Documented Hypersensitivity Reaction Research Articles

Efficacy of a Standardized Premedication and Therapeutic Drug Monitoring Protocol for Pegaspargase to Prevent Hypersensitivity Reactions.

The purpose of this study was to evaluate the efficacy of a standardized premedication and therapeutic drug monitoring (TDM) protocol to prevent hypersensitivity reactions from pegaspargase infusions. Pegaspargase is an essential therapeutic agent used for the treatment of acute lymphoblastic leukemia (ALL) in pediatric patients. This study was a retrospective cohort study conducted at Wolfson Children's Hospital, Jacksonville, Florida, and included pediatric ALL patients 0 to 21 years old. Patients were excluded if they had not received the appropriate premedication after protocol implementation or had received premedication before protocol implementation. Patients were separated into 2 groups: those who received premedication before pegaspargase infusion and those who did not. The primary endpoint was the incidence of documented hypersensitivity reactions. Observational data endpoints included incidence of silent inactivation and cost savings from reducing complicated drug substitutions. A total of 38 patients (50 doses in no premedication group; 80 doses in premedication group) were evaluated. There was not a significant reduction in the incidence of hypersensitivity reactions for patients receiving premedication and TDM (5.3% vs 6.4%, p = 1.0). A trend towards patients reacting earlier with more severe reactions in the post-implementation group was observed. There were no incidences of silent inactivation. Observational cost analysis predicts potential drug cost savings of $106,550.45. A standardized premedication protocol did not reduce the incidence of hypersensitivity reactions. Premedication to prevent hypersensitivity reactions may provide a potential drug cost savings. Further investigation is warranted to assess the efficacy of a standardized premedication and TDM protocol to prevent hypersensitivity reactions.

2103. Emergency Department (ED) Stewardship: Stratifying ED Sepsis Order Sets by Penicillin (PCN) Allergy Severity

BackgroundThe Surviving Sepsis Campaign Guidelines recommends administration of broad-spectrum antibiotics within 1 hour of sepsis diagnosis; electronic order sets drive antibiotic selection with pre-populated regimens based on the suspected infectious indication. Given the low rate of cephalosporin cross-reactivity in patients with a PCN allergy, we modified our ED sepsis order set (Images 1 and 2) to include cephalosporin options in patients with reported mild-to-moderate PCN reaction histories. This was a single-center, retrospective analysis evaluating the impact of this change on antibiotic prescribing and associated outcomes.MethodsAn electronic medical record (EMR) report identified patients ≥18 years of age with a documented PCN allergy that received antibiotics via the ED sepsis order set from December 30, 2012 to September 28, 2013 (pre-intervention) and January 3, 2014 to July 18, 2015 (post-intervention). The primary objective was to compare antibiotic days of therapy (DOT) and length of therapy (LOT) between the pre- and post-groups. The secondary objectives included 30-day readmission and mortality, hospital length of stay (LOS), incidence of C. difficile within 6 months and documented hypersensitivity reactions. Bivariate analyses, with chi-square, Mann–Whitney U, and Poisson means test, were used.ResultsA total of 180 patients (90 pre- and 90 post-intervention) were included. Demographics were similar between groups, with the exception of congestive heart failure (CHF) which was more prevalent in the post-intervention group (P = 0.039). Aztreonam, vancomycin, aminoglycoside, and fluoroquinolone DOTs were significantly reduced (P < 0.001) while cephalosporin DOTs significantly increased (P < 0.001) in the post-intervention group. There were no statistical differences in antibiotic LOT, 30-day readmission and mortality, hospital LOS, or incidence of C. difficile infection. For those patients that received cephalosporin antibiotics, there were no hypersensitivity reactions documented in the EMR.ConclusionStratifying ED sepsis order sets by PCN allergy history severity is a safe and effective intervention that reduces second-line antibiotics in PCN allergic patients presenting to the ED with suspected sepsis. Disclosures All authors: No reported disclosures.

MON-598 Self-Reported Allergy to Thyroid Replacement Therapy: A Retrospective Chart Review

Introduction: Thyroid replacement therapy (TRT) is the treatment of choice for hypothyroidism. Levothyroxine is among the most commonly prescribed medications in the United States with over 70 million prescriptions annually. Documented hypersensitivity reactions (HSR) to TRT are rare with only a few case reports. Objectives: To determine patterns of adverse drug reactions, including hypersensitivity reactions, to TRT. Methods: A retrospective medical chart review of 11 years (2008 - 2018) identified patients with suspected HSR to TRT. HSR were defined as IgE-related symptoms secondary to TRT. Results: Of the 843 cases reviewed, 466 met our criteria. Median age was 61.2 years old; 85.8% were women, and 94.4% were Caucasian. The principal indication for TRT was primary hypothyroidism (73.6%), followed by postsurgical hypothyroidism (17.4%), and subclinical hypothyroidism (6.7%). Most patients reported a hypersensitivity reaction to the generic presentation of levothyroxine (60%), followed by Synthroid® (31.5%) and Levoxyl® (4.07%). Eighty percent of the patients reported other hypersensitivities to different medications. Non-hypersensitivity manifestations to TRT were reported more commonly than hypersensitivity manifestations (53% vs. 47%).The most frequently reported of the former were palpitations (16.4%), nausea/vomiting (9.3%), and tremor (6.3%), while rash (23.8%), hives (9.5%), and pruritus (7.1%) were the most common regarding the latter . Fifty-six percent of the patients tolerated different TRT presentations after the initial reaction. Discussion: A substantial proportion of patients with self-reported hypersensitivity reactions did not have HSR symptoms upon review of the medical record. We found that patient self-reported allergy to TRT is most likely a side effect to the medication rather than a hypersensitivity reaction. In our study, most of the patients evaluated were placed on an equally efficacious TRT presentation without further reactions. Patients may develop hypersensitivity reactions to the active ingredient, excipients, or fillers in the TRT. Patients with a suspected history of hypersensitivity reaction to TRT should undergo a thorough reaction history and when appropriate, referred for an allergy consultation.

Gadolinium use for interventional pain procedures: where we are and where we are heading.

In recent years as the use of interventional pain procedures has soared, so too has outside and internal scrutiny. This scrutiny includes agreater emphasis on weighing the risks and benefits of procedures, increased surveillance for adverse events, and cost containment strategies. In 2016, the first reports of gadolinium deposition in the central nervous system began to surface, though retention in other organ systems has been appreciated for over a decade. In this issue of Regional Anesthesia & Pain Medicine, Benzon et al. report a series of patients with document edhypersensitivity reactions to iodinated contrast medium who were inadvertently administered iodine-based contrast without adverse consequences. In this article, we discuss the epidemiology of contrast-mediated adverse effects, the mechanistic basis for hypersensitivity reactions, the risks and benefits of various approaches in the patient with a documented contrast hypersensitivity reaction, and risk mitigation strategies.

Documented hypersensitivity reactions with dipyrone

Documented hypersensitivity reactions with dipyrone

Population Pharmacokinetic Modeling of Intravenous Asparaginase Erwinia Chrysanthemi: Impact of Varied Infusion Rates on Exposure

Introduction: Asparaginase Erwinia chrysanthemi (Erwinia), an asparagine-specific enzyme indicated as a component of a multiagent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E coli-derived asparaginase, is approved in the US for intramuscular and intravenous (IV) administration (Erwinaze USPI 2016). IV administration of proteins, such as asparaginase, may be associated with infusion reactions that may be mitigated by prolongation of the infusion time. Pharmacokinetic (PK) simulations based on a population PK (PPK) model were performed to evaluate PK of IV Erwinia infusions over 2 hours vs 1 hour.Methods: The serum asparaginase activity (SAA) levels from a phase 2, open label, single arm, multicenter, PK study following Erwinia treatment by IV infusion in ALL subjects (1-30 years old) with a previously documented hypersensitivity reaction (≥Grade 2) to pegaspargase were characterized by nonlinear mixed-effects modeling using NONMEM® software. The PPK model included data after 6 doses (1 cycle) of IV Erwinia administered over 1 hour at a 25,000 IU/m2 dose given on a Monday/Wednesday/Friday schedule. The PPK base model for IV Erwinia was identified by comparing different structural and error models. A stepwise approach with forward addition and backward elimination was used to identify important covariates. Visual predictive checks (VPC) were used to demonstrate PPK model predictability. Resampling of the original PK population was used to create a virtual patient population (n = 9999) to simulate average SAA levels and corresponding variability for both 1- and 2-hour IV infusion regimens, summarized by 95% prediction intervals.Results: The PK analysis set contained 24 subjects with 331 evaluable PK samples collected over 6 cycles of therapy. The majority of PK samples were collected during Cycle 1 (55%) with the majority of subjects being male (62.5%) and Caucasian (79%). The median (range) for age was 6.5 years (1-17) and for weight 21.4 kg (10.9 to 118.3). Trough SAA levels ≥0.1 IU/mL at 48 hours post dose 5 (primary endpoint) were achieved by 83% of the evaluable subjects in Cycle 1 (95% CI: 63%-95%). A 2-compartment model with inter-individual variability on clearance (CL) was found to best describe the PK of Erwinia. The final model for CL was:CL [mL/hr] = 123[mL/hr] + 17[mL/hr] * (weight [kg] / 21.4 kg)The central and peripheral volumes of distribution were 1.59 L and 0.154 L, respectively. As more PK samples were available for Cycle 1, separate proportional error models partitioned residual variability for Cycle 1 (36.6%) vs Cycles 2-6 (48.6%). The derived mean half-life estimate (CV%) was 7.51 hours (23.9%). The VPC demonstrated the bulk (>90%) of the observed SAA falling within the 95% PPK model-based simulation prediction intervals. The PPK model-based SAA simulation results after 1- and 2-hour IV infusions are displayed in Table 1 and Figure 1. Despite different initial rates of rise, similar SAA vs time profiles were observed when comparing 1- vs 2-hour infusion durations (Figure 1), with a similar number of subjects achieving therapeutic trough levels ≥ 0.1 IU/mL (Table 1).Conclusions: The final PPK model demonstrated a good ability to predict SAA allowing estimation of elimination characteristics and the application of subsequent model-based simulations.The PK simulations for 1- vs 2-hour IV Erwinia showed similar mean 48-hour trough SAA levels, as well as similar proportions of subjects having therapeutic 48-hour trough SAA ≥ 0.1 IU/mL. Based on these PK results, duration of IV Erwinia could be increased from 1 to 2 hours, which may reduce symptoms of infusion reactions. Reducing infusion reactions may potentially enablemore patients to complete Erwinia treatment. Upon approval from FDA in 2016, IV infusion duration in the Erwinaze USPI was revised from 1 hour to 1-2 hours; this is also consistent with the updated Children’s Oncology Group protocols.Support: Jazz Pharmaceuticals. [Display omitted] [Display omitted] DisclosuresZomorodi:Jazz Pharmaceuticals: Employment, Equity Ownership. Dumas:Quintiles: Employment; Jazz Pharmaceuticals: Consultancy. Berry:Quintiles: Employment; Jazz Pharmaceuticals: Consultancy. Johnston:Jazz Pharmaceuticals: Consultancy; Quintiles: Employment. Eller:Jazz Pharmaceuticals: Employment, Equity Ownership.

How accurate is the label "allergic to iodinated contrast agents"?

Iodinated contrast agents (ICAs) are crucial to the use of many imaging studies. Reported allergies to ICAs in the medical record can interfere with optimal diagnostic imaging workups. To investigate the accuracy with which the label "allergic to ICAs" is applied. The medical records of 500 patients labeled "allergic to ICAs" at a single tertiary care hospital were reviewed. Patients were separated into three groups based on documentation in their medical records, as follows: Group 1, documented hypersensitivity reaction to ICAs; Group 2, documented ICA exposure with non-hypersensitivity adverse event (Group 2a) or without documented reaction (Group 2b); and Group 3, no documented prior exposure to an ICA. We then further reviewed the EMR to determine whether or not patients had subsequent administration of an ICA, whether or not they were given specific premedication, and whether or not they had a subsequent ICA-related event. A total of 16.6% of patients (n = 83) listed as "allergic to ICAs" had a documented hypersensitivity reaction following ICA administration (Group 1) while 58.6% (n = 293) of patients (Group 2) had a documented exposure to ICAs with either: (i) a non-hypersensitivity adverse event (23.5%, n = 69) or (ii) no record of a reaction to ICAs (76.5%, n = 224). The remaining 24.8% (n = 124), Group 3, had no record of exposure to an ICA, yet still carried the label. The majority of patients carrying the label "allergic to ICAs" had no record of a prior hypersensitivity reaction to ICAs.

Ticagrelor Use in a Patient With a Documented Clopidogrel Hypersensitivity.

To report the use of ticagrelor in a patient with a documented hypersensitivity reaction to clopidogrel. A 64-year-old woman presented with non-ST-segment elevation myocardial infarction (NSTEMI) with a history significant for a hypersensitivity reaction to clopidogrel and was medically managed. Based on the patient's past medical history and current evidence available, the determination was made to use ticagrelor in this patient. Ticagrelor was administered without reaction during the hospital stay and on assessment at 2 and 4 weeks postdischarge. Hypersensitivity occurs in approximately 1% of patients receiving clopidogrel. Although the risk of hypersensitivity reaction to clopidogrel is low, evidence to support alternative antiplatelets in this setting is relatively limited. Prasugrel has a similar structure to clopidogrel and, therefore, may cross-react. Furthermore, prasugrel is not recommended in the medical management of NSTEMI. Ticagrelor is a newer P2Y12 inhibitor that contains a cyclopentyltriazolopyrimidine structure. Because of the difference in structure, a lower theoretical risk of cross-reactivity with the thienopyridines would be anticipated. However, there are no reports to date that investigate the use of this agent in patients with a documented thienopyridine allergy. The current case report describes the use of ticagrelor in a patient with documented hypersensitivity to clopidogrel. In this patient, ticagrelor was well tolerated during hospital admission and at 2 and 4 weeks postdischarge following administration.

Use of Prasugrel in a Patient with Clopidogrel Hypersensitivity

To report a case of successful use of prasugrel following percutaneous coronary intervention with placement of a bare metal stent in a patient with a documented hypersensitivity reaction to clopidogrel. A 61-year-old male with a history of coronary artery disease with coronary stent placement presented with ST-elevation myocardial infarction. The patient had developed Stephens-Johnson syndrome 6 years earlier following clopidogrel administration, characterized by erythematous plaques and subsequent desquamation of the hands and feet; clopidogrel was discontinued and he was subsequently treated with ticlopidine in addition to aspirin. The third-generation thienopyridine prasugrel was initiated as a therapeutic alternative to clopidogrel after placement of a bare metal stent; a 60-mg dose was administered after extubation, followed by 10 mg/day. No signs of allergic reaction were observed in the days, weeks, and months following administration. Thienopyridines, specifically clopidogrel, are the standard of care for prevention of coronary stent thrombosis; however, there are few data available on cross-hypersensitivity between these agents. One study demonstrated that 27% of patients who developed an allergic or hematologic reaction to clopidogrel developed a similar reaction to ticlopidine. Other therapeutic options for patients with clopidogrel hypersensitivity who are undergoing a percutaneous coronary intervention with stent placement include clopidogrel desensitization, warfarin plus aspirin, cilostazol, ticagrelor, and ticlopidine. However, these options are limited by efficacy and/or toxicity. With its approval in 2009, prasugrel has become a potential treatment option. Prasugrel may be considered a therapeutic alternative in some patients allergic or intolerant to clopidogrel, but additional data are warranted to make a strong conclusion.

A novel, accelerated method of desensitization in a patient with a documented hypersensitivity reaction to clopidogrel

Current standard of care following a percutaneous coronary intervention with stent placement necessitates the use of dual anti-platelet therapy with aspirin and commonly clopidogrel. There is a subset of patients who have a significant clopidogrel allergy and life-threatening hypersensitivity reactions. Desensitization is the process of inducing tolerance to a sensitizing agent via repeated exposure to the agent. There have been previously reported protocols for clopidogrel desensitization. These protocols differ in length and dose escalation and a universally accepted clopidogrel desensitization protocol has yet to be established. We discuss here a novel accelerated approach to clopidogrel desensitization in a patient with a documented hypersensitivity reaction.

Intraoperative floppy-iris syndrome associated with previously documented hypersensitivity reaction to adrenaline

Intraoperative floppy-iris syndrome associated with previously documented hypersensitivity reaction to adrenaline

Carboplatin hypersensitivity reactions: re-treatment with cisplatin desensitisation

Objectives This aim of this study was to investigate the feasibility of re-treating patients who had experienced a hypersensitivity reaction to carboplatin with cisplatin following desensitisation. Methods Five patients with recurrent ovarian cancer who had a previous documented hypersensitivity reaction to carboplatin and a good clinical indication for continuing treatment with platinum were retreated following cisplatin desensitisation. All patients were rechallenged with cisplatin following a prolonged desensitisation protocol and the initial four patients then received subsequent cycles with a shortened protocol in an attempt to simplify and shorten the procedure. Results All five patients tolerated their first cycle of cisplatin on rechallenge using the full desensitisation protocol with no adverse reactions. Two patients received further treatments (one and three cycles) with a shortened protocol but treatment was terminated due to further adverse hypersensitivity reactions. Two patients received one further cycle with a shortened protocol and did not experience problems with hypersensitivity but treatment was stopped due to evidence of disease progression One patient received a further two cycles using the full desensitisation protocol without problems but treatment was stopped due to evidence of disease progression. Conclusions A full cisplatin desensitisation protocol appears to be an effective way to re-treat patients who have previously experienced a hypersensitivity reaction to carboplatin. Attempts to shorten the procedure were associated with further allergic reactions, suggesting that the full protocol should be followed with each treatment.

Cross-reactivity in HIV-infected patients switched from trimethoprim-sulfamethoxazole to dapsone.

To evaluate the cross-reactivity of dapsone after a documented hypersensitivity reaction to trimethoprim-sulfamethoxazole (TMP-SMX) during prophylaxis for Pneumocystis carinii pneumonia. Retrospective, chart review, cohort study. Two university-affiliated teaching hospitals. Sixty patients infected with the human immunodeficiency virus. Thirteen patients (21.7%) had cross-reactivity to dapsone after the reaction to TMP-SMX. No significant risk factors for this response were identified. Most reactions were of mild or moderate severity and rated as possibly or probably caused by one of the agents. Of the 13 patients, 4 (30.8%) continued therapy. Although cross-reactivity can occur, dapsone may be considered in patients with mild hypersensitivity reactions to TMP-SMX.