Zoledronic Acid Seacross 4mg/100ml Solution For Infusion
PACKAGE LEAFLET: INFORMATION FOR THE USER Zoledronic Acid 4 mg/100 ml solution for infusion
Zoledronic acid
Read all of this leaflet carefully before you are given 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, pharmacist or nurse.
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.
What is in this leaflet:
1. What Zoledronic Acid is and what it is used for
2. What you need to know before you are given Zoledronic Acid
3. How Zoledronic Acid is used
4. Possible side effects
5. How to store Zoledronic Acid
6. Contents of the pack and other information
1. WHAT ZOLEDRONIC ACID IS AND WHAT IT IS USED FOR
The active substance in Zoledronic Acid 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).
• 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).
2. WHAT YOU NEED TO KNOW BEFORE YOU ARE GIVEN ZOLEDRONIC ACID
Follow carefully all instructions given to you by your doctor. Your doctor will carry out blood tests before you start treatment with Zoledronic Acid and will check your response to treatment at regular intervals.
You should not be given Zoledronic Acid:
• if you are breast-feeding.
• if you are allergic to zoledronic acid, another bisphosphonate (the group of substances to which Zoledronic Acid 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 Zoledronic Acid:
• 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 Zoledronic Acid.
Reduced levels of calcium in the blood (hypocalcaemia) sometimes leading to muscle cramps, dry skin, burning sensation, have been reported in patients treated with Zoledronic Acid.
Irregular heart beat (cardiac arrhythmia), seizures, spasm and twitching (tetany) have been reported as secondary to severe hypocalcaemia. In some instances the hypocalcaemia may be life-threatening. If any of these apply to you, tell your doctor straight away.
Patients aged 65 years and over
Zoledronic Acid 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
Zoledronic Acid is not recommended for use in adolescents and children below the age of 18 years.
Other medicines and Zoledronic Acid
Tell your doctor 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:
• 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 and are used to treat osteoporosis and other non-cancer diseases of the bone, or any other bisphosphonate, since the combined effects of these medicines taken together with Zoledronic Acid are unknown.
• Anti-angiogenic medicines (used to treat cancer), since the combination of these with Zoledronic Acid has been associated with an increased risk of osteonecrosis of the jaw (ONJ).
Pregnancy and breast-feeding
You should not be given Zoledronic Acid if you are pregnant. Tell your doctor if you are or think that you may be pregnant. You must not be given Zoledronic Acid if you are breastfeeding.
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 zoledronic acid. You should therefore be careful when driving, using machinery or performing other tasks that need full attention.
Zoledronic Acid contains sodium citrate
This medicinal product contains less than 1 mmol sodium
(23 mg) per dose (100 ml), i.e. essentially ‘sodium-free’.
3. HOW ZOLEDRONIC ACID IS USED
• Zoledronic Acid 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, pharmacist or nurse.
How much Zoledronic Acid 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 Zoledronic Acid is given
• If you are being treated for the prevention of bone complications due to bone metastases, you will be given one infusion of Zoledronic Acid 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 Zoledronic Acid.
How Zoledronic Acid is given
• Zoledronic Acid 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 Zoledronic Acid 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.
-X
X
The following information is intended for healthcare professionals only:
How to prepare and administer Zoledronic Acid 1
Denmark
Finland
Germany
Italy
Netherlands
Norway
Sweden
4. POSSIBLE SIDE EFFECTS
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 serious 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.
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.
Very rare (may affect up to 1 in 10,000 people)
• As a consequence of low calcium values: irregular heart beat (cardiac arrhythmia; secondary to hypocalcaemia), seizures, numbness and tetany (secondary to hypocalcaemia).
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)
• Hypersensitivity reactions.
• Low blood pressure.
• Chest pain.
• Skin reactions (redness and swelling) at the infusion site, rash, itching.
• High blood pressure, shortness of breath, dizziness, sleep disturbances, tingling or numbness of the hands or feet, diarrhoea.
• Low counts of white blood cells and blood platelets.
• Low level of magnesium and potassium in the blood. Your doctor will monitor this and take any necessary measures.
• Sleepiness.
• Tearing of the eye, eye sensitivity to light.
• Sudden coldness with fainting, limpness or collapse.
• Difficulty in breathing with wheezing or coughing.
• Urticaria.
Rare (may affect up to 1 in 1,000 people)
• Slow heartbeat.
• 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.
• Interstitial lung disease (inflammation of the tissue around the air sacks of the lungs).
• Flu-like symptoms including arthritis and joint swelling.
Very rare (may affect up to 1 in 10,000 people)
• Fainting due to low blood pressure.
• Severe bone, joint and/or muscle pain, occasionally incapacitating.
• Painful redness and/or swelling of the eye.
X-
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. Also, you can help make sure medicines remain as safe as possible by reporting any unwanted side effects via the internet at www.mhra.aov.uk/vellowcard. Alternatively you can call Freephone 0808 100 3352 (available between 10am-2pm Monday - Friday) or All in a paper form available from your local pharmacy. By reporting side effects, you can help provide more information on the safety of this medicine.
5. HOW TO STORE ZOLEDRONIC ACID
Your doctor, pharmacist or nurse knows how to store Zoledronic Acid properly (see section 6).
After first opening, Zoledronic Acid should be used immediately. If the solution is not used immediately, it should be stored in a refrigerator at 2°C - 8°C but no longer than 24 hours.
6. CONTENTS OF THE PACK AND OTHER INFORMATION
What Zoledronic Acid contains:
• The active substance is zoledronic acid. One vial contains 4 mg zoledronic acid, corresponding to 4.264 mg zoledronic acid monohydrate.
• The other ingredients are: mannitol (E421) sodium citrate (E331) water for injections.
What Zoledronic Acid looks like and contents of the pack:
Zoledronic Acid solution for infusion is a clear, colourless solution, free from visible particles.
Zoledronic Acid is supplied as a solution in a vial. One vial contains 4 mg of zoledronic acid.
Each pack contains the vial with solution.
Zoledronic Acid is supplied as packs containing:
1 vial of 100 ml 4 vials of 100 ml
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer:
The Marketing Authorisation Holder is:
Seacross Pharmaceuticals Limited,
17 Hanover Square, Mayfair, London, W1S1HU, UK.
The Manufacturer is:
IPG Pharma Limited, Atrium Court, The Ring, Bracknell,
RG12 1BW, UK
or,
Agila Specialties Polska Sp. Zo.o., 10, Daniszewska Str.,
03-230 W&rsaw, Poland
or,
Sanochemia Pharmazeutica AG, Landeggerstrasse 7, 2491 Neufeld an der Leitha, Austria.
This medicinal product is authorised in the Member States of the EEA under the following names:
Zoledronsyre Seacross
Zoledronic acid Seacross 4mg/100ml
Infuusioneste, liuos
Zoledronsaure Seacross 4mg/100ml
Infusionslosung
Acido Zoledronico Seacross
Zoledroninezuur Seacross 4mg/100ml,
Oplossing voor infusie
Zoledronsyre Seacross
Zoledronsyra Seacross 4mg/100ml
Infusionsvatska, losning
This leaflet was last revised in 06/2014
A184/D/UK
— —X
Table 1: Preparation of reduced doses of Zoledronic Acid 4 mg/100 ml solution for infusion
|
Baseline creatinine clearance (ml/min) |
Remove the following amount of Zoledronic Acid solution for infusion (ml) |
Replace with the following volume of sterile sodium chloride 9 mg/ml (0.9%) or 5% glucose solution for injection (ml) |
Adjusted dose (mg zoledronic acid in 100 ml) |
|
50-60 |
12.0 |
12.0 |
3.5 |
|
40-49 |
18.0 |
18.0 |
3.3 |
|
30-39 |
25.0 |
25.0 |
3.0 |
Zoledronic Acid contains 4 mg of zoledronic acid in 100 ml of infusion solution for immediate use in patients with normal renal function.
• 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.
• Chemical and physical stability has been demonstrated for 24 hours at 2°C - 8°C and at 25°C. 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.
The refrigerated solution should be equilibrated to room temperature prior to administration.
• The solution containing zoledronic acid must not be further diluted or mixed with other infusion solutions. It 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 Zoledronic Acid to assure that they are adequately hydrated.
• Zoledronic Acid 4 mg/100 ml solution for infusion can be used immediately without further preparation for patients with normal renal function. In patients with mild to moderate renal impairment, reduced doses should be prepared as instructed below To prepare reduced doses for patients with baseline CLcr s 60 ml/min, refer to Table 1 below.
Remove the volume of Zoledronic Acid solution indicated from the vial and replace with an equal volume of sterile sodium chloride 9 mg/ml (0.9%) solution for injection, or 5% glucose solution for injection.