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ZOLEDRONIC ACID SYNTHON 4 MG/5 ML CONCENTRATE FOR SOLUTION FOR INFUSION
Active substance(s): ZOLEDRONIC ACID
Zoledronic acid 4 mg / 5 ml
concentrate for solution for infusion
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.
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
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
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
Warnings and precautions
• Talk to your doctor, pharmacist or nurse before you are given
– 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.
your doctor if you are pregnant, think that you may be pregnant or
planning to have a baby.
You must not be given Zoledronic acid 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 Zoledronic acid. You should therefore be careful
when driving, using machinery or performing other tasks that
need full attention.
Zoledronic acid contains less than 1 mmol sodium (23 mg)
per vial (5 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, nurse or pharmacist.
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
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
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
Reduced levels of calcium in the blood (hypocalcaemia), sometimes may develop serum electrolyte abnormalities (e.g. abnormal levels
of calcium, phosphorus and magnesium) and/or changes in
leading to muscle cramps, dry skin, burning sensation, have been
kidney function, including severe kidney impairment. If your level
reported in patients treated with Zoledronic acid. Irregular heart
of calcium falls too low, you may have to be given supplemental
beat (cardiac arrhythmia), seizures, spasm and twitching (tetany)
calcium by infusion.
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.
Other medicines and Zoledronic acid
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
• 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 Zoledronic acid 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
Zoledronic acid can be given to people aged 65 years and over.
There is no evidence to suggest that any extra precautions are
Children and adolescents
Zoledronic acid is not recommended for use in adolescents and
children below the age of 18 years.
Pregnancy and breast-feeding
You should not be given Zoledronic acid if you are pregnant. Tell
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 side effects
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).
Marketing Authorisation Holder:
Synthon BV, Microweg 22, 6545 CM Nijmegen, The Netherlands
Tell your doctor about any of the following side effects as
soon as possible:
Synthon Hispania SL , Castelló 1, Polígono Las Salinas
08830 Sant Boi de Llobregat, Spain
Very common (may affect more than 1 in 10 people)
Low level of phosphate in the blood
Distributed by: Consilient Health (UK) Limited.
No.1 Church Road, Richmond upon Thames, Surrey. TW9 2QE
Synthon BV, Microweg 22, 6545 CM Nijmegen, The Netherlands
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. This leaflet was last revised in February 2016
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
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 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 • Interstitial lung disease (inflammation
of the tissue around the air sacks of the lungs).
Very rare (may affect up to 1 in 10,000 people)
Painful redness and/or swelling of the eye.
INFORMATION FOR THE HEALTHCARE
The following information is intended for
healthcare professionals only:
How to prepare and administer Zoledronic acid
• To prepare an infusion solution containing 4 mg zoledronic
acid, further dilute the zoledronic acid concentrate (5.0 ml)
with 100 ml of calcium-free or other divalent cation-free
infusion solution. If a lower dose of zoledronic acid 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 Zoledronic acid concentrate with calcium
containing or other divalent cation-containing solutions
such as lactated Ringer’s solution.
Instructions for preparing reduced doses of Zoledronic acid:
Withdraw the appropriate volume of the liquid concentrate,
• 4.4 ml for 3.5 mg dose
• 4.1 ml for 3.3 mg dose
• 3.8 ml for 3.0 mg dose
If you get any side effects, talk to your doctor, pharmacist
or nurse. This includes any side effects not listed in this
• For single use only. Any unused solution should be
5. HOW TO STORE Zoledronic acid
• From a microbiological point of view, the diluted solution
Keep this medicine out of the sight and reach of children.
Your doctor, nurse or pharmacist knows how to store Zoledronic
acid 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
After first opening, Zoledronic acid 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
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.
6. Contents of the pack and other
What Zoledronic acid 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
What Zoledronic acid looks like and contents of the pack
Zoledronic acid concentrate for solution for infusion is a clear,
colourless solution, free from visible particles.
discarded. Only clear solution free from particles and
discolouration should be used. Aseptic techniques must be
followed during the preparation of the infusion.
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
• 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 Zoledronic acid 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,
zoledronic acid must not be mixed with other medications/
substances and should always be given through a separate
How to store Zoledronic acid
• Keep zoledronic acid out of the sight and reach of children.
• Do not use zoledronic acid after the expiry date stated on
• This medicinal product does not require any special storage
The diluted zoledronic acid infusion solution should be used
immediately in order to avoid microbial contamination.
Zoledronic acid is supplied as a liquid concentrate in a vial. One
vial contains 4 mg of zoledronic acid.
Each pack contains the vial with concentrate. Zoledronic acid is
supplied as packs containing 1, 4, 5 or 10 vials.
Not all pack sizes may be marketed.