Severe Adverse Drug Reactions Research Articles

Clinical Characterization of Mogamulizumab-Associated Rash During Treatment of Mycosis Fungoides or Sézary Syndrome

Mogamulizumab is a monoclonal antibody against CCR4 approved for treatment for mycosis fungoides (MF) and Sézary syndrome (SS). Mogamulizumab-associated rash (MAR) is difficult to differentiate from cutaneous MF or SS, which can lead to unnecessary discontinuation of drug use because of concern for severe drug reaction or incorrect presumption of disease relapse or progression in the skin. To examine the most common clinical presentations of MAR in patients with MF or SS and the diagnostic and management challenges. This retrospective case series assessed patients from a multidisciplinary cutaneous lymphoma clinic and supportive oncodermatology clinic at a major academic referral center who had a diagnosis of MF or SS and received mogamulizumab from January 1, 2013, to January 1, 2020. Treatment was followed by new or worsening rash with skin biopsy results compatible with drug eruption determined by clinicopathologic correlation and molecular testing to exclude active malignant disease. At least 1 dose of mogamulizumab. Mogamulizumab-associated rash was characterized by clinical features, including time to onset, clinical presentation, histopathologic features, and management approach. The study included 19 patients with MF or SS who developed MAR (median age, 65 years; age range, 38-82 years; 10 [52.6%] male). Median time to MAR onset was 119 days (range, 56 days to 3.8 years). Patients with MAR exhibited 4 predominant clinical presentations: (1) folliculotropic MF-like scalp plaques with alopecia, (2) papules and/or plaques, (3) photoaccentuated dermatitis, and (4) morbilliform or erythrodermic dermatitis. The most common anatomical region involved was the head and neck, including the scalp. Histopathologic findings were variable and did not correspond to primary clinical morphologic findings. Immunohistochemistry and T-cell clonality ancillary testing were helpful to distinguish MAR from disease. Most patients with MAR (14 of 19) discontinued mogamulizumab treatment; however, no life-threatening severe cutaneous adverse drug reactions occurred, and the decision for drug therapy cessation was usually multifactorial. Four patients were treated again with mogamulizumab with no life-threatening drug-related events. Approaches to management of MAR include topical corticosteroids, systemic corticosteroids, and/or methotrexate. This case series found that mogamulizumab-associated rash had a heterogeneous clinical presentation with variable and delayed onset in patients with MF or SS. Mogamulizumab-associated rash exhibited a predilection for the head and neck and was difficult to clinically distinguish from relapse or progression of disease. Recognition of the most common clinical presentations can help prevent unnecessary discontinuation of mogamulizumab treatment. The presence of MAR does not necessitate permanent discontinuation of or avoidance of retreatment with mogamulizumab.

Identification of Adverse Drug Reactions in Congestive Heart Failure Patients in a Tertiary Care Hospital, West Nusa Tenggara, Indonesia

Congestive Heart Failure (CHF) is a progressive health problem with high mortality and morbidity and has the potential to develop adverse drug reactions (ADRs). This study was conducted to determine the prevalence of potential ADRs, the types of drugs that cause ADRs, the types of ADRs, and the risk factors that affect the ADRs in CHF patients. Data were collected using medical record of hospitalized patient at the West Nusa Tenggara (NTB) Provincial Hospital, Indonesia, in 2017 to 2019. The assessment of the causality and severity of ADRs used the Naranjo algorithm and the Hartwig and Siegel scale. This study used 325 CHF patients’ data. Of 325 CHF patients, 223 patients (69%) were recorded as having ADRs with 446 total cases of ADRs, consisted of 4 (0.9%) highly probable, 187 (41.9%) probable, and 255 (57.2%) possible. The drugs that cause ADRs with a highly probable status are bisoprolol and ramipril. The most ADRs categories were level 1 (76.0%), followed by level 2 (17.3%), level 3 (6.5%), and level 4A (0.2%). The most affected organ systems were the muscles, joints, and nervous system (n=136, 37.7%), followed by renal, and gastrointestinal system. No association between ADRs with several risk factors, such as gender, age, and comorbidities. The prevalence of ADRs in CHF patients in this study was 69%, with the highly probable category in causing ADRs were bisoprolol and ramipril. ADRs that mostly occurred were in the mild category. ADRs monitoring in CHF patients is especially important to achieve optimal therapeutic results.

In Silico Prediction and Pharmacokinetic Comparison of Ursodeoxycholic Acid and Obeticholic Acid in the Management of Primary Biliary Cholangitis

Background: Primary Biliary Cholangitis (PBC) is a persistent liver disease. Ursodeoxycholic acid is used as a first-line treatment for the past two decades. However, concurrent use of Ursodeoxycholic acid reported with a severe adverse drug reaction. Obeticholic acid has been started utilizing as monotherapy and also with Ursodeoxycholic acid in a patient who is intolerant to Ursodeoxycholic acid therapy. We primarily aimed to compare the pharmacokinetic & toxicity profiles of Ursodeoxycholic acid and Obeticholic acid using in silico methods. Method: The pharmacokinetic profile of UDCA & OCA was observed from PKCSM server online database, OSIRIS® property Explorer, T.E.S.T. (Toxicity estimation software tool) & Molinspiration® is used to estimate the drug toxicity profiles. Result: This computer-aided response provides a great understanding and creates a gap between the theoretical and clinical evidence for UDCA & OCA's preference in PBC management. Conclusion: Co-administration of Obeticholic acid with Ursodeoxycholic acid will be an effective treatment for PBC in patients with UDCA intolerants. However, both medications are well-recognized substrates of the CYP3A4 enzyme and may lead to unintended drug interactions and side effects. Keywords: Primary Biliary Cholangitis, Obeticholic acid, Ursodeoxycholic acid, CYP3A4, Drug Interactions, Pharmacokinetics.

Hypersensitivity reactions to paclitaxel: The Mexican experience of rapid desensitization.

Taxanes adjuvant therapy is recommended in certain high risk or metastatic tumors, particularly in lung and breast cancer, but also in other types of cancer like ovarian. The incidence of severe adverse drug reactions to paclitaxel is of approximately 10%. Analyze type I hypersensitivity reactions to paclitaxel and their management in the Mexican population. It is a retrospective, observational and descriptive study that included type I hypersensitivity reactions to paclitaxel reported from our database. Symptoms of hypersensitivity reactions to paclitaxel were classified and skin testing was performed with a 6 mg/mL paclitaxel concentration. The desensitization procedure consisted of a 12-steps, 3-bags of 250 mL protocol with a 6-7-hour duration. A total of 60 desensitization procedures were performed and were all completed successfully. All participants in our group were female, their median age was 44.5 years.All of our patients had hypersensitivity adverse drug reaction to paclitaxel during their first exposure and within the first 10 minutes of infusion. 63.6% of the patients had a moderate hypersensitivity reaction to paclitaxel and 36.4% had a severe reaction. Paclitaxel continues to be a common use drug and has a high rate of adverse drug reactions. This is the first study of hypersensitivity to paclitaxel in a Mexican population.

Disproportionality analysis of anaphylactic reactions after vaccination with messenger RNA coronavirus disease 2019 vaccines in the United States

Disproportionality analysis of anaphylactic reactions after vaccination with messenger RNA coronavirus disease 2019 vaccines in the United States

A Case Report on Naproxen Induced Psoriasis: The Immunosuppressant and Corticosteroid Therapy

Psoriasis is a chronic inflammatory mucocutaneous skin disorder clinically characterized by erythematous, sharply demarcated papules and rounded plaques covered by a silverywhite micaceous scales. In this case study a 58 years old male patient was having spinal pain since 1 year and he was on continuous medication like naproxen to manage the spinal pain. Where suddenly he developed a erythematous fluid filled lesions on all over the body like chest, abdomen, stomach & lower limbs within 3 days. It is one of the most severe adverse drug reaction seen in this study. We are reporting that it is a drug induced chronic plaque psoriasis and the patient was treated with systemic corticosteroidal therapy, Immunosuppressants, vitamin d analogues and some topical creams like steroids.

Drug-related problems of antipsychotics in treating delirium among elderly patients: A real-world observational study.

Delirium is more common and life-threatening among the elderly. Currently, no other medications, including antipsychotics, have been approved for delirium. The number of practice guidelines recommends antipsychotics to be the first option among selected patients. This study aimed to identify the type of drug-related problems (DRPs) concerning antipsychotics use among elderly patients with delirium. A retrospective observational study was conducted by collecting data from 2013 to 2016 in Maharaj Nakorn Chiang Mai Hospital, Thailand. Inpatients who were 60years and over, diagnosed with delirium by ICD-10 diseases coding F05.X and treated with antipsychotics for delirium were included. A modified version of the American Society of Hospital Pharmacists classification criteria (mASHP-delirium) was used. A total of 379 patients were enrolled. Mean daily dose of haloperidol (oral) was 1.06±1.33mg, haloperidol (intramuscular) 2.71±1.88mg, haloperidol (intravenous; IV) 3.42±1.97mg, risperidone was 0.71±0.52mg, and quetiapine was 19.26±15.63mg. Among all, 427 events were classified as DRPs. The most common DRPs included inappropriate duration, dose, route of administration or dosage form accounting for the 416 events (97.4%), followed by actual adverse drug reactions (extrapyramidal symptoms; EPS), 6 events (1.4%) and potential drug-drug interactions for 5 events (1.2%). Of those 416 events, 200 events (48.1%) antipsychotics were continued after discharge and continued for more than 10days. Dosage exceeding initial dose or maximum daily dose accounted for 179 events (43.0%). Other DRPs such as inappropriate route haloperidol IV and receiving the extended-release dosage form of quetiapine involve 26 (6.3%) and 11 (2.6%) events, respectively. To the best of our knowledge, this is the first study using mASHP-delirium to identify DRPs of antipsychotics in treating delirium among elderly patients. Several DRPs were found that might lead to severe adverse drug reactions, particularly EPS and QTc interval prolongation. However, all DRPs could be prevented by developing antipsychotic setting protocols and specialty consulting systems to communicate among healthcare providers caring for vulnerable groups of patients. In addition, a prospective pharmacist intervention is required.

Implementation of Pharmacogenomic Information on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Drug-related Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are rare but severe adverse drug reactions, termed as idiosyncratic reactions; however, predicting their onset remains challenging. Pharmacogenomic information associated with SJS/TEN has accumulated on several drugs in the last 15 years, with clinically useful information now included on drug labels in several countries/regions or guidelines of the Clinical Pharmacogenetics Implementation Consortium (CPIC) for implementation. However, label information might be different among countries. This mini-review summarizes pharmacogenomic information on drug labels of five drugs in six countries and compared descriptions of drug labels and CPIC guidelines. Finally, we discuss future perspectives of this issue. Pharmacogenomic information on drug labels is not well-harmonized across countries/regions, but CPIC guidelines are a scientifically sound goal for future pharmacogenomic implementation.

DRESS and AGEP Reactions to Iodinated Contrast Media: A French Case Series

Drug reactions with eosinophilia and systemic symptoms (DRESSs) and acute generalized exanthematous pustulosis (AGEP) are potentially severe cutaneous adverse drug reactions. To describe the clinical findings and sensitization profiles of DRESS and AGEP patients who had been administered iodinated contrast media (ICM). All adult patients in the dermatologist's French Investigators for Skin Adverse Reactions to Drugs (FISARD) network diagnosed with a DRESS or AGEP highly suspected to have been caused by an ICM were included retrospectively. Thirteen DRESS patients and 19 AGEP patients who had been administered ICM were included, and the median delay in DRESS and AGEP occurrence after ICM administration was short, 4 and 1 days, respectively. Five AGEP patients had systemic involvement. A high cosensitization rate (46%) was observed among the DRESS patients, mainly with beta-lactam antibiotics. Overall, 77% of our patients were sensitized to several ICM. Patch tests identified the suspected ICM for 21 cases (72%). The retrospective nature, the limited number of subjects, the absence of a control group of healthy individuals, and the lack of detailed information on previous exposure to sensitizing drugs are limitations of this study. We report a large series of DRESSs and AGEPs related to ICM administration. Skin tests appear useful for diagnosis and potentially to identify alternative ICM.

Amoxycillin-clavulanic Acid Induced Stevens Johnson Syndrome: A Pediatric Case Report

Stevens Johnson Syndrome is an unlikely, lethal, severe skin and mucosal hypersensitive reaction of delayed type, identified by detachment of epidermis, necrosis of mucosa with stomatitis and purulent conjunctivitis requiring prompt medical intervention. Drugs like antibiotics, anticonvulsants and oxide inhibitors are the vital cause of developing Stevens Johnson syndrome. A 12 year old female patient was admitted in pediatric department with the chief complaints of oral lesions on the bilateral buccal mucosa and hard palate causing difficulty in opening mouth and swallowing since 10 days. Past medical history revealed that the patient had fever and sore throat and was prescribed tablet amoxyclav (amoxicillin – clavulanic acid) by a local medical practitioner, after that patient developed ulcer in the buccal cavity and around the lips. The patient was managed with cephalosporin antibiotic (ceftriaxone), betadine mouthwash, candid ointment, nutritional supplements and systemic steroids (dexamethasone). Naranjo causality assessment score was 6 in our patient and amoxicillin clavulanic acid induced Stevens Johnson syndrome was probable and moreover on severity assessment by Hartwigs Severity Assessment Scale the severity level for the suspected adverse drug reactions was 5 therefore amoxicillin clavulanic acid induced Stevens johnson syndrome was a severe adverse drug reaction. Early detection of symptoms of Stevens johnson syndrome followed by prompt withdrawal of offending drug and timely management can improve the clinical condition of patients. Key words: Amoxicillin - clavulanic acid, Hartwigs Severity Assesment Scale, Stevens Johnson Syndrome, Hypersensitivity reaction, Naranjo Causality Assessment.

Commentary on "The risk of anti-osteoporotic agent-induced severe cutaneous adverse drug reactions and their association with HLA" by W-H Chung et al.

Linked article: C.‐B. Chen et al. J Eur Acad Dermatol Venereol 2021; 35: 712‐720. https://doi.org/10.1111/jdv.16924.

Adverse drug reaction monitoring study in hospitalized patients: support for pharmacovigilance at a tertiary care hospital

Background: Adverse drug reaction (ADR) reporting is an integral component of pharmacovigilance. However, under-reporting of ADR is commonly observed. The present study has been planned with aim to assess the pattern of reported ADRs in terms of its frequency, causality and severity so as to reinforce pharmacovigilance activities.Methods: This prospective observational study was conducted with the aim to evaluate suspected ADRs in hospitalized patients in departments of Medicine, Surgery and Orthopaedics of a tertiary care hospital in North India for a period of 6 months. The ADRs were assessed in terms of the demographic parameters, organ system affected, drugs implicated, type of ADRs by Rawlin’s and Thompson classification, causality using WHO-UMC scale and severity of ADR by Modified Hartwig’s and Siegel scale.Results: A total of 111 ADRs were reported during the study period. There was male preponderance (54.96%) with majority of ADRs in age group of 18-60 years (79.28%). Gastrointestinal system was most commonly affected (36.36%). The most common drug implicated in causing ADRs was Ceftriaxone (11.71%). Majority of ADRs were Type A reactions (86.49%). Causality assessment using WHO-UMC scale depicted that 74.77% of ADRs were possible. Severity analysis showed that 82.88% of ADRs were mild as per Modified Hartwig’s and Siegel scale.Conclusions: ADR reporting should be encouraged among health-care professionals, para-medical staff and patients in general so that the ultimate goal of pharmacovigilance can be fulfilled.

Acute generalized exanthematous pustulosis: Epidemiology, clinical course, and treatment outcomes of patients treated in an Asian academic medical center

BackgroundAcute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous adverse drug reaction. Although acutely patients have significant morbidity and occasional systemic involvement, the clinical course is generally self-limited. To date, there has been no consensus on treatment.ObjectiveThe aim of our current study was to evaluate the clinical features, drug association, treatment, and outcomes in a cohort of patients treated in an academic medical center.MethodsA retrospective review of electronic medical records over a period of 10 years from 2009 to 2018 in a single tertiary academic medical center in Singapore was performed. Forty-three medical records with probable/definite diagnosis of AGEP were identified and analyzed for statistical significance.ResultsDrug association was identified in 93% of cases. The most frequent drug class was antibiotics, including penicillins, cephalosporins, and vancomycin. Systemic involvement was reported in 13.9% of patients. All cases of AGEP resolved with cessation of the offending drug. There was no mortality attributed to AGEP. Treatment with systemic steroid was associated with a decreased length of hospital stay (P = .035) in patients with AGEP.ConclusionAGEP was a self-limiting adverse drug reaction that was commonly caused by antibiotics. Although there was no difference in mortality, there was a significant reduction in the length of hospitalization with systemic corticosteroid treatment compared with that of topical corticosteroid treatment of AGEP.

A feasibility study evaluating lisdexamfetamine dimesylate for the treatment of adults with bulimia nervosa.

This study examined the feasibility, safety, and potential efficacy of lisdexamfetamine (LDX) as a treatment for adults with bulimia nervosa (BN). An open-label 8-week feasibility study was conducted in participants with BN. Enrollment rate, dropout rate, safety outcomes, and eating disorder symptom change were examined. Eighteen of 23 participants completed the study per protocol. There was no participant-initiated dropout due to adverse drug reactions and no severe and unexpected adverse drug reactions. An average increase in heart rate of 12.1 beats/min was observed. There was a mean weight reduction of 2.1 kg and one participant was withdrawn for clinically significant weight loss. In the intent-to-treat sample, there were reductions in objective binge episodes and compensatory behaviors from Baseline to Post/End-of-Treatment (mean difference = -29.83, 95% confidence interval: -43.38 to -16.27; and mean difference = -33.78, 95% confidence interval: -48.74 to -18.82, respectively). Results of this study indicate that a randomized controlled trial would be feasible with close monitoring of certain safety parameters (especially over a longer time period as long-term safety is unknown). However, the results should not be used as evidence for clinicians to prescribe LDX to individuals with BN before its efficacy and safety are properly tested. NCT03397446.

A Novel Allele-Specific PCR Protocol for the Detection of the HLA-C*03:02 Allele, a Pharmacogenetic Marker, in Vietnamese Kinh People.

BackgroundAllopurinol, a common anti-hyperuricemia drug, is well known as an inducer of severe cutaneous adverse drug reactions (SCARs). One of the most well-defined risk factors of allopurinol-induced SCARs is the presence of polymorphic alleles of human leukocyte antigen (HLA) genes, such as HLA-B*58:01 and HLA-C*03:02 alleles. There is no commercial test or published in-house protocol for the specific detection of the HLA-C*03:02 allele. In this article, we established for the first time a simple allele-specific (AS) PCR method to identify HLA-C*03:02 allele carriers, and at the same time, determine their zygosities.MethodsA two-step AS-PCR protocol, using four primer sets, was designed to specifically amplify and differentiate the HLA-C*03:02 allele from 17 other HLA-C alleles found in Vietnamese people. The protocol was validated with PCR-sequencing-based typing (SBT) of 100 samples of unknown genotypes.ResultsThe PCR protocol can detect the HLA-C*03:02 allele and determine the zygosity. The results of this protocol were highly consistent with those of the SBT (ĸ = 0.98, p < 0.001). Regarding the specific detection of the HLA-C*03:02 allele, the PCR protocol had a sensitivity of 100% (95% CI: 91.61–100%) and specificity of 98.3% (95% CI: 90.9–99.7%). The protocol was used to determine the distribution of the HLA-C*03:02 allele in 810 unrelated Vietnamese Kinh people, 14.2% of which were HLA-C*03:02 carriers, the allele frequency was 7.5%.ConclusionA novel AS-PCR protocol with a sensitivity of 100% for the detection of the HLA-C*03:02 allele was established. The protocol can be used for personalized treatment with allopurinol in order to minimize the risk of SCARs in Vietnamese people as well as in other Asian populations with similar genetic characteristics.

Prevalence, Pattern and Monitoring of Adverse Drug Reaction in Tertiary Care Psychiatry Setting- A Hospital Based Study in South Kerala

Pharmacovigilance programs usually aim to gather information on the effect of prescribed drugs in the real world rather than in groups of short-lived and carefully selected clinical trial populations. Adverse drug reactions (ADR) associated with psychiatric medications may vary among different populations. As compared with other fields, in Kerala the research related to ADRs and Prescription patterns in psychiatry is scarce. A hospital based cross sectional observational study was undertaken in the Mental Health Centre, Trivandrum. All psychiatric drugs were closely monitor for adverse drug reaction irrespective of their psychiatric diagnosis. CDSCO Suspected adverse drug reaction reporting form was used for the documentation of adverse drug reaction and the causality assessment was done with naranjo scale .The severity of ADR was assessed using Hartwing scale and Preventability assessment using Modified schumock. In this study it was found the highest incident of ADR was reported with risperidone (24%) followed by valproate (20.1%), clozapine (17%) etc. The patient in psychiatry cant identify the adverse effect due to the cognitive impairment. So special attention is necessary for psychiatric patient to find out the incidence of adverse drug reaction and provide the proper management to them.

Utilization of the Naranjo scale to evaluate adverse drug reactions at a free-standing children's hospital.

The relationship between the Naranjo scaling system and pediatric adverse drug reactions (ADR) is poorly understood. We performed a retrospective review of 1,676 pediatric ADRs documented at our hospital from 2014–2018. We evaluated patient demographics, implicated medication, ADR severity, calculated Naranjo score, associated symptoms, and location within the hospital in which the ADR was documented. ADR severity was poorly correlated with Naranjo interpretation. Out of the 10 Naranjo scale questions, 4 had a response of “unknown” greater than 85% of the time. Cardiovascular and oncological/immunologic agents were more likely to have a probable or definite Naranjo interpretation compared to antimicrobials. Further strategies are needed to enhance the causality assessment of pediatric ADRs in clinical care.

Genetic Markers for Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis in the Asian Indian Population: Implications on Prevention

This review attempts to collate all the studies performed in India or comprising a population originating from India and to find out if there is an association between the HLA (human leucocyte antigen) type of individual and development of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) subsequent to medication use. The authors performed a PubMed search of all articles published in English from 2009 to 2019 for articles that studied HLA type in patients who developed SJS/TEN after intake of a specific drug in the Asian Indian population or in individuals of Asian Indian origin. The selection criteria were satisfied by a total of 11 studies that reported HLA associations with specific drugs, which induced SJS/TEN, mainly anti-epileptic drugs, and cold medicine/non-steroidal anti-inflammatory drugs. These studies involved a small number of patients, and hence, there is limited evidence to conclude if these associations can be extrapolated to a larger population of the same ethnicity. Similar multi-center studies need to be conducted with a larger sample size to confirm these associations. This would have implications in policy making and for understanding the potential of using genetic markers as a screening tool before prescribing a drug to a patient, which might make them susceptible to developing a potentially life-threatening disease such as SJS/TEN. This is possibly the only mode of primary prevention for this potentially fatal severe cutaneous adverse drug reaction.

Allopurinol-Induced Severe Cutaneous Adverse Drug Reactions: An Analysis of Spontaneous Reports in Malaysia (2000-2018).

Allopurinol-induced severe cutaneous adverse drug reactions (SCARs) are potentially debilitating and life-threatening reactions, which can cause a financial burden to the healthcare system. We aimed to identify risk factors for allopurinol-induced SCARs and to assess their impact on fatality. Adverse drug reaction (ADR) reports with allopurinol as suspected drug were extracted from the Malaysian pharmacovigilance database from year 2000 to 2018. Multiple logistic regression analysis was used to identify significant predictors of allopurinol-induced SCARs. We further analysed the association between covariates and SCARs-related fatality in a separate model. Level of significance was set at p value < 0.05. Out of 1747 allopurinol ADR reports, 612 involved SCARs (35%). The strongest predictors significantly associated with SCARs were underlying renal disease (odds ratio [OR] 2.02; 95% confidence interval [CI] 1.36, 3.00; p = 0.001), allopurinol-prescribed dose of 300mg/day or higher (OR 1.72; 95% CI 1.38, 2.15; p < 0.001), females (OR 1.54; 95% CI 1.24, 1.93; p < 0.001), age 65years and above (OR 1.31; 95% CI 1.04, 1.64; p = 0.020), and allopurinol-prescribed indication. SCARs cases were higher in patients who received allopurinol for unspecified hyperuricaemia (OR 1.87; 95% CI 1.29, 2.70; p = 0.001) and off-label indications (OR 3.45; 95% CI 2.20, 5.42; p < 0.001) compared to registered indications. Fatality was associated with older age and a diagnosis of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) overlap or TEN. Malaysian pharmacovigilance data show that predictors of allopurinol-induced SCARs were elderly females, patients with underlying renal disease and high allopurinol doses. These patients need close monitoring and must be educated to stop allopurinol at the first signs of rash.

TPMT and HLA-DQA1-HLA-DRB genetic profiling to guide the use of azathioprine in the treatment of interstitial lung disease: First experience

BackgroundThe choice of immunosuppressive therapy in interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF) is based on safety profile and expected efficacy. Azathioprine is one of the most commonly used agents to treat ILD. The immunosuppressive effect and pancreatitis risk of azathioprine are influenced by the activity of the enzyme thiopurine methyltransferase (TPMT) and by the genetic mutations in HLA-DQA1-HLA-DRB locus, respectively. We hypothesized that systematic genotyping prior to starting azathioprine improves the rate of discontinuation of immunosuppressive therapy and the total incidence of adverse drug reactions (ADRs). MethodsEighty-two patients with ILD other than IPF were included in the study. The rate of immunosuppressive therapy discontinuation due to major ADRs and the total incidence of ADRs were compared between a cohort of genotyped patients (n = 49) and an untested cohort of patients (n = 33). ResultsThirty-seven out of 49 patients in the genotyped cohort and 27 out of 33 patients in the untested cohort were started on azathioprine. The rate of immunosuppressive therapy discontinuation due to major ADRs was significantly lower (6/49) in the genotyped cohort compared to the untested cohort (11/33; p = 0.0276). All but one discontinuation due to severe ADRs occurred within a month of therapy. However, the total incidence rate of ADRs was very similar in the 2 cohorts (0.025 in the genotyped cohort vs. 0.023 in the untested cohort). ConclusionIn patients with ILD other than IPF, genotyping for azathioprine metabolism prior to starting therapy is associated with a significantly reduced rate of immunosuppressive therapy discontinuation due to major ADRs, with prevention of bone marrow suppression and pancreatitis, but without a reduction of the total incidence of ADRs. While these data support the use of genetic profiling prior to starting azathioprine to treat ILD, its cost effectiveness remains to be established.