levamisole hydrochloride
Ergamisol

Pharmacologic classification: immunomodulator
Therapeutic classification: antineoplastic
Pregnancy risk category C


Available forms
Available by prescription only
Tablets: 50 mg

Indications and dosages
 Adjuvant treatment with fluorouracil after surgical resection in patients with Dukes’ stage C colon cancer. Adults: Initially, 50 mg P.O. q 8 hours for 3 days starting 7 to 30 days after surgery. Repeat q 14 days for 1 year. Administer with fluorouracil 450 mg/m2 daily by rapid I.V. push for 5 days with a 3-day course of levamisole, starting 21 to 34 days after surgery.
 If levamisole therapy begins 7 to 20 days after surgery, start fluorouracil with the second course of levamisole at 21 to 34 days. If levamisole begins 21 to 30 days after surgery, start fluorouracil simultaneously with the first course of therapy.
 Maintenance dosage is 50 mg P.O. q 8 hours for 3 days q 2 weeks. Give with fluorouracil 450 mg/m2.

Pharmacodynamics
Antineoplastic action: Drug is an immunomodulator. Mechanism of action with fluorouracil is unknown. Its effects on the immune system are complete, but it appears to restore depressed immune function rather than stimulate response to above-normal levels. It also can stimulate antibody formation; enhance T-cell responses by stimulating T-cell activation and proliferation; potentiate monocyte and macrophage formation, including phagocytosis and chemotaxis; increase neutrophil mobility adherence and chemotaxis; and inhibit alkaline phosphatase. Levamisole also has cholinergic activity.

Pharmacokinetics
Absorption: Rapidly absorbed from GI tract.
Distribution: No information available.
Metabolism: Extensively metabolized by liver.
Excretion: 70% of metabolites excreted in urine over 3 days, 5% in feces; less than 5% of unchanged drug excreted in urine, less than 2% in feces.

Route Onset Peak Duration
P.O. Rapid 1 1/2-2 hr Unknown


Contraindications and precautions
Contraindicated in patients hypersensitive to drug.

Interactions
Drug-drug. Phenytoin: Increases phenytoin levels. Monitor plasma phenytoin levels; decrease dosage as needed.
Warfarin: May excessively prolong PT and INR. Monitor PT and INR and adjust warfarin dosage as needed.
Drug-lifestyle. Alcohol use: Causes disulfiram-like reaction. Discourage alcohol use.

Adverse reactions
CNS: dizziness, headache, paresthesia, somnolence, depression, nervousness, insomnia, anxiety, fatigue, fever.
CV: chest pain, edema.
EENT: blurred vision, conjunctivitis, stomatitis, dysgeusia, altered sense of smell.
GI: nausea, diarrhea, vomiting, anorexia, abdominal pain, constipation, flatulence, dyspepsia.
Hematologic: agranulocytosis, leukopenia, thrombocytopenia, anemia.
Musculoskeletal: arthralgia, myalgia.
Skin: alopecia, dermatitis, exfoliative dermatitis, pruritus, urticaria.
Other: rigors, infection.

Effects on lab test results
• May increase bilirubin levels.
• May decrease hemoglobin and granulocyte, WBC, and platelet counts.

Overdose and treatment
Fatalities have been reported after ingestion of 15 mg/kg by a 3-year-old child and of 32 mg/kg by an adult.
 In case of overdose, gastric lavage is recommended, with symptomatic and supportive measures.

Special considerations
• Don’t use drug in higher than recommended dosage or administer more frequently than indicated.
• Before drug therapy begins, patient should be ambulatory, maintain normal oral nutrition, have well-healed wounds, be fully recovered from any postsurgical complications, and not be hospitalized.
• Obtain CBC with differential, platelet counts, electrolyte levels, and liver function test results before therapy. CBC with differential and platelet counts should be performed weekly before each fluorouracil treatment; electrolyte and liver function tests every 3 months for 1 year. Modify doses as needed.
• If WBC count is 2,500 to 3,500/mm3, defer fluorouracil dose until count is over 3,500/mm3. If WBC count is below 2,500/mm3, defer fluorouracil dose until count is above 3,500/mm3, and then reduce dose by 20%. If WBC count remains below 2,500/mm3 for longer than 10 days even after deferring fluorouracil, stop drug. Defer both if platelet counts are below 100,000/mm3.
• If stomatitis or diarrhea develops during initial fluorouracil administration schedule, stop course before full five doses are given. If stomatitis or diarrhea occurs during weekly maintenance therapy, defer next dose of fluorouracil until it subsides. If adverse reactions are moderate to severe, reduce fluorouracil dose by 20% when treatment is resumed.
• If an acute neurologic syndrome occurs, consider stopping drug immediately.
Pediatric patients
• Safety and efficacy in children haven’t been established.
Breast-feeding patients
• Although it’s unknown whether drug appears in breast milk, potential for serious adverse reactions in infants must be considered.

Patient education
• Advise patient to use a soft toothbrush and electric razor to avoid trauma and excessive bleeding.
• Tell patient to report unusual bruising or bleeding.
• Flu syndrome frequently accompanies onset of agranulocytosis but may also occur in the absence of agranulocytosis. Instruct patient to report flulike symptoms immediately.
• Advise patient to avoid exposure to persons with infection.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use