Sunosi (solriamfetol HCl)

Dosage of solriamfetol hydrochloride is expressed in terms of solriamfetol.

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

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Bupropion; Solriamfetol/Mao Inhibitors

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Bupropion and solriamfetol increase dopamine and norepinephrine concentrations via blockade of the dopamine and norepinephrine reuptake transporters.(1-4) Monoamine oxidase inhibitors (MAOIs) block the metabolism of norepinephrine and dopamine, also leading to increased neuronal concentrations of norepinephrine and dopamine.(5)

CLINICAL EFFECTS: The concurrent administration of bupropion or solriamfetol and MAOIs may increase the risk for hypertensive crisis, severe hypertension, or other adverse reactions,(3-4) including mania, psychosis or agitation with bupropion,(3) and headache, nausea, anorexia, or anxiety with solriamfetol.(4)

PREDISPOSING FACTORS: Patients with pre-existing hypertension may be more likely to experience treatment-emergent hypertension.(3) Patients with moderate to severe renal impairment may be at higher risk for increases in blood pressure and heart rate from solriamfetol due to prolonged drug exposure.(4)

PATIENT MANAGEMENT: The US manufacturers of bupropion and solriamfetol state that concurrent use of bupropion or solriamfetol with a MAOI is contraindicated due to the risk for hypertensive reactions.(3,4) The US manufacturer of phenelzine states that concurrent use of bupropion is contraindicated.(5) At least 14 days should elapse between the discontinuation of a MAOI and the initiation of bupropion or solriamfetol,(3-5) except in the case of methylene blue.(6) Do not initiate bupropion or solriamfetol therapy in patients receiving methylene blue until 24 hours after the last dose of these agents.(3,6) In emergency situations in patients maintained on bupropion or solriamfetol, weigh the availability and safety of alternatives to methylene blue against the risk of acute hypertension. If methylene blue therapy is required, the patient's bupropion or solriamfetol should be immediately discontinued. Patients' blood pressure should be closely monitored for 2 weeks or until 24 hours after the last dose of methylene blue, whichever comes first.(3,6) In non-emergency situations in patients maintained on bupropion or solriamfetol when methylene blue therapy is planned, discontinue the patient's bupropion or solriamfetol at least 2 weeks in advance of methylene blue therapy. The patient's bupropion or solriamfetol therapy may be resumed 24 hours after the last dose of linezolid or methylene blue.(3,6) If concurrent therapy is warranted, patients should be monitored for signs and symptoms of hypertensive crisis.

DISCUSSION: The US manufacturers of bupropion and solriamfetol state that concurrent use of bupropion or solriamfetol with a MAOI is contraindicated.(3,4) The US manufacturer of phenelzine states that concurrent use of bupropion is contraindicated.(5) At least 14 days should elapse between the discontinuation of a MAOI and the initiation of bupropion or solriamfetol.(1-5) Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A.(6,7) Metaxalone is a weak inhibitor of MAO.(8,9) FDA alerts in July 2011(6) described the risk for serotonin syndrome when bupropion is used concurrently with methylene blue or other MAOIs. In October 2011 FDA updated these alerts, describing the risk for serotonin syndrome when MAOIs are combined with bupropion (and selected other psychiatric agents not associated with case reports of serotonin syndrome) as unclear.(7) Subsequent bupropion and solriamfetol prescribing information describes an increased risk for hypertensive reactions when co-prescribed with MAOIs.(3,4)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Bupropion; Solriamfetol/Linezolid

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Bupropion and solriamfetol increase dopamine and norepinephrine concentrations via blockade of the dopamine and norepinephrine reuptake transporters.(1-4) Linezolid is a weak, nonselective monoamine oxidase inhibitor (MAOI) that blocks the metabolism of norepinephrine and dopamine, also leading to increased neuronal concentrations of norepinephrine and dopamine.(5)

CLINICAL EFFECTS: The concurrent administration of bupropion or solriamfetol and linezolid may increase the risk for serotonin syndrome and/or severe hypertensive, or other adverse reactions, including mania, psychosis or agitation with bupropion, and headache, nausea, anorexia, or anxiety with solriamfetol.(1-2) Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.

PREDISPOSING FACTORS: Patients with pre-existing hypertension may be more likely to experience treatment-emergent hypertension.(1) Patients with moderate to severe renal impairment may be at higher risk for increases in blood pressure and heart rate from solriamfetol due to prolonged drug exposure.(2)

PATIENT MANAGEMENT: The US manufacturers of bupropion and solriamfetol state that concurrent use of bupropion or solriamfetol with a MAOI is contraindicated due to the risk for hypertensive reactions.(1,2) The manufacturer of linezolid does not contraindicate the use of serotonergic agents but states that they should not be coadministered unless clinically appropriate and the patient is closely monitored.(5) This recommendation is consistent with the 2011 FDA Drug Safety Communication on linezolid and serotonergic psychiatric medications.(6,7) In non-emergency situations in patients maintained on bupropion or solriamfetol when linezolid therapy is planned, discontinue the patient's bupropion or solriamfetol at least 2 weeks in advance of linezolid therapy.(1,6) In emergency situations in patients maintained on bupropion or solriamfetol, weigh the availability and safety of alternatives to linezolid against the risk of acute hypertension. If linezolid therapy is required, the patient's bupropion or solriamfetol should be immediately discontinued. Patients' blood pressure should be closely monitored for 2 weeks or until 24 hours after the last dose of linezolid, whichever comes first.(1,6) The patient's bupropion or solriamfetol therapy may be resumed 24 hours after the last dose of linezolid.(1,6) Clinical studies have found a low incidence of serotonin syndrome in patients on concomitant linezolid and serotonergic agents, ranging from 0.24% to 4%, depending on the quality and size of the study. While linezolid-associated serotonin syndrome is potentially serious and fatal, if treated early, it is quickly reversible with discontinuation of offending agents and supportive care. Therefore, some authors suggest that use of serotonergic medications should not preclude the use of linezolid but that the clinical situation should be assessed. If concurrent use of linezolid without a washout is warranted, the patient should be closely monitored.(8-13) If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea.

DISCUSSION: The US manufacturers of bupropion and solriamfetol state that concurrent use of bupropion or solriamfetol with a MAOI is contraindicated.(1,2) An FDA alert in July 2011(6) described the risk for serotonin syndrome when bupropion is used concurrently with linezolid. In October 2011 FDA updated these alerts, describing the risk for serotonin syndrome when MAOIs are combined with bupropion (and selected other psychiatric agents not associated with case reports of serotonin syndrome) as unclear.(7) Subsequent bupropion and solriamfetol prescribing information describes an increased risk for hypertensive reactions when co-prescribed with MAOIs.(1,2)

There are no moderate interactions for this drug.

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

• Chronic kidney disease stage 5 (failure) GFr<15 ml/min

• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min

• Bipolar disorder
• Hypertension
• Kidney disease with likely reduction in glomerular filtration rate (GFr)
• Psychotic disorder

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. In clinical trials, headache, nausea, decreased appetite, anxiety, diarrhea, and dry mouth were dose related.

Less Frequent

• Hypertension

More Frequent

• Anorexia
• Headache disorder
• Insomnia
• Nausea
• Symptoms of anxiety

Less Frequent

• Agitation
• Bruxism
• Chest discomfort
• Chest pain
• Constipation
• Cough
• Diarrhea
• Disturbance of attention
• Dizziness
• Dyspnea
• Hyperhidrosis
• Irritability
• Nervousness
• Palpitations
• Polydipsia
• Tachycardia
• Tremor
• Vomiting
• Weight loss
• Xerostomia

No enhanced messaging available.

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

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

Teratogenicity, fetal toxicity, and developmental toxicity have been observed in animal studies. 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. 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. 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.

The manufacturer has established a pregnancy registry to monitor fetal outcomes of pregnant women exposed to solriamfetol. Clinicians are encouraged to register pregnant patients, or pregnant women may enroll themselves in the registry, by calling 877-283-6220 or visiting http://www.SunosiPregnancyRegistry.com.

It is not known whether solriamfetol or its metabolites are distributed into human milk, affect breast-fed infants, or affect milk production. Solriamfetol is distributed into milk in rats. 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. 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.

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. No clinically important differences in safety or efficacy were observed between geriatric patients and younger adults.

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. 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. (See Dosage and Administration: Special Populations.)