Zoledroninezuur Chiesi 4 mg/5 ml, steriel concentraat

The active substance in [Product name] is zoledronic acid, which belongs to a group of substances called bisphosphonates. Zoledronic acid works by attaching itself to the bone and slowing down the rate of bone change. It is used:

• To prevent bone complications e.g. fractures, in adult patients with bone metastases (spread of cancer from primary site to the bone)

issue date: 14‐05‐12

Document: M1.3.1_03.ZLE.mhy.vial.001.05.core.WD

Author: PL

Common Technical Document	CBG‐MEB
Zoledronic acid (as monohydrate) 4 mg/ 5 ml
concentrate for solution for infusion
Module 1 ‐Section 3.5 Core SPC, Labelling	page 2/11
and Package Leaflet

• To reduce the amount of calcium in the blood in adult patients where it is too high due to the presence of a tumour. Tumours can accelerate normal bone change in such a way that the release of calcium from bone is increased. This condition is known as tumour‐induced hypercalcaemia (TIH).

Follow carefully all instructions given to you by your doctor.

Your doctor will carry out blood tests before you start treatment with [Product name] and will check your response to treatment at regular intervals.

You should not be given [Product name]:

• if you are breast‐feeding.
• if you are allergic to zoledronic acid, another bisphosphonate (the group of substances to which [Product name]belongs), or any of the other ingredients of this medicine (listed in section 6)

Warnings and precautions

• Talk to your doctor, pharmacist or nurse before you are given [Product name]:
• if you have or have had a kidney problem.
• if you have or have had pain, swelling or numbness of the jaw, a feeling of heaviness in the jaw or loosening of a tooth.

• if you are having dental treatment or are due to undergo dental surgery, tell your dentist that you are being treated with [Product name] .

Other medicines and [Product name]

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

It is especially important that you tell your doctor if you are also taking:

issue date: 14‐05‐12

Document: M1.3.1_03.ZLE.mhy.vial.001.05.core.WD

Author: PL

Common Technical Document	CBG‐MEB
Zoledronic acid (as monohydrate) 4 mg/ 5 ml
concentrate for solution for infusion
Module 1 ‐Section 3.5 Core SPC, Labelling	page 3/11
and Package Leaflet

• Aminoglycosides (medicines used to treat severe infections), since the combination of these with bisphosphonates may cause the calcium level in the blood to become too low.
• Thalidomide (a medicine used to treat a certain type of blood cancer involving the bone) or any other medicines which may harm your kidneys.
• Other medicines that also contain zoledronic acid, or any other bisphosphonate, since the combined effects of these medicines taken together with [Product name] are unknown.
• Anti‐angiogenic medicines (used to treat cancer), since the combination of these with zoledronic acid has been associated with reports of osteonecrosis of the jaw (ONJ).

Patients aged 65 years and over

[Product name] can be given to people aged 65 years and over. There is no evidence to suggest that any extra precautions are needed.

Children and adolescents

[Product name] is not recommended for use in adolescents and children below the age of 18 years.

issue date: 14‐05‐12

Document: M1.3.1_03.ZLE.mhy.vial.001.05.core.WD

Author: PL

Common Technical Document	CBG‐MEB
Zoledronic acid (as monohydrate) 4 mg/ 5 ml
concentrate for solution for infusion
Module 1 ‐Section 3.5 Core SPC, Labelling	page 4/11
and Package Leaflet

Pregnancy and breast‐feeding

You should not be given [Product name] if you are pregnant. Tell your doctor if you are pregnant, think that you may be pregnant or planning to have a baby.

You must not be given [Product name] if you are breast‐feeding.

If you are pregnant or breast‐feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

There have been very rare cases of drowsiness and sleepiness with the use of [Product name]. You should therefore be careful when driving, using machinery or performing other tasks that need full attention.

[Product name] contains less than 1 mmol sodium (23 mg) per vial (5 ml), i.e. essentially “sodium-free”.

• [Product name] must only be given by healthcare professionals trained in administering bisphosphonates intravenously, i.e. through a vein. ‐ Your doctor will recommend that you drink enough water before each treatment to help prevent dehydration.

‐ Carefully follow all the other instructions given to you by your doctor, nurse or pharmacist.

How much [Product name] is given

• The usual single dose given is 4 mg.
• If you have a kidney problem, your doctor will give you a lower dose depending on the severity of your kidney problem.

How often [Product name] is given

• If you are being treated for the prevention of bone complications

issue date: 14‐05‐12

Document: M1.3.1_03.ZLE.mhy.vial.001.05.core.WD

Author: PL

Common Technical Document	CBG‐MEB
Zoledronic acid (as monohydrate) 4 mg/ 5 ml
concentrate for solution for infusion
Module 1 ‐Section 3.5 Core SPC, Labelling	page 5/11
and Package Leaflet

due to bone metastases , you will be given one infusion of [Product name] every three to four weeks.

‐ If you are being treated to reduce the amount of calcium in your blood, you will normally only be given one infusion of [Product name]

How [Product name] is given

‐[Product name] is given as a drip (infusion) into a vein which should take at least 15 minutes and should be administered as a single intravenous solution in a separate infusion line.

Patients whose blood calcium levels are not too high will also be prescribed calcium and vitamin D supplements to be taken each day.

If you are given more [Product name] than you should be

If you have received doses higher than those recommended, you must be carefully monitored by your doctor. This is because you may develop serum electrolyte abnormalities (e.g. abnormal levels of calcium, phosphorus and magnesium) and/or changes in kidney function, including severe kidney impairment. If your level of calcium falls too low, you may have to be given supplemental calcium by infusion.

Like all medicines, this medicine can cause side effects, although not everybody gets them. The most common ones are usually mild and will probably disappear after a short time.

Tell your doctor about any of the following side effects straight away:

Common (may affect up to 1 in 10 people):

• Severe kidney impairment (will normally be determined by your doctor with certain specific blood tests).
• Low level of calcium in the blood.

issue date: 14‐05‐12

Document: M1.3.1_03.ZLE.mhy.vial.001.05.core.WD

Author: PL

Common Technical Document	CBG‐MEB
Zoledronic acid (as monohydrate) 4 mg/ 5 ml
concentrate for solution for infusion
Module 1 ‐Section 3.5 Core SPC, Labelling	page 6/11
and Package Leaflet

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

• Pain in the mouth, teeth and/or jaw, swelling or sores inside the mouth, numbness or a feeling of heaviness in the jaw, or loosening of a tooth. These could be signs of bone damage in the jaw (osteonecrosis). Tell your doctor and dentist immediately if you experience such symptoms.
• Irregular heart rhythm (atrial fibrillation) has been seen in patients receiving zoledronic acid for postmenopausal osteoporosis. It is currently unclear whether zoledronic acid causes this irregular heart rhythm but you should report it to your doctor if you experience such symptoms after you have received zoledronic acid.
• Severe allergic reaction: shortness of breath, swelling mainly of the face and throat.

Tell your doctor about any of the following side effects as soon as possible:

Very common (may affect more than 1 in 10 people)

Low level of phosphate in the blood

Common (may affect up to 1 in 10 people)

Headache and a flu‐like syndrome consisting of fever, fatigue, weakness, drowsiness, chills and bone, joint and/or muscle ache. In most cases no specific treatment is required and the symptoms disappear after a short time (couple of hours or days) • Gastrointestinal reactions such as nausea and vomiting as well as loss of appetite • Conjunctivitis • Low level of red blood cells (anaemia)

Uncommon (may affect up to 1 in 100 people)

Low counts of white blood cells and blood platelets • Hypersensitivity reactions • Anxiety, sleep disturbances • Dizziness, tingling or numbness of the hands or feet, taste disturbance, increased or decreased sensitivity to stimulation, tremor, somnolence • Tearing of the eye, eye sensitivity to light • High blood pressure, low blood pressure, sudden coldness with fainting, limpness or collapse • Difficulty breathing, cough • Diarrhoea, constipation, abdominal pain, indigestion, inflammation of the mouth, dry mouth • Itching, rash, increased sweating • Muscle

issue date: 14‐05‐12

Document: M1.3.1_03.ZLE.mhy.vial.001.05.core.WD

Author: PL

Common Technical Document	CBG‐MEB
Zoledronic acid (as monohydrate) 4 mg/ 5 ml
concentrate for solution for infusion
Module 1 ‐Section 3.5 Core SPC, Labelling	page 7/11
and Package Leaflet

cramps • Kidney failure, blood in the urine, proteins in the urine • Feeling of weakness, swelling of the ankles, feet or fingers, skin reactions (redness and swelling) at the infusion site, chest pain , weight increase, hives • Low level of magnesium and potassium in the blood. Your doctor will monitor this and take any necessary measures.

Rare (may affect up to 1 in 1,000 people)

Slow heart beat • Confusion • 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 • Severe reduction in blood cells which can cause weakness, bruising or make infections more likely • Serious allergic reaction which causes swelling of the face or throat • High levels of blood potassium which can cause abnormal heart rhythm, high levels of blood sodium which can cause confusion, muscle twitching or abnormal heart rhythm.

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

Painful redness and/or swelling of the eye.

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

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

Your doctor, nurse or pharmacist knows how to store [Product name] properly (see section 6, Further information).

Do not use this medicine after the expiry date which is stated on the carton and on the vial. The expiry date refers to the last days of that month.

This medicinal product does not require any special storage conditions.

issue date: 14‐05‐12

Document: M1.3.1_03.ZLE.mhy.vial.001.05.core.WD

Author: PL

Common Technical Document	CBG‐MEB
Zoledronic acid (as monohydrate) 4 mg/ 5 ml
concentrate for solution for infusion
Module 1 ‐Section 3.5 Core SPC, Labelling	page 8/11
and Package Leaflet

After first opening, [Product name] should be used immediately. If the solution is not used immediately, storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C – 8°C. The refrigerated solution should then be equilibrated to room temperature prior to administration.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

What [Product name] contains

• The active substance is zoledronic acid. One vial contains 4 mg of zoledronic acid (anhydrous) corresponding to 4.264 mg zoledronic acid monohydrate.
• The other ingredients are: mannitol (E421), sodium citrate dihydrate (E331), sodium hydroxide (E524) for pH‐adjustment, hydrochloric acid (E507) for pH adjustment and water for injections.

What [Product name] looks like and contents of the pack

[Product name] concentrate for solution for infusion is a clear, colourless solution, free from visible particles.

[Product name] is supplied as a liquid concentrate in a vial. One vial contains 4 mg of zoledronic acid.

Each pack contains the vial with concentrate. [Product name] is supplied as packs containing 1, 4, 5 or 10 vials.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Chiesi Farmaceutici S.p.A.

Via Palermo, 26/A

43122 Parma

Italië

Manufacturers:

Synthon BV

Microweg 22

issue date: 14‐05‐12

Document: M1.3.1_03.ZLE.mhy.vial.001.05.core.WD

Author: PL

Common Technical Document	CBG‐MEB
Zoledronic acid (as monohydrate) 4 mg/ 5 ml
concentrate for solution for infusion
Module 1 ‐Section 3.5 Core SPC, Labelling	page 9/11
and Package Leaflet
6545 CM Nijmegen
Nederland

Synthon Hispania SL

Castelló 1, Polígono Las Salinas

08830 Sant Boi de Llobregat Spanje

Dit geneesmiddel is geregistreerd onder:

Zoledroninezuur Chiesi 4 mg/5 ml, steriel concentraat RVG 109530

<This medicinal product is authorised in the Member States of the EEA under the following names:>

Nederland	Zoledroninezuur Chiesi 4 mg/5 ml, steriel concentraat
Italië	Acido zoledronico Chiesi

This leaflet was last revised in januari 2013

issue date: 14‐05‐12

Document: M1.3.1_03.ZLE.mhy.vial.001.05.core.WD

Author: PL

Common Technical Document	CBG‐MEB
Zoledronic acid (as monohydrate) 4 mg/ 5 ml
concentrate for solution for infusion
Module 1 ‐Section 3.5 Core SPC, Labelling	page 10/11
and Package Leaflet

INFORMATION FOR THE HEALTHCARE PROFESSIONAL

The following information is intended for healthcare professionals only:

How to prepare and administer [Product name]

• To prepare an infusion solution containing 4 mg zoledronic acid, further dilute the [Product name] concentrate (5.0 ml) with 100 ml of calcium‐free or other divalent cation‐free infusion solution. If a lower dose of [Product name] is required, first withdraw the appropriate volume as indicated below and then dilute it further with 100 ml of infusion solution. To avoid potential incompatibilities, the infusion solution used for dilution must be either 9 mg/ml sodium chloride or 50 mg/ml glucose solution. Do not mix [Product name] concentrate with calcium-containing or other divalent cation-containing solutions such as lactated Ringer’s solution. Instructions for preparing reduced doses of [Product name]: Withdraw the appropriate volume of the liquid concentrate, as follows:
  • 4.4 ml for 3.5 mg dose
  • 4.1 ml for 3.3 mg dose
  • 3.8 ml for 3.0 mg dose
• For single use only. Any unused solution should be discarded. Only clear solution free from particles and discolouration should be used. Aseptic techniques must be followed during the preparation of the infusion.
• From a microbiological point of view, the diluted solution for infusion 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°C – 8°C and at 25°C. The refrigerated solution should be equilibrated to room temperature prior to administration.

issue date: 14‐05‐12

Document: M1.3.1_03.ZLE.mhy.vial.001.05.core.WD

Author: PL

Common Technical Document	CBG‐MEB
Zoledronic acid (as monohydrate) 4 mg/ 5 ml
concentrate for solution for infusion
Module 1 ‐Section 3.5 Core SPC, Labelling	page 11/11
and Package Leaflet

• The solution containing zoledronic acid is given as a single 15‐minute intravenous infusion in a separate infusion line. The hydration status of patients must be assessed prior to and following administration of [Product name] to ensure that they are adequately hydrated.

‐Studies with several types of infusion lines made from polyvinylchloride, polyethylene and polypropylene showed no incompatibility with zoledronic acid.

• Since no data are available on the compatibility of zoledronic acid with other intravenously administered substances, [Product name] must not be mixed with other medications/substances and should always be given through a separate infusion line.

How to store [Product name]

• Keep [Product name] out of the reach and sight of children.
• Do not use [Product name] after the expiry date stated on the pack.
• This medicinal product does not require any special storage conditions.

The diluted [Product name] infusion solution should be used immediately in order to avoid microbial contamination.

issue date: 14‐05‐12

Document: M1.3.1_03.ZLE.mhy.vial.001.05.core.WD

Author: PL