Iasibon 1 mg concentrate for solution for infusion

The active substance of Iasibon, ibandronic acid, belongs to the group of medicines known as bisphosphonates. It inhibits increased loss of calcium from the bones (bone resorption), thus normalising elevated serum calcium levels. It also prevents bone complications and fractures related to the spread of cancer cells into bone.

Iasibon is indicated in adults for:

• Pathologically (abnormally) elevated serum calcium levels (hypercalcaemia) as a result of tumours
• Prevention of skeletal events (pathological fractures, bone complications requiring radiotherapy or surgery) in patients with breast cancer and bone metastases (neoplasms).

Do not use Iasibon

• if you are allergic (hypersensitive) to the active substance or any of the other ingredients of Iasibon.
• if you have low calcium levels in your blood (hypocalcaemia).

During treatment your blood may be monitored to ensure that you are receiving the correct dose of Iasibon.

If you are under dental treatment or will undergo dental surgery, tell your dentist that you are being treated with Iasibon.

Iasibon should not be used in children below 18 years old.

Take special care with Iasibon

if you know or believe that you may have:

• hypersensitivity to other bisphosphonates
• low blood calcium
• other disturbances of mineral metabolism (such as vitamin D deficiency)
• moderate or severe kidney disease (renal insufficiency)
• overhydratation (if you are at risk of cardiac failure).

Using other medicines

Please inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Caution is advised when bisphosphonates are administered with aminoglycosides (antibacterial medicines) since both medicines can lower serum calcium levels in your blood for long periods. Caution should also be paid to the possible existence of simultaneous reduced magnesium levels (hypomagnesaemia).

Pregnancy and breast-feeding

You should not be given Iasibon if you are pregnant or if you are breast-feeding.
Ask your doctor or pharmacist for advice before taking any medicines.

Driving and using machines

No studies on the effects on the ability to drive and use machines have been performed.

Important information about some of the ingredients of Iasibon

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ?sodium-free?.

You will be given Iasibon as an infusion by your doctor or nurse. Your doctor will determine how much Iasibon you will be given depending on your illness.
The recommended dose for prevention of skeletal events in patients with breast cancer and bone metastases is 6 mg given every 3-4 weeks.
In most patients with severe hypercalcaemia 4 mg is an adequate single dose.
Your doctor may adjust your dose if you have kidney problems.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Like all medicines, Iasibon can cause side effects although not everybody gets them.

The side effects listed below were seen when Iasibon was given intravenously.

Very common side effects (affects more than 1 user in 10):

rise in body temperature.

Common side effects (affects 1 to 10 users in 100):
flu-like symptoms (including fever, chills, bone pain and aching muscles), tiredness, diarrhea, indigestion, vomiting, headache, dizziness, gastrointestinal pain, sore throat, and swelling of the lower limbs. These symptoms usually disappear within a couple of hours/days. Less commonly patients have reported infections, strange taste, cataracts, bundle branch block, tooth disorder, skin problems, aching joints, arthritis and thirst.

Rare side effects (affects 1 to 10 users in 10,000):
gastroenteritis, oral thrush, vaginitis, benign skin growth, sleep disturbance, anxiety, affect lability, memory loss, numbness round the mouth (paraesthesia circumoral), hyperaesthesia, hypertonia, nerve root lesion, neuralgia, migraine, cerebrovascular disorder, parosmia, deafness, heart and circulatory problems (including palpitations, myocardial ischaemia, hypertension, varicose veins), lymphoedema,

lung oedema, stridor, inflammation of the stomach (gastritis), cheilitis, difficulty swallowing (dysphagia), mouth ulceration, gall stones cholelithiasis, rash, hair loss, cystitis, renal cyst, urinary retention, pelvic pain, injection site pain, weight loss, and hypothermia.

Iasibon may also cause changes in laboratory tests carried out by your doctor, these include; low calcium (metal), low phosphate (mineral), raised liver enzyme and raised creatinine, parathyroid disorder (hormone) in the blood, low hemoglobin (and rarely blood dyscrasia).

Very rare side effects (affects less than 1 user in 10,000):
allergic reaction to Iasibon which may cause wheezing and breathlessness or skin rashes.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Do not use Iasibon 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 Iasibon if you notice that the solution is not clear or contains particles.

Unused solution should be discarded.

What Iasibon contains

• One ampoule with 1 ml concentrate for solution for infusion contains 1 mg ibandronic acid (as 1.125 mg ibandronic acid, monosodium salt, monohydrate).
• The other ingredients are sodium chloride, glacial acetic acid, sodium acetate trihydrate and water for injections.

What Iasibon looks like and contents of the pack

Iasibon is a colourless, clear solution.

Iasibon 1 mg is supplied as pack containing 1 ampoule (2 ml type I glass ampoule).

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Pharmathen S.A.
Dervenakion 6
Pallini 15351
Attiki
Greece

Manufacturer
Pharmathen S.A.
Dervenakion 6
Pallini 15351

Attiki
Greece

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

BelgiëBelgiqueBelgien Pharmathen S.A. TélTel 30 210 66 65 067 LuxembourgLuxemburg Portfarma ehf.. TélTel 354 534 4030

Alvogen Pharma Bulgaria Ltd Te. 359 2 400 555 2 Magyarország Pharmathen S.A. Tel. 30 210 66 65 067

eská republika Pharmathen S.A. Tel 30 210 66 65 067 Malta Pharmathen S.A. Tel 30 210 66 65 067

Danmark Pharmathen S.A. Tlf 30 210 66 65 067 Nederland Pharmathen S.A. Tel 30 210 66 65 067

Deutschland Pharmathen S.A. Tel 30 210 66 65 067 Norge Pharmathen S.A. Tlf 30 210 66 65 067

Eesti Estonia Portfarma ehf. Tel 354 534 4030 Österreich Pharmathen S.A. Tel 30 210 66 65 067

Pharmathen S.A. 30 210 66 65 067 Polska Pharmathen S.A. Tel. 30 210 66 65 067

España Pharmathen S.A. Tel 30 210 66 65 067 Portugal Pharmathen S.A. Tel 30 210 66 65 067

France Pharmathen S.A. Tél 30 210 66 65 067 România Alvogen Pharma Bulgaria Ltd Tel 40 744 543249

Ireland Aspire Pharma Ltd Tel 44 1730 234527 Slovenija Pharmathen S.A. Tel 30 210 66 65 067

Ísland Portfarma ehf. Sími 354 534 4030 Slovenská republika Pharmathen S.A. Tel 30 210 66 65 067

Italia Pharmathen S.A. Tel 30 210 66 65 067 SuomiFinland Pharmathen S.A. PuhTel 30 210 66 65 067

P.T. Hagjigeorgiou Co Ltd 357 25372425 Sverige Pharmathen S.A. Tel 30 210 66 65 067

Latvija Portfarma ehf. Tel 354 534 4030 United Kingdom Aspire Pharma Ltd Tel 44 1730 234527

Lietuva

Portfarma ehf.
Tel: +354 534 4030

This leaflet was last approved in

--------------------------------------------------------------------------------------------------------------------- The following information is intended for medical or healthcare professionals only

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 6 mg intravenously given every 3-4 weeks. The dose should be infused over at least 15 minutes. For infusion, the contents of the vial(s) should only be added to 100 ml isotonic sodium chloride solution or 100 ml 5% glucose solution.

A shorter (i.e. 15 min) infusion time should only be used for patients with normal renal function or mild renal impairment. There are no data available characterizing the use of a shorter infusion time in patients with creatinine clearance below 50 ml/min. Prescribers should consult the section Patients with Renal Impairment (see section 4.2) for recommendations on dosing and administration in this patient group.

Treatment of tumour-induced hypercalcemia

Prior to treatment with Iasibon the patient should be adequately rehydrated with 9 mg/ml (0.9%) sodium chloride. Consideration should be given to the severity of the hypercalcaemia as well as the tumour type. In general patients with osteolytic bone metastases require lower doses than patients with the humoral type of hypercalcaemia. In most patients with severe hypercalcaemia (albumin-corrected serum calcium* ?3 mmol/l or ?12 mg/dl) 4 mg is an adequate single dosage. In patients with moderate hypercalcaemia (albumin-corrected serum calcium <3 mmol/l or <12 mg/dl) 2 mg is an effective dose. The highest dose used in clinical trials was 6 mg 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.

In most cases a raised serum calcium level can be reduced to the normal range within 7 days. The median time to relapse (return of serum albumin-corrected serum calcium above 3 mmol/l) was 18-19 days for the 2 mg and 4 mg doses. The median time to relapse was 26 days with a dose of 6 mg.

Method and route of administration

Iasibon therapy should only be initiated by physicians experienced in the treatment of cancer. For intravenous administration.

For single use only. Only clear solution without particles should be used.

Iasibon concentrate for solution for infusion should be administered as an intravenous infusion. For this purpose, the contents of the vials are to be added to 500 ml isotonic sodium chloride solution (or 500 ml 5% dextrose solution) and infused over two hours.

As the inadvertent intra-arterial administration of preparations not expressly recommended for this purpose as well as paravenous administration can lead to tissue damage, care must be taken to ensure that Iasibon concentrate for solution for infusion is administered intravenously.

Note:
To avoid potential incompatibilities Iasibon concentrate for solution for infusion should only be diluted with isotonic sodium chloride solution or 5% glucose solution.
Iasibon should not be mixed with calcium containing solutions.

Chemical and physical in-use stability has been demonstrated for 24 hours at 2 - 8°C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8 °C, unless reconstitution has taken place in controlled and validated aseptic conditions.
(see point 5 of this leaflet ?HOW TO STORE IASIBON?).

Frequency of administration

The recommended dose for prevention of skeletal events in patients with breast cancer and bone metastases is 6 mg intravenous injection given every 3-4 weeks. The dose should be infused over at least 15 minutes.

In most patients with severe hypercalcaemia (albumin-corrected serum calcium* ?3 mmol/l or ?12 mg/dl) 4 mg is an adequate single dosage.

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.

Overdose

Up to now there is no experience of acute poisoning with Iasibon 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.