Drugs

Koufakis, Theocharis; Mustafa, Omar G.; Ajjan, Ramzi A.; Garcia-Moll, Xavier; Zebekakis, Pantelis; Dimitriadis, George; Kotsa, Kalliopi

doi: 10.1007/s40265-022-01730-2pmid: 35678922

The management of hyperglycemia in patients admitted to hospital is mainly based on insulin therapy. However, the positive and rapid effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on cardiorenal outcomes raises the possibility that they might confer benefits to hospitalized patients. In recent, well designed, randomized trials (SOLOIST-WHF and EMPULSE) recruiting inpatients with heart failure (HF), SGLT2i demonstrated the potential to improve survival and quality of life and reduce the number of HF events, time to first HF event, hospitalizations, and urgent visits for HF compared with placebo. They were also well tolerated, whereas incidence of diabetic ketoacidosis was low. In EMBODY, empagliflozin was shown to be protective against the deleterious effects of cardiac injury in patients with acute myocardial infarction. In DARE-19, the administration of dapagliflozin to inpatients with cardiometabolic risk factors and COVID-19 was based on the hypothesis that the anti-inflammatory properties of SGLT2i could alleviate organ damage. Although the findings did not reach statistical significance, the efficacy and safety profiles of the drug were encouraging. These promising findings in the field of cardiometabolic medicine set the stage for future research to explore whether the benefits of gliflozins can expand to inpatients with non-cardiometabolic disorders, including sepsis, cirrhotic ascites, and malignancies. The concept of inpatient use of SGLT2i has evolved greatly over the past few years. The latest evidence suggests that SGLT2i may be effective and safe in the hospital setting, provided patients are carefully selected and closely monitored. Real-world data will prove whether present hope about inpatient use of gliflozins will transform into future confidence.

Rizk, John G.; Lippi, Giuseppe; Henry, Brandon M.; Forthal, Donald N.; Rizk, Youssef

doi: 10.1007/s40265-022-01742-ypmid: 35763248

Human monkeypox is a zoonotic orthopoxvirus with presentation similar to smallpox. Monkeypox is transmitted incidentally to humans when they encounter infected animals. Reports have shown that the virus can also be transmitted through direct contact (sexual or skin-to-skin), respiratory droplets, and via fomites such as towels and bedding. Multiple medical countermeasures are stockpiled for orthopoxviruses such as monkeypox. Two vaccines are currently available, JYNNEOSTM (live, replication incompetent vaccinia virus) and ACAM2000® (live, replication competent vaccinia virus). While most cases of monkeypox will have mild and self-limited disease, with supportive care being typically sufficient, antivirals (e.g. tecovirimat, brincidofovir, cidofovir) and vaccinia immune globulin intravenous (VIGIV) are available as treatments. Antivirals can be considered in severe disease, immunocompromised patients, pediatrics, pregnant and breastfeeding women, complicated lesions, and when lesions appear near the mouth, eyes, and genitals. The purpose of this short review is to describe each of these countermeasures.

Peng, Teng J.; Viscoli, Catherine; Khatri, Pooja; Wolfe, Stacey Q.; Bhatt, Nirav R.; Girotra, Tarun; Kamel, Hooman; Sheth, Kevin N.

doi: 10.1007/s40265-022-01729-9pmid: 35657478

Spontaneous intracerebral hemorrhage (ICH) constitutes 10–15% of all strokes, and is a significant cause of mortality and morbidity. Survivors of ICH, especially those with atrial fibrillation (AF), are at risk for both recurrent hemorrhagic and ischemic cerebrovascular events. A conundrum in the field of vascular neurology, neurosurgery, and cardiology has been the decision to initiate or resume versus withhold anticoagulation in survivors of ICH with AF. To initiate anticoagulation would decrease the risk of ischemic stroke but may increase the risk of hemorrhage. To withhold anticoagulation maintains a lower risk of hemorrhage but does not decrease the risk of ischemic stroke. In this narrative review, we discuss the evidence for and against the use of antithrombotics in ICH survivors with AF, focusing on recently completed and ongoing clinical trials.

Abuhelwa, Ziad; Alloghbi, Abdurahman; Alqahtani, Ali; Nagasaka, Misako

doi: 10.1007/s40265-022-01736-wpmid: 35759121

Background and ObjectiveTrastuzumab deruxtecan (T-DXd) is a novel anti-ERBB2 antibody drug conjugate that appears to be associated with an increased risk of lung toxicity. We performed a systematic review to describe the incidence, severity, and management of T-DXd-induced interstitial lung disease (ILD) or pneumonitis.MethodsWe searched PubMed/MEDLINE, Embase, Cochrane, and Web of Sciences through to 1 January, 2022, for human clinical trials that assessed T-DXd in adults with ERBB2-positive advanced solid tumors and described the rate of ILD/pneumonitis. Study screening was performed by two researchers. Data were extracted from the full-text articles.ResultsFourteen studies with a total of 1193 patients with different types of advanced solid malignancies were included in our systematic review. The overall incidence of all-grade ILD/pneumonitis cases that were adjudicated by an independent committee was 11.40% (ILD/pneumonitis cases, n = 136 out of total n = 1193). Grading of the adjudicated T-DXd-induced ILD/pneumonitis was reported in 122 patients with the majority of the cases (78.69%, n = 96) occurring as grade 1 or 2. Death was reported in 13 out of 122 (10.66%) patients. The highest incidence of ILD/pneumonitis was seen in patients with uterine carcinomatosis (26.47%) and non-small cell lung cancer (24.77%). Interstitial lung disease/pneumonitis events were treated with a dose interruption or reduction, treatment discontinuation, corticosteroids, and supportive care.ConclusionsInterstitial lung disease/pneumonitis is a well-described, serious, and potentially life-threatening adverse event that is associated with T-DXd. Further studies are needed to identify the risk factors and the underlying pathophysiology of T-DXd-induced ILD/pneumonitis to prevent occurrence and to develop effective management strategies.

Shirley, Matt

doi: 10.1007/s40265-022-01733-zpmid: 35793027

The introduction of multi-valent pneumococcal vaccines around the world, such as the 13-valent pneumococcal conjugate vaccine (PCV13), has had a significant effect in reducing the burden of disease caused by Streptococcus pneumoniae infection globally. However, S. pneumoniae serotypes not covered by PCV13 still cause significant disease. A 20-valent pneumococcal conjugate vaccine (PCV20; Prevnar20®; Apexxnar®) has recently been licensed for active immunisation for the prevention of invasive disease and pneumonia caused by S. pneumoniae in adults. PCV20 contains all components of PCV13 with the addition of polysaccharide conjugates of seven more serotypes, selected based on their generalised geographic distribution and relative prevalence as a cause of pneumococcal disease. The immunogenicity of PCV20 in adults has been demonstrated in a well-designed program of clinical trials which showed that PCV20 administered as a single dose by intramuscular injection induced robust immune responses to all 20 S. pneumoniae serotypes covered by the vaccine. PCV20 was well tolerated, with a tolerability and safety profile similar to that for PCV13. By expanding the coverage of disease-causing S. pneumoniae serotypes relative to other PCVs, PCV20 presents a valuable new tool with the potential to further reduce the impact of pneumococcal disease.

Keam, Susan J.

doi: 10.1007/s40265-022-01731-1pmid: 35727563

Tixagevimab 150 mg and cilgavimab 150 mg (EVUSHELDTM 150 mg + 150 mg solution for injection; tixagevimab + cilgavimab) is an intramuscular (IM) long-acting monoclonal antibody combination developed by AstraZeneca for the prevention and treatment of COVID-19. In March 2022, tixagevimab + cilgavimab was approved in the UK for pre-exposure prophylaxis of COVID-19 in adults who are not currently infected with SARS-CoV-2 and who have not had a known recent exposure to an individual infected with SARS-CoV-2 and who are unlikely to mount an adequate immune response to COVID-19 vaccination or for whom COVID-19 vaccination is not recommended, and in the EU for the prevention of COVID-19 in adults and adolescents aged ≥ 12 years and weighing ≥40 kg. In December 2021, tixagevimab + cilgavimab was granted Emergency Use Authorization by the US FDA for the pre-exposure prophylaxis of COVID-19 in adults and paediatric individuals (≥ 12 years of age and weighing ≥ 40 kg). This article summarizes the milestones in the development of tixagevimab + cilgavimab leading to this first approval for pre-exposure prophylaxis of COVID-19 in individuals who are not currently infected with SARS-CoV-2.

Dhillon, Sohita

doi: 10.1007/s40265-022-01732-0pmid: 35723803

Carotegrast methyl (Carogra®) is a small-molecule α4 integrin antagonist being developed by EA Pharma (formerly Ajinomoto Pharmaceuticals) and Kissei Pharmaceutical for the treatment of ulcerative colitis. The active metabolite of carotegrast methyl exerts an anti-inflammatory effect by blocking the interaction of α4β1 or α4β7 integrins and their ligands, VCAM-1 and MAd-CAM-1, thereby inhibiting the adhesion of inflammatory cells, including T cells, to vascular endothelial cells and extravasation into inflammatory sites. In March 2022, carotegrast methyl received its first approval in Japan for the treatment of moderate ulcerative colitis in patients who had inadequate response to 5-aminosalicylic acid. This article summarizes the milestones in the development of carotegrast methyl leading to this first approval for the treatment of moderate ulcerative colitis.

Hoy, Sheridan M.

doi: 10.1007/s40265-022-01734-ypmid: 35713845

Oteseconazole (VIVJOA™) is an orally administered azole antifungal agent developed by Mycovia Pharmaceuticals for the treatment of fungal infections. It inhibits cytochrome P450 (CYP) 51, thereby affecting the formation and integrity of the fungal cell membrane, but has a low affinity for human CYP enzymes due to its tetrazole metal-binding group. Oteseconazole is the first agent to be approved (in April 2022) for recurrent vulvovaginal candidiasis (RVVC) in the USA, where it is indicated to reduce the incidence of RVVC in females with a history of RVVC who are NOT of reproductive potential. Clinical development for the treatment of onychomycosis, and invasive and opportunistic infections is ongoing. This article summarizes the milestones in the development of oteseconazole leading to this first approval for reducing the incidence of RVVC in females with a history of RVVC who are NOT of reproductive potential.

Lamb, Yvette N.

doi: 10.1007/s40265-022-01737-9pmid: 35689762