REYVOW® (lasmiditan): Metabolism and Elimination

Additional Information Regarding Metabolism and Elimination

Metabolism

Lasmiditan undergoes hepatic and extrahepatic metabolism primarily by non-CYP enzymes.¹

Lasmiditan is primarily eliminated via metabolism. Major metabolites of lasmiditan identified in plasma and urine are

• S-M8, through ketone reduction to the alcohol (major pathway), 

• M7, through oxidation on piperidine ring, and

• M18, through a combination of M7 and M8 pathways.¹

Relative to lasmiditan, these metabolites exhibited considerably lower affinity (~1000-fold lower K_i) for the target 5-HT_1F receptor and are considered pharmacologically inactive.¹

The following enzymes are not involved in metabolism of lasmiditan, including

• MAO-A

• MAO-B

• flavin monooxygenase 3

• CYP450 reductase

• xanthine oxidase

• alcohol dehydrogenase 

• aldehyde dehydrogenase, and

• aldo-keto reductases.¹

Excretion

Renal excretion is a minor route of lasmiditan clearance with approximately 3% of the dose recovered as unchanged lasmiditan in urine. Metabolite S-M8 represented approximately 66% of the dose in urine, with the majority of recovery within 48 hours post-dose.¹

Enclosed Prescribing Information

REYVOW® (lasmiditan) tablets, for oral use, CV, Lilly

References

1. Reyvow [package insert]. Indianapolis, IN: Eli Lilly and Company; 2020.

Glossary

5-HT_1F = serotonin-1F 

CYP = cytochrome P450

K_i = inhibition constant

MAO = monoamine oxidase