How should Sunosi (solriamfetol) be initiated, titrated, and monitored in an adult with excessive daytime sleepiness due to narcolepsy or obstructive sleep apnea, who has controlled blood pressure, no serious cardiovascular disease, and moderate renal impairment, and what alternative wake‑promoting agents are available?

Sunosi (Solriamfetol) for Excessive Daytime Sleepiness

Initiation and Titration Protocol

For patients with moderate renal impairment (eGFR 30-59 mL/min/1.73 m²), initiate solriamfetol at 37.5 mg once daily upon awakening, regardless of whether the indication is narcolepsy or obstructive sleep apnea, and titrate to a maximum of 75 mg once daily after at least 7 days based on efficacy and tolerability. 1

Standard Dosing for Normal Renal Function

• Obstructive Sleep Apnea: Start at 37.5 mg once daily, double the dose at intervals of at least 3 days based on response, with a maximum of 150 mg once daily 1
• Narcolepsy: Start at 75 mg once daily, double the dose at intervals of at least 3 days based on response, with a maximum of 150 mg once daily 1

Modified Dosing for Renal Impairment

Your patient with moderate renal impairment requires dose adjustment:

• Moderate renal impairment (eGFR 30-59): Start 37.5 mg daily, wait minimum 7 days before increasing to maximum 75 mg daily 1
• Severe renal impairment (eGFR 15-29): Use only 37.5 mg daily as both starting and maximum dose 1
• End-stage renal disease (eGFR <15): Solriamfetol is not recommended 1

Administration Details

• Administer upon awakening with or without food 1
• Avoid taking within 9 hours of planned bedtime to prevent sleep interference 1
• The 75 mg tablets are functionally scored and can be split in half to achieve 37.5 mg dosing 1

Pre-Treatment Requirements

Blood pressure must be adequately controlled before initiating solriamfetol, as the medication increases blood pressure and heart rate through dopamine/norepinephrine reuptake inhibition. 1

• Measure baseline blood pressure and ensure it is controlled (ideally <130/80 mm Hg) 1
• Solriamfetol is contraindicated with concurrent MAO inhibitor use or within 14 days of MAO inhibitor discontinuation due to hypertensive reaction risk 1
• Ensure OSA patients have been treated with CPAP or other airway modalities for at least one month before starting solriamfetol, as the drug does not treat underlying airway obstruction 1

Monitoring Protocol

Cardiovascular Monitoring

• Check blood pressure at baseline and monitor regularly during titration, as solriamfetol causes dose-related increases in blood pressure and heart rate 1
• Monitor for palpitations, arrhythmias, chest discomfort, and hypertension at each dose adjustment 2

Efficacy Assessment

• Use the Epworth Sleepiness Scale at baseline and reassess at 2-4 weeks after reaching stable dose to quantify improvement in excessive daytime sleepiness 3, 4
• Most patients (64%) adjust dosages once and reach stable doses over a median of 14 days in real-world practice 3

Common Adverse Events

The most frequently reported adverse events include:

• Headache, decreased appetite, insomnia, nausea, and chest discomfort (most are mild to moderate in severity) 2
• Nasopharyngitis, dry mouth, anxiety, and upper respiratory tract infection 4
• Most adverse events occur within 2 weeks of treatment initiation and typically resolve within 2 weeks 5

Evidence Base and Clinical Efficacy

The American Academy of Sleep Medicine issues a STRONG recommendation for solriamfetol use in narcolepsy based on high-quality evidence from 3 randomized controlled trials demonstrating clinically significant improvements in excessive daytime sleepiness and disease severity. 2

• Solriamfetol produces significant increases in mean sleep latency (MD = 9.52 minutes, 95% CI: 7.60 to 11.44) and reductions in Epworth Sleepiness Scale scores (MD = -3.74,95% CI: -4.38 to -3.09) compared to placebo 6
• Benefits are sustained through 52 weeks of treatment with continued improvements in functional status, work productivity, and quality of life 4
• The 150 mg dose is the most appropriate and stable dose for excessive sleepiness in patients without renal impairment 6

Alternative Wake-Promoting Agents

First-Line Alternatives

Modafinil/armodafinil represent the primary alternatives:

• Armodafinil: Conditional recommendation from the American Academy of Sleep Medicine based on moderate-quality evidence; typical dosing 150-250 mg once daily upon awakening 2
• Modafinil: Similar efficacy profile; dosing 200-400 mg daily, starting at 100 mg in elderly patients 7
• Both are Schedule IV controlled substances and may reduce oral contraceptive effectiveness 2

Traditional Stimulants

Dextroamphetamine and methylphenidate are reserved for refractory cases:

• Dextroamphetamine: Conditional recommendation based on very low-quality evidence; Schedule II controlled substance with black box warning for high abuse potential 2
• Methylphenidate: Start 2.5-5 mg with breakfast, second dose at lunch if needed 7
• Both carry significantly higher abuse and dependence risk compared to solriamfetol 2

Pitolisant

• Histamine-3 receptor inverse agonist effective for both excessive daytime sleepiness and cataplexy (if present) 8
• Not a controlled substance, making it attractive for patients with substance abuse concerns 8
• Moderate-quality evidence from 3 RCTs showing clinically significant improvements 8

Critical Safety Considerations

Controlled Substance Status

• Solriamfetol is a Schedule IV federally controlled substance due to potential for abuse or dependency 2
• Lower abuse potential compared to Schedule II stimulants (amphetamines, methylphenidate) 2

Pregnancy and Breastfeeding

• Based on animal data, solriamfetol may cause fetal harm; human data are insufficient to determine risk 2
• The balance of risks and harms differs for pregnant and breastfeeding women, requiring careful risk-benefit assessment 2

Cardiovascular Contraindications

• Use caution in patients with serious cardiovascular disease, as solriamfetol increases blood pressure and heart rate 1
• Your patient's controlled blood pressure and absence of serious cardiovascular disease make solriamfetol appropriate, but ongoing monitoring remains essential 1

Common Pitfalls to Avoid

• Do not exceed 75 mg daily in moderate renal impairment, as higher doses increase adverse event risk without proportional efficacy benefit 1
• Do not initiate solriamfetol in OSA patients until CPAP adherence is established for at least one month, as the medication does not treat underlying airway obstruction 1
• Do not combine with MAO inhibitors or initiate within 14 days of MAO inhibitor discontinuation due to hypertensive crisis risk 1
• Do not assume all wake-promoting agents are equivalent—solriamfetol does NOT treat cataplexy, unlike sodium oxybate or pitolisant 8