Provigil and PPIs (Omeprazole, Pantoprazole): Interaction Explained

What the Provigil label says about PPIs

Modafinil is a wakefulness-promoting drug approved for excessive sleepiness in adults with narcolepsy, obstructive sleep apnea and shift work disorder [1]. It is also a CYP2C19 inhibitor [1].

The drug interaction section names CYP2C19 substrates and gives examples: phenytoin, diazepam, propranolol, omeprazole and clomipramine. It says their elimination may be prolonged by Provigil via inhibition of metabolic enzymes, with resultant higher systemic exposure, and that dose adjustments of these drugs may be necessary when they are used with Provigil [1].

Omeprazole is the only PPI in that list, and pantoprazole is not one of the examples [1]. No specific adjustment for omeprazole is written out in that section; the statement is a general one about CYP2C19 substrates [1].

Higher exposure means more of the PPI in the body than the same dose would produce on its own.

Which direction does the interaction go?

The Provigil interaction section is written from one side: what modafinil does to other drugs. It covers CYP3A4/5 substrates such as steroidal contraceptives, cyclosporine, midazolam and triazolam; CYP2C19 substrates including omeprazole; warfarin; and MAO inhibitors [1].

Modafinil is a CYP3A4/5 inducer and a CYP2C19 inhibitor [1]. CYP2C19 is an enzyme involved in PPI metabolism [2], and omeprazole is mainly cleared by it.

Omeprazole versus pantoprazole

Omeprazole is the PPI the Provigil label uses as its example of a CYP2C19 substrate whose elimination may be prolonged [1].

Pantoprazole does not appear in that list [1]. Being named in a label's list, or left off it, does not measure how much a PPI's blood level moves when modafinil is added. It means omeprazole is the PPI the label specifically flags, and pantoprazole is not addressed by name.

Esomeprazole (Nexium) is the S-enantiomer of omeprazole [3].