All three gepants are principally cleared by hepatic metabolism and are sensitive substrates of CYP3A4, suggesting that gepant pharmacokinetics is potentially influenced by CYP3A4 inhibitors/inducers. DHE is not an in vitro inhibitor of CYP3A4 activity. Clinically relevant in vivo DDIs arising from inhibition of hepatic/gastrointestinal CYP3A4 by DHE can be excluded. DHE is principally cleared by hepatic metabolism and is considered a CYP3A4 substrate; coadministration of potent CYP3A4 inhibitors with DHE is contraindicated. None of the three gepants is a potent inhibitor/inducer of CYP3A4. Data exclude clinically relevant DDIs from hepatic/gastrointestinal metabolic inhibition by gepants or from nasal metabolic inhibition of DHE. No clinically relevant DDIs from inhibition of, or being a substrate for, transporter proteins by gepants or DHE are anticipated because of limited data, but cannot be excluded.

Based on available data, no DDIs of clinical concern are predicted when recommended clinical doses of INP104 and gepants are coadministered.