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Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Nilutamide has two distinct side effects, interstitial pneumonitis and delayed adaption to darkness, both of which limit its use. Although rare, interstitial lung changes leading to hospitalization and death were observed postmarketing, and led to an FDA “Boxed Warning” being added to the commercial product. Most cases of lung toxicity occur within the first three months of therapy and reverse after the drug is stopped. Therefore, routine chest X-rays should be taken before starting treatment, along with baseline pulmonary function tests. Also, patients are instructed to report new or worsening symptoms including shortness of breath, chest pain, wheezing, or dry cough, that should trigger immediate withdrawal of treatment. The side effect of delayed adaption to darkness is unusual and unique to this agent, and of great concern to patients who are still driving, or who could otherwise endanger themselves during the night. Other possible side effects include GI symptoms (e.g., loss of appetite, upper stomach pain, nausea, vomiting, clay-colored stools), fever, flu-like symptoms, pale and/or itching skin, fatigue, dark urine, and jaundice.
Sources of Data to Enable Benefit–Risk Assessment
Published in Qi Jiang, Weili He, Benefit-Risk Assessment Methods in Medical Product Development, 2017
Christy Chuang-Stein, George Quartey, Weili He, Qi Jiang, Haijun Ma, Jonathan Norton, John Scott, Jesse A. Berlin
Ultimately, the manufacturer identified duration of therapy, prior use of immunosuppressants, and presence of anti-JC virus antibodies as the major risk factors for PML in patients receiving natalizumab. These risk factors were included in a boxed Warning and the “Warnings and Precautions” section of the label.
Tigecycline
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Several studies report a trend of increased risk of mortality for those who have received tigecycline, compared to other antibiotics. This has been described for both approved use and off label use (and especially for patients with HAP/VAP). Cai et al. (2011) and Tasina et al. (2011) found a nonsignificant overall increase in mortality. Yahav et al. (2011) and Prasad et al. (2012) state that differences in mortality between tigecycline users and controls are statistically significant. However, death has not been attributed to direct toxic effects of tigecycline. The definitive cause of increased mortality is unknown (Dixit et al., 2014). Progressive infection and the intrinsic weak activity of tigeycline are proposed as causes (FDA, 2010). Inadequate AUC/MIC ratios (especially in the treatment of HAP/VAP) may also be factors (Freire et al., 2010; De Rosa et al., 2015). AUC/MIC ratios might be optimized by higher dosing regimes. Others point to underlying risk factors as confounders of mortality data (Verde and Curcio, 2011). Nevertheless, a safety alert was issued by the FDA in 2010 and renewed as a boxed warning in 2013, stating tigecycline should only be used “in situations when alternative treatments are not suitable.” (FDA, 2010; FDA, 2013).
Varenicline (Chantix): The Smoking Cessation Medication Prescribers May Be Avoiding
Published in Issues in Mental Health Nursing, 2022
A bit of history: varenicline arrived in 2006, and almost immediately, data from the FDA’s Adverse Event Reporting System pointed to varenicline as a trigger for suicidal ideation, suicide attempts, depressive symptoms, psychotic symptoms, and increased irritability and aggression. One of the most frequently cited articles on this consumer data had strong language for varenicline, asserting it was not safe enough to be a first-line option (Moore et al., 2011). By 2009, the FDA had added a Boxed Warning on varenicline, noting the risks of serious neuropsychiatric adverse events. In the United States, there is no stronger decree than a Boxed Warning—or more colloquially, a black box warning—as it is the final word of caution from the FDA before the medication is removed from the market. Expectedly, the use of varenicline quickly declined in the United States (Shah et al., 2017).
Xanthine oxidase inhibitors: patent landscape and clinical development (2015–2020)
Published in Expert Opinion on Therapeutic Patents, 2020
Jatinder Vir Singh, Preet Mohinder Singh Bedi, Harbinder Singh, Sahil Sharma
Undoubtedly, Febuxostat is more efficacious XO inhibitor than Allopurinol in terms of its potency, safety and better tolerability in hyperuricemic patients. However, one study in 2019 showed that 26 deaths (out of which 15 deaths with heart-related complications) for every 1000 patients were observed with the use of Febuxostat in one year. In this respect, the FDA started a postmarket clinical trial to assess its safety. The trial was completed in 2017, showed that Febuxostat is associated with an increased risk of heart-related deaths. (clinicaltrial.gov registry number: NCT02500641) [108]. After these prominent findings, FDA in February 2019, issued a warning, specifically a ‘Boxed warning,’ which means that this drug can be used only for patients not responding to other antihyperuricemic drugs or experiencing side effects with the use of other drugs. Apart from this, various clinical assessments are also in progress on its safety and drug–drug interaction measurements.
The identification of farnesoid X receptor modulators as treatment options for nonalcoholic fatty liver disease
Published in Expert Opinion on Drug Discovery, 2021
Stefano Fiorucci, Michele Biagioli, Monia Baldoni, Patrizia Ricci, Valentina Sepe, Angela Zampella, Eleonora Distrutti
In 2017 a cluster of severe side effects including liver failure requiring intensive. The severity of these effects, including deaths, has led the FDA to issue a drug safety communication on 1 February 2018, [source: FDA – Drug safety communication 02/01/2019] and a boxed warning was added. The warning highlights that in patients with liver cirrhosis the initial dose of OCA should not exceed 5 mg once a week (keeping in mind that dose tested in Phase II and III trials were 5, 10, 25 and 50 mg/day) [35]. It has been suggested that under cholestatic conditions, OCA accumulates in the liver where it may reach toxic concentrations [132]. In mice, FXR gene ablation or its pharmacological inhibition protects from injury induced by OCA in the ANIT model of cholestasis.