General Information

Sunosi (solriamfetol) is a dopamine and norepinephrine reuptake inhibitor.

Sunosi is specifically indicated to improve wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea (OSA).

Sunosi is supplied as a tablet for oral administration. Administer Sunosi orally upon awakening with or without food. Avoid taking Sunosi within 9 hours of planned bedtime because of the potential to interfere with sleep if taken too late in the day. Sunosi 75 mg tablets are functionally scored tablets that can be split in half (37.5 mg) at the score line. The recommended dose is as follows:

Dosage in Narcolepsy: Initiate Sunosi at 75 mg once daily in adults with narcolepsy. The recommended dose range for Sunosi is 75 mg to 150 mg once daily. Based on efficacy and tolerability, the dosage of Sunosi may be doubled at intervals of at least 3 days. The maximum recommended dose is 150 mg once daily. Dosages above 150 mg daily do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions.

Dosage in OSA: Initiate Sunosi at 37.5 mg once daily in adults with OSA. The recommended dosage range for Sunosi is 37.5 mg to 150 mg once daily. Based on efficacy and tolerability, the dosage of Sunosi may be doubled at intervals of at least 3 days. The maximum recommended dosage is 150 mg once daily. Dosages above 150 mg daily do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions.

Mechanism of Action

Sunosi (solriamfetol) is a dopamine and norepinephrine reuptake inhibitor. The mechanism of action of solriamfetol to improve wakefulness in patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea is unclear. However, its efficacy could be mediated through its activity as a dopamine and norepinephrine reuptake inhibitor (DNRI).

Side Effects

Adverse effects associated with the use of Sunosi may include, but are not limited to, the following:

• headache
• nausea
• decreased appetite
• insomnia
• anxiety

Clinical Trial Results

The FDA approval of Sunosi was based on the following clinical trials:

Narcolepsy

The efficacy of Sunosi in improving wakefulness and reducing excessive daytime sleepiness was demonstrated in a 12-week, multi-center, randomized, double-blind, placebo-controlled, parallel-group study in adult patients with a diagnosis of narcolepsy according to the ICSD-3 or DSM-5 criteria. A total of 239 patients with narcolepsy were randomized to receive Sunosi 75 mg, 150 mg, or 300 mg (two times the maximum recommended daily dose), or placebo once daily. Patients randomized to the 150-mg dose received 75 mg for the first 3 days before increasing to 150 mg. Wakefulness and sleepiness were assessed using the Maintenance of Wakefulness Test (MWT) and the Epworth Sleepiness Scale (ESS). The co-primary efficacy endpoints were change from baseline in MWT and ESS at Week 12. Compared to the placebo group, patients randomized to 150 mg Sunosi showed statistically significant improvements on the MWT (treatment effect difference: 7.7 minutes) and on the ESS (treatment effect difference: 3.8 points) at Week 12. These effects were apparent at Week 1 and consistent with the results at Week 12. 

Obstructive Sleep Apnea

The efficacy of Sunosi in improving wakefulness and reducing excessive daytime sleepiness in patients with OSA was demonstrated in a 12-week multi-center, randomized, double-blind, placebo-controlled study in adults diagnosed with OSA according to ICSD-3 criteria. The co-primary efficacy endpoints were change from baseline in MWT and ESS at Week 12. A total of 476 patients with OSA were randomized to receive Sunosi 37.5 mg, 75 mg, 150 mg, or 300 mg (two times the maximum recommended daily dose), or placebo once daily. Patients randomized to the 150-mg dose received 75 mg for the first 3 days before increasing to 150 mg. Compared to the placebo group, patients randomized to 37.5 mg, 75 mg, and 150 mg Sunosi showed statistically significant improvements on the MWT (treatment effect difference: 4.5 minutes, 8.9 minutes, and 10.7 minutes respectively) and ESS (treatment effect difference: 1.9 points, 1.7 points, and 4.5 points respectively) at Week 12. These effects were apparent at Week 1 and consistent with the results at Week 12.

Maintenance of Efficacy in Narcolepsy and OSA

The maintenance of effect of Sunosi in improving wakefulness and reducing excessive daytime sleepiness in patients with narcolepsy and OSA was assessed in two randomized-withdrawal, placebo-controlled studies, Study 3 and Study 4.

Study 3 was a 6-week, multi-center, double-blind, placebo-controlled, randomized-withdrawal study in 174 adult patients with a diagnosis of OSA. The co-primary efficacy endpoints were change from the beginning to the end of the randomized withdrawal period in MWT and ESS. During a 2-week, open-label titration phase, patients were started on Sunosi 75 mg once daily, and were titrated to the maximum tolerable dose between 75 mg and 300 mg per day (two times the maximum recommended daily dose). Patients were continued on this dose for a 2-week stable-dose phase. At the end of the stable-dose phase, 124 patients who reported “much” or “very much” improvement on the PGIc and who showed improvements on the MWT and ESS entered a double-blind withdrawal phase and were randomized 1:1 to either continue Sunosi at the dose received in the stable-dose phase or switch to placebo. Compared to patients who remained on Sunosi, patients randomized to placebo experienced statistically significant worsening of sleepiness as measured by the MWT and ESS.

Study 4 was a 52-week, open-label study in 638 patients with either narcolepsy or OSA who had completed a prior trial. During a 2-week, open-label titration phase, patients were started on Sunosi 75 mg once daily, and were titrated to the maximum tolerable dose between 75 mg and 300 mg per day (two times the maximum recommended daily dose). Patients remained on this dose during a subsequent open-label treatment period of either 38 (for patients previously enrolled in Study 1 or Study 2) or 50 (all others) weeks. A 2-week randomized-withdrawal period was incorporated into the study. After 6 months of stable-dose treatment, 282 patients (79 with narcolepsy; 203 with OSA) entered the randomized-withdrawal period. Patients were randomized 1:1 to either continue to receive Sunosi at the dose received in the maintenance phase or to switch to placebo. The primary efficacy endpoint was change from the beginning to the end of the randomized-withdrawal period in ESS. Compared to patients who remained on Sunosi, patients randomized to placebo experienced statistically significant worsening of sleepiness as measured by the ESS.