Is Adderall XR (amphetamine and dextroamphetamine) released equivalently throughout the day?

From the Guidelines

Adderall XR is not released equivalently throughout the day, as it has a dual-release mechanism that delivers medication in two phases, creating two distinct peaks in medication levels. This is based on the most recent evidence from 1, which discusses the pharmacological treatment options for ADHD in children and adolescents. The medication is designed to provide coverage for about 10-12 hours, though individual responses may vary. Some key points to consider when prescribing Adderall XR include:

• The dual-release mechanism, which delivers medication in two phases
• The potential for uneven or insufficient coverage, which may require supplementing with a small immediate-release dose later in the day
• The availability of alternative medications with different release profiles, such as Vyvanse, which may provide more gradual and consistent coverage throughout the day
• The importance of individualizing treatment and regularly assessing medication adherence, as lack of adherence can lead to reduced effectiveness and increased adverse events. As noted in 1, once-daily dosing should generally be preferred over twice-daily dosing, and factors such as patient attitudes, physician-patient relationship, family support, and knowledge about the disorder and medication should be evaluated and improved if possible to increase medication adherence. In terms of specific guidance, Adderall XR should be taken once daily in the morning, and patients should be monitored for potential issues with adherence and coverage. If necessary, alternative medications or supplemental doses can be considered to ensure optimal treatment outcomes. It's also important to note that, as discussed in 1, stimulant medication effects on ADHD are concentrated within the early part of the absorption phase, and the rate of absorption of psychostimulants is very rapid, delivering a quick, large peak in plasma concentration. However, more recent studies have shown that a gradual ascending increase in medication plasma concentration over the day can produce equivalent reduction in ADHD symptoms, which is the basis for the design of extended-release formulations like Adderall XR.

From the FDA Drug Label

The extent of bioavailability of the sustained-release capsule was similar compared to the immediate-release tablet. Following administration of one 15 mg sustained-release capsule, maximal dextroamphetamine plasma concentrations were obtained approximately 8 hours after dosing. The Adderall XR is designed to release the active ingredient, dextroamphetamine, in a sustained manner, with maximal plasma concentrations obtained approximately 8 hours after dosing.

• The pharmacokinetics of the sustained-release capsule indicate that the release of the active ingredient is not immediate, but rather occurs over a period of time.
• The plasma concentrations of dextroamphetamine reach their maximum level approximately 8 hours after administration of the sustained-release capsule. However, the label does not explicitly state that the release is equivalent all day. Based on the information provided, it can be inferred that the medication is released over a period of time, but the exact release profile is not clearly defined as being equivalent throughout the day 2.

From the Research

Adderall XR Release Mechanism

• Adderall XR is a long-acting psychostimulant preparation that provides a 12-hour duration of action 3, 4, 5.
• The formulation includes immediate-release pellets of mixed amphetamine salts that release the first half of the dose upon ingestion and delayed-release pellets that begin to release active drug approximately 4 hours later 5.
• This two-stage delivery system allows for a rapid onset of action, within 1.5 hours, and provides 12 hours of coverage 5.

Efficacy and Safety

• Clinical studies have demonstrated the efficacy and safety of Adderall XR in the management of attention-deficit/hyperactivity disorder (ADHD) in school-age children, adolescents, and adults 3, 4, 5, 6.
• Adderall XR has been shown to improve both behavioral and cognitive performance measures throughout the school day and into post-school activities 3.
• The incidence of common stimulant-emergent side effects with Adderall XR was no different than that seen with the existing Adderall preparation 3.

Bioavailability and Administration

• The bioavailability of Adderall XR has been assessed in healthy adults, and the formulation has been shown to be bioequivalent to immediate-release Adderall 7.
• Adderall XR can be administered in different ways, including as an intact capsule with or without food, or sprinkled in applesauce, without affecting its bioavailability 7.