Chlorambucil

Registered South African indications:

• Hodgkin’s disease
• Certain forms of non-Hodgkin’s lymphoma
• Chronic lymphocytic leukaemia
• Waldenstrom’s macroglobulinaemia

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients

Cautions

• Pregnancy
• Breastfeeding
• Men and women of childbearing potential
• Renal impairment
• Hepatic impairment
• Elderly
• Children with nephrotic syndrome
• High pulse dosing regimens
• History of seizure disorder
• Recent radiotherapy
• Prior administration of other cytotoxic agents
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption

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

Used for the treatment of

• Hodgkin’s disease
• Non-Hodgkin’s lymphoma
• Chronic lymphocytic leukaemia
• Waldenstrom’s macroglobulinaemia

Consult specialist for dosages and regimens

Paed. forms avail. In SA and covered in this monograph: tab

Used for the treatment of

Hodgkin’s disease
Non-Hodgkin’s lymphoma

Consult specialist for dosages and regimens

Pregnancy

• Caution
• As with all cytotoxic therapy chemotherapy, adequate contraceptive precautions should be advised when either partner is receiving chlorambucil
• As with other cytotoxic agents, chlorambucil is potentially teratogenic
• The use of chlorambucil should be avoided whenever possible during pregnancy, particularly during the first trimester. In any individual case, the potential hazard to the foetus must be balanced against the expected benefit to the mother

Breastfeeding

• Caution; not recommended
• Mothers receiving chlorambucil should not breastfeed

Fertility

• Chlorambucil may cause suppression of ovarian function and amenorrhoea has been reported following chlorambucil therapy
• Azoospermia has been observed as a result of therapy with chlorambucil although it is estimated that a total dose of at least 400mg is necessary
• Varying degrees of recovery of spermatogenesis have been reported in patients with lymphoma following treatment with chlorambucil in total doses of 410-2600mg

Renal Impairment

• Caution; no dose adjustment recommended
  Patients with evidence of impaired renal function should be carefully monitored as they are prone to additional myelosuppression associated with azotaemia

Hepatic Impairment

• Mild to moderate: Caution; no dose adjustment recommended
• Severe: Caution; dose adjustment recommended
  Insufficient data to provide a specific dosing recommendation. Patients with hepatic impairment should be closely monitored for signs and symptoms of toxicity

Elderly            

• Caution; no information available
  Monitor renal and hepatic function and exercise caution if impairment is present. Initiate therapy at the low end of the dosing range

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Seizures
• Movement disorders
  - Tremor
  - Muscle twitching
  - Myoclonus in the absence of convulsions
• Peripheral neuropathy

Respiratory Disorders

• Interstitial pulmonary fibrosis
• Interstitial pneumonia

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Mouth ulceration

Hepatobiliary Disorders

• Hepatoxicity
• Jaundice

Genitourinary Disorders

• Sterile cystitis
• Amenorrhoea
• Azoospermia

Skin and Subcutaneous Tissue Disorders

• Rash
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis

Immune, Blood and Lymphatic System Disorders

• Acute secondary haematologic malignancies
• Leukaemia
• Myelodysplastic syndrome
• Leukopenia
• Neutropenia
• Thrombocytopenia
• Pancytopenia  
• Bone marrow suppression
• Anaemia
• Irreversible bone marrow failure
• Hypersensitivity
• Urticaria
• Angioneurotic oedema  
• Fever

• Live vaccines
• Purine nucleoside analogues 
• Fludarabine
• Pentostatin
• Cladribine

• Hepatic function
• Full blood count with differential

Mutagenicity and Carcinogenicity

• Chlormabucil has been shown to cause chromatid or chromosome damage in man
• Secondary malignancies, most commonly acute secondary haematologic malignancies (especially leukaemia and myelodysplastic syndrome) have been reported, particularly after long term treatment
• A comparison of patients with ovarian cancer who received alkylating agents with those who did not, showed that the use of alkylating agents, including chlorambucil, significantly increased the incidence of acute leukaemia
• Acute myelogenous leukaemia has been reported in a small proportion of patients receiving chlorambucil as long term adjuvant therapy for breast cancer
• The leukemogenic risk must be balanced against the therapeutic benefit when considering the use of chlorambucil

Chlorambucil is an aromatic nitrogen mustard derivative which acts as a bifunctional alkylating agent. In addition to interference with DNA replication, chlorambucil induces cellular apoptosis via the accumulation of cytosolic p53 and subsequent activation of an apoptosis promoter (Bax).

Tablet 2mg

• Leukeran (Pharmacare)