No

Antineoplastic Agent, Alkylating Agent

Treatment of brain tumors and Hodgkin's disease, non-Hodgkin's lymphoma, melanoma, renal carcinoma, lung cancer, colon cancer

D

Hypersensitivity to lomustine or any component

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal for antineoplastic agents be considered. Bone marrow suppression, notably thrombocytopenia and leukopenia, may lead to bleeding and overwhelming infections in an already compromised patient; will last for at least 6 weeks after a dose, do not administer courses more frequently than every 6 weeks because the toxicity is cumulative. Use with caution in patients with depressed platelet, leukocyte or erythrocyte counts, liver function abnormalities.

>10%:

Gastrointestinal: Nausea and vomiting occur 3-6 hours after oral administration; this is due to a centrally mediated mechanism, not a direct effect on the GI lining; if vomiting occurs, it is not necessary to replace the dose unless it occurs immediately after drug administration

Emetic potential:

<60 mg: Moderately high (60% to 90%)

greater than or equal to 60 mg: High (>90%)

Time course of nausea/vomiting: Onset: 2-6 hours; Duration: 4-6 hours

Hematologic: Myelosuppression: Anemia; effects occur 4-6 weeks after a dose and may persist for 1-2 weeks

WBC: Moderate

Platelets: Severe

Onset (days): 14

Nadir (weeks): 4-5

Recovery (weeks): 6

1% to 10%:

Central nervous system: Neurotoxicity

Dermatologic: Skin rash

Gastrointestinal: Stomatitis, diarrhea

Hematologic: Anemia

<1%: Disorientation, lethargy, ataxia, alopecia, hepatotoxicity, dysarthria, pulmonary fibrosis with cumulative doses >600 mg, renal failure

Symptoms of overdose include nausea, vomiting, leukopenia; there are no known antidotes

Treatment is primarily symptomatic and supportive

CYP2D6 enzyme inhibitor

Increased toxicity with cimetidine, reported to cause bone marrow suppression or to potentiate the myelosuppressive effects of lomustine

Refrigerate (<40°C/<104°F)

Inhibits DNA and RNA synthesis via carbamylation of DNA polymerase, alkylation of DNA, and alteration of RNA, proteins, and enzymes

Duration: Marrow recovery may require 6 weeks

Absorption: Complete from GI tract; appears in plasma within 3 minutes after administration

Distribution: Crosses blood-brain barrier to a greater degree than BNCU and CNS concentrations are equal to that of plasma

Protein binding: 50%

Metabolism: Rapid in the liver by hydroxylation produces at least 2 active metabolites

Half-life: Parent drug: 16-72 hours

Active metabolite: Terminal half-life: 1.3-2 days

Time to peak serum concentration: Active metabolite: Within 3 hours

Elimination: Enterohepatically recycled; excreted in the urine, feces (<5%), and in the expired air (<10%)

Oral (refer to individual protocols):

Adults: 100-130 mg/m² as a single dose every 6 weeks; readjust after initial treatment according to platelet and leukocyte counts

With compromised marrow function: Initial dose: 100 mg/m² as a single dose every 6 weeks

Repeat courses should only be administered after adequate recovery: WBC >4000 and platelet counts >100,000

Subsequent dosing adjustment based on nadir:

Leukocytes 2000-2900/mm³, platelets 25,000-74,999/mm³: Administer 70% of prior dose

Leukocytes <2000/mm³, platelets <25,000/mm³: Administer 50% of prior dose

Dosage adjustment in renal impairment:

Cl_cr 10-50 mL/minute: Administer 75% of normal dose

Cl_cr <10 mL/minute: Administer 50% of normal dose

Hemodialysis: Supplemental dose is not necessary

Peritoneal dialysis: Significant drug removal is unlikely based on physiochemical characteristics

Should be administered with fluids on an empty stomach; no food or drink for 2 hours after administration to decrease nausea

CBC with differential and platelet count, hepatic and renal function tests, pulmonary function tests

Liver function tests

May rarely cause sedation or disorientation

Myelosuppression is common; avoid usage with clozapine and carbamazepine; concurrent use with phenobarbital may result in diminished efficacy of both drugs

No information available to require special precautions

No effects or complications reported

Take with fluids on an empty stomach; do not eat or drink for 2 hours following administration. Do not use alcohol, aspirin, or aspirin-containing medications and OTC medications without consulting prescriber. Maintain adequate fluid balance (2-3 L/day of fluids unless instructed to restrict fluid intake). May cause hair loss (reversible); easy bleeding or bruising (use soft toothbrush or cotton swabs and frequent mouth care, use electric razor, avoid sharp knives or scissors); increased susceptibility to infection (avoid crowds or exposure to infection - do not have any vaccinations unless approved by prescriber). Report unusual bleeding or bruising or persistent fever or sore throat; blood in urine, stool, or vomitus; delayed healing of any wounds; skin rash; yellowing of skin or eyes; changes in color of urine of stool. 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. Do not breast-feed.

Capsule: 10 mg, 40 mg, 100 mg

Dose Pack: 10 mg (2s); 100 mg (2s); 40 mg (2s)

Berg SL, Grisell DL, DeLaney TF, et al, "Principles of Treatment of Pediatric Solid Tumors," Pediatr Clin North Am, 1991, 38(2):249-67.

Bono VH, "Review of Mechanism of Action Studies of the Nitrosoureas," Cancer Treat Rep, 1976, 60(6):699-702.

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.

Lee FY, Workman P, Roberts JT, et al, "Clinical Pharmacokinetics or Oral CCNU (Lomustine)," Cancer Chemother Pharmacol, 1985, 14(2):125-31.

Oliverio VT, "Pharmacology of the Nitrosoureas: An Overview," Cancer Treat Rep, 1976, 60(6):703-7.

Pendergrass TW, Milstein JM, Geyer JR, et al, "Eight Drugs in One Day Chemotherapy for Brain Tumors: Experience in 107 Children and Rationale for Preradiation Chemotherapy," J Clin Oncol, 1987, 5(8):1221-31.

Wasserman TH, Slavik M, and Carter SK, "Clinical Comparison of the Nitrosoureas," Cancer, 1975, 36(4);1258-68.

Weiss RB and Issell BF, "The Nitrosoureas: Carmustine (BCNU) and Lomustine (CCNU)," Cancer Treat Rev, 1982, 9(4):313-30.