Skip to Content

UK Edition. Click here for US version.

ZOLEDRONIC ACID MYLAN 4 MG/100 ML SOLUTION FOR INFUSION

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

View full screen / Print PDF » Download PDF ⇩

PDF Transcript

Package leaflet: Information for the user
Zoledronic acid Mylan 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 Mylan 4 mg/100 ml solution for infusion is and what it is used
for
2.
What you need to know before you are given Zoledronic acid Mylan 4 mg/100 ml
solution for infusion
3.
How Zoledronic acid Mylan 4 mg/100 ml solution for infusion is used
4.
Possible side effects
5.
How to store Zoledronic acid Mylan 4 mg/100 ml solution for infusion
6.
Contents of the pack and other information

1.
What Zoledronic acid Mylan 4 mg/100 ml solution for infusion is and what it is
used for
The active substance in Zoledronic acid Mylan 4 mg/100 ml solution for infusion 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 tumourinduced hypercalcaemia (TIH).
The product will be referred to as Zoledronic acid for the remaining portion of this leaflet.

2.
What you need to know before you are given Zoledronic acid Mylan 4 mg/100 ml
solution for infusion
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 must 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, pharmacist or nurse 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 (ONJ).
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.
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 (see section 4
‘Possible side effects’).
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 (fits), numbness and twitching
(tetany) have been reported a result of 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 starting the first
dose of zoledronic acid. You will be given adequate calcium and vitamin D supplements.
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 taking:

– Aminoglycosides (medicines used to treat severe infections), calcitonin (a medicine
used to treat post-menopausal osteoporosis and hypercalcaemia), loop diuretics (a
medicine used to treat high blood pressure or welling) 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.
– Other medicines that also contain Zoledronic acid and which 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.
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 cases of dizziness 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
This medicinal product contains less than 1 mmol sodium (23 mg) per dose (100ml), i.e.
essentially ‘sodium-free’.

3.

How Zoledronic acid Mylan 4 mg/100 ml solution for infusion 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 recommended dose given is 4 mg.
If you have a kidney problem, your doctor may 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.
Patients who have low blood calcium levels 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.
Tell your doctor immediately or if serious, go to your nearest hospital emergency
department if you get any of the following side effects:
Common (may affect up to 1 in 10 people):
- Low levels of calcium in the blood which can be seen in a blood test. This may lead to
muscle cramps or a tingling sensation especially around the mouth.
Uncommon (may affect up to 1 in 100 people):
- Producing little or no urine, pain when passing urine, urine is cloudy or dark coloured
possibly with lower back pain. These may be signs of severe kidney problems.
- Pain in the mouth, teeth and/or jaw, swelling or non-healing 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).
- A very fast and irregular heart rhythm (atrial fibrillation). This 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 reactions such as a red itchy skin rash (known as nettle rash or hives),
a feeling of light headedness with possible collapse and unconsciousness.
- Low blood pressure leading to fainting or circulatory shock. You may be confused,
have changes in your heart beat, clammy skin, thirst or a low body temperature.
Rare (may affect up to 1 in 1,000 people):

-

-

Other problems with your heart beat (cardiac arrhythmia) which can be seen in an
ECG. This may be as a result of low levels of calcium.
Swelling of the face, lips, mouth, tongue or throat causing difficulty breathing or
swallowing.
A kidney function disorder called Fanconi syndrome (will normally be determined by
your doctor with certain urine tests).

Very rare (may affect up to 1 in 10,000 people):
- Seizures (fits), numbness and twitching. These may be as a result of low levels of
calcium.
- 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.
Other possible side effects:
Very common (may affect more than 1 in 10 people):
- Low levels of phosphate in the blood which can be seen in a blood test.
Common (may affect up to 1 in 10 people):
- Headache
- Fever
- A flu-like syndrome consisting of headache, fever, tiredness, weakness, drowsiness,
generally feeling unwell, flushing, chills, pain in the hands or feet, feeling sick
(nausea), being sick (vomiting) and/or diarrhoea. In most cases no specific treatment
is required and the symptoms disappear after a short time (couple of hours or days).
- Feeling sick (nausea), being sick (vomiting), decrease in appetite.
- Bone pain, muscle or joint ache, general pain.
- Swollen, runny eyes or a feeling of grit in the eyes (conjunctivitis).
- Tiredness, shortness of breath, looking pale. These may be signs of low level of red
blood cells (anaemia).
- Other kidney problems that affect urination
- Creatinine and urea levels in the blood increased which can be seen in a blood test.
Uncommon (may affect up to 1 in 100 people):
- Other allergic reactions
- An increase in the number of infections causing fever, severe chills, mouth ulcers or
sore throat. These may be signs of low levels of white bloods cells.
- Redness or visible blood vessels on the whites of the eye, severe eye pain, pain in the
eyebrow, temple or jaw, watery eyes, sensitivity to light.
- High blood pressure or low blood pressure.
- Chest pain.
- Skin reactions (pain, irritation, swelling or a hard lump) at the infusion site, rash,
itching.
- Dizziness, anxiety, sleep disturbances, taste disturbances, trembling, tingling or
numbness of the hands or feet, decrease or increase in sensitivity touch.
- Diarrhoea, constipation, stomach pain, indigestion, mouth ulcers or cold sores, dry
mouth.
- Unexplained bruising or bleeding for longer than normal. These may be signs of low
levels of blood platelets.
- Low levels of magnesium or potassium in the blood which can be seen in a blood test.

-

Your doctor will monitor this and take any necessary measures.
Weight increase.
Increased sweating.
Sleepiness.
Blurred vision.
Thightness of the chest with wheezing or coughing.
Cough.
Lack of energy.
Sweling of the hands, ankles or feet.
Muscle spasms.
Blood in your unrine.
Protein in the urine which can be seen in a urine test.

Rare (may affect up to 1 in 1,000 people):
- Tiredness, weakness, being short of breath, looking pale with unexplained bruising or
bleeding for longer than normal and signs of low levels of white blood cells (see
description in ‘Uncommon’ above). These may be signs of low levels of all types of
blood cells.
- Red eye with blurred or cloudy vision, shadows, dots or veils that move across the
field of vision (floaters) in one or both eyes.
- Shortness of breath that gets worse over time with a dry and non-productive cough
possibly with loss of weight. These may be signs of problems with your lungs.
- 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.
- Slow heartbeat.
- Confusion.
High levels of potassium or sodium in the blood which can be seen in a blood test.
- Disease of the joints (arthritis) and joint swelling which may only last for a few days.
Very rare (may affect up to 1 in 10,000 people):
- Mild ache or soreness of the eyes.
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
national reporting system:
UK
The Yellow Card Scheme, at www.mhra.gov.uk/yellowcard
IRELAND
HPRA
Pharmacovigilance
Earlsfort Terrace
IRL – Dublin 2
Tel: +353 1 6764971

Fax: +353 1 6762517
Website: www.hpra.ie
e-mail: medsafety@hpra.ie
By reporting side effects you can help provide more information on the safety of this
medicine.
5.

How to store Zoledronic acid Mylan 4 mg/100 ml solution for infusion

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 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) (see section 2
‘Zoledronic acid contains sodium’), water for injections.
What Zoledronic acid looks like and the contents of the pack
Zoledronic acid 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 is supplied as packs containing:
1, 4 or 5 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Generics [UK] Ltd., Potters Bar, Hertfordshire, EN6 1TL, United Kingdom
Manufacturer
Agila Specialties Polska Sp. Zo.o., 10, Daniszewska Str., 03-230 Warsaw, Poland
Sanochemia Pharmazeutica AG, Landeggerstrasse 7, A - 2491 Neufeld an der Leitha, Austria

This leaflet was last revised in
12/2016
This medicinal product is authorised in the Member States of the EEA under the
following names:
NETHERLANDS

Zoledroninezuur Mylan 4 mg/100
ml, oplossing voor infusie

BELGIUM
GERMANY
SPAIN
FINLAND
ITALY

Zoledronic acid Mylan 4 mg/100 ml
oplossing voor infusie
Zoledronsäure Mylan 4 mg/100ml
Infusionslösung
Ácido zoledrónico MYLAN 4
mg/100 ml concentrado para
solución para perfusión EFG
Zoledronic acid Mylan 4 mg/100 ml
infuusioneste, liuos
Acido zoledronico Mylan

CZECH
REPUBLIC

Zoledronic acid Mylan 4 mg/100 ml
infusionsvätska, lösning
Zoledronic acid Mylan 4 mg/100 ml,
infúzny roztok
Zoledronic acid Mylan 4 mg/100 ml,
solution for infusion
Zoledronsäure Arcana 4 mg/100 ml
Infusionslösung
Zoledronic acid Mylan 4 mg/100 ml,
infuzní roztok

DENMARK

Zolemyl

FRANCE

Acide Zolédronique Mylan Pharma 4
mg/100 ml solution pour perfusion

GREECE

Zoledronic acid / Mylan Generics

SWEDEN
SLOVAKIA
UNITED
KINGDOM
AUSTRIA

IRELAND
NORWAY

Zoledronic acid Mylan 4 mg/100 ml
solution for infusion
Zoledronic acid Mylan 4 mg/100 ml
infusjonsvæske, oppløsning

POLAND

Zoledronic Acid Mylan

PORTUGAL

Ácido Zoledrónico Mylan

SLOVENIA

Zoledronska kislina Mylan 4 mg/100
ml raztopina za infundiranje

<-------------------------------------------------------------------------------------------------------->
The following information is intended for healthcare professionals only:
How to prepare and administer Zoledronic acid
-

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.

-

If refrigerated, allow the refrigerated solution to reach room temperature before

administration.
-

It is given as a single 15-minute intravenous infusion. 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 hydration status of patients must
be assessed prior to and following administration of Zoledronic acid to ensure that
they are adequately hydrated.

-

Zoledronic acid 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.
Table 1: Preparation of reduced doses of Zoledronic acid
Baseline creatinine
clearance (ml/min)

50-60

Remove the
following amount of
Zoledronic acid (ml)

40-49

12.0
18.0

30-39

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.

How to store Zoledronic acid
- Keep this medicine out of the sight and reach of children.
- Do not use Zoledronic acid after the expiry date stated on the pack. The expiry date
refers to the last day of that month.
- This medicinal product does not require any special storage conditions.
- After first opening or after preparation of reduced zoledronic acid doses (as described
above): 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.
Do not throw away any medicines via wastewater. These measures will help protect
the environment.

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.

Hide