Version August 2025
The following material represents a subset of new drugs, drug approvals, drug warnings, and drugs removed from the market from the past six months. This is not a complete list; it includes those topics considered by the authors and editors to be of particular interest or importance. For a complete list of new drug approvals, see /lco/action/index/newapprovals/patch_f (an additional subscription may be required).
You can check drug interactions by going to the drug interactions program included with UpToDate.
GENERAL DRUG THERAPY
Two-bag acetylcysteine dosing protocol for acetaminophen poisoning (April 2025)
There are many acetylcysteine (N-acetylcysteine) dosing protocols for acetaminophen poisoning, including the 21-hour three-bag intravenous (IV) protocol and a simplified 20-hour two-bag IV protocol. A meta-analysis with more than 7600 patients found that a two-bag protocol, as compared with the three-bag protocol, was associated with fewer nonallergic anaphylactic reactions and other adverse events (3 versus 11 percent) without an increased risk of hepatoxicity [1]. Given these findings, we suggest use of the two-bag protocol instead of other protocols. For a patient with an acute acetaminophen ingestion, regardless of which protocol is chosen, it should deliver at least 300 mg/kg acetylcysteine orally or IV during the first 20 to 24 hours of treatment. The acetylcysteine IV solution product label has been updated to include the two-bag protocol. (See "Acetaminophen (paracetamol) poisoning: Management in adults and children", section on 'Simplified 20-hour (two-bag) intravenous protocol'.)
Inhaled sevoflurane not beneficial in acute respiratory distress syndrome (April 2025)
Preliminary data suggested that the gaseous anesthetic sevoflurane may be efficacious as a sedative in mechanically ventilated patients. However, in a trial of 687 patients with early moderate to severe acute respiratory distress syndrome (ARDS), compared with patients treated with propofol, patients randomized to sevoflurane had fewer ventilator-free days (between-group difference -2.1, 95% CI -3.6 to -0.7) and lower 7- and 90-day survival (90.6 versus 86.5 percent; 47.1 versus 55.7 percent, respectively) [2]. In addition, patients receiving sevoflurane had higher lactate levels, acute kidney injury rates, and sevoflurane-specific adverse effects (eg, arginine vasopressin resistance and malignant hyperthermia). These findings do not support inhaled sevoflurane use as a sedative in patients with ARDS. (See "Sedative-analgesia in ventilated adults: Medication properties, dose regimens, and adverse effects", section on 'Sevoflurane'.)
Procalcitonin and antibiotic duration in sepsis (April 2025)
While procalcitonin (PCT) has a clear role in determining antibiotic duration for patients with community-acquired pneumonia, its role in managing sepsis is less clear. A recent multicenter randomized trial of 2760 adults with sepsis, reported a reduction in antibiotic duration for patients in whom a daily PCT-guided protocol was implemented compared with standard care (9.8 versus 10.7 days) [3]. However, over half of study participants had lower respiratory tract infections which may have impacted the outcome. Based upon these and other cumulating data in patients with sepsis, we support measuring PCT to guide antibiotic duration. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Initial investigations'.)
Treatment of Helicobacter pylori infection in adults (November 2024)
Over half of individuals in the United States with Helicobacter pylori infection continue to receive clarithromycin-based treatment regimens, despite rising rates of H. pylori resistance to clarithromycin and declining rates of treatment success with these regimens [4]. Recent guidelines from the American College of Gastroenterology reinforce the importance of using non-clarithromycin-based regimens for the initial and salvage treatment of H. pylori infection [5]. Preferred regimens for the empiric management of H. pylori infection in treatment-naïve adults include optimized bismuth quadruple therapy, rifabutin triple therapy, and vonoprazan-amoxicillin dual therapy. The guidelines also emphasize testing to confirm H. pylori eradication after treatment and discuss the role of antimicrobial susceptibility testing in H. pylori management. Based on available evidence, we suggest optimized bismuth quadruple therapy as the preferred regimen for H. pylori infection in treatment-naïve adults. (See "Treatment of Helicobacter pylori infection in adults".)
DRUG INTERACTIONS
Concurrent administration of parenteral olanzapine and a benzodiazepine not associated with increased risk of tracheal intubation (November 2024)
Concurrent use of intravenous or intramuscular olanzapine with a parenteral benzodiazepine has been discouraged based on a post-marketing report of excess sedation and respiratory depression, including 29 fatalities. In a retrospective study of nearly 700 patients treated for agitation in the emergency department, the 144 patients receiving parenteral olanzapine and a benzodiazepine within 60 minutes of each other had similar rates of tracheal intubation compared with those receiving two doses of parenteral olanzapine only (549 patients, 3.8 versus 3.5 percent, respectively) [6]. Other studies (most retrospective) have also found similar rates of complications. Combining parenteral olanzapine with a benzodiazepine is likely not associated with an increased risk of complications compared with olanzapine alone or other sedative agents; potential complications can be mitigated with proper monitoring and avoidance of this coadministration in patients with alcohol intoxication or compromised respiratory function. (See "The acutely agitated or violent adult: Pharmacologic management", section on 'Second-generation (atypical) antipsychotics'.)
DRUG OR INDICATION WITHDRAWALS
Inhaled sevoflurane not beneficial in acute respiratory distress syndrome (April 2025)
Preliminary data suggested that the gaseous anesthetic sevoflurane may be efficacious as a sedative in mechanically ventilated patients. However, in a trial of 687 patients with early moderate to severe acute respiratory distress syndrome (ARDS), compared with patients treated with propofol, patients randomized to sevoflurane had fewer ventilator-free days (between-group difference -2.1, 95% CI -3.6 to -0.7) and lower 7- and 90-day survival (90.6 versus 86.5 percent; 47.1 versus 55.7 percent, respectively) [2]. In addition, patients receiving sevoflurane had higher lactate levels, acute kidney injury rates, and sevoflurane-specific adverse effects (eg, arginine vasopressin resistance and malignant hyperthermia). These findings do not support inhaled sevoflurane use as a sedative in patients with ARDS. (See "Sedative-analgesia in ventilated adults: Medication properties, dose regimens, and adverse effects", section on 'Sevoflurane'.)
Lack of overall survival benefit for sacituzumab govitecan in metastatic urothelial carcinoma (December 2024)
Sacituzumab govitecan, an antibody-drug conjugate, initially received accelerated approval from the US Food and Drug Administration (FDA) for patients with advanced or metastatic urothelial carcinoma (mUC) previously treated with platinum-based chemotherapy and immunotherapy. However, in a randomized trial of over 700 such patients, sacituzumab govitecan failed to improve overall survival over chemotherapy [7]. Based on these data, the FDA withdrew regulatory approval for sacituzumab govitecan for the above indications [8], and we also no longer use it as later-line treatment of mUC. (See "Treatment of metastatic urothelial carcinoma of the bladder and urinary tract", section on 'No role for sacituzumab govitecan'.)
ADVERSE REACTIONS AND WARNINGS
Hypophosphatemia with intravenous ferric carboxymaltose (April 2025)
Several intravenous iron formulations are available, with similar efficacy and mostly similar adverse effects profiles. However, recent reports have emphasized a high rate of hypophosphatemia with ferric carboxymaltose (FCM). A new systematic review reported high rates of hypophosphatemia with FCM in randomized trials (50 to 92 percent, versus 2 to 8 percent with other intravenous iron formulations) [9]. This supports our practice of monitoring serum phosphate in all patients receiving more than one dose of FCM, especially individuals with borderline phosphate levels at baseline or receiving repeated doses. (See "Treatment of iron deficiency anemia in adults", section on 'Hypophosphatemia and cardiac iron uptake'.)
Monitoring neutrophil count during clozapine treatment (March 2025)
Clozapine is effective for treatment of resistant schizophrenia or schizophrenia accompanied by persistent suicidality. However, the need for frequent neutrophil count monitoring through the Clozapine Risk Evaluation and Mitigation Strategy (REMS) program has been a barrier resulting in its underutilization. The US Food and Drug Administration has voted to abolish the REMS program after determining that it did not measurably mitigate the risk of neutropenia beyond what the labeling alone could accomplish [10]. Clinicians are encouraged to monitor neutrophil counts as detailed in the prescribing information until new evidence-based guidelines for clozapine initiation and monitoring are suggested. (See "Schizophrenia in adults: Guidelines for prescribing clozapine".)
Safety of obeticholic acid for treating primary biliary cholangitis (February 2025)
The US Food and Drug Administration has updated safety information on obeticholic acid for treating primary biliary cholangitis (PBC). Since 2021, use of obeticholic acid has been limited to patients who do not have decompensated cirrhosis [11]. The recent safety update recommends monitoring patients receiving obeticholic acid with liver biochemistries because cases of liver injury have been reported in patients without cirrhosis. When we use obeticholic acid as second-line therapy for PBC in patients without cirrhosis, we monitor for symptoms of liver decompensation (eg, jaundice) and measure liver biochemistries every three months. (See "Overview of the management of primary biliary cholangitis", section on 'Subsequent therapy'.)
JAK inhibitors for Stevens-Johnson syndrome/toxic epidermal necrolysis (December 2024)
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe drug-induced mucocutaneous reaction for which there is no established pharmacologic treatment other than supportive care. Based on in vitro and preclinical data showing marked upregulation of the JAK/STAT pathway in both keratinocytes and immune cells in SJS/TEN, seven patients were treated with an oral JAK inhibitor (abrocitinib or tofacitinib) for two weeks [12]. All patients also received high-dose intravenous glucocorticoids. In all patients, JAK inhibition was associated with rapid clinical improvement and re-epithelialization without treatment-related adverse events. These findings suggest a beneficial effect of JAK inhibitors for SJS/TEN, but further studies are needed to confirm their efficacy and optimal use. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Management, prognosis, and long-term sequelae", section on 'JAK inhibitors'.)
Neutropenia/agranulocytosis from deferiprone (November 2024)
Deferiprone is an oral iron-chelating agent used to treat iron overload when phlebotomy cannot be tolerated. The most concerning adverse effect is neutropenia/agranulocytosis. A recent review of data from 15 clinical studies (977 patients) found 22 cases of agranulocytosis and 3 serious infections, 1 of which was fatal [13]. Review of post-marketing reports identified 176 cases of agranulocytosis, 19 serious infections, and 11 deaths, mostly from sepsis. Lower neutrophil counts (<200/microL) conferred the greatest risk, and the mean time to onset of agranulocytosis was approximately two years. These data emphasize the need to closely monitor neutrophil counts throughout deferiprone therapy. (See "Iron chelation: Choice of agent, dosing, and adverse effects", section on 'Deferiprone dosing + AEs (Ferriprox)'.)
Levonorgestrel intrauterine devices and breast cancer risk (November 2024)
Estrogen-progestin contraceptives have been associated with a small increase in risk of breast cancer, whereas the impact of progestin-only intrauterine devices (IUD) has been less clear. In an administrative database study, first-time levonorgestrel (LNG) IUD users (any dose) had a small increase in overall risk of breast cancer compared with matched nonusers of hormonal contraception (hazard ratio 1.4), in line with some prior studies [14]. To provide context and assist patients with assessing their own risk, we inform them that the breast cancer risk conferred by LNG IUDs appears to be modestly increased and similar to that of estrogen-progestin contraceptive pills. (See "Intrauterine contraception: Background and device types", section on 'Risk of cancer'.)
RECENT APPROVALS - ANTIMICROBIALS
Gepotidacin for acute simple cystitis (April 2025)
In 2025, the US Food and Drug Administration approved gepotidacin, a novel antibiotic that retains activity against organisms resistant to fluoroquinolones and other antibiotic classes, for treatment of acute simple cystitis (uncomplicated urinary tract infection [UTI]) in adult females. In trials, gepotidacin resulted in combined clinical and microbiologic cure rates that were either similar to (51 versus 47 percent) or higher than (59 versus 43 percent) those with nitrofurantoin [15]. Diarrhea was common. Because of antimicrobial stewardship concerns, we reserve this agent for directed therapy of gram-negative pathogens that are resistant to other drug classes; it is not indicated for complicated UTI (including pyelonephritis). (See "Acute simple cystitis in female adults", section on 'Directed antimicrobial selection'.)
Aztreonam-avibactam for complicated intra-abdominal infections (March 2025)
The US Food and Drug Administration has approved aztreonam-avibactam to be used in combination with metronidazole for treatment of complicated intra-abdominal infections (cIAI) [16]. Approval was based primarily on a randomized trial of 422 patients with either cIAI or hospital-acquired pneumonia that found similar rates of clinical cure and all-cause mortality with aztreonam-avibactam (plus metronidazole for cIAI) compared with meropenem (with or without colistin) [17]. Aztreonam-avibactam may be particularly useful for infections due to carbapenem-resistant Enterobacterales spp that produce metallo-beta-lactamases. The combination drug was approved for use in Europe in 2024. (See "Carbapenem-resistant E. coli, K. pneumoniae, and other Enterobacterales (CRE)", section on 'Carbapenemase testing is positive'.)
Sulopenem etzadroxil-probenicid for acute simple cystitis (November 2024)
In 2024, the US Food and Drug Administration approved sulopenem etzadroxil-probenecid, an oral penem antibiotic that has activity against some extended-spectrum beta-lactamase (ESBL)-producing organisms, for treatment of acute simple cystitis (uncomplicated urinary tract infection [UTI]) in adult females. In trials, differences in the combined clinical and microbiologic cure rates were not statistically significant when comparing sulopenem etzadroxil-probenecid with amoxicillin-clavulanate (62 versus 55 percent) or ciprofloxacin (66 versus 68 percent) [18,19]. Because of antimicrobial stewardship concerns, we reserve this agent for gram-negative pathogens that are resistant to all other drug classes; it is not active against Pseudomonas and should not be used for complicated UTI (including pyelonephritis). (See "Acute simple cystitis in female adults", section on 'Directed antimicrobial selection'.)
RECENT APPROVALS - CARDIOVASCULAR
Olezarsen for familial chylomicronemia syndrome (February 2025)
Olezarsen, a small interfering RNA that reduces apolipoprotein C-III (APOC3) production and reduces plasma triglycerides (TG), is now approved in the United States as an adjunct to diet for patients with familial chylomicronemia syndrome (FCS) who have severe hypertriglyceridemia and a high risk of acute pancreatitis [20]. Approval was based on a randomized trial in 66 patients with FCS comparing monthly subcutaneous olezarsen (50 or 80 mg) with placebo for 49 weeks [21]. Both doses of olezarsen reduced APOC3 levels and the incidence of acute pancreatitis at 53 weeks, but only the 80 mg olezarsen dose significantly reduced TG levels at six months. The most common adverse reactions with olezarsen were injection site reactions, decreased platelet count, and arthralgias. Based on these results, we recommend olezarsen as a component of treatment for individuals with FCS. (See "Hypertriglyceridemia in adults: Management".)
RECENT APPROVALS - DERMATOLOGIC AND ALLERGY THERAPIES
Topical roflumilast for atopic dermatitis (February 2025)
Roflumilast is a selective, highly potent phosphodiesterase-4 inhibitor with anti-inflammatory properties. In two identical randomized trials including over 1300 patients with mild or moderate atopic dermatitis (AD), more patients assigned to roflumilast cream 0.15% once daily achieved the primary endpoint of Investigator Global Assessment (IGA) clear/almost clear at four weeks compared with those assigned to a vehicle control [22]. Treatment-emergent adverse effects were mild or moderate and included headache, nausea, application site pain, and nasopharyngitis. Based on these data, topical roflumilast cream 0.15% was approved by the United States Food and Drug Administration for the treatment of mild to moderate AD in adults and children ≥6 years. (See "Treatment of atopic dermatitis (eczema)", section on 'Topical roflumilast'.)
RECENT APPROVALS - ENDOCRINE AND KIDNEY DISEASE THERAPIES
Crinecerfont receives regulatory approval for adjunctive management of hyperandrogenism in children ≥4 years with 21OHD CAH (April 2025)
Crinecerfont, a selective oral antagonist of the corticotropin-releasing factor (CRF) receptor type 1, was approved by the US Food and Drug Administration as an adjunctive therapy to glucocorticoids for patients age ≥4 years with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (classic 21-OHD CAH) who require supraphysiologic doses of glucocorticoids to suppress adrenal androgen production or who have signs of glucocorticoid excess despite appropriate glucocorticoid dosing [23]. Approval was based on effective suppression of adrenal androgens with lower glucocorticoid doses in a randomized trial of more than 100 children aged 2 to 17 years with classic 21-OHD CAH [24]. Additional data are needed to determine optimal dosing and approach to adjustment of glucocorticoid doses for patients treated with crinecerfont. (See "Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children: Treatment", section on 'Corticotropin-releasing factor (CRF) type 1 receptor antagonist (crinecerfont)'.)
Expanded approval for intranasal glucagon for hypoglycemia in young children with diabetes (April 2025)
The US Food and Drug Administration (FDA) has expanded regulatory approval for intranasal glucagon for the treatment of severe hypoglycemia in patients with type 1 and type 2 diabetes; while previously it was approved for those aged ≥4 years old, approval now includes those aged ≥1 year old. This expanded approval was based on a phase 1 single-arm study of seven patients age 1.8 to 4 years with type 1 diabetes [25]. All patients experienced an increase in blood glucose ≥20 mg/dL from baseline within 30 minutes of administration of 3 mg of intranasal glucagon. No serious adverse events were reported, although several minor events occurred (eg, vomiting, epistaxis, nasal discomfort and eye irritation). Based on these data, we consider intranasal glucagon to be a safe and effective alternative to intramuscular glucagon for the treatment of severe hypoglycemia in patients with diabetes aged 1 year and older. (See "Type 1 diabetes in children and adolescents: Prevention and management of hypoglycemia", section on 'Glucagon'.)
RECENT APPROVALS - HEMATOLOGIC AND ANTICOAGULANT
Concizumab for hemophilia A or B without inhibitors (January 2025)
Concizumab is a non-factor prophylaxis for hemophilia A and B that works by inhibiting tissue factor pathway inhibitor (TFPI). It was previously shown to be effective in individuals with hemophilia and an inhibitor and approved by the US Food and Drug administration (FDA) in late 2024 for this indication. A new randomized trial (explorer8) evaluated the safety and efficacy of concizumab in 148 people with hemophilia A or B without inhibitors and reported that, compared with no prophylaxis controls, individuals assigned to concizumab had reduced annualized bleeding rates [26]. These results suggest that concizumab may be more broadly useful as a form of non-factor prophylaxis for people with hemophilia. (See "Hemophilia A and B: Routine management including prophylaxis", section on 'Products that can be used for hemophilia A or B'.)
Remestemcel (mesenchymal stromal cells) approved for acute graft-versus-host disease in children (January 2025)
Systemic glucocorticoids effectively treat grade ≥2 acute graft-versus-host disease (aGVHD) in more than one-half of patients undergoing allogeneic hematopoietic cell transplantation, but there is no consensus on the preferred treatment for steroid-refractory (SR) aGVHD. Remestemcel-L, the first commercially available mesenchymal stromal cell (MSC) product, was associated with day-100 response in more than two-thirds of 54 children with SR aGVHD, including 44 percent complete responses [27]. No infusion-related or other adverse effects were reported. Remestemcel-L was recently approved by the US Food and Drug Administration for SR aGVHD in children ≥2 months, and we consider it an acceptable option for treating pediatric SR aGVHD. (See "Treatment of acute graft-versus-host disease", section on 'Mesenchymal stromal cells (MSCs)'.)
Revumenib for relapsed or refractory KMT2A-rearranged acute lymphoblastic leukemia (January 2025)
Revumenib is a novel inhibitor of binding of the lysine methyltransferase KMT2A with menin, which is seen in chromosome 11q23/KMT2A-rearranged acute lymphoblastic leukemia (ALL) and is associated with an especially poor prognosis. In a study of 57 patients with relapsed/refractory (r/r) KMT2A-rearranged ALL, revumenib was associated with a 63 percent response rate, including 23 percent complete remissions; 40 percent of patients were able to proceed to allogeneic transplantation [28]. Adverse effects include differentiation syndrome, QT interval prolongation, febrile neutropenia, and embryo-fetal toxicity. Revumenib was recently approved by the US Food and Drug Administration based on these data, and we now suggest its use for treatment of KMT2A-rearranged r/r ALL in patients ≥1 year of age. (See "Treatment of relapsed or refractory acute lymphoblastic leukemia in adults", section on 'KMT2A (chromosome 11q23) rearranged'.)
RECENT APPROVALS - NEUROLOGIC AND PSYCHIATRIC
Tenecteplase versus alteplase for intravenous thrombolysis of acute ischemic stroke (November 2024, Modified March 2025)
The benefit of intravenous thrombolysis (IVT) for acute ischemic stroke was initially established by randomized trials using alteplase. However, tenecteplase is easier to administer than alteplase, and there is mounting evidence that tenecteplase has efficacy and safety outcomes similar to alteplase. This evidence is bolstered by a recent meta-analysis of 11 randomized trials of IVT within 4.5 hours of acute ischemic stroke comparing tenecteplase (n = 3788) with alteplase (n = 3757) [29]. Tenecteplase and alteplase had similar rates of both excellent and good functional outcomes and similarly low rates of symptomatic intracerebral hemorrhage and mortality. For eligible patients with acute ischemic stroke, we recommend IVT using either alteplase or tenecteplase for treatment within 3 hours of the time last known well, and we suggest IVT with alteplase or tenecteplase for treatment within 3 to 4.5 hours of the time last known well. Tenecteplase was approved by the US Food and Drug Administration for this purpose in February 2025 [30]. (See "Approach to reperfusion therapy for acute ischemic stroke", section on 'Tenecteplase'.)
Mirdametinib for NF1-associated plexiform neurofibromas (February 2025)
The US Food and Drug Administration has approved a second mitogen-activated protein kinase (MEK) inhibitor, mirdametinib, for treatment of symptomatic, inoperable plexiform neurofibromas (PNs) in patients with neurofibromatosis type 1 (NF1) [31]. In a phase II multicenter trial in 114 such patients, miradametinib led to ≥20 percent volumetric tumor reduction in 41 percent of adults and 52 percent of children, with a median duration of response of 22 months [32]. Adverse effects were similar to those seen with selumetinib and other MEK inhibitors, including a risk of reduced left ventricular ejection fraction that requires regular monitoring with echocardiography during treatment. We use MEK inhibitors to manage PNs in patients with NF1 who have uncontrolled symptoms despite optimal surgical and supportive care. (See "Neurofibromatosis type 1 (NF1): Management and prognosis", section on 'Plexiform neurofibromas'.)
RECENT APPROVALS - ONCOLOGIC
Tislelizumab plus chemotherapy for metastatic esophageal squamous cell carcinoma (April 2025)
Tislelizumab, a PD-1 inhibitor, has been approved by the US Food and Drug Administration in combination with platinum-containing chemotherapy for the first-line treatment of advanced unresectable or metastatic esophageal squamous cell carcinoma (SCC) that expresses PD-L1 (≥1) [8]. This approval is based on the results of a randomized trial in which almost 500 such patients with a combined positive score (CPS) ≥1 experienced improved overall survival (OS) with the addition of tislelizumab to chemotherapy (median 17 versus 10 months) and had few side effects [33]. Based on these data, we consider tislelizumab plus chemotherapy to be an appropriate option for initial therapy for patients with advanced unresectable or metastatic esophageal SCC and CPS ≥1. (See "Initial systemic therapy for metastatic esophageal and gastric cancer", section on 'Tislelizumab plus chemotherapy'.)
Nivolumab-hyaluronidase for advanced renal cell carcinoma (March 2025)
There is interest in the use of nivolumab-hyaluronidase, a subcutaneous form of nivolumab, in cancers such as renal cell carcinoma (RCC) to reduce drug preparation and administration time. In a randomized trial of almost 500 patients with treatment-refractory advanced or metastatic clear cell RCC and no prior immunotherapy, nivolumab-hyaluronidase demonstrated similar pharmacokinetics and objective response rates relative to intravenous (IV) nivolumab (24 versus 18 percent) [34]. Based on these data, the United States Food and Drug Administration approved nivolumab-hyaluronidase in patients with advanced RCC that is intermediate or poor risk as maintenance therapy following combination IV nivolumab plus ipilimumab as well as those with advanced RCC who received prior antiangiogenic therapy [8]. (See "Systemic therapy for advanced and metastatic clear cell renal cell carcinoma", section on 'Nivolumab-hyaluronidase (subcutaneous)'.)
Vimseltinib for tenosynovial giant cell tumor (March 2025)
Vimseltinib, a tyrosine kinase inhibitor, has been approved by the US Food and Drug Administration for patients with tenosynovial giant cell tumor (TGCT) for whom additional surgery would cause functional limitations or severe morbidity [35]. It was approved based on an earlier placebo-controlled randomized trial that demonstrated an objective response rate of 40 percent in such patients [36]. In the trial there were no cases of drug-induced liver injury or potentially fatal hepatotoxicity, which has been observed with pexidartinib, an alternative agent for TGCT. We now suggest vimseltinib instead of pexidartinib for adult patients with TGCT. (See "Treatment for tenosynovial giant cell tumor and other benign neoplasms affecting soft tissue and bone", section on 'Vimseltinib (preferred)'.)
FOLFOX plus cetuximab and encorafenib for metastatic colorectal cancer (January 2025, Modified February 2025)
For patients with BRAF V600E-mutated metastatic colorectal cancer (mCRC), there is interest in using novel treatment approaches, such as encorafenib (a BRAF inhibitor) in combination with cetuximab (an epidermal growth factor receptor [EGFR] inhibitor). In a randomized trial of almost 500 patients with mCRC, at median follow-up of ten months, initial systemic therapy with FOLFOX plus cetuximab and encorafenib improved one-year overall survival (80 versus 66 percent) and objective response rates (61 versus 40 percent) compared with oxaliplatin-based chemotherapy with or without bevacizumab [37]. Based on these data, the US Food and Drug Administration approved encorafenib in combination with cetuximab and FOLFOX for the treatment of mCRC with a BRAF V600E mutation [38], and we recommend initial therapy with this combination. (See "Initial systemic therapy for metastatic colorectal cancer", section on 'RAS wild-type, BRAF V600E-mutant tumors'.)
Trastuzumab deruxtecan in hormone receptor-positive, HER2-low or ultralow breast cancer (September 2024, Modified February 2025)
Trastuzumab deruxtecan (T-DxD) has an expanding role in patients with hormone receptor-positive advanced breast cancer refractory to endocrine treatment, both for HER2-low (immunohistochemistry [IHC] 1+ or 2+ and in situ hybridization negative) and ultralow cancers (IHC 0 with membrane staining). In a randomized trial in 866 patients with hormone receptor-positive, HER2-low or ultralow disease who had received at least one line of endocrine based-therapy and no prior chemotherapy for metastatic disease, trastuzumab deruxtecan improved progression-free survival relative to chemotherapy (13.2 versus 8.1 months) [39]. Benefits were similar among patients with HER2-low and ultralow disease. Grade 3 or higher adverse events occurred in 53 and 44 percent of patients, respectively. Overall survival results are not yet mature. Based on these results, the US Food and Drug Administration has expanded approval of T-DxD to include patients with hormone receptor-positive, HER2-low or ultralow disease that has progressed on at least one line of endocrine therapy [39]. (See "Endocrine therapy resistant, hormone receptor-positive, HER2-negative advanced breast cancer".)
Zolbetuximab plus chemotherapy for advanced esophageal and gastric adenocarcinoma (January 2025)
For patients with advanced esophageal and gastric cancer, studies are evaluating novel targeted agents, such as zolbetuximab, an antibody against the protein Claudin 18.2 (CLDN18.2). In a combined analysis of two separate randomized trials with over 1000 patients with unresectable, HER2-negative, CLDN18.2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma, the addition of zolbetuximab to chemotherapy improved overall survival (HR 0.77) [40]. Based on these data, zolbetuximab in combination with fluoropyrimidine- and platinum-containing chemotherapy was approved by the US Food and Drug Administration for initial treatment of locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma that is CLDN18.2 positive [8]. Given other data showing benefit for immunotherapy in those with high combined positive scores (CPS), we consider both CLDN18.2 expression and CPS in choosing whether to pair zolbetuximab versus immunotherapy with chemotherapy in patients with advanced HER2-negative esophageal and gastric adenocarcinoma. (See "Initial systemic therapy for metastatic esophageal and gastric cancer", section on 'Zolbetuximab plus chemotherapy'.)
Tislelizumab plus chemotherapy for metastatic gastric and esophageal adenocarcinoma (January 2025)
Tislelizumab, a PD-1 inhibitor, has been approved by the US Food and Drug Administration in combination with platinum- and fluoropyrimidine-based chemotherapy for the first-line treatment of unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma that expresses PD-L1 (≥1) [8]. This approval is based on the results of a randomized trial in which the addition of tislelizumab to chemotherapy improved overall survival (OS) in approximately 1000 patients with such cancers regardless of PD-L1 expression status; however, this OS benefit was mostly driven by those with a combined positive score (CPS) ≥5. Based on these data, we consider tislelizumab plus chemotherapy to be an appropriate option for initial therapy for patients with advanced HER2-negative gastric and esophageal adenocarcinoma and CPS ≥5. (See "Initial systemic therapy for metastatic esophageal and gastric cancer", section on 'Tislelizumab plus fluorouracil and platinum'.)
Zanidatamab for HER2-positive metastatic biliary tract cancers (December 2024)
For patients with advanced or metastatic HER2-positive biliary tract cancers (cholangiocarcinoma and gallbladder cancer), there is interest in novel therapies such as zanidatamab, a bispecific antibody that targets two distinct HER2 epitopes. In a phase II trial of 80 patients with advanced or metastatic HER2-positive biliary tract cancers who progressed on gemcitabine-based therapy and had no prior exposure to HER2-targeted therapy, zanidatamab demonstrated an objective response rate of 41 percent and was well tolerated [41]. Based on these data, the US Food and Drug Administration granted accelerated approval to zanidatamab for adult patients with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer, and we consider it to be an acceptable option in this population. (See "Systemic therapy for advanced unresectable and metastatic cholangiocarcinoma", section on 'Zanidatamab'.)
Inavolisib in hormone receptor-positive, HER2-negative breast cancer (November 2024)
Trials are evaluating novel treatment strategies in those with advanced hormone receptor (HR)-positive/HER2-negative breast cancer with endocrine therapy-resistant disease, with promising results among those with PIK3CA-mutated cancers. In a randomized trial in 325 such patients who experienced recurrence on or within 12 months of adjuvant endocrine therapy, the addition of the alpha isoform-specific PI3K inhibitor and degrader inavolisib to fulvestrant and palbociclib improved progression-free survival (15 versus 7.3 months) [42]. There was a trend favoring overall survival that did not reach statistical significance, although survival data are immature (hazard ratio 0.64). Grade ≥3 adverse events occurred in 88 versus 82 percent. For patients with locally advanced or metastatic, endocrine therapy-resistant PIK3CA-mutated, HR-positive, HER2-negative breast cancer, we consider the combination of inavolisib with palbociclib and fulvestrant to be appropriate option, which now has regulatory approval in the United States [43]. (See "Treatment for hormone receptor-positive, HER2-negative advanced breast cancer", section on 'Alterations in the PI3K pathway'.)
Zenocutuzumab for advanced pancreatic or NSCLC cancers with an NRG1 fusion (December 2024, Modified February 2024)
The US Food and Drug Administration has approved the bispecific HER2- and HER3-directed antibody zenocutuzumab for two types of NRG1 fusion-positive advanced malignancies progressive on prior therapy; pancreatic adenocarcinoma and non-small cell lung cancer (NSCLC) [44]:
●In an open-label phase II trial that included 36 patients with advanced or metastatic NRG1-fusion positive pancreatic adenocarcinoma who progressed on prior systemic therapy, the objective response rate was 42 percent, with a median duration of response of seven months [45]. In the same study, in a subset of 93 patients with NSCLC, the response rate was 29 percent with a median duration of response of 12.7 months.
●Treatment-related grade ≥3 toxicities occurred in 7 percent of patients and included anemia, nausea, diarrhea, vomiting, abdominal pain, and elevated AST or ALT (1 percent or less for each).
We agree with the use of zenocutuzumab in these settings. (See "Second- and later-line systemic therapy for metastatic exocrine pancreatic cancer", section on 'NRG1 fusion-positive tumors' and "Personalized, genotype-directed therapy for advanced non-small cell lung cancer", section on 'NRG1 fusions'.
RECENT APPROVALS - OTHER
Inebilizumab for IgG4-related disease (April 2025)
Although rituximab (an anti-CD20 monoclonal antibody) is commonly used for the treatment of IgG4 related disease (IgG4 RD) refractory to glucocorticoids, this practice has not been well validated in clinical trials. Recently, the US Food and Drug Administration (FDA) granted approval for the use of inebilizumab, an anti-CD19 monoclonal antibody, for the treatment of IgG4 RD based on a trial of 135 patients with IgG4 RD randomized to receive inebilizumab (300 mg intravenous infusions on days 1 and 15 and week 26) or placebo [46]. At the end of 52 weeks of observation, patients treated with inebilizumab had fewer flares than patients treated with placebo (10 versus 62 percent). Patients assigned to inebilizumab were also more likely to have a flare-free, glucocorticoid-free, complete remission, than patients treated with placebo (odds ratio 5.0). Theoretically, antibodies directed against CD19 result in deeper depletion of the B-cell compartment than anti-CD20 antibodies; however, absent comparative data, the choice between these agents is based on payor preferences and the clinician’s experience with these agents. (See "Treatment and prognosis of IgG4-related disease", section on 'Rituximab or inebilizumab'.)
New copper 175 mm2 intrauterine device (March 2025)
Patients who desire long-acting contraception will have two copper intrauterine devices (IUDs) to consider. The novel copper 175 mm2 device (commercial name Miudella) has been approved for three years of use and will be commercially available later in 2025 [47]. Compared with the copper 380 mm2 IUD, the new device has less than half the copper, which may reduce uterine cramping and bleeding; the applicator has a smaller diameter and is rounded, which may make placement easier for nulliparous patients or those with cervical stenosis; and the nitinol frame is flexible, which may better adapt to the intrauterine cavity and potentially reduce expulsion risk. (See "Intrauterine contraception: Background and device types", section on 'Device types and characteristics'.)
Suzetrigine, a first-in-class nonopioid analgesic, now available for acute pain (March 2025)
Suzetrigine, a first-in-class nonopioid oral analgesic, has been approved by the US Food and Drug Administration for management of acute pain in adults and is now available. Suzetrigine is a selective inhibitor of the Nav 1.8 voltage-gated sodium channel, which is expressed in the dorsal root ganglia and is involved in transmission of nociceptive signals to the spinal cord. In randomized trials of 303 patients who had acute pain after abdominoplasty and 274 patients after bunionectomy, suzetrigine (100 mg orally followed by 50 mg orally every 12 hours) reduced pain scores compared with hydrocodone/acetaminophen (5 mg/325 mg orally every six hours) or placebo [48]. Further study is required to determine the role of suzetrigine in acute pain management. (See "Nonopioid pharmacotherapy for acute pain in adults", section on 'Suzetrigine, a novel Nav1.8 inhibitor'.)
Mirikizumab for moderate to severe Crohn disease (January 2025)
Mirikizumab (a monoclonal antibody that targets the p19 subunit of interleukin-23) is now approved in the United States for treating moderate to severe Crohn disease [49]. Approval was based on a randomized trial comparing mirikizumab with placebo in over 1000 patients with Crohn disease refractory to prior biologic or immunosuppressive therapy. Mirikizumab resulted in higher rates of achieving a composite endpoint defined as symptomatic improvement at week 12 in addition to clinical remission at week 52 (45 versus 20 percent) [50]. Rates of serious adverse events were lower in the mirikizumab group (10 versus 17 percent). We anticipate using mirikizumab as first- or second-line therapy in adults with moderate to severe Crohn disease. (See "Medical management of moderate to severe Crohn disease in adults", section on 'Anti-interleukin (IL) antibody therapy'.)
Guselkumab for moderate to severe ulcerative colitis (December 2024)
Therapeutic options for moderate to severe ulcerative colitis (UC) are expanding. In an induction trial comparing guselkumab (an anti-interleukin-23 antibody) with placebo in 701 patients with UC, guselkumab (200 mg at weeks 0, 4, and 8) resulted in higher rates of clinical remission after 12 weeks (23 versus 8 percent) [51]. In the maintenance trial including 568 patients, guselkumab (200 mg every four weeks or 100 mg every eight weeks) resulted in higher rates of clinical remission after 44 weeks (50 and 45 percent, respectively, versus 19 percent). The US Food and Drug Administration has approved guselkumab for adults with moderate to severe UC, and we may use it as first- or second-line therapy [52]. (See "Management of moderate to severe ulcerative colitis in adults", section on 'Anti-interleukin (IL) antibody-based therapy'.)
Extended-release sodium oxybate in children with narcolepsy (November 2024)
Extended-release sodium oxybate, dosed once nightly at bedtime, has been approved by the US Food and Drug Administration for use in children with narcolepsy who are ≥7 years of age [53]. This formulation is more convenient than immediate-release sodium oxybate, which requires patients to be awoken in the middle of the night for a second dose. The lowest starting dose is 4.5 g; if there is concern that this dose is too high (eg, for children weighing <45 kg), we advise starting with the immediate-release formulation to allow for a lower starting dose and more flexible titration (table 1). (See "Management and prognosis of narcolepsy in children", section on 'Sodium oxybate'.)
VACCINES
Revised dosing schedule for MenB-4C (Bexsero) (February 2025)
In December 2024, the US Centers for Disease Control published an updated dosing schedule for MenB-4C (Bexsero), one of two available meningococcal serogroup B vaccines [54]. Routine vaccination of healthy individuals now consists of two doses, separated by ≥6 months (table 2). Three doses (zero, one to two, and six months) should be administered to those at increased risk for serogroup B meningococcal disease and during an outbreak (table 3 and table 4). Previously MenB-4C was administered as two doses, separated by ≥1 month. This change was based on improved immunogenicity with the revised dosing schedule. MenB-4C is also available as part of a pentavalent vaccine (Penmenvy), which was approved for use in February 2025 [55]; updated recommendations on the use of this vaccine are pending. When administering serogroup B meningococcal vaccines, a single manufacturer's MenB products must be used for each dose of the primary series and all booster doses. Vaccine formulations are not interchangeable. (See "Meningococcal vaccination in children and adults", section on 'Vaccine schedules'.)
2025 immunization schedules for adults in the United States (February 2025)
The United States Centers for Disease Control and Prevention (CDC) has published the 2025 immunization schedule for adults (figure 1 and figure 2) [56]. Persons 65 years of age or older are now recommended to receive two or more doses of a 2024-2025 COVID-19 vaccine. Pneumococcal vaccine is now recommended for all adults 50 years or older, and the newest conjugate vaccine (PCV21) is now included in the recommendations. Respiratory syncytial virus (RSV) vaccine has a stronger recommendation for persons 75 years or older. Our approach to immunization is largely consistent with these recommendations. (See "Standard immunizations for nonpregnant adults", section on 'Immunization schedule for nonpregnant adults'.)
Egg allergy no longer a concern for any vaccines (February 2025)
Some vaccines contain trace amounts of egg protein (table 5), but none contain enough to cause reactions in egg-allergic patients. For the last several years, it has been recommended that patients not be asked about egg allergy prior to receiving influenza vaccine. More recently, data have accumulated to show that egg allergy is similarly not a concern for administration of the yellow fever vaccine. In the largest study to date, 171 children with egg allergy, including 24 percent with a history of anaphylaxis, underwent skin testing with the yellow fever vaccine and then received it regardless of skin test results, with no allergic reactions [57]. Thus, we no longer inquire about egg allergy prior to the administration of any vaccine. Vaccine providers should remain prepared to treat rare allergic reactions that may occur after any vaccine, but no special precautions are necessary for recipients with egg allergy. (See "Allergic reactions to vaccines", section on 'Hen's egg'.)
RSV vaccination and Guillain-Barré syndrome (January 2025)
In January of 2025, the US Food and Drug Administration issued a warning about Guillain-Barré syndrome (GBS) in persons receiving either of the glycoprotein subunit RSV vaccines [58]. In analyses of observational data from persons ≥65 years, there were an estimated seven excess cases of GBS per million doses of the adjuvanted vaccine (Arexvy) and nine excess cases of GBS per million doses of the bivalent vaccine (Abrysvo). By contrast, RSV disease in adults ≥65 years causes 60,000 to 160,000 hospitalizations and 6000 to 10,000 deaths annually. This information is important for patients considering RSV vaccination, with decisions tailored to individualized risk assessment for severe RSV disease (table 6). (See "Respiratory syncytial virus infection in adults", section on 'Risk of Guillain Barré'.)
2025 immunization schedule for infants, children, and adolescents published by the CDC (December 2024)
The United States Centers for Disease Control and Prevention has provided the 2025 updates for the routine immunization schedules for infants, children, and adolescents ≤18 years of age [59]. Notable changes in the 2025 schedules include an additional dose of COVID-19 vaccine for moderately or severely immunocompromised individuals and the addition of Vaxelis to PedvaxHIB as a preferred Hib vaccine for American Indian and Alaska Native infants. (See "Standard immunizations for children and adolescents: Overview", section on 'Routine schedule'.)
Lower age cutoff for pneumococcal vaccine indications (November 2024)
In October 2024, the United States Advisory Committee (ACIP) extended pneumococcal vaccination recommendations to include all adults ≥50 years of age, regardless of risk factors (table 7) [60]. Previously, the age threshold was ≥65 years for healthy adults and ≥19 years for those at risk for pneumococcal infection or severe complications from pneumococcal infection. This decision is based on knowledge that the incidence of pneumococcal disease starts to increase at age 50 (table 8) and the predicted reduction in invasive pneumococcal disease cases in certain underrepresented ethnic/racial groups within the United States. We agree with the new guidelines from the ACIP and now suggest pneumococcal vaccination beginning at age 50 for all adults. (See "Pneumococcal vaccination in adults", section on 'Indications for vaccination'.)
RSV vaccine effective in mild to moderately immunocompromised individuals (October 2024)
The respiratory syncytial virus (RSV) vaccine is recommended for immunocompromised individuals aged 60 and above, although the data on the efficacy of the RSV vaccine in this population is limited. In an electronic health records-based observational study that included over 10,000 predominantly mild to moderately immunocompromised individuals ≥60 years old (46 percent of whom had a malignancy), the adjusted RSV vaccine effectiveness against respiratory virus-associated hospitalizations in the first year of follow-up was 73 percent [61]. This study provides preliminary evidence of vaccine efficacy in this patient population and supports vaccination against RSV in immunocompromised individuals aged 60 and above. (See "Immunizations in adults with cancer", section on 'Respiratory syncytial virus (RSV)'.)
