Current drug safety最新文献

Background: Tumor necrosis factor alpha (TNF-α) inhibitors, such as adalimumab, have significantly advanced the treatment of inflammatory diseases. However, these therapies are associated with various cutaneous adverse reactions.

Case presentation: We describe two rare instances of isolated facial hyperpigmentation induced by adalimumab. Both patients presented with asymptomatic, isolated brown macules on the cheeks following adalimumab treatment for ankylosing spondylitis. The hyperpigmentation appeared shortly after starting the medication in both cases. In one case, the hyperpigmentation persisted despite stopping the medication, while in the second case, it completely resolved within one month after discontinuation. However, in the second patient, the hyperpigmentation recurred after switching to certolizumab, another TNF-α inhibitor. No skin biopsies were performed, and both patients were otherwise healthy, with normal laboratory evaluations.

Conclusion: Hyperpigmentation is an uncommon adverse reaction of this class of drugs, with only a few reported cases in the literature. The recurrence of hyperpigmentation after switching to another TNF-α agent, certolizumab, further suggests that this reaction may be a class effect, adding new insights into the spectrum of cutaneous side effects associated with TNF-α inhibitors. Clinicians should consider this potential side effect in patients presenting with hyperpigmentation, and sun protection should be recommended as a preventive measure.

Background: Adverse Drug Reactions (ADR) are one of the essential causes of hospital admissions and pose a significant clinical and economic burden on the healthcare system. The Adverse Drug Reaction Monitoring Centre (AMC) in JIPMER functioning under the Pharmacovigilance Programme of India (PvPI) plays a vital role in ensuring medication safety by routinely detecting and monitoring ADRs. Hence, this study aimed to assess the characteristics of ADR reported from 2010 to 2020 in AMC JIPMER and to detect signals, if any.

Objectives: To study the characteristics of Adverse Drug Reactions (ADR) reported to a regional ADR monitoring center from 2010 to 2020 and to detect signals of disproportionate reporting (SDRs) if any from the reported ADRs.

Materials and methods: A total of 6007 ADR reports with a single suspect drug were included for analysis from 2010 to 2020. The characteristics of these reports, including patient's age and gender, Number and percentage of ADRs, the causality of ADR using WHO UMC (World Health Organization-Uppsala Monitoring Scale), the seriousness of the ADR, and outcome were collected from the ADR reports. MedDRA (Medical Dictionary for Regulatory Activities) Preferred Terms (PT) were used to classify adverse drug reactions. Causality analysis using the Naranjo Algorithm and Preventability using Modified Schumock and Thornton criteria were performed for the ADRs. The number and percentage of severe ADRs were analyzed. The System Organ class of all the ADRs was enumerated. ADRs not mentioned in the US FDA (United States Food and Drug Administration) product label (unlabelled reactions) were documented. Unlabeled reactions with ≥3 ADR reports were included for signal detection by disproportionality analysis.

Results: Antineoplastic drugs, followed by antimicrobials, anticonvulsants, Anti snake venom, and NSAID were the most common drugs implicated in ADRs. Skin and subcutaneous tissue disorders were the most common System Organ Class (SOC) involved in the ADRs. Among the 6007 reports, 19.2% were serious ADRs. Most of the ADR reports were of possible causality followed by probable and certain as per WHO UMC and Naranjo causality scales. Only ten ADRs were preventable and one reaction (Tamoxifen-induced neuropathy) was eligible for signal detection. Disproportionality analysis using a 2x2 contingency table showed insignificant signal detection using the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR).

Conclusion: Analysis of ADRs from an ADR Monitoring center functioning in a tertiary care hospital shows antineoplastic drugs to be the most common drugs associated with adverse drug reactions, with rash being the most common adverse effect. The majority of the ADRs were not preventable. No Signals of Disproportionate Reporting (SDR) were detected in our study.

Considering the fact that two available and commonly used formulations of amphotericin B could be used instead of each other by mistake. Also, an updated and comprehensive data regarding management of this medication error was not available; the current review was conducted to gather available data among the pediatric population and discuss management and outcome of patients in case such an error occurs. We review all the cases of amphotericin B overdose which reported in PubMed and google scholar so far then discuss an 8-years-old girl diagnosed with Ewing sarcoma who inadvertently received five times more than therapeutic dose of amphotericin B deoxycholate (5mg/kg/day).In total, ten of the cases were exactly matched to our purpose of the study. In our case, fluid and electrolyte management was aggressively undertaken and she was put under cardiac monitoring for 7 days following detection of the medication error. Finally, she was discharged from hospital with stable condition. Reviewed data in this manuscript showed that amphotericin B deoxycholate overdose could cause severe complications and lead to cardio toxicity, electrolyte imbalance and death. Aggressive cardiac, fluid and electrolyte monitoring and management of any problem as soon as they were detected was the pathway followed by the authors of this review and others who faced this medication error. The role of NAC and hydrocortisone in the managing amphotericin B deoxycholate overdose requires further investigation.

Introduction/aim: The study examines how chronic resveratrol administration affects behavioral and neurochemical changes caused by Lorazepam (LZP), a classical anti-anxiety medicine associated with neurodegenerative and neurological problems.

Method: Forty male rats were placed into four groups: a control group receiving 1% Tween 80, the LZP group receiving 2 mg/kg/day, the Resveratrol group receiving 50 mg/kg/day, and the LZP plus resveratrol group receiving the same doses of LZP and Resveratrol. Oral therapy was given daily for 6 weeks. The animals were euthanized after open field and Y maze behavioral tests. In specific brain regions, neurochemical analyses were performed on GABA, glutamic acid, monoamines (norepinephrine, dopamine, and serotonin) and their metabolites, DNA fragmentation (8-hydroxy-2-deoxyguanosine or 8-HdG), brain-derived neurotrophic factor (BDNF), and Ca-ATPase.

Results: Resveratrol therapy improved GABA, glutamic acid, monoamines, and their metabolites in the cerebral cortex, hippocampus, and striatum. Additionally, it reduced DNA fragmentation (8- HdG) and counteracted LZP-induced Ca-ATPase downregulation at a significant level (p < 0.05). Resveratrol also reversed LZP-induced behavioral changes in the Y maze and open field tests.

Conclusion: Resveratrol has anxiolytic-like actions like benzodiazepines and neuroprotective capabilities against LZP-induced adverse effects.

Background: Imipenem-cilastatin, a carbapenem antibiotic, is commonly used for severe bacterial infections. While generally well-tolerated, it can rarely cause central nervous system toxicity, including seizures. We have, herein, reported a case of imipenem-cilastatin-induced seizure in a 20-year-old patient.

Case presentation: A 20-year-old male was admitted to the intensive care unit for febrile status epilepticus and acute respiratory distress syndrome. Initial evaluations ruled out underlying causes and anti-epileptic treatment has been initiated. Despite having an effective anti-epileptic treatment for three months of hospitalization, seizure recurrence occurred, leading to antibiotic regimen adjustment as the imputability of imipenem-cilastatin was suspected. After discontinuation of the involved drug, the patient remained neurologically stable. Previous literature has reported cases of imipenem-cilastatin-induced seizures, particularly in elderly patients or at higher dosages. The causality assessment was conducted using the updated French method, which rated the chronological criterion as C2 and the semiological criterion as S2. The intrinsic imputability score was I3, indicating plausible causality, and the extrinsic bibliographic score was B3.

Conclusion: Our case has highlighted the importance of promptly recognizing imipenem-cilastatin- induced epileptic seizures in order to treat them more effectively and thus optimize the patient's care. Therefore, we emphasize that clinicians be vigilant about the side effects of its use, particularly in patients with neurological susceptibilities. We also advocate a personalized choice of antibiotics, taking into account both antimicrobial efficacy and potential adverse effects, for better outcomes with fewer risks.

Background: Although diuretic-induced Acute Pancreatitis (AP) cases are typically mild to moderate, severe and potentially fatal occurrences can arise. Case Series and Literature Review: We have, herein, presented a series of diuretic-induced AP cases from March 2018 to February 2024 of a 54-year-old woman treated with chlorthalidone, a 45-year-old male treated with hydrochlorothiazide, and a 48-year-old male treated with frusemide. The literature search has identified 26 cases published to date, 10 from frusemide and 16 from thiazide diuretics. The Naranjo adverse reaction probability scale has categorized all three drugs as "probable". All cases have responded to conservative treatment and cessation of the offending drug. Various mechanisms, such as hypersensitization, ischemia, direct cytotoxic effects, hypercalcemia, and dose-dependent idiosyncrasy, have been found to lead to intrapancreatic activation of pancreatic enzymes, resulting in drug-induced AP.

Conclusion: Further research into the mechanisms and genetic factors contributing to diureticinduced AP is essential for enabling early diagnosis and management of diuretic-induced AP.

The blood-brain barrier (BBB) is based on the unique pattern of the microvasculature of the central nervous system (CNS), which controls the transport of molecules between the CNS and the blood. The blood-brain barrier is mainly composed of endothelial cells, pericytes, and basement membrane, as well as the astrocytes and immune cells as perivascular macrophages and microglial cells. The dysfunction of this barrier can cause serious neuronal disorders due to the transport of hazardous molecules and immune cells to the CNS. Mitochondria plays a major role in cellular homeostasis in terms of health and disease. This review evaluated the published data about the effect of the drugs on the cells of BBB. Only seven articles were found that considered the effect of drugs on the barrier endothelial cells and mitochondria via different assays. Further studies are recommended to evaluate the impact of used medications on BBB cell bioenergetics. Also, the effect of the newly studied pharmaceutical agents on the BBB bioenergetics should be included within their safety profile studies.

Background: Adverse Drug Reactions (ADRs) are unexpected reactions to a medicine administered in the correct manner and at the proper dosage. Drug Rash with Eosinophilia and Systemic Symptoms syndrome (DRESS syndrome) is a Severe Cutaneous Adverse Reaction (SCAR) type of ADR with complicated clinical features involving several organ systems of the body; frequently involved organs are the liver, kidney, lungs, and other organs. Prompt recognition and correct diagnosis, followed by withdrawal of the causative agent, can promote appropriate treatment, accelerate recovery, and reduce the related morbidity and mortality.

Case presentation: We have, herein, presented a case of a 42-year-old female with a history of leflunomide intake for plantar fasciitis. The patient subsequently developed fever, gastrointestinal tract disturbance, facial edema, liver injury, skin rash, hematologic abnormalities (eosinophilia), hepatosplenomegaly, and lymph node enlargement. The probability of leflunomide-induced DRESS syndrome was rated as "definite", with seven scores graded by RegiSCAR. The suspected causative agent was withdrawn, and the patient was managed symptomatically. Following her management and discharge, she again encountered similar complaints after administration of the cefuroxime tablet. The causality assessment of the reactions was done using the WHO-UMC scale and Naranjo's assessment scale, and a "probable" reaction was found for both drugs.

Conclusion: The presented case contributes to the existing global literature regarding exceptional clinical presentations. Leflunomide and cefuroxime drugs have the potential to cause DRESS syndrome. Thus, they should be handled cautiously, and if such a reaction occurs, it should be reported to the responsible authorities.

Introduction: It is essential to exclude other causes, such as autoimmune diseases and bacterial infections, before attributing cutaneous/systemic vasculitis to drug use.

Case study: This report discusses the case of a young man who developed multi-organ failure and cutaneous vasculitis following the use of antifungal medications (terbinafine and itraconazole) for dermatophyte infections. Tests for autoimmune diseases and infections were negative. Given his drug history and a skin biopsy indicating leukocytoclastic vasculitis, it was inferred that the vasculitis was likely drug-induced. Despite treatment with steroids, intravenous immunoglobulins, and plasmapheresis, the patient did not survive, possibly due to delayed diagnosis and treatment.

Conclusion: In community practice, Drug-induced Vasculitis (DIV) is frequently overlooked. When patients present with skin rash, fever, and multi-organ dysfunction, DIV should be considered, particularly in the context of recent drug use. Over-the-counter antifungals, like terbinafine or itraconazole, can cause DIV and may be fatal if not promptly diagnosed and treated.

Infliximab (INF), a murine human monoclonal antibody, is a substantially more successful biologic than topical drugs for treating mild to severe psoriasis because it clears the skin rapidly due to its fast onset of action. Loss of responsiveness over time and some adverse effects, especially the experience of infusion reactions, are the major causes of non-compliance with INF medication. Therefore, evaluation of the long-term reliability of anti-tumor necrosis factor (TNF) medications is necessary for the assessment of the risks associated with long-term anti-TNF therapy. For psoriasis, there are registered safety statistics; however, these individuals might not receive the same level of care as those in a randomized study. Few assessments of the safety of anti- TNF medications across indications, including their biosimilars, are present, but it's still unknown how anti-infliximab antibodies arise and produce harmful effects. INF biosimilars, when subjected to human studies to reduce cost and improve access, provide therapeutic benefits with associated adverse events, showing variations in incidence depending upon varying patient populations and no new safety indications. During therapy, certain individuals develop antibodies against INF, which are believed to be linked to a loss of response (LOR). Additional research aimed at identifying individuals who are susceptible to treatment resistance is likely to assist doctors in accurately selecting the appropriate candidates for anti-TNF-α therapy and enhancing the long-term effectiveness of the treatment. From clinical studies, we expect to learn about how to utilize INF or its biosimilars more effectively in the management of psoriasis. Therefore, the paper focuses on the efficacy and safety monitoring of INF and developed biological therapies.