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LEUKERAN is a brand name for Chlorambucil, supplied as a tablet. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: LEUKERAN® (chlorambucil) is indicated as monotherapy in the treatment of chronic lymphocytic leukemia. It is also indicated as monotherapy or in combination with other agents in non-Hodgkin’s lymphomas including follicular lymphoma, indolent lymphoma, MALT-lymphoma, mantle-cell lymphoma; Waldenström’s…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations Geriatrics: While clinical experience has not revealed age-related differences in response, drug dosage should be titrated carefully in older patients, usually initiating therapy at the low end of the dosage range (See ACTION AND CLINICAL PHARMACOLOGY/Pharmacokinetics/Special Populations and Conditions).
Hepatic Insufficiency: 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 (See ACTION AND CLINICAL PHARMACOLOGY/Pharmacokinetics/Special Populations and Conditions).
2 Recommended Dose and Dosage Adjustment Chlorambucil tablets are administered orally and should be taken daily on an empty stomach (at least one hour before meals or three hours after meals). Chronic Lymphocytic Leukemia Treatment with LEUKERAN® (chlorambucil) is usually started after the patient has developed symptoms or when there is evidence of impaired bone marrow function (but not marrow failure) as indicated by the peripheral blood count.
15 mg/kg/day until the total leukocyte count is formed to 10 000 per μL. 1 mg/kg/day. In a proportion of patients, usually after about two years of treatment, the blood leukocyte 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 chlorambucil but no significant difference in therapeutic response or frequency of side effects was observed between the two treatment groups.
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. © 2019 Aspen Group of companies or its licensor. All rights reserved. Page 6 of 20 LEUKERAN® is useful in the management of patients with advanced 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. 2 mg/kg/day for 4-8 weeks. LEUKERAN® is usually included in combination therapy and a number of regimes have been used.
1 Adverse Reaction Overview 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.
2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse drug reaction information © 2019 Aspen Group of companies or its licensor. All rights reserved. Page 10 of 20 from clinical trials is useful for identifying drug-related adverse events and for approximating rates. 01%); Not known (cannot be estimated from the available data).
Body System Side Effects Neoplasms benign, malignant and unspecified (including cysts and polyps) Common Acute secondary hematologic malignancies (especially leukemia and myelodysplastic syndrome), particularly after long term treatment.
Blood and lymphatic system disorders Very common Leukopenia, neutropenia, thrombocytopenia, pancytopenia or bone marrow suppression1. Common Anaemia. Very rare Irreversible bone marrow failure. Immune system disorders Rare Hypersensitivity such as urticaria and angioneurotic oedema following initial or subsequent dosing.
(See Skin and subcutaneous tissue disorders) Nervous system disorders Common Seizures in the paediatric population with nephrotic syndrome. Rare Convulsions 2, partial and/or generalised in the paediatric population 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. Respiratory, thoracic and mediastinal disorders Very rare Interstitial pulmonary fibrosis3, interstitial pneumonia.
Please see the Serious Warnings and Precautions Box at the beginning of Part I:
Health Professional Information. General LEUKERAN® (chlorambucil), a derivative of nitrogen mustard, is a potent drug. It is for use only under the direction of physicians experienced in the administration of cancer chemotherapeutic drugs.
Patients who will potentially have autologous stem cell transplantation should not be treated with chlorambucil long term. 1 mg/kg body weight. Carcinogenesis and Mutagenesis Acute secondary hematologic malignancies (especially leukemia and myelodysplastic syndrome) have been reported, particularly after long term treatment (see ADVERSE REACTIONS).
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 leukemia. Acute myelogenous leukemia has been reported in a small proportion of patients receiving chlorambucil as long-term adjuvant therapy for breast cancer.
The leukemogenic risk must be balanced against the potential therapeutic benefit when considering the use of chlorambucil. Driving and Operating Machinery Due caution should be exercised when driving or operating a vehicle or potentially dangerous machinery.
Hematologic Blood counts should be taken once or twice weekly. Discontinue or reduce the dosage upon evidence of abnormal depression of the bone marrow (see Monitoring and Laboratory Tests). © 2019 Aspen Group of companies or its licensor.
All rights reserved. Page 8 of 20 Hepatic/Biliary/Pancreatic Consideration should be given to dose reduction in patients with gross hepatic dysfunction. Immune Immunisation using a live organism vaccine has a potential to cause infection in immunocompromised hosts.
Patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container. For a complete listing, see the DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING section of the product monograph.
LEUKERAN® (chlorambucil) should not be administered to patients who are resistant to the drug or who have developed hypersensitivity to it. There may be cross-hypersensitivity (skin rash) between chlorambucil and other alkylating agents.
Chlorambucil should not be used within four weeks of a full course of radiation or chemotherapy.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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LEUKERAN® may also be used as an alternative to nitrogen mustard with a reduction in toxicity but similar therapy results. Waldenström's Macroglobulinaemia LEUKERAN® is the one of the treatment choices in this indication. 1 mg/kg/day PO Health Canada has not authorized an indication for pediatric (<18 years of age) use.
(see INDICATIONS/Pediatrics)
Gastrointestinal disorders Common Gastro-intestinal disorders such as nausea and vomiting, diarrhoea and mouth ulceration. Hepatobiliary disorders Rare Hepatoxicity, jaundice. Skin and subcutaneous tissue disorders Uncommon Rash. Rare Stevens-Johnson syndrome, toxic epidermal necrolysis4.
(See Immune system disorders) Renal and urinary disorders Very rare Sterile cystitis. Reproductive system and breast disorders Not known Amenorrhoea, azoospermia, infertility. General disorders and administration site conditions Rare Pyrexia.
1. Although bone marrow suppression frequently occurs, it is usually reversible if the chlorambucil is withdrawn early enough. However, irreversible bone marrow failure has been reported. (See Serious WARNINGS AND PRECAUTIONS) © 2019 Aspen Group of companies or its licensor.
All rights reserved. Page 11 of 20 2. Patients with a history of seizure disorder may be particularly susceptible (see WARNINGS AND PRECAUTIONS/Neurologic). 3. Severe interstitial pulmonary fibrosis has occasionally been reported in patients with chronic lymphocytic leukemia on long-term chlorambucil therapy.
Pulmonary fibrosis may be reversible on withdrawal of chlorambucil. (see WARNINGS AND PRECAUTIONS/Respiratory) 4. Skin rash has been reported to progress to serious conditions including Stevens-Johnson syndrome and toxic epidermal necrolysis.
(see WARNINGS AND PRECAUTIONS/Skin)
Therefore, immunisations with live organism vaccines are not recommended. Monitoring and Laboratory Tests Since LEUKERAN® (chlorambucil) is capable of producing irreversible bone marrow depression, blood counts should be monitored once or twice weekly in patients under treatment.
At therapeutic dosage, LEUKERAN® depresses lymphocytes and has less effect on neutrophil and platelet counts and on hemoglobin 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.
Neurologic Patients with nephrotic syndrome, patients prescribed high pulse dose 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.
As with any potentially epileptogenic drug, caution should be exercised when administering chlorambucil to patients with a history of seizure disorder, head trauma, or receiving other potentially epileptogenic drugs. Renal Patients with evidence of impaired renal function should be carefully monitored as they are prone to additional myelosuppression associated with azotemia.
Respiratory Severe interstitial pulmonary fibrosis has been reported in patients with chronic lymphocytic leukemia on long-term chlorambucil therapy. Pulmonary fibrosis may be reversible on withdrawal of chlorambucil. Sexual Function/Reproduction Chlorambucil may cause suppression of ovarian function.
Amenorrhea 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 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 to 2600 mg.
As with other cytotoxic agents LEUKERAN® is potentially teratogenic. © 2019 Aspen Group of companies or its licensor. All rights reserved. Page 9 of 20 As with all cytotoxic chemotherapy, adequate contraceptive precautions should be advised when either partner is receiving chlorambucil.
Chlorambucil has been shown to cause chromatid or chromosome damage in man. Skin Rare instances of skin rash progressing to erythema multiforme, toxic epidermal necrolysis, or Stevens-Johnson syndrome have been reported. Chlorambucil should be discontinued promptly in patients who develop skin reactions.
1 Pregnant Women The use of chlorambucil should be avoided whenever possible during pregnancy. However, when cytotoxic drugs are used in pregnancy, the possible teratogenic effect on the fetus should be kept in mind. It is therefore advisable to delay treatment with these drugs as long as possible and certainly until after the first three months of pregnancy.
In any individual case, the potential hazard to the fetus must be balanced against the expected benefit to the mother. 2 Breast-feeding Mothers receiving LEUKERAN® should not breast feed. It is unknown if the drug is excreted in human milk.
Because many drugs are excreted in human milk precaution should be exercised. 3 Pediatrics Pediatrics (< 18 years of age): The safety and effectiveness in children have not been established. 4 Geriatrics Geriatrics (> 65 years of age): No data is available.