Usage
Levamisole is an anthelmintic (anti-parasitic) medication primarily used to treat parasitic worm infections, specifically ascariasis (roundworm infection) and hookworm infections. It is also used as an immunomodulatory agent and has been used as adjunctive therapy in colon cancer and in some autoimmune conditions like nephrotic syndrome in children.
Alternate Names
- Generic Name: Levamisole hydrochloride
- Brand Name: Ergamisol (no longer available in the US)
How It Works
Pharmacodynamics: Levamisole acts as a nicotinic acetylcholine receptor agonist in nematode nerve ganglia, causing depolarizing neuromuscular paralysis in susceptible worms. This paralysis leads to expulsion of the worms from the intestines through normal peristaltic action, typically within 24 hours of administration. Additionally, levamisole has immunomodulatory effects in humans, enhancing cellular immune responses, including T-cell activation and proliferation, and potentiating monocyte and macrophage functions like phagocytosis and chemotaxis. It also increases neutrophil mobility, adherence, and chemotaxis.
Pharmacokinetics:
- Absorption: Levamisole is rapidly and almost completely absorbed from the gastrointestinal tract, reaching peak plasma concentrations within 1.5 to 2 hours after oral administration.
- Metabolism: It is extensively metabolized in the liver, primarily to p-hydroxylevamisole and its glucuronide.
- Elimination: Levamisole is excreted mainly in the urine (70% as metabolites and 5% as unchanged drug) and in small amounts in the feces. It has a plasma half-life of about 4 hours.
Dosage
Standard Dosage
Adults:
- Ascariasis: 150 mg as a single oral dose.
- Hookworm Infection: 2.5 mg/kg as a single oral dose, repeated after 7 days in severe cases.
- Adjunctive therapy in colon cancer: 50 mg orally every 8 hours for 3 days (starting 7-30 days post-surgery). Maintenance therapy may be given as 3 days of treatment at 2-week intervals for 1 year.
Children:
- Ascariasis: 3 mg/kg as a single oral dose.
- Hookworm Infection: 2.5 mg/kg as a single oral dose, repeated after 7 days in severe cases.
- Idiopathic Nephrotic Syndrome: 2–2.5 mg/kg on alternate days for 12–24 months (requires regular monitoring of leukocyte counts). Maximum dose of 150mg.
Special Cases:
- Elderly Patients: No specific dosage adjustments are recommended, but caution is advised due to potential age-related decline in hepatic and renal function.
- Patients with Renal Impairment: Caution is advised in patients with severe renal impairment.
- Patients with Hepatic Dysfunction: Caution is advised in patients with hepatic impairment due to the extensive hepatic metabolism of levamisole.
- Patients with Comorbid Conditions: Pre-existing blood disorders and rheumatoid arthritis are contraindications. Caution is also recommended in patients with epilepsy or Sjögren’s syndrome.
Side Effects
Common Side Effects:
- Nausea
- Vomiting
- Diarrhea
- Abdominal pain
- Dizziness
- Headache
- Loss of appetite
- Change in taste and smell
- Muscle aches
- Fatigue
- Skin Rash
- Flu-like symptoms (fever, chills, weakness, sore throat)
Rare but Serious Side Effects:
- Agranulocytosis (severe decrease in white blood cells)
- Leucopenia (low white blood cell count)
- Thrombocytopenia (low platelet count)
- Vasculitis (inflammation of blood vessels)
- Encephalopathy (brain dysfunction)
- Seizures (with prolonged use)
- Allergic reactions (itching, hives, rash)
Long-Term Effects:
- Temporary hair loss
- Sexual and reproductive dysfunction
Contraindications
- Hypersensitivity to levamisole
- Pre-existing blood disorders
- Pregnancy
- Breastfeeding (use only if essential, and with caution)
- Rheumatoid arthritis
- Severe renal impairment
Drug Interactions
- Alcohol: Disulfiram-like reaction (flushing, headache, nausea, vomiting)
- Phenytoin: Increased phenytoin toxicity
- Ivermectin: Increased ivermectin bioavailability
- Albendazole: Decreased albendazole bioavailability
- Warfarin: Potential increased risk of bleeding
- Anticancer drugs (e.g., doxorubicin, fluorouracil): Potential increased risk of side effects
Pregnancy and Breastfeeding
Levamisole is contraindicated during pregnancy due to potential embryotoxic effects. It should be avoided during breastfeeding unless absolutely necessary. If used during breastfeeding, the infant should be monitored for potential adverse effects. The World Health Organization recommends against breastfeeding during maternal levamisole therapy.
Drug Profile Summary
- Mechanism of Action: Nicotinic acetylcholine receptor agonist in nematodes, causing paralysis and expulsion; immunomodulatory effects in humans.
- Side Effects: Nausea, vomiting, diarrhea, abdominal pain, dizziness, headache, agranulocytosis, leucopenia, thrombocytopenia.
- Contraindications: Hypersensitivity, pre-existing blood disorders, pregnancy, breastfeeding, rheumatoid arthritis, severe renal impairment.
- Drug Interactions: Alcohol, phenytoin, ivermectin, albendazole, warfarin, anticancer drugs.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Varies depending on the indication and age group (see detailed dosage section above).
- Monitoring Parameters: Complete blood count (especially white blood cell count), liver function tests.
Popular Combinations
Levamisole is used in combination with fluorouracil for the treatment of colon cancer.
Precautions
- Monitor complete blood counts regularly during treatment, especially for patients with nephrotic syndrome.
- Avoid alcohol consumption during treatment and for at least 24 hours after the last dose.
- Exercise caution in patients with hepatic or renal impairment.
- Driving may be impaired due to potential side effects like dizziness or fatigue.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Levamisole?
A: The dosage varies depending on the indication and age group. Please refer to the detailed dosage guidelines provided above.
Q2: What is the mechanism of action of Levamisole?
A: Levamisole works by paralyzing intestinal worms and by modulating the immune system. See “How it Works” above for details.
Q3: What are the most serious side effects of Levamisole?
A: Agranulocytosis, leucopenia, thrombocytopenia, vasculitis and encephalopathy.
Q4: Can Levamisole be used during pregnancy or breastfeeding?
A: Levamisole is contraindicated during pregnancy and should be avoided during breastfeeding unless considered essential by a physician.
Q5: What are the common drug interactions with Levamisole?
A: Levamisole interacts with alcohol, phenytoin, ivermectin, albendazole, and warfarin, among other drugs. Refer to the drug interactions section for further details.
Q6: How should Levamisole be administered?
A: Levamisole is administered orally, preferably after a light meal.
Q7: What should I do if a patient experiences side effects while taking Levamisole?
A: If a patient experiences any side effects, particularly those that are severe or persistent, they should discontinue the medication and contact their healthcare provider immediately.
Q8: Is Levamisole still used to treat colon cancer?
A: Levamisole is no longer used to treat colon cancer in the United States due to the risk of serious side effects like agranulocytosis. It is, however, still used in some countries as an anthelmintic.
Q9: What monitoring parameters should be considered during treatment with Levamisole?
A: Complete blood count (CBC), especially white blood cell count, should be regularly monitored during levamisole treatment, along with liver function tests.
Q10: Is there a risk of agranulocytosis with Levamisole use?
A: Yes, agranulocytosis is a rare but serious side effect of levamisole. Close monitoring of CBC, especially white blood cell count, is essential. Patients should be educated about signs of infection and instructed to seek immediate medical attention if they develop such symptoms.
