No

Antineoplastic Agent, Alkylating Agent

Management of chronic lymphocytic leukemia, Hodgkin's and non-Hodgkin's lymphoma; breast and ovarian carcinoma; Waldenström's macroglobulinemia, testicular carcinoma, thrombocythemia, choriocarcinoma

D

Clinical effects on the fetus: Carcinogenic and mutagenic in humans

Previous resistance; hypersensitivity to chlorambucil or any component or other alkylating agents

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Use with caution in patients with seizure disorder and bone marrow suppression; reduce initial dosage if patient has received radiation therapy, myelosuppressive drugs or has a depressed baseline leukocyte or platelet count within the previous 4 weeks. Can severely suppress bone marrow function; affects human fertility; carcinogenic in humans and probably mutagenic and teratogenic as well; chromosomal damage has been documented; secondary AML may be associated with chronic therapy.

>10%:

Hematologic: Myelosuppressive: Use with caution when receiving radiation; bone marrow suppression frequently occurs and occasionally bone marrow failure has occurred; blood counts should be monitored closely while undergoing treatment; leukopenia, thrombocytopenia, anemia

WBC: Moderate

Platelets: Moderate

Onset (days): 7

Nadir (days): 10-14

Recovery (days): 28

1% to 10%:

Dermatologic: Skin rashes

Endocrine & metabolic: Hyperuricemia, menstrual changes

Gastrointestinal: Nausea, vomiting, diarrhea, oral ulceration are all infrequent

Emetic potential: Low (<10%)

<1%: Confusion, agitation, drug fever, ataxia, hallucination; rarely generalized or focal seizures, rash, fertility impairment: Has caused chromosomal damage in men, both reversible and permanent sterility have occurred in both sexes; can produce amenorrhea in females, oral ulceration, oligospermia, hepatotoxicity, hepatic necrosis, weakness, tremors, muscular twitching, peripheral neuropathy, pulmonary fibrosis, secondary malignancies; Increased incidence of AML; skin hypersensitivity

Symptoms of overdose include vomiting, ataxia, coma, seizures, pancytopenia

There are no known antidotes for chlorambucil intoxication, and treatment is mainly supportive, directed at decontaminating the GI tract and controlling symptoms; blood products may be used to treat the hematologic toxicity

Patients may experience impaired immune response to vaccines; possible infection after administration of live vaccines in patients receiving immunosuppressants

Store at room temperature

Interferes with DNA replication and RNA transcription by alkylation and cross-linking the strands of DNA

Duration: ~4 weeks

Absorption/bioavailability: 70% to 80%; food will interfere with absorption resulting in a 10% to 20% decrease in bioavailability

Distribution: V_d: 0.14-0.24 L/kg, thought to cross the placenta

Protein binding: ~99% bound to albumin; extensive binding to tissues and plasma proteins

Metabolism: In the liver to an active metabolite

Half-life: 90 minutes to 2 hours

Elimination: 60% excreted in urine within 24 hours, principally as metabolites; probably not dialyzable

Oral (refer to individual protocols):

General short courses: 0.1-0.2 mg/kg/day OR 4.5 mg/m²/day for 3-6 weeks for remission induction (usual: 4-10 mg/day); maintenance therapy: 0.03-0.1 mg/kg/day (usual: 2-4 mg/day)

Nephrotic syndrome: 0.1-0.2 mg/kg/day every day for 5-15 weeks with low-dose prednisone

Chronic lymphocytic leukemia (CLL):

Biweekly regimen: Initial: 0.4 mg/kg/dose every 2 weeks; increase dose by 0.1 mg/kg every 2 weeks until a response occurs and/or myelosuppression occurs

Monthly regimen: Initial: 0.4 mg/kg, increase dose by 0.2 mg/kg every 4 weeks until a response occurs and/or myelosuppression occurs

Malignant lymphomas:

Non-Hodgkin's lymphoma: 0.1 mg/kg/day

Hodgkin's lymphoma: 0.2 mg/kg/day

Adults: 0.1-0.2 mg/kg/day OR 3-6 mg/m²/day for 3-6 weeks, then adjust dose on basis of blood counts. Pulse dosing has been used in CLL as intermittent, biweekly, or monthly doses of 0.4 mg/kg and increased by 0.1 mg/kg until the disease is under control or toxicity ensues. An alternate regimen is 14 mg/m²/day for 5 days, repeated every 21-28 days.

Hemodialysis: Supplemental dosing is not necessary

Peritoneal dialysis: Supplemental dosing is not necessary

Avoid acidic foods, hot foods, and spices; may be administered with chilled liquids

Liver function tests, CBC, leukocyte counts, platelets, serum uric acid

May rarely produce agitation, confusion, and hallucinations

Myelosuppression is common; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

Take exactly as directed (may be taken with chilled liquids). Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). Avoid alcohol, acidic, spicy, or hot foods, aspirin, or OTC medications unless approved by prescriber. Hair may be lost during treatment (reversible). You may experience menstrual irregularities and/or sterility. You will be more susceptible to infection; avoid crowds and exposure to infection. Frequent mouth care with soft toothbrush or cotton swab may reduce occurrence of mouth sores. Report easy bruising or bleeding; fever or chills; numbness, pain, or tingling of extremities; muscle cramping or weakness; unusual swelling of extremities; menstrual irregularities; or any difficulty breathing. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not get pregnant during or for 1 month following therapy. Male: Do not cause a female to become pregnant. Male/female: Consult prescriber for instruction on appropriate barrier contraceptive measures. This drug may cause severe fetal defects. Consult prescriber if breast-feeding.

Stability: Protect from light

Tablet, sugar coated: 2 mg

A 2 mg/mL suspension was stable for 7 days when refrigerated and compounded as follows: Pulverize sixty 2 mg tablets; levigate with a small amount of glycerin; add 20 mL Cologel® and levigate until a uniform mixture is obtained; add a 2:1 simple syrup/cherry syrup mixture to make a total volume of 60 mL

Baluarte HJ, Hiner L, and Gruskin AB, "Chlorambucil Dosage in Frequently Relapsing Nephrotic Syndrome: A Controlled Clinical Trial," J Pediatr, 1978, 92(2):295-8.

Begleiter A, Mowat M, Israels LG, et al, "Chlorambucil in Chronic Lymphocytic Leukemia: Mechanism of Action," Leuk Lymphoma, 1996, 23(3-4):187-201.

Brittinger G, Hellriegel KP, and Hiddemann W, "Chronic Lymphocytic Leukemia and Hairy-Cell Leukemia-Diagnosis and Treatment: Results of a Consensus Meeting of the German CLL Cooperative Group," Ann Hematol, 1997, 74(6):291-4.

Byrne TN Jr, Moseley TA III, and Finer MA, "Myoclonic Seizures Following Chlorambucil Overdose," Ann Neurol, 1981, 9(2):191-4.

Green AA and Naiman JL, "Chlorambucil Poisoning," Am J Dis Child, 1968, 116(2):190-1.

Harris J and Dodds LJ, "Handling Wastes From Patients Receiving Cytotoxic Drugs," Pharm J, 1985, 235:289-91.

Hutchins LF and Lipschitz DA, "Cancer, Clinical Pharmacology, and Aging," Clin Geriatr Med, 1987, 3(3):483-503.

Jeffrey LP, Chairman, National Study Commission on Cytotoxic Exposure. Position Statement. "The Handling of Cytotoxic Agents by Women Who Are Pregnant, Attempting to Conceive, or Breast-Feeding," January 12, 1987.

Kaplan HG, "Use of Cancer Chemotherapy in the Elderly," Drug Treatment in the Elderly, Vestal RE, ed, Boston, MA: ADIS Health Science Press, 1984, 338-49.

Portlock CS, Fischer DS, Cadman E, et al, "High-Dose Pulse Chlorambucil in Advanced, Low-Grade Non-Hodgkin's Lymphoma," Cancer Treat Rep, 1987, 71(11):1029-31.

Rozman C and Montserrat E, "Chronic Lymphocytic Leukemia," N Engl J Med, 1995, 333(16);1052-7.

Vandenberg SA, Kulig K, Spoerke DG, et al, "Chlorambucil Overdose: Accidental Ingestion of an Antineoplastic Drug," J Emerg Med, 1988, 6(6):495-8.