given to dose reduction in patients with gross hepatic dysfunction.
Mutagenicity and carcinogenicity:-
Chlorambucil has been shown to cause chromatid or chromosome damage in man and has been shown to be carcinogenic in animals.
The possibility of a similar effect should be borne in mind when designing the long-term management of the patient.
Acute secondary haematologic malignancies (especially leukaemia and myelodysplastic syndrome) have been reported, particularly after long term treatment (see section 4.8 Undesirable Effects').
A comparison of patients with ovarian cancer, who received alkylating agents with those who did not, showed that the use of alkylating agents, including chlorambucil, significantly increased the incidence of acute leukaemia.
Acute myelogenous leukaemia has been reported in a small proportion of patients receiving chlorambucil as long term adjuvant therapy for breast cancer.
The leukaemogenic risk must be balanced against the potential therapeutic benefit when considering the use of chlorambucil.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Vaccinations with live organism vaccines are not recommended in immunocompromised individuals (see Warnings and Precautions).
Animal studies indicate that patients who receive phenylbutazone may require a reduction of the standard chlorambucil doses because of the possibility of enhanced chlorambucil toxicity.
4.6 Pregnancy and lactation
Effects on fertility:-
Chlorambucil may cause suppression of ovarian function and amenorrhoea has been reported following chlorambucil therapy.
Azoospermia has been observed as a result of therapy with chlorambucil although it is estimated that a total dose of least 400 mg is necessary.
Varying degrees of recovery of spermatogenesis have been reported in patients with lymphoma following treatment with chlorambucil in total doses of 410-2600 mg.
Teratogenicity:-
As with other cytotoxic agents Leukeran is potentially teratogenic.
Pregnancy:-
As with all cytotoxic chemotherapy, adequate contraceptive precautions should be advised when either partner is receiving Leukeran. Partners should be informed of the drugs affect on germ cells.
This product should not be used in pregnancy, particularly in the first trimester, unless considered absolutely essential by the physician.
Lactation:-
Mothers receiving Leukeran should not breast-feed.
4.7 Effects on ability to drive and use machines
No data.
4.8 Undesirable effects
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 (incl cysts and polyps):
Common: Acute secondary haematologic malignancies (especially leukaemia and myelodysplastic syndrome), particularly after long term treatment.
Blood and lymp |
