Armodafinil

• Narcolepsy
• Obstructive Sleep Apnea
• Shift Work Disorder
• Excessive Daytime Sleepiness

Armodafinil is a wakefulness-promoting agent used to treat excessive sleepiness associated with narcolepsy, obstructive sleep apnea, and shift work disorder. As the R-enantiomer of modafinil, armodafinil provides similar therapeutic effects with a longer duration of action.

Mechanism of Action

The precise mechanism by which armodafinil promotes wakefulness is not fully understood. Unlike traditional stimulants, armodafinil does not appear to work primarily through catecholamine release. Current evidence suggests it may bind to the dopamine transporter and inhibit dopamine reuptake, leading to increased extracellular dopamine levels in specific brain regions. Armodafinil also appears to modulate GABA, glutamate, histamine, and orexin/hypocretin systems. The net effect is promotion of wakefulness without the jitteriness, euphoria, or significant cardiovascular effects associated with amphetamines.

Available Formulations

Armodafinil is available as oral tablets in 50 mg, 150 mg, 200 mg, and 250 mg strengths. The tablets can be taken with or without food, though food may delay absorption slightly. It is a Schedule IV controlled substance in the United States due to its potential for abuse and dependence.

Medical Uses

Armodafinil is FDA-approved to improve wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea (as an adjunct to CPAP therapy), and shift work disorder. It is important to note that armodafinil does not treat the underlying cause of sleepiness and, in obstructive sleep apnea, should not replace CPAP or other primary treatments. Off-label uses include treatment of fatigue associated with multiple sclerosis, cancer, and other conditions.

Dosing Guidelines

For narcolepsy and obstructive sleep apnea, the recommended dose is 150-250 mg taken orally once daily in the morning. For shift work disorder, 150 mg should be taken approximately one hour before the start of the work shift. Doses above 250 mg daily have not shown additional benefit. For patients with severe hepatic impairment, the dose should be reduced. The medication should be taken at the same time each day for consistency.

Important Safety Information

Armodafinil can cause serious skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis, which can be fatal. Treatment should be discontinued at the first sign of rash, unless clearly not drug-related. Multi-organ hypersensitivity reactions have been reported. Psychiatric symptoms including anxiety, mania, hallucinations, and suicidal ideation may occur. Armodafinil may reduce the effectiveness of hormonal contraceptives; alternative contraception is recommended during treatment and for one month after discontinuation.

Drug Interactions

Armodafinil is a moderate inducer of CYP3A4 and may reduce plasma levels of drugs metabolized by this enzyme, including hormonal contraceptives, cyclosporine, and midazolam. It is a weak inhibitor of CYP2C19 and may increase levels of drugs metabolized by this pathway (omeprazole, phenytoin, diazepam). Coadministration with alcohol is not recommended. Strong CYP3A4 inducers may reduce armodafinil effectiveness.

Special Populations

There are no adequate studies in pregnant women; the medication should be used during pregnancy only if the potential benefit justifies the potential risk. Armodafinil or its metabolites are excreted in rat milk; caution should be exercised in nursing mothers. Safety and efficacy have not been established in pediatric patients. Elderly patients may have reduced clearance; consider lower doses. Dose reduction is recommended in severe hepatic impairment. The medication is largely eliminated through hepatic metabolism, so severe renal impairment has minimal impact on pharmacokinetics.