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ZOLEDRONIC ACID 4MG/100ML SOLUTION FOR INFUSION

Active substance(s): ZOLEDRONIC ACID MONOHYDRATE

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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 (hypersensitive) 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 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.
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.
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.
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, 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).
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
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 sodium citrate
This medicinal product contains less than 1
mmol sodium (23 mg) per dose (100ml), 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.
Patients whose blood calcium levels are not too
high will also be prescribed calcium and vitamin
D supplements to be taken each day.
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.
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.
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.

- - - - - - - - - - - - - - -- - - - - - - - - - - - - --

The following information is intended for healthcare professionals only:

How to prepare and administer Zoledronic Acid
- 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.
- 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 ensure that they are adequately hydrated.
- Zoledronic Acid 4mg/100ml 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 ≤ 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.

Size: 148mm X 600mm
Date: 21 Dec 15
Update: Prac
Colours: Black & Pantone 273
Designer: SAB

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).
- Muscle cramps, dry skin or burning sensation
(low blood calcium).
Uncommon (may affect up to 1 in 100
people):
- Pain in the mouth, teeth and/or jaw, swelling
or non-healing sores inside the mouth or jaw,
numbness or a feeling of heaviness in the
jaw, discharge, 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.
- Serious life-threatening allergic reaction with
sudden signs of allergy such as rash, itching
or hives on the skin, swelling of the face, lips,
tongue, and throat, shortness of breath,
wheezing or trouble breathing.
- Acute kidney failure – where little or no urine
is passed. Other symptoms may include
presence of blood or protein in the urine
(detected during urine tests).
Rare (may affect up to 1 in 1,000 people):
- Serious allergic reaction causing swelling of
the face, lips, tongue or throat which may
cause difficulty in swallowing or breathing.
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 blood phosphate levels found
during a blood test.
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.
- Red and watery eyes (conjunctivitis).
- Reduction in red blood cells which can make
the skin pale and cause weakness or
breathlessness.
- Increases in blood urea and creatinine levels
observed during blood tests.

- High levels of blood potassium which can
cause abnormal heart rhythm.
- 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.
- 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.
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 at www.mhra.gov.uk/yellowcard. 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).
• Keep this medicine out of the sight and reach
of children.
• Do not use this medicine after the expiry date
which is stated on the carton and vial after
EXP. The expiry date refers to the last day of
that month.
• The unopened vial does not require any
special storage conditions.
• After first opening:
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
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 then be
equilibrated to room temperature prior to
administration.
• Do not throw away any medicines via
wastewater. 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
INFORMATION

Uncommon (may affect up to 1 in 100
people):
- Hypersensitivity reactions e.g skin rash or
fever.
- 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
disturbance, tingling or numbness of the
hands and feet, tremor, blurred vision,
diarrhoea, constipation, stomach pain,
indigestion, mouth ulcers, dry mouth,
increased sweating, muscle cramps, feeling of
weakness, swelling of the ankles, feet or
fingers.
- Reduction in blood platelets leading to
increased risk of bleeding or bruising.
- Reduction in the white cells of the blood
increasing the risk of infection..
- 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):
- A rare type of anaemia in which red blood
cells, white blood cells, and platelets are all
reduced in number.
- High levels of blood sodium which can cause
confusion, muscle twitching or abnormal heart
rhythm.

What Zoledronic Acid contains
- The active substance is zoledronic acid. One
vial contains 4 mg zoledronic acid,
corresponding to 4.26 mg zoledronic acid
monohydrate.
- The other ingredients are:
mannitol (E421), sodium citrate (E331)
water for injections.
What Zoledronic Acid looks like and the
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.
Zoledronic Acid 4mg/100ml solution for infusion
is supplied as packs containing:
1 vial, 4 vials, 5 vials, 10 vials
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Beacon Pharmaceuticals Ltd., High Street,
Tunbridge Wells, Kent, TN1 1YG
Manufacturer
Agila Specialties Polska Sp. Zo.o. 10,
Daniszewska Str., 03-230 Warsaw, Poland
or
Sanochemia Pharmazeutika AG, Landeggerstrasse 33, 2491 Neufeld an der Leitha, Austria
This leaflet was last revised in 12/2015

AGXP265BNC
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- - - - - - - - - - - - - - -- - - - - - - - - - - - - -Table 1: Preparation of reduced doses of Zoledronic Acid 4 mg/100 ml solution for infusion
Baseline
Creatinine
Clearance
(ml/min)
50-60
40-49
30-39

Remove the following
Amount of Zoledronic
Acid solution for infusion
(ml)
12.0
18.0
25.0

Replace with the following volume
Of sterile sodium chloride 9 mg/ml
(0.9%) or 5% glucose solution for
injection (ml)
12.0
18.0
25.0

Adjusted dose
(mg zoledronic
acid in 100 ml)*
3.5
3.3
3.0

*Doses have been calculated assuming target AUC of 0.66 (mg•hr/l) (CLcr = 75 ml/min). The reduced
doses for patients with renal impairment are expected to achieve the same AUC as that seen in
patients with creatinine clearance of 75 ml/min.
- 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 infusion line.
How to store Zoledronic Acid
- Keep Zoledronic Acid out of the reach and sight of children.
- Do not use Zoledronic Acid after the expiry date stated on the pack.
- This medicinal product does not require any special storage conditions.
- The diluted Zoledronic Acid infusion solution should be used immediately in order to avoid microbial
contamination.

Size: 148mm X 600mm
Date: 21 Dec 15
Update: Prac
Colours: Black & Pantone 273
Designer: SAB

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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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