Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2012 Publisher: Aspen Pharma Trading Limited 12/13 Exchange Place I.F.S.C Dublin 1 Ireland
Hypersensitivity to chlorambucil or to any of the excipients.
Continued treatment with chlorambucil should be assessed if a rash develops since there have been reports of Stevens-Johnson Syndrome in patients receiving chlorambucil (see section 4.8).
Leukeran is an active cytotoxic agent for use only under the direction of physicians experienced in the administration of such agents.
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.
Patients with evidence of impaired renal function should be carefully monitored as they are prone to additional myelosuppression associated with azotaemia.
The metabolism of Leukeran is still under investigation and consideration should be given to dose reduction in patients with gross hepatic dysfunction.
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 (see Section 4.8).
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.
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.
Vaccinations with live organism vaccines are not recommended in immunocompromised individuals (see Section 4.4 Special Warnings and Precautions for use).
Patients receiving phenylbutazone may require a reduced dose of Leukeran.
As with other cytotoxic agents Leukeran is potentially teratogenic. The use of Leukeran should be avoided whenever possible during pregnancy, particularly during the first trimester. In any individual case, the potential hazard to the foetus must be balanced against the expected benefit to the mother.
As with all cytotoxic chemotherapy, adequate contraceptive precautions should be advised when either partner is receiving Leukeran.
Mothers receiving Leukeran should not breast feed.
None known.
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).
Common: Acute secondary haematologic malignancies (especially leukaemia and myelodysplastic syndrome), particularly after long term treatment.
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.
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.
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.
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.
Common: Gastro-intestinal disturbances such as nausea and vomiting, diarrhoea and oral ulceration.
Rare: Hepatoxicity, jaundice.
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.
Very rare: Sterile cystitis.
Rare: Drug fever.
None known.
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