onal useof stimulants. Results from this clinical study demonstrated that SUNOSI produced Drug Likingscores similar to or lower than phentermine. In this crossover study, elevated mood was reportedby 2.4% of placebo-treated subjects, 8 to 24% of SUNOSI-treated subjects, and 10 to 18% ofphentermine-treated subjects. A ‘feeling of relaxation’ was reported in 5% of placebo-treatedsubjects, 5 to 19% of SUNOSI-treated subjects and 15 to 20% of phentermine-treated subjects.
Physicians should carefully eva luate patients for a recent history of drug abuse, especially thosewith a history of stimulant (e.g., methylphenidate, amphetamine, or cocaine) or alcohol abuse,and follow such patients closely, observing them for signs of misuse or abuse of SUNOSI (e.g.,incrementation of doses, drug-seeking behavior).
9.3 Dependence
In a long-term safety and maintenance of efficacy study, the effects of abrupt discontinuation ofSUNOSI were eva luated following at least 6 months of SUNOSI use in patients with narcolepsyor OSA. The effects of abrupt discontinuation of SUNOSI were also eva luated during the twoweeksafety follow-up periods in the Phase 3 studies. There was no evidence that abruptdiscontinuation of SUNOSI resulted in a consistent pattern of adverse events in individualsubjects that was suggestive of physical dependence or withdrawal.
10 OVERDOSAGE
A specific reversal agent for SUNOSI is not available. Hemodialysis removed approximately21% of a 75 mg dose in end stage renal disease patients. Overdoses should be managed withprimarily supportive care, including cardiovascular monitoring.
Consult with a Certified Poison Control Center at 1-800-222-1222 for latest recommendations.
11 DESCRIPTION
SUNOSI contains solriamfetol, a dopamine and norepinephrine reuptake inhibitor (DNRI).
Solriamfetol is a phenylalanine derivative with the systematic name (R)-2-amino-3-phenylpropylcarbamate hydrochloride.
The molecular formula is C10H15N2O2Cl, and the molecular weight is 230.69.
The chemical structure is:
Solriamfetol hydrochloride is a white to off-white solid that is freely soluble in water.
SUNOSI tablets are intended for oral administration. Each 75 mg SUNOSI film-coated tabletcontains 75 mg solriamfetol (equivalent to 89.3 mg solriamfetolhydrochloride). Each 150 mgSUNOSI film-coated tablet contains 150 mg solriamfetol (equivalent to 178.5 mg solriamfetolhydrochloride). The inactive ingredients are hydroxypropyl cellulose and magnesium stearate. Inaddition, the film coating contains: iron oxide yellow, polyethylene glycol, polyvinyl alcohol,talc, and titanium dioxide.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
The mechanism of action of solriamfetol to improve wakefulness in patients with excessivedaytime sleepiness associated with narcolepsy or obstructive sleep apnea is unclear. However, its efficacy could be mediated through its activity as a dopamine and norepinephrine reuptakeinhibitor (DNRI).
12.2 Pharmacodynamics
Solriamfetol binds to the dopamine transporter and norepinephrine transporter with low affinity(Ki=14.2 µM and 3.7 µM, respectively), and inhibits the reuptake of dopamine andnorepinephrine with low potency (IC50 =2.9 μM and 4.4 μM, respectively). Solriamfetol has noappreciable binding affinity for the serotonin transporter (Ki=81.5 µM) and does not inhibitserotonin reuptake (IC50 > 100 μM) |
