Levamisole Hydrochloride

Approved Indications:

• Ascariasis (Roundworm infection): Used as a single-dose treatment for Ascaris lumbricoides infections.
• Hookworm infections: Effective against Ancylostoma duodenale and Necator americanus.
• Adjuvant therapy in Stage III colon cancer: Used in combination with 5-fluorouracil after surgical resection of Dukes’ Stage C colon cancer.

Clinically Accepted (Off-label) Uses:

• Steroid-sensitive nephrotic syndrome: Used to reduce relapse frequency in pediatric and adult patients.
• Rheumatoid arthritis: Occasionally used as an immunomodulatory agent.
• Cutaneous warts and aphthous ulcers: Used off-label due to immune-enhancing effects.
• Strongyloidiasis: Employed in certain regions as an alternative treatment.

Route: Oral

Ascariasis:

• Adults and children ≥2 years: 2.5 mg/kg as a single dose (maximum: 150 mg). Repeat dose after 7 days if required.

Hookworm infection:

• Adults and children: 2.5 mg/kg once daily for 2–3 days.

Colon cancer (Adjuvant with 5-FU):

• Adults: 50 mg orally every 8 hours for 3 days, starting on the same day as 5-fluorouracil. Repeat every 2 weeks for 1 year.

Nephrotic syndrome (off-label):

• Children: 2.5 mg/kg orally on alternate days or 2–3 times weekly for 6–12 months.
• Adults: Dose adjusted individually; typically 50–150 mg 2–3 times weekly.

Special Populations:

• Renal impairment: Use with caution; dose adjustment may be necessary.
• Hepatic impairment: Use with caution; insufficient data available.
• Elderly: Start at the lower end of dosing range with close monitoring.
• Children under 2 years: Not recommended due to insufficient safety data.

Levamisole exerts its anthelmintic effect by acting as an agonist at the nicotinic acetylcholine receptors of parasitic nematodes. This leads to sustained muscle contraction and subsequent paralysis of the worm, facilitating its expulsion by peristalsis. In humans, Levamisole functions as an immunomodulator by enhancing T-cell activity, stimulating macrophage function, and increasing cytokine production, contributing to its therapeutic effects in autoimmune conditions and as an adjuvant in cancer treatment.

• Absorption: Rapid and well absorbed; bioavailability ~80–90%.
• Distribution: Widely distributed; ~70% plasma protein binding.
• Metabolism: Extensively metabolized in the liver.
• Half-life: Approximately 3–4 hours.
• Excretion: Primarily via urine (mostly as metabolites); ~70% excreted in 3 days.
• Onset of action: Typically within hours after oral administration.

• Pregnancy: Category C. Animal studies have shown adverse fetal effects; no adequate studies in pregnant women. Use only if clearly needed.
• Lactation: Unknown whether excreted in human milk. Caution advised. Avoid breastfeeding during treatment and for at least 24 hours after the last dose.
• General Advice: Use during pregnancy or lactation only if benefits outweigh potential risks.

• Primary Class: Anthelmintic
• Secondary Class: Immunomodulatory Agent
• Subclass: Nicotinic receptor agonist (in helminths)

• Known hypersensitivity to Levamisole or its components
• Severe hepatic or renal impairment
• Pre-existing hematologic disorders (e.g., agranulocytosis)
• History of seizures or neurological disorders
• Use during pregnancy unless absolutely necessary
• Concurrent use of other myelotoxic or nephrotoxic drugs

• Hematologic toxicity: May cause agranulocytosis. Monitor white blood cell counts regularly, especially with prolonged use.
• Neurologic effects: May cause confusion, dizziness, or seizures. Advise caution with driving or machinery.
• Hepatic effects: Periodic liver function testing is advised during extended use.
• Infection risk: Immediate discontinuation recommended if fever, sore throat, or signs of infection occur.
• High-risk populations: Use cautiously in elderly, immunocompromised patients, and those with chronic illnesses.

Common:

• Gastrointestinal: Nausea, vomiting, abdominal discomfort, metallic taste
• Neurologic: Headache, dizziness, fatigue
• Dermatologic: Rash, pruritus

Less Common:

• Flu-like symptoms (fever, chills, malaise)
• Insomnia or mood changes
• Myalgia and arthralgia

Serious Adverse Effects:

• Agranulocytosis or severe leukopenia
• Hepatotoxicity
• Seizures
• Vasculitis or necrotizing skin reactions (rare)
• Anaphylactic reactions (very rare)

Onset: Most mild side effects occur within 24–48 hours. Serious effects may develop after 1–3 weeks of therapy.

• Myelotoxic agents (e.g., methotrexate): Increased risk of bone marrow suppression.
• Phenytoin: May increase phenytoin plasma levels; monitor serum levels.
• Warfarin and other anticoagulants: Potentiation of anticoagulant effect possible; monitor INR.
• Alcohol: May enhance CNS side effects; avoid alcohol during therapy.
• CYP enzyme interactions: Though not clearly defined, Levamisole may interact with CYP450 substrates due to hepatic metabolism.

• Nephrotic syndrome (2023–2024): Recent pediatric nephrology guidelines support Levamisole as a steroid-sparing agent in frequently relapsing steroid-sensitive nephrotic syndrome.
• Oncology (Colon Cancer): Some updated oncology guidelines suggest reduced preference for Levamisole-based regimens due to limited efficacy and increased hematologic risk compared to newer agents.
• Hematologic safety: Emphasis on routine white blood cell monitoring during prolonged or off-label immunomodulatory use has been reinforced in recent pharmacovigilance updates.

• Temperature: Store at or below 25°C (77°F)
• Humidity: Store in a dry place
• Light protection: Keep in original packaging; protect from light
• Handling: Keep out of reach of children; discard unused portions appropriately
• Liquid forms (if applicable): Shake well before use; refrigerate only if instructed by the label