Busulfan 6 mg Solution

BUSULFAN 6 mg/mL FRESENIUS contains busulfan, which belongs to a group of medicines called alkylating agents. BUSULFAN 6 mg/mL FRESENIUS destroys the original bone marrow before the transplant. BUSULFAN 6 mg/mL FRESENIUS is used in adults as a treatment prior to transplantation in combination with cyclophosphamide.

BUSULFAN 6 mg/mL FRESENIUS should not be administered to you:

• if you are hypersensitive (allergic) to busulfan or any of the other ingredients of BUSULFAN 6 mg/mL FRESENIUS (listed in section 6).
• if you are pregnant or think you may be pregnant or breastfeeding.
• if you suffer from liver problems.

Warnings and precautions

BUSULFAN 6 mg/mL FRESENIUS is a potent cytotoxic medicine that results in profound decrease of blood cells. At the recommended dose, this is the desired effect. Therefore, blood tests and careful monitoring will be performed throughout treatment and recovery. Your doctor may give you antibiotics to prevent and manage infection that may occur during your treatment.

Tell your doctor or healthcare provider before being given the injection:

• Special care should be taken with BUSULFAN 6 mg/mL FRESENIUS if you have a liver, kidney, heart or lung problem.
• if you have a history of seizures, you should receive sufficient anti-epileptic or anti-seizure treatment.
• if you are currently taking other medicines.
• If you have previously had radiation therapy, chemotherapy or a progenitor cell transplant.

It is possible that use of BUSULFAN 6 mg/mL FRESENIUS may increase the risk of suffering another malignancy in the future. 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.

Do not share medicines prescribed for you with any other person. You will not be expected to give yourself BUSULFAN 6 mg/mL FRESENIUS. It will be given to you by a person who is qualified to do so.

In adults: The usual dose of BUSULFAN 6 mg/mL FRESENIUS will be calculated according to your body weight. The recommended dose of busulfan is 0,8 mg/kg. Each infusion will last 2 hours. BUSULFAN 6 mg/mL FRESENIUS will be administered every 6 hours during 4 consecutive days prior to transplant.

Before receiving BUSULFAN 6 mg/mL FRESENIUS you will be medicated with:

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

If you use more BUSULFAN 6 mg/mL FRESENIUS than you should Since a healthcare provider will administer BUSULFAN 6 mg/mL FRESENIUS, he/she will control the dosage. However, in the event of overdosage your doctor will manage the overdosage.

If you forget to use BUSULFAN 6 mg/mL FRESENIUS Since a healthcare provider will administer BUSULFAN 6 mg/mL FRESENIUS, it is unlikely that the dose will be missed.

BUSULFAN 6 mg/mL FRESENIUS can have side effects. Not all side effects reported for BUSULFAN 6 mg/mL FRESENIUS are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking BUSULFAN 6 mg/mL FRESENIUS, please consult your healthcare provider for advice.

If any of the following happens, tell your doctor or healthcare professional in the hospital immediately or if you are at home, go to the oncology clinic.

• an allergic reaction such as sudden wheeziness, difficulty in breathing, swelling of eyelids, face or lips, rash or itching (especially affecting the whole body), and you may feel you are going to faint
• infection with symptoms of fever and chills, nausea and vomiting, body aches
• liver disorders including blocking of a liver vein (when the small blood vessels that lead into the liver and are inside the liver become blocked), enlarged liver, jaundice, graft versus host disease (the graft attacks your body)
• lung (pulmonary) complications - respiratory failure where usual exchange between oxygen and carbon dioxide in the lungs does not occur, coughing up blood, collapse of small portions of the lung, fluid around the lung causing pain
• bloody urine
• paralysis of the gut (muscle of the stomach is paralysed), vomiting blood, bleeding in the stomach and/or the gut
• cerebral haemorrhage (stroke), and seizure (fits)
• clotting of femoral artery

Your doctor will monitor your blood counts and liver enzymes regularly to detect and manage these events. These are all very serious side effects. If you have them, you may have had a serious reaction to BUSULFAN 6 mg/mL FRESENIUS. 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 urine output
• fluid retention or inflammation around the heart, decreased heart output
• depression
• increase in heart rate, increase or decrease of blood pressure, and blood clots
• inflammation of the mucosa (lining) of the mouth
• liquid in the abdomen
• chest pain, inflammation of the mucosa (lining)
• elevated liver enzymes
• changes and abnormalities in heart rhythm
• asthma
• inflammation of the mucosa of oesophagus (lining of tube from the throat to stomach)
• moderate kidney insufficiency, kidney disorder
• damage to the brain that may result in abnormal brain function
• extra heart beats, decrease in heart rate, diffuse leak of fluid from the capillaries (small blood vessels)
• decrease in blood oxygen
• collection of pus that develops in the brain due to an infection known as brain abscess

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:
• insomnia, anxiety, dizziness
• loss of appetite, decrease in magnesium, calcium, potassium, phosphate, increase in blood enzyme albumin in blood, and increase in blood sugar
• shortness of breath, nasal secretion (rhinitis), sore throat, cough, hiccup, nosebleeds, abnormal breath sounds
• nausea, vomiting, abdominal pain, diarrhoea, constipation, heart burn, anus discomfort
• rash, itching, loss of hairs
• back, muscle and joint pain
• increase in blood enzyme creatinine elimination, discomfort in urination
• fever, headache, weakness, chills, pain, oedema (swelling caused by buildup of liquid), general pain or inflammation at injection site
• weight increased
• confusion, nervous system disorders
• low blood sodium
• increase in breath rhythm
• skin colour disorder, redness of the skin, skin desquamation (an unintended damage to and loss of the upper layer of skin)
• increase in the amount of nitrogen components in the blood stream
• Less frequent side effects:
• an abrupt change in the brain that causes mental confusion and emotional disruption known as delirium, nervousness, hallucination, agitation
• Frequency of side effects unknown:
• sex glands dysfunction
• lens disorders including clouding of the lens of the eye (cataract), and blurred vision (corneal thinning)
• menopausal symptoms and female infertility
• inflammation of the skin, generalised infection
• increase of the enzyme lactate dehydrogenase in the blood
• increase of waste by-product uric acid and urea in the blood
• incomplete development of teeth.

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 Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. By reporting side effects, you can help provide more information on the safety of BUSULFAN 6 mg/mL FRESENIUS. Patients are asked to report any suspected adverse drug reactions to their healthcare provider or Holder of the Certificate of Registration at the following email address: [email protected] and to the relevant medicine’s regulatory authority in the country where the product is marketed.

• Store all medicines out of reach of children.

• Hospital staff will store your medicine safely:

• Store at or between 2 °C – 8 °C (in a refrigerator). Do not freeze.
• Do not freeze the diluted solution.
• Store in the original package/container.
• Keep the container in the outer carton.
• Keep the container tightly closed.

• Do not use after the expiry date stated on the label.

• Return all unused medicine to your pharmacist.

• Do not dispose of unused medicine in drains or sewerage systems (e.g. toilets).