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Phase III clinical study comparing olaparib (PARP-1/2 inhibitor; 300 mg bid) to physician’s choice (enzalutamide or abiraterone plus prednisone) in patients with metastatic castration-resistant prostate cancer. The most common adverse events (AEs) related to olaparib were anemia (39%), nausea and fatigue/asthenia (32% each). Olaparib-related fatal AEs were pneumonia and neutropenia (1 each). Other AEs are listed.

Phase I dose-escalation/expansion study of sapanisertib (TAK-228; mTOR inhibitor) in 198 patients with advanced solid tumors (116 in the dose-escalation phase and 82 in the expansion phase). Dose-limiting toxicities (DLTs) included hyperglycemia, maculo-papular rash, asthenia and stomatitis (all grade 3). The most common treatment-related adverse events (TRAEs) were hyperglycemia, nausea, stomatitis, vomiting, decreased appetite and diarrhea. 1 patient died from ventricular fibrillation and cardiac arrest (considered possibly related to sapanisertib). Other TRAEs and DLTs are listed.

Analysis of FAERS assessing the safety profile of DPP4 inhibitors (saxagliptin, sitagliptin, linagliptin and vildagliptin). The most frequently reported standardized MedDRA queries and preferred terms of interest with a statistically significant association with DPP4 inhibitors are listed.

Phase III study of Padcev (enfortumab vedotin-ejfv; nectin-4 inhibitor/tubulin polymerization inhibitor) in patients with urothelial cancer. The most common grade ≥3 adverse events (>5% patients) were rash, hyperglycemia, decreased neutrophil count, fatigue, anemia and decreased appetite. [Data from a Seattle Genetics communication announcing results from a phase III study of Padcev for urothelial cancer] Company Communication

Phase III study of Actemra/RoActemra (tocilizumab; interleukin-6 receptor, alpha subunit antagonist) for COVID-19 associated pneumonia. The most common adverse events reported in patients receiving tocilizumab were constipation (5.6%), anxiety (5.2%) and headache (3.2%). [Data from a Roche communication announcing results from a phase III study of Actemra/RoActemra for COVID-19 associated pneumonia] Company Communication

The most common side effects of Phelinun (melphalan; DNA alkylating agent) are myelosuppression, hematological toxicities, gastrointestinal toxicity and immune system disorders. Amenorrhea, ovarian disorders and premature menopause were also common. Major causes of morbidity and mortality in the allogeneic hematopoietic stem cell transplantation setting were infections and acute/chronic graft-versus-host disease. [Data from EMA summary of opinion for Phelinun] Regulatory Agency Communication

The most common side effects of Obiltoxaximab SFL (obiltoxaximab; protective antigen inhibitor) in healthy volunteers were headache, pruritus and urticaria. 10% subjects reported hypersensitivity reactions (including rash) and <1% reported anaphylaxis. [Data from EMA summary of opinion for Obiltoxaximab SFL] Regulatory Agency Communication

The most common side effects of Exparel (bupivacaine; sodium channel blocker) are dysgeusia and oral hypoesthesia. [Data from EMA summary of opinion for Exparel] Regulatory Agency Communication

The EMA’s CHMP has recommended the indication of Orfadin (nitisinone; 4-hydroxyphenylpyruvate dioxygenase inhibitor) be extended to include the treatment of alkaptonuria in adult patients. This is based on data from a clinical study comparing nitisinone to no treatment in 138 patients with alkaptonuria. The most common side effects were elevated levels of tyrosine, eye disorders such as eye pain and inflammation of the cornea (including keratopathy) and infections of the airways. Regulatory Agency Communication

The EMA’s CHMP has recommended the indication of Olumiant (baricitinib; JAK1/2 inhibitor) be extended to include the treatment of moderate-to-severe atopic dermatitis (MtSAD). This is based on 3 phase III studies of Olumiant as monotherapy or in combination with topical treatments in adults with MtSAD. The most common side effects included increased LDL cholesterol, upper respiratory tract infections and headache. Other infections were also reported, including herpes simplex. Regulatory Agency Communication

The EMA’s CHMP has recommended the indication of Velphoro (sucroferric oxyhydroxide; phosphate sequestrant) be extended to include control of serum phosphorus levels in children with chronic kidney disease (CKD). This is based on a phase III study of Velphoro including 85 children with CKD and hyperphosphatemia. The most frequent adverse reactions were gastrointestinal disorders, including diarrhea, vomiting, gastritis and discolored feces. Regulatory Agency Communication

Phase II study of lenvatinib plus pembrolizumab in 31 patients with previously-treated ovarian cancer. Treatment-related adverse events (≥10%) included hypertension (17 [55%] any grade; 6 [19%] grade 3), fatigue (13 [42%]; 3 [10%]), hypothyroidism (13 [42%]), decreased appetite (12 [39]), diarrhea (12 [39%]; 1 [3%]) and proteinuria (10 [32%]; 2 [6%]). 1 treatment-related death was reported due to hypovolemic shock. Congress Alert

Phase Ib study of elacestrant (estrogen receptor degrader; 400 mg qd) in 16 patients with advanced breast cancer. The most common treatment-emergent adverse events (TEAEs) were nausea (11 [68.8%] patients), fatigue (8 [50%]), dyspepsia (7 [43.8%]), vomiting (6 [37.5%]), decreased appetite, dysphagia and hot flush (5 [31.3%] each). Grade 3 TEAEs included anemia, circulatory collapse, esophagitis, cystitis and pulmonary embolism (1 [6.3%] each). 15 (93.8%) patients had elacestrant-related AEs, the most common being gastrointestinal disorders. Other TEAEs, including serious AEs, are listed.

Phase I study of ibezapolstat (DNA polymerase IIIC inhibitor) in 62 healthy volunteers. Treatment-related adverse events (TRAEs) were cough, dizziness, epigastric pain, headache, nasal congestion, dyspepsia and tachycardia. Other TRAEs are listed.

The FDA has updated the product information of Botox (onabotulinumtoxinA; synaptosomal-associated protein 25 inhibitor) to include eyelid edema following periocular injection as an adverse reaction reported postmarketing. Regulatory Agency Communication

Preliminary results from a phase Ib study of cavrotolimod (TLR9 agonist) plus pembrolizumab (PD-1 inhibitor) in patients with solid tumors. The most common adverse events were flu-like symptoms and injection-site reactions, which were possibly related to cavrotolimod’s mechanism of action. [Data from an Exicure communication announcing the results from a clinical trial of cavrotolimod] Company Communication

The special warnings and precautions for use section of the EMA EPAR for Blenrep indicates that it may cause corneal adverse reactions (the most common being keratopathy or microcyst-like epithelial changes in corneal epithelium); thrombocytopenia and platelet count decreased; and infusion-related reactions. Other warnings and precautions of belantamab mafodotin are listed. [Data from EMA European public assessment report for Blenrep (belantamab mafodotin; BCMA inhibitor/tubulin polymerization inhibitor)] Regulatory Agency Communication

Phase I study of LFA102 (prolactin receptor antagonist; 3-40 mg/kg q4w) in 14 patients with advanced breast or castration-resistant prostate cancer. Drug-related toxicities were reported in 64% patients. The most common adverse events (AEs) were nausea (21%), dry skin and peripheral edema (14% each). Other AEs are listed.

Characterization of the novel opioid kappa receptor agonist SHR0687. In vitro studies showed that SHR0687 has low affinity for hERG channels, indicating a high cardiac safety margin. In vivo experiments in rats showed that the blood barrier penetration capacity of SHR0687 is limited, suggesting a low risk of adverse central nervous system effects.

The Summary of Product Characteristics for Imbruvica (ibrutinib; BTK inhibitor) has been updated to include new safety and efficacy data from a phase III study of ibrutinib plus rituximab for chronic lymphocytic leukemia. Increased blood creatinine has been included to ibrutinib's product information as an adverse drug reaction. Regulatory Agency Communication

In a phase I clinical trial of the COVID-19 mRNA vaccine BNT162b2, adverse events reported after the second dose of 30 mcg BNT162b2 included fatigue (75% patients aged 18-55-years-old; 42% patients aged 65-85-years-old), headache (67%; 25%), muscle pain (58%; 25%), chills (58%; 17%), fever and joint pain (17%; 8% each). Diarrhea was observed after the first dose in 8% patients aged 18-55-years-old. [Data from a Pfizer presentation summarizing the company’s COVID-19 programs] Company Communication

Health Canada is reviewing the potential association between Fibristal (ulipristal acetate; progesterone receptor modulator) and the risk of serious liver injury. This follows the report of a new case of liver injury leading to liver transplantation in a patient treated with ulipristal acetate. Regulatory Agency Communication

First-in-human phase I study of MEDI1873 (efgivanermin alfa; GITR agonist; 1.5-750 mg) in 40 patients with advanced solid tumors. The most common treatment-related adverse events (TRAEs) were headache (10 patients [25%]), decreased appetite, infusion-related reaction (7 each [17.5%]), fatigue, nausea, vomiting (6 each [15%]) and diarrhea (5 [12.5%]). Other TRAEs are listed.

Conclusions from a Periodic Safety Update Report of Vemlidy (tenofovir alafenamide; reverse transcriptase inhibitor). Based on data from 21 spontaneous reports of renal events, the PRAC considers that prescribers and health care professionals must be informed about the need to monitor renal function prior to and during therapy with Vemlidy. Regulatory Agency Communication

The EMA has updated the product information of Reyataz (atazanavir sulphate; HIV protease inhibitor) to include new drug-drug interactions between Reyataz and lomitapide and the direct oral anticoagulants (DOACs) apixaban, dabigatran, edoxaban and rivaroxaban. These interactions are dependent on CYP3A4 and/or P-gp and may potentially lead to increased transaminases and hepatotoxicity with co-administration of lomitapide, Reyataz and ritonavir, and a higher risk of bleeding due to increased concentrations of the aforementioned DOACs. Regulatory Agency Communication

Health Canada has issued a safety review evaluating the potential association between Imbruvica (ibrutinib; BTK inhibitor) and the risk of hemophagocytic lymphohistiocytosis. 25 case reports of hemophagocytic lymphohistiocytosis during treatment with Imbruvica were identified. 10 cases were considered possibly related to treatment, 7 of these cases had fatal outcomes. Health Canada concluded that there is not enough evidence to establish an association between Imbruvica and hemophagocytic lymphohistiocytosis. Regulatory Agency Communication

Based on data from a Periodic Safety Update Report of ixazomib, the PRAC has recommended that the product information of products containing ixazomib should be updated to include the risk of thrombotic microangiopathy. Regulatory Agency Communication

The EMA has updated the product information of Darzalex (daratumumab; CD38 inhibitor) to include sepsis (frequency “common”) in section 4.8 of the SmPC. Information on the incidence of fatal infections and adverse reactions in elderly patients has also been added. Regulatory Agency Communication

Post-hoc analysis of a phase III study of lemborexant (OX1/2 receptor antagonist) in elderly patients with insomnia disorder. The most common treatment-emergent adverse events (TEAEs) during the first 6 months of treatment were somnolence (8.1% patients on 5 mg; 19% on 10 mg; 0% on placebo) and headache (9.3%; 1.2%; 6.7%). TEAEs observed with lemborexant 10 mg during the second 6 months of the study included headache and urinary tract infection (6.3% each). [Data from an Eisai communication announcing the presentation of clinical data of lemborexant in the SLEEP 2020 congress] Company Communication

Post-hoc analysis of 2 phase III trials of lemborexant (OX1/2 receptor antagonist) in patients with insomnia disorder and fatigue. Common treatment-emergent adverse events included somnolence (4.5% patients on 5 mg; 8.5% on 10 mg; 1.7% on placebo) after 1 month of treatment; somnolence (9.4%; 14.9%; 1.2%) and headache (7.7%; 7.4%; 6.5%) after 6 months; and nasopharyngitis (9.3%; 8.7%) after 12 months. [Data from an Eisai communication announcing the presentation of clinical data of lemborexant in the SLEEP 2020 congress] Company Communication

First-in-human study of ARO-APOC3 (apolipoprotein C3 expression inhibitor) in 12 healthy volunteers. Adverse events occurring in >1 subject were injection-site reactions (e.g. erythema, bruising; 58%), diarrhea (33%), vascular access-site bruising, headache (25% each), upper respiratory tract infection and dermatitis contact (17% each). Congress Alert

Meta-analysis evaluating serious adverse events associated with corticosteroids (dexamethasone, hydrocortisone and methylprednisolone) in patients with COVID-19 infection. Safety data is listed.

Study reporting the discovery of PF-07304814 and its active metabolite PF-00835231 (replicase polyprotein 1a inhibitors) as potential treatments for COVID-19. PF-07304814 and PF-00835231 were negative in the bacterial reverse mutation assay and did not induce the formation of micronuclei. Rats receiving intravenous PF-00835231 at doses up to 246 mg/kg/day showed drug-related elevations in triglyceride, cholesterol and phosphorus levels.

The special warnings and precautions for use section of the EMA EPAR for Rozlytrek (entrectinib) indicates that it may cause cognitive disorders including confusion, mental status changes, memory impairment and hallucinations; fractures including fractures localized in the lower extremity (with a predilection for hip, femur and tibia); hyperuricemia; congestive heart failure; QTc interval prolongation and fetal harm. Other warnings and precautions of entrectinib are listed. [Data from EMA European public assessment report for Rozlytrek (entrectinib; ALK/Ros/TRK inhibitor)] Regulatory Agency Communication

Health Canada has updated the product information of Esbriet (pirfenidone; TGFbeta inhibitor) to include the risk of drug-induced liver injury (manifested as elevations in transaminase levels). Pirfenidone-induced liver injury has been rarely associated with serious and/or fatal outcomes. Regulatory Agency Communication

In a phase III study in patients with diabetic macular edema, the rate of intraocular inflammation was equivalent for Beovu (brolucizumab) and aflibercept. [Data from a Novartis communication reporting topline results from a phase III trial comparing Beovu and aflibercept] Company Communication

Phase III trial of AR19 (immediate-release amphetamine; DAT/NET inhibitor; 20 or 40 mg qd) in 320 subjects with attention-deficit/hyperactivity disorder. The most common treatment-emergent adverse events were insomnia (8.4% patients at 20 mg qd; 9.3% at 40 mg qd), dry mouth (5.6%; 11.2%), decreased appetite (10.3%; 13.1%), palpitations (1.9%; 6.5%) and tachycardia (5.6%; 3.7%). [Data from an Arbor Pharmaceuticals communication announcing positive results from a pivotal study of AR19] Company Communication

Analysis of clinical trials evaluating the efficacy and safety of remdesivir (viral RNA polymerase inhibitor). The most common adverse events (AEs) were increased transaminases, nausea, headache and rash. Other common AEs included acute kidney injury, decreased glomerular filtration rate, decreased creatinine clearance or increased blood creatinine (7.4% with remdesivir vs 7.3% with placebo); pyrexia (5% vs 3.3%); and hyperglycemia or increased blood glucose (4.1% vs 3.3%). Hypersensitivity reactions (including infusion-related reactions and anaphylactic reactions) can occur during treatment with remdesivir.

Clinical study comparing the efficacy and tolerability of a fixed-dose combination of pitavastatin/fenofibrate (2/160 mg) to pitavastatin alone in 347 patients with mixed dyslipidemia. Common adverse drug reactions (ADRs) included ALT elevation (2/172 patients [1.16%] with pitavastatin/fenofibrate vs 1/171 [0.58%] with pitavastatin), AST elevation (2 [1.16%] vs 0) and increased GGT (1 [0.58%] vs 1 [0.58%]). Other ADRs are listed, including those reported in the extension study.

Preclinical studies evaluating the safety and immunogenicity of BBV152 (SARS-CoV-2 proteins-directed immunity inducer; 3-6 mcg) adjuvated with Algel or Algel-IMDG in mice, rats and rabbits. Histopathological examination of the injection site showed local inflammatory reactions likely caused by the aluminum salt of the vaccine adjuvant preparation. Other safety issues are listed.

Dogs receiving Librela (bedinvetmab; nerve growth factor inhibitor) may uncommonly experience mild reactions at the injection site (such as swelling and heat). [Data from EMA summary of opinion of Librela for pain associated with osteoarthritis in dogs] Regulatory Agency Communication

Phase III clinical trial of lumateperone (5-HT2A/D2 receptor antagonist/SERT inhibitor; 42 mg qd) as adjunctive therapy for treating major depressive episodes associated with bipolar disorder. The most common adverse events (≥5% and at least twice as frequent as with placebo) were somnolence, dizziness and nausea. [Data from an Intra-Cellular Therapies communication announcing positive topline results from a phase III study of lumateperone as adjunctive therapy in patients with bipolar depression] Company Communication

Disproportionality analysis of spontaneous reports of esketamine (NMDA receptor antagonist) submitted to FAERS. Safety signals were detected for dissociation, sedation, feeling drunk, nasal discomfort, oral hypoesthesia, dysgeusia, increased blood pressure, throat irritation, anxiety, hypertension, vomiting, dizziness, hypoesthesia, nausea, somnolence, dissociative disorder, autoscopy, derealization, euphoric mood, logorrhea, panic attack, paranoia, ataxia, akathisia, mania, fear, sensory disturbance, delusion, visual hallucination, taste disorder, oral discomfort, increased body temperature, hypokinesia, hallucination, retching, agitation, psychotic disorder, feeling abnormal, nightmare, disorientation, dysarthria, nervousness and speech disorder.

Phase II clinical trial of brensocatib (cathepsin C inhibitor; 10 or 25 mg qd) in patients with bronchiectasis. The most common adverse events (AEs) were cough (15/81 patients [19%] with 10 mg; 12/89 [13%] with 25 mg vs 10/85 [12%] with placebo), headache (8 [10%]; 12 [13%] vs 3 [4%]), increased sputum (9 [11%]; 9 [10%]; 6 [7%]) and dyspnea (3 [4%]; 9 [10%]; 2 [2%]). Other AEs are listed.

Phase II study of rozanolixizumab (IgG receptor FcRn large subunit p51 antagonist) in 66 patients with primary immune thrombocytopenia. The most common treatment-related adverse events (TRAEs) were headache (15 [22.7%] patients), vomiting (5 [7.6%]), diarrhea (4 [6.1%]) and pyrexia (3 [4.5%]). Other TRAEs are listed.

First-in-human phase I study of ARO-ANG3 (angiopoietin like 3 expression inhibitor; 100, 200 or 300 mg) in 12 healthy volunteers. Common adverse events included upper respiratory tract infection, vascular access site bruising/swelling (4 subjects each [33%]), ligament sprain/muscle strain/tendon injury (3 [25%]), diarrhea, injection-site bruising/discoloration, lethargy and abdominal pain/lower abdominal pain (2 each [17%]). Congress Alert

Case report of a 66-year-old female patient with COVID-19 who developed posterior reversible encephalopathy syndrome after anti-interleukin treatment with anakinra and tocilizumab.

Phase IV study of fixed-dose and shock-dependent hydrocortisone (glucocorticoid receptor modulator) in 384 patients with severe COVID-19. 2 events considered possibly related to treatment were reported in the fixed-dose hydrocortisone group: severe neuromyopathy and fungemia.

Phase II/III clinical trial of the recombinant granulocyte macrophage colony-stimulating factor molgramostim (300 mcg qd continuously or every other week) in 138 patients with autoimmune pulmonary alveolar proteinosis. Adverse events (AEs) included cough (32.6% with continuous molgramostim; 26.7% with intermittent molgramostim vs 23.4% with placebo), chest pain (21.7%; 4.4% vs 2.1%), nasopharyngitis (15.2%; 22.2% vs 12.8%), headache (13%; 15.6% vs 14.9%), dyspnea (10.9%; 15.6% vs 8.5%) and productive cough (8.7%; 6.7% vs 6.4%). Other AEs are listed.

Phase I study of TTI-621 (CD47 inhibitor) in patients with advanced relapsed/refractory hematologic malignancies. Platelet decreases and infusion-related reactions (IRRs) were observed. One dose-limiting toxicity of grade 3 IRR occurred at 1 mg/kg. [Data from a Trillium communication announcing updated data from 2 ongoing dose-escalation studies of TTI-622 and TTI-621] Company Communication

Phase III study comparing oral tebipenem HBr and intravenous ertapenem (bacterial penicillin-binding protein inhibitors) in patients with complicated urinary tract infection or acute pyelonephritis. The most common treatment-emergent adverse events (TEAEs) in both treatment groups were diarrhea (5%) and headache (3.8%). 3 Clostridioides difficile‑associated TEAEs were observed in the ertapenem group. [Data from a Spero communication announcing positive topline results from a phase III clinical trial of oral tebipenem HBr in complicated urinary tract infection and acute pyelonephritis] Company Communication

In a phase III clinical trial evaluating the efficacy and safety of odevixibat (ASBT inhibitor) in patients with progressive familial intrahepatic cholestasis, the most common treatment-related gastrointestinal adverse events were diarrhea/frequent bowel movements (9.5% with odevixibat vs 5% with placebo). [Data from an Albireo communication announcing positive topline results from a phase III study of odevixibat in progressive familial intrahepatic cholestasis] Company Communication

Whole-exome sequencing study evaluating the association between TNFRSF13B variants and the risk of pulmonary arterial hypertension. Results suggested that patients carrying a deleterious mutation in TNFRSF13B (c.226G>A [p.Gly76Ser]) are at high risk of developing pulmonary arterial hypertension. Congress Alert

A phase III study of AZD1222 (SARS-CoV-2 proteins-directed immunity inducer) has been put on clinical hold after a patient experienced an unexplained illness. Other sources suggest that the patient could have been diagnosed with transverse myelitis. Company Communication

The PMDA has updated the package insert of Relumina (relugolix; GnRH receptor antagonist) to include the risk of severe abnormal uterine bleeding. Regulatory Agency Communication

The PMDA has updated the package insert of Plaquenil (hydroxychloroquine sulfate; TLR7/9 antagonist), adding the risk of QT interval prolongation, ventricular tachycardia and torsades de pointes to the "Clinically Significant Adverse Reactions” section. Regulatory Agency Communication

The FDA has updated the product information of Vfend (voriconazole; fungal lanosterol 14-alpha demethylase inhibitor), adding the risk of toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms (DRESS) to the “warnings and precautions” section for severe cutaneous adverse reactions. The “adverse reactions” section has also been updated to include the risk of erythema multiforme (reported in clinical trials) and DRESS (reported in clinical trials and during postmarketing experience). Regulatory Agency Communication

The FDA has updated the product information of Piqray (alpelisib; PI3Kalpha/delta inhibitor) to include the risk of toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms (DRESS) in the “warnings and precautions” section for severe cutaneous adverse reactions. DRESS has been also added as an adverse reaction reported postmarketing. Regulatory Agency Communication

The FDA has updated the product information of Lamictal (lamotrigine; sodium channel blocker), adding tubulointerstitial nephritis (which may be accompanied by uveitis) as an adverse reaction reported postmarketing. Regulatory Agency Communication

The FDA has updated the product information of Erleada (apalutamide; androgen receptor antagonist) to include Stevens-Johnson syndrome and toxic epidermal necrolysis as adverse reactions reported postmarketing. Regulatory Agency Communication

Phase II clinical trial of oral emixustat hydrochloride (retinoid isomerohydrolase inhibitor; 5-40 mg qwk) in patients with proliferative diabetic retinopathy. Adverse events occurring more frequently than with placebo included delayed dark adaptation (9/12 patients [75%] with emixustat vs 1/11 [9.1%] with placebo), visual impairment (6 [50%] vs 1 [9.1%]), chromatopsia (4 [33.3%] vs 0), reduced visual acuity (4 [33.3%] vs 1 [9.1%]), vitreous floaters (4 [33.3%] vs 2 [18.2%]), day blindness (4 [33.3%] vs 3 [27.3%]) and vitreous hemorrhage (3 [25%] vs 1 [9.1%]). Erythropsia was more common with emixustat than with placebo. 1 patient experienced grade 3 delayed dark adaptation, which was considered drug-related.

Phase III study comparing azithromycin/hydroxychloroquine combination to hydroxychloroquine alone in 397 patients with severe COVID-19. Serious adverse events (SAEs) included acute kidney failure (147/241 patients [61%] with azithromycin/hydroxychloroquine vs 103/198 [52%] with hydroxychloroquine), gastrointestinal intolerance (61 [25%] vs 48 [24%]), QTc prolongation (47 [20%] vs 42 [21%]), decreased lymphocytes (27 [11%] vs 21 [11%]) and cardiac arrest (16 [7%] vs 13 [7%]). 2 (1%) patients in the azithromycin group and 3 (2%) in the control group died due to acute kidney failure. Other SAEs are listed.

First-in-human phase I study of RUC-4 (integrin alphaIIbbeta3 antagonist) in healthy volunteers and patients with coronary artery disease. Injection-site reactions (including bruising and bleeding) were reported.

First-in-human study of S62798 (carboxypeptidase B2 inhibitor) in healthy male volunteers. 1 treatment-related adverse event of infusion-site hematoma was reported in the lowest-dose cohort (3.2 mg). Congress Alert

The Australian Therapeutic Goods Administration (TGA) will remove bufexamac-containing creams from the market due to inadequate efficacy and high risk of serious skin reactions (such as allergic contact dermatitis). Regulatory Agency Communication

Phase I/IIa clinical trial of 177Lu-lilotomab satetraxetan (CD37 inhibitor) in 74 patients with non-Hodgkin lymphoma. The most common grade 3/4 drug-related adverse events (AEs) were neutropenia (16 patients [21%] grade 3; 8 [11%] grade 4), thrombocytopenia (14 [18%]; 6 [8%]), leukopenia (13 [17%]; 2 [3%]) and lymphopenia (12 [16%]; 1 [1%]). Dose-limiting toxicities included neutropenia, thrombocytopenia, hyponatremia, epistaxis and hematuria. One patient died from chronic myelomonocytic leukemia, considered possibly treatment-related. Other AEs are listed.

The warnings and precautions section of the FDA approved drug report for Gavreto indicates that it may cause interstitial lung disease and pneumonitis (including fatal reactions); grade 3 hypertension; hepatotoxicity (including serious hepatic adverse reactions); hemorrhagic events (one patient developed a fatal hemorrhagic event); and embryo-fetal toxicity (malformations and embryolethality have been observed following oral administration of pralsetinib to pregnant rats). Other warnings and precautions are listed. [Data from FDA approved drug report for Gavreto (pralsetinib; RET inhibitor)] Regulatory Agency Communication

The PRAC has recommended revoking the marketing authorization of ulipristal acetate (progesterone receptor modulator) for uterine fibroids based on reported cases of serious liver injury, including the need for liver transplantation. Regulatory Agency Communication

The FDA has updated the product information of Ultravate (halobetasol propionate; glucocorticoid receptor agonist), adding a warning about ophthalmic adverse reactions (including posterior subcapsular cataracts and glaucoma), which have been reported during postmarketing experience with topical corticosteroids. Regulatory Agency Communication

The FDA has updated the product information of Aristada (aripiprazole lauroxil; 5-HT1A receptor agonist and 5-HT2A/D2 receptor antagonist) to include oculogyric crisis and drug reaction with eosinophilia and systemic symptoms as adverse reactions reported postmarketing. Regulatory Agency Communication

2 phase I/II studies assessing the safety and immunogenicity of 2 formulations of Gam-COVID-Vac, a vector-based COVID-19 vaccine carrying the rAd26-S and rAd5-S genes, in 76 healthy subjects. The most common systemic and local reactions were pain at injection site (44 [58%]), hyperthermia (38 [50%]), headache (32 [42%]), asthenia (21 [28%]) and muscle and joint pain (18 [24%]). Other changes in laboratory parameters and systemic and local adverse events are listed.

The development of BI 1467335 (membrane primary amine oxidase inhibitor) for non-proliferative diabetic retinopathy has been discontinued due to the lack of a clear efficacy signal and the risk of dose-dependent drug interactions. [Data from a Boehringer Ingelheim communication announcing the discontinuation of the development of BI 1467335] Company Communication

Based on data from a Periodic Safety Update Report of atezolizumab (PD-L1 inhibitor), the PRAC considers that there is enough evidence to establish causal relationship between atezolizumab and uveitis (which is within the immune-related events already known for the class) and psoriasis. Regulatory Agency Communication

The PMDA is currently reviewing the association between tazobactam/piperacillin hydrate and the risk of hypokalemia. Regulatory Agency Communication

First case report of a 71-year-old man with chronic lymphocytic leukemia who developed a spontaneous hemothorax secondary to ibrutinib (BTK inhibitor). Congress Alert

First-in-human phase I study of M4112 (indoleamine 2,3-dioxygenase 1/tryptophan 2,3-dioxygenase inhibitor) in 15 patients with advanced solid tumors. The most frequent treatment-emergent adverse events (TEAEs) were fatigue (33.3%), nausea and vomiting (26.7% each). 1 serious TEAE of grade 3 allergic dermatitis was reported, considered related to treatment. 1 patient in the 800 mg bid arm experienced a dose-limiting toxicity of grade 3 allergic dermatitis. 2 patients in the 600 mg bid group required dose reductions due to grade 3 diarrhea and grade 3 rash. Other TEAEs are listed.

Phase I study of tafolecimab (PCSK9 inhibitor) in 58 healthy subjects. Treatment-emergent adverse events occurring more commonly with tafolecimab than with placebo included blood creatine phosphokinase increase, upper respiratory tract infection, white blood cells in urine, electrocardiogram QT prolongation, asthenia and arthralgia. Congress Alert

Study analyzing the JADER database for immune-related adverse events associated with immune checkpoint inhibitors. The RORs of pneumonitis, including interstitial lung disease, for nivolumab, pembrolizumab and ipilimumab were 7.02 (95 CI: 6.55-7.52), 9.08 (8.28-9.97) and 1.74 (1.27-2.38), respectively. The median onsets of myocarditis caused by nivolumab and pembrolizumab were 28.0 (quartiles 25-75%: 15.5-60.5) and 18.0 (13.0-44.5) days, respectively.

Phase III study of nitisinone (4-hydroxyphenylpyruvate dioxygenase inhibitor; 10 mg qd) in patients with alkaptonuria. The most common adverse events (AEs) occurring more frequently than with placebo were increased weight (14/69 [20.3%] with nitisinone vs. 4/69 [5.8%] with placebo), keratopathy (9 [13%] vs. 0), fall (8 [11.6%] vs. 6 [8.7%]), eye pain (8 [11.6%] vs. 0), arthralgia (6 [8.7%] vs. 4 [5.8%]), headache (6 [8.7%] vs. 2 [2.9%]) and dry eye (6 [8.7%] vs. 1 [1.4%]). Severe AEs included pulmonary embolism, myocardial infarction, pneumonia (2 each), cardiac arrest, cardiac failure, deep vein thrombosis, pathological fracture, endometrial cancer and eye pain (1 each). Other AEs are listed.

The FDA has updated the product information of Vumerity (diroximel fumarate; kelch-like ECH-associated protein 1/NF-kappaB inhibitor) to include serious herpes zoster and other opportunistic infections to the "Postmarketing Experience" section. A new warning has been added for herpes zoster and opportunistic infections (viral, fungal and bacterial). Regulatory Agency Communication

The FDA has updated the product information of Stribild (cobicistat + elvitegravir + emtricitabine + tenofovir disoproxil fumarate) to include a warning on autoimmune hepatitis. Regulatory Agency Communication

The FDA has updated the product information of Cubicin (daptomycin) to include drug reaction with eosinophilia and systemic symptoms (DRESS) and tubulointerstitial nephritis (TIN) to the "Postmarketing Experience" section. A new warning has been added for DRESS and TIN. Regulatory Agency Communication

The FDA has updated the product information of Bevyxxa (betrixaban; coagulation factor Xa inhibitor) to include a warning about the increased risk of thrombosis in patients with triple positive antiphospholipid syndrome. The “Adverse Reactions” has been updated accordingly. Regulatory Agency Communication

Case report of 2 patients with severe bradykinin-mediated angioedema from a phase I study of IONIS-PKK-LRx (plasma kallikrein expression inhibitor). Patients were first treated with IONIS-PKKRx for 12-16 weeks and then with IONIS-PKK-LRx for 7-8 months. During treatment with IONIS-PKKRx both patients had injection-site reactions, whereas hospitalizations for Haemophilus influenzae pneumonia with respiratory failure and central-venous-catheter-associated infection were reported in 1 patient during treatment with IONIS-PKK-LRx. Safety data reported in the phase I study is listed.

The EMA has updated the product information of Effentora (fentanyl; opioid mu receptor agonist) to strengthen the warning of drug abuse and dependence and add information about endocrine effects. Regulatory Agency Communication

Results from two phase III studies comparing vadadustat (HIF-prolyl hydroxylase inhibitor) and darbepoetin alfa (erythropoietin receptor agonist) in patients with anemia due to chronic kidney disease. Treatment-emergent adverse events reported in the Correction study were end-stage renal disease (34.7% with vadadustat vs. 35.2% with darbepoetin alfa), hypertension (17.7% vs. 22.1%), diarrhea (13.9% vs. 10%), urinary tract infection (12.9% vs. 12%), peripheral edema (12.5% vs. 10.5%), hyperkalemia (12.3% vs. 15.6%), nausea (10% vs. 8.2%) and fall (9.6% vs. 10%). In the Conversion study pneumonia was also reported (10% vs. 9.7%). Vadadustat users did not have a lower risk of major adverse cardiovascular events (including non-fatal myocardial infarct and stroke) than darbepoetin alfa users (HR=1.17 [1.01-1.36]). [Data from an Akebia Therapeutics communication announcing top-line phase III data of vadadustat for anemia due to chronic kidney disease] Company Communication

The PMDA is currently reviewing the association between vonoprazan fumarate-containing medicines (listed) and the risk of shock, anaphylaxis and hepatic impairment. Regulatory Agency Communication

Review on remdesivir (viral RNA polymerase inhibitor) for COVID-19 in pediatric patients. Remdesivir is not recommended in pediatric patients with hepatic impairment or hepatotoxicity at baseline as it increases liver aminotransferase levels (11.7%). Increased ALT was observed in a 5-year-old child with acute lymphoblastic leukemia receiving remdesivir for concomitant SARS-CoV-2 infection. Drug-drug interactions have also been reported with remdesivir in combination with P-glycoprotein inhibitors such as hydroxychloroquine, azithromycin, cyclosporine, tacrolimus and amiodarone, which may have caused the hepatocellular toxicity.

Compass Pathways has filed paperwork for a Nasdaq initial public offering to take COMP360 (psilocybin; 5-HT2A receptor agonist) to phase III. In an ongoing phase IIb study in 216 patients, serious adverse reactions possibly drug-related have been reported in 2 patients, which consisted of adjustment disorder and suicidal ideation leading to hospitalization.

New Zealand’s Medsafe has issued a communication alerting of the risk of meningiomas associated with cyproterone acetate (androgen receptor antagonist). Regulatory Agency Communication

Phase I results of a phase I/II trial of NVX-CoV2373 (SARS-CoV-2 proteins-directed immunity inducer; 5-25 mcg) in 131 healthy adults. Common adverse events (AE) included injection site pain and tenderness, fatigue, malaise, muscle pain, myalgia, nausea and vomiting. Grade 3 AEs included arthralgia and headache. Abnormal levels of hemoglobin, ALT, AST, sodium, bilirubin and urea were noted. Other AEs are listed.

Medications associated with Kounis syndrome include beta-lactam antibiotics, non-steroidal anti-inflammatory drugs, intravenous iron preparations, rocuronium, diclofenac, carboplatin, clopidogrel and Mersyndol (paracetamol + codeine + doxylamine). [Data from the Medsafe Prescriber Update of September 2020] Regulatory Agency Communication

Case report of a patient receiving amphotericin B who developed hyperkalemia with subsequent fatal cardiac arrest. [Data from the Medsafe Prescriber Update of September 2020] Regulatory Agency Communication

Phase I/II study of selpercatinib (RET inhibitor) in patients with RET-mutant medullary thyroid cancer. Treatment-related adverse events (TRAEs) included dry mouth (39%), hypertension (30%; 12% grade 3), increased AST (28%; 7% grade 3; 1% grade 4) and increased ALT (26%; 10% grade 3; 1% grade 4). 2% patients discontinued selpercatinib due to TRAEs, including increased ALT and drug hypersensitivity (2 patients each). Other TRAEs are listed.

Results from the third dose cohort (n = 3) of a first-in-human phase I trial evaluating the effect of ADP-A2AFP specific peptide enhanced affinity receptor T-cells (5.1-5.6 E9 cells) in patients with hepatocellular carcinoma. One patient experienced abnormal liver chemistries considered possibly related to ADP-A2AFP. Patients had cytopenias (up to grade 4 leukopenia, lymphopenia and neutropenia) and febrile neutropenia related to lymphodepleting chemotherapy (fludarabine + cyclophosphamide). Congress Alert

First-in-human study of HM15211 (GIP/GLP-1/glucagon receptor agonist) in 41 obese adults. The most common adverse events were gastrointestinal disorders (9/31 subjects; 29%). 12 participants developed anti-drug antibodies. Congress Alert

The warnings and precautions section of the FDA approved drug report for Sogroya indicates that it may cause fluid retention and lipohypertrophy/lipoatrophy. Growth hormone products may cause increased mortality in patients with acute critical illness; increased risk of malignancy progression and neoplasms (including new skin malignancies); new onset type 2 diabetes mellitus and glucose intolerance; intracranial hypertension; serious systemic hypersensitivity reactions (including anaphylactic reactions and angioedema) in the postmarketing setting; hypoadrenalism; worsen hypothyroidism; pancreatitis; and increased levels of inorganic phosphorus, alkaline phosphatase and parathyroid hormone with somatropin therapy. Other warnings and precautions of growth hormone therapies are listed. [Data from FDA approved drug report for Sogroya (somapacitan-beco; growth hormone receptor agonist)] Regulatory Agency Communication

First-in-human study of FM101 (A3 receptor antagonist) in healthy volunteers. The most frequent adverse events (AEs) were in the gastrointestinal tract, including nausea and diarrhea. Other AEs included fatigue and headache. Congress Alert

First-in-human phase I study of GB002 (PK-10571; PDGFRalpha/beta inhibitor) in 62 healthy volunteers. The most common adverse events were respiratory-related events such as throat irritation and cough. Congress Alert

Meta-analysis reporting an association between systemic lupus erythematosus and TNFSF4 polymorphisms rs1234315T/C (favoring T; odds ratio = 1.40; 95% CI: 1.15-1.70; 0.00087), rs2205960G/T (favoring T; 1.32; 1.09-1.60; 0.0037) and rs704840T/G (favoring G; 1.41; 1.17-1.7; 0.0003) in Mexican patients.

Case report of a 70-year-old man receiving olanzapine for severe chronic psychosis (5-HT2A/2C/3 and D2 receptor antagonist) who suffered fecaloma leading to fatal multi-organ failure.

Review of itolizumab (CD6 inhibitor) and its application in treating COVID-19. In a phase II study, adverse events (AEs) included infusion-related reactions (IRRs) such as chills (5.69%) and pyrexia (4.88%). In a phase III study, AEs included IRRs, pyrexia, upper respiratory tract infections, pruritus, diarrhea and a reduction in the mean absolute lymphocyte count.

Phase I clinical study of TQA3526 (farnesoid X receptor agonist) in healthy Chinese subjects. The most common treatment-emergent adverse events were pruritus, liver injury and abdominal disorders, which were suspected to be due to the drug’s mechanism. Congress Alert

The FDA has updated the product information of hydrochlorothiazide-containing products to include the risk of non-melanoma skin cancer, mainly squamous cell carcinoma, as an adverse event identified postmarketing. Regulatory Agency Communication

Phase I trial of human umbilical cord-derived mesenchymal stem cells infusions (3E7 cells) in 18 patients with COVID-19 pulmonary disease. Infusion associated events occurred in 2 patients, including facial flushing and fever.

The special warnings and precautions for use section of the EMA EPAR for Idefirix (imlifidase) indicates that it may cause infusion-related reactions; reactivation of live-attenuated vaccines and/or latent tuberculosis and respiratory tract infections due to temporary reduction of IgG (hypogammaglobulinemia); temporary reduction of vaccine protection; anti-imlifidase antibodies formation; and antibody-mediated rejection as a consequence of rebound of donor-specific antibodies. [Data from EMA European public assessment report for Idefirix (imlifidase)] Regulatory Agency Communication

Based on data from a Periodic Safety Update Report of pancuronium (muscle-type nicotinic receptor antagonist), the PRAC has recommended updating the product information to include the risk of myopathy and post-operative pulmonary complications. Regulatory Agency Communication

The warnings and precautions section of the FDA approved drug report for Winlevi indicates that it may cause local skin reactions (including erythema/redness, pruritus, scaling/ dryness); and hypothalamic-pituitary-adrenal axis suppression. [Data from FDA approved drug report for Winlevi (clascoterone); androgen receptor antagonist)] Regulatory Agency Communication

Phase I/IIa study of BAY 1817080 (P2X3 receptor antagonist; 10-750 mg bid) in 61 patients with refractory chronic cough. Taste-related adverse events were reported in 5%, 10%, 15% and 21% of patients on 10, 50, 200, and 750 mg, respectively, and 3% patients on placebo. Congress Alert

Phase II clinical trial evaluating the safety and efficacy of CR4056 (imidazoline I2 receptor agonist) in 213 patients with various osteoarthritis phenotypes. The most common adverse event was mild headache. Congress Alert

The EMA has updated the product information of Zejula (niraparib; PARP-1/2 inhibitor) to include hypersensitivity, confusional state and pneumonitis as adverse drug reactions with frequency "common", "uncommon" and "uncommon", respectively. Regulatory Agency Communication

Phase I study of tenalisib (PI3Kdelta/gamma inhibitor) in 58 patients with T-cell lymphoma. The most common treatment-related adverse events (TRAEs) were increased alanine aminotransferase, increased aspartate aminotransferase (18 [31%] each), diarrhea (12 [20.7%]), fatigue (9 [15.5%]) and increased gamma-glutamyltransferase (7 [12.1%]). Grade 3/4 adverse were anemia (5 [8.6%]), neutropenia, hyponatremia (4 [6.9% each]) and thrombocytopenia (3 [5.2%]). Serious TRAEs were pyrexia, increased international normalization ratio, sepsis syndrome, diplopia, hypersensitivity and skin infection. Dose-limiting toxicities were grade 3 increased alanine aminotransferase and erythematous rash. Other TRAEs are listed.

Observational study of ruxolitinib (JAK1/JAK2 inhibitor; 5 or 10 mg bid) in 34 patients with Covid-19 infection. The most common adverse events (AEs) were anemia (19 [55.9%]), urinary tract infection (10 [29.4%]), increased creatinine (8 [23.5%]), thrombocytopenia and increased aminotransferase (5 [14.7%]). Grade 3 AEs included anemia (10 [29.4%]), increased creatinine (3 [8.8%]), bleeding, sepsis, stroke, thrombocytopenia and thrombosis (1 [2.9%]). Other AEs are listed.

Study assessing the adverse events (AE) profile of the CD20 inhibitors rituximab and ocrelizumab using the FAERS database. The most common AEs of rituximab (n = 623) and ocrelizumab (n = 7948) were infusion-related reaction (4.82%) and urinary tract infection (10.52%), respectively. The strongest drug-AE associations for rituximab and ocrelizumab were ear pruritus (ROR = 47.53) and oral herpes (ROR = 38.99), respectively. Infections were more common with ocrelizumab than rituximab (21.93% vs. 11.05%).

Clinical study of 531 patients with RET fusion-positive non-small-cell lung cancer treated with selpercatinib (RET inhibitor). The most common grade ≥3 adverse events (AEs) were hypertension (14%), increased alanine aminotransferase levels (12%), increased aspartate aminotransferase levels (10%), hyponatremia (6%) and lymphopenia (in 6%). 2% patients discontinued selpercatinib due to a drug-related AE. Other AEs are listed.

The UK MHRA has issued a reminder of the risk and precautions associated with isotretinoin (retinoic acid receptor agonist). Isotretinoin has teratogenic effects and has been linked to psychiatric reactions (including depression, anxiety, psychotic symptoms and suicidal thoughts/attempts) and sexual dysfunction (mainly erectile dysfunction, decreased libido and vaginal dryness). Regulatory Agency Communication

The UK MHRA has issued a drug safety update on the link between baricitinib (JAK inhibitor) and the risk of diverticulitis, which has been added to the drug’s product information with frequency “uncommon”. Gastointestinal perforation as a complication of diverticulitis has been reported in 5 cases. Diverticulitis is also a potential side effect of tofacitinib. Regulatory Agency Communication

Phase II trial of dabrafenib and trametinib combination therapy in 43 patients with BRAF(V600E)-mutated biliary tract cancer. The most common adverse events (AEs) were pyrexia (grade 1-2 60%; grade 3 7%), nausea (42%; 0%), vomiting (33%; 2%), fatigue (33%; 0%) and diarrhea (30%; 0%). 9 patients (21%) had treatment-related serious adverse events, the most frequent being pyrexia (8 patients [19%]). Other AEs are listed.

First-in-human phase I study of MK-1248 (GITR agonist) alone or in combination with pembrolizumab in patients with advanced solid tumors. The most common adverse events (AEs) in the MK-1248 group were vomiting, abdominal pain (5/20 each), cough (4), headache, upper abdominal pain and diarrhea (3 each). In the combination group, the most common AEs were vomiting (8/17), anemia, decreased appetite (7 each), myalgia, nausea and fatigue (4 each). 2 patients receiving MK-1248 alone had a serious anaphylactoid reaction, considered treatment-related. Other AEs are listed.

The special warnings and precautions for use section of the EMA EPAR for Methylthioninium chloride Cosmo (methylthioninium chloride) indicates that it may cause serotonin syndrome in combination with serotonergic medicinal products; photosensitivity including cutaneous photosensitivity reaction; and general coloration (including blue-green color to urine, feces and a blue color to skin). [Data from EMA European public assessment report for Methylthioninium chloride Cosmo (methylthioninium chloride; NOS/MAO-A inhibitor and Tau aggregation inhibitor)] Regulatory Agency Communication

The FDA is removing the boxed warning about the risk of leg and foot amputations with Invokana (canagliflozin; SGLT2 inhibitor). This follows a review of new clinical trial data in which canagliflozin has shown benefits on heart and kidney disease and a lower risk of amputation than previously described, particularly when appropriately monitored. However, the amputation risk remains and is still described in the Warnings and Precautions section. Regulatory Agency Communication

Conclusions from a Periodic Safety Update Report on Exjade (deferasirox; iron sequestrant). The CHMP has recommended updating the drug's product information to include the risk of hepatic failure, gastrointestinal hemorrhage and gastric ulcer. Regulatory Agency Communication

Results from the phase I clinical trial of mRNA-1273 vaccine (SARS-CoV-2 proteins-directed immunity inducer; 25-250 mcg) against SARS-CoV-2 in healthy volunteers. Systemic symptoms reported after vaccination were arthralgia, fatigue, fever, chills, headache, myalgia and nausea. Local symptoms included induration, swelling and pain. Grade 3 fatigue, erythema and redness were reported. [Data from a Moderna presentation on the updated clinical results of its COVID-19 vaccine candidate] Company Communication

First case report of a 41-year-old patient with chronic hepatitis B who presented halitosis, gingival swelling and tooth loss after receiving tenofovir disoproxil fumarate (reverse transcriptase inhibitor).

Phase I study evaluating the safety and pharmacokinetics of VU319 (M1 receptor positive allosteric modulator; 60-600 mg) in 40 healthy adults. Adverse events (AEs) included headache, dizziness, blurry vision, olfactory auras, dysgeusia, warm ear and sweating. Other AEs are listed. Congress Alert

Phase I study of LY3372689 (protein O-GlcNAcase inhibitor) in 23 healthy volunteers. Treatment-related adverse events included pain of skin (3), headache, limb discomfort, pain in extremity (2 each), chest discomfort, muscle fatigue, nausea and macular rash (1 each). Congress Alert

First-in-human phase I study evaluating the safety and pharmacokinetics of NTRX-07 (CB2 receptor agonist; 0.3-8 mg/kg orally) in 36 healthy volunteers aged 18-60 years. Lightheadedness (vertigo) and mild subjective symptoms were reported in 2 subjects from the 4 mg/kg cohort and deemed to be dose-limiting. The dose in the next cohort was adjusted down from 6 mg/kg to 3.5 mg/kg. In the 3.5 mg/kg cohort 2 subjects reported light headedness (vertigo) and mild subjective symptoms. Congress Alert

Case report of an 80-year-old man with SARS-CoV-2 pneumonia who developed ritonavir- and lopinavir-induced eryptosis.

Phase Ib study of the FZD1/2/5/7/8 antagonist vantictumab plus paclitaxel in 48 patients with HER2-negative breast cancer. The most common adverse events (AEs) related to any study treatment were nausea (54.2%), alopecia (52.1%), fatigue (47.9%), peripheral neuropathy (43.8%) and neutropenia (31.3%). Grade 3-4 AEs related to any study treatment were neutropenia (20.1%) and peripheral neuropathy (6.3%). AEs related to vantictumab were fatigue (25%), nausea (22.9%) and constipation (16.7%). Other AEs are listed.

Phase III clinical study comparing combined tesetaxel (27 mg/m2) and capecitabine (1,650 mg/m2/day) to capecitabine monotherapy (2,500 mg/m2/day) in 685 patients with metastatic breast cancer. The most common grade ≥3 treatment-emergent adverse events (TEAEs) were neutropenia (71.2% with tesetaxel plus capecitabine vs 8.3% with capecitabine), diarrhea (13.4% vs 8.9%), hand-foot syndrome (6.8% vs 12.2%), febrile neutropenia (12.8% vs 1.2%), fatigue (8.6% vs 4.5%), hypokalemia (8.6% vs 2.7%), leukopenia (10.1% vs 0.9%) and anemia (8% vs 2.1%). Other TEAEs are listed. Company Communication

The FDA has updated the product information of Doptelet (avatrombopag) adding hypersensitivity reactions (including pruritus, rash, choking sensation, erythema, pharyngeal edema, pruritus generalized, macular rash, swelling face and swollen tongue) as adverse reactions identified postmarketing. Regulatory Agency Communication

Phase II study of soticlestat (cholesterol 24-hydroxylase inhibitor) in children with Dravet syndrome or Lennox-Gastaut syndrome. Treatment-emergent adverse events occurring in soticlestat-treated patients (≥5% difference in incidence compared to those receiving placebo) were lethargy and constipation. [Data from a Takeda communication announcing that a phase II study of soticlestat has met its primary endpoint] Company Communication

The special warnings and precautions for use section of the EMA EPAR for Kaftrio (elexacaftor/ivacaftor/tezacaftor) indicates that it may cause effect on liver function tests (including elevated transaminases and events of ALT or AST >5 x the ULN, or ALT or AST >3 x ULN); rash events, particularly in females taking hormonal contraceptives; and cataracts (including cases of non-congenital lens opacities without impact on vision) in pediatric patients. [Data from EMA European public assessment report for Kaftrio (elexacaftor/ivacaftor/tezacaftor)] Regulatory Agency Communication

The Australian Therapeutic Goods Administration will update the Product Information and Consumer Medicine information for hydrochlorothiazide-containing medications to include the increased risk of non-melanoma skin cancer (NMSC). The most common types of NMSC are basal cell carcinoma and squamous cell carcinoma. The increased risk of NMSC may be related to photosensitivity caused by hydrochlorothiazide. Regulatory Agency Communication

Health Canada has limited use of prescription cough and cold products containing codeine, hydrocodone or normethadone to adults only. This is due to the link between these products and opioid use disorders and related harms in children and adolescents. Regulatory Agency Communication

Phase II study comparing the long-term safety and efficacy of lemborexant (OX1/2 receptor antagonist; 5-15 mg) and placebo in 62 patients with irregular sleep-wake rhythm disorder and Alzheimer’s disease dementia. The most common treatment-emergent adverse events (TEAEs) included nasopharyngitis, fall and somnolence. Somnolence/sedation led to dose reduction in 4 patients (16%). Other TEAEs are listed. Congress Alert

Audentes Therapeutics have reported that a third patient treated with AT132 (myotubularin gene therapy; 3 x 10^14 vg/kg) in the ASPIRO trial has died from gastrointestinal bleeding. The patient also showed signs of liver dysfunction within 3-4 weeks after dosing. [Data from an Audentes Therapeutics communication announcing updated data from the ASPIRO clinical trial of AT132 for X-linked myotubular myopathy] Company Communication

Conclusions from a Periodic Safety Update Report on Jylamvo (methotrexate; DHFR inhibitor). The CHMP has recommended updating the drug's product information (section 4.8) to include skin exfoliation, exfoliative dermatitis, paresthesia, hypoesthesia and edema. Regulatory Agency Communication

Phase II study of Velexbru (tirabrutinib hydrochloride; BTK inhibitor; 80 mg) for Waldenström’s macroglobulinemia or lymphoplasmacytic lymphoma. The most common grade ≥3 adverse events were neutropenia, lymphopenia (11.1% each) and leukopenia (7.4%). [Data from an ONO communication announcing supplemental approval in Japan for Velexbru for Waldenström’s macroglobulinemia or lymphoplasmacytic lymphoma] Company Communication

Pharmacovigilance disproportionality analysis comparing safety profiles for TNF-alpha inhibitors using data from the Japanese Adverse Drug Event Report (JADER) database. Adverse events significantly associated with TNF-alpha inhibitors included tuberculous pleurisy (ROR = 47.4; 95% CI [39.6-56.7]), tuberculosis (32.7 [27.7-38.6]), disseminated tuberculosis (31.9 [27.6-36.7]), pulmonary tuberculosis (27.9 [25.3-30.9]), infusion-related reactions (29.2 [26.6-32]), lymphoma (14.9 [13.5-16.5]), bacterial arthritis (13.7 [11.8-16]), organizing pneumonia (13.6 [11.9-15.5]), breast cancer (12.5 [10.9-14.3]), bacterial pneumonia (11.5 [10.5-12.5]), Pneumocystis jirovecii pneumonia (11.8 [11.1-12.5]), pleurisy (10.8 [9.34-12.5]) and pyelonephritis (10.4 [9.19-11.7]). Other safety signals are listed.

Phase II study of Auxora (CRAC blocker) in adults with COVID-19 pneumonia. Adverse events considered related to Auxora were itching, increased alkaline phosphate and rash (1 patient each).

Systematic review and meta-analysis assessing the risk of prostate cancer in patients treated with calcium channel blockers. A significant association between calcium channel blockers and prostate cancer was identified (risk ratio = 1.08; 95% CI [1.05-1.11]).