Busulfan 6 mg/ml concentrate for solution for infusion

• 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 Busulfan is and what it is used for
2. What you need to know before you use Busulfan
3. How to use Busulfan
4. Possible side effects
5. How to store Busulfan
6. Contents of the pack and other information

• if you are allergic to busulfan or any of the other ingredients of this medicine listed in section 6,
• if you are pregnant, or think you may be pregnant.

Busulfan is a potent cytotoxic medicine that results in a 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:

• if you have a liver, kidney, heart or lung problem,
• if you have a history of seizures,
• if you are currently taking any 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.

Tell your doctor if you are taking, or have recently taken or might take any other medicines, including medicines obtained without a prescription. Busulfan may interact with other medicines.

In particular, tell your doctor or pharmacist if you are taking the following:

• Deferasirox (a medicine used to remove excess iron from your body).

Particular caution should be taken if you use itraconazole and metronidazole (used for certain types of infections) or ketobemidone (used to treat pain), because these may increase the side-effects.

The use of paracetamol during the 72 hours prior to or with Busulfan administration should be used with caution.

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 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.

The dose of Busulfan will be calculated according to your body weight.

In adults:

Busulfan in combination with cyclophosphamide:

• The recommended dose of Busulfan is 0.8 mg/kg.
• Each infusion will last 2 hours.
• Busulfan will be administered every 6 hours, during 4 consecutive days, prior to transplant.

Busulfan in combination with fludarabine:

• The recommended dose of Busulfan is 3.2 mg/kg.
• Each infusion will last 3 hours.
• 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.

• Each infusion will last 2 hours.
• Busulfan will be administered every 6 hours during 4 consecutive days prior to transplant.

Before receiving Busulfan, you will be treated with:

• anticonvulsive medicines to prevent seizures (fits) (phenytoin or benzodiazepines) and
• antiemetic medicines to prevent you from being sick (vomiting).

Very common (may affect more than 1 in 10 people):

• a decrease in the number of blood circulating cells (red and white) and platelets
• infections
• insomnia, anxiety, dizziness and depression
• loss of appetite, a decrease in magnesium, calcium, potassium, phosphate, albumin in the blood, and an increase in blood sugar
• an increase in heart rate, an increase or decrease in blood pressure, vasodilation (widening of the blood vessels) and blood clots
• shortness of breath, nasal secretion (rhinitis), sore throat, cough, hiccups, nosebleeds, abnormal breathing
• nausea, inflammation of the membrane of the mouth (mucosa), vomiting, abdominal pain, diarrhoea, constipation, heartburn, discomfort in the opening of the bottom (anus), fluid in the abdomen
• enlarged liver, jaundice (yellowing of the skin or whites of the eyes), blocking of a liver vein
• rash, itching, loss of hair
• back pain, muscle pain and joint pain
• an increase in removal of a chemical waste product, creatinine, that passes through kidneys to be filtered and eliminated in urine, (creatinine elimination), discomfort when passing urine, a decrease in urine output and bloody urine
• fever, headache, weakness, chills, pain, allergic reaction, oedema (fluid build up), general pain or inflammation at the injection site, chest pain, inflammation of the membrane which lines bodily organs
• high levels of liver enzymes and weight increase
• paralysis of the gut

Common (may affect up to 1 in 10 people):

• confusion, nervous system disorders
• low blood sodium (salt) levels
• changes and abnormalities in heart rhythm, fluid retention or inflammation around the heart, a decrease in the amount of blood that the heart pumps to the circulatory system (heart output)
• an increase in breathing rate, respiratory failure, bleeding from the air-filled sacs within the lungs called alveoli (alveolar haemorrhages), asthma, collapsing of small parts of the lung, fluid around the lungs
• inflammation of the gullet (oesophagus) membrane, paralysis (loss of movement) of the gut, vomitting blood (sick)
• skin discolouration, redness of the skin, scaley skin (desquamation)
• an increase in the amount of nitrogen within the blood stream, moderate kidney insufficiency, kidney disorder

Uncommon (may affect up to 1 in 100 people):

• delirium (severe confusion), nervousness, hallucination (seeing things that are not there), agitation (anxiety or nervousness), abnormal brain function, brain haemorrhage, and seizure
• clotting of the artery in the thigh (femoral artery), increased heartbeat, a decrease in heart rate, fluid leakage from the capillaries (small blood vessels)
• decrease in blood oxygen levels
• bleeding in the stomach and/or the gut

Not known (frequency cannot be estimated from the available data)

• Sex glands dysfunction
• Eye disorders, including the clouding of the lens of the eye (cataract), and blurred vision (corneal thinning)
• Menopausal symptoms and female infertility
• Brain abscess, inflammation of the skin, general infection
• Liver disorders
• An increase in the enzyme called lactate dehydrogenase
• An increase of uric acid and urea in the blood
• Incomplete development of teeth

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard 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.

• The active ingredient is busulfan. One ml of concentrate contains 6 mg busulfan (60 mg of busulfan in the vial). After dilution: one ml of solution contains approximately 0.5 mg of busulfan.
• The other ingredients are N, N-Dimethylacetamide, Macrogol 400 and citric acid anhydrous.

Busulfan consists of a concentrate for solution for infusion and is supplied in colourless glass vials, each vial containing 60 mg of busulfan.

Busulfan is available in single packs of 1 vial or multipacks comprising 8 vials. When diluted, Busulfan is a clear colourless solution.

Vials may or may not be sleeved with plastic shrink sleeve/bottom (puck). This plastic sleeving is not in contact with the drug product and is there to provide additional protection during transportation. This improves the safe handling of the medicinal product by both healthcare professionals and pharmaceutical personnel.

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