Rare Adverse Drug Reaction Research Articles

Prospective,multi-center,and large-scale hospital centralized monitoring of clinical safety of Reduning Injection in 100249 children cases

This study utilized a prospective, large-sample, multi-center, and registered key specialty approach of hospitals to monitor the application of Reduning Injection. A total of 100 249 adolescent patients aged 14 years and below who received Reduning Injection were monitored, resulting in 83 cases of adverse events, with 76 of them being classified as adverse drug reaction(ADR). The calculated incidence rate of ADR for Reduning Injection was 0.076%, indicating a very rare ADR. The main symptoms of ADR were pruritus, diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsion, and chills. All ADR cases were reported for the first time, including three new ADR cases and 73 known ADR cases. The categories of ADR was general ADR. All ADR was mild in severity. There were more males than females in ADR patients. One patient had a history of ADR, and the drug causing ADR was buprofen. The largest number of ADR cases occurred when the dosage of Reduning injection was 5-10 mL. The dropping speed was 30 drops or less per min, and the solvent type was 5% glucose injection. The most common manifestation of ADR patients was pruritus, followed by diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsions, and chills. 72 patients(94.74% of ADR patients) discontinued the drug, and three patients(3.95% of ADR patients) were given oxygen inhalation. 47 cases(61.84% of ADR patients) were treated with medication, of which dexamethasone was the most used(24 cases, 46.15% of ADR patients). 76 ADR patients were cured or improved. ADRs are more likely to occur when diagnosed with acute bronchitis by western medicine and cough by traditional Chinese medicine(TCM), TCM syndrome type is wind heat syndrome, and the combination medicine is ambroxol hydrochloride and bromhexine hydrochloride injection, ascorbic acid/vitamin C injection. This result provides an evidence-based safety basis for active pharmacovigilance of Reduning Injection in adolescents aged 14 years and below.

Drug-induced Tongue Disorders: A Comprehensive Literature Review.

Some drugs cause tongue disorders as adverse effects. Most of the druginduced tongue disorders are benign and will resolve after drug discontinuation. However, the changes in the color or appearance of the tongue may frighten patients and decrease compliance with drug therapy. To review the literature to find all reports of drug-induced tongue disorders, their presentation, management, and outcome of patients Methods: The search was conducted in Google Scholar and PubMed using key words "ageusia," "burning tongue," "coated tongue," "drug-induced taste disturbances," "dysgeusia," "glossitis," "glossodynia," "hairy tongue," "hypogeusia," "stomatodynia," "stomatopyrosis," "swollen tongue" "tongue discoloration," "tongue irritation," "tongue numbness, "tongue oedema," and "tongue ulcer. All reports that were published from 1980 to 2022 in the English language were included in the study. Reports that were not in English language but had English abstracts with adequate data for extraction were also included. A total of 208 case reports and case series were included. The most reported drug classes were antineoplastic and immunomodulating agents and anti-infectives for systemic use, and the most common tongue disorders were tongue discoloration and black hairy tongue. Having good oral hygiene and discontinuing the offending drug could manage and resolve the problem. Drug-induced tongue disorders are not rare adverse drug reactions. They are benign in most cases, and withholding offending agents results in significant improvement or complete resolution of tongue lesions.

Adverse reactions of piperacillin: A literature review of case reports.

This study aimed to summarize case reports of adverse drug reactions (ADRs) caused by piperacillin and explore their effects on human organs in real-world settings. Case reports of piperacillin ADRs were collected by searching databases such as PubMed, Embase, Web of Science, CNKI, WanFang, and VIP from inception to December 2022. A total of 170 patients were ultimately included. The results revealed that ADRs caused by piperacillin were primarily associated with the entire body, followed by the blood system, skin and soft tissues, and the nervous system. The most frequently reported cases included anaphylactic shock, drug fever, rash, and thrombocytopenia. The most severe ADRs were identified as anaphylactic shock and bullous epidermal necrolysis. Furthermore, a comparison was made between systemic adverse reactions caused by piperacillin as a single drug and two composite preparations of piperacillin/β-lactamase inhibitor. ADRs not mentioned in the instructions included convulsions or hallucinations and Kounis syndrome (KS). This review suggests that the most severe ADRs associated with piperacillin are toxic epidermal necrolysis and anaphylactic shock. Rare ADRs caused by piperacillin, such as myoclonic jerks, hallucinations, and KS, were identified. The most common symptom with domestic preparations of piperacillin/sulbactam and piperacillin sodium was dyspnea.

Drug-induced Pruritus to Escitalopram

ABSTRACT Drug-induced pruritus is a dermatological adverse event that is usually underreported. The negative impacts of the unpleasant itching sensation largely affect the quality of life and adherence to the treatment. Here, we report a case of drug-induced pruritus to escitalopram – the most widely used medication in the treatment of depression and anti-anxiety in India; hence, it is pertinent to be familiar with such rare adverse drug reactions which may assist in early detection and better quality of care to the patient.

Conducting and interpreting disproportionality analyses derived from spontaneous reporting systems

Spontaneous reporting systems remain pivotal for post-marketing surveillance and disproportionality analysis (DA) represents a recognized approach for early signal detection. Although DAs cannot be used per se as a standalone approach to assess a drug-related risk and cannot replace clinical judgment in the individual patient, their role remain irreplaceable for rapid detection of rare and unpredictable adverse drug reactions with strong drug-attributable component (e.g., designated medical events), especially when developed by a multidisciplinary team and combined with a careful case-by-case analysis (individual inspection of reports for causality assessment or to uncover reporting patterns and clinical features). In the recent past, a remarkable increase in publications of pharmacovigilance studies using DAs was observed, albeit the quality was debated: several publications contained “spin”, namely, misinterpretation of results to infer causality, calculate incidence, or provide risk stratification, which may ultimately result in unjustified alarm. The development of dedicated Guidelines by the international READUS-PV project (https://readus-statement.org/) will allow reproducible and transparent publication of accurate DAs, thus supporting their real transferability and exploitation by regulators and clinicians. This review offered a perspective on methodological aspects (and understanding) of DAs, their rationale, design, reporting, and interpretation.

A retrospective and observational study of the adverse drug reactions reported in a tertiary care hospital

Background: Adverse drug reaction (ADR) is considered a common cause of prolonged hospitalization and death among patients. Pharmacovigilance is essential in the surveillance of adverse drug reactions. The responsibility of a healthcare professional is to report any adverse reaction that occurs with the use of drugs. This helps in providing a database and improving the safety of patients. The aim of the study was to determine the incidence of ADR, assess causality, severity, and preventability of the submitted adverse drug reactions, increase the awareness of preventability of adverse drug reactions in health care professionals by conducting regular workshops on ADR, and document occurrence of a rare ADR. Methods: A retrospective observational study was conducted to assess the ADR reported to the ADR monitoring Centre, for the past 6 years included in the study. The data were entered into Microsoft excel and analyzed using descriptive statistics. Mean and standard deviation were calculated for the categorical data. Drugs were classified according to the class. Reactions were analyzed using scales and presented in descriptive statistics. Results: A total of 95 ADR reports were received and reported. These ADRs were associated with a total of 108 drugs that were prescribed- the occurrence of ADRs dominated among females 60% (57). Antimicrobials were causing the highest number of adverse reactions 21 (19.44%) and antituberculosis drugs and radiocontrast media were associated with the following larger number of the ADRs 19 (17.59%). Intravenous at 40% was the most common route related to the development of ADR. The most common ADR caused by antimicrobials was rash (9), antitubercular therapy commonly caused hepatitis, and chills and rigors were more common with radiocontrast media. Most of the reactions observed in the patients were moderate reactions at 52.63% with 3.16% fatal ones. Conclusions: In this study, the predominant causative drugs associated with ADR were antimicrobials, antitubercular drugs, and radiocontrast media. The number of ADRs reported though was less there was a wide range of drugs causing ADR that were reported which gave a broader spectrum for analysis. There is a requirement for active monitoring of ADRs to understand the occurrence as well as help in prevention.

The development and characterization of a CRISPR/Cas9-mediated PD-1 functional knockout rat as a tool to study idiosyncratic drug reactions.

Idiosyncratic drug reactions are rare but serious adverse drug reactions unrelated to the known therapeutic properties of the drug and manifest in only a small percentage of the treated population. Animal models play an important role in advancing mechanistic studies examining idiosyncratic drug reactions. However, to be useful, they must possess similarities to those seen clinically. Although mice currently represent the dominant mammalian genetic model, rats are advantageous in many areas of pharmacologic study where their physiology can be examined in greater detail and is more akin to that seen in humans. In the area of immunology, this includes autoimmune responses and susceptibility to diabetes, in which rats more accurately mimic disease states in humans compared with mice. For example, oral nevirapine treatment can induce an immune-mediated skin rash in humans and rats, but not in mice due to the absence of the sulfotransferase required to form reactive metabolites of nevirapine within the skin. Using CRISPR-mediated gene editing, we developed a modified line of transgenic rats in which a segment of IgG-like ectodomain containing the core PD-1 interaction motif containing the native ligand and therapeutic antibody domain in exon 2 was deleted. Removal of this region critical for mediating PD-1/PD-L1 interactions resulted in animals with an increased immune response resulting in liver injury when treated with amodiaquine.

Pediatric drug reaction with eosinophilia and systemic symptoms: A 12-year retrospective study in a tertiary center.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and severe adverse drug reaction involving multiple organs. Data on DRESS syndrome among children are currently limited. The purpose of this study was to determine the clinical features, causative drugs, systemic organ involvement, laboratory findings, disease severity score, and treatment outcomes in pediatric DRESS patients. The medical records of all pediatric DRESS patients, based on the RegiSCAR diagnostic criteria and admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand from January 2010 to December 2021, were reviewed. Twenty-two cases were identified (males 54.5%) with a median age of 9.5 years. Anticonvulsants (54.5%) and antibiotics (27.3%) were the leading culprit drugs. Skin rash was reported in all cases, followed closely by liver involvement (95.5%). Eosinophilia and atypical lymphocytosis were identified in 54.5% and 31.8% of cases, respectively. The median latency period was 17.5 days. Liver enzyme elevation was detected at an average onset of 20.0 days and hepatocellular type was the most common pattern of liver injury. Nineteen patients (86.4%) were treated with systemic corticosteroids with prednisolone being the most prescribed medication. One case developed Graves' disease after DRESS and multiple relapses of DRESS. One case (4.5%) died due to refractory status epilepticus that was unrelated to DRESS. Anticonvulsants were the major cause of DRESS in pediatric patients. High suspicion for DRESS is crucial in patients receiving these drugs and presenting with fever, rash, and internal organ involvement.

Outcomes of Community Pharmacy Interventions on Patients with Medicines Under Additional Monitoring.

Additional monitoring (AM) medicines include (i) medicines containing a new active substance; (ii) biological medicines; (iii) medicines with conditional approval or authorized in special situations; (iv) medicines which require further studies; (v) medicines that have specific requirements regarding the reporting of suspected adverse drug reactions (ADRs). When AM medicines are marketed, their most common ADRs are known, but safety information is limited because relatively rare ADRs are often not detected in clinical trials. Their AM status warrants real-world studies to identify other safety issues; however, such studies are lacking. Correct use and adherence to dosage regimen by patients are key factors for the evaluation of the safety and efficacy of medicines. The objective of this work was assessing the impact on safety, adherence, use and knowledge (U&K) about medicines and patient's quality of life (QOL), of community pharmacist (CP)-led interventions in a new service focused on AM medicines targeted at three prevalent chronic diseases: diabetes mellitus type 2, chronic obstructive pulmonary disease and cardiovascular disease. A prospective interventional cohort study was conducted with a 6-month follow-up in 27 community pharmacies (145 patients). Safety, adherence to treatment, patient U&K and QOL were assessed at follow-up visits (months 0, 3 and 6). The number of detected ADRs was 163 with 41 patients referred to the doctor. At baseline, 24.1% of the patients were non-adherent, mainly due to unintentional causes. After six months and 130 interventions by CPs on adherence, a significant reduction to lower than 5.8% was achieved. The inadequate U&K of medicines also decreased, from 47.6% to 7.9% after 182 interventions. Also, the patient's QOL improved. A new patient-centered pharmacy service provides some evidence on the important role of CP in assisting the proper and safe use of AM medicines, improving patient health outcomes.

Gabapentin-induced Alopecia: A Rare Adverse Effect Unveiled

Abstract Gabapentin is an antiepileptic drug which is effective in managing specific forms of neuropathic pain. It is widely used due to its efficacy and safety. Alopecia is a rare adverse drug reaction of gabapentin. We herein report the case of a 73-year-old female who developed severe hair loss after initiating treatment with gabapentin for thoracic radiculopathy.

A case report on bortezomib-induced paralytic ileus

Bortezomib is the first anticancer proteasome inhibitor used in the initial treatment of multiple myeloma in combination with cyclophosphamide and dexamethasone. Subcutaneous and intravenous forms of bortezomib are available. The common adverse drug reactions (ADRs) associated with bortezomib include peripheral neuropathy, fatigue, neuralgia, dizziness, diarrhea, constipation, and abdominal pain. Paralytic ileus is a rare ADR of bortezomib. We report the case of a patient with multiple myeloma who developed paralytic ileus and presented with abdominal distension and constipation; all of which resolved with medical attention once the medication was stopped, indicating a clear causal link.

Ampicillin-Sulbactam-Induced Liver Injury in a Pediatric Patient

Drug-induced liver injury (DILI) is a rare adverse drug reaction (ADR) in pediatric patients and limited reports exist examining ampicillin-sulbactam-induced liver injury. This report summarizes a 12-year-old male who received ampicillin-sulbactam and subsequently developed liver injury characterized by elevated serum aminotransferases and bilirubin. Ampicillin-sulbactam was subsequently discontinued and the patient’s liver function tests (LFTs) rapidly improved. This report describes the rare adverse reaction of ampicillin-sulbactam-induced liver injury.

Nifedipine-induced agranulocytosis: A rare case report and literature review

Rationale: Drug-induced agranulocytosis (DIAG) is a fatal idiosyncratic reaction characterized by a peripheral neutrophil count <0.5 × 109/L. Almost all classes of medications have been implicated with DIAG. However, agranulocytosis induced by antihypertensive drugs is rare worldwide. To the best of our knowledge, this is the first case of nifedipine-associated agranulocytosis with a positive rechallenge. Patient concerns: An 82-year-old man was admitted to our hospital due to uncontrolled fasting blood sugar. He had a history of hypertension and underwent treatment with nifedipine 6 years prior to admission. Blood tests showed white blood cell count of 2.30 × 109/L with a neutrophil count of 0.49 × 109/L. Diagnosis: Other malignancies that contributed to agranulocytosis were excluded, and the patient was diagnosed with DIAG. Interventions and outcomes: At first, gliclazide, rather than nifedipine, was considered as the culprit for DIAG and it was discontinued. Neutrophil count improved upon hematopoietic growth factors and traditional Chinese medicine. During the follow-up, the neutrophil count decreased again, and nifedipine was thought to be the offending agent for agranulocytosis. The neutrophil count increased to 0.91 × 109/L 2 months after nifedipine discontinuation. However, the patient was re-exposed to nifedipine and the neutrophil count decreased to 0.70 × 109/L. Lessons: Nifedipine-induced agranulocytosis is a rare but serious adverse drug reaction. For any patients with clinical suspicion or diagnosis of DIAG, a full drug history should be chronologically and completely taken in order to identify the suspected agents. Sometimes diagnosis of DIAG is challenging since some patients may be entirely asymptomatic. Management of DIAG starts with immediate discontinuation of the implicated drug. Empirical broad-spectrum antibiotics and hematopoietic growth factors may improve patient outcomes and reduce recovery time.

Characteristics of adverse drug reactions due to nonsteroidal anti-inflammatory drugs: a cross-sectional study.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for treating pain and inflammation. Spontaneous adverse drug reaction (ADR) reports represent a rich data source for the detection of unknown and rare ADRs. This cross-sectional study aimed to analyze the characteristics of ADRs due to NSAIDs in Thailand. All ADR reports of NSAIDs for systemic use from 2015 to 2019 were extracted from the national database in Thailand. Patient characteristics, drug use information, adverse event information, and source of senders in 32,857 reports were analyzed. The annual number of ADR reports due to NSAIDs decreased from 7,008 in 2015 to 5,922 in 2019. The most frequently reported drug was ibuprofen (n=12,645, 38.5%) followed by diclofenac (n=7,795, 23.7%), most patients were 40-59 years old, and the major adverse reaction was angioedema (n=7,513, 22.9%). Serious reactions were recorded in 20.7% (n=6,801) of the total ADRs. Most patients (n=20,593, 62.7%) recovered without sequelae, but there were 5,420 patients (16.5%) who could not recover and 3,109 patients (9.5%) who were recovering. Eight patients (0.02%) died of Stevens-Johnson syndrome (n=3), toxic epidermal necrolysis (n=4), and anaphylactic shock (n=1), which were possibly related to ADRs. The number of ADR reports due to NSAIDs decreased from 2015 to 2019 in Thailand. Serious ADRs and death cases accounted for 20.7% and 0.02%, respectively. Most fatal cases exhibited severe drug-induced skin reactions.

Levetiracetam-induced rash and desquamation: An extremely rare adverse drug reaction

Abstract: Levetiracetam is a second-generation antiepileptic medication with a diverse array of mechanisms of action. Cutaneous adverse drug reactions (CADRs) associated with levetiracetam are infrequently reported in the literature. We present a case of a patient who developed a rash and desquamation due to levetiracetam treatment, which was completely resolved on cessation of the medication. We conduct a comprehensive review of the literature on CADRs associated with levetiracetam and propose a hypothesis regarding the underlying mechanism of this uncommon complication. We also highlight the importance of health-care providers being aware of the full range of potential adverse drug reactions associated with levetiracetam, including the occurrence of rash and desquamation. Prompt discontinuation of therapy is essential to reverse the associated effects. Further studies are needed to elucidate the pathophysiology of CADRs associated with levetiracetam and to develop strategies for prevention and management.

Nicolau syndrome with pemphigus vulgaris: a rare case report and review of literature

BackgroundNicolau syndrome is a rare adverse drug reaction clinically presented with painful erythema and tissue necrosis often accompanied by intramuscular injections of NSAIDS (diclofenac), penicillin, corticosteroids and local anesthetics.Case presentationThis case report describes a 29-year-old male patient who was repeatedly hospitalized for the treatment of recalcitrant pemphigus vulgaris. When the patient visited for the fourth time to our hospital, he complained of unusual sharp pain over the right gluteal region ever since the administration of diclofenac 75 mg intramuscular injection for persistent back pain during his previous stay. On physical examination, the right gluteal region showed a globular swelling with erythema and pus filled necrosed tissue. The CT scan did not show any presence of hematoma, ruling out any possibility of compartment syndrome. Based on this clinical evidence he was diagnosed with Nicolau Syndrome secondary to diclofenac injection. The tissue injury necessitated surgical debridement and after a span of 2 months, it healed leaving a permanent scar. In addition, this case report highlights the treatment of recalcitrant pemphigus vulgaris with rituximab therapy.ConclusionClinical pharmacist plays a vital role in educating healthcare professionals about following right protocol for administration of injectable drugs, early detection and management of the ADR. Similarly, patient receiving injections should be educated about warning signs and symptoms of such adverse drug reaction.

Pharmacists' Perceptions on Safety Alerts of the Drug Utilization Review (DUR) in Electronic Health Records in a Tertiary Healthcare Hospital.

Electronic Drug Alarms and Drug Utilization Reviews (DURs) are crucial in improving patient safety by reducing the dispensing of contraindicated medications and minimizing adverse drug events. The DUR system often generates low-level alerts, making it challenging for pharmacists and doctors to discern more critical alerts. This can result in alert fatigue, causing burnout and jeopardizing patient safety. A cross-sectional study was conducted in a tertiary hospital to explore pharmacists' perspectives and experience with the DUR system. This study aimed to identify their responses to alerts indicating a need to change the original prescription and the difficulties encountered. Out of all the participants, 85% had prior experience with DUR alerts. However, 40% of them expressed dissatisfaction with the alerts. Moreover, 88% of the participants received highly frequent DUR alerts, but only 40% believed that DUR alerts could identify rare adverse drug reactions. Additionally, only 27% of the participants altered their prescriptions based on alerts for the MAOI/serotonin modulator. The survey showed that 66% of participants believe improvements are necessary for the DUR system. Specifically, 77% of participants felt that more information is needed on overlapping prescriptions, 82% on patients with chronic diseases, and 82% on potential reactions caused by co-administration. At the same time, 75% raised concern about the need for backup for any server breakdown. Positive perceptions about DUR lead to changing the prescription in response to an alert. Therefore, improving the DUR system is crucial to prevent pharmacists from missing important alerts and to increase their awareness of clinically significant alarm signals. By doing so, we can optimize patient safety and contribute to providing high-quality healthcare services.

Development of autoimmune pemphigus vulgaris following Chadox1 nCov-19 coronavirus vaccine (recombinant)

Pemphigus vulgaris is a rare IgG-mediated autoimmune disease that affects the skin and mucous membranes, causing painful blistering. Pemphigus vulgaris has been reported to be triggered or exacerbated by various factors, including genetic vulnerability, certain drugs, and malignant diseases. We present a case of a patient who was admitted to the dermatology ward with complaints of multiple fluid-filled lesions, initially over the chest, containing clear fluid-filled, ruptured within 1 to 2 hours to leave behind painful raw areas, predominantly over the trunk, scalp, face, upper limbs in the past 2 weeks, and single raw erosions inside the oral cavity after receiving the second dose of Chadox1 nCov-19 coronavirus vaccine (Covishield™), and also mentioned he had developed similar symptoms after the 1st dose of COVID vaccine. We chose to report this case because of the unusual presentation of a rare COVID vaccine adverse drug reaction seen in India.

Prescribed Drugs and Self-Directed Violence: A Descriptive Study in the Spanish Pharmacovigilance Database.

Self-inflicted violence is a major and growing public health problem and its prediction and prevention is challenging for healthcare systems worldwide. Our aim was to identify prescribed drugs associated with self-directed violent behaviors in Spain. A descriptive, longitudinal and retrospective study of spontaneous reports of adverse drug reactions corresponding to self-directed violence was recorded in the Spanish Pharmacovigilance Database (FEDRA®) from 1984 to 31 March 2021. A total of 710 cases were reported in the study period. The mean age was 45.52 years (range 1-94). There were no gender differences except in children, where most reports were of male children. The main therapeutic groups that were involved included drugs for the nervous system (64.5%) and anti-infectives for systemic use (13.2%). The most commonly reported drugs were varenicline, fluoxetine, lorazepam, escitalopram, venlafaxine, veralipride, pregabalin, roflumilast and bupropion. There were reports of montelukast, hydroxychloroquine, isotretinoin, methylphenidate, infliximab, natalizumab, ribavirin and efavirenz, which were less known to be involved in self-directed violence. This study shows that self-directed violence is a rare adverse drug reaction, and can be related to the use of some medicines. It is important for healthcare professionals to consider this risk in their clinical praxis, implementing person-centred approaches. Further studies are needed, considering comorbidities and potential interactions.

A Case Report of Phenytoin-Induced Stevens-Johnson Syndrome

Stevens-Johnson syndrome and Toxic epidermal necrosis are acute, self-limited diseases, rare but life-threatening adverse drug reactions. Anti-epileptic drug-induced Steven-Johnson syndrome is a severe cutaneous adverse reaction, among anti-epileptic drugs carbamazepine and phenytoin are the major culprit. We report here a case of Steven-Johnson syndrome due to phenytoin. A 22-year-old female reported the chief complaint of fever and multiple rashes all over the body with skin peeling, gradual onset, and progressive in nature. The reaction was evoked after intake of T. Phenytoin for 1 ½ months. She started heavy skin eruption all over the body for 15 days. She was treated with corticosteroids, anti-microbial, and anti-fungal agents. Healthcare providers must carefully regard the adverse effect of the drug, especially the one that is Steven-Johnson syndrome which is a potentially fatal condition. The most commonly prescribed drug regimen should also be used and continuously monitored to prevent adverse drug reactions. Keywords: Steven-Johnson syndrome, Adverse drug reaction, Phenytoin, Skin eruption