What are the effects of Ivermectin on the liver?

From the Guidelines

Ivermectin is generally well-tolerated and has minimal effects on the liver when used at standard therapeutic doses. While rare, liver injury can occur with ivermectin use, typically presenting as mild, asymptomatic elevations in liver enzymes that resolve once the medication is discontinued 1. Severe liver damage from ivermectin is extremely uncommon in humans. Patients with pre-existing liver disease should use ivermectin with caution and may require dose adjustments or more frequent monitoring of liver function tests. Some key points to consider when evaluating the liver effects of ivermectin include:

• The medication is primarily metabolized in the liver through the cytochrome P450 system, specifically the CYP3A4 enzyme, which explains its potential, though limited, hepatic impact 1.
• If symptoms like yellowing of the skin or eyes, dark urine, abdominal pain, or unusual fatigue occur while taking ivermectin, patients should contact their healthcare provider immediately as these could indicate liver problems.
• For most patients taking standard doses for approved indications, routine liver function monitoring is not required unless there are specific risk factors or symptoms suggesting liver involvement. It's also worth noting that ivermectin has been shown to have anti-inflammatory effects in in vitro and in vivo studies, which may be beneficial in certain contexts 1. However, the primary concern when considering ivermectin's effects on the liver is the potential for rare but significant liver injury, and patients should be monitored accordingly.

From the FDA Drug Label

Ivermectin is metabolized in the liver, and ivermectin and/or its metabolites are excreted almost exclusively in the feces over an estimated 12 days, with less than 1% of the administered dose excreted in the urine. The liver plays a role in the metabolism of ivermectin, but there is no direct information on the effects of ivermectin on the liver.

• The drug label does not provide information on liver toxicity or hepatotoxicity.
• Key points:
  • Ivermectin is metabolized by the liver.
  • No direct information on liver effects is available. 2 2

From the Research

Ivermectin Effects on the Liver

• The use of ivermectin has been associated with hepatic disorders, including hepatitis, hepatocellular injury, and cholestasis 3.
• A case report described a patient who developed jaundice and liver injury after initiating ivermectin for COVID-19 prevention, with liver histology showing a pattern of injury that was both portal and lobular 4.
• Another study found that ivermectin had been used for COVID-19 in 25 cases, with 6 of those cases experiencing hepatic disorders, including increased alanine aminotransferase and/or aspartate aminotransferase levels, and abnormal liver function tests 3.
• While ivermectin has been shown to have anti-parasitic, anti-inflammatory, anti-viral, and anticancer effects, its potential to cause liver injury is a concern that should be studied more exhaustively 3, 4, 5.

Mechanism of Action and Potential Risks

• Ivermectin's mechanism of action in parasitic diseases involves interfering with the glutamate-gated chloride channels in invertebrates, but its effects on the liver are not fully understood 5.
• The ability of ivermectin to block the nuclear factor kappa-light-chain enhancer of the activated B (NF-κB) pathway may contribute to its anti-inflammatory effects, but may also play a role in its potential to cause liver injury 5.
• Further studies are needed to fully understand the potential risks and benefits of using ivermectin, particularly in the context of COVID-19 treatment 3, 4, 6.