Patient leaflet - BUSULFAN 6 MG / ML CONCENTRATE FOR SOLUTION FOR INFUSION
Package leaflet: Information for the user
Busulfan
Read all of this leaflet carefully before you start using this medicine because it contains important information for you.
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– Keep this leaflet. You may need to read it again.
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– If you have any further questions, ask your doctor or pharmacist.
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– If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.
What is in this leaflet
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1. What Busulfan is and what it is used for
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2. What you need to know before you use Busulfan
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3. How to use Busulfan
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4. Possible side effects
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5. How to store Busulfan
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6. Contents of the pack and other information
1. what busulfan is and what it is used for
Busulfan contains the active substance busulfan, which belongs to a group of medicines called alkylating agents. Busulfan destroys the original bone marrow before the transplant.
Busulfan is used in adults, new-born infants, children and adolescents as a treatment prior to transplantation.
In adults Busulfan is used in combination with cyclophosphamide or fludarabine.
In new-born infants, children and adolescents, Busulfan 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- if you are allergic to busulfan or any of the other ingredients of this medicine (listed in section 6).
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– if you are pregnant, or think you may be pregnant.
Warnings and precautions
Talk to your doctor or pharmacist before using Busulfan.
Busulfan 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 may increase the risk of suffering another malignancy in the future.
You should tell your doctor:
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– if you have a liver, kidney, heart or lung problem,
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– if you have a history of seizures,
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– if you are currently taking other medicines.
Cases of formation of blood clots in the small blood vessels may appear after hematopoietic cell transplantation (HCT) with high-dose of your treatment in combination with other medicines.
Other medicines and Busulfan
Tell your doctor if you are using, have recently used or might use any other medicines including medicines obtained without a prescription. Busulfan may interact with other medicines.
Particular caution should be taken if you use itraconazole and metronidazole (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 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.
Women must not be pregnant during treatment with Busulfan and up to 6 months after treatment. Women must stop breast-feeding before starting their treatment with Busulfan.
Adequate contraceptive precautions should be used when either partner is receiving Busulfan. 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 can also produce symptoms of menopause and in pre-adolescent girls it can prevent the onset of puberty.
Men treated with Busulfan are advised not to father child during and up to 6 months after treatment.
3. how to use busulfanthe dose of busulfan will be calculated according to your body weight.
In adults:
Busulfan in combination with cyclophosphamide :
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– The recommended dose of Busulfan is 0.8 mg/kg
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– Each infusion will last 2 hours
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– Busulfan will be administered every 6 hours during 4 consecutive days prior to transplant.
Busulfan in combination with fludarabine
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– The recommended dose of Busulfan is 3.2 mg/kg
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– Each infusion will last 3 hours
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– Busulfan 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 in combination with cyclophosphamide or melphalan is based on your body weight varying between 0.8 and 1.2 mg/kg.
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– Each infusion will last 2 hours
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– Busulfan will be administered every 6 hours during 4 consecutive days prior to transplant.
Medicines before you receive Busulfan:
Before receiving Busulfan, you will be medicated with
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– anticonvulsive medicines to prevent seizures (phenytoin or benzodiazepines) and
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– 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:
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 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.
Incomplete development of teeth.
Reporting of side effects
If your child gets 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: or search for ‘MHRA Yellow Card’ in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.
5. how to store busulfan
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 label and carton after EXP. The expiry date refers to the last day of that month.
Unopened vials:
Store in a refrigerator (2°C – 8°C), Keep the vial in the outer carton in order to protect from light.
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 8 hours (including infusion time) after dilution when stored at 20°C ± 5°C or 12 hours after dilution when stored at 2°C – 8°C followed by 3 hours stored at 20°C ± 5°C (including infusion time). Do not freeze.
Do not throw away any medicines via wastewater or household waste. 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- 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 approximately 0.5 mg of busulfan.
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– The other ingredients are dimethylacetamide and macrogol 400.
What Busulfan looks like and contents of the pack
Busulfan is a clear colorless solution.
10 ml of concentrate for solution for infusion in clear type-1 glass vial with chlorobutyl flurotec coated rubber stopper and aluminium flip off orange colour seal.
Each pack contains 1 vial or Multipack containing 8 vials. Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Neon Healthcare Ltd
Mill Studio, Crane Mead, Ware, SG12 9PY, UK
This leaflet was last revised in 11/2020
The following information is intended for medical or healthcare professionals only:
PREPARATION GUIDE
Busulfan 6 mg/ml concentrate for solution for infusion
Busulfan
Read this guide prior to the preparation and administration of Busulfan.
1. PRESENTATION
Busulfan is supplied as a clear colourless solution in 10 ml clear glass vials (type I). Busulfan 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:
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– The use of gloves and protective clothing is recommended.
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– If Busulfan or diluted Busulfan solution contacts the skin or mucosa, wash them thoroughly with water immediately.
Calculation of the quantity of Busulfan to be diluted and of the diluent
Busulfan 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 ensuring the final concentration of busulfan remains at approximately 0.5 mg/ml.
The amount of Busulfan and diluent to be administered would be calculated as follows: for a patient with a Y kg body weight:
- Quantity of Busulfan:
Y (kg) x D (mg/kg)
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--- 7,–--, & = A ml of Busulfan to be diluted
6 (mg/ml)
Y: body weight of the patient in kg
D: dose of Busulfan (see SPC section 4.2)
- Quantity of diluent:
(A ml Busulfan) x (10) = B ml of diluent
To prepare the final solution for infusion, add (A) ml of Busulfan 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 must be prepared by a healthcare professional using sterile transfer techniques.
- Using a non polycarbonate syringe fitted with a needle:
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– the calculated volume of Busulfan must be removed from the vial.
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– 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 must always be added to the diluent, not the diluent to Busulfan. Busulfan 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%.
- The diluted solution must be mixed thoroughly by inverting several times
After dilution, 1 ml of solution for infusion contains 0.5 mg of busulfan
Diluted Busulfan 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 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 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 infusion and then flushed with sodium chloride 9 mg/ml (0.9%) solution for injection or glucose (5%) solution for injection.
Busulfan must not be infused concomitantly with another intravenous solution. Polycarbonate syringes must not be used with Busulfan.
For single use only. Only a clear solution without particles should be used.
Storage conditions
Unopened vials:
Store in a refrigerator (2°C – 8°C), Keep the vial in the outer carton in order to protect from light.
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 8 hours (including infusion time) after dilution when stored at 20°C ± 5°C or 12 hours after dilution when stored at 2 °C-8 °C followed by 3 hours stored at 20°C ± 5°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.
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