Skip to Content

BUSULFAN 6 MG/ML CONCENTRATE FOR SOLUTION FOR INFUSION

Active substance(s): BUSULFAN

View full screen / Print PDF » Download PDF ⇩
Transcript
Package leaflet: Information for the user

Busulfan 6 mg/ml
concentrate for solution
for infusion
busulfan

Read all of this leaflet carefully before you
start using 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.
- If you get any side effects, talk to your doctor.
This includes any possible side effects not listed
in this leaflet.
What is in this leaflet
1. What Busulfan Injection is and what it is used
for
2. What you need to know before you use
Busulfan Injection
3. How to use Busulfan Injection
4. Possible side effects
5. How to store Busulfan Injection
6. Contents of the pack and other information

1. What Busulfan Injection is
and what it is used for
Busulfan Injection contains the active substance
busulfan, which belongs to a group of medicines
called alkylating agents. Busulfan Injection
destroys the original bone marrow before the
transplant.
Busulfan Injection is used in adults, new-born
infants, children and adolescents as a treatment
prior to transplantation.
In adults Busulfan Injection is used in
combination with cyclophosphamide or
fludarabine.
In new-born infants, children and adolescents,
Busulfan Injection is used in combination with
cyclophosphamide or melphalan.
You will receive this preparative medicine before
receiving a transplant of either bone marrow or
haematopoietic progenitor cell.

2. What you need to know before
you use Busulfan Injection
Do not use Busulfan Injection
if you are allergic to busulfan or any of the other
ingredients of Busulfan Injection listed in section 6,
- if you are pregnant, or think you may be
pregnant.
Warnings and precautions
Busulfan Injection is a potent cytotoxic medicine
that results in profound decrease of blood cells.
At the recommended dose, this is the desired
effect. Therefore careful monitoring will be
performed.
It is possible that use of Busulfan Injection may
increase the risk of suffering another malignancy
in the future.
You should tell your doctor:
- if you have a liver, kidney, heart or lung
problem,
- if you have a history of seizures,
- if you are currently taking other medicines.
Other medicines and Busulfan Injection
Tell your doctor if you are taking or have recently
taken or might take any other medicines,
including medicines obtained without a
prescription. Busulfan Injection may interact with
other medicines.
Particular caution should be taken if you use
itraconazole (used for certain types of infections)
or ketobemidone (used to treat pain), because
this may increase the side-effects.
The use of paracetamol during the 72 hours prior
to or with Busulfan Injection administration should
be used with caution.
Pregnancy, breast-feeding and fertility
If you are pregnant or breast-feeding, think you
may be pregnant or are planning to have a baby,
ask your doctor before you receive treatment with
Busulfan Injection. Women must not be pregnant

The following information is intended for medical
or healthcare professionals only
PREPARATION GUIDE
Busulfan Injection 6 mg/ml concentrate for
solution for infusion
Busulfan
Read this guide prior to the preparation and
administration of Busulfan Injection
1. PRESENTATION
Busulfan Injection is supplied as a clear
colourless solution in 10 ml clear glass vials
(type I). Busulfan Injection must be diluted prior
to administration.
2. RECOMMENDATION FOR SAFE HANDLING
Procedures for proper handling and disposal of
anticancer medicinal products should be
considered.
All transfer procedures require strict adherence to
aseptic techniques, preferably employing a
vertical laminar flow safety hood.
As with other cytotoxic compounds, caution
should be exercised in handling and preparing
the busulfan solution:
- The use of gloves and protective clothing is
recommended.
- If the concentrate or diluted busulfan solution
contacts the skin or mucosa, wash them
thoroughly with water immediately.

during treatment with Busulfan Injection and up to
6 months after treatment.
Women must stop breast-feeding before starting
their treatment with Busulfan Injection.
Adequate contraceptive precautions should be
used when either partner is receiving Busulfan
Injection.
It may no longer be possible for you to achieve a
pregnancy (infertility) after treatment with
busulfan. If you are concerned about having
children, you should discuss this with your doctor
before treatment. Busulfan Injection can also
produce symptoms of menopause and in
pre-adolescent girls it can prevent the onset of
puberty.
Men treated with Busulfan Injection are advised
not to father child during and up to 6 months after
treatment.

3. How to use Busulfan Injection
Dose and administration:
The dose of Busulfan Injection will be calculated
according to your body weight.
In adults:
Busulfan Injection in combination with
cyclophosphamide:
- The recommended dose of Busulfan Injectionis
0.8 mg/kg
- Each infusion will last 2 hours
- Busulfan Injection will be administered every 6
hours during 4 consecutive days prior to
transplant.
Busulfan Injection in combination with fludarabine
- The recommended dose of Busulfan Injection is
3.2 mg/kg
- Each infusion will last 3 hours
- Busulfan Injection will be administered once
daily during 2 or 3 consecutive days prior to
transplant.
In new-born infants, children and adolescents (0
to 17 years):
The recommended dose of Busulfan Injection in
combination with cyclophosphamide or
melphalan is based on your body weight varying
between 0.8 and 1.2 mg/kg.
- Each infusion will last 2 hours
- Busulfan Injection will be administered every 6
hours during 4 consecutive days prior to
transplant.
Medicines before you receive Busulfan
Injection:
Before receiving Busulfan Injection, you will be
medicated with
- anticonvulsive medicines to prevent seizures
(phenytoin or benzodiazepines) and
- antiemetic medicines to prevent vomiting.

4. Possible side effects
Like all medicines, this medicine can cause side
effects, although not everybody gets them.
Serious side effects:
The most serious side effects of busulfan therapy
or the transplant procedure may include
decrease in circulating blood cell counts
(intended effect of the medicine to prepare you
for your transplant infusion), infection, liver
disorders including blocking of a liver vein, graft
versus host disease (the graft attacks your body)
and pulmonary complications. Your doctor will
monitor your blood counts and liver enzymes
regularly to detect and manage these events.
Other side effects may include:
Very common (may affect more than 1 in 10
people):
Blood: decrease of blood circulating cells (red
and white) and platelets. Infections. Nervous
system: insomnia, anxiety, dizziness, and
depression. Nutrition: loss of appetite, decrease
in magnesium, calcium, potassium, phosphate,
albumine in blood, and increase in blood sugar.
Cardiac: increase in heart rate, increase or
decrease of blood pressure, vasodilatation (a
state of increased calibre of the blood vessels),
and blood clots. Respiratory: shortness of
breath, nasal secretion (rhinitis), sore throat,
cough, hiccup, nosebleeds, abnormal breath
sounds. Gastro-intestinal: nausea, inflammation
of the mucosa of the mouth, vomiting, abdominal

Calculation of the quantity of Busulfan Injection to
be diluted and of the diluent
Busulfan Injection must be diluted prior to use
with either sodium chloride 9 mg/ml (0.9%)
solution for injection or glucose solution for
injection 5%.
The quantity of the diluent must be 10 times the
volume of Busulfan Injection ensuring the final
concentration of busulfan remains at
approximately 0.5 mg/ml.
The amount of Busulfan Injection and diluent to
be administered would be calculated as follows:
for a patient with a Y kg body weight:
• Quantity of Busulfan Injection:
Y (kg) x D (mg/kg) = A ml of Busulfan Injection to
6 (mg/ml)
be diluted
Y: body weight of the patient in kg
D: dose of busulfan (see SPC section 4.2)
• Quantity of diluent:
(A ml Busulfan Injection x (10) = B ml of diluent
To prepare the final solution for infusion, add (A)
ml of Busulfan Injection to (B) ml of diluent
(sodium chloride 9 mg/ml (0.9%) solution for
injection or glucose solution for injection 5%)
Preparation of the solution for infusion
Busulfan Injection must be prepared by a
healthcare professional using sterile transfer
techniques.
• Using a non polycarbonate syringe fitted with a
needle:

pain, diarrhoea, constipation, heart burn, anus
discomfort, liquid in the abdomen. Hepatic:
enlarged liver, jaundice, blocking of a liver vein.
Skin: rash, itching, loss of hairs. Muscle and
bone: back, muscle and joint pain. Renal:
increase in creatinine elimination, discomfort in
urination, decrease in urine output and bloody
urine. General: fever, headache, weakness,
chills, pain, allergic reaction, oedema, general
pain or inflammation at injection site, chest pain,
inflammation of the mucosa. Investigations:
elevated liver enzymes and weight increased.
Common (may affect up to 1 in 10 people):
Nervous system: confusion, nervous system
disorders. Nutrition: low blood sodium. Cardiac:
changes and abnormalities in heart rhythm, fluid
retention or inflammation around the heart,
decrease heart output. Respiratory: increase in
breath rhythm, respiratory failure, alveolar
haemorrhages, asthma, collapse of small
portions of the lung, fluid around the lung.
Gastro-intestinal: inflammation of the mucosa of
oesophagus, paralysis of the gut, vomiting blood.
Skin: Skin colour disorder, redness of the skin,
skin desquamation. Renal: increase in the
amount of nitrogen components in the blood
stream, moderate renal insufficiency, renal
disorder.
Uncommon (may affect up to 1 in 100 people):
Nervous system: delirium, nervousness,
hallucination, agitation, abnormal brain function,
cerebral haemorrhage, and seizure. Cardiac:
clotting of femoral artery, extra heart beats,
decrease in heart rate, diffuse leak of fluid from
the capillaries (small blood vessels).
Respiratory: decrease in blood oxygen.
Gastro-intestinal: bleeding in the stomach
and/or the gut.
Not known (frequency cannot be estimated
from the available data)
Sex glands dysfunction.
Lens disorders including clouding of the lens of
the eye (cataract), and blurred vision (corneal
thinning).
Menopausal symptoms and female infertility.
Brain abscess, Inflammation of the skin,
generalised infection.
Liver disorders.
Increase of lactate dehydrogenase in the blood.
Increase of uric acid and urea in the blood.

6. Contents of the pack and
other information
What Busulfan Injection contains
- The active substance is busulfan. One ml of
concentrate contains 6 mg busulfan (60 mg in
the vial). After dilution: one ml of solution
contains 0.5 mg of busulfan.
- The other ingredients are dimethylacetamide
and macrogol 400.
What Busulfan Injection looks like and
contents of the pack
Busulfan Injection consists of a concentrate for
solution for infusion and is supplied in colourless
glass vials, each vial containing 60 mg of
busulfan.
Busulfan Injection is a clear colourless solution
free from visible particles and is available in pack
containing 1 vial or 8 vials of 10 ml concentrate
for solution for infusion.
Not all pack sizes may be marketed.
When diluted Busulfan Injection is a clear
colourless solution.
Marketing Authorisation Holder and
Manufacturer
Marketing Authorisation Holder
Accord Healthcare Limited
Sage House,
319 Pinner Road,
North Harrow,
Middlesex HA1 4HF,
United Kingdom
Manufacturer
Accord Healthcare Limited
Sage House,
319 Pinner Road,
North Harrow,
Middlesex HA1 4HF,
United Kingdom
Wessling Hungary Kft
Fòti ùt 56, Budapest
1047 Hungary
This leaflet was last revised in 04/2016.

Reporting of side effects
If you get any side effects, talk to your doctor.
This includes any possible side effects not listed
in this leaflet. You can also report side effects
directly via the national reporting 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 Busulfan
Injection
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 vial label and the carton
after EXP.
Unopened vials:
Store in a refrigerator (2°C - 8°C).
Diluted solution:
Chemical and physical in-use stability after
dilution in glucose 5% or sodium chloride 9 mg/ml
(0.9%) solution for injection has been
demonstrated for:
− 4 hours (including infusion time) after dilution
when stored at 20 °C - 25 °C
− 15 hours after dilution when stored at 2 °C – 8 °C
followed by 3 hours stored at 20 °C - 25 °C
(including infusion time).
Do not freeze.
From a microbiological point of view, the product
should be used immediately after dilution. If not
used immediately, in-use storage times and
conditions prior to use are the responsibility of
the user.
Do not throw away any medicine via wastewater
or household waste. Ask your pharmacist how to
throw away medicine you no longer use. These
measures will help protect environment.

- the calculated volume of Busulfan Injection
must be removed from the vial.
- the contents of the syringe must be dispensed
into an intravenous bag (or syringe) which
already contains the calculated amount of the
selected diluent. Busulfan Injection must always
be added to the diluent, not the diluent to
Busulfan Injection. Busulfan Injection must not
be put into an intravenous bag that does not
contain sodium chloride 9 mg/ml (0.9%) solution
for injection or glucose solution for injection 5%.

with minimal priming space should be used
(i.e. 0.3-0.6 ml), primed with medicinal product
solution prior to beginning the actual Busulfan
Injection infusion and then flushed with sodium
chloride 9 mg/ml (0.9%) solution for injection or
glucose (5%) solution for injection.
Busulfan Injection must not be infused
concomitantly with another intravenous solution.
Polycarbonate syringes must not be used with
Busulfan Injection.

• The diluted solution must be mixed thoroughly
by inverting several times.

For single use only. Only a clear solution without
particles should be used.

After dilution, 1 ml of solution for infusion
contains 0.5 mg of busulfan.

Storage conditions
Unopened vials:
Store in a refrigerator (2°C – 8°C).

Diluted Busulfan Injection is a clear colourless
solution.
Instructions for use
Prior to and following each infusion, flush the
indwelling catheter line with approximately 5 ml of
sodium chloride 9 mg/ml (0.9%) solution for
injection or glucose (5%) solution for injection.
The residual medicinal product must not be
flushed in the administration tubing as rapid
infusion of busulfan has not been tested and is
not recommended.
The entire prescribed Busulfan Injection dose
should be delivered over two or three hours
depending on the conditioning regimen.
Small volumes may be administered over 2 hours
using electric syringes. In that case infusion sets

Diluted solution:
Chemical and physical in-use stability after
dilution in glucose 5% or sodium chloride 9 mg/ml
(0.9%) solution for injection has been
demonstrated for 4 hours (including infusion time)
after dilution when stored at 20 °C - 25 °C or 15
hours after dilution when stored at 2 °C – 8 °C
followed by 3 hours stored at 20 °C - 25 °C
(including infusion time).
For a microbiological point of view, the diluted
solution should be used immediately.
3. PROCEDURE FOR PROPER DISPOSAL
Any unused medicinal product or waste should
be disposed of in accordance with local
requirements for cytotoxic medicinal products.

Expand view ⇕

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