Busulfan 60 mg/10 ml Injection

DETENER contains the active substance busulfan, which belongs to a group of medicines called alkylating medicines. DETENER destroys the original bone marrow before the transplant. DETENER is used in adults as a treatment prior to transplantation in combination with cyclophosphamide. You will receive this preparative medicine before receiving a transplant of either bone marrow or haematopoietic progenitor cell.

DETENER should not be administered to you:

• if you are hypersensitive (allergic) to busulfan or any of the other ingredients of DETENER (listed in section 6)
• if you are pregnant or breast feeding your baby
• if you suffer from hepatic insufficiency

Warnings and precautions

Special care should be taken with DETENER: DETENER 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.

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.

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. Acute respiratory distress syndrome (severe shortness of breath) has been reported. Busulfan can impair fertility.

Other medicines and DETENER

Always tell your health care provider if you are taking any other medicine. (This includes complementary or traditional medicines.) DETENER may interact with other medicines. Particular caution should be taken if you use itraconazole (used to treat fungal infections) and 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 DETENER administration should be used with caution.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, please consult your health care provider for advice before you receive treatment with DETENER. Women must not be pregnant during treatment with DETENER and up to 6 months after treatment. Breast-feeding Women must stop breast-feeding before starting their treatment with DETENER. Fertility It may no longer be possible for you to achieve a pregnancy (infertility) after treatment with DETENER. If you are concerned about having children, you should discuss this with your doctor before treatment. Adequate contraceptive precautions should be used when either partner is receiving DETENER. Men treated with DETENER are advised not to father child during and up to 6 months after treatment.

You will not be expected to give yourself DETENER. It will be given to you by a health care provider who is qualified to do so.

The dose will be calculated according to your body weight. The recommended dose is 0,8 mg/kg of body weight in adult patients in combination with cyclophosphamide.

Medicines before you receive DETENER:

• anticonvulsive medicines to prevent seizures
• antiemetic medicines to prevent vomiting

Route of administration

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

If you take more DETENER than you should Since a health care provider will administer DETENER, he/she will control the dosage. However, in the unlikely event of overdosage your doctor will manage the overdosage.

DETENER can have side effects. Not all side effects reported for DETENER are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking DETENER, please consult your health care provider for advice.

If any of the following happens, you will have to stop taking DETENER:

• swelling of the hands, feet, ankles, face, lips and mouth or throat, which may cause difficulty in swallowing or breathing
• rash or itching
• fainting

These are all very serious side effects. If you have them, you may have had a serious reaction to DETENER. You may need urgent medical attention or hospitalisation.

Tell your doctor immediately or go to the casualty department at your nearest hospital if you notice any of the following:

• decrease in circulating blood cell counts as shown by the blood tests (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 lung complications.

Your doctor will monitor your blood counts and liver enzymes regularly to detect and manage these events. These are all serious side effects. You may need urgent medical attention.

Tell your doctor if you notice any of the following:

Frequent side effects:

• decrease of blood circulating cells (red and white) and platelets
• insomnia
• anxiety
• dizziness
• depression
• confusion
• decrease in magnesium, calcium, potassium phosphate and sodium in blood
• increase in blood sugar
• increase in heart rate
• increase or decrease of blood pressure
• vasodilation
• blood clots
• changes and abnormalities in heart rhythm
• fluid retention or inflammation around the heart
• decreased heart output
• shortness of breath
• nasal secretion
• sore throat
• cough
• hiccup
• nosebleeds
• abnormal breath sounds

Less frequent side effects:

• delirium
• nervousness
• hallucination
• agitation
• abnormal brain function
• cerebral haemorrhage
• seizure
• clotting of femoral artery
• thrombosis

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

Reporting of side effects If you get side effects, talk to your doctor, pharmacist or nurse. You can also report side effects to SAHPRA via the “6.04 Adverse Drug Reaction Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8. By reporting side effects, you can help provide more information on the safety of DETENER.

Store all medicines out of reach of children. Do not freeze.

Unopened vials: Store in a refrigerator between 2 °C to 8 °C. Excursions not permitted.

Chemical and physical in-use stability after dilution: 8 hours (including infusion time) after dilution in glucose 5% or sodium chloride 9 mg/ml (0.9%) solution for injection when stored at 20 °C ± 5 °C.

6 hours after dilution in sodium chloride 9 mg/ml (0.9%) solution for injection when stored at 2 °C-8 °C followed by 3 hours stored at 20 °C ± 5 °C (including infusion time).