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ZOLEDRONIC ACID 4 MG/100ML SOLUTION FOR INFUSION

Active substance(s): ZOLEDRONIC ACID MONOHYDRATE

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Zoledronic Acid Amneal 4 mg/100 ml solution for infusion - UK - PIL

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).

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.
INFORMATION FOR THE HEALTHCARE
PROFESSIONAL
The following information is intended for healthcare
professionals only:
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.
− 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 then 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.

Min. Font Size: 9 pt
Date: 05/07/16

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 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
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 taking this 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.

3. How Zoledronic Acid is used

While being treated with Zoledronic acid, you should
maintain good oral hygiene (including regular teeth
brushing) and receive routine dental check-ups.

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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 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.

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
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.

PIL Size : 155 x 460 mm

Review - 3

− 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.

− 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 ≤ 60 ml/min, refer to Table 1 below.
Remove the volume of Zoledronic Acid solution
indicated from the bag and replace with an equal
volume of sterile sodium chloride 9 mg/ml (0,9%)
solution for injection, or 5% glucose solution for
injection.

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Zoledronic Acid Amneal 4 mg/100 ml solution for infusion - UK - PIL

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
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.
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).
− 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:

Review - 3

− 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.
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.
− Painful redness and/or swelling of the eye
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 MHRA 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).

6. Contents of the pack and other
information
What Zoledronic Acid contains
− The active substance of Zoledronic Acid is
zoledronic acid. One bag contains 4 mg
zoledronic acid, corresponding to 4.264 mg
zoledronic acid monohydrate.
− The other ingredients are: mannitol (E-421),
sodium citrate (E-331) and water for injections.
What Zoledronic Acid looks like and contents of the
pack
Zoledronic Acid is supplied as a clear and colourless
solution. It comes in 100 ml bags as a ready-to-use
solution for infusion.
Zoledronic Acid is supplied as a unit pack containing
one bag.
Marketing Authorisation Holder and Manufacturer

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
Amneal Pharma Europe Limited
70 Sir John Rogerson’s Quay
Dublin 2, Ireland
Manufacturer
Laboratorios NORMON, S.A.
Ronda de Valdecarrizo, 6
28760 Tres Cantos – Madrid
SPAIN
This leaflet was last revised in July 2016

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.
Table 1: Preparation of reduced doses of Zoledronic
Acid 4 mg/100 ml solution for infusion
Baseline Remove the Replace
Adjusted
creatinine following
with the
dose (mg
clearance amount of following zoledronic
(ml/min) Zoledronic volume of
acid in
Acid Amneal
sterile
100 ml)
4 mg
sodium
solution for chloride
infusion
9 mg/ml
(ml)
(0,9%) or
5% glucose
solution for
injection
(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
*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 this medicine out of the sight and reach of
children.
− Do not use this medicine after the expiry date
which is stated on the pack after EXP.
− The unopened bag does not require any special
temperature storage conditions. Store in the
original package.
− After opening the bag, the product should be used
immediately in order to avoid microbial
contamination. 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. Allow the
refrigerated solution to reach room temperature
before administration.

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

PIL Size : 155 x 460 mm
Min. Font Size: 9 pt
Date: 05/07/16

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Back

Patient Reminder Card
Zoledronic Acid
This reminder card contains important safety information that you need to be aware of before and during
treatment with Zoledronic Acid injections for cancer-related conditions
Your doctor has recommended that you receive Zoledronic Acid injections to help prevent bone complications (e.g.
fractures) caused by bone metastases, or bone cancers or to help reduce the amount of calcium in the blood in adult
patients where it is too high due to the presence of a tumour.
A side effect called osteonecrosis of the jaw (ONJ) (bone damage in the jaw) has been reported in very rare occasions in
patients receiving Zoledronic Acid injections for cancer-related conditions. ONJ can also occur after stopping treatment.
In order to reduce the risk of developing osteonecrosis of the jaw, there are some precautions you should take:
Before starting treatment:
• Ask your doctor to tell you about ONJ before you start treatment
• Check with your doctor whether a dental examination is recommended before you start treatment with Zoledronic Acid.
• Tell your doctor/nurse (health care professional) if you have any problems with your mouth or teeth.
Patients undergoing dental surgery (e.g. tooth extractions), who do not receive routine dental care or have gum disease,
are smokers, who get different types of cancer treatments or who were previously treated with a bisphosphonate (used to
treat or prevent bone disorders) may have a higher risk of developing ONJ.
While being treated:
• You should maintain good oral hygiene, make sure your dentures fit properly and receive routine dental check-ups.
• If you are under dental treatment or will undergo dental surgery (e.g. tooth extractions), inform your doctor and tell your
dentist that you are being treated with Zoledronic Acid.
• Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth such as loose
teeth, pain or swelling, non-healing of sores or discharge, as these could be signs of osteonecrosis of the jaw
Read the package leaflet for further information.

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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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