Adderall XR Compounded vs Branded: A Clinical Comparison

Is compounded Adderall XR the same product?

No. Adderall XR is one specific approved product: extended-release capsules from Takeda under NDA 021303, first approved 11 October 2001 [1]. A compounded capsule is a pharmacy preparation, and compounded drugs are not FDA-approved. FDA does not verify their safety, effectiveness or quality before they are marketed [2].

What the Adderall XR label defines

Adderall XR contains the same four salts as the immediate-release tablets (dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate and amphetamine sulfate) in a d- to l-amphetamine ratio of about 3.1 to 1, split between immediate-release and delayed-release beads that prolong release [5].

Peak plasma concentrations arrive about 7 hours after a dose, about 4 hours later than with the immediate-release tablets, and a single 20 mg capsule reproduces the profile of 10 mg immediate-release taken twice, 4 hours apart [5]. Food does not change the amount absorbed but delays the peak by about 2.5 hours; after a 30 mg dose the d-amphetamine peak came at 5.2 to 7.7 hours [5]. Mean half-life of d-amphetamine is about 10 hours in adults [5].

The label says to swallow the capsule whole, or open it and sprinkle the entire contents on applesauce and swallow without chewing, and not to divide the contents [5].

Where a compounded capsule can differ

FDA says poor compounding practices can result in serious drug quality problems such as contamination or a drug that contains too much or too little active ingredient, which can lead to serious patient injury and death [2]. Oversight depends on where and how the drug is made. FDA says drugs compounded in outsourcing facilities are subject to current good manufacturing practice requirements, while drugs compounded by a licensed pharmacist in a state-licensed pharmacy, in accordance with the conditions set out in federal law, are not [2].

The two-bead release pattern, the 7-hour peak and the roughly 10-hour half-life are label properties of Adderall XR [5]. A compounded capsule has no FDA-approved release profile.

What the Adderall labels say to watch for

Adderall XR contains amphetamine and is a Schedule II controlled substance [5]. Its boxed warning covers abuse, misuse and addiction: misuse and abuse of CNS stimulants can result in overdose and death, and that risk is increased with higher doses or unapproved methods of administration such as snorting or injection [5].

The Adderall tablet label says CNS stimulants raise blood pressure by a mean of about 2 to 4 mm Hg and heart rate by about 3 to 6 bpm, and some patients have larger increases [4]. In the Adderall XR adult trial (191 on drug, 64 on placebo, forced titration up to 60 mg), dry mouth occurred in 35% on drug versus 5% on placebo, decreased appetite in 33% versus 3%, and insomnia in 27% versus 13% [5].

The Adderall immediate-release tablet label lists taking a monoamine oxidase inhibitor, or having stopped one within 14 days, as a contraindication because of hypertensive crisis. It says co-administration with gastrointestinal alkalinizing agents such as antacids should be avoided because they raise amphetamine blood levels, while acidifying agents such as ascorbic acid lower them [4].

Adderall XR dosing in the label

The Adderall XR label gives once-daily dosing on awakening and says to avoid afternoon doses: 20 mg per day for adults, a 10 mg start for children aged 6 to 12 with adjustment by 5 or 10 mg weekly to a maximum of 30 mg per day, and a 10 mg start for adolescents aged 13 to 17, which may rise to 20 mg after a week [5]. In severe renal impairment the label specifies 15 mg for adults and 5 mg for children and adolescents, and says the drug is not recommended in end-stage renal disease [5]. Adderall XR is not recommended under age 6 [5].