From the Guidelines
Gabapentin is not associated with significant hepatotoxicity, as it does not undergo significant liver metabolism and is primarily eliminated by the kidneys. According to the study published in Hepatology in 2020 1, gabapentin's metabolism and excretion are characterized as "M: None E: Renal 75%, fecal 25%", indicating that it is not metabolized by the liver to a significant extent. This characteristic makes it unlikely to cause liver damage in most patients.
The study also notes that gabapentin has not been studied in patients with alcoholic liver disease (ALD), but it suggests monitoring closely for renal dysfunction and worsening mental status/sedation 1. While there may be rare cases of liver injury associated with gabapentin use, these are extremely uncommon and often involve patients with pre-existing liver conditions or those taking multiple medications.
Key points to consider when prescribing gabapentin include:
- Gabapentin is primarily eliminated by the kidneys, reducing the risk of hepatotoxicity
- Patients with normal liver function do not typically require specific liver monitoring
- Patients with pre-existing liver disease should be monitored more closely and may require dose adjustments
- Rare cases of liver injury associated with gabapentin use have been reported, often in patients with pre-existing liver conditions or those taking multiple medications.
Overall, the available evidence suggests that gabapentin is a safe option for patients without significant liver disease, and its potential for hepatotoxicity is low 1.
From the Research
Hepatotoxicity Associated with Gabapentin
- There is evidence to suggest that gabapentin may be associated with hepatotoxicity, although the mechanism by which it produces liver injury is still unknown 2.
- A study reported a case of acute liver injury probably secondary to gabapentin in a 56-year-old male patient with a history of chronic kidney disease on hemodialysis and narrowing of the spinal canal 2.
- Another study found that high doses of gabapentin (100 mg/kg) administered to adult male rats for 45 days resulted in significant increases in liver enzymes and histopathological changes, whereas therapeutic doses (20 mg/kg) did not cause significant liver damage 3.
- However, gabapentin is not metabolized by the liver and does not induce hepatic enzymes, which suggests a low risk of hepatotoxicity 4.
- Gabapentin is also listed as a medication that may increase the risk of hepatic encephalopathy in patients with cirrhosis, although the evidence for this association is not directly related to hepatotoxicity 5.
Key Findings
- Gabapentin may cause hepatotoxicity, but the evidence is limited to case reports and animal studies 2, 3.
- The mechanism of gabapentin-induced hepatotoxicity is unknown 2.
- Therapeutic doses of gabapentin appear to be safe in terms of liver function and hepatocellular damage 3.
- Gabapentin is not metabolized by the liver and does not induce hepatic enzymes, which suggests a low risk of hepatotoxicity 4.