In this leaflet:

• 1. What Busilvex is and what it is used for
• 2. Before you use Busilvex
• 3. How to use Busilvex
• 4. Possible side effects
• 5. Storing Busilvex
• 6. Further information

Do not use Busilvex:

• if you are hypersensitive to busulfan or any of the other ingredients of Busilvex
• if you are pregnant, or think you may be pregnant.

Take special care with Busilvex:

Busilvex is a potent cytotoxic drug 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 Busilvex 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
• you have a history of seizures
• you are currently taking other drugs.

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. Busilvex can also produce symptoms of menopause and in pre-adolescent girls it can prevent the onset of puberty.

Men treated with Busilvex are advised not to father a child during and up to 6 months after treatment.

Pregnancy and breast-feeding

Tell your doctor if you are pregnant, think you may be pregnant or are breast-feeding, before you receive treatment with Busilvex. Women should avoid becoming pregnant during treatment with Busilvex and up to 6 months after treatment.

Women should not breast-feed during their treatment with Busilvex.

Adequate contraceptive precautions should be used when either partner is receiving Busilvex.

Taking other medicines:

Please inform your doctor if you are taking or have recently taken any other medicines, even those not prescribed. Busilvex may interact with other drugs.

Particular caution should be taken if you use itraconazol (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 Busilvex administration should be used with caution.

Dosage:

In adults:

The dose will be calculated according to your body weight.

The recommended dose of Busilvex is 0.8 mg per kg of body weight, in combination with cyclophosphamide.

In new-born infants, children and adolescent (0 to 17 years):

The recommended dose is based on your body weight varying between 0.8 and 1.2 mg/kg.

Administration:

• Busilvex is administered by a qualified healthcare professional as a central intravenous infusion, after dilution of the individual ampoule. Each infusion will last 2 hours.
• Busilvex will be administered every 6 hours during 4 consecutive days prior to transplant.

Medication before you receive Busilvex:

Before receiving Busilvex, you will be medicated with

• anticonvulsive drugs to prevent seizures (phenytoin and benzodiazepines) and
• antiemetic drugs to prevent vomiting.

Serious side effects:

The most serious side effects of Busilvex therapy or the transplant procedure may include decrease in circulating blood cell counts (intended effect of the drug 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.

 

Very common side effects (reported in more than 1 patient out of 10):

Blood : decrease of blood circulating cells (red and white) and platelets. Nervous system : insomnia, anxiety, dizziness, and depression. Nutrition : loss of appetite, decrease in magnesium, calcium, potassium, phosphate 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. Skin: rash, itching, loss of hairs. Muscleand bone: back, muscle and joint pain. Renal: increase in creatinine elimination, discomfort in urination, and decrease in urine output. 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, weight increased

Common side effects (reported in 1 to 10 patients out of 100 patients):

Nervous system: confusion. 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, blood in urine, moderate renal insufficiency.

Uncommon side effects (reported in 1 to 10 patients out of 1000 patients):

Nervous system: delirium, nervousness, hallucination, agitation, abnormal brain function, cerebral haemorrhage, and seizure. Cardiac : clotting of femoral artery, thrombosis, 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.

If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.