armodafinil

General Information

Armodafinil (Nuvigil) is a wakefulness-promoting medication indicated to improve wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea (OSA), or shift work disorder (SWD) (label).

It is the longer-acting R-enantiomer of modafinil and is a Schedule IV controlled substance. It is sometimes discussed off-label for fatigue or residual sleepiness in psychiatric settings, but use is individualized and requires monitoring for activation and insomnia (label/clinical).

Serious rash and hypersensitivity reactions are rare but safety-critical; discontinuation is recommended at the first sign of rash unless clearly not drug-related (label).

Psychiatric adverse reactions (anxiety, agitation, mania, psychosis, suicidal ideation) have been reported; monitoring is especially important in bipolar-spectrum illness, psychosis, or high baseline anxiety (label/clinical).

The armodafinil compare view, evidence feed, and print page support review of activation, insomnia, and interaction profiles.

Armodafinil is widely used for excessive sleepiness and may be preferred when longer duration is desired, but careful patient selection is important due to psychiatric activation risk, serious rash warnings, and CYP-mediated drug–drug interaction potential (label/clinical).

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

The precise mechanism is not fully established. Clinical descriptions emphasize wake-promoting effects and effects on monoaminergic signaling, including dopaminergic pathways (label/clinical).

Armodafinil is the R-enantiomer of modafinil; compared with racemic modafinil, systemic exposure of the R-enantiomer is higher at steady state, contributing to a longer duration profile (label).

• Wakefulness promotion (mechanism not fully established; label).

Metabolism and Pharmacokinetics

• Apparent terminal elimination half-life is ~15 hours; steady state is reached within about 7 days with once-daily dosing (label).
• Armodafinil induces CYP3A4/5 and can inhibit CYP2C19, which may reduce exposure to CYP3A substrates and increase exposure to CYP2C19 substrates; interaction review is clinically important (label).

Dosing and Administration

• Narcolepsy or OSA: 150–250 mg once daily in the morning (label).
• Shift work disorder: 150 mg once daily approximately 1 hour prior to the start of the work shift (label).
• For OSA, armodafinil is not a substitute for primary therapies; it is used as adjunctive therapy when residual sleepiness persists alongside an OSA management plan (label/clinical).
• In clinical practice, late-day dosing is avoided due to insomnia risk; dose timing is a frequent early follow-up topic (clinical).

Monitoring & Labs

• Rash and hypersensitivity monitoring, especially early in treatment (label).
• Blood pressure and heart rate monitoring, especially with cardiac risk factors (label/clinical).
• Mood and psychiatric symptom monitoring (anxiety, agitation, mania/psychosis) (label/clinical).
• Sleep disruption monitoring (insomnia, timing effects) (clinical).
• Drug interaction review (CYP3A induction; CYP2C19 inhibition), including contraception counseling (label).

Adverse Effects

Interactions

• CYP3A4 induction can reduce exposure to steroidal contraceptives and other CYP3A substrates; counseling about reduced hormonal contraceptive effectiveness is an important practical step (label).
• CYP2C19 inhibition can increase exposure to CYP2C19 substrates (diazepam, propranolol, omeprazole, some tricyclic antidepressants); interaction review is important in polypharmacy (label/clinical).
• Combined use with other activating agents can increase anxiety, insomnia, and cardiovascular effects; monitoring is commonly considered (clinical).

Other Useful Information

• AASM evidence reviews and guidelines support wake-promoting agents for excessive daytime sleepiness in central hypersomnolence disorders, but medication choice is individualized based on comorbidities, interaction burden, and adverse-effect profiles (AASM/clinical).
• In psychiatric augmentation discussions (fatigue/residual sleepiness), clinicians often document symptom targets and a time-bounded reassessment plan to reduce long-term polypharmacy without clear benefit (clinical).

References

1. NUVIGIL (armodafinil) tablets prescribing information — DailyMed (2025)
2. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline — Journal of Clinical Sleep Medicine (2021)
3. Treatment OF Central Disorders OF Hypersomnolence: AN American Academy OF Sleep Medicine Systematic Review, Meta Analysis, AND Grade Assessment — Journal of Clinical Sleep Medicine (2021)
4. The efficacy and safety of armodafinil as treatment for adults with excessive sleepiness associated with narcolepsy — Current Medical Research and Opinion (2006)