
- pain or sore in your mouth or jaw. You may have early signs
of severe jaw problems (necrosis (dead bone tissue) in the
jaw bone).
- itching, swelling of your face, lips, tongue and throat, with
difficulty breathing. You may be having a serious, potentially
life threatening allergic reaction (see section 2).
•severe adverse skin reactions
- ear pain, discharge from the ear, and / or an ear infection.
These could be signs of bone damage in the ear.
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)
•rise in body temperature
- flu-like symptoms, including fever, shaking and shivering,
feeling of discomfort, fatigue, bone pain and aching muscles
and joints. These symptoms usually disappear within a
couple of hours or days. Talk to a nurse or doctor if any effects
become troublesome or last more than a couple of days.
- stomach and tummy pain, indigestion, being sick vomiting or
having diarrhoea (loose bowels)
•low calcium or phosphate levels in your blood
•changes in blood test results such as Gamma GT or creatinine
•a heart rhythm problem called ‘bundle branch block’
•pain in your bone or muscles
•headache, feeling dizzy or feeling weak
•feeling thirsty, sore throat, changes in taste
•swollen legs or feet
•aching joints, arthritis, or other joint problems
•problems with your parathyroid gland
•bruising
•infections
•a problem with your eyes called ‘cataracts’
•skin problems
•tooth problems.
Uncommon (may affect less than 1 in 100 people)
•shaking or shivering
•your body temperature getting too low (‘hypothermia’)
- a condition affecting the blood vessels in your brain called
‘cerebrovascular disorder’ (stroke or brain bleeding)
- heart and circulatory problems (including palpitations, heart
attack, hypertension (high blood pressure) and varicose veins)
•changes in your blood cells (‘anaemia’)
•a high level of alkaline phosphatase in your blood
•fluid build up and swelling (‘lymphoedema’)
•fluid in your lungs
•stomach problems such as ‘gastroenteritis’ or ‘gastritis’
•gallstones
- being unable to pass water (urine), cystitis
(bladder inflammation)
•migraine
•pain in your nerves, damaged nerve root
•deafness
- increased sensitivity of sound, taste or touch or changes
in smell
•difficulty swallowing
•mouth ulcers, swollen lips (‘cheilitis’), oral thrush
•itching or tingling skin around your mouth
•pelvic pain, discharge, itching or pain in the vagina
•a skin growth called a ‘benign skin neoplasm’
•memory loss
- sleep problems, feeling anxious, emotional instability, or
mood swings
•skin rash
•hair loss
•injury or pain at the injection site
•weight loss
•kidney cyst (fluid-filled sac in the kidney).
In most cases a raised serum calcium level can be reduced to the normal range within 7 days. The median time to relapse (re-increase of serum albumin-corrected serum calcium above 3mmol/L) was 18-19 days for the 2mg and 4mg doses. The median time to relapse was 26 days with a dose of 6mg.
Method and route of administration
Ibandronic acid concentrate for solution for infusion should be administered as an intravenous infusion. For this purpose the contents of the vial are to be used as follows:
- Prevention of Skeletal Events in patients with breast cancer and bone metastases - added to 100ml isotonic sodium chloride solution or 100ml 5% dextrose solution and infused over at least 15 minutes. See also dosage section above for patients with renal impairment.
- Treatment of tumour-induced hypercalcaemia - added to 500ml isotonic sodium chloride solution or 500ml 5% dextrose solution and infused over 2 hours.
Note: In order to avoid potential incompatibilities ibandronic acid concentrate for solution for infusion should only be diluted with isotonic sodium chloride solution or 5% dextrose solution. Calcium containing solutions should not be mixed with ibandronic acid concentrate for solution for infusion.
Diluted solutions are for single use. Only clear solutions without particles should be used.
It is recommended that the product once diluted be used immediately (see point 5 of this leaflet “How to store this medicine”). Ibandronic acid concentrate for solution for infusion should be administered as an intravenous infusion. Care must be taken not to administer ibandronic acid concentrate for solution for infusion via intra-arterial or paravenous administration, as this could lead to tissue damage.
Frequency of administration
For treatment of tumour induced hypercalcaemia, ibandronic acid concentrate for solution for infusion is generally given as a single infusion.
For the prevention of skeletal events in patients with breast cancer and bone metastases, the ibandronic acid infusion is repeated at 3-4 week intervals.
Duration of treatment
A limited number of patients (50 patients) have received a second infusion for hypercalcaemia. Repeated treatment may be considered in case of recurrent hypercalcaemia or insufficient efficacy. For patients with breast cancer and bone metastases, ibandronic acid infusion should be administered every 3-4 weeks. In clinical trials, therapy has continued for up to 96 weeks.
Overdose
Up to now there is no experience of acute poisoning with ibandronic acid concentrate for solution for infusion. Since both the kidney and the liver were found to be target organs for toxicity in preclinical studies with high doses, kidney and liver function should be monitored.
Clinically relevant hypocalcaemia (very low serum calcium levels) should be corrected by intravenous administration of calcium gluconate.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.
How to store this medicine
•Keep this medicine out of the sight and reach of children.
- Do not use this medicine after the expiry date which is stated on the folding box and on the label after EXP. The expiry date refers to the last day of that month.
- After dilution the infusion solution is stable for 24 hours at 2-8 °C (in a refrigerator).
- Do not use this medicine if you notice that the solution is not clear or contains particles.
Content of the pack and other information
What this medicine contains
•The active substance is ibandronic acid.
- One ampoule with 1ml of a concentrate for solution for infusion contains 1mg ibandronic acid (as sodium monohydrate).
- One ampoule with 2ml of a concentrate for solution for infusion contains 2mg ibandronic acid (as sodium monohydrate).
- One vial with 6ml of a concentrate for solution for infusion contains 6mg ibandronic acid (as sodium monohydrate).
- The other ingredients are sodium chloride, glacial acetic acid, sodium acetate trihydrate and water for injections.
What this medicine looks like and contents of the pack This medicine is a colourless, clear solution.
Ibandronic acid 1mg concentrate for solution for infusion is supplied in a pack containing 1 ampoule (2ml type I glass ampoule).
Ibandronic acid 2mg concentrate for solution for infusion is supplied in a pack containing 1 ampoule (4ml type I glass ampoule).
Ibandronic acid 6mg concentrate for solution for infusion is supplied in packs containing 1, 5 and 10 vials (9ml type I glass vial with a bromobutyl rubber stopper).
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Pharmathen S.A.
Dervenakion 6
Pallini 15351
Attiki
Greece
Manufacturer
Pharmathen S.A.
Dervenakion 6
Pallini 15351
Attiki
Greece
Distributor
Aspire Pharma Ltd
Unit 4, Rotherbrook Court
Bedford Road
Petersfield
Hampshire, GU32 3QG
United Kingdom
This leaflet was last revised in 02/2022
XXXXXXX - P1.2
Date of revision: 28.2.22
Colours: As swatches Font(s): Strada Pro Condensed A/W software: Indesign 2022