What is the equivalent dose of Vyvanse (lisdexamfetamine) to dexamfetamine in an adult patient with Attention Deficit Hyperactivity Disorder (ADHD) or narcolepsy?

Equivalent Dose Conversion: Vyvanse to Dexamfetamine

Vyvanse (lisdexamfetamine) 100 mg is approximately equivalent to dexamfetamine 40 mg, representing a 2.5:1 conversion ratio. This conversion is based on the molecular composition of lisdexamfetamine, which is a prodrug that releases dexamfetamine after enzymatic hydrolysis 1, 2.

Understanding the Pharmacological Basis

• Lisdexamfetamine is a therapeutically inactive prodrug comprised of dexamfetamine covalently bonded to L-lysine 1, 3.
• After oral administration, lisdexamfetamine undergoes rate-limited enzymatic hydrolysis primarily in red blood cells to release active dexamfetamine and L-lysine 1, 4.
• The parent drug (lisdexamfetamine) does not bind to sites responsible for norepinephrine and dopamine reuptake; only the released dexamfetamine is pharmacologically active 1, 3.

Molecular Weight-Based Conversion

• Lisdexamfetamine dimesylate has a molecular weight of 455.60, while the active dexamfetamine component represents approximately 40% of the total molecular weight 1.
• A 70 mg capsule of lisdexamfetamine dimesylate contains 40.5 mg of lisdexamfetamine base, which releases approximately 28.9 mg of dexamfetamine 1.
• The practical conversion ratio is approximately 2.5:1 (lisdexamfetamine to dexamfetamine), meaning 100 mg lisdexamfetamine delivers roughly 40 mg of active dexamfetamine 2.

Clinical Equivalence Evidence

• A randomized, double-blind, placebo-controlled crossover study in 24 healthy subjects directly compared equimolar doses of lisdexamfetamine 100 mg and dexamfetamine 40 mg 2.
• No differences in maximal plasma concentrations (Cmax) or total drug exposure (AUC) were found between lisdexamfetamine 100 mg and dexamfetamine 40 mg 2.
• Peak subjective effects (drug liking, stimulation, well-being) and cardiovascular effects (blood pressure, heart rate) were similar between the two formulations, confirming pharmacodynamic equivalence 2.

Dosing Conversion Table for Clinical Practice

For ADHD in adults:

• Dexamfetamine 5 mg ≈ Lisdexamfetamine 12.5-15 mg
• Dexamfetamine 10 mg ≈ Lisdexamfetamine 25-30 mg
• Dexamfetamine 20 mg ≈ Lisdexamfetamine 50 mg
• Dexamfetamine 30 mg ≈ Lisdexamfetamine 70 mg (maximum approved dose)
• Dexamfetamine 40 mg ≈ Lisdexamfetamine 100 mg 5, 2

For narcolepsy in adults:

• The American Academy of Sleep Medicine recommends dexamfetamine for narcolepsy treatment, though specific dosing equivalents to lisdexamfetamine are not established in guidelines 6.
• The same 2.5:1 conversion ratio applies based on pharmacokinetic principles 2.

Critical Timing Differences Despite Equivalent Exposure

• Lisdexamfetamine has a 0.6-hour longer lag time before plasma concentrations begin rising compared to immediate-release dexamfetamine 2.
• Peak plasma concentrations occur approximately 1.1 hours later with lisdexamfetamine (Tmax ~3.5-4.4 hours) compared to immediate-release dexamfetamine (Tmax ~2-3 hours) 1, 2.
• Despite identical total drug exposure, the delayed and prolonged release profile of lisdexamfetamine provides extended duration of action (13-14 hours) compared to immediate-release dexamfetamine (4-6 hours) 7.

Common Pitfalls to Avoid

• Do not assume lisdexamfetamine provides lower peak effects than dexamfetamine—when comparing equivalent doses, peak subjective and cardiovascular effects are identical, only delayed by approximately 1 hour 2.
• Do not use a 1:1 mg conversion—this would result in significant underdosing, as lisdexamfetamine requires 2.5 times the mg dose to deliver equivalent dexamfetamine exposure 1, 2.
• Do not expect reduced abuse potential with oral administration—despite being a prodrug, lisdexamfetamine produces equivalent drug liking and subjective effects when taken orally at equimolar doses 2.
• The prodrug design primarily reduces abuse potential through alternative routes (injection, insufflation), not oral administration 3, 4.