Equivalent Dose Conversion: Vyvanse to Dexamfetamine
Use a 2.5:1 conversion ratio when switching from lisdexamfetamine (Vyvanse) to dexamfetamine, meaning 100 mg of Vyvanse is approximately equivalent to 40 mg of dexamfetamine. 1
Understanding the Pharmacological Basis
Lisdexamfetamine is a prodrug that requires enzymatic hydrolysis to release active dexamfetamine, with this conversion occurring primarily in the blood through rate-limited hydrolysis 2, 3. After oral ingestion, lisdexamfetamine is hydrolyzed to l-lysine (a naturally occurring essential amino acid) and active d-amphetamine, which is responsible for the therapeutic activity 2.
The conversion is unaffected by gastrointestinal pH and variations in normal transit times, providing consistent plasma concentrations throughout the day 3. This enzymatic conversion process results in a delayed onset but prolonged duration of action compared to immediate-release dexamfetamine 4.
Practical Conversion Table
- Lisdexamfetamine 30 mg = Dexamfetamine 12 mg
- Lisdexamfetamine 50 mg = Dexamfetamine 20 mg
- Lisdexamfetamine 70 mg = Dexamfetamine 28 mg
- Lisdexamfetamine 100 mg = Dexamfetamine 40 mg 1
Pharmacokinetic Differences to Consider
The increase in plasma amphetamine concentrations shows a 0.6-hour longer lag time and reaches peak levels 1.1 hours later after lisdexamfetamine administration compared with immediate-release dexamfetamine 4. However, maximal concentrations and total exposure (AUC) are equivalent between equimolar doses 4.
Lisdexamfetamine provides an extended duration of effect continuing for 13 hours post-dosing in children and 14 hours in adults, compared to the shorter duration of immediate-release dexamfetamine 3, 5. The onset of action for lisdexamfetamine occurs within 1-2 hours post-dose 5.
Clinical Implications When Converting
When switching from lisdexamfetamine to dexamfetamine, expect the patient to experience a faster onset of effect but shorter duration of action with dexamfetamine 4. The subjective and cardiovascular stimulant effects occur earlier with dexamfetamine compared to lisdexamfetamine, though peak ratings of potentially abuse-related subjective drug effects are similar 4.
If converting from once-daily lisdexamfetamine to dexamfetamine, consider splitting the equivalent dexamfetamine dose into 2-3 divided doses throughout the day to maintain symptom coverage 6. For example, if a patient is on lisdexamfetamine 70 mg once daily, convert to dexamfetamine 28 mg total daily dose, administered as 10 mg in the morning, 10 mg at midday, and 8 mg in the early afternoon 6.
Monitoring During Conversion
Monitor blood pressure and pulse at baseline and with each dose adjustment, as both medications produce similar peak increases in mean arterial blood pressure, heart rate, body temperature, and pupil size 4. Assess ADHD symptom control using standardized rating scales to ensure adequate coverage throughout the day after conversion 7.
Evaluate both therapeutic effects and side effects before finalizing the conversion dose, particularly assessing for appetite suppression, sleep disturbances, and cardiovascular symptoms 7. The adverse effect profile is consistent between lisdexamfetamine and dexamfetamine, with decreased appetite, insomnia, irritability, and weight loss being the most common 3, 8.
Common Pitfalls to Avoid
Do not assume that because lisdexamfetamine is a prodrug, patients will require higher total daily doses of dexamfetamine—the 2.5:1 ratio accounts for the molecular weight difference and provides equivalent amphetamine exposure 1, 4. Avoid converting to once-daily dexamfetamine when the patient was previously on once-daily lisdexamfetamine, as immediate-release dexamfetamine lacks the extended duration and will require multiple daily doses for equivalent symptom coverage 3, 5.