Leukeran (chlorambucil)

WARNING

Leukeran (chlorambucil) can severely suppress bone marrow function. Chlorambucil is a carcinogen in humans. Chlorambucil is probably mutagenic and teratogenic in humans. Chlorambucil produces human infertility.

Leukeran may cause serious side effects including:

• hives,
• difficulty breathing,
• swelling of your face, lips, tongue, or throat,
• seizures,
• unusual mass or lump,
• severe vomiting or diarrhea,
• new or worsening cough,
• easy bruising,
• unusual bleeding (nose, mouth, vagina, or rectum),
• purple or red pinpoint spots under skin,
• nausea,
• upper stomach pain,
• itching,
• tiredness,
• loss of appetite,
• dark urine,
• clay-colored stools,
• yellowing of the skin or eyes (jaundice),
• fever,
• swollen gums,
• painful mouth sores,
• pain when swallowing,
• skin sores,
• cold or flu symptoms,
• cough,
• trouble breathing,
• sore throat,
• skin pain, and
• a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling

Get medical help right away, if you have any of the symptoms listed above.

The most common side effects of Leukeran include:

• fever,
• bleeding, and
• flu symptoms

Tell the doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Leukeran. For more information, ask your doctor or pharmacist.

• The usual oral dosage is 0.1 to 0.2 mg/kg body weight daily for 3 to 6 weeks as required. This usually amounts to 4 to 10 mg per day for the average patient.
• The entire daily dose may be given at one time. These dosages are for initiation of therapy or for short courses of treatment.
• The dosage must be carefully adjusted according to the response of the patient and must be reduced as soon as there is an abrupt fall in the white blood cell count.
• Patients with Hodgkin’s disease usually require 0.2 mg/kg daily, whereas patients with other lymphomas or chronic lymphocytic leukemia usually require only 0.1 mg/kg daily.
• When lymphocytic infiltration of the bone marrow is present, or when the bone marrow is hypoplastic, the daily dose should not exceed 0.1 mg/kg (about 6 mg for the average patient).
• Alternate schedules for the treatment of chronic lymphocytic leukemia employing intermittent, biweekly, or oncemonthly pulse doses of chlorambucil have been reported.
• Intermittent schedules of chlorambucil begin with an initial single dose of 0.4 mg/kg.
• Doses are generally increased by 0.1 mg/kg until control of lymphocytosis or toxicity is observed. Subsequent doses are modified to produce mild hematologic toxicity.
•  It is felt that the response rate of chronic lymphocytic leukemia to the biweekly or once-monthly schedule of chlorambucil administration is similar or better to that previously reported with daily administration and that hematologic toxicity was less than or equal to that encountered in studies using daily chlorambucil.
• Radiation and cytotoxic drugs render the bone marrow more vulnerable to damage, and chlorambucil should be used with particular caution within 4 weeks of a full course of radiation therapy or chemotherapy. However, small doses of palliative radiation over isolated foci remote from the bone marrow will not usually depress the neutrophil and platelet count. In these cases chlorambucil may be given in the customary dosage.
• It is presently felt that short courses of treatment are safer than continuous maintenance therapy, although both methods have been effective.
• It must be recognized that continuous therapy may give the appearance of “maintenance” in patients who are actually in remission and have no immediate need for further drug.
• If maintenance dosage is used, it should not exceed 0.1 mg/kg daily and may well be as low as 0.03 mg/kg daily. A typical maintenance dose is 2 mg to 4 mg daily, or less, depending on the status of the blood counts. It may, therefore, be desirable to withdraw the drug after maximal control has been achieved, since intermittent therapy reinstituted at time of relapse may be as effective as continuous treatment.
• Procedures for proper handling and disposal of anticancer drugs should be used. Several guidelines on this subject have been published.^1-4 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

Special Populations

Hepatic Impairment

• Patients with hepatic impairment should be closely monitored for toxicity.
• As chlorambucil is primarily metabolized in the liver, dose reduction may be considered in patients with hepatic impairment when treated with LEUKERAN.
• However, there are insufficient data in patients with hepatic impairment to provide a specific dosing recommendation.

• Chlorambucil can cause fetal harm when administered to a pregnant woman.
• Unilateral renal agenesis has been observed in 2 offspring whose mothers received chlorambucil during the first trimester.
• It is not known whether this drug is excreted in human milk.
• Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from chlorambucil, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.