Is a washout period necessary when switching from dextroamphetamine to lisdexamfetamine or vice versa?

Switching Between Dextroamphetamine and Lisdexamfetamine

No washout period is necessary when switching between dextroamphetamine and lisdexamfetamine, as lisdexamfetamine is a prodrug that converts to dextroamphetamine in the body.

Pharmacological Relationship Between the Medications

Lisdexamfetamine is a prodrug comprising l-lysine amino acid covalently bonded to dextroamphetamine. After oral ingestion, lisdexamfetamine is hydrolyzed to l-lysine and active d-amphetamine (dextroamphetamine), which is responsible for the therapeutic effect 1. This means:

• Lisdexamfetamine itself is therapeutically inactive until converted
• The active metabolite is identical to dextroamphetamine
• The conversion occurs through rate-limited hydrolysis in the body

Direct Switch Protocol

When switching between these medications, you can implement a direct switch approach:

1. Discontinue one medication and start the other the next day

   • No washout period is required since both medications ultimately work through the same active compound (dextroamphetamine)
   • The patient will not experience withdrawal symptoms during the transition

2. Dosage Equivalence Considerations:

   • 70 mg of lisdexamfetamine provides similar exposure to approximately 30 mg of dextroamphetamine 2
   • When switching from dextroamphetamine to lisdexamfetamine, use this approximate conversion ratio

Clinical Advantages of Each Formulation

Lisdexamfetamine Advantages

• Reduced abuse potential due to its prodrug nature 3
• Once-daily dosing with extended duration of action
• Less variable blood levels throughout the day
• Cannot produce high dextroamphetamine levels when injected or snorted 3

Dextroamphetamine Advantages

• More immediate onset of action
• More flexible dosing options for patients who need precise timing control
• May be preferred for patients who need shorter duration of effect

Monitoring During Transition

During the switch, monitor for:

• Changes in effectiveness of symptom control
• Differences in side effect profiles
• Sleep patterns and appetite changes
• Blood pressure and heart rate (standard monitoring for stimulants) 4

Important Considerations

• Unlike switching between different classes of medications (such as stimulants to non-stimulants like atomoxetine), no gradual cross-tapering is required 5
• This differs significantly from antidepressant switching, which often requires careful tapering and washout periods 6
• The American Academy of Pediatrics recommends regular monitoring every 3-4 weeks during any stimulant dose adjustments 4

Potential Pitfalls to Avoid

• Don't assume identical clinical response: Despite the same active compound, differences in pharmacokinetics may affect individual response
• Don't overlook timing of administration: Lisdexamfetamine has a longer duration of action, so timing of the daily dose is important
• Don't ignore patient feedback: Some patients may respond better to one formulation despite the pharmacological similarities

This straightforward approach to switching between dextroamphetamine and lisdexamfetamine simplifies medication management while maintaining effective ADHD symptom control.