he following convention has been utilised for the classification of frequency: Very common ( 1/10), common ( 1/100 and <1/10), uncommon ( 1/1000 and <1/100), rare ( 1/10,000 and <1/1000) and very rare ( <1/10,000).
Neoplasms, benign, malignant and unspecified (incl cysts and polyps):
Common: Acute secondary haematologic malignancies (especially leukaemia and myelodysplastic syndrome), particularly after long term treatment.
Blood and lymphatic system disorders
Very common: Leucopenia, neutropenia, thrombocytopenia, panyctopenia or bone marrow suppression.
Common: Anaemia
Very rare: Irreversible bone marrow failure.
Although bone marrow suppression frequently occurs, it is usually reversible if chlorambucil is withdrawn early enough.
Immune system disorders
Uncommon: Rash.
Rare: Allergic reactions such as urticaria and angioneurotic oedema following initial or subsequent dosing.
Stevens-Johnson syndrome and toxic epidermal necrolysis.
(See Skin and subcutaneous tissue disorders)
On rare occasions skin rash has been reported to progress to serious conditions including Stevens-Johnson syndrome and toxic epidermal necrolysis.
Nervous system disorders
Common: Seizures in children with nephrotic syndrome.
Rare: Seizures#, focal and/or generalised in children and adults receiving therapeutic daily doses or high pulse dosing regimens of chlorambucil.
Very rare: Movement disorders including tremor, twitching and myoclonia in the absence of convulsions. Peripheral neuropathy.
#Patients with a history of seizure disorder may be particularly susceptible.
Respiratory, thoracic and mediastinal disorders
Very rare: Interstitial pulmonary fibrosis, interstitial pneumonia.
Severe interstitial pulmonary fibrosis has occasionally been reported in patients with chronic lymphocytic leukaemia on long term chlorambucil therapy. Pulmonary fibrosis may be reversible on withdrawal of chlorambucil.
Gastrointestinal disorders
Common: Gastro-intestinal disturbances such as nausea and vomiting, diarrhoea and oral ulceration.
Hepatobiliary disorders
Rare: Hepatoxicity, jaundice.
Skin and subcutaneous tissue disorders
Uncommon: Rash.
Rare: Allergic reactions such as urticaria and angioneurotic oedema following initial or subsequent dosing.
Stevens-Johnson syndrome and toxic epidermal necrolysis.
(See Immune system disorders)
On rare occasions skin rash has been reported to progress to serious conditions including Stevens-Johnson syndrome and toxic epidermal necrolysis.
Renal and urinary disorders
Very rare: Sterile cystitis.
General disorders and administration site conditions
Rare: Drug fever.
4.9 Overdose
Symptoms and signs:
Reversible pancytopenia was the main finding of inadvertent overdoses of chlorambucil.
Neurological toxicity ranging from agitated behaviour and ataxia to multiple grand mal seizures has also occurred. As there is no known antidote the blood picture should be closely monitored and general supportive measures should be instituted, together with appropriate blood transfusion if necessary.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic Group: Alkylating agents, nitrogen mustard analogue
