How does it work?

Busilvex infusion contains the active ingredient busulfan, which a type of chemotherapy medicine called an alkylating agent.

Busulfan works by binding to DNA in cells. This stops the cells from growing and multiplying, particularly cells that multiply quickly such as blood cells.

Busilvex is used to treat people who are going to have a bone marrow transplant (also called a stem cell transplant). The bone marrow is where blood cells are made. Stem cells are blood cells at their earliest stage of development. Stem cells in the bone marrow mature into different cell types and are then released into the bloodstream. A stem cell transplant is used as a treatment for certain types of cancers involving the blood cells.

Busulfan is given before a stem cell transplant to destroy the existing stem cells and blood cells in the bone marrow and any remaining cancer cells. Other chemotherapy medicines are used as well.

Busilvex infusion is usually given every six hours for four days, starting seven days before the transplant. A total of 16 infusions (drips) are given, each infusion session lasts for two hours.

After the chemotherapy, the next step is to give an infusion of stem cells to replace the ones that have been destroyed. These stem cells find their way into the bone marrow, where they will then mature into new red blood cells, white blood cells and platelets.

What is it used for?

• To prepare the bone marrow before a stem cell transplant operation.

Cyclophosphamide or melphalan will be given at least 24 hours after the last infusion of busulfan.

Warning!

• This medicine will profoundly decrease the number of blood cells in your blood. A low white blood cell count can increase your susceptibility to infections; a low red blood cell count causes anaemia and a low platelet count can cause problems with blood clotting. For this reason, you will need regular blood tests to monitor your blood cells during treatment with this medicine and while your blood cells recover following the transplant. While your blood counts are low you will be given antimicrobials to prevent infections and supportive treatments such as red cell and platelet transfusions. Following the transplant you will need to tell your doctor immediately if you experience any of the following symptoms, as they may indicate problems with your blood cells: unexplained bruising or bleeding, purple spots, sore mouth or throat, mouth ulcers, high temperature (fever) or other signs of infection, or suddenly feeling tired, breathless, or generally unwell. Your specialist will give you more advice.
• This medicine may be harmful to an unborn baby, and for this reason it is important to avoid becoming pregnant or fathering a child during treatment. You should continue to use contraception to prevent pregnancy for at least six months after having treatment with this medicine. Discuss this with your doctor.
• Your ability to become pregnant or father a child may be affected by this medicine. It is important to discuss fertility with your doctor before starting treatment.

Use with caution in

• Decreased kidney function.
• Decreased liver function.
• People who are having or have recently had radiotherapy.
• People with a high level of uric acid in their blood (hyperuricaemia). Your doctor will want to correct this before treatment is started.
• People with gout.
• People with epilepsy or a history of seizures.
• An inherited blood problem called thalassaemia.
• Hereditary blood disorders called porphyrias.

Not to be used in

• Pregnancy.
• Breastfeeding.

This medicine should not be used if you are allergic to any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.

If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

Pregnancy and breastfeeding

Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

• This medicine should not be used in pregnancy, unless considered essential by your doctor due to life-threatening disease, because it may be harmful to a developing baby.
• Women who could get pregnant should use effective contraception to prevent pregnancy, and men should use effective contraception to prevent fathering a child, both during treatment, and for at least six months after treatment is finished. Seek further medical advice from your doctor.
• It is not known if this medicine passes into breast milk. Mothers who need treatment with this medicine should not breastfeed. Seek medical advice from your doctor.

Side effects

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here, it does not mean that all people using this medicine will experience that or any side effect.

This is a high dose chemotherapy treatment and as such is likely to be unpleasant. The medical staff involved in treating you are highly trained to help minimise any side effects and discomfort you may experience. You will be given anticonvulsant medicine and antisickness medicine before and during the treatment.

Very common (affect more than 1 in 10 people)

• Decrease in the number of white blood cells in the blood (leukopenia and neutropenia).
• Decrease in the number of platelets in the blood (thrombocytopenia).
• Low red blood cell count (anaemia).
• Raised blood glucose (hyperglycaemia).
• Headache.
• Dizziness.
• Anxiety.
• Depression.
• Difficulty with sleeping.
• Faster than normal heart beat (tachycardia).
• Changes in blood pressure.
• Disturbances of the gut such as nausea, vomiting, constipation, indigestion, abdominal pain, diarrhoea or anal discomfort.
• Inflammation of the lining of the mouth (stomatitis).
• Enlarged liver (hepatomegaly).
• Yellowing of the skin and eyes (jaundice).
• Skin reactions such as itching and rash.
• Hair loss (alopecia).
• Muscle and joint pain.
• Pain or difficulty urinating (dysuria).
• Feeling weak or tired.
• Fever.
• Excessive fluid retention in the body tissues, resulting in swelling (oedema).
• Accumulation of fluid in the abdomen (ascites)
• Inflammation of the mucous membranes in the intestinal tract (mucositis).
• Difficulty in breathing (dyspnoea).
• Cough.
• Chest pain.
• Runny nose.
• Nosebleeds.
• Sore throat.
• Raised liver enzymes.
• Blood clot inside a blood vessel (thrombosis).
• Pain at site of injection.
• Imbalance of salt concentrations in the blood (electrolyte imbalance).

Common (affect between 1 in 10 and 1 in 100 people)

• Low blood sodium levels (hyponatraemia).
• Abnormal rhythm of the heartbeat (arrhythmia).
• An irregular heart beat (atrial fibrillation).
• Fluid around the lungs.
• Inflammation of the food pipe (oesophagitis).
• Changes in skin pigmentation.
• Redness of skin.
• Blood in the urine.

Uncommon (affect between 1 in 100 and 1 in 1000 people)

• Bleeding in the gut.
• Delirium.
• Nervousness.
• Hallucination.
• Agitation.
• Slow heart rate (bradycardia).
• Seizures.

The side effects listed above may not include all of the side effects reported by the medicine's manufacturer.

For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.

How can this medicine affect other medicines?

It is important to tell your doctor or pharmacist what medicinesyou are already taking, including those bought without a prescription andherbal medicines, before you start treatment with this medicine. Similarly,check with your doctor or pharmacist before taking any new medicines duringtreatment this one, to ensure that thecombination is safe.

Chemotherapy decreases the body's immune response. This meansthat vaccines may be less effective if given during treatment, and livevaccines may cause serious infections. Live vaccines include: measles, mumps,rubella, MMR, oral polio, oral typhoid and yellow fever. If live vaccines areneeded they should be postponed until at least six months after finishingchemotherapy.

There may be an increased risk of side effects if this medicine is used in combination with the following medicines:

• cyclophosphamide (your first dose of cyclophosphamide should not be given for at least 24 hours after your last dose of busulfan)
• itraconazole
• oral metronidazole
• other chemotherapy medicines
• paracetamol (also if used in the 72 hours before the infusion)
• tioguanine.

Phenytoin may decrease the amount of busulfan in the blood, which could make it less effective. Your doctor will monitor your blood cells to check that the busulfan is working correctly.

Other medicines containing the same active ingredient