Andrew J. Fratoni, PharmD and Kevin W. Chamberlin, PharmD

Narcolepsy and obstructive sleep apnea (OSA) are associated with excessive sleepiness. Several monoamines such as norepinephrine and dopamine impact wake-promotion and have been popular drug targets.

Solriamfetol (Sunosi, Jazz Pharmaceuticals) to treat excessive sleepiness in adult patients with narcolepsy or obstructive sleep apnea was approved on March 20, 2019.

 Solriamfetol is a dopamine and norepinephrine reuptake inhibitor (DNRI) and is categorized as a schedule IV controlled substance (low potential for abuse and low risk of dependence).

For each indication (Narcolepsy and OSA), separate 12-week, multi-center, randomized, double-blind, placebo-controlled studies were conducted. Primary Endpoints were the change from baseline in the Maintenance of Wakefulness Test (MWT) and the Epworth Sleepiness Scale (ESS). The MWT measures an individual’s ability to remain awake during the daytime in a darkened, quiet environment. The ESS is an 8-item questionnaire by which patients rate their perceived likelihood of falling asleep during usual daily life activities.

In the narcolepsy study, NCT02348593, patients randomized toreceive 150 mg of solriamfetol (received 75 mg for the first 3 days) showed statistically significant improvement in both MWT (+7.7 mins) and ESS (-3.8 points) compared to placebo. The study arm randomized to receive 75 mg did not achieve statistical significance.

The OSA study, NCT02348606, compared placebo to solriamfetol doses of 37.5, 75, and 150 mg (75 mg for the first 3 days) for 12 weeks. Patients in all three treatment arms showed statistically significant improvements on the MWT (+4.5, 8.9, and 10.7 mins, respectively) and ESS (-1.9, 1.7, and 4.5 points respectively) compared to the placebo group.

Solriamfetol comes to market with warnings and precautions for its use. This drug can increase systolic blood pressure, diastolic blood pressure, and heart rate in a dose-dependent fashion. Patients with risk factors for major adverse cardiovascular events are at increased risk and should be monitored. In clinical trials, patients have also experienced psychiatric adverse effects like anxiety, irritability, and insomnia.

 Use caution in patients with history of psychosis or bipolar disorders. Other less serious, but common (>5% incidence) side effects include nausea, vomiting, headache and decrease in appetite.

Concurrent treatment with a monoamine oxidase inhibitor (MAOI) or use of an MAOI within the preceding 14 days is contraindicated with solriamfetol.

Solriamfetol is available in 75 and 150 mg tablets. The 75 mg tablet is scored and may be split for 37.5 mg doses.

 Initial dosing for narcolepsy is 75 mg by mouth upon awakening; dose may be doubled 3 days later based on efficacy and tolerability to a max of 150 mg/day. Initial dosing for OSA is 37.5 mg by mouth upon awakening; dose may be doubled at intervals of at least 3 days based on efficacy and tolerability to a max of 150 mg/day. Avoid use within 9 hours of planned bedtime. Solriamfetol may be taken with or without food.

Ninety-five percent of solriamfetol is renally excreted unchanged, which necessitates dose adjustments in renal impairment.

1. Solriamfetol (Sunosi) package insert. Palo Alto, CA. Jazz Pharmaceuticals, Inc.; 2019.

2. Schweitzer PK, et al. Solriamfetol for Excessive Sleepiness in Obstructive Sleep Apnea (TONES 3). A Randomized Controlled Trial. 

. 2019 Jun 1;199(11):1421-1431. doi: 10.1164/rccm.201806-1100OC.

3. Solriamfetol. Micromedex (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. Available at: micromedexsolutions. com/. Accessed June 19, 2019.

Author | Andrew J. Fratoni, PharmD and Kevin W. Chamberlin, PharmD

Articles

Sunosi for Excessive Sleepiness in Adults with Narcolepsy or Obstructive Sleep Apnea