Armodafinil (Nuvigil)

Class

Wakefulness-promoting agent

Mechanism

Similar to modafinil; thought to enhance wakefulness by inhibiting dopamine transporter and modulating glutamate and GABA neurotransmission

FDA-Approved Use

Narcolepsy, shift work sleep disorder, obstructive sleep apnea (OSA)-related sleepiness

Off-Label Use

Augmentation in major depressive disorder and bipolar disorder; fatigue in neurological conditions

Formulation

Oral tablets

Titration

Start at 150 mg p.o. in the morning; titrate between 150–250 mg/day as clinically indicated

Dose Range

150–250 mg/day

Kinetics

Longer half-life than modafinil (~15 hours); metabolized primarily by CYP3A4

Common AEs

Headache, insomnia, nausea, anxiety, dry mouth

Serious/Rare AEs

Severe rash (including Stevens-Johnson syndrome), mood destabilization in bipolar disorder

Monitoring

Monitor for rash and mood changes; assess cardiovascular status including baseline ECG and periodic blood pressure monitoring in patients with cardiac risk factors or older adults; monitor contraceptive efficacy in women using hormonal birth control

Black Box Warning

None

Considerations

Armodafinil is supported for treating excessive daytime sleepiness in traumatic brain injury (TBI). Evidence for benefit in multiple sclerosis (MS), Parkinson’s disease (PD), dementia, and post-stroke fatigue is limited or lacking. Use cautiously in bipolar disorder due to risk of mood switching. In patients with cardiovascular disease, consider baseline ECG and periodic blood pressure monitoring, especially in older adults or those with cardiac risk factors.