Chlorambucil (Specialist drug)

Source: UK SPC (eMC) §4.2 for Chlorambucil 2 mg tablets (https://www.medicines.org.uk/emc/product/4656/smpc). VERBATIM (CLL): 'Initially Chlorambucil is given at a dosage of 0.15 mg/kg/day until the total leucocyte count has fallen to 10,000 per microlitre. Treatment may be resumed 4 weeks after the end of the first course and continued at a dosage of 0.1 mg/kg/day.' VERBATIM (Hodgkin's disease): '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.' VERBATIM (non-Hodgkin's lymphoma): '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.' WALDENSTROM'S MACROGLOBULINAEMIA (adults): 'Starting doses of 6-12 mg daily until leukopenia occurs are recommended followed by 2-8 mg daily indefinitely.' SUPERVISION: '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.' CLL — patients with evidence of bone marrow failure should first be treated with prednisolone, and evidence of marrow regeneration should be obtained before commencing chlorambucil; intermittent high-dose therapy showed no significant difference in therapeutic response or side-effect frequency versus daily dosing. MONITORING: blood counts should be closely monitored — chlorambucil is capable of producing irreversible bone marrow suppression; discontinuation is not necessary at the first sign of a fall in neutrophils, but the fall may continue for 10 days or more after the last dose. Chlorambucil should not be given to patients who have recently undergone radiotherapy or received other cytotoxic agents. Patients who will potentially have autologous stem cell transplantation should not be treated with chlorambucil long term. Assess continued treatment if a rash develops (Stevens-Johnson syndrome has been reported). HEPATIC IMPAIRMENT: monitor closely for signs and symptoms of toxicity; as chlorambucil is primarily metabolised in the liver, dose reduction should be considered in severe hepatic impairment, but there are insufficient data to provide a specific dosing recommendation. OLDER PEOPLE: no specific studies; monitor renal or hepatic function and exercise caution if impaired; titrate dose carefully, usually initiating at the low end of the dosage range. PAEDIATRIC — NON-NUMERIC, so paedDose is null: the SPC states for both Hodgkin's disease and non-Hodgkin's lymphoma that 'Chlorambucil may be used in the management of [the disease] in children. The dosage regimes are similar to those used in adults' — it gives NO separate paediatric figure, and the US LEUKERAN label states 'The safety and effectiveness in pediatric patients have not been established.' Any under-18 dose must be verified against a children's formulary and specialist protocol. The SPC also warns that children with nephrotic syndrome, patients on high pulse dosing regimens and patients with a history of seizure disorder should be closely monitored, as they may have an increased risk of seizures. SUGAR INTOLERANCE: patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medication. HANDLING: procedures for the proper handling and disposal of anticancer drugs should be used (SPC §6.6). US CROSS-CHECK (LEUKERAN, Waylis Therapeutics LLC, 2025-01-08): 'The usual oral dosage is 0.1 to 0.2 mg/kg body weight daily for 3 to 6 weeks as required. This usually amounts to 4 to 10 mg per day for the average patient... Patients with Hodgkin's disease usually require 0.2 mg/kg daily, whereas patients with other lymphomas or chronic lymphocytic leukemia usually require only 0.1 mg/kg daily.' The US label also describes intermittent CLL schedules beginning with an initial single dose of 0.4 mg/kg, increased generally by 0.1 mg/kg until control of lymphocytosis or toxicity is observed, and states that if a maintenance dosage is used it should not exceed 0.1 mg/kg daily and may be as low as 0.03 mg/kg daily (typical maintenance 2 mg to 4 mg daily or less). NOTE: the US and UK schedules differ in detail — the UK SPC values above are the primary source. The §4.8 adverse-effects table and the US adverse reactions section were truncated at the source-fetch limit.