Pentosan associated retinal pigmentary changes: FDA's perspective on an emerging postmarketing safety finding.

INTRODUCTION AND HYPOTHESIS: Recent publications describe pigmentary changes in the retina associated with the use of pentosan polysulfate sodium, the only FDA-approved oral agent for relief of bladder pain or discomfort associated with interstitial cystitis. METHODS: To evaluate this association, we reviewed data from the FDA Adverse Event Reporting System and published case reports and observational studies. RESULTS: The totality of clinical and epidemiology evidence does not resolve the question of causation between pentosan use and retinal pigmentary changes; however, several elements support a potential association. CONCLUSION: Here, we provide our perspective on the available evidence the agency weighed when retinal pigmentary changes were added to pentosan labeling. It is important for urogynecologists prescribing pentosan to be aware of this potential association and be vigilant about assessing eye health in pentosan users.

Disseminated Gonococcal Infections in Patients Receiving Eculizumab: A Case Series.

BACKGROUND: Gonorrhea is the second most commonly reported notifiable condition in the United States. Infrequently, Neisseria gonorrhoeae can cause disseminated gonococcal infection (DGI). Eculizumab, a monoclonal antibody, inhibits terminal complement activation, which impairs the ability of the immune system to respond effectively to Neisseria infections. This series describes cases of N. gonorrhoeae infection among patients receiving eculizumab. METHODS: Pre- and postmarketing safety reports of N. gonorrhoeae infection in patients receiving eculizumab worldwide were obtained from US Food and Drug Administration safety databases and the medical literature, including reports from the start of pivotal clinical trials in 2004 through 31 December 2017. Included patients had at least 1 eculizumab dose within the 3 months prior to N. gonorrhoeae infection. RESULTS: Nine cases of N. gonorrhoeae infection were identified; 8 were classified as disseminated (89%). Of the disseminated cases, 8 patients required hospitalization, 7 had positive blood cultures, and 2 required vasopressor support. One patient required mechanical ventilation. Neisseria gonorrhoeae may have contributed to complications prior to death in 1 patient; however, the fatality was attributed to underlying disease per the reporter. CONCLUSIONS: Patients receiving eculizumab may be at higher risk for DGI than the general population. Prescribers are encouraged to educate patients receiving eculizumab on their risk for serious gonococcal infections and perform screening for sexually transmitted diseases (STDs) per the Centers for Disease Control and Prevention STD treatment guidelines or in suspected cases. If antimicrobial prophylaxis is used during eculizumab therapy, prescribers should consider trends in gonococcal antimicrobial susceptibility due to emerging resistance concerns.

Serious Skin Injuries Following Exposure to Unapproved Mole and Skin Tag Removers.

Objective: We sought to describe skin injuries associated with unapproved topical mole and skin tag removers containing concentrated salicylic acid, Sanguinaria canadensis, or other caustic agents. Methods: We identified skin injuries associated with unapproved non-device topical mole and skin tag removers reported to the US Food and Drug Administration (FDA) through October 30, 2021 or described in Amazon consumer product reviews between 2019 and 2021. Results: We identified 38 cases, including 30 from Amazon consumer product reviews and eight reported to the FDA. Twenty-eight were from 2021. The most common reason for use was for mole and/or skin tag removal. Listed ingredients included salicylic acid, Sanguinaria canadensis, botanicals (includes homeopathic products), and calcium oxide. Seven cases involved products without ingredients listed. Adverse events included burns, pain, and ulceration, some resulting in permanent scarring and disfigurement. There were 14 facial injuries, including four adjacent to the eye. Reported treatments included antibiotics, hospital care, wound care, and dermatology advice to have a skin graft. Limitations: Limitations include underreporting of adverse events to the FDA, limited clinical details and potential bias in consumer reviews, and poor replicability of review searches due to the dynamic nature of the Amazon website. Conclusion: Unapproved, non-device topical mole and skin tag removers are associated with serious skin injuries. We found Amazon consumer reviews to be a novel and useful data source for safety surveillance of these types of skin products. When dermatologists are consulted about skin injuries, exposure to these products should be considered in the differential diagnosis.

Trends in pediatric nonprescription analgesic/antipyretic exposures during the COVID-19 pandemic.

OBJECTIVE: To examine pediatric exposure trends involving selected nonprescription analgesics/antipyretics, before and during the COVID-19 pandemic. METHODS: Using descriptive and interrupted time-series analyses, we assessed monthly United States poison center data involving pediatric (<18 years) exposures to nonprescription paracetamol (acetaminophen), ibuprofen, acetylsalicylic acid, and naproxen before (January 2015-February 2020) and during (March 2020-April 2021) the pandemic. Statins and proton pump inhibitors (prescription or nonprescription) served as controls. RESULTS: Most nonprescription analgesic/antipyretic exposures (75-90%) were single-substance; unintentional exposures typically involved children <6 years (84-92%), while intentional exposures involved females (82-85%) and adolescents, 13-17 years (91-93%). Unintentional exposures among children <6 years, declined for all four analgesics/antipyretics immediately after the World Health Organization declared COVID-19 a pandemic (March 11, 2020), but most significantly for ibuprofen (30-39%). Most intentional exposures were classified as suspected suicide. Intentional exposures were relatively low and stable among males. Intentional exposures in females declined immediately after the pandemic was announced but subsequently increased to pre-pandemic levels for acetylsalicylic acid and naproxen and above pre-pandemic levels for paracetamol and ibuprofen. For paracetamol, female intentional exposures increased from 513 average monthly cases in the pre-pandemic to 641 average monthly cases during the pandemic; and reached 888 cases by the end of the study period in April 2021. While for ibuprofen, average monthly cases rose from 194 in the pre-pandemic, to 223 during the pandemic; and reached 352 cases in April 2021. Patterns were similar among females 6-12 and 13-17 years. CONCLUSION: Nonprescription analgesic/antipyretic unintentional exposure cases declined among young children, while intentional exposure cases increased among females, 6-17 years, during the pandemic. Findings highlight the importance of safely storing medications and being alert to signs that adolescents may be in need of mental health support services; caregivers should seek medical care or call poison control centers for any suspected poisoning event.

Accidental Flibanserin Ingestion in Children Causing Acute Respiratory and Central Nervous System Depression: What Health Care Professionals Need to Know.

This commentary serves to raise awareness for health care professionals about the potential risks of accidental ingestion of flibanserin tablets by children. Flibanserin was approved by the U.S. Food and Drug Administration (FDA) for the treatment of acquired generalized hypoactive sexual desire disorder in premenopausal women. Since its approval in 2015, the FDA has identified five reports of serious accidental ingestion by toddlers. All five children, boys with ages ranging from 18 months to 2 years, presented with central nervous system and respiratory depression, and two of them required intubation. A combination of hypertension, hyperthermia, and seizure-like activity was also seen in four of the five children. The clinical manifestation resembles serotonin syndrome (eg, tachycardia, hypertension, and muscle stiffness). As flibanserin use increases, greater awareness by health care professionals regarding the risk of accidental pediatric ingestion is needed to facilitate preventative counseling for patients with young children.

Unusual Neisseria species as a cause of infection in patients taking eculizumab.

BACKGROUND: Non-meningococcal, non-gonococcal Neisseria spp. are typically commensal and rarely cause invasive disease. Eculizumab is a terminal complement inhibitor that increases susceptibility to meningococcal disease, but data on disease caused by typically-commensal Neisseria spp. are lacking. This series describes postmarketing reports of typically-commensal Neisseria spp. disease in patients receiving eculizumab. METHODS: We searched the FDA Adverse Event Reporting System (FAERS) and medical literature for reports of commensal Neisseria spp. disease in patients receiving eculizumab, from eculizumab U.S. approval (2007) through January 31, 2018. RESULTS: We identified seven FAERS reports (including one case also reported in the literature) of non-meningococcal, non-gonococcal Neisseria disease, including N. sicca (mucosa)/subflava (n = 2), N. cinerea (n = 2), N. sicca (mucosa) (n = 1), N. mucosa (n = 1, with concurrent alpha-hemolytic Streptococcus bacteremia), and N. flavescens (subflava) (n = 1). Four cases had sources of patient immunosuppression in addition to eculizumab. Three patients had sepsis (n = 2) or septic shock (n = 1). Five patients were bacteremic. All patients were hospitalized; the infections resolved with antibiotics. CONCLUSIONS: Our search identified seven cases of disease from typically commensal Neisseria spp. in eculizumab recipients. These findings suggest that any Neisseria spp. identified from a normally sterile site in an eculizumab recipient could represent true infection warranting prompt treatment.