Is levamisole safe to use during pregnancy?

Levamisole in Pregnancy: Safety Assessment

Primary Recommendation

Levamisole should be avoided during pregnancy unless the maternal condition is life-threatening and no safer alternatives exist, as there is insufficient safety data and the drug was withdrawn from human use in the United States in 2000 due to severe adverse effects. 1

Evidence-Based Risk Assessment

Limited Human Safety Data

• The only controlled epidemiological study of levamisole in pregnancy (Hungarian Case-Control Surveillance, 1980-1996) did not demonstrate a statistically significant increase in congenital abnormalities, though this represents limited evidence from a single population 2
• Mean gestational age and birth weight were similar between exposed and unexposed groups in this study (adjusted t = 1.04, p = 0.30 for gestational age; adjusted t = 0.36, p = 0.72 for birth weight) 2
• The drug was withdrawn from human use by the FDA in 2000 specifically due to severe adverse effects, limiting contemporary safety data 1

Maternal Toxicity Concerns

• Levamisole causes significant autoimmune-related adverse effects including agranulocytosis, leukopenia, purpura, and necrotizing skin lesions 1, 3
• Agranulocytosis (neutrophils <20%) occurs most frequently in women and is spontaneously reversible when treatment is discontinued, though it compromises immune function during pregnancy 3
• Individuals with levamisole-compromised immune systems have increased susceptibility to infections 1
• Blood dyscrasias occur predominantly in a small subpopulation but can be severe enough to necessitate treatment discontinuation 3

Fetal Risk Considerations

• Levamisole has broad immunomodulatory effects with both stimulatory and inhibitory actions on immune responses, raising theoretical concerns for fetal immune development 1
• The drug is rapidly metabolized with at least 2 known active metabolites, though placental transfer data are not available 1
• No formal FDA pregnancy category was assigned before the drug's withdrawal 1

Clinical Decision Algorithm

When Levamisole Might Be Considered (Rare Circumstances)

1. Life-threatening maternal condition requiring levamisole with no safer alternatives available 4
2. Risk-benefit calculation must demonstrate that maternal death or severe morbidity without treatment clearly outweighs unknown fetal risks 4
3. Informed consent documenting limited safety data and potential for maternal agranulocytosis 1, 3

Preferred Alternatives by Indication

• For parasitic infections: Use albendazole or mebendazole after first trimester, which have more established safety profiles 5
• For autoimmune conditions: Consider hydroxychloroquine, sulfasalazine, azathioprine, or TNF inhibitors, which are compatible with pregnancy 6
• For any indication: Defer treatment until postpartum if the condition is not immediately life-threatening 4

Monitoring Requirements If Use Is Unavoidable

• Weekly complete blood count to detect agranulocytosis or leukopenia early 3
• Immediate discontinuation if neutrophil count drops below 20% or white blood cell count falls below 3000 cells/mm³ 3
• Close surveillance for skin rash, purpura, or febrile illness requiring treatment cessation 3
• Fetal growth monitoring via serial ultrasounds given unknown placental transfer 2

Common Pitfalls to Avoid

• Do not assume "natural" or antiparasitic drugs are automatically safe in pregnancy—levamisole has documented severe maternal toxicity 1, 3, 5
• Do not use levamisole for routine helminthic infections—safer alternatives exist for nearly all parasitic indications 5
• Do not fail to obtain baseline and serial CBCs—agranulocytosis can develop rapidly and requires immediate recognition 3
• Do not continue treatment if any blood dyscrasia develops—bone marrow suppression is reversible only with prompt discontinuation 3

Breastfeeding Considerations

• No data exist on levamisole excretion in human breast milk 1
• Given the drug's immunosuppressive effects and risk of neonatal exposure to active metabolites, breastfeeding should be avoided during levamisole treatment 1
• The principle of avoiding potentially harmful medications during lactation applies when safety data are absent 4