Perspectives
Clinical News: August 2024
August 28, 2024Your monthly source for drug information highlights
Clinical News
Your monthly source for drug information highlights
Hot topics
FDA SAFETY ALERT ON COMPOUNDED SEMAGLUTIDE
Following reports of serious adverse events, some requiring hospitalization, the U.S. Food and Drug Administration (FDA) issued a safety alert on dosing errors observed with compounded injectable semaglutide products. Reported adverse events ranged from gastrointestinal effects (e.g., nausea, vomiting, abdominal pain) to acute pancreatitis, dehydration, and gallstones. Other reports included adverse effects of fainting, headache, and migraine. Most reports included patient dosing errors caused by drawing up greater than the prescribed dose from a multiple-dose vial for self-administration with doses ranging from five to 20 times greater than the intended dose. In general, patients were not able to measure the intended dose using a syringe. Additional reports of five to 10-time greater doses occurred due to health care professionals (HCPs) miscalculating the intended dose when converting from milligrams to units or milliliters. Compounded semaglutide products can be supplied in various containers (e.g., multi-dose vials, prefilled syringes) as well as different concentrations. Instructions accompanying compounded products may state to administer in units; however, the volume of this may vary depending on the concentration. In some cases, the product syringes supplied with the semaglutide have been significantly larger than the prescribed volume. The FDA reminds HCPs, patients, and compounders that compounded products should only be used when medical needs are unable to be met by an FDA-approved medication as these products carry a higher risk due to lack of premarket review for safety, efficacy, or quality.
ILLEGAL SALES OF SEMAGLUTIDE ONLINE
A Research Letter published in JAMA Network Open summarizes a qualitative study evaluating the safety and risk of no-prescription online semaglutide purchases. Following online searches conducted in July 2023 on Google and Bing for websites advertising sale of semaglutide without a prescription, two 0.25 mg per dose prefilled pens or equivalent semaglutide injection vials were ordered from each website. Visual inspection of the product compared to the genuine Ozempic® 1 mg prefilled pen was performed as well as quality assessments evaluating sterility and microbiological contamination. Liquid chromatography–mass spectrometry (LC-MS) was utilized to quantify active ingredients in the products. Of the 1,080 hyperlinks identified from the searches, 29.35% (317) were for online pharmacies with nearly half of these (134 sites) belonging to illegal pharmacy operations. Most sites (70% [763]) did not offer products for sale with many of these being news or informational in nature. Approximately 14% of the sites were for telemedicine and required a consultation to obtain a prescription before purchase. Test buys were conducted for six online vendors that were not recommended or were considered rogue by LegitScript and/or National Association of Boards of Pharmacy. Only three of the six products were received as three of the vendors had non-delivery scams requesting extra payments. Of the delivered products, visual inspection demonstrated discrepancies in regulatory registration information and labeling. One sample demonstrated elevated endotoxin levels (potential contamination). Although all samples contained semaglutide, purity levels were lower (7% to 14%) than advertised (99%) and measured semaglutide was substantially greater than the labeled amount for each sample (29% to 39%) resulting in consumers receiving up to 39% more semaglutide per injection. Authors concluded semaglutide products are being sold through illegal online pharmacies without a prescription and increased calls to U.S. poison centers further demonstrate the importance of increased pharmacovigilance of illegal online sales. The FDA has sent warning letters to two of the websites for unlawful sale of unapproved and misbranded semaglutide.
More trending topics
BEHAVIORAL HEALTH CORNER
The Centers for Disease Control and Prevention (CDC) has released the Youth Risk Behavior Survey (YRBS) Data Summary & Trends Report: 2013–2023 providing a summary of data as well as trends from 2013 to 2023 for adolescents’ sexual behavior, substance use, exposure to violence, mental health, and suicidal thoughts and behaviors. The report reflects data collected every two years from a sample of U.S. high school students that is representative of adolescents nationwide. Data for substance use (e.g., ever used select illicit drugs, ever misused prescription opioids, current alcohol use, current marijuana use) and sexual risk behaviors (e.g., ever and current sexual activity, having four or more lifetime sexual partners) have shown continued improvement in 10-year trends. However, worsening trends were reported for protective sexual behaviors, experiences of violence, persistent sadness or hopelessness, and suicidal thoughts and behaviors. Disparities persist for female students as well as for students who identify as lesbian, gay, bisexual, transgender, questioning, or another non-heterosexual identity (LGBTQ+). For example, in 2023, more than half of female students reported persistent feelings of sadness or hopelessness in the prior year, and LGBTQ+ students were more likely than their peers to have used or misused substances and to have experienced all forms of violence, signs of poor mental health, and suicidal thoughts and behaviors. The CDC has developed an action guide to assist schools in supporting students’ mental health, and nationally, additional resources have been developed. Efforts continue to support adolescents and ensure these individuals have the knowledge and resources needed.
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. 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. Generic amphetamine aspartate monohydrate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate immediate release (IR) tablet shortages also continue from a few manufacturers. Brand name Adderall® IR tablets from Teva are available.
WEIGHT MANAGEMENT CORNER
Data from IQVIA’s National Prescription Audit PayerTrak published in a JAMA Health Forum Research Letter have demonstrated the number of semaglutide (Ozempic®, Wegovy®, Rybelsus®) prescriptions filled increased by 442% between January 2021 and December 2023 (from 471,876 to 2,555,308) with Ozempic® being > 70% of fills. Prescription fills increased by 392% for Ozempic® between January 2021 and December 2023, and 1,361% for Wegovy® between July 2021 and December 2023. These data from IQVIA encompass 92% of prescriptions dispensed to individuals at retail pharmacies across the U.S. Analysis was also conducted to evaluate payment method (e.g., commercial insurance, Medicaid, Medicare Part D, cash). Although monthly semaglutide claims increased for all payment methods, prescriptions processed through commercial insurance consistently demonstrated the largest number of fills, especially for Wegovy®.
A nationwide population-based emulation target trial based on electronic health records between December 2017 and March 2023 suggests an association between semaglutide and a significantly lower risk for medical encounters for tobacco use disorder diagnosis in patients with type 2 diabetes mellitus (T2DM) compared with other antidiabetic medications. Findings were based on seven target trials that were emulated across eligible patients with T2DM and tobacco use disorder. New use of semaglutide was compared with insulins, metformin, dipeptidyl-peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, sulfonylureas, thiazolidinediones, and other GLP-1 receptor agonists (RAs). Further studies are needed to assess semaglutide’s role in tobacco use disorder treatment.
In recent months, shortages of GLP-1 RAs that are indicated for select patients as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management have been reported by the FDA. As of August 2024, some of these shortages appear to be resolving or improving. Eli Lilly’s tirzepatide (Zepbound®) is being reported as currently available in all strengths, as is the tirzepatide (Mounjaro®) formulation indicated as an adjunct to diet and exercise in adults with T2DM. Additionally, all strengths of Novo Nordisk’s semaglutide (Ozempic®) formulation for select patients with T2DM are available, along with all strengths, except for the 0.25 mg strength, of the semaglutide product indicated for weight management (Wegovy®). Novo Nordisk’s liraglutide (Saxenda®) has limited availability, as does the liraglutide (Victoza®) formulation indicated for select patients with T2DM. The GLP-1 RA dulaglutide (Trulicity®), indicated for select patients with T2DM, has availability in the 0.75 mg and 1.5 mg strengths; the 3 mg and 4.5 mg products have limited availability through the third quarter of 2024 due to increased demand for the drug.
BEHAVIORAL HEALTH CORNER
The Centers for Disease Control and Prevention (CDC) has released the Youth Risk Behavior Survey (YRBS) Data Summary & Trends Report: 2013–2023 providing a summary of data as well as trends from 2013 to 2023 for adolescents’ sexual behavior, substance use, exposure to violence, mental health, and suicidal thoughts and behaviors. The report reflects data collected every two years from a sample of U.S. high school students that is representative of adolescents nationwide. Data for substance use (e.g., ever used select illicit drugs, ever misused prescription opioids, current alcohol use, current marijuana use) and sexual risk behaviors (e.g., ever and current sexual activity, having four or more lifetime sexual partners) have shown continued improvement in 10-year trends. However, worsening trends were reported for protective sexual behaviors, experiences of violence, persistent sadness or hopelessness, and suicidal thoughts and behaviors. Disparities persist for female students as well as for students who identify as lesbian, gay, bisexual, transgender, questioning, or another non-heterosexual identity (LGBTQ+). For example, in 2023, more than half of female students reported persistent feelings of sadness or hopelessness in the prior year, and LGBTQ+ students were more likely than their peers to have used or misused substances and to have experienced all forms of violence, signs of poor mental health, and suicidal thoughts and behaviors. The CDC has developed an action guide to assist schools in supporting students’ mental health, and nationally, additional resources have been developed. Efforts continue to support adolescents and ensure these individuals have the knowledge and resources needed.
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. 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. Generic amphetamine aspartate monohydrate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate immediate release (IR) tablet shortages also continue from a few manufacturers. Brand name Adderall® IR tablets from Teva are available.
WEIGHT MANAGEMENT CORNER
Data from IQVIA’s National Prescription Audit PayerTrak published in a JAMA Health Forum Research Letter have demonstrated the number of semaglutide (Ozempic®, Wegovy®, Rybelsus®) prescriptions filled increased by 442% between January 2021 and December 2023 (from 471,876 to 2,555,308) with Ozempic® being > 70% of fills. Prescription fills increased by 392% for Ozempic® between January 2021 and December 2023, and 1,361% for Wegovy® between July 2021 and December 2023. These data from IQVIA encompass 92% of prescriptions dispensed to individuals at retail pharmacies across the U.S. Analysis was also conducted to evaluate payment method (e.g., commercial insurance, Medicaid, Medicare Part D, cash). Although monthly semaglutide claims increased for all payment methods, prescriptions processed through commercial insurance consistently demonstrated the largest number of fills, especially for Wegovy®.
A nationwide population-based emulation target trial based on electronic health records between December 2017 and March 2023 suggests an association between semaglutide and a significantly lower risk for medical encounters for tobacco use disorder diagnosis in patients with type 2 diabetes mellitus (T2DM) compared with other antidiabetic medications. Findings were based on seven target trials that were emulated across eligible patients with T2DM and tobacco use disorder. New use of semaglutide was compared with insulins, metformin, dipeptidyl-peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, sulfonylureas, thiazolidinediones, and other GLP-1 receptor agonists (RAs). Further studies are needed to assess semaglutide’s role in tobacco use disorder treatment.
In recent months, shortages of GLP-1 RAs that are indicated for select patients as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management have been reported by the FDA. As of August 2024, some of these shortages appear to be resolving or improving. Eli Lilly’s tirzepatide (Zepbound®) is being reported as currently available in all strengths, as is the tirzepatide (Mounjaro®) formulation indicated as an adjunct to diet and exercise in adults with T2DM. Additionally, all strengths of Novo Nordisk’s semaglutide (Ozempic®) formulation for select patients with T2DM are available, along with all strengths, except for the 0.25 mg strength, of the semaglutide product indicated for weight management (Wegovy®). Novo Nordisk’s liraglutide (Saxenda®) has limited availability, as does the liraglutide (Victoza®) formulation indicated for select patients with T2DM. The GLP-1 RA dulaglutide (Trulicity®), indicated for select patients with T2DM, has availability in the 0.75 mg and 1.5 mg strengths; the 3 mg and 4.5 mg products have limited availability through the third quarter of 2024 due to increased demand for the drug.
Drug information happenings & highlights
DRUG INFORMATION HIGHLIGHTS
- Supply remains variable for the three different strengths of penicillin G benzathine (Bicillin® L-A). The shortage is due to increased demand for the drug. In addition to allowing temporary importation of benzathine benzylpenicillin (Extencilline®) due to the shortage, the FDA is also allowing for temporary importation of benzathine benzylpenicillin tetrahydrate (Lentocilin®). Both imported products are available.
- Abbvie has announced discontinuation of brand-name memantine extended-release (Namenda XR®) capsules; generic versions remain available. Namenda XR® is indicated for the treatment of moderate to severe dementia of the Alzheimer’s type.
- Pfizer has announced supply of the 5 mg brand-name glipizide (Glucotrol® XL) tablet is expected to be depleted in mid- September 2024. This is due to discontinuation of the manufacturing of the drug.
- Teva will discontinue the manufacture of brand name bisoprolol/hydrochlorothiazide (Ziac®) 2.5 mg/6.25 mg, 5 mg/6.25 mg, and 10 mg/6.25 mg tablets; generics remain available. Ziac® is indicated for the management of hypertension.
- Merck is discontinuing the manufacture of brand name posaconazole (Noxafil®) 100 mg delayed release tablets; generics remain. Noxafil is indicated for prevention and treatment of various fungal infections.
DRUG INFORMATION HAPPENINGS
- The CDC has published an update to the 2016 U.S. Selected Practice Recommendations for Contraceptive Use in the MMWR. Updated recommendations are provided on the provision of medications for intrauterine device (IUD) placement and management of bleeding irregularities during implant use; new recommendations on testosterone use and risk for pregnancy as well as self-administration of injectable contraception are also provided.
- Emergency Use Instructions (EUI) for oseltamivir (Tamiflu®) have been released by the CDC for the treatment and post-exposure prophylaxis (PEP) of pandemic influenza A viruses and novel influenza A viruses with pandemic potential. The EUI includes information that differs from or extends beyond information provided in the product labeling.
- A health advisory has been issued by the CDC on the recent increases in human parvovirus B19 (Fifth Disease) activity in the U.S. Common symptoms of this highly transmissible seasonal respiratory virus include a red rash on the face – a “slapped cheek” rash as well as joint pain in adults; however, the virus can result in adverse health outcomes in individuals who have not previously been exposed and are pregnant, immunocompromised, or have chronic hemolytic disorders.
- The American Academy of Pediatrics has released a new clinical report which provides guidance on health supervision for children and adolescents with sickle cell disease (SCD). The focus of the report is on the practical management of these patients with SCD as well as complications that may be managed by pediatric primary care providers.
- Initial study findings from the phase 3 SUMMIT trial assessing tirzepatide (Mounjaro®, Zepbound®) in adults with heart failure with preserved ejection fraction (HFpEF) and obesity demonstrated statistically significant improvements compared to placebo in both primary endpoints assessing the risk of heart failure outcomes and heart failure symptoms and physical limitations. Additionally, tirzepatide resulted in 15.7% weight loss in patients with and without T2DM.
The content in this publication is not a substitute for professional medical advice. For questions regarding any medical condition or if you need medical advice, please contact your health care provider.
All brand names are property of their respective owners.
Glossary
GLP-1 = glucagon-like peptide-1
HCl = hydrochloride
MMWR = Morbidity and Mortality Weekly Report
Editorial team
EDITOR-IN-CHIEF: Maryam Tabatabai, PharmD
EXECUTIVE EDITOR: Anna Schreck Bird, PharmD
DEPUTY EDITORS: Erik Hamel, PharmD; Olivia Pane, PharmD, CDCES
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