hatic 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Although bone marrow suppression frequently occurs, it is usually reversible if chlorambucil is withdrawn early enough.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 analogues
ATC Code: L01AA02
Chlorambucil is an aromatic nitrogen mustard derivative which acts as a bifunctional alkylating agent. Alkylation takes place through the formation of a highly reactive ethylenimonium radical. A probable mode of action involves cross-linkage of the ethylenimonium derivative between 2 strands of helical DNA and subsequent interference with replication.
5.2 Pharmacokinetic properties
In a study of 12 patients administered chlorambucil 0.2 mg/kg bodyweight orally, the mean dose adjusted maximum plasma concentration (492 ± 160 ng/ml) occurred between 0.25 and 2 hours aft |
