Factors Interfering with Vyvanse Conversion
Lisdexamfetamine (Vyvanse) is enzymatically hydrolyzed primarily in red blood cells to its active form d-amphetamine, and this conversion process is notably resistant to most common interference—it is unaffected by gastrointestinal pH variations or normal transit time changes. 1, 2
Mechanism of Conversion
Lisdexamfetamine is a therapeutically inactive prodrug that requires enzymatic hydrolysis, predominantly in the blood by red blood cells, to release active d-amphetamine and the amino acid l-lysine. 3, 1, 4
The conversion is rate-limited and occurs systemically rather than in the gastrointestinal tract, which distinguishes it from other extended-release formulations. 5, 2
This blood-based hydrolysis mechanism provides consistent plasma concentrations throughout the day and reduces variability from gastrointestinal factors. 1
Factors That Do NOT Interfere
Gastrointestinal pH changes do not affect lisdexamfetamine conversion, unlike some other ADHD medications that rely on pH-dependent absorption mechanisms. 1
Variations in normal gastrointestinal transit times do not impact the conversion process since hydrolysis occurs after absorption into the bloodstream. 1
Potential Interference Factors
Drug Interactions
CYP2D6 inhibitors may increase exposure to d-amphetamine (the active metabolite), potentially intensifying effects rather than blocking conversion. 6
Monoamine oxidase inhibitors (MAOIs) are contraindicated with lisdexamfetamine due to risk of hypertensive crisis, though this represents a pharmacodynamic interaction with the active metabolite rather than interference with conversion. 6
Serotonergic drugs combined with CYP2D6 inhibitors may increase risk of serotonin syndrome by increasing d-amphetamine exposure. 6
Theoretical Considerations
Since conversion depends on enzymatic hydrolysis in red blood cells, severe hematologic conditions affecting red blood cell function could theoretically impact conversion, though no published studies specifically examine this scenario. 3, 5
The enzymatic process is relatively robust and not easily saturated, making clinically significant interference uncommon in typical medical practice. 2
Clinical Implications
The pharmacokinetic properties of lisdexamfetamine make it relatively predictable with small likelihood of reduced effect from drug interactions, which is an advantage over immediate-release amphetamine formulations. 2
When prescribing with CYP2D6 inhibitors or serotonergic agents, initiate lisdexamfetamine at lower doses and monitor for increased amphetamine effects rather than reduced efficacy. 6
The conversion mechanism provides consistent 13-14 hour duration of action in children and adults respectively, with minimal variability between patients. 1, 4