What is the effect of Aricept (donepezil) on liver function tests?

Effect of Donepezil (Aricept) on Liver Function Tests

Donepezil has no significant impact on liver function tests during short-term use, but long-term use may cause slight elevations in liver enzymes while still remaining within normal reference ranges. 1

Pharmacokinetics and Hepatic Metabolism

Donepezil is primarily metabolized through the following pathways:

• Metabolized by CYP450 isoenzymes 2D6 and 3A4 2
• Undergoes glucuronidation 2
• Approximately 57% of the drug is excreted in urine and 15% in feces 2
• About 17% of the donepezil dose is recovered in urine as unchanged drug 2

Unlike tacrine (an earlier cholinesterase inhibitor), donepezil does not cause hepatotoxicity, which is a significant advantage in its safety profile 3.

Short-Term Effects on Liver Function

In short-term evaluations (one month of treatment at 5 mg/day), no significant differences were observed in liver function parameters compared to baseline values 1. This suggests that donepezil is well-tolerated by the liver during initial treatment phases.

Long-Term Effects on Liver Function

With long-term use (up to six years at 10 mg/day), studies have shown:

• AST and ALT levels increased significantly compared to pretreatment levels after two years of use 1
• Despite these increases, values remained within normal reference ranges 1
• Levels at four years were similar to those measured at two years, suggesting stabilization of hepatic effects 1

Hepatic Disease Considerations

In patients with pre-existing liver disease:

• A study of 10 patients with stable alcoholic cirrhosis showed that clearance of donepezil was decreased by 20% compared to healthy matched subjects 2
• Donepezil may be used in patients with stable hepatic disease, but more frequent laboratory and clinical monitoring is recommended 4

Monitoring Recommendations

For patients taking donepezil:

• Routine liver function monitoring is not necessary for most patients without pre-existing liver disease 4
• For patients with pre-existing liver disease or who develop abnormal liver function, liver function tests should be measured monthly and when symptoms occur 4
• Customized dosage according to hepatic function may be necessary for patients with significant liver disease 1

Comparison to Other Cholinesterase Inhibitors

Donepezil has a favorable hepatic safety profile compared to other medications in its class:

• Unlike tacrine, which requires liver function monitoring due to hepatotoxicity, donepezil has no significant hepatotoxicity 4, 3
• Galantamine is contraindicated for use in patients with hepatic impairment 4
• Rivastigmine has not been associated with significant liver effects 4

Clinical Implications

When prescribing donepezil:

• No dose adjustment is needed for patients with mild to moderate hepatic disease 5
• The 5 mg dose can be given safely to patients with mild-to-moderate hepatic disease 5
• More caution and potentially lower dosing may be needed in patients with severe hepatic impairment
• The benefits of donepezil in treating Alzheimer's disease (improved cognition, activities of daily living, and behavior) 6 should be weighed against any potential hepatic effects

In conclusion, while donepezil may cause slight elevations in liver enzymes with long-term use, these changes typically remain within normal reference ranges and do not require discontinuation of therapy in most patients. However, monitoring is recommended for patients with pre-existing liver disease.