Solriamfetol

• Narcolepsy
• Obstructive Sleep Apnea
• Excessive Daytime Sleepiness

Solriamfetol is a dopamine and norepinephrine reuptake inhibitor (DNRI) used to treat excessive daytime sleepiness (EDS) in adults with narcolepsy or obstructive sleep apnea (OSA). Unlike traditional stimulants, it has a unique pharmacological profile.

Mechanism of Action

Solriamfetol enhances dopaminergic and noradrenergic transmission:

• Dopamine reuptake inhibition: Blocks dopamine transporter (DAT)
• Norepinephrine reuptake inhibition: Blocks norepinephrine transporter (NET)
• No direct catecholamine release: Unlike amphetamines, does not cause monoamine release
• Promotes wakefulness: Through enhanced dopamine and norepinephrine signaling in wake-promoting brain regions

This mechanism provides alertness without the abuse potential associated with amphetamine-like release mechanisms.

Available Formulations

Solriamfetol is available as tablets:

• 75 mg tablets
• 150 mg tablets

Also available as a 37.5 mg tablet (for titration).

Medical Uses

FDA-Approved Indications:

• Excessive daytime sleepiness (EDS) in adult patients with narcolepsy
• Excessive daytime sleepiness in adult patients with obstructive sleep apnea (OSA)

For OSA, solriamfetol does not treat the underlying airway obstruction; primary OSA therapy (e.g., CPAP) should be continued.

Dosing Guidelines

Narcolepsy:

• Starting dose: 75 mg once daily upon awakening
• May increase to 150 mg after at least 3 days
• Maximum: 150 mg daily

Obstructive Sleep Apnea:

• Starting dose: 37.5 mg once daily upon awakening
• May double dose weekly to 75 mg, then 150 mg
• Maximum: 150 mg daily

Renal Impairment:

• eGFR 30-59: Max 75 mg daily
• eGFR 15-29: Max 37.5 mg daily
• eGFR <15: Avoid use

Important Safety Information

Controlled Substance:

• Schedule IV controlled substance

Contraindications:

• Concomitant use with MAOIs or within 14 days of MAOI discontinuation

Warnings and Precautions:

• Blood pressure and heart rate increases: May elevate BP and HR; assess before starting and monitor during treatment
• Psychiatric symptoms: Anxiety, insomnia, and irritability may occur
• Abuse potential: Schedule IV; assess for history of substance abuse
• Not for use in severe OSA as sole therapy: Continue CPAP or other OSA treatment

Drug Interactions

• MAOIs: Contraindicated (hypertensive crisis risk)
• Dopaminergic drugs: Potential for additive effects; use with caution
• Other CNS stimulants: Use with caution; additive cardiovascular and CNS effects
• CYP450: No significant interactions (minimal CYP metabolism)

Special Populations

• Hepatic Impairment: No adjustment for mild to moderate; not studied in severe
• Renal Impairment: Dose adjustment required (see above)
• Pregnancy: Limited data; use only if benefit outweighs risk
• Lactation: Unknown if excreted in milk
• Elderly: No adjustment; consider renal function
• Pediatric: Safety and efficacy not established