|teva uk Ret: 231-30-11775-E LEA IBANDRONIC ACID 2mg/ml & 6mg/ml SOL TEVAH <SYN

Version: 2    10 March 2016

| teva uk Ret: 231-30-11775-E LEA IBANDRONIC ACID 2mg/ml & 6mg/ml SOL TEVAH <SYN

ion: 2    10 March 2016

TTW71

HOSPITALS

PACKAGE LEAFLET: INFORMATION FOR THE USER

Ibandronic Acid 2mg/2ml & 6mg/6ml Concentrate for Solution for Infusion

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

•    Keep this leaflet. You may need to read it again.

•    If you have any further questions, ask your doctor or pharmacist.

•    If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

What is in this leaflet:

1.    What Ibandronic Acid is and what it is used for

2.    What you need to know before you receive Ibandronic Acid

3.    How to receive Ibandronic Acid

4.    Possible side effects

5.    How to store Ibandronic Acid

6.    Contents of the pack and other information

OWhat Ibandronic Acid is and what it is used for

Ibandronic Acid concentrate for solution for infusion contains the active substance ibandronic acid.

Ibandronic acid belongs to a group of medicines called bisphosphonates.

Ibandronic acid is indicated 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.

Ibandronic acid can also be prescribed if you have a raised calcium level in your blood due to a tumour. Ibandronic acid works by reducing the amount of calcium that is lost from your bones. This helps to stop your bones from getting weaker.

OWhat you need to know before you receive Ibandronic Acid

Do not receive Ibandronic Acid

if you are allergic (hypersensitive) 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 ibandronic acid.

Warnings and precautions Take special care with Ibandronic Acid • if you are allergic (hypersensitive) to any other bisphosphonates

• if you have high or low levels of vitamin D or any other minerals

• if you have kidney problems.

Talk to your doctor of pharmacist before using Ibandronic Acid.

If you are having dental treatment or surgery or know that you need some in the future, tell your dentist that you are being treated with ibandronic acid.

Children and adolescents

Ibandronic acid should not be used in children and teenagers below age 18 years.

Other medicines and Ibandronic Acid Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including those obtained without a prescription. 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 ibandronic acid if you are pregnant, planning to get pregnant or if you are breast-feeding.Ask your doctor or pharmacist for advice before taking any medicines.

Driving and using machines

It is not known if ibandronic acid affects your ability to drive, use machines or tools. Talk to your doctor first if you want to drive, use machines or tools.

Ibandronic Acid Concentrate for Solution for Infusion contains sodium

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

How to receive Ibandronic Acid

Receiving this medicine

•    Ibandronic acid is normally given by a doctor or other medical staff.

•    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 use

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 3 vials (6 mg) every 3-4 weeks, as an infusion to your vein over at least 15

If you have a raised calcium level in your blood due to a tumour then the recommended dose is a single administration of 1 vial (2 mg) or 2 vials (4 mg), depending on the severity of your illness. The medicine should be administered as an infusion to 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.

^4 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:

•    rash, itching, swelling of your face, lips, tongue and throat, with difficulty breathing. You may be having an allergic reaction to the medicine

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The following information is intended for medical or healthcare professionals only Dosage: 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.

Patients with renal impairment

For patients with mild renal impairment (CLcr >50 and <80 mL/min) no dosage adjustment is necessary. For patients with moderate renal impairment (CLcr >30 and <50 mL/min) or severe renal impairment (CLcr <30 mL/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    Administration every 3 to 4 week

²    0.9% sodium chloride solution or 5% glucose solution

A 15 minute infusion time has not been studied in cancer patients with CLCr <50 mL/min.

Dosage: Tumour-induced Hypercalcemia

Ibandronic acid is usually administered in a hospital setting. The dose is determined by the doctor considering the following

Prior to treatment with ibandronic acid 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 most patients with severe hypercalcaemia (albumin-corrected serum calcium” >3 mmol/l or >12 mg/dl) 4 mg will be 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    = Serum calcium (mmol/l) - [0.02 x albumin (g/l)] + 0.8

(mmol/l)

Albumin-corrected    = Serum calcium (mg/dl) + 0.8 x [4 - albumin (g/dl)]

Serum calcium (mg/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 (reincrease 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.

•    problems breathing.

•    pain or sore in your mouth or jaw

•    eye pain and inflammation (if prolonged)

•    talk to your doctor if you have ear pain, discharge from the ear, and/or an ear infection. These could be signs of bone damage in the ear.

Other possible side effects

Very common (affects more than 1 in 10 people)

Rise in body temperature.

Common (affects less than 1 in 10 people)

Stomach pain, indigestion, being sick or having diarrhoea • Low calcium or phosphate levels in your blood • Changes in blood test results such as Gamma GT or creatinine • A heart problem called "bundle branch block" • Flu-like symptoms (including fever, chills, bone pain and aching muscles). These symptoms usually disappear within a couple of hours or days. •

Pain or stiffness in your 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 (affects 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" • Heart and circulatory problems (including palpitations, heart attack, hypertension 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 • 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 • Hair loss • Pain or injury at the injection site • Weight loss • Kidney cyst.

Rare (affects less than 1 in 1000 people)

Eye pain or inflammation • Unusual fracture of the thigh bone particularly in patients on long-term treatment for osteoporosis may occur rarely. Contact your doctor if you experience pain, weakness or discomfort in your thigh, hip or groin as this may be an early indication of a possible fracture of the thigh bone. Very rare (affects less than 1 in 10000 people)

A condition involving exposed bone in the mouth called "osteonecrosis of the jaw".

©Contents of the pack and other information

What Ibandronic Acid Concentrate for Solution for Infusion contains

2mg/2ml:

One vial with 2 ml concentrate for solution for infusion contains 2 mg ibandronic acid (as 2.25 mg ibandronic acid, monosodium salt, monohydrate).

6mg/6ml:

One vial with 6 ml of a concentrate for solution for infusion contains 6 mg ibandronic acid (as 6.75 mg ibandronic acid, monosodium salt, monohydrate).

One ml concentrate for solution for infusion contains 1 mg ibandronic acid (as 1.13 mg ibandronic acid, monosodium salt, monohydrate).

The other ingredients are sodium chloride, sodium hydroxide (E524) (for pH adjustment), acetic acid, glacial (E260), sodium acetate trihydrate and water for injections.

What Ibandronic Acid Concentrate for Solution for Infusion looks like and contents of the pack

Ibandronic Acid Concentrate for Solution for Infusion is a clear and colourless solution.

It is available in packs of 2mg/2ml:

1 clear, colourless glass vial 6mg/6ml:

1 or 5 clear, colourless glass vials The vials are closed with a rubber stopper. Two ml vials have an orange flip-off cap while 6 ml vials have a turquoise (greenish blue) flip-off cap.

Not all pack sizes may be marketed.

Marketing Authorisation Holder:

Teva UK Limited, Eastbourne, BN22 9AG, UK

Manufacturers:

Merckle GmbH, Ludwig-Merckle-Strade 3, 89143 Blaubeuren, Germany

This leaflet was last revised in March 2016

PL 00289/1757 PL 00289/1758

rg| How to store Ibandronic Acid

Keep this medicine out of the sight and reach of children.

This medicinal product does not require any special storage conditions.

After dilution the infusion solution is stable for 24 hours at 2-8 °C (in a refrigerator).

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.

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

Unused solution should be discarded.

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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:

•    Hypercalcaemia - added to 500 ml isotonic sodium chloride solution or 500 ml 5% dextrose solution and infused over

•    Prevention of Skeletal Events - added to 100 ml isotonic sodium chloride solution or 100 ml 5% dextrose solution and infused over at least 15 minutes. See also dosage section above for patients with renal impairment.

Note:

In order to avoid potential incompatibilities, ibandronic acid concentrate for solution for infusion should only be mixed with isotonic sodium chloride solution or with 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 IBANDRONIC ACID").

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 ibandronic acid concentrate for solution for infusion is administered intravenously.

Frequency of administration

For treatment of tumour induced hypercalcemia, 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.

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