Meliora 6 mg Solution

MELIORA contains the active substance busulfan, which belongs to a group of medicines called alkylating medicines. MELIORA destroys the original bone marrow before the transplant. MELIORA 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.

MELIORA should not be administered to you:

• if you are hypersensitive (allergic) to busulfan or any of the other ingredients of MELIORA (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 MELIORA: MELIORA 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 MELIORA

Always tell your health care provider if you are taking any other medicine. (This includes complementary or traditional medicines.) MELIORA 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 MELIORA administration should be used with caution.

You will not be expected to give yourself MELIORA. 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 MELIORA:

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

Route of administration

MELIORA 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. MELIORA will be administered every 6 hours during 4 consecutive days prior to transplant.

If you take more MELIORA than you should

Since a health care provider will administer MELIORA, he/she will control the dosage. However, in the unlikely event of overdosage your doctor will manage the overdosage.

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

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

• 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 MELIORA. 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

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).