Limonene - Provigil (Modafinil) Interaction
Herbal: Limonene
Drug: Modafinil
Brand names:
Provigil, Sparlon, Alertec

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
May 25, 2025
Interaction Details
Modafinil is classified as belonging to the following category: Cytochrome P450 2C19 (Cyp2C19) Inhibitors
There's preliminary evidence that limonene might be a substrate for cytochrome P450 2C19 (CYP2C19). So far, this interaction has not been reported in humans. However, watch for an increase in the limonene levels when it is taken with drugs that inhibit CYP2C19. Some drugs that inhibit CYP2C19 include cimetidine (Tagamet), fluvoxamine (Luvox), omeprazole (Prilosec); ticlopidine (Ticlid), topiramate (Topamax), and others.
Interaction Rating
Likelihood of Occurrence
PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists
References
- Crowell PL. Prevention and therapy of cancer by dietary monoterpenes. J Nutr 1999;129:775S-778S.
- Miyazawa M, Shindo M, Shimada T. Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes. Drug Metab Dispos 2002;30:602-7.
Interaction Details
Modafinil is classified as belonging to the following category: Cytochrome P450 2C9 (Cyp2C9) Inhibitors
There's preliminary evidence that limonene might be a substrate for cytochrome P450 2C9 (CYP2C9). So far, this interaction has not been reported in humans. However, watch for side effects in patients taking limonene and CYP2C9 inhibitors. Some CYP2C9 inhibitors include amiodarone (Cordarone), fluconazole (Diflucan), lovastatin (Mevacor), paroxetine (Paxil), zafirlukast (Accolate), and many others.
Interaction Rating
Likelihood of Occurrence
PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists
References
- Crowell PL. Prevention and therapy of cancer by dietary monoterpenes. J Nutr 1999;129:775S-778S.
- Miyazawa M, Shindo M, Shimada T. Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes. Drug Metab Dispos 2002;30:602-7.
Modafinil Overview
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Modafinil is used to treat excessive sleepiness caused by narcolepsy (a condition that causes excessive daytime sleepiness) or shift work sleep disorder (sleepiness during scheduled waking hours and difficulty falling asleep or staying asleep during scheduled sleeping hours in people who work at night or on rotating shifts). Modafinil is also used along with breathing devices or other treatments to prevent excessive sleepiness caused by obstructive sleep apnea/hypopnea syndrome (OSAHS; a sleep disorder in which the patient briefly stops breathing or breathes shallowly many times during sleep and therefore doesn't get enough restful sleep). Modafinil is in a class of medications called wakefulness promoting agents. It works by changing the amounts of certain natural substances in the area of the brain that controls sleep and wakefulness.
Limonene - More Interactions
Limonene interacts with 224 drugs
Interaction Rating Key
These severity listings are for informational use only. Never start, stop or otherwise change your therapy before speaking with your provider.
Major | The combined use of these agents is strongly discouraged as serious side effects or other negative outcomes could occur. |
Moderate | Use cautiously under the care of a healthcare professional or avoid this combination. A significant interaction or negative outcome could occur. |
Minor | Be aware that there is a chance of an interaction. Watch for warning signs of a potential interaction. |
Unknown | No interactions have been reported or no interaction data is currently available. |
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DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.
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Drug descriptions are provided by MedlinePlus.