ADDERALL XR - Drug Safety Warnings and Pharmacology (NDA 21-303/S-010) - Page 3-5

Oct 12, 2026

ADDERALL XR® extended-release capsules include a once-daily, double-pulsed amphetamine delivery designed to prolong drug release compared with immediate-release tablets. The text emphasizes high abuse potential and risks including drug dependence, non-therapeutic use or distribution concerns, misuse-associated sudden death, and serious cardiovascular adverse events. It describes composition across 5–30 mg strengths, inactive ingredients, pharmacodynamics involving norepinephrine and dopamine reuptake and release, and pharmacokinetics showing delayed Tmax (~7 hours) and linear kinetics with food effects on Tmax.

LanguageEnglish

CategoryGeneral

FormatPDF

Pages13

Reading Time5 min

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NDA 21-303/S-010 - Page 3

Description

Clinical Pharmacology

Pharmacodynamics

Pharmacokinetics

NDA 21-303/S-010 - Page 4

Mean plasma concentrations

Dose comparability and half-life

Linear pharmacokinetics and food effect

NDA 21-303/S-010 - Page 5

Metabolism and Excretion

NDA 21-303/S-010 Page 3 ADDERALL® XR CAPSULES CII Rx Only AMPHETAMINES HAVE A HIGH POTENTIAL FOR ABUSE. ADMINISTRATION OF AMPHETAMINES FOR PROLONGED PERIODS OF TIME MAY LEAD TO DRUG DEPENDENCE. PARTICULAR ATTENTION SHOULD BE PAID TO THE POSSIBILITY OF SUBJECTS OBTAINING AMPHETAMINES FOR NON-THERAPEUTIC USE OR DISTRIBUTION TO OTHERS AND THE DRUGS SHOULD BE PRESCRIBED OR DISPENSED SPARINGLY. MISUSE OF AMPHETAMINE MAY CAUSE SUDDEN DEATH AND SERIOUS CARDIOVASCULAR ADVERSE EVENTS. DESCRIPTION ADDERALL XR® is a once daily extended-release, single-entity amphetamine product. ADDERALL XR® combines the neutral sulfate salts of dextroamphetamine and amphetamine, with the dextro isomer of amphetamine saccharate and d,l-amphetamine aspartate monohydrate. The ADDERALL XR® capsule contains two types of drug-containing beads designed to give a double-pulsed delivery of amphetamines, which prolongs the release of amphetamine from ADDERALL XR® compared to the conventional ADDERALL® (immediaterelease) tablet formulation. EACH CAPSULE CONTAINS: 5 mg 10 mg 15 mg 20 mg 25 mg 30 mg Dextroamphetamine Saccharate 1.25 mg 2.5 mg 3.75 mg 5.0 mg 6.25 mg 7.5 mg Amphetamine Aspartate Monohydrate 1.25 mg 2.5 mg 3.75 mg 5.0 mg 6.25 mg 7.5 mg Dextroamphetamine Sulfate USP 1.25 mg 2.5 mg 3.75 mg 5.0 mg 6.25 mg 7.5 mg Amphetamine Sulfate USP 1.25 mg 2.5 mg 3.75 mg 5.0 mg 6.25 mg 7.5 mg Total amphetamine base equivalence 3.1 mg 6.3 mg 9.4 mg 12.5 mg 15.6 mg 18.8 mg Inactive Ingredients and Colors: The inactive ingredients in ADDERALL XR® capsules include: gelatin capsules, hydroxypropyl methylcellulose, methacrylic acid copolymer, opadry beige, sugar spheres, talc, and triethyl citrate. Gelatin capsules contain edible inks, kosher gelatin, and titanium dioxide. The 5 mg, 10 mg, and 15 mg capsules also contain FD&C Blue \#2 . The 20 mg, 25 mg, and 30 mg capsules also contain red iron oxide and yellow iron oxide. CLINICAL PHARMACOLOGY Pharmacodynamics Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. The mode of therapeutic action in Attention Deficit Hyperactivity Disorder (ADHD) is not known. Amphetamines are thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. PHARMACOKINETICS Pharmacokinetic studies of ADDERALL XR® have been conducted in healthy adult and pediatric (6-12 yrs) subjects, and adolescent (13-17 yrs) and pediatric patients with ADHD. Both ADDERALL® (immediaterelease) tablets and ADDERALL XR® capsules contain d-amphetamine and l-amphetamine salts in the ratio of 3:1 . Following administration of ADDERALL® (immediate-release), the peak plasma concentrations occurred in about 3 hours for both d-amphetamine and l-amphetamine. The time to reach maximum plasma concentration (Tmax) for ADDERALL XR® is about 7 hours, which isabout 4 hours longer compared to ADDERALL® (immediate-release) . This is consistent with the extendedrelease nature of the product. NDA 21-303/S-010 Page 4 MEAN PLASMA CONCENTRATIONS OF DEXTRO AND LEVOAMPHETAMINE (ng/mL) 30 25 20 15 10 5 0 DEXTROAMPHETAMINE ADDERALL XR® 20 mg qd ADDERALL® 10 mg bid LEVOAMPHETAMINE ADDERALL XR® 20 mg qd ADDERALL® 10 mg bid 0 4 8 12 16 20 24 TIME (HOURS) Figure 1 Mean d-amphetamine and l-amphetamine plasma concentrations following administration of ADDERALL XR® 20 mg (8am) and ADDERALL® (immediate-release) 10 mg bid (8am and 12 noon) in the fed state. A single dose of ADDERALL XR® 20 mg capsules provided comparable plasma concentration profiles of both d-amphetamine and l-amphetamine to ADDERALL® (immediate-release) 10 mg bid administered 4 hours apart. The mean elimination half-live for d-amphetamine is 10 hours in adults; 11 hours in adolescents aged 13-17 years and weighing less than or equal to 75 kg/165 lbs; and 9 hours in children aged 6 to 12 years. For the lamphetamine, the mean elimin

FAQs

What safety risks does the document highlight for amphetamines in ADDERALL XR?

It warns that amphetamines have a high potential for abuse and that prolonged administration may lead to drug dependence. It also emphasizes risks related to misuse, including sudden death and serious cardiovascular adverse events.

How does ADDERALL XR® delivery differ from immediate-release ADDERALL®?

ADDERALL XR® is an extended-release, once-daily product with a double-pulsed delivery design intended to prolong amphetamine release compared with the conventional immediate-release tablet formulation.

What pharmacokinetic effect is reported for ADDERALL XR® compared with immediate-release?

The time to reach maximum plasma concentration (Tmax) for ADDERALL XR® is about 7 hours, roughly 4 hours longer than immediate-release.

Oct 12, 2026

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