ERGAMISOL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ERGAMISOL (ERGAMISOL).
Levamisole is an anthelmintic and immunomodulator. It acts as a nicotinic acetylcholine receptor agonist at the neuromuscular junction in nematodes, causing spastic paralysis. Its immunomodulatory effects are thought to involve stimulation of T-cell activation and phagocytosis.
| Metabolism | Hepatic metabolism primarily via CYP450 enzymes (CYP2B6 and CYP3A4) to active metabolites. Levamisole undergoes extensive biotransformation to its major metabolites, p-hydroxy-levamisole and levamisole sulfoxide. |
| Excretion | Renal (parent drug and metabolites): ~70% in urine; Fecal: ~25% primarily as metabolites; <5% unchanged in urine. |
| Half-life | 2-4 hours (terminal); prolonged in hepatic impairment (up to 8-12 hours) and renal impairment (increase by 1.5- to 2-fold). |
| Protein binding | 20-30%, primarily to albumin. |
| Volume of Distribution | 1.0-1.5 L/kg; indicates extensive tissue distribution, including penetration into liver and kidneys. |
| Bioavailability | Oral: 40-60% (extensive first-pass metabolism). |
| Onset of Action | Oral: 30-60 minutes; Intravenous: immediate (<5 minutes). |
| Duration of Action | 4-6 hours following single oral dose; may extend to 8-12 hours in hepatic impairment. Clinical effects (immunomodulation) persist for days after drug clearance. |
150 mg orally once daily
| Dosage form | TABLET |
| Renal impairment | GFR 30-60 mL/min: no adjustment; GFR <30 mL/min: not recommended |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B or C: avoid use |
| Pediatric use | 2.5 mg/kg orally once daily; maximum 150 mg daily |
| Geriatric use | No specific adjustment; monitor for renal function and potential QT prolongation |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ERGAMISOL (ERGAMISOL).
| Breastfeeding | Levamisole is excreted in human milk in low amounts; M/P ratio is not established. Because of potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
| Teratogenic Risk | Ergamisole (levamisole) is classified as FDA Pregnancy Category C. Animal studies have shown embryotoxicity and teratogenicity at doses comparable to human doses. There are no adequate and well-controlled studies in pregnant women. Use only if potential benefit justifies potential risk to fetus. In first trimester, avoid use; second and third trimester, use with caution if indicated. |
■ FDA Black Box Warning
None specifically required for ergamisol (levamisole). However, use of levamisole as an immunomodulator has been associated with agranulocytosis and other severe hematologic reactions.
| Serious Effects |
Known hypersensitivity to levamisole; patients with a history of agranulocytosis induced by levamisole; concomitant use with alcohol (disulfiram-like reaction); caution in patients with hepatic or renal impairment.
| Precautions | Agranulocytosis (may occur weeks after initiation and is reversible upon discontinuation), hemolytic anemia (especially in patients with G6PD deficiency), neurologic effects (seizures, dizziness, headache), hepatotoxicity, and hypersensitivity reactions. |
| Food/Dietary | Avoid alcohol during therapy due to potential disulfiram-like reaction (nausea, vomiting, flushing). No specific food restrictions; maintain adequate hydration. Grapefruit juice may inhibit CYP2C19 metabolism, potentially increasing levamisole levels; consider avoidance. |
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| Fetal Monitoring | Monitor maternal complete blood count with differential, liver function tests, and renal function regularly. In pregnancy, monitor fetal growth and well-being via ultrasound if drug is used. Observe for maternal symptoms of agranulocytosis, hepatotoxicity, or vasculitis. |
| Fertility Effects | Levamisole has been associated with reversible impairment of fertility in animal studies. In humans, no specific data on fertility effects; however, due to immunomodulatory effects, potential for impact on reproductive function cannot be excluded. |
| Clinical Pearls | Levamisole (ERGAMISOL) is primarily used as an immunomodulator in adjuvant therapy for stage III colon cancer after surgical resection. It is often combined with fluorouracil. Monitor for agranulocytosis, especially in patients with poor metabolizer status of CYP2D6. Agranulocytosis can occur weeks to months after initiation; obtain baseline CBC and repeat periodically. Levamisole can cause a metallic taste and reversible ANCA-positive vasculitis. Avoid in patients with known hypersensitivity or bone marrow depression. |
| Patient Advice | Take levamisole exactly as prescribed, usually for 3 days every 2 weeks for 1 year. Do not miss doses. · Report any signs of infection (fever, sore throat, mouth sores) immediately as it can lower white blood cell count. · You may experience a metallic taste; this is harmless and may resolve with time. · Avoid alcohol consumption as it may increase risk of adverse effects. · Inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding. · Do not take any other medications or supplements without consulting your doctor. |