Role of human leukocyte antigen in anti-epileptic drugs-induced Stevens-Johnson Syndrome/toxic epidermal necrolysis: A meta-analysis.

PURPOSE: Antiepileptic drugs (AEDs) are extensively used to manage epilepsy and other comorbidities associated with seizures. Human Leukocyte Antigen (HLA) has a strong association with AED-induced severe cutaneous adverse drug reactions. OBJECTIVE: We aimed to perform a systematic review and meta-analysis to identify, critically evaluate, and synthesize the best possible evidence on HLA-associated AED-induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN). METHODS: MEDLINE/PubMed, Scopus, and the Cochrane Library were searched for literature from inception up to July 2022. We included case control studies analyzing association between HLA and AED-induced SJS/TEN. We assessed the studies' risk of bias in using Quality of genetic studies (Q-genie) tool. Outcomes focused on association (risk) between HLA and AED-induced SJS/TEN. The estimated risk was presented in the form of odds ratio (OR). RESULTS: We included 37 studies (51,422 participants; 7027 cases and 44,395 controls). There was a significantly higher risk of Carbamazepine-induced SJS/TEN with HLA-A (OR: 1.50; 95% CI: 1.03 to 2.17), HLA-B (OR: 1.94; 95% CI: 1.45 to 2.58), HLA-C (OR: 7.83; 95% CI: 4.72 to 12.98), and HLA-DRB1 (OR: 2.82; 95% CI: 1.94 to 4.12). Lamotrigine-induced SJS/TEN posed a higher risk with HLA-A (OR: 2.38; 95% CI: 1.26 to 4.46) and HLA-B (OR: 2.79; 95% CI: 1.75 to 4.46). Phenytoin-induced SJS/TEN showed a higher risk with HLA-A (OR: 3.47; 95% CI: 2.17 to 5.56), HLA-B (OR: 1.72; 95% CI: 1.38 to 2.15), and HLA-C (OR: 2.92; 95% CI: 1.77 to 4.83). Phenobarbital-induced SJS/TEN had a higher risk with HLA-A (OR: 6.98; 95% CI: 1.81 to 26.84), HLA-B (OR: 2.40; 95% CI: 1.39 to 4.17), and HLA-C (OR: 3.37; 95% CI: 1.03 to 11.01). Zonisamide-induced SJS/TEN was significantly associated with HLA-A*02:07 (OR: 9.77; 95% CI: 3.07 to 31.1), HLA-B*46:01 (OR: 6.73; 95% CI: 2.12 to 21.36), and HLA-DRB1×08:03 (OR: 3.78; 95% CI: 1.20 to 11.97). All other alleles of HLA were observed to have a non-significant association with AED-induced SJS/TEN. All included studies were of good quality, with a score of >50 and a mean score of 54.96 out of 77. CONCLUSION: Our study showed a significant association between few variants of HLA alleles and AED-induced SJS/TEN. Evidences from our study could help in population-based studies and in implementation of individualized treatment regimens. These findings could be part of translational research helping in precision therapy.

Ciprofloxacin-induced cutaneous adverse drug events: a systematic review of descriptive studies.

OBJECTIVES: Ciprofloxacin (CIPRO) is a fluroquinolone class antibiotic used commonly for the treatment of various acute and chronic bacterial infections. However, recently there is increase in the case reports of CIPRO-induced Cutaneous Adverse Drug Reactions (CADRs). We aim to systematically review all the descriptive studies of CIPRO induced CADRs. METHODS: Medline (via PubMed) was searched without any language or date restriction from inception to March 2019 using search terms of "Ciprofloxacin" and "Cutaneous reactions." We included only the descriptive studies, which elucidate the CADRs experienced by the patients following the administration of CIPRO. Two reviewers involved in study selection, data extraction and quality assessment of the included studies. Discrepancies were resolved by consensus between the reviewers. RESULTS: Thirty-nine studies (out of 446) were found to be eligible for the final inclusion. The dose of CIPRO among the included studies was ranging from 500 to 1,000 mg/day and duration of treatment was between 7 and 10 days. The most common CADRs observed were toxic epidermal necrolysis, Stevens-Johnson syndrome, fixed drug eruptions, bullous fixed drug reaction, acute generalized pustulosis, erythema multiforme, drug rash with eosinophilia and systemic symptoms and erythema nodosum. CONCLUSIONS: Management of the CIPRO-induced CADRs is recommended with the complete cessation of the CIPRO, followed by supportive management with oral or topical glucocorticoids, emollients, and topical moisturizers. CIPRO is likely to cause CADRs, physicians should be vigilant while prescribing it to the patients.

Linezolid Induced Skin Reactions in a Multi Drug Resistant Infective Endocarditis Patient: A Rare Case.

RATIONALE: Linezolid (LNZ) induced Cutaneous Adverse Drug Reactions (CADRs) have rare atypical presentation. Till date, there are very few published case reports on LNZ induced CADRs among the multidrug-resistant patients suffering from Infective Endocarditis (MDR IE). Here, we present a rare case report of LNZ induced CARs in a MDR IE patient. CASE REPORT: A 24-year-old female patient was admitted to the hospital with chief complaints of fever (101°C) associated with rigors, chills, and shortness of breath (grade IV) for the past 4 days. She was diagnosed with MDR IE, having a prior history of rheumatic heart disease. She was prescribed LNZ 600mg IV BD for MDR IE, against Staphylococcus coagulase-negative. The patient experienced flares of cutaneous reactions with multiple hyper-pigmented maculopapular lesions all over the body after one week of LNZ therapy. Upon causality assessment, she was found to be suffering from LNZ induced CADRs. LNZ dose was tapered gradually and discontinued. The patient was prescribed corticosteroids along with other supportive care. Her reactions completely subsided and infection got controlled following 1 month of therapy. CONCLUSION: Healthcare professionals should be vigilant for rare CADRs, while monitoring the patients on LNZ therapy especially in MDR patients as they are exposed to multiple drugs. Moreover, strengthened spontaneous reporting is required for better quantification.

Levetiracetam and cutaneous adverse reactions: A systematic review of descriptive studies.

PURPOSE: Recently, there have been an increased number of reports on levetiracetam (LEV) induced cutaneous adverse drug reactions (CADRs). We aimed to identify and critically evaluate all the descriptive studies on LEV induced-CADRs and to describe the possible clinical manifestations, management, and treatment outcomes of the condition. METHODOLOGY: PubMed and grey literature databases were searched from inception to June 2019 without any restriction. We also performed a bibliographic search for additional studies. Only descriptive studies on LEV-induced CADRs were included for our review. Study selection, data abstraction and quality assessment were performed by two contributors independently and disagreements were settled through consensus or through discussion with a third reviewer. RESULTS: Data from 24 out of 88 studies, which included 25 patients (12 female and 13 male) aged from 40 weeks to 73 years, were reviewed. Patients received between 500 mg/day to 3000 mg/day of LEV. Drug reaction with eosinophilia and systemic symptoms syndrome, Steven-Johnson syndrome, toxic epidermal necrolysis, acute generalised exanthematous pustulosis, generalised hyperpigmentation and leucocytoclastic vasculitis were observed among the included patients. Immediate cessation of LEV, providing supportive care and use of topical antihistamines and anti-inflammatory drugs appeared to be the mainstay of management, and all patients were found to have recovered. CONCLUSION: Clinicians should be aware of the possible CADRs induced by LEV to avoid the development of a potentially fatal condition. Immediate withdrawal of the drug and supporting care seem to be effective in the management of the CADRs. REGISTRATION NUMBER: International Prospective Register for Systematic Reviews (PROSPERO) number CRD42019141002.

Cost analysis of various branded versus generic chemotherapeutic agents used for the treatment of early breast cancer- a deep insight from India.

BACKGROUND: Breast cancer (BC) stands first with high incidence and mortality in India. Most of the oncologists are unaware of cost savings by utilising generic drugs. AIM: To perform a cost minimization analysis of generic versus branded chemotherapeutic regimen for treatment of BC. METHODOLOGY: CIMS (current index of medical stores) was referred for the cost of branded drugs and the generic cost was taken from Jan Aushadhi scheme. The percentage cost variation and potential cost-saving particular to BC regimens on substituting available generic drug was calculated using standard formula and costs were presented in Indian Rupees and US Dollars (as of 2019). RESULTS: Among the branded agents considered, a range of 25% to 606.11% cost variation was observed with cyclophosphamide and 5-Fluorouracil respectively. Gemcitabine proposed the highest cost variation (373.68%-990.78%) and cyclophosphamide (71.42%-114.28%) with the lowest variation when compared to generic drugs. The highest level of cost-saving (₹60,807.3 to ₹1,31,864.1) with TAC regimen and the lowest range (₹12,15.84 to ₹15,667.2) with AC regimen was observed among adjuvant therapy regimens. CONCLUSION: Our evaluation inferred that substituting generic chemotherapeutic drugs can bring potential cost savings. Healthcare professionals and patients should aware and opt generic drugs to achieve goals of BC therapy.

Prevalence and Predictors of Self-Medication Practices in India: A Systematic Literature Review and Meta-Analysis.

BACKGROUND: Self-Medication (SM) is a practice of using medications to treat selfdiagnosed symptoms without a legitimate prescription by a health care professional. Alongside posing a burden on a patient, SM practices are associated with certain unfavourable health conditions such as drug-resistance, adverse effects, drug-interactions, including death. OBJECTIVE: To systematically review and quantify the prevalence of SM practices and its associated factors in India. METHODS: A comprehensive systematic search was performed using scientific databases such as PubMed and Cochrane library for the peer-reviewed research articles that were conducted in India without any language and date restrictions. Studies which were cross-sectional by design and assessing the prevalence and predictors of SM practices in India were considered for the review, and all the relevant articles were screened for their eligibility. RESULTS: Of 248 articles, a total of 17 articles comprising of 10,248 participants were included in the meta-analysis. Overall, the mean prevalence of SM practices in India was observed to be 53.57%. Familiarity with the medication appears to be a major reason to practice SM (PR: 30.45; 95% Confidence Interval [CI]: 17.08-43.82; 6 studies), and the practice was noticed more among individuals from a middle-lower class family with a prevalence rate of 26.31 (95%CI: 2.02-50.60; P<0.0001). Minor ailments were the primary reason for practicing SM (PR: 42.46; 95%CI: 21.87- 63.06), among which headache was the most commonly reported (PR: 41.53; 95%CI: 18.05-65.02). CONCLUSION: Self-medication practices are quite frequent in India. While NSAIDs and anti-allergens are the most frequently utilized self-medicated drugs used for headache and cold and cough.

Impact of pharmacist-led home medicines review services on drug-related problems among the elderly population: a systematic review.

OBJECTIVES: To address and elucidate the impact of pharmacist-led home medicines review (HMR) services on identifying drug-related problems (DRPs) among the elderly population in home care settings. METHODS: A comprehensive systematic search was performed using electronic scientific databases such as PubMed, Scopus, Embase, and Web of Science for studies published between January 1, 2008 and December 31, 2018, pertaining to HMR services by pharmacists for identifying DRPs. RESULTS: In total, 4,292 studies were retrieved from the searches, of which 24 were excluded as duplicates. Titles and abstracts were screened for the remaining 4,268 studies, of which 4,239 were excluded due to the extraneous nature of the titles and/or abstracts. Subsequently, 29 full-text articles were assessed, and 19 were removed for lacking the outcome of interest and/or not satisfying the study's inclusion criteria. Finally, 10 studies were included in the review; however, publication bias was not assessed, which is a limitation of this study. In all studies, pharmacists identified a highly significant amount of DRPs through HMR services. The most common types of DRPs were potential drug-drug interactions, serious adverse drug reactions, need for an additional drug, inappropriate medication use, non-adherence, untreated indications, excessive doses, and usage of expired medications. CONCLUSIONS: HMR is a novel extended role played by pharmacists. The efficiency of such programs in identifying and resolving DRPs could minimize patients' health-related costs and burden, thereby enhancing the quality of life and well-being among the elderly.

Valproic acid and Stevens-Johnson syndrome: a systematic review of descriptive studies.

Valproic acid (VPA) is a commonly used antiepileptic drug (AED). Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis are the rare but fatal cutaneous adverse drug reactions for VPA. We aimed to identify and critically evaluate all the literature of SJS in association with VPA and to describe the clinical features of the condition. A literature search was conducted in MEDLINE/PubMed from inception to December 2017 and updated in July 2018 without any restrictions, and the references of included studies were also searched. The descriptive studies discussing any patients who experienced SJS followed by the use of VPA alone or along with any other AED for its main indication were included. Two authors were independently involved in the study selection and data extraction. Disagreements were resolved by consensus or by the discussion with a third reviewer. A total of 19 studies including 17 case reports and two case series of 98 were included in the review. In all studies, the dose of VPA ranged from 100 mg/day to a maximum dose of 1,000 mg/day and was administered for indications including epilepsy, seizures, schizophrenic affective disorders, and bipolar disorder. The mortality seen with severe cutaneous adverse drug reactions can be decreased by immediate withdrawal of opposing medications, providing symptomatic relief, and offering supportive care, all of which are the mainstay of controlling the condition. It is essential for healthcare professionals to be aware of the importance of monitoring SJS or any other cutaneous reactions followed by the use of valproic acid even though the incidence is low, but it is injurious to the patient.