Solriamfetol

Indications

Solriamfetol is used for: Narcolepsy, Obstructive Sleep Apnea

Adult Dose

Narcolepsy Indicated to improve wakefulness in adults with excessive daytime sleepiness associated with narcolepsy Initial: 75 mg PO qDay upon awakening Based on efficacy and tolerability, dose may be doubled at intervals of at least 3 days; not to exceed 150 mg qDay Dosages >150 mg/day do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions Obstructive Sleep Apnea Indicated to improve wakefulness in adults with excessive daytime sleepiness associated with obstructive sleep apnea (OSA) Initial: 37.5 mg PO qDay upon awakening Based on efficacy and tolerability, dose may be doubled at intervals of at least 3 days; not to exceed 150 mg qDay Dosages >150 mg/day do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions Hepatic impairment: No dosage adjustment required (predominantly eliminated by the kidney)

Child Dose

Renal Dose

Renal impairment Mild (eGFR 60-89 mL/min/1.73 m²): No dosage adjustment required Moderate (eGFR 30-59 mL/min/1.73 m²): Initiate at 37.5 mg qDay; based on efficacy and tolerability, may increase to maximum of 75 mg qDay after at least 7 days Severe (eGFR 15-29 mL/min/1.73 m²): 37.5 mg qDay; do not increase dose End-stage renal disease (eGFR <15 mL/min/1.73 m²): Not recommended

Administration

Take with or without food upon awakening for the day Avoid taking within 9 hr of planned bedtime; may interfere with sleep if taken too late in the day 75-mg tablets are functionally scored and can be split in half (37.5 mg)

Contra Indications

Coadministration with MAO inhibitors or within 14 days after discontinuing MAO inhibitor

Precautions

Blood pressure and heart rate increase Increases systolic blood pressure, diastolic blood pressure, and heart rate in a dose-dependent fashion Assess blood pressure and control hypertension before initiating treatment Monitor blood pressure regularly during treatment and treat new-onset hypertension and exacerbations of preexisting hypertension Caution in patients at higher risk of major adverse cardiovascular events (MACE), particularly patients with known cardiovascular and cerebrovascular disease, preexisting hypertension, and advanced age If increases in blood pressure or heart rate cannot be managed with dose reduction or other appropriate medical intervention, consider discontinuation of therapy Psychiatric symptoms Psychiatric adverse reactions observed during clinical trials, including anxiety, insomnia, and irritability Caution in patients with history of psychosis or bipolar disorders, as these patients were not evaluated in clinical trials Patients with moderate or severe renal impairment may be at a higher risk of psychiatric symptoms because of the prolonged half-life Observe patient for the possible emergence or exacerbation of psychiatric symptoms; reduce dose or consider discontinuing drug if psychiatric symptoms develop

Pregnancy-Lactation

Pregnancy Available data from case reports are not sufficient to determine drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcome Animal studies Administration during organogenesis caused maternal and fetal toxicities in rats and rabbits at doses >4 and 5 times and was teratogenic at doses 19 and ?5 times, respectively, the maximum recommended human dose (MRHD) of 150 mg based on mg/m² Administration to pregnant rats during pregnancy and lactation at doses >7 times the MRHD based on mg/m² resulted in maternal toxicity and adverse effects on fertility, growth, and development in offspring Lactation No data are available on the presence of solriamfetol or its metabolites in human milk, effects on breastfed infants, or effects on milk production Solriamfetol is present in rat milk; when a drug is present in animal milk, it is likely that the drug will be present in human milk Clinical considerations: Monitor breastfed infants for adverse effects (eg, agitation, insomnia, anorexia, reduced weight gain) The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed child or from the underlying maternal condition

Interactions

Drugs that increase blood pressure/heart rate: Caution; coadministration might result in pharmacodynamic interactions Dopaminergic drugs: Caution; coadministration might result in pharmacodynamic interactions MAO inhibitors Contraindicated; do not use concomitantly or within 14 days after discontinuing MAO inhibitor Coadministration of MAO inhibitors and noradrenergic drugs may increase risk of hypertensive reaction Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure

Adverse Effects

Side effects of Solriamfetol : >10% (Narcolepsy) Headache (16%) 1-10% (Narcolepsy) Decreased appetite (9%) Nausea (7%) Anxiety (6%) Insomnia (5%) Dry mouth (4%) Constipation (3%) Palpitations (2%) Constipation (1%) <2% Psychiatric disorders: Agitation, bruxism, irritability Respiratory, thoracic, and mediastinal disorders: Cough Skin and subcutaneous tissue disorders: Hyperhidrosis General disorders and administration site conditions: Feeling jittery, thirst, chest discomfort, chest pain Investigations: Weight decreased

Mechanism of Action

Dopamine and norepinephrine reuptake inhibitor (DNRI) The mechanism of action of solriamfetol to improve wakefulness in patients with excessive daytime sleepiness associated with narcolepsy or OSA is unclear Efficacy thought to be mediated through its DNRI activity