Clinical News: December 2023

December 29, 2023

Your monthly source for drug information highlights

Clinical News

Your monthly source for drug information highlights

Hot topics

FDA DRUG SAFETY COMMUNICATION

The U.S. Food and Drug Administration (FDA) has issued a Drug Safety Communication on the potential for life-threatening drug reactions with eosinophilia and systemic symptoms (DRESS) with the antiseizure medications levetiracetam (Keppra®, Keppra XR®, Elepsia™ XR, Spritam®) and clobazam (Onfi®, Sympazan®). New warnings about DRESS will be added to the prescribing information for these products. Symptoms of DRESS usually begin 2 to 8 weeks after initiation of the medication but could occur earlier or later. Patients who experience any unusual symptoms, including rash, at any time while using these drugs should immediately seek emergency care. Although fever with rash and swollen lymph nodes or swelling of the face are common with DRESS, some individuals do not develop a rash. Patients should not stop taking levetiracetam or clobazam unless advised to do so by an HCP, as abrupt discontinuation may result in uncontrolled seizures.

FDA INVESTIGATION OF T-CELL MALIGNANCY

Following reports of T-cell malignancies in patients treated with B-cell maturation antigen (BCMA)-directed or cluster of differentiation (CD)19-directed autologous chimeric antigen receptor (CAR) T-cell immunotherapies, the FDA is investigating the risk and assessing whether regulatory action will be required for these products. Labeling for products in these classes already includes a class warning on the potential for secondary malignancies. Risk of T-cell malignancies applies to all currently approved BCMA-directed and CD19-directed genetically modified autologous CAR T cell immunotherapies, including the following agents: idecabtagene vicleucel (Abecma®), lisocabtagene maraleucel (Breyanzi®), ciltacabtagene autoleucel (Carvykti®), tisagenlecleucel (Kymriah®), brexucabtagene autoleucel (Tecartus®), and axicabtagene ciloleucel (Yescarta®). Although the FDA has determined that the benefits of these gene therapy products currently outweigh the risks for the indicated uses, the investigation is ongoing. T-cell malignancy can lead to hospitalization and death. Patients who receive these agents should be monitored indefinitely for the development of new malignancies.

More trending topics

WEIGHT MANAGEMENT CORNER

Results from the double-blind, randomized SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) trial have been published in the New England Journal of Medicine. The time-to-first-event analysis assessed the primary cardiovascular (CV) endpoint as the composite of death from CV causes, non-fatal myocardial infarction, or non-fatal stroke. The trial enrolled a total of 17,604 adults ≥ 45 years of age with a body-mass index ≥ 27 kg/m2 and pre-existing CV disease with no prior history of diabetes mellitus. At a mean follow-up of 39.8 months, treatment with semaglutide (Wegovy®) 2.4 mg SC weekly resulted in a significant reduction in the primary CV endpoint, with 6.5% of patients in the semaglutide group experiencing an event compared with 8% in the placebo group (hazard ratio, 0.8; 95% confidence interval, 0.72 to 0.9; p<0.001). Significantly more patients in the semaglutide arm (16.6%) compared to placebo (8.2%) experienced an adverse event that led to permanent discontinuation of study drug (p<0.001).

CLINICAL CORNER

Valneva has received FDA approval of the first vaccine for chikungunya: chikungunya vaccine, live (Ixchiq®). This vaccine is indicated for the prevention of disease caused by chikungunya virus (CHIKV) in individuals ≥ 18 years of age who are at increased risk of exposure to CHIKV. Chikungunya is considered an emerging global health threat and is predominantly transmitted through infected mosquitos. The vaccine was approved under Accelerated Approval based on anti-CHIKV neutralizing antibody titers; continued approval may require demonstration of benefit in confirmatory clinical trials. Ixchiq should be administered by an HCP as a single IM dose of approximately 0.5 mL. Product will be available as a single-dose vial of lyophilized antigen component, live and a prefilled syringe of sterile water diluent. This application received Breakthrough Therapy, Fast Track, and Priority Review designations from the FDA.

BEHAVIORAL HEALTH CORNER

The U.S. Preventive Services Task Force (USPSTF) released its 13th Annual Report to Congress which highlights high-priority evidence gaps. The report calls for more research evaluating the benefits versus harms of screening for suicide risk in children/adolescents and screening for anxiety disorders/depression in younger children. More research is also needed to evaluate screening for anxiety disorders in adults ≥ 65 years of age, as well as screening for suicide risk in all adults.

COVID-19: NOTABLE DEVELOPMENTS

The FDA has published a notice to HCPs to ensure that the correct dosage of Moderna COVID-19 vaccine (2023–2024 formula) is administered to individuals 6 months through 11 years of age. The CDC is tracking a SARS-CoV-2 variant called BA.2.86 and has published an MMWR on early detection/surveillance of this variant between July and October 2023. The CDC has also published an MMWR on COVID-19 mRNA vaccine effectiveness among infants and children 6 months to 4 years of age from July 2022 to September 2023.

WEIGHT MANAGEMENT CORNER

Results from the double-blind, randomized SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) trial have been published in the New England Journal of Medicine. The time-to-first-event analysis assessed the primary cardiovascular (CV) endpoint as the composite of death from CV causes, non-fatal myocardial infarction, or non-fatal stroke. The trial enrolled a total of 17,604 adults ≥ 45 years of age with a body-mass index ≥ 27 kg/m2 and pre-existing CV disease with no prior history of diabetes mellitus. At a mean follow-up of 39.8 months, treatment with semaglutide (Wegovy®) 2.4 mg SC weekly resulted in a significant reduction in the primary CV endpoint, with 6.5% of patients in the semaglutide group experiencing an event compared with 8% in the placebo group (hazard ratio, 0.8; 95% confidence interval, 0.72 to 0.9; p<0.001). Significantly more patients in the semaglutide arm (16.6%) compared to placebo (8.2%) experienced an adverse event that led to permanent discontinuation of study drug (p<0.001).

CLINICAL CORNER

Valneva has received FDA approval of the first vaccine for chikungunya: chikungunya vaccine, live (Ixchiq®). This vaccine is indicated for the prevention of disease caused by chikungunya virus (CHIKV) in individuals ≥ 18 years of age who are at increased risk of exposure to CHIKV. Chikungunya is considered an emerging global health threat and is predominantly transmitted through infected mosquitos. The vaccine was approved under Accelerated Approval based on anti-CHIKV neutralizing antibody titers; continued approval may require demonstration of benefit in confirmatory clinical trials. Ixchiq should be administered by an HCP as a single IM dose of approximately 0.5 mL. Product will be available as a single-dose vial of lyophilized antigen component, live and a prefilled syringe of sterile water diluent. This application received Breakthrough Therapy, Fast Track, and Priority Review designations from the FDA.

BEHAVIORAL HEALTH CORNER

The U.S. Preventive Services Task Force (USPSTF) released its 13th Annual Report to Congress which highlights high-priority evidence gaps. The report calls for more research evaluating the benefits versus harms of screening for suicide risk in children/adolescents and screening for anxiety disorders/depression in younger children. More research is also needed to evaluate screening for anxiety disorders in adults ≥ 65 years of age, as well as screening for suicide risk in all adults.

COVID-19: NOTABLE DEVELOPMENTS

The FDA has published a notice to HCPs to ensure that the correct dosage of Moderna COVID-19 vaccine (2023–2024 formula) is administered to individuals 6 months through 11 years of age. The CDC is tracking a SARS-CoV-2 variant called BA.2.86 and has published an MMWR on early detection/surveillance of this variant between July and October 2023. The CDC has also published an MMWR on COVID-19 mRNA vaccine effectiveness among infants and children 6 months to 4 years of age from July 2022 to September 2023.

Drug information happenings & highlights

DRUG INFORMATION HIGHLIGHTS

  • In October 2023, the FDA instructed consumers to stop use of more than 20 over-the-counter (OTC) eye drop products due to the risk for eye infections that could lead to partial vision loss or blindness. Subsequently, Harvard Drug Group issued a voluntary recall to the consumer level for all lots of certain Rugby® brand ophthalmic drugs supplied by Velocity. Cardinal Health also issued a voluntary recall to the consumer level for all lots of certain Leader™ brand ophthalmic drops supplied by Velocity. In addition, Kilitch Healthcare India Limited voluntarily recalled all lots within expiry of certain ophthalmic products to the consumer level. These ophthalmic products are being recalled due to potential safety concerns after FDA investigators found unsanitary manufacturing conditions.
  • Bayer has voluntarily recalled 1 lot of larotrectinib (Vitrakvi®) oral solution 20 mg/mL in 100 mL glass bottles to the consumer/user level due to microbial contamination (Penicillium brevicompactum) found during stability testing.
  • Novartis has recalled 2 lots of cyclosporine (Sandimmune®) oral solution in the strength of 100 mg/mL to the consumer level due to crystal formation observed in some bottles; this could potentially result in incorrect dosing. The issue was found during an investigation of crystallization in a different lot.
  • Insight voluntarily recalled 2 lots of Ting® 2% Miconazole Nitrate Athlete’s Foot Antifungal Spray Powder to the consumer level following detection of the presence of benzene. Benzene is not an ingredient in this OTC product and is considered a human carcinogen.
  • KinderFarms recalled all lots of KinderMed™ Infants’ Pain & Fever oral suspension (acetaminophen – 160 mg/5 mL) and KinderMed Kids’ Pain & Fever oral suspension (acetaminophen – 160 mg/5 mL) to the retail and consumer level. These OTC products were recalled due to acetaminophen instability as sample batches showed that some lots were not within range and thereby may lead to a health risk.
  • InvaGen has voluntarily recalled 1 lot of vigabatrin for oral solution, USP 500 mg, to the consumer level due to seal integrity issues that allowed for powder leakage from the foil pouch. Leakage of powder containing the active ingredient could result in lower vigabatrin levels inside the pouch, leading to potential underdosing of the anticonvulsant.
  • The FDA has announced that Novo Nordisk will discontinue manufacture of Levemir® 100 unit/mL FlexPen® and vials. Discontinuation of Levemir FlexPen will occur on April 1, 2024; however, supply disruptions are expected, starting in mid-January 2024. Vials will be available until the end of 2024. Full brand discontinuation will occur on December 31, 2024.

DRUG INFORMATION HAPPENINGS

  • The FDA has published a communication instructing wholesalers, pharmacies, HCPs, and patients to check their product supply for counterfeit semaglutide (Ozempic®) 1 mg injection following seizure of counterfeit product from the U.S. drug supply chain.  
  • Novo Nordisk is taking action to protect patients/consumers from adulterated and misbranded injectable compounded products claiming to contain semaglutide.  
  • The American Academy of Dermatology (AAD) published updated guidelines on the use of phototherapy and systemic therapies for adults with atopic dermatitis.
  • The American Society of Clinical Oncology (ASCO) published clinical guidance on alternative treatments due to drug shortages in oncology.

CDC PULSE POINTS

  • The CDC has released recommendations on the 2024 immunization schedule for adults (≥ 19 years of age) and children/adolescents (≤ 18 years of age).
  • More than 77,000 additional doses of nirsevimab-alip (Beyfortus™) 100 mg have been released and will be distributed through the Vaccines for Children Program and commercial pathways. The long-acting monoclonal antibody is indicated for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in (1) neonates and infants born during or entering their first RSV season and (2) children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season.
  • The CDC has announced that it will expand testing of international air traveler samples through its Traveler-based Genomic Surveillance (TGS) program to test for influenza, RSV, SARS-CoV-2, and other select respiratory viruses.
Glossary

CDC = Centers for Disease Control and Prevention

HCP = health care professional

IM = intramuscular

MMWR = Morbidity and Mortality Weekly Report

mRNA = messenger ribonucleic acid

SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2

SC = subcutaneous

USP = U.S. Pharmacopeia

Editorial Staff

EDITOR-IN-CHIEF: Maryam Tabatabai, PharmD

EXECUTIVE EDITOR: Anna Schreck Bird, PharmD

DEPUTY EDITORS: Erik Hamel, PharmD

Olivia Pane, PharmD, CDCES

Related news

Perspectives

July 16, 2024

LISTEN NOW: Beyond the business – Stories of corporate kindness | Pharmacy Friends Podcast

In this episode, we talk about how our employees' help goes beyond our work in health care, aiding in philanthropic efforts

Perspectives

July 12, 2024

August 2024 decisions expected from the FDA

Your monthly synopsis of new drugs expected to hit the market

Perspectives

July 12, 2024

High-Cost Therapy Profile: July 2024

Detailed information about Afamitresgene autoleucel Intravenous (IV)