What are the side effects of an ivermectin overdose?

Ivermectin Overdose: Clinical Manifestations and Management

Ivermectin overdose primarily causes neurological toxicity including ataxia, altered mental status, mydriasis, and tremors, with gastrointestinal symptoms (nausea, vomiting, diarrhea) also common; management is entirely supportive with activated charcoal if presenting early, as no specific antidote exists. 1

Neurological Manifestations

The most prominent features of ivermectin toxicity involve the central nervous system:

• Altered consciousness: Ranges from somnolence and sedation to coma, depending on dose 1, 2, 3
• Movement disorders: Ataxia, tremors, and decreased motor activity are characteristic findings 1, 4
• Pupillary changes: Mydriasis (dilated pupils) with potentially slow or absent pupillary light reflexes 1, 5
• Psychiatric symptoms: Complex visual hallucinations and restlessness can occur 3
• Seizures: Reported in severe cases, though less common 1
• Cerebral edema: In fatal cases, diffuse cerebral edema and intracranial hypertension have been documented 6

Gastrointestinal and Other Systemic Effects

Beyond neurological symptoms, patients develop:

• Gastrointestinal distress: Nausea, vomiting, and diarrhea are among the most frequently reported symptoms 1, 4, 2
• Cardiovascular effects: Bradypnea (slow breathing), tachycardia, and clinically significant hypotension requiring pressor support 1, 5
• Dermatological reactions: Rash, edema, urticaria, and contact dermatitis 1
• Other symptoms: Headache, dizziness, asthenia (weakness), abdominal pain, and paresthesia 1

Dose-Response Relationship

The severity correlates with ingested dose:

• Standard therapeutic dosing: 200-250 μg/kg for approved parasitic infections 7
• Toxic doses in humans: A case report documented survival after ingesting ~100 times the standard dose (approximately 1200 mg total), though with significant neurological symptoms 2
• Animal toxicity data: Significant lethality observed at 25-50 mg/kg in mice/rats and 40-50 mg/kg in rats, with no significant lethality in dogs up to 10 mg/kg 1

Management Algorithm

Immediate interventions (if presenting within hours of ingestion):

1. Gastrointestinal decontamination: Induce emesis and/or perform gastric lavage as soon as possible, followed by purgatives 1
2. Activated charcoal: Administer via orogastric tube to prevent absorption of ingested material 1, 3
3. Consider mineral oil: May be administered 6 hours after activated charcoal 5

Supportive care (mainstay of treatment):

• Respiratory support: Provide oxygen and mechanical ventilation if necessary for bradypnea or respiratory distress 1, 6
• Fluid and electrolyte management: Administer parenteral fluids and electrolytes as indicated 1
• Hemodynamic support: Use pressor agents if clinically significant hypotension develops 1
• Monitoring: Close observation of hemodynamic parameters for at least 5 days 2

Experimental therapies (limited evidence):

• Intravenous lipid emulsion: One veterinary case report showed rapid improvement with 20% IV lipid emulsion (2 mL/kg IV bolus over 15 minutes, followed by 0.008 mL/kg/min IV infusion), though this is based on animal data only 5
• AntiGABAergic convulsants: Picrotoxin and pentylenetetrazol showed some benefit in animal studies but are not recommended for human use 4

Critical Pitfalls to Avoid

• Delayed presentation: Early treatment is crucial to prevent severe neurological complications and secondary organ damage 5, 6
• Underestimating severity: Even with massive overdoses (~100x therapeutic dose), patients can survive with aggressive supportive care, so do not prematurely withdraw treatment 2
• Ignoring secondary complications: Monitor for acute respiratory distress syndrome, acute renal tubular necrosis, and cerebral edema in severe cases 5, 6
• High-risk populations: Patients with severe liver disease are at increased risk for toxicity and require heightened vigilance 7

Clinical Course and Prognosis

Most patients show improvement within 24-72 hours with supportive care alone 2, 3. However, fatal outcomes have been reported, particularly with transdermal overdose leading to cerebral edema 6. The plasma concentration in one fatal case was documented at 27 ng/mL 6.