AHFS Class:

• Wakefulness-promoting Agents 28:20.80

Generic Name(s):

• Solriamfetol Hydrochloride

Chemical Name:

• [(2R)-2-amino-3-phenylpropyl] carbamate, monohydrochloride

Molecular Formula:

• C₁₀H₁₄N₂O₂•HCl

Solriamfetol hydrochloride, a dopamine- and norepinephrine-reuptake inhibitor (DNRI), is a wakefulness-promoting agent.1,2,3,4

Obstructive Sleep Apnea

Solriamfetol hydrochloride is used in the symptomatic treatment of obstructive sleep apnea to improve wakefulness in patients with excessive daytime sleepiness.1,3,9,10,11 The drug should be used as an adjunct to standard treatment(s) for the underlying obstruction (e.g., nasal continuous positive airway pressure [CPAP]).1 Solriamfetol is not indicated to treat the underlying airway obstruction, nor is it a substitute for standard treatments for airway obstruction.1 Standard treatments should be provided for at least one month prior to initiating solriamfetol therapy and should be continued during therapy with the drug.1

Efficacy of solriamfetol in improving wakefulness and reducing excessive daytime sleepiness associated with obstructive sleep apnea was established in a 12-week, randomized, double-blind, placebo-controlled, parallel-group study (TONES 3; NCT02348606) in 476 adults who met International Classification of Sleep Disorders, Third Edition (ICSD-3) criteria for obstructive sleep apnea.1,3 Patients in this study were randomized in a 1:1:2:2:2 ratio to receive solriamfetol 37.5, 75, 150, or 300 mg once daily or placebo.1,3 Those randomized to receive either the 150- or 300-mg daily dosage received one-half the assigned dosage (i.e., 75 or 150 mg daily, respectively) for the first 3 days prior to receiving the full dosage.1,3 Efficacy of solriamfetol was evaluated principally by sleep latency on the Maintenance of Wakefulness Test (MWT), an objective measure of the ability to remain awake for a defined period of time during the daytime, and by the Epworth Sleepiness Scale (ESS), an 8-item questionnaire by which patients rate their perceived likelihood of falling asleep during usual daily life activities.1,3,9 Change in overall symptom severity also was assessed by the Patient Global Impression of Change (PGI-C) scale, a 7-point patient-reported scale ranging from “very much improved” to “very much worse.”1,3

At week 12 in TONES 3, all 4 dosages of solriamfetol were associated with greater improvements in wakefulness and reductions in excessive daytime sleepiness, as measured by the MWT and ESS, compared with placebo, and all dosages except the 37.5-mg daily dosage were associated with improved patient-reported overall symptom severity, as measured by the PGI-C scale, compared with placebo.1,3 Dose-related improvements in wakefulness and reductions in excessive daytime sleepiness were observed at week 1 and the magnitude of effect generally remained stable over 12 weeks of treatment.1,3 At week 12, serial MWT assessments (5 assessments performed at 2-hour intervals beginning 1 hour after the dose) showed improvements in wakefulness with solriamfetol at dosages of 75-300 mg daily compared with placebo beginning 1 hour after dosing and persisting through approximately 9 hours after dosing.1,3 Compliance with standard treatment for obstructive sleep apnea (e.g., CPAP device) was similar across all treatment groups at baseline and did not change during the 12-week study period in any treatment group.1,3 Age, race, and sex did not appear to affect response.1 Nighttime sleep as measured by polysomnography was not affected by use of solriamfetol.1,3 Certain adverse effects generally appeared to be dose related,1,3 and FDA has concluded that dosages exceeding 150 mg daily do not provide sufficient additional clinical benefit to outweigh the risk of dose-related adverse effects.1 (See Cardiovascular Effects under Cautions: Warnings/Precautions and also see Cautions: Common Adverse Effects.)

Efficacy of solriamfetol in improving wakefulness and reducing excessive daytime sleepiness associated with obstructive sleep apnea also is supported by a 6-week, double-blind, placebo-controlled, randomized-withdrawal study (TONES 4; NCT02348619) in 174 adults who met ICSD-3 criteria for obstructive sleep apnea.1,9,11 The study included a 2-week open-label dosage titration phase, in which solriamfetol was initiated at a dosage of 75 mg once daily and titrated to the maximum tolerated dosage within the range of 75-300 mg daily, followed by a 2-week stable-dosage phase; the 124 patients who reported “much” or “very much” improvement on the PGI-C and who showed improvements in sleep latency on the MWT and ESS from baseline to week 4 of the study entered a double-blind withdrawal phase and were randomized to continue their current dosage of solriamfetol or switch to placebo for 2 weeks.1,9,11 Worsening of sleepiness, as measured by the MWT and ESS, over the 2-week randomized-withdrawal phase was observed in patients who switched to placebo compared with those who continued receiving solriamfetol.1,9,11

Results of a long-term, open-label study (TONES 5; NCT02348632) in patients with obstructive sleep apnea or narcolepsy who had completed a prior study of solriamfetol (mainly TONES 2 or TONES 3) suggested that the drug was effective through up to 52 weeks of treatment.1,9,10 After 6 months of treatment at dosages of 75-300 mg daily (titrated individually to the maximum tolerated dosage), a subgroup of 282 patients, including 203 patients with obstructive sleep apnea, entered a 2-week, placebo-controlled, randomized-withdrawal phase.1,9,10 Worsening of sleepiness, as measured by the ESS, over the 2-week randomized-withdrawal phase was observed in patients who switched to placebo compared with those who continued receiving solriamfetol.1,9,10

Narcolepsy

Solriamfetol hydrochloride is used in the symptomatic treatment of narcolepsy to improve wakefulness in patients with excessive daytime sleepiness.1,2,9,10 Solriamfetol has been designated an orphan drug by FDA for use in the treatment of narcolepsy.13 Narcolepsy is a neurologic sleep disorder characterized by chronic excessive daytime sleepiness, short sleep latency, and sleep-onset rapid eye movement (REM) periods.2,5,12 Other manifestations may include cataplexy (sudden and transient loss of muscle tone during wakefulness), disrupted nocturnal sleep, hypnagogic hallucinations, and/or sleep paralysis.2,5,12

Efficacy of solriamfetol in improving wakefulness and reducing excessive daytime sleepiness associated with narcolepsy was established in a 12-week, randomized, double-blind, placebo-controlled, parallel-group study (TONES 2; NCT02348593) in 239 adults who met ICSD-3 or Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for narcolepsy.1,2 Approximately 51% of patients in the study had cataplexy.1,2 Patients in this study were randomized in a 1:1:1:1 ratio to receive solriamfetol 75, 150, or 300 mg once daily or placebo.1,2 Those randomized to receive either the 150- or 300-mg daily dosage received one-half the assigned dosage (i.e., 75 or 150 mg daily, respectively) for the first 3 days prior to receiving the full dosage.1,2 Efficacy of solriamfetol was evaluated principally by sleep latency on the MWT and by the ESS.1,2 Change in overall symptom severity also was assessed by the PGI-C scale.1,2

In TONES 2, both the 150- and 300-mg daily dosages of solriamfetol were associated with greater improvements in wakefulness and reductions in excessive daytime sleepiness, as measured by the MWT, ESS, and PGI-C, compared with placebo at week 12;1,2 improvements were observed at week 1 and the magnitude of effect generally remained stable over 12 weeks of treatment.1,2 The 75-mg daily dosage resulted in improvements as measured by the ESS but not as measured by the MWT.2 At week 12, serial MWT assessments (5 assessments performed at 2-hour intervals beginning 1 hour after the dose) showed improvements in wakefulness with solriamfetol 150 or 300 mg daily compared with placebo beginning 1 hour after dosing and persisting through approximately 9 hours after dosing.1,2 Efficacy of the drug was not affected by the presence of cataplexy or by age, race, or sex.1 Nighttime sleep as measured by polysomnography was not affected by use of solriamfetol.1 Certain adverse effects appeared to be dose related,1,2 and FDA has concluded that dosages exceeding 150 mg daily do not provide sufficient additional clinical benefit to outweigh the risk of dose-related adverse effects.1 (See Cardiovascular Effects under Cautions: Warnings/Precautions and also see Cautions: Common Adverse Effects.)

Results of a long-term, open-label study (TONES 5; NCT02348632) in patients with narcolepsy or obstructive sleep apnea who had completed a prior study of solriamfetol (mainly TONES 2 or TONES 3) suggested that the drug was effective through up to 52 weeks of treatment.1,9,10 After 6 months of treatment at dosages of 75-300 mg daily (titrated individually to the maximum tolerated dosage), a subgroup of 282 patients, including 79 patients with narcolepsy, entered a 2-week, placebo-controlled, randomized-withdrawal phase.1,9,10 Worsening of sleepiness, as measured by the ESS, over the 2-week randomized-withdrawal phase was observed in patients who switched to placebo compared with those who continued receiving solriamfetol.1,9,10

General

Adequate control of blood pressure should be ensured prior to initiation of solriamfetol therapy.1 (See Cardiovascular Effects under Cautions: Warnings/Precautions.)

Administration

In patients with obstructive sleep apnea or narcolepsy, solriamfetol is administered orally once daily upon awakening;1 the drug may be administered without regard to food.1,6 Administration within 9 hours of planned bedtime should be avoided because of the potential for interference with sleep.1

Dosage

Dosage of solriamfetol hydrochloride is expressed in terms of solriamfetol.1

Obstructive Sleep Apnea

The recommended initial dosage of solriamfetol in adults with obstructive sleep apnea is 37.5 mg once daily upon awakening.1 The recommended dosage range is 37.5-150 mg once daily.1 Based on efficacy and tolerability, dosage may be doubled at intervals of at least 3 days up to a maximum dosage of 150 mg once daily.1 Dosages exceeding 150 mg daily do not provide sufficient additional clinical benefit to outweigh the risk of dose-related adverse effects.1 (See Cardiovascular Effects under Cautions: Warnings/Precautions and also see Cautions: Common Adverse Effects.)

Narcolepsy

The recommended initial dosage of solriamfetol in adults with narcolepsy is 75 mg once daily upon awakening.1 The recommended dosage range is 75-150 mg once daily.1 Based on efficacy and tolerability, dosage may be doubled at intervals of at least 3 days up to a maximum dosage of 150 mg once daily.1 Dosages exceeding 150 mg daily do not provide sufficient additional clinical benefit to outweigh the risk of dose-related adverse effects.1 (See Cardiovascular Effects under Cautions: Warnings/Precautions and also see Cautions: Common Adverse Effects.)

Special Populations

Dosage adjustment is not required in patients with mild renal impairment (estimated glomerular filtration rate [eGFR] of 60-89 mL/minute per 1.73 m²).1 In patients with moderate renal impairment (eGFR of 30-59 mL/minute per 1.73 m²), solriamfetol should be initiated at a dosage of 37.5 mg once daily; based on efficacy and tolerability, dosage may be increased after at least 7 days to a maximum dosage of 75 mg once daily.1 In patients with severe renal impairment (eGFR of 15-29 mL/minute per 1.73 m²), solriamfetol should be given at a dosage of 37.5 mg once daily; the maximum recommended dosage in such patients is 37.5 mg daily.1 Use of solriamfetol in patients with end-stage renal disease (eGFR less than 15 mL/minute per 1.73 m²) is not recommended.1 (See Renal Impairment under Warnings/Precautions: Specific Populations, in Cautions.)

Because geriatric patients are more likely to have decreased renal function, dosage adjustments based on eGFR may be required.1 Lower dosages and close monitoring should be considered in this population.1 (See Geriatric Use under Warnings/Precautions: Specific Populations, in Cautions.)

The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.1 (See Hepatic Impairment under Warnings/Precautions: Specific Populations, in Cautions.)

Contraindications

Solriamfetol is contraindicated in patients who are currently receiving or have recently (within 14 days) received therapy with a monoamine oxidase (MAO) inhibitor.1 (See Cardiovascular Effects under Cautions: Warnings/Precautions and also see Drug Interactions: Monoamine Oxidase Inhibitors.)

Warnings/Precautions

Cardiovascular Effects

Solriamfetol produces dose-dependent increases in systolic and diastolic blood pressure and heart rate.1

Epidemiologic data indicate that chronically elevated blood pressure increases the risk of major adverse cardiovascular events, including stroke, myocardial infarction, and cardiovascular death.1 The magnitude of the increase in absolute risk is dependent on the increase in blood pressure and underlying cardiovascular risk.1 Many patients with obstructive sleep apnea or narcolepsy have multiple cardiovascular risk factors, including hypertension, diabetes mellitus, hyperlipidemia, and high body mass index (BMI).1

Blood pressure should be assessed and hypertension controlled prior to initiation of solriamfetol therapy.1 Blood pressure should be monitored regularly during therapy with the drug, and new or exacerbated hypertension should be managed appropriately.1 Caution should be exercised in patients at higher risk of major adverse cardiovascular events, particularly older patients and those with known cardiovascular and cerebrovascular disease or preexisting hypertension.1 Caution also is advised in patients receiving concomitant therapy with drugs known to increase blood pressure and heart rate.1 Because the half-life of solriamfetol is prolonged in patients with moderate or severe renal impairment, these patients may be at increased risk for elevations in blood pressure and heart rate.1

The need for continued solriamfetol therapy should be reassessed periodically.1 If increases in blood pressure or heart rate occur and cannot be managed by solriamfetol dosage reduction or other appropriate medical intervention, discontinuance of solriamfetol therapy should be considered.1

Psychiatric Effects

Adverse psychiatric effects (e.g., anxiety, insomnia, irritability) have been reported in clinical trials in patients receiving solriamfetol.1 The drug has not been evaluated in patients with psychosis or bipolar disorders, and caution should be exercised in patients with a history of such disorders.1

Patients with moderate or severe renal impairment may be at a higher risk of experiencing psychiatric symptoms because of the prolonged half-life of solriamfetol in such patients.1

Patients receiving solriamfetol should be monitored for the possible emergence or exacerbation of psychiatric symptoms.1 If psychiatric symptoms develop, dosage reduction or discontinuance of solriamfetol should be considered.1

Abuse, Misuse, and Dependence Potential

Solriamfetol is classified under the Federal Controlled Substances Act as a schedule IV (C-IV) drug.1

In a study evaluating the abuse potential of solriamfetol (300, 600, and 1200 mg) compared with that of the Schedule IV drug phentermine hydrochloride (45 and 90 mg) in individuals with a history of recreational use of stimulants, solriamfetol produced “drug liking”scores similar to or lower than those observed with phentermine.1,8 In this crossover study, elevated mood was reported with placebo, solriamfetol, or phentermine use in 2.4, 8-24, or 10-18% of individuals, while a feeling of relaxation was reported with these respective treatments in 5, 5-19, or 15-20% of individuals.1,8

The effects of abrupt discontinuance of solriamfetol in patients with obstructive sleep apnea or narcolepsy were evaluated following at least 6 months of therapy in a long-term safety and maintenance of efficacy study, as well as during the 2-week safety follow-up periods in the phase 3 studies.1 These studies provided no evidence that abrupt discontinuance produced a consistent pattern of adverse events suggestive of physical dependence or withdrawal in individual patients.1

The manufacturer states that patients should be evaluated carefully for a history of recent drug abuse, particularly alcohol or stimulant (e.g., amphetamine, cocaine, methylphenidate) abuse, and patients with such history should be monitored closely for possible signs of misuse or abuse (e.g., incrementation of doses, drug-seeking behavior).1

Specific Populations

Pregnancy

Available data from case reports are insufficient to determine solriamfetol-associated risks of major birth defects, spontaneous abortion, or adverse maternal or fetal outcomes.1

Teratogenicity, fetal toxicity, and developmental toxicity have been observed in animal studies.1 In reproduction studies in rats, maternal toxicity (hyperactivity, decreased body weight, reduced weight gain, reduced food consumption) and fetal toxicity (resorption, post-implantation loss, decreased fetal weight) were observed at dosages of 4 or more times the maximum recommended human dose (MRHD); fetal malformations (sternebrae malalignment, hindlimb rotation, bent limb bones, situs inversu) were observed at dosages of 19 times the MRHD.1 In reproduction studies in rabbits, maternal toxicity was observed at dosages of 10 times the MRHD and fetal malformations (sternebrae malalignment) and toxicity (decreased fetal weight) were observed at dosages of 5 or more times the MRHD.1 Administration to rats during pregnancy and lactation at dosages of 7 or more times the MRHD resulted in maternal toxicity and adverse effects on fertility, growth, and development in the offspring.1

The manufacturer has established a pregnancy registry to monitor fetal outcomes of pregnant women exposed to solriamfetol.1 Clinicians are encouraged to register pregnant patients, or pregnant women may enroll themselves in the registry, by calling 877-283-6220 or visiting [Web].1

Lactation

It is not known whether solriamfetol or its metabolites are distributed into human milk, affect breast-fed infants, or affect milk production.1 Solriamfetol is distributed into milk in rats.1 The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for solriamfetol and any potential adverse effects on the breast-fed child from the drug or from the underlying maternal condition.1 Nursing infants should be monitored for adverse effects (e.g., agitation, insomnia, anorexia, reduced weight gain) potentially resulting from exposure to the drug through breast milk.1

Pediatric Use

Safety and efficacy of solriamfetol in pediatric patients have not been established.1

Geriatric Use

Of the total number of patients with obstructive sleep apnea or narcolepsy receiving solriamfetol in clinical trials, 13% were 65 years of age or older.1 No clinically important differences in safety or efficacy were observed between geriatric patients and younger adults.1

Population pharmacokinetic analysis indicates that age does not have a clinically important effect on the pharmacokinetics of solriamfetol, and no dosage adjustments were made in clinical trials that included patients 65 of age or older.1 However, because geriatric patients are more likely to have decreased renal function and solriamfetol is eliminated mainly by the kidneys, dosage adjustment may be necessary; consideration should be given to the use of lower dosages and close monitoring in this population.1 (See Dosage and Administration: Special Populations.)

Renal Impairment

Clearance of solriamfetol decreases with worsening renal function.1,7 Systemic exposure to the drug is increased by 53, 129, or 339% in patients with mild (estimated glomerular filtration rate [eGFR] of 60-89 mL/minute per 1.73 m²), moderate (eGFR of 30-59 mL/minute per 1.73 m²), or severe (eGFR less than 30 mL/minute per 1.73 m²) renal impairment, respectively, compared with individuals with normal renal function, while half-life of the drug is increased by approximately 1.2-, 1.9-, or 3.9-fold in these respective populations.1,7 In general, renal impairment does not appreciably alter peak plasma concentration or time to peak plasma concentration.1,7 In patients with end-stage renal disease (eGFR less than 15 mL/minute per 1.73 m²), systemic exposure to solriamfetol is increased approximately fourfold (with hemodialysis) or fivefold (without hemodialysis) compared with that observed in individuals with normal renal function, while half-life of the drug exceeds 100 hours in patients with end-stage renal disease.7 A 4-hour hemodialysis session removes approximately 21% of a solriamfetol dose.1,7

Because the half-life of solriamfetol is prolonged in patients with moderate or severe renal impairment, such patients may be at increased risk for elevations in blood pressure and heart rate.1

Dosage adjustment is recommended in patients with moderate to severe renal impairment.1,7 (See Dosage and Administration: Special Populations.) Use of solriamfetol in patients with end-stage renal disease is not recommended.1,7

Hepatic Impairment

Because solriamfetol undergoes minimal metabolism, hepatic impairment is not expected to affect the pharmacokinetics of the drug.5

Common Adverse Effects

Adverse effects reported in clinical trials in 5% of more of patients receiving solriamfetol and more frequently with the drug than with placebo include headache, nausea, decreased appetite, insomnia, and anxiety.1 In clinical trials, headache, nausea, decreased appetite, anxiety, diarrhea, and dry mouth were dose related.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

In vitro data indicate that solriamfetol undergoes minimal metabolism.1 Solriamfetol does not inhibit cytochrome P-450 (CYP) isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A4 in vitro, nor does it induce CYP isoenzyme 1A2, 2B6, or 3A4 at clinically relevant concentrations.1 Based on in vitro data, clinically important interactions involving major CYP isoenzymes are not expected.1

Drugs Metabolized by Uridine-diphosphate Glucuronosyltransferase

Solriamfetol does not induce uridine-diphosphate glucuronosyltransferase (UGT) 1A1 in vitro at clinically relevant concentrations.1

Drugs Affecting or Affected by Transport Systems

Solriamfetol is a low-avidity substrate of organic cation transporter (OCT) 2, multidrug and toxin extrusion transporter (MATE) 1, and organic cation transporters novel (OCTN) 1 and 2.1 Solriamfetol weakly inhibits OCT2 and MATE1, and does not inhibit OCT1, MATE2-K, OCTN1, or OCTN2.1 Solriamfetol does not appear to be a substrate or inhibitor of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transport polypeptide (OATP) 1B1 or 1B3, or organic anion transporter (OAT) 1 or 3.1 Based on in vitro data, clinically important interactions involving major transport systems are not expected.1

Drugs that Increase Blood Pressure or Heart Rate

Concomitant use of solriamfetol with other drugs that increase blood pressure and/or heart rate has not been evaluated, and such combination therapy should be used with caution.1 (See Cardiovascular Effects under Cautions: Warning/Precautions.)

Dopaminergic Drugs

Drugs that increase dopamine concentrations or bind directly to dopaminergic receptors may result in pharmacodynamic interactions with solriamfetol.1 Interactions with dopaminergic drugs have not been evaluated to date.1 Dopaminergic drugs should be used concomitantly with caution in patients receiving solriamfetol.1

Monoamine Oxidase Inhibitors

Concomitant use of monoamine oxidase (MAO) inhibitors and noradrenergic drugs may increase the risk of hypertensive reactions, potentially resulting in death, stroke, myocardial infarction, aortic dissection, ophthalmologic complications, eclampsia, pulmonary edema, and renal failure.1 Solriamfetol is contraindicated in patients who are currently receiving or have recently (within 14 days) received an MAO inhibitor.1

Description

Solriamfetol, a derivative of the amino acid phenylalanine, is a dopamine- and norepinephrine-reuptake inhibitor (DNRI).1,4,9 Solriamfetol binds to dopamine and norepinephrine transporters with low affinity and inhibits the reuptake of dopamine and norepinephrine with low potency.1,4 Solriamfetol has no appreciable binding affinity for serotonin transporter and does not inhibit serotonin reuptake.1,4 Solriamfetol also has no appreciable binding affinity for dopamine, serotonin, norepinephrine, γ-aminobutyric acid (GABA), adenosine, histamine, orexin, benzodiazepine, muscarinic acetylcholine, or nicotinic acetylcholine receptors.1,4 The exact mechanism by which solriamfetol promotes wakefulness in patients with excessive daytime sleepiness associated with obstructive sleep apnea or narcolepsy is not known but may involve inhibition of dopamine and norepinephrine reuptake resulting from binding of the drug to dopamine and norepinephrine transporters in the brainstem arousal systems.1,4,9

Solriamfetol exhibits linear pharmacokinetics over a dose range of 42-1008 mg; once-daily administration is expected to result in minimal accumulation.1 Solriamfetol is readily (95%) absorbed following oral administration.1 Following oral administration under fasted conditions, peak plasma concentration is achieved at a median of 2 hours (range: 1.25-3 hours).1 Administration with a high-fat meal delays the peak plasma concentration by approximately 1 hour, but results in minimal change in overall exposure (peak concentration or area under the plasma concentration-time curve [AUC]).1,6 Solriamfetol is approximately 13-19% bound to plasma proteins.1 The drug exhibits first-order elimination, with a mean apparent elimination half-life of about 7.1 hours.1 Solriamfetol is eliminated mainly (95%) in urine as unchanged drug; 1% or less of an administered dose is recovered as the minor inactive metabolite N -acetylsolriamfetol.1 Active tubular secretion is likely involved in renal clearance of the parent drug.1 Age, sex, and race do not have clinically important effects on the pharmacokinetics of solriamfetol.1

Advice to Patients

Advise patients to read the manufacturer's patient information (medication guide).1

Advise patients that solriamfetol is a controlled substance and has the potential to be abused.1 Advise patients to keep their medication in a secure place and to dispose of unused solriamfetol as recommended in the medication guide.1

Inform patients with obstructive sleep apnea that solriamfetol is not indicated to treat the underlying airway obstruction and that they should use standard treatments, such as nasal continuous positive airway pressure (CPAP), as prescribed.1 Solriamfetol is not a substitute for such therapy.1

Advise patients that solriamfetol can increase blood pressure and pulse rate and that they should be monitored for such effects.1

Instruct patients to contact their clinician if they experience anxiety, insomnia, irritability, agitation, or symptoms of psychosis or bipolar disorders.1

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Women who are breast-feeding should be advised to monitor their infants for adverse effects such as agitation, insomnia, anorexia, and reduced weight gain.1 Importance of encouraging pregnant women who have been exposed to solriamfetol to enroll in the manufacturer's pregnancy registry.1 (See Pregnancy under Warnings/Precautions: Specific Populations, in Cautions.)

Importance of informing patients of other important precautionary information.1 (See Cautions.)

Additional Information

Overview^® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

1. Jazz Pharmaceuticals. Sunosi^® (solriamfetol hydrochloride) tablets prescribing information. Palo Alto, CA; 2019 Jun.

2. Thorpy MJ, Shapiro C, Mayer G et al. A randomized study of solriamfetol for excessive sleepiness in narcolepsy. Ann Neurol . 2019; 85:359-370. [PubMed 30694576][PubMedCentral]

3. Schweitzer PK, Rosenberg R, Zammit GK et al. Solriamfetol for Excessive Sleepiness in Obstructive Sleep Apnea (TONES 3). A Randomized Controlled Trial. Am J Respir Crit Care Med . 2019; 199:1421-1431. [PubMed 30521757][PubMedCentral]

4. 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; 366:367-376. [PubMed 29891587]

5. Thorpy MJ. Recently Approved and Upcoming Treatments for Narcolepsy. CNS Drugs . 2020; 34:9-27. [PubMed 31953791][PubMedCentral]

6. Zomorodi K, Kankam M, Lu Y. A Phase I, Randomized, Crossover, Open-label Study of the Pharmacokinetics of Solriamfetol (JZP-110) in Healthy Adult Subjects With and Without Food. Clin Ther . 2019; 41:196-204. [PubMed 30598342]

7. Zomorodi K, Chen D, Lee L et al. Single-Dose Pharmacokinetics and Safety of Solriamfetol in Participants With Normal or Impaired Renal Function and With End-Stage Renal Disease Requiring Hemodialysis. J Clin Pharmacol . 2019; 59:1120-1129. [PubMed 30865315][PubMedCentral]

8. Carter LP, Henningfield JE, Wang YG et al. A randomized, double-blind, placebo-controlled, crossover study to evaluate the human abuse liability of solriamfetol, a selective dopamine and norepinephrine reuptake inhibitor. J Psychopharmacol . 2018; 32:1351-1361. [PubMed 30269642][PubMedCentral]

9. US Food and Drug Administration. Center for Drug Evaluation and Research. Application numbers 211230Orig1s000 and 211230Orig2s000: Summary review. From FDA website. [Web]

10. Malhotra A, Shapiro C, Pepin JL et al. Long-term study of the safety and maintenance of efficacy of solriamfetol (JZP-110) in the treatment of excessive sleepiness in participants with narcolepsy or obstructive sleep apnea. Sleep . 2020; 43 [PubMed 31691827]

11. Strollo PJ Jr, Hedner J, Collop N et al. Solriamfetol for the Treatment of Excessive Sleepiness in OSA: A Placebo-Controlled Randomized Withdrawal Study. Chest . 2019; 155:364-374. [PubMed 30471270]

12. Sahni AS, Carlucci M, Malik M et al. Management Of Excessive Sleepiness In Patients With Narcolepsy And OSA: Current Challenges And Future Prospects. Nat Sci Sleep . 2019; 11:241-252. [PubMed 31695533][PubMedCentral]

13. Food and Drug Administration. FDA Application: Search Orphan Drug Designations and Approvals. Silver Spring, MD. From FDA website ([Web]). Accessed 2020 Jul 10.