SUNOSI safety and tolerability
Dose-dependent adverse reactions ≥2% in patients treated with SUNOSI and greater than placebo in pooled, 12-week, placebo-controlled studies in OSA and narcolepsy1*
OSA=obstructive sleep apnea.
*Reflects pooled OSA and narcolepsy data. The 37.5-mg column is OSA only.1
†“Headache” includes headache, tension headache, and head discomfort.1
‡“Nausea” includes nausea and vomiting.1
SUNOSI has an established safety profile based on multiple clinical trials1
Discontinuation rate of 3% due to ARs1
(across SUNOSI doses vs <1% for placebo)1‡
Discontinuation ratesSelect Important Safety Information
Physicians should carefully evaluate patients for history of drug abuse, especially those with a history of stimulant or alcohol abuse, and follow such patients closely, observing them for signs of misuse or abuse of SUNOSI.1
AR=adverse reaction; CYP=cytochrome P450; DEA=Drug Enforcement Administration; ESS=Epworth Sleepiness Scale; MAOI=monoamine oxidase inhibitor; OSA=obstructive sleep apnea; PK=pharmacokinetic.
*SUNOSI contains solriamfetol, a Schedule IV controlled substance, which has potential for abuse. Schedule IV drugs are defined by the DEA as drugs with a low potential for abuse and low risk of dependence.1,2
†SUNOSI is contraindicated in patients receiving concomitant treatment with MAOIs, or within 14 days following discontinuation of an MAOI, because of the risk of hypertensive reaction. Based on in vitro data, clinically significant PK drug interactions with major CYPs and transporters are not expected in patients taking SUNOSI.1
‡As documented in 12-week, placebo-controlled studies of 622 adult patients with OSA or narcolepsy (SUNOSI: n=396; placebo: n=226).1
Adverse reactions ≥2% in patients treated with SUNOSI and greater than placebo in pooled, 12-week, placebo-controlled narcolepsy studies1
System Organ Class | Placebo | SUNOSI |
|---|---|---|
Metabolism and Nutrition Disorders | ||
Decreased appetite | 1 | 9 |
Psychiatric Disorders | ||
Insomnia* | 4 | 5 |
Anxiety† | 1 | 6 |
Nervous System Disorders | ||
Headache‡ | 7 | 16 |
Cardiac Disorders | ||
Palpitations | 1 | 2 |
Gastrointestinal Disorders | ||
Nausea§ | 4 | 7 |
Dry mouth | 2 | 4 |
Constipation | 1 | 3 |
SUNOSI is contraindicated in patients receiving concomitant treatment with MAOIs, or within 14 days following discontinuation of an MAOI, because of the risk of hypertensive reaction.1
MAOI=monoamine oxidase inhibitor.
*“Insomnia” includes insomnia, initial insomnia, middle insomnia, and terminal insomnia.1
†“Anxiety” includes anxiety, nervousness, and panic attack.1
‡“Headache” includes headache, tension headache, and head discomfort.1
§“Nausea” includes nausea and vomiting.1
Blood pressure and heart rate increases seen with SUNOSI1
Select Important Safety Information
SUNOSI increases systolic blood pressure, diastolic blood pressure, and heart rate in a dose-dependent fashion.
Epidemiological data show that chronic elevations in blood pressure increase the risk of major adverse cardiovascular events (MACE), including stroke, heart attack, and cardiovascular death.
Physicians should assess blood pressure and control hypertension before initiating treatment with SUNOSI. Monitor blood pressure regularly during treatment and treat new-onset hypertension and exacerbations of pre-existing hypertension.
See the charts below for readings on blood pressure and heart rate in patients who were taking SUNOSI.
Blood pressure and heart rate by 24-hour ambulatory monitoring: mean change (95% CI) from baseline at week 81
Narcolepsy
STUDY 1
SBP
DBP
HR
-0.4 (-3.1, 2.4)
-0.2 (-1.9, 2.0)
0.0 (-1.9, 2.0)
-
-
-
1.6 (-0.4, 3.5)
1.0 (-0.4, 2.5)
0.2 (-2.1, 2.4)
-0.5 (-2.1, 1.1)
0.8 (-0.4, 2.0)
1.0 (-1.2, 3.2)
OSA
STUDY 2
SBP
DBP
HR
-0.2 (-1.8, 1.4)
0.2 (-0.9, 1.3)
-0.4 (-1.7, 0.9)
1.8 (-1.1, 4.6)
1.4 (-0.4, 3.2)
0.4 (-1.4, 2.2)
2.6 (0.02, 5.3)
1.5 (-0.04, 3.1)
1.0 (-0.9, 2.81)
-0.2 (-2.0, 1.6)
-0.1 (-1.1, 1.0)
1.7 (0.5, 2.9)
ABPM=ambulatory blood pressure monitoring; CI=confidence interval; DBP=diastolic blood pressure; HR=heart rate; OSA=obstructive sleep apnea; SBP=systolic blood pressure.
*Number of patients who had at least 50% valid ABPM readings.1
Maximal mean changes in blood pressure and heart rate assessed at MWT sessions from baseline through week 12: mean (95% CI)1*
Narcolepsy
STUDY 1
n
SBP
52
3.5 (0.7, 6.4)
51
3.1 (0.1, 6.0)
49
4.9 (1.7, 8.2)
n
DBP
23
1.8 (-1.8, 5.5)
-
47
2.2 (0.2, 4.1)
49
4.2 (2.0, 6.5)
n
HR
48
2.3 (-0.1, 4.7)
-
26
3.7 (0.4, 6.9)
49
4.9 (2.3, 7.6)
OSA
STUDY 2
n
SBP
35
1.7 (-1.4, 4.9)
17
4.6 (-1.1, 10.2)
54
3.8 (1.2, 6.4)
103
2.4 (0.4, 4.4)
n
DBP
99
1.4 (-0.1, 2.9)
17
1.9 (-2.3, 6.0)
17
3.2 (-0.9, 7.3)
107
1.8 (0.4, 3.2)
n
HR
106
1.7 (0.1, 3.3)
17
1.9 (-1.9, 5.7)
51
3.3 (0.6, 6.0)
102
2.9 (1.4, 4.4)
n
SBP
n
DBP
n
HR
n
SBP
n
DBP
n
HR
n
SBP
n
DBP
n
HR
n
SBP
n
DBP
n
HR
Narcolepsy
STUDY 1
52
3.5 (0.7, 6.4)
23
1.8 (-1.8, 5.5)
48
2.3 (-0.1, 4.7)
-
-
-
51
3.1 (0.1, 6.0)
47
2.2 (0.2, 4.1)
26
3.7 (0.4, 6.9)
49
4.9 (1.7, 8.2)
49
4.2 (2.0, 6.5)
49
4.9 (2.3, 7.6)
OSA
STUDY 2
35
1.7 (-1.4, 4.9)
99
1.4 (-0.1, 2.9)
106
1.7 (0.1, 3.3)
17
4.6 (-1.1, 10.2)
17
1.9 (-2.3, 6.0)
17
1.9 (-1.9, 5.7)
54
3.8 (1.2, 6.4)
17
3.2 (-0.9, 7.3)
51
3.3 (0.6, 6.0)
103
2.4 (0.4, 4.4)
107
1.8 (0.4, 3.2)
102
2.9 (1.4, 4.4)
CI=confidence interval; DBP=diastolic blood pressure; HR=heart rate; MWT=Maintenance of Wakefulness Test; OSA=obstructive sleep apnea; SBP=systolic blood pressure.
*For study weeks 1, 4, and 12, SBP, DBP, and HR were assessed pre-dose and every 1-2 hours for 10 hours after test drug administration. For all time points at all visits, the mean change from baseline was calculated, by indication and dose, for all patients with a valid assessment. The table shows, by indication and dose, the mean changes from baseline for the week and time point with the maximal change in SBP, DBP, and HR.1
Weight changes in patients with narcolepsy treated with SUNOSI3
In an exploratory analysis that evaluated weight change from baseline to week 12, SUNOSI treatment was associated with decreases in body weight in a dose-related manner. This study was not powered to determine statistical significance.*†
IQR, interquartile range.
*As seen in a randomized, double-blind, placebo-controlled, phase 3 study of adult patients with narcolepsy. All data were evaluated for patients in the safety population (n=236), defined as those who received ≥1 dose of SUNOSI. Body weight was assessed as part of routine physical examinations and measured at every clinic visit.3
†From baseline to week 12 among participants with narcolepsy: -0.07% (-2.04 to 0.84) median (IQR) percent weight change across all SUNOSI doses and 3.08% (0.84 to 5.55) median percent weight change with placebo.3
INDICATION AND IMPORTANT SAFETY INFORMATION
INDICATION
SUNOSI is indicated to improve wakefulness in adults with excessive daytime sleepiness (EDS) associated with narcolepsy or obstructive sleep apnea (OSA).
LIMITATIONS OF USE
SUNOSI is not indicated to treat the underlying obstruction in OSA. Ensure that the underlying airway obstruction is treated (e.g., with continuous positive airway pressure (CPAP)) for at least one month prior to initiating SUNOSI. SUNOSI is not a substitute for these modalities, and the treatment of the underlying airway obstruction should be continued.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
SUNOSI is contraindicated in patients receiving concomitant treatment with monoamine oxidase inhibitors (MAOIs), or within 14 days following discontinuation of an MAOI, because of the risk of hypertensive reaction.
WARNINGS AND PRECAUTIONS
Blood Pressure and Heart Rate Increases
SUNOSI increases systolic blood pressure, diastolic blood pressure, and heart rate in a dose-dependent fashion.
Blood Pressure and Heart Rate Increases (Cont’d)
Epidemiological data show that chronic elevations in blood pressure increase the risk of major adverse cardiovascular events (MACE), including stroke, heart attack, and cardiovascular death. The magnitude of the increase in absolute risk is dependent on the increase in blood pressure and the underlying risk of MACE in the population being treated. Many patients with narcolepsy and OSA have multiple risk factors for MACE, including hypertension, diabetes, hyperlipidemia, and high body mass index (BMI).
Assess blood pressure and control hypertension before initiating treatment with SUNOSI. Monitor blood pressure regularly during treatment and treat new-onset hypertension and exacerbations of pre-existing hypertension. Exercise caution when treating patients at higher risk of MACE, particularly patients with known cardiovascular and cerebrovascular disease, pre-existing hypertension, and patients with advanced age. Use caution with other drugs that increase blood pressure and heart rate.
Periodically reassess the need for continued treatment with SUNOSI. If a patient experiences increases in blood pressure or heart rate that cannot be managed with dose reduction of SUNOSI or other appropriate medical intervention, consider discontinuation of SUNOSI.
Patients with moderate or severe renal impairment could be at a higher risk of increases in blood pressure and heart rate because of the prolonged half-life of SUNOSI.
Psychiatric Symptoms
Psychiatric adverse reactions have been observed in clinical trials with SUNOSI, including anxiety, insomnia, and irritability.
Exercise caution when treating patients with SUNOSI who have a history of psychosis or bipolar disorders, as SUNOSI has not been evaluated in these patients.
Patients with moderate or severe renal impairment may be at a higher risk of psychiatric symptoms because of the prolonged half-life of SUNOSI.
Observe SUNOSI patients for the possible emergence or exacerbation of psychiatric symptoms. Consider dose reduction or discontinuation of SUNOSI if psychiatric symptoms develop.
MOST COMMON ADVERSE REACTIONS
The most common adverse reactions (incidence ≥5%) reported more frequently with the use of SUNOSI than placebo in either narcolepsy or OSA were headache, nausea, decreased appetite, anxiety, and insomnia.
Dose-Dependent Adverse Reactions
In the 12-week placebo-controlled clinical trials that compared doses of 37.5 mg, 75 mg, and 150 mg/day of SUNOSI to placebo, the following adverse reactions were dose-related: headache, nausea, decreased appetite, anxiety, diarrhea, and dry mouth.
DRUG INTERACTIONS
Do not administer SUNOSI concomitantly with MAOIs or within 14 days after discontinuing MAOI treatment. Concomitant use of MAOIs and noradrenergic drugs may increase the risk of a hypertensive reaction. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure.
Concomitant use of SUNOSI with other drugs that increase blood pressure and/or heart rate has not been evaluated, and combinations should be used with caution.
Dopaminergic drugs that increase levels of dopamine or that bind directly to dopamine receptors might result in pharmacodynamic interactions with SUNOSI. Interactions with dopaminergic drugs have not been evaluated with SUNOSI. Use caution when concomitantly administering dopaminergic drugs with SUNOSI.
USE IN SPECIFIC POPULATIONS
Renal Impairment
Dosage adjustment is not required for patients with mild renal impairment (eGFR 60-89 mL/min/1.73 m2). Dosage adjustment is recommended for patients with moderate to severe renal impairment (eGFR 15-59 mL/min/1.73 m2). SUNOSI is not recommended for patients with end stage renal disease (eGFR <15 mL/min/1.73 m2).
ABUSE
SUNOSI contains solriamfetol, a Schedule IV controlled substance. Carefully evaluate patients for a recent history of drug abuse, especially those with a history of stimulant or alcohol abuse, and follow such patients closely, observing them for signs of misuse or abuse of SUNOSI (e.g., drug-seeking behavior).
SUN HCP ISI 05/2022
Please see full Prescribing Information.
REFERENCES:
- SUNOSI (solriamfetol) [prescribing information]. New York, NY: Axsome Therapeutics, Inc.
- Drug Scheduling. United States Drug Enforcement Administration. Accessed January 9, 2025. https://www.dea.gov/drug-scheduling
- Malhotra A, Strollo PJ Jr, Pepin JL, et al. Effects of solriamfetol treatment on body weight in participants with obstructive sleep apnea or narcolepsy. Sleep Med. 2022;100:165-173.
- Baladi MG, Forster MJ, Gatch MB, et al. Characterization of the neurochemical and behavioral effects of solriamfetol (JZP-110), a selective dopamine and norepinephrine reuptake inhibitor. J Pharmacol Exp Ther. 2018;366(2):367-376.
- Thorpy MJ, Shapiro C, Mayer G, et al. A randomized study of solriamfetol for excessive sleepiness in narcolepsy [published correction appears in Ann Neurol. 2020 Jan;87(1):157]. Ann Neurol. 2019;85(3):359-370.