Chlorambucil – Uses, Dosage, Side Effects, Interaction

Chlorambucil is an antineoplastic in the class of alkylating agents that is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor? growth by cross-linking guanine bases in DNA double-helix strands – directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result – disruption of DNA function and cell death.

Use in Cancer

CHLORAMBUCIL-PREDNISONE is used to treat:

• Chronic lymphocytic leukemia (CLL).

This combination may also be used with other drugs or treatments or to treat other types of cancer.

Contraindications

• are allergic to chlorambucil or any ingredients of this medication
• have had a full course of radiation or chemotherapy within the previous 4 weeks
• a bad infection?
• acute leukemia
• decreased function of bone marrow?
• anemia?
• decreased blood platelets
• low levels of white blood cells
• low levels of a type of white blood cell called neutrophils
• a decreased number of lymphocytes in the blood
• a low seizure? threshold
• a type of inflammation? of the lung called interstitial pneumonitis
• a condition where there is formation of fibrous tissue in the lung called pulmonary fibrosis?
• damage to the liver? and inflammation
• liver problems
• nephrotic syndrome, a type of kidney? disorder
• seizures
• pregnancy
• a patient who is producing milk and breastfeeding
• spread of malignant cancer to the bone marrow

Dosage?

Strengths: 2 mg

Hodgkin’s Disease

NOTE: The literature and/or local protocol should be consulted for full details of the treatment schedules used.

For initiation of therapy or for short courses of treatment:

• 0.1 to 0.2 mg/kg orally 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
• The dosage should be adjusted according to the response of the patient and should 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.
• Patients with other lymphomas or chronic lymphocytic leukemia usually require 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 once-monthly pulse doses have been reported. Intermittent schedules 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 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 doses.

Chronic Lymphocytic Leukemia

For initiation of therapy or for short courses of treatment:

• 0.1 to 0.2 mg/kg orally 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
• The dosage should be adjusted according to the response of the patient and should 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.
• Patients with other lymphomas or chronic lymphocytic leukemia usually require 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 once-monthly pulse doses have been reported. Intermittent schedules 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 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 doses.

Lymphoma

NOTE: The literature and/or local protocol should be consulted for full details of the treatment schedules used.

For initiation of therapy or for short courses of treatment:

• 0.1 to 0.2 mg/kg orally 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
• The dosage should be adjusted according to the response of the patient and should 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.
• Patients with other lymphomas or chronic lymphocytic leukemia usually require 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 once-monthly pulse doses have been reported. Intermittent schedules 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 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 doses.

Usual Pediatric Dose

Non-Hodgkin’s Lymphoma

• The manufacturer does not recommend the use of this drug in children; however, it has been used in children with Hodgkin’s disease and non-Hodgkin’s lymphoma. The dosage regimens are similar to those used in adults.

Hodgkin’s Disease

• The manufacturer does not recommend the use of this drug in children; however, it has been used in children with Hodgkin’s disease and non-Hodgkin’s lymphoma. The dosage regimens are similar to those used in adults.

Side Effects

The Most Common

• nausea?
• vomiting
• sores in the mouth and throat
• tiredness
• missed menstrual periods (in girls and women)
• skin rash
• unusual bruising or bleeding
• black, tarry stools
• red urine
• cough
• sore throat
• congestion
• fever
• difficulty breathing
• seizures
• yellowing of the skin or eyes
• pain in the upper right part of the stomach
• dark colored urine
• frequent urination
• unusual lumps or masses

More Common

• allergic reaction (difficulty breathing, swelling in your face or throat, hives)
• or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).
• a seizure
• any unusual lump or mass,
• severe diarrhea or vomiting,
• a cough that is new or worsening,
• signs of bone marrow suppression eg. dizziness, feeling tired or short of breath, pale lips or fingernail beds, fast heart rate,
• signs of liver problems eg. low appetite,  pain in the upper right side of the stomach, dark urine, clay-colored stools, yellowing of the skin or eyes, or
• signs of low blood cell count eg. high body temperature, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands, and feet, feeling light-headed or short of breath.
• nausea, vomiting, or diarrhea,
• white patches or sores in or around your mouth,
• bone marrow suppression,
• low blood cell counts,
• missed menstrual periods in women.

Rare

• mouth ulcers
• muscle twitching or jerking movements
• muscle weakness or numbness
• numbness or tingling in fingers and toes
• persistent cough with shortness of breath
• signs of anemia (low red blood cells; e.g., dizziness, pale skin, unusual tiredness or weakness, shortness of breath)
• signs of bladder inflammation (e.g., pain or burning with urination, frequent or urgent need to urinate)
• signs of clotting problems (e.g., unusual nosebleeds, bruising, blood in urine, coughing blood,  bleeding gums, cuts that don’t stop bleeding)
• signs of liver problems (e.g., nausea, vomiting, diarrhea, loss of appetite, weight loss, yellowing of the skin or whites of the eyes, dark urine, pale stools)
• skin rash
• symptoms of an infection such as fever, chills, or painful and difficult urination
• tremors
• blisters on skin
• seizures
• severe skin rash or skin blisters
• symptoms of a serious allergic reaction such as hives; difficulty breathing; or swelling of the eyelids, throat, and mouth

Drug Interaction

Pregnancy and Lactation

FDA Pregnancy Category D

Pregnancy

There is a possibility of birth defects if either the man or woman is taking chlorambucil at the time of conception, or if it is taken during pregnancy. Infertility may occur with the use of chlorambucil. Use effective birth control while taking this medication. If you become pregnant while taking this medication, contact your doctor immediately.

Lactation

This medication may pass into breast milk. Women taking this medication should not breastfeed. The safety and effectiveness of using this medication have not been established for children.

References