Section 10 · Monograph

Armodafinil

Reviewed Nov 2026FDA label

NuvigilWake-promoting agent

Indications

Improve wakefulness in adult patients with excessive sleepiness associated with obstructive sleep apnea (OSA) — as an adjunct to standard OSA treatment.FDA-labeled
Improve wakefulness in adult patients with excessive sleepiness associated with narcolepsy.FDA-labeled
Improve wakefulness in adult patients with excessive sleepiness associated with shift work disorder (SWD).FDA-labeled

Adjunctive treatment for fatigue/sleepiness in major depressive disorder (including bipolar depression) — off-label.Off-label
Fatigue associated with multiple sclerosis or cancer-related fatigue — off-label, limited evidence.Off-label
Adult ADHD — off-label, not FDA approved.Off-label

Armodafinil is the R-enantiomer (longer half-life, more slowly cleared component) of racemic modafinil; precise mechanism of wake-promoting activity is unknown.
Produces wake-promoting effects similar to sympathomimetic agents but with a distinct pharmacologic profile from classic amphetamine-type stimulants.
Binds to the dopamine transporter and inhibits dopamine reuptake, increasing extracellular dopamine; wake-promoting activity is attenuated by dopamine receptor antagonists.
Does not show significant direct binding affinity for most receptors classically involved in sleep/wake regulation.

OSA and narcolepsy: 150-250 mg orally once daily in the morning (150 mg is as effective as 250 mg in most patients).
Shift work disorder: 150 mg orally once daily, approximately 1 hour prior to the start of the work shift.
Geriatric patients: consider lower starting dose and slower titration.

No renal dose adjustment specifically established, but caution advised in severe renal impairment.

Known hypersensitivity to armodafinil or modafinil, or to any inactive ingredient in the formulation.

Hormonal contraceptives: armodafinil induces CYP3A4, reducing contraceptive effectiveness.
CYP2C19 substrates (phenytoin, diazepam, propranolol, omeprazole, clomipramine): armodafinil inhibits CYP2C19.
Sensitive CYP3A4 substrates (triazolam, cyclosporine): may have reduced plasma concentrations.
Warfarin: monitor INR more closely during initiation or dosage changes.
MAO inhibitors: caution; no formal interaction studies performed.
CNS-active drugs and alcohol: armodafinil does not reverse the impairing effects of alcohol/sedatives on complex tasks such as driving.

Most common (≥5%): headache, nausea, dizziness, and insomnia.
Serious skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis, and DRESS — rare but potentially life-threatening; typically within 1-5 weeks of starting.
Multi-organ hypersensitivity reactions; discontinue immediately if suspected.
Angioedema and anaphylaxis.
Psychiatric symptoms: anxiety, agitation, irritability; postmarketing reports of mania, hallucinations, suicidal ideation, and aggression.
Cardiovascular effects: increased blood pressure/heart rate possible; avoid in patients with left ventricular hypertrophy or mitral valve prolapse with prior CNS stimulant-associated cardiac symptoms.
Persistent sleepiness — does not eliminate the need for adequate sleep.

Blood pressure and heart rate at baseline and periodically, especially with cardiovascular disease.
Skin — counsel patients to report any new rash immediately.
Mental status/mood for new or worsening anxiety, psychosis, mania, or suicidality.
Ongoing assessment of excessive sleepiness severity and driving/occupational safety.
Hepatic function in patients with baseline hepatic impairment.
Contraceptive counseling for patients on hormonal contraception.

Pregnancy: Limited human data; based on data with modafinil (armodafinil is the R-enantiomer), there is concern for increased risk of congenital malformations, particularly cardiac. Animal studies showed developmental toxicity. Encourage enrollment in the pregnancy exposure registry (1-866-404-4106).
Lactation: No data on presence in human milk, effects on the breastfed infant, or on milk production.