What amount of d-amphetamine is contained in Vyvanse (lisdexamfetamine) 10mg?

Amphetamine Content in Vyvanse 10mg

Vyvanse 10mg contains 10mg of lisdexamfetamine dimesylate, which is equivalent to approximately 2.9mg of d-amphetamine base. 1

Understanding the Conversion

• Lisdexamfetamine dimesylate is a prodrug that must be metabolized in the body to release active d-amphetamine 1
• The FDA label specifies that lisdexamfetamine dimesylate capsules contain the following d-amphetamine equivalents:
  • 10mg lisdexamfetamine dimesylate = 5.8mg lisdexamfetamine base (not 5.8mg d-amphetamine) 1
  • The actual d-amphetamine released after metabolism is approximately 29% of the lisdexamfetamine dimesylate dose 1

Pharmacological Mechanism

• Lisdexamfetamine is a therapeutically inactive molecule until it undergoes hydrolysis in the blood to release d-amphetamine and L-lysine 2, 3
• The conversion occurs through rate-limited hydrolysis, with red blood cells cleaving the lysine molecule to gradually release pharmacologically active d-amphetamine 4, 3
• This prodrug design results in delayed absorption compared to immediate-release amphetamine formulations, with peak d-amphetamine concentrations occurring approximately 3.5 hours post-dose versus 1 hour for the parent lisdexamfetamine compound 1

Clinical Implications of the Prodrug Design

• The delayed conversion mechanism produces lower peak plasma concentrations (Cmax) of d-amphetamine compared to equivalent doses of immediate-release d-amphetamine, while maintaining similar total drug exposure (AUC) 5, 6
• This pharmacokinetic profile was designed to reduce abuse potential, as lisdexamfetamine produces lower "Drug Liking" scores compared to immediate-release d-amphetamine in abuse liability studies 1, 7
• The prodrug must be ingested orally and metabolized to be active; alternative routes of administration (snorting or injection) do not bypass this requirement effectively 4

Important Caveat

• While Vyvanse 10mg releases approximately 2.9mg of d-amphetamine, this does not mean it is clinically equivalent to 2.9mg of immediate-release Adderall, as the extended-release profile and rate-limited conversion create different pharmacodynamic effects 5, 6