Posology : מינונים

4.2 Posology and method of administration

THE RELEVANT LETERATURE 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.

Posology

HODGKIN'S DISEASE
Adults

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.

Paediatric population

Leukeran may be used in the management of Hodgkin’s disease in children. The dosage regimes are similar to those used in adults.
NON-HODGKIN'S LYMPHOMA

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.

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.

Paediatric population

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


CHRONIC LYMPHOCYTIC LEUKAEMIA
Adults

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%.

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.


WALDENDSTROM'S MACROGLOBULINAEMIA
Adults
Leukeran 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.

SPECIAL POPULATIONS

Renal impairment
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.

Hepatic impairment:
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.
Older people
No specific studies have been carried out in older people, however, it may be advisable to monitor renal or 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.

Method of administration

Leukeran tablets are administered orally and should be taken daily on an empty stomach (at least one hour before meals or three hours after meals).