Amphetamine Extended-Release Oral Suspension Research Articles

From the Editor-in-Chief's Desk

Journal of Child and Adolescent PsychopharmacologyVol. 33, No. 1 EditorialFree AccessFrom the Editor-in-Chief's DeskHarold S. KoplewiczHarold S. KoplewiczChild Mind Institute, New York, New York, USA.Search for more papers by this authorPublished Online:14 Feb 2023https://doi.org/10.1089/cap.2022.29234.editorialAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail To Our Readers:I hope the beginning of 2023 has brought joy and a renewed sense of purpose to everyone! The first thing I would like to share is an exciting update from the Child Mind Institute. I am pleased to announce our latest initiative in collaboration with the State of California, the Youth Mental Health Academy.In its inaugural year, the academy will identify and support 2500 talented and diverse high school students with an interest in child and adolescent mental health, and engage them in summer internships with stipends, peer mentorship, and professional development. Recruitment for the academy will be from groups under-represented in our field today, including young people of color and LGBT youth. While moving our field toward being more representative and understanding of the populations in need of our services, we will inspire and cultivate the mental health leaders of tomorrow.I would like to highlight two articles in this issue of the journal. In “Efficacy of Amphetamine Extended-Release Oral Suspension in Children with Attention-Deficit/Hyperactivity Disorder: Effect Size Across the Day,” Faraone et al. report evidence of this treatment's usefulness in children ages 6–12 years. Their study applies a post-hoc analysis to a randomized double-blind placebo-controlled assessment to evaluate outcomes at different timepoints from morning through evening.The authors emphasize the need for medication that works throughout the day, pointing out the pervasive effects of attention-deficit/hyperactivity disorder (ADHD) in children's lives both in the classroom and outside of school. The analysis yielded a large and consistent effect size across the day. But they point out two limitations to their promising findings: the nature of the analysis is posthoc and the sample size is relatively small.The second article I would like to highlight discusses a study that sets out to determine any effects on the cognitive, emotional, and physical development of children ages 6–16 years after treatment with sertraline for up to 3 years. In their article titled, “Effects of Long-Term Sertraline Use on Pediatric Growth and Development: The Sertraline Pediatric Registry for The Evaluation of Safety (SPRITES),” Kolitsopoulos et al. explain that their study compared 695 participants who were exposed to sertraline with or without psychotherapy with 245 participants who were exposed to psychotherapy alone.Of the original participants, 432 completed the full 3-year study. A small but statistically significant increase in weight was observed in the participants exposed to sertraline, but otherwise, results for the group exposed to sertraline displayed normal development and showed no significant changes over time.I hope you find the articles in this issue helpful and informative. Welcome to the new year!Harold S. Koplewicz, MDEditor-in-ChiefFiguresReferencesRelatedDetails Volume 33Issue 1Feb 2023 InformationCopyright 2023, Mary Ann Liebert, Inc., publishersTo cite this article:Harold S. Koplewicz.From the Editor-in-Chief's Desk.Journal of Child and Adolescent Psychopharmacology.Feb 2023.1-1.http://doi.org/10.1089/cap.2022.29234.editorialPublished in Volume: 33 Issue 1: February 14, 2023PDF download

Efficacy of Amphetamine Extended-Release Oral Suspension in Children with Attention-Deficit/Hyperactivity Disorder: Effect Size Across the Day.

Objective: To evaluate the treatment effect size throughout the day of amphetamine extended-release oral suspension (AMPH EROS; Tris Pharma, Inc., Monmouth Junction, NJ, USA) in a laboratory classroom study conducted in children aged 6-12 years with attention-deficit/hyperactivity disorder (ADHD). Methods: A post hoc analysis was performed to assess the overall effect size as well as the effect size at each time point from early morning through evening (1, 2, 4, 6, 8, 10, 12, and 13 hours postdose) for each efficacy measure evaluated in a 5-week, randomized, dose-optimized, double-blind, placebo-controlled, laboratory classroom assessment, efficacy, and safety study of AMPH EROS (N = 99). Change from baseline of the primary (Swanson, Kotkin, Agler, M-Flynn, Pelham [SKAMP]-C) and key secondary (secondary efficacy assessments included the SKAMP attention [SKAMP-A], SKAMP-deportment subscale [SKAMP-D], Permanent Product Measure of Performance-number of problems attempted [PERMP-A], PERMP-number of problems correct [PERMP-C]) efficacy measures were analyzed using a linear mixed model repeated-measures analysis model. Comparisons among treatments were adjusted for multiple comparisons using the Bonferroni method. The effect size was estimated using Cohen's d, to determine "small," (0.2), "medium," (0.5), or "large" (0.8) magnitudes of treatment effects. Results: Large overall effect sizes were observed for all primary and key secondary efficacy assessments. Moreover, the SKAMP-C, PERMP-number of problems attempted, and PERMP-C scores showed large effect sizes at each time point evaluated across the day, from 1 to 13 hours postdose. The SKAMP-A and SKAMP-D scores showed a medium to large effect size at each time point. Conclusions: AMPH EROS demonstrated a large and consistent effect size across the day, including early in the morning, in the treatment of symptoms of ADHD in children aged 6-12 years. Trial Registration: clinicaltrials.gov identifier: NCT02083783.

A single-dose, comparative bioavailability study comparing amphetamine extended-release oral suspension with extended-release mixed amphetamine salts capsules.

To evaluate the relative bioavailability of a single dose of amphetamine extended-release oral suspension (AMPH EROS) compared with a single dose of extended-release mixed amphetamine salts (ER MAS) in healthy, fasted adult subjects. The study population consisted of healthy adult volunteers. The study drug used in this study was 7.5mL of 2.5mg/mL AMPH EROS equivalent to 18.8mg of amphetamine base administered after an overnight fast of at least 10hours. AMPH EROS comprises a 3.2:1 enantiomeric ratio of d-amphetamine to l-amphetamine. The reference product was one 30mg ER MAS capsule (equivalent to 18.8mg of amphetamine base). Relative bioavailability between the products was determined by a statistical comparison of the area under the curve and maximum concentration (Cmax) for d-amphetamine and l-amphetamine. PK (PK) blood samples were collected prior to dosing (0-hour) and at 1, 2, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 12, 14, 16, 24, 36, 48, and 60hours after drug administration, totaling 20 samples in each period. The mean subject age was 35.0 (standard deviation ±8) years, and the overall study population comprised 19 (63.3%) males and 11 (36.7%) females. The contrasts for geometric mean ratios for all assessed PK parameters (for both l- and d-amphetamine) between the test article AMPH EROS and reference product ER MAS fell within the prescribed 80% to 125% limits. The overall PK profile of single-dose AMPH EROS 7.5mL was found to be comparable with a single dose of oral ER MAS 30mg.

178 Single-Dose Pharmacokinetics of Amphetamine Extended-Release Tablet Compared with Amphetamine Extended-Release Oral Suspension

Evaluate comparative bioavailability of single-dose amphetamine extended-release tablet (AMPH ER TAB, Tris Pharma, Inc., Monmouth Junction, NJ) 20 mg, swallowed whole or chewed and amphetamine extended-release oral suspension (AMPH EROS) 2.5 mg/mL; and evaluate whether a PK food effect exists on AMPH ER TAB (contains a 3.2:1 ratio of d- to l-amphetamine). Healthy volunteers (18-55 yr) were randomized to 1 dose of AMPH ER TAB 20 mg swallowed (fasted), chewed (fed/fasted), or 20 mg AMPH EROS (fasted).A crossover design was used. Samples were collected each period pre-dose and at time points to 60 h post-dose. D-and l-amphetamine were measured, and PK was calculated (90% CIs of the ratios of the geometric mean plasma levels) for Cmax, AUCt, and AUC0∞. Comparative bioavailability was determined when ratios were within 80 and 125%. Safety was also assessed. 32 subjects completed the study. Based on the calculated bioavailability ratios, for AMPH ER TAB swallowed vs. AMPH EROS fasted: d-amphetamine total and peak exposures were found to be similar: AUC0-t: 100.68-108.08%, AUC0-∞:101.47-109.52%, Cmax: 98.10-103.17%. For l-amphetamine, the total and peak exposures were similar: AUC0-t: 100.31-108.57%, AUC0-∞:101.27-111.09%, Cmax: 98.2-103.37%.AMPH ER TAB chewed vs. AMPH EROS fasted: For d-amphetamine, the total and peak exposures were similar: AUC0-t: 99.23-106.62%, AUC0-∞: 99.58-107.59%, Cmax: 99.91-105.14%. For l-amphetamine, the total and peak exposure was similar: AUC0-t: 98.16-106.35%, AUC0-∞: 98.44-108.11%, Cmax: 99.53-104.75%.Food effect: AMPH ER TAB, chewed, fasted vs. fed: For d-amphetamine, the total and peak exposure was similar: AUC0-t: 92.57-99.49%, AUC0-∞: 91.12-98.48%, Cmax: 94.22-99.17%.For l-amphetamine, the total and peak exposure was similar: AUC0-t: 91.27-98.91%, AUC0-∞: 88.44-97.17%, Cmax: 94.52-99.50%).No serious AEs were reported during the conduct of this study, and the AE profiles were observed to be similar in frequency of events and severity to other amphetamine formulations used in ADHD. Bioavailability of single dose of AMPH ER TAB for both d- and l-amphetamine was comparable, swallowed whole or chewed, to an equivalent 20 mg dose of the reference product AMPH EROS, 2.5 mg/mL fasted, and showed equivalent peak and overall exposure.No food effect was observed for AMPH ER TAB administered chewed. All AEs were mild in severity and AE profiles were similar to other amphetamine formulations used for treatment of ADHD. Tris Pharma, Inc.

6.46 SINGLE-DOSE PHARMACOKINETICS OF AMPHETAMINE EXTENDED-RELEASE ORAL SUSPENSION (AMPH EROS) IN CHILDREN WITH ADHD

The objective of this study was to evaluate the pharmacokinetics (PK) of fasting conditions with a single dose of 10 mg of amphetamine extended-release oral suspension (AMPH EROS; 2.5 mg/ml) in pediatric patients with ADHD (ages 6–12 years). AMPH EROS comprises a 3.2:1 ratio of d- and l-amphetamine delivered using the LiquiXR drug technology.

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

ABSTRACTIntroduction: 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.

Single-Dose Pharmacokinetics of Amphetamine Extended-Release Oral Suspension in Healthy Adults

Purpose: This single-dose pivotal study evaluated the pharmacokinetics of amphetamine extended-release oral suspension (AMPH EROS) under fasted and fed conditions and the relative bioavailability of AMPH EROS and immediate-release mixed amphetamine salts (IR MAS) in adults. Methods: This open-label, randomized, three-period, three-treatment, six-sequence crossover study enrolled 30 healthy adult participants who were randomly assigned to receive either 1 dose of AMPH EROS 18.8 mg under fed or fasted conditions or 30 mg of IR MAS under fasted conditions. Participants crossed over with a 7-day washout period between each of the three periods. Plasma samples were measured for Cmax, AUC0-t, AUC0-5, AUC5-t, and AUC0-∞ for comparative bioavailability. Results: The geometric mean ratios for Cmax, AUC0-t, and AUC0-∞ were within the 90% confidence limits [80.0%, 125.0%] for comparable bioavailability. There was no food effect for AMPH EROS. Both the AMPH EROS and IR MAS formulations were generally well tolerated with no serious adverse events reported. Conclusions: The bioavailability of a single dose of AMPH EROS was comparable to two 15 mg doses of IR MAS, given 4 hr apart, with no food effect or safety concerns observed.

32 Early-Onset Efficacy and Safety Pilot Study of Amphetamine Extended-Release Oral Suspension (AMPH EROS) in the Treatment of Children with Attention-Deficit/Hyperactivity Disorder

ObjectiveTo determine whether amphetamine extended-release oralsuspension (AMPH EROS) has an onset of effect at 30minutes postdose inchildren with ADHD.MethodsThis randomized, double-blind, 2-treatment, 2-sequence, placebo-controlled crossover pilot study enrolled subjects aged 6 to 12 years withattention-deficit/hyperactivity disorder (ADHD) and ADHD-Rating Scale-5 scores of ≥90th percentile for sex and age. A dose of 5 to 20mg/day of AMPH EROS was determined during a 1-week open-label phase based on medication history, symptom control, and tolerability. Subjects completed a practice laboratory classroom then received one day of double-blind active drug or placebo each in random sequence during 2 double-blind laboratory classroom days. Subjects completed the first double-blind laboratory classroom session, returned to open label drug for 5days then crossed over on day 6 during a second double-blind laboratory classroom session. DB dose was fixed at AMPH EROS 15, 17.5, or 20mg . The primary endpoint was change from predose in the Swanson, Kotkin, Agler, M-Flynn, Pelham rating scale-combined score (SKAMP-C) at 30minutes postdose on two DB days. The key secondary endpoint was change from predose in the SKAMP-C score at 3hours postdose for AMPH EROS compared with placebo. Safety assessments included vital signs and adverse events.ResultsEighteen subjects were enrolled in the study (14 males and 4 females) with a mean age of 9 years. At both 30minutes and 3hours postdose, changes from baseline in SKAMP-C for AMPH EROS vs. placebo were statistically significant (p<0.01 and p=0.0002, respectively) with corresponding effect sizes of 0.96 and 1.57. Adverse events (>10%) during the open-label phase included upper respiratory tract infection, fatigue, upper abdominal pain, headache, decreased appetite, and affect lability.ConclusionsAMPH EROS was effective in reducing ADHD symptoms at 30minutes postdose. AEs were mild or moderate and consistent with those of other extended-release amphetamines.Funding Acknowledgements: Support was provided by Tris Pharma, Inc.

Early-Onset Efficacy and Safety Pilot Study of Amphetamine Extended-Release Oral Suspension in the Treatment of Children with Attention-Deficit/Hyperactivity Disorder.

Objective: To determine whether amphetamine extended-release oral suspension (AMPH EROS) has an onset of effect at 30 minutes postdose in children with attention-deficit/hyperactivity disorder (ADHD).Methods: This randomized, double-blind, two-treatment, two-sequence, placebo-controlled crossover pilot study enrolled subjects aged 6–12 years with ADHD and ADHD-Rating Scale-5 scores of ≥90th percentile for sex and age. An optimized dose of 5–20 mg/day of AMPH EROS was determined during a 1-week open-label dose optimization phase based on medication history, symptom control, and tolerability. Subjects completed a practice laboratory classroom then received 1 day of double-blind active drug or placebo each in random sequence during two double-blind laboratory classroom days. Subjects completed the first double-blind laboratory classroom, returned to open-label drug for 5 days, and then crossed over on day 6 during a second double-blind laboratory classroom. Double-blind dose was fixed at AMPH EROS 15, 17.5, or 20 mg. The primary end point was change from predose in the Swanson, Kotkin, Agler, M-Flynn, Pelham-Combined (SKAMP-C) Rating Scale score at 30 minutes postdose on two double-blind days. The key secondary end points were change from predose in the SKAMP-C score at 3 hours postdose for AMPH EROS compared with placebo and change from baseline Permanent Product Measure of Performance (PERMP) scores at 30 minutes and 3 hours postdose compared with placebo. Safety assessments included vital signs and adverse events (AEs).Results: Eighteen subjects were enrolled in the study (14 males and 4 females) with a mean age of 9 years. At both 30 minutes and 3 hours postdose, changes from baseline in SKAMP-C for AMPH EROS versus placebo were statistically significant (p < 0.01 and p = 0.0002, respectively). PERMP scores were not statistically significantly improved at 30 minutes postdose for AMPH EROS relative to the placebo group. PERMP scores were statistically significantly improved at 3 hours postdose for AMPH EROS relative to the placebo group (PERMP problems attempted treatment difference least-squares [LS] mean [SE] = 60.3 [12.93], p = 0.0003; PERMP problems correct treatment difference LS mean [SE] = 61.6 [13.16], p = 0.0003). AEs (>10%) during the open-label phase included upper respiratory tract infection, fatigue, upper abdominal pain, headache, decreased appetite, and affect lability.Conclusions: AMPH EROS was effective in reducing ADHD symptoms at 30 minutes postdose as indicated by SKAMP-C score improvement, although improvements in PERMP scores at 30 minutes were not statistically significant. AEs were mild or moderate and consistent with those of other extended-release amphetamines.

Correction to: Amphetamine extended-release oral suspension (Adzenys ER™) and orally disintegrating tablets (Adzenys XR-ODT®) in attention-deficit hyperactivity disorder: a profile of their use

Correction to: Amphetamine extended-release oral suspension (Adzenys ER™) and orally disintegrating tablets (Adzenys XR-ODT®) in attention-deficit hyperactivity disorder: a profile of their use

2.19 Efficacy Measures in an Open-Label Dose-Optimization Study of an Amphetamine Extended-Release Oral Suspension in Children With ADHD

2.19 Efficacy Measures in an Open-Label Dose-Optimization Study of an Amphetamine Extended-Release Oral Suspension in Children With ADHD

Amphetamine extended-release oral suspension (Adzenys ER™) and orally disintegrating tablets (Adzenys XR-ODT®) in attention-deficit hyperactivity disorder: a profile of their use

Amphetamine extended-release oral suspension (Adzenys ER™) and extended-release orally disintegrating tablets (Adzenys XR-ODT®) are easy-to-administer, long-acting, and convenient CNS stimulant options for treating attention-deficit hyperactivity disorder (ADHD) in children aged ≥ 6 years, adolescents, and adults. The bioavailability of d- and l-amphetamine with Adzenys ER™ suspension and XR-ODT® is equivalent to that of a corresponding dose of the reference product [i.e. mixed amphetamine salt extended-release capsules (MAS ER)], which has well-established efficacy, tolerability, and safety profiles. As Adzenys ER™ suspension/XR-ODT® contain both immediate- and extended-release amphetamine particles, plasma concentrations of d- and l-amphetamine increase rapidly, remain relatively stable for several hours, then slowly decline, allowing for once-daily administration. The use of Adzenys ER™ suspension/XR-ODT® may be of particular benefit in individuals who require a rapid onset and prolonged reduction in ADHD symptoms, as well as those who have difficulty swallowing tablets or capsules whole (neither formulation requires swallowing whole tablets/capsules, and both may be taken without regard to food).

Efficacy and Safety of Amphetamine Extended-Release Oral Suspension in Children with Attention-Deficit/Hyperactivity Disorder.

Objectives: To determine the efficacy and safety of amphetamine extended-release oral suspension (AMPH EROS) in the treatment of attention-deficit/hyperactivity disorder (ADHD) in a dose-optimized, randomized, double-blind, parallel-group study.Methods: Boys and girls aged 6 to 12 years diagnosed with ADHD were enrolled. During a 5-week, open-label, dose-optimization phase, patients began treatment with 2.5 or 5 mg/day of AMPH EROS; doses were titrated until an optimal dose (maximum 20 mg/day) was reached. During the double-blind phase, patients were randomized to receive treatment with either their optimized dose (10–20 mg/day) of AMPH EROS or placebo for 1 week. Efficacy was assessed in a laboratory classroom setting on the final day of double-blind treatment using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP) test. Safety was assessed measuring adverse events (AEs) and vital signs.Results: The study was completed by 99 patients. The primary efficacy endpoint (change from predose SKAMP-Combined score at 4 hours postdose) and secondary endpoints (change from predose SKAMP-Combined scores at 1, 2, 6, 8, 10, 12, and 13 hours postdose) were statistically significantly improved with AMPH EROS treatment versus placebo at all time points. Onset of treatment effect was present by 1 hour postdosing, the first time point measured, and duration of efficacy lasted 13 hours postdosing. PERMP data mirrored the SKAMP-Combined score data. AEs (>5%) reported during dose optimization were decreased appetite, insomnia, affect lability, upper abdominal pain, mood swings, and headache.Conclusion: AMPH EROS was effective in reducing symptoms of ADHD and had a rapid onset and extended duration of effect. Reported AEs were consistent with those of other extended-release amphetamine products.

A Single-Dose, Two-Way Crossover, Open-Label Bioequivalence Study of an Amphetamine Extended-Release Oral Suspension in Healthy Adults

Objective: The purpose of this study was to compare the pharmacokinetics of a new extended-release amphetamine oral suspension (AMP XR-OS) with a standard extended-release mixed amphetamine salts product, Adderall XR®. Method: In this single-dose, open-label, randomized, two-period, two-treatment crossover study, 42 healthy adult volunteers received 15 mL of AMP XR-OS in one period and a 30 mg Adderall XR capsule in another period (both containing 18.8 mg of amphetamine base) under fasted conditions. Blood samples were analyzed for d - and l -amphetamine concentrations, and pharmacokinetic parameters Cmax, AUC0-5, AUC5-last, and AUCinf were calculated to determine bioequivalence. Safety was monitored throughout the study. Results: The 90% confidence intervals (CIs) for the log-transformed Cmax, AUC0-5, AUC5-last, and AUCinf fell within the accepted 80% to 125% range for establishing bioequivalence for d - and l -amphetamine. The most common adverse events were nausea and decreased appetite. Conclusion: AMP XR-OS is bioequivalent to Adderall XR in healthy adult participants.

Pharmacokinetics of a New Amphetamine Extended-release Oral Liquid Suspension Under Fasted and Fed Conditions in Healthy Adults: A Randomized, Open-label, Single-dose, 3-treatment Study

PurposeA new amphetamine extended-release liquid formulation (AMP XR-OS), intended for the treatment of attention-deficit/hyperactivity disorder, has been developed. This study was performed to determine if administration with food affected the rate of absorption or bioavailability of AMP XR-OS. The formulation was also compared with an equivalent dose of an extended-release mixed amphetamine salts reference product (30 mg) under fed conditions. MethodsThirty adult volunteers participated in this single-dose, open-label, randomized, 3-period, 3-treatment crossover study. Each participant received a single 15-mL dose of AMP XR-OS (equivalent to 30 mg of the reference drug) under fasted conditions, a single 15-mL dose of AMP XR-OS under fed conditions, and a single dose of the reference drug under fed conditions. A 7-day washout separated the 3 treatment periods. Blood samples were collected at predetermined time points and analyzed for d- and l-amphetamine. Pharmacokinetic parameters reported are AUC0–5, AUC0–last, AUC5–last, and AUC0–∞; Cmax; elimination t1/2; and Tmax. The geometric mean ratios and 90% CIs of Cmax, AUC0–last, and AUC0–∞were determined for the comparison of AMP XR-OS fed and fasted, and Cmax, AUC0–5, AUC5–last, and AUC0–∞ were calculated for AMP XR-OS compared with the reference drug under fed conditions. Safety was also assessed. FindingsTwenty-nine subjects completed the study. Subjects were mostly male, white, and of Hispanic/Latino ethnicity with a mean age of 35.83 years and a mean BMI of 25.36kg/m2. The 90% CIs of Cmax, AUC0–last, and AUC0–∞ for AMP XR-OS fasted versus fed were within the accepted 80% to 125% range, indicating lack of a food effect. In the comparison of AMP XR-OS fed versus the reference product, Cmax, AUC5–last, and AUC0–∞ were within the range to establish bioequivalence; however, AUC0–5 was significantly higher for AMP XR-OS compared with that of the reference drug. This difference between products was likely due to the known delay of Tmax and decreased exposure when the extended-release mixed amphetamine salts reference product is administered with food. A total of 36 mild or moderate adverse events were reported; 1 subject withdrew due to an adverse event, and no deaths occurred. These adverse events were consistent with the known pharmacodynamic effects of amphetamine. ImplicationsThe absence of a food effect may allow for AMP XR-OS to be administered with or without a meal.

New drugs and dosage forms

Amphetamine extended-release oral suspension (Adzenys ER, Neos Therapeutics): An orange-flavored, sorbitol-sweetened liquid formulation has been added to the product line. The suspension contains a 3:1 ratio of d-amphetamine to l-amphetamine and is not to be substituted milligram for milligram with other amphetamine products. The drug is a Schedule II controlled substance and subject to FDA Medication Guide requirements. Bevacizumab-awwb solution for i.v. infusion (Mvasi, Amgen): The biosimilar to bevacizumab, a vascular endothelial growth factor inhibitor, is indicated for use in combination with fluorouracil in the treatment of metastatic colorectal cancer; in combination with chemotherapy regimens containing fluoropyrimidine and irinotecan or fluoropyrimidine and oxaliplatin, for the treatment of metastatic colorectal cancer that has progressed after first-line bevacizumab therapy; in combination with carboplatin and paclitaxel, for the first-line treatment of unresectable, locally advanced nonsquamous non–small cell lung cancer that has recurred or metastasized; in combination with interferon alfa, for the treatment of metastatic renal cell carcinoma; in combination with regimens containing paclitaxel and cisplatin or paclitaxel and topotecan, in the treatment of cervical cancer that persists or has recurred or metastasized; and for treatment of progressive glioblastoma in adults who received prior therapy.

6.9 Early-Onset Efficacy and Safety Pilot Study of Amphetamine Extended-Release Oral Suspension in the Treatment of Children With Attention-Deficit/Hyperactivity Disorder (ADHD)

6.9 Early-Onset Efficacy and Safety Pilot Study of Amphetamine Extended-Release Oral Suspension in the Treatment of Children With Attention-Deficit/Hyperactivity Disorder (ADHD)