IUPAC Name
(2S)-2,6-diamino-N-[(2S)-1-phenylpropan-2-yl]hexanamide
Current Scheduling Status
None
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Summary
Lisdexamfetamine, chemical name (2S)-2,6-diamino-N-[(2S)-1-phenylpropan- 2-yl]hexanamide,(2S)-2,6-diamino-N-[(1S)-1-methyl-2-phenylethyl] hexanamidedimethanesulfonate, had not previously been reviewed by the Committee.
As a central nervous system stimulant, lisdexamfetamine is used as an adjunct in the treatment of attention deficit hyperactivity disorder (ADHD). As a pro-drug, lisdexamfetamine was specifically designed as an abuse- resistant product. After oral administration and absorption, enzyme hydrolysis following contact with red blood cells will break lisdexamfetamine into lysine, a naturally occurring essential amino acid, and active dexamfetamine, which is responsible for the substance’s pharmacological activity. The safety and efficacy of lisdexamfetamine in the treatment of ADHD in children and adults has been established and the toxicology and adverse effect profile appears similar to other stimulant drugs for this indication. Although lisdexamfetamine self- administration is limited in preclinical and clinical studies, lisdexamfetamine does produce similar subjective and discriminative effects to those of dexamfetamine in humans and animals, respectively. The observation in preclinical studies that lisdexamfetamine produces substantial and sustained increases in catecholaminergic neurotransmission in the prefrontal cortex and striatum without inducing locomotor activation is consistent with the clinical observations that lisdexamfetamine has a long duration of action and a reasonable separation between its beneficial effects in treating ADHD and the induction of psychostimulant adverse events. To date, there appears to be little evidence of non-medical use of lisdexamfetamine based on data from DAWN Live (Drug Abuse Warning Network1), Internet and media monitoring, supply-chain monitoring, post-marketing adverse event reports, and Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®) especially in comparison to immediate-release stimulant medicines for ADHD. Nevertheless, the fact that lisdexamfetamine is a pro-drug of dexamfetamine implies a need for similar clinical oversight and precautions for the monitoring and scheduling of this central nervous system stimulant.
Recommendation
Based on the evidence available regarding dependence, abuse and risks to public health, the Committee recommended that a critical review for lisdexamfetamine is not warranted at this time.
Lisdexamfetamine, chemical name (2S)-2,6-diamino-N-[(2S)-1-phenylpropan- 2-yl]hexanamide,(2S)-2,6-diamino-N-[(1S)-1-methyl-2-phenylethyl] hexanamidedimethanesulfonate, had not previously been reviewed by the Committee.
As a central nervous system stimulant, lisdexamfetamine is used as an adjunct in the treatment of attention deficit hyperactivity disorder (ADHD). As a pro-drug, lisdexamfetamine was specifically designed as an abuse- resistant product. After oral administration and absorption, enzyme hydrolysis following contact with red blood cells will break lisdexamfetamine into lysine, a naturally occurring essential amino acid, and active dexamfetamine, which is responsible for the substance’s pharmacological activity. The safety and efficacy of lisdexamfetamine in the treatment of ADHD in children and adults has been established and the toxicology and adverse effect profile appears similar to other stimulant drugs for this indication. Although lisdexamfetamine self- administration is limited in preclinical and clinical studies, lisdexamfetamine does produce similar subjective and discriminative effects to those of dexamfetamine in humans and animals, respectively. The observation in preclinical studies that lisdexamfetamine produces substantial and sustained increases in catecholaminergic neurotransmission in the prefrontal cortex and striatum without inducing locomotor activation is consistent with the clinical observations that lisdexamfetamine has a long duration of action and a reasonable separation between its beneficial effects in treating ADHD and the induction of psychostimulant adverse events. To date, there appears to be little evidence of non-medical use of lisdexamfetamine based on data from DAWN Live (Drug Abuse Warning Network1), Internet and media monitoring, supply-chain monitoring, post-marketing adverse event reports, and Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®) especially in comparison to immediate-release stimulant medicines for ADHD. Nevertheless, the fact that lisdexamfetamine is a pro-drug of dexamfetamine implies a need for similar clinical oversight and precautions for the monitoring and scheduling of this central nervous system stimulant.
Recommendation
Based on the evidence available regarding dependence, abuse and risks to public health, the Committee recommended that a critical review for lisdexamfetamine is not warranted at this time.
ECDD Recommendation
No change in scheduling
Link to full TRS
who_trs_991_eng.pdf1.3 MB
MS Questionnaire Report