EDITORIAL STAFF
EDITOR-IN-CHIEF
Maryam Tabatabai
PharmD
EXECUTIVE EDITOR
Anna Schreck Bird
PharmD
DEPUTY EDITORS
Jessica Czechowski PharmD
Carole Kerzic
RPh
Olivia Pane PharmD, CDCES
Leslie Pittman
PharmD
Devon Trumbower PharmD, BCPS
BIOSIMILAR CORNER
DRUG INFORMATION HAPPENINGS & HIGHLIGHTS
RECENT FDA APPROVALS
A full prescription (Rx) to over-the-counter (OTC) switch has been approved for Narcan (naloxone HCl) nasal spray, marking approval of the first naloxone product approved for use without a Rx. The Drug Facts Panel uses are (1) to “revive” someone during an overdose from many prescription pain medications or street drugs such as heroin; (2) this medicine can save a life. Directions are to (1) check for a suspected overdose; (2) give first dose in the nose (1 nasal spray device contains 1 dose); (3) call 911 immediately after giving the first dose; (4) wait 2 to 3 minutes after the first dose; if the person wakes up, stay until the ambulance arrives and give another dose if the person becomes very sleepy again — if the person does not wake up, continue to give doses every 2 to 3 minutes until the person wakes up. The nonprescription product will be supplied as 2 devices of 4 mg of naloxone HCl in each package (each device sprays only 1 time) and utilizes the same device, strength, and formulation as Rx Narcan Nasal Spray. The OTC opioid reversal agent will be available in-store and online by late summer 2023 from Emergent BioSolutions. Until launch of the OTC product, the Rx version will continue to be available. Other formulations of naloxone will continue to be available with a Rx only. The Rx to OTC application received Priority Review and was reviewed at an FDA advisory committee meeting in early 2023, where members voted unanimously for availability of the product without a Rx.
The FDA released a Drug Safety Communication describing multiple updates to the prescribing information of opioid pain medications. These updates provide added guidance for safe use and include a new warning about the potential for opioid-induced hyperalgesia. The required label updates are for both immediate release (IR) and extended-release/ long-acting (ER/LA) opioids. The safety updates are to add clarity on intended patient populations, appropriate dosage and administration, and updated details on the risks associated with using these medications. The agency will also require opioid manufacturers to offer prepaid mail-back envelopes for outpatient pharmacies to assist patients in the proper disposal of unused opioids.
The FDA has amended the EUAs for Moderna and PfizerBiontech COVID-19 vaccines to authorize use of the bivalent (original and omicron BA.4/BA.5) vaccines to be used for all doses in individuals ≥ 6 months old; a second bivalent dose is also authorized in individuals ≥ 65 years old and immunocompromised patients. Monovalent Moderna and Pfizer-Biontech vaccines are no longer authorized for use. CDC’s ACIP endorsed the amendments. The Lucira™ COVID-19 & Flu Home Test, an OTC at-home diagnostic test, is now available at lucirahealth.com. The single-use nasal test kit is the first OTC at-home diagnostic test that differentiates between influenza and SARS-CoV-2 viruses in approximately 30 minutes. The diagnostic test received EUA in February 2023. As of April 10, 2023, the national COVID-19 emergency declared on March 13, 2020 has been terminated. Please refer to the COVID-19 disclaimer at the end of the publication.
Adalimumab-atto (Amjevita™) has been approved as an additional 10 mg/0.2 mL single-dose prefilled syringe. Existing presentations include single-dose prefilled glass syringes in the strengths of 20 mg/0.4 mL and 40 mg/0.8 mL as well as a 40 mg/0.8 mL single-dose prefilled SureClick ® autoinjector. Amjevita became commercially available at the end of January 2023, marking the launch of the first biosimilar to adalimumab (Humira®) to become available in the US.
The agency has approved Sandoz’s citrate-free, highconcentration formulation (HCF) of adalimumab-adaz (Hyrimoz®), a biosimilar to adalimumab (Humira). The new formulation will be supplied as 10 mg/0.1 mL and 20 mg/0.2 mL prefilled syringes and 40 mg/0.4 mL and 80 mg/0.8 mL prefilled syringes and autoinjectors (Sensoready® Pen). Hyrimoz was previously approved as a 40 mg/0.8 mL prefilled syringe and Sensoready pen, and a 10 mg/0.2 mL prefilled syringe. The citrate-free HCF is expected to launch on July 1, 2023. Hyrimoz has also received approval for the treatment of adults with moderate-to-severe hidradenitis suppurativa; existing indications include select patients with RA, JIA, PsA, AS, CD, UC, and PsO.
• Sandoz has discontinued Proventil ® HFA 90 mcg inhaler (albuterol sulfate), indicated for patients ≥ 4 years old for treatment/prevention of bronchospasm with reversible obstructive airway disease and for prevention of exercise-induced bronchospasm.
• Ascend Laboratories has voluntarily recalled 10 lots of dabigatran etexilate capsules, 75 mg and 150 mg, to the consumer level due to N-nitroso-dabigatran (NDAB) — a nitrosamine impurity — being above the established acceptable daily intake limit. The recalled product was distributed from June to October 2022.
• Camber has issued a voluntary recall to the consumer level of 1 lot of atovaquone 750 mg/5 mL oral suspension, due to the potential for Bacillus cereus contamination. To date, no ADRs have been reported; however, the potential exists that contamination of the suspension may result in life-threatening infections in patients who are immunocompromised.
• A second dose of pilocarpine HCl ophthalmic solution ( Vuity ® ) has been approved for the treatment of presbyopia in adults. Product labeling previously stated that the recommended dosage was 1 drop in each eye once daily. This information remains, but a second dose (1 additional drop per eye) can now also be administered 3 to 6 hours following the first dose.
• The manufacturer of ibrutinib (Imbruvica®), Abbvie, has announced plans to voluntarily withdraw the Accelerated Approvals for use in patients with (1) mantle cell lymphoma who have received ≥ 1 prior therapy and (2) marginal zone lymphoma who require systemic therapy and have received ≥ 1 prior anti-CD20-based therapy. The other FDA-approved indications will remain as is. The withdrawals are based on findings from the confirmatory trials for these uses, a requirement of the Accelerated Approvals.
• The FDA has approved dabrafenib (Tafinlar ® ) in combination with trametinib (Mekinist ® ) for the treatment of pediatric patients ≥ 1 year old with lowgrade glioma (LGG) with a BRAF V600E mutation, and who require systemic therapy. New oral formulations of both agents also received approval for patients who cannot swallow tablets/capsules. This approval marks the first FDA approval of a systemic therapy for the first-line setting of pediatric patients with LGG with a BRAF V600E mutation. An estimated 15% to 20% of pediatric LGGs carry the BRAF V600 mutation, and LGGs are the most common type of pediatric brain cancer. The new oral formulations are a 10 mg tablet for oral suspension of dabrafenib and an oral solution of 4.7 mg of trametinib per bottle (0.05 mg/mL once reconstituted).
• ICER issued a final evidence report on use of lecanemab (Leqembi™) for early Alzheimer’s disease, rating treatment as “promising but inconclusive”, noting net health benefits but also the possibility of net harm from ARIA.
• The FDA has updated shortage information on the ADHD medication amphetamine aspartate/amphetamine sulfate/dextroamphetamine saccharate/dextroamphetamine sulfate tablets (Adderall®).
• The generic ADHD medication methamphetamine HCl tablets are on shortage; estimated resolution of Mayne’s product is expected in September 2023. Key Therapeutics’ brand-name Desoxyn® continues to be available.
• The agency is reporting availability of semaglutide (Ozempic®) 1 mg, 2 mg, and 0.25 mg/0.5 mg (2 mg/3 mL) presentations; however, the 0.25 mg/0.5 mg (2 mg/1.5 mL) product is being discontinued. Prescribers should transition patients to the 0.25 mg /0.5 mg (2 mg/3 mL) presentation.
• USPSTF issued a final recommendation determining there is not enough evidence to recommend for or against visual screening for skin cancer in adolescents and adults without symptoms. This recommendation does not apply to people with a family history or signs/symptoms of skin cancer.
adalimumab 100 mg/mL (biosimilar for Abbvie’s Humira)
Celltrion
PF-06928316 Pfizer
natalizumab (biosimilar to Biogen’s Tysabri®) Polpharma/Sandoz
pegunigalsidase alfa Chiesi
(vic-) trastuzumab duocarmazine Byondis
beremagene geperpavec Krystal
epcoritamab Genmab/Abbvie
fezolinetant Astellas
nalmefene Opiant
TAK-003 Takeda
nogapendekin alfa inbakicept Immunitybio
sotagliflozin Lexicon
nirmatrelvir/ritonavir (Paxlovid™)
Pfizer
delandistrogene moxeparvovec Sarepta/Genentech
• SC
• Tumor necrosis factor (TNF)-alpha inhibitor
• IM
• Pre-fusion protein viral vaccine
• IV
• Anti-alpha-4-integrin antibody
RSV prevention (ages ≥ 60 years) May 2023
CD; MS May-June 2023
• Agalsidase beta Fabry disease
• IV
• IV
• Anti-HER2 antibody cytotoxic agent
• Topical
• Gene therapy
• SC
• Anti-CD20/Anti-CD3 antibody
• Oral
• Neurokinin-3 (NK3) receptor antagonist
• Intranasal
• Opioid antagonist
• SC
• Tetravalent, live, attenuated viral vaccine
• Intravesical
• Interleukin (IL)-15 agonist
• Oral
• SGLT1/SGLT2 inhibitor
• Oral
• Protease inhibitor
• IV
• Gene therapy
Breast cancer (HER2+, unresectable locally advanced or metastatic)
Epidermolysis bullosa (dystrophic)
Diffuse large B cell lymphoma (≥ 3rd-line) 05/21/2023
Menopause vasomotor symptoms 05/22/2023
Opioid overdose 05/22/2023
Dengue fever prevention (ages 4 to 60 years) 05/22/2023
Bladder cancer (BCG-unresponsive, non-muscle invasive CIS, in combination with BCG)
Heart failure (in patients with or without T2DM)
COVID-19 treatment (high-risk individuals)
Duchenne muscular dystrophy (ambulatory patients)
05/23/2023
05/26/2023
05/28/2023
05/29/2023
rezafungin (Rezzayo™)
Melinta
rizatriptan (RizaFilm®)
IntelGenx
• NDA approval 03/22/2023; Orphan Drug, Priority Review, Qualified Infectious Disease Product
• Indicated for patients ≥ 18 years old who have limited or no alternative options for the treatment of candidemia and invasive candidiasis; approval is based on limited clinical safety and efficacy data
• It has not been studied in patients with endocarditis, osteomyelitis, and meningitis due to Candida
• Echinocandin antifungal
• Injection: 200 mg as a solid (cake or powder) in an SDV for reconstitution
• Recommended dosage is administered by an HCP once weekly by IV infusion, with an initial 400 mg loading dose, then a 200 mg dose once weekly thereafter; administered over 1 hour; the infusion may be slowed, interrupted, or restarted at a lower rate, if needed, due to infusion-related reactions; the safety has not been established for use past 4 weekly doses
• Product availability is expected summer 2023
• 505(b)(2) NDA approval 04/14/2023; Standard Review
• Indicated for the acute treatment of migraine with or without aura in adults and pediatric patients 12 to 17 years old weighing ≥ 40 kg; use is limited to treatment only after a clear diagnosis of migraine has been established
• Not indicated for preventive treatment of migraine or treatment of cluster headache
• Serotonin (5-HT) 1B/1D receptor agonist (triptan)
• Oral film: 10 mg
• Recommended dosage for adults is a 10 mg single dose administered on the tongue; repeat doses should be separated by ≥ 2 hours; maximum dosage in 24 hours is 30 mg; safety of treating > 4 headaches in 30 days has not been established
• Recommended dosage for pediatric patients 12 to 17 years old weighing ≥ 40 kg: 10 mg single dose; use of > 1 dose in 24 hours has not been established
omidubicel-onlv (Omisirge®) Gamida Cell
tofersen (Qalsody™)
Biogen
• BLA approval 04/17/2023; Breakthrough Therapy, Orphan Drug, Priority Review
• Indicated for use in adults and pediatric patients ≥ 12 years old with hematologic malignancies, who are planned for umbilical cord blood transplantation following myeloablative conditioning, to reduce the time to neutrophil recovery and incidence of infection
• Nicotinamide-modified allogeneic hematopoietic progenitor cord blood-based cell therapy
• Cell suspension: cultured fraction (minimum of 8 × 108 total viable cells with a minimum of 8.7% CD34+ cells and a minimum of 9.2 × 107 CD34+ cells) and noncultured fraction (minimum of 4 × 108 total viable cells with a minimum of 2.4 × 107 CD3+ cells)
• Recommended dosage is single-dose treatment of a cultured fraction and a noncultured fraction supplied cryopreserved separately in 2 bags and administered by IV infusion (central venous access) under the supervision of a physician experienced in treatment of hematologic malignancies, in a medical facility with expertise in hematopoietic stem cell transplants
• Boxed warnings for infusion reactions, graft versus host disease, engraftment syndrome, and graft failure
• NDA approval 04/25/2023; Accelerated Approval, Fast Track, Orphan Drug, Priority Review
• Indicated for the treatment of amyotrophic lateral sclerosis (ALS) in adults who have a superoxide dismutase 1 (SOD1) gene mutation; approved under Accelerated Approval based on reduction in plasma neurofilament light chain, continued approval for this use may require a demonstration of benefit in confirmatory clinical trials
• Antisense oligonucleotide
• Injection: 100 mg/15 mL solution in an SDV
• BLA approval 04/26/2023; Breakthrough Therapy, Orphan Drug, Priority Review
• Indicated to prevent recurrence of Clostridioides difficile infection (CDI) following antibacterial treatment for recurrent CDI (rCDI) in adults
• Recommended dosage is 100 mg administered intrathecally by an HCP as 3 loading doses at 14-day intervals, followed by every 28-day doses thereafter fecal microbiota spores, live-brpk (Vowst™)
Aimmune
• Not indicated for the treatment of CDI
• Bacterial spore suspension
• Oral capsule: manufactured from human fecal matter from qualified donors
• Recommended dosage is 4 capsules once daily for 3 consecutive days taken on an empty stomach before the first meal of the day; antibacterial treatment for rCDI should be completed 2 to 4 days prior to initiating therapy
• Product availability is expected in June 2023
505(b)(2) = FDA approval pathway that allows for submission of data from studies not conducted by or for the applicant.
COVID-19 Disclaimer: For the most current COVID-19 information, visit the FDA, CDC, NIH, NIH guidelines, and WHO websites. State and local health departments also provide valuable information regarding management in local communities. As the COVID-19 landscape is fluid, assumptions are subject to change.
Glossary:
ACIP Advisory Committee on Immunization Practices
ADHD attention-deficit/hyperactivity disorder
ADR adverse reaction
ARIA amyloid related imaging abnormalities
AS ankylosing spondylitis
BCG Bacillus Calmette-Guérin
BLA Biologics License Application
BRAF V-Raf Murine Sarcoma Viral Oncogene
Homolog B
CD Crohn’s disease
CD20 cluster of differentiate 20
CD3 cluster of differentiate 3
CDC Centers for Disease Control and Prevention
CIS carcinoma in situ
COVID-19 Coronavirus Disease 2019
EUA Emergency Use Authorization
FDA Food and Drug Administration
HCl hydrochloride
HCP healthcare professional
HER2 human epidermal growth factor receptor 2
HFA hydrofluoroalkane
ICER Institute for Clinical and Economic Review
IM intramuscular
IV intravenous
JIA juvenile idiopathic arthritis
MS multiple sclerosis
NDA New Drug Application
NIH National Institutes of Health
PsA psoriatic arthritis
PsO plaque psoriasis
RA rheumatoid arthritis
RSV respiratory syncytial virus
SARS-CoV-2 severe acute respiratory syndrome coronavirus 2
SC subcutaneous
SDV single-dose vial
SGLT sodium-glucose cotransporter
T2DM type 2 diabetes mellitus
UC ulcerative colitis
US United States
USPSTF US Preventive Services Task Force
WHO World Health Organization
References:
cdc.gov fda.gov icer.org congress.gov uspstf.org
Disclaimer: 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 healthcare provider.