Busulfan Fresenius Kabi - patient leaflet, side effects, dosage

Patient leaflet - Busulfan Fresenius Kabi

1. What Busulfan Fresenius Kabi is and what it is used for

This medicine contains the active substance busulfan, which belongs to a group of medicines called alkylating agents. Busulfan Fresenius Kabi destroys the original bone marrow before the transplant.

Busulfan Fresenius Kabi is used in adults, new-born infants, children and adolescents as a treatment prior to transplantation.

In adults Busulfan Fresenius Kabi is used in combination with cyclophosphamide or fludarabine.

In new-born infants, children and adolescents, this medicine is used in combination with cyclophosphamide or melphalan.

You will receive this preparative medicine before receiving a transplant of either bone marrow or haematopoietic progenitor cell.

2. What you need to know before you use Busulfan Fresenius Kabi

Do not use Busulfan Fresenius Kabi:

– if you are allergic to busulfan or any of the other ingredients of this medicine listed in section 6.
– if you are pregnant, or think you may be pregnant.

Warnings and precautions

Busulfan Fresenius Kabi 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.

It is possible that use of Busulfan Fresenius Kabi 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,

– 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.

Other medicines and Busulfan Fresenius Kabi

Tell your doctor if you are taking or have recently taken or might take any other medicines, including medicines obtained without a prescription. Busulfan Fresenius Kabi may interact with other medicines.

Particular caution should be taken if you use itraconazol and metronidazole (used for certain types of infections) or ketobemidone (used to treat pain) or deferasirox (a medicine used to remove excess iron from your body), because this may increase the side-effects.

The use of paracetamol during the 72 hours prior to or with Busulfan Fresenius Kabi administration should be used with caution.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor before you receive treatment with Busulfan Fresenius Kabi. Women must not be pregnant during treatment with Busulfan Fresenius Kabi and up to 6 months after treatment.

Women must stop breast-feeding before starting their treatment with Busulfan Fresenius Kabi.

Adequate contraceptive precautions should be used when either partner is receiving Busulfan Fresenius Kabi.

It may no longer be possible for you to achieve a pregnancy (infertility) after treatment with Busulfan Fresenius Kabi. If you are concerned about having children, you should discuss this with your doctor before treatment. Busulfan Fresenius Kabi can also produce symptoms of menopause and in pre-adolescent girls it can prevent the onset of puberty.

Men treated with Busulfan Fresenius Kabi are advised not to father child during and up to 6 months after treatment.

3. How to use Busulfan Fresenius Kabi

Dose and administration

The dose of busulfan will be calculated according to your body weight.

In adults:

Busulfan Fresenius Kabi in combination with cyclophosphamide :

– The recommended dose of Busulfan Fresenius Kabi is 0.8 mg/kg
– Each infusion will last 2 hours
– Busulfan will be administered every 6 hours during 4 consecutive days prior to transplant.

Busulfan Fresenius Kabi in combination with fludarabine

– The recommended dose of busulfan is 3.2 mg/kg
– Each infusion will last 3 hours
– Busulfan will be administered once daily during 2 or 3 consecutive days prior to transplant.

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

The recommended dose of Busulfan Fresenius Kabi in combination with cyclophosphamide or melphalan is based on your body weight varying between 0.8 and 1.2 mg/kg.

Medicines before you receive Busulfan Fresenius Kabi:

Before receiving Busulfan Fresenius Kabi, you will be medicated with

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

4. Possible side effects

Like all medicines, Busulfan Fresenius Kabi can cause side effects, although not everybody gets them.

Serious side effects:

The most serious side effects of busulfan therapy or the transplant procedure may include decrease in circulating blood cell counts (intended effect of the medicine 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. Contact your doctor immediately if you get any of the following symptoms. Your doctor will monitor your blood counts and liver enzymes regularly to detect and manage these events.

Other side effects may include:

Very common (may affect more than 1 in 10 people):

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

Common (may affect up to 1 in 10 people):

Nervous system: confusion, nervous system disorders. 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, moderate renal insufficiency, renal disorder.

Uncommon (may affect up to 1 in 100 people):

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

Not known (frequency cannot be estimated from the available data)

Sex glands dysfunction

Lens disorders including clouding of the lens of the eye (cataract), and blurred vision (corneal thinning)

Menopausal symptoms and female infertility.

Brain abscess, Inflammation of the skin, generalised infection.

Liver disorders.

Increase of lactate dehydrogenase in the blood.

Increase of uric acid and urea in the blood.

Incomplete development of teeth

Reporting of side effects

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V.

By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Busulfan Fresenius Kabi

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the vial label and the carton after EXP.

Unopened vials:

Store in a refrigerator (2°C – 8°C).

Diluted solution:

Chemical and physical in-use stability after dilution in glucose 5% or sodium chloride 9 mg/ml (0.9%) solution for injection has been demonstrated for 8 hours (including infusion time) after dilution when stored at 25°C ± 2°C or 12 hours after dilution when stored at 2°C-8°C followed by 3 hours stored at 25°C ± 2°C (including infusion time). Do not freeze.

Do not throw away any medicine via wastewater or household waste. Ask your pharmacist how to throw away medicine you no longer use. These measures will help protect environment.

6. Contents of the pack and other information

What Busulfan Fresenius Kabi contains

– The active substance is busulfan. One ml of concentrate contains 6 mg busulfan (60 mg in the

vial). After dilution: one ml of solution contains approximately 0.5 mg of busulfan.

– The other ingredients are dimethylacetamide and macrogol 400.

What Busulfan Fresenius Kabi looks like and contents of the pack

Busulfan Fresenius Kabi consists of a concentrate for solution for infusion. When diluted Busulfan Fresenius Kabi is a clear colourless viscous solution.

Busulfan Fresenius Kabi is supplied in colourless glass vials, each vial containing 60 mg of busulfan. Each vial is sleeved with shrinkable plastic film.

Each vial contains 10 ml of concentrate.

Pack size

1 pack containing 8 vials (8 cartons of 1 vial).

Marketing Authorisation Holder

Fresenius Kabi Deutschland GmbH

Else-Kröner-Straße 1,

61352 Bad Homburg v.d.Höhe

Germany

Manufacturer

Fresenius Kabi Deutschland GmbH

Pfingstweide 53

61169 Friedberg

Germany

For any information about this medicine, please contact the Marketing Authorisation Holder

This leaflet was last revised in {MM/YYYY}

Other sources of information

Detailed information on this product is available on the website of European Medicinal

Agency

The following information is intended for healthcare professionals only

PREPARATION GUIDE

Busulfan Fresenius Kabi 6 mg/ml concentrate for solution for infusion

Busulfan

Read this guide prior to the preparation and administration of Busulfan Fresenius Kabi.

1. PRESENTATION

Busulfan Fresenius Kabi is supplied as a clear colourless viscous solution in 10 ml clear, colourless glass vials (type I). Busulfan Fresenius Kabi must be diluted prior to administration.

2. RECOMMENDATION FOR SAFE HANDLING

Procedures for proper handling and disposal of anticancer medicinal products should be considered.

All transfer procedures require strict adherence to aseptic techniques, preferably employing a vertical laminar flow safety hood.

As with other cytotoxic compounds, caution should be exercised in handling and preparing the busulfan solution:

– The use of gloves and protective clothing is recommended.
– If the concentrate or diluted busulfan solution contacts the skin or mucosa, wash them thoroughly

with water immediately.

Calculation of the quantity of Busulfan Fresenius Kabi to be diluted and of the diluent

Busulfan Fresenius Kabi must be diluted prior to use with either sodium chloride 9 mg/ml (0.9%) solution for injection or glucose solution for injection 5%.

The quantity of the diluent must be 10 times the volume of Busulfan Fresenius Kabi ensuring the final concentration of busulfan remains at approximately 0.5 mg/ml.

The amount of Busulfan Fresenius Kabi and diluent to be administered would be calculated as follows: for a patient with a Y kg body weight:

Quantity of Busulfan Fresenius Kabi:

Y (kg) x D (mg/kg)

= A ml of Busulfan Fresenius Kabi to be diluted

6 (mg/ml)

Y: body weight of the patient in kg

D: dose of busulfan (see SPC section 4.2)

Quantity of diluent:

(A ml Busulfan Fresenius Kabi) x (10) = B ml of diluent

To prepare the final solution for infusion, add (A) ml of Busulfan Fresenius Kabi to (B) ml of diluent (sodium chloride 9 mg/ml (0.9%) solution for injection or glucose solution for injection 5%).

Preparation of the solution for infusion

Busulfan Fresenius Kabi must be prepared by a healthcare professional using sterile transfer techniques.

Using a non polycarbonate syringe fitted with a needle:
– the calculated volume of Busulfan Fresenius Kabi must be removed from the vial.
– the contents of the syringe must be dispensed into an intravenous bag (or syringe) which

already contains the calculated amount of the selected diluent. Busulfan Fresenius Kabi must always be added to the diluent, not the diluent to the Busulfan Fresenius Kabi. Busulfan Fresenius Kabi must not be put into an intravenous bag that does not contain sodium chloride 9 mg/ml (0.9%) solution for injection or glucose solution for injection 5%.

The diluted solution must be mixed thoroughly by inverting several times.

After dilution, 1 ml of solution for infusion contains 0.5 mg of busulfan.

Diluted Busulfan Fresenius Kabi is a clear colourless solution

Instructions for use

Prior to and following each infusion, flush the indwelling catheter line with approximately 5 ml of sodium chloride 9 mg/ml (0.9%) solution for injection or glucose (5%) solution for injection.

The residual medicinal product must not be flushed in the administration tubing as rapid infusion of busulfan has not been tested and is not recommended.

The entire prescribed busulfan dose should be delivered over two or three hours depending on the conditioning regimen.

Small volumes may be administered over 2 hours using electric syringes. In that case infusion sets with minimal priming space should be used (i.e 0.3–0.6 ml), primed with medicinal product solution prior to beginning the actual busulfan infusion and then flushed with sodium chloride 9 mg/ml (0.9%) solution for injection or glucose (5%) solution for injection.

Busulfan must not be infused concomitantly with another intravenous solution.

Due to incompatibility, do not use infusion components containing polycarbonate with busulfan.

For single use only. Only a clear solution without particles should be used.

Storage conditions