Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2015 Publisher: Aspen Pharma Trading Limited, 3016 Lake Drive, Citywest Business Campus, Dublin 24, Ireland
Hypersensitivity to chlorambucil or to any of the excipients listed in section 6.1.
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).
Safe Handling of Chlorambucil tablets: See section 6.6.
Immunisation using a live organism vaccine has the potential to cause infection in immunocompromised hosts. Therefore, immunisations with live organism vaccines are not recommended.
Patients who will potentially have autologous stem cell transplantation should not be treated with chlorambucil long term.
Since Chlorambucil is capable of producing irreversible bone marrow suppression, blood counts should be closely monitored in patients under treatment.
At therapeutic dosage Chlorambucil depresses lymphocytes and has less effect on neutrophil and platelet counts and on haemoglobin levels. Discontinuation of Chlorambucil 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.
Chlorambucil 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 Chlorambucil, as they may have an increased risk of seizures.
Chlorambucil 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 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 medication.
Vaccinations with live organism vaccines are not recommended in immunocompromised individuals (see section 4.4).
Purine nucleoside analogues (such as fludarabine, pentostatin and cladribine) increased the cytotoxicity of chlorambucil ex vivo; however, the clinical significance of this finding is unknown.
As with all cytotoxic therapy chemotherapy, adequate contraceptive precautions should be advised when either partner is receiving Chlorambucil.
The use of Chlorambucil 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.
Mothers receiving Chlorambucil should not breast feed.
Chlorambucil may cause suppression of ovarian function and amenorrhoea has been reported following chlorambucil therapy.
Azoospermia have been observed as a result of therapy with chlorambucil although it is estimated that a total dose of at 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.
As with other cytotoxic agents Chlorambucil is potentially teratogenic.
No information on the effects of Chlorambucil on the ability to drive and use machines is available.
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), not known (cannot be estimated from the available data).
Common: Acute secondary haematologic malignancies (especially leukaemia and myelodysplastic syndrome), particularly after long term treatment.
Very common: Leukopenia, neutropenia, thrombocytopenia, pancytopenia or bone marrow suppression1.
Common: Anaemia.
Very rare: Irreversible bone marrow failure.
Rare: Hypersensitivity such as urticaria and angioneurotic oedema following initial or subsequent dosing.
(See Skin and subcutaneous tissue disorders)
Common: Convulsions in children with nephrotic syndrome.
Rare: Convulsions2, partial and/or generalised in children and adults receiving therapeutic daily doses or high pulse dosing regimens of chlorambucil.
Very rare: Movement disorders including tremor, muscle twitching and myoclonus in the absence of convulsions. Peripheral neuropathy.
Very rare: Interstitial pulmonary fibrosis3, interstitial pneumonia.
Common: Gastro-intestinal disorders such as nausea and vomiting, diarrhoea and mouth ulceration.
Rare: Hepatoxicity, jaundice.
Uncommon: Rash.
Rare: Stevens-Johnson syndrome, toxic epidermal necrolysis4 (see Immune system disorders)
Very rare: Sterile cystitis.
Not known: Amenorrhoea, azoospermia.
Rare: Pyrexia.
1 Although bone marrow suppression frequently occurs, it is usually reversible if Chlorambucil is withdrawn early enough.
2 Patients with a history of seizure disorder may be particularly susceptible.
3 Severe interstitial pulmonary fibrosis has occasionally been reported in patients with chronic lymphocytic leukaemia on long-term Chlorambucil therapy. However, this may be reversible on withdrawal of Chlorambucil.
4 Skin rash has been reported to progress to serious conditions including Stevens-Johnson syndrome and toxic epidermal necrolysis.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.
None known.
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