Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2015 Publisher: Aspen Pharma Trading Limited, 3016 Lake Drive, Citywest Business Campus, Dublin 24, Ireland
Chlorambucil is indicated in the treatment of Hodgkin’s disease, certain forms of non-Hodgkin’s lymphoma, chronic lymphocytic leukaemia, and Waldenstrom’s macroglobulinaemia.
The relevant literature should be consulted for full details of the treatment schedules used.
Chlorambucil is an active cytotoxic agent for use only under the direction of physicians experienced in the administration of such agents.
Used as a single agent in the palliative treatment of advanced disease a typical dosage is 0.2 mg/kg/day for 4-8 weeks. Chlorambucil is usually included in combination therapy and a number of regimes have been used. Chlorambucil has been used as an alternative to nitrogen mustard with a reduction in toxicity but similar therapeutic results.
Chlorambucil may be used in the management of Hodgkin’s disease in children. The dosage regimes are similar to those used in adults.
Used as a single agent the usual dosage is 0.1-0.2 mg/kg/day for 4-8 weeks initially, maintenance therapy is then given either by a reduced daily dosage or intermittent courses of treatment.
Chlorambucil is useful in the management of patients with advanced diffuse lymphocytic lymphoma and those who have relapsed after radiotherapy. There is no significant difference in the overall response rate obtained with chlorambucil as a single agent and combination chemotherapy in patients with advanced non-Hodgkin’s lymphocytic lymphoma.
Chlorambucil may be used in the management of non Hodgkin’s disease in children. The dosage regimes are similar to those used in adults.
Treatment with Chlorambucil is usually started after the patient has developed symptoms or when there is evidence of impaired bone marrow function (but not bone marrow failure) as indicated by the peripheral blood count. Initially Chlorambucil is given at a dosage of 0.15 mg/kg/day until the total leucocyte count has fallen to 10,000 per µL. Treatment may be resumed 4 weeks after the end of the first course and continued at a dosage of 0.1 mg/kg/day.
In a proportion of patients, usually after about 2 years of treatment, the blood leucocyte count is reduced to the normal range, enlarged spleen and lymph nodes become impalpable and the proportion of lymphocytes in the bone marrow is reduced to less than 20%.
Patients with evidence of bone marrow failure should first be treated with prednisolone and evidence of marrow regeneration should be obtained before commencing treatment with Chlorambucil. Intermittent high dose therapy has been compared with daily Chlorambucil but no significant difference in therapeutic response or frequency of side effects was observed between the two treatment groups.
Chlorambucil is one of the treatment choices in this indication.
Starting doses of 6-12 mg daily until leukopenia occurs are recommended followed by 2-8 mg daily indefinitely.
Dose adjustment is not considered necessary in renal impaired patients.
Patients with evidence of impaired renal function should be carefully monitored as they are prone to additional myelosuppression associated with azotaemia.
Patients with hepatic impairment should be closely monitored for signs and symptoms of toxicity.
Since chlorambucil is primarily metabolized in the liver, dose reduction should be considered in patients with severe hepatic impairment. However, there are insufficient data in patients with hepatic impairment to provide a specific dosing recommendation.
No specific studies have been carried out in older people, however, it may be advisable to monitor renalor hepatic function and if there is impairment then caution should be exercised.
While clinical experience has not revealed age-related differences in response, drug dosage generally should be titrated carefully in older patients, usually initiating therapy at the low end of the dosage range.
Chlorambucil tablets are administered orally and should be taken daily on an empty stomach (at least one hour before meals or three hours after meals).
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.
Shelf life: 3 years.
Store in a refrigerator (2°C-8°C).
Chlorambucil tablets are brown, round, biconvex, film-coated tablets, one side engraved with ‘L’ and the other side engraved ‘GX EG3’, supplied in amber glass bottles with a child resistant closure containing 25 tablets.
Chlorambucil is an active cytotoxic agent for use only under the direction of physicians experienced in the administration of such agents.
The handling of Chlorambucil Tablets should follow guidelines for the handling of cytotoxic drugs according to prevailing local recommendations and/or regulations (for example, Royal Pharmaceutical Society of Great Britain Working Party on the Handling of Cytotoxic Drugs).
Provided that the outer coating of the tablet is intact, there is no risk in handling Chlorambucil Tablets.
Chlorambucil Tablets should not be divided.
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