Eleven Potentially Practice-Changing Drugs Were Approved by the FDA in 2023

As drug experts, pharmacists have a responsibility to not only themselves but their patients to stay up to date about changing medication therapies. On average, about 43 novel drugs are approved each year in the United States, making it unrealistic to expect health care professionals to stay caught up on every single approved drug for the year.¹ This article will highlight some of the drugs that may have interesting mechanisms, unique use, or that may support expanded indications in the future.

Daprodustat

Daprodustat (Jesduvroq; GSK) is an oral medication indicated for the treatment of anemia in adults on hemodialysis for 4 or more months with chronic kidney disease (CKD).² Currently, anemia in patients on hemodialysis with CKD is treated with iron supplementation and erythropoiesis-stimulating agents (ESAs).³ ESAs trigger an increase in the body’s production of red blood cells whereas daprodustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, stimulates production of the erythropoietin hormone, which creates an endogenous increase in the rate of red blood cell production. Daprodustat was found to be noninferior to ESAs according to a clinical trial comparing the hemoglobin raising abilities of the novel drug to ESAs. The average change in hemoglobin in the daprodustat group was 0.28∓ 0.02 g per deciliter and 0.10∓ 0.02 g per deciliter in the ESA group (95% confidence interval [CI], 0.12 to 0.24).

Daprodustat has a boxed warning for increased risk of death, myocardial infarction, venous thromboembolism, stroke, and thrombosis of vascular access. However, as severe as these appear, one clinical trial found daprodustat to be noninferior to ESAs in terms of first occurrence of major cardiovascular events (hazard ratio, 0.93; 95% CI, 0.81 to 1.07) with 25.2% (n=374) of patients receiving daprodustat experiencing a major cardiovascular event and 26.7% (n=394) of patients receiving an ESA.⁵ In general, having an oral agent now available offers a strong advancement for patients with kidney disease.

Taurolidine and Heparin

Taurolidine and heparin (Defencath; CorMedix) is a combination of the anticoagulant heparin and the antimicrobial agent taurolidine, which was approved to help reduce the rate of occurrence of catheter related bloodstream infection (CRBSI) in adult patients receiving chronic hemodialysis through a central venous catheter.⁶ This combination product significantly reduced the risk of CRBSI when compared to heparin alone due to taurolidine binding to lipopolysaccharides, which prevents bacterial adherence to host epithelial cells and bacterial invasion of uninfected host cells.^7,8

Taurolidine appears to have an extremely broad spectrum with known activity against many gram positive and gram negative bacteria, including several antibiotic resistant strains, mycobacteria, and many species of fungi.⁷ Its use in clinical trials resulted in a 71% reduction in CRBSIs compared to when heparin was used alone (P=0.0006).⁷ Overall the medication is well tolerated.

One less common but serious adverse effect (AE) of this drug is the development of heparin-induced thrombocytopenia, which is expected given the heparin component.⁶ The AEs that may develop from the taurolidine component of taurolidine and heparin are hypersensitivity reactions, such as those that occur with other antimicrobials. These AEs should be taken into consideration when prescribing or recommending the use of taurolidine and heparin. However, in general, this represents a potentially practice-changing medication with a good potential to reduce blood stream infections in a vulnerable population.

Lotilamer Ophthalmic Solution

Lotilamer ophthalmic solution (Xdemvy; Tarsus Pharmaceuticals) is a recently approved medication for the treatment of demodex blepharitis. Demodex blepharitis is a condition characterized by inflammation of the eyelid due to a Demodex mite infestation, which is being observed in 84% of the population at age 60 years and in 100% of those older than age 70 years.^9,10 As of August 2023, this was the first medication approved to treat demodex blepharitis.

Lotilamer was shown to eliminate mites in 50% of all patients who received the drug.¹¹ According to a prospective, randomized, controlled trial, statistically significant improvement of mite eradication and complete collarette cure was seen in comparison to the control.¹² Lotilamer eradicates mites in 67.9% of patients compared to 17.6% of patients in the control group (P<0.0001). This medication could allow for significant improvements in quality of life for patients who are susceptible to demodex blepharitis. Because of the FDA approval of this medication, a large population of older adults will be able to seek treatment for this uncomfortable disease to which they may be susceptible.

Because of the FDA approval of this medication, a large population of older adults will be able to seek treatment for this uncomfortable disease to which they may be susceptible. Image Credit: © wladimir1804 - stock.adobe.com

Zuranolone

This year the first oral medication indicated for postpartum depression was approved by the FDA. Zuranolone (Zurzuvae; Biogen), a neuroactive steroid and gamma-aminobutyric (GABA) acid receptor agonist, may be a life-altering medication for some new mothers who are experiencing persistent depressive symptoms longer than 2 weeks after childbirth.¹³ The once daily medication is taken by postpartum females for 14 days. Studies demonstrated improvement in symptoms on day 14 of treatment as well as maintenance of efficacy for 4 weeks after stopping the medication. In 2 studies, there was an average decrease of 15.6 to 17.8 in Hamilton Rating Scale for Depression (HAMD-17) score observed in women taking zuranolone, which was significantly better than those taking placebo (P<0.05).

It is worth noting that zuranolone does pass into breast milk and is not yet known if it can cause harm to the baby, and therefore formula feeding may be required.¹⁴ Since this medication affects GABA receptors, it can cause extreme sedation limiting driving and everyday tasks as a new mother. Until the patient knows how she will function on the medication, it may be advisable to have someone else around when caring for the infant. It is also important to note that because of its mechanism of action, this drug is pending scheduling from the DEA, which may be a barrier to use for some patients. Zuranolone should be available in 2024 after a determination on DEA scheduling is made.

Gepirone

Gepirone (Exuaa; Mission Pharmacal Company) is approved for the treatment of adults with major depressive disorder (MDD). Gepirone is a first-in-class selective 5HT1a receptor agonist and is unique due to the fact it selectively targets the serotonin 1a receptor, which acts developmentally to establish normal anxiety-like behaviors.^15-17 Gepirone has been shown to not only be efficacious in acute treatment of MDD but also continued treatment of MDD. A clinical trial found the use of gepirone lead to a significant improvement of HAMD-17 score from baseline to 8 weeks when compared to the placebo (-9.04 vs. -6.75; P<0.05).¹⁶

Sexual dysfunction is a common AE associated with many of the treatments for MDD and has been a barrier to treatment for some patients. Because of this medication’s mechanism of action, sexual dysfunction is notshown to be an AE of gepirone and could be a consideration in patients who have experienced this untoward effect with other antidepressants or for whom are resistant to treatment over concerns about sexual dysfunction potential. Unfortunately, while gepirone has been shown to be effective and well tolerated compared to placebo, there are no ongoing trials comparing gepirone to other agents on the market and its overall place in therapy remains unknown.

RSV Prevention

RSV Vaccine, Adjuvanted

One of the most talked about topics in pharmacy in 2023 was the approval of the respiratory syncytial virus (RSV) vaccine, adjuvanted (Arexvy; GSK) for adults aged 60 years and older. The RSV vaccine, adjuvanted was shown to be 86.7% (95% CI, 53.8 to 96.5) effective against symptomatic RSV infection. Only 6% (2 of 31 patients) of patients inoculated with the virus became infected after receiving the vaccine.¹⁸

RSVpreF Vaccine

In September 2023, RSVpreF vaccine (Abrysvo; Pfizer) was approved for pregnant women to help protect infants from RSV.¹⁹ This vaccine reduces RSV hospitalizations in babies by 57% within the first 6 months of life. For optimal protection, it is recommended that mothers receive one dose of the vaccine between weeks 32 and 36 of pregnancy. RSVpreF can be given by any health care provider certified to administer vaccinations, but it will most likely be administered at prenatal care check-ups rather in the pharmacy.

Nirsevimab-alip

Another advancement toward prevention of RSV includes the monoclonal antibody injection nirsevimab-alip (Beyfortus; Sanofi) indicated for all infants who are less than 8 months of age and born during or are entering their first RSV season; it should be given at least 2 weeks prior to the start of RSV season (which may vary by region) for adequate protection.^22,23 Previous RSV prevention options for infants were reserved only for those who were born prematurely. Children between the ages of 8 and 19 months who are considered at high risk for RSV infection, and entering their second RSV season, may also receive this injection.²⁰

In one clinical study, nirsevimab-alip reduced medically attended RSV lower respiratory tract infections (MA RSV LRTI) by 70%, with significantly fewer infants who received the medication experiencing MA RSV LRTI compared to those who received placebo (2.6% vs. 9.5%; p< 0.05).²² Infants born within 14 days after their mother receives the RSVpreF vaccine should also receive an injection of nirsevimab-alip,because the mother has likely not produced antibodies yet by the time of the child’s birth.²¹ However, babies born to mothers who received RSVpreF more than 2 weeks before delivery should be adequately protected and do not need to receive nisevimab-alip. It’s possible this dosing recommendation may be confusing to providers and patients, and it is important that this distinction be clearly made to ensure appropriate vaccine stewardship.

Clindamycin Phosphate, Adapalene, and Benzoyl Peroxide

The FDA recently approved the first triple-combination topical treatment for acne in patients aged 12 years and older. Clindamycin phosphate, adapalene, and benzoyl peroxide (Cabtreo; Bausch Health Companies) is a topical agent containing adapalene, benzoyl peroxide, and clindamycin phosphate, all of which are known to be efficacious agents for reducing acne.²⁴ Most patients dealing with acne have extensive skincare regimens that involve multiple agents which can be burdensome to use. The approval of an agent that combines multiple medications into one product is an encouraging step into improving patient adherence and makes treatment more convenient.

Clindamycin phosphate, adapalene, and benzoyl peroxide has been shown to reduce inflammatory lesions by an average of 75.7% and noninflammatory lesions by over 72%.²⁵ However, the clindamycin component of the product lends the most barriers to use. For this reason, it should not be used in patients with a history of ulcerative colitis due to the risk of bloody diarrhea, severe colitis, and other untoward gastrointestinal effects associated with clindamycin use.

Acetaminophen and Ibuprofen

Acetaminophen and ibuprofen (Combogesic IV; AFT Pharmaceuticals) combines acetaminophen at 1000 mg and ibuprofen at 300 mg into one parenteral agent which has the potential to improve the safety and efficacy of pain management, particularly in the surgical setting.²⁶ Because of the increasing opioid abuse issue in the United States, companies are desperately searching for opioid alternatives, which makes this product a great option for pain relief.

Acetaminophen and ibuprofen was shown to have a quicker onset of action and higher pain relief compared to the individual products alone and was shown to reduce opioid use.²⁶ However, it was only compared to either ibuprofen or acetaminophen, and whether it provides better analgesic activity than administering the 2 medications separately is not currently known.

Vonoprazan

Vonoprazan (Voquezna; Phathom Pharmaceuticals), a potassium-competitive acid blocker, is a first-in-class medication approved in early November 2023 for the treatment of erosive esophagitis.²⁷ Vonoprazan’s mechanism of action differs from that of a typical proton pump inhibitor (PPI) in that it does not require acid activation due to the potassium-competitive binding.^28,29

Erosive esophagitis is a complication of one of the most prevalent gastrointestinal disorders in the United States, gastroesophageal reflux disorder (GERD). Erosive esophagitis has typically been recommended to be treated with a PPI or a histamine type-2 receptor antagonist.^29,30 Vonoprazan offers an alternative option for treatment which may have quicker onset of antisecretory effects, with an onset of action of 2 to 3 hours. Affordability of this medication may be a barrier for some patients, as a one month’s supply may cost as much as $600. Currently, vonoprazan is being studied for use in GERD in children and adults, as well as for the prevention of gastric and duodenal ulcers, and for use in the treatment of Helicobacter pylori infections.³¹ It is possible its role in therapy will expand in the future but may remain a second-line therapy in many patients due to cost considerations.

Conclusion

Because the pharmacy industry is always growing, it’s important to be knowledgeable about what’s to come so that pharmacists can treat their patients with the best therapies available. Dozens of medications are approved for use in the United States each year, though not all are novel or potentially practice changing. This article reviewed several key approvals from 2023, but many more highly anticipated approvals are expected from the FDA in 2024. These pipeline medications include novel treatments for management of phosphorous levels in hemodialysis patients, the use of MDMA in posttraumatic stress disorder, and new therapeutic options for Parkinson disease.^32-34 It is also possible that many of the medications approved in 2023 will receive expanded indications, if not in 2024 than within a few years following.

However, it is important to note that most of these medications have limited data available, which makes it difficult to determine their place in therapy, with the exception of those approved for conditions where no treatment previously existed. This is particularly true given the increased cost that these medications will likely pose compared to older agents. As more data becomes available, it is reasonable to expect indications and recommendations to change. Overall, the approval of these medications with the potential to make positive impacts on patient care is encouraging.

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