Pauline Gerard, from the University of Colorado School of Medicine in Aurora, and colleagues conducted a retrospective cohort study to examine the relationship between cardiomyopathy and duration of stimulant medication use in adults diagnosed with ADHD aged 20 to 40 years. The window of analysis was limited to 30 years after ADHD diagnosis.

A total of 12,759 pairs of patients categorized by the presence or absence of stimulant medication prescription with a decade-long record were matched. The researchers found that the prevalence of cardiomyopathy was 0.36 and 0.31% in the one-year stimulant and nonstimulant groups, respectively. This prevalence increased to 0.72 and 0.53% in the 10-year stimulant and nonstimulant groups, respectively. The one-year stimulant group had higher odds of cardiomyopathy (odds ratio, 1.17), which increased at 8 years (odds ratio, 1.57), then decreased slightly at 10 years (odds ratio, 1.37).

“The longer you leave patients on these medications, the more likely they are to develop cardiomyopathy, but the risk of that is very low,” Gerard said in a statement.

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HealthDay News — Neurodevelopment and growth in offspring is not negatively impacted by prenatal exposure to attention-deficit/hyperactivity disorder (ADHD) medication, according to a study published online February 9 in Molecular Psychiatry.

Kathrine Bang Madsen, PhD, from Aarhus University in Denmark, and colleagues assessed whether in utero exposure to ADHD medication was associated with adverse long-term neurodevelopmental and growth outcomes in offspring. The analysis included 898 children exposed to ADHD medication in utero and 1270 children whose mothers discontinued ADHD medication before pregnancy, who were born from 1998 to 2015 and followed through 2018.

After adjusting for demographic and psychiatric characteristics of the mother, the researchers observed no increased risk for any offspring developmental disorders for either combined (adjusted hazard ratio, 0.97; 95% CI, 0.81 to 1.17) or separate subcategories. In the negative control and sibling-controlled analyses, there was no increased risk seen for any subcategories of outcomes.

“We can see that the number of women of childbearing age who are medicated for ADHD is rapidly increasing, and therefore it is very important to garner more knowledge to be able to counsel these women,” a coauthor said in a statement. “There are still unknowns, but these results may contribute to women making informed decisions about using ADHD medication during pregnancy.”

Several authors disclosed financial ties to the pharmaceutical industry.

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Heidi Taipale, PhD, from the Karolinska Institutet in Stockholm, and colleagues examined the association between use of specific ADHD medications and hospitalization outcomes and work disability in a nationwide register-based cohort study involving adolescents and adults with ADHD during 2006 to 2021. The study cohort included 221,714 persons with ADHD.

The most commonly used ADHD medication was methylphenidate, followed by lisdexamphetamine (68.5 and 35.2%). The researchers found that amphetamine, lisdexamphetamine, ADHD drug polytherapy, dexamphetamine, and methylphenidate were associated with a reduced risk for psychiatric hospitalizations (adjusted hazard ratios, 0.74, 0.80, 0.85, 0.88, and 0.93, respectively). There were no associations seen for modafinil, atomoxetine, clonidine, or guanfacine. Use of dexamphetamine, lisdexamphetamine, and methylphenidate was associated with a reduced risk for suicidal behavior (adjusted hazard ratios, 0.69, 0.76, and 0.92, respectively). Amphetamine, lisdexamphetamine, polytherapy, dexamphetamine, methylphenidate, and atomoxetine were associated with a reduced risk for nonpsychiatric hospitalization. Regarding work disability, the results were only significant for use of atomoxetine (adjusted hazard ratio, 0.89), especially for those aged 16 to 29 years (adjusted hazard ratio, 0.82).

“Considering the high prevalence of psychiatric comorbidity in persons with ADHD, these results suggest that ADHD medication use can reduce morbidity in adolescents and adults with ADHD,” the authors write.

Several authors disclosed ties to the pharmaceutical industry.

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Lan Li, PhD, from the Karolinska Institutet in Stockholm, and colleagues examined whether initiation of ADHD pharmacotherapy was associated with reduced mortality risk among individuals with ADHD in an observational nationwide cohort study conducted in Sweden. Individuals aged 6 through 64 years with an incident diagnosis of ADHD from 2007 through 2018 and no ADHD medication dispensation before diagnosis were identified; 56.7% of the 148,578 individuals with ADHD initiated ADHD medication.

The researchers found that the two-year mortality risk was lower in the initiation treatment strategy group than the non-initiation treatment strategy group (39.1 vs 48.1 per 10,000 individuals). Significantly lower rates of all-cause mortality and unnatural-cause mortality were observed in association with ADHD medication initiation (hazard ratio, 0.79 and 0.75, respectively); no significant difference was seen in natural-cause mortality.

“ADHD medication may reduce the risk of unnatural-cause mortality by alleviating the core symptoms of ADHD and its psychiatric comorbidities, leading to improved impulse control and decision-making, ultimately reducing the occurrence of fatal events,” the authors write.

One author disclosed ties to Shire/Takeda, Evolan, and Medici.

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Azurity Pharmaceuticals, Inc is recalling 1 lot of Zenzedi^® (dextroamphetamine sulfate) 30mg tablets due to a mislabeled package.

The recall was initiated after a pharmacist from Nebraska reported that a bottle of Zenzedi 30mg tablets contained carbinoxamine maleate tablets. The affected product, Zenzedi (dextroamphetamine sulfate tablets, USP) 30mg tablets; NDC No. 24338-856-03; Lot No. F230169A; Exp. Date 6/2025, was distributed nationwide to wholesalers between August 23, 2023 and November 29, 2023. 

Zenzedi is a schedule II controlled substance indicated for the treatment of attention deficit hyperactivity disorder and narcolepsy. Carbinoxamine maleate is an antihistamine indicated for the symptomatic treatment of allergic and vasomotor rhinitis, allergic conjunctivitis, urticaria, angioedema, reactions to blood, and dermatographism; it is also indicated for use as an adjunct in anaphylaxis.

The Zenzedi 30mg tablet can be identified by its light yellow color and hexagonal shape. The tablet is debossed with “30” on one side and “MIA” on the other side. The carbinoxamine maleate 4mg tablets that were reported by the pharmacist were white round tablets with imprints of “GL” on one side and “211” on the other side.

Due to the sedating effects of carbinoxamine, there is a possibility of functional impairment in patients who unknowingly consume the drug instead of Zenzedi. To date, the Company has not received any reports of serious adverse events related to this recall. 

Any adverse events associated with the recall should be reported to the FDA’s MedWatch program.

HealthDay News — From 2000 to 2021, there was an almost 300% increase in the annual frequency of cases of pediatric out-of-hospital therapeutic errors related to attention-deficit/hyperactivity disorder (ADHD) medications, according to a study published online September 18 in Pediatrics.

Mikaela M. DeCoster, from the Abigail Wexner Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, and colleagues analyzed data from the National Poison Data System from 2000 through 2021 to identify characteristics and trends of out-of-hospital ADHD medication-related therapeutic errors among youth.

The researchers found that from 2000 through 2021, there were 124,383 ADHD medication-related therapeutic errors reported to U.S. poison centers, with a 299% increase in the annual frequency during that period. Of the 87,691 first-ranked exposures, 66.6% involved children aged 6 to 12 years; 76.4% were seen among boys; and 50.5% involved amphetamines and related compounds. Overall, 79.7% of the therapeutic errors were single-substance exposures. Most of the individuals (82.7%) did not receive treatment in a health care facility (HCF), but 2.3 and 4.2% were admitted to an HCF and had a serious medical outcome, respectively. The likelihood of experiencing a serious medical outcome or being admitted to an HCF was increased for children younger than 6 years of age versus those aged 6 to 9 years (odds ratios, 2.1 and 3.4, respectively).

“Because therapeutic errors are preventable, more attention should be given to patient and caregiver education and development of improved child-resistant medication dispensing and tracking systems,” the authors write.

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HealthDay News — From 2016 to 2021, there was an increase in the percentage of adolescent and adult females and adult males receiving prescription stimulant fills, according to research published in the March 31 issue of the US Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report, released to coincide with a related publication in the Journal of Attention Disorders.

Melissa L. Danielson, MSPH, from the CDC in Atlanta, and colleagues analyzed MarketScan commercial claims data to describe trends in prescription stimulant fills before and during the COVID-19 pandemic. The annual percentage of enrollees aged 5 to 64 years in employer-sponsored health plans with one or more prescription stimulant fills was examined overall and by sex and age group.

The researchers found that from 2016 to 2021, there was an increase in the percentage of enrollees with one or more prescription stimulant fills from 3.6 to 4.1%. During 2020 to 2021, there was a more than 10% increase in the percentages of females aged 15 to 44 years and males aged 25 to 44 years with prescription stimulant fills.

“These results could guide continued monitoring of and research concerning factors contributing to increases in stimulant prescribing and other changes in care for ADHD symptoms before and during the pandemic, and how they might differ among adults and adolescent females,” the authors write. “This study also suggests a growing need for resources to help clinicians accurately diagnose, manage, and treat adults with attention-deficit/hyperactivity disorder.”

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The Food and Drug Administration (FDA) is requiring updated warnings for prescription stimulants to ensure the safe use of these medications.

Specifically, the Boxed Warning in the prescribing information for the entire class of prescription stimulants will be updated to describe the risks of misuse, abuse, addiction, and overdose. Other sections of the labeling will also be significantly changed to ensure consistent messaging regarding these serious risks. To address these concerns, health care providers are being advised to counsel patients not to share their medications; education on proper storage and disposal is also being encouraged.

The requested updates to the labeling were made based on a review of medical literature (between January 2006 and May 2020) that showed family members and friends were the most common source of prescription stimulants for nonmedical use. These shared medications were most commonly used by individuals 18 to 25 years of age. According to the literature, use of prescription stimulants by individuals who were not prescribed these medications has been associated with a higher risk of developing substance use disorder and addiction.

While being treated with prescription stimulants, health care providers should regularly assess and monitor for the signs and symptoms of nonmedical use and addiction. In addition, careful records should be kept that indicate the quantity, frequency, and renewal requests for these medications.

Adverse events involving prescription stimulants should be reported to the FDA’s MedWatch Program.

In light of the current shortage of prescription stimulant medications, the Food and Drug Administration (FDA) and the Drug Enforcement Administration (DEA) are asking key stakeholders to work together to ensure that patients who need these medications are able to access them.

In a joint letter, the FDA and DEA provide an update on the steps being taken to resolve the shortages, which began last fall because of a manufacturing delay experienced by one pharmaceutical company. This, coupled with record-high prescription rates for stimulant medications has resulted in a continued shortage in supply.

Being controlled substances, the DEA sets a quota on how much stimulant medication can be produced on a yearly basis. According to the agency, manufacturers had not produced the full amount they were permitted to make in 2022 and data from 2023 show a similar trend. In an effort to increase supply, the DEA is asking manufacturers to confirm that they will be working toward increasing production to their allotted quota. Those who do not wish to increase production are being asked to relinquish their quota allotment so that it may be redistributed to other manufacturers.

Reviewing the appropriateness of prescription stimulant use and considering alternatives for certain patients should also be considered, according to the FDA. Additional treatment options available include an FDA-cleared game-based digital therapeutic for children with attention-deficit hyperactivity disorder (ADHD), as well as nonstimulant medication.

Additionally, the FDA recently required manufacturers to update the labeling for prescription stimulants to address continuing concerns of misuse, addiction and overdose. The requested updates were made based on a review of medical literature that showed family members and friends were the most common source of prescription stimulants for nonmedical use.

“We want to make sure those who need stimulant medications have access,” said FDA Commissioner Robert M. Califf, MD and DEA Administrator Anne Milgram in the letter. “However, it is also an appropriate time to take a closer look at how we can best ensure these drugs are being prescribed thoughtfully and responsibly.”

HealthDay News — Americans are facing shortages of drugs critical for cancer treatment, respiratory conditions, and more; shortages that increased nearly 30% between 2021 and 2022, a new report shows. The report, commissioned by the US Senate and discussed during a Senate committee hearing on Wednesday, revealed a record five-year high of 295 active drug shortages.

The problem is not likely to get better soon because of how the system is regulated and the fact that many drugs or their ingredients are made outside the US, the report noted.

“Since 2007, the FDA [US Food and Drug Administration] identified an average of over 100 separate drug shortages per year,” ranking committee member Sen. Rand Paul (R-Ky) said during the hearing before the Senate’s Homeland Security and Governmental Affairs Committee. “In 2011, the FDA identified a whopping 267 drugs in short supply, and despite possessing the most innovative medical industry in the world, the US is unable to maintain a consistent supply of the most crucial medicines.”

Though 295 drugs were in shortage last year, the latest number is 130, according to the FDA. The average length of a shortage is 1.5 years, though some drugs are in short supply for much longer. About 15 critical drug products have been scarce for a decade, CNN reported. Albuterol sulfate is among them. The FDA has reported it as in short supply since October, while the American Society of Health-System Pharmacists has been warning of a shortage since last summer. A major supplier to US hospitals closed this month, likely exacerbating the issue.

Other drugs in short supply include the attention-deficit/hyperactivity disorder (ADHD) drug Adderall. Medications like the antibiotic amoxicillin are also more likely to face shortages because they are generic and lower-priced, according to the nonprofit U.S. Pharmacopeia, which presented its analysis at the hearing, CNN reported. US Pharmacopeia works to strengthen global supply chains.

Experts blame market consolidation as another contributor to shortages, CNN reported. In addition, there is a lack of transparency. About 80 percent of manufacturing facilities for ingredients for drugs sold in the US market are in other countries, typically in China or India, where work stoppages can have a major effect. On top of that, no US agency tracks those manufacturers, so shortages can come as a surprise.

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Kathryn E. Kyler, MD, from Children’s Mercy Kansas City in Missouri, and colleagues conducted a cross-sectional study of children aged 0 to 18 years with one or more ambulatory encounter and 2 or more dispensed outpatient prescriptions to examine the prevalence of major DDI exposure and factors associated with higher DDI exposure rates among children in an outpatient setting. Data were included for 781,019 children with two or more medication exposures.

The researchers found that 21.4% of the children experienced one or more major DDI exposures. Increased odds of DDI exposure were seen in association with age and with medical and mental health complexity. Clonidine, psychiatric medications, and asthma medications were frequently implicated drugs. Per 100 children included, the highest adverse physiologic effect exposure rate was for increased drug concentrations, central nervous system depression, and heart rate-corrected QT interval prolongation (14.6, 13.6, and 9.9, respectively).

“Prescribers should consider how and when to counsel patients about the risk of adverse drug events associated with DDIs, or when to simply monitor for adverse drug events in patients knowingly exposed to DDIs when the risk/benefit balance is favorable,” the authors write.

Two authors disclosed ties to the biopharmaceutical industry.

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