Clinical Highlights: October 2024 - Prime Therapeutics
Clinical Highlights: October 2024
Your monthly source for drug information highlights.
The Centers for Disease Control and Prevention (CDC) has released new population data demonstrating that at least 20% of adults in each U.S. state have obesity. These 2023 data also show that 35% of adults have obesity in 23 U.S. states. In contrast, prior to 2013, no states had obesity levels ≥ 35%. For adults, obesity is defined as a body mass index of ≥ 30 kg/m² and is associated with numerous health conditions, including asthma, heart disease, stroke, type 2 diabetes mellitus (T2DM), certain cancers, and potentially severe complications from respiratory infections. Data were collected from the Behavioral Risk Factor Surveillance System, a state-based telephone interview survey conducted by the CDC and state health departments based on self-reported weight and height. Obesity prevalence varies by race, ethnic group, education level, and age based on data from 2021 to 2023. The CDC notes obesity treatment can include obesity medications (e.g., GLP-1 receptor agonists) used in combination with healthy behaviors and lifestyle interventions.
The American Society of Nephrology (ASN) has published guidance on the management of obesity in adults with kidney diseases. The guidelines promote a combination of interventions to achieve and maintain weight loss and address the psychosocial, lifestyle, pharmacologic, and surgical management options. As evidence accumulates suggesting beneficial effects of anti-obesity medications (AOMs) in this patient population, the ASN advises a comprehensive approach to counsel patients on these FDA-approved therapies. Specifically, incretin mimetics (e.g., GLP-1 receptor agonists and glucose-dependent insulinotropic polypeptides [GIPs]) are considered to be the most efficacious for these patients as these agents have cardiovascular (CV), renal, metabolic and mortality benefits. To minimize gastrointestinal (GI) symptoms associated with incretin mimetics, patients should slowly consume small meals as well as avoid high-fat, calorie-dense foods. AOMs that can be used in patients with kidney diseases stage 1 to 3b are available but may require dose adjustment in patients with more advanced kidney disease. Naltrexone/bupropion lacks data in patients with kidney disease and is contraindicated in patients with uncontrolled hypertension or end-stage kidney disease (ESKD). Orlistat can increase urine oxalate levels and is associated with GI adverse effects. Furthermore, long-term renal and CV disease outcomes have not been fully evaluated with this agent. Phentermine/topiramate requires dose adjustment based on renal function and should not be used in advanced renal disease. Additionally, its effects on renal outcomes and CV mortality and morbidity have not been established. Metformin and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are also reviewed in the guidance as medications with some weight loss but are not FDA-approved for this use.
A systematic review published in Health Affairs has evaluated the intended and unintended outcomes following the FDA’s warnings regarding use of antidepressants in pediatric patients. In 2003, the FDA warned that antidepressants may be associated with suicidal thoughts and behaviors in youth, and in 2005 a black box warning was added to product labeling regarding this risk in patients < 18 years of age. In 2007, the black box warning was expanded to include young adults through 24 years of age. The intent of the warnings was to increase HCP monitoring for these adverse outcomes. Eleven of 34 studies evaluating the warnings’ outcomes met inclusion criteria for the systematic review and assessed changes in outcomes following either the 2003 FDA advisory or the 2005 black box warning. Following the FDA warnings, multiple studies demonstrated substantial decreases in HCP visits for depression and depression diagnoses, decreases in antidepressant treatment, and increases in psychotropic drug poisonings and suicide deaths for pediatric patients. Furthermore, before the warnings, rates of depression diagnosis and treatment were increasing, and rates of psychotropic drug poisonings/suicide deaths were declining. Across various pediatric subpopulations and data sources, the findings demonstrated a substantial and immediate impact on unintended outcomes following implementation of the FDA’s warnings. The authors concluded the results support reassessment of the risk-benefit analysis for the FDA’s black box warnings on antidepressant medications.
The FDA has granted clearance to Big Health’s digital therapeutic, DaylightRx, intended to treat generalized anxiety disorder (GAD) as an adjunct to usual care in patients ≥ 22 years of age. Authorization marks the first FDA-cleared digital therapeutic for this use. DaylightRx is a prescription device that delivers cognitive behavioral therapy (CBT) for GAD through evidence-based techniques. The 90-day treatment provides interactive lessons on applied relaxation to decrease tension, stimulus control to reduce worry frequency, cognitive restructuring to impede anxious thoughts, and exposure to decrease worry intensity. Guided practice exercises help patients to integrate these techniques into daily life. In randomized controlled trials, remission rates of > 70% were observed as well as a significant reduction in anxiety for at least six months or longer.
Shortage Updates
On Oct. 2, 2024, the FDA determined that Eli Lilly’s tirzepatide (Mounjaro, Zepbound) shortage had resolved. However, the agency is reevaluating its decision, following a subsequent compounding trade group lawsuit challenging FDA’s action. This shortage began in Dec. 2022 due to increased demand.
Novo Nordisk has asked the FDA to place semaglutide on the list of drug products that demonstrate difficulties for compounding (otherwise known as the FDCA 503 Demonstrable Difficulties for Compounding [DDC] lists). Novo Nordisk sites that semaglutide products meet all of the FDA criteria for being on the list, namely that they have complex “formulations, delivery mechanisms, dosage forms, achievement of bioavailability, compounding processes, and physicochemical and analytical testing,” which could result in an adverse impact on the safety or efficacy of the drug. The FDA generally consults an advisory committee on compounding prior to adding products to the DCC lists.
All strengths of Novo Nordisk’s semaglutide (Ozempic) formulation for select patients with T2DM are available, along with all strengths of the semaglutide product indicated for weight management (Wegovy). Novo Nordisk’s liraglutide (Saxenda) for weight management has limited availability, as does the liraglutide (Victoza) formulation indicated for select patients with T2DM; an authorized generic of Victoza distributed by Teva is available. The GLP-1 receptor agonist dulaglutide (Trulicity), indicated for select patients with T2DM, is available in all strengths.
Shortages of stimulants for the treatment of attention-deficit/hyperactivity disorder (ADHD) continue to be reported. Availability of generic methylphenidate HCl extended-release (ER) tablets is variable depending on the manufacturer. Brand-name Relexxii from Vertical, as well as brand-name Concerta from Janssen, are currently available. Generic amphetamine aspartate monohydrate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate immediate release (IR) tablet shortages are also being reported; most strengths of brand-name Adderall IR tablets from Teva are available. Shortages of the generic version of Vyvanse, lisdexamfetamine dimesylate capsules and chewable tablets persist. Brand-name Vyvanse capsules and chewable tablets remain available from Takeda.
The FDA has published “7 Things to Know About Drug Shortage Management” detailing how the drug shortage staff manages drug shortages as well as the criteria required for a drug to be considered in “shortage” or “resolved.” The FDA published final guidance for industry on temporary policies for compounding certain parenteral drug products; this is related to the public health emergencies following Hurricanes Helene and Milton.
The Secretary of the Department of Health and Human Services (HHS) has released a letter to health care leaders and stakeholders regarding the impact of Hurricane Helene on the supply chain. Additional updates will also be provided by the HHS on the impact from Hurricane Milton.
Drug Information Highlights
The FDA has authorized marketing of the first home influenza and COVID-19 combination test outside of EUA. Healgen Rapid Check COVID-19/Flu A&B Antigen Test is authorized for over-the-counter use by individuals with respiratory symptoms and provides at-home results in about 15 minutes for both influenza and COVID-19 with use of a nasal swab sample. The test is authorized for individuals ≥ 2 years of age (adult caregiver collects sample); individuals ≥ 14 years of age can take their own nasal swab sample.
MedImmune's influenza vaccine live, intranasal (FluMist) has been approved for self- or caregiver-administration in a non-clinical setting. With this approval, FluMist becomes the first influenza vaccine that does not require HCP administration. FluMist is indicated for the active immunization for the prevention of influenza disease caused by influenza virus subtypes A and type B in individuals 2 through 49 years of age. For self/caregiver administration, FluMist will be available through a third-party online pharmacy with home delivery expected for the 2025–2026 flu season.
The CDC conducted an Internet panel survey from March 26 through April 11, 2024 to determine maternal and infant respiratory syncytial virus (RSV) immunization coverage for the 2023 to 2024 RSV season. During this period, maternal RSV vaccination coverage among eligible pregnant women was 33%, and nirsevimab (Beyfortus) coverage among infants was 45%. This resulted in 56% of infants being protected by either or both products.
The CDC issued a Morbidity and Mortality Weekly Report (MMWR) on differences in COVID-19 outpatient antiviral medication use among adults ≥ 65 years of age in the U.S. from April 2022 to September 2023. Less than half of adults ≥ 65 years of age with an outpatient COVID-19 diagnosis received a recommended COVID-19 antiviral medication.
The CDC published an MMWR describing COVID-19-associated hospitalizations among U.S. adults ≥ 18 years of age across 12 states between October 2023 to April 2024. During this time frame, adults ≥ 65 years of age accounted for 70% of all COVID-19–associated hospitalizations among adults. The majority of adults who were hospitalized had several underlying conditions and only 12% had received the updated 2023–2024 formula COVID-19 vaccine.
Drug Information Happenings
The American Academy of Pediatrics (AAP) published its first clinical practice guideline on opioid prescribing for acute pain management in children and adolescents in outpatient settings. The guideline highlights the importance of a multimodal approach for pain management (e.g., nonpharmacological options, nonopioid medications, opioids when needed).
The CDC released a statement regarding the potential public health risk associated with ordering counterfeit prescription medications from online pharmacies. The counterfeit medications are reported to frequently contain fentanyl and methamphetamine putting patients at risk for an overdose.
The Infectious Diseases Society of America (IDSA) has issued updated guidance on the treatment of antimicrobial-resistant (AMR) gram-negative infections. The guideline focuses on infections caused by extended-spectrum β-lactamase-producing Enterobacterales, AmpC β-lactamase-producing Enterobacterales, carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa with difficult-to-treat resistance, carbapenem-resistant Acinetobacter baumannii, and Stenotrophomonas maltophilia in the U.S.
All brand names are property of their respective owners.
COVID-19 = coronavirus 2019
EUA = emergency use authorization
FDA = Food & Drug Administration
FDCA = Federal Food, Drug, & Cosmetic Act
GLP-1 = glucagon-like peptide-1
HCl = hydrochloride
HCP = health care professional
Executive Editor: Anna Schreck Bird, PharmD
Deputy Editors: Erik Hamel, PharmD; Olivia Pane, PharmD, CDCES
