Duration of Action of Vyvanse (Lisdexamfetamine)
Vyvanse (lisdexamfetamine) has a duration of action of 14 hours in adults with ADHD, making it one of the longest-acting stimulant medications available for ADHD treatment. 1
Pharmacokinetics and Mechanism
Lisdexamfetamine is a prodrug that requires enzymatic conversion to its active form:
- Lisdexamfetamine itself has a short half-life of less than one hour 2
- After oral administration, it is converted to dextroamphetamine (the active component) and l-lysine primarily in the blood due to hydrolytic activity of red blood cells 2
- The conversion is not dependent on cytochrome P450 enzymes 2
- The plasma elimination half-life of dextroamphetamine is approximately:
- 8.6 to 9.5 hours in pediatric patients (6-12 years)
- 10 to 11.3 hours in healthy adults 2
Clinical Duration of Effect
The clinical effect of Vyvanse extends beyond what might be expected from the half-life alone:
- In controlled clinical trials using analog classroom protocols, lisdexamfetamine demonstrated efficacy for up to 14 hours post-dose in adults 3, 1
- This duration is longer than other long-acting stimulants, which typically provide 8-12 hours of symptom control 1
- Steady-state dextroamphetamine concentration is reached by day 5 of daily dosing 4
- After discontinuation, 95% of dextroamphetamine is eliminated within 48 hours following the final dose 4
Pharmacodynamics
The extended duration of action is related to its unique pharmacodynamic properties:
- Dextroamphetamine (the active metabolite) blocks the reuptake of norepinephrine and dopamine into presynaptic neurons 2
- It also increases the release of these monoamines into the extraneuronal space 2, 5
- The prodrug formulation provides a more gradual onset and extended duration compared to immediate-release amphetamine formulations
Clinical Implications
The 14-hour duration of action has important clinical implications:
- Allows for once-daily dosing in the morning 3
- Provides coverage of ADHD symptoms throughout the entire day and into the evening hours
- May eliminate the need for additional short-acting stimulant doses later in the day
- Helps maintain consistent symptom control without the "peaks and valleys" associated with shorter-acting medications
Potential Limitations and Considerations
- Individual response may vary based on metabolism, body weight, and other factors
- Food prolongs the time to maximum concentration (Tmax) by approximately 1 hour but does not significantly affect the overall exposure to the active drug 2
- The chewable tablet formulation may have slightly different pharmacokinetics, with about 15% lower exposure to lisdexamfetamine compared to the capsule formulation, though the exposure to dextroamphetamine remains similar 2
The extended 14-hour duration of action makes Vyvanse particularly suitable for patients who require symptom control throughout the entire day and into the evening hours.