Amphetamine extended-release oral suspension for attention-deficit/hyperactivity disorder

ABSTRACT

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder known to respond to amphetamine (AMPH). Multiple AMPH formulations have been developed during the past two decades and have focused mainly on extending the duration of effect. AMPH extended-release oral suspension, Dyanavel XR, (AMPH EROS) was developed to address the unmet needs of patients who have difficulty swallowing intact extended-release (ER) tablets and capsules.

Areas covered: The pharmacokinetic profile of the AMPH EROS in children and adults is discussed along with the technology responsible for its release profile. Efficacy data from two clinical trials are presented and AMPH EROS is compared with other marketed AMPH ER formulations in the United States.

Expert opinion: Multiple AMPH ER formulations that do not require ingestion of an intact tablet or capsule have been developed. Initial products allowed for sprinkling or dissolving of capsule contents. Recently, oral disintegrating tablets, chewable tablets, and oral suspensions have been marketed. Each formulation has positive attributes. Tablets may be more portable. However, as a suspension, AMPH EROS dosing can differ depending on daily requirements. Dose can also be titrated with a single prescription. Despite its convenience, AMPH EROS is a branded product, so price may be prohibitive for some patients.

KEYWORDS:

• Attention-deficit/hyperactivity disorder
• ADHD
• amphetamine
• amphetamine extended-release oral suspension

Article Highlights

• AMPH EROS is an extended-release (ER) amphetamine oral suspension.

• The ER mechanism is not pH-dependent and food effect on the release is limited.

• AMPH EROS is bioequivalent to two doses of mixed AMPH salts dosed 4 h apart.

• A fast onset of efficacy (30 min) and extended duration of effect (13 h) for AMPH EROS were demonstrated laboratory classroom studies.

• Although there are limited data with AMPH EROS, adverse events appear similar to those of other AMPH products and include decreased appetite, insomnia, affect lability, upper abdominal pain, mood swings, and headache.

Declaration of interest

A Childress has received grant support from the US Food and Drug Administration and served on advisory boards for Akili, Cingulate, Ironshore, Neos, Neurovance, NLS, Noven, Otsuka, Pfizer, Rhodes, Shire, Sunovion, Supernus and Tris. A Childress is a consultant for Shire, Akili, Arbor, Ironshore, KemPharm, Neos, Neurovance, Purdue, Rhodes, Sunovion, Supernus and Tris. A Childress is a speaker for Arbor, Neos, Shire, Ironshore and Tris. A Childress has received research support from Alcobra, Akili, Arbor, Eli Lilly, Ironshore, KemPharm, Lundbeck, Neos, Neurovance, Noven, Otsuka, Pearson, Pfizer, Purdue, Rhodes, Shire, Sunovion and Supernus and Tris. A Childress has received writing support from Arbor, Ironshore, Neos, Pfizer, Rhodes, Shire, Sunovion, and Tris. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Tris Pharma, Inc. provided a scientific accuracy review at the request of the journal editor.

Information resources

• Berry SA, Belden H. Single-Dose Pharmacokinetics of Amphetamine Extended-Release Oral Suspension (AMPH EROS) Compared with Immediate-Release Mixed Amphetamine Salts. The American Professional Society of ADHD and Related Disorders; January 13–15, 2017; Washington D.C.

• Childress AC, Wigal SB, Brams MN, et al. Efficacy and Safety of Amphetamine Extended-Release Oral Suspension in Children with Attention-Deficit/Hyperactivity Disorder. J Child Adolesc Psychopharmacol 2018;28(5):306–13.

• Childress AC, Kando JC, King TR, et al. Early-Onset Efficacy and Safety Pilot Study of Amphetamine Extended-Release Oral Suspension in the Treatment of Children with Attention-Deficit/Hyperactivity Disorder. J Child Adolesc Psychopharmacol 2018.

• DYANAVEL XR (amphetamine) extended-release oral suspension, CII. HIGHLIGHTS OF PRESCRIBING INFORMATION [cited 24 June 2018]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208147s000lbl.pdf

Additional information

Funding

This paper was not funded.