Fludarabine

Registered South African indications:

• B-cell chronic lymphocytic leukaemia

Registered South African contraindications

Injection

• Hypersensitivity to fludarabine or to any of the excipients
• Pregnancy
• Breastfeeding
• Severe renal function impairment (patients with creatinine clearance <30 ml/minute)
• Haemolytic anaemia
• Chickenpox or herpes zoster
• The safety and effectiveness of fludarabine in children has not been established

Film-coated tablet

• Hypersensitivity to fludarabine or to any of the excipients
• Severe renal function impairment (patients with creatinine clearance <30 ml/minute)
• Haemolytic anaemia
• The safety and effectiveness of fludarabine in children has not been established

Contraindications registered in other jurisdictions

• Hypersensitivity to the active substance or to any of the excipients
• Renal impairment with creatinine clearance <30 ml/min
• Decompensated haemolytic anaemia
• Lactation

• Pregnancy (Recommendations in other jurisdictions) (South African recommendations (tab))
• Breastfeeding (South African recommendations (tab)
• Mild to moderate renal impairment
• Hepatic impairment
• Elderly
• High doses
• Cranial or total body irradiation
• Hematopoietic cell transplantation
• Graft versus host disease
• Hepatic encephalopathy
• Impaired state of health
• Severe impairment of bone marrow function 
• History of opportunistic infection
• Immunocompromised patients
• Pre-existing skin cancer lesions
• Patients at risk of developing tumour lysis syndrome 
• History of autoimmune processes
• Childbearing potential
• Galactose intolerance (tab)
• Lapp lactase deficiency (tab)
• Glucose-galactose malabsorption (tab)

Forms avail. in SA and covered in this monograph: tab, inj

Used for the treatment of

B-cell chronic lymphocytic leukaemia
- Initial treatment
- With sufficient bone marrow reserve who have not responded to or whose disease has progressed during or after treatment with at least one standard alkylating-agent containing regimen

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Consult specialist for dosages and regimens

Not established for use in children

Pregnancy

South African recommendations

Injection

• Contraindicated

Film-coated tablet

• Caution; not recommended

Recommendations in other jurisdictions

• Caution; not recommended

Breastfeeding

South African recommendations

Injection

• Contraindicated

Film-coated tablet

• Caution; not recommended

Recommendations in other jurisdictions

• Contraindicated

Renal Impairment

• Mild to Moderate: Caution; dose adjustment recommended 
• Severe: Contraindicated

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly

• Caution; no dose adjustment recommended

Central Nervous System Disorders

• Confusion
• Coma
• Seizures
• Agitation
• Cerebral haemorrhage
• Leukoencephalopathy
• Acute toxic leukoencephalopathy
• Reversible posterior leukoencephalopathy syndrome 
• Peripheral neuropathy
• Fatigue

Cardiovascular Disorders

• Cardiac failure
• Arryhthmia

Respiratory Disorders

• Pneumonia
• Cough
• Pulmonary haemorrhage
• Pulmonary toxicity

Gastrointestinal Disorders

• Diarrhoea
• Nausea and vomiting
• Stomatitis
• Gastrointestinal haemorrhage
• Abnormal pancreatic enzymes 

Hepatobiliary Disorders

• Abnormal hepatic enzymes

Genitourinary Disorders

• Haemorrhagic cystitis

Endocrine and Metabolic Disorders

• Anorexia
• Tumour lysis syndrome

Musculoskeletal Disorders

• Weakness

Skin and Subcutaneous Tissue Disorders

• Rash
• Skin cancer
• Toxic epidermal necrolysis
• Stevens-Johnson syndrome
• Oedema
• Mucositis

Immune, Blood and Lymphatic System Disorders

• Lymphoproliferative disorder 
• Infections
• Opportunistic infections 
• Myelodysplastic syndrome 
• Acute myeloid leukaemia
• Neutropenia
• Anaemia
• Thrombocytopenia
• Myelosuppression
• Autoimmune disorder 
• Fever

Sensory Disorders

• Visual disturbances
• Blindness
• Optic neuritis
• Optic neuropathy

• Pentostatin 
• Adenosine uptake inhibitors
• Cytarabine 
• Live vaccines 

• Full blood count with differential
• Hepatic function
• Renal function

Fludarabine phosphate is dephosphorylated to 2-fluoro-ara-A which is taken up by cells and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. This metabolite has been shown to inhibit ribonucleotide reductase, DNA polymerase α/δ and ε, DNA primase and DNA ligase thereby inhibiting DNA synthesis. Furthermore, partial inhibition of RNA polymerase II and consequent reduction in protein synthesis occurs. .

Tablet 10mg

• Fludara (Sanofi) originator

Injection (per vial) 50mg/2ml

• Fludara (Sanofi) originator
• Teva Fludarabine (Teva)