What dose of Vyvanse (lisdexamfetamine) will achieve a comparable maximum concentration (Cmax) of amphetamine to Adderall XR (mixed amphetamine salts)?

From the Guidelines

To achieve a Cmax equivalent of amphetamine compared to Adderall XR, a dose of 70 mg of Vyvanse is recommended, as it is the maximum daily dose and would likely provide the closest equivalent peak amphetamine levels. When considering the dose of Vyvanse needed to achieve a Cmax equivalent of amphetamine compared to Adderall XR, it's essential to understand the pharmacokinetics of both medications. Vyvanse, or lisdexamfetamine, is a prodrug that is converted to dextroamphetamine in the body, as noted in the study by Scoten 1. The study provides information on the usual starting dose and titration of Vyvanse, which is 20-30 mg po qam, with an increase by 10 mg weekly to a maximum of 70 mg daily. Given that the goal is to match the peak amphetamine levels of Adderall XR, and considering the maximum daily dose of Vyvanse is 70 mg, this dose is likely the best option to achieve the desired Cmax. However, it's crucial to work with a healthcare provider to determine the appropriate dose for individual needs, as responses to medication can vary significantly. Starting at a lower dose and titrating up under medical supervision is the safest approach, as indicated by the dosing recommendations for Vyvanse 1. Never adjust medication dosages without consulting your healthcare provider, as this can lead to adverse effects or reduced efficacy. Some key points to consider when comparing Vyvanse to Adderall XR include:

• The pharmacokinetic profiles of the two medications, with Vyvanse being a prodrug and Adderall XR containing a mixture of immediate and delayed-release amphetamine salts
• The potential for differences in side effects and efficacy between the two medications
• The importance of individualized dosing and medical supervision to ensure safe and effective treatment.

From the FDA Drug Label

After single-dose oral administration of lisdexamfetamine dimesylate capsules (30 mg, 50 mg, or 70 mg) in patients ages 6 to 12 years with ADHD under fasted conditions, Tmax of lisdexamfetamine and dextroamphetamine was reached at approximately 1 hour and 3. 5 hours post dose, respectively. Weight/Dose normalized AUC and Cmax values were the same in pediatric patients ages 6 to 12 years as the adults following single doses of 30 mg to 70 mg lisdexamfetamine dimesylate capsules The exposure (Cmax and AUCinf) of dextroamphetamine is similar between Vyvanse chewable tablet and lisdexamfetamine dimesylate capsules

The FDA drug label does not provide a direct comparison of the Cmax of dextroamphetamine (the active metabolite of Vyvanse) to Adderall XR.

• Key points:
  • Dose proportionality: The pharmacokinetics of dextroamphetamine was found to be linear between 30 mg and 70 mg in a pediatric study, and between 50 mg and 250 mg in an adult study.
  • Exposure: The exposure (Cmax and AUCinf) of dextroamphetamine is similar between Vyvanse chewable tablet and lisdexamfetamine dimesylate capsules.
  • No direct comparison: There is no direct comparison of the Cmax of dextroamphetamine to Adderall XR in the provided drug label 2.

From the Research

Pharmacokinetics of Lisdexamfetamine and D-Amphetamine

• The pharmacokinetics of lisdexamfetamine and D-amphetamine have been compared in a study, which found that lisdexamfetamine has a prolonged pharmacokinetic profile compared to oral D-amphetamine 3.
• The study found that the increase in plasma concentrations of amphetamine had a 0.6 ± 0.6 h longer lag time and reached peak levels 1.1 ± 1.5 h later after lisdexamfetamine administration compared to D-amphetamine administration 3.
• However, no differences in maximal concentrations or total exposure (AUC) were found between the two treatments 3.

Dose Comparison

• A study compared equimolar doses of D-amphetamine (40 mg) and lisdexamfetamine (100 mg) and found that the pharmacokinetics and pharmacodynamics of lisdexamfetamine are similar to D-amphetamine administered 1h later 3.
• To achieve a Cmax equivalent of amphetamine compared to Adderall XR, the dose of Vyvanse (lisdexamfetamine) would need to be determined based on the pharmacokinetic profile of the two drugs.
• However, based on the available data, it appears that a dose of 100 mg of Vyvanse may be equivalent to a dose of 40 mg of D-amphetamine 3.

Clinical Implications

• The safety and efficacy of lisdexamfetamine have been established in several studies, including those in adults with attention-deficit/hyperactivity disorder (ADHD) 4, 5, 6.
• Lisdexamfetamine has been shown to be effective in improving symptoms of ADHD, including inattention and hyperactivity, and has a safety profile consistent with other long-acting stimulants 4, 5, 6.
• However, the optimal dose of Vyvanse for achieving a Cmax equivalent of amphetamine compared to Adderall XR would need to be determined based on individual patient response and pharmacokinetic profiles.