Omeprazole (caution): CYP2C19 inhibition. Rowland 2018 (PMID:29178272) verbatim: "Following dosing of modafinil to steady state (200 mg for 7 days), AUC ratios for caffeine, dextromethorphan, losartan, midazolam and omeprazole were 0.90 (± 0.16), 0.79 (± 0.09), 0.98 (± 0.11), 0.66 (± 0.12) and 1.90 (± 0.53), respectively". Open-label cocktail design. Omeprazole AUC 1.90× → Ki ≈ 10/0.90 = 11.1 µM. The canonical modafinil FDA-label DDI.
Midazolam (caution): CYP3A4 induction at steady state. Rowland 2018 (PMID:29178272) verbatim: same cocktail study, modafinil 200 mg/d × 7d gave midazolam AUC ratio "0.66 (± 0.12)". Single-dose modafinil arm showed no effect on midazolam (AUC 0.98) — induction emerges only at SS. AUC ratio 0.66 → induction_factor 1/0.66 = 1.52.
Dextromethorphan (caution): Mild CYP2D6 induction at steady state. Rowland 2018 (PMID:29178272) verbatim: same cocktail study, modafinil 200 mg/d × 7d gave dextromethorphan AUC ratio "0.79 (± 0.09)". Single-dose modafinil had no effect (AUC 1.01) — induction emerges only at SS. AUC ratio 0.79 → induction_factor 1.27. Mild but reproducible across the 12-subject cohort.
Notes
Prescription-only in most jurisdictions. Slow absorption; Tmax ~2-4h. DAT (dopamine transporter) occupancy is the primary mechanism per Volkow 2009 PET data: Ki ~2 µM = ~0.55 mg/L (modafinil MW 273). Therapeutic Cmax ~3-5 mg/L gives ~85-90% DAT occupancy — clinically informative range where the Hill curve is not yet at saturation.