Basic Principles of Antifungal Treatment
Firza Alexander Gronthoud in Practical Clinical Microbiology and Infectious Diseases, 2020
Monitor signs of drug toxicity All antifungal drugs can cause hepatotoxicity, lowest risk seen with echinocandins.Azoles: Prolonged QT interval. Visual disturbances and encephalopathy can be seen with voriconazole. IV voriconazole can result in renal toxicity.Echinocandins: Low toxicity profile. Infusion-related reaction is a rare side effect.Amphotericin B: Infusion-related reaction (lower with liposomal amphotericin B), renal toxicity, hypokalaemia, hepatotoxicity.
High-Dose Chemotherapy with Haematopoietic Stem Cell Transplantation in Primary Systemic Vasculitis, Behcet’s Disease and Sjogren’s Syndrome
Richard K. Burt, Alberto M. Marmont in Stem Cell Therapy for Autoimmune Disease, 2019
The first step of treatment either in PSV, Behcet’s disease or in severe organ involvement of Sjogren’s syndrome should be effective and result in rapid remission induction, in order to limit organ damage. Induction therapy is followed by mild, long-term maintenance therapy for prevention or relapse. This maintenance therapy may lead to chronic and severe drug toxicity. The National Institutes of Health experience with Wegener’s granulomatosis reported the contribution of treatment toxicity to permanent damage in over 50% of their patients.25 In a large, international randomized trial in patients with ANCA-positive systemic vasculitis, severe or life-threatening adverse effects have been observed in 26% of patients (maintenance therapy with oral cyclophosphamide or azathioprine).26
Clinical Development Optimization
Mark Chang, John Balser, Jim Roach, Robin Bliss in Innovative Strategies, Statistical Solutions and Simulations for Modern Clinical Trials, 2019
Drug toxicity can be measured differently for disease indications. Generally, drug toxicity is considered as tolerable if the toxicity is manageable and reversible. For oncology, the standardization of the level of drug toxicity is the Common Toxicity Criteria (CTC) developed by the United States National Cancer Institute (NCI). Any adverse event (AE) related to treatment of CTC category of Grade 3 and higher is often considered a dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) is defined as the maximum dose with a DLT rate that is no more frequent than a predetermined value. The initial dose given to the first patients in a phase I study should be low enough to avoid severe toxicity. The commonly used starting dose is the dose at which 10% mortality (LD10) occurs in mice.
Characteristics of fatal gabapentinoid-related poisoning in Australia, 2000–2020
Published in Clinical Toxicology, 2022
Shane Darke, Johan Duflou, Amy Peacock, Michael Farrell, Julia Lappin
Toxicological testing is conducted according to local protocols. In all cases of suspected drug toxicity, protocol is that a toxicological screen be conducted where relevant and technically feasible in order for the laboratory quantitation of blood drug levels to be performed. Toxicological data in this study were reported for the detection of pregabalin, gabapentin, opioids, psychostimulants, cannabis (Δ-9-THC), hallucinogens, synthetic cannabinoid receptor agonists, alcohol, hypnosedatives (benzodiazepines, z-class hypnotics, barbiturates), antidepressants and antipsychotics, doxylamine, ketamine and GHB. Blood samples for toxicological analysis were taken from peripheral sites in 844 cases, the aorta in 21 cases and the liver in six cases. As neither pregabalin or gabapentin undergoes significant post-mortem redistribution, peripheral and central blood sources are comparable [1]. Gabapentinoid concentrations were reported for peripheral/aortic blood samples only, as liver tissue concentrations are not directly comparable. In 46 cases of hospitalisation prior to death, antemortem blood samples taken on or near admission to hospital were reported, and drugs administered by medical staff excluded. All samples were tested using a range of methodologies specific to that laboratory, including a combination of one or more of immunoassay, gas chromatography, high-performance liquid chromatography (HPLC) and liquid chromatography-quadrupole time of flight mass spectrometry (LC-QTOF-MS) for commonly “recreational” drugs and select therapeutic substances. All specimens were stored at 4 °C prior to testing.
The reporting of observational studies of drug effectiveness and safety: recommendations to extend existing guidelines
Published in Expert Opinion on Drug Safety, 2021
Jacquelyn J. Cragg, Laurent Azoulay, Gary Collins, Mary A. De Vera, Mahyar Etminan, Fawziah Lalji, Andrea S. Gershon, Gordon Guyatt, Mark Harrison, Catherine Jutzeler, Rosemin Kassam, Tetyana Kendzerska, Larry Lynd, Mohammad Ali Mansournia, Mohsen Sadatsafavi, Bobo Tong, Freda M. Warner, Helen Tremlett
Several funding bodies, including the European Commission (Horizon 2020), the USA’s National Institutes of Health (NIH) and the Canadian Institutes of Health Research (CIHR) require research designs that incorporate sex- (biological) and/or gender-based (socio-cultural) differences [32–34]. The rationale for these recommendations includes the recognition that aggregating sexes may mask differences and produce spurious results. Drug toxicity and drug safety profiles in particular can differ between sexes [35]. Table 1 (e.g. 2.7) shows two examples from published literature: one of antivirals in HIV-infected individuals, and the other examining the association between NSAIDs and the risk of gastrointestinal bleeds [36,37]. While the current STROBE statement includes an item to ‘describe any methods used to examine subgroups and interactions’ (under methods) and ‘report other analyses done-eg analyses of subgroups and interactions’ (under results), sex and gender-based analyses are not explicitly stated in the checklist. In reporting checklists, the methods and results section should include a description of sex- and gender-based considerations, including analyses and results (under subgroup effects).
A comparison of blood toxicology in fatalities involving alcohol and other drugs in patients with an opioid use disorder treated with methadone, buprenorphine, and implant naltrexone
Published in The American Journal of Drug and Alcohol Abuse, 2020
Erin Kelty, Gary Hulse, David Joyce
Drug toxicity was judged to be a cause of death or a contributor to death in 148 of the total 314 deaths in the study population, based on circumstances of death, postmortem examination findings and blood or liver toxicology. These represented 66/158 (41.8%), 54/106 (50.9%) and 28/50 (56.0%) of total deaths in the methadone, buprenorphine and naltrexone groups, respectively. These were not significantly different between the three treatment groups. Comprehensive toxicology results were available for 147 of the 148 cases. Three deaths were attributed primarily to carbon monoxide poisoning, sharp injury and drowning, with a drug contribution deemed also present in all. Fourteen cases died by suicide. Drug intoxication was the principal cause of death in all but one of the suicide cases.
Related Knowledge Centers
- Adverse Event
- Idiosyncratic Drug Reaction
- Pharmacovigilance
- Warfarin
- Digoxin
- Medication
- Drug
- Side Effect
- Therapeutic Index
- Intracranial Hemorrhage