Is the dosage of lisdexamfetamine in Vyvanse (lisdexamfetamine) equivalent to the dosage of amphetamine and dextroamphetamine in Adderall (amphetamine and dextroamphetamine) in terms of milligrams?

Vyvanse and Adderall Dosing Equivalence

No, Vyvanse (lisdexamfetamine) and Adderall (amphetamine/dextroamphetamine) are not equivalent on a milligram-per-milligram basis. Lisdexamfetamine is a prodrug that requires conversion to active d-amphetamine, and the molecular weight difference means approximately 30 mg of Adderall XR converts to roughly 50 mg of Vyvanse (a 1:1.67 ratio). 1

Understanding the Molecular Difference

• Lisdexamfetamine is dextroamphetamine with an additional lysine molecule attached, making it therapeutically inactive until metabolized in the body 2, 3
• After oral ingestion, lisdexamfetamine is hydrolyzed in the blood to release active d-amphetamine and l-lysine (a naturally occurring amino acid) 3, 4
• The added lysine molecule increases the molecular weight, which is why higher milligram doses of Vyvanse are needed to deliver equivalent amounts of active amphetamine 4

Practical Conversion Ratio

• When switching from Adderall XR 30 mg to Vyvanse, start with 50 mg once daily in the morning, representing a conservative 1:1.67 conversion ratio 1
• This conversion accounts for the prodrug metabolism and provides comparable therapeutic effect 1
• Equimolar doses (40 mg d-amphetamine vs 100 mg lisdexamfetamine) produce similar total drug exposure (AUC) and peak concentrations, but with delayed onset 5

Pharmacokinetic Differences

• Lisdexamfetamine has a 0.6-hour longer lag time and reaches peak levels approximately 1.1 hours later compared to immediate d-amphetamine administration 5
• Despite the delayed onset, the maximal concentrations and total drug exposure are equivalent when equimolar doses are compared 5
• The rate-limited hydrolysis provides a more gradual release of active d-amphetamine, which is the basis for its once-daily dosing 4, 6

Maximum Dosing Considerations

• The maximum recommended daily dose for amphetamines is 40-50 mg total in adults 7, 8
• Vyvanse can be titrated up to a maximum of 70 mg daily for adults with ADHD 7, 1
• When calculating total amphetamine exposure, remember that 70 mg Vyvanse delivers approximately 42 mg of d-amphetamine equivalent 1

Common Pitfall to Avoid

• Never combine Adderall and Vyvanse due to excessive total amphetamine exposure and increased risk of cardiovascular and psychiatric adverse effects 7
• If Vyvanse 50 mg is inadequate, titrate upward in 10-20 mg increments weekly (up to 70 mg maximum) rather than adding another amphetamine-based stimulant 7, 1
• Consider switching to methylphenidate-based stimulants or non-stimulant options (atomoxetine, guanfacine) if amphetamines are ineffective at maximum doses 7