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ZOLEDRONIC ACID 4 MG/ 5 ML CONCENTRATE FOR SOLUTION FOR INFUSION

Active substance(s): ZOLEDRONIC ACID MONOHYDRATE / ZOLEDRONIC ACID MONOHYDRATE / ZOLEDRONIC ACID MONOHYDRATE

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Package leaflet: Information for the user

Zoledronic acid 4 mg/5 ml concentrate
for 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.

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1 What Zoledronic acid is and what it is used for
The active substance 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).

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.

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.

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.

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Pregnancy and breast-feeding
You should not be given Zoledronic acid if you are pregnant or
breast-feeding. If you are pregnant or breast-feeding, think
you may be pregnant or are planning to have a baby, ask your
doctor for advice before being given this medicine.

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.

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.

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).
-

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

Warnings and precautions

3 How Zoledronic acid is used

Talk to your doctor 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.
Your doctor may recommend a dental examination before
you start treatment with Zoledronic acid.
- if you are having dental treatment or are due to undergo
dental surgery, tell your dentist that you are being treated
with Zoledronic acid and inform your doctor about your
dental treatment.
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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.
-

While being treated with Zoledronic acid, you should
maintain good oral hygiene (including regular teeth brushing)
and receive routine dental check-ups.
Contact your doctor and dentist immediately if you
experience any problems with your mouth or teeth such as
loose teeth, pain or swelling, or non-healing of sores or
discharge, as these could be signs of a condition called
osteonecrosis of the jaw.

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.

Patients who are undergoing chemotherapy and/or
radiotherapy, who are taking steroids, who are undergoing
dental surgery, who do not receive routine dental care, who
have gum disease, who are smokers, or who were previously
treated with a bisphosphonate (used to treat or prevent bone
disorders) may have a higher risk of developing osteonecrosis
of the jaw.

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.

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.
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. You can also report side effects directly
via the Yellow Card Scheme www.mhra.gov.uk/yellowcard.
By reporting side effects, you can help provide more
information on the safety of this medicine.

4 Possible side effects

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

5 How to store Zoledronic acid
Your doctor, pharmacist or nurse knows how to store
Zoledronic acid properly (see section 6).
Keep this medicine out of the sight and reach of children.

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.

Do not use this medicine after expiry date which is stated on
the carton/bottle after "EXP". The expiry date refers to the last
day of that month.

Uncommon (may affect up to 1 in 100 people):
Pain in the mouth, teeth and/or jaw, swelling or nonhealing sores inside the mouth or jaw, discharge,
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 while being treated with
Zoledronic acid or after stopping treatment.
- 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.
-

After dilution: Chemical and physical in-use stability has been
demonstrated for 24 hours at 2°C - 8°C and room temperature
(20 -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 should not be longer than
24 hours at 2°C- 8°C. The refrigerated solution should then be
equilibrated to room temperature prior to administration.
6 Contents of the pack and other information
What Zoledronic acid contains

Rare (may affect up to 1 in 1,000 people):
- As a consequence of low calcium values: irregular heart
beat (cardiac arrhythmia; secondary to hypocalcaemia).
Very rare (may affect up to 1 in 10,000 people):
As a consequence of low calcium values: seizures,
numbness and tetany (secondary to hypocalcaemia).
- 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.
Tell your doctor about any of the following side effects as
soon as possible:
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The active substance is zoledronic acid. One vial contains
4 mg zoledronic acid, corresponding to 4.264 mg
zoledronic acid monohydrate. One ml concentrate
contains zoledronic acid (as monohydrate to 0.8 mg
zoledronic acid (anhydrous)

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The other ingredients are: mannitol (E421), sodium citrate
(E331), water for injections.

What Zoledronic acid looks like and contents of the pack
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 or 10 vials. Not all pack
sizes may be marketed.

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).

Marketing Authorisation Holder and Manufacturer

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Marketing Authorisation Holder:
Tillomed Laboratories Ltd
3 Howard Road
Eaton Socon, St Neots
Cambridgeshire
PE19 8ET UK
Manufacturer:
Emcure Pharma UK Ltd
Basepoint Business Centre
110 Butterfield, Great Marlings
Luton
LU2 8DL, UK

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,
anxiety, sleep disturbances, taste disturbances, trembling,
tingling or numbness of the hands or feet, diarrhoea,
constipation, abdominal pain, dry mouth.
- 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.
- Weight increase.
- Increased sweating.
- Sleepiness.
- Blurred vision, tearing of the eye, eye sensitivity to light.
- Sudden coldness with fainting, limpness or collapse.
- Difficulty in breathing with wheezing or coughing.
- Urticaria.
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This medicinal product is authorised in the Member States
of the EEA under the following names:
United Kingdom
Germany

Spain

Italy
France

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.
- Interstitial lung disease (inflammation of the tissue around

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,

INFORMATION FOR THE HEALTHCARE PROFESSIONAL

Zoledronic acid 4 mg/5 ml concentrate
for solution for infusion
Zoledronsäure Tillomed 4 mg/5 ml
Konzentrat zur Herstellung einer
Infusionslösung
Ácido zoledrónico Tillomed 4 mg/5 ml
concentrado para solución para
perfusión EFG
Acido Zoledronico Tillomed
Acide zoledronique Tillomed 4
mg/5 ml, solution à diluer pour
perfusion

This leaflet was last revised in 10/2016.

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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

the air sacks of the lungs)
Flu-like symptoms including arthritis and joint swelling.
Painful redness and/or swelling of the eye.

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2 What you need to know before you are given

Zoledronic acid

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

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), calcitonin (a type of medicine used to treat
post-menopausal osteoporosis and hypercalcaemia), loop
diuretics (a type of medicine to treat high blood pressure or
oedema) or other calcium-lowering medicines, 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.
- Any other medicine that also contains zoledronic acid and
is 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).

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to you, tell your doctor straight away. If you have pre-existing
hypocalcaemia, it must be corrected before initiating the first
dose of Zoledronic acid. You will be given adequate calcium
and vitamin D supplements.

Children and adolescents
Zoledronic acid is not recommended for use in adolescents
and children below the age of 18 years.

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

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After dilution: Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C- 8°C and room temperature
(20 -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 should not be longer than
24 hours at 2°C- 8°C. The refrigerated solution should then be equilibrated to room temperature prior to administration.

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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.

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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 infusion line.

The following information is intended for medical or healthcare professionals only (see section 3):

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, 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

How to store Zoledronic acid
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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.

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Keep Zoledronic acid out of the reach and sight of children.
Do not use Zoledronic acid after the expiry date stated on the pack.
The unopened vial does not require any specific storage conditions.
The diluted Zoledronic acid infusion solution should be used immediately in order to avoid
microbial contamination.

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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 0.9% w/v sodium chloride or 5% w/v glucose solution.

Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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