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ZOLEDRONIC ACID 4 MG/100 ML 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.

1.

What Zoledronic acid is and what it is
used for

The active substance in Zoledronic acid solution 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 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.

Pregnancy and 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 this
medicine.
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.
Ask your doctor for advice before taking any medicine
while you are pregnant or breast-feeding.
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 solution contains sodium
This medicinal product contains less than 1 mmol
(23 mg) sodium per dose, i.e. essentially ‘sodiumfree’.

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.

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 solution for infusion should be used
immediately after first opening. 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, unless dilution has taken place in controlled
and validated aseptic conditions. The refrigerated solution should then 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.







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 to prepare and administer Zoledronic acid

Zoledronic acid 4 mg/100 ml solution for infusion contains 4 mg zoledronic acid in
100 ml of infusion solution for immediate use in patients with normal renal
function.

INFORMATION FOR THE HEALTHCARE PROFESSIONAL

The following information is intended for healthcare professionals only:

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).

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 bottle and
replace with an equal volume of sterile sodium chloride 9 mg/ml (0.9%) solution for
injection, or 5% glucose solution for injection.

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

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.





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 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 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
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,
website 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).
After first opening, Zoledronic acid solution for
infusion should preferably be used immediately. If the
solution is not used immediately, it should be stored in
a refrigerator at 2°C-8°C.
For further information please refer also to the
information for the healthcare professional at the end
of this leaflet.

6.

Contents of the pack and other
information

What Zoledronic acid solution contains

The active substance is zoledronic acid. One
bottle contains 4 mg zoledronic acid,
corresponding to 4.264 mg zoledronic acid
monohydrate.

The other ingredients are mannitol, sodium
citrate and water for injections.
What Zoledronic acid solution looks like and
contents of the pack
Zoledronic acid solution is a clear and colourless
solution for infusion in a clear tubular glass vial. One
vial contains 100 ml solution.
Zoledronic acid is supplied in packs containing 1, 4 or
5 vials. Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Dr. Reddy’s Laboratories (UK) Ltd., 6 Riverview
Road, Beverley, East Yorkshire, HU17 0LD, United
Kingdom
This leaflet was last revised in 03/2014

50-60

Baseline
creatinine
clearance
(ml/min)

18.0

12.0

Remove the following
amount of Zoledronic
acid solution for
infusion (ml)

25.0

18.0

12.0

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

3.0

3.3

3.5

Adjusted
dose (mg
zoledronic
acid in
100 ml)

Table 1: Preparation of reduced doses of Zoledronic acid 4 mg/100 ml solution for infusion

40-49

25.0

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

30-39



*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.


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 sight and reach of children.

Do not use Zoledronic acid after the expiry date stated on the pack.

The unopened bottle does not require any special storage conditions.

After first opening: 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.

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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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