Fludara

Generic Name: Fludarabine phosphate
Product Name: Fludara

Indication

Fludara is used in the treatment of B-cell chronic lymphocytic leukaemia. It is used as a second line treatment in patients who have not responded to or whose disease has progressed during treatment with at least one standard alkylating-agent containing regimen.

Action

Fludarabine is an anticancer drug. It works by inhibiting a number of enzymes involved in production of DNA. It also inhibits the production of RNA and protein. These effects cause inhibition of cell growth and multiplication, and active cell killing effects have also been observed.

Dose advice

Fludara requires prescription, and is available in tablet and injection forms.

Injection form (administered into the veins):

• Dosage: 25 mg/m2 body surface per day for consecutive 5 days of a 28-day cycle.
• Each vial of the drug contains 50mg of the active fludarabine phosphate, therefore diluting in 2mL water makes each mL of the resulting solution contain 25mg of fludarabine phosphate.
• The required dose is calculated based on the patient’s body surface.
• The dose is further diluted in 10mL of saline if given as a bolus (a large dose to achieve therapeutic effect rapidly); but it is diluted in 100mL of saline instead if it is given as infusion over 30 minutes.
• Dosage depends on the presence of blood or nervous system toxicity/poisoning.
• Duration of treatment depends on individual success and tolerability of the drug. It is usually administered for 6 cycles until the patient is completely or partially free of the disease.

Oral administration:

• Dosage: 40mg/m2/day for consecutive 5 days of a 28-day cycle.
• The tablets can be taken with or without food.
• The tablets have to be swallowed whole, without being broken or chewed.
• Duration of treatment depends on individual success and tolerability of the drug. It is usually administered for 6 cycles until the patient is completely or partially free of the disease.

Schedule

Schedule 4

Common side effects

• Bone marrow suppression
• resulting in anaemia
• decreased white blood cells (therefore more prone to infection)
• decreased platelets (higher risk of bleeding)
• Fever and chills
• Nausea and vomiting
• Diarrhoea
• Gastrointestinal bleeding
• Constipation
• Mouth ulcers
• Weakness
• Loss of appetite
• Peripheral neuropathy (disturbance of skin sensation and occasionally muscle function in limbs)
• Hearing and visual disturbances
• Difficulty in sleeping
• Changes in blood sugar levels and liver function
• Rash, itchiness, swelling
• Headache

Uncommon side effects

• Pneumonia
• Agitation
• Confusion
• Over sleeping
• Changes to the lungs (pneumonitis, fibrosis)
• Worsening of pre-existing skin cancer lesions
• Partial intestinal obstruction
• Severe neurological effects (including seizures, coma and blindness)
• Autoimmune destruction of red blood cells and platelets (autoimmune haemolytic anaemia)
• Blood in the urine (haematuria) (may be sign of tumour lysis syndrome in patients with high tumour loads, need to see the doctor)
• Severe skin reactions
• Pain in the flank (fleshy part on the side between the ribs and the hip) (may be sign of tumour lysis syndrome in patients with high tumour loads, need to see the doctor)

References

1. Keating MJ, Smith TL, Lerner S et al. Prediction of prognosis following fludarabine used as secondary therapy for chronic lymphocytic leukemia. Leuk Lymphoma. 2000;37(1-2):71-85.
2. Mims online – Prescribing information of Fludara [online]. 2004 [cited 2005 September 7th]. Available from: [URL Link]
3. Optimal dosing in patients with alkylating-agent refractory B-cell CLL [online]. [cited 2005 September 9th]. Avalaible from: [URL Link]

For further information talk to your doctor.