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Drug Details

LEUKERAN Tablets 2 mg

• Drug Class Description
  bifunctional alkylating agent
• Generic Name
  chlorambucil
• Presentation
  Film-coated tablet
• Description
  Each tablet contains 2 mg of the active ingredient chlorambucil.
• Indications
  

  Leukeran is indicated in the treatment of Hodgkin's disease, certain forms of non-Hodgkin's lymphoma, chronic lymphocytic leukaemia, and Waldenstrom's macroglobulinaemia.

• Adult Dosage
  

  Adults:  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. Leukeran is usually included in combination therapy and a number of regimes have been used. Leukeran has been used as an alternative to nitrogen mustard with a reduction in toxicity but similar therapeutic results.

  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. Leukeran 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.

  Chronic Lymphocytic Leukaemia: Treatment with Leukeran 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 Leukeran 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 per cent. 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 Leukeran. Intermittent high dose therapy has been compared with daily Leukeran but no significant difference in therapeutic response or frequency of side effects was observed between the two treatment groups.

  Waldenstrom's Macroglobulinaemia: Leukeran is the treatment of choice in this indication. Starting doses of 6-12 mg daily until leucopenia occurs are recommended followed by 2-8 mg daily indefinitely.

• Child Dosage
  

  Leukeran may be used in the management of Hodgkin's disease and non-Hodgkin's lymphomas in children. The dosage regimes are similar to those used in adults.

• Elderly Dosage
  

  No specific studies have been carried out in the elderly, however, it may be advisable to monitor renal or hepatic function and if there is serious impairment then caution should be exercised.

• Contra Indications
  

  Hypersensitivity to chlorambucil or to any of the excipients.

• Special Precautions
  

  Continued treatment with chlorambucil should be assessed if a rash develops since there have been reports of Stevens-Johnson Syndrome in patients receiving chlorambucil.

  Leukeran is an active cytotoxic agent for use only under the direction of physicians experienced in the administration of such agents.

  Safe Handling of Leukeran tablets:

  See 6.6 Instructions for Use/Handling

  Immunisation using a live organism vaccine has the potential to cause infection in immunocompromised hosts. Therefore, immunisations with live organism vaccines are not recommended.

  Monitoring: Since Leukeran is capable of producing irreversible bone marrow suppression, blood counts should be closely monitored in patients under treatment.

  At therapeutic dosage Leukeran depresses lymphocytes and has less effect on neutrophil and platelet counts and on haemoglobin levels. Discontinuation of Leukeran is not necessary at the first sign of a fall in neutrophils but it must be remembered that the fall may continue for 10 days or more after the last dose.

  Leukeran should not be given to patients who have recently undergone radiotherapy or received other cytotoxic agents.

  When lymphocytic infiltration of the bone marrow is present or the bone marrow is hypoplastic, the daily dose should not exceed 0.1 mg/kg body weight.

  Children with nephrotic syndrome, patients prescribed high pulse dosing regimens and patients with a history of seizure disorder, should be closely monitored following administration of Leukeran, as they may have an increased risk of seizures.

  Renal impairment:

  Patients with evidence of impaired renal function should be carefully monitored as they are prone to additional myelosuppression associated with azotaemia.

  Hepatic impairment:

  The metabolism of Leukeran is still under investigation and consideration should be given to dose reduction in patients with gross hepatic dysfunction.

  Mutagenicity and Carcinogenicity:

  Leukeran 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 Leukeran, significantly increased the incidence of acute leukaemia.

  Acute myelogenous leukaemia has been reported in a small proportion of patients receiving Leukeran as long term adjuvant therapy for breast cancer.

  The leukaemogenic risk must be balanced against the potential therapeutic benefit when considering the use of Leukeran.

  Sugar intolerances:

  Patients with rare hereditary problems of glucose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medication. Each Leukeran 2mg tablet contains 68mg of lactose.

• Interactions
  

  Vaccinations with live organism vaccines are not recommended in immunocompromised individuals.

  Patients receiving phenylbutazone may require a reduced dose of Leukeran.

• Adverse Drug Reactions
  

  For this product there is no modern clinical documentation which can be used as support for determining the frequency of undesirable effects. Undesirable effects may vary in their incidence depending on the dose received and also when given in combination with other therapeutic agents.

  The 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 (including 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, pancytopenia or bone marrow suppression.
  Common:	Anaemia.
  Very rare:	Irreversible bone marrow failure.
  Although bone marrow suppression frequently occurs, it is usually reversible if Leukeran 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 Leukeran therapy. However, this may be reversible on withdrawal of Leukeran.

  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.